Patent application title: GENES ASSOCIATED WITH MECHANICAL STRESS, EXPRESSION PRODUCTS THEREFROM, AND USES THEREOF

Inventors: Paz Einat (Ness Ziona, IL) Orit Segev (Rehovot, IL) Rami Skaliter (Ness Ziona, IL) Elena Feinstein (Rehovot, IL) Alexander Faerman (Bnei Aiish, IL) Aviva Samach (D.n. Emek Soreq, IL)
Assignees: Quark Biotech, Inc.
IPC8 Class: AA61K39395FI
USPC Class: 4241391
Class name: Binds antigen or epitope whose amino acid sequence is disclosed in whole or in part (e.g., binds specifically-identified amino acid sequence, etc.)
Publication date: 10/15/2009
Patent application number: 20090258021

Abstract:

The disclosure relates to human and mechanical stress induced genes, in particular gene 608, and functional equivalents, probes therefor, tests to identify such genes, polypeptide expression products of such genes, antibodies to the polypeptides, uses for such genes, expression products and antibodies, e.g., in diagnosis (for instance risk determination), treatment, prevention, or control, of osteoporosis or fractures; and to diagnostic, treatment, prevention, or control methods or processes, as well as compositions therefor and methods or processes for making and using such compositions, and receptors therefor and methods or processes for obtaining and using such receptors.

Claims:

1. An isolated polypeptide encoded by a nucleic acid molecule comprising consecutive nucleotides having a sequence set forth in SEQ ID NO:6, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29 or SEQ ID NO:31 or comprising nucleotides having a sequence incorporated in plasmids deposited under ATCC Accession Nos. PTA-3638, PTA-3876, PTA-3877, PTA-3878 complements thereof or a polynucleotide having a sequence that differs due to the degeneracy of the genetic code from SEQ ID NO:6, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:31 or a sequence incorporated in plasmids deposited under ATCC Accession Nos. PTA-3638, PTA-3876, PTA-3877 or PTA-3878, or a sequence which hybridizes under stringent conditions to SEQ ID NO:6, SEQ ID NO: 20, SEQ ID NO: 23, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29 or SEQ ID NO:31 or to a sequence incorporated in plasmids deposited under ATCC Accession Nos. PTA-3638, PTA-3876, PTA-3877 or PTA-3878 or a functional portion thereof or a polynucleotide which is at least substantially homologous thereto.

2. The isolated polypeptide of claim 1, wherein the polypeptide is identified as human protein 608, or a functional portion of protein 608 or Adlican-2, or a polypeptide which is at least substantially homologous thereto.

3. The isolated polypeptide of claim 2, wherein the polypeptide comprises about 663 to about 1634 amino acids.

4. An antibody which specifically binds to a polypeptide of claim 2 or a functional portion thereof.

5. An isolated polypeptide wherein the functional portion comprises consecutive amino acids having a sequence set forth in SEQ ID NO:16, SEQ ID NO: 24, SEQ ID NO: 30 or SEQ ID NO: 32.

6. The isolated polypeptide of claim 5 wherein the sequence comprises about the first 663 amino acids of the sequence set forth in SEQ ID NO:16, SEQ ID NO: 24, SEQ ID NO: 30 or SEQ ID NO: 32.

7. The isolated polypeptide of claim 6 wherein the sequence comprises about the first 741 amino acids of the sequence set forth in SEQ ID NO:16, SEQ ID NO: 24, SEQ ID NO: 30 or SEQ ID NO: 32.

8. The isolated polypeptide of claim 5, wherein the polypeptide is identified as human 608 protein or human Adlican-2 protein or a functional portion thereof or a polypeptide which is at least substantially homologous thereto.

9. An isolated polypeptide of claim 5 comprising consecutive amino acids having a sequence set forth in SEQ ID NO:32, designated human 608 protein.

10. An isolated polypeptide of claim 5 comprising consecutive amino acids having a sequence set forth in SEQ ID NO: 30 designated Adlican-2 polypeptide.

11. An isolated polypeptide of claim 10 comprising consecutive amino acids having a sequence set forth in SEQ ID NO: 30 deleted of amino acids 6-215.

12. An antibody which binds specifically to a polypeptide of claim 9.

13. An antibody which binds specifically to a polypeptide of claim 10.

14. An antibody of claim 12, which does not bind specifically to a rat 608 polypeptide.

15. An antibody of claim 14, wherein the rat polypeptide has a sequence set forth in SEQ ID NO: 34.

16. A composition comprising the antibody of claim 14

Description:

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001]The present application is a divisional of U.S. patent application Ser. No. 10/454,351, filed Jun. 4, 2003, which, in turn, was a continuation-in-part of International Application No. PCT/US01/46400, filed Dec. 4, 2001, the entire contents of which are hereby incorporated by reference, and also a continuation-in-part of U.S. patent application Ser. No. 09/312,216, filed May 14, 1999, the entire contents of which are also hereby incorporated by reference. Each document or reference cited in those applications is hereby expressly incorporated herein by reference. Documents or references are also cited in the following text, and these documents or references ("herein-cited documents or references"), as well as each document or reference cited in each of the herein-cited documents or references, are hereby expressly incorporated herein by reference.

FIELD OF THE INVENTION

[0002]This invention relates to mechanical stress induced genes and their functional equivalents, probes therefor, tests to identify such genes, expression products of such genes, uses for such genes and expression products, e.g., in diagnosis (for instance risk determination), treatment, prevention, or control, of osteoporosis or factors or processes which lead to osteoporosis, osteopenia, osteopetrosis, osteosclerosis, osteoarthritis, periodontosis and bone fractures; and, to diagnosis, treatment, prevention, or control methods or processes, as well as compositions therefor and methods or processes for making and using such compositions, and receptors for such expression products and methods or processes for obtaining and using such receptors.

BACKGROUND OF THE INVENTION

[0003]Bone is composed of a collagen-rich organic matrix impregnated with mineral, largely calcium and phosphate. Two major forms of bone exist, compact cortical bone forms the external envelopes of the skeleton and trabecular or medullary bone forms plates that traverse the internal cavities of the skeleton. The responses of these two forms to metabolic influences and their susceptibility to fracture differ.

[0004]Bone undergoes continuous remodeling (turnover, renewal) throughout life. Mechanical and electrical forces, hormones and local regulatory factors influence remodeling. Bone is renewed by two opposing activities that are coupled in time and space. Parfitt (1979) Calcify Tis. Int. 28:1-5. These activities, resorption and formation, are contained within a temporary anatomic structure known as a bone-remodeling unit. Parfitt (1981) Res. Staff Physic. Dec.: 60-72. Within a given bone-remodeling unit, old bone is resorbed by osteoclasts. The resorbed cavity created by osteoclasts is subsequently filled with new bone by osteoblasts, synthesizing bone organic matrix.

[0005]Peak bone mass is mainly genetically determined, though dietary factors and physical activity can have positive effects. Peak bone mass is attained at the point when skeletal growth ceases, after which time bone loss starts.

[0006]In contrast to the positive balance that occurs during growth, in osteoporosis, the resorbed cavity is not completely refilled by bone. Parfitt (1988), Osteoporosis: Etiology, Diagnosis, and Management (Riggs and Melton, eds.) Raven Press, New York, pp. 74-93. Osteoporosis, or porous bone, is a progressive and chronic disease characterized by low bone mass and structural deterioration of bone tissue, leading to bone fragility and an increased susceptibility to fractures of the hip, spine, and wrist (diminishing bone strength).

[0007]Bone loss occurs without symptoms. The Consensus Development Conference ((1993) Am. J. Med. 94:646-650) defined osteoporosis as "a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture."

[0008]Common types of osteoporosis include postmenopausal osteoporosis; and senile osteoporosis, which generally occurs in later life, e.g., 70+ years. See, e.g., U.S. Pat. No. 5,691,153. Osteoporosis is estimated to affect more than 25 million people in the United States (Rosen (1997) Calcif. Tis. Int. 60:225-228); and, at least one estimate asserts that osteoporosis affects 1 in 3 women. Keen et al. (1997) Drugs Aging 11:333-337. Moreover, life expectancy has increased, and in the western world, 17% of women are now over 50 years of age: a woman can expect to live one third of her life after menopause. Thus, some estimate that 1 out of every 2 women and 1 out of 5 men will eventually develop osteoporosis; and, that 75 million people in the U.S., Japan and Europe have osteoporosis. The World Summit of Osteoporosis Societies estimates that more than 200 million people worldwide are afflicted with the disease. The actual incidence of the disease is difficult to estimate since the condition is often asymptomatic until a bone fracture occurs. It is believed that there are over 1.5 million osteoporosis-associated bone fractures per year in the U.S. Of these, 300,000 are hip fractures that usually require hospitalization and surgery and may result in lengthy or permanent disability or even death. See a minireview by Spangler et al. "The Genetic Component of Osteoporosis" (1997) Cambridge Scientific Abstracts".

[0009]Osteoporosis is also a major health problem in virtually all societies. Eisman (1996); Wark (1996) Maturitas 23:193-207; and U.S. Pat. No. 5,834,200. There is a20-30% mortality rate related to hip fractures in elderly women (U.S. Pat. No. 5,691,153); and, such a patient with a hip fracture has a 10-15% greater chance of dying than others of the same age. Further, although men suffer fewer hip injuries than women, men are 25% more likely than women to die within one year of the injury. See Spangler et al., supra. Also, about 20% of the patients who lived independently before a hip fracture remain confined in a long-term health care facility one year later. The treatment of osteoporosis and related fractures costs over $10 billion annually.

[0010]Osteoporosis treatment helps stop further bone loss and fractures. Common therapeutics include HRT (hormone replacement therapy), bisphosphonates, e.g., alendronate (Fosamax), estrogen and estrogen receptor modulators, progestin, calcitonin, and vitamin D. While there may be numerous factors that determine whether any particular person will develop osteoporosis, a step towards prevention, control or treatment of osteoporosis is determining whether one is at risk for osteoporosis. Genetic factors also play an important role in the pathogenesis of osteoporosis. Ralston (1997); see also Keen et al. (1997); Eisman (1996); Rosen (1997); Cole (1998); Johnston et al. (1995) Bone 17(2 Suppl)19S-22S; Gong et al. (1996) Am. J. Hum. Genet. 59:146-151; and Wasnich (1996) Bone 18(3 Suppl): 179S-183S. Some attribute 50-60% of total bone variation (bone mineral density: "BMD"), depending upon the bone area, to genetic effects. Livshits et al. (1996) Hum. Biol. 68:540-554. However, up to 85%-90% of the variance in bone mineral density may be genetically determined.

[0011]Studies have shown from family histories, twin studies, and racial factors, that there may be a predisposition for osteoporosis. Jouanny et al. (1995) Arthritis Rheum. 38:61-67; Garnero et al. (1996) J. Clin. Endrocrinol. Metab. 81:140-146; Cummings (1996) Bone 18(3 Suppl): 165S-167S; and Lonzer et al. (1996) Clin. Pediatr. 35:185-189. Several candidate genes may be involved in this, most probably multigenic, process.

[0012]Cytokines are powerful regulators of bone resorption and formation under control of estrogen/testosterone, parathyroid hormone and 1,25(OH)₂D3. Some cytokines primarily enhance osteoclastic bone resorption e.g. IL-1 (interleukin-1), TNF (tumor necrosis factor) and IL-6 (interleukin-6); while others primarily stimulate bone formation e.g. TGF-β (transforming growth factor-β), IGF (insulin-like growth factor) and PDGF (platelet derived growth factor).

[0013]There is need for clinical and epidemiological research for the prevention and treatment of osteoporosis for gaining greater knowledge of factors controlling bone cell activity and regulation of bone mineral and matrix formation and remodeling.

[0014]Bone develops via a number of processes. Mesenchymal cells can differentiate directly into bone, as occurs in the flat bones of the craniofacial skeleton; this process is termed intramembranous ossification. Alternatively, cartilage provides a template for bone morphogenesis, as occurs in the majority of human bones. The cartilage template is replaced by bone in a process known as endochondral ossification. Reddi (1981) Collagen Rel. Res. 1:209-226. Bone is also continuously modeled during growth and development and remodeled throughout the life of the organism in response to physical and chemical signals. Development and maintenance of cartilage and bone tissue during embryogenesis and throughout the lifetime of vertebrates is very complex. It is widely accepted that a multitude of factors, from systemic hormones to local regulatory factors such as the members of the TGF-β superfamily, cytokines and prostaglandins, act in concert to regulate the continuous processes of bone formation and bone resorption. Disturbance of the balance between osteoblastic bone deposition and osteoclastic bone resorption is responsible for many skeletal diseases.

[0015]Diseases of bone loss are a major public health problem especially for women in all Western communities. The most common cause of osteopenia is osteoporosis; other causes include osteomalacia and bone disease related to hyperparathyroidism. Osteopenia has been defined as the appearance of decreased bone mineral content on radiography, but the term more appropriately refers to a phase in the continuum from decreased bone mass to fractures and infirmity.

[0016]It is estimated that 30 million Americans are at risk for osteoporosis, the most common among these diseases, and there are probably 100 million people similarly at risk worldwide. Melton (1995) Bone Min. Res. 10:175. These numbers are growing as the proportion of the elderly in the world population increases. Despite recent successes with drugs that inhibit bone resorption, there is a clear need for specific anabolic agents that will considerably increase bone formation in people who have already suffered substantial bone loss. There are no such drugs currently approved.

[0017]Mechanical stimulation induces new bone formation in vivo and increases osteoblastic differentiation and metabolic activity in culture. Mechanotransduction in bone tissue involves several steps: 1) mechanochemical transduction of the signal; 2) cell-to-cell signaling; and 3) increased number and activity of osteoblasts. Cell-to-cell signaling after mechanical stimulus involves prostaglandins, especially those produced by COX-2, and nitric oxide. Prostaglandins induce new bone formation by promoting both proliferation and differentiation of osteoprogenitor cells.

OBJECTS AND SUMMARY OF THE INVENTION

[0018]In a search for agents that enhance osteoblast proliferation/differentiation and bone formation, mechanical force was employed as an osteogenesis inducer and a proprietary gene discovery methodology was carried out to detect genes that are specifically expressed in very early osteo-, chondro-progenitor cells.

[0019]The present invention provides human mechanical stress induced genes and their functional equivalents, expression products of such genes, uses for such genes and expression products for treatment, prevention, control, of osteoporosis or factors or processes which are involved in bone diseases including, but not limited to, osteoporosis, osteopenia, osteopetrosis, osteosclerosis, osteoarthritis, periodontosis and bone fracture. The invention further provides diagnostic, treatment, prevention, control methods or processes as well as compositions.

[0020]The invention additionally provides an isolated nucleic acid molecule, and the complement thereof, encoding the protein 608 or a functional portion thereof or a polypeptide, which is at least substantially homologous thereto. The invention encompasses an isolated nucleic acid molecule encoding human protein 608 (or "OCP") or a functional portion thereof.

[0021]The invention further encompasses a method for preventing, treating or controlling osteoporosis or low bone density or other factors associated with, causing or contributing to bone diseases including, but not limited to, osteopenia, osteopetrosis, osteosclerosis, osteoarthritis, periodontosis or symptoms thereof, or other conditions involving mechanical stress or a lack thereof, by administering to a subject in need thereof, a polypeptide or portion thereof provided herein; and accordingly, the invention comprehends uses of polypeptides in preparing a medicament or therapy for such prevention, treatment or control.

[0022]The invention also comprehends a method for preventing, treating or controlling osteoporosis or low bone density or other factors causing or contributing to osteoporosis or symptoms thereof or other conditions involving mechanical stress or a lack thereof, by administering a composition comprising a gene or functional portion thereof, the expression product of that gene or a functional portion thereof, an antibody or portion thereof elicited by such an expression product or portion thereof, and, the invention thus further comprehends uses of such genes, expression products, antibodies, portions thereof, in the preparation of a medicament or therapy for such control, prevention or treatment.

[0023]Analogously with the OCP-related description above, the invention further encompasses methods of use of Adlican and a novel polypeptide Adlican-2 as described herein for any use of OCP. The Adlican gene, or Adlican-2 gene, or functional portions thereof, can likewise be used for any purpose described herein for an OCP gene. The invention further encompasses compositions comprising a physiologically acceptable excipient and at least one of Adlican, the Adlican gene and antibodies specific to Adlican, and at least one of Adlican-2, the Adlican-2 gene and antibodies specific to Adlican-2.

[0024]The invention additionally provides receptors for expression products of human mechanical stress induced genes and their functional equivalents, such as OCP and Adlican, and methods or processes for obtaining and using such receptors. The invention also provides methods of using such receptors in assays, for instance for identifying proteins or polypeptides that bind to, associate with or block the receptors, and for testing the effects of such polypeptides. These and other embodiments are disclosed or are obvious from and encompassed by, the Detailed Description which follows the Brief Description of the Figures below.

BRIEF DESCRIPTION OF THE FIGURES

[0025]The following Detailed Description, given by way of example, but not intended to limit the invention to specific embodiments described, may be understood in conjunction with the accompanying Figures, in which

[0026]FIG. 1 shows the rat 608 cDNA sequence (SEQ ID NO:1).

[0027]FIG. 2 shows the pcDNA3.1-608 construct.

[0028]FIG. 3 shows the OCP rat protein amino acid sequence (SEQ ID NO:2).

[0029]FIG. 4 shows the mouse OCP exon and intron map.

[0030]FIG. 5 shows the OCP map of exon-intron borders.

[0031]FIG. 6 shows the human OCP exon and intron list.

[0032]FIG. 7 shows the OCP human cDNA sequence (predicted coding region) (nucleotides 1-7796 of SEQ ID NO:6).

[0033]FIGS. 8A-8D show the percent identity between FIG. 8A. rat protein/human protein; FIG. 8B. rat protein/mouse protein; FIG. 8C. rat cDNA/human cDNA; and FIG. 8D. rat cDNA/mouse cDNA, based on the OCP human cDNA sequence of FIG. 7

[0034]FIG. 9 shows the partial mouse OCP protein amino acid sequence (236 aa) (SEQ ID NO:15).

[0035]FIG. 10 shows the OCP human protein amino acid sequence (2587 aa) (SEQ ID NO:16), based on the OCP human cDNA sequence of FIG. 7.

[0036]FIGS. 11A-11B show a list of expression patterns of OCP in primary cells and various other cell lines. A. Northern blot of poly A+ RNA RT-PCR from rat primary calvaria cells and MC3T3 cells is shown. The main 8.9 kb transcript is present only in calvaria cells. RT-PCR assays with specific OCP primers were performed on total RNA from various lines as indicated on the right side of the figure. In all assays similar amounts of GapDH RT-PCR products were detected in all RNA samples. In addition, B. no GapDH products were detected in any RNA samples, when RT was omitted. (-) represents no expression of OCP, while (+) represents expression. When (-+) are indicated, the expression of OCP is induced only upon specific conditions.

[0037]FIG. 12 shows responsiveness of CMF608 expression to mechanical stimulation by Northern blot analysis using polyA RNA from primary rat calvaria cells before and after mechanical stress (m.s.)--see left of Figure. In these cells, CMF608 is transcribed as a single RNA species of approximately 9 Kb. On tissue blot, CMF608-specific 9 Kb mRNA transcript was hardly detectable in any other tissue type except for the bone (B)--see right of Figure.

[0038]FIG. 13 shows that OCP is an early marker of endochondral ossification in P7 rat femoral epiphysis.

[0039]FIG. 14 shows that OCP is induced during osteoblastic differentiation of bone marrow stroma cells and is a specific marker of early osteoblastic differentiation in bone marrow.

[0040]FIG. 15 shows in vivo regulation of OCP expression in bone marrow formation by various treatments. The results shown are representative of three experiments using total cellular RNA from treated two-month old mice. The different treatments are indicated. The RT-PCR products are marked. Control mice did not undergo any treatment. In each treatment group the left lane represents negative control without the addition of RT, the central lane represents the OCP RT-PCR product and the right lane represents the GapDH RT-PCR product. Bone formation is shown with blood loss and estrogen administration; bone loss is shown with sciatic neurotomy models.

[0041]FIG. 16 shows a low power photomicrograph of fractured bone one week after the operation. Note that well-developed woven bone and fibrocartilagenous callus formed at the fracture site. Bone marrow tissue was mainly destroyed by insertion of the wire used for the fracture immobilization. Marked areas are presented at higher magnification in the following figures.

[0042]FIGS. 17A-17B show photomicrographs of the central part of callus, FIG. 17A. brightfield and FIG. 17B. darkfield. Cells expressing the OCP gene can be seen in the fibrous part of the callus. There was no hybridization signal from chondrocytes.

[0043]FIGS. 18A-18B show photomicrographs of the callus area marked by 2 in FIG. 16, FIG. 18A. brightfield and FIG. 18B. darkfield. Cells expressing the OCP gene can be seen in a highly vascularized subperiosteal area bordering the cartilagenous part of the callus.

[0044]FIGS. 19A-B show photomicrographs of the highly vascularized endosteal tissue. This was developed in reaction to the wire insertion (area 3 on FIG. 16), FIG. 19A. brightfield and FIG. 19B. darkfield. This tissue contains many cells expressing the OCP gene.

[0045]FIG. 20 shows a high power photomicrograph of perivascular cells. The perivascular cells express the 608 gene within lacuna of woven bone arrowheads.

[0046]FIG. 21 shows a high power photomicrograph of periosteum covering the woven bone. Multiple cells display expression of the 608 gene in periosteum. Arrowheads point to two 608 expressing cells within the woven bone.

[0047]FIGS. 22A-22B show FIG. 22A. brightfield and FIG. 22B. darkfield photomicrographs of a section of fractured bone healed for 4 weeks. Multiple cells in periosteal tissue area of active remodeling of the cancellous bone covering the callus show a hybridization signal.

[0048]FIG. 23 shows the boxed area of FIG. 22 presented at higher magnification. Several OCP-expressing cells are concentrated in vascular tissue that fills the cavities resulting from osteoclast activity (marked by asterisks).

[0049]FIG. 24 shows increased osteoblast differentiation in OCP-transfected ROS cells. RT-PCR assays were with OCP, Cbfa1, ALP, BSP and GapDH specific primers as indicated above. The results shown are representative of two experiments using total cellular RNA from: (1) the stable OCP-expressed ROS cell line; and (2) the control ROS cell line (stable transfection with pcDNA). The OCP RT-PCR product is 1020 bp, the Cbfa1 product is 289 bp, the ALP product is 226 bp, the BSP product is 1048 bp and the GapDH (control) product is 450 bp long. M represents protein markers.

[0050]FIG. 25 shows increased osteoblast proliferation in OCP-transfected ROS cells.

[0051]FIG. 26 shows the sequences of the primer (SEQ ID NO:19) and QB3 (CMF608) (SEQ ID NO:20).

[0052]FIG. 27 shows the Adlican amino acid sequence (SEQ ID NO: 21).

[0053]FIG. 28 shows the Adlican DNA sequence (SEQ ID NO: 22)

[0054]FIG. 29 shows the predicted DNA sequence of the coding region-ORF of human OCP (SEQ ID NO: 23).

[0055]FIG. 30 shows the predicted amino acid sequence corresponding to the predicted coding region-ORF of human OCP (SEQ ID NO: 24).

[0056]FIG. 31 shows the sequence of the N-terminal 663 amino acid fragment derived from the OCP rat protein (SEQ ID NO: 25).

[0057]FIG. 32 shows the pCM-H-608-663-N-term construct map.

[0058]FIG. 33 shows the structure of the pKS H608 5'-2.4 Kb bAc#1 construct (deposited on Nov. 21, 2001 under the terms of the Budapest Treaty with the American Type Culture Collection (ATCC), P.O. Box 1549, Manassas, Va. 20108, USA, under ATCC accession number PTA-3878).

[0059]FIG. 34 shows the physical sequence of the 5' fragment (A) cloned into pBluescript KS to NotI (5') and HindIII (3') sites. Fragment A is comprised of the 5' region (2440 bp) of the complete human OCP sequence and includes, in addition, at the 5' end, 21 nucleotides of the β-actin "Kozak" region (SEQ ID NO:26).

[0060]FIG. 35 shows the structure of the pKS H608 m.FRG.3.5 Kb#34 construct (deposited on Nov. 21, 2001 under the terms of the Budapest Treaty with the American Type Culture Collection (ATCC), P.O. Box 1549, Manassas, Va. 20108, USA, under ATCC accession number PTA-3876)

[0061]FIG. 36 shows the physical sequence of the middle fragment (B) cloned into pBluescript KS to HindIII (5') and SalI (3') sites. Fragment B is comprised of the central region (3518 bp) of the complete human OCP sequence (SEQ ID NO:27).

[0062]FIG. 37 shows the structure of the pM H608 3'-1.9 Kb HSTG#3.3 construct (deposited on Nov. 21, 2001 under the terms of the Budapest Treaty with the American Type Culture Collection (ATCC), P.O. Box 1549, Manassas, Va. 20108, USA, under ATCC accession number PTA-3877).

[0063]FIG. 38 shows the physical sequence of the 3' fragment (C) cloned into pMCS SV(A) to SalI (5') and SpeI (3') sites. Fragment C is comprised of the 3' region (1923 bp, not including the 3 bp stop codon) of the complete human OCP sequence and includes, at the 3' end, 18 nucleotides coding for 6 Histidine residues (SEQ ID NO:28). Also cloned fragment C contains a silent mutation (C>T transition) compared to the predicted sequence of human OCP ORF. This transition does not change the identity of the encoded amino acid residue.

[0064]FIG. 39 shows the predicted DNA sequence of Adlican-2 (SEQ ID NO:29). Bases 1555 and 5638 are presented as "g" but could be any other base.

[0065]FIG. 40 shows the predicted amino acid sequence of human Adlican-2 (SEQ ID NO:30).

[0066]FIG. 41 shows the amino acid sequence alignment of (i) human Adlican (SEQ ID NO: 21), (ii) human Adlican-2 full amino acid predicted sequence, as determined by the inventors (SEQ ID NO 30), (iii) deduced sequence (hLOC96359) of human Adlican-2 fragment of 539 amino acid residues as found in the database (residues 2036-2652 of SEQ ID NO 30), and (iv) deduced sequence (hLOC90792) of human Adlican-2-fragment of 617 amino acid residues as found in the database (residues 2114-2652 of SEQ ID NO 30).

[0067]FIG. 42 shows the complete physical DNA sequence of the coding region (ORF) of human OCP (SEQ ID NO: 31).

[0068]FIG. 43 shows the predicted amino acid sequence corresponding to the complete physical DNA sequence of the coding region (ORF) of human OCP (SEQ ID NO:32).

[0069]FIG. 44 shows the full rat 608 cDNA sequence (SEQ ID NO:33). This sequence is virtually identical to SEQ ID NO:1, but five unknown nucleotides (designated "n" in SEQ ID NO:1) have been identified. The ORF is from position 575 to 8368.

[0070]FIG. 45 shows the OCP rat protein amino acid sequence corresponding to the above ORF sequence (SEQ ID NO:34). Three previously unknown amino acids have been identified, as compared to SEQ ID NO:2, where these amino acids are designated "Xaa".

[0071]FIG. 46 shows that ALP, which is a biochemical serum marker of bone formation, is significantly increased in 3 month old 608 KO mice.

DETAILED DESCRIPTION OF THE INVENTION

[0072]The present invention is related to the discovery of a novel gene, 608 ("OCP"), the expression of which is upregulated by mechanical stress on primary calvaria cells. Several functional features identify OCP as a most specific early marker of osteo- or chondro-progenitor cells as well as an inducer of osteoblast proliferation and differentiation.

[0073]As used herein, the same gene of the invention may be referred to either as "608" or "OCP." RNA refers to RNA isolated from cell cultures, cultured tissues or cells or tissues isolated from organisms which are stimulated, differentiated, exposed to a chemical compound, infected with a pathogen, or otherwise stimulated. As used herein, translation is defined as the synthesis of protein encoded by an mRNA template.

[0074]As used herein, stimulation of translation, transcription, stability or transportation of unknown target mRNA or stimulating element, includes chemically, pathogenically, physically, or otherwise inducing or repressing an mRNA population encoded by genes derived from native tissues and/or cells under pathological and/or stress conditions. In other words, stimulating the expression of an mRNA with a stress inducing element or "stressor" includes, but is not limited to, the application of an external cue, stimulus, or stimuli that stimulates or initiates translation of an mRNA stored as untranslated mRNA in the cells from the sample. The stressor may cause an increase in stability of certain mRNAs, or induce the transport of specific mRNAs from the nucleus to the cytoplasm. The stressor may also induce specific gene transcription. In addition to stimulating translation of mRNA from genes in native cells/tissues, stimulation can include induction and/or repression of genes under pathological and/or stress conditions. The method utilizes a stimulus or stressor to identify unknown target genes regulated at the various possible levels by the stress inducing element or stressor.

[0075]More in particular, with respect to nucleic acid molecules (rat 608 and human 608 genes) and polypeptides expressed from them, the invention further comprehends isolated and/or purified nucleic acid molecules and isolated and/or purified polypeptides having at least about 70%, preferably at least about 75% or about 77% homology ("substantially homologous"); advantageously at least about 80% or about 83%, such as at least about 85% or about 87% homology ("significantly homologous"); for instance at least about 90% or about 93% homology ("highly homologous"); more advantageously at least about 95%, e.g., at least about 97%, about 98%, about 99% or even about 100% homology ("very highly homologous" to "100% (homologous"); or from about 84-100% homology considered "highly conserved". The invention also comprehends that these nucleic acid molecules and polypeptides can be used in the same fashion as the herein or aforementioned nucleic acid molecules and polypeptides.

[0076]Nucleotide sequence homology can be determined using the "Align" program of Myers and Miller, ((1988) CABIOS 4:11-17) and available at NCBI. Alternatively or additionally, the term "homology" for instance, with respect to a nucleotide or amino acid sequence, can indicate a quantitative measure of homology between two sequences. The percent sequence homology can be calculated as (N_ref-N_dif)*100/N_ref, wherein N_dif is the total number of non-identical residues in the two sequences when aligned and wherein N_ref is the number of residues in one of the sequences. Hence, AGTCAGTC has a sequence similarity of 75% to AATCAATC(N_ref=8; N_dif=2).

[0077]Alternatively or additionally, "homology" with respect to sequences can refer to the number of positions with identical nucleotides or amino acid residues divided by the number of nucleotides or amino acid residues in the shorter of the two sequences wherein alignment of the two sequences can be determined in accordance with the Wilbur and Lipman algorithm ((1983) Proc. Natl. Acad. Sci. USA 80:726), for instance, using a window size of 20 nucleotides, a word length of 4 nucleotides, and a gap penalty of 4, and computer-assisted analysis and interpretation of the sequence data including alignment can be conveniently performed using commercially available programs (e.g., Intelligenetics® Suite, Intelligenetics Inc., CA). When RNA sequences are said to be similar, or have a degree of sequence identity or homology with DNA sequences, thymidine (T) in the DNA sequence is considered equal to uracil (U) in the RNA sequence. RNA sequences within the scope of the invention can be derived from DNA sequences or their complements, by substituting thymidine (T) in the DNA sequence with uracil (U).

[0078]Additionally or alternatively, amino acid sequence similarity or identity or homology can be determined, for instance, using the BlastP program (Altschul et al. Nucl. Acids Res. 25:3389-3402) and available at NCBI. The following references provide algorithms for comparing the relative homology of amino acid residues of two proteins, and additionally, or alternatively, with respect to the foregoing, the teachings in these references can be used for determining percent homology. Smith et al. (1981) Adv. Appl. Math. 2:482-489; Smith et al. (1983) Nucl. Acids Res. 11:2205-2220; Devereux et al. (1984) Nucl. Acids Res. 12:387-395; Feng et al. (1987) J. Molec. Evol. 25:351-360; Higgins et al. (1989) CABIOS 5:151-153; and Thompson et al. (1994) Nucl. Acids Res. 22:4673-480.

[0079]As to uses, the inventive genes and expression products as well as genes identified by the herein disclosed methods and expression products thereof and the compositions comprising Adlican or the Adlican gene (including "functional" variations of such expression products, and truncated portions of herein defined genes such as portions of herein defined genes which encode a functional portion of an expression product) are useful in treating, preventing or controlling or diagnosing mechanical stress conditions or absence or reduced mechanical stress conditions.

[0080]As described herein, Adlican, including functional portions thereof, can be used in all methods suitable for OCP. The sequence homology between Adlican and human OCP provides this novel use of the Adlican protein. Adlican is provided, for instance, in AF245505.1:1.8487. Adlican is named for "Adhesion protein with Leucine-rich repeats has immunoglobulin domains related to perleCAN"; and shows elevated expression in cartilage from osteoarthritis patients. The Adlican gene, or functional portions thereof, can likewise be used for any purpose described herein for an OCP gene. The invention further encompasses compositions comprising a physiologically acceptable excipient and at least one of Adlican, the Adlican gene and antibodies specific to Adlican.

[0081]OCP expression is related to proliferation and differentation of osteoblasts and chondrocytes. The expression product of OCP, or cells or vectors expressing OCP may cause cells to selectively proliferate and differentiate and thereby increase or alter bone density. Detecting levels of OCP mRNA or expression and comparing it to "normal" non-osteopathic levels may allow one to detect subjects at risk for osteoporosis or lower levels of osteoblasts and chondrocytes.

[0082]The medicament or treatment can be any conventional medicament or treatment for osteoporosis. Alternatively, or additionally, the medicament or treatment can be the particular protein of the gene detected in the inventive methods, or that which inhibits that protein, e.g., binds to it. Similarly, additionally, or alternatively, the medicament or treatment can be a vector which expresses the protein of the gene detected in the inventive methods or that which inhibits expression of that gene; again, for instance, that which can bind to it and/or otherwise prevents its transcription or translation. The selection of administering a protein or that which expresses it, or of administering that which inhibits the protein or the gene expression, can be done without undue experimentation, e.g., based on down-regulation or up-regulation as determined by inventive methods (e.g., in the osteoporosis model).

[0083]In the practice of the invention, one can employ general methods in molecular biology. Standard molecular biology techniques known in the art and not specifically described are generally followed as in Sambrook et al. (1989, 1992) Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory, New York; and Ausubel et al. (1989) Current Protocols in Molecular Biology, John Wiley and Sons, Baltimore, Md.

[0084]PCR comprising the methods of the invention is performed in a reaction mixture comprising an amount, typically between <10 ng-200 ng template nucleic acid; 50-100 pmoles each oligonucleotide primer; 1-1.25 mM each deoxynucleotide triphosphate; a buffer solution appropriate for the polymerase used to catalyze the amplification reaction; and 0.5-2 Units of a polymerase, most preferably a thermostable polymerase (e.g., Taq polymerase or Tth polymerase).

[0085]Antibodies may be used in various aspects of the invention, e.g., in detection or treatment or prevention methods. Antibodies can be monoclonal, polyclonal or recombinant for use in the immunoassays or other methods of analysis necessary for the practice of the invention. By the term "antibody" as used in the present invention is meant both poly- and mono-clonal complete antibodies as well as fragments thereof, such as Fab, F(ab')₂, and Fv, which are capable of binding the epitopic determinant. These antibody fragments retain the ability to selectively bind with its antigen or receptor and are exemplified as follows, inter alia: [0086](1) Fab, the fragment which contains a monovalent antigen-binding fragment of an antibody molecule can be produced by digestion of whole antibody with the enzyme papain to yield a light chain and a portion of the heavy chain; [0087](2) (Fab')₂, the fragment of the antibody that can be obtained by treating whole antibody with the enzyme pepsin without subsequent reduction; F(ab'₂) is a dimer of two Fab fragments held together by two disulfide bonds; [0088](3) Fv, defined as a genetically engineered fragment containing the variable region of the light chain and the variable region of the heavy chain expressed as two chains; and [0089](4) Single chain antibody (SCA), defined as a genetically engineered molecule containing the variable region of the light chain and the variable region of the heavy chain linked by a suitable polypeptide linker as a genetically fused single chain molecule.

[0090]Conveniently, the antibodies may be prepared against the immunogen or antigenic portion thereof for example a synthetic peptide based on the sequence, or prepared recombinantly by cloning techniques or the natural gene product and/or portions thereof may be isolated and used as the immunogen. The genes are identified as set forth in the present invention and the gene product identified. Immunogens can be used to produce antibodies by standard antibody production technology well known to those skilled in the art as described generally in Harlow and Lane (1988) Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.; and Borrebaeck (1992) Antibody Engineering--A Practical Guide, W.H. Freeman and Co. Antibody fragments, as mentioned above, include Fab, F(ab')2, Fv and scFv prepared by methods known to those skilled in the art. Bird et al. (1988) Science 242:423-426. Any peptide having sufficient flexibility and length can be used as an scFv linker. Usually the linker is selected to have little to no immunogenicity. Linker sequences can also provide additional functions, such as a means for attaching a drug or a solid support.

[0091]For producing polyclonal antibodies, a host, such as a rabbit or goat, is immunized with the immunogen or an immunogenic fragment thereof, generally with an adjuvant and, if necessary, coupled to a carrier; and antibodies to the immunogen are collected from the sera of the immunized animal. The sera can be adsorbed against related immunogens so that no cross-reactive antibodies remain in the sera rendering the polyclonal antibody monospecific.

[0092]For producing monoclonal antibodies (mAbs), an appropriate donor, generally a mouse, is hyperimmunized with the immunogen and splenic antibody producing cells are isolated. These cells are fused to an immortal cell, such as a myeloma cell, to provide an immortal fused cell hybrid that secretes the antibody. The cells are then cultured, in bulk, and the mAbs are harvested from the culture media for use. Hybridoma cell lines provide a constant, inexpensive source of chemically identical antibodies and preparations of such antibodies can be easily standardized. Methods for producing mAbs are well known to those of ordinary skill in the art. See, e.g. U.S. Pat. No. 4,196,265.

[0093]For producing recombinant antibodies, mRNAs from antibody producing B lymphocytes of animals, or hybridomas are reverse-transcribed to obtain cDNAs. See generally, Huston et al. (1991) Met. Enzymol. 203:46-88; Johnson and Bird (1991) Met. Enzymol. 203:88-99; and Mernaugh and Memaugh (1995) In, Molecular Methods in Plant Pathology (Singh and Singh eds.) CRC Press Inc. Boca Raton, Fla., pp. 359-365). Antibody cDNA, which can be full or partial length, is amplified and cloned into a phage or a plasmid. The cDNA can be a partial length of heavy and light chain cDNA, separated or connected by a linker. The antibody, or antibody fragment, is expressed using a suitable expression system to obtain recombinant antibody. Antibody cDNA can also be obtained by screening pertinent expression libraries.

[0094]Antibodies can be bound to a solid support substrate or conjugated with a detectable moiety or be both bound and conjugated as is well known in the art. For a general discussion of conjugation of fluorescent or enzymatic moieties see, Johnston and Thorpe (1982) Immunochemistry in Practice, Blackwell Scientific Publications, Oxford. The binding of antibodies to a solid support substrate is also well known in the art. See for a general discussion, Harlow and Lane (1988); and Borrebaeck (1992). The detectable moieties contemplated with the present invention include, but are not limited to, fluorescent, metallic, enzymatic and radioactive markers such as biotin, gold, ferritin, alkaline phosphatase, β-galactosidase, peroxidase, urease, fluorescein, rhodamine, tritium, ¹³C and iodination.

[0095]Antibodies can also be used as an active agent in a therapeutic composition and such antibodies can be humanized, for instance, to enhance their effects. See, Huls et al. Nature Biotech. 17:1999. "Humanized" antibodies are antibodies in which at least part of the sequence has been altered from its initial form to render it more like human immunoglobulins. In one version, the H chain and L chain C regions are replaced with human sequence. In another version, the CDR regions comprise amino acid sequences from the antibody of interest, while the V framework regions have also been converted human sequences. See, for example, EP 0329400. In a third version, V regions are humanized by designing consensus sequences of human and mouse V regions, and converting residues outside the CDRs that are different between the consensus sequences. The invention encompasses humanized mAbs.

[0096]The expression product from the gene or portions thereof can be useful for generating antibodies such as monoclonal or polyclonal antibodies which are useful for diagnostic purposes or to block activity of expression products or portions thereof or of genes or a portion thereof, e.g., as therapeutics.

[0097]Note that some antibodies to the mouse or rat 608 polypeptide may also bind the human 608 polypeptide. A preferred set of antibodies encompassed by this invention are antibodies which bind human 608 polypeptide but which do not bind rat 608 polypeptide. Another preferred set of antibodies encompassed by this invention are antibodies which bind human 608 polypeptide but which do not bind mouse 608 polypeptide

[0098]The genes of the present invention or portions thereof, e.g., a portion thereof which expresses a protein which function the same as or analogously to the full length protein, or genes identified by the methods herein can be expressed recombinantly, e.g., in Escherichia coli or in another vector or plasmid for either in vivo expression or in vitro expression. The methods for making and/or administering a vector or recombinant or plasmid for expression of gene products of genes of the invention or identified by the invention or a portion thereof either in vivo or in vitro can be any desired method, e.g., a method which is by or analogous to the methods disclosed in: U.S. Pat. Nos. 4,603,112; 4,769,330; 5,174,993; 5,505,941; 5,338,683; 5,494,807; 4,394,448; 4,722,848; 4,745,051; 4,769,331; 5,591,639; 5,589,466; 4,945,050; 5,677,178; 5,591,439; 5,552,143; and 5,580,859; U.S. patent application Serial No. 920,197, filed Oct. 16, 1986; WO 94/16716; WO 96/39491; WO91/11525; WO 98/33510; WO 90/01543; EP 0 370 573; EP 265785; Paoletti (1996) Proc. Natl. Acad. Sci. USA 93:11349-11353; Moss (1996) Proc. Natl. Acad. Sci. USA 93:11341-11348; Richardson (Ed) (1995) Methods in Molecular Biology 39, "Baculovirus Expression Protocols," Humana Press Inc.; Smith et al. (1983) Mol. Cell. Biol. 3:2156-2165; Pennock et al. (1984) Mol. Cell. Biol. 4:399-406; RoizmanProc. Natl. Acad. Sci. USA 93:11307-11312; Andreansky et al. Proc. Natl. Acad. Sci. USA 93:11313-11318; Robertson et al. Proc. Natl. Acad. Sci. USA 93:11334-11340; Frolov et al. Proc. Natl. Acad. Sci. USA 93:11371-11377; Kitson et al. (1991) J. Virol. 65:3068-3075; Grunhaus et al. (1992) Sem. Virol. 3:237-52; Ballay et al. (1993) EMBO J. 4:3861-65; Graham (1990) Tibtech 8:85-87; Prevec et al. J. Gen. Virol. 70:429-434; Felgner et al. (1994) J. Biol. Chem. 269:2550-2561; (1993) Science 259:1745-49; McClements et al. (1996) Proc. Natl. Acad. Sci. USA 93:11414-11420; Ju et al. (1998) Diabetologia 41:736-739; and Robinson et al. (1997) Sem. Immunol. 9:271-283.

[0099]The expression product generated by vectors or recombinants can also be isolated and/or purified from infected or transfected cells; for instance, to prepare compositions for administration to patients. However, in certain instances, it may be advantageous to not isolate and/or purify an expression product from a cell; for instance, when the cell or portions thereof enhance the effect of the polypeptide.

[0100]As used herein, "treatment" refers to clinical intervention in an attempt to alter the natural course of the individual or cell being treated, and may be performed either for prophylaxis or during the course of clinical pathology. Desirable effects of the treatment include preventing occurrence or recurrence of disease, alleviation of symptoms, diminishment of any direct or indirect pathological consequences of the disease, preventing metastases, decreasing the rate of disease progression, amelioration or palliation of the disease state, and remission or improved prognosis.

[0101]An inventive vector or recombinant expressing a gene or a portion thereof identified herein or from a method herein can be administered in any suitable amount to achieve expression at a suitable dosage level, e.g., a dosage level analogous to the herein mentioned dosage levels (wherein the gene product is directly present). The inventive vector or recombinant nucleotide can be administered to a patient or infected or transfected into cells in an amount of about at least 10³ pfu; more preferably about 10⁴ pfu to about 10¹⁰ pfu, e.g., about 10⁵ pfu to about 10⁹ pfu, for instance about 10⁶ pfu to about 10⁸ pfu. In plasmid compositions, the dosage should be a sufficient amount of plasmid to elicit a response analogous to compositions wherein gene product or a portion thereof is directly present; or to have expression analogous to dosages in such compositions; or to have expression analogous to expression obtained in vivo by recombinant compositions. For instance, suitable quantities of plasmid DNA in plasmid compositions can be 1 μg to 100 mg, preferably 0.1 to 10 mg, e.g., 500 μg, but lower levels such as 0.1 to 2 mg or preferably 1-10 μg may be employed. Documents cited herein regarding DNA plasmid vectors can be consulted for the skilled artisan to ascertain other suitable dosages for DNA plasmid vector compositions of the invention, without undue experimentation.

[0102]Compositions for administering vectors can be as in or analogous to such compositions in documents cited herein or as in or analogous to compositions herein described, e.g., pharmaceutical or therapeutic compositions and the like.

[0103]Thus, the invention comprehends in vivo gene expression which is sometimes termed "gene therapy." Gene therapy can refer to the transfer of genetic material (e.g. DNA or RNA) of interest into a host subject or patient to treat or prevent a genetic or acquired disease, condition or phenotype. The particular gene that is to be used or which has been identified as the target gene is identified as set forth herein. The genetic material of interest encodes a product (e.g. a protein, polypeptide, peptide or functional RNA) the production in vivo of which is desired. For example, the genetic material of interest can encode a hormone, receptor, enzyme, polypeptide or peptide of therapeutic value. For a review see, in general, the text "Gene Therapy" (Advances in Pharmacology 40, Academic Press, 1997).

[0104]Two basic approaches to gene therapy have evolved: (1) ex vivo; and (2) in vivo gene therapy. In ex vivo gene therapy cells are removed from a patient, and while being cultured are treated in vitro. Generally, a functional replacement gene is introduced into the cell via an appropriate gene delivery vehicle/method (transfection, homologous recombination, etc.) and, an expression system as needed and then the modified cells are expanded in culture and returned to the host/patient. These genetically reimplanted cells have been shown to produce the transfected gene product in situ. In in vivo gene therapy, target cells are not removed from the subject; rather, the gene to be transferred is introduced into the cells of the recipient organism in situ, that is within the recipient. Alternatively, if the host gene is defective, the gene is repaired in situ. Culver (1998) Antisense DNA & RNA Based Therapeutics, February, 1998, Coronado, Calif. These genetically altered cells have been shown to produce the transfected gene product in situ.

[0105]The gene expression vehicle is capable of delivery/transfer of heterologous nucleic acid into a host cell. The expression vehicle may include elements to control targeting, expression and transcription of the nucleic acid in a cell-selective manner as is known in the art. It should be noted that often the 5'UTR and/or 3'UTR of the gene may be replaced by the 5' UTR and/or 3'UTR of the expression vehicle. Therefore, as used herein, the expression vehicle may, as needed, not include the 5'UTR and/or 3'UTR shown in sequences herein and only include the specific amino acid coding region.

[0106]The expression vehicle can include a promoter for controlling transcription of the heterologous material and can be either a constitutive or inducible promoter to allow selective transcription. Enhancers that may be required to obtain necessary transcription levels can optionally be included. Enhancers are generally any non-translated DNA sequence that works contiguously with the coding sequence (in cis) to change the basal transcription level dictated by the promoter. The expression vehicle can also include a selection gene as described herein.

[0107]Vectors can be introduced into cells or tissues by any one of a variety of known methods within the art. Such methods can be found generally described in Sambrook et al. (1989, 1992); Ausubel et al. (1989); Chang et al. (1995) Somatic Gene Therapy, CRC Press, Ann Arbor, Mich.; Vega et al. (1995) Gene Targeting, CRC Press, Ann Arbor, Mich.; Vectors: A Survey of Molecular Cloning Vectors and Their Uses, Butterworths, Boston Mass. (1988); and Gilboa et al. (1986) BioTech. 4:504-512, as well as other documents cited herein and include, for example, stable or transient transfection, lipofection, electroporation and infection with recombinant viral vectors. In addition, see U.S. Pat. No. 4,866,042 for vectors involving the central nervous system; and also U.S. Pat. Nos. 5,464,764 and 5,487,992 for positive-negative selection methods.

[0108]Introduction of nucleic acids by infection offers advantages over the other listed methods. Higher efficiency can be obtained due to their infectious nature. Moreover, viruses are very specialized and typically infect and propagate in specific cell types. Thus, their natural specificity can be used to target the vectors to specific cell types in vivo or within a tissue or mixed cell culture. Viral vectors can also be modified with specific receptors or ligands to alter target specificity through receptor-mediated events.

[0109]Additional features can be added to the vector to ensure its safety and/or enhance its therapeutic efficacy. Such features include, for example, markers that can be used to negatively select against cells infected with the recombinant virus. An example of such a negative selection marker is the TK gene described above that confers sensitivity to the antibiotic gancyclovir. Negative selection is therefore a means by which infection can be controlled because it provides inducible suicide through the addition of antibiotic. Such protection ensures that if, for example, mutations arise that produce altered forms of the viral vector or recombinant sequence, cellular transformation will not occur. Features that limit expression to particular cell types can also be included. Such features include, for example, promoter and regulatory elements that are specific for the desired cell type.

[0110]In addition, recombinant viral vectors are useful for in vivo expression of a desired nucleic acid because they offer advantages such as lateral infection and targeting specificity. Lateral infection is inherent in the life cycle of, for example, retrovirus and is the process by which a single infected cell produces many progeny virions that bud off and infect neighboring cells. The result is that a large area becomes rapidly infected, most of which was not initially infected by the original viral particles. This is in contrast to vertical-type of infection in which the infectious agent spreads only through daughter progeny. Viral vectors can also be produced that are unable to spread laterally. This characteristic can be useful if the desired purpose is to introduce a specified gene into only a localized number of targeted cells.

[0111]In particular, use of the 608 gene (or a functional fragment thereof) for treatment of osteoporosis, and/or osteoarthritis, and/or osteopetrosis, and/or osteosarcoma, and/or fracture healing is envisaged using gene therapy methods. As described above, a plasmid or DNA vector expressing the gene could be injected directly to the target tissue; alternatively a virus bearing a plasmid or DNA vector expressing the gene could be injected directly to the target tissue. Another embodiment is that cells transfected with a plasmid or DNA vector expressing the gene could be injected directly to the target tissue. These transfected cells should preferably be the patient's own cells for example mesenchymal stem cells drawn from the bone marrow.

[0112]Delivery of gene products (products from herein defined genes: genes identified herein or by inventive methods or portions thereof) and/or antibodies or portions thereof and/or agonists or antagonists (collectively or individually "therapeutics"), and compositions comprising the same, as well as of compositions comprising a vector expressing gene products, can be done without undue experimentation from this disclosure and the knowledge in the art.

[0113]The pharmaceutically "effective amount" for purposes herein is thus determined by such considerations as are known in the art. The amount must be effective to achieve improvement including but not limited to improved survival rate or more rapid recovery, or improvement or amelioration or elimination of symptoms and other indicators, e.g., of osteoporosis, for instance, improvement in bone density, as are selected as appropriate measures by those skilled in the art.

[0114]It is noted that humans are treated generally longer than the mice or other experimental animals exemplified herein. Human treatment has a length proportional to the length of the disease process and drug effectiveness. The doses may be single doses or multiple doses over a period of several days, but single doses are preferred. Thus, one can scale up from animal experiments, e.g., rats, mice, and the like, to humans, by techniques from this disclosure and the knowledge in the art, without undue experimentation.

[0115]The present invention provides an isolated nucleic acid molecule containing nucleotides having a sequence set forth in at least one of SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO: 6, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 29 or SEQ ID NO: 31 or as inserted in a plasmid designated pCm-H-608-663-N-term, deposited under ATCC Accession No. PTA-3638, supplements thereof and a polynucleotide having a sequence that differs from SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO: 6, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29 or SEQ ID NO: 31 or as inserted in a plasmid designated pCm-H-608-663-N-term, deposited under ATCC Accession No. PTA-3638 due to the degeneracy of the genetic code or a sequence which hybridizes under stringent conditions to a sequence in a plasmid designated pCm-H608-663-N-term or a functional portion thereof or a polynucleotide which is at least substantially homologous thereto. In a preferred embodiment, the nucleic acid molecule comprises a polynucleotide having at least 15 nucleotides from SEQ ID NO: 1, SEQ ID NO:3, SEQ ID NO: 6, SEQ ID NO: 20, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 29 or SEQ ID NO: 31 or as inserted in a plasmid designated pCm-H-608-663-N-term, deposited under ATCC Accession No. PTA-3638, preferably at least 50 nucleotides and more preferably at least 100 nucleotides.

[0116]The present invention further provides an isolated nucleic acid molecule containing nucleotides having a sequence set forth in at least one of SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO: 28, or SEQ ID NO:26 and SEQ ID NO:27 or SEQ ID NO:26 and SEQ ID NO:27 and SEQ ID NO: 28 or as inserted in a plasmid designated pKS H608 5'-2.4 Kb bAc#1 (deposited on Nov. 21, 2001 under the terms of the Budapest Treaty with the American Type Culture Collection (ATCC), P.O. Box 1549, Manassas, Va. 20108, USA, under ATCC accession number PTA-3878), pKS H608 m.FRG.3.5 Kb#34 (deposited on Nov. 21, 2001 under the terms of the Budapest Treaty with the American Type Culture Collection (ATCC), P.O. Box 1549, Manassas, Va. 20108, USA, under ATCC accession number PTA-3876) or pM H608 3'-1.9 Kb HSTG#3.3 (deposited on Nov. 21, 2001 under the terms of the Budapest Treaty with the American Type Culture Collection (ATCC), P.O. Box 1549, Manassas, Va. 20108, USA, under ATCC accession number PTA-3877), supplements thereof and a polynucleotide having a sequence that differs from SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO: 28, or SEQ ID NO:26 and SEQ ID NO:27 or SEQ ID NO:26 and SEQ ID NO:27 and SEQ ID NO: 28 or as inserted in a plasmid designated pKS H608 5'-2.4 Kb bAc#1, pKS H608 m.FRG.3.5 Kb#34 or pM H608 3'-1.9 Kb HSTG#3.3 due to the degeneracy of the genetic code or a sequence which hybridizes under stringent conditions to a sequence in a plasmid designated pKS H608 5'-2.4 Kb bAc#1, pKS H608 m.FRG.3.5 Kb#34 or pM H608 3'-1.9 Kb HSTG#3.3 or a functional portion thereof or a polynucleotide which is at least substantially homologous thereto. In a preferred embodiment, the nucleic acid molecule comprises a polynucleotide having at least 15 nucleotides from SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO: 28, or SEQ ID NO:26 and SEQ ID NO:27 or SEQ ID NO:26 and SEQ ID NO:27 and SEQ ID NO: 28 or as inserted in a plasmid designated pKS H608 5'-2.4 Kb bAc#1, pKS H608 m.FRG.3.5 Kb#34 or pM H608 3'-1.9 Kb HSTG#3.3, preferably at least 50 nucleotides and more preferably at least 100 nucleotides.

[0117]The present invention also provides a composition of the isolated nucleic acid molecule, a vector comprising the isolated nucleic acid molecule, a composition containing said vector and a method for preventing, treating or controlling bone diseases including, but not limited to, osteoporosis, osteopenia, osteopetrosis, osteosclerosis, osteoarthritis, periodontosis, bone fractures or low bone density or or other conditions involving mechanical stress or a lack thereof in a subject, comprising administering the inventive composition, or the inventive vector, and a method for preparing a polypeptide comprising expressing the isolated nucleic acid molecule or comprising expressing the polypeptide from the vector.

[0118]The present invention further provides a method for preventing, treating or controlling osteoporosis, osteopenia, osteopetrosis, osteosclerosis, osteoarthritis, periodontosis, bone fractures or low bone density or other factors causing or contributing to osteoporosis or symptoms thereof or other conditions involving mechanical stress or a lack thereof in a subject, comprising administering an isolated nucleic acid molecule or functional portion thereof or a polypeptide comprising an expression product of the gene or functional portion of the polypeptide or an antibody to the polypeptide or a functional portion of the antibody. In one embodiment of the invention, the isolated nucleic acid molecule encodes a 10 kD to 100 kD N-terminal cleavage product of the OCP protein. Preferably, the N-terminal cleavage product comprises of a polypeptide of about 25 kD. More preferably the N-terminal cleavage product comprises a polypeptide of about 70-80 kD, most preferably about 1-663 amino acids or about 1-741 amino acids of the OCP protein. The present invention provides an isolated polypeptide encoded by the inventive polynucleotide. In one embodiment of the invention, the polypeptide is identified as human 608 protein, rat 608 protein, human Adlican-2 protein or a functional portion thereof or a polypeptide which is at least substantially homologous thereto. More particularly this invention is directed to an isolated polypeptide wherein the functional portion comprises consecutive amino acids having a sequence set forth in SEQ ID NO:2, SEQ ID NO:16, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 30, SEQ ID NO: 32 or SEQ ID NO: 34. Particular fragments of the polypeptide are about the first 663 amino acids or about the first 741 amino acids of the sequence set forth in SEQ ID NO:2, SEQ ID NO:16, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 30, SEQ ID NO: 32 or SEQ ID NO: 34. Other particular fragments of the human 608 protein include amino acids 1-500, 501-1000, 1001-1500, 1501-2000, 2001-2500, and 2051-2623 of the sequence set forth in SEQ ID NO: 32. Further particular fragments of the human 608 protein include amino acids 250-749, 750-129, 1250-1749, 1750-2249 and 2250-2623 of the sequence set forth in SEQ ID NO: 32. Nucleic acid molecules (polynucleotides) encoding these particular fragments are also envisaged as aspects of the invention. Similar particular polypeptide fragments of the Adlican-2 protein (SEQ ID NO: 30), and similar particular polynucleotide fragments of the Adlican-2 nucleic acid (SEQ ID NO: 29) are also envisaged as aspects of the invention.

[0119]The present invention also provides a composition comprising one or of isolated polypeptides, an antibody specific for the polypeptide or a functional portion thereof, a composition comprising the antibody or a functional portion thereof, and a method for treating or preventing osteoporosis, or fracture healing, bone elongation, or periodontosis in a subject, comprising administering to the subject a N-terminal polypeptide having a molecular weight of between 10 kD and 100 kD, preferably about 25 kD to about 70-80 kD.

[0120]The present invention provides for a method of treating or preventing osteoarthritis, osteopetrosis, or osteosclerosis, comprising administering to a subject an effective amount of a chemical or a neutralizing mAbs that inhibit the activity of the N-terminal polypeptide having a molecular weight of between 10 kD and 30 kD, preferably about 25 kD.

[0121]As used herein, the term "subject," "patient," "host" include, but are not limited to human, bovine, pig, mouse, rat, goat, sheep and horse.

[0122]Those skilled in the art will recognize that the components of the compositions should be selected to be chemically inert with respect to the gene product and optional adjuvant or additive. This will present no problem to those skilled in chemical and pharmaceutical principles, or problems can be readily avoided by reference to standard texts or by simple experiments (not involving undue experimentation), from this disclosure and the documents cited herein.

[0123]The present invention provides receptors of the expression products of human mechanical stress induced genes and their functional equivalents, such as OCP and Adlican, and methods or processes for obtaining and using such receptors. The receptors of the present invention are those to which the expression products of mechanical stress induced genes and their functional equivalents bind or associate as determined by conventional assays, as well as in vivo. For example, binding of the polypeptides of the instant invention to receptors can be determined in vitro, using candidate receptor molecules that are associated with lipid membranes. See, e.g., Watson, J. et al., Development of FlashPlate® technology to measure (³⁵S) GTP gamma S binding to Chinese hamster ovary cell membranes expressing the cloned human 5-HT1B receptor, Journal of Biomolecular Screening. Summer, 1998; 3 (2) 101-105; Komesli-Sylviane et al., Chimeric extracellular domain of type II transforming growth factor (TGF)-beta receptor fused to the Fc region of human immunoglobulin as a TGF-beta antagonist, European Journal of Biochemistry. June, 1998; 254 (3) 505-513. See, generally, Darnell et al., Molecular Cell Biology, 644-646, Scientific American Books, New York (1986). Scanning electron microscopy ("SEM"), x-ray crystallography and reactions using labelled polypeptides are examples of conventional means for determining whether polypeptides have bound or associated with a receptor molecule. For instance, X-ray crystallography can provide detailed structural information to determine whether and to what extent binding or association has occurred. See, e.g., U.S. Pat. No. 6,037,117; U.S. Pat. No. 6,128,582 and U.S. Pat. No. 6,153,579. Further, crystallography, including X-ray crystallography, provides three-dimensional structures that show whether a candidate polypeptide ligand can or would bind or associate with a target molecule, such as a receptor. See, e.g., WO 99/45379; U.S. Pat. Nos. 6,087,478 and 6,110,672. Such binding or association shows that the receptor molecule is the receptor for the candidate polypeptide.

[0124]With the disclosures in the present specification of the inventive genes, expression products and uses thereof, those skilled in the art can obtain by conventional methods the receptors for the inventive expression products. The conventional means for obtaining the receptors include raising monoclonal antibodies (Mabs) to candidate receptors, purifying the receptors from a tissue sample by use of an affinity column, treatment with a buffer, and collection of the eluate receptor molecules. Other means of isolating and purifying the receptors are conventional in the art, for instance isolation and purification by dialysis, salting out, and electrophoretic (e.g. SDS-PAGE) and chromatographic (e.g. ion-exchange and gel-filtration, in additional to affinity) techniques. Such methods can be found generally described in Stryer, Biochemistry, 44-50, W.H. Freeman & Co., New York (3d ed. 1988); Darnell et al., Molecular Cell Biology, 77-80 (1986); Alberts et al., Molecular Biology of the Cell, 167-172, 193 Garland Publishing, New York (2d ed. 1989).

[0125]Sequencing of the isolated receptor involves methods known in the art, for instance directly sequencing a short N-terminal sequence of the receptor, constructing a nucleic-acid probe, isolating the receptor gene, and determining the entire amino-acid sequence of the receptor from the nucleic-acid sequence. Alternatively, the entire receptor protein can be sequenced directly. Automated Edman degradation is one conventional method used to partially or entirely sequence a receptor protein, facilitated by chemical or enzymatic cleavage. Automated sequenators, such as an ABI-494 Procise Sequencer (Applied Biosystems) can be used. See, generally, Stryer, Biochemistry, 50-58 (3d ed. 1988).

[0126]The invention provides methods for using such receptors in assays, for instance for identifying proteins or polypeptides that bind to, associate with or block the inventive receptors, determining binding constants and degree of binding, and for testing the effects of such polypeptides, for instance utilising membrane receptor preparations. See Watson (1998); Komesli-Sylviane (1998). For instance, FlashPlate® (Perkin-Elmer, Massachusetts, USA) technology can be used with the present invention to determine whether and to what degree candidate polypeptides bind to and are functional with respect to a receptor of the invention.

Diagnostics:

[0127]The gene and polypeptides of the invention can be employed as a diagnostic in several ways as follows:

1. Diagnosis of osteoarthritis by detection of 608 protein or parts of it, or detection of 608 RNA in synovial fluid.2. Diagnosis of osteoporosis by detection of 608 protein or fragments thereof, or detection of 608 RNA, preferably in a blood sample.3. Diagnosis of a fracture by detection of 608 protein or fragments thereof, or detection of 608 RNA, preferably in a blood sample.4. Diagnosis of succeptibility to osteoporosis, and/or osteoarthritis, and/or osteopetrosis, and/or osteosarcoma associated with mutated 608 by PCR or RT PCR of DNA or RNA respectively. DNA and/or RNA from bodily fluids or from a tissue, and preferably DNA from blood are tested.5. Diagnosis of a disease associated with mutated 608 by PCR or RT PCR of DNA or RNA respectively. DNA and/or RNA from bodily fluids or from a tissue and preferably DNA from blood are tested

[0128]The diagnostic methods to be utilized are described in more detail as follows.

[0129]In diagnosis, the sample is taken from a bodily fluid or from a tissue, preferably bone or cartilage tissue; the bodily fluid is selected from the group of fluid consisting of blood, lymph fluid, ascites, serous fluid, pleural effusion, sputum, cerebrospinal fluid, lacrimal fluid, synovial fluid, saliva, stool, sperm and urine, preferably blood or urine. Measurement of level of the 608 polypeptide may be determined by a method selected from the group consisting of immunohistochemistry, western blotting, ELISA, antibody microarray hybridization and targeted molecular imaging; antibodies have been described above. Such methods are well-known in the art, for example for immunohistochemistry: M. A. Hayat (2002) Microscopy, Immunohistochemistry and Antigen Retrieval Methods: For Light and Electron Microscopy, Kluwer Academic Publishers; Brown C (1998): "Antigen retrieval methods for immunohistochemistry", Toxicol Pathol; 26(6): 830-1); for western blotting: Laemmeli UK(1970): "Cleavage of structural proteins during the assembley of the head of a bacteriophage T4", Nature; 227: 680-685; and Egger & Bienz(1994) "Protein (western) blotting", Mol Biotechnol; 1(3): 289-305); for ELISA: Onorato et al.(1998) "Immunohistochemical and ELISA assays for biomarkers of oxidative stress in aging and disease", Ann NY Acad Sci 20; 854: 277-90); for antibody microarray hybridization: Huang(2001) "Detection of multiple proteins in an antibody-based protein microarray system, Immunol Methods 1; 255 (1-2): 1-13); and for targeted molecular imaging: Thomas (2001). Targeted Molecular Imaging in Oncology, Kim et al (Eds)., Springer Verlag, inter alia.

[0130]Measurement of level of 608 polynucleotide may be determined by a method selected from: RT-PCR analysis, in-situ hybridization, polynucleotide microarray and Northern blotting. Such methods are well-known in the art, for example for in-situ hybridization Andreeff & Pinkel (Editors) (1999), "Introduction to Fluorescence In Situ Hybridization: Principles and Clinical Applications", John Wiley & Sons Inc.; and for Northern blotting Trayhurn (1996) "Northern blotting", Proc Nutr Soc; 55(1B): 583-9 and Shifman & Stein(1995) "A reliable and sensitive method for non-radioactive Northern blot analysis of nerve growth factor mRNA from brain tissues", Journal of Neuroscience Methods; 59: 205-208 inter alia.

[0131]A better understanding of the present invention and of its many advantages will be had from the following examples, given by way of illustration and as a further description of the invention.

EXPERIMENTAL DETAILS

Example 1

608 Gene Expression by In Situ Hybridization

[0132]The 608 gene expression pattern was studied by in situ hybridization on sections of bones from ovariectomized and sham-operated rats. Female Wistar rats weighing 300-350g were subjected to ovariectomy under general anesthesia. Control rats were operated on in the same way but ovaries were not excised as a sham operation.

[0133]Three weeks after the operation, rats were sacrificed and tibia were excised together with the knee joint. Bones were fixed for three days in 4% paraformaldehyde and then decalcified for four days in a solution containing 5% formic acid and 10% formalin. Decalcified bones were postfixed in 10% formalin for three days and embedded into paraffin.

[0134]The ectopic bone formation model was employed to study the bone development 608 gene expression pattern. Rat bone marrow cells were seeded into cylinders of demineralized bone matrix prepared from rat tibiae. Cylinders were implanted subcutaneously into adult rats. After three weeks, rats were sacrificed and implants were decalcified and embedded into paraffin as described above for tibial bones.

[0135]The 6 μm sections were prepared and hybridized in situ. After hybridization, sections were dipped into nuclear track emulsion and exposed for three weeks at 4° C. Autoradiographs were developed, stained with hematoxylin-eosin and studied under microscopy using brightfield and darkfield illumination.

[0136]For further assessment of cell and tissue specificity of 608 gene expression, an in situ hybridization study was performed on sections of multitissue block containing multiple samples of adult rat tissues. The 608 expression developmental pattern was studied on sagittal sections of mouse embryos of 12.5, 14.5 and 16.5 days postconception (dpc) stages.

[0137]Microscopic study of hybridized sections of long bones revealed a peculiar pattern of 608 probe hybridization. The hybridization signal can be seen mainly in fibroblast-like cells found in several locations throughout the sections. Prominent accumulations of these cells can be seen in the area of periosteal modeling in metaphysis, and also in regions of active remodeling of compact bone in diaphysis: at the boundary between bone marrow and endosteal osteoblasts and in periosteum; also in close contact with osteoblasts. Perivascular connective tissue filling Volkmann's canals in compact bone in diaphysis and epiphysis also contains 608-expressing cells. No hybridization was found within cancellous bone and in bone marrow. This hybridization pattern suggests that cells expressing 608 are associated with areas of remodeling of preexisting bone and are not involved in primary endochondral ossification.

[0138]At the growth plate level, 608 expressing cells can be seen in the perichondral fibrous ring of LaCroix. Some investigators regard this fibrous tissue as the aggregation of residual mesenchymal cells able to differentiate into both osteoblasts and chondrocytes. In this respect it is noteworthy that single cells expressing 608 can be seen in epiphyseal cartilage. These 608-expressing cells are rounded cells within the lateral segment of epiphysis (sometimes in close vicinity to the LaCroix ring) and flattened cells covering the articulate surface. Most cells in articulate cartilage and all chondrocytes on the growth plate do not show 608 expression. Ovariectomy did not alter the intensity and pattern of 608 expression in bone tissue.

[0139]In ectopic bone sections, 608 hybridization signal can be seen in some fibroblast-like cells either scattered within unmineralized connective tissue matrix or concentrated at the boundary between this tissue and osteoblasts of immature bone. 608 gene expression patterns revealed by in situ hybridization in bone and cartilage indicate that its expression marks some skeletal tissue elements able to differentiate into two skeletal cell types--osteoblasts and chondrocytes. The terminal differentiation of these cells appears to be accompanied by down-regulation of 608 expression. The latter observation is supported by peculiar temporal pattern of 608 expression in primary cultures of osteogenic cells isolated from calvaria bones of rat fetuses. In these cultures, expression was revealed by in situ hybridization in the vast majority of cells after one and two weeks of incubation in vitro. Three and four week old cultures showing signs of ossification contained no 608 expressing cells. Significantly, no hybridization signal was found on sections of multitissue block hybridized to 608 probe suggesting high specificity of this gene expression for the skeletal tissue in adult organisms.

[0140]An in situ hybridization study of embryonic sections demonstrated that, at 12.5 dpc, a weak hybridization signal can be discerned in some mesenchymal cells in several locations throughout the embryonic body. The most prominent signal is found in the head in loose mesenchymal tissue surrounding the olfactory epithelium and underlying the surface epithelium of nose tip. Other mesenchymal cells in the head also show a hybridization signal: non-cartilaginous part of basisphenoid bone primordium and mesenchyme surrounding the dental laminae (tooth primordia) in the mandible.

[0141]In the trunk, expression can be detected in less developed vertebrae primordia in the thoraco-lumbar region. The hybridization signal here marks the condensed portion of sclerotomes. Another area of the trunk showing a hybridization signal is comprised of a thin layer of mesenchymal cells in the anterior part of the thoracic body wall.

[0142]At later stages of development, 14.5 and 16.5 dpc, probe 608 gave no hybridization signal. Thus, it appears that during embryonic development the 608 gene is transiently expressed by at least some mesenchymal and skeleton-forming cells. This expression is down-regulated at later stages of development. More detailed study of late embryonic and postnatal stages of development reveals the timing of appearance of cells expressing 608 in bone tissue.

[0143]Further experiments to study the expression of the OCP gene in embryonic development were performed as follows. The targeting vector used to produce OCP knockout mice included a "knock-in" of the β-galactosidase (LacZ) reporter gene into the OCP gene. The LacZ gene was fused to the first exon of the OCP gene--a non-coding exon. Thus, expression of LacZ is expected to depend on the OCP regulatory elements and to mark the cells expressing OCP.

[0144]Analysis of LacZ staining was performed during embryonic development on OCP knockout mice. The expression pattern revealed by this analysis reflects the activation of the OCP gene promoter, which results in expression of the knocked-in LacZ gene. This data in general supports the pattern detected by the in-situ hybridization described above.

[0145]At 10.5 dpc expression is seen in the apical ectodermal ridge (AER), in the forelimbs only. This specialized region, together with the zone of polarizing activity (ZPA), directs and coordinates the development of the limb bud.

[0146]At 12.5 dpc expression in AER is maintained in the forelimbs and appears also in hindlimbs. In addition, it appears in precartilagenous condensations of the ribs, in mesenchymal tissue in the face, in mesenchymal tissue rostral to the forelimb, a region of future muscle development, and in the tip of the genital tubercle.

[0147]At 14.5 dpc there is broader expression, in the head region, limbs, ribs, and back. Although no expression at 14.5 dpc was detected in the in situ RNA hybridization experiments described above, expression was detected in this experiment, probably because the lacZ staining is a more sensitive detection method.

[0148]To summarize: [0149]1. There is an interesting pattern of expression of gene OCP in embryonic development: in tissues originating from different germ layers (ectoderm and mesoderm), in critical regions of pattern formation (AER), and an apparently regulated pattern during cartilage and bone development. [0150]2. In mesodermal tissues, the gene is expressed mainly in skeletal lineages, but also in some myoblasts and some dermal cells as well. [0151]3. Ectodermal expression appears in the head mesenchyme, derived from neural crest cells, and cells in the apical ectodermal ridge.

[0152]The 608 expression pattern during embryonic development is closely coupled with regions of bone and cartilage development. This expression pattern strongly suggests a role for 608 in bone metabolism.

Example 2

Isolation of Rat OCP

[0153]Primary rat calvaria cells grown on elastic membranes that were stretched for 20 minutes provided a model system for a stimulator of bone formation following mechanical force. Gene expression patterns were compared before and after the application of mechanical force.

[0154]OCP expression was upregulated approximately 3-fold by mechanical force. This was detected both by microarray analysis and by Northern blot analysis using poly (A)+ RNA from rat calvaria cells before and after the mechanical stress. In rat calvaria primary cells and in rat bone extract this gene was expressed as a main RNA species of approximately 8.9 kb and a minor RNA transcript of approximately 9 kb. The hybridization signal was not detected in any other rat RNA from various tissue sources, including testis, colon, intestine, kidney, stomach, thymus, lung, uterus, heart, brain, liver, eye, and lymph node.

[0155]The partial OCP rat cDNA clone (4007 bp long) isolated from a rat calvaria cDNA phage library was found to contain a 3356 bp open reading frame closed at the 3' end. Comparison to public mouse databases revealed no sequence homologues. A complete OCP rat cDNA clone was isolated from the rat calvaria cDNA library by a combination of 5' RACE technique (Clontech), RT-PCR of 5' cDNA fragments, and ligation of the latter products to the original 3' clone. The full rat cDNA clone that was generated (shown in FIG. 1-SEQ ID NO:1) was sequenced, and no mutations were found. The full sequence stretch is 8883 bp long and contains an ORF (nt 575-8366) for a 2597 amino acid residue protein. FIG. 3-SEQ ID NO:2. The cDNA does not contain a polyadenylation site, but contains a 3' poly A stretch.

[0156]608 encodes a large protein that appears to be a part of the extra-cellular matrix. The gene may be actively involved in supporting osteoblast differentiation. Another option is that it is expressed in regions were remodeling takes place. Such an hypothesis is also compatible with a role in directing osteoclast action and thus it may be a target for inhibition by small molecules.

[0157]In normal bone formation, activation of osteoblasts leads to secretion of various factors that attract osteoclast precursors or mature osteoclasts to the sites of bone formation to initiate the process of bone resorption. In normal bone formation both functions are balanced. Imbalance to any side causes either osteitis deformans (osteoblast function overwhelms) or osteoporosis (osteoclast function overwhelms).

[0158]Among known osteoblast activators--mechanical force stimulation--is actually applied in the present model. As proof of principle, increased expression of several genes known to respond to mechanical stress by transcriptional upregulation were found. They include tenascin, endothelin and possibly trombospondin.

Example 3

Full-Length OCP cDNA Construction and Expression

[0159]TNT (transcription-translation) assays were performed according to the manufacturer's instructions (Promega--TNT coupled reticulocyte lysate systems), using specific fragments taken from various regions of the gene. In all assays a clear translation product was observed. The following fragments were tested:

TABLE-US-00001 TNT products Translation Frag. Location Fragment size (bp) product size (kD) Promoter 1 134-2147 2013 73 T7 2 3912-5014 1102 40 '' 3 574-1513 939 34 ''

Example 4

The Mouse OCP Gene

[0160]Two mouse genomic Bac clones containing the mouse OCP gene promoter region and part of the coding region were identified, based on their partial homology to the 5'UTR region of the rat-608 cDNA. These clones (23-261L4 and 23-241H7 with ˜200 Kb average insert length) were bought from TIGR.

[0161]Specific primers for the amplification of a part of the mouse-OCP promoter region were designed and used for PCR screening of a mouse genomic phage library (performed by Lexicon Genetics Inc. for the Applicants). One phage clone containing part of the genomic region of the mouse 608 gene was detected and completely sequenced. The length of this clone was reported to be 11,963 bp. Parts of the physical "Lexicon" clone were re-sequenced by the inventors and corrections were made. The resequenced clone is 11,967 bp long. Exon-location prediction (FIG. 4) was performed based on the alignment of the mouse genomic and the rat cDNA sequences.

Example 5

The Human OCP Gene

[0162]On the nucleotide level, the rat OCP cDNA sequence is homologous to the human genomic DNA sequence located on chromosome 3. Based on the homology and bioinformatic analysis (FIG. 6), a putative cDNA sequence was generated. FIG. 7. The highest similarity is evident between nt 1-1965 (1-655 a.a); 2179-2337 (727-779 a.a); and 4894-7833 (1635 a.a.-end) as presented in the table shown in FIG. 8. On the protein level, no homologues were found in the data bank.

Example 6

The Deduced OCP Protein

[0163]The deduced OCP protein was generated following the alignment of the rat, mouse and human cDNA sequences and the equivalent rat, mouse and human amino acid sequences, respectively. The following alignments were made: (a) alignment of rat, human, and mouse OCP cDNA coding regions (rat cDNA: SEQ ID NO:7; human 5+3 corrected: SEQ ID NO:8; and mus cDNA 5: SEQ ID NO:9)

(b) alignment of rat, human and mouse OCP proteins (rat: SEQ ID NO:10; human 5+3 corrected: SEQ ID NO:11; and mouse 5 corrected: SEQ ID NO: 12) and(c) alignment of rat and human OCP proteins (rat: SEQ ID NO:13; and human 5+3 corrected: SEQ ID NO:14).

[0164]The deduced OCP protein(FIG. 10): contains the following features

[0165]a. a cleavable, well-defined N-terminal signal peptide (aa 1-28);

[0166]b. a leucine-rich repeat region (aa 28-280). This region can be divided into N-terminal and C-terminal domains of leucine-rich repeats (aa 28-61 and 219-280, respectively). Between them, there are six leucine-rich repeat outliers (aa 74-96, 98-120, 122-144, 146-168, 178-200, 202-224). Leucine rich repeats are usually found in extracellular portions of a number of proteins with diverse functions. These repeats are thought to be involved in protein-protein interactions. Each leucine-rich repeat is composed of β-sheet and α-helix. Such units form elongated non-globular structures;

[0167]c. twelve immunoglobulin C-2 type repeats at amino acid positions 488-558, 586-652, 1635-1704, 1732-1801, 1829-1898, 1928-1997, 2025-2100, 2128-2194, 2233-2294, 2324-2392, 2419-2487, 2515-2586. Thus, two Ig-like repeats are found immediately downstream of a leucine-rich region, while the remaining 10 repeats are clustered at the protein's C-terminus. Immunoglobulin C-2 type repeats are involved in protein-protein interaction and are usually found in extracellular protein portions;

[0168]d. no transmembrane domain; and

[0169]5 nuclear localization domains (NLS) at: 724, 747, 1026, 1346 and 1618.

[0170]These observations indicate that OCP belongs to the Ig superfamily. OCP is a serine-rich protein (10.3% versus av. 6.3%), with a central nuclear prediction domain and an N-terminal extracellular prediction domain.

Example 7

Bone Fracture Healing

[0171]Expression of 608 RNA is bone-specific. Moreover, it seems to be specific to bone progenitors (as judged by their location in bone and involvement in normal bone modeling and remodeling processes) that do not yet express the known bone-specific markers. To further prove the relevance of 608-expressing cells to osteogenic lineage, the patterns of 608 expression in the animal model of bone fracture healing that imply the activation of bone formation processes were studied.

[0172]The sequence of physiological events following bone fracture is now relatively well understood. Healing takes place in three phases-inflammatory, reparative and remodeling. In each phase certain cells predominate and specific histological and biochemical events are observed. Although these phases are referred to separately, it is well known that events described in one phase persist into the next and events apparent in a subsequent phase begin before this particular phase predominates. These events have been described over the years in investigative reports and review articles. Ham (1969) In, Histology, 6th ed. Philadelphia, Lippincott, p. 441; and Urist and Johnson (1943) J. Bone Joint Surg. 25:375.

[0173]During the first phase immediately following fracture (the inflammatory phase), wide-spread vasodilatation and exudation of plasma lead to the acute edema visible in the region of a fresh fracture. Acute inflammatory cells migrate to the region, as do polymorphonuclear leukocytes and then macrophages. The cells that participate directly in fracture repair during the second phase (the reparative phase), are of mesenchymal origin and are pluripotent. These cells form collagen, cartilage and bone. Some cells are derived from the cambium layer of the periosteum and form the earliest bone. Endosteal cells also participate. However, the majority of cells directly taking part in fracture healing enter the fracture site with the granulation tissue that invades the region from surrounding vessels. Trueta (1963) J. Bone Joint Surg. 45:402. Note that the entire vascular bed of an extremity enlarges shortly after the fracture has occurred but the osteogenic response is limited largely to the zones surrounding the fracture itself. Wray (1963) Angiol. 14:134.

[0174]The invading cells produce tissue known as "callus" (made up of fibrous tissue, cartilage, and young, immature fibrous bone), rapidly enveloping the ends of the bone, with a resulting gradual increase in stability of the fracture fragments. Cartilage thus formed will eventually be resorbed by a process that is indistinguishable except for its lack of organization from endochondral bone formation. Bone will be formed by those cells having an adequate oxygen supply and subjected to the relevant mechanical stimuli.

[0175]Early in the repair process, cartilage formation predominates and glycosaminoglycans are found in high concentrations. Later, bone formation is more obvious. As this phase of repair takes place, the bone ends gradually become enveloped in a mass of callus containing increasing amounts of bone. In the middle of the reparative phase the remodeling phase begins, with resorption of portions of the callus and the laying down of trabecular bone along lines of stress. Finally, exercise increases the rate of bone repair. Heikkinen et al. Scand J. Clin. Lab. Invest. 25(suppl 113):32. In situ hybridization results have shown that OCP expression is confined to very specific regions where bone and cartilage formation is initiated.

[0176]In order to find out if OCP expression is induced in an animal model of bone fracture healing, a standard midshaft fracture was created in rat femur by means of a blunt guillotine, driven by a dropped weight. Bonnarens et al. (1984) Orthop. Res. 2:97-101. One, 2, 3 and 4 week-fractured bones were excised, fixed in buffered formalin, decalcified in EDTA solution and embedded in paraffin. All sections were hybridized with the OCP probe. The in-situ hybridization results show that a strong hybridization signal was apparent during the first and second weeks of fracture healing in the highly vascularized areas of the connective tissue within the callus (FIGS. 16-18), the endosteum (FIG. 19), the woven bone (FIG. 20) and the periosteum FIG. 21). The periosteum is regarded as a source of undifferentiated progenitors participating in callus formation at the site of bone fracture. The hybridization signal disappeared slowly during further differentiation stages of fracture healing (three and four weeks) and was retained only in the vascularized connective tissue. 22 displays brightfield (left) and darkfield (right) photomicrographs of a section of fractured bone healed for 4 weeks. In these later healing stages, the mature callus tissue was found to be comprised mainly by cancellous bone undergoing remodeling into compact bone, with little if any cartilage or woven bone present. The volume of the vascularized periosteal tissue is decreased but multiple cells in the periosteal tissue area of active remodeling of the cancellous bone covering the callus, show hybridization signal. This tissue covers the center of the callus and is also entrapped within the bone. See FIGS. 22 and 23. The box in FIG. 22 is enlarged in FIG. 23. As in the earlier stages, no hybridization signal was found in chondrocytes and osteoblasts. FIGS. 17 and 23. Several OCP expressing cells are concentrated in the vascular tissue that fills the cavities resulting from osteoclast activity (marked by asterisks).

[0177]Fractures in the young heal rapidly, while adult bone fractures heal slowly. The cause is a slower recruitment of specific chondro-/osteo-progenitors for the reparative process in the adult bone. Denervation retards fracture healing by diminishing the stress across the fracture site, while mechanical stress increases the rate of repair probably by increasing the proliferation and differentiation of specific bone progenitor cells and as a result, accelerates the rate of bone formation. The above results confirm our conclusions (see also hereunder) that OCP is most probably involved in induction of cortical and trabecular bone formation and remodeling, endochondral bone growth during development, and bone repair processes. In addition, there is strong evidence that OCP expression is tightly regulated, and induced during the earliest stages of bone fracture repair when osteo-/chondro-progenitor cells are recruited. This observation suggests that OCP plays a role in this process.

[0178]Taking into account the pattern of 608 expression during the process of bone fracture healing, it seems a reasonable hypothesis that 608-positive precursor cells are involved not only in remodeling of intact bone but also in the repair processes of the fractured bone as well.

Example 8

OCP Transcriptional Regulation

[0179]In order to clone the longest possible fragment which will contain the OCP regulatory region/s, bacs L4 and H7 were restricted with three different enzymes: BamHI, Bgl II and SauIIIA. The resulting fragments were cloned into the BamHI site of pKS. Ligation mixes were transformed into bacteria (E. coli-DH5α) and 1720 colonies were plated onto nitrocellulose filters which were screened with ³²P-labeled PCR fragment spanning the mouse-OCP-exonl. Positive colonies were isolated.

[0180]Two identical clones, 14C10 and 15E11, contained the largest inserts (BamHI-derived ˜13 Kb inserts). The 14C10 clone is longer than the OCP "Lexicon" clone by ˜8 Kb at the 5' end.

[0181]a. Cloning of Mouse OCP Promoter and UTR Upstream to the Reporter Gene-EGFP

[0182]The 1.4 Kb genomic region of the mouse OCP gene, flanked by BamHI site (nuc 5098 of the "Lexicon" clone which is the start site of clone p14C10) and the first ATG codon (first nucleotide of exon 2), was synthesized by genomic PCR using the "Lexicon" clone as template and pre-designed primers: 5'primer (For1) located upstream to the BamHI site (nucleotides 4587-4611 of the Lexicon clone) and 3' primer (Rev 2) located immediately upstream to the first ATG (nucleotides 6560-6540 of the Lexicon clone) and tailed by a NotI site. The PCR product was cut by BamHI and NotI and the resulting 1.4 Kb fragment was ligated to pMCSIE into BamHI/NotI sites upstream to the EGFP reporter gene. The resulting clone was designated pMCSIEm608prm1.4.

[0183]Clone p14C10 was cut by XbaI and BamHI and the excised 4.088 Kb fragment was ligated into the BamHI and XbaI sites of pMCSIEm608prm1.4, upstream to the 1.4 Kb insert. The resulting clone was designated pMCSIEm608prm5.5 and contains 5552 nucleotides of the mouse 608 promoter and UTR upstream to EGFP. The insert of pMCSIEm608prm5.5 clone was completely sequenced.

[0184]The whole 13 Kb insert of p14C₁₀ was excised by BamHI and ligated upstream to the 1.4 Kb insert of pMCSIEm608prm1.4 into the BamHI site. The resulting construct, pMCSIEm608prm14.5 contains a 14.5 Kb fragment of the mouse-OCP promoter and UTR upstream to EGFP.

[0185]b. Cloning Mouse OCP Promoter and UTR Upstream to the Reporter Gene-Luciferase

[0186]Both inserts of pMCSIEm608prm5.5 and of pMCSIEm608prm14.5 were also cloned upstream to luciferase, in Promega's pGL3-Basic vector. The 5.5 Kb insert of pMCSIEm608prm5.5 was excised by EcoRV and XbaI and ligated to SmaI and NheI sites of pGL3-Basic vector. The resulting clone is designated pGL3basicm608prm5.5.

[0187]Plasmid pMCSIEm608prm14.5 was restricted by NotI and the cohesive ends of the linearized plasmid were filled and turned into blunt ends. The 14.5 Kb insert was then excised by cutting the linear plasmid by SalI. The purified 14.5 Kb fragment was ligated to the XhoI and HindIII (filled in) sites of pGL3-basic upstream to the luciferase gene to create the construct designated pGL3basicm608prm14.5. SEQ ID NO:18 depicts 4610 bp that have been sequenced.

c. Analysis of TF Binding DNA Elements Common to Mouse and Human OCP

[0188]Known transcription factor (TF) binding DNA elements were analyzed for similarity upstream of human and mouse OCP ATG using the DiAlign program of Genomatix GmbH. The genomic pieces used are the proprietary mouse genomic OCP and reverse complement of AC024886 92001 to 11 1090. The locations of the ATG in these DNA pieces are: [0189]575 on rat cDNA [0190]*6521 on mouse genomic [0191]*3381 on the piece extracted from human genomic DNA AC002488614 elements were extracted in this procedure and analyzed for transcription binding motifs using the MatInspector.

[0192]Some of the main "master gene" binding sites are the osteoblast-/chondrocyte-specific Cbfa1 factor; the chondrocyte-specific SOX 9 factor; the myoblast-specific Myo-D and Myo-F factors; the brain- and bone-specific WT1; Egr 3 and Egr 2 factors (Egr superfamily); the vitamin D-responsive (VDR) factor; the adipocyte-specific PPAR factor; and the ubiquitous activator SP1.

Example 9

Expression Pattern and Regulation of Gene 608: Expression of Gene 608 in Regard to Other Osteogenic Lineage Markers

[0193]Expression of gene 608 was tested in primary cells and in cell lines with regard to expression of various markers of osteogenic and chondrogenic lineages. The results of this analysis are summarized in the following table and showed that expression of 608 is restricted to committed early osteoprogenitor cells.

TABLE-US-00002 Cells 608 Collagen I Collagen II Alk. Phos. Osteocalcin Cbfa1 Osteopontin STO - - + - + + + (fibroblasts) ROS - - - + + +/- + (osteosarcoma) MC3T3 (pre- + - - + + + + osteoblasts) C2C12(pre- - - - - + - + myoblasts) C6 (glioma) - - Calvaria mouse + + Calvaria rat + + C3H10T1/2 - - + - + - + (mesenchymal stem cells)

Example 10

OCP Expression is Mechanically Induced in MC3T3 E1 Cells

[0194]OCP transcription was detected by RT-PCR in mouse calvaria cells, U20S cells (human osteosarcoma cell line), and human embryonal bone. FIG. 14. OCP was initially discovered as being upregulated during mechanical stress in calvaria cells. In the present invention, we demonstrate that the influence of mechanical stress on OCP expression can be reproduced in another cell system using a different type of mechanical stimulation. In serum-deprived MC3T3-E1 pre-osteoblastic cells, mechanical stimulation caused by mild (287×g) centrifugation markedly induced OCP mRNA accumulation. FIG. 15. Other osteoblastic marker genes (osteopontin, ALP (staining--not shown) and Cbfa1) were transcriptionally augmented by this procedure. FIG. 15. The RT-PCR product of a non-osteoblastic marker gene (GAP-DH) was used as a control to compare RNA levels between samples. No increased expression was noticed when the latter primers were used. No expression was detected in non-osteoblastic cells (FIG. 14), suggesting that OCP expression is specifically induced in osteogenesis. Responsiveness of CMF608 expression to mechanical stimulation was confirmed by Northern blot analysis using polyA RNA from primary rat calvaria cells before and after mechanical stress (FIG. 12.).

Example 11

OCP Induction During Endochondral Growth--In Situ Hybridization Analysis

[0195]Our previous results demonstrated that OCP is expressed during adult mice bone modeling and remodeling. The expression was restricted to the following regions: [0196]1 perichondrium [0197]2 periosteum [0198]3 active remodeling and modeling regions [0199]4 perivascular connective tissue [0200]5 articular cartilage covering cells [0201]6 embryo-condensed mesenchymal cells-head, vertebrae and trunk [0202]7 ectopic bone formation

[0203]No previous observations suggest any role for OCP in bone development or initiation of endochondral ossification (longitudinal growth of long bones). Thus, the expression pattern of OCP by in situ hybridization on sections of bones from 1 week old mice was analyzed. At this stage of bone development, osteogenesis starts within the epiphysis (secondary ossification center). The hind limb skeleton of 1 week old rat pups (femur together with tibia) was fixed in buffered formalin and longitudinal sections of decalcified tissue were processed for in situ hybridization according to standard in-house protocol. Autoradiographs were developed, stained with hematoxylin-eosin and studied under microscope using brightfield and darkfield illumination.

[0204]A strong fluorescence signal was observed all over the second ossification center using OCP probes. FIG. 17 In addition, the hybridization signal delineates periosteal and perichondrial tissue in a way similar to that found earlier in adult bones. Surrounding mature chondrocytes displayed no signal. A very faint signal was observed using the osteocalcin probe which is a marker of mature osteoblasts.

[0205]In conclusion, OCP is expressed in osteoprogenitor cells that initiate endochondral ossification during bone development.

Example 12

In vivo Regulation by Stimuli Either Promoting or Suppressing Bone Formation Estrogen Administration, Blood Loss and Sciatic Neurotomy

[0206]Osteogenic cells are believed to derive from precursor cells present in the marrow stroma and along the bone surface. Blood loss, a condition that stimulates hemopoietic stem cells, activates osteoprogenitor cells in the bone marrow and initiates a systemic osteogenic response. High-dose estrogen administration also increases de novo medullary bone formation possibly via stimulation of generation of osteoblasts from bone marrow osteoprogenitor cells. In contrast, skeletal unweighting, whether due to space-flight, prolonged bed-rest, paralysis or cast immobilization leads to bone loss in humans and laboratory animal models. To detect alteration in OCP expression pattern following the above procedures, the following experiments were performed on two month old mice: [0207]estrogen administration (500 μg/animal/week), [0208]bleeding (withdrawing approximately 1.6% body weight), [0209]unilateral (right limb) sciatic neurotomy, [0210]control groups for each treatment

[0211]Total RNA was extracted from long bones after two-day treatment and RT-PCR using OCP-specific primers was performed. The results demonstrate that OCP expression was highly enhanced following blood loss and estro gen administration, while down-regulation was observed following sciatic neurotomy. FIG. 19.

[0212]By having a unique cell marker (OCP) we can show that the above procedures induce or reduce bone formation by increasing ordecreasing the number of osteoprogenitor cells. The above results suggest once more that OCP is a major member of a group of "bone specific genes" that regulate the accumulation of bone specific precursor cells.

Example 13

OCP Induction During Osteoblastic Differentiation of Bone Marrow Stroma Cells

[0213]Bone formation should be augmented in trabecular bone and cortical bone in osteoporotic patients. We have previously detected OCP expression in periosteum and endosteum (surrounding the cortical bone) but no signal was apparent in bone marrow cells. The latter cells normally differentiate to mature osteoblasts embedded in the trabecular and cortical bone matrix.

[0214]To further assess OCP expression in bone marrow progenitor cells, the inventors extracted total RNA from mouse and rat bone marrow immediately after obtaining it and after cultivation for up to 15 days in culture. No OCP-specific RT-PCR product was detected with RNA from freshly obtained bone marrow (both in adherent and non-adherent) cells. However, a faint signal was found after 5 days in culture, and it was further enhanced when RNA from cells grown for 15 days in culture was used. ALP (alkaline phosphatase) expression (an osteoblastic marker) was also found to be enhanced after 15 days. At both time points, adherent and non-adherent cells were reseeded, and RNA extractions were prepared 5 and 15 days later. A stronger RT-PCR product was observed with RNA extracted from originally adherent cells, suggesting the existence of less mature progenitors in the non-adherent population of bone marrow cells. The RT-PCR product of a non-osteoblastic marker gene (GAP-DH) was used as a control to compare RNA levels between samples.

[0215]In conclusion, bone marrow progenitor cells do not express OCP, but differentiate to more committed cells that do express this gene.

Example 14

OCP Role in Osteogenesis In Vitro

[0216]The ultimate test for the role of OCP as a crucial factor that induces osteoblast-related genes is its ability to up-regulate these genes in pre-osteoblastic and osteoblastic cells. Stable transfection of OCP to ROS 17/2.8 (differentiating osteoblast cell line) cells upregulated ALP and BSP expression. FIG. 24 In addition, marked increase in osteoblastic proliferation was observed; see FIG. 25

[0217]C3H10T1/2 cells were transfected with the following constructs containing the CMV promoter:

1. 608-663 a.a--Construct containing 5' untranslated region of β-actin, the OCP coding region from ATG at position 1 to the amino acid at position 663 of FIG. 3 (SEQ ID NO:2) and 3'Flag Tag. The functional portion of the mammalian OCP expressed using this construct contains the first 663 amino acids of the OCP polypeptide sequence, plus several additional amino acids of the 3'Flag tag

[0218]An additional construct was made, designated pCm-H608-663Nterm, which has the 5' untranslated region of β-actin, the human OCP coding region from which encodes polypeptide from the ATG at position 1 to the amino acid at position 663 of FIG. 30 (SEQ ID NO:24) but no Flag Tag; this construct was deposited in the ATCC on Aug. 14, 2001 under ATCC Number PTA-3638.

2. pCMV-neo--as negative control. This is the empty plasmid into which the 608-663aa was cloned to create vector #1 above. It serves as negative control to show that the effects are not caused by any other part of the #1 construct but by expression of the 608-663aa.

Example 15

Creation of a Readout System

[0219]A readout system is created to identify small molecules that can either activate or inactivate the OCP bone-precursor-specific promoter

Example 16

Bioinformatic Analysis of Human 608

[0220]A DNA sequence encoding a fragment of human OCP named AC024886 is found in htgs database but not in nt. There is no genomic DNA corresponding to the rat cDNA. Alignment of AC024886 against the rat cDNA using BLAST shows two areas of long alignment (and several shorter areas):

[0221]1. cDNA: 6462-8186 [0222]Genomic: 89228-90952 [0223]plus/plus orientation: 81% identity

[0224]2. cDNA: 5581-6451 [0225]Genomic: 107710-106840 [0226]Plus/minus orientation: 80% identity

[0227]Thus AC024886 was wrongly assembled in the region upstream of position 6462 (according to the rat cDNA), it was in the incorrect orientation. Using the incorrect orientation provided incorrect coding sequence and does not yield the human OCP protein.

[0228]The Genbank report on AC024886 was as follows:

LOCUS AC024886 175319 bp DNA

HTG 06-SEP-2000

[0229]DEFINITION Homo sapiens chromosome 3 clone RP11-25K₂₄, WORKING DRAFTSEQUENCE, 9 unordered pieces.

ACCESSION AC024886

VERSION AC024886.10 GI:9438330

KEYWORDS HTG; HTGS_PHASE1; HTGS_DRAFT.

[0230]SOURCE human.NOTE: This was a `working draft` sequence. It consisted of 9 contigs. The true order of the pieces was not known and their order in this sequence record was arbitrary. Gaps between the contigs are represented as runs of N, but the exact sizes of the gaps was unknown. [0231]1 62523: contig of 62523 bp in length [0232]62524 62623: gap of unknown length [0233]62624 85445: contig of 22822 bp in length [0234]85446 85545: gap of unknown length [0235]85546 106059: contig of 20514 bp in length [0236]106060 106159: gap of unknown length [0237]106160 127908: contig of 21749 bp in length [0238]127909 128008: gap of unknown length [0239]128009 143068: contig of 15060 bp in length [0240]143069 143168: gap of unknown length [0241]143169 158734: contig of 15566 bp in length [0242]158735 158834: gap of unknown length [0243]158835 170042: contig of 11208 bp in length [0244]170043 170142: gap of unknown length [0245]170143 173715: contig of 3573 bp in length [0246]173716 173815: gap of unknown length [0247]173816 175319: contig of 1504 bp in length.a. Mapping Human Genomic 608 Exons

[0248]Ten exons were mapped on the rat cDNA sequence from base 107 to 6451. Thus the first exon on the human genomic piece may be lacking. The human genomic piece (AC024886) upstream (19090 bases) of base 6462 of cDNA (reverse complement from base of AC024886 92001 to 111090) was compared with the rat cDNA using the program ExonMapper of Genomatix. In the Table, base 1 is actually 1131 in the genomic piece used so that the actual genomic location starts at 91870.

[0249]Two additional exons were mapped on the rat cDNA sequence from base 6462 to 8883. Thus bases 6452-6461 are lacking. The human genomic piece used is from base 165,337 to 17,5667 (10,331 bases). The same type of program was used to compare this sequence to the genomic mouse 608 sequence deduced as described above.

[0250]Connecting the exon/intron borders from the genomic sequences yielded the predicted human and mouse cDNAs. The mouse and human predicted cDNAs were modified in order to allow frame shifts that allow a good multiple alignment of the human, mouse and rat proteins. Alignment was done using CLUSTALX and Pretty.

[0251]The cDNA modifications after the alignment of human cDNA to rat cDNA by GeneWise were as follows. In the following two tables,-x indicates a deletion of nucleotide x in the cDNA sequence; +x indicates an insertion of nucleotide x in the cDNA sequence; and all changed positions are in relation to the original sequence

TABLE-US-00003 Position Change 1111 -g 4154 -c 4538 +g 4730 -a 4744-5 -aa 4830 +c 4852 -g 4902 +t 4942 +c 5370 +t 5387 -a 5395 +c

[0252]The corrections of frame-shifts in mouse 608 were as follows:

TABLE-US-00004 Position Change 678 -c 1106 -a

Chromosomal Location on the Human Chromosome:

[0253]Two different types of data exist. [0254]a. Genomic piece AC024886 has identity to the fragment identified as ACCESSION D14436 as described by Fukui et al. (1994) Biochem. Biophys. Res. Commun. 201:894-901. [0255]Alignment information: [0256]Identities=315/335 (94%), [0257]hrh1: 4-338 [0258]AC024886: 41662-41328 [0259]Hrh1 is mapped to chromosome 3 and to 3p25; and [0260]b. Identity to STS at 3q. STS: 20-432 is identified as ACCESSION G54370 and described by Joensuu et al. (2000) Genomics 63:409-416.

Example 17

Polyclonal Antibody Preparation

[0261]Polyclonal antibodies specific to the whole 608 putative protein are prepared by methods well-known in the art (the structure of 608 resembles that of growth factor precursors). Polyclonal antibodies are identified and the recombinant active form of 608 is prepared. The activities of the polyclonal antibodies are tested in vivo in mice. The antibodies can be used for the identification of the active form of this protein which is likely to constitute a fraction of the 608 protein.

Example 18

Stretch of Basic Amino Acids Found at the Boundary of the Rat and Human 608 Proteins, and its Implications

[0262]The homology between the rat and human N-terminal portions of the 608 protein is especially significant within the first 250 amino acids. At the boundary of this conserved region there is a completely conserved stretch of basic amino acids: KCKKDR (aa 242-247 and 240-245, in rat and human proteins, respectively). Stretches of basic amino acids frequently serve as protease cleavage sites. The fact that such a stretch is found on the boundary of more or less conserved sequences and the fact that it occurs within the C-terminal LRR, a generally conserved domain, suggests an underlying biological significance.

[0263]Accordingly, the 608 protein may undergo post-translational processing through the cleavage of its highly conserved N-terminal portion and this portion may be an active part of the 608 protein or possess at least part of its biological activities. Since the resulting 25 kD protein preserves the signal peptide, it would be secreted.

[0264]The biologically active 25 kD N-terminal cleavage product of 608 can thus be used for treatment and/or prevention of osteoporosis, fracture healing, bone elongation and periodontosis. As an indirect product (inhibition by either chemicals or by neutralizing mAbs), the fragment can be used for treatment and/or prevention of osteoarthritis, osteopetrosis, and osteosclerosis.

Example 19

The Adlican Protein and Gene

[0265]Adlican is a recently described protein. Crowl and Luk (2000) Arthritis Biol. Res. Adlican, a proteoglycan, was derived from placenta. The full amino acid sequence of Adlican is disclosed and identified as AF245505.1:1.8487, and is hereby incorporated by reference into this application; see FIG. 27.

[0266]The structure of Adlican was analyzed using methods described herein and found to have leucine-rich repeats and immunoglobulin regions similar to those of the OCP protein. The overall homology found between the amino acid residues of the indicated regions in the two proteins, is as follows:

TABLE-US-00005 OCP Adlican % 1-661 1-669 38.4 662-1629 670-1865 19.7 1630-2587 1866-2828 46.5 1-2587 1-2828 33.2

[0267]The invention therefor encompasses the use of Adlican in any manner described herein for the OCP protein. These functions and uses have not been disclosed previously for Adlican. They include use of Adlican, or a functional portion thereof, for preventing, treating or controlling osteoporosis, or for fracture healing, bone elongation or treatment of osteopenia, periodontosis, bone fractures or low bone density or other factors causing or contributing to osteoporosis or symptoms thereof or other conditions involving mechanical stress or lack thereof in a subject.

[0268]The Adlican gene, or functional portions thereof, can likewise be used for any purpose described herein for an OCP gene. Compositions comprising the Adlican gene, Adlican or antibodies specific for Adlican and physiologically acceptable excipients are likewise encompassed by the invention. Such excipients are known in the art and include saline, phosphate buffered saline and Ringer's solutions.

Example 20

Sequencing of the N-Terminal of the OCP Gene

[0269]Sequencing of the N-terminal fragment of the OCP gene using the 663 amino acid human construct (Example 14) added six additional nucleotides to the DNA sequence as shown in FIG. 29 (SEQ ID NO:23), where these 6 additional nucleotides are underlined.

[0270]The corresponding amino acid sequence of the encoded OCP protein thus has an additional two amino acids, as shown in FIG. 30,(SEQ ID NO:24) where these 2 additional amino acids are underlined.

Example 21

Preparation of a Recombinant Functional Portion of OCP

[0271]The 663 amino acid construct described in Example 14 was expressed in 293T cells. Western blot analysis of the medium, using antibody to the Flag tag, showed the presence of the 663 amino acid polypeptide. This polypeptide was purified from the medium, using a column of anti-Flag tag antibodies.

[0272]Our objective was to determine if the 1-663 amino acid polypeptide fragment of the 608 protein could induce proliferation in bone-related cell lines. Proliferation activity was tested by ³[H] thymidine incorporation assay on 4 bone related cell lines, with IGF1 or PTH as standards. (Pre-osteoblastic and osteoblastic proliferation is an activity that characterizes bone formation inducing factors such as IGF1 and PTH.)

[0273]In this key series of experiments, the purified 663 polypeptide showed a proliferative effect on W-20-17, a mouse bone marrow stromal cell line. This effect was reproduced with two 663-polypeptide batches in 5 independent experiments.

[0274]The activity of proliferation of bone marrow stromal cells demonstrated in the above experiments could be indicative of pre-osteoblastic proliferation activity induced by the 663 amino acid polypeptide. The 663 polypeptide activity could be mimicking the complete 608 protein in vivo activity. Alternatively, the 663 polypeptide activity could have a dominant negative effect, i.e. an effect that inhibits the whole 608 protein in vivo activity. Regardless of the mechanism, the 663 polypeptide could be used to induce proliferation of pre-osteoblastic stromal cells. This activity could help restore the pre-osteoblastic cell population that is known to be depleted in old-age or senile osteoporosis.

Example 22

Identification of RGD and Subtilisin-Like Proprotein Convertase (SPC) Motifs in Rat OCP

[0275]SEQ ID NO: 2 and SEQ ID NO: 34 depict the amino acid sequence of the rat 608 polypeptide. There is an RGD sequence at positions 729-731, and there is a putative cleavage motif subtilisin-like proprotein convertase (SPC) consensus sequence at positions 735-741.

[0276]The 608 protein was partially cleaved by SPC, in 293HEK cells. This putative peptide also contained the RGD sequence. Many adhesive proteins, present in extracellular matrices and in the blood, contain this tripeptide as their cell recognition site. Therefore, the 608 peptide comprising 1-741 amino acids, or a shorter fragment of the 608 protein containing the RGD sequence, may be a much more effective drug than the 663 amino acid fragment. The RGD and RxxRxxR (viz. R-aa1-aa2-R-aa3-aa4-R, i.e., SPC cleavage site) sequences are present in the human 608 protein sequence but are not present in Adlican or in Adlican-2.

Example 23

Natural Cleavage of Rat OCP

[0277]A polyclonal antibody against the rat 608 fragment comprising amino acid residues 1-312 was prepared by methods well-known in the art. This antibody was used to identify 608 peptides on Western blots. Several 608 sequences were expressed in cells derived from the transiently transfected 293T kidney cell line. The sequences were rat full length 608 polypeptide, rat 608 polypeptide fragment comprising amino acid residues 1-1634, and rat 608 polypeptide fragment comprising amino acid residues 1-663. The antibody identified a peptide of about 90 kDa in all three constructs produced. This peptide was detected by the anti-608 antibody in the conditioned medium of the cells, and not in cell extracts.

[0278]Table: Western blot analysis using polyclonal antibody to rat 608 fragment comprising 1-312 amino acid residues:

TABLE-US-00006 608 amino acid sequence Expected size Detected size 1-663 80 kDa 75-100 kDa 1-1634 196 kDa 75-100 kDa (larger than 1-663 aa peptide) 1-2597 (full length) 311 kDa 75-100 kDa (larger than 1-663 aa peptide) 1-741 89 kDa

[0279]The 608 full length and the 608 1-1634 aa proteins produced in 293T cells were cleaved and secreted into the medium. The cleaved products appeared to be of identical size. The 608 1-663 aa protein was also secreted into the medium, but appeared to be slightly smaller than the cleaved full length and 1-1634 aa proteins. The expected size of the 608 fragment from 1-741 aa, that is, the putative SPC cleavage product, was approximately 89 kDa.

[0280]In further experiments, mouse calvaria cells cultured in vitro were analyzed by western blotting with the antibody to the 608 fragment 1-312aa. No 608 specific band was detected in cell extracts. In the conditioned medium from the cells a band of approximately 350 kDa was detected by the anti 608 1-312aa. The size of this band correlates with the protein size expected from the full length 608 protein. This analysis probably indicates that the 608 full-length protein is secreted.

[0281]To summarize, in human embryonic kidney cells, which do not normally express the 608 gene, overexpression of 608 protein results in secretion of a cleaved part of the 608 protein. In mouse calvaria cells, which normally express the 608 gene, the naturally expressed 608 protein is probably secreted uncleaved. One possible explanation of this data is that 608 activity is regulated by proteases that are selectively expressed.

Example 24

Human Adlican as a Candidate for Osteoblast Proliferation and Differentiation

[0282]As discussed in Example 19, Adlican is a recently described protein. The Adlican protein has LRR (Leucine-rich-repeats) and immunoglobulin regions highly similar to those of the OCP protein. The overall homology found between the amino acid residues of the indicated regions in the two human proteins is as shown in Example 19.

[0283]The deduced Adlican protein comprises the following features:

[0284]a. A cleavable, well-defined N-terminal signal peptide at 1-26 aa,

[0285]b. A LRR region (26-205 aa). This region can be divided into N-terminal and C-terminal domains of LRR (aa 26-59 and 217-276, respectively). Between them, there are six LRR (aa 55-77, 78-101, 102-125, 126-149, 150-173, 182-205).

[0286]c. Twelve immunoglobulin C-2 type repeats at amino acid positions 492-562, 590 658, 1866-1935, 1963-2032, 2060-2129, 2159-2228, 2256-2331, 2359-2425, 2457-2525, 2555-2623, 2650-2718, 2746-2817. Thus, two Ig-like repeats are found immediately downstream of a LRR region, while the remaining 10 repeats are clustered at the protein's C-terminus, as in OCP.

[0287]d. 4 nuclear putative localization domains (NLS) at amino acids: 676-682, 1146-1165, 1230-1236, and 1747-1763.

[0288]Therefore, we have determined that Adlican is a good candidate as an inducer of osteoblast proliferation and differentiation.

[0289]In order to determine if human Adlican expression causes proliferation and differentation of osteoblasts and chondrocytes, the expression product of Adlican, or cells or vectors expressing Adlican are monitored to determine if they cause cells to selectively proliferate and differentiate and thereby increase or alter bone density. Detecting levels of Adlican mRNA or expression and comparing it to "normal" non-osteopathic levels will allow screening amd detection of individuals who may be at risk for developing osteoporosis or lower levels of osteoblasts and chondrocytes.

Example 25

The Deduced Adlican-2 Protein

[0290]The deduced Adlican-2 protein (Genomic location: Yq11.21) was generated following the alignment (shown in FIG. 41) comparing Adlican-2 predicted sequences (FIGS. 39 and 40) and the equivalent human Adlican amino acid sequences (FIG. 27). This DNA molecule and the encoded polypeptide are novel molecules and constitute an integral part of this invention.

[0291]A Y chromosome BAC clone (gi 8748884) shows 93% homology to Human Adlican. Two mRNA sequences 100% homologous to this BAC clone were submitted to the gene bank (gi 14719942, and gi 14719940). However, the sequence of these clones is not based on cDNA sequences, but on human genomic data and they cover a short stretch of the nucleotide sequence in the C-terminal Ig region. We performed upstream nucleotide and deduced amino acid sequencing. The sequence alignment of Adlican and Adlican-2 exists along the entire Adlican sequence with one possible exception. Alignment along aa 66-215 of Adlican may be missing from the Adlican-2 molecule. This is the area of the 6 LRR (leucine-rich repeats). Although the encoding nt's for the 6 LRR region have not yet been observed, their existence has not been definitely ruled out.

[0292]The invention therefore encompasses the use of Adlican-2 in any manner described herein for the OCP protein. No functions or uses have been disclosed previously for Adlican-2. The proposed uses include use of Adlican-2, or a functional portion thereof, for preventing, treating or controlling osteoporosis, or of fracture healing, bone elongation or treatment of osteopenia, periodontosis, bone fractures or low bone density or other factors causing or contributing to osteoporosis or symptoms thereof or other conditions involving maechanical stress or lack thereof in a subject. As an indirect product (inhibition by either chemicals or by neutralizing mAbs), Adlican-2 can be used for treatment and/or prevention of osteoarthritis, osteopetrosis, and osteosclerosis. The Adlican-2 gene, or functional portions thereof, can likewise be used for any purpose described herein for an OCP gene. Compositions comprising the Adlican-2 gene, Adlican-2 or antibodies specific for Adlican-2 and physiologically acceptable excipients are likewise encompassed by the invention. Such excipients are known in the art and include saline, phosphate buffered saline and Ringer's solutions.

Example 26

The Physical Sequence of the Human OCP

[0293]Obtaining the sequence of human OCP was a difficult task. Initially several attempts were made to do amplification via RT-PCR using rat primers from the rat OCP coding sequence, in order to obtain human OCP cDNA, but these efforts failed. Thereafter, a predicted sequence was created as described in Examples 5 and 16 by bioinformatic analysis of the human genome. Then primers specifically designed according to the predicted sequence were used to amplify human cDNA. This proved difficult, due to the large size of the gene and also to the problem of the low abundancy of OCP mRNA in human tissue and the unavailabilty of such tissue. Eventually, cell line U20S (human osteosarcoma cell line) was found to be a suitable source for OCP mRNA. It was also decide to clone the DNA in fragments.

[0294]The first section of the gene to be cloned was a small fragment corresponding to the first 663 amino acids, creating the plasmid described in Example 14 (ATCC Number PTA-3638), and giving a corrected predicted sequence.

[0295]Since the complete human OCP gene could not be amplified and cloned as one entity, three large overlapping fragments were amplified, spanning the complete ORF. These PCR fragments were sequenced and the physical sequence of the human OCP was determined accordingly. The physical sequence was found to contain inserts relative to the predicted sequence. The overlapping PCR fragments were subsequently cloned in three separate plasmids (described below) as continous clones (overlapping regions were removed).

[0296]FIG. 42 shows the physical DNA sequence of the coding region-ORF of human OCP (SEQ ID NO: 31) having 7872 base pairs, including the stop codon. The sequence contains a silent mutation (C>T transition) at position 6729 compared to the predicted sequence of human OCP ORF. This transition does not change the identity of the encoded amino acid residue.

[0297]FIG. 43 shows the predicted amino acid sequence corresponding to the physical DNA sequence of the coding region-ORF of human OCP (SEQ ID NO:32), having 2623 amino acids.

[0298]The three plasmids harboring the 5' fragment (A), middle fragment (B) and 3' fragment (C) are depicted in FIGS. 34, 36 and 38 respectively, and were deposited on Nov. 21, 2001 under the terms of the Budapest Treaty with the American Type Culture Collection (ATCC), P.O. Box 1549, Manassas, Va. 20108, USA, under ATCC accession numbers PTA-3878, PTA-3876 and PTA-3877 respectively.

[0299]FIG. 34 shows the physical sequence of the 5' fragment (A) cloned into pBluescript KS to NotI (5') and HindIII (3') sites. Fragment A is comprised of the 5' region (2440 bp) of the complete human OCP sequence and includes, in addition, at the 5' end, 21 nucleotides of the β-actin "Kozak" region (nucleotides 9-29) followed by the ATG initiation coNotI (5') and HindIII (3') sites are located at nucleotides 1-8 and 2464-2469 respectively (SEQ ID NO:26).

[0300]FIG. 36 shows the physical sequence of the middle fragment (B) cloned into pBluescript KS to HindIII (5') and SalI (3') sites. Fragment B is comprised of the central region (3518 bp) of the complete human OCP sequence; the HindIII (5') and SalI (3') sites are located at nucleotides 1-6 and 3513-3518 respectively (SEQ ID NO:27).

[0301]FIG. 38 shows the physical sequence of the 3' fragment (C) cloned into pMCS SV(A) to SalI (5') and SpeI (3') sites. Fragment C is comprised of the 3' region (1923 bp, not including the 3 bp stop codon) of the complete human OCP sequence and includes at the 3' end, 18 nucleotides coding for 6 Histidine residues, nucleotides 1924-1941, followed by the TGA stop codon.; the SalI (5') and SpeI (3') sites are located at nucleotides 1-6 and 1945-1950 respectively (SEQ ID NO:28).

[0302]Additionally, as discussed above, cloned fragment C contains a silent mutation (C>T transition) at nucleotide 783 compared to the predicted sequence of human OCP ORF; this transition does not change the identity of the encoded amino acid residue.

[0303]Note that if the number of OCP--encoding nucleotides in the three separate clones is added (viz., 2440+3518+1923), nine (9) more nucleotides are obtained than in the single complete sequence (7881 nucleotides vs 7872 nucleotides). This discrepancy is due to three reasons:

[0304]1. The restriction site that appears at the 3' end of fragment A and at the 5' end of fragment B is counted twice, once in each fragment, giving an extra 6 nucleotides

[0305]2. The restriction site that appears at the 3' end of fragment B and at the 5' end of fragment C is counted twice, once in each fragment, giving an extra 6 nucleotides

[0306]3. The sequence of fragment C does not include the 3 nucleotide stop codon at the 3' end, since it is interrupted by 18 nucleotides coding for 6 Histidine residues.

[0307]Therefore the difference is 6+6-3=9, which exactly explains the discrepancy mentioned above.

Example 27

608 Knockout Bone Phenotypes in Females with and without Ovariectomy

[0308]Introduction

[0309]Knockout (KO) mice deleted of the 608 gene were prepared by the method of Wattler et. al. BioTechniques 26:1150-1160, 1999. Comparison of 608 knockout (KO) mice to age, sex, and treatment matched wild type (WT) mice was performed to test the effect of 608 absence on bone parameters. Bone parameters of KO and WT were compared in untreated 3 and 4 months old females. KO and WT bone parameters were also compared in 3 months old female mice 5 weeks post ovariectomy (post-menopausal osteoporosis model).

[0310]The bone-related phenotypes were evaluated using two analyses: Peripheral Quantitative Computed Tomography (PQCT) of femur and tibia Rosen H N et. Al. Calcif. Tissue Int. 57:35-39, 1995) and serum Alkaline phosphatase (ALP) (Farley J R et. al. J Bone Miner Res 9:497-508, 1994. pQCT scanning is a 2D X-ray analysis that measures bone mineral density (BMD), bone mineral content (BMC), and bone geometric parameters. Serum ALP is a biochemical marker of bone formation.

[0311]Results

[0312]A. Untreated KO Females

[0313]It was found that the serum marker (serum ALP) of bone formation was significantly increased in 3 month old 608 KO mice. These results are depicted in FIG. 46.

[0314]pQCT scanning was performed for two groups of mice. pQCT of 3 months old untreated (sham operated) female mice gave parameters that were significantly different between WT and KO by two-way ANOVA analysis (pvalue<0.05), as shown in the Table below.

TABLE-US-00007 pQCT WT KO % Parameter Average Average P Value Increase Femur 3.572 4.070 P < 0.05 14 Metaphysis Total Area Tibia 0.296 0.314 P < 0.05 6.1 Diaphysis Cortical Thickness Femur 0.990 1.114 P < 0.05 12.5 Diaphysis Cortical Area

[0315]Similarly, pQCT of 4 months old untreated female mice also gave parameters that were significantly different between WT and KO by one-way ANOVA analysis (pvalue<0.05), as shown in the following Table.

TABLE-US-00008 pQCT WT KO % Parameter Average Average P Value Increase Tibia 833.4 911.6 0.001803 9.4 metaphysis cortical BMD Femur 3.38 3.8 0.004296 12.4 Metaphysis Total Area Tibia 1150.4 1192 0.015211 3.6 Diaphysis Cortical BMD Femur 1202.4 1241.5 0.015951 3.3 Diaphysis Cortical BMD

[0316]In summary, the bone related phenotype of untreated 608 KO females is as follows:

[0317]At 3 months old, serum ALP is significantly increased in 608 KO mice. This may indicate that bone metabolism is different due to lack of the 608 gene. At this age, the significant increases are in bone geometric parameters. Slightly larger bone diameter and increased cortical thickness could affect bone strength.

[0318]At 4 months old, there is also a significant increase in cortical BMD of both femur and tibia. The incidence of fracture is closely related to BMD. Patients who sustain fractures have significantly decreased BMD.

[0319]In all parameters that showed a significant difference, the 608KO values were higher compared to WT. This may implicate an inhibitory role for the 608 gene in bone metabolism.

B. Ovariectomized KO Females

[0320]None of the parameters that were significantly increased in untreated females showed differences in ovariectomized females. Loss of tibia metaphysis total BMD due to ovariectomy may be smaller in 608KO mice. However, this difference was not found significant. Increasing the number of animals in each group could improve the statistical results.

CONCLUSIONS

[0321]The bones of KO mice appeared to have some basic anatomical differences compared to the bones of WT mice. This observation is based on trends seen in parameters reflecting bone geometry, such as total slice area, periosteal circumference, cortical area and thickness. Compared to untreated WT mice, an increase in the femur metaphysis area was observed in KO animals, both in 4 month-old and 3 month-old mice. Distal femur total BMD was notably unaffected by genotype despite the differences in bone size. Similar increases in geometric parameters were noted in KO mice compared to WT at the femur diaphysis (cortical area) and at the tibia diaphysis (cortical thickness) in 3 month-old mice. At 4 months old there is also a significant increase in cortical BMD of both femur and tibia.

[0322]Consistent with these effects on bone mass, biochemical markers of bone turnover were increased in KO mice, relative to the WT controls, suggesting that bone metabolism is different. Parameters that could affect bone strength, such as a slightly larger bone diameter and increased cortical thickness, could contribute to bone strength.

[0323]The effects on bone mass and biochemical markers of bone turnover noted in the KO mice appear to be indicative of a protective effect of the KO phenotype on bone loss following ovariectomy, although the effects were small. A trend to a genotype-related prevention of bone loss in the distal femur metaphysis relative to the ovariectomized controls was observed in KO animals. A slight partial prevention of bone loss relative to the ovariectomized control group was observed in KO mice at the endocortical surface of femur and tibia metaphysis, although the effects were not marked.

[0324]In conclusion, the effects on bone mass and biochemical markers of bone turnover noted in the KO mice appear to be indicative of a protective effect of the KO genotype on bone loss following ovariectomy. Bone metabolism and bone geometry could be different in KO mice.

[0325]The following hypothesis may correlate the in vitro data in the previous Examples with this in vivo data from the KO mice analyses:

[0326]The function of the 608 protein could be to promote proliferation of the undifferentiated osteoprogenitor cell population. This hypothesis is based on the proliferative effect of the 608 1-663aa polypeptide on mouse bone marrow cell line, as shown in Example 21. In the absence of this protein the balance between proliferation and differentiation of osteoprogenitors is changed in favor of differentiation and therefore the increased bone parameters are obtained at a young age. It could be that in aged mice this change in balance causes a decrease in bone parameters due to the normal decrease in osteoprogenitors that occurres with aging. If this hypothesis is correct an intermittent administration of the 608 protein or fragments of it could be used as a treatment for osteoporosis. Administration of the 608 polypeptide would cause proliferation of osteoprogenitors. When 608 level is allowed to decrease to normal levels, differentiation could take place.

[0327]An example of timing of intermittent treatment may be daily e.g. daily administration, preferably by injection, preferably subcutaneous, as opposed to continuous administration e.g. by infusion. Other examples may be administration every other day, or every few days, or even once a week or once a month. In the case of parathyroid hormone (1-34 amino acid), daily subcutaneous injections of 20-40 μg were considered intermittent administration as opposed to continuous infusions; see Neer R. M. et. al. 2001, The New England Journal of Medicine. 344: 1434-1441, Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.

[0328]Alternatively the 663aa fragment may act as an inhibitor of 608 function, as discussed in Example 21.

Sequence CWU 1

3718883DNARattus speciesmisc_feature(1)..(8883)'n' can be any nucleotide 'a', 'c', 'g' or 't'. 1cgagagacga cagaaggtta cggctgcgag aagacgacag aagggtccag aaaaaggaaa 60gtgctggagg ggagtgggga caaaagcagc gaccaagtga atgtcacttc agtgactgag 120gccaggcaaa acgcgcggga aggattttgt gtagcttggg accctttcat agacactgat 180gacacgttta cgcaaaatag aaatttgagg agaaacgcct gggccttcgg aaaggagtga 240ttgattagta cttgcaagtt taggtgactt taaggagaac taactaatgt atactattga 300gggaggagga agagcattac agagtttcca gcagcagcag gaaagctttg gttaatttgg 360aaatggatga tagcattaaa ataacagaag cgcctccagg tctctgaagc ttcagtcccc 420cagctgaaag ccagaaaaga ctaagcccac taagcctttt gatccctttg gaagcaaaga 480actttccttc cctggggtga agactctcct cagaagattt cctgtctctg cctatgttac 540aagaggaatc aaaaccaaga cagaagagct caggatgcag gtgagaggca gggaagtcag 600cggcttgttg atctccctca ctgctgtctg cctggtggtc acccctggga gcagggcctg 660tcctcgccgc tgtgcctgct atgtgcccac agaggtgcac tgtacatttc ggtacctgac 720ctccatccca gatggcatcc cggccaatgt ggaacgaata aatttaggat ataacagcct 780tactagattg acagaaaacg actttgatgg cctgagcaaa ctggagttac tcatgctgca 840cagtaatggc attcacagag tcagtgacaa gaccttctcg ggcttgcagt ccttgcaggt 900cttaaaaatg agctataaca aagtccaaat cattcggaag gatactttct acggactcgg 960gagcttggtc cggttgcacc tggatcacaa caacattgaa ttcatcaacc ctgaggcctt 1020ttatggactt acctcgctcc gcttggtaca tttagaagga aaccggctca caaagctcca 1080tccagacaca tttgtctcat taagctatct ccagatattt aaaacctctt tcattaagta 1140cctgttcttg tctgataact tcctgacctc cctcccaaaa gaaatggtct cctacatgcc 1200aaacctagaa agcctgtatt tgcatggaaa cccatggacc tgtgactgcc atttaaagtg 1260gttgtctgag tggatgcagg gaaacccaga tataataaaa tgcaagaaag acagaagctc 1320ttccagtcct cagcaatgtc ccctttgcat gaaccccagg atctctaaag gcagaccctt 1380tgctatggta ccatctggag ctttcctatg tacaaagcca accattgatc catcactgaa 1440gtcaaagagc ctggttactc aggaggacaa tggatctgcc tccacctcac ctcaagattt 1500catagaaccc tttggctcct tgtctttgaa catgacanan ntntctggaa ataaggccga 1560catggtctgt agtatccaaa agccatcaag gacatcacca actgcattca ctgaagaaaa 1620tgactacatc atgctaaatg cgtcattttc cacaaatctt gtgtgcagtg tagattataa 1680tcacatccag ccagtgtggc aacttctggc tttatacagt gactctcctc tgatactaga 1740aaggaagccc cagcttaccg agactccttc actgtcttct agatataaac aggtggctct 1800taggcctgaa gacattttta ccagcataga ggctgatgtc agagcagacc ctttttggtt 1860ccaacaagaa aaaattgtct tgcagctgaa cagaactgcc accacactta gcacattaca 1920gatccagttt tccactgatg ctcaaatcgc tttaccaagg gcggagatga gagcggagag 1980actcaaatgg accatgatcc tgatgatgaa caatcccaaa ctggaacgca ctgtcctggt 2040tggcggcact attgccctga gctgtccagg caaaggcgac ccttcacctc acttggaatg 2100gcttctagct gatgggagta aagtgagagc cccttacgtt agcgaggatg ggcgaatcct 2160aatagacaaa aatgggaagt tggaactgca gatggctgac agctttgatg caggtcttta 2220ccactgcata agcaccaatg atgcagatgc ggatgttctc acatacagga taactgtggt 2280agagccctat ggagaaagca cacatgacag tggagtccag cacacagtgg ttacgggtga 2340gacgctcgac cttccatgcc tttccacggg tgttccagat gcttctatta gctggattct 2400tccagggaac actgtgttct ctcagccatc aagagacagg caaattctta acaatgggac 2460cttaagaata ttacaggtta cgccaaaaga tcaaggtcat taccaatgtg tggctgccaa 2520cccatcaggg gccgactttt ccagttttaa agtttcagtt caaaagaaag gccaaaggat 2580ggttgagcat gacagggagg caggtggatc tggacttgga gaacccaact ccagtgtttc 2640ccttaagcag ccagcatctt tgaaactctc tgcatcagct ttgacagggt cagaggctgg 2700aaaacaagtc tccggtgtac ataggaagaa caaacataga gacttaatac atcggcggcg 2760tggggattcc acgctccggc gattcaggga gcataggagg cagctccctc tctctgctcg 2820gagaattgac ccgcaacgct gggcagcact tctagaaaaa gccaaaaaga attctgtgcc 2880aaaaaagcaa gaaaatacca cagtaaagcc agtgccactg gctgttcccc tcgtggaact 2940cactgacgag gaaaaggatg cctctggcat gattcctcca gatgaagaat tcatggttct 3000gaaaactaag gcttctggtg tcccaggaag gtcaccaact gctgactctg gaccagtaaa 3060tcatggtttt atgacgagta tagcttctgg cacagaagtc tcaactgtga atccacaaac 3120actacaatct gagcaccttc ctgatttcaa attatttagt gtaacaaacg gtacagctgt 3180gacaaagagt atgaacccat ccatagcaag caaaatagaa gatacaacca accaaaaccc 3240aatcattatc tttccatcag tagctgaaat tcgagattct gctcaggcag gaagagcatc 3300ttcccaaagt gcacaccctg taacaggggg aaacatggct acctatggcc ataccaacac 3360atatagtagc tttaccagca aagccagtac agtcttgcag ccaataaatc caacagaaag 3420ttatggacct cagataccta ttacaggagt cagcagacct agcagtagtg acatctcttc 3480tcacactact gcagacccta gcttctccag tcacccttca ggttcacaca ccactgcctc 3540gtctttattt cacattccta gaaacaacaa tacaggtaac ttccccttgt ccaggcactt 3600gggaagagag aggacaattt ggagcagagg gagagttaaa aacccacata gaaccccagt 3660tctccgacgg catagacaca ggactgtgag gccagcaatc aagggacctg ctaacaaaaa 3720tgtgagccaa gttccagcca cagagtaccc tgggatgtgc cacacatgtc cttccgcaga 3780ggggctcaca gtggctactg cagcactgtc agttccaagt tcatcccaca gtgccctccc 3840caaaactaat aatgttgggg tcatagcaga agagtctacc actgtggtca agaaaccact 3900gttactattt aaggacaaac aaaatgtaga tattgagata ataacaacca ctacaaaata 3960ttccggaggg gaaagtaacc acgtgattcc tacggaagca agcatgactt ctgctccaac 4020atctgtatcc ctggggaaat ctcctgtaga caatagtggt cacctgagca tgcctgggac 4080catccaaact gggaaagatt cagtggaaac aacaccactt cccagccccc tcagcacacc 4140ctcaatacca acaagcacaa aattctcaaa gaggaaaact cccttgcacc agatctttgt 4200aaataaccag aagaaggagg ggatgttaaa gaatccatat caattcggtt tacaaaagaa 4260cccagccgca aagcttccca aaatagctcc tcttttaccc acaggtcaga gttccccctc 4320agattctaca actctcttga caagtccgcc accagctctg tctacaacaa tggctgccac 4380tcagaacaag ggcactgaag tagtatcagg tgccagaagt ctctcagcag ggaagaagca 4440gcccttcacc aactcctctc cagtgcttcc tagcaccata agcaagagat ctaatacatt 4500aaacttcttg tcaacggaaa cccccacagt gacaagtcct actgctactg catctgtcat 4560tatgtctgaa acccaacgaa caagatccaa agaagcaaaa gaccaaataa aggggcctcg 4620gaagaacaga aacaacgcaa acaccacccc caggcaggtt tctggctata gtgcatactc 4680agctctaaca acagctgata cccccttggc tttcagtcat tccccacgac aagatgatgg 4740tggaaatgta agtgcagttg cttatcactc aacaacctct cttctggcca taactgaact 4800gtttgagaag tacacccaga ctttgggaaa tacaacagct ttggaaacaa cgttgttgag 4860caaatcacag gagagtacca cagtgaaaag agcctcagac acaccaccac cactcctcag 4920cagtggggcg cccccagtgc ccactccttc cccacctcct tttactaagg gtgtggttac 4980agacagcaaa gtcacatcag ctttccagat gacgtcaaat agagtggtca ccatatatga 5040atcttcaagg cacaatacag atctgcagca accctcagca gaggctagcc ccaatcctga 5100gatcataact ggaaccactg actctccctc taatctgttt ccatccactt ctgtgccagc 5160actaagggta gataaaccac agaattctaa atggaagccc tctccctggc cagaacacaa 5220atatcagctc aagtcatact ccgaaaccat tgagaagggc aaaaggccag cagtaagcat 5280gtccccccac ctcagccttc cagaggccag cactcatgcc tcacactgga atacacagaa 5340gcatgcagaa aagagtgttt ttgataagaa acctggtcaa aacccaactt ccaaacatct 5400gccttacgtc tctctaccta agactctatt gaaaaagcca agaataattg gaggaaaggc 5460tgcaagcttt acagttccag ctaattcaga cgtttttctt ccttgtgagg ctgttggaga 5520cccactgccc atcatccact ggaccagagt ttcatcagga nttgaaatat cccaagggac 5580acagaaaagc cggttccacg tgcttcccaa tggcaccttg tccatccaga gggtcagtat 5640tcaggaccgt ggacagtacc tgtgctctgc atttaatcca ctgggcgtag accattttca 5700tgtctctttg tctgtggttt tttacccggc aaggattttg gacagacatg tcaaggagat 5760cacagttcac tttggaagta ctgtggaact aaagtgcaga gtggagggta tgccgaggcc 5820tacggtttcc tggatacttg caaaccaaac ggtggtctca gaaacggcca agggaagcag 5880aaaggtctgg gtaacacctg atggaacatt gatcatctat aatctgagtc tttatgatcg 5940tggtttttac aagtgtgtgg ccagcaaccc atctggccag gattcactgt tggttaagat 6000acaagtcatc acagctcccc ctgtcattat agagcaaaag aggcaagcca tcgttggggt 6060tttaggtgga agtttgaaac tgccctgcac tgcaaaagga actccccagc ctagtgttca 6120ctgggtcctt tatgatggga ctgaactaaa accattgcag ttgactcatt ccagattttt 6180cttgtatcca aatggaactc tgtatataag aagcatcgct ccttcagtga ggggcactta 6240tgagtgcatt gccaccagct cctcaggctc agagagaagg gtagtgattc ttactgtgga 6300agagggagag acaatcccca ggatagaaac tgcctctcag aaatggactg aggtgaattt 6360gggtgagaaa ttactactga actgctcagc tactggggat ccaaagccta gaataatctg 6420gaggctgcca tccaaggctg tcatcgacca gtggcacaga atgggcagcc gaatccacgt 6480ctacccaaat ggatccttgg tggttgggtc agtgacggaa aaagacgctg gtgactactt 6540atgtgtggca agaaacaaaa tgggagatga cctagtcctg atgcatgtcc gcctgagatt 6600gacacctgcc aaaattgaac agaagcagta ttttaagaag caagtgctcc atgggaaaga 6660tttccaagtt gactgcaagg cctctggctc ccctgtgcct gaggtatcct ggagtttgcc 6720tgatgggaca gtgctcaaca atgtagccca agctgatgac agtggctata ggaccaagag 6780gtacaccctt ttccacaatg gaaccttgta tttcaacaac gttgggatgg cagaggaagg 6840agattatatc tgctctgccc agaacacctt agggaaagat gagatgaaag tccacctaac 6900agttctaaca gccatcccac ggataaggca aagctacaag accaccatga ggctcagggc 6960tggagaaaca gctgtccttg actgcgaggt cactggggaa ccgaagccca atgtattttg 7020gttgctgcct tccaacaatg tcatttcatt ctccaatgac aggttcacat ttcatgccaa 7080tagaactttg tccatccata aagtgaaacc acttgactct ggggactatg tgtgcgtagc 7140tcagaatcct agtggggatg acactaagac atacaaactg gacattgtct ctaaacctcc 7200attaatcaat ggcctgtatg caaacaagac tgttattaaa gccacagcca ttcggcactc 7260caaaaaatac tttgactgca gagcagatgg gatcccatct tcccaggtca cgtggattat 7320gccaggcaat attttcctcc cagctccata ctttggaagc agagtcacgg tccatccaaa 7380tggaaccttg gagatgagga acatccggct ttctgactct gcggacttca cctgtgtggt 7440tcggagcgag ggaggagaga gtgtgttggt agtgcagtta gaagtcctag aaatgctgag 7500aagaccaaca ttcagaaacc cattcaacga aaaagtcatc gcccaagctg gcaagcccgt 7560agcactgaac tgctctgtgg atgggaaccc cccacctgaa attacctgga tcttacctga 7620cggcacacag tttgctaaca gaccacacaa ttccccgtat ctgatggcag gcaatggctc 7680tctcatcctt tacaaagcaa ctcggaacaa gtcagggaag tatcgctgtg cagccaggaa 7740taaggttggc tacatcgaga aactcatcct gttagagatt gggcagaagc cagtcattct 7800gacatacgaa ccagggatgg tgaagagcgt cagtggggaa ccgttatcac tgcattgtgt 7860gtctgatggg atccccaagc caaatgtcaa gtggactaca ccgggtggcc atgtaatcga 7920caggcctcaa gtggatggaa aatacatact gcatgaaaat ggcacgctgg tcatcaaagc 7980aacaacagct cacgaccaag gaaattatat ctgtagggct caaaacagtg ttggccaggc 8040agttattagc gtgtcagtga tggttgtggc ctaccctccc cgaatcataa actacctacc 8100caggaacatg ctcaggagga caggggaagc catgcagctc cactgtgtgg ccttgggaat 8160ccccaagcca aaagtcacct gggagacgcc aagacactcc ctgctctcaa aagcaacagc 8220aagaaaaccc catagaagtg agatgcttca cccacaaggt acgctggtca ttcagaatct 8280ccaaacctcg gattccggag tctataagtg cagagctcag aacctacttg ggactgatta 8340cgcaacaact tacatccagg tactctgaca ggaaggggga gactaaaatt caacagaagt 8400ccacatccac agggtttatt ttttggaaga agtttaatca aaggcagcca taggcatgta 8460aatgagtctg aatacattta cagtattaaa tttacaatgg acatgcgatg agacttgtaa 8520atgaaagcat tgtgaactga aaccgagtct ctgtggatct caaagcaaac tcttaactta 8580aggcactttg attttgccaa caaataataa caaacattaa gagaaaaaaa tgatccacta 8640cgaaataaca aacggctaat gcacctgaat tctcagtaaa aagacctttc tctcgctaac 8700agttgccagc tgcctcgtgt ctgtttccta ccaatgtcac aaacatcgca cacagggtga 8760atggagtcaa cgggaaagat taagtttgcg gtctgtgtaa atctcaatgt acaaatattc 8820tgtcnctggt ttataaacat tttgataaaa ccgaaaaaaa aaaaaaaaaa aaaaaaaaaa 8880aaa 888322597PRTRattus speciesmisc_feature(1)..(2597)'x' can be any amino acid 2Met Gln Val Arg Gly Arg Glu Val Ser Gly Leu Leu Ile Ser Leu Thr1 5 10 15Ala Val Cys Leu Val Val Thr Pro Gly Ser Arg Ala Cys Pro Arg Arg 20 25 30Cys Ala Cys Tyr Val Pro Thr Glu Val His Cys Thr Phe Arg Tyr Leu 35 40 45Thr Ser Ile Pro Asp Gly Ile Pro Ala Asn Val Glu Arg Ile Asn Leu 50 55 60Gly Tyr Asn Ser Leu Thr Arg Leu Thr Glu Asn Asp Phe Asp Gly Leu65 70 75 80Ser Lys Leu Glu Leu Leu Met Leu His Ser Asn Gly Ile His Arg Val 85 90 95Ser Asp Lys Thr Phe Ser Gly Leu Gln Ser Leu Gln Val Leu Lys Met 100 105 110Ser Tyr Asn Lys Val Gln Ile Ile Arg Lys Asp Thr Phe Tyr Gly Leu 115 120 125Gly Ser Leu Val Arg Leu His Leu Asp His Asn Asn Ile Glu Phe Ile 130 135 140Asn Pro Glu Ala Phe Tyr Gly Leu Thr Ser Leu Arg Leu Val His Leu145 150 155 160Glu Gly Asn Arg Leu Thr Lys Leu His Pro Asp Thr Phe Val Ser Leu 165 170 175Ser Tyr Leu Gln Ile Phe Lys Thr Ser Phe Ile Lys Tyr Leu Phe Leu 180 185 190Ser Asp Asn Phe Leu Thr Ser Leu Pro Lys Glu Met Val Ser Tyr Met 195 200 205Pro Asn Leu Glu Ser Leu Tyr Leu His Gly Asn Pro Trp Thr Cys Asp 210 215 220Cys His Leu Lys Trp Leu Ser Glu Trp Met Gln Gly Asn Pro Asp Ile225 230 235 240Ile Lys Cys Lys Lys Asp Arg Ser Ser Ser Ser Pro Gln Gln Cys Pro 245 250 255Leu Cys Met Asn Pro Arg Ile Ser Lys Gly Arg Pro Phe Ala Met Val 260 265 270Pro Ser Gly Ala Phe Leu Cys Thr Lys Pro Thr Ile Asp Pro Ser Leu 275 280 285Lys Ser Lys Ser Leu Val Thr Gln Glu Asp Asn Gly Ser Ala Ser Thr 290 295 300Ser Pro Gln Asp Phe Ile Glu Pro Phe Gly Ser Leu Ser Leu Asn Met305 310 315 320Thr Xaa Xaa Ser Gly Asn Lys Ala Asp Met Val Cys Ser Ile Gln Lys 325 330 335Pro Ser Arg Thr Ser Pro Thr Ala Phe Thr Glu Glu Asn Asp Tyr Ile 340 345 350Met Leu Asn Ala Ser Phe Ser Thr Asn Leu Val Cys Ser Val Asp Tyr 355 360 365Asn His Ile Gln Pro Val Trp Gln Leu Leu Ala Leu Tyr Ser Asp Ser 370 375 380Pro Leu Ile Leu Glu Arg Lys Pro Gln Leu Thr Glu Thr Pro Ser Leu385 390 395 400Ser Ser Arg Tyr Lys Gln Val Ala Leu Arg Pro Glu Asp Ile Phe Thr 405 410 415Ser Ile Glu Ala Asp Val Arg Ala Asp Pro Phe Trp Phe Gln Gln Glu 420 425 430Lys Ile Val Leu Gln Leu Asn Arg Thr Ala Thr Thr Leu Ser Thr Leu 435 440 445Gln Ile Gln Phe Ser Thr Asp Ala Gln Ile Ala Leu Pro Arg Ala Glu 450 455 460Met Arg Ala Glu Arg Leu Lys Trp Thr Met Ile Leu Met Met Asn Asn465 470 475 480Pro Lys Leu Glu Arg Thr Val Leu Val Gly Gly Thr Ile Ala Leu Ser 485 490 495Cys Pro Gly Lys Gly Asp Pro Ser Pro His Leu Glu Trp Leu Leu Ala 500 505 510Asp Gly Ser Lys Val Arg Ala Pro Tyr Val Ser Glu Asp Gly Arg Ile 515 520 525Leu Ile Asp Lys Asn Gly Lys Leu Glu Leu Gln Met Ala Asp Ser Phe 530 535 540Asp Ala Gly Leu Tyr His Cys Ile Ser Thr Asn Asp Ala Asp Ala Asp545 550 555 560Val Leu Thr Tyr Arg Ile Thr Val Val Glu Pro Tyr Gly Glu Ser Thr 565 570 575His Asp Ser Gly Val Gln His Thr Val Val Thr Gly Glu Thr Leu Asp 580 585 590Leu Pro Cys Leu Ser Thr Gly Val Pro Asp Ala Ser Ile Ser Trp Ile 595 600 605Leu Pro Gly Asn Thr Val Phe Ser Gln Pro Ser Arg Asp Arg Gln Ile 610 615 620Leu Asn Asn Gly Thr Leu Arg Ile Leu Gln Val Thr Pro Lys Asp Gln625 630 635 640Gly His Tyr Gln Cys Val Ala Ala Asn Pro Ser Gly Ala Asp Phe Ser 645 650 655Ser Phe Lys Val Ser Val Gln Lys Lys Gly Gln Arg Met Val Glu His 660 665 670Asp Arg Glu Ala Gly Gly Ser Gly Leu Gly Glu Pro Asn Ser Ser Val 675 680 685Ser Leu Lys Gln Pro Ala Ser Leu Lys Leu Ser Ala Ser Ala Leu Thr 690 695 700Gly Ser Glu Ala Gly Lys Gln Val Ser Gly Val His Arg Lys Asn Lys705 710 715 720His Arg Asp Leu Ile His Arg Arg Arg Gly Asp Ser Thr Leu Arg Arg 725 730 735Phe Arg Glu His Arg Arg Gln Leu Pro Leu Ser Ala Arg Arg Ile Asp 740 745 750Pro Gln Arg Trp Ala Ala Leu Leu Glu Lys Ala Lys Lys Asn Ser Val 755 760 765Pro Lys Lys Gln Glu Asn Thr Thr Val Lys Pro Val Pro Leu Ala Val 770 775 780Pro Leu Val Glu Leu Thr Asp Glu Glu Lys Asp Ala Ser Gly Met Ile785 790 795 800Pro Pro Asp Glu Glu Phe Met Val Leu Lys Thr Lys Ala Ser Gly Val 805 810 815Pro Gly Arg Ser Pro Thr Ala Asp Ser Gly Pro Val Asn His Gly Phe 820 825 830Met Thr Ser Ile Ala Ser Gly Thr Glu Val Ser Thr Val Asn Pro Gln 835 840 845Thr Leu Gln Ser Glu His Leu Pro Asp Phe Lys Leu Phe Ser Val Thr 850 855 860Asn Gly Thr Ala Val Thr Lys Ser Met Asn Pro Ser Ile Ala Ser Lys865 870 875 880Ile Glu Asp Thr Thr Asn Gln Asn Pro Ile Ile Ile Phe Pro Ser Val 885 890 895Ala Glu Ile Arg Asp Ser Ala Gln Ala Gly Arg Ala Ser Ser Gln Ser 900 905 910Ala His Pro Val Thr Gly Gly Asn Met Ala Thr Tyr Gly His Thr Asn 915 920 925Thr Tyr Ser Ser Phe Thr Ser Lys Ala Ser Thr Val Leu Gln Pro Ile 930 935 940Asn Pro Thr Glu Ser Tyr Gly Pro Gln Ile Pro Ile Thr Gly Val Ser945 950 955 960Arg Pro Ser Ser Ser Asp Ile Ser Ser His Thr Thr Ala Asp Pro Ser 965 970 975Phe Ser Ser His

Pro Ser Gly Ser His Thr Thr Ala Ser Ser Leu Phe 980 985 990His Ile Pro Arg Asn Asn Asn Thr Gly Asn Phe Pro Leu Ser Arg His 995 1000 1005Leu Gly Arg Glu Arg Thr Ile Trp Ser Arg Gly Arg Val Lys Asn 1010 1015 1020Pro His Arg Thr Pro Val Leu Arg Arg His Arg His Arg Thr Val 1025 1030 1035Arg Pro Ala Ile Lys Gly Pro Ala Asn Lys Asn Val Ser Gln Val 1040 1045 1050Pro Ala Thr Glu Tyr Pro Gly Met Cys His Thr Cys Pro Ser Ala 1055 1060 1065Glu Gly Leu Thr Val Ala Thr Ala Ala Leu Ser Val Pro Ser Ser 1070 1075 1080Ser His Ser Ala Leu Pro Lys Thr Asn Asn Val Gly Val Ile Ala 1085 1090 1095Glu Glu Ser Thr Thr Val Val Lys Lys Pro Leu Leu Leu Phe Lys 1100 1105 1110Asp Lys Gln Asn Val Asp Ile Glu Ile Ile Thr Thr Thr Thr Lys 1115 1120 1125Tyr Ser Gly Gly Glu Ser Asn His Val Ile Pro Thr Glu Ala Ser 1130 1135 1140Met Thr Ser Ala Pro Thr Ser Val Ser Leu Gly Lys Ser Pro Val 1145 1150 1155Asp Asn Ser Gly His Leu Ser Met Pro Gly Thr Ile Gln Thr Gly 1160 1165 1170Lys Asp Ser Val Glu Thr Thr Pro Leu Pro Ser Pro Leu Ser Thr 1175 1180 1185Pro Ser Ile Pro Thr Ser Thr Lys Phe Ser Lys Arg Lys Thr Pro 1190 1195 1200Leu His Gln Ile Phe Val Asn Asn Gln Lys Lys Glu Gly Met Leu 1205 1210 1215Lys Asn Pro Tyr Gln Phe Gly Leu Gln Lys Asn Pro Ala Ala Lys 1220 1225 1230Leu Pro Lys Ile Ala Pro Leu Leu Pro Thr Gly Gln Ser Ser Pro 1235 1240 1245Ser Asp Ser Thr Thr Leu Leu Thr Ser Pro Pro Pro Ala Leu Ser 1250 1255 1260Thr Thr Met Ala Ala Thr Gln Asn Lys Gly Thr Glu Val Val Ser 1265 1270 1275Gly Ala Arg Ser Leu Ser Ala Gly Lys Lys Gln Pro Phe Thr Asn 1280 1285 1290Ser Ser Pro Val Leu Pro Ser Thr Ile Ser Lys Arg Ser Asn Thr 1295 1300 1305Leu Asn Phe Leu Ser Thr Glu Thr Pro Thr Val Thr Ser Pro Thr 1310 1315 1320Ala Thr Ala Ser Val Ile Met Ser Glu Thr Gln Arg Thr Arg Ser 1325 1330 1335Lys Glu Ala Lys Asp Gln Ile Lys Gly Pro Arg Lys Asn Arg Asn 1340 1345 1350Asn Ala Asn Thr Thr Pro Arg Gln Val Ser Gly Tyr Ser Ala Tyr 1355 1360 1365Ser Ala Leu Thr Thr Ala Asp Thr Pro Leu Ala Phe Ser His Ser 1370 1375 1380Pro Arg Gln Asp Asp Gly Gly Asn Val Ser Ala Val Ala Tyr His 1385 1390 1395Ser Thr Thr Ser Leu Leu Ala Ile Thr Glu Leu Phe Glu Lys Tyr 1400 1405 1410Thr Gln Thr Leu Gly Asn Thr Thr Ala Leu Glu Thr Thr Leu Leu 1415 1420 1425Ser Lys Ser Gln Glu Ser Thr Thr Val Lys Arg Ala Ser Asp Thr 1430 1435 1440Pro Pro Pro Leu Leu Ser Ser Gly Ala Pro Pro Val Pro Thr Pro 1445 1450 1455Ser Pro Pro Pro Phe Thr Lys Gly Val Val Thr Asp Ser Lys Val 1460 1465 1470Thr Ser Ala Phe Gln Met Thr Ser Asn Arg Val Val Thr Ile Tyr 1475 1480 1485Glu Ser Ser Arg His Asn Thr Asp Leu Gln Gln Pro Ser Ala Glu 1490 1495 1500Ala Ser Pro Asn Pro Glu Ile Ile Thr Gly Thr Thr Asp Ser Pro 1505 1510 1515Ser Asn Leu Phe Pro Ser Thr Ser Val Pro Ala Leu Arg Val Asp 1520 1525 1530Lys Pro Gln Asn Ser Lys Trp Lys Pro Ser Pro Trp Pro Glu His 1535 1540 1545Lys Tyr Gln Leu Lys Ser Tyr Ser Glu Thr Ile Glu Lys Gly Lys 1550 1555 1560Arg Pro Ala Val Ser Met Ser Pro His Leu Ser Leu Pro Glu Ala 1565 1570 1575Ser Thr His Ala Ser His Trp Asn Thr Gln Lys His Ala Glu Lys 1580 1585 1590Ser Val Phe Asp Lys Lys Pro Gly Gln Asn Pro Thr Ser Lys His 1595 1600 1605Leu Pro Tyr Val Ser Leu Pro Lys Thr Leu Leu Lys Lys Pro Arg 1610 1615 1620Ile Ile Gly Gly Lys Ala Ala Ser Phe Thr Val Pro Ala Asn Ser 1625 1630 1635Asp Val Phe Leu Pro Cys Glu Ala Val Gly Asp Pro Leu Pro Ile 1640 1645 1650Ile His Trp Thr Arg Val Ser Ser Gly Xaa Glu Ile Ser Gln Gly 1655 1660 1665Thr Gln Lys Ser Arg Phe His Val Leu Pro Asn Gly Thr Leu Ser 1670 1675 1680Ile Gln Arg Val Ser Ile Gln Asp Arg Gly Gln Tyr Leu Cys Ser 1685 1690 1695Ala Phe Asn Pro Leu Gly Val Asp His Phe His Val Ser Leu Ser 1700 1705 1710Val Val Phe Tyr Pro Ala Arg Ile Leu Asp Arg His Val Lys Glu 1715 1720 1725Ile Thr Val His Phe Gly Ser Thr Val Glu Leu Lys Cys Arg Val 1730 1735 1740Glu Gly Met Pro Arg Pro Thr Val Ser Trp Ile Leu Ala Asn Gln 1745 1750 1755Thr Val Val Ser Glu Thr Ala Lys Gly Ser Arg Lys Val Trp Val 1760 1765 1770Thr Pro Asp Gly Thr Leu Ile Ile Tyr Asn Leu Ser Leu Tyr Asp 1775 1780 1785Arg Gly Phe Tyr Lys Cys Val Ala Ser Asn Pro Ser Gly Gln Asp 1790 1795 1800Ser Leu Leu Val Lys Ile Gln Val Ile Thr Ala Pro Pro Val Ile 1805 1810 1815Ile Glu Gln Lys Arg Gln Ala Ile Val Gly Val Leu Gly Gly Ser 1820 1825 1830Leu Lys Leu Pro Cys Thr Ala Lys Gly Thr Pro Gln Pro Ser Val 1835 1840 1845His Trp Val Leu Tyr Asp Gly Thr Glu Leu Lys Pro Leu Gln Leu 1850 1855 1860Thr His Ser Arg Phe Phe Leu Tyr Pro Asn Gly Thr Leu Tyr Ile 1865 1870 1875Arg Ser Ile Ala Pro Ser Val Arg Gly Thr Tyr Glu Cys Ile Ala 1880 1885 1890Thr Ser Ser Ser Gly Ser Glu Arg Arg Val Val Ile Leu Thr Val 1895 1900 1905Glu Glu Gly Glu Thr Ile Pro Arg Ile Glu Thr Ala Ser Gln Lys 1910 1915 1920Trp Thr Glu Val Asn Leu Gly Glu Lys Leu Leu Leu Asn Cys Ser 1925 1930 1935Ala Thr Gly Asp Pro Lys Pro Arg Ile Ile Trp Arg Leu Pro Ser 1940 1945 1950Lys Ala Val Ile Asp Gln Trp His Arg Met Gly Ser Arg Ile His 1955 1960 1965Val Tyr Pro Asn Gly Ser Leu Val Val Gly Ser Val Thr Glu Lys 1970 1975 1980Asp Ala Gly Asp Tyr Leu Cys Val Ala Arg Asn Lys Met Gly Asp 1985 1990 1995Asp Leu Val Leu Met His Val Arg Leu Arg Leu Thr Pro Ala Lys 2000 2005 2010Ile Glu Gln Lys Gln Tyr Phe Lys Lys Gln Val Leu His Gly Lys 2015 2020 2025Asp Phe Gln Val Asp Cys Lys Ala Ser Gly Ser Pro Val Pro Glu 2030 2035 2040Val Ser Trp Ser Leu Pro Asp Gly Thr Val Leu Asn Asn Val Ala 2045 2050 2055Gln Ala Asp Asp Ser Gly Tyr Arg Thr Lys Arg Tyr Thr Leu Phe 2060 2065 2070His Asn Gly Thr Leu Tyr Phe Asn Asn Val Gly Met Ala Glu Glu 2075 2080 2085Gly Asp Tyr Ile Cys Ser Ala Gln Asn Thr Leu Gly Lys Asp Glu 2090 2095 2100Met Lys Val His Leu Thr Val Leu Thr Ala Ile Pro Arg Ile Arg 2105 2110 2115Gln Ser Tyr Lys Thr Thr Met Arg Leu Arg Ala Gly Glu Thr Ala 2120 2125 2130Val Leu Asp Cys Glu Val Thr Gly Glu Pro Lys Pro Asn Val Phe 2135 2140 2145Trp Leu Leu Pro Ser Asn Asn Val Ile Ser Phe Ser Asn Asp Arg 2150 2155 2160Phe Thr Phe His Ala Asn Arg Thr Leu Ser Ile His Lys Val Lys 2165 2170 2175Pro Leu Asp Ser Gly Asp Tyr Val Cys Val Ala Gln Asn Pro Ser 2180 2185 2190Gly Asp Asp Thr Lys Thr Tyr Lys Leu Asp Ile Val Ser Lys Pro 2195 2200 2205Pro Leu Ile Asn Gly Leu Tyr Ala Asn Lys Thr Val Ile Lys Ala 2210 2215 2220Thr Ala Ile Arg His Ser Lys Lys Tyr Phe Asp Cys Arg Ala Asp 2225 2230 2235Gly Ile Pro Ser Ser Gln Val Thr Trp Ile Met Pro Gly Asn Ile 2240 2245 2250Phe Leu Pro Ala Pro Tyr Phe Gly Ser Arg Val Thr Val His Pro 2255 2260 2265Asn Gly Thr Leu Glu Met Arg Asn Ile Arg Leu Ser Asp Ser Ala 2270 2275 2280Asp Phe Thr Cys Val Val Arg Ser Glu Gly Gly Glu Ser Val Leu 2285 2290 2295Val Val Gln Leu Glu Val Leu Glu Met Leu Arg Arg Pro Thr Phe 2300 2305 2310Arg Asn Pro Phe Asn Glu Lys Val Ile Ala Gln Ala Gly Lys Pro 2315 2320 2325Val Ala Leu Asn Cys Ser Val Asp Gly Asn Pro Pro Pro Glu Ile 2330 2335 2340Thr Trp Ile Leu Pro Asp Gly Thr Gln Phe Ala Asn Arg Pro His 2345 2350 2355Asn Ser Pro Tyr Leu Met Ala Gly Asn Gly Ser Leu Ile Leu Tyr 2360 2365 2370Lys Ala Thr Arg Asn Lys Ser Gly Lys Tyr Arg Cys Ala Ala Arg 2375 2380 2385Asn Lys Val Gly Tyr Ile Glu Lys Leu Ile Leu Leu Glu Ile Gly 2390 2395 2400Gln Lys Pro Val Ile Leu Thr Tyr Glu Pro Gly Met Val Lys Ser 2405 2410 2415Val Ser Gly Glu Pro Leu Ser Leu His Cys Val Ser Asp Gly Ile 2420 2425 2430Pro Lys Pro Asn Val Lys Trp Thr Thr Pro Gly Gly His Val Ile 2435 2440 2445Asp Arg Pro Gln Val Asp Gly Lys Tyr Ile Leu His Glu Asn Gly 2450 2455 2460Thr Leu Val Ile Lys Ala Thr Thr Ala His Asp Gln Gly Asn Tyr 2465 2470 2475Ile Cys Arg Ala Gln Asn Ser Val Gly Gln Ala Val Ile Ser Val 2480 2485 2490Ser Val Met Val Val Ala Tyr Pro Pro Arg Ile Ile Asn Tyr Leu 2495 2500 2505Pro Arg Asn Met Leu Arg Arg Thr Gly Glu Ala Met Gln Leu His 2510 2515 2520Cys Val Ala Leu Gly Ile Pro Lys Pro Lys Val Thr Trp Glu Thr 2525 2530 2535Pro Arg His Ser Leu Leu Ser Lys Ala Thr Ala Arg Lys Pro His 2540 2545 2550Arg Ser Glu Met Leu His Pro Gln Gly Thr Leu Val Ile Gln Asn 2555 2560 2565Leu Gln Thr Ser Asp Ser Gly Val Tyr Lys Cys Arg Ala Gln Asn 2570 2575 2580Leu Leu Gly Thr Asp Tyr Ala Thr Thr Tyr Ile Gln Val Leu 2585 2590 2595311967DNAmouse spmisc_feature(1)..(11967)'n' can be any nucleotide 'a', 'c', 'g' or 't'. 3tttggaacca acccagatgc ccctcaacag agaaatgggc cagaaaatgt ggtccattta 60tccaatggaa tactactcaa cttattaaaa acaacgactt tcataaaatt tttaggcaaa 120tgnatggtct gnaggatctt gagtgaggta acccaatcac aaaagaacac tcatggtatg 180cactcactga taagtggcta tttgtctatg gagtgattta aaagggaaga agacacatag 240ctttttgtgt gtataatatt aagatggaaa tttgccagtg ctgtttggct tatgagtgaa 300tcttgtttca gtggattacc ggaagaaaat aataagtgaa ctgtaggaag aagtagttaa 360tcaaggtgac aaagtatcct gacacattgg gaaaagacca cagtccagga aactgagtct 420taaggattca tattaactcc agttccccat gtgcagctct gagactttgg cagatcagac 480acttaacttc accagcttcc tacacagagc agttactatc cttgcacttc acacatggag 540tgtgaccatt aagctgcact gaaacatgag tctgacttgt taataatctt aaaatacaaa 600ttgtgttgta aagtatgtga ccaaagagca tggtcatgct attaaccttt gatgttctat 660ggactcttaa ttttatggta gaaatgtcaa caagcttgtg gaggctggaa gatacaaggc 720ttaagaggat ggcctttcag ttttgaaagt aattcagtat gtgttctggc atcccttttc 780ctaaagcaat ttaacccccc aagtaggcat aattttaatg cttacttcat cagaatatgt 840ctaattgact cttctaaaaa gactttggta tgcataggat ctaaatgtaa atgtgattta 900ctgacataat aaataggaga aactgagcta gaataggtat aaaatatgtg ctggctttct 960aataggtctt ataggttata taagaggtgg gaaaggaata tttgaaacat ctagaagtaa 1020aatgatcctg agtagcgatc ctgggaaaat acgtactcta acacactgca atcatctctc 1080tgtggtttgc tggagctgag gtctggaagg ctcgaccttg gttagaaata acctaccgaa 1140tacagagcta tgacgttagt ctggaaggag ctttggaaga atgacaagct gtagctgccc 1200agaacatact agatgccata tttccaaggc aagtgtccac atgcggacat cttaagaata 1260tggttgtctc tgcagtgcta aggaccttgt tcgtgccaca caggtctcca gggttagtgc 1320taactctgac tgcttgactc tttaattcta ccttgatcat taatgactag aaatcacttg 1380gtgattagca actggatatg gaatattact aatttgtacc caagccaggc cacctcagct 1440ttggcagctc cattcattct gtggagccca gtcacgtggg tttgaatcaa ctgtactgtt 1500tctacttaca agacgcatta cctgagatga gtcatttttc ttcacaagtc tttttagaag 1560agtcaattag acatattctg atgaagtaag catataaagt gagagcagca tgaatgtgtt 1620ccatgtatgc tcatggatgc tattataatg tggaaataaa ctgactttaa aaaaaaaagc 1680ttatgatact tgtcacagag taaatcttcc ataaatatca tctgcattta taaattattt 1740tcataatcca tcaattaaaa acctttagaa attttgttaa cacaaagatc cctaggcccc 1800tgccctagga tggtctgtat ggtgggcctg agagatggag cttaagaact tacttgctcc 1860aggagcacat cttcagaaca tctgcctcaa aacatttatc ccaaatgctc atcaaaggct 1920cactcacatg tgcttcaacc acagggatta aacagtcatt ttagtcacat ttctcaaacg 1980gtggaagcct gctagaggaa caggatgtat caggataaca tccaacctta caaaaggatg 2040tcataaccct caccacaaca aacaacaacg acaacaaacc cataaaaatt atcacggcaa 2100atgaactaag ccatatgcag aaaaagtatt atatgttctc attgtggggt gtttttcctt 2160aatagtcaaa tatgcagaat atagacaaag atggtttatg caagtgggga tggcgaagga 2220tacttgtaga ttagaggaca caaagcaaca actacagagt gaagtaatcc agagacttaa 2280tgtataatat gaggactgta tttaataatt ctatttaaga tacacagcaa acgagtgtat 2340cttactaaca cacacactta catagagaga ataaagtgat agatacgttt gttttatctt 2400catgtagctg ataatttcat attgtacacc tcaaacatag ataaccaaca aagaggaaga 2460ggataggtgc ctctcccagg gcggaagagt acattcgaaa gtcagacacc attgtgtaga 2520tgtaccacat ggaggagcta gagaaagtag ccaaggagct aaagggatct gcaaccctat 2580aggtggaaca acattatgag ctaaccagta ccccggagct cttgactcta gctgcatata 2640tatcaaaaga tggcctaatc ggccatcact ggaaagagag gcccattgga cttgcaaact 2700ttatatgccc cagtacaggg gaataccagg gccaaaaagg gggagtgggt gggcagggga 2760gtgggggtgg gtggatatgg gggacttttg gtatagcatt ggaaatgtaa atgagttaaa 2820tacctaataa aaaatggaaa aaaaaaaaaa aaaaaaaaaa aaggaaggtc agacacctca 2880cttcactgct atctcaactt gcaaacagaa ggggagtcac aaacccagga caaaccacag 2940tgattgaagc gtctttgaat gttattgctg ttgttgttac caccatcatt agcatatatt 3000cattgtgaaa acttacgggg tctatgacat gtttttttat tcaagtatat cacatgctgt 3060cagcatattt ggcaccacta ccagccccag ccccctttgc cccgccccca acacacacac 3120acacacacac acacacacac acacacacac acacacacac acacacacct ttaccttctc 3180ctgggcatca tctgctcact cacccaccca agcttaatcc ttttccttcc ctgcaatagt 3240acctctccta tttttatgtc taggttcccc ctccccctgt taggagatgg gagaggtcac 3300gaaaggaaag aatttgtagc ccctgagcca gcccgggcca cagagcctgc caccagacag 3360gaaaagccca gggcttacca gcacaggagg agcaaactcg caggcgagcc tgggttggcg 3420ctggtggtcc cgggtcgatg gcccgcccat tcccagaagc cgaggctata gctgcgtcac 3480ctgccccgcc ctcctcccga gtgaagaccc ctagaggctg agcagacccc aaaggcggtg 3540caattccatt ggcccaaggc agaggtgagc ggctgctaat cccctcggga agtgaaggga 3600cccagagagt ctggtagatg tgggagctgg ggttcagggc gagacagagg gtgggatggg 3660cagaagggtc caggaaaagg aaagtactgg aggggagttg ggacaaaagc agcgaccaag 3720ggaacatcgc ttcagtgact gaagccaggc aaaaggagcg ggaaggatta tatgtagcct 3780gggacgcttt cataaacact gatgacgtgt ttgtgcaaag caagcaattt gaggagaaac 3840gcctgggacg tcggaaagaa ggagtgatcg attagtactt gtaagtttag gtgagtttga 3900gaactaacta acctatacta ttgagggaga aggaagagca ttccagcagc agcagcagca 3960gcagcaatca gataaaggaa agctttggtt agtttggaaa tgtatgatac cattaaaata 4020acagaagcgc ctccagttct ctgaagagtc agtcccccag ctagtgaaga ctaagcctac 4080taagcctttt gctcccgttg gaagcaaaga acgttccttc aatcaggtga aggctctcct 4140cagaagattt cctgtctctg cttatgttac aagaggattc aaaagcaaga cagaagagct 4200caggtattgc caactctttt gttaaataca gtttgaggct taagtgtacg ggaactcatg 4260tggtattcat ttacggctct cttctcttat aactaactct taaggtgcat atagtctctt 4320ctgtttccca gctaccttgt accatctttg tttatctaat aatagcaagc tcatctgctt 4380tttaatcatc acgcagagag tattcaaaaa tattcagtga tgtaacagtg acagtgtagg 4440catagaagta atcattagta aatcttaatt tgggttaaac tcattcataa cagctccagg 4500ttgggaggga tcactgagcc ttcgccacgt gcgggttaaa gatattttct aacaagagaa 4560gcagaattct tccttggcca tgctccccat cactgtgtca gtaagcagag gggtgtttcc 4620aagcagagaa agagcagaca gtgttatgcc tgcaaagtca gagactcagc cctcccagct 4680ggtcagttta ctgtcctccc ggtcattagt tggctctgaa aaggcccatg tgtccttatt 4740ggcaaggact tgcagacatg ctagaaagaa atttgacctt tttttctagt gggttattac 4800agctgtaaaa gtattttgga aggttaagcc aaataaataa aacacatatt aaataataca 4860atgttacaaa aattgatcat ataaagaagt acattcataa atgcaatgtg aaaaatatat 4920ataattttta tctatttact ggtgcaaagt tttctaaatt

gcacatgtac tatttttata 4980tttataaaaa tatttttaaa atgtatataa aagtgtaaaa ggctcttggt caaacaagag 5040agttaaattt acaaacttta attgtcccga taacattatt atgatctcta atgacaggga 5100tcctgctttt cattgggaaa tgagaagcta tgaagatatg tttacaataa taagcccatt 5160tagtgataaa gtccaatggg aagctagcac acactggttt ataaagagaa cagtttcctg 5220agtctatgca agtttacact ctagggaata agagttcctc tttctccaga tttcactagc 5280atttgttgtc atcatttatc ttcttgatga tgagcattat aagtggaata agataggatc 5340tcaaaggaat gtcaatttgg atgccctgaa caatctttca ggtctttctt tcagttcact 5400agtctattca tttattggat aattggggga tggtgttaat ttttttgcag ttcttatgga 5460attccaaaaa acaaaaaaca aacaaacaaa caaaaaacct ctgaaactag aactaccaat 5520ccattactgg gtatgtaaca aagagaaatc tgcacagaat ttattgctac attgttcatt 5580attcacgaca gccaagaatg tggaaccaac ttacgtagcc gtcaaaatat gaacggataa 5640agaaaatgtg gaaatgtgta caacagagtc ccatgtggcc ataaaagagt gaaatcatga 5700catatgcagg aaatggatgc aactggaaat caattgggct aatcaaaaca agacagactc 5760aaaaaggaaa caccgtgtag cttctctgac aaacagaagc tagatttaca cttgtacgtg 5820cgcatgtgtg tttagaattt tatttagtta tacactattc taatctgtga gtgtgtataa 5880aggcatgcat gtaaagcaaa aacaagctag ctggggtggg taggagagaa agcaatgaga 5940ggagttaata agaacgaagc atagtaacat aggtgccagg atgaaatgca ttaatttgta 6000tgctaactaa accacagaca ggaggcacac gttcaaacca gggtgaaatc ccagcacaga 6060gaaggggaag tagacacaaa gtttcgccac taaccaagaa gccatttgca gttgctgcct 6120gctgggaggg gcgttccagt tttctccagt ctgacactgt gtataacaac cagttgacaa 6180tacaaagttg gcatgatgga tggtttttgt gctatttttc attttttttc ttactgtttt 6240gttgttgtgg tggttgttgt ggtggtggct gtggttttca tttgtttctt ttgagagaga 6300gaaggaacat gaaattgggt gggtaggaag ctggaaacga tctggaagaa gttggggaaa 6360gagaaaaatt gtatggagca tatttaaaca aacaaacaaa caaacaaaag gttcattttg 6420ccacaaaaag gtgtgaatta aattaaccag ttacgactct taaagaaaat attcccaatt 6480attcccagag ttgctatgta tgctgtgcct aggactttgc ttgaactggc cctataactc 6540tggtgtggtg tcttttcagg atgcagaaga gaggcaggga agtcagctgc ttgctgatct 6600ccctcactgc catctgcctg gtggtcaccc ctgggagcag ggtctgtcct cgccgatgtg 6660cctgctatgt gcccacagag gtgcactgta catttcggga cctgacctcc atcccagacg 6720ggcatcccag ccaatgtgga acgagtcaat ttagggtgtg tggaccttgc ctgatctcct 6780tctcagagag ggaccactga ttttcctggt actttgcccc ccaaacacct gtgattactt 6840ttaatagttt tcttctaaaa tgggttcata caaaccttat attgtggaga caatgaacat 6900tttatcccaa tagtctttta ctagaacttg aagcccctct tagttgtttg ggagcctcat 6960aattatgggg cagctttatt ctgaatgaat tttaaatgaa aaagatacag tttctgttaa 7020caatcattat gataccaagg aagaggaatt gtcattgaat attttaaaaa agcatttctt 7080ttgcaattta taaataccca ttacaaaatg gcttacttaa aatacttgcc ttactaaatc 7140tgacaaatta tggtgatatt ttgaaggttt atgaaaattt gtttatgtgt ataaatgcac 7200aagaaatggg atatgccatc acctatgtgc cattagtgag catgtacagt atgccaaaca 7260ctattgttca cgtttggagg aagtaatggg ggtgggggag caacaagggt tataaccgta 7320tacccagtgc cttggaagcg attgcaaaca gtaaagactg acattgtgtt ctccctatga 7380gggaggggcc ttgggctgag cactttgcaa tgagcatttg ctcattgtgc tggcaggttt 7440tatgataact tgacccaagc tagagtcact ggagaggaag gaacttcaac tgagaacatg 7500cctgaagaag atcagattat aggcaggcct gtggggcatt ttcttaatta gtgattcatg 7560gggcagggcc cagtccattg ttcgtggtac catttctcag gcactattaa aaaaaaaaaa 7620acaggctgag caagtgtcaa ggagcaagtc agtgagcagc agccctaatg atctctgcat 7680cagctcctgc ctccaggttc ctaccctatt tgagttcctg tcctagctcc ctacagtgat 7740gaacaatgat gtggaagtat aagccaaata aatcctttct tccccaactt gctgttggtc 7800atgatgtttc atcacagtga taatagtcct catgaagatg ctggtgttta taacaccttt 7860ggactaaatt ctgttatcta tagctgagga aaatggagca tagaaagtct ccagactaca 7920ccagagtgta atctgggcct gagcttagaa tcacacccac gtgcactcca ctgccggggc 7980ttcttaaccg gaacacagtt gtaaaaggga attttctgtt tgtttccatt ttgacatgtg 8040gactttaatt gacgattcat ctgaagctga aaatgatttt ttttccaggt ataacagcct 8100cactagattg acagaaaatg acttttctgg cctgagcaga ctggagttac tcatgctgca 8160cagcaatggc attcacagag tcagtgacaa gaccttctcg ggcttgcagt ccttgcaggt 8220gagataggta gagggtgatg gaggctgaga agagaggtgc aactgtgggt tatacccaaa 8280agctgctgat tcccgtggga gacattctat aagcattcta taaactagag gcagatatca 8340aggaaggatt tcaattgtaa tgcaatttta tgagaaaatt tgaatattaa gaaaatgctg 8400gggaaaatgc ttacacaatt gcgaggacct aatttaggat ctccaatagc cacataaaaa 8460gcacagcatg gcggcagaca cctgcaattc ctgtccctgg aagcacctgt tcagaatccc 8520agagactcat tggccaaaca ctctattcaa tcaatgaagt ccatattcag tgacaaaact 8580tgactcagaa actaatgtgg aaagcatcag gaagacagcc aacatctggt ctctactcat 8640gcatgaataa gggatcccag agagaaggga agaaaaagga aggaaggaag gaaggaagga 8700aggaaggaag gaaggaagga aggaaggaag agagggagga aaggagggag ggaaggaagg 8760aaagggaaag gaaaaaagag atggggaggg agggaaggaa aggaaagggg gagaaagaag 8820agaagaaagg aaaataaata aattttcagg gattattaca cctttaaatt ttatccataa 8880aaggtcattt ccacctgttt gtctggaagt agagtgggat cccttatata agggcagtct 8940ttaacatagt agcattttat aaaccattac aaattttgag ttttctctac tttttatcct 9000ctaccatctt caaactgaaa ctacaattat tcccacaaat gaagaaaatg ctgtaagagt 9060tttcacacac cgaagtggga aacttaagga ttagacaagt ctaacaatga gaatggggag 9120aacaaaaaga gactgcacag ggagcccttt ctctgcttat aatcttgaca cttgagaagc 9180taattgacgc tgcatgacta ctcaactctt taagcaaaca atgctgttgt tcatgaaaag 9240cacaataaag tacatatgtc ccataatatt catcaaaatt tgcatgcagc acataatagc 9300aatcaaagca ataacaccca ctgttcacag agactttaaa catgaaactg gaactatgtc 9360tagtgttttg acttagggta catagtatgc tgtgtctgta tgtaccaatg ttgatttagg 9420tcatcagaca gcatttggaa catgtatctt caggaggaat cattcatgta tcctgcatga 9480aattctccac ctatgtttat tctcttagcc aggtttttct ctgatggaga aacattgggt 9540ttgaggtttt actcccaggt aacatttagg gaaaagctgt ctatgttctc agtttggctt 9600ttatttatga gggatgttgg tattccagaa aattctcttt tgaagagatt acaatttagg 9660tcaaaacaga aaaatatgta aaaagttatt gtttttatta gtatttcatg ttcttttctt 9720ttttaaaaat ggtatgctta gaactaatta agattagatt agattagatt agaaaataat 9780cagagaggga tttgatgaat gctaaagcat catgaaaaat tcaaaatttt ttgcttctaa 9840ttcagaatca attaaattca tattactata aaagacagca cgccagatgt gtgccagctg 9900aggagtggat aaactgtgta acgtgagtgc tatgtagaaa cagaaaggag tgaagggttg 9960atgtgcgctg caacatcttg aaaacattcg gctacatgat ggaagccagg cacaaaaagc 10020cacatattgc atggttatgt ttatatgaaa tgtttaaaat acatggattc ttagcaaaca 10080gagtaagatg ttacttaggg tcaggaaaag attaaaaaaa aaaaaactat tgatgtggaa 10140tgatcttaat ttggggaaaa gacaatttcc taagacgaaa tagttgaggt agatatagtt 10200atatccctgt ggatattgta ataaaccagc atgctgtgct ctgagaaggg cctaatgaag 10260gggcaggagg aagtgaaatg agatggtaga aaggaaagtc atataccatg gcttctctcg 10320tgggtggaat ctagatatgt taatatattg acataaagga aggaattgtt tagggaagga 10380tcaaaaccaa caggagtgag ggagacaata ggaaccaatg agaggcaaag ttcatggtca 10440atgtgtgtgg agacaccata ataaaactcc ttttttgttt gctaactaaa accactaaaa 10500tctaaaaaca aaacattttt gcacaagaat tatttattat tcaataaaga tgtttaaatg 10560ggggaagttg aagttcattg atagtctcat aaatcttaaa tgtatttaaa ctgcttttta 10620cgttttttat tattaattac tcttgctgtc attattatca tcatcattat cgtcatcatc 10680atcactaatg cttttcacca tacacaaatg taggcagaag agtgtaatcc acttagtgag 10740gcaatcttgg agagggaaag gaagcggatg cggggcagag gcacacagga ggacagtgag 10800agggaaatga acaagaaaaa atgtggacac atgcacaaaa attccatagt ccactacatt 10860actttgtatt ctaatattaa gaaaataata aacccatttc tgtgcactta tcacccaggc 10920tcaacagtta tcttggccac agatcctgtc tcactgcatc ctgtccacct gagtccactt 10980agcgttctga atccaatcca gggcatgatg cttactccta cacagaacta aagattaaag 11040agagtttaaa agtaaccatg acatctctct gttcctttag cgataagttc ttaatattta 11100tggctgcttg tgtatgttct aatttctcta atattgtcac atttagttgg caactacttt 11160gtttgaattg agttggagtt aaggtcccat aggattaatc tcaacatatt tctatattta 11220taaacttttc tctctttgtg aaagttcctt tgagaaaaca aatatgccca tatctttctt 11280tacaggtctt aaaaatgagc tataacaaag tccaaataat tgagaaggat actttgtatg 11340gactcaggag cttgacccgg ttgcacctgg atcacaacaa cattgagttt atcaaccccg 11400aggcgtttta cggactcacc ttgctccgct tggtacatct agaaggaaac cggctgacaa 11460agctccatcc agacacattt gtctctttga gctatctcca gatatttaaa acctccttca 11520ttaagnacct gtacttgtat gataacttca ttgacctccc tcccaaaaga aatggtctcc 11580tctatgccaa acctagaaag cctttacttg catggaaacc catggacctg tgactgccat 11640ttaaagtggt tgtccgagtg gatgcaggga aacccaggta actatcttgt ttgtttgttt 11700ctttttttat arkacgtatt ttcctcaatt tcatttagaa tgatatccca aaagtccccc 11760ataacctccc ccccacttcc ctacctaccc attcccattt tttggccctg gcattcccct 11820gtactggggc atataaagtt tgcgtgtcca atggacctct ctttccagtg atggccaact 11880aggccatctt ttgatacata tgcagctaga gtcaagagct ctggggtact ggttagttca 11940taatgttgtt gcacctacag ggttgaa 1196742404DNAhomo sapiens 4tgggcagctg gatccacgtc taccctaatg gatccctgtt tattggatca gtaacagaaa 60aagacagtgg tgtctacttg tgtgtggcaa gaaacaaaat gggggatgat ctgatactga 120tgcatgttag cctaagactg aaacctgcca aaattgacca caagcagtat tttagaaagc 180aagtgctcca tgggaaagat ttccaagtag attgcaaagc ttccggctcc ccagtgccag 240agatatcttg gagtttgcct gatggaacca tgatcaacaa tgcaatgcaa gccgatgaca 300gtggccacag gactaggaga tatacccttt tcaacaatgg aactttatac ttcaacaaag 360ttggggtagc ggaggaagga gattatactt gctatgccca gaacacccta gggaaagatg 420aaatgaaggt ccacttaaca gttataacag ctgctccccg gataaggcag agtaacaaaa 480ccaacaagag aatcaaagct ggagacacag ctgtccttga ctgtgaggtc actggggatc 540ccaaaccaaa aatattttgg ttgctgcctt ccaatgacat gatttccttc tccattgata 600ggtacacatt tcatgccaat gggtctttga ccatcaacaa agtgaaactg ctcgattctg 660gagagtacgt atgtgtagcc cgaaatccca gtggggatga caccaaaatg tacaaactgg 720atgtggtctc taaacctcca ttaatcaatg gtctgtatac aaacagaact gttattaaag 780ccacagctgt gagacattcc aaaaaacact ttgactgcag agctgaaggg acaccatctc 840ctgaagtcat gtggatcatg ccagacaata ttttcctcac agccccatac tatggaagca 900gaatcacagt ccataaaaat ggaaccttgg aaattaggaa tgtgaggctt tcagattcag 960ccgactttat ctgtgtggcc cgaaatgaag gtggagagag cgtgttggta gtacagttag 1020aagtactgga aatgctgaga agaccgacat ttagaaatcc atttaatgaa aaaatagttg 1080cccagctggg aaagtccaca gcattgaatt gctctgttga tggtaaccca ccacctgaaa 1140taatctggat tttaccaaat ggcacacgat tttccaatgg accacaaagt tatcagtatc 1200tgatagcaag caatggttct tttatcattt ctaaaacaac tcgggaggat gcaggaaaat 1260atcgctgtgc agctaggaat aaagttggct atattgagaa attagtcata ttagaaattg 1320gccagaagcc agttattctt acctatgcac cagggacagt aaaaggcatc agtggagaat 1380ctctatcact gcattgtgtg tctgatggaa tccctaagcc aaatatcaaa tggactatgc 1440caagtggtta tgtagtagac aggcctcaaa ttaatgggaa atacatattg catgacaatg 1500gcaccttagt cattaaagaa gcaacagctt atgacagagg aaactatatc tgtaaggctc 1560aaaatagtgt tggtcataca ctgattactg ttccagtaat gattgtagcc taccctcccc 1620gaattacaaa tcgtccaccc aggagtattg tcaccaggac aggggcagcc tttcagctcc 1680actgtgtggc cttgggagtt cccaagccag aaatcacatg ggagatgcct gaccactccc 1740ttctctcaac ggcaagtaaa gagaggacac atggaagtga gcagcttcac ttacaaggta 1800ccctagtcat tcagaatccc caaacctccg attctgggat atacaaatgc acagcaaaga 1860acccacttgg tagtgattat gcagcaacgt atattcaagt aatctgacat gaaataataa 1920agtcaacaac atctgggcag aatttatttt ttggaagaag tttaatcaaa ggcagccata 1980ggcatgtaaa tgaatttgaa tacatttaca gtattaaatt tacaatgaac atgcaaaata 2040aaaggacttg taaataaatg cattatgaac tgatgataag tctctgtgga tctcaaagca 2100aactcttaac ttaaggcact ttgctgattt atttaatgga tctcaaaaca aacttttaac 2160ttaaggcact tttattttgc caacaaataa caataaacaa acattgaaac ggttcactat 2220aaaataacaa atggctaatg tacctgaatt tttcagtaaa aaaatgaact tctaatacca 2280gttgcctagt gtccacctcc tatcaatgtt acaagcatgg cactcagaac agagacaatg 2340gaaaatatta aatctgcaat ctttatgatg taaatttacc atcctgatgt ataaatattt 2400tgtg 240458883DNARattus speciesmisc_feature(1)..(8916)n can be any amino acid 5cgagagacga cagaaggtta cggctgcgag aagacgacag aagggtccag aaaaaggaaa 60gtgctggagg ggagtgggga caaaagcagc gaccaagtga atgtcacttc agtgactgag 120gccaggcaaa acgcgcggga aggattttgt gtagcttggg accctttcat agacactgat 180gacacgttta cgcaaaatag aaatttgagg agaaacgcct gggccttcgg aaaggagtga 240ttgattagta cttgcaagtt taggtgactt taaggagaac taactaatgt atactattga 300gggaggagga agagcattac agagtttcca gcagcagcag gaaagctttg gttaatttgg 360aaatggatga tagcattaaa ataacagaag cgcctccagg tctctgaagc ttcagtcccc 420cagctgaaag ccagaaaaga ctaagcccac taagcctttt gatccctttg gaagcaaaga 480actttccttc cctggggtga agactctcct cagaagattt cctgtctctg cctatgttac 540aagaggaatc aaaaccaaga cagaagagct caggatgcag gtgagaggca gggaagtcag 600cggcttgttg atctccctca ctgctgtctg cctggtggtc acccctggga gcagggcctg 660tcctcgccgc tgtgcctgct atgtgcccac agaggtgcac tgtacatttc ggtacctgac 720ctccatccca gatggcatcc cggccaatgt ggaacgaata aatttaggat ataacagcct 780tactagattg acagaaaacg actttgatgg cctgagcaaa ctggagttac tcatgctgca 840cagtaatggc attcacagag tcagtgacaa gaccttctcg ggcttgcagt ccttgcaggt 900cttaaaaatg agctataaca aagtccaaat cattcggaag gatactttct acggactcgg 960gagcttggtc cggttgcacc tggatcacaa caacattgaa ttcatcaacc ctgaggcctt 1020ttatggactt acctcgctcc gcttggtaca tttagaagga aaccggctca caaagctcca 1080tccagacaca tttgtctcat taagctatct ccagatattt aaaacctctt tcattaagta 1140cctgttcttg tctgataact tcctgacctc cctcccaaaa gaaatggtct cctacatgcc 1200aaacctagaa agcctgtatt tgcatggaaa cccatggacc tgtgactgcc atttaaagtg 1260gttgtctgag tggatgcagg gaaacccaga tataataaaa tgcaagaaag acagaagctc 1320ttccagtcct cagcaatgtc ccctttgcat gaaccccagg atctctaaag gcagaccctt 1380tgctatggta ccatctggag ctttcctatg tacaaagcca accattgatc catcactgaa 1440gtcaaagagc ctggttactc aggaggacaa tggatctgcc tccacctcac ctcaagattt 1500catagaaccc tttggctcct tgtctttgaa catgacanan ntntctggaa ataaggccga 1560catggtctgt agtatccaaa agccatcaag gacatcacca actgcattca ctgaagaaaa 1620tgactacatc atgctaaatg cgtcattttc cacaaatctt gtgtgcagtg tagattataa 1680tcacatccag ccagtgtggc aacttctggc tttatacagt gactctcctc tgatactaga 1740aaggaagccc cagcttaccg agactccttc actgtcttct agatataaac aggtggctct 1800taggcctgaa gacattttta ccagcataga ggctgatgtc agagcagacc ctttttggtt 1860ccaacaagaa aaaattgtct tgcagctgaa cagaactgcc accacactta gcacattaca 1920gatccagttt tccactgatg ctcaaatcgc tttaccaagg gcggagatga gagcggagag 1980actcaaatgg accatgatcc tgatgatgaa caatcccaaa ctggaacgca ctgtcctggt 2040tggcggcact attgccctga gctgtccagg caaaggcgac ccttcacctc acttggaatg 2100gcttctagct gatgggagta aagtgagagc cccttacgtt agcgaggatg ggcgaatcct 2160aatagacaaa aatgggaagt tggaactgca gatggctgac agctttgatg caggtcttta 2220ccactgcata agcaccaatg atgcagatgc ggatgttctc acatacagga taactgtggt 2280agagccctat ggagaaagca cacatgacag tggagtccag cacacagtgg ttacgggtga 2340gacgctcgac cttccatgcc tttccacggg tgttccagat gcttctatta gctggattct 2400tccagggaac actgtgttct ctcagccatc aagagacagg caaattctta acaatgggac 2460cttaagaata ttacaggtta cgccaaaaga tcaaggtcat taccaatgtg tggctgccaa 2520cccatcaggg gccgactttt ccagttttaa agtttcagtt caaaagaaag gccaaaggat 2580ggttgagcat gacagggagg caggtggatc tggacttgga gaacccaact ccagtgtttc 2640ccttaagcag ccagcatctt tgaaactctc tgcatcagct ttgacagggt cagaggctgg 2700aaaacaagtc tccggtgtac ataggaagaa caaacataga gacttaatac atcggcggcg 2760tggggattcc acgctccggc gattcaggga gcataggagg cagctccctc tctctgctcg 2820gagaattgac ccgcaacgct gggcagcact tctagaaaaa gccaaaaaga attctgtgcc 2880aaaaaagcaa gaaaatacca cagtaaagcc agtgccactg gctgttcccc tcgtggaact 2940cactgacgag gaaaaggatg cctctggcat gattcctcca gatgaagaat tcatggttct 3000gaaaactaag gcttctggtg tcccaggaag gtcaccaact gctgactctg gaccagtaaa 3060tcatggtttt atgacgagta tagcttctgg cacagaagtc tcaactgtga atccacaaac 3120actacaatct gagcaccttc ctgatttcaa attatttagt gtaacaaacg gtacagctgt 3180gacaaagagt atgaacccat ccatagcaag caaaatagaa gatacaacca accaaaaccc 3240aatcattatc tttccatcag tagctgaaat tcgagattct gctcaggcag gaagagcatc 3300ttcccaaagt gcacaccctg taacaggggg aaacatggct acctatggcc ataccaacac 3360atatagtagc tttaccagca aagccagtac agtcttgcag ccaataaatc caacagaaag 3420ttatggacct cagataccta ttacaggagt cagcagacct agcagtagtg acatctcttc 3480tcacactact gcagacccta gcttctccag tcacccttca ggttcacaca ccactgcctc 3540gtctttattt cacattccta gaaacaacaa tacaggtaac ttccccttgt ccaggcactt 3600gggaagagag aggacaattt ggagcagagg gagagttaaa aacccacata gaaccccagt 3660tctccgacgg catagacaca ggactgtgag gccagcaatc aagggacctg ctaacaaaaa 3720tgtgagccaa gttccagcca cagagtaccc tgggatgtgc cacacatgtc cttccgcaga 3780ggggctcaca gtggctactg cagcactgtc agttccaagt tcatcccaca gtgccctccc 3840caaaactaat aatgttgggg tcatagcaga agagtctacc actgtggtca agaaaccact 3900gttactattt aaggacaaac aaaatgtaga tattgagata ataacaacca ctacaaaata 3960ttccggaggg gaaagtaacc acgtgattcc tacggaagca agcatgactt ctgctccaac 4020atctgtatcc ctggggaaat ctcctgtaga caatagtggt cacctgagca tgcctgggac 4080catccaaact gggaaagatt cagtggaaac aacaccactt cccagccccc tcagcacacc 4140ctcaatacca acaagcacaa aattctcaaa gaggaaaact cccttgcacc agatctttgt 4200aaataaccag aagaaggagg ggatgttaaa gaatccatat caattcggtt tacaaaagaa 4260cccagccgca aagcttccca aaatagctcc tcttttaccc acaggtcaga gttccccctc 4320agattctaca actctcttga caagtccgcc accagctctg tctacaacaa tggctgccac 4380tcagaacaag ggcactgaag tagtatcagg tgccagaagt ctctcagcag ggaagaagca 4440gcccttcacc aactcctctc cagtgcttcc tagcaccata agcaagagat ctaatacatt 4500aaacttcttg tcaacggaaa cccccacagt gacaagtcct actgctactg catctgtcat 4560tatgtctgaa acccaacgaa caagatccaa agaagcaaaa gaccaaataa aggggcctcg 4620gaagaacaga aacaacgcaa acaccacccc caggcaggtt tctggctata gtgcatactc 4680agctctaaca acagctgata cccccttggc tttcagtcat tccccacgac aagatgatgg 4740tggaaatgta agtgcagttg cttatcactc aacaacctct cttctggcca taactgaact 4800gtttgagaag tacacccaga ctttgggaaa tacaacagct ttggaaacaa cgttgttgag 4860caaatcacag gagagtacca cagtgaaaag agcctcagac acaccaccac cactcctcag 4920cagtggggcg cccccagtgc ccactccttc cccacctcct tttactaagg gtgtggttac 4980agacagcaaa gtcacatcag ctttccagat gacgtcaaat agagtggtca ccatatatga 5040atcttcaagg cacaatacag atctgcagca accctcagca gaggctagcc ccaatcctga 5100gatcataact ggaaccactg actctccctc taatctgttt ccatccactt ctgtgccagc 5160actaagggta gataaaccac agaattctaa atggaagccc tctccctggc cagaacacaa 5220atatcagctc aagtcatact ccgaaaccat tgagaagggc aaaaggccag cagtaagcat 5280gtccccccac ctcagccttc cagaggccag cactcatgcc tcacactgga atacacagaa 5340gcatgcagaa aagagtgttt ttgataagaa acctggtcaa aacccaactt ccaaacatct 5400gccttacgtc tctctaccta agactctatt gaaaaagcca agaataattg gaggaaaggc 5460tgcaagcttt

acagttccag ctaattcaga cgtttttctt ccttgtgagg ctgttggaga 5520cccactgccc atcatccact ggaccagagt ttcatcagga nttgaaatat cccaagggac 5580acagaaaagc cggttccacg tgcttcccaa tggcaccttg tccatccaga gggtcagtat 5640tcaggaccgt ggacagtacc tgtgctctgc atttaatcca ctgggcgtag accattttca 5700tgtctctttg tctgtggttt tttacccggc aaggattttg gacagacatg tcaaggagat 5760cacagttcac tttggaagta ctgtggaact aaagtgcaga gtggagggta tgccgaggcc 5820tacggtttcc tggatacttg caaaccaaac ggtggtctca gaaacggcca agggaagcag 5880aaaggtctgg gtaacacctg atggaacatt gatcatctat aatctgagtc tttatgatcg 5940tggtttttac aagtgtgtgg ccagcaaccc atctggccag gattcactgt tggttaagat 6000acaagtcatc acagctcccc ctgtcattat agagcaaaag aggcaagcca tcgttggggt 6060tttaggtgga agtttgaaac tgccctgcac tgcaaaagga actccccagc ctagtgttca 6120ctgggtcctt tatgatggga ctgaactaaa accattgcag ttgactcatt ccagattttt 6180cttgtatcca aatggaactc tgtatataag aagcatcgct ccttcagtga ggggcactta 6240tgagtgcatt gccaccagct cctcaggctc agagagaagg gtagtgattc ttactgtgga 6300agagggagag acaatcccca ggatagaaac tgcctctcag aaatggactg aggtgaattt 6360gggtgagaaa ttactactga actgctcagc tactggggat ccaaagccta gaataatctg 6420gaggctgcca tccaaggctg tcatcgacca gtggcacaga atgggcagcc gaatccacgt 6480ctacccaaat ggatccttgg tggttgggtc agtgacggaa aaagacgctg gtgactactt 6540atgtgtggca agaaacaaaa tgggagatga cctagtcctg atgcatgtcc gcctgagatt 6600gacacctgcc aaaattgaac agaagcagta ttttaagaag caagtgctcc atgggaaaga 6660tttccaagtt gactgcaagg cctctggctc ccctgtgcct gaggtatcct ggagtttgcc 6720tgatgggaca gtgctcaaca atgtagccca agctgatgac agtggctata ggaccaagag 6780gtacaccctt ttccacaatg gaaccttgta tttcaacaac gttgggatgg cagaggaagg 6840agattatatc tgctctgccc agaacacctt agggaaagat gagatgaaag tccacctaac 6900agttctaaca gccatcccac ggataaggca aagctacaag accaccatga ggctcagggc 6960tggagaaaca gctgtccttg actgcgaggt cactggggaa ccgaagccca atgtattttg 7020gttgctgcct tccaacaatg tcatttcatt ctccaatgac aggttcacat ttcatgccaa 7080tagaactttg tccatccata aagtgaaacc acttgactct ggggactatg tgtgcgtagc 7140tcagaatcct agtggggatg acactaagac atacaaactg gacattgtct ctaaacctcc 7200attaatcaat ggcctgtatg caaacaagac tgttattaaa gccacagcca ttcggcactc 7260caaaaaatac tttgactgca gagcagatgg gatcccatct tcccaggtca cgtggattat 7320gccaggcaat attttcctcc cagctccata ctttggaagc agagtcacgg tccatccaaa 7380tggaaccttg gagatgagga acatccggct ttctgactct gcggacttca cctgtgtggt 7440tcggagcgag ggaggagaga gtgtgttggt agtgcagtta gaagtcctag aaatgctgag 7500aagaccaaca ttcagaaacc cattcaacga aaaagtcatc gcccaagctg gcaagcccgt 7560agcactgaac tgctctgtgg atgggaaccc cccacctgaa attacctgga tcttacctga 7620cggcacacag tttgctaaca gaccacacaa ttccccgtat ctgatggcag gcaatggctc 7680tctcatcctt tacaaagcaa ctcggaacaa gtcagggaag tatcgctgtg cagccaggaa 7740taaggttggc tacatcgaga aactcatcct gttagagatt gggcagaagc cagtcattct 7800gacatacgaa ccagggatgg tgaagagcgt cagtggggaa ccgttatcac tgcattgtgt 7860gtctgatggg atccccaagc caaatgtcaa gtggactaca ccgggtggcc atgtaatcga 7920caggcctcaa gtggatggaa aatacatact gcatgaaaat ggcacgctgg tcatcaaagc 7980aacaacagct cacgaccaag gaaattatat ctgtagggct caaaacagtg ttggccaggc 8040agttattagc gtgtcagtga tggttgtggc ctaccctccc cgaatcataa actacctacc 8100caggaacatg ctcaggagga caggggaagc catgcagctc cactgtgtgg ccttgggaat 8160ccccaagcca aaagtcacct gggagacgcc aagacactcc ctgctctcaa aagcaacagc 8220aagaaaaccc catagaagtg agatgcttca cccacaaggt acgctggtca ttcagaatct 8280ccaaacctcg gattccggag tctataagtg cagagctcag aacctacttg ggactgatta 8340cgcaacaact tacatccagg tactctgaca ggaaggggga gactaaaatt caacagaagt 8400ccacatccac agggtttatt ttttggaaga agtttaatca aaggcagcca taggcatgta 8460aatgagtctg aatacattta cagtattaaa tttacaatgg acatgcgatg agacttgtaa 8520atgaaagcat tgtgaactga aaccgagtct ctgtggatct caaagcaaac tcttaactta 8580aggcactttg attttgccaa caaataataa caaacattaa gagaaaaaaa tgatccacta 8640cgaaataaca aacggctaat gcacctgaat tctcagtaaa aagacctttc tctcgctaac 8700agttgccagc tgcctcgtgt ctgtttccta ccaatgtcac aaacatcgca cacagggtga 8760atggagtcaa cgggaaagat taagtttgcg gtctgtgtaa atctcaatgt acaaatattc 8820tgtcnctggt ttataaacat tttgataaaa ccgaaaaaaa aaaaaaaaaa aaaaaaaaaa 8880aaa 888368262DNAhomo sapiensmisc_feature(1)..(8262)'n' can be any nucleotide 'a', 'c', 'g' or 't'. 6atgaaggtaa aaggcagagg aatcacctgc ttgctggtct cctttgctgt gatctgcctg 60gtcgccaccc ctgggggcaa ggcctgtcct cgccgctgtg cctgttatat gcctacggag 120gtacactgca catttcggta cctgacttcc atcccagaca gcatcccgcc caatgtggaa 180cgcatcaatt taggatacaa cagcttggtt agattgatgg aaacagattt ttctggcctg 240accaaactgg agttactcat gcttcacagc aatggcattc acacaatccc tgacaagacc 300ttctcagatt tgcaggcctt gcaggtctta aaaatgagct ataataaagt ccgaaaactt 360cagaaagata ctttttatgg cctcaggagc ttgacacgat tgcacatgga ccacaacaat 420attgagttta taaacccaga ggttttttat gggctcaact ttctccgcct ggtgcacttg 480gaaggaaatc agctcactaa gctccaccca gatacatttg tctctttgag ctacctccag 540atatttaaaa tctctttcat taagttccta tacttgtctg ataacttcct gacctccctc 600cctcaagaga tggtctccta tatgcctgac ctagacagcc tttacctgca tggaaaccca 660tggacctgtg attgccattt aaagtggttg tctgactgga tacaggnnnn nccagatgta 720ataaaatgca aaaaagatag aagtccctct agtgctcagc agtgtccact ttgcatgaac 780cctaggactt ctaaaggcaa gccgttagct atggtctcag ctgcagcttt ccagtgtgcc 840aagccaacca ttgactcatc cctgaaatca aagagcctga ctattctgga agacagtagt 900tctgctttca tctctcccca aggtttcatg gcaccctttg gctccctcac tttgaatatg 960acagatcagt ctggaaatga agctaacatg gtctgcagta ttcaaaagcc ctcaaggaca 1020tcacccattg cattcactga agaaaatgac tacatcgtgc taaatacttc attttcaaca 1080tttttggtgt gcaacataga ttacggtcac attcagccag tgtggcaaat tttggctttg 1140tacagtgatt ctcctctgat actagaaagg agccacttgc ttagtgaaac accgcagctc 1200tattacaaat ataaacaggt ggctcctaag cctgaagaca tttttaccaa catagaggca 1260gatctcagag cagatccctc ttggttaatg caagaccaaa tttccttgca gctgaacaga 1320actgccacca cattcagtac attacagatc cagtactcca gtgatgctca aatcacttta 1380ccaagagcag agatgaggcc agtgaaacac aaatggacta tgatttcaag ggataacaat 1440actaagctgg aacatactgt cttggtaggt ggaaccgttg gcctgaactg cccaggccaa 1500ggagacccca ccccacacgt ggattggctt ctagctgatg gaagtaaagt gagagcccct 1560tatgtcagtg aggatggacg gatcctaata gacaaaagtg gaaaattgga actccagatg 1620gctgatagtt ttgacacagg cgtatatcac tgtataagca gcaattatga tgatgcagat 1680attctcacct ataggataac tgtggtagaa cctttggtcg aagcctatca ggaaaatggg 1740attcatcaca cagttttcat tggtgaaaca cttgatcttc catgccattc tactggtatc 1800ccagatgcct ctattagctg ggttattcca ggaaacaatg tgctctatca gtcatcaaga 1860gacaagaaag ttctaaacaa tggcacatta agaatattac aggtcacccc gaaagaccaa 1920ggttattatc gctgtgtggc agccaaccca tcaggggttg attttttgat tttccaagtt 1980tcagtcaaga tgaaaggaca aaggcccttg gagcatgatg gagaaacaga gggatctgga 2040cttgatgagt ccaatcctat tgctcatctt aaggagccac caggtgcaca actccgtaca 2100tctgctctga tggaggctga ggttggaaaa cacacctcaa gcacaagtaa gaggcacaac 2160tatcgggaat taacactcca gcgacgtgga gattcaacac atcgacgttt tagggagaat 2220aggaggcatt tccctccctc tgctaggaga attgacccac aacattgggc ggcactgttg 2280gagaaagcta aaaagaatgc tatgccagac aagcgagaaa ataccacagt gagcccaccc 2340ccagtggtca cccaactccc aaacatacct ggtgaagaag acgattcctc aggcatgctc 2400gctctacatg aggaatttat ggtcccggcc actaaagctt tgaaccttcc agcaaggaca 2460gtgactgctg actccagaac aatatctgat agtcctatga caaacataaa ttatggcaca 2520gaactctccg ttgtgaattc acaaatacta ccacctgaag aacccacaga tttcaaactg 2580tctactgcta ttaaaactac agccatgtca aagaatataa acccaaccat gtcaagccaa 2640atacaaggca caaccaatca acattcatcc actgtctttc cactgctact tggagcaact 2700gaatttcagg actctgacag agggaagagg aagagagcat ttccagtaac ccccaataac 2760agtaaggact atgatcaaag atgntcaatg tcaaanatgc ttagtagcac caccaacaaa 2820ctattattag agtcagtaaa taccacaaat agtcatcaga catctgtaag agaagtgagt 2880gaacccaggc acaatcactt ctattctcac actactcaaa tacttagcac ctccacgttc 2940ccttcagatc cacacacagc tgctcattct cagtttccga tccctagann naatagtaca 3000gttaacatcc cgctgttcag acgctttggg aggcagagga aaattggcgg aagggggcgg 3060attatcagcc catatagaac tccagttctg cgacggcata gatacagcat tttcaggtca 3120acaaccagag gttcttctga aaaaagcact actgcattct cagccacagt gctcaatgtg 3180acatgtctgt cctgtcttcc cagggagagg ctcaccactg ccacagcagc attgtctttt 3240ccaagtgctg ctcccatcac cttccccaaa gctgacattg ctagagtccc atcagaagag 3300tctacaactc tagtccagaa tccactatta ctacttgaga acaaacccag tgtagannnn 3360gaaannacaa cacccacaat aaaatattca ggactngaaa tttcccaagt gactccaact 3420ggtgcagtca tgacatatgc tccaacatcc atacccatgg aaaaaactca caaagtaaac 3480gccagttacc cacgtgtgtc tagcaccaat gaagctaaaa gagattcagt gattacatcg 3540tcactttcag gtgctatcac caagccacca atgactatta tagccattac aaggttttca 3600agaaggaaaa ttccctggca acagaacttt gtaaataacc ataacccaaa aggcagatta 3660aggaatcaac ataaagttag tttacaaaaa agcacagctg tgatgcttcc taaaacatct 3720cctgctttac cacagagaca aagttcccct ttccatttca ccacactttc aacaagtgtg 3780atgcaaattc catctaatac cttgactacc gctcaccaca ctacgaccaa aacacacaat 3840cctggaagtc ttccaacaaa gaaggagctt cccttcccac cccttaaccc tatgcttcct 3900agtattataa gcaaagactc aagtacaaaa agcatcatat caacgcaaac agcaaccgca 3960acaactccta ccttccctgc atctgtcatc acttatgaaa cccaaacaga gagatctaga 4020gcacaaacaa tacaaagaga aggacctcaa aagaagaaca ggactgaccc aaacatctct 4080ccagaccaga gttctggctt cactacaccc actgctatga cnacctcctn ngctctnnnn 4140gcattcactc attccccacc agaaaacaca actgggattt caagcacaat cagttttcat 4200tcaagaactc ttaatctgac agatgtgatt gaagaactag cccaagcaag tactcagact 4260ttgaagagca caattgcttc tgaaacaact ttgtccagca aatcacacca gagtaccaca 4320actaggaaag catcattaga cactcaacca ccaccattct tgagcagcag tgctactcta 4380atgccagttc ccatctcccc tccctttact cagagagcag ttactgacaa cgtggcgact 4440cccatttccg ggcttatgac aaatacagtg gtcaagctgc acgaatcctc aaggcacaat 4500ccnnnnnnnc aaatgccaag ttcacnnaat tgngaaccnn nnactcnnnn nacttcatct 4560acntctaatc tgttacattc tactcccatg ccagcactaa caacagttaa atcacagaat 4620tccaaattaa ctccatctcc ctgggcagaa taccaatttt ggcacaaacc atactcagac 4680attgctgaaa aaggcaaaaa gccagaagta agcatgttgg ctactacagg cctgtccgag 4740gccaccactc ttgtttcaga ttgggatgga cagaagaaca caaagaagag tgactttgat 4800aagaaaccag ttcaagaagc aacaacttcc aaactccttc cctttgactc tttgtctagg 4860tatatatttg aaaagcccag gatagttgga ggaaaagctg caagttttac tattccagct 4920aactcagatg cctttcttcc ctgtgaagct gttggaaatc ccctgcccac cattcattgg 4980accagagtnn nntcaggact tgatttatct aagaggaaac agaatagcag ggtccaggtt 5040ctccccaatg gtaccctgtc catccagagg gtggaaattc aggaccgcgg acagtacttg 5100tgttccgcat ccaatctgtt tggcacagac caccttcatg tcaccttgtc tgtggtttcc 5160tatcctccca ggatcctgga gagacgtacc aaagagatca cagttcattc cggaagcact 5220gtggaactga agtgcagagc agaaggtagg ccaagcccta cagttacctg gattcttgca 5280aaccaaacag ttgtctcaga atcatcccag ggaagtaggc aggctgtggt gacggttgac 5340ggaacattgg tcctccacaa tctcagtatt tatgaccgtg gcttttacaa atgtgtggcc 5400agcaacccag gtggccagga ttcactgctg gttaaaatac aagtcattgc agcaccacct 5460gttattctag agcaaaggag gcaagtcatt gtaggcactt ggggtgaaag tttaaaactg 5520ccctgtactg caaaaggaac tcctcagccc agcgtttact gggtcctctc tgatggcact 5580gaagtgaaac cattacagtt taccaattcc aagttgttct tattttcaaa tgggactttg 5640tatataagaa acctagcctc ttcagacagg ggcacttatg aatgcattgc taccagttcc 5700actggttcgg agcgaagagt agtaatgctt acaatggaag agcgagtgac cagccccagg 5760atagaagctg catcccagaa aaggactgaa gtgaattttg gggacaaatt actactgaac 5820tgctcagcca ctggggagcc caaaccccaa ataatgtgga ggttaccatc caaggctgtg 5880gtcgaccagt gggcagctgg atccacgtct accctaatgg atccctgttt attggatcag 5940taacagaaaa agacagtggt gtctacttgt gtgtggcaag aaacaaaatg ggggatgatc 6000tgatactgat gcatgttagc ctaagactga aacctgccaa aattgaccac aagcagtatt 6060ttagaaagca agtgctccat gggaaagatt tccaagtaga ttgcaaagct tccggctccc 6120cagtgccaga gatatcttgg agtttgcctg atggaaccat gatcaacaat gcaatgcaag 6180ccgatgacag tggccacagg actaggagat ataccctttt caacaatgga actttatact 6240tcaacaaagt tggggtagcg gaggaaggag attatacttg ctatgcccag aacaccctag 6300ggaaagatga aatgaaggtc cacttaacag ttataacagc tgctccccgg ataaggcaga 6360gtaacaaaac caacaagaga atcaaagctg gagacacagc tgtccttgac tgtgaggtca 6420ctggggatcc caaaccaaaa atattttggt tgctgccttc caatgacatg atttccttct 6480ccattgatag gtacacattt catgccaatg ggtctttgac catcaacaaa gtgaaactgc 6540tcgattctgg agagtacgta tgtgtagccc gaaatcccag tggggatgac accaaaatgt 6600acaaactgga tgtggtctct aaacctccat taatcaatgg tctgtataca aacagaactg 6660ttattaaagc cacagctgtg agacattcca aaaaacactt tgactgcaga gctgaaggga 6720caccatctcc tgaagtcatg tggatcatgc cagacaatat tttcctcaca gccccatact 6780atggaagcag aatcacagtc cataaaaatg gaaccttgga aattaggaat gtgaggcttt 6840cagattcagc cgactttatc tgtgtggccc gaaatgaagg tggagagagc gtgttggtag 6900tacagttaga agtactggaa atgctgagaa gaccgacatt tagaaatcca tttaatgaaa 6960aaatagttgc ccagctggga aagtccacag cattgaattg ctctgttgat ggtaacccac 7020cacctgaaat aatctggatt ttaccaaatg gcacacgatt ttccaatgga ccacaaagtt 7080atcagtatct gatagcaagc aatggttctt ttatcatttc taaaacaact cgggaggatg 7140caggaaaata tcgctgtgca gctaggaata aagttggcta tattgagaaa ttagtcatat 7200tagaaattgg ccagaagcca gttattctta cctatgcacc agggacagta aaaggcatca 7260gtggagaatc tctatcactg cattgtgtgt ctgatggaat ccctaagcca aatatcaaat 7320ggactatgcc aagtggttat gtagtagaca ggcctcaaat taatgggaaa tacatattgc 7380atgacaatgg caccttagtc attaaagaag caacagctta tgacagagga aactatatct 7440gtaaggctca aaatagtgtt ggtcatacac tgattactgt tccagtaatg attgtagcct 7500accctccccg aattacaaat cgtccaccca ggagtattgt caccaggaca ggggcagcct 7560ttcagctcca ctgtgtggcc ttgggagttc ccaagccaga aatcacatgg gagatgcctg 7620accactccct tctctcaacg gcaagtaaag agaggacaca tggaagtgag cagcttcact 7680tacaaggtac cctagtcatt cagaatcccc aaacctccga ttctgggata tacaaatgca 7740cagcaaagaa cccacttggt agtgattatg cagcaacgta tattcaagta atctgacatg 7800aaataataaa gtcaacaaca tctgggcaga atttattttt tggaagaagt ttaatcaaag 7860gcagccatag gcatgtaaat gaatttgaat acatttacag tattaaattt acaatgaaca 7920tgcaaaataa aaggacttgt aaataaatgc attatgaact gatgatactg atttatttaa 7980tggatctcaa aacaaacttt taacttaagg cacttttatt ttgccaacaa ataacaataa 8040acaaacattg aaacggttca ctataaaata acaaatggct aatgtacctg aatttttcag 8100taaaaaaatg aacttctaat accagttgcc tagtgtccac ctcctatcaa tgttacaagc 8160atggcactca gaacagagac aatggaaaat attaaatctg caatctatgt ataaatattt 8220tgtggtttat aaattttttt gctaaaacct acagaaaata ag 826278883DNARattus speciesmisc_feature(1)..(8916)'n' can be any nucleotide 'a', 'c', 'g' or 't'. 7cgagagacga cagaaggtta cggctgcgag aagacgacag aagggtccag aaaaaggaaa 60gtgctggagg ggagtgggga caaaagcagc gaccaagtga atgtcacttc agtgactgag 120gccaggcaaa acgcgcggga aggattttgt gtagcttggg accctttcat agacactgat 180gacacgttta cgcaaaatag aaatttgagg agaaacgcct gggccttcgg aaaggagtga 240ttgattagta cttgcaagtt taggtgactt taaggagaac taactaatgt atactattga 300gggaggagga agagcattac agagtttcca gcagcagcag gaaagctttg gttaatttgg 360aaatggatga tagcattaaa ataacagaag cgcctccagg tctctgaagc ttcagtcccc 420cagctgaaag ccagaaaaga ctaagcccac taagcctttt gatccctttg gaagcaaaga 480actttccttc cctggggtga agactctcct cagaagattt cctgtctctg cctatgttac 540aagaggaatc aaaaccaaga cagaagagct caggatgcag gtgagaggca gggaagtcag 600cggcttgttg atctccctca ctgctgtctg cctggtggtc acccctggga gcagggcctg 660tcctcgccgc tgtgcctgct atgtgcccac agaggtgcac tgtacatttc ggtacctgac 720ctccatccca gatggcatcc cggccaatgt ggaacgaata aatttaggat ataacagcct 780tactagattg acagaaaacg actttgatgg cctgagcaaa ctggagttac tcatgctgca 840cagtaatggc attcacagag tcagtgacaa gaccttctcg ggcttgcagt ccttgcaggt 900cttaaaaatg agctataaca aagtccaaat cattcggaag gatactttct acggactcgg 960gagcttggtc cggttgcacc tggatcacaa caacattgaa ttcatcaacc ctgaggcctt 1020ttatggactt acctcgctcc gcttggtaca tttagaagga aaccggctca caaagctcca 1080tccagacaca tttgtctcat taagctatct ccagatattt aaaacctctt tcattaagta 1140cctgttcttg tctgataact tcctgacctc cctcccaaaa gaaatggtct cctacatgcc 1200aaacctagaa agcctgtatt tgcatggaaa cccatggacc tgtgactgcc atttaaagtg 1260gttgtctgag tggatgcagg gaaacccaga tataataaaa tgcaagaaag acagaagctc 1320ttccagtcct cagcaatgtc ccctttgcat gaaccccagg atctctaaag gcagaccctt 1380tgctatggta ccatctggag ctttcctatg tacaaagcca accattgatc catcactgaa 1440gtcaaagagc ctggttactc aggaggacaa tggatctgcc tccacctcac ctcaagattt 1500catagaaccc tttggctcct tgtctttgaa catgacanan ntntctggaa ataaggccga 1560catggtctgt agtatccaaa agccatcaag gacatcacca actgcattca ctgaagaaaa 1620tgactacatc atgctaaatg cgtcattttc cacaaatctt gtgtgcagtg tagattataa 1680tcacatccag ccagtgtggc aacttctggc tttatacagt gactctcctc tgatactaga 1740aaggaagccc cagcttaccg agactccttc actgtcttct agatataaac aggtggctct 1800taggcctgaa gacattttta ccagcataga ggctgatgtc agagcagacc ctttttggtt 1860ccaacaagaa aaaattgtct tgcagctgaa cagaactgcc accacactta gcacattaca 1920gatccagttt tccactgatg ctcaaatcgc tttaccaagg gcggagatga gagcggagag 1980actcaaatgg accatgatcc tgatgatgaa caatcccaaa ctggaacgca ctgtcctggt 2040tggcggcact attgccctga gctgtccagg caaaggcgac ccttcacctc acttggaatg 2100gcttctagct gatgggagta aagtgagagc cccttacgtt agcgaggatg ggcgaatcct 2160aatagacaaa aatgggaagt tggaactgca gatggctgac agctttgatg caggtcttta 2220ccactgcata agcaccaatg atgcagatgc ggatgttctc acatacagga taactgtggt 2280agagccctat ggagaaagca cacatgacag tggagtccag cacacagtgg ttacgggtga 2340gacgctcgac cttccatgcc tttccacggg tgttccagat gcttctatta gctggattct 2400tccagggaac actgtgttct ctcagccatc aagagacagg caaattctta acaatgggac 2460cttaagaata ttacaggtta cgccaaaaga tcaaggtcat taccaatgtg tggctgccaa 2520cccatcaggg gccgactttt ccagttttaa agtttcagtt caaaagaaag gccaaaggat 2580ggttgagcat gacagggagg caggtggatc tggacttgga gaacccaact ccagtgtttc 2640ccttaagcag ccagcatctt tgaaactctc tgcatcagct ttgacagggt cagaggctgg 2700aaaacaagtc tccggtgtac ataggaagaa caaacataga gacttaatac atcggcggcg 2760tggggattcc acgctccggc gattcaggga gcataggagg cagctccctc tctctgctcg 2820gagaattgac ccgcaacgct gggcagcact tctagaaaaa gccaaaaaga attctgtgcc 2880aaaaaagcaa gaaaatacca cagtaaagcc agtgccactg gctgttcccc tcgtggaact 2940cactgacgag gaaaaggatg cctctggcat gattcctcca gatgaagaat tcatggttct 3000gaaaactaag gcttctggtg tcccaggaag gtcaccaact gctgactctg gaccagtaaa 3060tcatggtttt atgacgagta tagcttctgg cacagaagtc tcaactgtga atccacaaac 3120actacaatct gagcaccttc ctgatttcaa

attatttagt gtaacaaacg gtacagctgt 3180gacaaagagt atgaacccat ccatagcaag caaaatagaa gatacaacca accaaaaccc 3240aatcattatc tttccatcag tagctgaaat tcgagattct gctcaggcag gaagagcatc 3300ttcccaaagt gcacaccctg taacaggggg aaacatggct acctatggcc ataccaacac 3360atatagtagc tttaccagca aagccagtac agtcttgcag ccaataaatc caacagaaag 3420ttatggacct cagataccta ttacaggagt cagcagacct agcagtagtg acatctcttc 3480tcacactact gcagacccta gcttctccag tcacccttca ggttcacaca ccactgcctc 3540gtctttattt cacattccta gaaacaacaa tacaggtaac ttccccttgt ccaggcactt 3600gggaagagag aggacaattt ggagcagagg gagagttaaa aacccacata gaaccccagt 3660tctccgacgg catagacaca ggactgtgag gccagcaatc aagggacctg ctaacaaaaa 3720tgtgagccaa gttccagcca cagagtaccc tgggatgtgc cacacatgtc cttccgcaga 3780ggggctcaca gtggctactg cagcactgtc agttccaagt tcatcccaca gtgccctccc 3840caaaactaat aatgttgggg tcatagcaga agagtctacc actgtggtca agaaaccact 3900gttactattt aaggacaaac aaaatgtaga tattgagata ataacaacca ctacaaaata 3960ttccggaggg gaaagtaacc acgtgattcc tacggaagca agcatgactt ctgctccaac 4020atctgtatcc ctggggaaat ctcctgtaga caatagtggt cacctgagca tgcctgggac 4080catccaaact gggaaagatt cagtggaaac aacaccactt cccagccccc tcagcacacc 4140ctcaatacca acaagcacaa aattctcaaa gaggaaaact cccttgcacc agatctttgt 4200aaataaccag aagaaggagg ggatgttaaa gaatccatat caattcggtt tacaaaagaa 4260cccagccgca aagcttccca aaatagctcc tcttttaccc acaggtcaga gttccccctc 4320agattctaca actctcttga caagtccgcc accagctctg tctacaacaa tggctgccac 4380tcagaacaag ggcactgaag tagtatcagg tgccagaagt ctctcagcag ggaagaagca 4440gcccttcacc aactcctctc cagtgcttcc tagcaccata agcaagagat ctaatacatt 4500aaacttcttg tcaacggaaa cccccacagt gacaagtcct actgctactg catctgtcat 4560tatgtctgaa acccaacgaa caagatccaa agaagcaaaa gaccaaataa aggggcctcg 4620gaagaacaga aacaacgcaa acaccacccc caggcaggtt tctggctata gtgcatactc 4680agctctaaca acagctgata cccccttggc tttcagtcat tccccacgac aagatgatgg 4740tggaaatgta agtgcagttg cttatcactc aacaacctct cttctggcca taactgaact 4800gtttgagaag tacacccaga ctttgggaaa tacaacagct ttggaaacaa cgttgttgag 4860caaatcacag gagagtacca cagtgaaaag agcctcagac acaccaccac cactcctcag 4920cagtggggcg cccccagtgc ccactccttc cccacctcct tttactaagg gtgtggttac 4980agacagcaaa gtcacatcag ctttccagat gacgtcaaat agagtggtca ccatatatga 5040atcttcaagg cacaatacag atctgcagca accctcagca gaggctagcc ccaatcctga 5100gatcataact ggaaccactg actctccctc taatctgttt ccatccactt ctgtgccagc 5160actaagggta gataaaccac agaattctaa atggaagccc tctccctggc cagaacacaa 5220atatcagctc aagtcatact ccgaaaccat tgagaagggc aaaaggccag cagtaagcat 5280gtccccccac ctcagccttc cagaggccag cactcatgcc tcacactgga atacacagaa 5340gcatgcagaa aagagtgttt ttgataagaa acctggtcaa aacccaactt ccaaacatct 5400gccttacgtc tctctaccta agactctatt gaaaaagcca agaataattg gaggaaaggc 5460tgcaagcttt acagttccag ctaattcaga cgtttttctt ccttgtgagg ctgttggaga 5520cccactgccc atcatccact ggaccagagt ttcatcagga nttgaaatat cccaagggac 5580acagaaaagc cggttccacg tgcttcccaa tggcaccttg tccatccaga gggtcagtat 5640tcaggaccgt ggacagtacc tgtgctctgc atttaatcca ctgggcgtag accattttca 5700tgtctctttg tctgtggttt tttacccggc aaggattttg gacagacatg tcaaggagat 5760cacagttcac tttggaagta ctgtggaact aaagtgcaga gtggagggta tgccgaggcc 5820tacggtttcc tggatacttg caaaccaaac ggtggtctca gaaacggcca agggaagcag 5880aaaggtctgg gtaacacctg atggaacatt gatcatctat aatctgagtc tttatgatcg 5940tggtttttac aagtgtgtgg ccagcaaccc atctggccag gattcactgt tggttaagat 6000acaagtcatc acagctcccc ctgtcattat agagcaaaag aggcaagcca tcgttggggt 6060tttaggtgga agtttgaaac tgccctgcac tgcaaaagga actccccagc ctagtgttca 6120ctgggtcctt tatgatggga ctgaactaaa accattgcag ttgactcatt ccagattttt 6180cttgtatcca aatggaactc tgtatataag aagcatcgct ccttcagtga ggggcactta 6240tgagtgcatt gccaccagct cctcaggctc agagagaagg gtagtgattc ttactgtgga 6300agagggagag acaatcccca ggatagaaac tgcctctcag aaatggactg aggtgaattt 6360gggtgagaaa ttactactga actgctcagc tactggggat ccaaagccta gaataatctg 6420gaggctgcca tccaaggctg tcatcgacca gtggcacaga atgggcagcc gaatccacgt 6480ctacccaaat ggatccttgg tggttgggtc agtgacggaa aaagacgctg gtgactactt 6540atgtgtggca agaaacaaaa tgggagatga cctagtcctg atgcatgtcc gcctgagatt 6600gacacctgcc aaaattgaac agaagcagta ttttaagaag caagtgctcc atgggaaaga 6660tttccaagtt gactgcaagg cctctggctc ccctgtgcct gaggtatcct ggagtttgcc 6720tgatgggaca gtgctcaaca atgtagccca agctgatgac agtggctata ggaccaagag 6780gtacaccctt ttccacaatg gaaccttgta tttcaacaac gttgggatgg cagaggaagg 6840agattatatc tgctctgccc agaacacctt agggaaagat gagatgaaag tccacctaac 6900agttctaaca gccatcccac ggataaggca aagctacaag accaccatga ggctcagggc 6960tggagaaaca gctgtccttg actgcgaggt cactggggaa ccgaagccca atgtattttg 7020gttgctgcct tccaacaatg tcatttcatt ctccaatgac aggttcacat ttcatgccaa 7080tagaactttg tccatccata aagtgaaacc acttgactct ggggactatg tgtgcgtagc 7140tcagaatcct agtggggatg acactaagac atacaaactg gacattgtct ctaaacctcc 7200attaatcaat ggcctgtatg caaacaagac tgttattaaa gccacagcca ttcggcactc 7260caaaaaatac tttgactgca gagcagatgg gatcccatct tcccaggtca cgtggattat 7320gccaggcaat attttcctcc cagctccata ctttggaagc agagtcacgg tccatccaaa 7380tggaaccttg gagatgagga acatccggct ttctgactct gcggacttca cctgtgtggt 7440tcggagcgag ggaggagaga gtgtgttggt agtgcagtta gaagtcctag aaatgctgag 7500aagaccaaca ttcagaaacc cattcaacga aaaagtcatc gcccaagctg gcaagcccgt 7560agcactgaac tgctctgtgg atgggaaccc cccacctgaa attacctgga tcttacctga 7620cggcacacag tttgctaaca gaccacacaa ttccccgtat ctgatggcag gcaatggctc 7680tctcatcctt tacaaagcaa ctcggaacaa gtcagggaag tatcgctgtg cagccaggaa 7740taaggttggc tacatcgaga aactcatcct gttagagatt gggcagaagc cagtcattct 7800gacatacgaa ccagggatgg tgaagagcgt cagtggggaa ccgttatcac tgcattgtgt 7860gtctgatggg atccccaagc caaatgtcaa gtggactaca ccgggtggcc atgtaatcga 7920caggcctcaa gtggatggaa aatacatact gcatgaaaat ggcacgctgg tcatcaaagc 7980aacaacagct cacgaccaag gaaattatat ctgtagggct caaaacagtg ttggccaggc 8040agttattagc gtgtcagtga tggttgtggc ctaccctccc cgaatcataa actacctacc 8100caggaacatg ctcaggagga caggggaagc catgcagctc cactgtgtgg ccttgggaat 8160ccccaagcca aaagtcacct gggagacgcc aagacactcc ctgctctcaa aagcaacagc 8220aagaaaaccc catagaagtg agatgcttca cccacaaggt acgctggtca ttcagaatct 8280ccaaacctcg gattccggag tctataagtg cagagctcag aacctacttg ggactgatta 8340cgcaacaact tacatccagg tactctgaca ggaaggggga gactaaaatt caacagaagt 8400ccacatccac agggtttatt ttttggaaga agtttaatca aaggcagcca taggcatgta 8460aatgagtctg aatacattta cagtattaaa tttacaatgg acatgcgatg agacttgtaa 8520atgaaagcat tgtgaactga aaccgagtct ctgtggatct caaagcaaac tcttaactta 8580aggcactttg attttgccaa caaataataa caaacattaa gagaaaaaaa tgatccacta 8640cgaaataaca aacggctaat gcacctgaat tctcagtaaa aagacctttc tctcgctaac 8700agttgccagc tgcctcgtgt ctgtttccta ccaatgtcac aaacatcgca cacagggtga 8760atggagtcaa cgggaaagat taagtttgcg gtctgtgtaa atctcaatgt acaaatattc 8820tgtcnctggt ttataaacat tttgataaaa ccgaaaaaaa aaaaaaaaaa aaaaaaaaaa 8880aaa 888388180DNAhomo sapiensmisc_feature(1)..(8180)'n' can be any nucleotide 'a', 'c', 'g' or 't'. 8tcacctgctt gctggtctcc tttgctgtga tctgcctggt cgccacccct gggggcaagg 60cctgtcctcg ccgctgtgcc tgttatatgc ctacggaggt acactgcaca tttcggtacc 120tgacttccat cccagacagc atcccgccca atgtggaacg catcaattta ggatacaaca 180gcttggttag attgatggaa acagattttt ctggcctgac caaactggag ttactcatgc 240ttcacagcaa tggcattcac acaatccctg acaagacctt ctcagatttg caggccttgc 300aggtcttaaa aatgagctat aataaagtcc gaaaacttca gaaagatact ttttatggcc 360tcaggagctt gacacgattg cacatggacc acaacaatat tgagtttata aacccagagg 420ttttttatgg gctcaacttt ctccgcctgg tgcacttgga aggaaatcag ctcactaagc 480tccacccaga tacatttgtc tctttgagct acctccagat atttaaaatc tctttcatta 540agttcctata cttgtctgat aacttcctga cctccctccc tcaagagatg gtctcctata 600tgcctgacct agacagcctt tacctgcatg gaaacccatg gacctgtgat tgccatttaa 660agtggttgtc tgactggata caggnnnnnc cagatgtaat aaaatgcaaa aaagatagaa 720gtccctctag tgctcagcag tgtccacttt gcatgaaccc taggacttct aaaggcaagc 780cgttagctat ggtctcagct gcagctttcc agtgtgccaa gccaaccatt gactcatccc 840tgaaatcaaa gagcctgact attctggaag acagtagttc tgctttcatc tctccccaag 900gtttcatggc accctttggc tccctcactt tgaatatgac agatcagtct ggaaatgaag 960ctaacatggt ctgcagtatt caaaagccct caaggacatc acccattgca ttcactgaag 1020aaaatgacta catcgtgcta aatacttcat tttcaacatt tttggtgtgc aacatagatt 1080acggtcacat tcagccagtg tggcaaattt tggctttgta cagtgattct cctctgatac 1140tagaaaggag ccacttgctt agtgaaacac cgcagctcta ttacaaatat aaacaggctt 1200ggttaatgca agaccaaatt tccttgcagc tgaacagaac tgccaccaca ttcagtacat 1260tacagatcca gtactccagt gatgctcaaa tcactttacc aagagcagag atgaggccag 1320tgaaacacaa atggactatg atttcaaggg ataacaatac taagctggaa catactgtct 1380tggtaggtgg aaccgttggc ctgaactgcc caggccaagg agaccccacc ccacacgtgg 1440attggcttct agctgatgga agtaaagtga gagcccctta tgtcagtgag gatggacgga 1500tcctaataga caaaagtgga aaattggaac tccagatggc tgatagtttt gacacaggcg 1560tatatcactg tataagcagc aattatgatg atgcagatat tctcacctat aggataactg 1620tggtagaacc tttggtcgaa gcctatcagg aaaatgggat tcatcacaca gttttcattg 1680gtgaaacact tgatcttcca tgccattcta ctggtatccc agatgcctct attagctggg 1740ttattccagg aaacaatgtg ctctatcagt catcaagaga caagaaagtt ctaaacaatg 1800gcacattaag aatattacag gtcaccccga aagaccaagg ttattatcgc tgtgtggcag 1860ccaacccatc aggggttgat tttttgattt tccaagtttc agtcaagatg aaaggacaaa 1920ggcccttgga gcatgatgga gaaacagagg gatctggact tgatgagtcc aatcctattg 1980ctcatcttaa ggagccacca ggtgcacaac tccgtacatc tgctctgatg gaggctgagg 2040ttggaaaaca cacctcaagc acaagtaaga ggcacaacta tcgggaatta acactccagc 2100gacgtggaga ttcaacacat cgacgtttta gggagaatag gaggcatttc cctccctctg 2160ctaggagaat tgacccacaa cattgggcgg cactgttgga gaaagctaaa aagaatgcta 2220tgccagacaa gcgagaaaat accacagtga gcccaccccc agtggtcacc caactcccaa 2280acatacctgg tgaagaagac gattcctcag gcatgctcgc tctacatgag gaatttatgg 2340tcccggccac taaagctttg aaccttccag caaggacagt gactgctgac tccagaacaa 2400tatctgatag tcctatgaca aacataaatt atggcacaga actctccgtt gtgaattcac 2460aaatactacc acctgaagaa cccacagatt tcaaactgtc tactgctatt aaaactacag 2520ccatgtcaaa gaatataaac ccaaccatgt caagccaaat acaaggcaca accaatcaac 2580attcatccac tgtctttcca ctgctacttg gagcaactga atttcaggac tctgacagag 2640ggaagaggaa gagagcattt ccagtaaccc ccaataacag taaggactat gatcaaagat 2700gntcaatgtc aaanatgctt agtagcacca ccaacaaact attattagag tcagtaaata 2760ccacaaatag tcatcagaca tctgtaagag aagtgagtga acccaggcac aatcacttct 2820attctcacac tactcaaata cttagcacct ccacgttccc ttcagatcca cacacagctg 2880ctcattctca gtttccgatc cctagannna atagtacagt taacatcccg ctgttcagac 2940gctttgggag gcagaggaaa attggcggaa gggggcggat tatcagccca tatagaactc 3000cagttctgcg acggcataga tacagcattt tcaggtcaac aaccagaggt tcttctgaaa 3060aaagcactac tgcattctca gccacagtgc tcaatgtgac atgtctgtcc tgtcttccca 3120gggagaggct caccactgcc acagcagcat tgtcttttcc aagtgctgct cccatcacct 3180tccccaaagc tgacattgct agagtcccat cagaagagtc tacaactcta gtccagaatc 3240cactattact acttgagaac aaacccagtg tagannnnga aannacaaca cccacaataa 3300aatattcagg actngaaatt tcccaagtga ctccaactgg tgcagtcatg acatatgctc 3360caacatccat acccatggaa aaaactcaca aagtaaacgc cagttaccca cgtgtgtcta 3420gcaccaatga agctaaaaga gattcagtga ttacatcgtc actttcaggt gctatcacca 3480agccaccaat gactattata gccattacaa ggttttcaag aaggaaaatt ccctggcaac 3540agaactttgt aaataaccat aacccaaaag gcagattaag gaatcaacat aaagttagtt 3600tacaaaaaag cacagctgtg atgcttccta aaacatctcc tgctttacca cagagacaaa 3660gttccccttt ccatttcacc acactttcaa caagtgtgat gcaaattcca tctaatacct 3720tgactaccgc tcaccacact acgaccaaaa cacacaatcc tggaagtctt ccaacaaaga 3780aggagcttcc cttcccaccc cttaacccta tgcttcctag tattataagc aaagactcaa 3840gtacaaaaag catcatatca acgcaaacag caaccgcaac aactcctacc ttccctgcat 3900ctgtcatcac ttatgaaacc caaacagaga gatctagagc acaaacaata caaagagaag 3960gacctcaaaa gaagaacagg actgacccaa acatctctcc agaccagagt tctggcttca 4020ctacacccac tgctatgacn acctcctnng ctctnnnngc attcactcat tccccaccag 4080aaaacacaac tgggatttca agcacaatca gttttcattc aagaactctt aatctgacag 4140atgtgattga agaactagcc caagcaagta ctcagacttt gaagagcaca attgcttctg 4200aaacaacttt gtccagcaaa tcacaccaga gtaccacaac taggaaagca tcattagaca 4260ctcaaccacc accattcttg agcagcagtg ctactctaat gccagttccc atctcccctc 4320cctttactca gagagcagtt actgacaacg tggcgactcc catttccggg cttatgacaa 4380atacagtggt caagctgcac gaatcctcaa ggcacaatcc nnnnnnncaa atgccaagtt 4440cacnnaattg ngaaccnnnn actcnnnnna cttcatctac ntctaatctg ttacattcta 4500ctcccatgcc agcactaaca acagttaaat cacagaattc caaattaact ccatctccct 4560gggcagaata ccaattttgg cacaaaccat actcagacat tgctgaaaaa ggcaaaaagc 4620cagaagtaag catgttggct actacaggcc tgtccgaggc caccactctt gtttcagatt 4680gggatggaca gaagaacaca aagaagagtg actttgataa gaaaccagtt caagaagcaa 4740caacttccaa actccttccc tttgactctt tgtctaggta tatatttgaa aagcccagga 4800tagttggagg aaaagctgca agttttacta ttccagctaa ctcagatgcc tttcttccct 4860gtgaagctgt tggaaatccc ctgcccacca ttcattggac cagagtnnnn tcaggacttg 4920atttatctaa gaggaaacag aatagcaggg tccaggttct ccccaatggt accctgtcca 4980tccagagggt ggaaattcag gaccgcggac agtacttgtg ttccgcatcc aatctgtttg 5040gcacagacca ccttcatgtc accttgtctg tggtttccta tcctcccagg atcctggaga 5100gacgtaccaa agagatcaca gttcattccg gaagcactgt ggaactgaag tgcagagcag 5160aaggtaggcc aagccctaca gttacctgga ttcttgcaaa ccaaacagtt gtctcagaat 5220catcccaggg aagtaggcag gctgtggtga cggttgacgg aacattggtc ctccacaatc 5280tcagtattta tgaccgtggc ttttacaaat gtgtggccag caacccaggt ggccaggatt 5340cactgctggt taaaatacaa gtcattgcag caccacctgt tattctagag caaaggaggc 5400aagtcattgt aggcacttgg ggtgaaagtt taaaactgcc ctgtactgca aaaggaactc 5460ctcagcccag cgtttactgg gtcctctctg atggcactga agtgaaacca ttacagttta 5520ccaattccaa gttgttctta ttttcaaatg ggactttgta tataagaaac ctagcctctt 5580cagacagggg cacttatgaa tgcattgcta ccagttccac tggttcggag cgaagagtag 5640taatgcttac aatggaagag cgagtgacca gccccaggat agaagctgca tcccagaaaa 5700ggactgaagt gaattttggg gacaaattac tactgaactg ctcagccact ggggagccca 5760aaccccaaat aatgtggagg ttaccatcca aggctgtggt cgaccagtgg gcagctggat 5820ccacgtctac cctaatggat ccctgtttat tggatcagta acagaaaaag acagtggtgt 5880ctacttgtgt gtggcaagaa acaaaatggg ggatgatctg atactgatgc atgttagcct 5940aagactgaaa cctgccaaaa ttgaccacaa gcagtatttt agaaagcaag tgctccatgg 6000gaaagatttc caagtagatt gcaaagcttc cggctcccca gtgccagaga tatcttggag 6060tttgcctgat ggaaccatga tcaacaatgc aatgcaagcc gatgacagtg gccacaggac 6120taggagatat acccttttca acaatggaac tttatacttc aacaaagttg gggtagcgga 6180ggaaggagat tatacttgct atgcccagaa caccctaggg aaagatgaaa tgaaggtcca 6240cttaacagtt ataacagctg ctccccggat aaggcagagt aacaaaacca acaagagaat 6300caaagctgga gacacagctg tccttgactg tgaggtcact ggggatccca aaccaaaaat 6360attttggttg ctgccttcca atgacatgat ttccttctcc attgataggt acacatttca 6420tgccaatggg tctttgacca tcaacaaagt gaaactgctc gattctggag agtacgtatg 6480tgtagcccga aatcccagtg gggatgacac caaaatgtac aaactggatg tggtctctaa 6540acctccatta atcaatggtc tgtatacaaa cagaactgtt attaaagcca cagctgtgag 6600acattccaaa aaacactttg actgcagagc tgaagggaca ccatctcctg aagtcatgtg 6660gatcatgcca gacaatattt tcctcacagc cccatactat ggaagcagaa tcacagtcca 6720taaaaatgga accttggaaa ttaggaatgt gaggctttca gattcagccg actttatctg 6780tgtggcccga aatgaaggtg gagagagcgt gttggtagta cagttagaag tactggaaat 6840gctgagaaga ccgacattta gaaatccatt taatgaaaaa atagttgccc agctgggaaa 6900gtccacagca ttgaattgct ctgttgatgg taacccacca cctgaaataa tctggatttt 6960accaaatggc acacgatttt ccaatggacc acaaagttat cagtatctga tagcaagcaa 7020tggttctttt atcatttcta aaacaactcg ggaggatgca ggaaaatatc gctgtgcagc 7080taggaataaa gttggctata ttgagaaatt agtcatatta gaaattggcc agaagccagt 7140tattcttacc tatgcaccag ggacagtaaa aggcatcagt ggagaatctc tatcactgca 7200ttgtgtgtct gatggaatcc ctaagccaaa tatcaaatgg actatgccaa gtggttatgt 7260agtagacagg cctcaaatta atgggaaata catattgcat gacaatggca ccttagtcat 7320taaagaagca acagcttatg acagaggaaa ctatatctgt aaggctcaaa atagtgttgg 7380tcatacactg attactgttc cagtaatgat tgtagcctac cctccccgaa ttacaaatcg 7440tccacccagg agtattgtca ccaggacagg ggcagccttt cagctccact gtgtggcctt 7500gggagttccc aagccagaaa tcacatggga gatgcctgac cactcccttc tctcaacggc 7560aagtaaagag aggacacatg gaagtgagca gcttcactta caaggtaccc tagtcattca 7620gaatccccaa acctccgatt ctgggatata caaatgcaca gcaaagaacc cacttggtag 7680tgattatgca gcaacgtata ttcaagtaat ctgacatgaa ataataaagt caacaacatc 7740tgggcagaat ttattttttg gaagaagttt aatcaaaggc agccataggc atgtaaatga 7800atttgaatac atttacagta ttaaatttac aatgaacatg caaaataaaa ggacttgtaa 7860ataaatgcat tatgaactga tgatactgat ttatttaatg gatctcaaaa caaactttta 7920acttaaggca cttttatttt gccaacaaat aacaataaac aaacattgaa acggttcact 7980ataaaataac aaatggctaa tgtacctgaa tttttcagta aaaaaatgaa cttctaatac 8040cagttgccta gtgtccacct cctatcaatg ttacaagcat ggcactcaga acagagacaa 8100tggaaaatat taaatctgca atctatgtat aaatattttg tggtttataa atttttttgc 8160taaaacctac agaaaataag 81809897DNAMus musculusmisc_feature(1)..(897)'n' can be any nucleotide 'a', 'c', 'g' or 't'. 9aagaacgttc cttcaatcag gtgaaggctc tcctcagaag atttcctgtc tctgcttatg 60tcagctgctt gctgatctcc ctcactgcca tctgcctggt ggtcacccct gggagcaggg 120tctgtcctcg ccgatgtgcc tgctatgtgc ccacagaggt gcactgtaca tttcgggacc 180tgacctccat cccagacggg catcccagcc aatgtggaac gagtcaattt agggtataac 240agcctcacta gattgacaga aaatgacttt tctggcctga gcagactgga gttactcatg 300ctgcacagca atggcattca cagagtcagt gacaagacct tctcgggctt gcagtccttg 360caggtcttaa aaatgagcta taacaaagtc caaataattg agaaggatac tttgtatgga 420ctcaggagct tgacccggtt gcacctggat cacaacaaca ttgagtttat caaccccgag 480gcgttttacg gactcacctt gctccgcttg gtacatctag aaggaaaccg gctgacaaag 540ctccatccag acacatttgt ctctttgagc tatctccaga tatttaaaac ctccttcatt 600aagnacctgt acttgtatga taacttcatt gacctccctc ccaaaagaaa tggtctcctc 660tatgccaaac ctagaaagcc tttacttgca tggaaaccca tggacctgtg actgccattt 720aaagtggttg tccgagtgga tgcagggaaa cccaggtaac tatcttgttt gtttgtttct 780ttttttatar kacgtatttt cctcaatttc atttagaatg atatcccaaa agtcccccat 840aacctccccc ccacttccct acctacccat tcccattttt

tggccctggc attcccc 897102597PRTRattus speciesmisc_feature(1)..(2597)'x' can be any amino acid 10Met Gln Val Arg Gly Arg Glu Val Ser Gly Leu Leu Ile Ser Leu Thr1 5 10 15Ala Val Cys Leu Val Val Thr Pro Gly Ser Arg Ala Cys Pro Arg Arg 20 25 30Cys Ala Cys Tyr Val Pro Thr Glu Val His Cys Thr Phe Arg Tyr Leu 35 40 45Thr Ser Ile Pro Asp Gly Ile Pro Ala Asn Val Glu Arg Ile Asn Leu 50 55 60Gly Tyr Asn Ser Leu Thr Arg Leu Thr Glu Asn Asp Phe Asp Gly Leu65 70 75 80Ser Lys Leu Glu Leu Leu Met Leu His Ser Asn Gly Ile His Arg Val 85 90 95Ser Asp Lys Thr Phe Ser Gly Leu Gln Ser Leu Gln Val Leu Lys Met 100 105 110Ser Tyr Asn Lys Val Gln Ile Ile Arg Lys Asp Thr Phe Tyr Gly Leu 115 120 125Gly Ser Leu Val Arg Leu His Leu Asp His Asn Asn Ile Glu Phe Ile 130 135 140Asn Pro Glu Ala Phe Tyr Gly Leu Thr Ser Leu Arg Leu Val His Leu145 150 155 160Glu Gly Asn Arg Leu Thr Lys Leu His Pro Asp Thr Phe Val Ser Leu 165 170 175Ser Tyr Leu Gln Ile Phe Lys Thr Ser Phe Ile Lys Tyr Leu Phe Leu 180 185 190Ser Asp Asn Phe Leu Thr Ser Leu Pro Lys Glu Met Val Ser Tyr Met 195 200 205Pro Asn Leu Glu Ser Leu Tyr Leu His Gly Asn Pro Trp Thr Cys Asp 210 215 220Cys His Leu Lys Trp Leu Ser Glu Trp Met Gln Gly Asn Pro Asp Ile225 230 235 240Ile Lys Cys Lys Lys Asp Arg Ser Ser Ser Ser Pro Gln Gln Cys Pro 245 250 255Leu Cys Met Asn Pro Arg Ile Ser Lys Gly Arg Pro Phe Ala Met Val 260 265 270Pro Ser Gly Ala Phe Leu Cys Thr Lys Pro Thr Ile Asp Pro Ser Leu 275 280 285Lys Ser Lys Ser Leu Val Thr Gln Glu Asp Asn Gly Ser Ala Ser Thr 290 295 300Ser Pro Gln Asp Phe Ile Glu Pro Phe Gly Ser Leu Ser Leu Asn Met305 310 315 320Thr Xaa Xaa Ser Gly Asn Lys Ala Asp Met Val Cys Ser Ile Gln Lys 325 330 335Pro Ser Arg Thr Ser Pro Thr Ala Phe Thr Glu Glu Asn Asp Tyr Ile 340 345 350Met Leu Asn Ala Ser Phe Ser Thr Asn Leu Val Cys Ser Val Asp Tyr 355 360 365Asn His Ile Gln Pro Val Trp Gln Leu Leu Ala Leu Tyr Ser Asp Ser 370 375 380Pro Leu Ile Leu Glu Arg Lys Pro Gln Leu Thr Glu Thr Pro Ser Leu385 390 395 400Ser Ser Arg Tyr Lys Gln Val Ala Leu Arg Pro Glu Asp Ile Phe Thr 405 410 415Ser Ile Glu Ala Asp Val Arg Ala Asp Pro Phe Trp Phe Gln Gln Glu 420 425 430Lys Ile Val Leu Gln Leu Asn Arg Thr Ala Thr Thr Leu Ser Thr Leu 435 440 445Gln Ile Gln Phe Ser Thr Asp Ala Gln Ile Ala Leu Pro Arg Ala Glu 450 455 460Met Arg Ala Glu Arg Leu Lys Trp Thr Met Ile Leu Met Met Asn Asn465 470 475 480Pro Lys Leu Glu Arg Thr Val Leu Val Gly Gly Thr Ile Ala Leu Ser 485 490 495Cys Pro Gly Lys Gly Asp Pro Ser Pro His Leu Glu Trp Leu Leu Ala 500 505 510Asp Gly Ser Lys Val Arg Ala Pro Tyr Val Ser Glu Asp Gly Arg Ile 515 520 525Leu Ile Asp Lys Asn Gly Lys Leu Glu Leu Gln Met Ala Asp Ser Phe 530 535 540Asp Ala Gly Leu Tyr His Cys Ile Ser Thr Asn Asp Ala Asp Ala Asp545 550 555 560Val Leu Thr Tyr Arg Ile Thr Val Val Glu Pro Tyr Gly Glu Ser Thr 565 570 575His Asp Ser Gly Val Gln His Thr Val Val Thr Gly Glu Thr Leu Asp 580 585 590Leu Pro Cys Leu Ser Thr Gly Val Pro Asp Ala Ser Ile Ser Trp Ile 595 600 605Leu Pro Gly Asn Thr Val Phe Ser Gln Pro Ser Arg Asp Arg Gln Ile 610 615 620Leu Asn Asn Gly Thr Leu Arg Ile Leu Gln Val Thr Pro Lys Asp Gln625 630 635 640Gly His Tyr Gln Cys Val Ala Ala Asn Pro Ser Gly Ala Asp Phe Ser 645 650 655Ser Phe Lys Val Ser Val Gln Lys Lys Gly Gln Arg Met Val Glu His 660 665 670Asp Arg Glu Ala Gly Gly Ser Gly Leu Gly Glu Pro Asn Ser Ser Val 675 680 685Ser Leu Lys Gln Pro Ala Ser Leu Lys Leu Ser Ala Ser Ala Leu Thr 690 695 700Gly Ser Glu Ala Gly Lys Gln Val Ser Gly Val His Arg Lys Asn Lys705 710 715 720His Arg Asp Leu Ile His Arg Arg Arg Gly Asp Ser Thr Leu Arg Arg 725 730 735Phe Arg Glu His Arg Arg Gln Leu Pro Leu Ser Ala Arg Arg Ile Asp 740 745 750Pro Gln Arg Trp Ala Ala Leu Leu Glu Lys Ala Lys Lys Asn Ser Val 755 760 765Pro Lys Lys Gln Glu Asn Thr Thr Val Lys Pro Val Pro Leu Ala Val 770 775 780Pro Leu Val Glu Leu Thr Asp Glu Glu Lys Asp Ala Ser Gly Met Ile785 790 795 800Pro Pro Asp Glu Glu Phe Met Val Leu Lys Thr Lys Ala Ser Gly Val 805 810 815Pro Gly Arg Ser Pro Thr Ala Asp Ser Gly Pro Val Asn His Gly Phe 820 825 830Met Thr Ser Ile Ala Ser Gly Thr Glu Val Ser Thr Val Asn Pro Gln 835 840 845Thr Leu Gln Ser Glu His Leu Pro Asp Phe Lys Leu Phe Ser Val Thr 850 855 860Asn Gly Thr Ala Val Thr Lys Ser Met Asn Pro Ser Ile Ala Ser Lys865 870 875 880Ile Glu Asp Thr Thr Asn Gln Asn Pro Ile Ile Ile Phe Pro Ser Val 885 890 895Ala Glu Ile Arg Asp Ser Ala Gln Ala Gly Arg Ala Ser Ser Gln Ser 900 905 910Ala His Pro Val Thr Gly Gly Asn Met Ala Thr Tyr Gly His Thr Asn 915 920 925Thr Tyr Ser Ser Phe Thr Ser Lys Ala Ser Thr Val Leu Gln Pro Ile 930 935 940Asn Pro Thr Glu Ser Tyr Gly Pro Gln Ile Pro Ile Thr Gly Val Ser945 950 955 960Arg Pro Ser Ser Ser Asp Ile Ser Ser His Thr Thr Ala Asp Pro Ser 965 970 975Phe Ser Ser His Pro Ser Gly Ser His Thr Thr Ala Ser Ser Leu Phe 980 985 990His Ile Pro Arg Asn Asn Asn Thr Gly Asn Phe Pro Leu Ser Arg His 995 1000 1005Leu Gly Arg Glu Arg Thr Ile Trp Ser Arg Gly Arg Val Lys Asn 1010 1015 1020Pro His Arg Thr Pro Val Leu Arg Arg His Arg His Arg Thr Val 1025 1030 1035Arg Pro Ala Ile Lys Gly Pro Ala Asn Lys Asn Val Ser Gln Val 1040 1045 1050Pro Ala Thr Glu Tyr Pro Gly Met Cys His Thr Cys Pro Ser Ala 1055 1060 1065Glu Gly Leu Thr Val Ala Thr Ala Ala Leu Ser Val Pro Ser Ser 1070 1075 1080Ser His Ser Ala Leu Pro Lys Thr Asn Asn Val Gly Val Ile Ala 1085 1090 1095Glu Glu Ser Thr Thr Val Val Lys Lys Pro Leu Leu Leu Phe Lys 1100 1105 1110Asp Lys Gln Asn Val Asp Ile Glu Ile Ile Thr Thr Thr Thr Lys 1115 1120 1125Tyr Ser Gly Gly Glu Ser Asn His Val Ile Pro Thr Glu Ala Ser 1130 1135 1140Met Thr Ser Ala Pro Thr Ser Val Ser Leu Gly Lys Ser Pro Val 1145 1150 1155Asp Asn Ser Gly His Leu Ser Met Pro Gly Thr Ile Gln Thr Gly 1160 1165 1170Lys Asp Ser Val Glu Thr Thr Pro Leu Pro Ser Pro Leu Ser Thr 1175 1180 1185Pro Ser Ile Pro Thr Ser Thr Lys Phe Ser Lys Arg Lys Thr Pro 1190 1195 1200Leu His Gln Ile Phe Val Asn Asn Gln Lys Lys Glu Gly Met Leu 1205 1210 1215Lys Asn Pro Tyr Gln Phe Gly Leu Gln Lys Asn Pro Ala Ala Lys 1220 1225 1230Leu Pro Lys Ile Ala Pro Leu Leu Pro Thr Gly Gln Ser Ser Pro 1235 1240 1245Ser Asp Ser Thr Thr Leu Leu Thr Ser Pro Pro Pro Ala Leu Ser 1250 1255 1260Thr Thr Met Ala Ala Thr Gln Asn Lys Gly Thr Glu Val Val Ser 1265 1270 1275Gly Ala Arg Ser Leu Ser Ala Gly Lys Lys Gln Pro Phe Thr Asn 1280 1285 1290Ser Ser Pro Val Leu Pro Ser Thr Ile Ser Lys Arg Ser Asn Thr 1295 1300 1305Leu Asn Phe Leu Ser Thr Glu Thr Pro Thr Val Thr Ser Pro Thr 1310 1315 1320Ala Thr Ala Ser Val Ile Met Ser Glu Thr Gln Arg Thr Arg Ser 1325 1330 1335Lys Glu Ala Lys Asp Gln Ile Lys Gly Pro Arg Lys Asn Arg Asn 1340 1345 1350Asn Ala Asn Thr Thr Pro Arg Gln Val Ser Gly Tyr Ser Ala Tyr 1355 1360 1365Ser Ala Leu Thr Thr Ala Asp Thr Pro Leu Ala Phe Ser His Ser 1370 1375 1380Pro Arg Gln Asp Asp Gly Gly Asn Val Ser Ala Val Ala Tyr His 1385 1390 1395Ser Thr Thr Ser Leu Leu Ala Ile Thr Glu Leu Phe Glu Lys Tyr 1400 1405 1410Thr Gln Thr Leu Gly Asn Thr Thr Ala Leu Glu Thr Thr Leu Leu 1415 1420 1425Ser Lys Ser Gln Glu Ser Thr Thr Val Lys Arg Ala Ser Asp Thr 1430 1435 1440Pro Pro Pro Leu Leu Ser Ser Gly Ala Pro Pro Val Pro Thr Pro 1445 1450 1455Ser Pro Pro Pro Phe Thr Lys Gly Val Val Thr Asp Ser Lys Val 1460 1465 1470Thr Ser Ala Phe Gln Met Thr Ser Asn Arg Val Val Thr Ile Tyr 1475 1480 1485Glu Ser Ser Arg His Asn Thr Asp Leu Gln Gln Pro Ser Ala Glu 1490 1495 1500Ala Ser Pro Asn Pro Glu Ile Ile Thr Gly Thr Thr Asp Ser Pro 1505 1510 1515Ser Asn Leu Phe Pro Ser Thr Ser Val Pro Ala Leu Arg Val Asp 1520 1525 1530Lys Pro Gln Asn Ser Lys Trp Lys Pro Ser Pro Trp Pro Glu His 1535 1540 1545Lys Tyr Gln Leu Lys Ser Tyr Ser Glu Thr Ile Glu Lys Gly Lys 1550 1555 1560Arg Pro Ala Val Ser Met Ser Pro His Leu Ser Leu Pro Glu Ala 1565 1570 1575Ser Thr His Ala Ser His Trp Asn Thr Gln Lys His Ala Glu Lys 1580 1585 1590Ser Val Phe Asp Lys Lys Pro Gly Gln Asn Pro Thr Ser Lys His 1595 1600 1605Leu Pro Tyr Val Ser Leu Pro Lys Thr Leu Leu Lys Lys Pro Arg 1610 1615 1620Ile Ile Gly Gly Lys Ala Ala Ser Phe Thr Val Pro Ala Asn Ser 1625 1630 1635Asp Val Phe Leu Pro Cys Glu Ala Val Gly Asp Pro Leu Pro Ile 1640 1645 1650Ile His Trp Thr Arg Val Ser Ser Gly Xaa Glu Ile Ser Gln Gly 1655 1660 1665Thr Gln Lys Ser Arg Phe His Val Leu Pro Asn Gly Thr Leu Ser 1670 1675 1680Ile Gln Arg Val Ser Ile Gln Asp Arg Gly Gln Tyr Leu Cys Ser 1685 1690 1695Ala Phe Asn Pro Leu Gly Val Asp His Phe His Val Ser Leu Ser 1700 1705 1710Val Val Phe Tyr Pro Ala Arg Ile Leu Asp Arg His Val Lys Glu 1715 1720 1725Ile Thr Val His Phe Gly Ser Thr Val Glu Leu Lys Cys Arg Val 1730 1735 1740Glu Gly Met Pro Arg Pro Thr Val Ser Trp Ile Leu Ala Asn Gln 1745 1750 1755Thr Val Val Ser Glu Thr Ala Lys Gly Ser Arg Lys Val Trp Val 1760 1765 1770Thr Pro Asp Gly Thr Leu Ile Ile Tyr Asn Leu Ser Leu Tyr Asp 1775 1780 1785Arg Gly Phe Tyr Lys Cys Val Ala Ser Asn Pro Ser Gly Gln Asp 1790 1795 1800Ser Leu Leu Val Lys Ile Gln Val Ile Thr Ala Pro Pro Val Ile 1805 1810 1815Ile Glu Gln Lys Arg Gln Ala Ile Val Gly Val Leu Gly Gly Ser 1820 1825 1830Leu Lys Leu Pro Cys Thr Ala Lys Gly Thr Pro Gln Pro Ser Val 1835 1840 1845His Trp Val Leu Tyr Asp Gly Thr Glu Leu Lys Pro Leu Gln Leu 1850 1855 1860Thr His Ser Arg Phe Phe Leu Tyr Pro Asn Gly Thr Leu Tyr Ile 1865 1870 1875Arg Ser Ile Ala Pro Ser Val Arg Gly Thr Tyr Glu Cys Ile Ala 1880 1885 1890Thr Ser Ser Ser Gly Ser Glu Arg Arg Val Val Ile Leu Thr Val 1895 1900 1905Glu Glu Gly Glu Thr Ile Pro Arg Ile Glu Thr Ala Ser Gln Lys 1910 1915 1920Trp Thr Glu Val Asn Leu Gly Glu Lys Leu Leu Leu Asn Cys Ser 1925 1930 1935Ala Thr Gly Asp Pro Lys Pro Arg Ile Ile Trp Arg Leu Pro Ser 1940 1945 1950Lys Ala Val Ile Asp Gln Trp His Arg Met Gly Ser Arg Ile His 1955 1960 1965Val Tyr Pro Asn Gly Ser Leu Val Val Gly Ser Val Thr Glu Lys 1970 1975 1980Asp Ala Gly Asp Tyr Leu Cys Val Ala Arg Asn Lys Met Gly Asp 1985 1990 1995Asp Leu Val Leu Met His Val Arg Leu Arg Leu Thr Pro Ala Lys 2000 2005 2010Ile Glu Gln Lys Gln Tyr Phe Lys Lys Gln Val Leu His Gly Lys 2015 2020 2025Asp Phe Gln Val Asp Cys Lys Ala Ser Gly Ser Pro Val Pro Glu 2030 2035 2040Val Ser Trp Ser Leu Pro Asp Gly Thr Val Leu Asn Asn Val Ala 2045 2050 2055Gln Ala Asp Asp Ser Gly Tyr Arg Thr Lys Arg Tyr Thr Leu Phe 2060 2065 2070His Asn Gly Thr Leu Tyr Phe Asn Asn Val Gly Met Ala Glu Glu 2075 2080 2085Gly Asp Tyr Ile Cys Ser Ala Gln Asn Thr Leu Gly Lys Asp Glu 2090 2095 2100Met Lys Val His Leu Thr Val Leu Thr Ala Ile Pro Arg Ile Arg 2105 2110 2115Gln Ser Tyr Lys Thr Thr Met Arg Leu Arg Ala Gly Glu Thr Ala 2120 2125 2130Val Leu Asp Cys Glu Val Thr Gly Glu Pro Lys Pro Asn Val Phe 2135 2140 2145Trp Leu Leu Pro Ser Asn Asn Val Ile Ser Phe Ser Asn Asp Arg 2150 2155 2160Phe Thr Phe His Ala Asn Arg Thr Leu Ser Ile His Lys Val Lys 2165 2170 2175Pro Leu Asp Ser Gly Asp Tyr Val Cys Val Ala Gln Asn Pro Ser 2180 2185 2190Gly Asp Asp Thr Lys Thr Tyr Lys Leu Asp Ile Val Ser Lys Pro 2195 2200 2205Pro Leu Ile Asn Gly Leu Tyr Ala Asn Lys Thr Val Ile Lys Ala 2210 2215 2220Thr Ala Ile Arg His Ser Lys Lys Tyr Phe Asp Cys Arg Ala Asp 2225 2230 2235Gly Ile Pro Ser Ser Gln Val Thr Trp Ile Met Pro Gly Asn Ile 2240 2245 2250Phe Leu Pro Ala Pro Tyr Phe Gly Ser Arg Val Thr Val His Pro 2255 2260 2265Asn Gly Thr Leu Glu Met Arg Asn Ile Arg Leu Ser Asp Ser Ala 2270 2275 2280Asp Phe Thr Cys Val Val Arg Ser Glu Gly Gly Glu Ser Val Leu 2285 2290 2295Val Val Gln Leu Glu Val Leu Glu Met Leu Arg Arg Pro Thr Phe 2300 2305 2310Arg Asn Pro Phe Asn Glu Lys Val Ile Ala Gln Ala Gly Lys Pro 2315 2320 2325Val Ala Leu Asn Cys Ser Val Asp Gly Asn Pro Pro Pro Glu Ile 2330 2335 2340Thr Trp Ile Leu Pro Asp Gly Thr Gln Phe Ala Asn Arg Pro His 2345 2350 2355Asn Ser Pro Tyr Leu Met Ala Gly Asn Gly Ser Leu Ile Leu Tyr 2360 2365 2370Lys Ala Thr Arg Asn Lys Ser Gly Lys Tyr Arg Cys Ala Ala Arg 2375 2380 2385Asn Lys Val Gly Tyr Ile Glu Lys Leu Ile Leu Leu Glu Ile Gly 2390 2395 2400Gln Lys Pro Val Ile Leu Thr Tyr Glu Pro Gly Met Val Lys Ser 2405 2410 2415Val Ser Gly Glu Pro Leu Ser Leu His Cys Val Ser Asp Gly Ile 2420 2425 2430Pro Lys

Pro Asn Val Lys Trp Thr Thr Pro Gly Gly His Val Ile 2435 2440 2445Asp Arg Pro Gln Val Asp Gly Lys Tyr Ile Leu His Glu Asn Gly 2450 2455 2460Thr Leu Val Ile Lys Ala Thr Thr Ala His Asp Gln Gly Asn Tyr 2465 2470 2475Ile Cys Arg Ala Gln Asn Ser Val Gly Gln Ala Val Ile Ser Val 2480 2485 2490Ser Val Met Val Val Ala Tyr Pro Pro Arg Ile Ile Asn Tyr Leu 2495 2500 2505Pro Arg Asn Met Leu Arg Arg Thr Gly Glu Ala Met Gln Leu His 2510 2515 2520Cys Val Ala Leu Gly Ile Pro Lys Pro Lys Val Thr Trp Glu Thr 2525 2530 2535Pro Arg His Ser Leu Leu Ser Lys Ala Thr Ala Arg Lys Pro His 2540 2545 2550Arg Ser Glu Met Leu His Pro Gln Gly Thr Leu Val Ile Gln Asn 2555 2560 2565Leu Gln Thr Ser Asp Ser Gly Val Tyr Lys Cys Arg Ala Gln Asn 2570 2575 2580Leu Leu Gly Thr Asp Tyr Ala Thr Thr Tyr Ile Gln Val Leu 2585 2590 2595112586PRTHomo sapiensmisc_feature(1)..(2586)'x' can be any amino acid 11Met Lys Val Lys Gly Arg Gly Ile Thr Cys Leu Leu Val Ser Phe Ala1 5 10 15Val Ile Cys Leu Val Ala Thr Pro Gly Gly Lys Ala Cys Pro Arg Arg 20 25 30Cys Ala Cys Tyr Met Pro Thr Glu Val His Cys Thr Phe Arg Tyr Leu 35 40 45Thr Ser Ile Pro Asp Ser Ile Pro Pro Asn Val Glu Arg Ile Asn Leu 50 55 60Gly Tyr Asn Ser Leu Val Arg Leu Met Glu Thr Asp Phe Ser Gly Leu65 70 75 80Thr Lys Leu Glu Leu Leu Met Leu His Ser Asn Gly Ile His Thr Ile 85 90 95Pro Asp Lys Thr Phe Ser Asp Leu Gln Ala Leu Gln Val Leu Lys Met 100 105 110Ser Tyr Asn Lys Val Arg Lys Leu Gln Lys Asp Thr Phe Tyr Gly Leu 115 120 125Arg Ser Leu Thr Arg Leu His Met Asp His Asn Asn Ile Glu Phe Ile 130 135 140Asn Pro Glu Val Phe Tyr Gly Leu Asn Phe Leu Arg Leu Val His Leu145 150 155 160Glu Gly Asn Gln Leu Thr Lys Leu His Pro Asp Thr Phe Val Ser Leu 165 170 175Ser Tyr Leu Gln Ile Phe Lys Ile Ser Phe Ile Lys Phe Leu Tyr Leu 180 185 190Ser Asp Asn Phe Leu Thr Ser Leu Pro Gln Glu Met Val Ser Tyr Met 195 200 205Pro Asp Leu Asp Ser Leu Tyr Leu His Gly Asn Pro Trp Thr Cys Asp 210 215 220Cys His Leu Lys Trp Leu Ser Asp Trp Ile Gln Pro Asp Val Ile Lys225 230 235 240Cys Lys Lys Asp Arg Ser Pro Ser Ser Ala Gln Gln Cys Pro Leu Cys 245 250 255Met Asn Pro Arg Thr Ser Lys Gly Lys Pro Leu Ala Met Val Ser Ala 260 265 270Ala Ala Phe Gln Cys Ala Lys Pro Thr Ile Asp Ser Ser Leu Lys Ser 275 280 285Lys Ser Leu Thr Ile Leu Glu Asp Ser Ser Ser Ala Phe Ile Ser Pro 290 295 300Gln Gly Phe Met Ala Pro Phe Gly Ser Leu Thr Leu Asn Met Thr Asp305 310 315 320Gln Ser Gly Asn Glu Ala Asn Met Val Cys Ser Ile Gln Lys Pro Ser 325 330 335Arg Thr Ser Pro Ile Ala Phe Thr Glu Glu Asn Asp Tyr Ile Val Leu 340 345 350Asn Thr Ser Phe Ser Thr Phe Leu Val Cys Asn Ile Asp Tyr Gly His 355 360 365Ile Gln Pro Val Trp Gln Ile Leu Ala Leu Tyr Ser Asp Ser Pro Leu 370 375 380Ile Leu Glu Arg Ser His Leu Leu Ser Glu Thr Pro Gln Leu Tyr Tyr385 390 395 400Lys Tyr Lys Gln Val Ala Pro Lys Pro Glu Asp Ile Phe Thr Asn Ile 405 410 415Glu Ala Asp Leu Arg Ala Asp Pro Ser Trp Leu Met Gln Asp Gln Ile 420 425 430Ser Leu Gln Leu Asn Arg Thr Ala Thr Thr Phe Ser Thr Leu Gln Ile 435 440 445Gln Tyr Ser Ser Asp Ala Gln Ile Thr Leu Pro Arg Ala Glu Met Arg 450 455 460Pro Val Lys His Lys Trp Thr Met Ile Ser Arg Asp Asn Asn Thr Lys465 470 475 480Leu Glu His Thr Val Leu Val Gly Gly Thr Val Gly Leu Asn Cys Pro 485 490 495Gly Gln Gly Asp Pro Thr Pro His Val Asp Trp Leu Leu Ala Asp Gly 500 505 510Ser Lys Val Arg Ala Pro Tyr Val Ser Glu Asp Gly Arg Ile Leu Ile 515 520 525Asp Lys Ser Gly Lys Leu Glu Leu Gln Met Ala Asp Ser Phe Asp Thr 530 535 540Gly Val Tyr His Cys Ile Ser Ser Asn Tyr Asp Asp Ala Asp Ile Leu545 550 555 560Thr Tyr Arg Ile Thr Val Val Glu Pro Leu Val Glu Ala Tyr Gln Glu 565 570 575Asn Gly Ile His His Thr Val Phe Ile Gly Glu Thr Leu Asp Leu Pro 580 585 590Cys His Ser Thr Gly Ile Pro Asp Ala Ser Ile Ser Trp Val Ile Pro 595 600 605Gly Asn Asn Val Leu Tyr Gln Ser Ser Arg Asp Lys Lys Val Leu Asn 610 615 620Asn Gly Thr Leu Arg Ile Leu Gln Val Thr Pro Lys Asp Gln Gly Tyr625 630 635 640Tyr Arg Cys Val Ala Ala Asn Pro Ser Gly Val Asp Phe Leu Ile Phe 645 650 655Gln Val Ser Val Lys Met Lys Gly Gln Arg Pro Leu Glu His Asp Gly 660 665 670Glu Thr Glu Gly Ser Gly Leu Asp Glu Ser Asn Pro Ile Ala His Leu 675 680 685Lys Glu Pro Pro Gly Ala Gln Leu Arg Thr Ser Ala Leu Met Glu Ala 690 695 700Glu Val Gly Lys His Thr Ser Ser Thr Ser Lys Arg His Asn Tyr Arg705 710 715 720Glu Leu Thr Leu Gln Arg Arg Gly Asp Ser Thr His Arg Arg Phe Arg 725 730 735Glu Asn Arg Arg His Phe Pro Pro Ser Ala Arg Arg Ile Asp Pro Gln 740 745 750His Trp Ala Ala Leu Leu Glu Lys Ala Lys Lys Asn Ala Met Pro Asp 755 760 765Lys Arg Glu Asn Thr Thr Val Ser Pro Pro Pro Val Val Thr Gln Leu 770 775 780Pro Asn Ile Pro Gly Glu Glu Asp Asp Ser Ser Gly Met Leu Ala Leu785 790 795 800His Glu Glu Phe Met Val Pro Ala Thr Lys Ala Leu Asn Leu Pro Ala 805 810 815Arg Thr Val Thr Ala Asp Ser Arg Thr Ile Ser Asp Ser Pro Met Thr 820 825 830Asn Ile Asn Tyr Gly Thr Glu Phe Ser Pro Val Val Asn Ser Gln Ile 835 840 845Leu Pro Pro Glu Glu Pro Thr Asp Phe Lys Leu Ser Thr Ala Ile Lys 850 855 860Thr Thr Ala Met Ser Lys Asn Ile Asn Pro Thr Met Ser Ser Gln Ile865 870 875 880Gln Gly Thr Thr Asn Gln His Ser Ser Thr Val Phe Pro Leu Leu Leu 885 890 895Gly Ala Thr Glu Phe Gln Asp Ser Asp Gln Met Gly Arg Gly Arg Glu 900 905 910His Phe Gln Ser Arg Pro Pro Ile Thr Val Arg Thr Met Ile Lys Asp 915 920 925Val Asn Val Lys Met Leu Ser Ser Thr Thr Asn Lys Leu Leu Leu Glu 930 935 940Ser Val Asn Thr Thr Asn Ser His Gln Thr Ser Val Arg Glu Val Ser945 950 955 960Glu Pro Arg His Asn His Phe Tyr Ser His Thr Thr Gln Ile Leu Ser 965 970 975Thr Ser Thr Phe Pro Ser Asp Pro His Thr Ala Ala His Ser Gln Phe 980 985 990Pro Ile Pro Arg Asn Ser Thr Val Asn Ile Pro Leu Phe Arg Arg Phe 995 1000 1005Gly Arg Gln Arg Lys Ile Gly Gly Arg Gly Arg Ile Ile Ser Pro 1010 1015 1020Tyr Arg Thr Pro Val Leu Arg Arg His Arg Tyr Ser Ile Phe Arg 1025 1030 1035Ser Thr Thr Arg Gly Ser Ser Glu Lys Ser Thr Thr Ala Phe Ser 1040 1045 1050Ala Thr Val Leu Asn Val Thr Cys Leu Ser Cys Leu Pro Arg Glu 1055 1060 1065Arg Leu Thr Thr Ala Thr Ala Ala Leu Ser Phe Pro Ser Ala Ala 1070 1075 1080Pro Ile Thr Phe Pro Lys Ala Asp Ile Ala Arg Val Pro Ser Glu 1085 1090 1095Glu Ser Thr Thr Leu Val Gln Asn Pro Leu Leu Leu Leu Glu Asn 1100 1105 1110Lys Pro Ser Val Glu Lys Thr Thr Pro Thr Ile Lys Tyr Phe Arg 1115 1120 1125Thr Glu Ile Ser Gln Val Thr Pro Thr Gly Ala Val Met Thr Tyr 1130 1135 1140Ala Pro Thr Ser Ile Pro Met Glu Lys Thr His Lys Val Asn Ala 1145 1150 1155Ser Tyr Pro Arg Val Ser Ser Thr Asn Glu Ala Lys Arg Asp Ser 1160 1165 1170Val Ile Thr Ser Ser Leu Ser Gly Ala Ile Thr Lys Pro Pro Met 1175 1180 1185Thr Ile Ile Ala Ile Thr Arg Phe Ser Arg Arg Lys Ile Pro Trp 1190 1195 1200Gln Gln Asn Phe Val Asn Asn His Asn Pro Lys Gly Arg Leu Arg 1205 1210 1215Asn Gln His Lys Val Ser Leu Gln Lys Ser Thr Ala Val Met Leu 1220 1225 1230Pro Lys Thr Ser Pro Ala Leu Pro Gln Arg Gln Ser Ser Pro Phe 1235 1240 1245His Phe Thr Thr Leu Ser Thr Ser Val Met Gln Ile Pro Ser Asn 1250 1255 1260Thr Leu Thr Thr Ala His His Thr Thr Thr Lys Thr His Asn Pro 1265 1270 1275Gly Ser Leu Pro Thr Lys Lys Glu Leu Pro Phe Pro Pro Leu Asn 1280 1285 1290Pro Met Leu Pro Ser Ile Ile Ser Lys Asp Ser Ser Thr Lys Ser 1295 1300 1305Ile Ile Ser Thr Gln Thr Ala Ile Pro Ala Thr Thr Pro Thr Phe 1310 1315 1320Pro Ala Ser Val Ile Thr Tyr Glu Thr Gln Thr Glu Arg Ser Arg 1325 1330 1335Ala Gln Thr Ile Gln Arg Glu Gln Glu Pro Gln Lys Lys Asn Arg 1340 1345 1350Thr Asp Pro Asn Ile Ser Pro Asp Gln Ser Ser Gly Phe Thr Thr 1355 1360 1365Pro Thr Ala Met Thr Pro Pro Ala Leu Ala Phe Thr His Ser Pro 1370 1375 1380Pro Glu Asn Thr Thr Gly Ile Ser Ser Thr Ile Ser Phe His Ser 1385 1390 1395Arg Thr Leu Asn Leu Thr Asp Val Ile Glu Glu Leu Ala Gln Ala 1400 1405 1410Ser Thr Gln Thr Leu Lys Ser Thr Ile Ala Ser Glu Thr Thr Leu 1415 1420 1425Ser Ser Lys Ser His Gln Ser Thr Thr Thr Arg Lys Ala Ser Leu 1430 1435 1440Asp Thr Pro Ile Pro Pro Phe Leu Ser Ser Ser Ala Thr Leu Met 1445 1450 1455Pro Val Pro Ile Ser Pro Pro Phe Thr Gln Arg Ala Val Thr Asp 1460 1465 1470Thr Arg Gly Asp Ser His Phe Arg Leu Met Thr Asn Thr Val Val 1475 1480 1485Lys Leu His Glu Ser Ser Arg His Asn Leu Gln Met Pro Ser Ser 1490 1495 1500Gln Leu Glu Pro Leu Thr Ser Ser Thr Ser Asn Leu Leu His Ser 1505 1510 1515Thr Pro Met Pro Ala Leu Thr Thr Val Lys Ser Gln Asn Ser Lys 1520 1525 1530Leu Thr Pro Ser Pro Trp Ala Glu Tyr Gln Phe Trp His Lys Pro 1535 1540 1545Tyr Ser Asp Ile Ala Glu Lys Gly Lys Lys Pro Glu Val Ser Met 1550 1555 1560Leu Ala Thr Thr Gly Leu Ser Glu Ala Thr Thr Leu Val Ser Asp 1565 1570 1575Trp Asp Gly Gln Lys Asn Thr Lys Lys Ser Asp Phe Asp Lys Lys 1580 1585 1590Pro Val Gln Glu Ala Thr Thr Ser Lys Leu Leu Pro Phe Asp Ser 1595 1600 1605Leu Ser Arg Tyr Ile Phe Glu Lys Pro Arg Ile Val Gly Gly Lys 1610 1615 1620Ala Ala Ser Phe Thr Ile Pro Ala Asn Ser Asp Ala Phe Leu Pro 1625 1630 1635Cys Glu Ala Val Gly Asn Pro Leu Pro Thr Ile His Trp Thr Arg 1640 1645 1650Val Ser Gly Leu Asp Leu Ser Arg Gly Asn Gln Asn Ser Arg Val 1655 1660 1665Gln Val Leu Pro Asn Gly Thr Leu Ser Ile Gln Arg Val Glu Ile 1670 1675 1680Gln Asp Arg Gly Gln Tyr Leu Cys Ser Ala Ser Asn Leu Phe Gly 1685 1690 1695Thr Asp His Leu His Val Thr Leu Ser Val Val Ser Tyr Pro Pro 1700 1705 1710Arg Ile Leu Glu Arg Arg Thr Lys Glu Ile Thr Val His Ser Gly 1715 1720 1725Ser Thr Val Glu Leu Lys Cys Arg Ala Glu Gly Arg Pro Ser Pro 1730 1735 1740Thr Val Thr Trp Ile Leu Ala Asn Gln Thr Val Val Ser Glu Ser 1745 1750 1755Ser Gln Gly Ser Arg Gln Ala Val Val Thr Val Asp Gly Thr Leu 1760 1765 1770Val Leu His Asn Leu Ser Ile Tyr Asp Arg Gly Phe Tyr Lys Cys 1775 1780 1785Val Ala Ser Asn Pro Gly Gly Gln Asp Ser Leu Leu Val Lys Ile 1790 1795 1800Gln Val Ile Ala Ala Pro Pro Val Ile Leu Glu Gln Arg Arg Gln 1805 1810 1815Val Ile Val Gly Thr Trp Gly Glu Ser Leu Lys Leu Pro Cys Thr 1820 1825 1830Ala Lys Gly Thr Pro Gln Pro Ser Val Tyr Trp Val Leu Ser Asp 1835 1840 1845Gly Thr Glu Val Lys Pro Leu Gln Phe Thr Asn Ser Lys Leu Phe 1850 1855 1860Leu Phe Ser Asn Gly Thr Leu Tyr Ile Arg Asn Leu Ala Ser Ser 1865 1870 1875Asp Arg Gly Thr Tyr Glu Cys Ile Ala Thr Ser Ser Thr Gly Ser 1880 1885 1890Glu Arg Arg Val Val Met Leu Thr Met Glu Glu Arg Val Thr Ser 1895 1900 1905Pro Arg Ile Glu Ala Ala Ser Gln Lys Arg Thr Glu Val Asn Phe 1910 1915 1920Gly Asp Lys Leu Leu Leu Asn Cys Ser Ala Thr Gly Glu Pro Lys 1925 1930 1935Pro Gln Ile Met Trp Arg Leu Pro Ser Lys Ala Val Val Asp Gln 1940 1945 1950Gly Ser Trp Ile His Val Tyr Pro Asn Gly Ser Leu Phe Ile Gly 1955 1960 1965Ser Val Thr Glu Lys Asp Ser Gly Val Tyr Leu Cys Val Ala Arg 1970 1975 1980Asn Lys Met Gly Asp Asp Leu Ile Leu Met His Val Ser Leu Arg 1985 1990 1995Leu Lys Pro Ala Lys Ile Asp His Lys Gln Tyr Phe Arg Lys Gln 2000 2005 2010Val Leu His Gly Lys Asp Phe Gln Val Asp Cys Lys Ala Ser Gly 2015 2020 2025Ser Pro Val Pro Glu Ile Ser Trp Ser Leu Pro Asp Gly Thr Met 2030 2035 2040Ile Asn Asn Ala Met Gln Ala Asp Asp Ser Gly His Arg Thr Arg 2045 2050 2055Arg Tyr Thr Leu Phe Asn Asn Gly Thr Leu Tyr Phe Asn Lys Val 2060 2065 2070Gly Val Ala Glu Glu Gly Asp Tyr Thr Cys Tyr Ala Gln Asn Thr 2075 2080 2085Leu Gly Lys Asp Glu Met Lys Val His Leu Thr Val Ile Thr Ala 2090 2095 2100Ala Pro Arg Ile Arg Gln Ser Asn Lys Thr Asn Lys Arg Ile Lys 2105 2110 2115Ala Gly Asp Thr Ala Val Leu Asp Cys Glu Val Thr Gly Asp Pro 2120 2125 2130Lys Pro Lys Ile Phe Trp Leu Leu Pro Ser Asn Asp Met Ile Ser 2135 2140 2145Phe Ser Ile Asp Arg Tyr Thr Phe His Ala Asn Gly Ser Leu Thr 2150 2155 2160Ile Asn Lys Val Lys Leu Leu Asp Ser Gly Glu Tyr Val Cys Val 2165 2170 2175Ala Arg Asn Pro Ser Gly Asp Asp Thr Lys Met Tyr Lys Leu Asp 2180 2185 2190Val Val Ser Lys Pro Pro Leu Ile Asn Gly Leu Tyr Thr Asn Arg 2195 2200 2205Thr Val Ile Lys Ala Thr Ala Val Arg His Ser Lys Lys His Phe 2210 2215 2220Asp Cys Arg Ala Glu Gly Thr Pro Ser Pro Glu Val Met Trp Ile 2225 2230 2235Met Pro Asp Asn Ile Phe Leu Thr Ala Pro Tyr Tyr Gly Ser Arg 2240 2245 2250Ile Thr Val His Lys Asn Gly Thr Leu Glu Ile Arg Asn Val Arg 2255 2260 2265Leu Ser Asp Ser Ala Asp Phe Ile Cys Val Ala Arg Asn Glu Gly

2270 2275 2280Gly Glu Ser Val Leu Val Val Gln Leu Glu Val Leu Glu Met Leu 2285 2290 2295Arg Arg Pro Thr Phe Arg Asn Pro Phe Asn Glu Lys Ile Val Ala 2300 2305 2310Gln Leu Gly Lys Ser Thr Ala Leu Asn Cys Ser Val Asp Gly Asn 2315 2320 2325Pro Pro Pro Glu Ile Ile Trp Ile Leu Pro Asn Gly Thr Arg Phe 2330 2335 2340Ser Asn Gly Pro Gln Ser Tyr Gln Tyr Leu Ile Ala Ser Asn Gly 2345 2350 2355Ser Phe Ile Ile Ser Lys Thr Thr Arg Glu Asp Ala Gly Lys Tyr 2360 2365 2370Arg Cys Ala Ala Arg Asn Lys Val Gly Tyr Ile Glu Lys Leu Val 2375 2380 2385Ile Leu Glu Ile Gly Gln Lys Pro Val Ile Leu Thr Tyr Ala Pro 2390 2395 2400Gly Thr Val Lys Gly Ile Ser Gly Glu Ser Leu Ser Leu His Cys 2405 2410 2415Val Ser Asp Gly Ile Pro Lys Pro Asn Ile Lys Trp Thr Met Pro 2420 2425 2430Ser Gly Tyr Val Val Asp Arg Pro Gln Ile Asn Gly Lys Tyr Ile 2435 2440 2445Leu His Asp Asn Gly Thr Leu Val Ile Lys Glu Ala Thr Ala Tyr 2450 2455 2460Asp Arg Gly Asn Tyr Ile Cys Lys Ala Gln Asn Ser Val Gly His 2465 2470 2475Thr Leu Ile Thr Val Pro Val Met Ile Val Ala Tyr Pro Pro Arg 2480 2485 2490Ile Thr Asn Arg Pro Pro Arg Ser Ile Val Thr Arg Thr Gly Ala 2495 2500 2505Ala Phe Gln Leu His Cys Val Ala Leu Gly Val Pro Lys Pro Glu 2510 2515 2520Ile Thr Trp Glu Met Pro Asp His Ser Leu Leu Ser Thr Ala Ser 2525 2530 2535Lys Glu Arg Thr His Gly Ser Glu Gln Leu His Leu Gln Gly Thr 2540 2545 2550Leu Val Ile Gln Asn Pro Gln Thr Ser Asp Ser Gly Ile Tyr Lys 2555 2560 2565Cys Thr Ala Lys Asn Pro Leu Gly Ser Asp Tyr Ala Ala Thr Tyr 2570 2575 2580Ile Gln Val 258512236PRTMus musculusmisc_feature(1)..(236)'x' can be any amino acid 12Met Gln Lys Arg Gly Arg Glu Val Ser Cys Leu Leu Ile Ser Leu Thr1 5 10 15Ala Ile Cys Leu Val Val Thr Pro Gly Ser Arg Val Cys Pro Arg Arg 20 25 30Cys Ala Cys Tyr Val Pro Thr Glu Val His Cys Thr Phe Arg Asp Leu 35 40 45Thr Ser Ile Pro Asp Gly Pro Ala Asn Val Glu Arg Val Asn Leu Gly 50 55 60Tyr Asn Ser Leu Thr Arg Leu Thr Glu Asn Asp Phe Ser Gly Leu Ser65 70 75 80Arg Leu Glu Leu Leu Met Leu His Ser Asn Gly Ile His Arg Val Ser 85 90 95Asp Lys Thr Phe Ser Gly Leu Gln Ser Leu Gln Val Leu Lys Met Ser 100 105 110Tyr Asn Lys Val Gln Ile Ile Glu Lys Asp Thr Leu Tyr Gly Leu Arg 115 120 125Ser Leu Thr Arg Leu His Leu Asp His Asn Asn Ile Glu Phe Ile Asn 130 135 140Pro Glu Ala Phe Tyr Gly Leu Thr Leu Leu Arg Leu Val His Leu Glu145 150 155 160Gly Asn Arg Leu Thr Lys Leu His Pro Asp Thr Phe Val Ser Leu Ser 165 170 175Tyr Leu Gln Ile Phe Lys Thr Ser Phe Ile Lys Xaa Leu Tyr Leu Tyr 180 185 190Asp Asn Phe Thr Ser Leu Pro Lys Glu Met Val Ser Ser Met Pro Asn 195 200 205Leu Glu Ser Leu Tyr Leu His Gly Asn Pro Trp Thr Cys Asp Cys His 210 215 220Leu Lys Trp Leu Ser Glu Trp Met Gln Gly Asn Pro225 230 235132597PRTRattus speciesmisc_feature(1)..(2597)'x' can be any amino acid 13Met Gln Val Arg Gly Arg Glu Val Ser Gly Leu Leu Ile Ser Leu Thr1 5 10 15Ala Val Cys Leu Val Val Thr Pro Gly Ser Arg Ala Cys Pro Arg Arg 20 25 30Cys Ala Cys Tyr Val Pro Thr Glu Val His Cys Thr Phe Arg Tyr Leu 35 40 45Thr Ser Ile Pro Asp Gly Ile Pro Ala Asn Val Glu Arg Ile Asn Leu 50 55 60Gly Tyr Asn Ser Leu Thr Arg Leu Thr Glu Asn Asp Phe Asp Gly Leu65 70 75 80Ser Lys Leu Glu Leu Leu Met Leu His Ser Asn Gly Ile His Arg Val 85 90 95Ser Asp Lys Thr Phe Ser Gly Leu Gln Ser Leu Gln Val Leu Lys Met 100 105 110Ser Tyr Asn Lys Val Gln Ile Ile Arg Lys Asp Thr Phe Tyr Gly Leu 115 120 125Gly Ser Leu Val Arg Leu His Leu Asp His Asn Asn Ile Glu Phe Ile 130 135 140Asn Pro Glu Ala Phe Tyr Gly Leu Thr Ser Leu Arg Leu Val His Leu145 150 155 160Glu Gly Asn Arg Leu Thr Lys Leu His Pro Asp Thr Phe Val Ser Leu 165 170 175Ser Tyr Leu Gln Ile Phe Lys Thr Ser Phe Ile Lys Tyr Leu Phe Leu 180 185 190Ser Asp Asn Phe Leu Thr Ser Leu Pro Lys Glu Met Val Ser Tyr Met 195 200 205Pro Asn Leu Glu Ser Leu Tyr Leu His Gly Asn Pro Trp Thr Cys Asp 210 215 220Cys His Leu Lys Trp Leu Ser Glu Trp Met Gln Gly Asn Pro Asp Ile225 230 235 240Ile Lys Cys Lys Lys Asp Arg Ser Ser Ser Ser Pro Gln Gln Cys Pro 245 250 255Leu Cys Met Asn Pro Arg Ile Ser Lys Gly Arg Pro Phe Ala Met Val 260 265 270Pro Ser Gly Ala Phe Leu Cys Thr Lys Pro Thr Ile Asp Pro Ser Leu 275 280 285Lys Ser Lys Ser Leu Val Thr Gln Glu Asp Asn Gly Ser Ala Ser Thr 290 295 300Ser Pro Gln Asp Phe Ile Glu Pro Phe Gly Ser Leu Ser Leu Asn Met305 310 315 320Thr Xaa Xaa Ser Gly Asn Lys Ala Asp Met Val Cys Ser Ile Gln Lys 325 330 335Pro Ser Arg Thr Ser Pro Thr Ala Phe Thr Glu Glu Asn Asp Tyr Ile 340 345 350Met Leu Asn Ala Ser Phe Ser Thr Asn Leu Val Cys Ser Val Asp Tyr 355 360 365Asn His Ile Gln Pro Val Trp Gln Leu Leu Ala Leu Tyr Ser Asp Ser 370 375 380Pro Leu Ile Leu Glu Arg Lys Pro Gln Leu Thr Glu Thr Pro Ser Leu385 390 395 400Ser Ser Arg Tyr Lys Gln Val Ala Leu Arg Pro Glu Asp Ile Phe Thr 405 410 415Ser Ile Glu Ala Asp Val Arg Ala Asp Pro Phe Trp Phe Gln Gln Glu 420 425 430Lys Ile Val Leu Gln Leu Asn Arg Thr Ala Thr Thr Leu Ser Thr Leu 435 440 445Gln Ile Gln Phe Ser Thr Asp Ala Gln Ile Ala Leu Pro Arg Ala Glu 450 455 460Met Arg Ala Glu Arg Leu Lys Trp Thr Met Ile Leu Met Met Asn Asn465 470 475 480Pro Lys Leu Glu Arg Thr Val Leu Val Gly Gly Thr Ile Ala Leu Ser 485 490 495Cys Pro Gly Lys Gly Asp Pro Ser Pro His Leu Glu Trp Leu Leu Ala 500 505 510Asp Gly Ser Lys Val Arg Ala Pro Tyr Val Ser Glu Asp Gly Arg Ile 515 520 525Leu Ile Asp Lys Asn Gly Lys Leu Glu Leu Gln Met Ala Asp Ser Phe 530 535 540Asp Ala Gly Leu Tyr His Cys Ile Ser Thr Asn Asp Ala Asp Ala Asp545 550 555 560Val Leu Thr Tyr Arg Ile Thr Val Val Glu Pro Tyr Gly Glu Ser Thr 565 570 575His Asp Ser Gly Val Gln His Thr Val Val Thr Gly Glu Thr Leu Asp 580 585 590Leu Pro Cys Leu Ser Thr Gly Val Pro Asp Ala Ser Ile Ser Trp Ile 595 600 605Leu Pro Gly Asn Thr Val Phe Ser Gln Pro Ser Arg Asp Arg Gln Ile 610 615 620Leu Asn Asn Gly Thr Leu Arg Ile Leu Gln Val Thr Pro Lys Asp Gln625 630 635 640Gly His Tyr Gln Cys Val Ala Ala Asn Pro Ser Gly Ala Asp Phe Ser 645 650 655Ser Phe Lys Val Ser Val Gln Lys Lys Gly Gln Arg Met Val Glu His 660 665 670Asp Arg Glu Ala Gly Gly Ser Gly Leu Gly Glu Pro Asn Ser Ser Val 675 680 685Ser Leu Lys Gln Pro Ala Ser Leu Lys Leu Ser Ala Ser Ala Leu Thr 690 695 700Gly Ser Glu Ala Gly Lys Gln Val Ser Gly Val His Arg Lys Asn Lys705 710 715 720His Arg Asp Leu Ile His Arg Arg Arg Gly Asp Ser Thr Leu Arg Arg 725 730 735Phe Arg Glu His Arg Arg Gln Leu Pro Leu Ser Ala Arg Arg Ile Asp 740 745 750Pro Gln Arg Trp Ala Ala Leu Leu Glu Lys Ala Lys Lys Asn Ser Val 755 760 765Pro Lys Lys Gln Glu Asn Thr Thr Val Lys Pro Val Pro Leu Ala Val 770 775 780Pro Leu Val Glu Leu Thr Asp Glu Glu Lys Asp Ala Ser Gly Met Ile785 790 795 800Pro Pro Asp Glu Glu Phe Met Val Leu Lys Thr Lys Ala Ser Gly Val 805 810 815Pro Gly Arg Ser Pro Thr Ala Asp Ser Gly Pro Val Asn His Gly Phe 820 825 830Met Thr Ser Ile Ala Ser Gly Thr Glu Val Ser Thr Val Asn Pro Gln 835 840 845Thr Leu Gln Ser Glu His Leu Pro Asp Phe Lys Leu Phe Ser Val Thr 850 855 860Asn Gly Thr Ala Val Thr Lys Ser Met Asn Pro Ser Ile Ala Ser Lys865 870 875 880Ile Glu Asp Thr Thr Asn Gln Asn Pro Ile Ile Ile Phe Pro Ser Val 885 890 895Ala Glu Ile Arg Asp Ser Ala Gln Ala Gly Arg Ala Ser Ser Gln Ser 900 905 910Ala His Pro Val Thr Gly Gly Asn Met Ala Thr Tyr Gly His Thr Asn 915 920 925Thr Tyr Ser Ser Phe Thr Ser Lys Ala Ser Thr Val Leu Gln Pro Ile 930 935 940Asn Pro Thr Glu Ser Tyr Gly Pro Gln Ile Pro Ile Thr Gly Val Ser945 950 955 960Arg Pro Ser Ser Ser Asp Ile Ser Ser His Thr Thr Ala Asp Pro Ser 965 970 975Phe Ser Ser His Pro Ser Gly Ser His Thr Thr Ala Ser Ser Leu Phe 980 985 990His Ile Pro Arg Asn Asn Asn Thr Gly Asn Phe Pro Leu Ser Arg His 995 1000 1005Leu Gly Arg Glu Arg Thr Ile Trp Ser Arg Gly Arg Val Lys Asn 1010 1015 1020Pro His Arg Thr Pro Val Leu Arg Arg His Arg His Arg Thr Val 1025 1030 1035Arg Pro Ala Ile Lys Gly Pro Ala Asn Lys Asn Val Ser Gln Val 1040 1045 1050Pro Ala Thr Glu Tyr Pro Gly Met Cys His Thr Cys Pro Ser Ala 1055 1060 1065Glu Gly Leu Thr Val Ala Thr Ala Ala Leu Ser Val Pro Ser Ser 1070 1075 1080Ser His Ser Ala Leu Pro Lys Thr Asn Asn Val Gly Val Ile Ala 1085 1090 1095Glu Glu Ser Thr Thr Val Val Lys Lys Pro Leu Leu Leu Phe Lys 1100 1105 1110Asp Lys Gln Asn Val Asp Ile Glu Ile Ile Thr Thr Thr Thr Lys 1115 1120 1125Tyr Ser Gly Gly Glu Ser Asn His Val Ile Pro Thr Glu Ala Ser 1130 1135 1140Met Thr Ser Ala Pro Thr Ser Val Ser Leu Gly Lys Ser Pro Val 1145 1150 1155Asp Asn Ser Gly His Leu Ser Met Pro Gly Thr Ile Gln Thr Gly 1160 1165 1170Lys Asp Ser Val Glu Thr Thr Pro Leu Pro Ser Pro Leu Ser Thr 1175 1180 1185Pro Ser Ile Pro Thr Ser Thr Lys Phe Ser Lys Arg Lys Thr Pro 1190 1195 1200Leu His Gln Ile Phe Val Asn Asn Gln Lys Lys Glu Gly Met Leu 1205 1210 1215Lys Asn Pro Tyr Gln Phe Gly Leu Gln Lys Asn Pro Ala Ala Lys 1220 1225 1230Leu Pro Lys Ile Ala Pro Leu Leu Pro Thr Gly Gln Ser Ser Pro 1235 1240 1245Ser Asp Ser Thr Thr Leu Leu Thr Ser Pro Pro Pro Ala Leu Ser 1250 1255 1260Thr Thr Met Ala Ala Thr Gln Asn Lys Gly Thr Glu Val Val Ser 1265 1270 1275Gly Ala Arg Ser Leu Ser Ala Gly Lys Lys Gln Pro Phe Thr Asn 1280 1285 1290Ser Ser Pro Val Leu Pro Ser Thr Ile Ser Lys Arg Ser Asn Thr 1295 1300 1305Leu Asn Phe Leu Ser Thr Glu Thr Pro Thr Val Thr Ser Pro Thr 1310 1315 1320Ala Thr Ala Ser Val Ile Met Ser Glu Thr Gln Arg Thr Arg Ser 1325 1330 1335Lys Glu Ala Lys Asp Gln Ile Lys Gly Pro Arg Lys Asn Arg Asn 1340 1345 1350Asn Ala Asn Thr Thr Pro Arg Gln Val Ser Gly Tyr Ser Ala Tyr 1355 1360 1365Ser Ala Leu Thr Thr Ala Asp Thr Pro Leu Ala Phe Ser His Ser 1370 1375 1380Pro Arg Gln Asp Asp Gly Gly Asn Val Ser Ala Val Ala Tyr His 1385 1390 1395Ser Thr Thr Ser Leu Leu Ala Ile Thr Glu Leu Phe Glu Lys Tyr 1400 1405 1410Thr Gln Thr Leu Gly Asn Thr Thr Ala Leu Glu Thr Thr Leu Leu 1415 1420 1425Ser Lys Ser Gln Glu Ser Thr Thr Val Lys Arg Ala Ser Asp Thr 1430 1435 1440Pro Pro Pro Leu Leu Ser Ser Gly Ala Pro Pro Val Pro Thr Pro 1445 1450 1455Ser Pro Pro Pro Phe Thr Lys Gly Val Val Thr Asp Ser Lys Val 1460 1465 1470Thr Ser Ala Phe Gln Met Thr Ser Asn Arg Val Val Thr Ile Tyr 1475 1480 1485Glu Ser Ser Arg His Asn Thr Asp Leu Gln Gln Pro Ser Ala Glu 1490 1495 1500Ala Ser Pro Asn Pro Glu Ile Ile Thr Gly Thr Thr Asp Ser Pro 1505 1510 1515Ser Asn Leu Phe Pro Ser Thr Ser Val Pro Ala Leu Arg Val Asp 1520 1525 1530Lys Pro Gln Asn Ser Lys Trp Lys Pro Ser Pro Trp Pro Glu His 1535 1540 1545Lys Tyr Gln Leu Lys Ser Tyr Ser Glu Thr Ile Glu Lys Gly Lys 1550 1555 1560Arg Pro Ala Val Ser Met Ser Pro His Leu Ser Leu Pro Glu Ala 1565 1570 1575Ser Thr His Ala Ser His Trp Asn Thr Gln Lys His Ala Glu Lys 1580 1585 1590Ser Val Phe Asp Lys Lys Pro Gly Gln Asn Pro Thr Ser Lys His 1595 1600 1605Leu Pro Tyr Val Ser Leu Pro Lys Thr Leu Leu Lys Lys Pro Arg 1610 1615 1620Ile Ile Gly Gly Lys Ala Ala Ser Phe Thr Val Pro Ala Asn Ser 1625 1630 1635Asp Val Phe Leu Pro Cys Glu Ala Val Gly Asp Pro Leu Pro Ile 1640 1645 1650Ile His Trp Thr Arg Val Ser Ser Gly Xaa Glu Ile Ser Gln Gly 1655 1660 1665Thr Gln Lys Ser Arg Phe His Val Leu Pro Asn Gly Thr Leu Ser 1670 1675 1680Ile Gln Arg Val Ser Ile Gln Asp Arg Gly Gln Tyr Leu Cys Ser 1685 1690 1695Ala Phe Asn Pro Leu Gly Val Asp His Phe His Val Ser Leu Ser 1700 1705 1710Val Val Phe Tyr Pro Ala Arg Ile Leu Asp Arg His Val Lys Glu 1715 1720 1725Ile Thr Val His Phe Gly Ser Thr Val Glu Leu Lys Cys Arg Val 1730 1735 1740Glu Gly Met Pro Arg Pro Thr Val Ser Trp Ile Leu Ala Asn Gln 1745 1750 1755Thr Val Val Ser Glu Thr Ala Lys Gly Ser Arg Lys Val Trp Val 1760 1765 1770Thr Pro Asp Gly Thr Leu Ile Ile Tyr Asn Leu Ser Leu Tyr Asp 1775 1780 1785Arg Gly Phe Tyr Lys Cys Val Ala Ser Asn Pro Ser Gly Gln Asp 1790 1795 1800Ser Leu Leu Val Lys Ile Gln Val Ile Thr Ala Pro Pro Val Ile 1805 1810 1815Ile Glu Gln Lys Arg Gln Ala Ile Val Gly Val Leu Gly Gly Ser 1820 1825 1830Leu Lys Leu Pro Cys Thr Ala Lys Gly Thr Pro Gln Pro Ser Val 1835 1840 1845His Trp Val Leu Tyr Asp Gly Thr Glu Leu Lys Pro Leu Gln Leu 1850 1855 1860Thr His Ser Arg Phe Phe Leu Tyr Pro Asn Gly Thr Leu Tyr Ile 1865 1870 1875Arg Ser Ile Ala Pro Ser Val Arg Gly Thr Tyr Glu Cys Ile Ala 1880 1885

1890Thr Ser Ser Ser Gly Ser Glu Arg Arg Val Val Ile Leu Thr Val 1895 1900 1905Glu Glu Gly Glu Thr Ile Pro Arg Ile Glu Thr Ala Ser Gln Lys 1910 1915 1920Trp Thr Glu Val Asn Leu Gly Glu Lys Leu Leu Leu Asn Cys Ser 1925 1930 1935Ala Thr Gly Asp Pro Lys Pro Arg Ile Ile Trp Arg Leu Pro Ser 1940 1945 1950Lys Ala Val Ile Asp Gln Trp His Arg Met Gly Ser Arg Ile His 1955 1960 1965Val Tyr Pro Asn Gly Ser Leu Val Val Gly Ser Val Thr Glu Lys 1970 1975 1980Asp Ala Gly Asp Tyr Leu Cys Val Ala Arg Asn Lys Met Gly Asp 1985 1990 1995Asp Leu Val Leu Met His Val Arg Leu Arg Leu Thr Pro Ala Lys 2000 2005 2010Ile Glu Gln Lys Gln Tyr Phe Lys Lys Gln Val Leu His Gly Lys 2015 2020 2025Asp Phe Gln Val Asp Cys Lys Ala Ser Gly Ser Pro Val Pro Glu 2030 2035 2040Val Ser Trp Ser Leu Pro Asp Gly Thr Val Leu Asn Asn Val Ala 2045 2050 2055Gln Ala Asp Asp Ser Gly Tyr Arg Thr Lys Arg Tyr Thr Leu Phe 2060 2065 2070His Asn Gly Thr Leu Tyr Phe Asn Asn Val Gly Met Ala Glu Glu 2075 2080 2085Gly Asp Tyr Ile Cys Ser Ala Gln Asn Thr Leu Gly Lys Asp Glu 2090 2095 2100Met Lys Val His Leu Thr Val Leu Thr Ala Ile Pro Arg Ile Arg 2105 2110 2115Gln Ser Tyr Lys Thr Thr Met Arg Leu Arg Ala Gly Glu Thr Ala 2120 2125 2130Val Leu Asp Cys Glu Val Thr Gly Glu Pro Lys Pro Asn Val Phe 2135 2140 2145Trp Leu Leu Pro Ser Asn Asn Val Ile Ser Phe Ser Asn Asp Arg 2150 2155 2160Phe Thr Phe His Ala Asn Arg Thr Leu Ser Ile His Lys Val Lys 2165 2170 2175Pro Leu Asp Ser Gly Asp Tyr Val Cys Val Ala Gln Asn Pro Ser 2180 2185 2190Gly Asp Asp Thr Lys Thr Tyr Lys Leu Asp Ile Val Ser Lys Pro 2195 2200 2205Pro Leu Ile Asn Gly Leu Tyr Ala Asn Lys Thr Val Ile Lys Ala 2210 2215 2220Thr Ala Ile Arg His Ser Lys Lys Tyr Phe Asp Cys Arg Ala Asp 2225 2230 2235Gly Ile Pro Ser Ser Gln Val Thr Trp Ile Met Pro Gly Asn Ile 2240 2245 2250Phe Leu Pro Ala Pro Tyr Phe Gly Ser Arg Val Thr Val His Pro 2255 2260 2265Asn Gly Thr Leu Glu Met Arg Asn Ile Arg Leu Ser Asp Ser Ala 2270 2275 2280Asp Phe Thr Cys Val Val Arg Ser Glu Gly Gly Glu Ser Val Leu 2285 2290 2295Val Val Gln Leu Glu Val Leu Glu Met Leu Arg Arg Pro Thr Phe 2300 2305 2310Arg Asn Pro Phe Asn Glu Lys Val Ile Ala Gln Ala Gly Lys Pro 2315 2320 2325Val Ala Leu Asn Cys Ser Val Asp Gly Asn Pro Pro Pro Glu Ile 2330 2335 2340Thr Trp Ile Leu Pro Asp Gly Thr Gln Phe Ala Asn Arg Pro His 2345 2350 2355Asn Ser Pro Tyr Leu Met Ala Gly Asn Gly Ser Leu Ile Leu Tyr 2360 2365 2370Lys Ala Thr Arg Asn Lys Ser Gly Lys Tyr Arg Cys Ala Ala Arg 2375 2380 2385Asn Lys Val Gly Tyr Ile Glu Lys Leu Ile Leu Leu Glu Ile Gly 2390 2395 2400Gln Lys Pro Val Ile Leu Thr Tyr Glu Pro Gly Met Val Lys Ser 2405 2410 2415Val Ser Gly Glu Pro Leu Ser Leu His Cys Val Ser Asp Gly Ile 2420 2425 2430Pro Lys Pro Asn Val Lys Trp Thr Thr Pro Gly Gly His Val Ile 2435 2440 2445Asp Arg Pro Gln Val Asp Gly Lys Tyr Ile Leu His Glu Asn Gly 2450 2455 2460Thr Leu Val Ile Lys Ala Thr Thr Ala His Asp Gln Gly Asn Tyr 2465 2470 2475Ile Cys Arg Ala Gln Asn Ser Val Gly Gln Ala Val Ile Ser Val 2480 2485 2490Ser Val Met Val Val Ala Tyr Pro Pro Arg Ile Ile Asn Tyr Leu 2495 2500 2505Pro Arg Asn Met Leu Arg Arg Thr Gly Glu Ala Met Gln Leu His 2510 2515 2520Cys Val Ala Leu Gly Ile Pro Lys Pro Lys Val Thr Trp Glu Thr 2525 2530 2535Pro Arg His Ser Leu Leu Ser Lys Ala Thr Ala Arg Lys Pro His 2540 2545 2550Arg Ser Glu Met Leu His Pro Gln Gly Thr Leu Val Ile Gln Asn 2555 2560 2565Leu Gln Thr Ser Asp Ser Gly Val Tyr Lys Cys Arg Ala Gln Asn 2570 2575 2580Leu Leu Gly Thr Asp Tyr Ala Thr Thr Tyr Ile Gln Val Leu 2585 2590 2595142586PRTHomo sapiens 14Met Lys Val Lys Gly Arg Gly Ile Thr Cys Leu Leu Val Ser Phe Ala1 5 10 15Val Ile Cys Leu Val Ala Thr Pro Gly Gly Lys Ala Cys Pro Arg Arg 20 25 30Cys Ala Cys Tyr Met Pro Thr Glu Val His Cys Thr Phe Arg Tyr Leu 35 40 45Thr Ser Ile Pro Asp Ser Ile Pro Pro Asn Val Glu Arg Ile Asn Leu 50 55 60Gly Tyr Asn Ser Leu Val Arg Leu Met Glu Thr Asp Phe Ser Gly Leu65 70 75 80Thr Lys Leu Glu Leu Leu Met Leu His Ser Asn Gly Ile His Thr Ile 85 90 95Pro Asp Lys Thr Phe Ser Asp Leu Gln Ala Leu Gln Val Leu Lys Met 100 105 110Ser Tyr Asn Lys Val Arg Lys Leu Gln Lys Asp Thr Phe Tyr Gly Leu 115 120 125Arg Ser Leu Thr Arg Leu His Met Asp His Asn Asn Ile Glu Phe Ile 130 135 140Asn Pro Glu Val Phe Tyr Gly Leu Asn Phe Leu Arg Leu Val His Leu145 150 155 160Glu Gly Asn Gln Leu Thr Lys Leu His Pro Asp Thr Phe Val Ser Leu 165 170 175Ser Tyr Leu Gln Ile Phe Lys Ile Ser Phe Ile Lys Phe Leu Tyr Leu 180 185 190Ser Asp Asn Phe Leu Thr Ser Leu Pro Gln Glu Met Val Ser Tyr Met 195 200 205Pro Asp Leu Asp Ser Leu Tyr Leu His Gly Asn Pro Trp Thr Cys Asp 210 215 220Cys His Leu Lys Trp Leu Ser Asp Trp Ile Gln Pro Asp Val Ile Lys225 230 235 240Cys Lys Lys Asp Arg Ser Pro Ser Ser Ala Gln Gln Cys Pro Leu Cys 245 250 255Met Asn Pro Arg Thr Ser Lys Gly Lys Pro Leu Ala Met Val Ser Ala 260 265 270Ala Ala Phe Gln Cys Ala Lys Pro Thr Ile Asp Ser Ser Leu Lys Ser 275 280 285Lys Ser Leu Thr Ile Leu Glu Asp Ser Ser Ser Ala Phe Ile Ser Pro 290 295 300Gln Gly Phe Met Ala Pro Phe Gly Ser Leu Thr Leu Asn Met Thr Asp305 310 315 320Gln Ser Gly Asn Glu Ala Asn Met Val Cys Ser Ile Gln Lys Pro Ser 325 330 335Arg Thr Ser Pro Ile Ala Phe Thr Glu Glu Asn Asp Tyr Ile Val Leu 340 345 350Asn Thr Ser Phe Ser Thr Phe Leu Val Cys Asn Ile Asp Tyr Gly His 355 360 365Ile Gln Pro Val Trp Gln Ile Leu Ala Leu Tyr Ser Asp Ser Pro Leu 370 375 380Ile Leu Glu Arg Ser His Leu Leu Ser Glu Thr Pro Gln Leu Tyr Tyr385 390 395 400Lys Tyr Lys Gln Val Ala Pro Lys Pro Glu Asp Ile Phe Thr Asn Ile 405 410 415Glu Ala Asp Leu Arg Ala Asp Pro Ser Trp Leu Met Gln Asp Gln Ile 420 425 430Ser Leu Gln Leu Asn Arg Thr Ala Thr Thr Phe Ser Thr Leu Gln Ile 435 440 445Gln Tyr Ser Ser Asp Ala Gln Ile Thr Leu Pro Arg Ala Glu Met Arg 450 455 460Pro Val Lys His Lys Trp Thr Met Ile Ser Arg Asp Asn Asn Thr Lys465 470 475 480Leu Glu His Thr Val Leu Val Gly Gly Thr Val Gly Leu Asn Cys Pro 485 490 495Gly Gln Gly Asp Pro Thr Pro His Val Asp Trp Leu Leu Ala Asp Gly 500 505 510Ser Lys Val Arg Ala Pro Tyr Val Ser Glu Asp Gly Arg Ile Leu Ile 515 520 525Asp Lys Ser Gly Lys Leu Glu Leu Gln Met Ala Asp Ser Phe Asp Thr 530 535 540Gly Val Tyr His Cys Ile Ser Ser Asn Tyr Asp Asp Ala Asp Ile Leu545 550 555 560Thr Tyr Arg Ile Thr Val Val Glu Pro Leu Val Glu Ala Tyr Gln Glu 565 570 575Asn Gly Ile His His Thr Val Phe Ile Gly Glu Thr Leu Asp Leu Pro 580 585 590Cys His Ser Thr Gly Ile Pro Asp Ala Ser Ile Ser Trp Val Ile Pro 595 600 605Gly Asn Asn Val Leu Tyr Gln Ser Ser Arg Asp Lys Lys Val Leu Asn 610 615 620Asn Gly Thr Leu Arg Ile Leu Gln Val Thr Pro Lys Asp Gln Gly Tyr625 630 635 640Tyr Arg Cys Val Ala Ala Asn Pro Ser Gly Val Asp Phe Leu Ile Phe 645 650 655Gln Val Ser Val Lys Met Lys Gly Gln Arg Pro Leu Glu His Asp Gly 660 665 670Glu Thr Glu Gly Ser Gly Leu Asp Glu Ser Asn Pro Ile Ala His Leu 675 680 685Lys Glu Pro Pro Gly Ala Gln Leu Arg Thr Ser Ala Leu Met Glu Ala 690 695 700Glu Val Gly Lys His Thr Ser Ser Thr Ser Lys Arg His Asn Tyr Arg705 710 715 720Glu Leu Thr Leu Gln Arg Arg Gly Asp Ser Thr His Arg Arg Phe Arg 725 730 735Glu Asn Arg Arg His Phe Pro Pro Ser Ala Arg Arg Ile Asp Pro Gln 740 745 750His Trp Ala Ala Leu Leu Glu Lys Ala Lys Lys Asn Ala Met Pro Asp 755 760 765Lys Arg Glu Asn Thr Thr Val Ser Pro Pro Pro Val Val Thr Gln Leu 770 775 780Pro Asn Ile Pro Gly Glu Glu Asp Asp Ser Ser Gly Met Leu Ala Leu785 790 795 800His Glu Glu Phe Met Val Pro Ala Thr Lys Ala Leu Asn Leu Pro Ala 805 810 815Arg Thr Val Thr Ala Asp Ser Arg Thr Ile Ser Asp Ser Pro Met Thr 820 825 830Asn Ile Asn Tyr Gly Thr Glu Phe Ser Pro Val Val Asn Ser Gln Ile 835 840 845Leu Pro Pro Glu Glu Pro Thr Asp Phe Lys Leu Ser Thr Ala Ile Lys 850 855 860Thr Thr Ala Met Ser Lys Asn Ile Asn Pro Thr Met Ser Ser Gln Ile865 870 875 880Gln Gly Thr Thr Asn Gln His Ser Ser Thr Val Phe Pro Leu Leu Leu 885 890 895Gly Ala Thr Glu Phe Gln Asp Ser Asp Gln Met Gly Arg Gly Arg Glu 900 905 910His Phe Gln Ser Arg Pro Pro Ile Thr Val Arg Thr Met Ile Lys Asp 915 920 925Val Asn Val Lys Met Leu Ser Ser Thr Thr Asn Lys Leu Leu Leu Glu 930 935 940Ser Val Asn Thr Thr Asn Ser His Gln Thr Ser Val Arg Glu Val Ser945 950 955 960Glu Pro Arg His Asn His Phe Tyr Ser His Thr Thr Gln Ile Leu Ser 965 970 975Thr Ser Thr Phe Pro Ser Asp Pro His Thr Ala Ala His Ser Gln Phe 980 985 990Pro Ile Pro Arg Asn Ser Thr Val Asn Ile Pro Leu Phe Arg Arg Phe 995 1000 1005Gly Arg Gln Arg Lys Ile Gly Gly Arg Gly Arg Ile Ile Ser Pro 1010 1015 1020Tyr Arg Thr Pro Val Leu Arg Arg His Arg Tyr Ser Ile Phe Arg 1025 1030 1035Ser Thr Thr Arg Gly Ser Ser Glu Lys Ser Thr Thr Ala Phe Ser 1040 1045 1050Ala Thr Val Leu Asn Val Thr Cys Leu Ser Cys Leu Pro Arg Glu 1055 1060 1065Arg Leu Thr Thr Ala Thr Ala Ala Leu Ser Phe Pro Ser Ala Ala 1070 1075 1080Pro Ile Thr Phe Pro Lys Ala Asp Ile Ala Arg Val Pro Ser Glu 1085 1090 1095Glu Ser Thr Thr Leu Val Gln Asn Pro Leu Leu Leu Leu Glu Asn 1100 1105 1110Lys Pro Ser Val Glu Lys Thr Thr Pro Thr Ile Lys Tyr Phe Arg 1115 1120 1125Thr Glu Ile Ser Gln Val Thr Pro Thr Gly Ala Val Met Thr Tyr 1130 1135 1140Ala Pro Thr Ser Ile Pro Met Glu Lys Thr His Lys Val Asn Ala 1145 1150 1155Ser Tyr Pro Arg Val Ser Ser Thr Asn Glu Ala Lys Arg Asp Ser 1160 1165 1170Val Ile Thr Ser Ser Leu Ser Gly Ala Ile Thr Lys Pro Pro Met 1175 1180 1185Thr Ile Ile Ala Ile Thr Arg Phe Ser Arg Arg Lys Ile Pro Trp 1190 1195 1200Gln Gln Asn Phe Val Asn Asn His Asn Pro Lys Gly Arg Leu Arg 1205 1210 1215Asn Gln His Lys Val Ser Leu Gln Lys Ser Thr Ala Val Met Leu 1220 1225 1230Pro Lys Thr Ser Pro Ala Leu Pro Gln Arg Gln Ser Ser Pro Phe 1235 1240 1245His Phe Thr Thr Leu Ser Thr Ser Val Met Gln Ile Pro Ser Asn 1250 1255 1260Thr Leu Thr Thr Ala His His Thr Thr Thr Lys Thr His Asn Pro 1265 1270 1275Gly Ser Leu Pro Thr Lys Lys Glu Leu Pro Phe Pro Pro Leu Asn 1280 1285 1290Pro Met Leu Pro Ser Ile Ile Ser Lys Asp Ser Ser Thr Lys Ser 1295 1300 1305Ile Ile Ser Thr Gln Thr Ala Ile Pro Ala Thr Thr Pro Thr Phe 1310 1315 1320Pro Ala Ser Val Ile Thr Tyr Glu Thr Gln Thr Glu Arg Ser Arg 1325 1330 1335Ala Gln Thr Ile Gln Arg Glu Gln Glu Pro Gln Lys Lys Asn Arg 1340 1345 1350Thr Asp Pro Asn Ile Ser Pro Asp Gln Ser Ser Gly Phe Thr Thr 1355 1360 1365Pro Thr Ala Met Thr Pro Pro Ala Leu Ala Phe Thr His Ser Pro 1370 1375 1380Pro Glu Asn Thr Thr Gly Ile Ser Ser Thr Ile Ser Phe His Ser 1385 1390 1395Arg Thr Leu Asn Leu Thr Asp Val Ile Glu Glu Leu Ala Gln Ala 1400 1405 1410Ser Thr Gln Thr Leu Lys Ser Thr Ile Ala Ser Glu Thr Thr Leu 1415 1420 1425Ser Ser Lys Ser His Gln Ser Thr Thr Thr Arg Lys Ala Ser Leu 1430 1435 1440Asp Thr Pro Ile Pro Pro Phe Leu Ser Ser Ser Ala Thr Leu Met 1445 1450 1455Pro Val Pro Ile Ser Pro Pro Phe Thr Gln Arg Ala Val Thr Asp 1460 1465 1470Thr Arg Gly Asp Ser His Phe Arg Leu Met Thr Asn Thr Val Val 1475 1480 1485Lys Leu His Glu Ser Ser Arg His Asn Leu Gln Met Pro Ser Ser 1490 1495 1500Gln Leu Glu Pro Leu Thr Ser Ser Thr Ser Asn Leu Leu His Ser 1505 1510 1515Thr Pro Met Pro Ala Leu Thr Thr Val Lys Ser Gln Asn Ser Lys 1520 1525 1530Leu Thr Pro Ser Pro Trp Ala Glu Tyr Gln Phe Trp His Lys Pro 1535 1540 1545Tyr Ser Asp Ile Ala Glu Lys Gly Lys Lys Pro Glu Val Ser Met 1550 1555 1560Leu Ala Thr Thr Gly Leu Ser Glu Ala Thr Thr Leu Val Ser Asp 1565 1570 1575Trp Asp Gly Gln Lys Asn Thr Lys Lys Ser Asp Phe Asp Lys Lys 1580 1585 1590Pro Val Gln Glu Ala Thr Thr Ser Lys Leu Leu Pro Phe Asp Ser 1595 1600 1605Leu Ser Arg Tyr Ile Phe Glu Lys Pro Arg Ile Val Gly Gly Lys 1610 1615 1620Ala Ala Ser Phe Thr Ile Pro Ala Asn Ser Asp Ala Phe Leu Pro 1625 1630 1635Cys Glu Ala Val Gly Asn Pro Leu Pro Thr Ile His Trp Thr Arg 1640 1645 1650Val Ser Gly Leu Asp Leu Ser Arg Gly Asn Gln Asn Ser Arg Val 1655 1660 1665Gln Val Leu Pro Asn Gly Thr Leu Ser Ile Gln Arg Val Glu Ile 1670 1675 1680Gln Asp Arg Gly Gln Tyr Leu Cys Ser Ala Ser Asn Leu Phe Gly 1685 1690 1695Thr Asp His Leu His Val Thr Leu Ser Val Val Ser Tyr Pro Pro 1700 1705 1710Arg Ile Leu Glu Arg Arg Thr Lys Glu Ile Thr Val His Ser Gly 1715 1720 1725Ser Thr Val Glu Leu Lys Cys Arg Ala Glu Gly Arg Pro Ser Pro 1730

1735 1740Thr Val Thr Trp Ile Leu Ala Asn Gln Thr Val Val Ser Glu Ser 1745 1750 1755Ser Gln Gly Ser Arg Gln Ala Val Val Thr Val Asp Gly Thr Leu 1760 1765 1770Val Leu His Asn Leu Ser Ile Tyr Asp Arg Gly Phe Tyr Lys Cys 1775 1780 1785Val Ala Ser Asn Pro Gly Gly Gln Asp Ser Leu Leu Val Lys Ile 1790 1795 1800Gln Val Ile Ala Ala Pro Pro Val Ile Leu Glu Gln Arg Arg Gln 1805 1810 1815Val Ile Val Gly Thr Trp Gly Glu Ser Leu Lys Leu Pro Cys Thr 1820 1825 1830Ala Lys Gly Thr Pro Gln Pro Ser Val Tyr Trp Val Leu Ser Asp 1835 1840 1845Gly Thr Glu Val Lys Pro Leu Gln Phe Thr Asn Ser Lys Leu Phe 1850 1855 1860Leu Phe Ser Asn Gly Thr Leu Tyr Ile Arg Asn Leu Ala Ser Ser 1865 1870 1875Asp Arg Gly Thr Tyr Glu Cys Ile Ala Thr Ser Ser Thr Gly Ser 1880 1885 1890Glu Arg Arg Val Val Met Leu Thr Met Glu Glu Arg Val Thr Ser 1895 1900 1905Pro Arg Ile Glu Ala Ala Ser Gln Lys Arg Thr Glu Val Asn Phe 1910 1915 1920Gly Asp Lys Leu Leu Leu Asn Cys Ser Ala Thr Gly Glu Pro Lys 1925 1930 1935Pro Gln Ile Met Trp Arg Leu Pro Ser Lys Ala Val Val Asp Gln 1940 1945 1950Gly Ser Trp Ile His Val Tyr Pro Asn Gly Ser Leu Phe Ile Gly 1955 1960 1965Ser Val Thr Glu Lys Asp Ser Gly Val Tyr Leu Cys Val Ala Arg 1970 1975 1980Asn Lys Met Gly Asp Asp Leu Ile Leu Met His Val Ser Leu Arg 1985 1990 1995Leu Lys Pro Ala Lys Ile Asp His Lys Gln Tyr Phe Arg Lys Gln 2000 2005 2010Val Leu His Gly Lys Asp Phe Gln Val Asp Cys Lys Ala Ser Gly 2015 2020 2025Ser Pro Val Pro Glu Ile Ser Trp Ser Leu Pro Asp Gly Thr Met 2030 2035 2040Ile Asn Asn Ala Met Gln Ala Asp Asp Ser Gly His Arg Thr Arg 2045 2050 2055Arg Tyr Thr Leu Phe Asn Asn Gly Thr Leu Tyr Phe Asn Lys Val 2060 2065 2070Gly Val Ala Glu Glu Gly Asp Tyr Thr Cys Tyr Ala Gln Asn Thr 2075 2080 2085Leu Gly Lys Asp Glu Met Lys Val His Leu Thr Val Ile Thr Ala 2090 2095 2100Ala Pro Arg Ile Arg Gln Ser Asn Lys Thr Asn Lys Arg Ile Lys 2105 2110 2115Ala Gly Asp Thr Ala Val Leu Asp Cys Glu Val Thr Gly Asp Pro 2120 2125 2130Lys Pro Lys Ile Phe Trp Leu Leu Pro Ser Asn Asp Met Ile Ser 2135 2140 2145Phe Ser Ile Asp Arg Tyr Thr Phe His Ala Asn Gly Ser Leu Thr 2150 2155 2160Ile Asn Lys Val Lys Leu Leu Asp Ser Gly Glu Tyr Val Cys Val 2165 2170 2175Ala Arg Asn Pro Ser Gly Asp Asp Thr Lys Met Tyr Lys Leu Asp 2180 2185 2190Val Val Ser Lys Pro Pro Leu Ile Asn Gly Leu Tyr Thr Asn Arg 2195 2200 2205Thr Val Ile Lys Ala Thr Ala Val Arg His Ser Lys Lys His Phe 2210 2215 2220Asp Cys Arg Ala Glu Gly Thr Pro Ser Pro Glu Val Met Trp Ile 2225 2230 2235Met Pro Asp Asn Ile Phe Leu Thr Ala Pro Tyr Tyr Gly Ser Arg 2240 2245 2250Ile Thr Val His Lys Asn Gly Thr Leu Glu Ile Arg Asn Val Arg 2255 2260 2265Leu Ser Asp Ser Ala Asp Phe Ile Cys Val Ala Arg Asn Glu Gly 2270 2275 2280Gly Glu Ser Val Leu Val Val Gln Leu Glu Val Leu Glu Met Leu 2285 2290 2295Arg Arg Pro Thr Phe Arg Asn Pro Phe Asn Glu Lys Ile Val Ala 2300 2305 2310Gln Leu Gly Lys Ser Thr Ala Leu Asn Cys Ser Val Asp Gly Asn 2315 2320 2325Pro Pro Pro Glu Ile Ile Trp Ile Leu Pro Asn Gly Thr Arg Phe 2330 2335 2340Ser Asn Gly Pro Gln Ser Tyr Gln Tyr Leu Ile Ala Ser Asn Gly 2345 2350 2355Ser Phe Ile Ile Ser Lys Thr Thr Arg Glu Asp Ala Gly Lys Tyr 2360 2365 2370Arg Cys Ala Ala Arg Asn Lys Val Gly Tyr Ile Glu Lys Leu Val 2375 2380 2385Ile Leu Glu Ile Gly Gln Lys Pro Val Ile Leu Thr Tyr Ala Pro 2390 2395 2400Gly Thr Val Lys Gly Ile Ser Gly Glu Ser Leu Ser Leu His Cys 2405 2410 2415Val Ser Asp Gly Ile Pro Lys Pro Asn Ile Lys Trp Thr Met Pro 2420 2425 2430Ser Gly Tyr Val Val Asp Arg Pro Gln Ile Asn Gly Lys Tyr Ile 2435 2440 2445Leu His Asp Asn Gly Thr Leu Val Ile Lys Glu Ala Thr Ala Tyr 2450 2455 2460Asp Arg Gly Asn Tyr Ile Cys Lys Ala Gln Asn Ser Val Gly His 2465 2470 2475Thr Leu Ile Thr Val Pro Val Met Ile Val Ala Tyr Pro Pro Arg 2480 2485 2490Ile Thr Asn Arg Pro Pro Arg Ser Ile Val Thr Arg Thr Gly Ala 2495 2500 2505Ala Phe Gln Leu His Cys Val Ala Leu Gly Val Pro Lys Pro Glu 2510 2515 2520Ile Thr Trp Glu Met Pro Asp His Ser Leu Leu Ser Thr Ala Ser 2525 2530 2535Lys Glu Arg Thr His Gly Ser Glu Gln Leu His Leu Gln Gly Thr 2540 2545 2550Leu Val Ile Gln Asn Pro Gln Thr Ser Asp Ser Gly Ile Tyr Lys 2555 2560 2565Cys Thr Ala Lys Asn Pro Leu Gly Ser Asp Tyr Ala Ala Thr Tyr 2570 2575 2580Ile Gln Val 258515236PRTMus musculusmisc_feature(1)..(236)'x' can be any amino acid 15Met Gln Lys Arg Gly Arg Glu Val Ser Cys Leu Leu Ile Ser Leu Thr1 5 10 15Ala Ile Cys Leu Val Val Thr Pro Gly Ser Arg Val Cys Pro Arg Arg 20 25 30Cys Ala Cys Tyr Val Pro Thr Glu Val His Cys Thr Phe Arg Asp Leu 35 40 45Thr Ser Ile Pro Asp Gly Pro Ala Asn Val Glu Arg Val Asn Leu Gly 50 55 60Tyr Asn Ser Leu Thr Arg Leu Thr Glu Asn Asp Phe Ser Gly Leu Ser65 70 75 80Arg Leu Glu Leu Leu Met Leu His Ser Asn Gly Ile His Arg Val Ser 85 90 95Asp Lys Thr Phe Ser Gly Leu Gln Ser Leu Gln Val Leu Lys Met Ser 100 105 110Tyr Asn Lys Val Gln Ile Ile Glu Lys Asp Thr Leu Tyr Gly Leu Arg 115 120 125Ser Leu Thr Arg Leu His Leu Asp His Asn Asn Ile Glu Phe Ile Asn 130 135 140Pro Glu Ala Phe Tyr Gly Leu Thr Leu Leu Arg Leu Val His Leu Glu145 150 155 160Gly Asn Arg Leu Thr Lys Leu His Pro Asp Thr Phe Val Ser Leu Ser 165 170 175Tyr Leu Gln Ile Phe Lys Thr Ser Phe Ile Lys Xaa Leu Tyr Leu Tyr 180 185 190Asp Asn Phe Thr Ser Leu Pro Lys Glu Met Val Ser Ser Met Pro Asn 195 200 205Leu Glu Ser Leu Tyr Leu His Gly Asn Pro Trp Thr Cys Asp Cys His 210 215 220Leu Lys Trp Leu Ser Glu Trp Met Gln Gly Asn Pro225 230 235162587PRThomo sapiens 16Met Lys Val Lys Gly Arg Gly Ile Thr Cys Leu Leu Val Ser Phe Ala1 5 10 15Val Ile Cys Leu Val Ala Thr Pro Gly Gly Lys Ala Cys Pro Arg Arg 20 25 30Cys Ala Cys Tyr Met Pro Thr Glu Val His Cys Thr Phe Arg Tyr Leu 35 40 45Thr Ser Ile Pro Asp Ser Ile Pro Pro Asn Val Glu Arg Ile Asn Leu 50 55 60Gly Tyr Asn Ser Leu Val Arg Leu Met Glu Thr Asp Phe Ser Gly Leu65 70 75 80Thr Lys Leu Glu Leu Leu Met Leu His Ser Asn Gly Ile His Thr Ile 85 90 95Pro Asp Lys Thr Phe Ser Asp Leu Gln Ala Leu Gln Val Leu Lys Met 100 105 110Ser Tyr Asn Lys Val Arg Lys Leu Gln Lys Asp Thr Phe Tyr Gly Leu 115 120 125Arg Ser Leu Thr Arg Leu His Met Asp His Asn Asn Ile Glu Phe Ile 130 135 140Asn Pro Glu Val Phe Tyr Gly Leu Asn Phe Leu Arg Leu Val His Leu145 150 155 160Glu Gly Asn Gln Leu Thr Lys Leu His Pro Asp Thr Phe Val Ser Leu 165 170 175Ser Tyr Leu Gln Ile Phe Lys Ile Ser Phe Ile Lys Phe Leu Tyr Leu 180 185 190Ser Asp Asn Phe Leu Thr Ser Leu Pro Gln Glu Met Val Ser Tyr Met 195 200 205Pro Asp Leu Asp Ser Leu Tyr Leu His Gly Asn Pro Trp Thr Cys Asp 210 215 220Cys His Leu Lys Trp Leu Ser Asp Trp Ile Gln Pro Asp Val Ile Lys225 230 235 240Cys Lys Lys Asp Arg Ser Pro Ser Ser Ala Gln Gln Cys Pro Leu Cys 245 250 255Met Asn Pro Arg Thr Ser Lys Gly Lys Pro Leu Ala Met Val Ser Ala 260 265 270Ala Ala Phe Gln Cys Ala Lys Pro Thr Ile Asp Ser Ser Leu Lys Ser 275 280 285Lys Ser Leu Thr Ile Leu Glu Asp Ser Ser Ser Ala Phe Ile Ser Pro 290 295 300Gln Gly Phe Met Ala Pro Phe Gly Ser Leu Thr Leu Asn Met Thr Asp305 310 315 320Gln Ser Gly Asn Glu Ala Asn Met Val Cys Ser Ile Gln Lys Pro Ser 325 330 335Arg Thr Ser Pro Ile Ala Phe Thr Glu Glu Asn Asp Tyr Ile Val Leu 340 345 350Asn Thr Ser Phe Ser Thr Phe Leu Val Cys Asn Ile Asp Tyr Gly His 355 360 365Ile Gln Pro Val Trp Gln Ile Leu Ala Leu Tyr Ser Asp Ser Pro Leu 370 375 380Ile Leu Glu Arg Ser His Leu Leu Ser Glu Thr Pro Gln Leu Tyr Tyr385 390 395 400Lys Tyr Lys Gln Val Ala Pro Lys Pro Glu Asp Ile Phe Thr Asn Ile 405 410 415Glu Ala Asp Leu Arg Ala Asp Pro Ser Trp Leu Met Gln Asp Gln Ile 420 425 430Ser Leu Gln Leu Asn Arg Thr Ala Thr Thr Phe Ser Thr Leu Gln Ile 435 440 445Gln Tyr Ser Ser Asp Ala Gln Ile Thr Leu Pro Arg Ala Glu Met Arg 450 455 460Pro Val Lys His Lys Trp Thr Met Ile Ser Arg Asp Asn Asn Thr Lys465 470 475 480Leu Glu His Thr Val Leu Val Gly Gly Thr Val Gly Leu Asn Cys Pro 485 490 495Gly Gln Gly Asp Pro Thr Pro His Val Asp Trp Leu Leu Ala Asp Gly 500 505 510Ser Lys Val Arg Ala Pro Tyr Val Ser Glu Asp Gly Arg Ile Leu Ile 515 520 525Asp Lys Ser Gly Lys Leu Glu Leu Gln Met Ala Asp Ser Phe Asp Thr 530 535 540Gly Val Tyr His Cys Ile Ser Ser Asn Tyr Asp Asp Ala Asp Ile Leu545 550 555 560Thr Tyr Arg Ile Thr Val Val Glu Pro Leu Val Glu Ala Tyr Gln Glu 565 570 575Asn Gly Ile His His Thr Val Phe Ile Gly Glu Thr Leu Asp Leu Pro 580 585 590Cys His Ser Thr Gly Ile Pro Asp Ala Ser Ile Ser Trp Val Ile Pro 595 600 605Gly Asn Asn Val Leu Tyr Gln Ser Ser Arg Asp Lys Lys Val Leu Asn 610 615 620Asn Gly Thr Leu Arg Ile Leu Gln Val Thr Pro Lys Asp Gln Gly Tyr625 630 635 640Tyr Arg Cys Val Ala Ala Asn Pro Ser Gly Val Asp Phe Leu Ile Phe 645 650 655Gln Val Ser Val Lys Met Lys Gly Gln Arg Pro Leu Glu His Asp Gly 660 665 670Glu Thr Glu Gly Ser Gly Leu Asp Glu Ser Asn Pro Ile Ala His Leu 675 680 685Lys Glu Pro Pro Gly Ala Gln Leu Arg Thr Ser Ala Leu Met Glu Ala 690 695 700Glu Val Gly Lys His Thr Ser Ser Thr Ser Lys Arg His Asn Tyr Arg705 710 715 720Glu Leu Thr Leu Gln Arg Arg Gly Asp Ser Thr His Arg Arg Phe Arg 725 730 735Glu Asn Arg Arg His Phe Pro Pro Ser Ala Arg Arg Ile Asp Pro Gln 740 745 750His Trp Ala Ala Leu Leu Glu Lys Ala Lys Lys Asn Ala Met Pro Asp 755 760 765Lys Arg Glu Asn Thr Thr Val Ser Pro Pro Pro Val Val Thr Gln Leu 770 775 780Pro Asn Ile Pro Gly Glu Glu Asp Asp Ser Ser Gly Met Leu Ala Leu785 790 795 800His Glu Glu Phe Met Val Pro Ala Thr Lys Ala Leu Asn Leu Pro Ala 805 810 815Arg Thr Val Thr Ala Asp Ser Arg Thr Ile Ser Asp Ser Pro Met Thr 820 825 830Asn Ile Asn Tyr Gly Thr Glu Phe Ser Pro Val Val Asn Ser Gln Ile 835 840 845Leu Pro Pro Glu Glu Pro Thr Asp Phe Lys Leu Ser Thr Ala Ile Lys 850 855 860Thr Thr Ala Met Ser Lys Asn Ile Asn Pro Thr Met Ser Ser Gln Ile865 870 875 880Gln Gly Thr Thr Asn Gln His Ser Ser Thr Val Phe Pro Leu Leu Leu 885 890 895Gly Ala Thr Glu Phe Gln Asp Ser Asp Gln Met Gly Arg Gly Arg Glu 900 905 910His Phe Gln Ser Arg Pro Pro Ile Thr Val Arg Thr Met Ile Lys Asp 915 920 925Val Asn Val Lys Met Leu Ser Ser Thr Thr Asn Lys Leu Leu Leu Glu 930 935 940Ser Val Asn Thr Thr Asn Ser His Gln Thr Ser Val Arg Glu Val Ser945 950 955 960Glu Pro Arg His Asn His Phe Tyr Ser His Thr Thr Gln Ile Leu Ser 965 970 975Thr Ser Thr Phe Pro Ser Asp Pro His Thr Ala Ala His Ser Gln Phe 980 985 990Pro Ile Pro Arg Asn Ser Thr Val Asn Ile Pro Leu Phe Arg Arg Phe 995 1000 1005Gly Arg Gln Arg Lys Ile Gly Gly Arg Gly Arg Ile Ile Ser Pro 1010 1015 1020Tyr Arg Thr Pro Val Leu Arg Arg His Arg Tyr Ser Ile Phe Arg 1025 1030 1035Ser Thr Thr Arg Gly Ser Ser Glu Lys Ser Thr Thr Ala Phe Ser 1040 1045 1050Ala Thr Val Leu Asn Val Thr Cys Leu Ser Cys Leu Pro Arg Glu 1055 1060 1065Arg Leu Thr Thr Ala Thr Ala Ala Leu Ser Phe Pro Ser Ala Ala 1070 1075 1080Pro Ile Thr Phe Pro Lys Ala Asp Ile Ala Arg Val Pro Ser Glu 1085 1090 1095Glu Ser Thr Thr Leu Val Gln Asn Pro Leu Leu Leu Leu Glu Asn 1100 1105 1110Lys Pro Ser Val Glu Lys Thr Thr Pro Thr Ile Lys Tyr Phe Arg 1115 1120 1125Thr Glu Ile Ser Gln Val Thr Pro Thr Gly Ala Val Met Thr Tyr 1130 1135 1140Ala Pro Thr Ser Ile Pro Met Glu Lys Thr His Lys Val Asn Ala 1145 1150 1155Ser Tyr Pro Arg Val Ser Ser Thr Asn Glu Ala Lys Arg Asp Ser 1160 1165 1170Val Ile Thr Ser Ser Leu Ser Gly Ala Ile Thr Lys Pro Pro Met 1175 1180 1185Thr Ile Ile Ala Ile Thr Arg Phe Ser Arg Arg Lys Ile Pro Trp 1190 1195 1200Gln Gln Asn Phe Val Asn Asn His Asn Pro Lys Gly Arg Leu Arg 1205 1210 1215Asn Gln His Lys Val Ser Leu Gln Lys Ser Thr Ala Val Met Leu 1220 1225 1230Pro Lys Thr Ser Pro Ala Leu Pro Gln Arg Gln Ser Ser Pro Phe 1235 1240 1245His Phe Thr Thr Leu Ser Thr Ser Val Met Gln Ile Pro Ser Asn 1250 1255 1260Thr Leu Thr Thr Ala His His Thr Thr Thr Lys Thr His Asn Pro 1265 1270 1275Gly Ser Leu Pro Thr Lys Lys Glu Leu Pro Phe Pro Pro Leu Asn 1280 1285 1290Pro Met Leu Pro Ser Ile Ile Ser Lys Asp Ser Ser Thr Lys Ser 1295 1300 1305Ile Ile Ser Thr Gln Thr Ala Ile Pro Ala Thr Thr Pro Thr Phe 1310 1315 1320Pro Ala Ser Val Ile Thr Tyr Glu Thr Gln Thr Glu Arg Ser Arg 1325 1330 1335Ala Gln Thr Ile Gln Arg Glu Gln Glu Pro Gln Lys Lys Asn Arg 1340 1345 1350Thr Asp Pro Asn Ile Ser Pro Asp Gln Ser Ser Gly Phe Thr

Thr 1355 1360 1365Pro Thr Ala Met Thr Pro Pro Ala Leu Ala Phe Thr His Ser Pro 1370 1375 1380Pro Glu Asn Thr Thr Gly Ile Ser Ser Thr Ile Ser Phe His Ser 1385 1390 1395Arg Thr Leu Asn Leu Thr Asp Val Ile Glu Glu Leu Ala Gln Ala 1400 1405 1410Ser Thr Gln Thr Leu Lys Ser Thr Ile Ala Ser Glu Thr Thr Leu 1415 1420 1425Ser Ser Lys Ser His Gln Ser Thr Thr Thr Arg Lys Ala Ser Leu 1430 1435 1440Asp Thr Pro Ile Pro Pro Phe Leu Ser Ser Ser Ala Thr Leu Met 1445 1450 1455Pro Val Pro Ile Ser Pro Pro Phe Thr Gln Arg Ala Val Thr Asp 1460 1465 1470Thr Arg Gly Asp Ser His Phe Arg Leu Met Thr Asn Thr Val Val 1475 1480 1485Lys Leu His Glu Ser Ser Arg His Asn Leu Gln Met Pro Ser Ser 1490 1495 1500Gln Leu Glu Pro Leu Thr Ser Ser Thr Ser Asn Leu Leu His Ser 1505 1510 1515Thr Pro Met Pro Ala Leu Thr Thr Val Lys Ser Gln Asn Ser Lys 1520 1525 1530Leu Thr Pro Ser Pro Trp Ala Glu Tyr Gln Phe Trp His Lys Pro 1535 1540 1545Tyr Ser Asp Ile Ala Glu Lys Gly Lys Lys Pro Glu Val Ser Met 1550 1555 1560Leu Ala Thr Thr Gly Leu Ser Glu Ala Thr Thr Leu Val Ser Asp 1565 1570 1575Trp Asp Gly Gln Lys Asn Thr Lys Lys Ser Asp Phe Asp Lys Lys 1580 1585 1590Pro Val Gln Glu Ala Thr Thr Ser Lys Leu Leu Pro Phe Asp Ser 1595 1600 1605Leu Ser Arg Tyr Ile Phe Glu Lys Pro Arg Ile Val Gly Gly Lys 1610 1615 1620Ala Ala Ser Phe Thr Ile Pro Ala Asn Ser Asp Ala Phe Leu Pro 1625 1630 1635Cys Glu Ala Val Gly Asn Pro Leu Pro Thr Ile His Trp Thr Arg 1640 1645 1650Val Ser Gly Leu Asp Leu Ser Arg Gly Asn Gln Asn Ser Arg Val 1655 1660 1665Gln Val Leu Pro Asn Gly Thr Leu Ser Ile Gln Arg Val Glu Ile 1670 1675 1680Gln Asp Arg Gly Gln Tyr Leu Cys Ser Ala Ser Asn Leu Phe Gly 1685 1690 1695Thr Asp His Leu His Val Thr Leu Ser Val Val Ser Tyr Pro Pro 1700 1705 1710Arg Ile Leu Glu Arg Arg Thr Lys Glu Ile Thr Val His Ser Gly 1715 1720 1725Ser Thr Val Glu Leu Lys Cys Arg Ala Glu Gly Arg Pro Ser Pro 1730 1735 1740Thr Val Thr Trp Ile Leu Ala Asn Gln Thr Val Val Ser Glu Ser 1745 1750 1755Ser Gln Gly Ser Arg Gln Ala Val Val Thr Val Asp Gly Thr Leu 1760 1765 1770Val Leu His Asn Leu Ser Ile Tyr Asp Arg Gly Phe Tyr Lys Cys 1775 1780 1785Val Ala Ser Asn Pro Gly Gly Gln Asp Ser Leu Leu Val Lys Ile 1790 1795 1800Gln Val Ile Ala Ala Pro Pro Val Ile Leu Glu Gln Arg Arg Gln 1805 1810 1815Val Ile Val Gly Thr Trp Gly Glu Ser Leu Lys Leu Pro Cys Thr 1820 1825 1830Ala Lys Gly Thr Pro Gln Pro Ser Val Tyr Trp Val Leu Ser Asp 1835 1840 1845Gly Thr Glu Val Lys Pro Leu Gln Phe Thr Asn Ser Lys Leu Phe 1850 1855 1860Leu Phe Ser Asn Gly Thr Leu Tyr Ile Arg Asn Leu Ala Ser Ser 1865 1870 1875Asp Arg Gly Thr Tyr Glu Cys Ile Ala Thr Ser Ser Thr Gly Ser 1880 1885 1890Glu Arg Arg Val Val Met Leu Thr Met Glu Glu Arg Val Thr Ser 1895 1900 1905Pro Arg Ile Glu Ala Ala Ser Gln Lys Arg Thr Glu Val Asn Phe 1910 1915 1920Gly Asp Lys Leu Leu Leu Asn Cys Ser Ala Thr Gly Glu Pro Lys 1925 1930 1935Pro Gln Ile Met Trp Arg Leu Pro Ser Lys Ala Val Val Asp Gln 1940 1945 1950Gly Ser Trp Ile His Val Tyr Pro Asn Gly Ser Leu Phe Ile Gly 1955 1960 1965Ser Val Thr Glu Lys Asp Ser Gly Val Tyr Leu Cys Val Ala Arg 1970 1975 1980Asn Lys Met Gly Asp Asp Leu Ile Leu Met His Val Ser Leu Arg 1985 1990 1995Leu Lys Pro Ala Lys Ile Asp His Lys Gln Tyr Phe Arg Lys Gln 2000 2005 2010Val Leu His Gly Lys Asp Phe Gln Val Asp Cys Lys Ala Ser Gly 2015 2020 2025Ser Pro Val Pro Glu Ile Ser Trp Ser Leu Pro Asp Gly Thr Met 2030 2035 2040Ile Asn Asn Ala Met Gln Ala Asp Asp Ser Gly His Arg Thr Arg 2045 2050 2055Arg Tyr Thr Leu Phe Asn Asn Gly Thr Leu Tyr Phe Asn Lys Val 2060 2065 2070Gly Val Ala Glu Glu Gly Asp Tyr Thr Cys Tyr Ala Gln Asn Thr 2075 2080 2085Leu Gly Lys Asp Glu Met Lys Val His Leu Thr Val Ile Thr Ala 2090 2095 2100Ala Pro Arg Ile Arg Gln Ser Asn Lys Thr Asn Lys Arg Ile Lys 2105 2110 2115Ala Gly Asp Thr Ala Val Leu Asp Cys Glu Val Thr Gly Asp Pro 2120 2125 2130Lys Pro Lys Ile Phe Trp Leu Leu Pro Ser Asn Asp Met Ile Ser 2135 2140 2145Phe Ser Ile Asp Arg Tyr Thr Phe His Ala Asn Gly Ser Leu Thr 2150 2155 2160Ile Asn Lys Val Lys Leu Leu Asp Ser Gly Glu Tyr Val Cys Val 2165 2170 2175Ala Arg Asn Pro Ser Gly Asp Asp Thr Lys Met Tyr Lys Leu Asp 2180 2185 2190Val Val Ser Lys Pro Pro Leu Ile Asn Gly Leu Tyr Thr Asn Arg 2195 2200 2205Thr Val Ile Lys Ala Thr Ala Val Arg His Ser Lys Lys His Phe 2210 2215 2220Asp Cys Arg Ala Glu Gly Thr Pro Ser Pro Glu Val Met Trp Ile 2225 2230 2235Met Pro Asp Asn Ile Phe Leu Thr Ala Pro Tyr Tyr Gly Ser Arg 2240 2245 2250Ile Thr Val His Lys Asn Gly Thr Leu Glu Ile Arg Asn Val Arg 2255 2260 2265Leu Ser Asp Ser Ala Asp Phe Ile Cys Val Ala Arg Asn Glu Gly 2270 2275 2280Gly Glu Ser Val Leu Val Val Gln Leu Glu Val Leu Glu Met Leu 2285 2290 2295Arg Arg Pro Thr Phe Arg Asn Pro Phe Asn Glu Lys Ile Val Ala 2300 2305 2310Gln Leu Gly Lys Ser Thr Ala Leu Asn Cys Ser Val Asp Gly Asn 2315 2320 2325Pro Pro Pro Glu Ile Ile Trp Ile Leu Pro Asn Gly Thr Arg Phe 2330 2335 2340Ser Asn Gly Pro Gln Ser Tyr Gln Tyr Leu Ile Ala Ser Asn Gly 2345 2350 2355Ser Phe Ile Ile Ser Lys Thr Thr Arg Glu Asp Ala Gly Lys Tyr 2360 2365 2370Arg Cys Ala Ala Arg Asn Lys Val Gly Tyr Ile Glu Lys Leu Val 2375 2380 2385Ile Leu Glu Ile Gly Gln Lys Pro Val Ile Leu Thr Tyr Ala Pro 2390 2395 2400Gly Thr Val Lys Gly Ile Ser Gly Glu Ser Leu Ser Leu His Cys 2405 2410 2415Val Ser Asp Gly Ile Pro Lys Pro Asn Ile Lys Trp Thr Met Pro 2420 2425 2430Ser Gly Tyr Val Val Asp Arg Pro Gln Ile Asn Gly Lys Tyr Ile 2435 2440 2445Leu His Asp Asn Gly Thr Leu Val Ile Lys Glu Ala Thr Ala Tyr 2450 2455 2460Asp Arg Gly Asn Tyr Ile Cys Lys Ala Gln Asn Ser Val Gly His 2465 2470 2475Thr Leu Ile Thr Val Pro Val Met Ile Val Ala Tyr Pro Pro Arg 2480 2485 2490Ile Thr Asn Arg Pro Pro Arg Ser Ile Val Thr Arg Thr Gly Ala 2495 2500 2505Ala Phe Gln Leu His Cys Val Ala Leu Gly Val Pro Lys Pro Glu 2510 2515 2520Ile Thr Trp Glu Met Pro Asp His Ser Leu Leu Ser Thr Ala Ser 2525 2530 2535Lys Glu Arg Thr His Gly Ser Glu Gln Leu His Leu Gln Gly Thr 2540 2545 2550Leu Val Ile Gln Asn Pro Gln Thr Ser Asp Ser Gly Ile Tyr Lys 2555 2560 2565Cys Thr Ala Lys Asn Pro Leu Gly Ser Asp Tyr Ala Ala Thr Tyr 2570 2575 2580Ile Gln Val Ile 2585175551DNAMus musculus 17tctagaagta aaatgatcct gagtagcgat cctgggaaaa tacgtactct aacacactgc 60aatcatctct ctgtggtttg ctggagctga ggtctggaag gctcgacctt ggttagaaat 120aacctaccga atacagagct atgacgttag tctggaagga gctttggaag aatgacaagc 180tgtagctgcc cagaacatac tagatgccat atttccaagg caagtgtcca catgcggaca 240tcttaagaat atggttgtct ctgcagtgct aaggaccttg ttcgtgccac acaggtctcc 300agggttagtg ctaactctga ctgcttgact ctttaattct accttgatca ttaatgacta 360gaaatcactt ggtgattagc aactggatat ggaatattac taatttgtac ccaagccagg 420ccacctcagc tttggcagct ccattcattc tgtggagccc agtcacgtgg gtttgaatca 480actgtactgt ttctacttac aagacgcatt acctgagatg agtcattttt cttcacaagt 540ctttttagaa gagtcaatta gacatattct gatgaagtaa gcatataaag tgagagcagc 600atgaatgtgt tccatgtatg ctcatggatg ctattataat gtggaaataa actgacttta 660aaaaaaaaag cttatgatac ttgtcacaga gtaaatcttc cataaatatc atctgcattt 720ataaattatt ttcataatcc atcaattaaa aacctttaga aattttgtta acacaaagat 780ccctaggccc ctgccctagg atggtctgta tggtgggcct gagagatgga gcttaagaac 840ttacttgctc caggagcaca tcttcagaac atctgcctca aaacatttat cccaaatgct 900catcaaaggc tcactcacat gtgcttcaac cacagggatt aaacagtcat tttagtcaca 960tttctcaaac ggtggaagcc tgctagagga acaggatgta tcaggataac atccaacctt 1020acaaaaggat gtcataaccc tcaccacaac aaacaacaac gacaacaaac ccataaaaat 1080tatcacggca aatgaactaa gccatatgca gaaaaagtat tatatgttct cattgtgggg 1140tgtttttcct taatagtcaa atatgcagaa tatagacaaa gatggtttat gcaagtgggg 1200atggcgaagg atacttgtag attagaggac acaaagcaac aactacagag tgaagtaatc 1260cagagactta atgtataata tgaggactgt atttaataat tctatttaag atacacagca 1320aacgagtgta tcttactaac acacacactt acatagagag aataaagtga tagatacgtt 1380tgttttatct tcatgtagct gataatttca tattgtacac ctcaaacata gataaccaac 1440aaagaggaag aggataggtg cctctcccag ggcggaagag tacattcgaa agtcagacac 1500cattgtgtag atgtaccaca tggaggagct agagaaagta gccaaggagc taaagggatc 1560tgcaacccta taggtggaac aacattatga gctaaccagt accccggagc tcttgactct 1620agctgcatat atatcaaaag atggcctaat cggccatcac tggaaagaga ggcccattgg 1680acttgcaaac tttatatgcc ccagtacagg ggaataccag ggccaaaaag ggggagtggg 1740tgggcagggg agtgggggtg ggtggatatg ggggactttt ggtatagcat tggaaatgta 1800aatgagttaa atacctaata aaaaatggaa aaaaaaaaaa aaaaaaaaaa aaaggaaggt 1860cagacacctc acttcactgc tatctcaact tgcaaacaga aggggagtca caaacccagg 1920acaaaccaca gtgattgaag cgtctttgaa tgttattgct gttgttgtta ccaccatcat 1980tagcatatat tcattgtgaa aacttacggg gtctatgaca tgttttttta ttcaagtata 2040tcacatgctg tcagcatatt tggcaccact accagcccca gccccctttg ccccgccccc 2100aacacacaca cacacacaca cacacacaca cacacacaca cacacacaca cacacacacc 2160tttaccttct cctgggcatc atctgctcac tcacccaccc aagcttaatc cttttccttc 2220cctgcaatag tacctctcct atttttatgt ctaggttccc cctccccctg ttaggagatg 2280ggagaggtca cgaaaggaaa gaatttgtag cccctgagcc agcccgggcc acagagcctg 2340ccaccagaca ggaaaagccc agggcttacc agcacaggag gagcaaactc gcaggcgagc 2400ctgggttggc gctggtggtc ccgggtcgat ggcccgccca ttcccagaag ccgaggctat 2460agctgcgtca cctgccccgc cctcctcccg agtgaagacc cctagaggct gagcagaccc 2520caaaggcggt gcaattccat tggcccaagg cagaggtgag cggctgctaa tcccctcggg 2580aagtgaaggg acccagagag tctggtagat gtgggagctg gggttcaggg cgagacagag 2640ggtgggatgg gcagaagggt ccaggaaaag gaaagtactg gaggggagtt gggacaaaag 2700cagcgaccaa gggaacatcg cttcagtgac tgaagccagg caaaaggagc gggaaggatt 2760atatgtagcc tgggacgctt tcataaacac tgatgacgtg tttgtgcaaa gcaagcaatt 2820tgaggagaaa cgcctgggac gtcggaaaga aggagtgatc gattagtact tgtaagttta 2880ggtgagtttg agaactaact aacctatact attgagggag aaggaagagc attccagcag 2940cagcagcagc agcagcaatc agataaagga aagctttggt tagtttggaa atgtatgata 3000ccattaaaat aacagaagcg cctccagttc tctgaagagt cagtccccca gctagtgaag 3060actaagccta ctaagccttt tgctcccgtt ggaagcaaag aacgttcctt caatcaggtg 3120aaggctctcc tcagaagatt tcctgtctct gcttatgtta caagaggatt caaaagcaag 3180acagaagagc tcaggtattg ccaactcttt tgttaaatac agtttgaggc ttaagtgtac 3240gggaactcat gtggtattca tttacggctc tcttctctta taactaactc ttaaggtgca 3300tatagtctct tctgtttccc agctaccttg taccatcttt gtttatctaa taatagcaag 3360ctcatctgct ttttaatcat cacgcagaga gtattcaaaa atattcagtg atgtaacagt 3420gacagtgtag gcatagaagt aatcattagt aaatcttaat ttgggttaaa ctcattcata 3480acagctccag gttgggaggg atcactgagc cttcgccacg tgcgggttaa agatattttc 3540taacaagaga agcagaattc ttccttggcc atgctcccca tcactgtgtc agtaagcaga 3600ggggtgtttc caagcagaga aagagcagac agtgttatgc ctgcaaagtc agagactcag 3660ccctcccagc tggtcagttt actgtcctcc cggtcattag ttggctctga aaaggcccat 3720gtgtccttat tggcaaggac ttgcagacat gctagaaaga aatttgacct ttttttctag 3780tgggttatta cagctgtaaa agtattttgg aaggttaagc caaataaata aaacacatat 3840taaataatac aatgttacaa aaattgatca tataaagaag tacattcata aatgcaatgt 3900gaaaaatata tataattttt atctatttac tggtgcaaag ttttctaaat tgcacatgta 3960ctatttttat atttataaaa atatttttaa aatgtatata aaagtgtaaa aggctcttgg 4020tcaaacaaga gagttaaatt tacaaacttt aattgtcccg ataacattat tatgatctct 4080aatgacaggg atcctgcttt tcattgggaa atgagaagct atgaagatat gtttacaata 4140ataagcccat ttagtgataa agtccaatgg gaagctagca cacactggtt tataaagaga 4200acagtttcct gagtctatgc aagtttacac tctagggaat aagagttcct ctttctccag 4260atttcactag catttgttgt catcatttat cttcttgatg atgagcatta taagtggaat 4320aagataggat ctcaaaggaa tgtcaatttg gatgccctga acaatctttc aggtctttct 4380ttcagttcac tagtctattc atttattgga taattggggg atggtgttaa tttttttgca 4440gttcttatgg aattccaaaa aacaaaaaac aaacaaacaa acaaaaaacc tctgaaacta 4500gaactaccaa tccattactg ggtatgtaac aaagagaaat ctgcacagaa tttattgcta 4560cattgttcat tattcacgac agccaagaat gtggaaccaa cttacgtagc cgtcaaaata 4620tgaacggata aagaaaatgt ggaaatgtgt acaacagagt cccatgtggc cataaaagag 4680tgaaatcatg acatatgcag gaaatggatg caactggaaa tcaattgggc taatcaaaac 4740aagacagact caaaaaggaa acaccgtgta gcttctctga caaacagaag ctagatttac 4800acttgtacgt gcgcatgtgt gtttagaatt ttatttagtt atacactatt ctaatctgtg 4860agtgtgtata aaggcatgca tgtaaagcaa aaacaagcta gctggggtgg gtaggagaga 4920aagcaatgag aggagttaat aagaacgaag catagtaaca taggtgccag gatgaaatgc 4980attaatttgt atgctaacta aaccacagac aggaggcaca cgttcaaacc agggtgaaat 5040cccagcacag agaaggggaa gtagacacaa agtttcgcca ctaaccaaga agccatttgc 5100agttgctgcc tgctgggagg ggcgttccag ttttctccag tctgacactg tgtataacaa 5160ccagttgaca atacaaagtt ggcatgatgg atggtttttg tgctattttt catttttttt 5220cttactgttt tgttgttgtg gtggttgttg tggtggtggc tgtggttttc atttgtttct 5280tttgagagag agaaggaaca tgaaattggg tgggtaggaa gctggaaacg atctggaaga 5340agttggggaa agagaaaaat tgtatggagc atatttaaac aaacaaacaa acaaacaaaa 5400ggttcatttt gccacaaaaa ggtgtgaatt aaattaacca gttacgactc ttaaagaaaa 5460tattcccaat tattcccaga gttgctatgt atgctgtgcc taggactttg cttgaactgg 5520ccctataact ctggtgtggt gtcttttcag g 5551184610DNAMus musculus 18cacagacctt cctcttctaa cctctctccc ccatcttgtt gcttcatccc agacttcaac 60accagcaagc acactctgct aatgcaaggg ctgctcctgt caggacaaca aggaggctga 120aggcagaccc acacgtttcc aactgctcct gagagtcaat ccccctagac tcatctatag 180caggaaacct gctgtgatct ccatttcttc tctgaccaca tccccaagtt atcacaagga 240gtttttcctc aaacctttcc tctccagcaa accccttcag ctccttgggt actttctcta 300gccccttcat tgggaaccct gtgctccatc caatggatgg ctgtgagcat ccacttctgt 360atagaatctt ggtcagtgca gtcttttgta tcctcaagaa cactgggtct gaaaatttta 420acccaaagaa ctgttttttg ttatgattgc tgcaatctct ttcaattcca ataaagagta 480agcatctcat tcctttgtct cctcctttca gtaccaccct gcctttgctg cctttctcaa 540agaatcaata aaaccaaagt gatatagatt catggcattc ctctaactgc tacatccact 600ccagtagtat ctcacttggc aggtgtaaaa gcctggaagc agtcacgagg cagtttcaca 660gaaacttagc ctcctggaac cttggcattc ccatagctag aatgccccag atttgtccct 720gagatattgt ggtgggtctt gcatgctttc ttgcagtatt ttactggata agagttagaa 780atctcagggc gagcttagca aaagtatacc tagaatcttc atgacagtca ggtattgcaa 840actacattgc atattagaag aaagttggta aattcttctg acaaatggag attccctaca 900gataacttaa aagaacagct aagtcacact catatgcaag aatttaccaa ggcctaggaa 960aggggggggg ggtactgctt tattcatgat aaggtctgct agagcagaac cccctggtgc 1020tagctttcac aaggttcaaa ggtgtagcat aaattgtgac tagagtgtga aatctttacc 1080tgtcattagc tgactctagg cagagctgtt ttatctttac tgtaaacatt acctggttcc 1140tgtcagtcct ttgaaggcat tcctctgttt tgtgacagat acttctatgt acctcgcctg 1200ctgtgacacc ctactccttt gttttctgta ttatataagc ctggtgttcc ctttgtgaaa 1260aattacatcc agatacagca ctcccttgtg tctgtgtcct tttgtcattt ctggccaact 1320ccatgcccac ctgccagaac ccctagtctt ttccacagat tgagggaggc cgactgagcc 1380tggtccatgg catctaacca ctgtcagctc actgttggtg actacctcaa ggtacaagct 1440ccattactaa tgaaacaaaa ttagataagt gtgggtccag gaagcaggtt gtacaccctg 1500tctgaatgaa cattatgaaa tgactgaaat aagttaaccc atctcttcct cgtttgctaa 1560tatagcaaat aaaccgagtt tctgagctgc tgctggtgtg tctccatcag agggcagagc 1620cagtctgatc ctagctttcc tgtatgtgtg tccattgttt cttcagttcc tgttgcccca 1680ttaggaaatc ctaagccatg aaagccatga atctgggaat gacttttcta agaaatgcca 1740cgtgaacctt gcgtttcaac gttttgcctg taaacaagat atatggtgcg cagtttataa 1800tcataataag ctttgaaata atatataact ccattctcat tctgcttcca cgctgagcat 1860cctgtttccc

cagggaccac aagagcattt gaaaagtagt gatttatgac ctgctttgtt 1920ctgttactat aaaagcttca tgaaagggca gccatgttga aacatggaac ttggggtgac 1980ctgtatctgt gttcctgggt cgtgctcact catatttgtc tccagaataa atgagtttat 2040caacttcgag gaaaaagttg tgtgtttgta tagcacgccc gtggagtccc accattctac 2100ttcctgtaat ctgtatatgg tagaaaaagt taatttatgt gattcttcca actccaaata 2160tttcaaatct tttagcccct cagcctggga tttctttgac taagtctatt gatttggaag 2220atctcagtgg ttaggatttg cagtcatgat gttcatacgt caggctaagc tgaaaaatat 2280gacaaatgaa atgtcaaatg tcatgtgcct gggaatgtga gtgttagggg gttttaaaga 2340aacaaatacc tactctaaat agttaataag tcccatggtt ctattctagt tttgaataat 2400gttccctagt atacagcaat ttaatttgaa atgaatagct tcttatcttg accaatctca 2460gtgacttcat ccgtcccaag tcatgttttc atattcataa ggataggtct cattcaacca 2520catgtttatc atttgggatc tgcatttttc tgatgcaaaa tgatttattc ttccagagca 2580ctggaattgg gttgaatcat cttataacgg ccaaaactaa atgcttctgt gctaaacaga 2640gagttacaag acctttttat gtggatggca gcattttagt catccttatg acagaatgtc 2700agagtggagc tcccactggg ggaggggctg gtccttggca ggattctctt ggaacatcac 2760acaaagaaat tccaaattat gaaatgcaca tgatccatcc agaatgtgac ttttgactct 2820tgaacatgag cttttaaagt acgtttggct gttcagacct tgactttgag gtgaaggaaa 2880gctcgccaac tcctttttat atgtaacaca atatatcaag atctaatgtg agacagtatg 2940ccagtcccaa gatctgtcaa tatgactgaa gacacattgc gatgttatca ctaaggcagg 3000agaaggcaag ctacagtgaa gcccagttca ctataaagct ttatgagaaa ttagataaga 3060agggtttcta atttttaaat tttttttatt agatattttc ttcatttaca tttcaaatgc 3120tatcccaaaa gtcccctata ctcccccctc accctgctcc cctacccacc cactcccatt 3180tcttggccct ggttacttgt gatagtggtc atatgatcca ccaagcttta catgctcact 3240atctggtcta ttgcaagaat ggctgccgag ctgatgcagt cagatacaga cacctacagc 3300caaacagtgg aaggaacttg gggactctta tggaagaaaa ggaggaaggg ttatgggccc 3360cggatgggga aaggaactcc acaggaagac caacatactt ggtcaactaa cctggaccct 3420tggggctctc agagtctgaa ccaccaacca tagaacattc atgggctgta cccaggcctc 3480tccactcata tgtaacagat atgtggcttg gccttcatct gggtcctgaa caactagatg 3540ggggttaggg gtggggatgg gggttatctc aaaagctgtt gcctgtatgt gggatatgtt 3600cttactgagc tgcctagtct ggcctcagtg ggagaggaag cacctagctt tagccttgta 3660aagacttgaa gttctgaggt gtcggtggag ggtatactca gggaggccct cacctgctag 3720gaagagaaga ggagggggaa gacttggggg agggggcagt gagcaggttg gtaaaatgaa 3780taagaaaaaa aaaataaaaa taattaaaaa aaaaaaagaa tggctgctga gccctactct 3840aaaaccattg catccccccc ccccaatcat tcagtgacta cgaattaaaa tcattgatac 3900taacaataga tgtaggaaac tattgttaac ttctttgtga ccacgagtgg tatttggaac 3960cttttttatt gaagctttca cacagagcct tgttctttca tttccctgta catgcatgta 4020gcttaatgat gttcagtgaa ttaaaaataa caatgaagaa taaagacaac tgtattttaa 4080ggattcttcg tatatattta aaaatctaag gtggtcacct ggaagaaatg tcttcagttt 4140ttctatatat gtttactcta tcgtatgtta attaattata tgcaataatt cataaaatct 4200acaacatagt atgtaactta taagaaagta aaacattcat gaaattgtga aggttacttt 4260tccttaccct cagaaacact gggtttgaat aattcttatt ttggtatcag tgaagaattt 4320gaaagaatgt aataacctac taaggcaaac atagaagttg aaattaaaaa gagtagacag 4380gagaagtaat aaggcaaata atgaatattt gctttaaata gttcttaatg tatcatctaa 4440ctagggtgtg attctccaga cttgactcca tccaaaatat ccaaaatgac tctaaccaca 4500gtcattgaaa caatgtgttg aaaataataa acatttccta cttgaaaatt cagatttctc 4560ctactttgct ttttattgct gtgataagca ccatgaccaa agcagcttat 461019424DNAArtificial Sequenceprimer 19taagcctttt gctcccgttg gaagcaaaga acgttccttc aatcaggtga aggctctcct 60cagaagattt catgtctcag cttatgttac aagaggattc aaaagcaaga cagaagagct 120caggtatagc caactctttt gttaaataca gtatgaggct taagtgtacg gcaactcatg 180tggtattcat ttgcggctct cttctcttat aactaactct taaggtgcat atagtctctt 240ctgtttccca gctaccttgc accatctttg tttatctaat aatagcaagc tcatctgctt 300tttaatcatc acgcagagag tattcaaaaa tattcagtga tgtaacagtg acagtgtagg 360catagaagta atcattagta aatcttaata tgggttaaac tcattcataa cagctccagg 420ttgg 4242011962DNAMus musculusmisc_feature(1)..(11962)'n' can be any nucleotide 'a', 'c', 'g' or 't'. 20tttggaacca acccagatgc ccctcaacag agaaatgggc cagaaaatgt ggtccattta 60tccaatggaa tactactcaa cttattaaaa acaacgactt tcataaaatt tttaggcaaa 120tgnatggtct gnaggatctt gagtgaggta acccaatcac aaaagaacac tcatggtatg 180cactcactga taagtggcta tttgtctatg gagtgattta aaagggaaga agacacatag 240ctttttgtgt gtataatatt aagatggaaa tttgccagtg ctgtttggct tatgagtgaa 300tcttgtttca gtggattacc ggaagaaaat aataagtgaa ctgtaggaag aagtagttaa 360tcaaggtgac aaagtatcct gacacattgg gaaaagacca cagtccagga aactgagtct 420taaggattca tattaactcc agttccccat gtgcagctct gagactttgg cagatcagac 480acttaacttc accagcttcc tacacagagc agttactatc cttgccttca cacatggagt 540gtgccattaa gtgcctgaac atgagtctga cttgttaata atctttaaaa tccaattgtg 600tgtaaagtat gtgaccaaag agcatggtca tgctattaac ctttgatgtt ctatggactc 660ttaattttat ggtagaaatg tcaacaagct tgtggaggct ggaagataca aggcttaaga 720ggatggcctt tcagttttga aagtaattca gtatgtgttc tggcatccct tttcctaaag 780caatttaacc ccccaagtag gcataatttt aatgcttact tcatcagaat atatctaatt 840gactcttcta aaaagacttt ggtatgcata ggatctaaat gtaaatgtga tttactgaca 900taataaatag gagaaactga gctagaatag gtataaaata tgtgctggct ttctaatagg 960tcttataggt tatataagag gtgggaaagg aatatttgaa acatctagaa gtaaaatgat 1020cctgagtagc gatcctggga aaatacgtac tctaacacac tgcaatcatc tctctgtggt 1080ttgctggagc tgaggtctgg aaggctcgac cttggttaga aataacctac cgaatacaga 1140gctatgacgt tagtctggaa ggagctttgg aagaatgaca agctgtagct gcccagaaca 1200tactagatgc catatttcca aggcaagtgt ccacatgcgg acatcttaag aatatggttg 1260tctctgcagt gctaaggacc ttgttcgtgc cacacaggtc tccagggtta gtgctaactc 1320tgactgcttg actctttaat tctcccttga tcattaatga ctagaaatca cttggtgatt 1380agcaactgga tatggaatat tacttaattt gtacccaagc caggccacct cagctttggc 1440agctccattc attctgtgga gcccagtcac gtgggtttga atcaactgta ctgtttctac 1500ttacaagacg cattacctga gatgagtcat ttttcttcac aagtcttttt agaagagtca 1560attagacata ttctgatgaa gtaagcatat aaagtgagag cagcatgaat gtgttccatg 1620tatgctcatg gatgctatta taatgtggaa ataaactgac tttaaaaaaa aaagcttatg 1680atacttgtca cagagtaaat cttccataaa tatcatctgc atttataaat tattttcata 1740atccatcaat taaaaacctt tagaaatttt gttaacacaa agatccctag gcccctgccc 1800taggatggtc tgtatggtgg gcctgagaga tggagcttaa gaacttactt gctccaggag 1860cacatcttca gaacatctgc ctcaaaacat ttatcccaaa tgctcatcaa aggctcactc 1920acatgtgctt caaccacagg gattaaacag tcattttagt cacatttctc aaacggtgga 1980agcctgctag aggaacagga tgtatcagga taacatccaa ccttacaaaa ggatgtcata 2040accctcacca caacaaacaa caacgacaac aaacccataa aaattatcac ggcaaatgaa 2100ctaagccata tgcagaaaaa gtattatatg ttctcattgt ggggtgtttt tccttaatag 2160tcaaatatgc agaatataga caaagatggt ttatgcaagt ggggatggcg aaggatactt 2220gtagattaga ggacacaaag caacaactac agagtgaagt aatccagaga cttaatgtat 2280aatatgagga ctgtatttaa taattctatt taagatacac agcaaacgag tgtatcttac 2340taacacacac acttacatag agagaataaa gtgatagata cgtttgtttt atcttcatgt 2400agctgataat ttcatattgt acacctcaaa catagataac caacaaagag gaagaggata 2460ggtgcctctc ccagggcgga agagtacatt cgaaagtcag acaccattgt gtagatgtac 2520cacatggagg agctagagaa agtagccaag gagctaaagg gatctgcaac cctataggtg 2580gaacaacatt atgagctaac cagtaccccg gagctcttga ctctagctgc atatatatca 2640aaagatggcc taatcggcca tcactggaaa gagaggccat tggacttgca aactttatat 2700gccccagtac aggggaatac cagggccaaa aagggggagt gggtgggcag gggagtgggg 2760gtgggtggat atgggggact tttggtatag cattggaaat gtaaatgagt taaataccta 2820ataaaaaatg gaaaaaaaaa aaaaaaaaaa aaaaaaggaa ggtcagacac ctcacttcac 2880tgctatctca acttgcaaac agaaggggag tcacaaaccc aggacaaacc acagtgattg 2940aagcgtcttt gaatgttatt gctgttgttg ttaccaccat cattagcata tattcattgt 3000gaaaacttac ggggtctatg acatgttttt ttattcaagt atatcacatg ctgtcagcat 3060atttggcacc actaccagcc ccagccccct ttgccccgcc cccaacacac acacacacac 3120acacacacac acacacacac acacacacac acacacacac acctttacct tctcctgggc 3180atcatctgct cactcaccca cccaagctta atccttttcc ttccctgcaa tagtacctct 3240cctattttta tgtctaggtt ccccctcccc ctgttaggag atgggagagg tcacgaaaga 3300aaggaatttg tagcccttga gccagcccgg gccacagagc ctgccaccag acaggaaaag 3360cccagggctt accagcacag gaggagcaaa ctcgcaggcg agcctgggtt ggcgctggtg 3420gtcccgggtc gatggcccgc ccattcccag aagccgaggc tatagctgcg tcacctgccc 3480cgccctcctc ccgagtgaag acccctagag gctgagcaga ccccaaaggc ggtgcaattc 3540cattggccca aggcagaggt gagcggctgc taatcccctc gggaagtgaa gggacccaga 3600gagtctggta gatgtgggag ctggggttca gggcgagaca gagggtggga tgggcagaag 3660ggtccaggaa aggaaagtac tggaggggag ttgggacaaa agcagcgacc aagggaacat 3720cgcttcagtg actgaagcca ggcaaaagga gcgggaagga ttatatgtag cctgggacgc 3780tttcataaac actgatgacg tgtttgtgca aagcaagcaa tttgaggaga aacgcctggg 3840acgtcggaaa gaaggagtga tcgattagta cttgtaagtt taggtgagtt tgagaactaa 3900ctaacctata ctattgaggg agaaggaaga gcattccagc agcagcagca gcagcagcaa 3960tcagataaag gaaagctttg gttagtttgg aaatgtatga taccattaaa ataacagaag 4020cgcctccagt tctctgaaga gtcagtcccc cagctagtga agactaagcc tactaagcct 4080tttgctcccg ttggaagcaa agaacgttcc ttcaatcagg tgaaggctct cctcagaaga 4140tttcctgtct ctgcttatgt tacaagagga ttcaaaagca agacagaaga gctcaggtat 4200tgccaactct tttgttaaat acagtttgag gcttaagtgt acgggaactc atgtggtatt 4260catttacggc tctcttctct tataactaac tcttaaggtg catatagtct cttctgtttc 4320ccagctacct tgtaccatct ttgtttatct aataatagca agctcatctg ctttttaatc 4380atcacgcaga gagtattcaa aaatattcag tgatgtaaca gtgacagtgt aggcatagaa 4440gtaatcatta gtaaatctta atttgggtta aactcattca taacagctcc aggttgggag 4500ggatcactga gccttcgcca cgtgcgggtt aaagatattt tctaacaaga gaagcagaat 4560tcttccttgg ccatgctccc catcactgtg tcagtaagca gaggggtgtt tccaagcaga 4620gaaagagcag acagtgttat gcctgcaaag tcagagactc agccctccca gctggtcagt 4680ttactgtcct cccggtcatt agttggctct gaaaaggccc atgtgtcctt attggcaagg 4740acttgcagac atgctagaaa gaaatttgac ctttttttct agtgggttat tacagctgta 4800aaagtatttt ggaaggttaa gccaaataaa taaaacacat attaaataat acaatgttac 4860aaaaattgat catataaaga agtacattca taaatgcaat gtgaaaaata tatataattt 4920ttatctattt actggtgcaa agttttctaa attgcacatg tactattttt atatttataa 4980aaatattttt aaaatgtata taaaagtgta aaaggctctt ggtcaaacaa gagagttaaa 5040tttacaaact ttaattgtcc cgataacatt attatgatct ctaatgacag ggatcctgct 5100tttcattggg aaatgagaag ctatgaagat atgtttacaa taataagccc atttagtgat 5160aaagtccaat gggaagctag cacacactgg tttataaaga gaacagtttc ctgagtctat 5220gcaagtttac actctaggga ataagagttc ctctttctcc agatttcact agcatttgtt 5280gtcatcattt atcttcttga tgatgagcat tataagtgga ataagatagg atctcaaagg 5340aatgtcaatt tggatgccct gaacaatctt tcaggtcttt ctttcagttc actagtctat 5400tcatttattg gataattggg gggatggtgg taattttttt gcagttctta tggaattcca 5460aaaaacaaaa aacaaaccaa ccaaccaaaa acctctgaaa ctagaactac caatccatta 5520ctgggtatgt aacaaagaga aatctgcaca gaatttattg ctacattgtt cattattcac 5580gacagccaag aatgtggaac caacttacgt agccgtcaaa atatgaacgg ataaagaaaa 5640tgtggaaatg tgtacaacag agtcccatgt ggccataaaa gagtgaaatc atgacatatg 5700caggaaatgg atgcaactgg aaatcaattg ggctaatcaa aacaagacag actcaaaaag 5760gaaacaccgt gtagcttctc tgacaaacag aagctagatt tacacttgta cgtgcgcatg 5820tgtgtttaga attttattta gttatacact attctaatct gtgagtgtgt ataaaggcat 5880gcatgtaaag caaaaacaag ctagctgggg tgggtaggag agaaagcaat gagaggagtt 5940aataagaacg aagcatagta acataggtgc caggatgaaa tgcattaatt tgtatgctaa 6000ctaaaccaca gacaggaggc acacgttcaa accagggtga aatcccagca cagagaaggg 6060gaagtagaca caaagtttcg ccactaacca agaagccatt tgcagttgct gcctgctggg 6120aaggggcgtt ccagttttct ccagtctgac actgtgtata acaaccagtt gacaatacaa 6180agttggcatg atggatggtt tttgtgctat ttttcatttt ttttcttact gttttgttgt 6240tgtggtggtt gttgtggtgg tggctgtggt tttcatttgt ttcttttgag agagagaagg 6300aacatgaaat tgggtgggta ggaagctgga aacgatctgg aagaagttgg ggaaagagaa 6360aaattgtatg gagcatattt aaacaaacaa acaaacaaac aaaaggttca ttttgccaca 6420aaaaggtgtg aattaaatta accagttacg actcttaaag aaaatattcc caattattcc 6480cagagttgct atgtatgctg tgcctaggac tttgcttgaa ctggccctat aactctggtg 6540tggtgtcttt tcaggatgca gaagagaggc agggaagtca gctgcttgct gatctccctc 6600actgccatct gcctggtggt cacccctggg agcagggtct gtcctcgccg atgtgcctgc 6660tatgtgccca cagaggtgca ctgtacattt cgggacctga cctccatccc agacgggcat 6720cccagccaat gtggaacgag tcaatttagg gtgtgtggac cttgcctgat ctccttctca 6780gagagggacc actgattttc ctggtacttt gccccccaaa cacctgtgat tacttttaat 6840agttttcttc taaaatgggt tcatacaaac cttatattgt ggagacaatg aacattttat 6900cccaatagtc ttttactaga acttgaagcc cctcttagtt gtttgggagc ctcataatta 6960tggggcagct ttattctgaa tgaattttaa atgaaaaaga tacagtttct gttaacaatc 7020attatgatac caaggaagag gaattgtcat tgaatatttt aaaaaagcat ttcttttgca 7080atttataaat acccattaca aaatggctta cttaaaatac ttgccttact aaatctgaca 7140aattatggtg atattttgaa ggtttatgaa aatttgttta tgtgtataaa tgcacaagaa 7200atgggatatg ccatcaccta tgtgccatta gtgagcatgt acagtatgcc aaacactatt 7260gttcacgttt ggaggaagta atgggggtgg gggagcaaca agggttataa ccgtataccc 7320agtgccttgg aagcgattgc aaacagtaaa gactgacatt gtgttctccc tatgagggag 7380gggccttggg ctgagcactt tgcaatgagc atttgctcat tgtgctggca ggttttatga 7440taacttgacc caagctagag tcactggaga ggaaggaact tcaactgaga acatgcctga 7500agaagatcag attataggca ggcctgtggg gcattttctt aattagtgat tcatggggca 7560gggcccagtc cattgttcgt ggtaccattt ctcaggcact attaaaaaaa aaaaaacagg 7620ctgagcaagt gtcaaggagc aagtcagtga gcagcagccc taatgatctc tgcatcagct 7680cctgcctcca ggttcctacc ctatttgagt tcctgtccta gctccctaca gtgatgaaca 7740atgatgtgga agtataagcc aaataaatcc tttcttcccc aacttgctgt tggtcatgat 7800gtttcatcac agtgataata gtcctcatga agatgctggt gtttataaca cctttggact 7860aaattctgtt atctatagct gaggaaaatg gagcatagaa agtctccaga ctacaccaga 7920gtgtaatctg ggcctgagct tagaatcaca cccacgtgca ctccactgcc ggggcttctt 7980aaccggaaca cagttgtaaa agggaatttt ctgtttgttt ccattttgac atgtggactt 8040taattgacga ttcatctgaa gctgaaaatg attttttttc caggtataac agcctcacta 8100gattgacaga aaatgacttt tctggcctga gcagactgga gttactcatg ctgcacagca 8160atggcattca cagagtcagt gacaagacct tctcgggctt gcagtccttg caggtgagat 8220aggtagaggg tgatggaggc tgagaagaga ggtgcaactg tgggttatac ccaaaagctg 8280ctgattcccg tgggagacat tctataagca ttctataaac tagaggcaga tatcaaggaa 8340ggatttcaat tgtaatgcaa ttttatgaga aaatttgaat attaagaaaa tgctggggaa 8400aatgcttaca caattgcgag gacctaattt aggatctcca atagccacat aaaaagcaca 8460gcatggcggc agacacctgc aattcctgtc cctggaagca cctgttcaga atcccagaga 8520ctcattggcc aaacactcta ttcaatcaat gaagtccata ttcagtgaca aaacttgact 8580cagaaactaa tgtggaaagc atcaggaaga cagccaacat ctggtctcta ctcatgcatg 8640aataagggat cccagagaga agggaagaaa aaggaaggaa ggaaggaagg aaggaaggaa 8700ggaaggaagg aaggaaggaa ggaagagagg gaggaaagga gggagggaag gaaggaaagg 8760gaaaggaaaa aagagatggg gagggaggga aggaaaggaa agggggagaa agaagagaag 8820aaaggaaaat aaataaattt tcagggatta ttacaccttt aaattttatc cataaaaggt 8880catttccacc tgtttgtctg gaagtagagt gggatccctt atataagggc agtctttaac 8940atagtagcat tttataaacc attacaaatt ttgagttttc tctacttttt atcctctacc 9000atcttcaaac tgaaactaca attattccca caaatgaaga aaatgctgta agagttttca 9060cacaccgaag tgggaaactt aaggattaga caagtctaac aatgagaatg gggagaacaa 9120aaagagactg cacagggagc cctttctctg cttataatct tgacacttga gaagctaatt 9180gacgctgcat gactactcaa ctctttaagc aaacaatgct gttgttcatg aaaagcacaa 9240taaagtacat atgtcccata atattcatca aaatttgcat gcagcacata atagcaatca 9300aagcaataac acccactgtt cacagagact ttaaacatga aactggaact atgtctagtg 9360ttttgactta gggtacatag tatgctgtgt ctgtatgtac caatgttgat ttaggtcatc 9420agacagcatt tggaacatgt atcttcagga ggaatcattc atgtatcctg catgaaattc 9480tccacctatg tttattctct tagccaggtt tttctctgat ggagaaacat tgggtttgag 9540gttttactcc caggtaacat ttagggaaaa gctgtctatg ttctcagttt ggcttttatt 9600tatgagggat gttggtattc cagaaaattc tcttttgaag agattacaat ttaggtcaaa 9660acagaaaaat atgtaaaaag ttattgtttt tattagtatt tcatgttctt ttctttttta 9720aaaatggtat gcttagaact aattaagatt agattagatt agattagaaa ataatcagag 9780agggatttga tgaatgctaa agcatcatga aaaattcaaa attttttgct tctaattcag 9840aatcaattaa attcatatta ctataaaaga cagcacgcca gatgtgtgcc agctgaggag 9900tggataaact gtgtaacgtg agtgctatgt agaaacagaa aggagtgaag ggttgatgtg 9960cgctgcaaca tcttgaaaac attcggctac atgatggaag ccaggcacaa aaagccacat 10020attgcatggt tatgtttata tgaaatgttt aaaatacatg gattcttagc aaacagagta 10080agatgttact tagggtcagg aaaagattaa aaaaaaaaaa actattgatg tggaatgatc 10140ttaatttggg gaaaagacaa tttcctaaga cgaaatagtt gaggtagata tagttatatc 10200cctgtggata ttgtaataaa ccagcatgct gtgctctgag aagggcctaa tgaaggggca 10260ggaggaagtg aaatgagatg gtagaaagga aagtcatata ccatggcttc tctcgtgggt 10320ggaatctaga tatgttaata tattgacata aaggaaggaa ttgtttaggg aaggatcaaa 10380accaacagga gtgagggaga caataggaac caatgagagg caaagttcat ggtcaatgtg 10440tgtggagaca ccataataaa actccttttt tgtttgctaa ctaaaaccac taaaatctaa 10500aaacaaaaca tttttgcaca agaattattt attattcaat aaagatgttt aaatggggga 10560agttgaagtt cattgatagt ctcataaatc ttaaatgtat ttaaactgct ttttacgttt 10620tttattatta attactcttg ctgtcattat tatcatcatc attatcgtca tcatcatcac 10680taatgctttt caccatacac aaatgtaggc agaagagtgt aatccactta gtgaggcaat 10740cttggagagg gaaaggaagc ggatgcgggg cagaggcaca caggaggaca gtgagaggga 10800aatgaacaag aaaaaatgtg gacacatgca caaaaattcc atagtccact acattacttt 10860gtattctaat attaagaaaa taataaaccc atttctgtgc acttatcacc caggctcaac 10920agttatcttg gccacagatc ctgtctcact gcatcctgtc cacctgagtc cacttagcgt 10980tctgaatcca atccagggca tgatgcttac tcctacacag aactaaagat taaagagagt 11040ttaaaagtaa ccatgacatc tctctgttcc tttagcgata agttcttaat atttatggct 11100gcttgtgtat gttctaattt ctctaatatt gtcacattta gttggcaact actttgtttg 11160aattgagttg gagttaaggt cccataggat taatctcaac atatttctat atttataaac 11220ttttctctct ttgtgaaagt tcctttgaga aaacaaatat gcccatatct ttctttacag 11280gtcttaaaaa tgagctataa caaagtccaa ataattgaga aggatacttt gtatggactc 11340aggagcttga cccggttgca cctggatcac aacaacattg agtttatcaa ccccgaggcg 11400ttttacggac tcaccttgct ccgcttggta catctagaag gaaaccggct gacaaagctc 11460catccagaca catttgtctc tttgagctat ctccagatat ttaaaacctc cttcattaag 11520nacctgtact tgtatgataa cttcattgac ctccctccca aaagaaatgg tctcctctat 11580gccaaaccta gaaagccttt acttgcatgg aaacccatgg acctgtgact gccatttaaa 11640gtggttgtcc gagtggatgc agggaaaccc aggtaactat cttgtttgtt

tgtttctttt 11700tttatarkac gtattttcct caatttcatt tagaatgata tcccaaaagt cccccataac 11760ctccccccca cttccctacc tacccattcc cattttttgg ccctggcatt cccctgtact 11820ggggcatata aagtttgcgt gtccaatgga cctctctttc cagtgatggc caactaggcc 11880atcttttgat acatatgcag ctagagtcaa gagctctggg gtactggtta gttcataatg 11940ttgttgcacc tacagggttg aa 11962212828PRThomo sapiens 21Met Pro Lys Arg Ala His Trp Gly Ala Leu Ser Val Val Leu Ile Leu1 5 10 15Leu Trp Gly His Pro Arg Val Ala Leu Ala Cys Pro His Pro Cys Ala 20 25 30Cys Tyr Val Pro Ser Glu Val His Cys Thr Phe Arg Ser Leu Ala Ser 35 40 45Val Pro Ala Gly Ile Ala Arg His Val Glu Arg Ile Asn Leu Gly Phe 50 55 60Asn Ser Ile Gln Ala Leu Ser Glu Thr Ser Phe Ala Gly Leu Thr Lys65 70 75 80Leu Glu Leu Leu Met Ile His Gly Asn Glu Ile Pro Ser Ile Pro Asp 85 90 95Gly Ala Leu Arg Asp Leu Ser Ser Leu Gln Val Phe Lys Phe Ser Tyr 100 105 110Asn Lys Leu Arg Val Ile Thr Gly Gln Thr Leu Gln Gly Leu Ser Asn 115 120 125Leu Met Arg Leu His Ile Asp His Asn Lys Ile Glu Phe Ile His Pro 130 135 140Gln Ala Phe Asn Gly Leu Thr Ser Leu Arg Leu Leu His Leu Glu Gly145 150 155 160Asn Leu Leu His Gln Leu His Pro Ser Thr Phe Ser Thr Phe Thr Phe 165 170 175Leu Asp Tyr Phe Arg Leu Ser Thr Ile Arg His Leu Tyr Leu Ala Glu 180 185 190Asn Met Val Arg Thr Leu Pro Ala Ser Met Leu Arg Asn Met Pro Leu 195 200 205Leu Glu Asn Leu Tyr Leu Gln Gly Asn Pro Trp Thr Cys Asp Cys Glu 210 215 220Met Arg Trp Phe Leu Glu Trp Asp Ala Lys Ser Arg Gly Ile Leu Lys225 230 235 240Cys Lys Lys Asp Lys Ala Tyr Glu Gly Gly Gln Leu Cys Ala Met Cys 245 250 255Phe Ser Pro Lys Lys Leu Tyr Lys His Glu Ile His Lys Leu Lys Asp 260 265 270Met Thr Cys Leu Lys Pro Ser Ile Glu Ser Pro Leu Arg Gln Asn Arg 275 280 285Ser Arg Ser Ile Glu Glu Glu Gln Glu Gln Glu Glu Asp Gly Gly Ser 290 295 300Gln Leu Ile Leu Glu Lys Phe Gln Leu Pro Gln Trp Ser Ile Ser Leu305 310 315 320Asn Met Thr Asp Glu His Gly Asn Met Val Asn Leu Val Cys Asp Ile 325 330 335Lys Lys Pro Met Asp Val Tyr Lys Ile His Leu Asn Gln Thr Asp Pro 340 345 350Pro Asp Ile Asp Ile Asn Ala Thr Val Ala Leu Asp Phe Glu Cys Pro 355 360 365Met Thr Arg Glu Asn Tyr Glu Lys Leu Trp Lys Leu Ile Ala Tyr Tyr 370 375 380Ser Glu Val Pro Val Lys Leu His Arg Glu Leu Met Leu Ser Lys Asp385 390 395 400Pro Arg Val Ser Tyr Gln Tyr Arg Gln Asp Ala Asp Glu Glu Ala Leu 405 410 415Tyr Tyr Thr Gly Val Arg Ala Gln Ile Leu Ala Glu Pro Glu Trp Val 420 425 430Met Gln Pro Ser Ile Asp Ile Gln Leu Asn Arg Arg Gln Ser Thr Ala 435 440 445Lys Lys Val Leu Leu Ser Tyr Tyr Thr Gln Tyr Ser Gln Thr Ile Ser 450 455 460Thr Lys Asp Thr Arg Gln Ala Arg Gly Arg Ser Trp Val Met Ile Glu465 470 475 480Pro Ser Gly Ala Val Gln Arg Asp Gln Thr Val Leu Glu Gly Gly Pro 485 490 495Cys Gln Leu Ser Cys Asn Val Lys Ala Ser Glu Ser Pro Ser Ile Phe 500 505 510Trp Val Leu Pro Asp Gly Ser Ile Leu Lys Ala Pro Met Asp Asp Pro 515 520 525Asp Ser Lys Phe Ser Ile Leu Ser Ser Gly Trp Leu Arg Ile Lys Ser 530 535 540Met Glu Pro Ser Asp Ser Gly Leu Tyr Gln Cys Ile Ala Gln Val Arg545 550 555 560Asp Glu Met Asp Arg Met Val Tyr Arg Val Leu Val Gln Ser Pro Ser 565 570 575Thr Gln Pro Ala Glu Lys Asp Thr Val Thr Ile Gly Lys Asn Pro Gly 580 585 590Glu Ser Val Thr Leu Pro Cys Asn Ala Leu Ala Ile Pro Glu Ala His 595 600 605Leu Ser Trp Ile Leu Pro Asn Arg Arg Ile Ile Asn Asp Leu Ala Asn 610 615 620Thr Ser His Val Tyr Met Leu Pro Asn Gly Thr Leu Ser Ile Pro Lys625 630 635 640Val Gln Val Ser Asp Ser Gly Tyr Tyr Arg Cys Val Ala Val Asn Gln 645 650 655Gln Gly Ala Asp His Phe Thr Val Gly Ile Thr Val Thr Lys Lys Gly 660 665 670Ser Gly Leu Pro Ser Lys Arg Gly Arg Arg Pro Gly Ala Lys Ala Leu 675 680 685Ser Arg Val Arg Glu Asp Ile Val Glu Asp Glu Gly Gly Ser Gly Met 690 695 700Gly Asp Glu Glu Asn Thr Ser Arg Arg Leu Leu His Pro Lys Asp Gln705 710 715 720Glu Val Phe Leu Lys Thr Lys Asp Asp Ala Ile Asn Gly Asp Lys Lys 725 730 735Ala Lys Lys Gly Arg Arg Lys Leu Lys Leu Trp Lys His Ser Glu Lys 740 745 750Glu Pro Glu Thr Asn Val Ala Glu Gly Arg Arg Val Phe Glu Ser Arg 755 760 765Arg Arg Ile Asn Met Ala Asn Lys Gln Ile Asn Pro Glu Arg Trp Ala 770 775 780Asp Ile Leu Ala Lys Val Arg Gly Lys Asn Leu Pro Lys Gly Thr Glu785 790 795 800Val Pro Pro Leu Ile Lys Thr Thr Ser Pro Pro Ser Leu Ser Leu Glu 805 810 815Val Thr Pro Pro Phe Pro Ala Val Ser Pro Pro Ser Ala Ser Pro Val 820 825 830Gln Thr Val Thr Ser Ala Glu Glu Ser Ser Ala Asp Val Pro Leu Leu 835 840 845Gly Glu Glu Glu His Val Leu Gly Thr Ile Ser Ser Ala Ser Met Gly 850 855 860Leu Glu His Asn His Asn Gly Val Ile Leu Val Glu Pro Glu Val Thr865 870 875 880Ser Thr Pro Leu Glu Glu Val Val Asp Asp Leu Ser Glu Lys Thr Glu 885 890 895Glu Ile Thr Ser Thr Glu Gly Asp Leu Lys Gly Thr Ala Ala Pro Thr 900 905 910Leu Ile Ser Glu Pro Tyr Glu Pro Ser Pro Thr Leu His Thr Leu Asp 915 920 925Thr Val Tyr Glu Lys Pro Thr His Glu Glu Thr Ala Thr Glu Gly Trp 930 935 940Ser Ala Ala Asp Val Gly Ser Ser Pro Glu Pro Thr Ser Ser Glu Tyr945 950 955 960Glu Pro Pro Leu Asp Ala Val Ser Leu Ala Glu Ser Glu Pro Met Gln 965 970 975Tyr Phe Asp Pro Asp Leu Glu Thr Lys Ser Gln Pro Asp Glu Asp Lys 980 985 990Met Lys Glu Asp Thr Phe Ala His Leu Thr Pro Thr Pro Thr Ile Trp 995 1000 1005Val Asn Asp Ser Ser Thr Ser Gln Leu Phe Glu Asp Ser Thr Ile 1010 1015 1020Gly Glu Pro Gly Val Pro Gly Gln Ser His Leu Gln Gly Leu Thr 1025 1030 1035Asp Asn Ile His Leu Val Lys Ser Ser Leu Ser Thr Gln Asp Thr 1040 1045 1050Leu Leu Ile Lys Lys Gly Met Lys Glu Met Ser Gln Thr Leu Gln 1055 1060 1065Gly Gly Asn Met Leu Glu Gly Asp Pro Thr His Ser Arg Ser Ser 1070 1075 1080Glu Ser Glu Gly Gln Glu Ser Lys Ser Ile Thr Leu Pro Asp Ser 1085 1090 1095Thr Leu Gly Ile Met Ser Ser Met Ser Pro Val Lys Lys Pro Ala 1100 1105 1110Glu Thr Thr Val Gly Thr Leu Leu Asp Lys Asp Thr Thr Thr Val 1115 1120 1125Thr Thr Thr Pro Arg Gln Lys Val Ala Pro Ser Ser Thr Met Ser 1130 1135 1140Thr His Pro Ser Arg Arg Arg Pro Asn Gly Arg Arg Arg Leu Arg 1145 1150 1155Pro Asn Lys Phe Arg His Arg His Lys Gln Thr Pro Pro Thr Thr 1160 1165 1170Phe Ala Pro Ser Glu Thr Phe Ser Thr Gln Pro Thr Gln Ala Pro 1175 1180 1185Asp Ile Lys Ile Ser Ser Gln Val Glu Ser Ser Leu Val Pro Thr 1190 1195 1200Ala Trp Val Asp Asn Thr Val Asn Thr Pro Lys Gln Leu Glu Met 1205 1210 1215Glu Lys Asn Ala Glu Pro Thr Ser Lys Gly Thr Pro Arg Arg Lys 1220 1225 1230His Gly Lys Arg Pro Asn Lys His Arg Tyr Thr Pro Ser Thr Val 1235 1240 1245Ser Ser Arg Ala Ser Gly Ser Lys Pro Ser Pro Ser Pro Glu Asn 1250 1255 1260Lys His Arg Asn Ile Val Thr Pro Ser Ser Glu Thr Ile Leu Leu 1265 1270 1275Pro Arg Thr Val Ser Leu Lys Thr Glu Gly Pro Tyr Asp Ser Leu 1280 1285 1290Asp Tyr Met Thr Thr Thr Arg Lys Ile Tyr Ser Ser Tyr Pro Lys 1295 1300 1305Val Gln Glu Thr Leu Pro Val Thr Tyr Lys Pro Thr Ser Asp Gly 1310 1315 1320Lys Glu Ile Lys Asp Asp Val Ala Thr Asn Val Asp Lys His Lys 1325 1330 1335Ser Asp Ile Leu Val Thr Gly Glu Ser Ile Thr Asn Ala Ile Pro 1340 1345 1350Thr Ser Arg Ser Leu Val Ser Thr Met Gly Glu Phe Lys Glu Glu 1355 1360 1365Ser Ser Pro Val Gly Phe Pro Gly Thr Pro Thr Trp Asn Pro Ser 1370 1375 1380Arg Thr Ala Gln Pro Gly Arg Leu Gln Thr Asp Ile Pro Val Thr 1385 1390 1395Thr Ser Gly Glu Asn Leu Thr Asp Pro Pro Leu Leu Lys Glu Leu 1400 1405 1410Glu Asp Val Asp Phe Thr Ser Glu Phe Leu Ser Ser Leu Thr Val 1415 1420 1425Ser Thr Pro Phe His Gln Glu Glu Ala Gly Ser Ser Thr Thr Leu 1430 1435 1440Ser Ser Ile Lys Val Glu Val Ala Ser Ser Gln Ala Glu Thr Thr 1445 1450 1455Thr Leu Asp Gln Asp His Leu Glu Thr Thr Val Ala Ile Leu Leu 1460 1465 1470Ser Glu Thr Arg Pro Gln Asn His Thr Pro Thr Ala Ala Arg Met 1475 1480 1485Lys Glu Pro Ala Ser Ser Ser Pro Ser Thr Ile Leu Met Ser Leu 1490 1495 1500Gly Gln Thr Thr Thr Thr Lys Pro Ala Leu Pro Ser Pro Arg Ile 1505 1510 1515Ser Gln Ala Ser Arg Asp Ser Lys Glu Asn Val Phe Leu Asn Tyr 1520 1525 1530Val Gly Asn Pro Glu Thr Glu Ala Thr Pro Val Asn Asn Glu Gly 1535 1540 1545Thr Gln His Met Ser Gly Pro Asn Glu Leu Ser Thr Pro Ser Ser 1550 1555 1560Asp Arg Asp Ala Phe Asn Leu Ser Thr Lys Leu Glu Leu Glu Lys 1565 1570 1575Gln Val Phe Gly Ser Arg Ser Leu Pro Arg Gly Pro Asp Ser Gln 1580 1585 1590Arg Gln Asp Gly Arg Val His Ala Ser His Gln Leu Thr Arg Val 1595 1600 1605Pro Ala Lys Pro Ile Leu Pro Thr Ala Thr Val Arg Leu Pro Glu 1610 1615 1620Met Ser Thr Gln Ser Ala Ser Arg Tyr Phe Val Thr Ser Gln Ser 1625 1630 1635Pro Arg His Trp Thr Asn Lys Pro Glu Ile Thr Thr Tyr Pro Ser 1640 1645 1650Gly Ala Leu Pro Glu Asn Lys Gln Phe Thr Thr Pro Arg Leu Ser 1655 1660 1665Ser Thr Thr Ile Pro Leu Pro Leu His Met Ser Lys Pro Ser Ile 1670 1675 1680Pro Ser Lys Phe Thr Asp Arg Arg Thr Asp Gln Phe Asn Gly Tyr 1685 1690 1695Ser Lys Val Phe Gly Asn Asn Asn Ile Pro Glu Ala Arg Asn Pro 1700 1705 1710Val Gly Lys Pro Pro Ser Pro Arg Ile Pro His Tyr Ser Asn Gly 1715 1720 1725Arg Leu Pro Phe Phe Thr Asn Lys Thr Leu Ser Phe Pro Gln Leu 1730 1735 1740Gly Val Thr Arg Arg Pro Gln Ile Pro Thr Ser Pro Ala Pro Val 1745 1750 1755Met Arg Glu Arg Lys Val Ile Pro Gly Ser Tyr Asn Arg Ile His 1760 1765 1770Ser His Ser Thr Phe His Leu Asp Phe Gly Pro Pro Ala Pro Pro 1775 1780 1785Leu Leu His Thr Pro Gln Thr Thr Gly Ser Pro Ser Thr Asn Leu 1790 1795 1800Gln Asn Ile Pro Met Val Ser Ser Thr Gln Ser Ser Ile Ser Phe 1805 1810 1815Ile Thr Ser Ser Val Gln Ser Ser Gly Ser Phe His Gln Ser Ser 1820 1825 1830Ser Lys Phe Phe Ala Gly Gly Pro Pro Ala Ser Lys Phe Trp Ser 1835 1840 1845Leu Gly Glu Lys Pro Gln Ile Leu Thr Lys Ser Pro Gln Thr Val 1850 1855 1860Ser Val Thr Ala Glu Thr Asp Thr Val Phe Pro Cys Glu Ala Thr 1865 1870 1875Gly Lys Pro Lys Pro Phe Val Thr Trp Thr Lys Val Ser Thr Gly 1880 1885 1890Ala Leu Met Thr Pro Asn Thr Arg Ile Gln Arg Phe Glu Val Leu 1895 1900 1905Lys Asn Gly Thr Leu Val Ile Arg Lys Val Gln Val Gln Asp Arg 1910 1915 1920Gly Gln Tyr Met Cys Thr Ala Ser Asn Leu His Gly Leu Asp Arg 1925 1930 1935Met Val Val Leu Leu Ser Val Thr Val Gln Gln Pro Gln Ile Leu 1940 1945 1950Ala Ser His Tyr Gln Asp Val Thr Val Tyr Leu Gly Asp Thr Ile 1955 1960 1965Ala Met Glu Cys Leu Ala Lys Gly Thr Pro Ala Pro Gln Ile Ser 1970 1975 1980Trp Ile Phe Pro Asp Arg Arg Val Trp Gln Thr Val Ser Pro Val 1985 1990 1995Glu Ser Arg Ile Thr Leu His Glu Asn Arg Thr Leu Ser Ile Lys 2000 2005 2010Glu Ala Ser Phe Ser Asp Arg Gly Val Tyr Lys Cys Val Ala Ser 2015 2020 2025Asn Ala Ala Gly Ala Asp Ser Leu Ala Ile Arg Leu His Val Ala 2030 2035 2040Ala Leu Pro Pro Val Ile His Gln Glu Lys Leu Glu Asn Ile Ser 2045 2050 2055Leu Pro Pro Gly Leu Ser Ile His Ile His Cys Thr Ala Lys Ala 2060 2065 2070Ala Pro Leu Pro Ser Val Arg Trp Val Leu Gly Asp Gly Thr Gln 2075 2080 2085Ile Arg Pro Ser Gln Phe Leu His Gly Asn Leu Phe Val Phe Pro 2090 2095 2100Asn Gly Thr Leu Tyr Ile Arg Asn Leu Ala Pro Lys Asp Ser Gly 2105 2110 2115Arg Tyr Glu Cys Val Ala Ala Asn Leu Val Gly Ser Ala Arg Arg 2120 2125 2130Thr Val Gln Leu Asn Val Gln Arg Ala Ala Ala Asn Ala Arg Ile 2135 2140 2145Thr Gly Thr Ser Pro Arg Arg Thr Asp Val Arg Tyr Gly Gly Thr 2150 2155 2160Leu Lys Leu Asp Cys Ser Ala Ser Gly Asp Pro Trp Pro Arg Ile 2165 2170 2175Leu Trp Arg Leu Pro Ser Lys Arg Met Ile Asp Ala Leu Phe Ser 2180 2185 2190Phe Asp Ser Arg Ile Lys Val Phe Ala Asn Gly Thr Leu Val Val 2195 2200 2205Lys Ser Val Thr Asp Lys Asp Ala Gly Asp Tyr Leu Cys Val Ala 2210 2215 2220Arg Asn Lys Val Gly Asp Asp Tyr Val Val Leu Lys Val Asp Val 2225 2230 2235Val Met Lys Pro Ala Lys Ile Glu His Lys Glu Glu Asn Asp His 2240 2245 2250Lys Val Phe Tyr Gly Gly Asp Leu Lys Val Asp Cys Val Ala Thr 2255 2260 2265Gly Leu Pro Asn Pro Glu Ile Ser Trp Ser Leu Pro Asp Gly Ser 2270 2275 2280Leu Val Asn Ser Phe Met Gln Ser Asp Asp Ser Gly Gly Arg Thr 2285 2290 2295Lys Arg Tyr Val Val Phe Asn Asn Gly Thr Leu Tyr Phe Asn Glu 2300 2305 2310Val Gly Met Arg Glu Glu Gly Asp Tyr Thr Cys Phe Ala Glu Asn 2315 2320 2325Gln Val Gly Lys Asp Glu Met Arg Val Arg Val Lys Val Val Thr 2330 2335 2340Ala Pro Ala Thr Ile Arg Asn Lys Thr Tyr Leu Ala Val Gln Val 2345 2350 2355Pro Tyr Gly Asp Val Val Thr Val Ala Cys Glu Ala Lys Gly Glu 2360 2365 2370Pro Met Pro Lys Val Thr Trp Leu Ser Pro Thr Asn Lys Val Ile 2375 2380 2385Pro Thr Ser Ser Glu Lys Tyr Gln Ile Tyr Gln Asp Gly Thr Leu 2390

2395 2400Leu Ile Gln Lys Ala Gln Arg Ser Asp Ser Gly Asn Tyr Thr Cys 2405 2410 2415Leu Val Arg Asn Ser Ala Gly Glu Asp Arg Lys Thr Val Trp Ile 2420 2425 2430His Val Asn Val Gln Pro Pro Lys Ile Asn Gly Asn Pro Asn Pro 2435 2440 2445Ile Thr Thr Val Arg Glu Ile Ala Ala Gly Gly Ser Arg Lys Leu 2450 2455 2460Ile Asp Cys Lys Ala Glu Gly Ile Pro Thr Pro Arg Val Leu Trp 2465 2470 2475Ala Phe Pro Glu Gly Val Val Leu Pro Ala Pro Tyr Tyr Gly Asn 2480 2485 2490Arg Ile Thr Val His Gly Asn Gly Ser Leu Asp Ile Arg Ser Leu 2495 2500 2505Arg Lys Ser Asp Ser Val Gln Leu Val Cys Met Ala Arg Asn Glu 2510 2515 2520Gly Gly Glu Ala Arg Leu Ile Val Gln Leu Thr Val Leu Glu Pro 2525 2530 2535Met Glu Lys Pro Ile Phe His Asp Pro Ile Ser Glu Lys Ile Thr 2540 2545 2550Ala Met Ala Gly His Thr Ile Ser Leu Asn Cys Ser Ala Ala Gly 2555 2560 2565Thr Pro Thr Pro Ser Leu Val Trp Val Leu Pro Asn Gly Thr Asp 2570 2575 2580Leu Gln Ser Gly Gln Gln Leu Gln Arg Phe Tyr His Lys Ala Asp 2585 2590 2595Gly Met Leu His Ile Ser Gly Leu Ser Ser Val Asp Ala Gly Ala 2600 2605 2610Tyr Arg Cys Val Ala Arg Asn Ala Ala Gly His Thr Glu Arg Leu 2615 2620 2625Val Ser Leu Lys Val Gly Leu Lys Pro Glu Ala Asn Lys Gln Tyr 2630 2635 2640His Asn Leu Val Ser Ile Ile Asn Gly Glu Thr Leu Lys Leu Pro 2645 2650 2655Cys Thr Pro Pro Gly Ala Gly Gln Gly Arg Phe Ser Trp Thr Leu 2660 2665 2670Pro Asn Gly Met His Leu Glu Gly Pro Gln Thr Leu Gly Arg Val 2675 2680 2685Ser Leu Leu Asp Asn Gly Thr Leu Thr Val Arg Glu Ala Ser Val 2690 2695 2700Phe Asp Arg Gly Thr Tyr Val Cys Arg Met Glu Thr Glu Tyr Gly 2705 2710 2715Pro Ser Val Thr Ser Ile Pro Val Ile Val Ile Ala Tyr Pro Pro 2720 2725 2730Arg Ile Thr Ser Glu Pro Thr Pro Val Ile Tyr Thr Arg Pro Gly 2735 2740 2745Asn Thr Val Lys Leu Asn Cys Met Ala Met Gly Ile Pro Lys Ala 2750 2755 2760Asp Ile Thr Trp Glu Leu Pro Asp Lys Ser His Leu Lys Ala Gly 2765 2770 2775Val Gln Ala Arg Leu Tyr Gly Asn Arg Phe Leu His Pro Gln Gly 2780 2785 2790Ser Leu Thr Ile Gln His Ala Thr Gln Arg Asp Ala Gly Phe Tyr 2795 2800 2805Lys Cys Met Ala Lys Asn Ile Leu Gly Ser Asp Ser Lys Thr Thr 2810 2815 2820Tyr Ile His Val Phe 2825229645DNAhomo sapiensmisc_feature(1)..(9645)'n' can be any nucleotide 'a', 'c', 'g' or 't'. 22atgcccaagc gcgcgcactg gggggccctc tccgtggtgc tgatcctgct ttggggccat 60ccgcgagtgg cgctggcctg cccgcatcct tgtgcctgct acgtccccag cgaggtccac 120tgcacgttcc gatccctggc ttccgtgccc gctggcattg ctagacacgt ggaaagaatc 180aatttggggt ttaatagcat acaggccctg tcagaaacct catttgcagg actgaccaag 240ttggagctac ttatgattca cggcaatgag atcccaagca tccccgatgg agctttaaga 300gacctcagct ctcttcaggt tttcaagttc agctacaaca agctgagagt gatcacagga 360cagaccctcc agggtctctc taacttaatg aggctgcaca ttgaccacaa caagatcgag 420tttatccacc ctcaagcttt caacggctta acgtctctga ggctactcca tttggaagga 480aatctcctcc accagctgca ccccagcacc ttctccacgt tcacattttt ggattatttc 540agactctcca ccataaggca cctctactta gcagagaaca tggttagaac tcttcctgcc 600agcatgcttc ggaacatgcc gcttctggag aatctttact tgcagggaaa tccgtggacc 660tgcgattgtg agatgagatg gtttttggaa tgggatgcaa aatccagagg aattctgaag 720tgtaaaaagg acaaagctta tgaaggcggt cagttgtgtg caatgtgctt cagtccaaag 780aagttgtaca aacatgagat acacaagctg aaggacatga cttgtctgaa gccttcaata 840gagtcccctc tgagacagaa caggagcagg agtattgagg aggagcaaga acaggaagag 900gatggtggca gccagctcat cctggagaaa ttccaactgc cccagtggag catctctttg 960aatatgaccg acgagcacgg gaacatggtg aacttggtct gtgacatcaa gaaaccaatg 1020gatgtgtaca agattcactt gaaccaaacg gatcctccag atattgacat aaatgcaaca 1080gttgccttgg actttgagtg tccaatgacc cgagaaaact atgaaaagct atggaaattg 1140atagcatact acagtgaagt tcccgtgaag ctacacagag agctcatgct cagcaaagac 1200cccagagtca gctaccagta caggcaggat gctgatgagg aagctcttta ctacacaggt 1260gtgagagccc agattcttgc agaaccagaa tgggtcatgc agccatccat agatatccag 1320ctgaaccgac gtcagagtac ggccaagaag gtgctacttt cctactacac ccagtattct 1380caaacaatat ccaccaaaga tacaaggcag gctcggggca gaagctgggt aatgattgag 1440cctagtggag ctgtgcaaag agatcagact gtcctggaag ggggtccatg ccagttgagc 1500tgcaacgtga aagcttctga gagtccatct atcttctggg tgcttccaga tggctccatc 1560ctgaaagcgc ccatggatga cccagacagc aagttctcca ttctcagcag tggctggctg 1620aggatcaagt ccatggagcc atctgactca ggcttgtacc agtgcattgc tcaagtgagg 1680gatgaaatgg accgcatggt atatagggta cttgtgcagt ctccctccac tcagccagcc 1740gagaaagaca cagtgacaat tggcaagaac ccaggggagt cggtgacatt gccttgcaat 1800gctttagcaa tacccgaagc ccaccttagc tggattcttc caaacagaag gataattaat 1860gatttggcta acacatcaca tgtatacatg ttgccaaatg gaactctttc catcccaaag 1920gtccaagtca gtgatagtgg ttactacaga tgtgtggctg tcaaccagca aggggcagac 1980cattttacgg tgggaatcac agtgaccaag aaagggtctg gcttgccatc caaaagaggc 2040agacgcccag gtgcaaaggc tctttccaga gtcagagaag acatcgtgga ggatgaaggg 2100ggctcgggca tgggagatga agagaacact tcaaggagac ttctgcatcc aaaggaccaa 2160gaggtgttcc tcaaaacaaa ggatgatgcc atcaatggag acaagaaagc caagaaaggg 2220agaagaaagc tgaaactctg gaagcattcg gaaaaagaac cagagaccaa tgttgcagaa 2280ggtcgcagag tgtttgaatc tagacgaagg ataaacatgg caaacaaaca gattaatccg 2340gagcgctggg ctgatatttt agccaaagtc cgtgggaaaa atctccctaa gggcacagaa 2400gtacccccgt tgattaaaac cacaagtcct ccatccttga gcctagaagt cacaccacct 2460tttcctgctg tttctccccc ctcagcatct cctgtgcaga cagtaaccag tgctgaagaa 2520tcctcagcag atgtacctct acttggtgaa gaagagcacg ttttgggtac catttcctca 2580gccagcatgg ggctagaaca caaccacaat ggagttattc ttgttgaacc tgaagtaaca 2640agcacacctc tggaggaagt tgttgatgac ctttctgaga agactgagga gataacttcc 2700actgaaggag acctgaaggg gacagcagcc cctacactta tatctgagcc ttatgaacca 2760tctcctactc tgcacacatt agacacagtc tatgaaaagc ccacccatga agagacggca 2820acagagggtt ggtctgcagc agatgttgga tcgtcaccag agcccacatc cagtgagtat 2880gagcctccat tggatgctgt ctccttggct gagtctgagc ccatgcaata ctttgaccca 2940gatttggaga ctaagtcaca accagatgag gataagatga aagaagacac ctttgcacac 3000cttactccaa cccccaccat ctgggttaat gactccagta catcacagtt atttgaggat 3060tctactatag gggaaccagg tgtcccaggc caatcacatc tacaaggact gacagacaac 3120atccaccttg tgaaaagtag tctaagcact caagacacct tactgattaa aaagggtatg 3180aaagagatgt ctcagacact acagggagga aatatgctag agggagaccc cacacactcc 3240agaagttctg agagtgaggg ccaagagagc aaatccatca ctttgcctga ctccacactg 3300ggtataatga gcagtatgtc tccagttaag aagcctgcgg aaaccacagt tggtaccctc 3360ctagacaaag acaccacaac agtaacaaca acaccaaggc aaaaagttgc tccgtcatcc 3420accatgagca ctcacccttc tcgaaggaga cccaacggga gaaggagatt acgccccaac 3480aaattccgcc accggcacaa gcaaacccca cccacaactt ttgccccatc agagactttt 3540tctactcaac caactcaagc acctgacatt aagatttcaa gtcaagtgga gagttctctg 3600gttcctacag cttgggtgga taacacagtt aataccccca aacagttgga aatggagaag 3660aatgcagaac ccacatccaa gggaacacca cggagaaaac acgggaagag gccaaacaaa 3720catcgatata ccccttctac agtgagctca agagcgtccg gatccaagcc cagcccttct 3780ccagaaaata aacatagaaa cattgttact cccagttcag aaactatact tttgcctaga 3840actgtttctc tgaaaactga gggcccttat gattccttag attacatgac aaccaccaga 3900aaaatatatt catcttaccc taaagtccaa gagacacttc cagtcacata taaacccaca 3960tcagatggaa aagaaattaa ggatgatgtt gccacaaatg ttgacaaaca taaaagtgac 4020attttagtca ctggtgaatc aattactaat gccataccaa cttctcgctc cttggtctcc 4080actatgggag aatttaagga agaatcctct cctgtaggct ttccaggaac tccaacctgg 4140aatccctcaa ggacggccca gcctgggagg ctacagacag acatacctgt taccacttct 4200ggggaaaatc ttacagaccc tccccttctt aaagagcttg aggatgtgga tttcacttcc 4260gagtttttgt cctctttgac agtctccaca ccatttcacc aggaagaagc tggttcttcc 4320acaactctct caagcataaa agtggaggtg gcttcaagtc aggcagaaac caccaccctt 4380gatcaagatc atcttgaaac cactgtggct attctccttt ctgaaactag accacagaat 4440cacaccccta ctgctgcccg gatgaaggag ccagcatcct cgtccccatc cacaattctc 4500atgtctttgg gacaaaccac caccactaag ccagcacttc ccagtccaag aatatctcaa 4560gcatctagag attccaagga aaatgttttc ttgaattatg tggggaatcc agaaacagaa 4620gcaaccccag tcaacaatga aggaacacag catatgtcag ggccaaatga attatcaaca 4680ccctcttccg accgggatgc atttaacttg tctacaaagc tggaattgga aaagcaagta 4740tttggtagta ggagtctacc acgtggccca gatagccaac gccaggatgg aagagttcat 4800gcttctcatc aactaaccag agtccctgcc aaacccatcc taccaacagc aacagtgagg 4860ctacctgaaa tgtccacaca aagcgcttcc agatactttg taacttccca gtcacctcgt 4920cactggacca acaaaccgga aataactaca tatccttctg gggctttgcc agagaacaaa 4980cagtttacaa ctccaagatt atcaagtaca acaattcctc tcccattgca catgtccaaa 5040cccagcattc ctagtaagtt tactgaccga agaactgacc aattcaatgg ttactccaaa 5100gtgtttggaa ataacaacat ccctgaggca agaaacccag ttggaaagcc tcccagtcca 5160agaattcctc attattccaa tggaagactc cctttcttta ccaacaagac tctttctttt 5220ccacagttgg gagtcacccg gagaccccag atacccactt ctcctgcccc agtaatgaga 5280gagagaaaag ttattccagg ttcctacaac aggatacatt cccatagcac cttccatctg 5340gactttggcc ctccggcacc tccgttgttg cacactccgc agaccacggg atcaccctca 5400actaacttac agaatatccc tatggtctct tccacccaga gttctatctc ctttataaca 5460tcttctgtcc agtcctcagg aagcttccac cagagcagct caaagttctt tgcaggagga 5520cctcctgcat ccaaattctg gtctcttggg gaaaagcccc aaatcctcac caagtcccca 5580cagactgtgt ccgtcaccgc tgagacagac actgtgttcc cctgtgaggc aacaggaaaa 5640ccaaagcctt tcgttacttg gacaaaggtt tccacaggag ctcttatgac tccgaatacc 5700aggatacaac ggtttgaggt tctcaagaac ggtaccttag tgatacggaa ggttcaagta 5760caagatcgag gccagtatat gtgcaccgcc agcaacctgc acggcctgga caggatggtg 5820gtcttgcttt cggtcaccgt gcagcaacct caaatcctag cctcccacta ccaggacgtc 5880actgtctacc tgggagacac cattgcaatg gagtgtctgg ccaaagggac cccagccccc 5940caaatttcct ggatcttccc tgacaggagg gtgtggcaaa ctgtgtcccc cgtggagagc 6000cgcatcaccc tgcacgaaaa ccggaccctt tccatcaagg aggcgtcctt ctcagacaga 6060ggcgtctata agtgcgtggc cagcaatgca gccggggcgg acagcctggc catccgcctg 6120cacgtggcgg cactgccccc cgttatccac caggagaagc tggagaacat ctcgctgccc 6180ccggggctca gcattcacat tcactgcact gccaaggctg cgcccctgcc cagcgtgcgc 6240tgggtgctcg gggacggtac ccagatccgc ccctcgcagt tcctccacgg gaacttgttt 6300gttttcccca acgggacgct ctacatccgc aacctcgcgc ccaaggacag cgggcgctat 6360gagtgcgtgg ccgccaacct ggtaggctcc gcgcgcagga cggtgcagct gaacgtgcag 6420cgtgcagcag ccaacgcgcg catcacgggc acctccccgc ggaggacgga cgtcaggtac 6480ggaggaaccc tcaagctgga ctgcagcgcc tcgggggacc cctggccgcg catcctctgg 6540aggctgccgt ccaagaggat gatcgacgcg ctcttcagtt ttgatagcag aatcaaggtg 6600tttgccaatg ggaccctggt ggtgaaatca gtgacggaca aagatgccgg agattacctg 6660tgcgtagctc gaaataaggt tggtgatgac tacgtggtgc tcaaagtgga tgtggtgatg 6720aaaccggcca agattgaaca caaggaggag aacgaccaca aagtcttcta cgggggtgac 6780ctgaaagtgg actgtgtggc caccgggctt cccaatcccg agatctcctg gagcctccca 6840gacgggagtc tggtgaactc cttcatgcag tcggatgaca gcggtggacg caccaagcgc 6900tatgtcgtct tcaacaatgg gacactctac tttaacgaag tggggatgag ggaggaagga 6960gactacacct gctttgctga aaatcaggtc gggaaggacg agatgagagt cagagtcaag 7020gtggtgacag cgcccgccac catccggaac aagacttact tggcggttca ggtgccctat 7080ggagacgtgg tcactgtagc ctgtgaggcc aaaggagaac ccatgcccaa ggtgacttgg 7140ttgtccccaa ccaacaaggt gatccccacc tcctctgaga agtatcagat ataccaagat 7200ggcactctcc ttattcagaa agcccagcgt tctgacagcg gcaactacac ctgcctggtc 7260aggaacagcg cgggagagga taggaagacg gtgtggattc acgtcaacgt ccagccaccc 7320aagatcaacg gtaaccccaa ccccatcacc accgtgcggg agatagcagc cgggggcagt 7380cggaaactga ttgactgcaa agctgaaggc atccccaccc cgagggtgtt atgggctttt 7440cccgagggtg tggttctgcc agctccatac tatggaaacc ggatcactgt ccatggcaac 7500ggttccctgg acatcaggag tttgaggaag agcgactccg tccagctggt atgcatggca 7560cgcaacgagg gaggggaggc gaggttgatc gtgcagctca ctgtcctgga gcccatggag 7620aaacccatct tccacgaccc gatcagcgag aagatcacgg ccatggcggg ccacaccatc 7680agcctcaact gctctgccgc ggggaccccg acacccagcc tggtgtgggt ccttcccaat 7740ggcaccgatc tgcagagtgg acagcagctg cagcgcttct accacaaggc tgacggcatg 7800ctacacatta gcggtctctc ctcggtggac gctggggcct accgctgcgt ggcccgcaat 7860gccgctggcc acacggagag gctggtctcc ctgaaggtgg gactgaagcc agaagcaaac 7920aagcagtatc ataacctggt cagcatcatc aatggtgaga ccctgaagct cccctgcacc 7980cctcccgggg ctgggcaggg acgtttctcc tggacgctcc ccaatggcat gcatctggag 8040ggcccccaaa ccctgggacg cgtttctctt ctggacaatg gcaccctcac ggttcgtgag 8100gcctcggtgt ttgacagggg tacctatgta tgcaggatgg agacggagta cggcccttcg 8160gtcaccagca tccccgtgat tgtgatcgcc tatcctcccc ggatcaccag cgagcccacc 8220ccggtcatct acacccggcc cgggaacacc gtgaaactga actgcatggc tatggggatt 8280cccaaagctg acatcacgtg ggagttaccg gataagtcgc atctgaaggc aggggttcag 8340gctcgtctgt atggaaacag atttcttcac ccccagggat cactgaccat ccagcatgcc 8400acacagagag atgccggctt ctacaagtgc atggcaaaaa acattctcgg cagtgactcc 8460aaaacaactt acatccacgt cttctgaaat gtggattcca gaatgattgc ttaggaactg 8520acaacaaagc ggggtttgta agggaagcca ggttggggaa taggagctct taaataatgt 8580gtcacagtgc atggtggcct ctggtgggtt tcaagttgag gttgatcttg atctacaatt 8640gttgggaaaa ggaagcaatg cagacacgag aaggagggct cagccttgct gagacacttt 8700cttttgtgtt tacatcatgc caggggcttc attcagggtg tctgtgctct gactgcaatt 8760tttcttcttt tgcaaatgcc actcgactgc cttcataagc gtccatagga tatctgagga 8820acattcatca aaaataagcc atagacatga acaacacctc actaccccat tgaagacgca 8880tcacctagtt aacctgctgc agtttttaca tgatagactt tgttccagat tgacaagtca 8940tctttcagtt atttcctctg tcacttcaaa actccagctt gcccaataag gatttagaac 9000cagagtgact gatatatata tatatatttt aattcagagt tacatacata cagctaccat 9060tttatatgaa aaaagaaaaa catttcttcc tggaactcac tttttatata atgttttata 9120tatatatttt ttcctttcaa atcagacgat gagactagaa ggagaaatac tttctgtctt 9180attaaaatta ataaattatt ggtctttaca agacttggat acattacagc agacatggaa 9240atataatttt aaaaaatttc tctccaacct ccttcaaatt cagtcaccac tgttatatta 9300ccttctccag gaaccctcca gtggggaagg ctgcgatatt agatttcctt gtatgcaaag 9360tttttgttga aagctgtgct cagaggaggt gagaggagag gaaggagaaa actgcatcat 9420aactttacag aattgaatct agagtcttcc ccgaaaagcc cagaaacttc tctgcagtat 9480ctggcttgtc catctggtct aaggtggctg cttcttcccc agccatgagt cagtttgtgc 9540ccatgaataa tacacgacct gttatttcca tgactgcttt actgtatttt taaggtcaat 9600atactgtaca tttgataata aaataatatt ctcccaaaaa aaaaa 9645237770DNAhomo sapien 23atgaaggtaa aaggcagagg aatcacctgc ttgctggtct cctttgctgt gatctgcctg 60gtcgccaccc ctgggggcaa ggcctgtcct cgccgctgtg cctgttatat gcctacggag 120gtacactgca catttcggta cctgacttcc atcccagaca gcatcccgcc caatgtggaa 180cgcatcaatt taggatacaa cagcttggtt agattgatgg aaacagattt ttctggcctg 240accaaactgg agttactcat gcttcacagc aatggcattc acacaatccc tgacaagacc 300ttctcagatt tgcaggcctt gcaggtctta aaaatgagct ataataaagt ccgaaaactt 360cagaaagata ctttttatgg cctcaggagc ttgacacgat tgcacatgga ccacaacaat 420attgagttta taaacccaga ggttttttat gggctcaact ttctccgcct ggtgcacttg 480gaaggaaatc agctcactaa gctccaccca gatacatttg tctctttgag ctacctccag 540atatttaaaa tctctttcat taagttccta tacttgtctg ataacttcct gacctccctc 600cctcaagaga tggtctccta tatgcctgac ctagacagcc tttacctgca tggaaaccca 660tggacctgtg attgccattt aaagtggttg tctgactgga tacaggagaa gccagatgta 720ataaaatgca aaaaagatag aagtccctct agtgctcagc agtgtccact ttgcatgaac 780cctaggactt ctaaaggcaa gccgttagct atggtctcag ctgcagcttt ccagtgtgcc 840aagccaacca ttgactcatc cctgaaatca aagagcctga ctattctgga agacagtagt 900tctgctttca tctctcccca aggtttcatg gcaccctttg gctccctcac tttgaatatg 960acagatcagt ctggaaatga agctaacatg gtctgcagta ttcaaaagcc ctcaaggaca 1020tcacccattg cattcactga agaaaatgac tacatcgtgc taaatacttc attttcaaca 1080tttttggtgt gcaacataga ttacggtcac attcagccag tgtggcaaat tttggctttg 1140tacagtgatt ctcctctgat actagaaagg agccacttgc ttagtgaaac accgcagctc 1200tattacaaat ataaacaggt ggctcctaag cctgaagaca tttttaccaa catagaggca 1260gatctcagag cagatccctc ttggttaatg caagaccaaa tttccttgca gctgaacaga 1320actgccacca cattcagtac attacagatc cagtactcca gtgatgctca aatcacttta 1380ccaagagcag agatgaggcc agtgaaacac aaatggacta tgatttcaag ggataacaat 1440actaagctgg aacatactgt cttggtaggt ggaaccgttg gcctgaactg cccaggccaa 1500ggagacccca ccccacacgt ggattggctt ctagctgatg gaagtaaagt gagagcccct 1560tatgtcagtg aggatggacg gatcctaata gacaaaagtg gaaaattgga actccagatg 1620gctgatagtt ttgacacagg cgtatatcac tgtataagca gcaattatga tgatgcagat 1680attctcacct ataggataac tgtggtagaa cctttggtcg aagcctatca ggaaaatggg 1740attcatcaca cagttttcat tggtgaaaca cttgatcttc catgccattc tactggtatc 1800ccagatgcct ctattagctg ggttattcca ggaaacaatg tgctctatca gtcatcaaga 1860gacaagaaag ttctaaacaa tggcacatta agaatattac aggtcacccc gaaagaccaa 1920ggttattatc gctgtgtggc agccaaccca tcaggggttg attttttgat tttccaagtt 1980tcagtcaaga tgaaaggaca aaggcccttg gagcatgatg gagaaacaga gggatctgga 2040cttgatgagt ccaatcctat tgctcatctt aaggagccac caggtgcaca actccgtaca 2100tctgctctga tggaggctga ggttggaaaa cacacctcaa gcacaagtaa gaggcacaac 2160tatcgggaat taacactcca gcgacgtgga gattcaacac atcgacgttt tagggagaat 2220aggaggcatt tccctccctc tgctaggaga attgacccac aacattgggc ggcactgttg 2280gagaaagcta aaaagaatgc tatgccagac aagcgagaaa ataccacagt gagcccaccc 2340ccagtggtca cccaactccc aaacatacct ggtgaagaag acgattcctc aggcatgctc 2400gctctacatg aggaatttat ggtcccggcc actaaagctt tgaaccttcc agcaaggaca 2460gtgactgctg actccagaac aatatctgat agtcctatga caaacataaa ttatggcaca 2520gaattctctc ctgttgtgaa ttcacaaata ctaccacctg aagaacccac agatttcaaa 2580ctgtctactg ctattaaaac tacagccatg tcaaagaata taaacccaac catgtcaagc 2640caaatacaag

gcacaaccaa tcaacattca tccactgtct ttccactgct acttggagca 2700actgaatttc aggactctga ccagatggga agaggaagag agcatttcca aagtagaccc 2760ccaataacag taaggactat gatcaaagat gtcaatgtca aaatgcttag tagcaccacc 2820aacaaactat tattagagtc agtaaatacc acaaatagtc atcagacatc tgtaagagaa 2880gtgagtgaac ccaggcacaa tcacttctat tctcacacta ctcaaatact tagcacctcc 2940acgttccctt cagatccaca cacagctgct cattctcagt ttccgatccc tagaaatagt 3000acagttaaca tcccgctgtt cagacgcttt gggaggcaga ggaaaattgg cggaaggggg 3060cggattatca gcccatatag aactccagtt ctgcgacggc atagatacag cattttcagg 3120tcaacaacca gaggttcttc tgaaaaaagc actactgcat tctcagccac agtgctcaat 3180gtgacatgtc tgtcctgtct tcccagggag aggctcacca ctgccacagc agcattgtct 3240tttccaagtg ctgctcccat caccttcccc aaagctgaca ttgctagagt cccatcagaa 3300gagtctacaa ctctagtcca gaatccacta ttactacttg agaacaaacc cagtgtagag 3360aaaacaacac ccacaataaa atatttcagg actgaaattt cccaagtgac tccaactggt 3420gcagtcatga catatgctcc aacatccata cccatggaaa aaactcacaa agtaaacgcc 3480agttacccac gtgtgtctag caccaatgaa gctaaaagag attcagtgat tacatcgtca 3540ctttcaggtg ctatcaccaa gccaccaatg actattatag ccattacaag gttttcaaga 3600aggaaaattc cctggcaaca gaactttgta aataaccata acccaaaagg cagattaagg 3660aatcaacata aagttagttt acaaaaaagc acagctgtga tgcttcctaa aacatctcct 3720gctttaccac agagacaaag ttcccctttc catttcacca cactttcaac aagtgtgatg 3780caaattccat ctaatacctt gactaccgct caccacacta cgaccaaaac acacaatcct 3840ggaagtcttc caacaaagaa ggagcttccc ttcccacccc ttaaccctat gcttcctagt 3900attataagca aagactcaag tacaaaaagc atcatatcaa cgcaaacagc aataccagca 3960acaactccta ccttccctgc atctgtcatc acttatgaaa cccaaacaga gagatctaga 4020gcacaaacaa tacaaagaga acaggagcct caaaagaaga acaggactga cccaaacatc 4080tctccagacc agagttctgg cttcactaca cccactgcta tgacacctcc tgctctggca 4140ttcactcatt ccccaccaga aaacacaact gggatttcaa gcacaatcag ttttcattca 4200agaactctta atctgacaga tgtgattgaa gaactagccc aagcaagtac tcagactttg 4260aagagcacaa ttgcttctga aacaactttg tccagcaaat cacaccagag taccacaact 4320aggaaagcat cattagacac tcccatacca ccattcttga gcagcagtgc tactctaatg 4380ccagttccca tctcccctcc ctttactcag agagcagtta ctgacacacg tggcgactcc 4440catttccggc ttatgacaaa tacagtggtc aagctgcacg aatcctcaag gcacaatctc 4500caaatgccaa gttcacaatt ggaaccactc acttcatcta cctctaatct gttacattct 4560actcccatgc cagcactaac aacagttaaa tcacagaatt ccaaattaac tccatctccc 4620tgggcagaat accaattttg gcacaaacca tactcagaca ttgctgaaaa aggcaaaaag 4680ccagaagtaa gcatgttggc tactacaggc ctgtccgagg ccaccactct tgtttcagat 4740tgggatggac agaagaacac aaagaagagt gactttgata agaaaccagt tcaagaagca 4800acaacttcca aactccttcc ctttgactct ttgtctaggt atatatttga aaagcccagg 4860atagttggag gaaaagctgc aagttttact attccagcta actcagatgc ctttcttccc 4920tgtgaagctg ttggaaatcc cctgcccacc attcattgga ccagagtttc aggacttgat 4980ttatctagag gaaaccagaa tagcagggtc caggttctcc ccaatggtac cctgtccatc 5040cagagggtgg aaattcagga ccgcggacag tacttgtgtt ccgcatccaa tctgtttggc 5100acagaccacc ttcatgtcac cttgtctgtg gtttcctatc ctcccaggat cctggagaga 5160cgtaccaaag agatcacagt tcattccgga agcactgtgg aactgaagtg cagagcagaa 5220ggtaggccaa gccctacagt tacctggatt cttgcaaacc aaacagttgt ctcagaatca 5280tcccagggaa gtaggcaggc tgtggtgacg gttgacggaa cattggtcct ccacaatctc 5340agtatttatg accgtggctt ttacaaatgt gtggccagca acccaggtgg ccaggattca 5400ctgctggtta aaatacaagt cattgcagca ccacctgtta ttctagagca aaggaggcaa 5460gtcattgtag gcacttgggg tgaaagttta aaactgccct gtactgcaaa aggaactcct 5520cagcccagcg tttactgggt cctctctgat ggcactgaag tgaaaccatt acagtttacc 5580aattccaagt tgttcttatt ttcaaatggg actttgtata taagaaacct agcctcttca 5640gacaggggca cttatgaatg cattgctacc agttccactg gttcggagcg aagagtagta 5700atgcttacaa tggaagagcg agtgaccagc cccaggatag aagctgcatc ccagaaaagg 5760actgaagtga attttgggga caaattacta ctgaactgct cagccactgg ggagcccaaa 5820ccccaaataa tgtggaggtt accatccaag gctgtggtcg accagtggag ctggatccac 5880gtctacccta atggatccct gtttattgga tcagtaacag aaaaagacag tggtgtctac 5940ttgtgtgtgg caagaaacaa aatgggggat gatctgatac tgatgcatgt tagcctaaga 6000ctgaaacctg ccaaaattga ccacaagcag tattttagaa agcaagtgct ccatgggaaa 6060gatttccaag tagattgcaa agcttccggc tccccagtgc cagagatatc ttggagtttg 6120cctgatggaa ccatgatcaa caatgcaatg caagccgatg acagtggcca caggactagg 6180agatataccc ttttcaacaa tggaacttta tacttcaaca aagttggggt agcggaggaa 6240ggagattata cttgctatgc ccagaacacc ctagggaaag atgaaatgaa ggtccactta 6300acagttataa cagctgctcc ccggataagg cagagtaaca aaaccaacaa gagaatcaaa 6360gctggagaca cagctgtcct tgactgtgag gtcactgggg atcccaaacc aaaaatattt 6420tggttgctgc cttccaatga catgatttcc ttctccattg ataggtacac atttcatgcc 6480aatgggtctt tgaccatcaa caaagtgaaa ctgctcgatt ctggagagta cgtatgtgta 6540gcccgaaatc ccagtgggga tgacaccaaa atgtacaaac tggatgtggt ctctaaacct 6600ccattaatca atggtctgta tacaaacaga actgttatta aagccacagc tgtgagacat 6660tccaaaaaac actttgactg cagagctgaa gggacaccat ctcctgaagt catgtggatc 6720atgccagaca atattttcct cacagcccca tactatggaa gcagaatcac agtccataaa 6780aatggaacct tggaaattag gaatgtgagg ctttcagatt cagccgactt tatctgtgtg 6840gcccgaaatg aaggtggaga gagcgtgttg gtagtacagt tagaagtact ggaaatgctg 6900agaagaccga catttagaaa tccatttaat gaaaaaatag ttgcccagct gggaaagtcc 6960acagcattga attgctctgt tgatggtaac ccaccacctg aaataatctg gattttacca 7020aatggcacac gattttccaa tggaccacaa agttatcagt atctgatagc aagcaatggt 7080tcttttatca tttctaaaac aactcgggag gatgcaggaa aatatcgctg tgcagctagg 7140aataaagttg gctatattga gaaattagtc atattagaaa ttggccagaa gccagttatt 7200cttacctatg caccagggac agtaaaaggc atcagtggag aatctctatc actgcattgt 7260gtgtctgatg gaatccctaa gccaaatatc aaatggacta tgccaagtgg ttatgtagta 7320gacaggcctc aaattaatgg gaaatacata ttgcatgaca atggcacctt agtcattaaa 7380gaagcaacag cttatgacag aggaaactat atctgtaagg ctcaaaatag tgttggtcat 7440acactgatta ctgttccagt aatgattgta gcctaccctc cccgaattac aaatcgtcca 7500cccaggagta ttgtcaccag gacaggggca gcctttcagc tccactgtgt ggccttggga 7560gttcccaagc cagaaatcac atgggagatg cctgaccact cccttctctc aacggcaagt 7620aaagagagga cacatggaag tgagcagctt cacttacaag gtaccctagt cattcagaat 7680ccccaaacct ccgattctgg gatatacaaa tgcacagcaa agaacccact tggtagtgat 7740tatgcagcaa cgtatattca agtaatctga 7770242589PRThomo sapien 24Met Lys Val Lys Gly Arg Gly Ile Thr Cys Leu Leu Val Ser Phe Ala1 5 10 15Val Ile Cys Leu Val Ala Thr Pro Gly Gly Lys Ala Cys Pro Arg Arg 20 25 30Cys Ala Cys Tyr Met Pro Thr Glu Val His Cys Thr Phe Arg Tyr Leu 35 40 45Thr Ser Ile Pro Asp Ser Ile Pro Pro Asn Val Glu Arg Ile Asn Leu 50 55 60Gly Tyr Asn Ser Leu Val Arg Leu Met Glu Thr Asp Phe Ser Gly Leu65 70 75 80Thr Lys Leu Glu Leu Leu Met Leu His Ser Asn Gly Ile His Thr Ile 85 90 95Pro Asp Lys Thr Phe Ser Asp Leu Gln Ala Leu Gln Val Leu Lys Met 100 105 110Ser Tyr Asn Lys Val Arg Lys Leu Gln Lys Asp Thr Phe Tyr Gly Leu 115 120 125Arg Ser Leu Thr Arg Leu His Met Asp His Asn Asn Ile Glu Phe Ile 130 135 140Asn Pro Glu Val Phe Tyr Gly Leu Asn Phe Leu Arg Leu Val His Leu145 150 155 160Glu Gly Asn Gln Leu Thr Lys Leu His Pro Asp Thr Phe Val Ser Leu 165 170 175Ser Tyr Leu Gln Ile Phe Lys Ile Ser Phe Ile Lys Phe Leu Tyr Leu 180 185 190Ser Asp Asn Phe Leu Thr Ser Leu Pro Gln Glu Met Val Ser Tyr Met 195 200 205Pro Asp Leu Asp Ser Leu Tyr Leu His Gly Asn Pro Trp Thr Cys Asp 210 215 220Cys His Leu Lys Trp Leu Ser Asp Trp Ile Gln Glu Lys Pro Asp Val225 230 235 240Ile Lys Cys Lys Lys Asp Arg Ser Pro Ser Ser Ala Gln Gln Cys Pro 245 250 255Leu Cys Met Asn Pro Arg Thr Ser Lys Gly Lys Pro Leu Ala Met Val 260 265 270Ser Ala Ala Ala Phe Gln Cys Ala Lys Pro Thr Ile Asp Ser Ser Leu 275 280 285Lys Ser Lys Ser Leu Thr Ile Leu Glu Asp Ser Ser Ser Ala Phe Ile 290 295 300Ser Pro Gln Gly Phe Met Ala Pro Phe Gly Ser Leu Thr Leu Asn Met305 310 315 320Thr Asp Gln Ser Gly Asn Glu Ala Asn Met Val Cys Ser Ile Gln Lys 325 330 335Pro Ser Arg Thr Ser Pro Ile Ala Phe Thr Glu Glu Asn Asp Tyr Ile 340 345 350Val Leu Asn Thr Ser Phe Ser Thr Phe Leu Val Cys Asn Ile Asp Tyr 355 360 365Gly His Ile Gln Pro Val Trp Gln Ile Leu Ala Leu Tyr Ser Asp Ser 370 375 380Pro Leu Ile Leu Glu Arg Ser His Leu Leu Ser Glu Thr Pro Gln Leu385 390 395 400Tyr Tyr Lys Tyr Lys Gln Val Ala Pro Lys Pro Glu Asp Ile Phe Thr 405 410 415Asn Ile Glu Ala Asp Leu Arg Ala Asp Pro Ser Trp Leu Met Gln Asp 420 425 430Gln Ile Ser Leu Gln Leu Asn Arg Thr Ala Thr Thr Phe Ser Thr Leu 435 440 445Gln Ile Gln Tyr Ser Ser Asp Ala Gln Ile Thr Leu Pro Arg Ala Glu 450 455 460Met Arg Pro Val Lys His Lys Trp Thr Met Ile Ser Arg Asp Asn Asn465 470 475 480Thr Lys Leu Glu His Thr Val Leu Val Gly Gly Thr Val Gly Leu Asn 485 490 495Cys Pro Gly Gln Gly Asp Pro Thr Pro His Val Asp Trp Leu Leu Ala 500 505 510Asp Gly Ser Lys Val Arg Ala Pro Tyr Val Ser Glu Asp Gly Arg Ile 515 520 525Leu Ile Asp Lys Ser Gly Lys Leu Glu Leu Gln Met Ala Asp Ser Phe 530 535 540Asp Thr Gly Val Tyr His Cys Ile Ser Ser Asn Tyr Asp Asp Ala Asp545 550 555 560Ile Leu Thr Tyr Arg Ile Thr Val Val Glu Pro Leu Val Glu Ala Tyr 565 570 575Gln Glu Asn Gly Ile His His Thr Val Phe Ile Gly Glu Thr Leu Asp 580 585 590Leu Pro Cys His Ser Thr Gly Ile Pro Asp Ala Ser Ile Ser Trp Val 595 600 605Ile Pro Gly Asn Asn Val Leu Tyr Gln Ser Ser Arg Asp Lys Lys Val 610 615 620Leu Asn Asn Gly Thr Leu Arg Ile Leu Gln Val Thr Pro Lys Asp Gln625 630 635 640Gly Tyr Tyr Arg Cys Val Ala Ala Asn Pro Ser Gly Val Asp Phe Leu 645 650 655Ile Phe Gln Val Ser Val Lys Met Lys Gly Gln Arg Pro Leu Glu His 660 665 670Asp Gly Glu Thr Glu Gly Ser Gly Leu Asp Glu Ser Asn Pro Ile Ala 675 680 685His Leu Lys Glu Pro Pro Gly Ala Gln Leu Arg Thr Ser Ala Leu Met 690 695 700Glu Ala Glu Val Gly Lys His Thr Ser Ser Thr Ser Lys Arg His Asn705 710 715 720Tyr Arg Glu Leu Thr Leu Gln Arg Arg Gly Asp Ser Thr His Arg Arg 725 730 735Phe Arg Glu Asn Arg Arg His Phe Pro Pro Ser Ala Arg Arg Ile Asp 740 745 750Pro Gln His Trp Ala Ala Leu Leu Glu Lys Ala Lys Lys Asn Ala Met 755 760 765Pro Asp Lys Arg Glu Asn Thr Thr Val Ser Pro Pro Pro Val Val Thr 770 775 780Gln Leu Pro Asn Ile Pro Gly Glu Glu Asp Asp Ser Ser Gly Met Leu785 790 795 800Ala Leu His Glu Glu Phe Met Val Pro Ala Thr Lys Ala Leu Asn Leu 805 810 815Pro Ala Arg Thr Val Thr Ala Asp Ser Arg Thr Ile Ser Asp Ser Pro 820 825 830Met Thr Asn Ile Asn Tyr Gly Thr Glu Phe Ser Pro Val Val Asn Ser 835 840 845Gln Ile Leu Pro Pro Glu Glu Pro Thr Asp Phe Lys Leu Ser Thr Ala 850 855 860Ile Lys Thr Thr Ala Met Ser Lys Asn Ile Asn Pro Thr Met Ser Ser865 870 875 880Gln Ile Gln Gly Thr Thr Asn Gln His Ser Ser Thr Val Phe Pro Leu 885 890 895Leu Leu Gly Ala Thr Glu Phe Gln Asp Ser Asp Gln Met Gly Arg Gly 900 905 910Arg Glu His Phe Gln Ser Arg Pro Pro Ile Thr Val Arg Thr Met Ile 915 920 925Lys Asp Val Asn Val Lys Met Leu Ser Ser Thr Thr Asn Lys Leu Leu 930 935 940Leu Glu Ser Val Asn Thr Thr Asn Ser His Gln Thr Ser Val Arg Glu945 950 955 960Val Ser Glu Pro Arg His Asn His Phe Tyr Ser His Thr Thr Gln Ile 965 970 975Leu Ser Thr Ser Thr Phe Pro Ser Asp Pro His Thr Ala Ala His Ser 980 985 990Gln Phe Pro Ile Pro Arg Asn Ser Thr Val Asn Ile Pro Leu Phe Arg 995 1000 1005Arg Phe Gly Arg Gln Arg Lys Ile Gly Gly Arg Gly Arg Ile Ile 1010 1015 1020Ser Pro Tyr Arg Thr Pro Val Leu Arg Arg His Arg Tyr Ser Ile 1025 1030 1035Phe Arg Ser Thr Thr Arg Gly Ser Ser Glu Lys Ser Thr Thr Ala 1040 1045 1050Phe Ser Ala Thr Val Leu Asn Val Thr Cys Leu Ser Cys Leu Pro 1055 1060 1065Arg Glu Arg Leu Thr Thr Ala Thr Ala Ala Leu Ser Phe Pro Ser 1070 1075 1080Ala Ala Pro Ile Thr Phe Pro Lys Ala Asp Ile Ala Arg Val Pro 1085 1090 1095Ser Glu Glu Ser Thr Thr Leu Val Gln Asn Pro Leu Leu Leu Leu 1100 1105 1110Glu Asn Lys Pro Ser Val Glu Lys Thr Thr Pro Thr Ile Lys Tyr 1115 1120 1125Phe Arg Thr Glu Ile Ser Gln Val Thr Pro Thr Gly Ala Val Met 1130 1135 1140Thr Tyr Ala Pro Thr Ser Ile Pro Met Glu Lys Thr His Lys Val 1145 1150 1155Asn Ala Ser Tyr Pro Arg Val Ser Ser Thr Asn Glu Ala Lys Arg 1160 1165 1170Asp Ser Val Ile Thr Ser Ser Leu Ser Gly Ala Ile Thr Lys Pro 1175 1180 1185Pro Met Thr Ile Ile Ala Ile Thr Arg Phe Ser Arg Arg Lys Ile 1190 1195 1200Pro Trp Gln Gln Asn Phe Val Asn Asn His Asn Pro Lys Gly Arg 1205 1210 1215Leu Arg Asn Gln His Lys Val Ser Leu Gln Lys Ser Thr Ala Val 1220 1225 1230Met Leu Pro Lys Thr Ser Pro Ala Leu Pro Gln Arg Gln Ser Ser 1235 1240 1245Pro Phe His Phe Thr Thr Leu Ser Thr Ser Val Met Gln Ile Pro 1250 1255 1260Ser Asn Thr Leu Thr Thr Ala His His Thr Thr Thr Lys Thr His 1265 1270 1275Asn Pro Gly Ser Leu Pro Thr Lys Lys Glu Leu Pro Phe Pro Pro 1280 1285 1290Leu Asn Pro Met Leu Pro Ser Ile Ile Ser Lys Asp Ser Ser Thr 1295 1300 1305Lys Ser Ile Ile Ser Thr Gln Thr Ala Ile Pro Ala Thr Thr Pro 1310 1315 1320Thr Phe Pro Ala Ser Val Ile Thr Tyr Glu Thr Gln Thr Glu Arg 1325 1330 1335Ser Arg Ala Gln Thr Ile Gln Arg Glu Gln Glu Pro Gln Lys Lys 1340 1345 1350Asn Arg Thr Asp Pro Asn Ile Ser Pro Asp Gln Ser Ser Gly Phe 1355 1360 1365Thr Thr Pro Thr Ala Met Thr Pro Pro Ala Leu Ala Phe Thr His 1370 1375 1380Ser Pro Pro Glu Asn Thr Thr Gly Ile Ser Ser Thr Ile Ser Phe 1385 1390 1395His Ser Arg Thr Leu Asn Leu Thr Asp Val Ile Glu Glu Leu Ala 1400 1405 1410Gln Ala Ser Thr Gln Thr Leu Lys Ser Thr Ile Ala Ser Glu Thr 1415 1420 1425Thr Leu Ser Ser Lys Ser His Gln Ser Thr Thr Thr Arg Lys Ala 1430 1435 1440Ser Leu Asp Thr Pro Ile Pro Pro Phe Leu Ser Ser Ser Ala Thr 1445 1450 1455Leu Met Pro Val Pro Ile Ser Pro Pro Phe Thr Gln Arg Ala Val 1460 1465 1470Thr Asp Thr Arg Gly Asp Ser His Phe Arg Leu Met Thr Asn Thr 1475 1480 1485Val Val Lys Leu His Glu Ser Ser Arg His Asn Leu Gln Met Pro 1490 1495 1500Ser Ser Gln Leu Glu Pro Leu Thr Ser Ser Thr Ser Asn Leu Leu 1505 1510 1515His Ser Thr Pro Met Pro Ala Leu Thr Thr Val Lys Ser Gln Asn 1520 1525 1530Ser Lys Leu Thr Pro Ser Pro Trp Ala Glu Tyr Gln Phe Trp His 1535 1540 1545Lys Pro Tyr Ser Asp Ile Ala Glu Lys Gly Lys Lys Pro Glu Val 1550 1555 1560Ser Met Leu Ala Thr Thr Gly Leu Ser Glu Ala Thr Thr Leu Val 1565 1570 1575Ser Asp Trp Asp Gly Gln Lys Asn Thr Lys Lys Ser Asp Phe Asp 1580 1585 1590Lys Lys Pro Val Gln Glu Ala Thr Thr Ser Lys Leu Leu Pro Phe 1595 1600 1605Asp Ser Leu Ser Arg Tyr Ile Phe Glu Lys

Pro Arg Ile Val Gly 1610 1615 1620Gly Lys Ala Ala Ser Phe Thr Ile Pro Ala Asn Ser Asp Ala Phe 1625 1630 1635Leu Pro Cys Glu Ala Val Gly Asn Pro Leu Pro Thr Ile His Trp 1640 1645 1650Thr Arg Val Ser Gly Leu Asp Leu Ser Arg Gly Asn Gln Asn Ser 1655 1660 1665Arg Val Gln Val Leu Pro Asn Gly Thr Leu Ser Ile Gln Arg Val 1670 1675 1680Glu Ile Gln Asp Arg Gly Gln Tyr Leu Cys Ser Ala Ser Asn Leu 1685 1690 1695Phe Gly Thr Asp His Leu His Val Thr Leu Ser Val Val Ser Tyr 1700 1705 1710Pro Pro Arg Ile Leu Glu Arg Arg Thr Lys Glu Ile Thr Val His 1715 1720 1725Ser Gly Ser Thr Val Glu Leu Lys Cys Arg Ala Glu Gly Arg Pro 1730 1735 1740Ser Pro Thr Val Thr Trp Ile Leu Ala Asn Gln Thr Val Val Ser 1745 1750 1755Glu Ser Ser Gln Gly Ser Arg Gln Ala Val Val Thr Val Asp Gly 1760 1765 1770Thr Leu Val Leu His Asn Leu Ser Ile Tyr Asp Arg Gly Phe Tyr 1775 1780 1785Lys Cys Val Ala Ser Asn Pro Gly Gly Gln Asp Ser Leu Leu Val 1790 1795 1800Lys Ile Gln Val Ile Ala Ala Pro Pro Val Ile Leu Glu Gln Arg 1805 1810 1815Arg Gln Val Ile Val Gly Thr Trp Gly Glu Ser Leu Lys Leu Pro 1820 1825 1830Cys Thr Ala Lys Gly Thr Pro Gln Pro Ser Val Tyr Trp Val Leu 1835 1840 1845Ser Asp Gly Thr Glu Val Lys Pro Leu Gln Phe Thr Asn Ser Lys 1850 1855 1860Leu Phe Leu Phe Ser Asn Gly Thr Leu Tyr Ile Arg Asn Leu Ala 1865 1870 1875Ser Ser Asp Arg Gly Thr Tyr Glu Cys Ile Ala Thr Ser Ser Thr 1880 1885 1890Gly Ser Glu Arg Arg Val Val Met Leu Thr Met Glu Glu Arg Val 1895 1900 1905Thr Ser Pro Arg Ile Glu Ala Ala Ser Gln Lys Arg Thr Glu Val 1910 1915 1920Asn Phe Gly Asp Lys Leu Leu Leu Asn Cys Ser Ala Thr Gly Glu 1925 1930 1935Pro Lys Pro Gln Ile Met Trp Arg Leu Pro Ser Lys Ala Val Val 1940 1945 1950Asp Gln Trp Ser Trp Ile His Val Tyr Pro Asn Gly Ser Leu Phe 1955 1960 1965Ile Gly Ser Val Thr Glu Lys Asp Ser Gly Val Tyr Leu Cys Val 1970 1975 1980Ala Arg Asn Lys Met Gly Asp Asp Leu Ile Leu Met His Val Ser 1985 1990 1995Leu Arg Leu Lys Pro Ala Lys Ile Asp His Lys Gln Tyr Phe Arg 2000 2005 2010Lys Gln Val Leu His Gly Lys Asp Phe Gln Val Asp Cys Lys Ala 2015 2020 2025Ser Gly Ser Pro Val Pro Glu Ile Ser Trp Ser Leu Pro Asp Gly 2030 2035 2040Thr Met Ile Asn Asn Ala Met Gln Ala Asp Asp Ser Gly His Arg 2045 2050 2055Thr Arg Arg Tyr Thr Leu Phe Asn Asn Gly Thr Leu Tyr Phe Asn 2060 2065 2070Lys Val Gly Val Ala Glu Glu Gly Asp Tyr Thr Cys Tyr Ala Gln 2075 2080 2085Asn Thr Leu Gly Lys Asp Glu Met Lys Val His Leu Thr Val Ile 2090 2095 2100Thr Ala Ala Pro Arg Ile Arg Gln Ser Asn Lys Thr Asn Lys Arg 2105 2110 2115Ile Lys Ala Gly Asp Thr Ala Val Leu Asp Cys Glu Val Thr Gly 2120 2125 2130Asp Pro Lys Pro Lys Ile Phe Trp Leu Leu Pro Ser Asn Asp Met 2135 2140 2145Ile Ser Phe Ser Ile Asp Arg Tyr Thr Phe His Ala Asn Gly Ser 2150 2155 2160Leu Thr Ile Asn Lys Val Lys Leu Leu Asp Ser Gly Glu Tyr Val 2165 2170 2175Cys Val Ala Arg Asn Pro Ser Gly Asp Asp Thr Lys Met Tyr Lys 2180 2185 2190Leu Asp Val Val Ser Lys Pro Pro Leu Ile Asn Gly Leu Tyr Thr 2195 2200 2205Asn Arg Thr Val Ile Lys Ala Thr Ala Val Arg His Ser Lys Lys 2210 2215 2220His Phe Asp Cys Arg Ala Glu Gly Thr Pro Ser Pro Glu Val Met 2225 2230 2235Trp Ile Met Pro Asp Asn Ile Phe Leu Thr Ala Pro Tyr Tyr Gly 2240 2245 2250Ser Arg Ile Thr Val His Lys Asn Gly Thr Leu Glu Ile Arg Asn 2255 2260 2265Val Arg Leu Ser Asp Ser Ala Asp Phe Ile Cys Val Ala Arg Asn 2270 2275 2280Glu Gly Gly Glu Ser Val Leu Val Val Gln Leu Glu Val Leu Glu 2285 2290 2295Met Leu Arg Arg Pro Thr Phe Arg Asn Pro Phe Asn Glu Lys Ile 2300 2305 2310Val Ala Gln Leu Gly Lys Ser Thr Ala Leu Asn Cys Ser Val Asp 2315 2320 2325Gly Asn Pro Pro Pro Glu Ile Ile Trp Ile Leu Pro Val Gly Thr 2330 2335 2340Arg Phe Ser Asn Gly Pro Gln Ser Tyr Gln Tyr Leu Ile Ala Ser 2345 2350 2355Asn Gly Ser Phe Ile Ile Ser Lys Thr Thr Arg Glu Asp Ala Gly 2360 2365 2370Lys Tyr Arg Cys Ala Ala Arg Asn Lys Val Gly Tyr Ile Glu Lys 2375 2380 2385Leu Val Ile Leu Glu Ile Gly Gln Lys Pro Val Ile Leu Thr Tyr 2390 2395 2400Ala Pro Gly Thr Val Lys Gly Ile Ser Gly Glu Ser Leu Ser Leu 2405 2410 2415His Cys Val Ser Asp Gly Ile Pro Lys Pro Asn Ile Lys Trp Thr 2420 2425 2430Met Pro Ser Gly Tyr Val Val Asp Arg Pro Gln Ile Asn Gly Lys 2435 2440 2445Tyr Ile Leu His Asp Asn Gly Thr Leu Val Ile Lys Glu Ala Thr 2450 2455 2460Ala Tyr Asp Arg Gly Asn Tyr Ile Cys Lys Ala Gln Asn Ser Val 2465 2470 2475Gly His Thr Leu Ile Thr Val Pro Val Met Ile Val Ala Tyr Pro 2480 2485 2490Pro Arg Ile Thr Asn Arg Pro Pro Arg Ser Ile Val Thr Arg Thr 2495 2500 2505Gly Ala Ala Phe Gln Leu His Cys Val Ala Leu Gly Val Pro Lys 2510 2515 2520Pro Glu Ile Thr Trp Glu Met Pro Asp His Ser Leu Leu Ser Thr 2525 2530 2535Ala Ser Lys Glu Arg Thr His Gly Ser Glu Gln Leu His Leu Gln 2540 2545 2550Gly Thr Leu Val Ile Gln Asn Pro Gln Thr Ser Asp Ser Gly Ile 2555 2560 2565Tyr Lys Cys Thr Ala Lys Asn Pro Leu Gly Ser Asp Tyr Ala Ala 2570 2575 2580Thr Tyr Ile Gln Val Ile 258525663PRTRattus Speciesmisc_feature(322)..(322)"x" can be any amino acid 25Met Gln Val Arg Gly Arg Glu Val Ser Gly Leu Leu Ile Ser Leu Thr1 5 10 15Ala Val Cys Leu Val Val Thr Pro Gly Ser Arg Ala Cys Pro Arg Arg 20 25 30Cys Ala Cys Tyr Val Pro Thr Glu Val His Cys Thr Phe Arg Tyr Leu 35 40 45Thr Ser Ile Pro Asp Gly Ile Pro Ala Asn Val Glu Arg Ile Asn Leu 50 55 60Gly Tyr Asn Ser Leu Thr Arg Leu Thr Glu Asn Asp Phe Asp Gly Leu65 70 75 80Ser Lys Leu Glu Leu Leu Met Leu His Ser Asn Gly Ile His Arg Val 85 90 95Ser Asp Lys Thr Phe Ser Gly Leu Gln Ser Leu Gln Val Leu Lys Met 100 105 110Ser Tyr Asn Lys Val Gln Ile Ile Arg Lys Asp Thr Phe Tyr Gly Leu 115 120 125Gly Ser Leu Val Arg Leu His Leu Asp His Asn Asn Ile Glu Phe Ile 130 135 140Asn Pro Glu Ala Phe Tyr Gly Leu Thr Ser Leu Arg Leu Val His Leu145 150 155 160Glu Gly Asn Arg Leu Thr Lys Leu His Pro Asp Thr Phe Val Ser Leu 165 170 175Ser Tyr Leu Gln Ile Phe Lys Thr Ser Phe Ile Lys Tyr Leu Phe Leu 180 185 190Ser Asp Asn Phe Leu Thr Ser Leu Pro Lys Glu Met Val Ser Tyr Met 195 200 205Pro Asn Leu Glu Ser Leu Tyr Leu His Gly Asn Pro Trp Thr Cys Asp 210 215 220Cys His Leu Lys Trp Leu Ser Glu Trp Met Gln Gly Asn Pro Asp Ile225 230 235 240Ile Lys Cys Lys Lys Asp Arg Ser Ser Ser Ser Pro Gln Gln Cys Pro 245 250 255Leu Cys Met Asn Pro Arg Ile Ser Lys Gly Arg Pro Phe Ala Met Val 260 265 270Pro Ser Gly Ala Phe Leu Cys Thr Lys Pro Thr Ile Asp Pro Ser Leu 275 280 285Lys Ser Lys Ser Leu Val Thr Gln Glu Asp Asn Gly Ser Ala Ser Thr 290 295 300Ser Pro Gln Asp Phe Ile Glu Pro Phe Gly Ser Leu Ser Leu Asn Met305 310 315 320Thr Xaa Xaa Ser Gly Asn Lys Ala Asp Met Val Cys Ser Ile Gln Lys 325 330 335Pro Ser Arg Thr Ser Pro Thr Ala Phe Thr Glu Glu Asn Asp Tyr Ile 340 345 350Met Leu Asn Ala Ser Phe Ser Thr Asn Leu Val Cys Ser Val Asp Tyr 355 360 365Asn His Ile Gln Pro Val Trp Gln Leu Leu Ala Leu Tyr Ser Asp Ser 370 375 380Pro Leu Ile Leu Glu Arg Lys Pro Gln Leu Thr Glu Thr Pro Ser Leu385 390 395 400Ser Ser Arg Tyr Lys Gln Val Ala Leu Arg Pro Glu Asp Ile Phe Thr 405 410 415Ser Ile Glu Ala Asp Val Arg Ala Asp Pro Phe Trp Phe Gln Gln Glu 420 425 430Lys Ile Val Leu Gln Leu Asn Arg Thr Ala Thr Thr Leu Ser Thr Leu 435 440 445Gln Ile Gln Phe Ser Thr Asp Ala Gln Ile Ala Leu Pro Arg Ala Glu 450 455 460Met Arg Ala Glu Arg Leu Lys Trp Thr Met Ile Leu Met Met Asn Asn465 470 475 480Pro Lys Leu Glu Arg Thr Val Leu Val Gly Gly Thr Ile Ala Leu Ser 485 490 495Cys Pro Gly Lys Gly Asp Pro Ser Pro His Leu Glu Trp Leu Leu Ala 500 505 510Asp Gly Ser Lys Val Arg Ala Pro Tyr Val Ser Glu Asp Gly Arg Ile 515 520 525Leu Ile Asp Lys Asn Gly Lys Leu Glu Leu Gln Met Ala Asp Ser Phe 530 535 540Asp Ala Gly Leu Tyr His Cys Ile Ser Thr Asn Asp Ala Asp Ala Asp545 550 555 560Val Leu Thr Tyr Arg Ile Thr Val Val Glu Pro Tyr Gly Glu Ser Thr 565 570 575His Asp Ser Gly Val Gln His Thr Val Val Thr Gly Glu Thr Leu Asp 580 585 590Leu Pro Cys Leu Ser Thr Gly Val Pro Asp Ala Ser Ile Ser Trp Ile 595 600 605Leu Pro Gly Asn Thr Val Phe Ser Gln Pro Ser Arg Asp Arg Gln Ile 610 615 620Leu Asn Asn Gly Thr Leu Arg Ile Leu Gln Val Thr Pro Lys Asp Gln625 630 635 640Gly His Tyr Gln Cys Val Ala Ala Asn Pro Ser Gly Ala Asp Phe Ser 645 650 655Ser Phe Lys Val Ser Val Gln 660262469DNAHomo sapiens 26gcggccgcca cacccgccac cagttcgcca tgaaggtaaa aggcagagga atcacctgct 60tgctggtctc ctttgctgtg atctgcctgg tcgccacccc tgggggcaag gcctgtcctc 120gccgctgtgc ctgttatatg cctacggagg tacactgcac atttcggtac ctgacttcca 180tcccagacag catcccgccc aatgtggaac gcatcaattt aggatacaac agcttggtta 240gattgatgga aacagatttt tctggcctga ccaaactgga gttactcatg cttcacagca 300atggcattca cacaatccct gacaagacct tctcagattt gcaggccttg caggtcttaa 360aaatgagcta taataaagtc cgaaaacttc agaaagatac tttttatggc ctcaggagct 420tgacacgatt gcacatggac cacaacaata ttgagtttat aaacccagag gttttttatg 480ggctcaactt tctccgcctg gtgcacttgg aaggaaatca gctcactaag ctccacccag 540atacatttgt ctctttgagc tacctccaga tatttaaaat ctctttcatt aagttcctat 600acttgtctga taacttcctg acctccctcc ctcaagagat ggtctcctat atgcctgacc 660tagacagcct ttacctgcat ggaaacccat ggacctgtga ttgccattta aagtggttgt 720ctgactggat acaggagaag ccagatgtaa taaaatgcaa aaaagataga agtccctcta 780gtgctcagca gtgtccactt tgcatgaacc ctaggacttc taaaggcaag ccgttagcta 840tggtctcagc tgcagctttc cagtgtgcca agccaaccat tgactcatcc ctgaaatcaa 900agagcctgac tattctggaa gacagtagtt ctgctttcat ctctccccaa ggtttcatgg 960caccctttgg ctccctcact ttgaatatga cagatcagtc tggaaatgaa gctaacatgg 1020tctgcagtat tcaaaagccc tcaaggacat cacccattgc attcactgaa gaaaatgact 1080acatcgtgct aaatacttca ttttcaacat ttttggtgtg caacatagat tacggtcaca 1140ttcagccagt gtggcaaatt ttggctttgt acagtgattc tcctctgata ctagaaagga 1200gccacttgct tagtgaaaca ccgcagctct attacaaata taaacaggtg gctcctaagc 1260ctgaagacat ttttaccaac atagaggcag atctcagagc agatccctct tggttaatgc 1320aagaccaaat ttccttgcag ctgaacagaa ctgccaccac attcagtaca ttacagatcc 1380agtactccag tgatgctcaa atcactttac caagagcaga gatgaggcca gtgaaacaca 1440aatggactat gatttcaagg gataacaata ctaagctgga acatactgtc ttggtaggtg 1500gaaccgttgg cctgaactgc ccaggccaag gagaccccac cccacacgtg gattggcttc 1560tagctgatgg aagtaaagtg agagcccctt atgtcagtga ggatggacgg atcctaatag 1620acaaaagtgg aaaattggaa ctccagatgg ctgatagttt tgacacaggc gtatatcact 1680gtataagcag caattatgat gatgcagata ttctcaccta taggataact gtggtagaac 1740ctttggtcga agcctatcag gaaaatggga ttcatcacac agttttcatt ggtgaaacac 1800ttgatcttcc atgccattct actggtatcc cagatgcctc tattagctgg gttattccag 1860gaaacaatgt gctctatcag tcatcaagag acaagaaagt tctaaacaat ggcacattaa 1920gaatattaca ggtcaccccg aaagaccaag gttattatcg ctgtgtggca gccaacccat 1980caggggttga ttttttgatt ttccaagttt cagtcaagat gaaaggacaa aggcccttgg 2040agcatgatgg agaaacagag ggatctggac ttgatgagtc caatcctatt gctcatctta 2100aggagccacc aggtgcacaa ctccgtacat ctgctctgat ggaggctgag gttggaaaac 2160acacctcaag cacaagtaag aggcacaact atcgggaatt aacactccag cgacgtggag 2220attcaacaca tcgacgtttt agggagaata ggaggcattt ccctccctct gctaggagaa 2280ttgacccaca acattgggcg gcactgttgg agaaagctaa aaagaatgct atgccagaca 2340agcgagaaaa taccacagtg agcccacccc cagtggtcac ccaactccca aacatacctg 2400gtgaagaaga cgattcctca ggcatgctcg ctctacatga ggaatttatg gtcccggcca 2460ctaaagctt 2469273518DNAHomo sapiens 27aagctttgaa ccttccagca aggacagtga ctgctgactc cagaacaata tctgatagtc 60ctatgacaaa cataaattat ggcacagaat tctctcctgt tgtgaattca caaatactac 120cacctgaaga acccacagat ttcaaactgt ctactgctat taaaactaca gccatgtcaa 180agaatataaa cccaaccatg tcaagccaaa tacaaggcac aaccaatcaa cattcatcca 240ctgtctttcc actgctactt ggagcaactg aatttcagga ctctgaccag atgggaagag 300gaagagagca tttccaaagt agacccccaa taacagtaag gactatgatc aaagatgtca 360atgtcaaaat gcttagtagc accaccaaca aactattatt agagtcagta aataccacaa 420atagtcatca gacatctgta agagaagtga gtgaacccag gcacaatcac ttctattctc 480acactactca aatacttagc acctccacgt tcccttcaga tccacacaca gctgctcatt 540ctcagtttcc gatccctaga aatagtacag ttaacatccc gctgttcaga cgctttggga 600ggcagaggaa aattggcgga agggggcgga ttatcagccc atatagaact ccagttctgc 660gacggcatag atacagcatt ttcaggtcaa caaccagagg ttcttctgaa aaaagcacta 720ctgcattctc agccacagtg ctcaatgtga catgtctgtc ctgtcttccc agggagaggc 780tcaccactgc cacagcagca ttgtcttttc caagtgctgc tcccatcacc ttccccaaag 840ctgacattgc tagagtccca tcagaagagt ctacaactct agtccagaat ccactattac 900tacttgagaa caaacccagt gtagagaaaa caacacccac aataaaatat ttcaggactg 960aaatttccca agtgactcca actggtgcag tcatgacata tgctccaaca tccataccca 1020tggaaaaaac tcacaaagta aacgccagtt acccacgtgt gtctagcacc aatgaagcta 1080aaagagattc agtgattaca tcgtcacttt caggtgctat caccaagcca ccaatgacta 1140ttatagccat tacaaggttt tcaagaagga aaattccctg gcaacagaac tttgtaaata 1200accataaccc aaaaggcaga ttaaggaatc aacataaagt tagtttacaa aaaagcacag 1260ctgtgatgct tcctaaaaca tctcctgctt tacccagaga caaagtctcc cctttccatt 1320tcaccacact ttcaacaagt gtgatgcaaa ttccatctaa taccttgact accgctcacc 1380acactacgac caaaacacac aatcctggaa gtcttccaac aaagaaggag cttcccttcc 1440caccccttaa ccctatgctt cctagtatta taagcaaaga ctcaagtaca aaaagcatca 1500tatcaacgca aacagcaata ccagcaacaa ctcctacctt ccctgcatct gtcatcactt 1560atgaaaccca aacagagaga tctagagcac aaacaataca aagagaacag gagcctcaaa 1620agaagaacag gactgaccca aacatctctc cagaccagag ttctggcttc actacaccca 1680ctgctatgac acctcctgtt ctaaccacag ccgaaacttc agtcaagccc agtgtctctg 1740cattcactca ttccccacca gaaaacacaa ctgggatttc aagcacaatc agttttcatt 1800caagaactct taatctgaca gatgtgattg aagaactagc ccaagcaagt actcagactt 1860tgaagagcac aattgcttct gaaacaactt tgtccagcaa atcacaccag agtaccacaa 1920ctaggaaagc aatcattaga cactcaacca taccaccatt cttgagcagc agtgctactc 1980taatgccagt tcccatctcc cctcccttta ctcagagagc agttactgac aacgtggcga 2040ctcccatttc cgggcttatg acaaatacag tggtcaagct gcacgaatcc tcaaggcaca 2100atgctaaacc acagcaatta gtagcagagg ttgcaacatc ccccaaggtt cacccaaatg 2160ccaagttcac aattggaacc actcacttca tctactctaa tctgttacat tctactccca 2220tgccagcact aacaacagtt aaatcacaga attctaaatt aactccatct ccctgggcag 2280aaaaccaatt ttggcacaaa ccatactcag aaattgctga aaaaggcaaa aagccagaag 2340taagcatgtt ggctactaca ggcctgtccg aggccaccac tcttgtttca

gattgggatg 2400gacagaagaa cacaaagaag agtgactttg ataagaaacc agttcaagaa gcaacaactt 2460ccaaactcct tccctttgac tctttgtcta ggtatatatt tgaaaagccc aggatagttg 2520gaggaaaagc tgcaagtttt actattccag ctaactcaga tgcctttctt ccctgtgaag 2580ctgttggaaa tcccctgccc accattcatt ggaccagagt cccatcagga cttgatttat 2640ctaagaggaa acagaatagc agggtccagg ttctccccaa tggtaccctg tccatccaga 2700gggtggaaat tcaggaccgc ggacagtact tgtgttccgc atccaatctg tttggcacag 2760accaccttca tgtcaccttg tctgtggttt cctatcctcc caggatcctg gagagacgta 2820ccaaagagat cacagttcat tccggaagca ctgtggaact gaagtgcaga gcagaaggta 2880ggccaagccc tacagttacc tggattcttg caaaccaaac agttgtctca gaatcatccc 2940agggaagtag gcaggctgtg gtgacggttg acggaacatt ggtcctccac aatctcagta 3000tttatgaccg tggcttttac aaatgtgtgg ccagcaaccc aggtggccag gattcactgc 3060tggttaaaat acaagtcatt gcagcaccac ctgttattct agagcaaagg aggcaagtca 3120ttgtaggcac ttggggtgaa agtttaaaac tgccctgtac tgcaaaagga actcctcagc 3180ccagcgttta ctgggtcctc tctgatggca ctgaagtgaa accattacag tttaccaatt 3240ccaagttgtt cttattttca aatgggactt tgtatataag aaacctagcc tcttcagaca 3300ggggcactta tgaatgcatt gctaccagtt ccactggttc ggagcgaaga gtagtaatgc 3360ttacaatgga agagcgagtg accagcccca ggatagaagc tgcatcccag aaaaggactg 3420aagtgaattt tggggacaaa ttactactga actgctcagc cactggggag cccaaacccc 3480aaataatgtg gaggttacca tccaaggctg tggtcgac 3518281950DNAHomo sapiens 28gtcgaccagc agcatagagt gggcagctgg atccacgtct accctaatgg atccctgttt 60attggatcag taacagaaaa agacagtggt gtctacttgt gtgtggcaag aaacaaaatg 120ggggatgatc tgatactgat gcatgttagc ctaagactga aacctgccaa aattgaccac 180aagcagtatt ttagaaagca agtgctccat gggaaagatt tccaagtaga ttgcaaagct 240tccggctccc cagtgccaga gatatcttgg agtttgcctg atggaaccat gatcaacaat 300gcaatgcaag ccgatgacag tggccacagg actaggagat ataccctttt caacaatgga 360actttatact tcaacaaagt tggggtagcg gaggaaggag attatacttg ctatgcccag 420aacaccctag ggaaagatga aatgaaggtc cacttaacag ttataacagc tgctccccgg 480ataaggcaga gtaacaaaac caacaagaga atcaaagctg gagacacagc tgtccttgac 540tgtgaggtca ctggggatcc caaaccaaaa atattttggt tgctgccttc caatgacatg 600atttccttct ccattgatag gtacacattt catgccaatg ggtctttgac catcaacaaa 660gtgaaactgc tcgattctgg agagtacgta tgtgtagccc gaaatcccag tggggatgac 720accaaaatgt acaaactgga tgtggtctct aaacctccat taatcaatgg tctgtataca 780aatagaactg ttattaaagc cacagctgtg agacattcca aaaaacactt tgactgcaga 840gctgaaggga caccatctcc tgaagtcatg tggatcatgc cagacaatat tttcctcaca 900gccccatact atggaagcag aatcacagtc cataaaaatg gaaccttgga aattaggaat 960gtgaggcttt cagattcagc cgactttatc tgtgtggccc gaaatgaagg tggagagagc 1020gtgttggtag tacagttaga agtactggaa atgctgagaa gaccgacatt tagaaatcca 1080tttaatgaaa aaatagttgc ccagctggga aagtccacag cattgaattg ctctgttgat 1140ggtaacccac cacctgaaat aatctggatt ttaccaaatg gcacacgatt ttccaatgga 1200ccacaaagtt atcagtatct gatagcaagc aatggttctt ttatcatttc taaaacaact 1260cgggaggatg caggaaaata tcgctgtgca gctaggaata aagttggcta tattgagaaa 1320ttagtcatat tagaaattgg ccagaagcca gttattctta cctatgcacc agggacagta 1380aaaggcatca gtggagaatc tctatcactg cattgtgtgt ctgatggaat ccctaagcca 1440aatatcaaat ggactatgcc aagtggttat gtagtagaca ggcctcaaat taatgggaaa 1500tacatattgc atgacaatgg caccttagtc attaaagaag caacagctta tgacagagga 1560aactatatct gtaaggctca aaatagtgtt ggtcatacac tgattactgt tccagtaatg 1620attgtagcct accctccccg aattacaaat cgtccaccca ggagtattgt caccaggaca 1680ggggcagcct ttcagctcca ctgtgtggcc ttgggagttc ccaagccaga aatcacatgg 1740gagatgcctg accactccct tctctcaacg gcaagtaaag agaggacaca tggaagtgag 1800cagcttcact tacaaggtac cctagtcatt cagaatcccc aaacctccga ttctgggata 1860tacaaatgca cagcaaagaa cccacttggt agtgattatg cagcaacgta tattcaagta 1920atccaccacc accaccacca ttgaactagt 1950299109DNAHomo sapiens 29atgcccaagc gcgcgcactg gggggccctc tctgtggtgc tgatcctgct ttggggtcat 60ccgcgagtgg cgctggcctg ccctcatcct tgtgcctgct acgtccccag cgaggtccac 120tgcacgttcc gatccctggc ttctgtgccc gctggcattg ctaaacatgt ggaaagaatc 180aatttggggt ttggaattct gaagtgtaaa aaggacaaag cttatgaagg cggtcagttg 240tgtgcaatgt gcttcagtcc aaagaagttg tacaaacatg agattcacaa gctgaaggac 300ctgacttgtc tgaagccttc catagagtct cctctgagac agaacaggag caggagtatt 360gaggaggagc aaaaacaaga agagaatggt gacagccagc tcatcctgga gaaaatccaa 420cttccccagt ggagcatctc tttgaatatg actgatgagc acgggaacct ggtgaacttg 480gtgtgtgaca tcaagaaacc aatggatgtg tacaaaattc acttgaacca aacagatcct 540ccagatattg acataaatgc aatggttgcc ttggactttg agtatccaat gacccaggaa 600aactatgaaa atctatggaa attgatagca tactacagtg aagttcccat gaagctacac 660agagagctca tgctcagcaa acaccccaga gtcagctacc agtacaggca agatgccgat 720gaagaagctc tttactacac aggtgtgaga gcccagattc ttgcagaacc agaatggatc 780atgcagccat ccatagatat ccagctgaac cgacctcaga gtacggccaa gaaggtgcta 840ctttcctact acaaccagta ttctcaaaca atagccacca aagatacaag gcaggctcgg 900ggcagaagct gggtaatgat tgagcctagt agagctgtgc aaaaagatca gactgtcctg 960gaagggggtc gatgccagtt gagctgcaat gtgaaagctt ctgagagtcc atctatcttc 1020tgggtgcttc cagatggctc catcctgaaa gtgcctgtgg atgacccaga cagcaagttc 1080tccattctca gcagtggctg gctgaggatc aagtccatgg agccatctga ctcgggcttg 1140taccagtgca ttgctcaagt gagggatgaa atggaccgca tggtatatag ggtacttgtg 1200cagtctccct ccactcagcc agccgagaaa gacacagtga caattggcaa gaacccaggg 1260gagccagtga tgttgccttg caatgcttta gctatacccg aagcccacct tagctggatt 1320cttccaaaca gaaggataat taatgatttg gctaacacat cacatgtata catgctgcca 1380aatggaactc tttccatccc aaaggtccaa gtcagtgaca gtggttacca cagatgtgtg 1440gctgtcaacc agcatggggc agaccatatc acggtgggaa tcacagtgac caagaaaggt 1500tctggctcgc catccaaaag aggcagatgg ccaggtccaa aggctctttc cagagtgaga 1560gaagacatcg tggaggatga aggggtctca ggcacgggag atgaagagaa cacttcaagg 1620agacttctac atccaaagca ccaagaggcg ttcctcaaaa caaaggatga tgccatcaat 1680ggagataaga aagccaagaa agggagaaga aagctgaaac tctggaagca ttcagaaaaa 1740gaaccagaga ccagtgttgc agaagatctc agagtgtttg aatcaagacg aaggataaac 1800gtggcaaaca aacagattaa tccggagcac tgggctgata ttttagccaa agtctttggg 1860aaaaatctcc ctacaggcac agaagtatcc ccaattatta aaaccacaag ttctccattc 1920ttgagcctag tagtcacacc acctttgcct gctgtttctc cccccttggc atctccaata 1980cagacagcaa caagtgctga agaatcctca gcagatgtac ctctactcag cgaaggaaag 2040cacattttga gtaccatttc ctcagccagc atgggactag aacaccacaa caatggagtt 2100attcttgttg aacctgaagt aacaagcaca cctctggaag aagttgttga tgagtattcc 2160aagaagactg aggagatgac ttccactgaa ggcgacctga aggggactgc agcctctaca 2220cttatatctg agccttatga acaatctcct actctacaca ccttagacac agtctatgaa 2280gagcccaccc atgaagagac ggaaacagag ggttggtctg cagcagatgt tggatcctca 2340ccagatccca catccagtga gtatgagctt ccattggttg ttgtctcctt ggctgagtct 2400aagcctgtgc aatactttga cccagatttg gagactaatt cacaaccaca tgaggataac 2460ataaaagaat acagttttgc acaccttact ccaaccgcca tcatctggtt taatgactct 2520agtacatcac tgtcatttga ggattctact gtaggggaac aaggtgtccc aggcaaatca 2580catctacaag gaccgacaga gaacatccag cttgtgaaaa gtagttttag cactcaagac 2640accttattga ttaaaaaagg tatgaaagag atgtctcaga cactacaggg aggaaatatg 2700ctagagggag accctacaca ctccagaagt tctgagaatg agggccaaga gagcaaatcc 2760atcactttac ctgactccac actgggtata acgagcagta cgtctccagt taagaagcct 2820gcggaaacca cagttgtcac cctgctacac aaagacacca caacagaaac aactccaagg 2880caaaaagtgg cttcatcatc caccatgagc actcaccctt ctcgaaggag acccaatggg 2940agaaaattac accctcacaa attccaccac cggcacaagc aaaccccacc cacaactttt 3000gctccattag agactttttc tactcaacca actcaagcaa ctgacattaa gatttcaaat 3060caaatggaga gttctctggt tcctacatct tgggagatta acacagttaa tacccccaaa 3120cagctggaaa tggagaagaa tgtagagctc atatcaaagg gaactccacg gagaaaacac 3180gggaagaggc caaacaaaca tcgatatacc ccttctacag tgagttcaag agcatctgca 3240tccaagccca gcccttctcc agaaaataaa catagaaaca ttgttactcc cagttcagaa 3300actacacttt tgcctagaaa tgtttctctg aaaactgagg gcgtttatga ttccttagat 3360tacacgacaa ccaccagaaa aatacattca tctcaccata aagtccaaga cacacttcca 3420gtcatgtata aacccacatc agatggaaaa gaaattcagg atgatgttgc cacaaatgtt 3480gacaaacata aaagtgacat tttagtccct ggtgagtcaa ttacaaatgt cacacaaact 3540tctcgctcct tggtctccac tatgggagaa tttaaggaag aatcctctcc tgtgggcttt 3600ccaggaattc caacctggaa tccctcaagg aaagctcagc ctgggaggct acagacagac 3660atacatgtta ccacttctgg ggaaacccct acagaccctc cccttgttaa cgagcttgag 3720gatgtggatt ttacttctga gtttttgtcc tctgtgacag tctccacacc atttcaccag 3780gaagaagctg gtttttccac aattctctca agcataaaag tggagatggc ttcaagtcag 3840gtagaaacta ccacccttgg tcaagatcat catgaaacca ctgtggctat tctccactct 3900gaaactagac cacagaatca catccttact gctgcctgga tgaaggagcc agcatctttg 3960tcccctccca tgattctcct gtctttggga caaaccacca ccactaagcc agaacttctc 4020agtccaagaa catctcaaat atgtaaagat tccaaggaaa atgttttctt gaattacatg 4080gggaatccag aaacagaagc aaccccagtg aaaaatgaag gaacacagcg tatgtcaggg 4140ccaaatgaat tatcaacacc atcttctgac cacgatgcat ttaacttgtc tacaaagcta 4200gaattggaaa agcaagtatt tgatagtagg agtctaacac gtggcccaga tagccaccac 4260caggatggaa gagttcatgc ttctcatcaa ctaaccagaa tccctgccaa acccatccta 4320ccaacaggaa cagtgaggct gcctgaaatg tccacacaaa gcacttccag atactttgta 4380actttccagc cacctcatca cgggaccaac aaaccagaaa taactacata tccttctagg 4440gctttgccag agagcaaaca gtttacaact ccaagagtag caagtacaac tcctctccta 4500tcacacatgt ccaaacccag catttctagt aagtttgctg acctaagaac tgaccaatcc 4560aatggctcct acaaagtgtt tggaaatagc aacatccctg aggcaagaaa ctcagttgga 4620aagcctctca gtccaagaat ttatcattat tccaatggaa gactcccttt ctttaccaac 4680aggactcttt ctttttcaca gttgggagtc acccggagac cccagatacc ctcttctcct 4740gtcccagtaa tgagagagag aaaagttaat ccaggttcct acaataggat atattcccat 4800agcaccttcc atctggactt tggccttcca gcacctccac tgttgcacac tccatggacc 4860atggtatcac ccccaactaa cttacagaat atccctatgg tctcatccac ccagagttct 4920gtctccttta taacatcttc tgtccagtcc tcaggaagca tccaccaaag cggctcaaag 4980ttctttgcag gaggaccgcc tgcatccaaa ttctggcctc ttggggaaaa gccccaaatc 5040ctcaccaagt ccccacagac tgtgtctgtc actgctgaaa cggacgctgt gttcccgtgt 5100gaggcaatag gaaaaccaaa gcctttcgtt acttggacaa aagtttccac aggagttctt 5160atgactccga ataccaggat acaacggttt gaggttctca agaacggtac cttagtgata 5220aggaagtttc aagtgcaaga tcgaggccag tatatgtgca ccgccagcaa cctgtacggc 5280ctggacagga tggtggtctt tctctgggtc accgtgcagc aacctcaaat cctagcctcc 5340cactaccagg acgtcaccgt ctacctggga gacaccatta caatggagtg tctggcgaaa 5400gggaccccag ccccccaaat ttcctggatc ttccgtgaca ggagggtgtg gcaaactctg 5460tcctccgtgg agggccggat caccctgcac caaaaccgga ccctttccat caaggaggcg 5520tccttctcag acagaggcgt ctataagtgc gtggccagca acgcaacccg ggcggacagc 5580gtgtccatcc gcctacacgt ggcggcactg ccccccatta tccaccagga gaagctggag 5640aacatctcgc tgcccccggg gctcagcatt cacattcact gcactgccaa agctgcgccc 5700ctgcccagcg tgctctgggt gctcggggat ggtacccaaa tccgcccctc gcatttcctc 5760caccggaact tgtttgtttt ccccaacggg acgctctaca tctgcaacct cgcgcccaag 5820gacagcgggc gctatgagtg cgtggccgcc aacctgatcg gctccgcgcg cagtacggtg 5880cagctgaacg tgcagcgcgc agcagcgaac gcgcgcatca cgggcacctc ctcgcagagg 5940acggacgtca ggtacggagg gaccctcaag ctggactgca gcgcctcggg ggatccctgg 6000ccgcgcatcc tctggaggct gccgtccaag aggacgatcg acgcgctttt cagttttgat 6060agtagaatca aggtgtttgc caacaggacc ctggtggtga aatcaatgac agacaaagac 6120gccggagatt acctgtgtgt agctcgaaat aaggttggtg atgactgcgt ggtgctcaag 6180gtggatgtga tgatgaaacc ggccaagatt gaacacaagg aggagaacga ccacaaagtc 6240ttctacaggg gtgacctgaa agtggactgt gtggccactg gacttcccaa tcccgagatc 6300tcctggagcc tcctggatgg gagtctggtg aactccttca tgcagtcaga tgacagtggt 6360ggacgcacca agcactatgt ggtcttcaac aatgggacac tctacttcag tgaagtgggg 6420atgagggagg aaggagacta cacctgcttt gctgaaaatc aggttgggaa ggatgagatg 6480agagtcagag tcaagatggt gacacctgcc accatctgga acaagactta cttggcagtt 6540caggtaccct atggagatgt ggtcactgta acctgtgagg ccaaaggaga acccatgccc 6600aaggtgactt ggttgtcccc agccaacagg gtgatcccca cctcctctga gaagtatcag 6660atataccaat atggcactct ccttattcag aaagcccagt gctctgacag cggcaactac 6720acctgcctgg tcaggaacag tgccggagag gataggaaga cagtgtggat tcacgtcaac 6780ctccagccac ccaagatcaa tggtaacccc aaccccatca ccaccgtgtg ggagatagca 6840gccgggggca gtcggaaact gattgactgc aaagctgaag gcatccccac cccgagggtg 6900ttatgggctt ttcccgaggg tgtggttctg ccagatccat actatggaaa ccggatcact 6960gtccatggca acggttccct ggacatcagg agtttgagga agagcgactc cgtccagctg 7020gtatgcatgg cacgcaacga gggaggggag gcgaggttga tcgtgcagct cactgtcctg 7080gagcccatgg agaaacccat cttccacgac ccgatcagcg agaagatcac ggccatggcg 7140ggccacacca tcagcctcaa ctgctctgcc gcggggaccc tgacacccag cctggtgtgg 7200gtccttccca atggcaccga tctgcagagt ggacagcagc tgcagcgctt ctaccacaag 7260gctgacggca tgctacacat tagcggtctc tcctcggtgg acgccggggc ctaccgctgc 7320gtggcccgca atgccgcggg ccacacggag aggctggtct ccctgaaggt gggactgaag 7380ccagaagcaa acaagcagta tcataacctg gtcagcatca tcaatggtga gaccctgaag 7440ctcccctgca cccctcctgc agctgggcag ggacatttct cctggacact ccccaatggc 7500atgcatctgg agggccccca aaccctggga cgcgtttctc ttctggacaa tggcaccctc 7560acggttcgtg aggcctcggt gtttgacagg ggtacctatg tatgcaggat ggagacggcg 7620tacggccctt cggtcaccag catccccgtg attgtgatcg cctatcctcc ccggatcacc 7680agcgagccta ccccagtcat ctacacccgt cccgggaaca ccgtgaaact gaactgcatg 7740gctatgggga ttcccaaagg tgacatcacg tgggagttac cggataagtt gcatctgaag 7800gcaggggttc aggctcgtct gtatggaaac agatttcttc acccccaggg atcactgacc 7860atccagcagg ccagacggag agacgctggc ttctacaagt gcacggcaaa aaacattctc 7920agcagtgact ccaaaacaac ttatatccat gtcttctgaa atgtggattc cagaatgatt 7980gctcaggaac tgacaacaaa gcggggtttg taagggaagc caggctgggg aatcagagct 8040cttaaataat gtgtcacagt gcatggtggc ccccggtggg attcaagttg aggttgatct 8100tgatctacaa ttgttgggaa aaggaagcaa tacagacatg agtaaaaggg ctcagcctca 8160ctgagaactt tcttttgtgt ttacatcatg ccaggggctt cattcagggt gtctgtgctc 8220tgactgtaat ttttattttt ttgcaaatgt cattcgactg cctgcgtaag tgtccatagg 8280atatctgagg aacattcacc gaaaataagc catagacatg aacaacacct cactccccca 8340ttgaagatgc atcgtctagt taacctgctg cagtttttac atgatagact ttgttccaga 8400ttgacaagtc atctttcagt tatttcctct atcacttcaa aactccagct tgcccaataa 8460ggatttagaa ctagagtgat tgttatatat ataatatata tattttaatt cagagttaca 8520tacatacagc taccatttta tatgaaaaaa acatttcttc ctggaaccca ctttttatgt 8580aattttttta tataaatatt tttcctttca aatcagatga tgagactaga aggagaaata 8640ctttctgtct cattaaaatt aataaatgat tggtctttac aagacttgga tacattacag 8700cagacatgga aatagaattt taaacaattc ctctccaacc tccttcaaat tcagtcgcta 8760ctgttatgtt actttctcca gcaaccctgc actggggaag gctgtgatat tagatttcct 8820tgtatgcaaa gtttttgttg aaagctgtgc tcagcggagg tgagaggaga ggaggagaaa 8880actgcatcat atctttccag aattgaatct agagtcttcc ctggaaagcc cagaaacttc 8940tctgcagtat ctgacttgtc catctggtct aaggtggctg cttcttccgc aaccatgagt 9000tagtctgtgt ccatgaataa tacaagatct gttatttcca tgactgcttt actgtaattt 9060tagggtcaat atactgtaca tttgataata aaatatattc tcccaaaaa 9109302652PRTHomo sapiens 30Met Pro Lys Arg Ala His Trp Gly Ala Leu Ser Val Val Leu Ile Leu1 5 10 15Leu Trp Gly His Pro Arg Val Ala Leu Ala Cys Pro His Pro Cys Ala 20 25 30Cys Tyr Val Pro Ser Glu Val His Cys Thr Phe Arg Ser Leu Ala Ser 35 40 45Val Pro Ala Gly Ile Ala Lys His Val Glu Arg Ile Asn Leu Gly Phe 50 55 60Gly Ile Leu Lys Cys Lys Lys Asp Lys Ala Tyr Glu Gly Gly Gln Leu65 70 75 80Cys Ala Met Cys Phe Ser Pro Lys Lys Leu Tyr Lys His Glu Ile His 85 90 95Lys Leu Lys Asp Leu Thr Cys Leu Lys Pro Ser Ile Glu Ser Pro Leu 100 105 110Arg Gln Asn Arg Ser Arg Ser Ile Glu Glu Glu Gln Lys Gln Glu Glu 115 120 125Asn Gly Asp Ser Gln Leu Ile Leu Glu Lys Ile Gln Leu Pro Gln Trp 130 135 140Ser Ile Ser Leu Asn Met Thr Asp Glu His Gly Asn Leu Val Asn Leu145 150 155 160Val Cys Asp Ile Lys Lys Pro Met Asp Val Tyr Lys Ile His Leu Asn 165 170 175Gln Thr Asp Pro Pro Asp Ile Asp Ile Asn Ala Met Val Ala Leu Asp 180 185 190Phe Glu Tyr Pro Met Thr Gln Glu Asn Tyr Glu Asn Leu Trp Lys Leu 195 200 205Ile Ala Tyr Tyr Ser Glu Val Pro Met Lys Leu His Arg Glu Leu Met 210 215 220Leu Ser Lys His Pro Arg Val Ser Tyr Gln Tyr Arg Gln Asp Ala Asp225 230 235 240Glu Glu Ala Leu Tyr Tyr Thr Gly Val Arg Ala Gln Ile Leu Ala Glu 245 250 255Pro Glu Trp Ile Met Gln Pro Ser Ile Asp Ile Gln Leu Asn Arg Pro 260 265 270Gln Ser Thr Ala Lys Lys Val Leu Leu Ser Tyr Tyr Asn Gln Tyr Ser 275 280 285Gln Thr Ile Ala Thr Lys Asp Thr Arg Gln Ala Arg Gly Arg Ser Trp 290 295 300Val Met Ile Glu Pro Ser Arg Ala Val Gln Lys Asp Gln Thr Val Leu305 310 315 320Glu Gly Gly Arg Cys Gln Leu Ser Cys Asn Val Lys Ala Ser Glu Ser 325 330 335Pro Ser Ile Phe Trp Val Leu Pro Asp Gly Ser Ile Leu Lys Val Pro 340 345 350Val Asp Asp Pro Asp Ser Lys Phe Ser Ile Leu Ser Ser Gly Trp Leu 355 360 365Arg Ile Lys Ser Met Glu Pro Ser Asp Ser Gly Leu Tyr Gln Cys Ile 370 375 380Ala Gln Val Arg Asp Glu Met Asp Arg Met Val Tyr Arg Val Leu Val385 390 395 400Gln Ser Pro Ser Thr Gln Pro Ala Glu Lys Asp Thr Val Thr Ile Gly 405 410 415Lys Asn Pro Gly Glu Pro Val Met Leu Pro Cys Asn Ala Leu Ala Ile 420 425 430Pro Glu Ala His Leu Ser Trp Ile Leu Pro Asn Arg Arg Ile Ile Asn 435 440 445Asp Leu Ala Asn

Thr Ser His Val Tyr Met Leu Pro Asn Gly Thr Leu 450 455 460Ser Ile Pro Lys Val Gln Val Ser Asp Ser Gly Tyr His Arg Cys Val465 470 475 480Ala Val Asn Gln His Gly Ala Asp His Ile Thr Val Gly Ile Thr Val 485 490 495Thr Lys Lys Gly Ser Gly Ser Pro Ser Lys Arg Gly Arg Trp Pro Gly 500 505 510Pro Lys Ala Leu Ser Arg Val Arg Glu Asp Ile Val Glu Asp Glu Gly 515 520 525Val Ser Gly Thr Gly Asp Glu Glu Asn Thr Ser Arg Arg Leu Leu His 530 535 540Pro Lys His Gln Glu Ala Phe Leu Lys Thr Lys Asp Asp Ala Ile Asn545 550 555 560Gly Asp Lys Lys Ala Lys Lys Gly Arg Arg Lys Leu Lys Leu Trp Lys 565 570 575His Ser Glu Lys Glu Pro Glu Thr Ser Val Ala Glu Asp Leu Arg Val 580 585 590Phe Glu Ser Arg Arg Arg Ile Asn Val Ala Asn Lys Gln Ile Asn Pro 595 600 605Glu His Trp Ala Asp Ile Leu Ala Lys Val Phe Gly Lys Asn Leu Pro 610 615 620Thr Gly Thr Glu Val Ser Pro Ile Ile Lys Thr Thr Ser Ser Pro Phe625 630 635 640Leu Ser Leu Val Val Thr Pro Pro Leu Pro Ala Val Ser Pro Pro Leu 645 650 655Ala Ser Pro Ile Gln Thr Ala Thr Ser Ala Glu Glu Ser Ser Ala Asp 660 665 670Val Pro Leu Leu Ser Glu Gly Lys His Ile Leu Ser Thr Ile Ser Ser 675 680 685Ala Ser Met Gly Leu Glu His His Asn Asn Gly Val Ile Leu Val Glu 690 695 700Pro Glu Val Thr Ser Thr Pro Leu Glu Glu Val Val Asp Glu Tyr Ser705 710 715 720Lys Lys Thr Glu Glu Met Thr Ser Thr Glu Gly Asp Leu Lys Gly Thr 725 730 735Ala Ala Ser Thr Leu Ile Ser Glu Pro Tyr Glu Gln Ser Pro Thr Leu 740 745 750His Thr Leu Asp Thr Val Tyr Glu Glu Pro Thr His Glu Glu Thr Glu 755 760 765Thr Glu Gly Trp Ser Ala Ala Asp Val Gly Ser Ser Pro Asp Pro Thr 770 775 780Ser Ser Glu Tyr Glu Leu Pro Leu Val Val Val Ser Leu Ala Glu Ser785 790 795 800Lys Pro Val Gln Tyr Phe Asp Pro Asp Leu Glu Thr Asn Ser Gln Pro 805 810 815His Glu Asp Asn Ile Lys Glu Tyr Ser Phe Ala His Leu Thr Pro Thr 820 825 830Ala Ile Ile Trp Phe Asn Asp Ser Ser Thr Ser Leu Ser Phe Glu Asp 835 840 845Ser Thr Val Gly Glu Gln Gly Val Pro Gly Lys Ser His Leu Gln Gly 850 855 860Pro Thr Glu Asn Ile Gln Leu Val Lys Ser Ser Phe Ser Thr Gln Asp865 870 875 880Thr Leu Leu Ile Lys Lys Gly Met Lys Glu Met Ser Gln Thr Leu Gln 885 890 895Gly Gly Asn Met Leu Glu Gly Asp Pro Thr His Ser Arg Ser Ser Glu 900 905 910Asn Glu Gly Gln Glu Ser Lys Ser Ile Thr Leu Pro Asp Ser Thr Leu 915 920 925Gly Ile Thr Ser Ser Thr Ser Pro Val Lys Lys Pro Ala Glu Thr Thr 930 935 940Val Val Thr Leu Leu His Lys Asp Thr Thr Thr Glu Thr Thr Pro Arg945 950 955 960Gln Lys Val Ala Ser Ser Ser Thr Met Ser Thr His Pro Ser Arg Arg 965 970 975Arg Pro Asn Gly Arg Lys Leu His Pro His Lys Phe His His Arg His 980 985 990Lys Gln Thr Pro Pro Thr Thr Phe Ala Pro Leu Glu Thr Phe Ser Thr 995 1000 1005Gln Pro Thr Gln Ala Thr Asp Ile Lys Ile Ser Asn Gln Met Glu 1010 1015 1020Ser Ser Leu Val Pro Thr Ser Trp Glu Ile Asn Thr Val Asn Thr 1025 1030 1035Pro Lys Gln Leu Glu Met Glu Lys Asn Val Glu Leu Ile Ser Lys 1040 1045 1050Gly Thr Pro Arg Arg Lys His Gly Lys Arg Pro Asn Lys His Arg 1055 1060 1065Tyr Thr Pro Ser Thr Val Ser Ser Arg Ala Ser Ala Ser Lys Pro 1070 1075 1080Ser Pro Ser Pro Glu Asn Lys His Arg Asn Ile Val Thr Pro Ser 1085 1090 1095Ser Glu Thr Thr Leu Leu Pro Arg Asn Val Ser Leu Lys Thr Glu 1100 1105 1110Gly Val Tyr Asp Ser Leu Asp Tyr Thr Thr Thr Thr Arg Lys Ile 1115 1120 1125His Ser Ser His His Lys Val Gln Asp Thr Leu Pro Val Met Tyr 1130 1135 1140Lys Pro Thr Ser Asp Gly Lys Glu Ile Gln Asp Asp Val Ala Thr 1145 1150 1155Asn Val Asp Lys His Lys Ser Asp Ile Leu Val Pro Gly Glu Ser 1160 1165 1170Ile Thr Asn Val Thr Gln Thr Ser Arg Ser Leu Val Ser Thr Met 1175 1180 1185Gly Glu Phe Lys Glu Glu Ser Ser Pro Val Gly Phe Pro Gly Ile 1190 1195 1200Pro Thr Trp Asn Pro Ser Arg Lys Ala Gln Pro Gly Arg Leu Gln 1205 1210 1215Thr Asp Ile His Val Thr Thr Ser Gly Glu Thr Pro Thr Asp Pro 1220 1225 1230Pro Leu Val Asn Glu Leu Glu Asp Val Asp Phe Thr Ser Glu Phe 1235 1240 1245Leu Ser Ser Val Thr Val Ser Thr Pro Phe His Gln Glu Glu Ala 1250 1255 1260Gly Phe Ser Thr Ile Leu Ser Ser Ile Lys Val Glu Met Ala Ser 1265 1270 1275Ser Gln Val Glu Thr Thr Thr Leu Gly Gln Asp His His Glu Thr 1280 1285 1290Thr Val Ala Ile Leu His Ser Glu Thr Arg Pro Gln Asn His Ile 1295 1300 1305Leu Thr Ala Ala Trp Met Lys Glu Pro Ala Ser Leu Ser Pro Pro 1310 1315 1320Met Ile Leu Leu Ser Leu Gly Gln Thr Thr Thr Thr Lys Pro Glu 1325 1330 1335Leu Leu Ser Pro Arg Thr Ser Gln Ile Cys Lys Asp Ser Lys Glu 1340 1345 1350Asn Val Phe Leu Asn Tyr Met Gly Asn Pro Glu Thr Glu Ala Thr 1355 1360 1365Pro Val Lys Asn Glu Gly Thr Gln Arg Met Ser Gly Pro Asn Glu 1370 1375 1380Leu Ser Thr Pro Ser Ser Asp His Asp Ala Phe Asn Leu Ser Thr 1385 1390 1395Lys Leu Glu Leu Glu Lys Gln Val Phe Asp Ser Arg Ser Leu Thr 1400 1405 1410Arg Gly Pro Asp Ser His His Gln Asp Gly Arg Val His Ala Ser 1415 1420 1425His Gln Leu Thr Arg Ile Pro Ala Lys Pro Ile Leu Pro Thr Gly 1430 1435 1440Thr Val Arg Leu Pro Glu Met Ser Thr Gln Ser Thr Ser Arg Tyr 1445 1450 1455Phe Val Thr Phe Gln Pro Pro His His Gly Thr Asn Lys Pro Glu 1460 1465 1470Ile Thr Thr Tyr Pro Ser Arg Ala Leu Pro Glu Ser Lys Gln Phe 1475 1480 1485Thr Thr Pro Arg Val Ala Ser Thr Thr Pro Leu Leu Ser His Met 1490 1495 1500Ser Lys Pro Ser Ile Ser Ser Lys Phe Ala Asp Leu Arg Thr Asp 1505 1510 1515Gln Ser Asn Gly Ser Tyr Lys Val Phe Gly Asn Ser Asn Ile Pro 1520 1525 1530Glu Ala Arg Asn Ser Val Gly Lys Pro Leu Ser Pro Arg Ile Tyr 1535 1540 1545His Tyr Ser Asn Gly Arg Leu Pro Phe Phe Thr Asn Arg Thr Leu 1550 1555 1560Ser Phe Ser Gln Leu Gly Val Thr Arg Arg Pro Gln Ile Pro Ser 1565 1570 1575Ser Pro Val Pro Val Met Arg Glu Arg Lys Val Asn Pro Gly Ser 1580 1585 1590Tyr Asn Arg Ile Tyr Ser His Ser Thr Phe His Leu Asp Phe Gly 1595 1600 1605Leu Pro Ala Pro Pro Leu Leu His Thr Pro Trp Thr Met Val Ser 1610 1615 1620Pro Pro Thr Asn Leu Gln Asn Ile Pro Met Val Ser Ser Thr Gln 1625 1630 1635Ser Ser Val Ser Phe Ile Thr Ser Ser Val Gln Ser Ser Gly Ser 1640 1645 1650Ile His Gln Ser Gly Ser Lys Phe Phe Ala Gly Gly Pro Pro Ala 1655 1660 1665Ser Lys Phe Trp Pro Leu Gly Glu Lys Pro Gln Ile Leu Thr Lys 1670 1675 1680Ser Pro Gln Thr Val Ser Val Thr Ala Glu Thr Asp Ala Val Phe 1685 1690 1695Pro Cys Glu Ala Ile Gly Lys Pro Lys Pro Phe Val Thr Trp Thr 1700 1705 1710Lys Val Ser Thr Gly Val Leu Met Thr Pro Asn Thr Arg Ile Gln 1715 1720 1725Arg Phe Glu Val Leu Lys Asn Gly Thr Leu Val Ile Arg Lys Phe 1730 1735 1740Gln Val Gln Asp Arg Gly Gln Tyr Met Cys Thr Ala Ser Asn Leu 1745 1750 1755Tyr Gly Leu Asp Arg Met Val Val Phe Leu Trp Val Thr Val Gln 1760 1765 1770Gln Pro Gln Ile Leu Ala Ser His Tyr Gln Asp Val Thr Val Tyr 1775 1780 1785Leu Gly Asp Thr Ile Thr Met Glu Cys Leu Ala Lys Gly Thr Pro 1790 1795 1800Ala Pro Gln Ile Ser Trp Ile Phe Arg Asp Arg Arg Val Trp Gln 1805 1810 1815Thr Leu Ser Ser Val Glu Gly Arg Ile Thr Leu His Gln Asn Arg 1820 1825 1830Thr Leu Ser Ile Lys Glu Ala Ser Phe Ser Asp Arg Gly Val Tyr 1835 1840 1845Lys Cys Val Ala Ser Asn Ala Thr Arg Ala Asp Ser Val Ser Ile 1850 1855 1860Arg Leu His Val Ala Ala Leu Pro Pro Ile Ile His Gln Glu Lys 1865 1870 1875Leu Glu Asn Ile Ser Leu Pro Pro Gly Leu Ser Ile His Ile His 1880 1885 1890Cys Thr Ala Lys Ala Ala Pro Leu Pro Ser Val Leu Trp Val Leu 1895 1900 1905Gly Asp Gly Thr Gln Ile Arg Pro Ser His Phe Leu His Arg Asn 1910 1915 1920Leu Phe Val Phe Pro Asn Gly Thr Leu Tyr Ile Cys Asn Leu Ala 1925 1930 1935Pro Lys Asp Ser Gly Arg Tyr Glu Cys Val Ala Ala Asn Leu Ile 1940 1945 1950Gly Ser Ala Arg Ser Thr Val Gln Leu Asn Val Gln Arg Ala Ala 1955 1960 1965Ala Asn Ala Arg Ile Thr Gly Thr Ser Ser Gln Arg Thr Asp Val 1970 1975 1980Arg Tyr Gly Gly Thr Leu Lys Leu Asp Cys Ser Ala Ser Gly Asp 1985 1990 1995Pro Trp Pro Arg Ile Leu Trp Arg Leu Pro Ser Lys Arg Thr Ile 2000 2005 2010Asp Ala Leu Phe Ser Phe Asp Ser Arg Ile Lys Val Phe Ala Asn 2015 2020 2025Arg Thr Leu Val Val Lys Ser Met Thr Asp Lys Asp Ala Gly Asp 2030 2035 2040Tyr Leu Cys Val Ala Arg Asn Lys Val Gly Asp Asp Cys Val Val 2045 2050 2055Leu Lys Val Asp Val Met Met Lys Pro Ala Lys Ile Glu His Lys 2060 2065 2070Glu Glu Asn Asp His Lys Val Phe Tyr Arg Gly Asp Leu Lys Val 2075 2080 2085Asp Cys Val Ala Thr Gly Leu Pro Asn Pro Glu Ile Ser Trp Ser 2090 2095 2100Leu Leu Asp Gly Ser Leu Val Asn Ser Phe Met Gln Ser Asp Asp 2105 2110 2115Ser Gly Gly Arg Thr Lys His Tyr Val Val Phe Asn Asn Gly Thr 2120 2125 2130Leu Tyr Phe Ser Glu Val Gly Met Arg Glu Glu Gly Asp Tyr Thr 2135 2140 2145Cys Phe Ala Glu Asn Gln Val Gly Lys Asp Glu Met Arg Val Arg 2150 2155 2160Val Lys Met Val Thr Pro Ala Thr Ile Trp Asn Lys Thr Tyr Leu 2165 2170 2175Ala Val Gln Val Pro Tyr Gly Asp Val Val Thr Val Thr Cys Glu 2180 2185 2190Ala Lys Gly Glu Pro Met Pro Lys Val Thr Trp Leu Ser Pro Ala 2195 2200 2205Asn Arg Val Ile Pro Thr Ser Ser Glu Lys Tyr Gln Ile Tyr Gln 2210 2215 2220Tyr Gly Thr Leu Leu Ile Gln Lys Ala Gln Cys Ser Asp Ser Gly 2225 2230 2235Asn Tyr Thr Cys Leu Val Arg Asn Ser Ala Gly Glu Asp Arg Lys 2240 2245 2250Thr Val Trp Ile His Val Asn Leu Gln Pro Pro Lys Ile Asn Gly 2255 2260 2265Asn Pro Asn Pro Ile Thr Thr Val Trp Glu Ile Ala Ala Gly Gly 2270 2275 2280Ser Arg Lys Leu Ile Asp Cys Lys Ala Glu Gly Ile Pro Thr Pro 2285 2290 2295Arg Val Leu Trp Ala Phe Pro Glu Gly Val Val Leu Pro Asp Pro 2300 2305 2310Tyr Tyr Gly Asn Arg Ile Thr Val His Gly Asn Gly Ser Leu Asp 2315 2320 2325Ile Arg Ser Leu Arg Lys Ser Asp Ser Val Gln Leu Val Cys Met 2330 2335 2340Ala Arg Asn Glu Gly Gly Glu Ala Arg Leu Ile Val Gln Leu Thr 2345 2350 2355Val Leu Glu Pro Met Glu Lys Pro Ile Phe His Asp Pro Ile Ser 2360 2365 2370Glu Lys Ile Thr Ala Met Ala Gly His Thr Ile Ser Leu Asn Cys 2375 2380 2385Ser Ala Ala Gly Thr Leu Thr Pro Ser Leu Val Trp Val Leu Pro 2390 2395 2400Asn Gly Thr Asp Leu Gln Ser Gly Gln Gln Leu Gln Arg Phe Tyr 2405 2410 2415His Lys Ala Asp Gly Met Leu His Ile Ser Gly Leu Ser Ser Val 2420 2425 2430Asp Ala Gly Ala Tyr Arg Cys Val Ala Arg Asn Ala Ala Gly His 2435 2440 2445Thr Glu Arg Leu Val Ser Leu Lys Val Gly Leu Lys Pro Glu Ala 2450 2455 2460Asn Lys Gln Tyr His Asn Leu Val Ser Ile Ile Asn Gly Glu Thr 2465 2470 2475Leu Lys Leu Pro Cys Thr Pro Pro Ala Ala Gly Gln Gly His Phe 2480 2485 2490Ser Trp Thr Leu Pro Asn Gly Met His Leu Glu Gly Pro Gln Thr 2495 2500 2505Leu Gly Arg Val Ser Leu Leu Asp Asn Gly Thr Leu Thr Val Arg 2510 2515 2520Glu Ala Ser Val Phe Asp Arg Gly Thr Tyr Val Cys Arg Met Glu 2525 2530 2535Thr Ala Tyr Gly Pro Ser Val Thr Ser Ile Pro Val Ile Val Ile 2540 2545 2550Ala Tyr Pro Pro Arg Ile Thr Ser Glu Pro Thr Pro Val Ile Tyr 2555 2560 2565Thr Arg Pro Gly Asn Thr Val Lys Leu Asn Cys Met Ala Met Gly 2570 2575 2580Ile Pro Lys Gly Asp Ile Thr Trp Glu Leu Pro Asp Lys Leu His 2585 2590 2595Leu Lys Ala Gly Val Gln Ala Arg Leu Tyr Gly Asn Arg Phe Leu 2600 2605 2610His Pro Gln Gly Ser Leu Thr Ile Gln Gln Ala Arg Arg Arg Asp 2615 2620 2625Ala Gly Phe Tyr Lys Cys Thr Ala Lys Asn Ile Leu Ser Ser Asp 2630 2635 2640Ser Lys Thr Thr Tyr Ile His Val Phe 2645 2650317872DNAHomo sapiens 31atgaaggtaa aaggcagagg aatcacctgc ttgctggtct cctttgctgt gatctgcctg 60gtcgccaccc ctgggggcaa ggcctgtcct cgccgctgtg cctgttatat gcctacggag 120gtacactgca catttcggta cctgacttcc atcccagaca gcatcccgcc caatgtggaa 180cgcatcaatt taggatacaa cagcttggtt agattgatgg aaacagattt ttctggcctg 240accaaactgg agttactcat gcttcacagc aatggcattc acacaatccc tgacaagacc 300ttctcagatt tgcaggcctt gcaggtctta aaaatgagct ataataaagt ccgaaaactt 360cagaaagata ctttttatgg cctcaggagc ttgacacgat tgcacatgga ccacaacaat 420attgagttta taaacccaga ggttttttat gggctcaact ttctccgcct ggtgcacttg 480gaaggaaatc agctcactaa gctccaccca gatacatttg tctctttgag ctacctccag 540atatttaaaa tctctttcat taagttccta tacttgtctg ataacttcct gacctccctc 600cctcaagaga tggtctccta tatgcctgac ctagacagcc tttacctgca tggaaaccca 660tggacctgtg attgccattt aaagtggttg tctgactgga tacaggagaa gccagatgta 720ataaaatgca aaaaagatag aagtccctct agtgctcagc agtgtccact ttgcatgaac 780cctaggactt ctaaaggcaa gccgttagct atggtctcag ctgcagcttt ccagtgtgcc 840aagccaacca ttgactcatc cctgaaatca aagagcctga ctattctgga agacagtagt 900tctgctttca tctctcccca aggtttcatg gcaccctttg gctccctcac tttgaatatg 960acagatcagt ctggaaatga agctaacatg gtctgcagta ttcaaaagcc ctcaaggaca 1020tcacccattg cattcactga agaaaatgac tacatcgtgc taaatacttc attttcaaca 1080tttttggtgt gcaacataga ttacggtcac attcagccag tgtggcaaat tttggctttg 1140tacagtgatt ctcctctgat actagaaagg agccacttgc ttagtgaaac accgcagctc 1200tattacaaat ataaacaggt ggctcctaag cctgaagaca tttttaccaa catagaggca 1260gatctcagag cagatccctc ttggttaatg caagaccaaa tttccttgca gctgaacaga 1320actgccacca cattcagtac attacagatc cagtactcca gtgatgctca aatcacttta 1380ccaagagcag agatgaggcc agtgaaacac aaatggacta tgatttcaag ggataacaat 1440actaagctgg aacatactgt cttggtaggt ggaaccgttg

gcctgaactg cccaggccaa 1500ggagacccca ccccacacgt ggattggctt ctagctgatg gaagtaaagt gagagcccct 1560tatgtcagtg aggatggacg gatcctaata gacaaaagtg gaaaattgga actccagatg 1620gctgatagtt ttgacacagg cgtatatcac tgtataagca gcaattatga tgatgcagat 1680attctcacct ataggataac tgtggtagaa cctttggtcg aagcctatca ggaaaatggg 1740attcatcaca cagttttcat tggtgaaaca cttgatcttc catgccattc tactggtatc 1800ccagatgcct ctattagctg ggttattcca ggaaacaatg tgctctatca gtcatcaaga 1860gacaagaaag ttctaaacaa tggcacatta agaatattac aggtcacccc gaaagaccaa 1920ggttattatc gctgtgtggc agccaaccca tcaggggttg attttttgat tttccaagtt 1980tcagtcaaga tgaaaggaca aaggcccttg gagcatgatg gagaaacaga gggatctgga 2040cttgatgagt ccaatcctat tgctcatctt aaggagccac caggtgcaca actccgtaca 2100tctgctctga tggaggctga ggttggaaaa cacacctcaa gcacaagtaa gaggcacaac 2160tatcgggaat taacactcca gcgacgtgga gattcaacac atcgacgttt tagggagaat 2220aggaggcatt tccctccctc tgctaggaga attgacccac aacattgggc ggcactgttg 2280gagaaagcta aaaagaatgc tatgccagac aagcgagaaa ataccacagt gagcccaccc 2340ccagtggtca cccaactccc aaacatacct ggtgaagaag acgattcctc aggcatgctc 2400gctctacatg aggaatttat ggtcccggcc actaaagctt tgaaccttcc agcaaggaca 2460gtgactgctg actccagaac aatatctgat agtcctatga caaacataaa ttatggcaca 2520gaattctctc ctgttgtgaa ttcacaaata ctaccacctg aagaacccac agatttcaaa 2580ctgtctactg ctattaaaac tacagccatg tcaaagaata taaacccaac catgtcaagc 2640caaatacaag gcacaaccaa tcaacattca tccactgtct ttccactgct acttggagca 2700actgaatttc aggactctga ccagatggga agaggaagag agcatttcca aagtagaccc 2760ccaataacag taaggactat gatcaaagat gtcaatgtca aaatgcttag tagcaccacc 2820aacaaactat tattagagtc agtaaatacc acaaatagtc atcagacatc tgtaagagaa 2880gtgagtgaac ccaggcacaa tcacttctat tctcacacta ctcaaatact tagcacctcc 2940acgttccctt cagatccaca cacagctgct cattctcagt ttccgatccc tagaaatagt 3000acagttaaca tcccgctgtt cagacgcttt gggaggcaga ggaaaattgg cggaaggggg 3060cggattatca gcccatatag aactccagtt ctgcgacggc atagatacag cattttcagg 3120tcaacaacca gaggttcttc tgaaaaaagc actactgcat tctcagccac agtgctcaat 3180gtgacatgtc tgtcctgtct tcccagggag aggctcacca ctgccacagc agcattgtct 3240tttccaagtg ctgctcccat caccttcccc aaagctgaca ttgctagagt cccatcagaa 3300gagtctacaa ctctagtcca gaatccacta ttactacttg agaacaaacc cagtgtagag 3360aaaacaacac ccacaataaa atatttcagg actgaaattt cccaagtgac tccaactggt 3420gcagtcatga catatgctcc aacatccata cccatggaaa aaactcacaa agtaaacgcc 3480agttacccac gtgtgtctag caccaatgaa gctaaaagag attcagtgat tacatcgtca 3540ctttcaggtg ctatcaccaa gccaccaatg actattatag ccattacaag gttttcaaga 3600aggaaaattc cctggcaaca gaactttgta aataaccata acccaaaagg cagattaagg 3660aatcaacata aagttagttt acaaaaaagc acagctgtga tgcttcctaa aacatctcct 3720gctttaccca gagacaaagt ctcccctttc catttcacca cactttcaac aagtgtgatg 3780caaattccat ctaatacctt gactaccgct caccacacta cgaccaaaac acacaatcct 3840ggaagtcttc caacaaagaa ggagcttccc ttcccacccc ttaaccctat gcttcctagt 3900attataagca aagactcaag tacaaaaagc atcatatcaa cgcaaacagc aataccagca 3960acaactccta ccttccctgc atctgtcatc acttatgaaa cccaaacaga gagatctaga 4020gcacaaacaa tacaaagaga acaggagcct caaaagaaga acaggactga cccaaacatc 4080tctccagacc agagttctgg cttcactaca cccactgcta tgacacctcc tgttctaacc 4140acagccgaaa cttcagtcaa gcccagtgtc tctgcattca ctcattcccc accagaaaac 4200acaactggga tttcaagcac aatcagtttt cattcaagaa ctcttaatct gacagatgtg 4260attgaagaac tagcccaagc aagtactcag actttgaaga gcacaattgc ttctgaaaca 4320actttgtcca gcaaatcaca ccagagtacc acaactagga aagcaatcat tagacactca 4380accataccac cattcttgag cagcagtgct actctaatgc cagttcccat ctcccctccc 4440tttactcaga gagcagttac tgacaacgtg gcgactccca tttccgggct tatgacaaat 4500acagtggtca agctgcacga atcctcaagg cacaatgcta aaccacagca attagtagca 4560gaggttgcaa catcccccaa ggttcaccca aatgccaagt tcacaattgg aaccactcac 4620ttcatctact ctaatctgtt acattctact cccatgccag cactaacaac agttaaatca 4680cagaattcta aattaactcc atctccctgg gcagaaaacc aattttggca caaaccatac 4740tcagaaattg ctgaaaaagg caaaaagcca gaagtaagca tgttggctac tacaggcctg 4800tccgaggcca ccactcttgt ttcagattgg gatggacaga agaacacaaa gaagagtgac 4860tttgataaga aaccagttca agaagcaaca acttccaaac tccttccctt tgactctttg 4920tctaggtata tatttgaaaa gcccaggata gttggaggaa aagctgcaag ttttactatt 4980ccagctaact cagatgcctt tcttccctgt gaagctgttg gaaatcccct gcccaccatt 5040cattggacca gagtcccatc aggacttgat ttatctaaga ggaaacagaa tagcagggtc 5100caggttctcc ccaatggtac cctgtccatc cagagggtgg aaattcagga ccgcggacag 5160tacttgtgtt ccgcatccaa tctgtttggc acagaccacc ttcatgtcac cttgtctgtg 5220gtttcctatc ctcccaggat cctggagaga cgtaccaaag agatcacagt tcattccgga 5280agcactgtgg aactgaagtg cagagcagaa ggtaggccaa gccctacagt tacctggatt 5340cttgcaaacc aaacagttgt ctcagaatca tcccagggaa gtaggcaggc tgtggtgacg 5400gttgacggaa cattggtcct ccacaatctc agtatttatg accgtggctt ttacaaatgt 5460gtggccagca acccaggtgg ccaggattca ctgctggtta aaatacaagt cattgcagca 5520ccacctgtta ttctagagca aaggaggcaa gtcattgtag gcacttgggg tgaaagttta 5580aaactgccct gtactgcaaa aggaactcct cagcccagcg tttactgggt cctctctgat 5640ggcactgaag tgaaaccatt acagtttacc aattccaagt tgttcttatt ttcaaatggg 5700actttgtata taagaaacct agcctcttca gacaggggca cttatgaatg cattgctacc 5760agttccactg gttcggagcg aagagtagta atgcttacaa tggaagagcg agtgaccagc 5820cccaggatag aagctgcatc ccagaaaagg actgaagtga attttgggga caaattacta 5880ctgaactgct cagccactgg ggagcccaaa ccccaaataa tgtggaggtt accatccaag 5940gctgtggtcg accagcagca tagagtgggc agctggatcc acgtctaccc taatggatcc 6000ctgtttattg gatcagtaac agaaaaagac agtggtgtct acttgtgtgt ggcaagaaac 6060aaaatggggg atgatctgat actgatgcat gttagcctaa gactgaaacc tgccaaaatt 6120gaccacaagc agtattttag aaagcaagtg ctccatggga aagatttcca agtagattgc 6180aaagcttccg gctccccagt gccagagata tcttggagtt tgcctgatgg aaccatgatc 6240aacaatgcaa tgcaagccga tgacagtggc cacaggacta ggagatatac ccttttcaac 6300aatggaactt tatacttcaa caaagttggg gtagcggagg aaggagatta tacttgctat 6360gcccagaaca ccctagggaa agatgaaatg aaggtccact taacagttat aacagctgct 6420ccccggataa ggcagagtaa caaaaccaac aagagaatca aagctggaga cacagctgtc 6480cttgactgtg aggtcactgg ggatcccaaa ccaaaaatat tttggttgct gccttccaat 6540gacatgattt ccttctccat tgataggtac acatttcatg ccaatgggtc tttgaccatc 6600aacaaagtga aactgctcga ttctggagag tacgtatgtg tagcccgaaa tcccagtggg 6660gatgacacca aaatgtacaa actggatgtg gtctctaaac ctccattaat caatggtctg 6720tatacaaaca gaactgttat taaagccaca gctgtgagac attccaaaaa acactttgac 6780tgcagagctg aagggacacc atctcctgaa gtcatgtgga tcatgccaga caatattttc 6840ctcacagccc catactatgg aagcagaatc acagtccata aaaatggaac cttggaaatt 6900aggaatgtga ggctttcaga ttcagccgac tttatctgtg tggcccgaaa tgaaggtgga 6960gagagcgtgt tggtagtaca gttagaagta ctggaaatgc tgagaagacc gacatttaga 7020aatccattta atgaaaaaat agttgcccag ctgggaaagt ccacagcatt gaattgctct 7080gttgatggta acccaccacc tgaaataatc tggattttac caaatggcac acgattttcc 7140aatggaccac aaagttatca gtatctgata gcaagcaatg gttcttttat catttctaaa 7200acaactcggg aggatgcagg aaaatatcgc tgtgcagcta ggaataaagt tggctatatt 7260gagaaattag tcatattaga aattggccag aagccagtta ttcttaccta tgcaccaggg 7320acagtaaaag gcatcagtgg agaatctcta tcactgcatt gtgtgtctga tggaatccct 7380aagccaaata tcaaatggac tatgccaagt ggttatgtag tagacaggcc tcaaattaat 7440gggaaataca tattgcatga caatggcacc ttagtcatta aagaagcaac agcttatgac 7500agaggaaact atatctgtaa ggctcaaaat agtgttggtc atacactgat tactgttcca 7560gtaatgattg tagcctaccc tccccgaatt acaaatcgtc cacccaggag tattgtcacc 7620aggacagggg cagcctttca gctccactgt gtggccttgg gagttcccaa gccagaaatc 7680acatgggaga tgcctgacca ctcccttctc tcaacggcaa gtaaagagag gacacatgga 7740agtgagcagc ttcacttaca aggtacccta gtcattcaga atccccaaac ctccgattct 7800gggatataca aatgcacagc aaagaaccca cttggtagtg attatgcagc aacgtatatt 7860caagtaatct ga 7872322623PRTHomo sapiens 32Met Lys Val Lys Gly Arg Gly Ile Thr Cys Leu Leu Val Ser Phe Ala1 5 10 15Val Ile Cys Leu Val Ala Thr Pro Gly Gly Lys Ala Cys Pro Arg Arg 20 25 30Cys Ala Cys Tyr Met Pro Thr Glu Val His Cys Thr Phe Arg Tyr Leu 35 40 45Thr Ser Ile Pro Asp Ser Ile Pro Pro Asn Val Glu Arg Ile Asn Leu 50 55 60Gly Tyr Asn Ser Leu Val Arg Leu Met Glu Thr Asp Phe Ser Gly Leu65 70 75 80Thr Lys Leu Glu Leu Leu Met Leu His Ser Asn Gly Ile His Thr Ile 85 90 95Pro Asp Lys Thr Phe Ser Asp Leu Gln Ala Leu Gln Val Leu Lys Met 100 105 110Ser Tyr Asn Lys Val Arg Lys Leu Gln Lys Asp Thr Phe Tyr Gly Leu 115 120 125Arg Ser Leu Thr Arg Leu His Met Asp His Asn Asn Ile Glu Phe Ile 130 135 140Asn Pro Glu Val Phe Tyr Gly Leu Asn Phe Leu Arg Leu Val His Leu145 150 155 160Glu Gly Asn Gln Leu Thr Lys Leu His Pro Asp Thr Phe Val Ser Leu 165 170 175Ser Tyr Leu Gln Ile Phe Lys Ile Ser Phe Ile Lys Phe Leu Tyr Leu 180 185 190Ser Asp Asn Phe Leu Thr Ser Leu Pro Gln Glu Met Val Ser Tyr Met 195 200 205Pro Asp Leu Asp Ser Leu Tyr Leu His Gly Asn Pro Trp Thr Cys Asp 210 215 220Cys His Leu Lys Trp Leu Ser Asp Trp Ile Gln Glu Lys Pro Asp Val225 230 235 240Ile Lys Cys Lys Lys Asp Arg Ser Pro Ser Ser Ala Gln Gln Cys Pro 245 250 255Leu Cys Met Asn Pro Arg Thr Ser Lys Gly Lys Pro Leu Ala Met Val 260 265 270Ser Ala Ala Ala Phe Gln Cys Ala Lys Pro Thr Ile Asp Ser Ser Leu 275 280 285Lys Ser Lys Ser Leu Thr Ile Leu Glu Asp Ser Ser Ser Ala Phe Ile 290 295 300Ser Pro Gln Gly Phe Met Ala Pro Phe Gly Ser Leu Thr Leu Asn Met305 310 315 320Thr Asp Gln Ser Gly Asn Glu Ala Asn Met Val Cys Ser Ile Gln Lys 325 330 335Pro Ser Arg Thr Ser Pro Ile Ala Phe Thr Glu Glu Asn Asp Tyr Ile 340 345 350Val Leu Asn Thr Ser Phe Ser Thr Phe Leu Val Cys Asn Ile Asp Tyr 355 360 365Gly His Ile Gln Pro Val Trp Gln Ile Leu Ala Leu Tyr Ser Asp Ser 370 375 380Pro Leu Ile Leu Glu Arg Ser His Leu Leu Ser Glu Thr Pro Gln Leu385 390 395 400Tyr Tyr Lys Tyr Lys Gln Val Ala Pro Lys Pro Glu Asp Ile Phe Thr 405 410 415Asn Ile Glu Ala Asp Leu Arg Ala Asp Pro Ser Trp Leu Met Gln Asp 420 425 430Gln Ile Ser Leu Gln Leu Asn Arg Thr Ala Thr Thr Phe Ser Thr Leu 435 440 445Gln Ile Gln Tyr Ser Ser Asp Ala Gln Ile Thr Leu Pro Arg Ala Glu 450 455 460Met Arg Pro Val Lys His Lys Trp Thr Met Ile Ser Arg Asp Asn Asn465 470 475 480Thr Lys Leu Glu His Thr Val Leu Val Gly Gly Thr Val Gly Leu Asn 485 490 495Cys Pro Gly Gln Gly Asp Pro Thr Pro His Val Asp Trp Leu Leu Ala 500 505 510Asp Gly Ser Lys Val Arg Ala Pro Tyr Val Ser Glu Asp Gly Arg Ile 515 520 525Leu Ile Asp Lys Ser Gly Lys Leu Glu Leu Gln Met Ala Asp Ser Phe 530 535 540Asp Thr Gly Val Tyr His Cys Ile Ser Ser Asn Tyr Asp Asp Ala Asp545 550 555 560Ile Leu Thr Tyr Arg Ile Thr Val Val Glu Pro Leu Val Glu Ala Tyr 565 570 575Gln Glu Asn Gly Ile His His Thr Val Phe Ile Gly Glu Thr Leu Asp 580 585 590Leu Pro Cys His Ser Thr Gly Ile Pro Asp Ala Ser Ile Ser Trp Val 595 600 605Ile Pro Gly Asn Asn Val Leu Tyr Gln Ser Ser Arg Asp Lys Lys Val 610 615 620Leu Asn Asn Gly Thr Leu Arg Ile Leu Gln Val Thr Pro Lys Asp Gln625 630 635 640Gly Tyr Tyr Arg Cys Val Ala Ala Asn Pro Ser Gly Val Asp Phe Leu 645 650 655Ile Phe Gln Val Ser Val Lys Met Lys Gly Gln Arg Pro Leu Glu His 660 665 670Asp Gly Glu Thr Glu Gly Ser Gly Leu Asp Glu Ser Asn Pro Ile Ala 675 680 685His Leu Lys Glu Pro Pro Gly Ala Gln Leu Arg Thr Ser Ala Leu Met 690 695 700Glu Ala Glu Val Gly Lys His Thr Ser Ser Thr Ser Lys Arg His Asn705 710 715 720Tyr Arg Glu Leu Thr Leu Gln Arg Arg Gly Asp Ser Thr His Arg Arg 725 730 735Phe Arg Glu Asn Arg Arg His Phe Pro Pro Ser Ala Arg Arg Ile Asp 740 745 750Pro Gln His Trp Ala Ala Leu Leu Glu Lys Ala Lys Lys Asn Ala Met 755 760 765Pro Asp Lys Arg Glu Asn Thr Thr Val Ser Pro Pro Pro Val Val Thr 770 775 780Gln Leu Pro Asn Ile Pro Gly Glu Glu Asp Asp Ser Ser Gly Met Leu785 790 795 800Ala Leu His Glu Glu Phe Met Val Pro Ala Thr Lys Ala Leu Asn Leu 805 810 815Pro Ala Arg Thr Val Thr Ala Asp Ser Arg Thr Ile Ser Asp Ser Pro 820 825 830Met Thr Asn Ile Asn Tyr Gly Thr Glu Phe Ser Pro Val Val Asn Ser 835 840 845Gln Ile Leu Pro Pro Glu Glu Pro Thr Asp Phe Lys Leu Ser Thr Ala 850 855 860Ile Lys Thr Thr Ala Met Ser Lys Asn Ile Asn Pro Thr Met Ser Ser865 870 875 880Gln Ile Gln Gly Thr Thr Asn Gln His Ser Ser Thr Val Phe Pro Leu 885 890 895Leu Leu Gly Ala Thr Glu Phe Gln Asp Ser Asp Gln Met Gly Arg Gly 900 905 910Arg Glu His Phe Gln Ser Arg Pro Pro Ile Thr Val Arg Thr Met Ile 915 920 925Lys Asp Val Asn Val Lys Met Leu Ser Ser Thr Thr Asn Lys Leu Leu 930 935 940Leu Glu Ser Val Asn Thr Thr Asn Ser His Gln Thr Ser Val Arg Glu945 950 955 960Val Ser Glu Pro Arg His Asn His Phe Tyr Ser His Thr Thr Gln Ile 965 970 975Leu Ser Thr Ser Thr Phe Pro Ser Asp Pro His Thr Ala Ala His Ser 980 985 990Gln Phe Pro Ile Pro Arg Asn Ser Thr Val Asn Ile Pro Leu Phe Arg 995 1000 1005Arg Phe Gly Arg Gln Arg Lys Ile Gly Gly Arg Gly Arg Ile Ile 1010 1015 1020Ser Pro Tyr Arg Thr Pro Val Leu Arg Arg His Arg Tyr Ser Ile 1025 1030 1035Phe Arg Ser Thr Thr Arg Gly Ser Ser Glu Lys Ser Thr Thr Ala 1040 1045 1050Phe Ser Ala Thr Val Leu Asn Val Thr Cys Leu Ser Cys Leu Pro 1055 1060 1065Arg Glu Arg Leu Thr Thr Ala Thr Ala Ala Leu Ser Phe Pro Ser 1070 1075 1080Ala Ala Pro Ile Thr Phe Pro Lys Ala Asp Ile Ala Arg Val Pro 1085 1090 1095Ser Glu Glu Ser Thr Thr Leu Val Gln Asn Pro Leu Leu Leu Leu 1100 1105 1110Glu Asn Lys Pro Ser Val Glu Lys Thr Thr Pro Thr Ile Lys Tyr 1115 1120 1125Phe Arg Thr Glu Ile Ser Gln Val Thr Pro Thr Gly Ala Val Met 1130 1135 1140Thr Tyr Ala Pro Thr Ser Ile Pro Met Glu Lys Thr His Lys Val 1145 1150 1155Asn Ala Ser Tyr Pro Arg Val Ser Ser Thr Asn Glu Ala Lys Arg 1160 1165 1170Asp Ser Val Ile Thr Ser Ser Leu Ser Gly Ala Ile Thr Lys Pro 1175 1180 1185Pro Met Thr Ile Ile Ala Ile Thr Arg Phe Ser Arg Arg Lys Ile 1190 1195 1200Pro Trp Gln Gln Asn Phe Val Asn Asn His Asn Pro Lys Gly Arg 1205 1210 1215Leu Arg Asn Gln His Lys Val Ser Leu Gln Lys Ser Thr Ala Val 1220 1225 1230Met Leu Pro Lys Thr Ser Pro Ala Leu Pro Arg Asp Lys Val Ser 1235 1240 1245Pro Phe His Phe Thr Thr Leu Ser Thr Ser Val Met Gln Ile Pro 1250 1255 1260Ser Asn Thr Leu Thr Thr Ala His His Thr Thr Thr Lys Thr His 1265 1270 1275Asn Pro Gly Ser Leu Pro Thr Lys Lys Glu Leu Pro Phe Pro Pro 1280 1285 1290Leu Asn Pro Met Leu Pro Ser Ile Ile Ser Lys Asp Ser Ser Thr 1295 1300 1305Lys Ser Ile Ile Ser Thr Gln Thr Ala Ile Pro Ala Thr Thr Pro 1310 1315 1320Thr Phe Pro Ala Ser Val Ile Thr Tyr Glu Thr Gln Thr Glu Arg 1325 1330 1335Ser Arg Ala Gln Thr Ile Gln Arg Glu Gln Glu Pro Gln Lys Lys 1340 1345 1350Asn Arg Thr Asp Pro Asn Ile Ser Pro Asp Gln Ser Ser Gly Phe 1355 1360 1365Thr Thr Pro Thr Ala Met Thr Pro Pro Val Leu Thr Thr Ala Glu 1370 1375 1380Thr Ser Val Lys Pro Ser Val Ser Ala Phe Thr His Ser Pro Pro 1385 1390 1395Glu Asn Thr Thr Gly Ile Ser Ser Thr Ile Ser Phe His

Ser Arg 1400 1405 1410Thr Leu Asn Leu Thr Asp Val Ile Glu Glu Leu Ala Gln Ala Ser 1415 1420 1425Thr Gln Thr Leu Lys Ser Thr Ile Ala Ser Glu Thr Thr Leu Ser 1430 1435 1440Ser Lys Ser His Gln Ser Thr Thr Thr Arg Lys Ala Ile Ile Arg 1445 1450 1455His Ser Thr Ile Pro Pro Phe Leu Ser Ser Ser Ala Thr Leu Met 1460 1465 1470Pro Val Pro Ile Ser Pro Pro Phe Thr Gln Arg Ala Val Thr Asp 1475 1480 1485Asn Val Ala Thr Pro Ile Ser Gly Leu Met Thr Asn Thr Val Val 1490 1495 1500Lys Leu His Glu Ser Ser Arg His Asn Ala Lys Pro Gln Gln Leu 1505 1510 1515Val Ala Glu Val Ala Thr Ser Pro Lys Val His Pro Asn Ala Lys 1520 1525 1530Phe Thr Ile Gly Thr Thr His Phe Ile Tyr Ser Asn Leu Leu His 1535 1540 1545Ser Thr Pro Met Pro Ala Leu Thr Thr Val Lys Ser Gln Asn Ser 1550 1555 1560Lys Leu Thr Pro Ser Pro Trp Ala Glu Asn Gln Phe Trp His Lys 1565 1570 1575Pro Tyr Ser Glu Ile Ala Glu Lys Gly Lys Lys Pro Glu Val Ser 1580 1585 1590Met Leu Ala Thr Thr Gly Leu Ser Glu Ala Thr Thr Leu Val Ser 1595 1600 1605Asp Trp Asp Gly Gln Lys Asn Thr Lys Lys Ser Asp Phe Asp Lys 1610 1615 1620Lys Pro Val Gln Glu Ala Thr Thr Ser Lys Leu Leu Pro Phe Asp 1625 1630 1635Ser Leu Ser Arg Tyr Ile Phe Glu Lys Pro Arg Ile Val Gly Gly 1640 1645 1650Lys Ala Ala Ser Phe Thr Ile Pro Ala Asn Ser Asp Ala Phe Leu 1655 1660 1665Pro Cys Glu Ala Val Gly Asn Pro Leu Pro Thr Ile His Trp Thr 1670 1675 1680Arg Val Pro Ser Gly Leu Asp Leu Ser Lys Arg Lys Gln Asn Ser 1685 1690 1695Arg Val Gln Val Leu Pro Asn Gly Thr Leu Ser Ile Gln Arg Val 1700 1705 1710Glu Ile Gln Asp Arg Gly Gln Tyr Leu Cys Ser Ala Ser Asn Leu 1715 1720 1725Phe Gly Thr Asp His Leu His Val Thr Leu Ser Val Val Ser Tyr 1730 1735 1740Pro Pro Arg Ile Leu Glu Arg Arg Thr Lys Glu Ile Thr Val His 1745 1750 1755Ser Gly Ser Thr Val Glu Leu Lys Cys Arg Ala Glu Gly Arg Pro 1760 1765 1770Ser Pro Thr Val Thr Trp Ile Leu Ala Asn Gln Thr Val Val Ser 1775 1780 1785Glu Ser Ser Gln Gly Ser Arg Gln Ala Val Val Thr Val Asp Gly 1790 1795 1800Thr Leu Val Leu His Asn Leu Ser Ile Tyr Asp Arg Gly Phe Tyr 1805 1810 1815Lys Cys Val Ala Ser Asn Pro Gly Gly Gln Asp Ser Leu Leu Val 1820 1825 1830Lys Ile Gln Val Ile Ala Ala Pro Pro Val Ile Leu Glu Gln Arg 1835 1840 1845Arg Gln Val Ile Val Gly Thr Trp Gly Glu Ser Leu Lys Leu Pro 1850 1855 1860Cys Thr Ala Lys Gly Thr Pro Gln Pro Ser Val Tyr Trp Val Leu 1865 1870 1875Ser Asp Gly Thr Glu Val Lys Pro Leu Gln Phe Thr Asn Ser Lys 1880 1885 1890Leu Phe Leu Phe Ser Asn Gly Thr Leu Tyr Ile Arg Asn Leu Ala 1895 1900 1905Ser Ser Asp Arg Gly Thr Tyr Glu Cys Ile Ala Thr Ser Ser Thr 1910 1915 1920Gly Ser Glu Arg Arg Val Val Met Leu Thr Met Glu Glu Arg Val 1925 1930 1935Thr Ser Pro Arg Ile Glu Ala Ala Ser Gln Lys Arg Thr Glu Val 1940 1945 1950Asn Phe Gly Asp Lys Leu Leu Leu Asn Cys Ser Ala Thr Gly Glu 1955 1960 1965Pro Lys Pro Gln Ile Met Trp Arg Leu Pro Ser Lys Ala Val Val 1970 1975 1980Asp Gln Gln His Arg Val Gly Ser Trp Ile His Val Tyr Pro Asn 1985 1990 1995Gly Ser Leu Phe Ile Gly Ser Val Thr Glu Lys Asp Ser Gly Val 2000 2005 2010Tyr Leu Cys Val Ala Arg Asn Lys Met Gly Asp Asp Leu Ile Leu 2015 2020 2025Met His Val Ser Leu Arg Leu Lys Pro Ala Lys Ile Asp His Lys 2030 2035 2040Gln Tyr Phe Arg Lys Gln Val Leu His Gly Lys Asp Phe Gln Val 2045 2050 2055Asp Cys Lys Ala Ser Gly Ser Pro Val Pro Glu Ile Ser Trp Ser 2060 2065 2070Leu Pro Asp Gly Thr Met Ile Asn Asn Ala Met Gln Ala Asp Asp 2075 2080 2085Ser Gly His Arg Thr Arg Arg Tyr Thr Leu Phe Asn Asn Gly Thr 2090 2095 2100Leu Tyr Phe Asn Lys Val Gly Val Ala Glu Glu Gly Asp Tyr Thr 2105 2110 2115Cys Tyr Ala Gln Asn Thr Leu Gly Lys Asp Glu Met Lys Val His 2120 2125 2130Leu Thr Val Ile Thr Ala Ala Pro Arg Ile Arg Gln Ser Asn Lys 2135 2140 2145Thr Asn Lys Arg Ile Lys Ala Gly Asp Thr Ala Val Leu Asp Cys 2150 2155 2160Glu Val Thr Gly Asp Pro Lys Pro Lys Ile Phe Trp Leu Leu Pro 2165 2170 2175Ser Asn Asp Met Ile Ser Phe Ser Ile Asp Arg Tyr Thr Phe His 2180 2185 2190Ala Asn Gly Ser Leu Thr Ile Asn Lys Val Lys Leu Leu Asp Ser 2195 2200 2205Gly Glu Tyr Val Cys Val Ala Arg Asn Pro Ser Gly Asp Asp Thr 2210 2215 2220Lys Met Tyr Lys Leu Asp Val Val Ser Lys Pro Pro Leu Ile Asn 2225 2230 2235Gly Leu Tyr Thr Asn Arg Thr Val Ile Lys Ala Thr Ala Val Arg 2240 2245 2250His Ser Lys Lys His Phe Asp Cys Arg Ala Glu Gly Thr Pro Ser 2255 2260 2265Pro Glu Val Met Trp Ile Met Pro Asp Asn Ile Phe Leu Thr Ala 2270 2275 2280Pro Tyr Tyr Gly Ser Arg Ile Thr Val His Lys Asn Gly Thr Leu 2285 2290 2295Glu Ile Arg Asn Val Arg Leu Ser Asp Ser Ala Asp Phe Ile Cys 2300 2305 2310Val Ala Arg Asn Glu Gly Gly Glu Ser Val Leu Val Val Gln Leu 2315 2320 2325Glu Val Leu Glu Met Leu Arg Arg Pro Thr Phe Arg Asn Pro Phe 2330 2335 2340Asn Glu Lys Ile Val Ala Gln Leu Gly Lys Ser Thr Ala Leu Asn 2345 2350 2355Cys Ser Val Asp Gly Asn Pro Pro Pro Glu Ile Ile Trp Ile Leu 2360 2365 2370Pro Asn Gly Thr Arg Phe Ser Asn Gly Pro Gln Ser Tyr Gln Tyr 2375 2380 2385Leu Ile Ala Ser Asn Gly Ser Phe Ile Ile Ser Lys Thr Thr Arg 2390 2395 2400Glu Asp Ala Gly Lys Tyr Arg Cys Ala Ala Arg Asn Lys Val Gly 2405 2410 2415Tyr Ile Glu Lys Leu Val Ile Leu Glu Ile Gly Gln Lys Pro Val 2420 2425 2430Ile Leu Thr Tyr Ala Pro Gly Thr Val Lys Gly Ile Ser Gly Glu 2435 2440 2445Ser Leu Ser Leu His Cys Val Ser Asp Gly Ile Pro Lys Pro Asn 2450 2455 2460Ile Lys Trp Thr Met Pro Ser Gly Tyr Val Val Asp Arg Pro Gln 2465 2470 2475Ile Asn Gly Lys Tyr Ile Leu His Asp Asn Gly Thr Leu Val Ile 2480 2485 2490Lys Glu Ala Thr Ala Tyr Asp Arg Gly Asn Tyr Ile Cys Lys Ala 2495 2500 2505Gln Asn Ser Val Gly His Thr Leu Ile Thr Val Pro Val Met Ile 2510 2515 2520Val Ala Tyr Pro Pro Arg Ile Thr Asn Arg Pro Pro Arg Ser Ile 2525 2530 2535Val Thr Arg Thr Gly Ala Ala Phe Gln Leu His Cys Val Ala Leu 2540 2545 2550Gly Val Pro Lys Pro Glu Ile Thr Trp Glu Met Pro Asp His Ser 2555 2560 2565Leu Leu Ser Thr Ala Ser Lys Glu Arg Thr His Gly Ser Glu Gln 2570 2575 2580Leu His Leu Gln Gly Thr Leu Val Ile Gln Asn Pro Gln Thr Ser 2585 2590 2595Asp Ser Gly Ile Tyr Lys Cys Thr Ala Lys Asn Pro Leu Gly Ser 2600 2605 2610Asp Tyr Ala Ala Thr Tyr Ile Gln Val Ile 2615 2620338883DNARattus rattusmisc_feature(8825)..(8825)n is a, c, g, or t 33cgagagacga cagaaggtta cggctgcgag aagacgacag aagggtccag aaaaaggaaa 60gtgctggagg ggagtgggga caaaagcagc gaccaagtga atgtcacttc agtgactgag 120gccaggcaaa acgcgcggga aggattttgt gtagcttggg accctttcat agacactgat 180gacacgttta cgcaaaatag aaatttgagg agaaacgcct gggccttcgg aaaggagtga 240ttgattagta cttgcaagtt taggtgactt taaggagaac taactaatgt atactattga 300gggaggagga agagcattac agagtttcca gcagcagcag gaaagctttg gttaatttgg 360aaatggatga tagcattaaa ataacagaag cgcctccagg tctctgaagc ttcagtcccc 420cagctgaaag ccagaaaaga ctaagcccac taagcctttt gatccctttg gaagcaaaga 480actttccttc cctggggtga agactctcct cagaagattt cctgtctctg cctatgttac 540aagaggaatc aaaaccaaga cagaagagct caggatgcag gtgagaggca gggaagtcag 600cggcttgttg atctccctca ctgctgtctg cctggtggtc acccctggga gcagggcctg 660tcctcgccgc tgtgcctgct atgtgcccac agaggtgcac tgtacatttc ggtacctgac 720ctccatccca gatggcatcc cggccaatgt ggaacgaata aatttaggat ataacagcct 780tactagattg acagaaaacg actttgatgg cctgagcaaa ctggagttac tcatgctgca 840cagtaatggc attcacagag tcagtgacaa gaccttctcg ggcttgcagt ccttgcaggt 900cttaaaaatg agctataaca aagtccaaat cattcggaag gatactttct acggactcgg 960gagcttggtc cggttgcacc tggatcacaa caacattgaa ttcatcaacc ctgaggcctt 1020ttatggactt acctcgctcc gcttggtaca tttagaagga aaccggctca caaagctcca 1080tccagacaca tttgtctcat taagctatct ccagatattt aaaacctctt tcattaagta 1140cctgttcttg tctgataact tcctgacctc cctcccaaaa gaaatggtct cctacatgcc 1200aaacctagaa agcctgtatt tgcatggaaa cccatggacc tgtgactgcc atttaaagtg 1260gttgtctgag tggatgcagg gaaacccaga tataataaaa tgcaagaaag acagaagctc 1320ttccagtcct cagcaatgtc ccctttgcat gaaccccagg atctctaaag gcagaccctt 1380tgctatggta ccatctggag ctttcctatg tacaaagcca accattgatc catcactgaa 1440gtcaaagagc ctggttactc aggaggacaa tggatctgcc tccacctcac ctcaagattt 1500catagaaccc tttggctcct tgtctttgaa catgacagac ctgtctggaa ataaggccga 1560catggtctgt agtatccaaa agccatcaag gacatcacca actgcattca ctgaagaaaa 1620tgactacatc atgctaaatg cgtcattttc cacaaatctt gtgtgcagtg tagattataa 1680tcacatccag ccagtgtggc aacttctggc tttatacagt gactctcctc tgatactaga 1740aaggaagccc cagcttaccg agactccttc actgtcttct agatataaac aggtggctct 1800taggcctgaa gacattttta ccagcataga ggctgatgtc agagcagacc ctttttggtt 1860ccaacaagaa aaaattgtct tgcagctgaa cagaactgcc accacactta gcacattaca 1920gatccagttt tccactgatg ctcaaatcgc tttaccaagg gcggagatga gagcggagag 1980actcaaatgg accatgatcc tgatgatgaa caatcccaaa ctggaacgca ctgtcctggt 2040tggcggcact attgccctga gctgtccagg caaaggcgac ccttcacctc acttggaatg 2100gcttctagct gatgggagta aagtgagagc cccttacgtt agcgaggatg ggcgaatcct 2160aatagacaaa aatgggaagt tggaactgca gatggctgac agctttgatg caggtcttta 2220ccactgcata agcaccaatg atgcagatgc ggatgttctc acatacagga taactgtggt 2280agagccctat ggagaaagca cacatgacag tggagtccag cacacagtgg ttacgggtga 2340gacgctcgac cttccatgcc tttccacggg tgttccagat gcttctatta gctggattct 2400tccagggaac actgtgttct ctcagccatc aagagacagg caaattctta acaatgggac 2460cttaagaata ttacaggtta cgccaaaaga tcaaggtcat taccaatgtg tggctgccaa 2520cccatcaggg gccgactttt ccagttttaa agtttcagtt caaaagaaag gccaaaggat 2580ggttgagcat gacagggagg caggtggatc tggacttgga gaacccaact ccagtgtttc 2640ccttaagcag ccagcatctt tgaaactctc tgcatcagct ttgacagggt cagaggctgg 2700aaaacaagtc tccggtgtac ataggaagaa caaacataga gacttaatac atcggcggcg 2760tggggattcc acgctccggc gattcaggga gcataggagg cagctccctc tctctgctcg 2820gagaattgac ccgcaacgct gggcagcact tctagaaaaa gccaaaaaga attctgtgcc 2880aaaaaagcaa gaaaatacca cagtaaagcc agtgccactg gctgttcccc tcgtggaact 2940cactgacgag gaaaaggatg cctctggcat gattcctcca gatgaagaat tcatggttct 3000gaaaactaag gcttctggtg tcccaggaag gtcaccaact gctgactctg gaccagtaaa 3060tcatggtttt atgacgagta tagcttctgg cacagaagtc tcaactgtga atccacaaac 3120actacaatct gagcaccttc ctgatttcaa attatttagt gtaacaaacg gtacagctgt 3180gacaaagagt atgaacccat ccatagcaag caaaatagaa gatacaacca accaaaaccc 3240aatcattatc tttccatcag tagctgaaat tcgagattct gctcaggcag gaagagcatc 3300ttcccaaagt gcacaccctg taacaggggg aaacatggct acctatggcc ataccaacac 3360atatagtagc tttaccagca aagccagtac agtcttgcag ccaataaatc caacagaaag 3420ttatggacct cagataccta ttacaggagt cagcagacct agcagtagtg acatctcttc 3480tcacactact gcagacccta gcttctccag tcacccttca ggttcacaca ccactgcctc 3540gtctttattt cacattccta gaaacaacaa tacaggtaac ttccccttgt ccaggcactt 3600gggaagagag aggacaattt ggagcagagg gagagttaaa aacccacata gaaccccagt 3660tctccgacgg catagacaca ggactgtgag gccagcaatc aagggacctg ctaacaaaaa 3720tgtgagccaa gttccagcca cagagtaccc tgggatgtgc cacacatgtc cttccgcaga 3780ggggctcaca gtggctactg cagcactgtc agttccaagt tcatcccaca gtgccctccc 3840caaaactaat aatgttgggg tcatagcaga agagtctacc actgtggtca agaaaccact 3900gttactattt aaggacaaac aaaatgtaga tattgagata ataacaacca ctacaaaata 3960ttccggaggg gaaagtaacc acgtgattcc tacggaagca agcatgactt ctgctccaac 4020atctgtatcc ctggggaaat ctcctgtaga caatagtggt cacctgagca tgcctgggac 4080catccaaact gggaaagatt cagtggaaac aacaccactt cccagccccc tcagcacacc 4140ctcaatacca acaagcacaa aattctcaaa gaggaaaact cccttgcacc agatctttgt 4200aaataaccag aagaaggagg ggatgttaaa gaatccatat caattcggtt tacaaaagaa 4260cccagccgca aagcttccca aaatagctcc tcttttaccc acaggtcaga gttccccctc 4320agattctaca actctcttga caagtccgcc accagctctg tctacaacaa tggctgccac 4380tcagaacaag ggcactgaag tagtatcagg tgccagaagt ctctcagcag ggaagaagca 4440gcccttcacc aactcctctc cagtgcttcc tagcaccata agcaagagat ctaatacatt 4500aaacttcttg tcaacggaaa cccccacagt gacaagtcct actgctactg catctgtcat 4560tatgtctgaa acccaacgaa caagatccaa agaagcaaaa gaccaaataa aggggcctcg 4620gaagaacaga aacaacgcaa acaccacccc caggcaggtt tctggctata gtgcatactc 4680agctctaaca acagctgata cccccttggc tttcagtcat tccccacgac aagatgatgg 4740tggaaatgta agtgcagttg cttatcactc aacaacctct cttctggcca taactgaact 4800gtttgagaag tacacccaga ctttgggaaa tacaacagct ttggaaacaa cgttgttgag 4860caaatcacag gagagtacca cagtgaaaag agcctcagac acaccaccac cactcctcag 4920cagtggggcg cccccagtgc ccactccttc cccacctcct tttactaagg gtgtggttac 4980agacagcaaa gtcacatcag ctttccagat gacgtcaaat agagtggtca ccatatatga 5040atcttcaagg cacaatacag atctgcagca accctcagca gaggctagcc ccaatcctga 5100gatcataact ggaaccactg actctccctc taatctgttt ccatccactt ctgtgccagc 5160actaagggta gataaaccac agaattctaa atggaagccc tctccctggc cagaacacaa 5220atatcagctc aagtcatact ccgaaaccat tgagaagggc aaaaggccag cagtaagcat 5280gtccccccac ctcagccttc cagaggccag cactcatgcc tcacactgga atacacagaa 5340gcatgcagaa aagagtgttt ttgataagaa acctggtcaa aacccaactt ccaaacatct 5400gccttacgtc tctctaccta agactctatt gaaaaagcca agaataattg gaggaaaggc 5460tgcaagcttt acagttccag ctaattcaga cgtttttctt ccttgtgagg ctgttggaga 5520cccactgccc atcatccact ggaccagagt ttcatcagga cttgaaatat cccaagggac 5580acagaaaagc cggttccacg tgcttcccaa tggcaccttg tccatccaga gggtcagtat 5640tcaggaccgt ggacagtacc tgtgctctgc atttaatcca ctgggcgtag accattttca 5700tgtctctttg tctgtggttt tttacccggc aaggattttg gacagacatg tcaaggagat 5760cacagttcac tttggaagta ctgtggaact aaagtgcaga gtggagggta tgccgaggcc 5820tacggtttcc tggatacttg caaaccaaac ggtggtctca gaaacggcca agggaagcag 5880aaaggtctgg gtaacacctg atggaacatt gatcatctat aatctgagtc tttatgatcg 5940tggtttttac aagtgtgtgg ccagcaaccc atctggccag gattcactgt tggttaagat 6000acaagtcatc acagctcccc ctgtcattat agagcaaaag aggcaagcca tcgttggggt 6060tttaggtgga agtttgaaac tgccctgcac tgcaaaagga actccccagc ctagtgttca 6120ctgggtcctt tatgatggga ctgaactaaa accattgcag ttgactcatt ccagattttt 6180cttgtatcca aatggaactc tgtatataag aagcatcgct ccttcagtga ggggcactta 6240tgagtgcatt gccaccagct cctcaggctc agagagaagg gtagtgattc ttactgtgga 6300agagggagag acaatcccca ggatagaaac tgcctctcag aaatggactg aggtgaattt 6360gggtgagaaa ttactactga actgctcagc tactggggat ccaaagccta gaataatctg 6420gaggctgcca tccaaggctg tcatcgacca gtggcacaga atgggcagcc gaatccacgt 6480ctacccaaat ggatccttgg tggttgggtc agtgacggaa aaagacgctg gtgactactt 6540atgtgtggca agaaacaaaa tgggagatga cctagtcctg atgcatgtcc gcctgagatt 6600gacacctgcc aaaattgaac agaagcagta ttttaagaag caagtgctcc atgggaaaga 6660tttccaagtt gactgcaagg cctctggctc ccctgtgcct gaggtatcct ggagtttgcc 6720tgatgggaca gtgctcaaca atgtagccca agctgatgac agtggctata ggaccaagag 6780gtacaccctt ttccacaatg gaaccttgta tttcaacaac gttgggatgg cagaggaagg 6840agattatatc tgctctgccc agaacacctt agggaaagat gagatgaaag tccacctaac 6900agttctaaca gccatcccac ggataaggca aagctacaag accaccatga ggctcagggc 6960tggagaaaca gctgtccttg actgcgaggt cactggggaa ccgaagccca atgtattttg 7020gttgctgcct tccaacaatg tcatttcatt ctccaatgac aggttcacat ttcatgccaa 7080tagaactttg tccatccata aagtgaaacc acttgactct ggggactatg tgtgcgtagc 7140tcagaatcct agtggggatg acactaagac atacaaactg gacattgtct ctaaacctcc 7200attaatcaat ggcctgtatg caaacaagac tgttattaaa gccacagcca ttcggcactc 7260caaaaaatac tttgactgca gagcagatgg gatcccatct tcccaggtca cgtggattat 7320gccaggcaat attttcctcc cagctccata ctttggaagc agagtcacgg tccatccaaa 7380tggaaccttg gagatgagga acatccggct ttctgactct gcggacttca cctgtgtggt 7440tcggagcgag

ggaggagaga gtgtgttggt agtgcagtta gaagtcctag aaatgctgag 7500aagaccaaca ttcagaaacc cattcaacga aaaagtcatc gcccaagctg gcaagcccgt 7560agcactgaac tgctctgtgg atgggaaccc cccacctgaa attacctgga tcttacctga 7620cggcacacag tttgctaaca gaccacacaa ttccccgtat ctgatggcag gcaatggctc 7680tctcatcctt tacaaagcaa ctcggaacaa gtcagggaag tatcgctgtg cagccaggaa 7740taaggttggc tacatcgaga aactcatcct gttagagatt gggcagaagc cagtcattct 7800gacatacgaa ccagggatgg tgaagagcgt cagtggggaa ccgttatcac tgcattgtgt 7860gtctgatggg atccccaagc caaatgtcaa gtggactaca ccgggtggcc atgtaatcga 7920caggcctcaa gtggatggaa aatacatact gcatgaaaat ggcacgctgg tcatcaaagc 7980aacaacagct cacgaccaag gaaattatat ctgtagggct caaaacagtg ttggccaggc 8040agttattagc gtgtcagtga tggttgtggc ctaccctccc cgaatcataa actacctacc 8100caggaacatg ctcaggagga caggggaagc catgcagctc cactgtgtgg ccttgggaat 8160ccccaagcca aaagtcacct gggagacgcc aagacactcc ctgctctcaa aagcaacagc 8220aagaaaaccc catagaagtg agatgcttca cccacaaggt acgctggtca ttcagaatct 8280ccaaacctcg gattccggag tctataagtg cagagctcag aacctacttg ggactgatta 8340cgcaacaact tacatccagg tactctgaca ggaaggggga gactaaaatt caacagaagt 8400ccacatccac agggtttatt ttttggaaga agtttaatca aaggcagcca taggcatgta 8460aatgagtctg aatacattta cagtattaaa tttacaatgg acatgcgatg agacttgtaa 8520atgaaagcat tgtgaactga aaccgagtct ctgtggatct caaagcaaac tcttaactta 8580aggcactttg attttgccaa caaataataa caaacattaa gagaaaaaaa tgatccacta 8640cgaaataaca aacggctaat gcacctgaat tctcagtaaa aagacctttc tctcgctaac 8700agttgccagc tgcctcgtgt ctgtttccta ccaatgtcac aaacatcgca cacagggtga 8760atggagtcaa cgggaaagat taagtttgcg gtctgtgtaa atctcaatgt acaaatattc 8820tgtcnctggt ttataaacat tttgataaaa ccgaaaaaaa aaaaaaaaaa aaaaaaaaaa 8880aaa 8883342597PRTRattus rattus 34Met Gln Val Arg Gly Arg Glu Val Ser Gly Leu Leu Ile Ser Leu Thr1 5 10 15Ala Val Cys Leu Val Val Thr Pro Gly Ser Arg Ala Cys Pro Arg Arg 20 25 30Cys Ala Cys Tyr Val Pro Thr Glu Val His Cys Thr Phe Arg Tyr Leu 35 40 45Thr Ser Ile Pro Asp Gly Ile Pro Ala Asn Val Glu Arg Ile Asn Leu 50 55 60Gly Tyr Asn Ser Leu Thr Arg Leu Thr Glu Asn Asp Phe Asp Gly Leu65 70 75 80Ser Lys Leu Glu Leu Leu Met Leu His Ser Asn Gly Ile His Arg Val 85 90 95Ser Asp Lys Thr Phe Ser Gly Leu Gln Ser Leu Gln Val Leu Lys Met 100 105 110Ser Tyr Asn Lys Val Gln Ile Ile Arg Lys Asp Thr Phe Tyr Gly Leu 115 120 125Gly Ser Leu Val Arg Leu His Leu Asp His Asn Asn Ile Glu Phe Ile 130 135 140Asn Pro Glu Ala Phe Tyr Gly Leu Thr Ser Leu Arg Leu Val His Leu145 150 155 160Glu Gly Asn Arg Leu Thr Lys Leu His Pro Asp Thr Phe Val Ser Leu 165 170 175Ser Tyr Leu Gln Ile Phe Lys Thr Ser Phe Ile Lys Tyr Leu Phe Leu 180 185 190Ser Asp Asn Phe Leu Thr Ser Leu Pro Lys Glu Met Val Ser Tyr Met 195 200 205Pro Asn Leu Glu Ser Leu Tyr Leu His Gly Asn Pro Trp Thr Cys Asp 210 215 220Cys His Leu Lys Trp Leu Ser Glu Trp Met Gln Gly Asn Pro Asp Ile225 230 235 240Ile Lys Cys Lys Lys Asp Arg Ser Ser Ser Ser Pro Gln Gln Cys Pro 245 250 255Leu Cys Met Asn Pro Arg Ile Ser Lys Gly Arg Pro Phe Ala Met Val 260 265 270Pro Ser Gly Ala Phe Leu Cys Thr Lys Pro Thr Ile Asp Pro Ser Leu 275 280 285Lys Ser Lys Ser Leu Val Thr Gln Glu Asp Asn Gly Ser Ala Ser Thr 290 295 300Ser Pro Gln Asp Phe Ile Glu Pro Phe Gly Ser Leu Ser Leu Asn Met305 310 315 320Thr Asp Leu Ser Gly Asn Lys Ala Asp Met Val Cys Ser Ile Gln Lys 325 330 335Pro Ser Arg Thr Ser Pro Thr Ala Phe Thr Glu Glu Asn Asp Tyr Ile 340 345 350Met Leu Asn Ala Ser Phe Ser Thr Asn Leu Val Cys Ser Val Asp Tyr 355 360 365Asn His Ile Gln Pro Val Trp Gln Leu Leu Ala Leu Tyr Ser Asp Ser 370 375 380Pro Leu Ile Leu Glu Arg Lys Pro Gln Leu Thr Glu Thr Pro Ser Leu385 390 395 400Ser Ser Arg Tyr Lys Gln Val Ala Leu Arg Pro Glu Asp Ile Phe Thr 405 410 415Ser Ile Glu Ala Asp Val Arg Ala Asp Pro Phe Trp Phe Gln Gln Glu 420 425 430Lys Ile Val Leu Gln Leu Asn Arg Thr Ala Thr Thr Leu Ser Thr Leu 435 440 445Gln Ile Gln Phe Ser Thr Asp Ala Gln Ile Ala Leu Pro Arg Ala Glu 450 455 460Met Arg Ala Glu Arg Leu Lys Trp Thr Met Ile Leu Met Met Asn Asn465 470 475 480Pro Lys Leu Glu Arg Thr Val Leu Val Gly Gly Thr Ile Ala Leu Ser 485 490 495Cys Pro Gly Lys Gly Asp Pro Ser Pro His Leu Glu Trp Leu Leu Ala 500 505 510Asp Gly Ser Lys Val Arg Ala Pro Tyr Val Ser Glu Asp Gly Arg Ile 515 520 525Leu Ile Asp Lys Asn Gly Lys Leu Glu Leu Gln Met Ala Asp Ser Phe 530 535 540Asp Ala Gly Leu Tyr His Cys Ile Ser Thr Asn Asp Ala Asp Ala Asp545 550 555 560Val Leu Thr Tyr Arg Ile Thr Val Val Glu Pro Tyr Gly Glu Ser Thr 565 570 575His Asp Ser Gly Val Gln His Thr Val Val Thr Gly Glu Thr Leu Asp 580 585 590Leu Pro Cys Leu Ser Thr Gly Val Pro Asp Ala Ser Ile Ser Trp Ile 595 600 605Leu Pro Gly Asn Thr Val Phe Ser Gln Pro Ser Arg Asp Arg Gln Ile 610 615 620Leu Asn Asn Gly Thr Leu Arg Ile Leu Gln Val Thr Pro Lys Asp Gln625 630 635 640Gly His Tyr Gln Cys Val Ala Ala Asn Pro Ser Gly Ala Asp Phe Ser 645 650 655Ser Phe Lys Val Ser Val Gln Lys Lys Gly Gln Arg Met Val Glu His 660 665 670Asp Arg Glu Ala Gly Gly Ser Gly Leu Gly Glu Pro Asn Ser Ser Val 675 680 685Ser Leu Lys Gln Pro Ala Ser Leu Lys Leu Ser Ala Ser Ala Leu Thr 690 695 700Gly Ser Glu Ala Gly Lys Gln Val Ser Gly Val His Arg Lys Asn Lys705 710 715 720His Arg Asp Leu Ile His Arg Arg Arg Gly Asp Ser Thr Leu Arg Arg 725 730 735Phe Arg Glu His Arg Arg Gln Leu Pro Leu Ser Ala Arg Arg Ile Asp 740 745 750Pro Gln Arg Trp Ala Ala Leu Leu Glu Lys Ala Lys Lys Asn Ser Val 755 760 765Pro Lys Lys Gln Glu Asn Thr Thr Val Lys Pro Val Pro Leu Ala Val 770 775 780Pro Leu Val Glu Leu Thr Asp Glu Glu Lys Asp Ala Ser Gly Met Ile785 790 795 800Pro Pro Asp Glu Glu Phe Met Val Leu Lys Thr Lys Ala Ser Gly Val 805 810 815Pro Gly Arg Ser Pro Thr Ala Asp Ser Gly Pro Val Asn His Gly Phe 820 825 830Met Thr Ser Ile Ala Ser Gly Thr Glu Val Ser Thr Val Asn Pro Gln 835 840 845Thr Leu Gln Ser Glu His Leu Pro Asp Phe Lys Leu Phe Ser Val Thr 850 855 860Asn Gly Thr Ala Val Thr Lys Ser Met Asn Pro Ser Ile Ala Ser Lys865 870 875 880Ile Glu Asp Thr Thr Asn Gln Asn Pro Ile Ile Ile Phe Pro Ser Val 885 890 895Ala Glu Ile Arg Asp Ser Ala Gln Ala Gly Arg Ala Ser Ser Gln Ser 900 905 910Ala His Pro Val Thr Gly Gly Asn Met Ala Thr Tyr Gly His Thr Asn 915 920 925Thr Tyr Ser Ser Phe Thr Ser Lys Ala Ser Thr Val Leu Gln Pro Ile 930 935 940Asn Pro Thr Glu Ser Tyr Gly Pro Gln Ile Pro Ile Thr Gly Val Ser945 950 955 960Arg Pro Ser Ser Ser Asp Ile Ser Ser His Thr Thr Ala Asp Pro Ser 965 970 975Phe Ser Ser His Pro Ser Gly Ser His Thr Thr Ala Ser Ser Leu Phe 980 985 990His Ile Pro Arg Asn Asn Asn Thr Gly Asn Phe Pro Leu Ser Arg His 995 1000 1005Leu Gly Arg Glu Arg Thr Ile Trp Ser Arg Gly Arg Val Lys Asn 1010 1015 1020Pro His Arg Thr Pro Val Leu Arg Arg His Arg His Arg Thr Val 1025 1030 1035Arg Pro Ala Ile Lys Gly Pro Ala Asn Lys Asn Val Ser Gln Val 1040 1045 1050Pro Ala Thr Glu Tyr Pro Gly Met Cys His Thr Cys Pro Ser Ala 1055 1060 1065Glu Gly Leu Thr Val Ala Thr Ala Ala Leu Ser Val Pro Ser Ser 1070 1075 1080Ser His Ser Ala Leu Pro Lys Thr Asn Asn Val Gly Val Ile Ala 1085 1090 1095Glu Glu Ser Thr Thr Val Val Lys Lys Pro Leu Leu Leu Phe Lys 1100 1105 1110Asp Lys Gln Asn Val Asp Ile Glu Ile Ile Thr Thr Thr Thr Lys 1115 1120 1125Tyr Ser Gly Gly Glu Ser Asn His Val Ile Pro Thr Glu Ala Ser 1130 1135 1140Met Thr Ser Ala Pro Thr Ser Val Ser Leu Gly Lys Ser Pro Val 1145 1150 1155Asp Asn Ser Gly His Leu Ser Met Pro Gly Thr Ile Gln Thr Gly 1160 1165 1170Lys Asp Ser Val Glu Thr Thr Pro Leu Pro Ser Pro Leu Ser Thr 1175 1180 1185Pro Ser Ile Pro Thr Ser Thr Lys Phe Ser Lys Arg Lys Thr Pro 1190 1195 1200Leu His Gln Ile Phe Val Asn Asn Gln Lys Lys Glu Gly Met Leu 1205 1210 1215Lys Asn Pro Tyr Gln Phe Gly Leu Gln Lys Asn Pro Ala Ala Lys 1220 1225 1230Leu Pro Lys Ile Ala Pro Leu Leu Pro Thr Gly Gln Ser Ser Pro 1235 1240 1245Ser Asp Ser Thr Thr Leu Leu Thr Ser Pro Pro Pro Ala Leu Ser 1250 1255 1260Thr Thr Met Ala Ala Thr Gln Asn Lys Gly Thr Glu Val Val Ser 1265 1270 1275Gly Ala Arg Ser Leu Ser Ala Gly Lys Lys Gln Pro Phe Thr Asn 1280 1285 1290Ser Ser Pro Val Leu Pro Ser Thr Ile Ser Lys Arg Ser Asn Thr 1295 1300 1305Leu Asn Phe Leu Ser Thr Glu Thr Pro Thr Val Thr Ser Pro Thr 1310 1315 1320Ala Thr Ala Ser Val Ile Met Ser Glu Thr Gln Arg Thr Arg Ser 1325 1330 1335Lys Glu Ala Lys Asp Gln Ile Lys Gly Pro Arg Lys Asn Arg Asn 1340 1345 1350Asn Ala Asn Thr Thr Pro Arg Gln Val Ser Gly Tyr Ser Ala Tyr 1355 1360 1365Ser Ala Leu Thr Thr Ala Asp Thr Pro Leu Ala Phe Ser His Ser 1370 1375 1380Pro Arg Gln Asp Asp Gly Gly Asn Val Ser Ala Val Ala Tyr His 1385 1390 1395Ser Thr Thr Ser Leu Leu Ala Ile Thr Glu Leu Phe Glu Lys Tyr 1400 1405 1410Thr Gln Thr Leu Gly Asn Thr Thr Ala Leu Glu Thr Thr Leu Leu 1415 1420 1425Ser Lys Ser Gln Glu Ser Thr Thr Val Lys Arg Ala Ser Asp Thr 1430 1435 1440Pro Pro Pro Leu Leu Ser Ser Gly Ala Pro Pro Val Pro Thr Pro 1445 1450 1455Ser Pro Pro Pro Phe Thr Lys Gly Val Val Thr Asp Ser Lys Val 1460 1465 1470Thr Ser Ala Phe Gln Met Thr Ser Asn Arg Val Val Thr Ile Tyr 1475 1480 1485Glu Ser Ser Arg His Asn Thr Asp Leu Gln Gln Pro Ser Ala Glu 1490 1495 1500Ala Ser Pro Asn Pro Glu Ile Ile Thr Gly Thr Thr Asp Ser Pro 1505 1510 1515Ser Asn Leu Phe Pro Ser Thr Ser Val Pro Ala Leu Arg Val Asp 1520 1525 1530Lys Pro Gln Asn Ser Lys Trp Lys Pro Ser Pro Trp Pro Glu His 1535 1540 1545Lys Tyr Gln Leu Lys Ser Tyr Ser Glu Thr Ile Glu Lys Gly Lys 1550 1555 1560Arg Pro Ala Val Ser Met Ser Pro His Leu Ser Leu Pro Glu Ala 1565 1570 1575Ser Thr His Ala Ser His Trp Asn Thr Gln Lys His Ala Glu Lys 1580 1585 1590Ser Val Phe Asp Lys Lys Pro Gly Gln Asn Pro Thr Ser Lys His 1595 1600 1605Leu Pro Tyr Val Ser Leu Pro Lys Thr Leu Leu Lys Lys Pro Arg 1610 1615 1620Ile Ile Gly Gly Lys Ala Ala Ser Phe Thr Val Pro Ala Asn Ser 1625 1630 1635Asp Val Phe Leu Pro Cys Glu Ala Val Gly Asp Pro Leu Pro Ile 1640 1645 1650Ile His Trp Thr Arg Val Ser Ser Gly Leu Glu Ile Ser Gln Gly 1655 1660 1665Thr Gln Lys Ser Arg Phe His Val Leu Pro Asn Gly Thr Leu Ser 1670 1675 1680Ile Gln Arg Val Ser Ile Gln Asp Arg Gly Gln Tyr Leu Cys Ser 1685 1690 1695Ala Phe Asn Pro Leu Gly Val Asp His Phe His Val Ser Leu Ser 1700 1705 1710Val Val Phe Tyr Pro Ala Arg Ile Leu Asp Arg His Val Lys Glu 1715 1720 1725Ile Thr Val His Phe Gly Ser Thr Val Glu Leu Lys Cys Arg Val 1730 1735 1740Glu Gly Met Pro Arg Pro Thr Val Ser Trp Ile Leu Ala Asn Gln 1745 1750 1755Thr Val Val Ser Glu Thr Ala Lys Gly Ser Arg Lys Val Trp Val 1760 1765 1770Thr Pro Asp Gly Thr Leu Ile Ile Tyr Asn Leu Ser Leu Tyr Asp 1775 1780 1785Arg Gly Phe Tyr Lys Cys Val Ala Ser Asn Pro Ser Gly Gln Asp 1790 1795 1800Ser Leu Leu Val Lys Ile Gln Val Ile Thr Ala Pro Pro Val Ile 1805 1810 1815Ile Glu Gln Lys Arg Gln Ala Ile Val Gly Val Leu Gly Gly Ser 1820 1825 1830Leu Lys Leu Pro Cys Thr Ala Lys Gly Thr Pro Gln Pro Ser Val 1835 1840 1845His Trp Val Leu Tyr Asp Gly Thr Glu Leu Lys Pro Leu Gln Leu 1850 1855 1860Thr His Ser Arg Phe Phe Leu Tyr Pro Asn Gly Thr Leu Tyr Ile 1865 1870 1875Arg Ser Ile Ala Pro Ser Val Arg Gly Thr Tyr Glu Cys Ile Ala 1880 1885 1890Thr Ser Ser Ser Gly Ser Glu Arg Arg Val Val Ile Leu Thr Val 1895 1900 1905Glu Glu Gly Glu Thr Ile Pro Arg Ile Glu Thr Ala Ser Gln Lys 1910 1915 1920Trp Thr Glu Val Asn Leu Gly Glu Lys Leu Leu Leu Asn Cys Ser 1925 1930 1935Ala Thr Gly Asp Pro Lys Pro Arg Ile Ile Trp Arg Leu Pro Ser 1940 1945 1950Lys Ala Val Ile Asp Gln Trp His Arg Met Gly Ser Arg Ile His 1955 1960 1965Val Tyr Pro Asn Gly Ser Leu Val Val Gly Ser Val Thr Glu Lys 1970 1975 1980Asp Ala Gly Asp Tyr Leu Cys Val Ala Arg Asn Lys Met Gly Asp 1985 1990 1995Asp Leu Val Leu Met His Val Arg Leu Arg Leu Thr Pro Ala Lys 2000 2005 2010Ile Glu Gln Lys Gln Tyr Phe Lys Lys Gln Val Leu His Gly Lys 2015 2020 2025Asp Phe Gln Val Asp Cys Lys Ala Ser Gly Ser Pro Val Pro Glu 2030 2035 2040Val Ser Trp Ser Leu Pro Asp Gly Thr Val Leu Asn Asn Val Ala 2045 2050 2055Gln Ala Asp Asp Ser Gly Tyr Arg Thr Lys Arg Tyr Thr Leu Phe 2060 2065 2070His Asn Gly Thr Leu Tyr Phe Asn Asn Val Gly Met Ala Glu Glu 2075 2080 2085Gly Asp Tyr Ile Cys Ser Ala Gln Asn Thr Leu Gly Lys Asp Glu 2090 2095 2100Met Lys Val His Leu Thr Val Leu Thr Ala Ile Pro Arg Ile Arg 2105 2110 2115Gln Ser Tyr Lys Thr Thr Met Arg Leu Arg Ala Gly Glu Thr Ala 2120 2125 2130Val Leu Asp Cys Glu Val Thr Gly Glu Pro Lys Pro Asn Val Phe 2135 2140 2145Trp Leu Leu Pro Ser Asn Asn Val Ile Ser Phe Ser Asn Asp Arg 2150 2155 2160Phe Thr Phe His Ala Asn Arg Thr Leu Ser Ile His Lys Val Lys 2165 2170 2175Pro Leu Asp Ser Gly Asp Tyr Val Cys Val Ala Gln Asn Pro Ser 2180 2185 2190Gly Asp Asp Thr Lys Thr Tyr Lys Leu Asp Ile Val Ser Lys Pro 2195 2200

2205Pro Leu Ile Asn Gly Leu Tyr Ala Asn Lys Thr Val Ile Lys Ala 2210 2215 2220Thr Ala Ile Arg His Ser Lys Lys Tyr Phe Asp Cys Arg Ala Asp 2225 2230 2235Gly Ile Pro Ser Ser Gln Val Thr Trp Ile Met Pro Gly Asn Ile 2240 2245 2250Phe Leu Pro Ala Pro Tyr Phe Gly Ser Arg Val Thr Val His Pro 2255 2260 2265Asn Gly Thr Leu Glu Met Arg Asn Ile Arg Leu Ser Asp Ser Ala 2270 2275 2280Asp Phe Thr Cys Val Val Arg Ser Glu Gly Gly Glu Ser Val Leu 2285 2290 2295Val Val Gln Leu Glu Val Leu Glu Met Leu Arg Arg Pro Thr Phe 2300 2305 2310Arg Asn Pro Phe Asn Glu Lys Val Ile Ala Gln Ala Gly Lys Pro 2315 2320 2325Val Ala Leu Asn Cys Ser Val Asp Gly Asn Pro Pro Pro Glu Ile 2330 2335 2340Thr Trp Ile Leu Pro Asp Gly Thr Gln Phe Ala Asn Arg Pro His 2345 2350 2355Asn Ser Pro Tyr Leu Met Ala Gly Asn Gly Ser Leu Ile Leu Tyr 2360 2365 2370Lys Ala Thr Arg Asn Lys Ser Gly Lys Tyr Arg Cys Ala Ala Arg 2375 2380 2385Asn Lys Val Gly Tyr Ile Glu Lys Leu Ile Leu Leu Glu Ile Gly 2390 2395 2400Gln Lys Pro Val Ile Leu Thr Tyr Glu Pro Gly Met Val Lys Ser 2405 2410 2415Val Ser Gly Glu Pro Leu Ser Leu His Cys Val Ser Asp Gly Ile 2420 2425 2430Pro Lys Pro Asn Val Lys Trp Thr Thr Pro Gly Gly His Val Ile 2435 2440 2445Asp Arg Pro Gln Val Asp Gly Lys Tyr Ile Leu His Glu Asn Gly 2450 2455 2460Thr Leu Val Ile Lys Ala Thr Thr Ala His Asp Gln Gly Asn Tyr 2465 2470 2475Ile Cys Arg Ala Gln Asn Ser Val Gly Gln Ala Val Ile Ser Val 2480 2485 2490Ser Val Met Val Val Ala Tyr Pro Pro Arg Ile Ile Asn Tyr Leu 2495 2500 2505Pro Arg Asn Met Leu Arg Arg Thr Gly Glu Ala Met Gln Leu His 2510 2515 2520Cys Val Ala Leu Gly Ile Pro Lys Pro Lys Val Thr Trp Glu Thr 2525 2530 2535Pro Arg His Ser Leu Leu Ser Lys Ala Thr Ala Arg Lys Pro His 2540 2545 2550Arg Ser Glu Met Leu His Pro Gln Gly Thr Leu Val Ile Gln Asn 2555 2560 2565Leu Gln Thr Ser Asp Ser Gly Val Tyr Lys Cys Arg Ala Gln Asn 2570 2575 2580Leu Leu Gly Thr Asp Tyr Ala Thr Thr Tyr Ile Gln Val Leu 2585 2590 25953521DNAArtificial Sequenceprimer 35gcactgaact gctctgtggat 213623DNAArtificial Sequenceprimer 36ccacagaagt aaggttcctt cac 23376PRThomo sapiens 37Lys Cys Lys Lys Asp Arg1 5

Patent applications by Elena Feinstein, Rehovot IL

Patent applications by Orit Segev, Rehovot IL

Patent applications by Quark Biotech, Inc.

Patent applications in class Binds antigen or epitope whose amino acid sequence is disclosed in whole or in part (e.g., binds specifically-identified amino acid sequence, etc.)

Patent applications in all subclasses Binds antigen or epitope whose amino acid sequence is disclosed in whole or in part (e.g., binds specifically-identified amino acid sequence, etc.)

User Contributions:

Comment about this patent or add new information about this topic:

Inventors list

Assignees list

Classification tree browser

Top 100 Inventors

Top 100 Assignees

Patent application title: GENES ASSOCIATED WITH MECHANICAL STRESS, EXPRESSION PRODUCTS THEREFROM, AND USES THEREOF

Abstract:

Claims:

Description: