(en)Novel human polynucleotide and polypeptide sequences are disclosed that can be used in therapeutic, diagnostic, and pharmacogenomic applications.

1.ApplicationNumber: US-18997102-A
1.PublishNumber: US-2003028907-A1
2.Date Publish: 20030206
3.Inventor: WALKE D. WADE
SCOVILLE JOHN
TURNER C. ALEXANDER

4.Inventor Harmonized: WALKE D WADE(US)
SCOVILLE JOHN(US)
TURNER C ALEXANDER(US)

5.Country: US
6.Claims:
(en)Novel human polynucleotide and polypeptide sequences are disclosed that can be used in therapeutic, diagnostic, and pharmacogenomic applications.

7.Description:
(en)[0001] The present application claims the benefit of U.S. Provisional Application Nos. 60/302,949 and 60/315,634, which were filed on Jul. 3, 2001 and Aug. 29, 2001, respectively, and are herein incorporated by reference in their entirety.



INTRODUCTION
[0002] The present invention relates to the discovery, identification, and characterization of novel human polynucleotides encoding proteins sharing sequence similarity with animal kielin proteins. The invention encompasses the described polynucleotides, host cell expression systems, the encoded proteins, fusion proteins, polypeptides and peptides, antibodies to the encoded proteins and peptides, and genetically engineered animals that either lack or overexpress the disclosed polynucleotides, antagonists and agonists of the proteins, and other compounds that modulate the expression or activity of the proteins encoded by the disclosed polynucleotides, which can be used for diagnosis, drug screening, clinical trial monitoring, the treatment of diseases and disorders, and cosmetic or nutriceutical applications.
BACKGROUND OF THE INVENTION
[0003] Kielins are secreted proteins that have been implicated in a number of biological processes and anomalies such as development and signal transduction. Therefore, kielins are good drug targets.
SUMMARY OF THE INVENTION
[0004] The present invention relates to the discovery, identification, and characterization of nucleotides that encode novel human proteins, and the corresponding amino acid sequences of these proteins. The novel human proteins (NHPs) described for the first time herein share structural similarity with animal kielin and chordin proteins, and other animal proteins including, but not limited to, human secreted proteins. The novel human nucleic acid sequence described herein encode alternative proteins/open reading frames (ORFs) of 1628, 1593, 1057, 1477, 1512, 1570, 1535, 1251, 1192, 1207, 759 and 1342 amino acids in length (SEQ ID NOS:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24, respectively).
[0005] The invention also encompasses agonists and antagonists of the described NHPs, including small molecules, large molecules, mutant NHPS, or portions thereof, that compete with native NHPs, peptides, and antibodies, as well as nucleotide sequences that can be used to inhibit the expression of the described NHPs (e.g., antisense and ribozyme molecules, and open reading frame or regulatory sequence replacement constructs) or to enhance the expression of the described NHPs (e.g., expression constructs that place the described polynucleotide under the control of a strong promoter system), and transgenic animals that express a NHP sequence, or “knock-outs” (which can be conditional) that do not express a functional NHP. Knock-out mice can be produced in several ways, one of which involves the use of mouse embryonic stem cell (“ES cell”) lines that contain gene trap mutations in a murine homolog of at least one of the described NHPs. When the unique NHP sequences described in SEQ ID NOS:1-25 are “knocked-out” they provide a method of identifying phenotypic expression of the particular gene, as well as a method of assigning function to previously unknown genes. In addition, animals in which the unique NHP sequences described in SEQ ID NOS:1-25 are “knocked-out” provide an unique source in which to elicit antibodies to homologous and orthologous proteins, which would have been previously viewed by the immune system as “self” and therefore would have failed to elicit significant antibody responses.
[0006] Additionally, the unique NHP sequences described in SEQ ID NOS:1-25 are useful for the identification of protein coding sequences, and mapping an unique gene to a particular chromosome. These sequences identify biologically verified exon splice junctions, as opposed to splice junctions that may have been bioinformatically predicted from genomic sequence alone. The sequences of the present invention are also useful as additional DNA markers for restriction fragment length polymorphism (RFLP) analysis, and in forensic biology, particularly given the presence of nucleotide polymorphisms within the described sequences, as described below.
[0007] Further, the present invention also relates to processes for identifying compounds that modulate, i.e., act as agonists or antagonists of, NHP expression and/or NHP activity that utilize purified preparations of the described NHPs and/or NHP products, or cells expressing the same. Such compounds can be used as therapeutic agents for the treatment of any of a wide variety of symptoms associated with biological disorders or imbalances.
DESCRIPTION OF THE SEQUENCE LISTING AND FIGURES
[0008] The Sequence Listing provides the sequences of NHP ORFs encoding the described NHP amino acid sequences. SEQ ID NO:25 describes a NHP ORF and flanking regions.



DETAILED DESCRIPTION OF THE INVENTION
[0009] The NHPs described for the first time herein are novel proteins that are apparently expressed in, inter alia, human cell lines, brain, bone marrow, adrenal gland, liver, lymph node, mammary gland, prostate, pancreas, pituitary, placenta, thymus, trachea, skeletal muscle, kidney, thyroid, testis, activated T-cells, spleen, fetal brain, lung, umbilical vein endothelium, and fetal kidney cells.
[0010] The present invention encompasses the nucleotides presented in the Sequence Listing, host cells expressing such nucleotides, the expression products of such nucleotides, and: (a) nucleotides that encode mammalian homologs of the described polynucleotides, including the specifically described NHPs, and related NHP products; (b) nucleotides that encode one or more portions of a NHP corresponding to a NHP functional domain(s), and the polypeptide products specified by such nucleotide sequences, including, but not limited to, the novel regions of any active domain(s); (c) isolated nucleotides that encode mutant versions, engineered or naturally occurring, of the described NHPs, in which all or a part of at least one domain is deleted or altered, and the polypeptide products specified by such nucleotide sequences, including, but not limited to, soluble proteins and peptides in which all or a portion of the signal sequence is deleted; (d) nucleotides that encode chimeric fusion proteins containing all or a portion of a coding region of a NHP, or one of its domains (e.g., a receptor or ligand binding domain, accessory protein/self-association domain, etc.), fused to another peptide or polypeptide; or (e) therapeutic or diagnostic derivatives of the described polynucleotides, such as oligonucleotides, antisense polynucleotides, ribozymes, dsRNA, or gene therapy constructs, comprising a sequence first disclosed in the Sequence Listing.
[0011] As discussed above, the present invention includes the human DNA sequences presented in the Sequence Listing (and vectors comprising the same), and additionally contemplates any nucleotide sequence encoding a contiguous NHP open reading frame (ORF) that hybridizes to a complement of a DNA sequence presented in the Sequence Listing under highly stringent conditions, e.g., hybridization to filter-bound DNA in 0.5M NaHPO 4 , 7% sodium dodecyl sulfate (SDS), 1 mM EDTA at 65° C., and washing in 0.1×SSC/0.1% SDS at 68° C. (Ausubel et al., eds., 1989, Current Protocols in Molecular Biology, Vol. I, Green Publishing Associates, Inc., and John Wiley & Sons, Inc., N.Y., at p. 2.10.3) and encodes a functionally equivalent expression product. Additionally contemplated are any nucleotide sequences that hybridize to the complement of a DNA sequence that encodes and expresses an amino acid sequence presented in the Sequence Listing under moderately stringent conditions, e.g., washing in 0.2×SSC/0.1% SDS at 42° C. (Ausubel et al., 1989, supra), yet still encode a functionally equivalent NHP product. Functional equivalents of a NHP include naturally occurring NHPs present in other species, and mutant NHPs, whether naturally occurring or engineered (by site directed mutagenesis, gene shuffling, directed evolution as described in, for example, U.S. Pat. No. 5,837,458 herein incorporated by reference). The invention also includes degenerate nucleic acid variants of the disclosed NHP polynucleotide sequences.
[0012] Additionally contemplated are polynucleotides encoding NHP ORFs, or their functional equivalents, encoded by polynucleotide sequences that are about 99, 95, 90, or about 85 percent similar or identical to corresponding regions of the nucleotide sequences of the Sequence Listing (as measured by BLAST sequence comparison analysis using, for example, the GCG sequence analysis package, as described herein, using standard default settings).
[0013] The invention also includes nucleic acid molecules, preferably DNA molecules, that hybridize to, and are therefore the complements of, the described NHP nucleotide sequences. Such hybridization conditions may be highly stringent or less highly stringent, as described herein. In instances where the nucleic acid molecules are deoxyoligonucleotides (“DNA oligos”), such molecules are generally about 16 to about 100 bases long, or about 20 to about 80 bases long, or about 34 to about 45 bases long, or any variation or combination of sizes represented therein that incorporate a contiguous region of sequence first disclosed in the Sequence Listing. Such oligonucleotides can be used in conjunction with the polymerase chain reaction (PCR) to screen libraries, isolate clones, and prepare cloning and sequencing templates, etc.
[0014] Alternatively, such NHP oligonucleotides can be used as hybridization probes for screening libraries, and assessing gene expression patterns (particularly using a microarray or high-throughput “chip” format). Additionally, a series of NHP oligonucleotide sequences, or the complements thereof, can be used to represent all or a portion of the described NHP sequences. An oligonucleotide or polynucleotide sequence first disclosed in at least a portion of one or more of the sequences of SEQ ID NOS:1-25 can be used as a hybridization probe in conjunction with a solid support matrix/substrate (resins, beads, membranes, plastics, polymers, metal or metallized substrates, crystalline or polycrystalline substrates, etc.). Of particular note are spatially addressable arrays (i.e., gene chips, microtiter plates, etc.) of oligonucleotides and polynucleotides, or corresponding oligopeptides and polypeptides, wherein at least one of the biopolymers present on the spatially addressable array comprises an oligonucleotide or polynucleotide sequence first disclosed in at least one of the sequences of SEQ ID NOS:1-25, or an amino acid sequence encoded thereby. Methods for attaching biopolymers to, or synthesizing biopolymers on, solid support matrices, and conducting binding studies thereon, are disclosed in, inter alia, U.S. Pat. Nos. 5,700,637, 5,556,752, 5,744,305, 4,631,211, 5,445,934, 5,252,743, 4,713,326, 5,424,186, and 4,689,405, the disclosures of which are herein incorporated by reference in their entirety.
[0015] Addressable arrays comprising sequences first disclosed in SEQ ID NOS:1-25 can be used to identify and characterize the temporal and tissue specific expression of a gene. These addressable arrays incorporate oligonucleotide sequences of sufficient length to confer the required specificity, yet be within the limitations of the production technology. The length of these probes is usually within a range of between about 8 to about 2000 nucleotides. Preferably the probes consist of 60 nucleotides, and more preferably 25 nucleotides, from the sequences first disclosed in SEQ ID NOS:1-25.
[0016] For example, a series of NHP oligonucleotide sequences, or the complements thereof, can be used in chip format to represent all or a portion of the described sequences. The oligonucleotides, typically between about 16 to about 40 (or any whole number within the stated range) nucleotides in length, can partially overlap each other, and/or the sequence may be represented using oligonucleotides that do not overlap. Accordingly, the described polynucleotide sequences shall typically comprise at least about two or three distinct oligonucleotide sequences of at least about 8 nucleotides in length that are each first disclosed in the described Sequence Listing. Such oligonucleotide sequences can begin at any nucleotide present within a sequence in the Sequence Listing, and proceed in either a sense (5′-to-3′) orientation vis-a-vis the described sequence or in an antisense orientation.
[0017] Microarray-based analysis allows the discovery of broad patterns of genetic activity, providing new understanding of gene functions, and generating novel and unexpected insight into transcriptional processes and biological mechanisms. The use of addressable arrays comprising sequences first disclosed in SEQ ID NOS:1-25 provides detailed information about transcriptional changes involved in a specific pathway, potentially leading to the identification of novel components, or gene functions that manifest themselves as novel phenotypes.
[0018] Probes consisting of sequences first disclosed in SEQ ID NOS:1-25 can also be used in the identification, selection, and validation of novel molecular targets for drug discovery. The use of these unique sequences permits the direct confirmation of drug targets, and recognition of drug dependent changes in gene expression that are modulated through pathways distinct from the intended target of the drug. These unique sequences therefore also have utility in defining and monitoring both drug-action and toxicity.
[0019] As an example of utility, the sequences first disclosed in SEQ ID NOS:1-25 can be utilized in microarrays, or other assay formats, to screen collections of genetic material from patients who have a particular medical condition. These investigations can also be carried out using the sequences first disclosed in SEQ ID NOS:1-25 in silico, and by comparing previously collected genetic databases and the disclosed sequences using computer software known to those in the art.
[0020] Thus the sequences first disclosed in SEQ ID NOS:1-25 can be used to identify mutations associated with a particular disease, and also in diagnostic or prognostic assays.
[0021] Although the presently described sequences have been specifically described using nucleotide sequence, it should be appreciated that each of the sequences can uniquely be described using any of a wide variety of additional structural attributes, or combinations thereof. For example, a given sequence can be described by the net composition of the nucleotides present within a given region of the sequence, in conjunction with the presence of one or more specific oligonucleotide sequence(s) first disclosed in SEQ ID NOS:1-25. Alternatively, a restriction map specifying the relative positions of restriction endonuclease digestion sites, or various palindromic or other specific oligonucleotide sequences, can be used to structurally describe a given sequence. Such restriction maps, which are typically generated by widely available computer programs (e.g., the University of Wisconsin GCG sequence analysis package, SEQUENCHER 3.0, Gene Codes Corp., Ann Arbor, Mich., etc.), can optionally be used in conjunction with one or more discrete nucleotide sequence(s) present in the sequence that can be described by the relative position of the sequence relative to one or more additional sequence(s) or one or more restriction sites present in the disclosed sequence.
[0022] For oligonucleotide probes, highly stringent conditions may refer, e.g., to washing in 6×SSC/0.05% sodium pyrophosphate at 37° C. (for 14-base oligos), 48° C. (for 17-base oligos), 55° C. (for 20-base oligos), and 60° C. (for 23-base oligos). These nucleic acid molecules may encode or act as NHP antisense molecules, useful, for example, in NHP gene regulation and/or as antisense primers in amplification reactions of NHP nucleic acid sequences. With respect to NHP gene regulation, such techniques can be used to regulate biological functions. Further, such sequences may be used as part of ribozyme and/or triple helix sequences that are also useful for NHP gene regulation.
[0023] Inhibitory antisense or double stranded oligonucleotides can additionally comprise at least one modified base moiety that is selected from the group including, but not limited to, 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xanthine, 4-acetylcytosine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3)w, and 2,6-diaminopurine.
[0024] The antisense oligonucleotide can also comprise at least one modified sugar moiety selected from the group including, but not limited to, arabinose, 2-fluoroarabinose, xylulose, and hexose.
[0025] In yet another embodiment, the antisense oligonucleotide will comprise at least one modified phosphate backbone selected from the group including, but not limited to, a phosphorothioate, a phosphorodithioate, a phosphoramidothioate, a phosphoramidate, a phosphordiamidate, a methylphosphonate, an alkyl phosphotriester, and a formacetal or analog thereof.
[0026] In yet another embodiment, the antisense oligonucleotide is an α-anomeric oligonucleotide. An α-anomeric oligonucleotide forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual β-units, the strands run parallel to each other (Gautier et al., 1987, Nucl. Acids Res. 15:6625-6641). The oligonucleotide is a 2′-O-methylribonucleotide (Inoue et al., 1987, Nucl. Acids Res. 15:6131-6148), or a chimeric RNA-DNA analogue (Inoue et al., 1987, FEBS Lett. 215:327-330). Alternatively, double stranded RNA can be used to disrupt the expression and function of a targeted NHP.
[0027] Oligonucleotides of the invention can be synthesized by standard methods known in the art, e.g., by use of an automated DNA synthesizer (such as are commercially available from Biosearch, Applied Biosystems, etc.). As examples, phosphorothioate oligonucleotides can be synthesized by the method of Stein et al. (1988, Nucl. Acids Res. 16:3209), and methylphosphonate oligonucleotides can be prepared by use of controlled pore glass polymer supports (Sarin et al., 1988, Proc. Natl. Acad. Sci. USA 85:7448-7451), etc.
[0028] Low stringency conditions are well-known to those of skill in the art, and will vary predictably depending on the specific organisms from which the library and the labeled sequences are derived. For guidance regarding such conditions see, for example, Sambrook et al., 1989, Molecular Cloning, A Laboratory Manual, Cold Spring Harbor Press, Cold Spring Harbor, N.Y. (and periodic updates thereof), and Ausubel et al., 1989, supra.
[0029] Alternatively, suitably labeled NHP nucleotide probes can be used to screen a human genomic library using appropriately stringent conditions or by PCR. The identification and characterization of human genomic clones is helpful for identifying polymorphisms (including, but not limited to, nucleotide repeats, microsatellite alleles, single nucleotide polymorphisms, or coding single nucleotide polymorphisms), determining the genomic structure of a given locus/allele, and designing diagnostic tests. For example, sequences derived from regions adjacent to the intron/exon boundaries of the human gene can be used to design primers for use in amplification assays to detect mutations within the exons, introns, splice sites (e.g., splice acceptor and/or donor sites), etc., that can be used in diagnostics and pharmacogenomics.
[0030] For example, the present sequences can be used in restriction fragment length polymorphism (RFLP) analysis to identify specific individuals. In this technique, an individual's genomic DNA is digested with one or more restriction enzymes, and probed on a Southern blot to yield unique bands for identification (as generally described in U.S. Pat. No. 5,272,057, incorporated herein by reference). In addition, the sequences of the present invention can be used to provide polynucleotide reagents, e.g., PCR primers, targeted to specific loci in the human genome, which can enhance the reliability of DNA-based forensic identifications by, for example, providing another “identification marker” (i.e., another DNA sequence that is unique to a particular individual). Actual base sequence information can be used for identification as an accurate alternative to patterns formed by restriction enzyme generated fragments.
[0031] Further, a NHP gene homolog can be isolated from nucleic acid from an organism of interest by performing PCR using two degenerate or “wobble” oligonucleotide primer pools designed on the basis of amino acid sequences within the NHP products disclosed herein. The template for the reaction may be genomic DNA, or total RNA, mRNA, and/or cDNA obtained by reverse transcription of mRNA prepared from human or non-human cell lines or tissue known to express, or suspected of expressing, an allele of a NHP gene. The PCR product can be subcloned and sequenced to ensure that the amplified sequences represent the sequence of the desired NHP gene. The PCR fragment can then be used to isolate a full length cDNA clone by a variety of methods. For example, the amplified fragment can be labeled and used to screen a cDNA library, such as a bacteriophage cDNA library. Alternatively, the labeled fragment can be used to isolate genomic clones via the screening of a genomic library.
[0032] PCR technology can also be used to isolate full length cDNA sequences. For example, RNA can be isolated, following standard procedures, from an appropriate cellular or tissue source (i.e., one known to express, or suspected of expressing, a NHP gene, such as, for example, testis tissue). A reverse transcription (RT) reaction can be performed on the RNA using an oligonucleotide primer specific for the most 5′ end of the amplified fragment for the priming of first strand synthesis. The resulting RNA/DNA hybrid may then be “tailed” using a standard terminal transferase reaction, the hybrid may be digested with RNase H, and second strand synthesis may then be primed with a complementary primer. Thus, cDNA sequences upstream of the amplified fragment can be isolated. For a review of cloning strategies that can be used, see, e.g., Sambrook et al., 1989, supra.
[0033] A cDNA encoding a mutant NHP sequence can be isolated, for example, by using PCR. In this case, the first cDNA strand may be synthesized by hybridizing an oligo-dT oligonucleotide to mRNA isolated from tissue known to express, or suspected of expressing, a NHP, in an individual putatively carrying a mutant NHP allele, and by extending the new strand with reverse transcriptase. The second strand of the cDNA is then synthesized using an oligonucleotide that hybridizes specifically to the 5′ end of the normal sequence. Using these two primers, the product is then amplified via PCR, optionally cloned into a suitable vector, and subjected to DNA sequence analysis through methods well-known to those of skill in the art. By comparing the DNA sequence of the mutant NHP allele to that of a corresponding normal NHP allele, the mutation(s) responsible for the loss or alteration of function of the mutant NHP gene product can be ascertained.
[0034] Alternatively, a genomic library can be constructed using DNA obtained from an individual suspected of carrying, or known to carry, a mutant NHP allele (e.g., a person manifesting a NHP-associated phenotype such as, for example, paralysis or palsy, nerve damage or degeneration, an inflammatory disorder, vision disorders, etc.), or a cDNA library can be constructed using RNA from a tissue known to express, or suspected of expressing, a mutant NHP allele. A normal NHP gene, or any suitable fragment thereof, can then be labeled and used as a probe to identify the corresponding mutant NHP allele in such libraries. Clones containing mutant NHP sequences can then be purified and subjected to sequence analysis according to methods well-known to those skilled in the art.
[0035] Additionally, an expression library can be constructed utilizing cDNA synthesized from, for example, RNA isolated from a tissue known to express, or suspected of expressing, a mutant NHP allele in an individual suspected of carrying, or known to carry, such a mutant allele. In this manner, gene products made by the putatively mutant tissue can be expressed and screened using standard antibody screening techniques in conjunction with antibodies raised against a normal NHP product, as described below (for screening techniques, see, for example, Harlow and Lane, eds., 1988, “Antibodies: A Laboratory Manual”, Cold Spring Harbor Press, Cold Spring Harbor, N.Y.).
[0036] Additionally, screening can be accomplished by screening with labeled NHP fusion proteins, such as, for example, alkaline phosphatase-NHP or NHP-alkaline phosphatase fusion proteins. In cases where a NHP mutation results in an expression product with altered function (e.g., as a result of a missense or a frameshift mutation), polyclonal antibodies to a NHP are likely to cross-react with a corresponding mutant NHP expression product. Library clones detected via their reaction with such labeled antibodies can be purified and subjected to sequence analysis according to methods well-known in the art.
[0037] The invention also encompasses: (a) DNA vectors that contain any of the foregoing NHP coding sequences and/or their complements (i.e., antisense); (b) DNA expression vectors that contain any of the foregoing NHP coding sequences operatively associated with a regulatory element that directs the expression of the coding sequences (for example, baculovirus as described in U.S. Pat. No. 5,869,336 herein incorporated by reference); (c) genetically engineered host cells that contain any of the foregoing NHP coding sequences operatively associated with a regulatory element that directs the expression of the coding sequences in the host cell; and (d) genetically engineered host cells that express an endogenous NHP sequence under the control of an exogenously introduced regulatory element (i.e., gene activation). As used herein, regulatory elements include, but are not limited to, inducible and non-inducible promoters, enhancers, operators, and other elements known to those skilled in the art that drive and regulate expression. Such regulatory elements include, but are not limited to, the cytomegalovirus (hCMV) immediate early gene, regulatable, viral elements (particularly retroviral LTR promoters), the early or late promoters of SV40 or adenovirus, the lac system, the trp system, the TAC system, the TRC system, the major operator and promoter regions of phage lambda, the control regions of fd coat protein, the promoter for 3-phosphoglycerate kinase (PGK), the promoters of acid phosphatase, and the promoters of the yeast α-mating factors.
[0038] The present invention also encompasses antibodies and anti-idiotypic antibodies (including Fab fragments), antagonists and agonists of a NHP, as well as compounds or nucleotide constructs that inhibit expression of a NHP sequence (transcription factor inhibitors, antisense and ribozyme molecules, or open reading frame sequence or regulatory sequence replacement constructs), or promote the expression of a NHP (e.g., expression constructs in which NHP coding sequences are operatively associated with expression control elements such as promoters, promoter/enhancers, etc.).
[0039] The NHPs or NHP peptides, NHP fusion proteins, NHP nucleotide sequences, antibodies, antagonists and agonists can be useful for the detection of mutant NHPs, or inappropriately expressed NHPs, for the diagnosis of disease. The NHPs or NHP peptides, NHP fusion proteins, NHP nucleotide sequences, host cell expression systems, antibodies, antagonists, agonists and genetically engineered cells and animals can be used for screening for drugs (or high throughput screening of combinatorial libraries) effective in the treatment of the symptomatic or phenotypic manifestations of perturbing the normal function of a NHP in the body. The use of engineered host cells and/or animals may offer an advantage in that such systems allow not only for the identification of compounds that bind to the endogenous receptor for a NHP, but can also identify compounds that trigger NHP-mediated activities or pathways.
[0040] Finally, the NHP products can be used as therapeutics. For example, soluble derivatives, such as a mature NHP, NHP peptides/domains corresponding to a NHP, NHP fusion protein products (especially NHP-Ig fusion proteins, i.e., fusions of a NHP, or a domain of a NHP, to an IgFc), NHP antibodies and anti-idiotypic antibodies (including Fab fragments), or antagonists or agonists (including compounds that modulate or act on downstream targets in a NHP-mediated pathway), can be used to directly treat diseases or disorders. For instance, the administration of an effective amount of a soluble NHP, a NHP-IgFc fusion protein, or an anti-idiotypic antibody (or its Fab) that mimics a NHP, could activate or effectively antagonize the endogenous NHP receptor. Soluble NHPs can also be modified by proteolytic cleavage to active peptide products (e.g., any novel peptide sequence initiating at any one of the amino acids presented in the Sequence Listing and ending at any downstream amino acid). Such products or peptides can be further subject to modification such as the construction of NHP fusion proteins and/or can be derivatized by being combined with pharmaceutically acceptable agents such as, but not limited to, polyethylene glycol (PEG).
[0041] Nucleotide constructs encoding such NHP products can be used to genetically engineer host cells to express such products in vivo; these genetically engineered cells function as “bioreactors” in the body delivering a continuous supply of a NHP, a NHP peptide, or a NHP fusion protein to the body. Nucleotide constructs encoding a functional NHP, mutant NHPs, as well as antisense and ribozyme molecules, can also be used in “gene therapy” approaches for the modulation of NHP expression. Thus, the invention also encompasses pharmaceutical formulations and methods for treating biological disorders.
[0042] Various aspects of the invention are described in greater detail in the subsections below.
THE NHP SEQUENCES
[0043] The cDNA sequences and corresponding deduced amino acid sequences of the described NHPs are presented in the Sequence Listing. The NHP nucleotides were obtained by aligning cDNAs from human kidney, fetal kidney, prostate, and lymph node mRNAs (Edge Biosystems, Gaithersburg, Md., Clontech, Palo Alto, Calif.) and human genomic DNA sequence. The described sequences are apparently encoded on human chromosome 7 (see GENBANK accession no. AC024952). As such, the described sequences are useful for mapping the coding region of the human genome and for identifying exon splice junctions.
[0044] A T/A polymorphism was identified in the disclosed sequences at the nucleotide position represented by, for example, position 550 of SEQ ID NOS:1 or 3, or position 349 of SEQ ID NOS:11 or 13, which can result in a cys or ser at the region corresponding to, for example, amino acid (aa) position 184 of SEQ ID NOS:2 or 4, or aa position 117 of SEQ ID NOS:12 or 14. As these polymorphisms are coding single nucleotide polymorphisms, they are particularly useful in forensic analysis.
[0045] An additional application of the described novel human polynucleotide sequences is their use in the molecular mutagenesis/evolution of proteins that are at least partially encoded by the described novel sequences using, for example, polynucleotide shuffling or related methodologies. Such approaches are described in U.S. Pat. Nos. 5,830,721 and 5,837,458, which are herein incorporated by reference in their entirety.
[0046] NHP gene products can also be expressed in transgenic animals. Animals of any species, including, but not limited to, worms, mice, rats, rabbits, guinea pigs, pigs, micro-pigs, birds, goats, and non-human primates, e.g., baboons, monkeys, and chimpanzees, may be used to generate NHP transgenic animals.
[0047] Any technique known in the art may be used to introduce a NHP transgene into animals to produce the founder lines of transgenic animals. Such techniques include, but are not limited to, pronuclear microinjection (Hoppe and Wagner, 1989, U.S. Pat. No. 4,873,191); retrovirus-mediated gene transfer into germ lines (Van der Putten et al., 1985, Proc. Natl. Acad. Sci. USA 82:6148-6152); gene targeting in embryonic stem cells (Thompson et al., 1989, Cell 56:313-321); electroporation of embryos (Lo, 1983, Mol Cell. Biol. 3:1803-1814); and sperm-mediated gene transfer (Lavitrano et al., 1989, Cell 57:717-723); etc. For a review of such techniques, see Gordon, 1989, Transgenic Animals, Intl. Rev. Cytol. 115:171-229, which is incorporated by reference herein in its entirety.
[0048] The present invention provides for transgenic animals that carry a NHP transgene in all their cells, as well as animals that carry a transgene in some, but not all their cells, i.e., mosaic animals or somatic cell transgenic animals. A transgene may be integrated as a single transgene, or in concatamers, e.g., head-to-head tandems or head-to-tail tandems. A transgene may also be selectively introduced into and activated in a particular cell-type by following, for example, the teaching of Lasko et al., 1992, Proc. Natl. Acad. Sci. USA 89:6232-6236. The regulatory sequences required for such a cell-type specific activation will depend upon the particular cell-type of interest, and will be apparent to those of skill in the art.
[0049] When it is desired that a NHP transgene be integrated into the chromosomal site of the endogenous NHP gene, gene targeting is preferred. Briefly, when such a technique is to be utilized, vectors containing some nucleotide sequences homologous to the endogenous NHP gene are designed for the purpose of integrating, via homologous recombination with chromosomal sequences, into and disrupting the function of the nucleotide sequence of the endogenous NHP gene (i.e., “knockout” animals).
[0050] The transgene can also be selectively introduced into a particular cell-type, thus inactivating the endogenous NHP gene in only that cell-type, by following, for example, the teaching of Gu et al., 1994, Science 265:103-106. The regulatory sequences required for such a cell-type specific inactivation will depend upon the particular cell-type of interest, and will be apparent to those of skill in the art.
[0051] Once transgenic animals have been generated, the expression of the recombinant NHP gene may be assayed utilizing standard techniques. Initial screening may be accomplished by Southern blot analysis or PCR techniques to analyze animal tissues to assay whether integration of the transgene has taken place. The level of mRNA expression of the transgene in the tissues of the transgenic animals may also be assessed using techniques that include, but are not limited to, Northern blot analysis of tissue samples obtained from the animal, in situ hybridization analysis, and RT-PCR. Samples of NHP gene-expressing tissue may also be evaluated immunocytochemically using antibodies specific for the NHP transgene product.
[0052] The present invention also provides for “knock-in” animals. Knock-in animals are those in which a polynucleotide sequence (i.e., a gene or a cDNA) that the animal does not naturally have in its genome is inserted in such a way that it is expressed. Examples include, but are not limited to, a human gene or cDNA used to replace its murine ortholog in the mouse, a murine cDNA used to replace the murine gene in the mouse, and a human gene or cDNA or murine cDNA that is tagged with a reporter construct used to replace the murine ortholog or gene in the mouse. Such replacements can occur at the locus of the murine ortholog or gene, or at another specific site. Such knock-in animals are useful for the in vivo study, testing and validation of, intra alia, human drug targets, as well as for compounds that are directed at the same, and therapeutic proteins.
NHPS AND NHP POLYPEPTIDES
[0053] NHPS, NHP polypeptides, NHP peptide fragments, mutated, truncated, or deleted forms of the NHPs, and/or NHP fusion proteins can be prepared for a variety of uses. These uses include, but are not limited to, the generation of antibodies, as reagents in diagnostic assays, for the identification of other cellular gene products related to a NHP, and as reagents in assays for screening for compounds that can be used as pharmaceutical reagents useful in the therapeutic treatment of mental, biological, or medical disorders and diseases. Given the similarity information and expression data, the described NHPs can be targeted (by drugs, oligos, antibodies, etc.) in order to treat disease, or to therapeutically augment the efficacy of therapeutic agents.
[0054] The Sequence Listing discloses the amino acid sequences encoded by the described NHP sequences. Bioinformatic analysis reveals that the NHPs are similar to, for example, kielins and chordins (note the high cysteine content). The NHPs display initiator methionines in DNA sequence contexts consistent with translation initiation sites, and incorporate signal sequences and hydrophobic sequences similar to those found in membrane and secreted proteins.
[0055] The NHP amino acid sequences of the invention include the amino acid sequences presented in the Sequence Listing, as well as analogues and derivatives thereof. Further, corresponding NHP homologues from other species are encompassed by the invention. In fact, any NHP product encoded by the NHP nucleotide sequences described herein are within the scope of the invention, as are any novel polynucleotide sequences encoding all or any novel portion of an amino acid sequence presented in the Sequence Listing. The degenerate nature of the genetic code is well-known, and, accordingly, each amino acid presented in the Sequence Listing is generically representative of the well-known nucleic acid “triplet” codon, or in many cases codons, that can encode the amino acid. As such, as contemplated herein, the amino acid sequences presented in the Sequence Listing, when taken together with the genetic code (see, for example, Table 4-1 at page 109 of “Molecular Cell Biology”, 1986, J. Darnell et al., eds., Scientific American Books, New York, N.Y., herein incorporated by reference), are generically representative of all the various permutations and combinations of nucleic acid sequences that can encode such amino acid sequences.
[0056] The invention also encompasses proteins that are functionally equivalent to the NHPs encoded by the presently described nucleotide sequences, as judged by any of a number of criteria, including, but not limited to, the ability to bind and cleave a substrate of a NHP, the ability to effect an identical or complementary downstream pathway, or a change in cellular metabolism (e.g., proteolytic activity, ion flux, tyrosine phosphorylation, etc.). Such functionally equivalent NHP proteins include, but are not limited to, additions or substitutions of amino acid residues within the amino acid sequences encoded by the NHP nucleotide sequences described herein, but that result in a silent change, thus producing a functionally equivalent expression product. Amino acid substitutions may be made on the basis of similarity in polarity, charge, solubility, hydrophobicity, hydrophilicity, and/or the amphipathic nature of the residues involved. For example, nonpolar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan, and methionine; polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine, and glutamine; positively charged (basic) amino acids include arginine, lysine, and histidine; and negatively charged (acidic) amino acids include aspartic acid and glutamic acid.
[0057] A variety of host-expression vector systems can be used to express the NHP nucleotide sequences of the invention. Where, as in the present instance, the NHP peptides or polypeptides are thought to be soluble or secreted molecules, the peptides or polypeptides can be recovered from the culture media. Such expression systems also encompass engineered host cells that express a NHP, or functional equivalent, in situ. Purification or enrichment of a NHP from such expression systems can be accomplished using appropriate detergents and lipid micelles and methods well-known to those skilled in the art. However, such engineered host cells themselves may be used in situations where it is important not only to retain the structural and functional characteristics of a NHP, but to assess biological activity, e.g., in certain drug screening assays.
[0058] The expression systems that may be used for purposes of the invention include, but are not limited to, microorganisms such as bacteria (e.g., E. coli, B. subtilis ) transformed with recombinant bacteriophage DNA, plasmid DNA or cosmid DNA expression vectors containing NHP nucleotide sequences; yeast (e.g., Saccharomyces, Pichia) transformed with recombinant yeast expression vectors containing NHP nucleotide sequences; insect cell systems infected with recombinant virus expression vectors (e.g., baculovirus) containing NHP nucleotide sequences; plant cell systems infected with recombinant virus expression vectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transformed with recombinant plasmid expression vectors (e.g., Ti plasmid) containing NHP nucleotide sequences; or mammalian cell systems (e.g., COS, CHO, BHK, 293, 3T3) harboring recombinant expression constructs containing NHP nucleotide sequences and promoters derived from the genome of mammalian cells (e.g., metallothionein promoter) or from mammalian viruses (e.g., the adenovirus late promoter; the vaccinia virus 7.5K promoter).
[0059] In bacterial systems, a number of expression vectors may be advantageously selected depending upon the use intended for the NHP product being expressed. For example, when a large quantity of such a protein is to be produced for the generation of pharmaceutical compositions of or containing a NHP, or for raising antibodies to a NHP, vectors that direct the expression of high levels of fusion protein products that are readily purified may be desirable. Such vectors include, but are not limited to, the E. coli expression vector pUR278 (Ruther et al., 1983, EMBO J. 2:1791), in which a NHP coding sequence may be ligated individually into the vector in-frame with the lacZ coding region so that a fusion protein is produced; pIN vectors (Inouye and Inouye, 1985, Nucleic Acids Res. 13:3101-3109; Van Heeke and Schuster, 1989, J. Biol. Chem. 264:5503-5509); and the like. pGEX vectors (Pharmacia or American Type Culture Collection) can also be used to express foreign polypeptides as fusion proteins with glutathione S-transferase (GST). In general, such fusion proteins are soluble and can easily be purified from lysed cells by adsorption to glutathione-agarose beads, followed by elution in the presence of free glutathione. The pGEX vectors are designed to include thrombin or factor Xa protease cleavage sites so that the cloned target expression product can be released from the GST moiety.
[0060] In an exemplary insect system, Autographa californica nuclear polyhedrosis virus (AcNPV) is used as a vector to express foreign polynucleotide sequences. The virus grows in Spodoptera frugiperda cells. A NHP coding sequence can be cloned individually into a non-essential region (for example the polyhedrin gene) of the virus and placed under control of an AcNPV promoter (for example the polyhedrin promoter). Successful insertion of a NHP coding sequence will result in inactivation of the polyhedrin gene and production of non-occluded recombinant virus (i.e., virus lacking the proteinaceous coat coded for by the polyhedrin gene). These recombinant viruses are then used to infect Spodoptera frugiperda cells in which the inserted sequence is expressed (e.g., see Smith et al., 1983, J. Virol. 46:584; Smith, U.S. Pat. No. 4,215,051).
[0061] In mammalian host cells, a number of viral-based expression systems can be utilized. In cases where an adenovirus is used as an expression vector, the NHP nucleotide sequence of interest may be ligated to an adenovirus transcription/translation control complex, e.g., the late promoter and tripartite leader sequence. This chimeric sequence may then be inserted in the adenovirus genome by in vitro or in vivo recombination. Insertion in a non-essential region of the viral genome (e.g., region E1 or E3) will result in a recombinant virus that is viable and capable of expressing a NHP product in infected hosts (e.g., see Logan and Shenk, 1984, Proc. Natl. Acad. Sci. USA 81:3655-3659). Specific initiation signals may also be required for efficient translation of inserted NHP nucleotide sequences. These signals include the ATG initiation codon and adjacent sequences. In cases where an entire NHP gene or cDNA, including its own initiation codon and adjacent sequences, is inserted into the appropriate expression vector, no additional translational control signals may be needed. However, in cases where only a portion of a NHP coding sequence is inserted, exogenous translational control signals, including, perhaps, the ATG initiation codon, may be provided. Furthermore, the initiation codon should be in phase with the reading frame of the desired coding sequence to ensure translation of the entire insert. These exogenous translational control signals and initiation codons can be of a variety of origins, both natural and synthetic. The efficiency of expression may be enhanced by the inclusion of appropriate transcription enhancer elements, transcription terminators, etc. (see Bitter et al., 1987, Methods in Enzymol. 153:516-544).
[0062] In addition, a host cell strain may be chosen that modulates the expression of the inserted sequences, or modifies and processes the expression product in the specific fashion desired. Such modifications (e.g., glycosylation) and processing (e.g., cleavage) of protein products may be important for the function of the protein. Different host cells have characteristic and specific mechanisms for the post-translational processing and modification of proteins and expression products. Appropriate cell lines or host systems can be chosen to ensure the desired modification and processing of the foreign protein expressed. To this end, eukaryotic host cells that possess the cellular machinery for the desired processing of the primary transcript, glycosylation, and phosphorylation of the expression product may be used. Such mammalian host cells include, but are not limited to, CHO, VERO, BHK, HeLa, COS, MDCK, 293, 3T3, WI38, and in particular, human cell lines.
[0063] For long-term, high-yield production of recombinant proteins, stable expression is preferred. For example, cell lines that stably express the NHP sequences described herein can be engineered. Rather than using expression vectors that contain viral origins of replication, host cells can be transformed with DNA controlled by appropriate expression control elements (e.g., promoter, enhancer sequences, transcription terminators, polyadenylation sites, etc.), and a selectable marker. Following the introduction of the foreign DNA, engineered cells may be allowed to grow for 1-2 days in an enriched media, and then switched to a selective media. The selectable marker in the recombinant plasmid confers resistance to the selection and allows cells to stably integrate the plasmid into their chromosomes and grow to form foci, which in turn can be cloned and expanded into cell lines. This method may advantageously be used to engineer cell lines that express a NHP product. Such engineered cell lines may be particularly useful in screening and evaluation of compounds that affect the endogenous activity of a NHP product.
[0064] A number of selection systems may be used, including, but not limited to, the herpes simplex virus thymidine kinase (Wigler et al., 1977, Cell 11:223), hypoxanthine-guanine phosphoribosyltransferase (Szybalska and Szybalski, 1962, Proc. Natl. Acad. Sci. USA 48:2026), and adenine phosphoribosyltransferase (Lowy et al., 1980, Cell 22:817) genes, which can be employed in tk − , hgprt − or aprt − cells, respectively. Also, antimetabolite resistance can be used as the basis of selection for the following genes: dhfr, which confers resistance to methotrexate (Wigler et al., 1980, Proc. Natl. Acad. Sci. USA 77:3567; O'Hare et al., 1981, Proc. Natl. Acad. Sci. USA 78:1527); gpt, which confers resistance to mycophenolic acid (Mulligan and Berg, 1981, Proc. Natl. Acad. Sci. USA 78:2072); neo, which confers resistance to the aminoglycoside G-418 (Colberre-Garapin et al., 1981, J. Mol. Biol. 150:1); and hygro, which confers resistance to hygromycin (Santerre et al., 1984, Gene 30:147).
[0065] Alternatively, any fusion protein can be readily purified by utilizing an antibody specific for the fusion protein being expressed. Another exemplary system allows for the ready purification of non-denatured fusion proteins expressed in human cell lines (Janknecht et al., 1991, Proc. Natl. Acad. Sci. USA 88:8972-8976). In this system, the sequence of interest is subcloned into a vaccinia recombination plasmid such that the sequence's open reading frame is translationally fused to an amino-terminal tag consisting of six histidine residues. Extracts from cells infected with recombinant vaccinia virus are loaded onto Ni 2+ ·nitriloacetic acid-agarose columns, and histidine-tagged proteins are selectively eluted with imidazole-containing buffers.
[0066] Also encompassed by the present invention are fusion proteins that direct a NHP to a target organ and/or facilitate transport across the membrane into the cytosol. Conjugation of NHPs to antibody molecules or their Fab fragments could be used to target cells bearing a particular epitope. Attaching an appropriate signal sequence to a NHP would also transport a NHP to a desired location within the cell. Alternatively targeting of a NHP or its nucleic acid sequence might be achieved using liposome or lipid complex based delivery systems. Such technologies are described in “Liposomes: A Practical Approach”, New, R. R. C., ed., Oxford University Press, N.Y., and in U.S. Pat. Nos. 4,594,595, 5,459,127, 5,948,767 and 6,110,490 and their respective disclosures, which are herein incorporated by reference in their entirety. Additionally embodied are novel protein constructs engineered in such a way that they facilitate transport of NHPs to a target site or desired organ, where they cross the cell membrane and/or the nucleus, where the NHPs can exert their functional activity. This goal may be achieved by coupling of a NHP to a cytokine or other ligand that provides targeting specificity, and/or to a protein transducing domain (see generally U.S. Provisional Patent Application Ser. Nos. 60/111,701 and 60/056,713, both of which are herein incorporated by reference, for examples of such transducing sequences), to facilitate passage across cellular membranes, and can optionally be engineered to include nuclear localization signals.
[0067] Additionally contemplated are oligopeptides that are modeled on an amino acid sequence first described in the Sequence Listing. Such NHP oligopeptides are generally between about 10 to about 100 amino acids long, or between about 16 to about 80 amino acids long, or between about 20 to about 35 amino acids long, or any variation or combination of sizes represented therein that incorporate a contiguous region of sequence first disclosed in the Sequence Listing. Such NHP oligopeptides can be of any length disclosed within the above ranges and can initiate at any amino acid position represented in the Sequence Listing.
[0068] The invention also contemplates “substantially isolated” or “substantially pure” proteins or polypeptides. By a “substantially isolated” or “substantially pure” protein or polypeptide is meant a protein or polypeptide that has been separated from at least some of those components that naturally accompany it. Typically, the protein or polypeptide is substantially isolated or pure when it is at least 60%, by weight, free from the proteins and other naturally-occurring organic molecules with which it is naturally associated in vivo. Preferably, the purity of the preparation is at least 75%, more preferably at least 90%, and most preferably at least 99%, by weight. A substantially isolated or pure protein or polypeptide may be obtained, for example, by extraction from a natural source, by expression of a recombinant nucleic acid encoding the protein or polypeptide, or by chemically synthesizing the protein or polypeptide.
[0069] Purity can be measured by any appropriate method, e.g., column chromatography such as immunoaffinity chromatography using an antibody specific for the protein or polypeptide, polyacrylamide gel electrophoresis, or HPLC analysis. A protein or polypeptide is substantially free of naturally associated components when it is separated from at least some of those contaminants that accompany it in its natural state. Thus, a polypeptide that is chemically synthesized or produced in a cellular system different from the cell from which it naturally originates will be, by definition, substantially free from its naturally associated components. Accordingly, substantially isolated or pure proteins or polypeptides include eukaryotic proteins synthesized in E. coli, other prokaryotes, or any other organism in which they do not naturally occur.
ANTIBODIES TO NHP PRODUCTS
[0070] Antibodies that specifically recognize one or more epitopes of a NHP, epitopes of conserved variants of a NHP, or peptide fragments of a NHP, are also encompassed by the invention. Such antibodies include, but are not limited to, polyclonal antibodies, monoclonal antibodies (mAbs), humanized or chimeric antibodies, single chain antibodies, Fab fragments, F(ab′) 2 fragments, fragments produced by a Fab expression library, anti-idiotypic (anti-Id) antibodies, and epitope-binding fragments of any of the above.
[0071] The antibodies of the invention may be used, for example, in the detection of a NHP in a biological sample and may, therefore, be utilized as part of a diagnostic or prognostic technique whereby patients may be tested for abnormal amounts of a NHP. Such antibodies may also be utilized in conjunction with, for example, compound screening schemes for the evaluation of the effect of test compounds on expression and/or activity of a NHP expression product. Additionally, such antibodies can be used in conjunction with gene therapy to, for example, evaluate normal and/or engineered NHP-expressing cells prior to their introduction into a patient. Such antibodies may additionally be used in methods for the inhibition of abnormal NHP activity. Thus, such antibodies may be utilized as a part of treatment methods.
[0072] For the production of antibodies, various host animals may be immunized by injection with a NHP, a NHP peptide (e.g., one corresponding to a functional domain of a NHP), a truncated NHP polypeptide (a NHP in which one or more domains have been deleted), functional equivalents of a NHP, or mutated variants of a NHP. Such host animals may include, but are not limited to, pigs, rabbits, mice, goats, and rats, to name but a few. Various adjuvants may be used to increase the immunological response, depending on the host species, including, but not limited to, Freund's adjuvant (complete and incomplete), mineral salts such as aluminum hydroxide or aluminum phosphate, chitosan, surface active substances such as lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, and potentially useful human adjuvants such as BCG (bacille Calmette-Guerin) and Corynebacterium parvum. Alternatively, the immune response could be enhanced by combination and/or coupling with molecules such as keyhole limpet hemocyanin, tetanus toxoid, diphtheria toxoid, ovalbumin, cholera toxin, or fragments thereof. Polyclonal antibodies are heterogeneous populations of antibody molecules derived from the sera of the immunized animals.
[0073] Monoclonal antibodies, which are homogeneous populations of antibodies to a particular antigen, can be obtained by any technique that provides for the production of antibody molecules by continuous cell lines in culture. These include, but are not limited to, the hybridoma technique of Kohler and Milstein, (1975, Nature 256:495-497; and U.S. Pat. No. 4,376,110), the human B-cell hybridoma technique (Kosbor et al., 1983, Immunology Today 4:72; Cole et al., 1983, Proc. Natl. Acad. Sci. USA 80:2026-2030), and the EBV-hybridoma technique (Cole et al., 1985, Monoclonal Antibodies And Cancer Therapy, Alan R. Liss, Inc., pp. 77-96). Such antibodies may be of any immunoglobulin class, including IgG, IgM, IgE, IgA, and IgD, and any subclass thereof. The hybridomas producing the mAbs of this invention may be cultivated in vitro or in vivo. Production of high titers of mAbs in vivo makes this the presently preferred method of production.
[0074] In addition, techniques developed for the production of “chimeric antibodies” (Morrison et al., 1984, Proc. Natl. Acad. Sci. USA 81:6851-6855; Neuberger et al., 1984, Nature, 312:604-608; Takeda et al., 1985, Nature, 314:452-454) by splicing the genes from a mouse antibody molecule of appropriate antigen specificity together with genes from a human antibody molecule of appropriate biological activity can be used. A chimeric antibody is a molecule in which different portions are derived from different animal species, such as those having a variable region derived from a murine mAb and a human immunoglobulin constant region. Such technologies are described in U.S. Pat. Nos. 6,114,598, 6,075,181 and 5,877,397 and their respective disclosures, which are herein incorporated by reference in their entirety. Also encompassed by the present invention is the use of fully humanized monoclonal antibodies, as described in U.S. Pat. No. 6,150,584 and respective disclosures, which are herein incorporated by reference in their entirety.
[0075] Alternatively, techniques described for the production of single chain antibodies (U.S. Pat. No. 4,946,778; Bird, 1988, Science 242:423-426; Huston et al., 1988, Proc. Natl. Acad. Sci. USA 85:5879-5883; and Ward et al., 1989, Nature 341:544-546) can be adapted to produce single chain antibodies against NHP expression products. Single chain antibodies are formed by linking the heavy and light chain fragments of the Fv region via an amino acid bridge, resulting in a single chain polypeptide.
[0076] Antibody fragments that recognize specific epitopes may be generated by known techniques. For example, such fragments include, but are not limited to: F(ab′) 2 fragments, which can be produced by pepsin digestion of an antibody molecule; and Fab fragments, which can be generated by reducing the disulfide bridges of F(ab′) 2 fragments. Alternatively, Fab expression libraries may be constructed (Huse et al., 1989, Science, 246:1275-1281) to allow rapid and easy identification of monoclonal Fab fragments with the desired specificity.
[0077] Antibodies to a NHP can, in turn, be utilized to generate anti-idiotype antibodies that “mimic” a given NHP, using techniques well-known to those skilled in the art (see, e.g., Greenspan and Bona, 1993, FASEB J. 7:437-444; and Nissinoff, 1991, J. Immunol. 147:2429-2438). For example, antibodies that bind to a NHP domain and competitively inhibit the binding of a NHP to its cognate receptor can be used to generate anti-idiotypes that “mimic” the NHP and, therefore, bind and activate or neutralize a receptor. Such anti-idiotypic antibodies, or Fab fragments of such anti-idiotypes, can be used in therapeutic regimens involving a NHP signaling pathway.
[0078] Additionally given the high degree of relatedness of mammalian NHPS, NHP knock-out mice (having never seen a NHP, and thus never been tolerized to a NHP) have an unique utility, as they can be advantageously applied to the generation of antibodies against the disclosed mammalian NHPs (i.e., a NHP will be immunogenic in NHP knock-out animals).
[0079] The present invention is not to be limited in scope by the specific embodiments described herein, which are intended as single illustrations of individual aspects of the invention, and functionally equivalent methods and components are within the scope of the invention. Indeed, various modifications of the invention, in addition to those shown and described herein, will become apparent to those skilled in the art from the foregoing description. Such modifications are intended to fall within the scope of the appended claims. All cited publications, patents, and patent applications are herein incorporated by reference in their entirety.



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25


1
4884
DNA
homo sapiens

1

atggccgggg tcggggccgc tgcgctgtcc cttctcctgc acctcggggc cctggcgctg 60

gccgcgggcg cggaaggtgg ggctgtcccc agggagcccc ctgggcagca gacaactgcc 120

cattcctcag tccttgctgg gaactcccag gagcagtggc accccctgcg agagtggctg 180

gggcgactgg aggctgcagt gatggagctc agagaacaga ataaggacct gcagacgagg 240

gtgaggcagc tggagtcctg tgagtgccac cctgcatctc cccagtgctg ggggctgggg 300

cgtgcctggc ccgagggggc acgctgggag cctgacgcct gcacagcctg cgtctgccag 360

gatggggccg ctcactgtgg cccccaagca cacctgcccc attgcagggg ctgcagccaa 420

aatggccaga cctacggcaa cggggagacc ttctccccag atgcctgcac cacctgccgc 480

tgtctggaag gtaccatcac ttgcaaccag aagccatgcc caagaggacc ctgccctgag 540

ccaggagcat gctgcccgca ctgtaagcca ggctgtgatt atgaggggca gctttatgag 600

gagggggtca ccttcctgtc cagctccaac ccttgtctac agtgcacctg cctgaggagc 660

cgagttcgct gcatggccct gaagtgcccg cctagcccct gcccagagcc agtgctgagg 720

cctgggcact gctgcccaac ctgccaaggc tgcacagaag gtggctctca ctgggaacat 780

ggccaagagt ggacaacacc tggggacccc tgccgaatct gccggtgcct ggagggtcac 840

atccagtgcc gccagcgaga atgtgccagc ctgtgtccat acccagcccg gcccctccca 900

ggcacctgct gccctgtgtg tgatggctgt ttcctaaacg ggcgggagca ccgcagcggg 960

gagcctgtgg gctcagggga cccctgctcg cactgccgct gtgctaatgg gagtgtccag 1020

tgtgagcctc tgccctgccc gccagtgccc tgcagacacc caggcaagat ccctgggcag 1080

tgctgccctg tctgcgatgg ctgtgagtac cagggacacc agtatcagag ccaggagacc 1140

ttcagactcc aagagcgggg cctctgtgtc cgctgctcct gccaggctgg cgaggtctcc 1200

tgtgaggagc aggagtgccc agtcaccccc tgtgccctgc ctgcctctgg ccgccagctc 1260

tgcccagcct gtgagctgga tggagaggag tttgctgagg gagtccagtg ggagcctgat 1320

ggtcggccct gcaccgcctg cgtctgtcaa gatggggtac ccaagtgcgg ggctgtgctc 1380

tgccccccag ccccctgcca gcaccccacc cagccccctg gtgcctgctg ccccagctgt 1440

gacagctgca cctaccacag ccaagtgtat gccaatgggc agaacttcac ggatgcagac 1500

agcccttgcc atgcctgcca ctgtcaggat ggaactgtga catgctcctt ggttgactgc 1560

cctcccacga cctgtgccag gccccagagt ggaccaggcc agtgttgccc caggtgccca 1620

gactgcatcc tggaggaaga ggtgtttgtg gacggcgaga gcttctccca cccccgagac 1680

ccctgccagg agtgccgatg ccaggaaggc catgcccact gccagcctcg cccctgcccc 1740

agggccccct gtgcccaccc gctgcctggg acctgctgcc cgaacgactg cagcggctgt 1800

gcctttggcg ggaaagagta ccccagcgga gcggacttcc cccacccctc tgacccctgc 1860

cgtctgtgtc gctgtctgag cggcaacgtg cagtgcctgg cccgccgctg cgtgccgctg 1920

ccctgtccag agcctgtcct gctgccggga gagtgctgcc cgcagtgccc agccgcccca 1980

gcccccgccg gctgcccacg gcccggcgcg gcccacgccc gccaccagga gtacttctcc 2040

ccgcccggcg atccctgccg ccgctgcctc tgcctcgacg gctccgtgtc ctgccagcgg 2100

ctgccctgcc cgcccgcgcc ctgcgcgcac ccgcgccagg ggccttgctg cccctcctgc 2160

gacggctgcc tgtaccaggg gaaggagttt gccagcgggg agcgcttccc atcgcccact 2220

gctgcctgcc acctctgcct ttgctgggag ggcagcgtga gctgcgagcc caaggcatgt 2280

gcccctgcac tgtgcccctt ccctgccagg ggcgactgct gccctgactg tgatggctgt 2340

gagtacctgg gggagtccta cctgagtaac caggagttcc cagacccccg agaaccctgc 2400

aacctgtgta cctgtcttgg aggcttcgtg acctgcggcc gccggccctg tgagcctccg 2460

ggctgcagcc acccactcat cccctctggg cactgctgcc cgacctgcca gggatgccgc 2520

taccatggcg tcactactgc ctccggagag acccttcctg acccacttga ccctacctgc 2580

tccctctgca cctgccagga aggttccatg cgctgccaaa agaagccatg tgccccagct 2640

ctctgccccc acccctctcc aggcccctgc ttctgccctg tttgccacag ttgtctctct 2700

cagggccggg agcaccagga tggggaggag tttgagggac cagcaggcag ctgtgagtgg 2760

tgtcgctgtc aggctggcca ggtcagctgt gtgcggctgc agtgcccacc ccttccctgc 2820

aagctccagg tcaccgagcg ggggagctgc tgccctcgct gcagaggctg cctggctcat 2880

ggggaagagc accccgaagg cagtagatgg gtgccccccg acagtgcctg ctcctcctgt 2940

gtgtgtcacg agggcgtcgt cacctgtgca cgcatccagt gcatcagctc ttgcgcccag 3000

ccccgccaag ggccccatga ctgctgtcct caatgctctg actgtgagca tgagggccgg 3060

aagtacgagc ctggggagag cttccagcct ggggcagacc cctgtgaagt gtgcatctgc 3120

gagccacagc ctgaggggcc tcccagcctt cgctgtcacc ggcggcagtg tcccagcctg 3180

gtgggctgcc cccccagcca gctcctgccc cctgggcccc agcactgctg tcccacctgt 3240

gccgaggcct tgagtaactg ttcagagggc ctgctgggat ctgagctagc cccaccagac 3300

ccctgctaca cgtgccagtg ccaggacctg acatggctct gcatccacca ggcttgtcct 3360

gagctcagct gtcccctctc agagcgccac actccccctg ggagctgctg ccccgtatgc 3420

cgggaatgtg tggtggaggc cgagggccgg agagtggcag atggagagag ctggcgggac 3480

cccagcaatg cgtgcatcgc ctgcacctgc catcggggcc atgtggagtg ccacctcgag 3540

gagtgccagg ccctctcctg cccccatggc tgggcgaagg tgccccaggc tgacagctgc 3600

tgtgagcgat gccaagctcc cacccagtcc tgcgtgcacc agggccgtga ggtggcctct 3660

ggagagcgct ggactgtgga cacctgcacc agctgctcct gcatggcggg caccgtgcgt 3720

tgccagagcc agcgctgctc accgctctcg tgtggccccg acaaggcccc tgccctgagt 3780

cctggcagct gctgcccccg ctgcctgcct cggcccgctt cctgcatggc cttcggagac 3840

ccccattacc gcaccttcga cggccgcctg ctgcacttcc agggcagttg cagctatgtg 3900

ctggccaagg actgccacag cggggacttc agtgtgcacg tgaccaatga tgaccggggc 3960

cggagcggtg tggcctggac ccaggaggtg gcggtgctgc tgggagacat ggccgtgcgg 4020

ctgctgcagg acggggcagt cacggtggat gggcacccgg tggccttgcc cttcctgcag 4080

gagccgctgc tgtatgtgga gctgcgagga cacactgtga tcctgcacgc ccagcccggg 4140

ctccaggtgc tgtgggatgg gcagtcccag gtggaggtga gcgtacctgg ctcctaccag 4200

ggccggactt gtgggctctg tgggaacttc aatggctttg cccaggacga tctgcagggc 4260

cctgaggggc tgctcctgcc ctcggaggct gcgtttggga atagctggca ggtctcagag 4320

gggctgtggc ctggccggcc ctgttctgca ggccgagagg tggatccgtg ccgggcagca 4380

ggttaccgtg ccaggcgtga ggccaatgcc cggtgtgggg tgctgaagtc ctccccattc 4440

agtcgctgcc atgctgtggt gccaccggag cccttctttg ccgcctgtgt gtatgacctg 4500

tgtgcctgtg gccctggctc ctccgctgat gcctgcctct gtgatgccct ggaagcctac 4560

gccagtcact gtcgccaggc aggagtgaca cctacctggc gaggccccac gctgtgtgtg 4620

gtaggctgcc ccctggagcg tggcttcgtg tttgatgagt gcggcccacc ctgtccccgc 4680

acctgcttca atcagcatat ccccctgggg gagctggcag cccactgcgt gaggccctgc 4740

gtgcccggct gccagtgccc tgcaggcctg gtggagcatg aggcccactg catcccaccc 4800

gaggcctgcc cccaagtcct gctcactgga gaccagccac ttggtgctcg gcccagcccc 4860

agccgggagc cccaggagac accc 4884



2
1628
PRT
homo sapiens

2

Met Ala Gly Val Gly Ala Ala Ala Leu Ser Leu Leu Leu His Leu Gly
1 5 10 15

Ala Leu Ala Leu Ala Ala Gly Ala Glu Gly Gly Ala Val Pro Arg Glu
20 25 30

Pro Pro Gly Gln Gln Thr Thr Ala His Ser Ser Val Leu Ala Gly Asn
35 40 45

Ser Gln Glu Gln Trp His Pro Leu Arg Glu Trp Leu Gly Arg Leu Glu
50 55 60

Ala Ala Val Met Glu Leu Arg Glu Gln Asn Lys Asp Leu Gln Thr Arg
65 70 75 80

Val Arg Gln Leu Glu Ser Cys Glu Cys His Pro Ala Ser Pro Gln Cys
85 90 95

Trp Gly Leu Gly Arg Ala Trp Pro Glu Gly Ala Arg Trp Glu Pro Asp
100 105 110

Ala Cys Thr Ala Cys Val Cys Gln Asp Gly Ala Ala His Cys Gly Pro
115 120 125

Gln Ala His Leu Pro His Cys Arg Gly Cys Ser Gln Asn Gly Gln Thr
130 135 140

Tyr Gly Asn Gly Glu Thr Phe Ser Pro Asp Ala Cys Thr Thr Cys Arg
145 150 155 160

Cys Leu Glu Gly Thr Ile Thr Cys Asn Gln Lys Pro Cys Pro Arg Gly
165 170 175

Pro Cys Pro Glu Pro Gly Ala Cys Cys Pro His Cys Lys Pro Gly Cys
180 185 190

Asp Tyr Glu Gly Gln Leu Tyr Glu Glu Gly Val Thr Phe Leu Ser Ser
195 200 205

Ser Asn Pro Cys Leu Gln Cys Thr Cys Leu Arg Ser Arg Val Arg Cys
210 215 220

Met Ala Leu Lys Cys Pro Pro Ser Pro Cys Pro Glu Pro Val Leu Arg
225 230 235 240

Pro Gly His Cys Cys Pro Thr Cys Gln Gly Cys Thr Glu Gly Gly Ser
245 250 255

His Trp Glu His Gly Gln Glu Trp Thr Thr Pro Gly Asp Pro Cys Arg
260 265 270

Ile Cys Arg Cys Leu Glu Gly His Ile Gln Cys Arg Gln Arg Glu Cys
275 280 285

Ala Ser Leu Cys Pro Tyr Pro Ala Arg Pro Leu Pro Gly Thr Cys Cys
290 295 300

Pro Val Cys Asp Gly Cys Phe Leu Asn Gly Arg Glu His Arg Ser Gly
305 310 315 320

Glu Pro Val Gly Ser Gly Asp Pro Cys Ser His Cys Arg Cys Ala Asn
325 330 335

Gly Ser Val Gln Cys Glu Pro Leu Pro Cys Pro Pro Val Pro Cys Arg
340 345 350

His Pro Gly Lys Ile Pro Gly Gln Cys Cys Pro Val Cys Asp Gly Cys
355 360 365

Glu Tyr Gln Gly His Gln Tyr Gln Ser Gln Glu Thr Phe Arg Leu Gln
370 375 380

Glu Arg Gly Leu Cys Val Arg Cys Ser Cys Gln Ala Gly Glu Val Ser
385 390 395 400

Cys Glu Glu Gln Glu Cys Pro Val Thr Pro Cys Ala Leu Pro Ala Ser
405 410 415

Gly Arg Gln Leu Cys Pro Ala Cys Glu Leu Asp Gly Glu Glu Phe Ala
420 425 430

Glu Gly Val Gln Trp Glu Pro Asp Gly Arg Pro Cys Thr Ala Cys Val
435 440 445

Cys Gln Asp Gly Val Pro Lys Cys Gly Ala Val Leu Cys Pro Pro Ala
450 455 460

Pro Cys Gln His Pro Thr Gln Pro Pro Gly Ala Cys Cys Pro Ser Cys
465 470 475 480

Asp Ser Cys Thr Tyr His Ser Gln Val Tyr Ala Asn Gly Gln Asn Phe
485 490 495

Thr Asp Ala Asp Ser Pro Cys His Ala Cys His Cys Gln Asp Gly Thr
500 505 510

Val Thr Cys Ser Leu Val Asp Cys Pro Pro Thr Thr Cys Ala Arg Pro
515 520 525

Gln Ser Gly Pro Gly Gln Cys Cys Pro Arg Cys Pro Asp Cys Ile Leu
530 535 540

Glu Glu Glu Val Phe Val Asp Gly Glu Ser Phe Ser His Pro Arg Asp
545 550 555 560

Pro Cys Gln Glu Cys Arg Cys Gln Glu Gly His Ala His Cys Gln Pro
565 570 575

Arg Pro Cys Pro Arg Ala Pro Cys Ala His Pro Leu Pro Gly Thr Cys
580 585 590

Cys Pro Asn Asp Cys Ser Gly Cys Ala Phe Gly Gly Lys Glu Tyr Pro
595 600 605

Ser Gly Ala Asp Phe Pro His Pro Ser Asp Pro Cys Arg Leu Cys Arg
610 615 620

Cys Leu Ser Gly Asn Val Gln Cys Leu Ala Arg Arg Cys Val Pro Leu
625 630 635 640

Pro Cys Pro Glu Pro Val Leu Leu Pro Gly Glu Cys Cys Pro Gln Cys
645 650 655

Pro Ala Ala Pro Ala Pro Ala Gly Cys Pro Arg Pro Gly Ala Ala His
660 665 670

Ala Arg His Gln Glu Tyr Phe Ser Pro Pro Gly Asp Pro Cys Arg Arg
675 680 685

Cys Leu Cys Leu Asp Gly Ser Val Ser Cys Gln Arg Leu Pro Cys Pro
690 695 700

Pro Ala Pro Cys Ala His Pro Arg Gln Gly Pro Cys Cys Pro Ser Cys
705 710 715 720

Asp Gly Cys Leu Tyr Gln Gly Lys Glu Phe Ala Ser Gly Glu Arg Phe
725 730 735

Pro Ser Pro Thr Ala Ala Cys His Leu Cys Leu Cys Trp Glu Gly Ser
740 745 750

Val Ser Cys Glu Pro Lys Ala Cys Ala Pro Ala Leu Cys Pro Phe Pro
755 760 765

Ala Arg Gly Asp Cys Cys Pro Asp Cys Asp Gly Cys Glu Tyr Leu Gly
770 775 780

Glu Ser Tyr Leu Ser Asn Gln Glu Phe Pro Asp Pro Arg Glu Pro Cys
785 790 795 800

Asn Leu Cys Thr Cys Leu Gly Gly Phe Val Thr Cys Gly Arg Arg Pro
805 810 815

Cys Glu Pro Pro Gly Cys Ser His Pro Leu Ile Pro Ser Gly His Cys
820 825 830

Cys Pro Thr Cys Gln Gly Cys Arg Tyr His Gly Val Thr Thr Ala Ser
835 840 845

Gly Glu Thr Leu Pro Asp Pro Leu Asp Pro Thr Cys Ser Leu Cys Thr
850 855 860

Cys Gln Glu Gly Ser Met Arg Cys Gln Lys Lys Pro Cys Ala Pro Ala
865 870 875 880

Leu Cys Pro His Pro Ser Pro Gly Pro Cys Phe Cys Pro Val Cys His
885 890 895

Ser Cys Leu Ser Gln Gly Arg Glu His Gln Asp Gly Glu Glu Phe Glu
900 905 910

Gly Pro Ala Gly Ser Cys Glu Trp Cys Arg Cys Gln Ala Gly Gln Val
915 920 925

Ser Cys Val Arg Leu Gln Cys Pro Pro Leu Pro Cys Lys Leu Gln Val
930 935 940

Thr Glu Arg Gly Ser Cys Cys Pro Arg Cys Arg Gly Cys Leu Ala His
945 950 955 960

Gly Glu Glu His Pro Glu Gly Ser Arg Trp Val Pro Pro Asp Ser Ala
965 970 975

Cys Ser Ser Cys Val Cys His Glu Gly Val Val Thr Cys Ala Arg Ile
980 985 990

Gln Cys Ile Ser Ser Cys Ala Gln Pro Arg Gln Gly Pro His Asp Cys
995 1000 1005

Cys Pro Gln Cys Ser Asp Cys Glu His Glu Gly Arg Lys Tyr Glu Pro
1010 1015 1020

Gly Glu Ser Phe Gln Pro Gly Ala Asp Pro Cys Glu Val Cys Ile Cys
1025 1030 1035 1040

Glu Pro Gln Pro Glu Gly Pro Pro Ser Leu Arg Cys His Arg Arg Gln
1045 1050 1055

Cys Pro Ser Leu Val Gly Cys Pro Pro Ser Gln Leu Leu Pro Pro Gly
1060 1065 1070

Pro Gln His Cys Cys Pro Thr Cys Ala Glu Ala Leu Ser Asn Cys Ser
1075 1080 1085

Glu Gly Leu Leu Gly Ser Glu Leu Ala Pro Pro Asp Pro Cys Tyr Thr
1090 1095 1100

Cys Gln Cys Gln Asp Leu Thr Trp Leu Cys Ile His Gln Ala Cys Pro
1105 1110 1115 1120

Glu Leu Ser Cys Pro Leu Ser Glu Arg His Thr Pro Pro Gly Ser Cys
1125 1130 1135

Cys Pro Val Cys Arg Glu Cys Val Val Glu Ala Glu Gly Arg Arg Val
1140 1145 1150

Ala Asp Gly Glu Ser Trp Arg Asp Pro Ser Asn Ala Cys Ile Ala Cys
1155 1160 1165

Thr Cys His Arg Gly His Val Glu Cys His Leu Glu Glu Cys Gln Ala
1170 1175 1180

Leu Ser Cys Pro His Gly Trp Ala Lys Val Pro Gln Ala Asp Ser Cys
1185 1190 1195 1200

Cys Glu Arg Cys Gln Ala Pro Thr Gln Ser Cys Val His Gln Gly Arg
1205 1210 1215

Glu Val Ala Ser Gly Glu Arg Trp Thr Val Asp Thr Cys Thr Ser Cys
1220 1225 1230

Ser Cys Met Ala Gly Thr Val Arg Cys Gln Ser Gln Arg Cys Ser Pro
1235 1240 1245

Leu Ser Cys Gly Pro Asp Lys Ala Pro Ala Leu Ser Pro Gly Ser Cys
1250 1255 1260

Cys Pro Arg Cys Leu Pro Arg Pro Ala Ser Cys Met Ala Phe Gly Asp
1265 1270 1275 1280

Pro His Tyr Arg Thr Phe Asp Gly Arg Leu Leu His Phe Gln Gly Ser
1285 1290 1295

Cys Ser Tyr Val Leu Ala Lys Asp Cys His Ser Gly Asp Phe Ser Val
1300 1305 1310

His Val Thr Asn Asp Asp Arg Gly Arg Ser Gly Val Ala Trp Thr Gln
1315 1320 1325

Glu Val Ala Val Leu Leu Gly Asp Met Ala Val Arg Leu Leu Gln Asp
1330 1335 1340

Gly Ala Val Thr Val Asp Gly His Pro Val Ala Leu Pro Phe Leu Gln
1345 1350 1355 1360

Glu Pro Leu Leu Tyr Val Glu Leu Arg Gly His Thr Val Ile Leu His
1365 1370 1375

Ala Gln Pro Gly Leu Gln Val Leu Trp Asp Gly Gln Ser Gln Val Glu
1380 1385 1390

Val Ser Val Pro Gly Ser Tyr Gln Gly Arg Thr Cys Gly Leu Cys Gly
1395 1400 1405

Asn Phe Asn Gly Phe Ala Gln Asp Asp Leu Gln Gly Pro Glu Gly Leu
1410 1415 1420

Leu Leu Pro Ser Glu Ala Ala Phe Gly Asn Ser Trp Gln Val Ser Glu
1425 1430 1435 1440

Gly Leu Trp Pro Gly Arg Pro Cys Ser Ala Gly Arg Glu Val Asp Pro
1445 1450 1455

Cys Arg Ala Ala Gly Tyr Arg Ala Arg Arg Glu Ala Asn Ala Arg Cys
1460 1465 1470

Gly Val Leu Lys Ser Ser Pro Phe Ser Arg Cys His Ala Val Val Pro
1475 1480 1485

Pro Glu Pro Phe Phe Ala Ala Cys Val Tyr Asp Leu Cys Ala Cys Gly
1490 1495 1500

Pro Gly Ser Ser Ala Asp Ala Cys Leu Cys Asp Ala Leu Glu Ala Tyr
1505 1510 1515 1520

Ala Ser His Cys Arg Gln Ala Gly Val Thr Pro Thr Trp Arg Gly Pro
1525 1530 1535

Thr Leu Cys Val Val Gly Cys Pro Leu Glu Arg Gly Phe Val Phe Asp
1540 1545 1550

Glu Cys Gly Pro Pro Cys Pro Arg Thr Cys Phe Asn Gln His Ile Pro
1555 1560 1565

Leu Gly Glu Leu Ala Ala His Cys Val Arg Pro Cys Val Pro Gly Cys
1570 1575 1580

Gln Cys Pro Ala Gly Leu Val Glu His Glu Ala His Cys Ile Pro Pro
1585 1590 1595 1600

Glu Ala Cys Pro Gln Val Leu Leu Thr Gly Asp Gln Pro Leu Gly Ala
1605 1610 1615

Arg Pro Ser Pro Ser Arg Glu Pro Gln Glu Thr Pro
1620 1625



3
4779
DNA
homo sapiens

3

atggccgggg tcggggccgc tgcgctgtcc cttctcctgc acctcggggc cctggcgctg 60

gccgcgggcg cggaaggtgg ggctgtcccc agggagcccc ctgggcagca gacaactgcc 120

cattcctcag tccttgctgg gaactcccag gagcagtggc accccctgcg agagtggctg 180

gggcgactgg aggctgcagt gatggagctc agagaacaga ataaggacct gcagacgagg 240

gtgaggcagc tggagtcctg tgagtgccac cctgcatctc cccagtgctg ggggctgggg 300

cgtgcctggc ccgagggggc acgctgggag cctgacgcct gcacagcctg cgtctgccag 360

gatggggccg ctcactgtgg cccccaagca cacctgcccc attgcagggg ctgcagccaa 420

aatggccaga cctacggcaa cggggagacc ttctccccag atgcctgcac cacctgccgc 480

tgtctggaag gtaccatcac ttgcaaccag aagccatgcc caagaggacc ctgccctgag 540

ccaggagcat gctgcccgca ctgtaagcca ggctgtgatt atgaggggca gctttatgag 600

gagggggtca ccttcctgtc cagctccaac ccttgtctac agtgcacctg cctgaggagc 660

cgagttcgct gcatggccct gaagtgcccg cctagcccct gcccagagcc agtgctgagg 720

cctgggcact gctgcccaac ctgccaaggc tgcacagaag gtggctctca ctgggaacat 780

ggccaagagt ggacaacacc tggggacccc tgccgaatct gccggtgcct ggagggtcac 840

atccagtgcc gccagcgaga atgtgccagc ctgtgtccat acccagcccg gcccctccca 900

ggcacctgct gccctgtgtg tgatggctgt ttcctaaacg ggcgggagca ccgcagcggg 960

gagcctgtgg gctcagggga cccctgctcg cactgccgct gtgctaatgg gagtgtccag 1020

tgtgagcctc tgccctgccc gccagtgccc tgcagacacc caggcaagat ccctgggcag 1080

tgctgccctg tctgcgatgg ctgtgagtac cagggacacc agtatcagag ccaggagacc 1140

ttcagactcc aagagcgggg cctctgtgtc cgctgctcct gccaggctgg cgaggtctcc 1200

tgtgaggagc aggagtgccc agtcaccccc tgtgccctgc ctgcctctgg ccgccagctc 1260

tgcccagcct gtgagctgga tggagaggag tttgctgagg gagtccagtg ggagcctgat 1320

ggtcggccct gcaccgcctg cgtctgtcaa gatggggtac ccaagtgcgg ggctgtgctc 1380

tgccccccag ccccctgcca gcaccccacc cagccccctg gtgcctgctg ccccagctgt 1440

gacagctgca cctaccacag ccaagtgtat gccaatgggc agaacttcac ggatgcagac 1500

agcccttgcc atgcctgcca ctgtcaggat ggaactgtga catgctcctt ggttgactgc 1560

cctcccacga cctgtgccag gccccagagt ggaccaggcc agtgttgccc caggtgccca 1620

gactgcatcc tggaggaaga ggtgtttgtg gacggcgaga gcttctccca cccccgagac 1680

ccctgccagg agtgccgatg ccaggaaggc catgcccact gccagcctcg cccctgcccc 1740

agggccccct gtgcccaccc gctgcctggg acctgctgcc cgaacgactg cagcggctgt 1800

gcctttggcg ggaaagagta ccccagcgga gcggacttcc cccacccctc tgacccctgc 1860

cgtctgtgtc gctgtctgag cggcaacgtg cagtgcctgg cccgccgctg cgtgccgctg 1920

ccctgtccag agcctgtcct gctgccggga gagtgctgcc cgcagtgccc agccgcccca 1980

gcccccgccg gctgcccacg gcccggcgcg gcccacgccc gccaccagga gtacttctcc 2040

ccgcccggcg atccctgccg ccgctgcctc tgcctcgacg gctccgtgtc ctgccagcgg 2100

ctgccctgcc cgcccgcgcc ctgcgcgcac ccgcgccagg ggccttgctg cccctcctgc 2160

gacggctgcc tgtaccaggg gaaggagttt gccagcgggg agcgcttccc atcgcccact 2220

gctgcctgcc acctctgcct ttgctgggag ggcagcgtga gctgcgagcc caaggcatgt 2280

gcccctgcac tgtgcccctt ccctgccagg ggcgactgct gccctgactg tgatggctgt 2340

gagtacctgg gggagtccta cctgagtaac caggagttcc cagacccccg agaaccctgc 2400

aacctgtgta cctgtcttgg aggcttcgtg acctgcggcc gccggccctg tgagcctccg 2460

ggctgcagcc acccactcat cccctctggg cactgctgcc cgacctgcca gggatgccgc 2520

taccatggcg tcactactgc ctccggagag acccttcctg acccacttga ccctacctgc 2580

tccctctgca cctgccaggg ccgggagcac caggatgggg aggagtttga gggaccagca 2640

ggcagctgtg agtggtgtcg ctgtcaggct ggccaggtca gctgtgtgcg gctgcagtgc 2700

ccaccccttc cctgcaagct ccaggtcacc gagcggggga gctgctgccc tcgctgcaga 2760

ggctgcctgg ctcatgggga agagcacccc gaaggcagta gatgggtgcc ccccgacagt 2820

gcctgctcct cctgtgtgtg tcacgagggc gtcgtcacct gtgcacgcat ccagtgcatc 2880

agctcttgcg cccagccccg ccaagggccc catgactgct gtcctcaatg ctctgactgt 2940

gagcatgagg gccggaagta cgagcctggg gagagcttcc agcctggggc agacccctgt 3000

gaagtgtgca tctgcgagcc acagcctgag gggcctccca gccttcgctg tcaccggcgg 3060

cagtgtccca gcctggtggg ctgccccccc agccagctcc tgccccctgg gccccagcac 3120

tgctgtccca cctgtgccga ggccttgagt aactgttcag agggcctgct gggatctgag 3180

ctagccccac cagacccctg ctacacgtgc cagtgccagg acctgacatg gctctgcatc 3240

caccaggctt gtcctgagct cagctgtccc ctctcagagc gccacactcc ccctgggagc 3300

tgctgccccg tatgccggga atgtgtggtg gaggccgagg gccggagagt ggcagatgga 3360

gagagctggc gggaccccag caatgcgtgc atcgcctgca cctgccatcg gggccatgtg 3420

gagtgccacc tcgaggagtg ccaggccctc tcctgccccc atggctgggc gaaggtgccc 3480

caggctgaca gctgctgtga gcgatgccaa gctcccaccc agtcctgcgt gcaccagggc 3540

cgtgaggtgg cctctggaga gcgctggact gtggacacct gcaccagctg ctcctgcatg 3600

gcgggcaccg tgcgttgcca gagccagcgc tgctcaccgc tctcgtgtgg ccccgacaag 3660

gcccctgccc tgagtcctgg cagctgctgc ccccgctgcc tgcctcggcc cgcttcctgc 3720

atggccttcg gagaccccca ttaccgcacc ttcgacggcc gcctgctgca cttccagggc 3780

agttgcagct atgtgctggc caaggactgc cacagcgggg acttcagtgt gcacgtgacc 3840

aatgatgacc ggggccggag cggtgtggcc tggacccagg aggtggcggt gctgctggga 3900

gacatggccg tgcggctgct gcaggacggg gcagtcacgg tggatgggca cccggtggcc 3960

ttgcccttcc tgcaggagcc gctgctgtat gtggagctgc gaggacacac tgtgatcctg 4020

cacgcccagc ccgggctcca ggtgctgtgg gatgggcagt cccaggtgga ggtgagcgta 4080

cctggctcct accagggccg gacttgtggg ctctgtggga acttcaatgg ctttgcccag 4140

gacgatctgc agggccctga ggggctgctc ctgccctcgg aggctgcgtt tgggaatagc 4200

tggcaggtct cagaggggct gtggcctggc cggccctgtt ctgcaggccg agaggtggat 4260

ccgtgccggg cagcaggtta ccgtgccagg cgtgaggcca atgcccggtg tggggtgctg 4320

aagtcctccc cattcagtcg ctgccatgct gtggtgccac cggagccctt ctttgccgcc 4380

tgtgtgtatg acctgtgtgc ctgtggccct ggctcctccg ctgatgcctg cctctgtgat 4440

gccctggaag cctacgccag tcactgtcgc caggcaggag tgacacctac ctggcgaggc 4500

cccacgctgt gtgtggtagg ctgccccctg gagcgtggct tcgtgtttga tgagtgcggc 4560

ccaccctgtc cccgcacctg cttcaatcag catatccccc tgggggagct ggcagcccac 4620

tgcgtgaggc cctgcgtgcc cggctgccag tgccctgcag gcctggtgga gcatgaggcc 4680

cactgcatcc cacccgaggc ctgcccccaa gtcctgctca ctggagacca gccacttggt 4740

gctcggccca gccccagccg ggagccccag gagacaccc 4779



4
1593
PRT
homo sapiens

4

Met Ala Gly Val Gly Ala Ala Ala Leu Ser Leu Leu Leu His Leu Gly
1 5 10 15

Ala Leu Ala Leu Ala Ala Gly Ala Glu Gly Gly Ala Val Pro Arg Glu
20 25 30

Pro Pro Gly Gln Gln Thr Thr Ala His Ser Ser Val Leu Ala Gly Asn
35 40 45

Ser Gln Glu Gln Trp His Pro Leu Arg Glu Trp Leu Gly Arg Leu Glu
50 55 60

Ala Ala Val Met Glu Leu Arg Glu Gln Asn Lys Asp Leu Gln Thr Arg
65 70 75 80

Val Arg Gln Leu Glu Ser Cys Glu Cys His Pro Ala Ser Pro Gln Cys
85 90 95

Trp Gly Leu Gly Arg Ala Trp Pro Glu Gly Ala Arg Trp Glu Pro Asp
100 105 110

Ala Cys Thr Ala Cys Val Cys Gln Asp Gly Ala Ala His Cys Gly Pro
115 120 125

Gln Ala His Leu Pro His Cys Arg Gly Cys Ser Gln Asn Gly Gln Thr
130 135 140

Tyr Gly Asn Gly Glu Thr Phe Ser Pro Asp Ala Cys Thr Thr Cys Arg
145 150 155 160

Cys Leu Glu Gly Thr Ile Thr Cys Asn Gln Lys Pro Cys Pro Arg Gly
165 170 175

Pro Cys Pro Glu Pro Gly Ala Cys Cys Pro His Cys Lys Pro Gly Cys
180 185 190

Asp Tyr Glu Gly Gln Leu Tyr Glu Glu Gly Val Thr Phe Leu Ser Ser
195 200 205

Ser Asn Pro Cys Leu Gln Cys Thr Cys Leu Arg Ser Arg Val Arg Cys
210 215 220

Met Ala Leu Lys Cys Pro Pro Ser Pro Cys Pro Glu Pro Val Leu Arg
225 230 235 240

Pro Gly His Cys Cys Pro Thr Cys Gln Gly Cys Thr Glu Gly Gly Ser
245 250 255

His Trp Glu His Gly Gln Glu Trp Thr Thr Pro Gly Asp Pro Cys Arg
260 265 270

Ile Cys Arg Cys Leu Glu Gly His Ile Gln Cys Arg Gln Arg Glu Cys
275 280 285

Ala Ser Leu Cys Pro Tyr Pro Ala Arg Pro Leu Pro Gly Thr Cys Cys
290 295 300

Pro Val Cys Asp Gly Cys Phe Leu Asn Gly Arg Glu His Arg Ser Gly
305 310 315 320

Glu Pro Val Gly Ser Gly Asp Pro Cys Ser His Cys Arg Cys Ala Asn
325 330 335

Gly Ser Val Gln Cys Glu Pro Leu Pro Cys Pro Pro Val Pro Cys Arg
340 345 350

His Pro Gly Lys Ile Pro Gly Gln Cys Cys Pro Val Cys Asp Gly Cys
355 360 365

Glu Tyr Gln Gly His Gln Tyr Gln Ser Gln Glu Thr Phe Arg Leu Gln
370 375 380

Glu Arg Gly Leu Cys Val Arg Cys Ser Cys Gln Ala Gly Glu Val Ser
385 390 395 400

Cys Glu Glu Gln Glu Cys Pro Val Thr Pro Cys Ala Leu Pro Ala Ser
405 410 415

Gly Arg Gln Leu Cys Pro Ala Cys Glu Leu Asp Gly Glu Glu Phe Ala
420 425 430

Glu Gly Val Gln Trp Glu Pro Asp Gly Arg Pro Cys Thr Ala Cys Val
435 440 445

Cys Gln Asp Gly Val Pro Lys Cys Gly Ala Val Leu Cys Pro Pro Ala
450 455 460

Pro Cys Gln His Pro Thr Gln Pro Pro Gly Ala Cys Cys Pro Ser Cys
465 470 475 480

Asp Ser Cys Thr Tyr His Ser Gln Val Tyr Ala Asn Gly Gln Asn Phe
485 490 495

Thr Asp Ala Asp Ser Pro Cys His Ala Cys His Cys Gln Asp Gly Thr
500 505 510

Val Thr Cys Ser Leu Val Asp Cys Pro Pro Thr Thr Cys Ala Arg Pro
515 520 525

Gln Ser Gly Pro Gly Gln Cys Cys Pro Arg Cys Pro Asp Cys Ile Leu
530 535 540

Glu Glu Glu Val Phe Val Asp Gly Glu Ser Phe Ser His Pro Arg Asp
545 550 555 560

Pro Cys Gln Glu Cys Arg Cys Gln Glu Gly His Ala His Cys Gln Pro
565 570 575

Arg Pro Cys Pro Arg Ala Pro Cys Ala His Pro Leu Pro Gly Thr Cys
580 585 590

Cys Pro Asn Asp Cys Ser Gly Cys Ala Phe Gly Gly Lys Glu Tyr Pro
595 600 605

Ser Gly Ala Asp Phe Pro His Pro Ser Asp Pro Cys Arg Leu Cys Arg
610 615 620

Cys Leu Ser Gly Asn Val Gln Cys Leu Ala Arg Arg Cys Val Pro Leu
625 630 635 640

Pro Cys Pro Glu Pro Val Leu Leu Pro Gly Glu Cys Cys Pro Gln Cys
645 650 655

Pro Ala Ala Pro Ala Pro Ala Gly Cys Pro Arg Pro Gly Ala Ala His
660 665 670

Ala Arg His Gln Glu Tyr Phe Ser Pro Pro Gly Asp Pro Cys Arg Arg
675 680 685

Cys Leu Cys Leu Asp Gly Ser Val Ser Cys Gln Arg Leu Pro Cys Pro
690 695 700

Pro Ala Pro Cys Ala His Pro Arg Gln Gly Pro Cys Cys Pro Ser Cys
705 710 715 720

Asp Gly Cys Leu Tyr Gln Gly Lys Glu Phe Ala Ser Gly Glu Arg Phe
725 730 735

Pro Ser Pro Thr Ala Ala Cys His Leu Cys Leu Cys Trp Glu Gly Ser
740 745 750

Val Ser Cys Glu Pro Lys Ala Cys Ala Pro Ala Leu Cys Pro Phe Pro
755 760 765

Ala Arg Gly Asp Cys Cys Pro Asp Cys Asp Gly Cys Glu Tyr Leu Gly
770 775 780

Glu Ser Tyr Leu Ser Asn Gln Glu Phe Pro Asp Pro Arg Glu Pro Cys
785 790 795 800

Asn Leu Cys Thr Cys Leu Gly Gly Phe Val Thr Cys Gly Arg Arg Pro
805 810 815

Cys Glu Pro Pro Gly Cys Ser His Pro Leu Ile Pro Ser Gly His Cys
820 825 830

Cys Pro Thr Cys Gln Gly Cys Arg Tyr His Gly Val Thr Thr Ala Ser
835 840 845

Gly Glu Thr Leu Pro Asp Pro Leu Asp Pro Thr Cys Ser Leu Cys Thr
850 855 860

Cys Gln Gly Arg Glu His Gln Asp Gly Glu Glu Phe Glu Gly Pro Ala
865 870 875 880

Gly Ser Cys Glu Trp Cys Arg Cys Gln Ala Gly Gln Val Ser Cys Val
885 890 895

Arg Leu Gln Cys Pro Pro Leu Pro Cys Lys Leu Gln Val Thr Glu Arg
900 905 910

Gly Ser Cys Cys Pro Arg Cys Arg Gly Cys Leu Ala His Gly Glu Glu
915 920 925

His Pro Glu Gly Ser Arg Trp Val Pro Pro Asp Ser Ala Cys Ser Ser
930 935 940

Cys Val Cys His Glu Gly Val Val Thr Cys Ala Arg Ile Gln Cys Ile
945 950 955 960

Ser Ser Cys Ala Gln Pro Arg Gln Gly Pro His Asp Cys Cys Pro Gln
965 970 975

Cys Ser Asp Cys Glu His Glu Gly Arg Lys Tyr Glu Pro Gly Glu Ser
980 985 990

Phe Gln Pro Gly Ala Asp Pro Cys Glu Val Cys Ile Cys Glu Pro Gln
995 1000 1005

Pro Glu Gly Pro Pro Ser Leu Arg Cys His Arg Arg Gln Cys Pro Ser
1010 1015 1020

Leu Val Gly Cys Pro Pro Ser Gln Leu Leu Pro Pro Gly Pro Gln His
1025 1030 1035 1040

Cys Cys Pro Thr Cys Ala Glu Ala Leu Ser Asn Cys Ser Glu Gly Leu
1045 1050 1055

Leu Gly Ser Glu Leu Ala Pro Pro Asp Pro Cys Tyr Thr Cys Gln Cys
1060 1065 1070

Gln Asp Leu Thr Trp Leu Cys Ile His Gln Ala Cys Pro Glu Leu Ser
1075 1080 1085

Cys Pro Leu Ser Glu Arg His Thr Pro Pro Gly Ser Cys Cys Pro Val
1090 1095 1100

Cys Arg Glu Cys Val Val Glu Ala Glu Gly Arg Arg Val Ala Asp Gly
1105 1110 1115 1120

Glu Ser Trp Arg Asp Pro Ser Asn Ala Cys Ile Ala Cys Thr Cys His
1125 1130 1135

Arg Gly His Val Glu Cys His Leu Glu Glu Cys Gln Ala Leu Ser Cys
1140 1145 1150

Pro His Gly Trp Ala Lys Val Pro Gln Ala Asp Ser Cys Cys Glu Arg
1155 1160 1165

Cys Gln Ala Pro Thr Gln Ser Cys Val His Gln Gly Arg Glu Val Ala
1170 1175 1180

Ser Gly Glu Arg Trp Thr Val Asp Thr Cys Thr Ser Cys Ser Cys Met
1185 1190 1195 1200

Ala Gly Thr Val Arg Cys Gln Ser Gln Arg Cys Ser Pro Leu Ser Cys
1205 1210 1215

Gly Pro Asp Lys Ala Pro Ala Leu Ser Pro Gly Ser Cys Cys Pro Arg
1220 1225 1230

Cys Leu Pro Arg Pro Ala Ser Cys Met Ala Phe Gly Asp Pro His Tyr
1235 1240 1245

Arg Thr Phe Asp Gly Arg Leu Leu His Phe Gln Gly Ser Cys Ser Tyr
1250 1255 1260

Val Leu Ala Lys Asp Cys His Ser Gly Asp Phe Ser Val His Val Thr
1265 1270 1275 1280

Asn Asp Asp Arg Gly Arg Ser Gly Val Ala Trp Thr Gln Glu Val Ala
1285 1290 1295

Val Leu Leu Gly Asp Met Ala Val Arg Leu Leu Gln Asp Gly Ala Val
1300 1305 1310

Thr Val Asp Gly His Pro Val Ala Leu Pro Phe Leu Gln Glu Pro Leu
1315 1320 1325

Leu Tyr Val Glu Leu Arg Gly His Thr Val Ile Leu His Ala Gln Pro
1330 1335 1340

Gly Leu Gln Val Leu Trp Asp Gly Gln Ser Gln Val Glu Val Ser Val
1345 1350 1355 1360

Pro Gly Ser Tyr Gln Gly Arg Thr Cys Gly Leu Cys Gly Asn Phe Asn
1365 1370 1375

Gly Phe Ala Gln Asp Asp Leu Gln Gly Pro Glu Gly Leu Leu Leu Pro
1380 1385 1390

Ser Glu Ala Ala Phe Gly Asn Ser Trp Gln Val Ser Glu Gly Leu Trp
1395 1400 1405

Pro Gly Arg Pro Cys Ser Ala Gly Arg Glu Val Asp Pro Cys Arg Ala
1410 1415 1420

Ala Gly Tyr Arg Ala Arg Arg Glu Ala Asn Ala Arg Cys Gly Val Leu
1425 1430 1435 1440

Lys Ser Ser Pro Phe Ser Arg Cys His Ala Val Val Pro Pro Glu Pro
1445 1450 1455

Phe Phe Ala Ala Cys Val Tyr Asp Leu Cys Ala Cys Gly Pro Gly Ser
1460 1465 1470

Ser Ala Asp Ala Cys Leu Cys Asp Ala Leu Glu Ala Tyr Ala Ser His
1475 1480 1485

Cys Arg Gln Ala Gly Val Thr Pro Thr Trp Arg Gly Pro Thr Leu Cys
1490 1495 1500

Val Val Gly Cys Pro Leu Glu Arg Gly Phe Val Phe Asp Glu Cys Gly
1505 1510 1515 1520

Pro Pro Cys Pro Arg Thr Cys Phe Asn Gln His Ile Pro Leu Gly Glu
1525 1530 1535

Leu Ala Ala His Cys Val Arg Pro Cys Val Pro Gly Cys Gln Cys Pro
1540 1545 1550

Ala Gly Leu Val Glu His Glu Ala His Cys Ile Pro Pro Glu Ala Cys
1555 1560 1565

Pro Gln Val Leu Leu Thr Gly Asp Gln Pro Leu Gly Ala Arg Pro Ser
1570 1575 1580

Pro Ser Arg Glu Pro Gln Glu Thr Pro
1585 1590



5
3173
DNA
homo sapiens

5

atgcccactg ccagcctcgc ccctgcccca gggccccctg tgcccacccg ctgcctggga 60

cctgctgccc gaacgactgc agcggctgtg cctttggcgg gaaagagtac cccagcggag 120

cggacttccc ccacccctct gacccctgcc gtctgtgtcg ctgtctgagc ggcaacgtgc 180

agtgcctggc ccgccgctgc gtgccgctgc cctgtccaga gcctgtcctg ctgccgggag 240

agtgctgccc gcagtgccca gccgccccag cccccgccgg ctgcccacgg cccggcgcgg 300

cccacgcccg ccaccaggag tacttctccc cgcccggcga tccctgccgc cgctgcctct 360

gcctcgacgg ctccgtgtcc tgccagcggc tgccctgccc gcccgcgccc tgcgcgcacc 420

cgcgccaggg gccttgctgc ccctcctgcg acggctgcct gtaccagggg aaggagtttg 480

ccagcgggga gcgcttccca tcgcccactg ctgcctgcca cctctgcctt tgctgggagg 540

gcagcgtgag ctgcgagccc aaggcatgtg cccctgcact gtgccccttc cctgccaggg 600

gcgactgctg ccctgactgt gatggctgtg agtacctggg ggagtcctac ctgagtaacc 660

aggagttccc agacccccga gaaccctgca acctgtgtac ctgtcttgga ggcttcgtga 720

cctgcggccg ccggccctgt gagcctccgg gctgcagcca cccactcatc ccctctgggc 780

actgctgccc gacctgccag ggatgccgct accatggcgt cactactgcc tccggagaga 840

cccttcctga cccacttgac cctacctgct ccctctgcac ctgccaggaa ggttccatgc 900

gctgccaaaa gaagccatgt gccccagctc tctgccccca cccctctcca ggcccctgct 960

tctgccctgt ttgccacagt tgtctctctc agggccggga gcaccaggat ggggaggagt 1020

ttgagggacc agcaggcagc tgtgagtggt gtcgctgtca ggctggccag gtcagctgtg 1080

tgcggctgca gtgcccaccc cttccctgca agctccaggt caccgagcgg gggagctgct 1140

gccctcgctg cagaggctgc ctggctcatg gggaagagca ccccgaaggc agtagatggg 1200

tgccccccga cagtgcctgc tcctcctgtg tgtgtcacga gggcgtcgtc acctgtgcac 1260

gcatccagtg catcagctct tgcgcccagc cccgccaagg gccccatgac tgctgtcctc 1320

aatgctctga ctgtgagcat gagggccgga agtacgagcc tggggagagc ttccagcctg 1380

gggcagaccc ctgtgaagtg tgcatctgcg agccacagcc tgaggggcct cccagccttc 1440

gctgtcaccg gcggcagtgt cccagcctgg tgggctgccc ccccagccag ctcctgcccc 1500

ctgggcccca gcactgctgt cccacctgtg ccgaggcctt gagtaactgt tcagagggcc 1560

tgctgggatc tgagctagcc ccaccagacc cctgctacac gtgccagtgc caggacctga 1620

catggctctg catccaccag gcttgtcctg agctcagctg tcccctctca gagcgccaca 1680

ctccccctgg gagctgctgc cccgtatgcc gggaatgtgt ggtggaggcc gagggccgga 1740

gagtggcaga tggagagagc tggcgggacc ccagcaatgc gtgcatcgcc tgcacctgcc 1800

atcggggcca tgtggagtgc cacctcgagg agtgccaggc cctctcctgc ccccatggct 1860

gggcgaaggt gccccaggct gacagctgct gtgagcgatg ccaagctccc acccagtcct 1920

gcgtgcacca gggccgtgag gtggcctctg gagagcgctg gactgtggac acctgcacca 1980

gctgctcctg catggcgggc accgtgcgtt gccagagcca gcgctgctca ccgctctcgt 2040

gtggccccga caaggcccct gccctgagtc ctggcagctg ctgcccccgc tgcctgcctc 2100

ggcccgcttc ctgcatggcc ttcggagacc cccattaccg caccttcgac ggccgcctgc 2160

tgcacttcca gggcagttgc agctatgtgc tggccaagga ctgccacagc ggggacttca 2220

gtgtgcacgt gaccaatgat gaccggggcc ggagcggtgt ggcctggacc caggaggtgg 2280

cggtgctgct gggagacatg gccgtgcggc tgctgcagga cggggcagtc acggtggatg 2340

ggcacccggt ggccttgccc ttcctgcagg agccgctgct gtatgtggag ctgcgaggac 2400

acactgtgat cctgcacgcc cagcccgggc tccaggtgct gtgggatggg cagtcccagg 2460

tggaggtgag cgtacctggc tcctaccagg gccggacttg tgggctctgt gggaacttca 2520

atggctttgc ccaggacgat ctgcagggcc ctgaggggct gctcctgccc tcggaggctg 2580

cgtttgggaa tagctggcag gtctcagagg ggctgtggcc tggccggccc tgttctgcag 2640

gccgagaggt ggatccgtgc cgggcagcag gttaccgtgc caggcgtgag gccaatgccc 2700

ggtgtggggt gctgaagtcc tccccattca gtcgctgcca tgctgtggtg ccaccggagc 2760

ccttctttgc cgcctgtgtg tatgacctgt gtgcctgtgg ccctggctcc tccgctgatg 2820

cctgcctctg tgatgccctg gaagcctacg ccagtcactg tcgccaggca ggagtgacac 2880

ctacctggcg aggccccacg ctgtgtgtgg taggctgccc cctggagcgt ggcttcgtgt 2940

ttgatgagtg cggcccaccc tgtccccgca cctgcttcaa tcagcatatc cccctggggg 3000

agctggcagc ccactgcgtg aggccctgcg tgcccggctg ccagtgccct gcaggcctgg 3060

tggagcatga ggcccactgc atcccacccg aggcctgccc ccaagtcctg ctcactggag 3120

accagccact tggtgctcgg cccagcccca gccgggagcc ccaggagaca ccc 3173



6
1057
PRT
homo sapiens

6

Met Pro Thr Ala Ser Leu Ala Pro Ala Pro Gly Pro Pro Val Pro Thr
1 5 10 15

Arg Cys Leu Gly Pro Ala Ala Arg Thr Thr Ala Ala Ala Val Pro Leu
20 25 30

Ala Gly Lys Ser Thr Pro Ala Glu Arg Thr Ser Pro Thr Pro Leu Thr
35 40 45

Pro Ala Val Cys Val Ala Val Ser Gly Asn Val Gln Cys Leu Ala Arg
50 55 60

Arg Cys Val Pro Leu Pro Cys Pro Glu Pro Val Leu Leu Pro Gly Glu
65 70 75 80

Cys Cys Pro Gln Cys Pro Ala Ala Pro Ala Pro Ala Gly Cys Pro Arg
85 90 95

Pro Gly Ala Ala His Ala Arg His Gln Glu Tyr Phe Ser Pro Pro Gly
100 105 110

Asp Pro Cys Arg Arg Cys Leu Cys Leu Asp Gly Ser Val Ser Cys Gln
115 120 125

Arg Leu Pro Cys Pro Pro Ala Pro Cys Ala His Pro Arg Gln Gly Pro
130 135 140

Cys Cys Pro Ser Cys Asp Gly Cys Leu Tyr Gln Gly Lys Glu Phe Ala
145 150 155 160

Ser Gly Glu Arg Phe Pro Ser Pro Thr Ala Ala Cys His Leu Cys Leu
165 170 175

Cys Trp Glu Gly Ser Val Ser Cys Glu Pro Lys Ala Cys Ala Pro Ala
180 185 190

Leu Cys Pro Phe Pro Ala Arg Gly Asp Cys Cys Pro Asp Cys Asp Gly
195 200 205

Cys Glu Tyr Leu Gly Glu Ser Tyr Leu Ser Asn Gln Glu Phe Pro Asp
210 215 220

Pro Arg Glu Pro Cys Asn Leu Cys Thr Cys Leu Gly Gly Phe Val Thr
225 230 235 240

Cys Gly Arg Arg Pro Cys Glu Pro Pro Gly Cys Ser His Pro Leu Ile
245 250 255

Pro Ser Gly His Cys Cys Pro Thr Cys Gln Gly Cys Arg Tyr His Gly
260 265 270

Val Thr Thr Ala Ser Gly Glu Thr Leu Pro Asp Pro Leu Asp Pro Thr
275 280 285

Cys Ser Leu Cys Thr Cys Gln Glu Gly Ser Met Arg Cys Gln Lys Lys
290 295 300

Pro Cys Ala Pro Ala Leu Cys Pro His Pro Ser Pro Gly Pro Cys Phe
305 310 315 320

Cys Pro Val Cys His Ser Cys Leu Ser Gln Gly Arg Glu His Gln Asp
325 330 335

Gly Glu Glu Phe Glu Gly Pro Ala Gly Ser Cys Glu Trp Cys Arg Cys
340 345 350

Gln Ala Gly Gln Val Ser Cys Val Arg Leu Gln Cys Pro Pro Leu Pro
355 360 365

Cys Lys Leu Gln Val Thr Glu Arg Gly Ser Cys Cys Pro Arg Cys Arg
370 375 380

Gly Cys Leu Ala His Gly Glu Glu His Pro Glu Gly Ser Arg Trp Val
385 390 395 400

Pro Pro Asp Ser Ala Cys Ser Ser Cys Val Cys His Glu Gly Val Val
405 410 415

Thr Cys Ala Arg Ile Gln Cys Ile Ser Ser Cys Ala Gln Pro Arg Gln
420 425 430

Gly Pro His Asp Cys Cys Pro Gln Cys Ser Asp Cys Glu His Glu Gly
435 440 445

Arg Lys Tyr Glu Pro Gly Glu Ser Phe Gln Pro Gly Ala Asp Pro Cys
450 455 460

Glu Val Cys Ile Cys Glu Pro Gln Pro Glu Gly Pro Pro Ser Leu Arg
465 470 475 480

Cys His Arg Arg Gln Cys Pro Ser Leu Val Gly Cys Pro Pro Ser Gln
485 490 495

Leu Leu Pro Pro Gly Pro Gln His Cys Cys Pro Thr Cys Ala Glu Ala
500 505 510

Leu Ser Asn Cys Ser Glu Gly Leu Leu Gly Ser Glu Leu Ala Pro Pro
515 520 525

Asp Pro Cys Tyr Thr Cys Gln Cys Gln Asp Leu Thr Trp Leu Cys Ile
530 535 540

His Gln Ala Cys Pro Glu Leu Ser Cys Pro Leu Ser Glu Arg His Thr
545 550 555 560

Pro Pro Gly Ser Cys Cys Pro Val Cys Arg Glu Cys Val Val Glu Ala
565 570 575

Glu Gly Arg Arg Val Ala Asp Gly Glu Ser Trp Arg Asp Pro Ser Asn
580 585 590

Ala Cys Ile Ala Cys Thr Cys His Arg Gly His Val Glu Cys His Leu
595 600 605

Glu Glu Cys Gln Ala Leu Ser Cys Pro His Gly Trp Ala Lys Val Pro
610 615 620

Gln Ala Asp Ser Cys Cys Glu Arg Cys Gln Ala Pro Thr Gln Ser Cys
625 630 635 640

Val His Gln Gly Arg Glu Val Ala Ser Gly Glu Arg Trp Thr Val Asp
645 650 655

Thr Cys Thr Ser Cys Ser Cys Met Ala Gly Thr Val Arg Cys Gln Ser
660 665 670

Gln Arg Cys Ser Pro Leu Ser Cys Gly Pro Asp Lys Ala Pro Ala Leu
675 680 685

Ser Pro Gly Ser Cys Cys Pro Arg Cys Leu Pro Arg Pro Ala Ser Cys
690 695 700

Met Ala Phe Gly Asp Pro His Tyr Arg Thr Phe Asp Gly Arg Leu Leu
705 710 715 720

His Phe Gln Gly Ser Cys Ser Tyr Val Leu Ala Lys Asp Cys His Ser
725 730 735

Gly Asp Phe Ser Val His Val Thr Asn Asp Asp Arg Gly Arg Ser Gly
740 745 750

Val Ala Trp Thr Gln Glu Val Ala Val Leu Leu Gly Asp Met Ala Val
755 760 765

Arg Leu Leu Gln Asp Gly Ala Val Thr Val Asp Gly His Pro Val Ala
770 775 780

Leu Pro Phe Leu Gln Glu Pro Leu Leu Tyr Val Glu Leu Arg Gly His
785 790 795 800

Thr Val Ile Leu His Ala Gln Pro Gly Leu Gln Val Leu Trp Asp Gly
805 810 815

Gln Ser Gln Val Glu Val Ser Val Pro Gly Ser Tyr Gln Gly Arg Thr
820 825 830

Cys Gly Leu Cys Gly Asn Phe Asn Gly Phe Ala Gln Asp Asp Leu Gln
835 840 845

Gly Pro Glu Gly Leu Leu Leu Pro Ser Glu Ala Ala Phe Gly Asn Ser
850 855 860

Trp Gln Val Ser Glu Gly Leu Trp Pro Gly Arg Pro Cys Ser Ala Gly
865 870 875 880

Arg Glu Val Asp Pro Cys Arg Ala Ala Gly Tyr Arg Ala Arg Arg Glu
885 890 895

Ala Asn Ala Arg Cys Gly Val Leu Lys Ser Ser Pro Phe Ser Arg Cys
900 905 910

His Ala Val Val Pro Pro Glu Pro Phe Phe Ala Ala Cys Val Tyr Asp
915 920 925

Leu Cys Ala Cys Gly Pro Gly Ser Ser Ala Asp Ala Cys Leu Cys Asp
930 935 940

Ala Leu Glu Ala Tyr Ala Ser His Cys Arg Gln Ala Gly Val Thr Pro
945 950 955 960

Thr Trp Arg Gly Pro Thr Leu Cys Val Val Gly Cys Pro Leu Glu Arg
965 970 975

Gly Phe Val Phe Asp Glu Cys Gly Pro Pro Cys Pro Arg Thr Cys Phe
980 985 990

Asn Gln His Ile Pro Leu Gly Glu Leu Ala Ala His Cys Val Arg Pro
995 1000 1005

Cys Val Pro Gly Cys Gln Cys Pro Ala Gly Leu Val Glu His Glu Ala
1010 1015 1020

His Cys Ile Pro Pro Glu Ala Cys Pro Gln Val Leu Leu Thr Gly Asp
1025 1030 1035 1040

Gln Pro Leu Gly Ala Arg Pro Ser Pro Ser Arg Glu Pro Gln Glu Thr
1045 1050 1055

Pro



7
4431
DNA
homo sapiens

7

atggccgggg tcggggccgc tgcgctgtcc cttctcctgc acctcggggc cctggcgctg 60

gccgcgggcg cggaaggtgg ggctgtcccc agggagcccc ctgggcagca gacaactgcc 120

cattcctcag tccttgctgg gaactcccag gagcagtggc accccctgcg agagtggctg 180

gggcgactgg aggctgcagt gatggagctc agagaacaga ataaggacct gcagacgagg 240

gtgaggcagc tggagtcctg tgagtgccac cctgcatctc cccagtgctg ggggctgggg 300

cgtgcctggc ccgagggggc acgctgggag cctgacgcct gcacagcctg cgtctgccag 360

gatggggccg ctcactgtgg cccccaagca cacctgcccg gctgcacaga aggtggctct 420

cactgggaac atggccaaga gtggacaaca cctggggacc cctgccgaat ctgccggtgc 480

ctggagggtc acatccagtg ccgccagcga gaatgtgcca gcctgtgtcc atacccagcc 540

cggcccctcc caggcacctg ctgccctgtg tgtgatggct gtttcctaaa cgggcgggag 600

caccgcagcg gggagcctgt gggctcaggg gacccctgct cgcactgccg ctgtgctaat 660

gggagtgtcc agtgtgagcc tctgccctgc ccgccagtgc cctgcagaca cccaggcaag 720

atccctgggc agtgctgccc tgtctgcgat ggctgtgagt accagggaca ccagtatcag 780

agccaggaga ccttcagact ccaagagcgg ggcctctgtg tccgctgctc ctgccaggct 840

ggcgaggtct cctgtgagga gcaggagtgc ccagtcaccc cctgtgccct gcctgcctct 900

ggccgccagc tctgcccagc ctgtgagctg gatggagagg agtttgctga gggagtccag 960

tgggagcctg atggtcggcc ctgcaccgcc tgcgtctgtc aagatggggt acccaagtgc 1020

ggggctgtgc tctgcccccc agccccctgc cagcacccca cccagccccc tggtgcctgc 1080

tgccccagct gtgacagctg cacctaccac agccaagtgt atgccaatgg gcagaacttc 1140

acggatgcag acagcccttg ccatgcctgc cactgtcagg atggaactgt gacatgctcc 1200

ttggttgact gccctcccac gacctgtgcc aggccccaga gtggaccagg ccagtgttgc 1260

cccaggtgcc cagactgcat cctggaggaa gaggtgtttg tggacggcga gagcttctcc 1320

cacccccgag acccctgcca ggagtgccga tgccaggaag gccatgccca ctgccagcct 1380

cgcccctgcc ccagggcccc ctgtgcccac ccgctgcctg ggacctgctg cccgaacgac 1440

tgcagcggct gtgcctttgg cgggaaagag taccccagcg gagcggactt cccccacccc 1500

tctgacccct gccgtctgtg tcgctgtctg agcggcaacg tgcagtgcct ggcccgccgc 1560

tgcgtgccgc tgccctgtcc agagcctgtc ctgctgccgg gagagtgctg cccgcagtgc 1620

ccagccgccc cagcccccgc cggctgccca cggcccggcg cggcccacgc ccgccaccag 1680

gagtacttct ccccgcccgg cgatccctgc cgccgctgcc tctgcctcga cggctccgtg 1740

tcctgccagc ggctgccctg cccgcccgcg ccctgcgcgc acccgcgcca ggggccttgc 1800

tgcccctcct gcgacggctg cctgtaccag gggaaggagt ttgccagcgg ggagcgcttc 1860

ccatcgccca ctgctgcctg ccacctctgc ctttgctggg agggcagcgt gagctgcgag 1920

cccaaggcat gtgcccctgc actgtgcccc ttccctgcca ggggcgactg ctgccctgac 1980

tgtgatggct gtgagtacct gggggagtcc tacctgagta accaggagtt cccagacccc 2040

cgagaaccct gcaacctgtg tacctgtctt ggaggcttcg tgacctgcgg ccgccggccc 2100

tgtgagcctc cgggctgcag ccacccactc atcccctctg ggcactgctg cccgacctgc 2160

cagggatgcc gctaccatgg cgtcactact gcctccggag agacccttcc tgacccactt 2220

gaccctacct gctccctctg cacctgccag ggccgggagc accaggatgg ggaggagttt 2280

gagggaccag caggcagctg tgagtggtgt cgctgtcagg ctggccaggt cagctgtgtg 2340

cggctgcagt gcccacccct tccctgcaag ctccaggtca ccgagcgggg gagctgctgc 2400

cctcgctgca gaggctgcct ggctcatggg gaagagcacc ccgaaggcag tagatgggtg 2460

ccccccgaca gtgcctgctc ctcctgtgtg tgtcacgagg gcgtcgtcac ctgtgcacgc 2520

atccagtgca tcagctcttg cgcccagccc cgccaagggc cccatgactg ctgtcctcaa 2580

tgctctgact gtgagcatga gggccggaag tacgagcctg gggagagctt ccagcctggg 2640

gcagacccct gtgaagtgtg catctgcgag ccacagcctg aggggcctcc cagccttcgc 2700

tgtcaccggc ggcagtgtcc cagcctggtg ggctgccccc ccagccagct cctgccccct 2760

gggccccagc actgctgtcc cacctgtgcc gaggccttga gtaactgttc agagggcctg 2820

ctgggatctg agctagcccc accagacccc tgctacacgt gccagtgcca ggacctgaca 2880

tggctctgca tccaccaggc ttgtcctgag ctcagctgtc ccctctcaga gcgccacact 2940

ccccctggga gctgctgccc cgtatgccgg gaatgtgtgg tggaggccga gggccggaga 3000

gtggcagatg gagagagctg gcgggacccc agcaatgcgt gcatcgcctg cacctgccat 3060

cggggccatg tggagtgcca cctcgaggag tgccaggccc tctcctgccc ccatggctgg 3120

gcgaaggtgc cccaggctga cagctgctgt gagcgatgcc aagctcccac ccagtcctgc 3180

gtgcaccagg gccgtgaggt ggcctctgga gagcgctgga ctgtggacac ctgcaccagc 3240

tgctcctgca tggcgggcac cgtgcgttgc cagagccagc gctgctcacc gctctcgtgt 3300

ggccccgaca aggcccctgc cctgagtcct ggcagctgct gcccccgctg cctgcctcgg 3360

cccgcttcct gcatggcctt cggagacccc cattaccgca ccttcgacgg ccgcctgctg 3420

cacttccagg gcagttgcag ctatgtgctg gccaaggact gccacagcgg ggacttcagt 3480

gtgcacgtga ccaatgatga ccggggccgg agcggtgtgg cctggaccca ggaggtggcg 3540

gtgctgctgg gagacatggc cgtgcggctg ctgcaggacg gggcagtcac ggtggatggg 3600

cacccggtgg ccttgccctt cctgcaggag ccgctgctgt atgtggagct gcgaggacac 3660

actgtgatcc tgcacgccca gcccgggctc caggtgctgt gggatgggca gtcccaggtg 3720

gaggtgagcg tacctggctc ctaccagggc cggacttgtg ggctctgtgg gaacttcaat 3780

ggctttgccc aggacgatct gcagggccct gaggggctgc tcctgccctc ggaggctgcg 3840

tttgggaata gctggcaggt ctcagagggg ctgtggcctg gccggccctg ttctgcaggc 3900

cgagaggtgg atccgtgccg ggcagcaggt taccgtgcca ggcgtgaggc caatgcccgg 3960

tgtggggtgc tgaagtcctc cccattcagt cgctgccatg ctgtggtgcc accggagccc 4020

ttctttgccg cctgtgtgta tgacctgtgt gcctgtggcc ctggctcctc cgctgatgcc 4080

tgcctctgtg atgccctgga agcctacgcc agtcactgtc gccaggcagg agtgacacct 4140

acctggcgag gccccacgct gtgtgtggta ggctgccccc tggagcgtgg cttcgtgttt 4200

gatgagtgcg gcccaccctg tccccgcacc tgcttcaatc agcatatccc cctgggggag 4260

ctggcagccc actgcgtgag gccctgcgtg cccggctgcc agtgccctgc aggcctggtg 4320

gagcatgagg cccactgcat cccacccgag gcctgccccc aagtcctgct cactggagac 4380

cagccacttg gtgctcggcc cagccccagc cgggagcccc aggagacacc c 4431



8
1477
PRT
homo sapiens

8

Met Ala Gly Val Gly Ala Ala Ala Leu Ser Leu Leu Leu His Leu Gly
1 5 10 15

Ala Leu Ala Leu Ala Ala Gly Ala Glu Gly Gly Ala Val Pro Arg Glu
20 25 30

Pro Pro Gly Gln Gln Thr Thr Ala His Ser Ser Val Leu Ala Gly Asn
35 40 45

Ser Gln Glu Gln Trp His Pro Leu Arg Glu Trp Leu Gly Arg Leu Glu
50 55 60

Ala Ala Val Met Glu Leu Arg Glu Gln Asn Lys Asp Leu Gln Thr Arg
65 70 75 80

Val Arg Gln Leu Glu Ser Cys Glu Cys His Pro Ala Ser Pro Gln Cys
85 90 95

Trp Gly Leu Gly Arg Ala Trp Pro Glu Gly Ala Arg Trp Glu Pro Asp
100 105 110

Ala Cys Thr Ala Cys Val Cys Gln Asp Gly Ala Ala His Cys Gly Pro
115 120 125

Gln Ala His Leu Pro Gly Cys Thr Glu Gly Gly Ser His Trp Glu His
130 135 140

Gly Gln Glu Trp Thr Thr Pro Gly Asp Pro Cys Arg Ile Cys Arg Cys
145 150 155 160

Leu Glu Gly His Ile Gln Cys Arg Gln Arg Glu Cys Ala Ser Leu Cys
165 170 175

Pro Tyr Pro Ala Arg Pro Leu Pro Gly Thr Cys Cys Pro Val Cys Asp
180 185 190

Gly Cys Phe Leu Asn Gly Arg Glu His Arg Ser Gly Glu Pro Val Gly
195 200 205

Ser Gly Asp Pro Cys Ser His Cys Arg Cys Ala Asn Gly Ser Val Gln
210 215 220

Cys Glu Pro Leu Pro Cys Pro Pro Val Pro Cys Arg His Pro Gly Lys
225 230 235 240

Ile Pro Gly Gln Cys Cys Pro Val Cys Asp Gly Cys Glu Tyr Gln Gly
245 250 255

His Gln Tyr Gln Ser Gln Glu Thr Phe Arg Leu Gln Glu Arg Gly Leu
260 265 270

Cys Val Arg Cys Ser Cys Gln Ala Gly Glu Val Ser Cys Glu Glu Gln
275 280 285

Glu Cys Pro Val Thr Pro Cys Ala Leu Pro Ala Ser Gly Arg Gln Leu
290 295 300

Cys Pro Ala Cys Glu Leu Asp Gly Glu Glu Phe Ala Glu Gly Val Gln
305 310 315 320

Trp Glu Pro Asp Gly Arg Pro Cys Thr Ala Cys Val Cys Gln Asp Gly
325 330 335

Val Pro Lys Cys Gly Ala Val Leu Cys Pro Pro Ala Pro Cys Gln His
340 345 350

Pro Thr Gln Pro Pro Gly Ala Cys Cys Pro Ser Cys Asp Ser Cys Thr
355 360 365

Tyr His Ser Gln Val Tyr Ala Asn Gly Gln Asn Phe Thr Asp Ala Asp
370 375 380

Ser Pro Cys His Ala Cys His Cys Gln Asp Gly Thr Val Thr Cys Ser
385 390 395 400

Leu Val Asp Cys Pro Pro Thr Thr Cys Ala Arg Pro Gln Ser Gly Pro
405 410 415

Gly Gln Cys Cys Pro Arg Cys Pro Asp Cys Ile Leu Glu Glu Glu Val
420 425 430

Phe Val Asp Gly Glu Ser Phe Ser His Pro Arg Asp Pro Cys Gln Glu
435 440 445

Cys Arg Cys Gln Glu Gly His Ala His Cys Gln Pro Arg Pro Cys Pro
450 455 460

Arg Ala Pro Cys Ala His Pro Leu Pro Gly Thr Cys Cys Pro Asn Asp
465 470 475 480

Cys Ser Gly Cys Ala Phe Gly Gly Lys Glu Tyr Pro Ser Gly Ala Asp
485 490 495

Phe Pro His Pro Ser Asp Pro Cys Arg Leu Cys Arg Cys Leu Ser Gly
500 505 510

Asn Val Gln Cys Leu Ala Arg Arg Cys Val Pro Leu Pro Cys Pro Glu
515 520 525

Pro Val Leu Leu Pro Gly Glu Cys Cys Pro Gln Cys Pro Ala Ala Pro
530 535 540

Ala Pro Ala Gly Cys Pro Arg Pro Gly Ala Ala His Ala Arg His Gln
545 550 555 560

Glu Tyr Phe Ser Pro Pro Gly Asp Pro Cys Arg Arg Cys Leu Cys Leu
565 570 575

Asp Gly Ser Val Ser Cys Gln Arg Leu Pro Cys Pro Pro Ala Pro Cys
580 585 590

Ala His Pro Arg Gln Gly Pro Cys Cys Pro Ser Cys Asp Gly Cys Leu
595 600 605

Tyr Gln Gly Lys Glu Phe Ala Ser Gly Glu Arg Phe Pro Ser Pro Thr
610 615 620

Ala Ala Cys His Leu Cys Leu Cys Trp Glu Gly Ser Val Ser Cys Glu
625 630 635 640

Pro Lys Ala Cys Ala Pro Ala Leu Cys Pro Phe Pro Ala Arg Gly Asp
645 650 655

Cys Cys Pro Asp Cys Asp Gly Cys Glu Tyr Leu Gly Glu Ser Tyr Leu
660 665 670

Ser Asn Gln Glu Phe Pro Asp Pro Arg Glu Pro Cys Asn Leu Cys Thr
675 680 685

Cys Leu Gly Gly Phe Val Thr Cys Gly Arg Arg Pro Cys Glu Pro Pro
690 695 700

Gly Cys Ser His Pro Leu Ile Pro Ser Gly His Cys Cys Pro Thr Cys
705 710 715 720

Gln Gly Cys Arg Tyr His Gly Val Thr Thr Ala Ser Gly Glu Thr Leu
725 730 735

Pro Asp Pro Leu Asp Pro Thr Cys Ser Leu Cys Thr Cys Gln Gly Arg
740 745 750

Glu His Gln Asp Gly Glu Glu Phe Glu Gly Pro Ala Gly Ser Cys Glu
755 760 765

Trp Cys Arg Cys Gln Ala Gly Gln Val Ser Cys Val Arg Leu Gln Cys
770 775 780

Pro Pro Leu Pro Cys Lys Leu Gln Val Thr Glu Arg Gly Ser Cys Cys
785 790 795 800

Pro Arg Cys Arg Gly Cys Leu Ala His Gly Glu Glu His Pro Glu Gly
805 810 815

Ser Arg Trp Val Pro Pro Asp Ser Ala Cys Ser Ser Cys Val Cys His
820 825 830

Glu Gly Val Val Thr Cys Ala Arg Ile Gln Cys Ile Ser Ser Cys Ala
835 840 845

Gln Pro Arg Gln Gly Pro His Asp Cys Cys Pro Gln Cys Ser Asp Cys
850 855 860

Glu His Glu Gly Arg Lys Tyr Glu Pro Gly Glu Ser Phe Gln Pro Gly
865 870 875 880

Ala Asp Pro Cys Glu Val Cys Ile Cys Glu Pro Gln Pro Glu Gly Pro
885 890 895

Pro Ser Leu Arg Cys His Arg Arg Gln Cys Pro Ser Leu Val Gly Cys
900 905 910

Pro Pro Ser Gln Leu Leu Pro Pro Gly Pro Gln His Cys Cys Pro Thr
915 920 925

Cys Ala Glu Ala Leu Ser Asn Cys Ser Glu Gly Leu Leu Gly Ser Glu
930 935 940

Leu Ala Pro Pro Asp Pro Cys Tyr Thr Cys Gln Cys Gln Asp Leu Thr
945 950 955 960

Trp Leu Cys Ile His Gln Ala Cys Pro Glu Leu Ser Cys Pro Leu Ser
965 970 975

Glu Arg His Thr Pro Pro Gly Ser Cys Cys Pro Val Cys Arg Glu Cys
980 985 990

Val Val Glu Ala Glu Gly Arg Arg Val Ala Asp Gly Glu Ser Trp Arg
995 1000 1005

Asp Pro Ser Asn Ala Cys Ile Ala Cys Thr Cys His Arg Gly His Val
1010 1015 1020

Glu Cys His Leu Glu Glu Cys Gln Ala Leu Ser Cys Pro His Gly Trp
1025 1030 1035 1040

Ala Lys Val Pro Gln Ala Asp Ser Cys Cys Glu Arg Cys Gln Ala Pro
1045 1050 1055

Thr Gln Ser Cys Val His Gln Gly Arg Glu Val Ala Ser Gly Glu Arg
1060 1065 1070

Trp Thr Val Asp Thr Cys Thr Ser Cys Ser Cys Met Ala Gly Thr Val
1075 1080 1085

Arg Cys Gln Ser Gln Arg Cys Ser Pro Leu Ser Cys Gly Pro Asp Lys
1090 1095 1100

Ala Pro Ala Leu Ser Pro Gly Ser Cys Cys Pro Arg Cys Leu Pro Arg
1105 1110 1115 1120

Pro Ala Ser Cys Met Ala Phe Gly Asp Pro His Tyr Arg Thr Phe Asp
1125 1130 1135

Gly Arg Leu Leu His Phe Gln Gly Ser Cys Ser Tyr Val Leu Ala Lys
1140 1145 1150

Asp Cys His Ser Gly Asp Phe Ser Val His Val Thr Asn Asp Asp Arg
1155 1160 1165

Gly Arg Ser Gly Val Ala Trp Thr Gln Glu Val Ala Val Leu Leu Gly
1170 1175 1180

Asp Met Ala Val Arg Leu Leu Gln Asp Gly Ala Val Thr Val Asp Gly
1185 1190 1195 1200

His Pro Val Ala Leu Pro Phe Leu Gln Glu Pro Leu Leu Tyr Val Glu
1205 1210 1215

Leu Arg Gly His Thr Val Ile Leu His Ala Gln Pro Gly Leu Gln Val
1220 1225 1230

Leu Trp Asp Gly Gln Ser Gln Val Glu Val Ser Val Pro Gly Ser Tyr
1235 1240 1245

Gln Gly Arg Thr Cys Gly Leu Cys Gly Asn Phe Asn Gly Phe Ala Gln
1250 1255 1260

Asp Asp Leu Gln Gly Pro Glu Gly Leu Leu Leu Pro Ser Glu Ala Ala
1265 1270 1275 1280

Phe Gly Asn Ser Trp Gln Val Ser Glu Gly Leu Trp Pro Gly Arg Pro
1285 1290 1295

Cys Ser Ala Gly Arg Glu Val Asp Pro Cys Arg Ala Ala Gly Tyr Arg
1300 1305 1310

Ala Arg Arg Glu Ala Asn Ala Arg Cys Gly Val Leu Lys Ser Ser Pro
1315 1320 1325

Phe Ser Arg Cys His Ala Val Val Pro Pro Glu Pro Phe Phe Ala Ala
1330 1335 1340

Cys Val Tyr Asp Leu Cys Ala Cys Gly Pro Gly Ser Ser Ala Asp Ala
1345 1350 1355 1360

Cys Leu Cys Asp Ala Leu Glu Ala Tyr Ala Ser His Cys Arg Gln Ala
1365 1370 1375

Gly Val Thr Pro Thr Trp Arg Gly Pro Thr Leu Cys Val Val Gly Cys
1380 1385 1390

Pro Leu Glu Arg Gly Phe Val Phe Asp Glu Cys Gly Pro Pro Cys Pro
1395 1400 1405

Arg Thr Cys Phe Asn Gln His Ile Pro Leu Gly Glu Leu Ala Ala His
1410 1415 1420

Cys Val Arg Pro Cys Val Pro Gly Cys Gln Cys Pro Ala Gly Leu Val
1425 1430 1435 1440

Glu His Glu Ala His Cys Ile Pro Pro Glu Ala Cys Pro Gln Val Leu
1445 1450 1455

Leu Thr Gly Asp Gln Pro Leu Gly Ala Arg Pro Ser Pro Ser Arg Glu
1460 1465 1470

Pro Gln Glu Thr Pro
1475



9
4536
DNA
homo sapiens

9

atggccgggg tcggggccgc tgcgctgtcc cttctcctgc acctcggggc cctggcgctg 60

gccgcgggcg cggaaggtgg ggctgtcccc agggagcccc ctgggcagca gacaactgcc 120

cattcctcag tccttgctgg gaactcccag gagcagtggc accccctgcg agagtggctg 180

gggcgactgg aggctgcagt gatggagctc agagaacaga ataaggacct gcagacgagg 240

gtgaggcagc tggagtcctg tgagtgccac cctgcatctc cccagtgctg ggggctgggg 300

cgtgcctggc ccgagggggc acgctgggag cctgacgcct gcacagcctg cgtctgccag 360

gatggggccg ctcactgtgg cccccaagca cacctgcccg gctgcacaga aggtggctct 420

cactgggaac atggccaaga gtggacaaca cctggggacc cctgccgaat ctgccggtgc 480

ctggagggtc acatccagtg ccgccagcga gaatgtgcca gcctgtgtcc atacccagcc 540

cggcccctcc caggcacctg ctgccctgtg tgtgatggct gtttcctaaa cgggcgggag 600

caccgcagcg gggagcctgt gggctcaggg gacccctgct cgcactgccg ctgtgctaat 660

gggagtgtcc agtgtgagcc tctgccctgc ccgccagtgc cctgcagaca cccaggcaag 720

atccctgggc agtgctgccc tgtctgcgat ggctgtgagt accagggaca ccagtatcag 780

agccaggaga ccttcagact ccaagagcgg ggcctctgtg tccgctgctc ctgccaggct 840

ggcgaggtct cctgtgagga gcaggagtgc ccagtcaccc cctgtgccct gcctgcctct 900

ggccgccagc tctgcccagc ctgtgagctg gatggagagg agtttgctga gggagtccag 960

tgggagcctg atggtcggcc ctgcaccgcc tgcgtctgtc aagatggggt acccaagtgc 1020

ggggctgtgc tctgcccccc agccccctgc cagcacccca cccagccccc tggtgcctgc 1080

tgccccagct gtgacagctg cacctaccac agccaagtgt atgccaatgg gcagaacttc 1140

acggatgcag acagcccttg ccatgcctgc cactgtcagg atggaactgt gacatgctcc 1200

ttggttgact gccctcccac gacctgtgcc aggccccaga gtggaccagg ccagtgttgc 1260

cccaggtgcc cagactgcat cctggaggaa gaggtgtttg tggacggcga gagcttctcc 1320

cacccccgag acccctgcca ggagtgccga tgccaggaag gccatgccca ctgccagcct 1380

cgcccctgcc ccagggcccc ctgtgcccac ccgctgcctg ggacctgctg cccgaacgac 1440

tgcagcggct gtgcctttgg cgggaaagag taccccagcg gagcggactt cccccacccc 1500

tctgacccct gccgtctgtg tcgctgtctg agcggcaacg tgcagtgcct ggcccgccgc 1560

tgcgtgccgc tgccctgtcc agagcctgtc ctgctgccgg gagagtgctg cccgcagtgc 1620

ccagccgccc cagcccccgc cggctgccca cggcccggcg cggcccacgc ccgccaccag 1680

gagtacttct ccccgcccgg cgatccctgc cgccgctgcc tctgcctcga cggctccgtg 1740

tcctgccagc ggctgccctg cccgcccgcg ccctgcgcgc acccgcgcca ggggccttgc 1800

tgcccctcct gcgacggctg cctgtaccag gggaaggagt ttgccagcgg ggagcgcttc 1860

ccatcgccca ctgctgcctg ccacctctgc ctttgctggg agggcagcgt gagctgcgag 1920

cccaaggcat gtgcccctgc actgtgcccc ttccctgcca ggggcgactg ctgccctgac 1980

tgtgatggct gtgagtacct gggggagtcc tacctgagta accaggagtt cccagacccc 2040

cgagaaccct gcaacctgtg tacctgtctt ggaggcttcg tgacctgcgg ccgccggccc 2100

tgtgagcctc cgggctgcag ccacccactc atcccctctg ggcactgctg cccgacctgc 2160

cagggatgcc gctaccatgg cgtcactact gcctccggag agacccttcc tgacccactt 2220

gaccctacct gctccctctg cacctgccag gaaggttcca tgcgctgcca aaagaagcca 2280

tgtgccccag ctctctgccc ccacccctct ccaggcccct gcttctgccc tgtttgccac 2340

agttgtctct ctcagggccg ggagcaccag gatggggagg agtttgaggg accagcaggc 2400

agctgtgagt ggtgtcgctg tcaggctggc caggtcagct gtgtgcggct gcagtgccca 2460

ccccttccct gcaagctcca ggtcaccgag cgggggagct gctgccctcg ctgcagaggc 2520

tgcctggctc atggggaaga gcaccccgaa ggcagtagat gggtgccccc cgacagtgcc 2580

tgctcctcct gtgtgtgtca cgagggcgtc gtcacctgtg cacgcatcca gtgcatcagc 2640

tcttgcgccc agccccgcca agggccccat gactgctgtc ctcaatgctc tgactgtgag 2700

catgagggcc ggaagtacga gcctggggag agcttccagc ctggggcaga cccctgtgaa 2760

gtgtgcatct gcgagccaca gcctgagggg cctcccagcc ttcgctgtca ccggcggcag 2820

tgtcccagcc tggtgggctg cccccccagc cagctcctgc cccctgggcc ccagcactgc 2880

tgtcccacct gtgccgaggc cttgagtaac tgttcagagg gcctgctggg atctgagcta 2940

gccccaccag acccctgcta cacgtgccag tgccaggacc tgacatggct ctgcatccac 3000

caggcttgtc ctgagctcag ctgtcccctc tcagagcgcc acactccccc tgggagctgc 3060

tgccccgtat gccgggaatg tgtggtggag gccgagggcc ggagagtggc agatggagag 3120

agctggcggg accccagcaa tgcgtgcatc gcctgcacct gccatcgggg ccatgtggag 3180

tgccacctcg aggagtgcca ggccctctcc tgcccccatg gctgggcgaa ggtgccccag 3240

gctgacagct gctgtgagcg atgccaagct cccacccagt cctgcgtgca ccagggccgt 3300

gaggtggcct ctggagagcg ctggactgtg gacacctgca ccagctgctc ctgcatggcg 3360

ggcaccgtgc gttgccagag ccagcgctgc tcaccgctct cgtgtggccc cgacaaggcc 3420

cctgccctga gtcctggcag ctgctgcccc cgctgcctgc ctcggcccgc ttcctgcatg 3480

gccttcggag acccccatta ccgcaccttc gacggccgcc tgctgcactt ccagggcagt 3540

tgcagctatg tgctggccaa ggactgccac agcggggact tcagtgtgca cgtgaccaat 3600

gatgaccggg gccggagcgg tgtggcctgg acccaggagg tggcggtgct gctgggagac 3660

atggccgtgc ggctgctgca ggacggggca gtcacggtgg atgggcaccc ggtggccttg 3720

cccttcctgc aggagccgct gctgtatgtg gagctgcgag gacacactgt gatcctgcac 3780

gcccagcccg ggctccaggt gctgtgggat gggcagtccc aggtggaggt gagcgtacct 3840

ggctcctacc agggccggac ttgtgggctc tgtgggaact tcaatggctt tgcccaggac 3900

gatctgcagg gccctgaggg gctgctcctg ccctcggagg ctgcgtttgg gaatagctgg 3960

caggtctcag aggggctgtg gcctggccgg ccctgttctg caggccgaga ggtggatccg 4020

tgccgggcag caggttaccg tgccaggcgt gaggccaatg cccggtgtgg ggtgctgaag 4080

tcctccccat tcagtcgctg ccatgctgtg gtgccaccgg agcccttctt tgccgcctgt 4140

gtgtatgacc tgtgtgcctg tggccctggc tcctccgctg atgcctgcct ctgtgatgcc 4200

ctggaagcct acgccagtca ctgtcgccag gcaggagtga cacctacctg gcgaggcccc 4260

acgctgtgtg tggtaggctg ccccctggag cgtggcttcg tgtttgatga gtgcggccca 4320

ccctgtcccc gcacctgctt caatcagcat atccccctgg gggagctggc agcccactgc 4380

gtgaggccct gcgtgcccgg ctgccagtgc cctgcaggcc tggtggagca tgaggcccac 4440

tgcatcccac ccgaggcctg cccccaagtc ctgctcactg gagaccagcc acttggtgct 4500

cggcccagcc ccagccggga gccccaggag acaccc 4536



10
1512
PRT
homo sapiens

10

Met Ala Gly Val Gly Ala Ala Ala Leu Ser Leu Leu Leu His Leu Gly
1 5 10 15

Ala Leu Ala Leu Ala Ala Gly Ala Glu Gly Gly Ala Val Pro Arg Glu
20 25 30

Pro Pro Gly Gln Gln Thr Thr Ala His Ser Ser Val Leu Ala Gly Asn
35 40 45

Ser Gln Glu Gln Trp His Pro Leu Arg Glu Trp Leu Gly Arg Leu Glu
50 55 60

Ala Ala Val Met Glu Leu Arg Glu Gln Asn Lys Asp Leu Gln Thr Arg
65 70 75 80

Val Arg Gln Leu Glu Ser Cys Glu Cys His Pro Ala Ser Pro Gln Cys
85 90 95

Trp Gly Leu Gly Arg Ala Trp Pro Glu Gly Ala Arg Trp Glu Pro Asp
100 105 110

Ala Cys Thr Ala Cys Val Cys Gln Asp Gly Ala Ala His Cys Gly Pro
115 120 125

Gln Ala His Leu Pro Gly Cys Thr Glu Gly Gly Ser His Trp Glu His
130 135 140

Gly Gln Glu Trp Thr Thr Pro Gly Asp Pro Cys Arg Ile Cys Arg Cys
145 150 155 160

Leu Glu Gly His Ile Gln Cys Arg Gln Arg Glu Cys Ala Ser Leu Cys
165 170 175

Pro Tyr Pro Ala Arg Pro Leu Pro Gly Thr Cys Cys Pro Val Cys Asp
180 185 190

Gly Cys Phe Leu Asn Gly Arg Glu His Arg Ser Gly Glu Pro Val Gly
195 200 205

Ser Gly Asp Pro Cys Ser His Cys Arg Cys Ala Asn Gly Ser Val Gln
210 215 220

Cys Glu Pro Leu Pro Cys Pro Pro Val Pro Cys Arg His Pro Gly Lys
225 230 235 240

Ile Pro Gly Gln Cys Cys Pro Val Cys Asp Gly Cys Glu Tyr Gln Gly
245 250 255

His Gln Tyr Gln Ser Gln Glu Thr Phe Arg Leu Gln Glu Arg Gly Leu
260 265 270

Cys Val Arg Cys Ser Cys Gln Ala Gly Glu Val Ser Cys Glu Glu Gln
275 280 285

Glu Cys Pro Val Thr Pro Cys Ala Leu Pro Ala Ser Gly Arg Gln Leu
290 295 300

Cys Pro Ala Cys Glu Leu Asp Gly Glu Glu Phe Ala Glu Gly Val Gln
305 310 315 320

Trp Glu Pro Asp Gly Arg Pro Cys Thr Ala Cys Val Cys Gln Asp Gly
325 330 335

Val Pro Lys Cys Gly Ala Val Leu Cys Pro Pro Ala Pro Cys Gln His
340 345 350

Pro Thr Gln Pro Pro Gly Ala Cys Cys Pro Ser Cys Asp Ser Cys Thr
355 360 365

Tyr His Ser Gln Val Tyr Ala Asn Gly Gln Asn Phe Thr Asp Ala Asp
370 375 380

Ser Pro Cys His Ala Cys His Cys Gln Asp Gly Thr Val Thr Cys Ser
385 390 395 400

Leu Val Asp Cys Pro Pro Thr Thr Cys Ala Arg Pro Gln Ser Gly Pro
405 410 415

Gly Gln Cys Cys Pro Arg Cys Pro Asp Cys Ile Leu Glu Glu Glu Val
420 425 430

Phe Val Asp Gly Glu Ser Phe Ser His Pro Arg Asp Pro Cys Gln Glu
435 440 445

Cys Arg Cys Gln Glu Gly His Ala His Cys Gln Pro Arg Pro Cys Pro
450 455 460

Arg Ala Pro Cys Ala His Pro Leu Pro Gly Thr Cys Cys Pro Asn Asp
465 470 475 480

Cys Ser Gly Cys Ala Phe Gly Gly Lys Glu Tyr Pro Ser Gly Ala Asp
485 490 495

Phe Pro His Pro Ser Asp Pro Cys Arg Leu Cys Arg Cys Leu Ser Gly
500 505 510

Asn Val Gln Cys Leu Ala Arg Arg Cys Val Pro Leu Pro Cys Pro Glu
515 520 525

Pro Val Leu Leu Pro Gly Glu Cys Cys Pro Gln Cys Pro Ala Ala Pro
530 535 540

Ala Pro Ala Gly Cys Pro Arg Pro Gly Ala Ala His Ala Arg His Gln
545 550 555 560

Glu Tyr Phe Ser Pro Pro Gly Asp Pro Cys Arg Arg Cys Leu Cys Leu
565 570 575

Asp Gly Ser Val Ser Cys Gln Arg Leu Pro Cys Pro Pro Ala Pro Cys
580 585 590

Ala His Pro Arg Gln Gly Pro Cys Cys Pro Ser Cys Asp Gly Cys Leu
595 600 605

Tyr Gln Gly Lys Glu Phe Ala Ser Gly Glu Arg Phe Pro Ser Pro Thr
610 615 620

Ala Ala Cys His Leu Cys Leu Cys Trp Glu Gly Ser Val Ser Cys Glu
625 630 635 640

Pro Lys Ala Cys Ala Pro Ala Leu Cys Pro Phe Pro Ala Arg Gly Asp
645 650 655

Cys Cys Pro Asp Cys Asp Gly Cys Glu Tyr Leu Gly Glu Ser Tyr Leu
660 665 670

Ser Asn Gln Glu Phe Pro Asp Pro Arg Glu Pro Cys Asn Leu Cys Thr
675 680 685

Cys Leu Gly Gly Phe Val Thr Cys Gly Arg Arg Pro Cys Glu Pro Pro
690 695 700

Gly Cys Ser His Pro Leu Ile Pro Ser Gly His Cys Cys Pro Thr Cys
705 710 715 720

Gln Gly Cys Arg Tyr His Gly Val Thr Thr Ala Ser Gly Glu Thr Leu
725 730 735

Pro Asp Pro Leu Asp Pro Thr Cys Ser Leu Cys Thr Cys Gln Glu Gly
740 745 750

Ser Met Arg Cys Gln Lys Lys Pro Cys Ala Pro Ala Leu Cys Pro His
755 760 765

Pro Ser Pro Gly Pro Cys Phe Cys Pro Val Cys His Ser Cys Leu Ser
770 775 780

Gln Gly Arg Glu His Gln Asp Gly Glu Glu Phe Glu Gly Pro Ala Gly
785 790 795 800

Ser Cys Glu Trp Cys Arg Cys Gln Ala Gly Gln Val Ser Cys Val Arg
805 810 815

Leu Gln Cys Pro Pro Leu Pro Cys Lys Leu Gln Val Thr Glu Arg Gly
820 825 830

Ser Cys Cys Pro Arg Cys Arg Gly Cys Leu Ala His Gly Glu Glu His
835 840 845

Pro Glu Gly Ser Arg Trp Val Pro Pro Asp Ser Ala Cys Ser Ser Cys
850 855 860

Val Cys His Glu Gly Val Val Thr Cys Ala Arg Ile Gln Cys Ile Ser
865 870 875 880

Ser Cys Ala Gln Pro Arg Gln Gly Pro His Asp Cys Cys Pro Gln Cys
885 890 895

Ser Asp Cys Glu His Glu Gly Arg Lys Tyr Glu Pro Gly Glu Ser Phe
900 905 910

Gln Pro Gly Ala Asp Pro Cys Glu Val Cys Ile Cys Glu Pro Gln Pro
915 920 925

Glu Gly Pro Pro Ser Leu Arg Cys His Arg Arg Gln Cys Pro Ser Leu
930 935 940

Val Gly Cys Pro Pro Ser Gln Leu Leu Pro Pro Gly Pro Gln His Cys
945 950 955 960

Cys Pro Thr Cys Ala Glu Ala Leu Ser Asn Cys Ser Glu Gly Leu Leu
965 970 975

Gly Ser Glu Leu Ala Pro Pro Asp Pro Cys Tyr Thr Cys Gln Cys Gln
980 985 990

Asp Leu Thr Trp Leu Cys Ile His Gln Ala Cys Pro Glu Leu Ser Cys
995 1000 1005

Pro Leu Ser Glu Arg His Thr Pro Pro Gly Ser Cys Cys Pro Val Cys
1010 1015 1020

Arg Glu Cys Val Val Glu Ala Glu Gly Arg Arg Val Ala Asp Gly Glu
1025 1030 1035 1040

Ser Trp Arg Asp Pro Ser Asn Ala Cys Ile Ala Cys Thr Cys His Arg
1045 1050 1055

Gly His Val Glu Cys His Leu Glu Glu Cys Gln Ala Leu Ser Cys Pro
1060 1065 1070

His Gly Trp Ala Lys Val Pro Gln Ala Asp Ser Cys Cys Glu Arg Cys
1075 1080 1085

Gln Ala Pro Thr Gln Ser Cys Val His Gln Gly Arg Glu Val Ala Ser
1090 1095 1100

Gly Glu Arg Trp Thr Val Asp Thr Cys Thr Ser Cys Ser Cys Met Ala
1105 1110 1115 1120

Gly Thr Val Arg Cys Gln Ser Gln Arg Cys Ser Pro Leu Ser Cys Gly
1125 1130 1135

Pro Asp Lys Ala Pro Ala Leu Ser Pro Gly Ser Cys Cys Pro Arg Cys
1140 1145 1150

Leu Pro Arg Pro Ala Ser Cys Met Ala Phe Gly Asp Pro His Tyr Arg
1155 1160 1165

Thr Phe Asp Gly Arg Leu Leu His Phe Gln Gly Ser Cys Ser Tyr Val
1170 1175 1180

Leu Ala Lys Asp Cys His Ser Gly Asp Phe Ser Val His Val Thr Asn
1185 1190 1195 1200

Asp Asp Arg Gly Arg Ser Gly Val Ala Trp Thr Gln Glu Val Ala Val
1205 1210 1215

Leu Leu Gly Asp Met Ala Val Arg Leu Leu Gln Asp Gly Ala Val Thr
1220 1225 1230

Val Asp Gly His Pro Val Ala Leu Pro Phe Leu Gln Glu Pro Leu Leu
1235 1240 1245

Tyr Val Glu Leu Arg Gly His Thr Val Ile Leu His Ala Gln Pro Gly
1250 1255 1260

Leu Gln Val Leu Trp Asp Gly Gln Ser Gln Val Glu Val Ser Val Pro
1265 1270 1275 1280

Gly Ser Tyr Gln Gly Arg Thr Cys Gly Leu Cys Gly Asn Phe Asn Gly
1285 1290 1295

Phe Ala Gln Asp Asp Leu Gln Gly Pro Glu Gly Leu Leu Leu Pro Ser
1300 1305 1310

Glu Ala Ala Phe Gly Asn Ser Trp Gln Val Ser Glu Gly Leu Trp Pro
1315 1320 1325

Gly Arg Pro Cys Ser Ala Gly Arg Glu Val Asp Pro Cys Arg Ala Ala
1330 1335 1340

Gly Tyr Arg Ala Arg Arg Glu Ala Asn Ala Arg Cys Gly Val Leu Lys
1345 1350 1355 1360

Ser Ser Pro Phe Ser Arg Cys His Ala Val Val Pro Pro Glu Pro Phe
1365 1370 1375

Phe Ala Ala Cys Val Tyr Asp Leu Cys Ala Cys Gly Pro Gly Ser Ser
1380 1385 1390

Ala Asp Ala Cys Leu Cys Asp Ala Leu Glu Ala Tyr Ala Ser His Cys
1395 1400 1405

Arg Gln Ala Gly Val Thr Pro Thr Trp Arg Gly Pro Thr Leu Cys Val
1410 1415 1420

Val Gly Cys Pro Leu Glu Arg Gly Phe Val Phe Asp Glu Cys Gly Pro
1425 1430 1435 1440

Pro Cys Pro Arg Thr Cys Phe Asn Gln His Ile Pro Leu Gly Glu Leu
1445 1450 1455

Ala Ala His Cys Val Arg Pro Cys Val Pro Gly Cys Gln Cys Pro Ala
1460 1465 1470

Gly Leu Val Glu His Glu Ala His Cys Ile Pro Pro Glu Ala Cys Pro
1475 1480 1485

Gln Val Leu Leu Thr Gly Asp Gln Pro Leu Gly Ala Arg Pro Ser Pro
1490 1495 1500

Ser Arg Glu Pro Gln Glu Thr Pro
1505 1510



11
4710
DNA
homo sapiens

11

atggagctca gagaacagaa taaggacctg cagacgaggg tgaggcagct ggagtcctgt 60

gagtgccacc ctgcatctcc ccagtgctgg gggctggggc gtgcctggcc cgagggggca 120

cgctgggagc ctgacgcctg cacagcctgc gtctgccagg atggggccgc tcactgtggc 180

ccccaagcac acctgcccca ttgcaggggc tgcagccaaa atggccagac ctacggcaac 240

ggggagacct tctccccaga tgcctgcacc acctgccgct gtctggaagg taccatcact 300

tgcaaccaga agccatgccc aagaggaccc tgccctgagc caggagcatg ctgcccgcac 360

tgtaagccag gctgtgatta tgaggggcag ctttatgagg agggggtcac cttcctgtcc 420

agctccaacc cttgtctaca gtgcacctgc ctgaggagcc gagttcgctg catggccctg 480

aagtgcccgc ctagcccctg cccagagcca gtgctgaggc ctgggcactg ctgcccaacc 540

tgccaaggct gcacagaagg tggctctcac tgggaacatg gccaagagtg gacaacacct 600

ggggacccct gccgaatctg ccggtgcctg gagggtcaca tccagtgccg ccagcgagaa 660

tgtgccagcc tgtgtccata cccagcccgg cccctcccag gcacctgctg ccctgtgtgt 720

gatggctgtt tcctaaacgg gcgggagcac cgcagcgggg agcctgtggg ctcaggggac 780

ccctgctcgc actgccgctg tgctaatggg agtgtccagt gtgagcctct gccctgcccg 840

ccagtgccct gcagacaccc aggcaagatc cctgggcagt gctgccctgt ctgcgatggc 900

tgtgagtacc agggacacca gtatcagagc caggagacct tcagactcca agagcggggc 960

ctctgtgtcc gctgctcctg ccaggctggc gaggtctcct gtgaggagca ggagtgccca 1020

gtcaccccct gtgccctgcc tgcctctggc cgccagctct gcccagctca ccctgaccag 1080

cctgccccac ccacctgtga gctggatgga gaggagtttg ctgagggagt ccagtgggag 1140

cctgatggtc ggccctgcac cgcctgcgtc tgtcaagatg gggtacccaa gtgcggggct 1200

gtgctctgcc ccccagcccc ctgccagcac cccacccagc cccctggtgc ctgctgcccc 1260

agctgtgaca gctgcaccta ccacagccaa gtgtatgcca atgggcagaa cttcacggat 1320

gcagacagcc cttgccatgc ctgccactgt caggatggaa ctgtgacatg ctccttggtt 1380

gactgccctc ccacgacctg tgccaggccc cagagtggac caggccagtg ttgccccagg 1440

tgcccagact gcatcctgga ggaagaggtg tttgtggacg gcgagagctt ctcccacccc 1500

cgagacccct gccaggagtg ccgatgccag gaaggccatg cccactgcca gcctcgcccc 1560

tgccccaggg ccccctgtgc ccacccgctg cctgggacct gctgcccgaa cgactgcagc 1620

ggctgtgcct ttggcgggaa agagtacccc agcggagcgg acttccccca cccctctgac 1680

ccctgccgtc tgtgtcgctg tctgagcggc aacgtgcagt gcctggcccg ccgctgcgtg 1740

ccgctgccct gtccagagcc tgtcctgctg ccgggagagt gctgcccgca gtgcccagcc 1800

gccccagccc ccgccggctg cccacggccc ggcgcggccc acgcccgcca ccaggagtac 1860

ttctccccgc ccggcgatcc ctgccgccgc tgcctctgcc tcgacggctc cgtgtcctgc 1920

cagcggctgc cctgcccgcc cgcgccctgc gcgcacccgc gccaggggcc ttgctgcccc 1980

tcctgcgacg gctgcctgta ccaggggaag gagtttgcca gcggggagcg cttcccatcg 2040

cccactgctg cctgccacct ctgcctttgc tgggagggca gcgtgagctg cgagcccaag 2100

gcatgtgccc ctgcactgtg ccccttccct gccaggggcg actgctgccc tgactgtgat 2160

ggctgtgagt acctggggga gtcctacctg agtaaccagg agttcccaga cccccgagaa 2220

ccctgcaacc tgtgtacctg tcttggaggc ttcgtgacct gcggccgccg gccctgtgag 2280

cctccgggct gcagccaccc actcatcccc tctgggcact gctgcccgac ctgccaggga 2340

tgccgctacc atggcgtcac tactgcctcc ggagagaccc ttcctgaccc acttgaccct 2400

acctgctccc tctgcacctg ccaggaaggt tccatgcgct gccaaaagaa gccatgtgcc 2460

ccagctctct gcccccaccc ctctccaggc ccctgcttct gccctgtttg ccacagttgt 2520

ctctctcagg gccgggagca ccaggatggg gaggagtttg agggaccagc aggcagctgt 2580

gagtggtgtc gctgtcaggc tggccaggtc agctgtgtgc ggctgcagtg cccacccctt 2640

ccctgcaagc tccaggtcac cgagcggggg agctgctgcc ctcgctgcag aggctgcctg 2700

gctcatgggg aagagcaccc cgaaggcagt agatgggtgc cccccgacag tgcctgctcc 2760

tcctgtgtgt gtcacgaggg cgtcgtcacc tgtgcacgca tccagtgcat cagctcttgc 2820

gcccagcccc gccaagggcc ccatgactgc tgtcctcaat gctctgactg tgagcatgag 2880

ggccggaagt acgagcctgg ggagagcttc cagcctgggg cagacccctg tgaagtgtgc 2940

atctgcgagc cacagcctga ggggcctccc agccttcgct gtcaccggcg gcagtgtccc 3000

agcctggtgg gctgcccccc cagccagctc ctgccccctg ggccccagca ctgctgtccc 3060

acctgtgccg aggccttgag taactgttca gagggcctgc tgggatctga gctagcccca 3120

ccagacccct gctacacgtg ccagtgccag gacctgacat ggctctgcat ccaccaggct 3180

tgtcctgagc tcagctgtcc cctctcagag cgccacactc cccctgggag ctgctgcccc 3240

gtatgccggg aatgtgtggt ggaggccgag ggccggagag tggcagatgg agagagctgg 3300

cgggacccca gcaatgcgtg catcgcctgc acctgccatc ggggccatgt ggagtgccac 3360

ctcgaggagt gccaggccct ctcctgcccc catggctggg cgaaggtgcc ccaggctgac 3420

agctgctgtg agcgatgcca agctcccacc cagtcctgcg tgcaccaggg ccgtgaggtg 3480

gcctctggag agcgctggac tgtggacacc tgcaccagct gctcctgcat ggcgggcacc 3540

gtgcgttgcc agagccagcg ctgctcaccg ctctcgtgtg gccccgacaa ggcccctgcc 3600

ctgagtcctg gcagctgctg cccccgctgc ctgcctcggc ccgcttcctg catggccttc 3660

ggagaccccc attaccgcac cttcgacggc cgcctgctgc acttccaggg cagttgcagc 3720

tatgtgctgg ccaaggactg ccacagcggg gacttcagtg tgcacgtgac caatgatgac 3780

cggggccgga gcggtgtggc ctggacccag gaggtggcgg tgctgctggg agacatggcc 3840

gtgcggctgc tgcaggacgg ggcagtcacg gtggatgggc acccggtggc cttgcccttc 3900

ctgcaggagc cgctgctgta tgtggagctg cgaggacaca ctgtgatcct gcacgcccag 3960

cccgggctcc aggtgctgtg ggatgggcag tcccaggtgg aggtgagcgt acctggctcc 4020

taccagggcc ggacttgtgg gctctgtggg aacttcaatg gctttgccca ggacgatctg 4080

cagggccctg aggggctgct cctgccctcg gaggctgcgt ttgggaatag ctggcaggtc 4140

tcagaggggc tgtggcctgg ccggccctgt tctgcaggcc gagaggtgga tccgtgccgg 4200

gcagcaggtt accgtgccag gcgtgaggcc aatgcccggt gtggggtgct gaagtcctcc 4260

ccattcagtc gctgccatgc tgtggtgcca ccggagccct tctttgccgc ctgtgtgtat 4320

gacctgtgtg cctgtggccc tggctcctcc gctgatgcct gcctctgtga tgccctggaa 4380

gcctacgcca gtcactgtcg ccaggcagga gtgacaccta cctggcgagg ccccacgctg 4440

tgtgtggtag gctgccccct ggagcgtggc ttcgtgtttg atgagtgcgg cccaccctgt 4500

ccccgcacct gcttcaatca gcatatcccc ctgggggagc tggcagccca ctgcgtgagg 4560

ccctgcgtgc ccggctgcca gtgccctgca ggcctggtgg agcatgaggc ccactgcatc 4620

ccacccgagg cctgccccca agtcctgctc actggagacc agccacttgg tgctcggccc 4680

agccccagcc gggagcccca ggagacaccc 4710



12
1570
PRT
homo sapiens

12

Met Glu Leu Arg Glu Gln Asn Lys Asp Leu Gln Thr Arg Val Arg Gln
1 5 10 15

Leu Glu Ser Cys Glu Cys His Pro Ala Ser Pro Gln Cys Trp Gly Leu
20 25 30

Gly Arg Ala Trp Pro Glu Gly Ala Arg Trp Glu Pro Asp Ala Cys Thr
35 40 45

Ala Cys Val Cys Gln Asp Gly Ala Ala His Cys Gly Pro Gln Ala His
50 55 60

Leu Pro His Cys Arg Gly Cys Ser Gln Asn Gly Gln Thr Tyr Gly Asn
65 70 75 80

Gly Glu Thr Phe Ser Pro Asp Ala Cys Thr Thr Cys Arg Cys Leu Glu
85 90 95

Gly Thr Ile Thr Cys Asn Gln Lys Pro Cys Pro Arg Gly Pro Cys Pro
100 105 110

Glu Pro Gly Ala Cys Cys Pro His Cys Lys Pro Gly Cys Asp Tyr Glu
115 120 125

Gly Gln Leu Tyr Glu Glu Gly Val Thr Phe Leu Ser Ser Ser Asn Pro
130 135 140

Cys Leu Gln Cys Thr Cys Leu Arg Ser Arg Val Arg Cys Met Ala Leu
145 150 155 160

Lys Cys Pro Pro Ser Pro Cys Pro Glu Pro Val Leu Arg Pro Gly His
165 170 175

Cys Cys Pro Thr Cys Gln Gly Cys Thr Glu Gly Gly Ser His Trp Glu
180 185 190

His Gly Gln Glu Trp Thr Thr Pro Gly Asp Pro Cys Arg Ile Cys Arg
195 200 205

Cys Leu Glu Gly His Ile Gln Cys Arg Gln Arg Glu Cys Ala Ser Leu
210 215 220

Cys Pro Tyr Pro Ala Arg Pro Leu Pro Gly Thr Cys Cys Pro Val Cys
225 230 235 240

Asp Gly Cys Phe Leu Asn Gly Arg Glu His Arg Ser Gly Glu Pro Val
245 250 255

Gly Ser Gly Asp Pro Cys Ser His Cys Arg Cys Ala Asn Gly Ser Val
260 265 270

Gln Cys Glu Pro Leu Pro Cys Pro Pro Val Pro Cys Arg His Pro Gly
275 280 285

Lys Ile Pro Gly Gln Cys Cys Pro Val Cys Asp Gly Cys Glu Tyr Gln
290 295 300

Gly His Gln Tyr Gln Ser Gln Glu Thr Phe Arg Leu Gln Glu Arg Gly
305 310 315 320

Leu Cys Val Arg Cys Ser Cys Gln Ala Gly Glu Val Ser Cys Glu Glu
325 330 335

Gln Glu Cys Pro Val Thr Pro Cys Ala Leu Pro Ala Ser Gly Arg Gln
340 345 350

Leu Cys Pro Ala His Pro Asp Gln Pro Ala Pro Pro Thr Cys Glu Leu
355 360 365

Asp Gly Glu Glu Phe Ala Glu Gly Val Gln Trp Glu Pro Asp Gly Arg
370 375 380

Pro Cys Thr Ala Cys Val Cys Gln Asp Gly Val Pro Lys Cys Gly Ala
385 390 395 400

Val Leu Cys Pro Pro Ala Pro Cys Gln His Pro Thr Gln Pro Pro Gly
405 410 415

Ala Cys Cys Pro Ser Cys Asp Ser Cys Thr Tyr His Ser Gln Val Tyr
420 425 430

Ala Asn Gly Gln Asn Phe Thr Asp Ala Asp Ser Pro Cys His Ala Cys
435 440 445

His Cys Gln Asp Gly Thr Val Thr Cys Ser Leu Val Asp Cys Pro Pro
450 455 460

Thr Thr Cys Ala Arg Pro Gln Ser Gly Pro Gly Gln Cys Cys Pro Arg
465 470 475 480

Cys Pro Asp Cys Ile Leu Glu Glu Glu Val Phe Val Asp Gly Glu Ser
485 490 495

Phe Ser His Pro Arg Asp Pro Cys Gln Glu Cys Arg Cys Gln Glu Gly
500 505 510

His Ala His Cys Gln Pro Arg Pro Cys Pro Arg Ala Pro Cys Ala His
515 520 525

Pro Leu Pro Gly Thr Cys Cys Pro Asn Asp Cys Ser Gly Cys Ala Phe
530 535 540

Gly Gly Lys Glu Tyr Pro Ser Gly Ala Asp Phe Pro His Pro Ser Asp
545 550 555 560

Pro Cys Arg Leu Cys Arg Cys Leu Ser Gly Asn Val Gln Cys Leu Ala
565 570 575

Arg Arg Cys Val Pro Leu Pro Cys Pro Glu Pro Val Leu Leu Pro Gly
580 585 590

Glu Cys Cys Pro Gln Cys Pro Ala Ala Pro Ala Pro Ala Gly Cys Pro
595 600 605

Arg Pro Gly Ala Ala His Ala Arg His Gln Glu Tyr Phe Ser Pro Pro
610 615 620

Gly Asp Pro Cys Arg Arg Cys Leu Cys Leu Asp Gly Ser Val Ser Cys
625 630 635 640

Gln Arg Leu Pro Cys Pro Pro Ala Pro Cys Ala His Pro Arg Gln Gly
645 650 655

Pro Cys Cys Pro Ser Cys Asp Gly Cys Leu Tyr Gln Gly Lys Glu Phe
660 665 670

Ala Ser Gly Glu Arg Phe Pro Ser Pro Thr Ala Ala Cys His Leu Cys
675 680 685

Leu Cys Trp Glu Gly Ser Val Ser Cys Glu Pro Lys Ala Cys Ala Pro
690 695 700

Ala Leu Cys Pro Phe Pro Ala Arg Gly Asp Cys Cys Pro Asp Cys Asp
705 710 715 720

Gly Cys Glu Tyr Leu Gly Glu Ser Tyr Leu Ser Asn Gln Glu Phe Pro
725 730 735

Asp Pro Arg Glu Pro Cys Asn Leu Cys Thr Cys Leu Gly Gly Phe Val
740 745 750

Thr Cys Gly Arg Arg Pro Cys Glu Pro Pro Gly Cys Ser His Pro Leu
755 760 765

Ile Pro Ser Gly His Cys Cys Pro Thr Cys Gln Gly Cys Arg Tyr His
770 775 780

Gly Val Thr Thr Ala Ser Gly Glu Thr Leu Pro Asp Pro Leu Asp Pro
785 790 795 800

Thr Cys Ser Leu Cys Thr Cys Gln Glu Gly Ser Met Arg Cys Gln Lys
805 810 815

Lys Pro Cys Ala Pro Ala Leu Cys Pro His Pro Ser Pro Gly Pro Cys
820 825 830

Phe Cys Pro Val Cys His Ser Cys Leu Ser Gln Gly Arg Glu His Gln
835 840 845

Asp Gly Glu Glu Phe Glu Gly Pro Ala Gly Ser Cys Glu Trp Cys Arg
850 855 860

Cys Gln Ala Gly Gln Val Ser Cys Val Arg Leu Gln Cys Pro Pro Leu
865 870 875 880

Pro Cys Lys Leu Gln Val Thr Glu Arg Gly Ser Cys Cys Pro Arg Cys
885 890 895

Arg Gly Cys Leu Ala His Gly Glu Glu His Pro Glu Gly Ser Arg Trp
900 905 910

Val Pro Pro Asp Ser Ala Cys Ser Ser Cys Val Cys His Glu Gly Val
915 920 925

Val Thr Cys Ala Arg Ile Gln Cys Ile Ser Ser Cys Ala Gln Pro Arg
930 935 940

Gln Gly Pro His Asp Cys Cys Pro Gln Cys Ser Asp Cys Glu His Glu
945 950 955 960

Gly Arg Lys Tyr Glu Pro Gly Glu Ser Phe Gln Pro Gly Ala Asp Pro
965 970 975

Cys Glu Val Cys Ile Cys Glu Pro Gln Pro Glu Gly Pro Pro Ser Leu
980 985 990

Arg Cys His Arg Arg Gln Cys Pro Ser Leu Val Gly Cys Pro Pro Ser
995 1000 1005

Gln Leu Leu Pro Pro Gly Pro Gln His Cys Cys Pro Thr Cys Ala Glu
1010 1015 1020

Ala Leu Ser Asn Cys Ser Glu Gly Leu Leu Gly Ser Glu Leu Ala Pro
1025 1030 1035 1040

Pro Asp Pro Cys Tyr Thr Cys Gln Cys Gln Asp Leu Thr Trp Leu Cys
1045 1050 1055

Ile His Gln Ala Cys Pro Glu Leu Ser Cys Pro Leu Ser Glu Arg His
1060 1065 1070

Thr Pro Pro Gly Ser Cys Cys Pro Val Cys Arg Glu Cys Val Val Glu
1075 1080 1085

Ala Glu Gly Arg Arg Val Ala Asp Gly Glu Ser Trp Arg Asp Pro Ser
1090 1095 1100

Asn Ala Cys Ile Ala Cys Thr Cys His Arg Gly His Val Glu Cys His
1105 1110 1115 1120

Leu Glu Glu Cys Gln Ala Leu Ser Cys Pro His Gly Trp Ala Lys Val
1125 1130 1135

Pro Gln Ala Asp Ser Cys Cys Glu Arg Cys Gln Ala Pro Thr Gln Ser
1140 1145 1150

Cys Val His Gln Gly Arg Glu Val Ala Ser Gly Glu Arg Trp Thr Val
1155 1160 1165

Asp Thr Cys Thr Ser Cys Ser Cys Met Ala Gly Thr Val Arg Cys Gln
1170 1175 1180

Ser Gln Arg Cys Ser Pro Leu Ser Cys Gly Pro Asp Lys Ala Pro Ala
1185 1190 1195 1200

Leu Ser Pro Gly Ser Cys Cys Pro Arg Cys Leu Pro Arg Pro Ala Ser
1205 1210 1215

Cys Met Ala Phe Gly Asp Pro His Tyr Arg Thr Phe Asp Gly Arg Leu
1220 1225 1230

Leu His Phe Gln Gly Ser Cys Ser Tyr Val Leu Ala Lys Asp Cys His
1235 1240 1245

Ser Gly Asp Phe Ser Val His Val Thr Asn Asp Asp Arg Gly Arg Ser
1250 1255 1260

Gly Val Ala Trp Thr Gln Glu Val Ala Val Leu Leu Gly Asp Met Ala
1265 1270 1275 1280

Val Arg Leu Leu Gln Asp Gly Ala Val Thr Val Asp Gly His Pro Val
1285 1290 1295

Ala Leu Pro Phe Leu Gln Glu Pro Leu Leu Tyr Val Glu Leu Arg Gly
1300 1305 1310

His Thr Val Ile Leu His Ala Gln Pro Gly Leu Gln Val Leu Trp Asp
1315 1320 1325

Gly Gln Ser Gln Val Glu Val Ser Val Pro Gly Ser Tyr Gln Gly Arg
1330 1335 1340

Thr Cys Gly Leu Cys Gly Asn Phe Asn Gly Phe Ala Gln Asp Asp Leu
1345 1350 1355 1360

Gln Gly Pro Glu Gly Leu Leu Leu Pro Ser Glu Ala Ala Phe Gly Asn
1365 1370 1375

Ser Trp Gln Val Ser Glu Gly Leu Trp Pro Gly Arg Pro Cys Ser Ala
1380 1385 1390

Gly Arg Glu Val Asp Pro Cys Arg Ala Ala Gly Tyr Arg Ala Arg Arg
1395 1400 1405

Glu Ala Asn Ala Arg Cys Gly Val Leu Lys Ser Ser Pro Phe Ser Arg
1410 1415 1420

Cys His Ala Val Val Pro Pro Glu Pro Phe Phe Ala Ala Cys Val Tyr
1425 1430 1435 1440

Asp Leu Cys Ala Cys Gly Pro Gly Ser Ser Ala Asp Ala Cys Leu Cys
1445 1450 1455

Asp Ala Leu Glu Ala Tyr Ala Ser His Cys Arg Gln Ala Gly Val Thr
1460 1465 1470

Pro Thr Trp Arg Gly Pro Thr Leu Cys Val Val Gly Cys Pro Leu Glu
1475 1480 1485

Arg Gly Phe Val Phe Asp Glu Cys Gly Pro Pro Cys Pro Arg Thr Cys
1490 1495 1500

Phe Asn Gln His Ile Pro Leu Gly Glu Leu Ala Ala His Cys Val Arg
1505 1510 1515 1520

Pro Cys Val Pro Gly Cys Gln Cys Pro Ala Gly Leu Val Glu His Glu
1525 1530 1535

Ala His Cys Ile Pro Pro Glu Ala Cys Pro Gln Val Leu Leu Thr Gly
1540 1545 1550

Asp Gln Pro Leu Gly Ala Arg Pro Ser Pro Ser Arg Glu Pro Gln Glu
1555 1560 1565

Thr Pro
1570



13
4605
DNA
homo sapiens

13

atggagctca gagaacagaa taaggacctg cagacgaggg tgaggcagct ggagtcctgt 60

gagtgccacc ctgcatctcc ccagtgctgg gggctggggc gtgcctggcc cgagggggca 120

cgctgggagc ctgacgcctg cacagcctgc gtctgccagg atggggccgc tcactgtggc 180

ccccaagcac acctgcccca ttgcaggggc tgcagccaaa atggccagac ctacggcaac 240

ggggagacct tctccccaga tgcctgcacc acctgccgct gtctggaagg taccatcact 300

tgcaaccaga agccatgccc aagaggaccc tgccctgagc caggagcatg ctgcccgcac 360

tgtaagccag gctgtgatta tgaggggcag ctttatgagg agggggtcac cttcctgtcc 420

agctccaacc cttgtctaca gtgcacctgc ctgaggagcc gagttcgctg catggccctg 480

aagtgcccgc ctagcccctg cccagagcca gtgctgaggc ctgggcactg ctgcccaacc 540

tgccaaggct gcacagaagg tggctctcac tgggaacatg gccaagagtg gacaacacct 600

ggggacccct gccgaatctg ccggtgcctg gagggtcaca tccagtgccg ccagcgagaa 660

tgtgccagcc tgtgtccata cccagcccgg cccctcccag gcacctgctg ccctgtgtgt 720

gatggctgtt tcctaaacgg gcgggagcac cgcagcgggg agcctgtggg ctcaggggac 780

ccctgctcgc actgccgctg tgctaatggg agtgtccagt gtgagcctct gccctgcccg 840

ccagtgccct gcagacaccc aggcaagatc cctgggcagt gctgccctgt ctgcgatggc 900

tgtgagtacc agggacacca gtatcagagc caggagacct tcagactcca agagcggggc 960

ctctgtgtcc gctgctcctg ccaggctggc gaggtctcct gtgaggagca ggagtgccca 1020

gtcaccccct gtgccctgcc tgcctctggc cgccagctct gcccagctca ccctgaccag 1080

cctgccccac ccacctgtga gctggatgga gaggagtttg ctgagggagt ccagtgggag 1140

cctgatggtc ggccctgcac cgcctgcgtc tgtcaagatg gggtacccaa gtgcggggct 1200

gtgctctgcc ccccagcccc ctgccagcac cccacccagc cccctggtgc ctgctgcccc 1260

agctgtgaca gctgcaccta ccacagccaa gtgtatgcca atgggcagaa cttcacggat 1320

gcagacagcc cttgccatgc ctgccactgt caggatggaa ctgtgacatg ctccttggtt 1380

gactgccctc ccacgacctg tgccaggccc cagagtggac caggccagtg ttgccccagg 1440

tgcccagact gcatcctgga ggaagaggtg tttgtggacg gcgagagctt ctcccacccc 1500

cgagacccct gccaggagtg ccgatgccag gaaggccatg cccactgcca gcctcgcccc 1560

tgccccaggg ccccctgtgc ccacccgctg cctgggacct gctgcccgaa cgactgcagc 1620

ggctgtgcct ttggcgggaa agagtacccc agcggagcgg acttccccca cccctctgac 1680

ccctgccgtc tgtgtcgctg tctgagcggc aacgtgcagt gcctggcccg ccgctgcgtg 1740

ccgctgccct gtccagagcc tgtcctgctg ccgggagagt gctgcccgca gtgcccagcc 1800

gccccagccc ccgccggctg cccacggccc ggcgcggccc acgcccgcca ccaggagtac 1860

ttctccccgc ccggcgatcc ctgccgccgc tgcctctgcc tcgacggctc cgtgtcctgc 1920

cagcggctgc cctgcccgcc cgcgccctgc gcgcacccgc gccaggggcc ttgctgcccc 1980

tcctgcgacg gctgcctgta ccaggggaag gagtttgcca gcggggagcg cttcccatcg 2040

cccactgctg cctgccacct ctgcctttgc tgggagggca gcgtgagctg cgagcccaag 2100

gcatgtgccc ctgcactgtg ccccttccct gccaggggcg actgctgccc tgactgtgat 2160

ggctgtgagt acctggggga gtcctacctg agtaaccagg agttcccaga cccccgagaa 2220

ccctgcaacc tgtgtacctg tcttggaggc ttcgtgacct gcggccgccg gccctgtgag 2280

cctccgggct gcagccaccc actcatcccc tctgggcact gctgcccgac ctgccaggga 2340

tgccgctacc atggcgtcac tactgcctcc ggagagaccc ttcctgaccc acttgaccct 2400

acctgctccc tctgcacctg ccagggccgg gagcaccagg atggggagga gtttgaggga 2460

ccagcaggca gctgtgagtg gtgtcgctgt caggctggcc aggtcagctg tgtgcggctg 2520

cagtgcccac cccttccctg caagctccag gtcaccgagc gggggagctg ctgccctcgc 2580

tgcagaggct gcctggctca tggggaagag caccccgaag gcagtagatg ggtgcccccc 2640

gacagtgcct gctcctcctg tgtgtgtcac gagggcgtcg tcacctgtgc acgcatccag 2700

tgcatcagct cttgcgccca gccccgccaa gggccccatg actgctgtcc tcaatgctct 2760

gactgtgagc atgagggccg gaagtacgag cctggggaga gcttccagcc tggggcagac 2820

ccctgtgaag tgtgcatctg cgagccacag cctgaggggc ctcccagcct tcgctgtcac 2880

cggcggcagt gtcccagcct ggtgggctgc ccccccagcc agctcctgcc ccctgggccc 2940

cagcactgct gtcccacctg tgccgaggcc ttgagtaact gttcagaggg cctgctggga 3000

tctgagctag ccccaccaga cccctgctac acgtgccagt gccaggacct gacatggctc 3060

tgcatccacc aggcttgtcc tgagctcagc tgtcccctct cagagcgcca cactccccct 3120

gggagctgct gccccgtatg ccgggaatgt gtggtggagg ccgagggccg gagagtggca 3180

gatggagaga gctggcggga ccccagcaat gcgtgcatcg cctgcacctg ccatcggggc 3240

catgtggagt gccacctcga ggagtgccag gccctctcct gcccccatgg ctgggcgaag 3300

gtgccccagg ctgacagctg ctgtgagcga tgccaagctc ccacccagtc ctgcgtgcac 3360

cagggccgtg aggtggcctc tggagagcgc tggactgtgg acacctgcac cagctgctcc 3420

tgcatggcgg gcaccgtgcg ttgccagagc cagcgctgct caccgctctc gtgtggcccc 3480

gacaaggccc ctgccctgag tcctggcagc tgctgccccc gctgcctgcc tcggcccgct 3540

tcctgcatgg ccttcggaga cccccattac cgcaccttcg acggccgcct gctgcacttc 3600

cagggcagtt gcagctatgt gctggccaag gactgccaca gcggggactt cagtgtgcac 3660

gtgaccaatg atgaccgggg ccggagcggt gtggcctgga cccaggaggt ggcggtgctg 3720

ctgggagaca tggccgtgcg gctgctgcag gacggggcag tcacggtgga tgggcacccg 3780

gtggccttgc ccttcctgca ggagccgctg ctgtatgtgg agctgcgagg acacactgtg 3840

atcctgcacg cccagcccgg gctccaggtg ctgtgggatg ggcagtccca ggtggaggtg 3900

agcgtacctg gctcctacca gggccggact tgtgggctct gtgggaactt caatggcttt 3960

gcccaggacg atctgcaggg ccctgagggg ctgctcctgc cctcggaggc tgcgtttggg 4020

aatagctggc aggtctcaga ggggctgtgg cctggccggc cctgttctgc aggccgagag 4080

gtggatccgt gccgggcagc aggttaccgt gccaggcgtg aggccaatgc ccggtgtggg 4140

gtgctgaagt cctccccatt cagtcgctgc catgctgtgg tgccaccgga gcccttcttt 4200

gccgcctgtg tgtatgacct gtgtgcctgt ggccctggct cctccgctga tgcctgcctc 4260

tgtgatgccc tggaagccta cgccagtcac tgtcgccagg caggagtgac acctacctgg 4320

cgaggcccca cgctgtgtgt ggtaggctgc cccctggagc gtggcttcgt gtttgatgag 4380

tgcggcccac cctgtccccg cacctgcttc aatcagcata tccccctggg ggagctggca 4440

gcccactgcg tgaggccctg cgtgcccggc tgccagtgcc ctgcaggcct ggtggagcat 4500

gaggcccact gcatcccacc cgaggcctgc ccccaagtcc tgctcactgg agaccagcca 4560

cttggtgctc ggcccagccc cagccgggag ccccaggaga caccc 4605



14
1535
PRT
homo sapiens

14

Met Glu Leu Arg Glu Gln Asn Lys Asp Leu Gln Thr Arg Val Arg Gln
1 5 10 15

Leu Glu Ser Cys Glu Cys His Pro Ala Ser Pro Gln Cys Trp Gly Leu
20 25 30

Gly Arg Ala Trp Pro Glu Gly Ala Arg Trp Glu Pro Asp Ala Cys Thr
35 40 45

Ala Cys Val Cys Gln Asp Gly Ala Ala His Cys Gly Pro Gln Ala His
50 55 60

Leu Pro His Cys Arg Gly Cys Ser Gln Asn Gly Gln Thr Tyr Gly Asn
65 70 75 80

Gly Glu Thr Phe Ser Pro Asp Ala Cys Thr Thr Cys Arg Cys Leu Glu
85 90 95

Gly Thr Ile Thr Cys Asn Gln Lys Pro Cys Pro Arg Gly Pro Cys Pro
100 105 110

Glu Pro Gly Ala Cys Cys Pro His Cys Lys Pro Gly Cys Asp Tyr Glu
115 120 125

Gly Gln Leu Tyr Glu Glu Gly Val Thr Phe Leu Ser Ser Ser Asn Pro
130 135 140

Cys Leu Gln Cys Thr Cys Leu Arg Ser Arg Val Arg Cys Met Ala Leu
145 150 155 160

Lys Cys Pro Pro Ser Pro Cys Pro Glu Pro Val Leu Arg Pro Gly His
165 170 175

Cys Cys Pro Thr Cys Gln Gly Cys Thr Glu Gly Gly Ser His Trp Glu
180 185 190

His Gly Gln Glu Trp Thr Thr Pro Gly Asp Pro Cys Arg Ile Cys Arg
195 200 205

Cys Leu Glu Gly His Ile Gln Cys Arg Gln Arg Glu Cys Ala Ser Leu
210 215 220

Cys Pro Tyr Pro Ala Arg Pro Leu Pro Gly Thr Cys Cys Pro Val Cys
225 230 235 240

Asp Gly Cys Phe Leu Asn Gly Arg Glu His Arg Ser Gly Glu Pro Val
245 250 255

Gly Ser Gly Asp Pro Cys Ser His Cys Arg Cys Ala Asn Gly Ser Val
260 265 270

Gln Cys Glu Pro Leu Pro Cys Pro Pro Val Pro Cys Arg His Pro Gly
275 280 285

Lys Ile Pro Gly Gln Cys Cys Pro Val Cys Asp Gly Cys Glu Tyr Gln
290 295 300

Gly His Gln Tyr Gln Ser Gln Glu Thr Phe Arg Leu Gln Glu Arg Gly
305 310 315 320

Leu Cys Val Arg Cys Ser Cys Gln Ala Gly Glu Val Ser Cys Glu Glu
325 330 335

Gln Glu Cys Pro Val Thr Pro Cys Ala Leu Pro Ala Ser Gly Arg Gln
340 345 350

Leu Cys Pro Ala His Pro Asp Gln Pro Ala Pro Pro Thr Cys Glu Leu
355 360 365

Asp Gly Glu Glu Phe Ala Glu Gly Val Gln Trp Glu Pro Asp Gly Arg
370 375 380

Pro Cys Thr Ala Cys Val Cys Gln Asp Gly Val Pro Lys Cys Gly Ala
385 390 395 400

Val Leu Cys Pro Pro Ala Pro Cys Gln His Pro Thr Gln Pro Pro Gly
405 410 415

Ala Cys Cys Pro Ser Cys Asp Ser Cys Thr Tyr His Ser Gln Val Tyr
420 425 430

Ala Asn Gly Gln Asn Phe Thr Asp Ala Asp Ser Pro Cys His Ala Cys
435 440 445

His Cys Gln Asp Gly Thr Val Thr Cys Ser Leu Val Asp Cys Pro Pro
450 455 460

Thr Thr Cys Ala Arg Pro Gln Ser Gly Pro Gly Gln Cys Cys Pro Arg
465 470 475 480

Cys Pro Asp Cys Ile Leu Glu Glu Glu Val Phe Val Asp Gly Glu Ser
485 490 495

Phe Ser His Pro Arg Asp Pro Cys Gln Glu Cys Arg Cys Gln Glu Gly
500 505 510

His Ala His Cys Gln Pro Arg Pro Cys Pro Arg Ala Pro Cys Ala His
515 520 525

Pro Leu Pro Gly Thr Cys Cys Pro Asn Asp Cys Ser Gly Cys Ala Phe
530 535 540

Gly Gly Lys Glu Tyr Pro Ser Gly Ala Asp Phe Pro His Pro Ser Asp
545 550 555 560

Pro Cys Arg Leu Cys Arg Cys Leu Ser Gly Asn Val Gln Cys Leu Ala
565 570 575

Arg Arg Cys Val Pro Leu Pro Cys Pro Glu Pro Val Leu Leu Pro Gly
580 585 590

Glu Cys Cys Pro Gln Cys Pro Ala Ala Pro Ala Pro Ala Gly Cys Pro
595 600 605

Arg Pro Gly Ala Ala His Ala Arg His Gln Glu Tyr Phe Ser Pro Pro
610 615 620

Gly Asp Pro Cys Arg Arg Cys Leu Cys Leu Asp Gly Ser Val Ser Cys
625 630 635 640

Gln Arg Leu Pro Cys Pro Pro Ala Pro Cys Ala His Pro Arg Gln Gly
645 650 655

Pro Cys Cys Pro Ser Cys Asp Gly Cys Leu Tyr Gln Gly Lys Glu Phe
660 665 670

Ala Ser Gly Glu Arg Phe Pro Ser Pro Thr Ala Ala Cys His Leu Cys
675 680 685

Leu Cys Trp Glu Gly Ser Val Ser Cys Glu Pro Lys Ala Cys Ala Pro
690 695 700

Ala Leu Cys Pro Phe Pro Ala Arg Gly Asp Cys Cys Pro Asp Cys Asp
705 710 715 720

Gly Cys Glu Tyr Leu Gly Glu Ser Tyr Leu Ser Asn Gln Glu Phe Pro
725 730 735

Asp Pro Arg Glu Pro Cys Asn Leu Cys Thr Cys Leu Gly Gly Phe Val
740 745 750

Thr Cys Gly Arg Arg Pro Cys Glu Pro Pro Gly Cys Ser His Pro Leu
755 760 765

Ile Pro Ser Gly His Cys Cys Pro Thr Cys Gln Gly Cys Arg Tyr His
770 775 780

Gly Val Thr Thr Ala Ser Gly Glu Thr Leu Pro Asp Pro Leu Asp Pro
785 790 795 800

Thr Cys Ser Leu Cys Thr Cys Gln Gly Arg Glu His Gln Asp Gly Glu
805 810 815

Glu Phe Glu Gly Pro Ala Gly Ser Cys Glu Trp Cys Arg Cys Gln Ala
820 825 830

Gly Gln Val Ser Cys Val Arg Leu Gln Cys Pro Pro Leu Pro Cys Lys
835 840 845

Leu Gln Val Thr Glu Arg Gly Ser Cys Cys Pro Arg Cys Arg Gly Cys
850 855 860

Leu Ala His Gly Glu Glu His Pro Glu Gly Ser Arg Trp Val Pro Pro
865 870 875 880

Asp Ser Ala Cys Ser Ser Cys Val Cys His Glu Gly Val Val Thr Cys
885 890 895

Ala Arg Ile Gln Cys Ile Ser Ser Cys Ala Gln Pro Arg Gln Gly Pro
900 905 910

His Asp Cys Cys Pro Gln Cys Ser Asp Cys Glu His Glu Gly Arg Lys
915 920 925

Tyr Glu Pro Gly Glu Ser Phe Gln Pro Gly Ala Asp Pro Cys Glu Val
930 935 940

Cys Ile Cys Glu Pro Gln Pro Glu Gly Pro Pro Ser Leu Arg Cys His
945 950 955 960

Arg Arg Gln Cys Pro Ser Leu Val Gly Cys Pro Pro Ser Gln Leu Leu
965 970 975

Pro Pro Gly Pro Gln His Cys Cys Pro Thr Cys Ala Glu Ala Leu Ser
980 985 990

Asn Cys Ser Glu Gly Leu Leu Gly Ser Glu Leu Ala Pro Pro Asp Pro
995 1000 1005

Cys Tyr Thr Cys Gln Cys Gln Asp Leu Thr Trp Leu Cys Ile His Gln
1010 1015 1020

Ala Cys Pro Glu Leu Ser Cys Pro Leu Ser Glu Arg His Thr Pro Pro
1025 1030 1035 1040

Gly Ser Cys Cys Pro Val Cys Arg Glu Cys Val Val Glu Ala Glu Gly
1045 1050 1055

Arg Arg Val Ala Asp Gly Glu Ser Trp Arg Asp Pro Ser Asn Ala Cys
1060 1065 1070

Ile Ala Cys Thr Cys His Arg Gly His Val Glu Cys His Leu Glu Glu
1075 1080 1085

Cys Gln Ala Leu Ser Cys Pro His Gly Trp Ala Lys Val Pro Gln Ala
1090 1095 1100

Asp Ser Cys Cys Glu Arg Cys Gln Ala Pro Thr Gln Ser Cys Val His
1105 1110 1115 1120

Gln Gly Arg Glu Val Ala Ser Gly Glu Arg Trp Thr Val Asp Thr Cys
1125 1130 1135

Thr Ser Cys Ser Cys Met Ala Gly Thr Val Arg Cys Gln Ser Gln Arg
1140 1145 1150

Cys Ser Pro Leu Ser Cys Gly Pro Asp Lys Ala Pro Ala Leu Ser Pro
1155 1160 1165

Gly Ser Cys Cys Pro Arg Cys Leu Pro Arg Pro Ala Ser Cys Met Ala
1170 1175 1180

Phe Gly Asp Pro His Tyr Arg Thr Phe Asp Gly Arg Leu Leu His Phe
1185 1190 1195 1200

Gln Gly Ser Cys Ser Tyr Val Leu Ala Lys Asp Cys His Ser Gly Asp
1205 1210 1215

Phe Ser Val His Val Thr Asn Asp Asp Arg Gly Arg Ser Gly Val Ala
1220 1225 1230

Trp Thr Gln Glu Val Ala Val Leu Leu Gly Asp Met Ala Val Arg Leu
1235 1240 1245

Leu Gln Asp Gly Ala Val Thr Val Asp Gly His Pro Val Ala Leu Pro
1250 1255 1260

Phe Leu Gln Glu Pro Leu Leu Tyr Val Glu Leu Arg Gly His Thr Val
1265 1270 1275 1280

Ile Leu His Ala Gln Pro Gly Leu Gln Val Leu Trp Asp Gly Gln Ser
1285 1290 1295

Gln Val Glu Val Ser Val Pro Gly Ser Tyr Gln Gly Arg Thr Cys Gly
1300 1305 1310

Leu Cys Gly Asn Phe Asn Gly Phe Ala Gln Asp Asp Leu Gln Gly Pro
1315 1320 1325

Glu Gly Leu Leu Leu Pro Ser Glu Ala Ala Phe Gly Asn Ser Trp Gln
1330 1335 1340

Val Ser Glu Gly Leu Trp Pro Gly Arg Pro Cys Ser Ala Gly Arg Glu
1345 1350 1355 1360

Val Asp Pro Cys Arg Ala Ala Gly Tyr Arg Ala Arg Arg Glu Ala Asn
1365 1370 1375

Ala Arg Cys Gly Val Leu Lys Ser Ser Pro Phe Ser Arg Cys His Ala
1380 1385 1390

Val Val Pro Pro Glu Pro Phe Phe Ala Ala Cys Val Tyr Asp Leu Cys
1395 1400 1405

Ala Cys Gly Pro Gly Ser Ser Ala Asp Ala Cys Leu Cys Asp Ala Leu
1410 1415 1420

Glu Ala Tyr Ala Ser His Cys Arg Gln Ala Gly Val Thr Pro Thr Trp
1425 1430 1435 1440

Arg Gly Pro Thr Leu Cys Val Val Gly Cys Pro Leu Glu Arg Gly Phe
1445 1450 1455

Val Phe Asp Glu Cys Gly Pro Pro Cys Pro Arg Thr Cys Phe Asn Gln
1460 1465 1470

His Ile Pro Leu Gly Glu Leu Ala Ala His Cys Val Arg Pro Cys Val
1475 1480 1485

Pro Gly Cys Gln Cys Pro Ala Gly Leu Val Glu His Glu Ala His Cys
1490 1495 1500

Ile Pro Pro Glu Ala Cys Pro Gln Val Leu Leu Thr Gly Asp Gln Pro
1505 1510 1515 1520

Leu Gly Ala Arg Pro Ser Pro Ser Arg Glu Pro Gln Glu Thr Pro
1525 1530 1535



15
3753
DNA
homo sapiens

15

atgggagtgt ccagtgtgag cctctgccct gcccgccagt gccctgcaga cacccaggca 60

agatccctgg gcagtgctgc cctgtctgcg atggctgtga gtaccaggga caccagtatc 120

agagccagga gaccttcaga ctccaagagc ggggcctctg tgtccgctgc tcctgccagg 180

ctggcgaggt ctcctgtgag gagcaggagt gcccagtcac cccctgtgcc ctgcctgcct 240

ctggccgcca gctctgccca gctcaccctg accagcctgc cccacccagg tgcctgctgc 300

cccagctgtg acagctgcac ctaccacagc caagtgtatg ccaatgggca gaacttcacg 360

gatgcagaca gcccttgcca tgcctgccac tgtcaggatg gaactgtgac atgctccttg 420

gttgactgcc ctcccacgac ctgtgccagg ccccagagtg gaccaggcca gtgttgcccc 480

aggtgcccag actgcatcct ggaggaagag gtgtttgtgg acggcgagag cttctcccac 540

ccccgagacc cctgccagga gtgccgatgc caggaaggcc atgcccactg ccagcctcgc 600

ccctgcccca gggccccctg tgcccacccg ctgcctggga cctgctgccc gaacgactgc 660

agcggctgtg cctttggcgg gaaagagtac cccagcggag cggacttccc ccacccctct 720

gacccctgcc gtctgtgtcg ctgtctgagc ggcaacgtgc agtgcctggc ccgccgctgc 780

gtgccgctgc cctgtccaga gcctgtcctg ctgccgggag agtgctgccc gcagtgccca 840

gccgccccag cccccgccgg ctgcccacgg cccggcgcgg cccacgcccg ccaccaggag 900

tacttctccc cgcccggcga tccctgccgc cgctgcctct gcctcgacgg ctccgtgtcc 960

tgccagcggc tgccctgccc gcccgcgccc tgcgcgcacc cgcgccaggg gccttgctgc 1020

ccctcctgcg acggctgcct gtaccagggg aaggagtttg ccagcgggga gcgcttccca 1080

tcgcccactg ctgcctgcca cctctgcctt tgctgggagg gcagcgtgag ctgcgagccc 1140

aaggcatgtg cccctgcact gtgccccttc cctgccaggg gcgactgctg ccctgactgt 1200

gatggctgtg agtacctggg ggagtcctac ctgagtaacc aggagttccc agacccccga 1260

gaaccctgca acctgtgtac ctgtcttgga ggcttcgtga cctgcggccg ccggccctgt 1320

gagcctccgg gctgcagcca cccactcatc ccctctgggc actgctgccc gacctgccag 1380

ggatgccgct accatggcgt cactactgcc tccggagaga cccttcctga cccacttgac 1440

cctacctgct ccctctgcac ctgccaggaa ggttccatgc gctgccaaaa gaagccatgt 1500

gccccagctc tctgccccca cccctctcca ggcccctgct tctgccctgt ttgccacagt 1560

tgtctctctc agggccggga gcaccaggat ggggaggagt ttgagggacc agcaggcagc 1620

tgtgagtggt gtcgctgtca ggctggccag gtcagctgtg tgcggctgca gtgcccaccc 1680

cttccctgca agctccaggt caccgagcgg gggagctgct gccctcgctg cagaggctgc 1740

ctggctcatg gggaagagca ccccgaaggc agtagatggg tgccccccga cagtgcctgc 1800

tcctcctgtg tgtgtcacga gggcgtcgtc acctgtgcac gcatccagtg catcagctct 1860

tgcgcccagc cccgccaagg gccccatgac tgctgtcctc aatgctctga ctgtgagcat 1920

gagggccgga agtacgagcc tggggagagc ttccagcctg gggcagaccc ctgtgaagtg 1980

tgcatctgcg agccacagcc tgaggggcct cccagccttc gctgtcaccg gcggcagtgt 2040

cccagcctgg tgggctgccc ccccagccag ctcctgcccc ctgggcccca gcactgctgt 2100

cccacctgtg ccgaggcctt gagtaactgt tcagagggcc tgctgggatc tgagctagcc 2160

ccaccagacc cctgctacac gtgccagtgc caggacctga catggctctg catccaccag 2220

gcttgtcctg agctcagctg tcccctctca gagcgccaca ctccccctgg gagctgctgc 2280

cccgtatgcc gggaatgtgt ggtggaggcc gagggccgga gagtggcaga tggagagagc 2340

tggcgggacc ccagcaatgc gtgcatcgcc tgcacctgcc atcggggcca tgtggagtgc 2400

cacctcgagg agtgccaggc cctctcctgc ccccatggct gggcgaaggt gccccaggct 2460

gacagctgct gtgagcgatg ccaagctccc acccagtcct gcgtgcacca gggccgtgag 2520

gtggcctctg gagagcgctg gactgtggac acctgcacca gctgctcctg catggcgggc 2580

accgtgcgtt gccagagcca gcgctgctca ccgctctcgt gtggccccga caaggcccct 2640

gccctgagtc ctggcagctg ctgcccccgc tgcctgcctc ggcccgcttc ctgcatggcc 2700

ttcggagacc cccattaccg caccttcgac ggccgcctgc tgcacttcca gggcagttgc 2760

agctatgtgc tggccaagga ctgccacagc ggggacttca gtgtgcacgt gaccaatgat 2820

gaccggggcc ggagcggtgt ggcctggacc caggaggtgg cggtgctgct gggagacatg 2880

gccgtgcggc tgctgcagga cggggcagtc acggtggatg ggcacccggt ggccttgccc 2940

ttcctgcagg agccgctgct gtatgtggag ctgcgaggac acactgtgat cctgcacgcc 3000

cagcccgggc tccaggtgct gtgggatggg cagtcccagg tggaggtgag cgtacctggc 3060

tcctaccagg gccggacttg tgggctctgt gggaacttca atggctttgc ccaggacgat 3120

ctgcagggcc ctgaggggct gctcctgccc tcggaggctg cgtttgggaa tagctggcag 3180

gtctcagagg ggctgtggcc tggccggccc tgttctgcag gccgagaggt ggatccgtgc 3240

cgggcagcag gttaccgtgc caggcgtgag gccaatgccc ggtgtggggt gctgaagtcc 3300

tccccattca gtcgctgcca tgctgtggtg ccaccggagc ccttctttgc cgcctgtgtg 3360

tatgacctgt gtgcctgtgg ccctggctcc tccgctgatg cctgcctctg tgatgccctg 3420

gaagcctacg ccagtcactg tcgccaggca ggagtgacac ctacctggcg aggccccacg 3480

ctgtgtgtgg taggctgccc cctggagcgt ggcttcgtgt ttgatgagtg cggcccaccc 3540

tgtccccgca cctgcttcaa tcagcatatc cccctggggg agctggcagc ccactgcgtg 3600

aggccctgcg tgcccggctg ccagtgccct gcaggcctgg tggagcatga ggcccactgc 3660

atcccacccg aggcctgccc ccaagtcctg ctcactggag accagccact tggtgctcgg 3720

cccagcccca gccgggagcc ccaggagaca ccc 3753



16
1251
PRT
homo sapiens

16

Met Gly Val Ser Ser Val Ser Leu Cys Pro Ala Arg Gln Cys Pro Ala
1 5 10 15

Asp Thr Gln Ala Arg Ser Leu Gly Ser Ala Ala Leu Ser Ala Met Ala
20 25 30

Val Ser Thr Arg Asp Thr Ser Ile Arg Ala Arg Arg Pro Ser Asp Ser
35 40 45

Lys Ser Gly Ala Ser Val Ser Ala Ala Pro Ala Arg Leu Ala Arg Ser
50 55 60

Pro Val Arg Ser Arg Ser Ala Gln Ser Pro Pro Val Pro Cys Leu Pro
65 70 75 80

Leu Ala Ala Ser Ser Ala Gln Leu Thr Leu Thr Ser Leu Pro His Pro
85 90 95

Gly Ala Cys Cys Pro Ser Cys Asp Ser Cys Thr Tyr His Ser Gln Val
100 105 110

Tyr Ala Asn Gly Gln Asn Phe Thr Asp Ala Asp Ser Pro Cys His Ala
115 120 125

Cys His Cys Gln Asp Gly Thr Val Thr Cys Ser Leu Val Asp Cys Pro
130 135 140

Pro Thr Thr Cys Ala Arg Pro Gln Ser Gly Pro Gly Gln Cys Cys Pro
145 150 155 160

Arg Cys Pro Asp Cys Ile Leu Glu Glu Glu Val Phe Val Asp Gly Glu
165 170 175

Ser Phe Ser His Pro Arg Asp Pro Cys Gln Glu Cys Arg Cys Gln Glu
180 185 190

Gly His Ala His Cys Gln Pro Arg Pro Cys Pro Arg Ala Pro Cys Ala
195 200 205

His Pro Leu Pro Gly Thr Cys Cys Pro Asn Asp Cys Ser Gly Cys Ala
210 215 220

Phe Gly Gly Lys Glu Tyr Pro Ser Gly Ala Asp Phe Pro His Pro Ser
225 230 235 240

Asp Pro Cys Arg Leu Cys Arg Cys Leu Ser Gly Asn Val Gln Cys Leu
245 250 255

Ala Arg Arg Cys Val Pro Leu Pro Cys Pro Glu Pro Val Leu Leu Pro
260 265 270

Gly Glu Cys Cys Pro Gln Cys Pro Ala Ala Pro Ala Pro Ala Gly Cys
275 280 285

Pro Arg Pro Gly Ala Ala His Ala Arg His Gln Glu Tyr Phe Ser Pro
290 295 300

Pro Gly Asp Pro Cys Arg Arg Cys Leu Cys Leu Asp Gly Ser Val Ser
305 310 315 320

Cys Gln Arg Leu Pro Cys Pro Pro Ala Pro Cys Ala His Pro Arg Gln
325 330 335

Gly Pro Cys Cys Pro Ser Cys Asp Gly Cys Leu Tyr Gln Gly Lys Glu
340 345 350

Phe Ala Ser Gly Glu Arg Phe Pro Ser Pro Thr Ala Ala Cys His Leu
355 360 365

Cys Leu Cys Trp Glu Gly Ser Val Ser Cys Glu Pro Lys Ala Cys Ala
370 375 380

Pro Ala Leu Cys Pro Phe Pro Ala Arg Gly Asp Cys Cys Pro Asp Cys
385 390 395 400

Asp Gly Cys Glu Tyr Leu Gly Glu Ser Tyr Leu Ser Asn Gln Glu Phe
405 410 415

Pro Asp Pro Arg Glu Pro Cys Asn Leu Cys Thr Cys Leu Gly Gly Phe
420 425 430

Val Thr Cys Gly Arg Arg Pro Cys Glu Pro Pro Gly Cys Ser His Pro
435 440 445

Leu Ile Pro Ser Gly His Cys Cys Pro Thr Cys Gln Gly Cys Arg Tyr
450 455 460

His Gly Val Thr Thr Ala Ser Gly Glu Thr Leu Pro Asp Pro Leu Asp
465 470 475 480

Pro Thr Cys Ser Leu Cys Thr Cys Gln Glu Gly Ser Met Arg Cys Gln
485 490 495

Lys Lys Pro Cys Ala Pro Ala Leu Cys Pro His Pro Ser Pro Gly Pro
500 505 510

Cys Phe Cys Pro Val Cys His Ser Cys Leu Ser Gln Gly Arg Glu His
515 520 525

Gln Asp Gly Glu Glu Phe Glu Gly Pro Ala Gly Ser Cys Glu Trp Cys
530 535 540

Arg Cys Gln Ala Gly Gln Val Ser Cys Val Arg Leu Gln Cys Pro Pro
545 550 555 560

Leu Pro Cys Lys Leu Gln Val Thr Glu Arg Gly Ser Cys Cys Pro Arg
565 570 575

Cys Arg Gly Cys Leu Ala His Gly Glu Glu His Pro Glu Gly Ser Arg
580 585 590

Trp Val Pro Pro Asp Ser Ala Cys Ser Ser Cys Val Cys His Glu Gly
595 600 605

Val Val Thr Cys Ala Arg Ile Gln Cys Ile Ser Ser Cys Ala Gln Pro
610 615 620

Arg Gln Gly Pro His Asp Cys Cys Pro Gln Cys Ser Asp Cys Glu His
625 630 635 640

Glu Gly Arg Lys Tyr Glu Pro Gly Glu Ser Phe Gln Pro Gly Ala Asp
645 650 655

Pro Cys Glu Val Cys Ile Cys Glu Pro Gln Pro Glu Gly Pro Pro Ser
660 665 670

Leu Arg Cys His Arg Arg Gln Cys Pro Ser Leu Val Gly Cys Pro Pro
675 680 685

Ser Gln Leu Leu Pro Pro Gly Pro Gln His Cys Cys Pro Thr Cys Ala
690 695 700

Glu Ala Leu Ser Asn Cys Ser Glu Gly Leu Leu Gly Ser Glu Leu Ala
705 710 715 720

Pro Pro Asp Pro Cys Tyr Thr Cys Gln Cys Gln Asp Leu Thr Trp Leu
725 730 735

Cys Ile His Gln Ala Cys Pro Glu Leu Ser Cys Pro Leu Ser Glu Arg
740 745 750

His Thr Pro Pro Gly Ser Cys Cys Pro Val Cys Arg Glu Cys Val Val
755 760 765

Glu Ala Glu Gly Arg Arg Val Ala Asp Gly Glu Ser Trp Arg Asp Pro
770 775 780

Ser Asn Ala Cys Ile Ala Cys Thr Cys His Arg Gly His Val Glu Cys
785 790 795 800

His Leu Glu Glu Cys Gln Ala Leu Ser Cys Pro His Gly Trp Ala Lys
805 810 815

Val Pro Gln Ala Asp Ser Cys Cys Glu Arg Cys Gln Ala Pro Thr Gln
820 825 830

Ser Cys Val His Gln Gly Arg Glu Val Ala Ser Gly Glu Arg Trp Thr
835 840 845

Val Asp Thr Cys Thr Ser Cys Ser Cys Met Ala Gly Thr Val Arg Cys
850 855 860

Gln Ser Gln Arg Cys Ser Pro Leu Ser Cys Gly Pro Asp Lys Ala Pro
865 870 875 880

Ala Leu Ser Pro Gly Ser Cys Cys Pro Arg Cys Leu Pro Arg Pro Ala
885 890 895

Ser Cys Met Ala Phe Gly Asp Pro His Tyr Arg Thr Phe Asp Gly Arg
900 905 910

Leu Leu His Phe Gln Gly Ser Cys Ser Tyr Val Leu Ala Lys Asp Cys
915 920 925

His Ser Gly Asp Phe Ser Val His Val Thr Asn Asp Asp Arg Gly Arg
930 935 940

Ser Gly Val Ala Trp Thr Gln Glu Val Ala Val Leu Leu Gly Asp Met
945 950 955 960

Ala Val Arg Leu Leu Gln Asp Gly Ala Val Thr Val Asp Gly His Pro
965 970 975

Val Ala Leu Pro Phe Leu Gln Glu Pro Leu Leu Tyr Val Glu Leu Arg
980 985 990

Gly His Thr Val Ile Leu His Ala Gln Pro Gly Leu Gln Val Leu Trp
995 1000 1005

Asp Gly Gln Ser Gln Val Glu Val Ser Val Pro Gly Ser Tyr Gln Gly
1010 1015 1020

Arg Thr Cys Gly Leu Cys Gly Asn Phe Asn Gly Phe Ala Gln Asp Asp
1025 1030 1035 1040

Leu Gln Gly Pro Glu Gly Leu Leu Leu Pro Ser Glu Ala Ala Phe Gly
1045 1050 1055

Asn Ser Trp Gln Val Ser Glu Gly Leu Trp Pro Gly Arg Pro Cys Ser
1060 1065 1070

Ala Gly Arg Glu Val Asp Pro Cys Arg Ala Ala Gly Tyr Arg Ala Arg
1075 1080 1085

Arg Glu Ala Asn Ala Arg Cys Gly Val Leu Lys Ser Ser Pro Phe Ser
1090 1095 1100

Arg Cys His Ala Val Val Pro Pro Glu Pro Phe Phe Ala Ala Cys Val
1105 1110 1115 1120

Tyr Asp Leu Cys Ala Cys Gly Pro Gly Ser Ser Ala Asp Ala Cys Leu
1125 1130 1135

Cys Asp Ala Leu Glu Ala Tyr Ala Ser His Cys Arg Gln Ala Gly Val
1140 1145 1150

Thr Pro Thr Trp Arg Gly Pro Thr Leu Cys Val Val Gly Cys Pro Leu
1155 1160 1165

Glu Arg Gly Phe Val Phe Asp Glu Cys Gly Pro Pro Cys Pro Arg Thr
1170 1175 1180

Cys Phe Asn Gln His Ile Pro Leu Gly Glu Leu Ala Ala His Cys Val
1185 1190 1195 1200

Arg Pro Cys Val Pro Gly Cys Gln Cys Pro Ala Gly Leu Val Glu His
1205 1210 1215

Glu Ala His Cys Ile Pro Pro Glu Ala Cys Pro Gln Val Leu Leu Thr
1220 1225 1230

Gly Asp Gln Pro Leu Gly Ala Arg Pro Ser Pro Ser Arg Glu Pro Gln
1235 1240 1245

Glu Thr Pro
1250



17
3576
DNA
homo sapiens

17

atggccaaga gtggacaaca cctggggacc cctgccgaat ctgccggtgc ctggagggtc 60

acatccagtg ccgccagcga gaatgtgcca gcctgtgtcc atacccagcc cggcccctcc 120

caggcacctg ctgccctgtg tgtgatgaat gggagtgtcc agtgtgagcc tctgccctgc 180

ccgccagtgc cctgcagaca cccaggcaag atccctgggc agtgctgccc cagctgtgac 240

agctgcacct accacagcca agtgtatgcc aatgggcaga acttcacgga tgcagacagc 300

ccttgccatg cctgccactg tcaggatgga actgtgacat gctccttggt tgactgccct 360

cccacgacct gtgccaggcc ccagagtgga ccaggccagt gttgccccag gtgcccagac 420

tgcatcctgg aggaagaggt gtttgtggac ggcgagagct tctcccaccc ccgagacccc 480

tgccaggagt gccgatgcca ggaaggccat gcccactgcc agcctcgccc ctgccccagg 540

gccccctgtg cccacccgct gcctgggacc tgctgcccga acgactgcag cggctgtgcc 600

tttggcggga aagagtaccc cagcggagcg gacttccccc acccctctga cccctgccgt 660

ctgtgtcgct gtctgagcgg caacgtgcag tgcctggccc gccgctgcgt gccgctgccc 720

tgtccagagc ctgtcctgct gccgggagag tgctgcccgc agtgcccagc cgccccagcc 780

cccgccggct gcccacggcc cggcgcggcc cacgcccgcc accaggagta cttctccccg 840

cccggcgatc cctgccgccg ctgcctctgc ctcgacggct ccgtgtcctg ccagcggctg 900

ccctgcccgc ccgcgccctg cgcgcacccg cgccaggggc cttgctgccc ctcctgcgac 960

ggctgcctgt accaggggaa ggagtttgcc agcggggagc gcttcccatc gcccactgct 1020

gcctgccacc tctgcctttg ctgggagggc agcgtgagct gcgagcccaa ggcatgtgcc 1080

cctgcactgt gccccttccc tgccaggggc gactgctgcc ctgactgtga tggctgtgag 1140

tacctggggg agtcctacct gagtaaccag gagttcccag acccccgaga accctgcaac 1200

ctgtgtacct gtcttggagg cttcgtgacc tgcggccgcc ggccctgtga gcctccgggc 1260

tgcagccacc cactcatccc ctctgggcac tgctgcccga cctgccaggg atgccgctac 1320

catggcgtca ctactgcctc cggagagacc cttcctgacc cacttgaccc tacctgctcc 1380

ctctgcacct gccagggccg ggagcaccag gatggggagg agtttgaggg accagcaggc 1440

agctgtgagt ggtgtcgctg tcaggctggc caggtcagct gtgtgcggct gcagtgccca 1500

ccccttccct gcaagctcca ggtcaccgag cgggggagct gctgccctcg ctgcagaggc 1560

tgcctggctc atggggaaga gcaccccgaa ggcagtagat gggtgccccc cgacagtgcc 1620

tgctcctcct gtgtgtgtca cgagggcgtc gtcacctgtg cacgcatcca gtgcatcagc 1680

tcttgcgccc agccccgcca agggccccat gactgctgtc ctcaatgctc tgactgtgag 1740

catgagggcc ggaagtacga gcctggggag agcttccagc ctggggcaga cccctgtgaa 1800

gtgtgcatct gcgagccaca gcctgagggg cctcccagcc ttcgctgtca ccggcggcag 1860

tgtcccagcc tggtgggctg cccccccagc cagctcctgc cccctgggcc ccagcactgc 1920

tgtcccacct gtgccgaggc cttgagtaac tgttcagagg gcctgctggg atctgagcta 1980

gccccaccag acccctgcta cacgtgccag tgccaggacc tgacatggct ctgcatccac 2040

caggcttgtc ctgagctcag ctgtcccctc tcagagcgcc acactccccc tgggagctgc 2100

tgccccgtat gccgggaatg tgtggtggag gccgagggcc ggagagtggc agatggagag 2160

agctggcggg accccagcaa tgcgtgcatc gcctgcacct gccatcgggg ccatgtggag 2220

tgccacctcg aggagtgcca ggccctctcc tgcccccatg gctgggcgaa ggtgccccag 2280

gctgacagct gctgtgagcg atgccaagct cccacccagt cctgcgtgca ccagggccgt 2340

gaggtggcct ctggagagcg ctggactgtg gacacctgca ccagctgctc ctgcatggcg 2400

ggcaccgtgc gttgccagag ccagcgctgc tcaccgctct cgtgtggccc cgacaaggcc 2460

cctgccctga gtcctggcag ctgctgcccc cgctgcctgc ctcggcccgc ttcctgcatg 2520

gccttcggag acccccatta ccgcaccttc gacggccgcc tgctgcactt ccagggcagt 2580

tgcagctatg tgctggccaa ggactgccac agcggggact tcagtgtgca cgtgaccaat 2640

gatgaccggg gccggagcgg tgtggcctgg acccaggagg tggcggtgct gctgggagac 2700

atggccgtgc ggctgctgca ggacggggca gtcacggtgg atgggcaccc ggtggccttg 2760

cccttcctgc aggagccgct gctgtatgtg gagctgcgag gacacactgt gatcctgcac 2820

gcccagcccg ggctccaggt gctgtgggat gggcagtccc aggtggaggt gagcgtacct 2880

ggctcctacc agggccggac ttgtgggctc tgtgggaact tcaatggctt tgcccaggac 2940

gatctgcagg gccctgaggg gctgctcctg ccctcggagg ctgcgtttgg gaatagctgg 3000

caggtctcag aggggctgtg gcctggccgg ccctgttctg caggccgaga ggtggatccg 3060

tgccgggcag caggttaccg tgccaggcgt gaggccaatg cccggtgtgg ggtgctgaag 3120

tcctccccat tcagtcgctg ccatgctgtg gtgccaccgg agcccttctt tgccgcctgt 3180

gtgtatgacc tgtgtgcctg tggccctggc tcctccgctg atgcctgcct ctgtgatgcc 3240

ctggaagcct acgccagtca ctgtcgccag gcaggagtga cacctacctg gcgaggcccc 3300

acgctgtgtg tggtaggctg ccccctggag cgtggcttcg tgtttgatga gtgcggccca 3360

ccctgtcccc gcacctgctt caatcagcat atccccctgg gggagctggc agcccactgc 3420

gtgaggccct gcgtgcccgg ctgccagtgc cctgcaggcc tggtggagca tgaggcccac 3480

tgcatcccac ccgaggcctg cccccaagtc ctgctcactg gagaccagcc acttggtgct 3540

cggcccagcc ccagccggga gccccaggag acaccc 3576



18
1192
PRT
homo sapiens

18

Met Ala Lys Ser Gly Gln His Leu Gly Thr Pro Ala Glu Ser Ala Gly
1 5 10 15

Ala Trp Arg Val Thr Ser Ser Ala Ala Ser Glu Asn Val Pro Ala Cys
20 25 30

Val His Thr Gln Pro Gly Pro Ser Gln Ala Pro Ala Ala Leu Cys Val
35 40 45

Met Asn Gly Ser Val Gln Cys Glu Pro Leu Pro Cys Pro Pro Val Pro
50 55 60

Cys Arg His Pro Gly Lys Ile Pro Gly Gln Cys Cys Pro Ser Cys Asp
65 70 75 80

Ser Cys Thr Tyr His Ser Gln Val Tyr Ala Asn Gly Gln Asn Phe Thr
85 90 95

Asp Ala Asp Ser Pro Cys His Ala Cys His Cys Gln Asp Gly Thr Val
100 105 110

Thr Cys Ser Leu Val Asp Cys Pro Pro Thr Thr Cys Ala Arg Pro Gln
115 120 125

Ser Gly Pro Gly Gln Cys Cys Pro Arg Cys Pro Asp Cys Ile Leu Glu
130 135 140

Glu Glu Val Phe Val Asp Gly Glu Ser Phe Ser His Pro Arg Asp Pro
145 150 155 160

Cys Gln Glu Cys Arg Cys Gln Glu Gly His Ala His Cys Gln Pro Arg
165 170 175

Pro Cys Pro Arg Ala Pro Cys Ala His Pro Leu Pro Gly Thr Cys Cys
180 185 190

Pro Asn Asp Cys Ser Gly Cys Ala Phe Gly Gly Lys Glu Tyr Pro Ser
195 200 205

Gly Ala Asp Phe Pro His Pro Ser Asp Pro Cys Arg Leu Cys Arg Cys
210 215 220

Leu Ser Gly Asn Val Gln Cys Leu Ala Arg Arg Cys Val Pro Leu Pro
225 230 235 240

Cys Pro Glu Pro Val Leu Leu Pro Gly Glu Cys Cys Pro Gln Cys Pro
245 250 255

Ala Ala Pro Ala Pro Ala Gly Cys Pro Arg Pro Gly Ala Ala His Ala
260 265 270

Arg His Gln Glu Tyr Phe Ser Pro Pro Gly Asp Pro Cys Arg Arg Cys
275 280 285

Leu Cys Leu Asp Gly Ser Val Ser Cys Gln Arg Leu Pro Cys Pro Pro
290 295 300

Ala Pro Cys Ala His Pro Arg Gln Gly Pro Cys Cys Pro Ser Cys Asp
305 310 315 320

Gly Cys Leu Tyr Gln Gly Lys Glu Phe Ala Ser Gly Glu Arg Phe Pro
325 330 335

Ser Pro Thr Ala Ala Cys His Leu Cys Leu Cys Trp Glu Gly Ser Val
340 345 350

Ser Cys Glu Pro Lys Ala Cys Ala Pro Ala Leu Cys Pro Phe Pro Ala
355 360 365

Arg Gly Asp Cys Cys Pro Asp Cys Asp Gly Cys Glu Tyr Leu Gly Glu
370 375 380

Ser Tyr Leu Ser Asn Gln Glu Phe Pro Asp Pro Arg Glu Pro Cys Asn
385 390 395 400

Leu Cys Thr Cys Leu Gly Gly Phe Val Thr Cys Gly Arg Arg Pro Cys
405 410 415

Glu Pro Pro Gly Cys Ser His Pro Leu Ile Pro Ser Gly His Cys Cys
420 425 430

Pro Thr Cys Gln Gly Cys Arg Tyr His Gly Val Thr Thr Ala Ser Gly
435 440 445

Glu Thr Leu Pro Asp Pro Leu Asp Pro Thr Cys Ser Leu Cys Thr Cys
450 455 460

Gln Gly Arg Glu His Gln Asp Gly Glu Glu Phe Glu Gly Pro Ala Gly
465 470 475 480

Ser Cys Glu Trp Cys Arg Cys Gln Ala Gly Gln Val Ser Cys Val Arg
485 490 495

Leu Gln Cys Pro Pro Leu Pro Cys Lys Leu Gln Val Thr Glu Arg Gly
500 505 510

Ser Cys Cys Pro Arg Cys Arg Gly Cys Leu Ala His Gly Glu Glu His
515 520 525

Pro Glu Gly Ser Arg Trp Val Pro Pro Asp Ser Ala Cys Ser Ser Cys
530 535 540

Val Cys His Glu Gly Val Val Thr Cys Ala Arg Ile Gln Cys Ile Ser
545 550 555 560

Ser Cys Ala Gln Pro Arg Gln Gly Pro His Asp Cys Cys Pro Gln Cys
565 570 575

Ser Asp Cys Glu His Glu Gly Arg Lys Tyr Glu Pro Gly Glu Ser Phe
580 585 590

Gln Pro Gly Ala Asp Pro Cys Glu Val Cys Ile Cys Glu Pro Gln Pro
595 600 605

Glu Gly Pro Pro Ser Leu Arg Cys His Arg Arg Gln Cys Pro Ser Leu
610 615 620

Val Gly Cys Pro Pro Ser Gln Leu Leu Pro Pro Gly Pro Gln His Cys
625 630 635 640

Cys Pro Thr Cys Ala Glu Ala Leu Ser Asn Cys Ser Glu Gly Leu Leu
645 650 655

Gly Ser Glu Leu Ala Pro Pro Asp Pro Cys Tyr Thr Cys Gln Cys Gln
660 665 670

Asp Leu Thr Trp Leu Cys Ile His Gln Ala Cys Pro Glu Leu Ser Cys
675 680 685

Pro Leu Ser Glu Arg His Thr Pro Pro Gly Ser Cys Cys Pro Val Cys
690 695 700

Arg Glu Cys Val Val Glu Ala Glu Gly Arg Arg Val Ala Asp Gly Glu
705 710 715 720

Ser Trp Arg Asp Pro Ser Asn Ala Cys Ile Ala Cys Thr Cys His Arg
725 730 735

Gly His Val Glu Cys His Leu Glu Glu Cys Gln Ala Leu Ser Cys Pro
740 745 750

His Gly Trp Ala Lys Val Pro Gln Ala Asp Ser Cys Cys Glu Arg Cys
755 760 765

Gln Ala Pro Thr Gln Ser Cys Val His Gln Gly Arg Glu Val Ala Ser
770 775 780

Gly Glu Arg Trp Thr Val Asp Thr Cys Thr Ser Cys Ser Cys Met Ala
785 790 795 800

Gly Thr Val Arg Cys Gln Ser Gln Arg Cys Ser Pro Leu Ser Cys Gly
805 810 815

Pro Asp Lys Ala Pro Ala Leu Ser Pro Gly Ser Cys Cys Pro Arg Cys
820 825 830

Leu Pro Arg Pro Ala Ser Cys Met Ala Phe Gly Asp Pro His Tyr Arg
835 840 845

Thr Phe Asp Gly Arg Leu Leu His Phe Gln Gly Ser Cys Ser Tyr Val
850 855 860

Leu Ala Lys Asp Cys His Ser Gly Asp Phe Ser Val His Val Thr Asn
865 870 875 880

Asp Asp Arg Gly Arg Ser Gly Val Ala Trp Thr Gln Glu Val Ala Val
885 890 895

Leu Leu Gly Asp Met Ala Val Arg Leu Leu Gln Asp Gly Ala Val Thr
900 905 910

Val Asp Gly His Pro Val Ala Leu Pro Phe Leu Gln Glu Pro Leu Leu
915 920 925

Tyr Val Glu Leu Arg Gly His Thr Val Ile Leu His Ala Gln Pro Gly
930 935 940

Leu Gln Val Leu Trp Asp Gly Gln Ser Gln Val Glu Val Ser Val Pro
945 950 955 960

Gly Ser Tyr Gln Gly Arg Thr Cys Gly Leu Cys Gly Asn Phe Asn Gly
965 970 975

Phe Ala Gln Asp Asp Leu Gln Gly Pro Glu Gly Leu Leu Leu Pro Ser
980 985 990

Glu Ala Ala Phe Gly Asn Ser Trp Gln Val Ser Glu Gly Leu Trp Pro
995 1000 1005

Gly Arg Pro Cys Ser Ala Gly Arg Glu Val Asp Pro Cys Arg Ala Ala
1010 1015 1020

Gly Tyr Arg Ala Arg Arg Glu Ala Asn Ala Arg Cys Gly Val Leu Lys
1025 1030 1035 1040

Ser Ser Pro Phe Ser Arg Cys His Ala Val Val Pro Pro Glu Pro Phe
1045 1050 1055

Phe Ala Ala Cys Val Tyr Asp Leu Cys Ala Cys Gly Pro Gly Ser Ser
1060 1065 1070

Ala Asp Ala Cys Leu Cys Asp Ala Leu Glu Ala Tyr Ala Ser His Cys
1075 1080 1085

Arg Gln Ala Gly Val Thr Pro Thr Trp Arg Gly Pro Thr Leu Cys Val
1090 1095 1100

Val Gly Cys Pro Leu Glu Arg Gly Phe Val Phe Asp Glu Cys Gly Pro
1105 1110 1115 1120

Pro Cys Pro Arg Thr Cys Phe Asn Gln His Ile Pro Leu Gly Glu Leu
1125 1130 1135

Ala Ala His Cys Val Arg Pro Cys Val Pro Gly Cys Gln Cys Pro Ala
1140 1145 1150

Gly Leu Val Glu His Glu Ala His Cys Ile Pro Pro Glu Ala Cys Pro
1155 1160 1165

Gln Val Leu Leu Thr Gly Asp Gln Pro Leu Gly Ala Arg Pro Ser Pro
1170 1175 1180

Ser Arg Glu Pro Gln Glu Thr Pro
1185 1190



19
3621
DNA
homo sapiens

19

atgggagtgt ccagtgtgag cctctgccct gcccgccagt gccctgcaga cacccaggca 60

agatccctgg gcagtgctgc cctgtctgcg atggctgtga gtaccaggga caccagtatc 120

agagccagga gaccttcaga ctccaagagc ggggcctctg tgtccgctgc tcctgccagg 180

ctggcgaggt ctcctgtgag gagcaggagt gcccagtcac cccctgtgcc ctgcctgcct 240

ctggccgcca gctctgccca gggtgcctgc tgccccagct gtgacagctg cacctaccac 300

agccaagtgt atgccaatgg gcagaacttc acggatgcag acagcccttg ccatgcctgc 360

cactgtcagg atggaactgt gacatgctcc ttggttgact gccctcccac gacctgtgcc 420

aggccccaga gtggaccagg ccagtgttgc cccaggtgcc cagactgcat cctggaggaa 480

gaggtgtttg tggacggcga gagcttctcc cacccccgag acccctgcca ggagtgccga 540

tgccaggaag gccatgccca ctgccagcct cgcccctgcc ccagggcccc ctgtgcccac 600

ccgctgcctg ggacctgctg cccgaacgac tgcagcggct gtgcctttgg cgggaaagag 660

taccccagcg gagcggactt cccccacccc tctgacccct gccgtctgtg tcgctgtctg 720

agcggcaacg tgcagtgcct ggcccgccgc tgcgtgccgc tgccctgtcc agagcctgtc 780

ctgctgccgg gagagtgctg cccgcagtgc ccagccgccc cagcccccgc cggctgccca 840

cggcccggcg cggcccacgc ccgccaccag gagtacttct ccccgcccgg cgatccctgc 900

cgccgctgcc tctgcctcga cggctccgtg tcctgccagc ggctgccctg cccgcccgcg 960

ccctgcgcgc acccgcgcca ggggccttgc tgcccctcct gcgacggctg cctgtaccag 1020

gggaaggagt ttgccagcgg ggagcgcttc ccatcgccca ctgctgcctg ccacctctgc 1080

ctttgctggg agggcagcgt gagctgcgag cccaaggcat gtgcccctgc actgtgcccc 1140

ttccctgcca ggggcgactg ctgccctgac tgtgatggct gtgagtacct gggggagtcc 1200

tacctgagta accaggagtt cccagacccc cgagaaccct gcaacctgtg tacctgtctt 1260

ggaggcttcg tgacctgcgg ccgccggccc tgtgagcctc cgggctgcag ccacccactc 1320

atcccctctg ggcactgctg cccgacctgc cagggatgcc gctaccatgg cgtcactact 1380

gcctccggag agacccttcc tgacccactt gaccctacct gctccctctg cacctgccag 1440

ggccgggagc accaggatgg ggaggagttt gagggaccag caggcagctg tgagtggtgt 1500

cgctgtcagg ctggccaggt cagctgtgtg cggctgcagt gcccacccct tccctgcaag 1560

ctccaggtca ccgagcgggg gagctgctgc cctcgctgca gaggctgcct ggctcatggg 1620

gaagagcacc ccgaaggcag tagatgggtg ccccccgaca gtgcctgctc ctcctgtgtg 1680

tgtcacgagg gcgtcgtcac ctgtgcacgc atccagtgca tcagctcttg cgcccagccc 1740

cgccaagggc cccatgactg ctgtcctcaa tgctctgact gtgagcatga gggccggaag 1800

tacgagcctg gggagagctt ccagcctggg gcagacccct gtgaagtgtg catctgcgag 1860

ccacagcctg aggggcctcc cagccttcgc tgtcaccggc ggcagtgtcc cagcctggtg 1920

ggctgccccc ccagccagct cctgccccct gggccccagc actgctgtcc cacctgtgcc 1980

gaggccttga gtaactgttc agagggcctg ctgggatctg agctagcccc accagacccc 2040

tgctacacgt gccagtgcca ggacctgaca tggctctgca tccaccaggc ttgtcctgag 2100

ctcagctgtc ccctctcaga gcgccacact ccccctggga gctgctgccc cgtatgccgg 2160

gaatgtgtgg tggaggccga gggccggaga gtggcagatg gagagagctg gcgggacccc 2220

agcaatgcgt gcatcgcctg cacctgccat cggggccatg tggagtgcca cctcgaggag 2280

tgccaggccc tctcctgccc ccatggctgg gcgaaggtgc cccaggctga cagctgctgt 2340

gagcgatgcc aagctcccac ccagtcctgc gtgcaccagg gccgtgaggt ggcctctgga 2400

gagcgctgga ctgtggacac ctgcaccagc tgctcctgca tggcgggcac cgtgcgttgc 2460

cagagccagc gctgctcacc gctctcgtgt ggccccgaca aggcccctgc cctgagtcct 2520

ggcagctgct gcccccgctg cctgcctcgg cccgcttcct gcatggcctt cggagacccc 2580

cattaccgca ccttcgacgg ccgcctgctg cacttccagg gcagttgcag ctatgtgctg 2640

gccaaggact gccacagcgg ggacttcagt gtgcacgtga ccaatgatga ccggggccgg 2700

agcggtgtgg cctggaccca ggaggtggcg gtgctgctgg gagacatggc cgtgcggctg 2760

ctgcaggacg gggcagtcac ggtggatggg cacccggtgg ccttgccctt cctgcaggag 2820

ccgctgctgt atgtggagct gcgaggacac actgtgatcc tgcacgccca gcccgggctc 2880

caggtgctgt gggatgggca gtcccaggtg gaggtgagcg tacctggctc ctaccagggc 2940

cggacttgtg ggctctgtgg gaacttcaat ggctttgccc aggacgatct gcagggccct 3000

gaggggctgc tcctgccctc ggaggctgcg tttgggaata gctggcaggt ctcagagggg 3060

ctgtggcctg gccggccctg ttctgcaggc cgagaggtgg atccgtgccg ggcagcaggt 3120

taccgtgcca ggcgtgaggc caatgcccgg tgtggggtgc tgaagtcctc cccattcagt 3180

cgctgccatg ctgtggtgcc accggagccc ttctttgccg cctgtgtgta tgacctgtgt 3240

gcctgtggcc ctggctcctc cgctgatgcc tgcctctgtg atgccctgga agcctacgcc 3300

agtcactgtc gccaggcagg agtgacacct acctggcgag gccccacgct gtgtgtggta 3360

ggctgccccc tggagcgtgg cttcgtgttt gatgagtgcg gcccaccctg tccccgcacc 3420

tgcttcaatc agcatatccc cctgggggag ctggcagccc actgcgtgag gccctgcgtg 3480

cccggctgcc agtgccctgc aggcctggtg gagcatgagg cccactgcat cccacccgag 3540

gcctgccccc aagtcctgct cactggagac cagccacttg gtgctcggcc cagccccagc 3600

cgggagcccc aggagacacc c 3621



20
1207
PRT
homo sapiens

20

Met Gly Val Ser Ser Val Ser Leu Cys Pro Ala Arg Gln Cys Pro Ala
1 5 10 15

Asp Thr Gln Ala Arg Ser Leu Gly Ser Ala Ala Leu Ser Ala Met Ala
20 25 30

Val Ser Thr Arg Asp Thr Ser Ile Arg Ala Arg Arg Pro Ser Asp Ser
35 40 45

Lys Ser Gly Ala Ser Val Ser Ala Ala Pro Ala Arg Leu Ala Arg Ser
50 55 60

Pro Val Arg Ser Arg Ser Ala Gln Ser Pro Pro Val Pro Cys Leu Pro
65 70 75 80

Leu Ala Ala Ser Ser Ala Gln Gly Ala Cys Cys Pro Ser Cys Asp Ser
85 90 95

Cys Thr Tyr His Ser Gln Val Tyr Ala Asn Gly Gln Asn Phe Thr Asp
100 105 110

Ala Asp Ser Pro Cys His Ala Cys His Cys Gln Asp Gly Thr Val Thr
115 120 125

Cys Ser Leu Val Asp Cys Pro Pro Thr Thr Cys Ala Arg Pro Gln Ser
130 135 140

Gly Pro Gly Gln Cys Cys Pro Arg Cys Pro Asp Cys Ile Leu Glu Glu
145 150 155 160

Glu Val Phe Val Asp Gly Glu Ser Phe Ser His Pro Arg Asp Pro Cys
165 170 175

Gln Glu Cys Arg Cys Gln Glu Gly His Ala His Cys Gln Pro Arg Pro
180 185 190

Cys Pro Arg Ala Pro Cys Ala His Pro Leu Pro Gly Thr Cys Cys Pro
195 200 205

Asn Asp Cys Ser Gly Cys Ala Phe Gly Gly Lys Glu Tyr Pro Ser Gly
210 215 220

Ala Asp Phe Pro His Pro Ser Asp Pro Cys Arg Leu Cys Arg Cys Leu
225 230 235 240

Ser Gly Asn Val Gln Cys Leu Ala Arg Arg Cys Val Pro Leu Pro Cys
245 250 255

Pro Glu Pro Val Leu Leu Pro Gly Glu Cys Cys Pro Gln Cys Pro Ala
260 265 270

Ala Pro Ala Pro Ala Gly Cys Pro Arg Pro Gly Ala Ala His Ala Arg
275 280 285

His Gln Glu Tyr Phe Ser Pro Pro Gly Asp Pro Cys Arg Arg Cys Leu
290 295 300

Cys Leu Asp Gly Ser Val Ser Cys Gln Arg Leu Pro Cys Pro Pro Ala
305 310 315 320

Pro Cys Ala His Pro Arg Gln Gly Pro Cys Cys Pro Ser Cys Asp Gly
325 330 335

Cys Leu Tyr Gln Gly Lys Glu Phe Ala Ser Gly Glu Arg Phe Pro Ser
340 345 350

Pro Thr Ala Ala Cys His Leu Cys Leu Cys Trp Glu Gly Ser Val Ser
355 360 365

Cys Glu Pro Lys Ala Cys Ala Pro Ala Leu Cys Pro Phe Pro Ala Arg
370 375 380

Gly Asp Cys Cys Pro Asp Cys Asp Gly Cys Glu Tyr Leu Gly Glu Ser
385 390 395 400

Tyr Leu Ser Asn Gln Glu Phe Pro Asp Pro Arg Glu Pro Cys Asn Leu
405 410 415

Cys Thr Cys Leu Gly Gly Phe Val Thr Cys Gly Arg Arg Pro Cys Glu
420 425 430

Pro Pro Gly Cys Ser His Pro Leu Ile Pro Ser Gly His Cys Cys Pro
435 440 445

Thr Cys Gln Gly Cys Arg Tyr His Gly Val Thr Thr Ala Ser Gly Glu
450 455 460

Thr Leu Pro Asp Pro Leu Asp Pro Thr Cys Ser Leu Cys Thr Cys Gln
465 470 475 480

Gly Arg Glu His Gln Asp Gly Glu Glu Phe Glu Gly Pro Ala Gly Ser
485 490 495

Cys Glu Trp Cys Arg Cys Gln Ala Gly Gln Val Ser Cys Val Arg Leu
500 505 510

Gln Cys Pro Pro Leu Pro Cys Lys Leu Gln Val Thr Glu Arg Gly Ser
515 520 525

Cys Cys Pro Arg Cys Arg Gly Cys Leu Ala His Gly Glu Glu His Pro
530 535 540

Glu Gly Ser Arg Trp Val Pro Pro Asp Ser Ala Cys Ser Ser Cys Val
545 550 555 560

Cys His Glu Gly Val Val Thr Cys Ala Arg Ile Gln Cys Ile Ser Ser
565 570 575

Cys Ala Gln Pro Arg Gln Gly Pro His Asp Cys Cys Pro Gln Cys Ser
580 585 590

Asp Cys Glu His Glu Gly Arg Lys Tyr Glu Pro Gly Glu Ser Phe Gln
595 600 605

Pro Gly Ala Asp Pro Cys Glu Val Cys Ile Cys Glu Pro Gln Pro Glu
610 615 620

Gly Pro Pro Ser Leu Arg Cys His Arg Arg Gln Cys Pro Ser Leu Val
625 630 635 640

Gly Cys Pro Pro Ser Gln Leu Leu Pro Pro Gly Pro Gln His Cys Cys
645 650 655

Pro Thr Cys Ala Glu Ala Leu Ser Asn Cys Ser Glu Gly Leu Leu Gly
660 665 670

Ser Glu Leu Ala Pro Pro Asp Pro Cys Tyr Thr Cys Gln Cys Gln Asp
675 680 685

Leu Thr Trp Leu Cys Ile His Gln Ala Cys Pro Glu Leu Ser Cys Pro
690 695 700

Leu Ser Glu Arg His Thr Pro Pro Gly Ser Cys Cys Pro Val Cys Arg
705 710 715 720

Glu Cys Val Val Glu Ala Glu Gly Arg Arg Val Ala Asp Gly Glu Ser
725 730 735

Trp Arg Asp Pro Ser Asn Ala Cys Ile Ala Cys Thr Cys His Arg Gly
740 745 750

His Val Glu Cys His Leu Glu Glu Cys Gln Ala Leu Ser Cys Pro His
755 760 765

Gly Trp Ala Lys Val Pro Gln Ala Asp Ser Cys Cys Glu Arg Cys Gln
770 775 780

Ala Pro Thr Gln Ser Cys Val His Gln Gly Arg Glu Val Ala Ser Gly
785 790 795 800

Glu Arg Trp Thr Val Asp Thr Cys Thr Ser Cys Ser Cys Met Ala Gly
805 810 815

Thr Val Arg Cys Gln Ser Gln Arg Cys Ser Pro Leu Ser Cys Gly Pro
820 825 830

Asp Lys Ala Pro Ala Leu Ser Pro Gly Ser Cys Cys Pro Arg Cys Leu
835 840 845

Pro Arg Pro Ala Ser Cys Met Ala Phe Gly Asp Pro His Tyr Arg Thr
850 855 860

Phe Asp Gly Arg Leu Leu His Phe Gln Gly Ser Cys Ser Tyr Val Leu
865 870 875 880

Ala Lys Asp Cys His Ser Gly Asp Phe Ser Val His Val Thr Asn Asp
885 890 895

Asp Arg Gly Arg Ser Gly Val Ala Trp Thr Gln Glu Val Ala Val Leu
900 905 910

Leu Gly Asp Met Ala Val Arg Leu Leu Gln Asp Gly Ala Val Thr Val
915 920 925

Asp Gly His Pro Val Ala Leu Pro Phe Leu Gln Glu Pro Leu Leu Tyr
930 935 940

Val Glu Leu Arg Gly His Thr Val Ile Leu His Ala Gln Pro Gly Leu
945 950 955 960

Gln Val Leu Trp Asp Gly Gln Ser Gln Val Glu Val Ser Val Pro Gly
965 970 975

Ser Tyr Gln Gly Arg Thr Cys Gly Leu Cys Gly Asn Phe Asn Gly Phe
980 985 990

Ala Gln Asp Asp Leu Gln Gly Pro Glu Gly Leu Leu Leu Pro Ser Glu
995 1000 1005

Ala Ala Phe Gly Asn Ser Trp Gln Val Ser Glu Gly Leu Trp Pro Gly
1010 1015 1020

Arg Pro Cys Ser Ala Gly Arg Glu Val Asp Pro Cys Arg Ala Ala Gly
1025 1030 1035 1040

Tyr Arg Ala Arg Arg Glu Ala Asn Ala Arg Cys Gly Val Leu Lys Ser
1045 1050 1055

Ser Pro Phe Ser Arg Cys His Ala Val Val Pro Pro Glu Pro Phe Phe
1060 1065 1070

Ala Ala Cys Val Tyr Asp Leu Cys Ala Cys Gly Pro Gly Ser Ser Ala
1075 1080 1085

Asp Ala Cys Leu Cys Asp Ala Leu Glu Ala Tyr Ala Ser His Cys Arg
1090 1095 1100

Gln Ala Gly Val Thr Pro Thr Trp Arg Gly Pro Thr Leu Cys Val Val
1105 1110 1115 1120

Gly Cys Pro Leu Glu Arg Gly Phe Val Phe Asp Glu Cys Gly Pro Pro
1125 1130 1135

Cys Pro Arg Thr Cys Phe Asn Gln His Ile Pro Leu Gly Glu Leu Ala
1140 1145 1150

Ala His Cys Val Arg Pro Cys Val Pro Gly Cys Gln Cys Pro Ala Gly
1155 1160 1165

Leu Val Glu His Glu Ala His Cys Ile Pro Pro Glu Ala Cys Pro Gln
1170 1175 1180

Val Leu Leu Thr Gly Asp Gln Pro Leu Gly Ala Arg Pro Ser Pro Ser
1185 1190 1195 1200

Arg Glu Pro Gln Glu Thr Pro
1205



21
2277
DNA
homo sapiens

21

atgcgctgcc aaaagaagcc atgtgcccca gctctctgcc cccacccctc tccaggcccc 60

tgcttctgcc ctgtttgcca cagttgtctc tctcagggcc gggagcacca ggatggggag 120

gagtttgagg gaccagcagg cagctgtgag tggtgtcgct gtcaggctgg ccaggtcagc 180

tgtgtgcggc tgcagtgccc accccttccc tgcaagctcc aggtcaccga gcgggggagc 240

tgctgccctc gctgcagagg ctgcctggct catggggaag agcaccccga aggcagtaga 300

tgggtgcccc ccgacagtgc ctgctcctcc tgtgtgtgtc acgagggcgt cgtcacctgt 360

gcacgcatcc agtgcatcag ctcttgcgcc cagccccgcc aagggcccca tgactgctgt 420

cctcaatgct ctgactgtga gcatgagggc cggaagtacg agcctgggga gagcttccag 480

cctggggcag acccctgtga agtgtgcatc tgcgagccac agcctgaggg gcctcccagc 540

cttcgctgtc accggcggca gtgtcccagc ctggtgggct gcccccccag ccagctcctg 600

ccccctgggc cccagcactg ctgtcccacc tgtgccgagg ccttgagtaa ctgttcagag 660

ggcctgctgg gatctgagct agccccacca gacccctgct acacgtgcca gtgccaggac 720

ctgacatggc tctgcatcca ccaggcttgt cctgagctca gctgtcccct ctcagagcgc 780

cacactcccc ctgggagctg ctgccccgta tgccgggaat gtgtggtgga ggccgagggc 840

cggagagtgg cagatggaga gagctggcgg gaccccagca atgcgtgcat cgcctgcacc 900

tgccatcggg gccatgtgga gtgccacctc gaggagtgcc aggccctctc ctgcccccat 960

ggctgggcga aggtgcccca ggctgacagc tgctgtgagc gatgccaagc tcccacccag 1020

tcctgcgtgc accagggccg tgaggtggcc tctggagagc gctggactgt ggacacctgc 1080

accagctgct cctgcatggc gggcaccgtg cgttgccaga gccagcgctg ctcaccgctc 1140

tcgtgtggcc ccgacaaggc ccctgccctg agtcctggca gctgctgccc ccgctgcctg 1200

cctcggcccg cttcctgcat ggccttcgga gacccccatt accgcacctt cgacggccgc 1260

ctgctgcact tccagggcag ttgcagctat gtgctggcca aggactgcca cagcggggac 1320

ttcagtgtgc acgtgaccaa tgatgaccgg ggccggagcg gtgtggcctg gacccaggag 1380

gtggcggtgc tgctgggaga catggccgtg cggctgctgc aggacggggc agtcacggtg 1440

gatgggcacc cggtggcctt gcccttcctg caggagccgc tgctgtatgt ggagctgcga 1500

ggacacactg tgatcctgca cgcccagccc gggctccagg tgctgtggga tgggcagtcc 1560

caggtggagg tgagcgtacc tggctcctac cagggccgga cttgtgggct ctgtgggaac 1620

ttcaatggct ttgcccagga cgatctgcag ggccctgagg ggctgctcct gccctcggag 1680

gctgcgtttg ggaatagctg gcaggtctca gaggggctgt ggcctggccg gccctgttct 1740

gcaggccgag aggtggatcc gtgccgggca gcaggttacc gtgccaggcg tgaggccaat 1800

gcccggtgtg gggtgctgaa gtcctcccca ttcagtcgct gccatgctgt ggtgccaccg 1860

gagcccttct ttgccgcctg tgtgtatgac ctgtgtgcct gtggccctgg ctcctccgct 1920

gatgcctgcc tctgtgatgc cctggaagcc tacgccagtc actgtcgcca ggcaggagtg 1980

acacctacct ggcgaggccc cacgctgtgt gtggtaggct gccccctgga gcgtggcttc 2040

gtgtttgatg agtgcggccc accctgtccc cgcacctgct tcaatcagca tatccccctg 2100

ggggagctgg cagcccactg cgtgaggccc tgcgtgcccg gctgccagtg ccctgcaggc 2160

ctggtggagc atgaggccca ctgcatccca cccgaggcct gcccccaagt cctgctcact 2220

ggagaccagc cacttggtgc tcggcccagc cccagccggg agccccagga gacaccc 2277



22
759
PRT
homo sapiens

22

Met Arg Cys Gln Lys Lys Pro Cys Ala Pro Ala Leu Cys Pro His Pro
1 5 10 15

Ser Pro Gly Pro Cys Phe Cys Pro Val Cys His Ser Cys Leu Ser Gln
20 25 30

Gly Arg Glu His Gln Asp Gly Glu Glu Phe Glu Gly Pro Ala Gly Ser
35 40 45

Cys Glu Trp Cys Arg Cys Gln Ala Gly Gln Val Ser Cys Val Arg Leu
50 55 60

Gln Cys Pro Pro Leu Pro Cys Lys Leu Gln Val Thr Glu Arg Gly Ser
65 70 75 80

Cys Cys Pro Arg Cys Arg Gly Cys Leu Ala His Gly Glu Glu His Pro
85 90 95

Glu Gly Ser Arg Trp Val Pro Pro Asp Ser Ala Cys Ser Ser Cys Val
100 105 110

Cys His Glu Gly Val Val Thr Cys Ala Arg Ile Gln Cys Ile Ser Ser
115 120 125

Cys Ala Gln Pro Arg Gln Gly Pro His Asp Cys Cys Pro Gln Cys Ser
130 135 140

Asp Cys Glu His Glu Gly Arg Lys Tyr Glu Pro Gly Glu Ser Phe Gln
145 150 155 160

Pro Gly Ala Asp Pro Cys Glu Val Cys Ile Cys Glu Pro Gln Pro Glu
165 170 175

Gly Pro Pro Ser Leu Arg Cys His Arg Arg Gln Cys Pro Ser Leu Val
180 185 190

Gly Cys Pro Pro Ser Gln Leu Leu Pro Pro Gly Pro Gln His Cys Cys
195 200 205

Pro Thr Cys Ala Glu Ala Leu Ser Asn Cys Ser Glu Gly Leu Leu Gly
210 215 220

Ser Glu Leu Ala Pro Pro Asp Pro Cys Tyr Thr Cys Gln Cys Gln Asp
225 230 235 240

Leu Thr Trp Leu Cys Ile His Gln Ala Cys Pro Glu Leu Ser Cys Pro
245 250 255

Leu Ser Glu Arg His Thr Pro Pro Gly Ser Cys Cys Pro Val Cys Arg
260 265 270

Glu Cys Val Val Glu Ala Glu Gly Arg Arg Val Ala Asp Gly Glu Ser
275 280 285

Trp Arg Asp Pro Ser Asn Ala Cys Ile Ala Cys Thr Cys His Arg Gly
290 295 300

His Val Glu Cys His Leu Glu Glu Cys Gln Ala Leu Ser Cys Pro His
305 310 315 320

Gly Trp Ala Lys Val Pro Gln Ala Asp Ser Cys Cys Glu Arg Cys Gln
325 330 335

Ala Pro Thr Gln Ser Cys Val His Gln Gly Arg Glu Val Ala Ser Gly
340 345 350

Glu Arg Trp Thr Val Asp Thr Cys Thr Ser Cys Ser Cys Met Ala Gly
355 360 365

Thr Val Arg Cys Gln Ser Gln Arg Cys Ser Pro Leu Ser Cys Gly Pro
370 375 380

Asp Lys Ala Pro Ala Leu Ser Pro Gly Ser Cys Cys Pro Arg Cys Leu
385 390 395 400

Pro Arg Pro Ala Ser Cys Met Ala Phe Gly Asp Pro His Tyr Arg Thr
405 410 415

Phe Asp Gly Arg Leu Leu His Phe Gln Gly Ser Cys Ser Tyr Val Leu
420 425 430

Ala Lys Asp Cys His Ser Gly Asp Phe Ser Val His Val Thr Asn Asp
435 440 445

Asp Arg Gly Arg Ser Gly Val Ala Trp Thr Gln Glu Val Ala Val Leu
450 455 460

Leu Gly Asp Met Ala Val Arg Leu Leu Gln Asp Gly Ala Val Thr Val
465 470 475 480

Asp Gly His Pro Val Ala Leu Pro Phe Leu Gln Glu Pro Leu Leu Tyr
485 490 495

Val Glu Leu Arg Gly His Thr Val Ile Leu His Ala Gln Pro Gly Leu
500 505 510

Gln Val Leu Trp Asp Gly Gln Ser Gln Val Glu Val Ser Val Pro Gly
515 520 525

Ser Tyr Gln Gly Arg Thr Cys Gly Leu Cys Gly Asn Phe Asn Gly Phe
530 535 540

Ala Gln Asp Asp Leu Gln Gly Pro Glu Gly Leu Leu Leu Pro Ser Glu
545 550 555 560

Ala Ala Phe Gly Asn Ser Trp Gln Val Ser Glu Gly Leu Trp Pro Gly
565 570 575

Arg Pro Cys Ser Ala Gly Arg Glu Val Asp Pro Cys Arg Ala Ala Gly
580 585 590

Tyr Arg Ala Arg Arg Glu Ala Asn Ala Arg Cys Gly Val Leu Lys Ser
595 600 605

Ser Pro Phe Ser Arg Cys His Ala Val Val Pro Pro Glu Pro Phe Phe
610 615 620

Ala Ala Cys Val Tyr Asp Leu Cys Ala Cys Gly Pro Gly Ser Ser Ala
625 630 635 640

Asp Ala Cys Leu Cys Asp Ala Leu Glu Ala Tyr Ala Ser His Cys Arg
645 650 655

Gln Ala Gly Val Thr Pro Thr Trp Arg Gly Pro Thr Leu Cys Val Val
660 665 670

Gly Cys Pro Leu Glu Arg Gly Phe Val Phe Asp Glu Cys Gly Pro Pro
675 680 685

Cys Pro Arg Thr Cys Phe Asn Gln His Ile Pro Leu Gly Glu Leu Ala
690 695 700

Ala His Cys Val Arg Pro Cys Val Pro Gly Cys Gln Cys Pro Ala Gly
705 710 715 720

Leu Val Glu His Glu Ala His Cys Ile Pro Pro Glu Ala Cys Pro Gln
725 730 735

Val Leu Leu Thr Gly Asp Gln Pro Leu Gly Ala Arg Pro Ser Pro Ser
740 745 750

Arg Glu Pro Gln Glu Thr Pro
755



23
4026
DNA
homo sapiens

23

atggccaaga gtggacaaca cctggggacc cctgccgaat ctgccggtgc ctggagggtc 60

acatccagtg ccgccagcga gaatgtgcca gcctgtgtcc atacccagcc cggcccctcc 120

caggcacctg ctgccctgtg tgtgatgaat gggagtgtcc agtgtgagcc tctgccctgc 180

ccgccagtgc cctgcagaca cccaggcaag atccctgggc agtgctgccc tgtctgcgat 240

ggctgtgagt accagggaca ccagtatcag agccaggaga ccttcagact ccaagagcgg 300

ggcctctgtg tccgctgctc ctgccaggct ggcgaggtct cctgtgagga gcaggagtgc 360

ccagtcaccc cctgtgccct gcctgcctct ggccgccagc tctgcccagc ctgtgagctg 420

gatggagagg agtttgctga gggagtccag tgggagcctg atggtcggcc ctgcaccgcc 480

tgcgtctgtc aagatggggt acccaagtgc ggggctgtgc tctgcccccc agccccctgc 540

cagcacccca cccagccccc tggtgcctgc tgccccagct gtgacagctg cacctaccac 600

agccaagtgt atgccaatgg gcagaacttc acggatgcag acagcccttg ccatgcctgc 660

cactgtcagg atggaactgt gacatgctcc ttggttgact gccctcccac gacctgtgcc 720

aggccccaga gtggaccagg ccagtgttgc cccaggtgcc cagactgcat cctggaggaa 780

gaggtgtttg tggacggcga gagcttctcc cacccccgag acccctgcca ggagtgccga 840

tgccaggaag gccatgccca ctgccagcct cgcccctgcc ccagggcccc ctgtgcccac 900

ccgctgcctg ggacctgctg cccgaacgac tgcagcggct gtgcctttgg cgggaaagag 960

taccccagcg gagcggactt cccccacccc tctgacccct gccgtctgtg tcgctgtctg 1020

agcggcaacg tgcagtgcct ggcccgccgc tgcgtgccgc tgccctgtcc agagcctgtc 1080

ctgctgccgg gagagtgctg cccgcagtgc ccagccgccc cagcccccgc cggctgccca 1140

cggcccggcg cggcccacgc ccgccaccag gagtacttct ccccgcccgg cgatccctgc 1200

cgccgctgcc tctgcctcga cggctccgtg tcctgccagc ggctgccctg cccgcccgcg 1260

ccctgcgcgc acccgcgcca ggggccttgc tgcccctcct gcgacggctg cctgtaccag 1320

gggaaggagt ttgccagcgg ggagcgcttc ccatcgccca ctgctgcctg ccacctctgc 1380

ctttgctggg agggcagcgt gagctgcgag cccaaggcat gtgcccctgc actgtgcccc 1440

ttccctgcca ggggcgactg ctgccctgac tgtgatggct gtgagtacct gggggagtcc 1500

tacctgagta accaggagtt cccagacccc cgagaaccct gcaacctgtg tacctgtctt 1560

ggaggcttcg tgacctgcgg ccgccggccc tgtgagcctc cgggctgcag ccacccactc 1620

atcccctctg ggcactgctg cccgacctgc cagggatgcc gctaccatgg cgtcactact 1680

gcctccggag agacccttcc tgacccactt gaccctacct gctccctctg cacctgccag 1740

gaaggttcca tgcgctgcca aaagaagcca tgtgccccag ctctctgccc ccacccctct 1800

ccaggcccct gcttctgccc tgtttgccac agttgtctct ctcagggccg ggagcaccag 1860

gatggggagg agtttgaggg accagcaggc agctgtgagt ggtgtcgctg tcaggctggc 1920

caggtcagct gtgtgcggct gcagtgccca ccccttccct gcaagctcca ggtcaccgag 1980

cgggggagct gctgccctcg ctgcagaggc tgcctggctc atggggaaga gcaccccgaa 2040

ggcagtagat gggtgccccc cgacagtgcc tgctcctcct gtgtgtgtca cgagggcgtc 2100

gtcacctgtg cacgcatcca gtgcatcagc tcttgcgccc agccccgcca agggccccat 2160

gactgctgtc ctcaatgctc tgactgtgag catgagggcc ggaagtacga gcctggggag 2220

agcttccagc ctggggcaga cccctgtgaa gtgtgcatct gcgagccaca gcctgagggg 2280

cctcccagcc ttcgctgtca ccggcggcag tgtcccagcc tggtgggctg cccccccagc 2340

cagctcctgc cccctgggcc ccagcactgc tgtcccacct gtgccgaggc cttgagtaac 2400

tgttcagagg gcctgctggg atctgagcta gccccaccag acccctgcta cacgtgccag 2460

tgccaggacc tgacatggct ctgcatccac caggcttgtc ctgagctcag ctgtcccctc 2520

tcagagcgcc acactccccc tgggagctgc tgccccgtat gccgggaatg tgtggtggag 2580

gccgagggcc ggagagtggc agatggagag agctggcggg accccagcaa tgcgtgcatc 2640

gcctgcacct gccatcgggg ccatgtggag tgccacctcg aggagtgcca ggccctctcc 2700

tgcccccatg gctgggcgaa ggtgccccag gctgacagct gctgtgagcg atgccaagct 2760

cccacccagt cctgcgtgca ccagggccgt gaggtggcct ctggagagcg ctggactgtg 2820

gacacctgca ccagctgctc ctgcatggcg ggcaccgtgc gttgccagag ccagcgctgc 2880

tcaccgctct cgtgtggccc cgacaaggcc cctgccctga gtcctggcag ctgctgcccc 2940

cgctgcctgc ctcggcccgc ttcctgcatg gccttcggag acccccatta ccgcaccttc 3000

gacggccgcc tgctgcactt ccagggcagt tgcagctatg tgctggccaa ggactgccac 3060

agcggggact tcagtgtgca cgtgaccaat gatgaccggg gccggagcgg tgtggcctgg 3120

acccaggagg tggcggtgct gctgggagac atggccgtgc ggctgctgca ggacggggca 3180

gtcacggtgg atgggcaccc ggtggccttg cccttcctgc aggagccgct gctgtatgtg 3240

gagctgcgag gacacactgt gatcctgcac gcccagcccg ggctccaggt gctgtgggat 3300

gggcagtccc aggtggaggt gagcgtacct ggctcctacc agggccggac ttgtgggctc 3360

tgtgggaact tcaatggctt tgcccaggac gatctgcagg gccctgaggg gctgctcctg 3420

ccctcggagg ctgcgtttgg gaatagctgg caggtctcag aggggctgtg gcctggccgg 3480

ccctgttctg caggccgaga ggtggatccg tgccgggcag caggttaccg tgccaggcgt 3540

gaggccaatg cccggtgtgg ggtgctgaag tcctccccat tcagtcgctg ccatgctgtg 3600

gtgccaccgg agcccttctt tgccgcctgt gtgtatgacc tgtgtgcctg tggccctggc 3660

tcctccgctg atgcctgcct ctgtgatgcc ctggaagcct acgccagtca ctgtcgccag 3720

gcaggagtga cacctacctg gcgaggcccc acgctgtgtg tggtaggctg ccccctggag 3780

cgtggcttcg tgtttgatga gtgcggccca ccctgtcccc gcacctgctt caatcagcat 3840

atccccctgg gggagctggc agcccactgc gtgaggccct gcgtgcccgg ctgccagtgc 3900

cctgcaggcc tggtggagca tgaggcccac tgcatcccac ccgaggcctg cccccaagtc 3960

ctgctcactg gagaccagcc acttggtgct cggcccagcc ccagccggga gccccaggag 4020

acaccc 4026



24
1342
PRT
homo sapiens

24

Met Ala Lys Ser Gly Gln His Leu Gly Thr Pro Ala Glu Ser Ala Gly
1 5 10 15

Ala Trp Arg Val Thr Ser Ser Ala Ala Ser Glu Asn Val Pro Ala Cys
20 25 30

Val His Thr Gln Pro Gly Pro Ser Gln Ala Pro Ala Ala Leu Cys Val
35 40 45

Met Asn Gly Ser Val Gln Cys Glu Pro Leu Pro Cys Pro Pro Val Pro
50 55 60

Cys Arg His Pro Gly Lys Ile Pro Gly Gln Cys Cys Pro Val Cys Asp
65 70 75 80

Gly Cys Glu Tyr Gln Gly His Gln Tyr Gln Ser Gln Glu Thr Phe Arg
85 90 95

Leu Gln Glu Arg Gly Leu Cys Val Arg Cys Ser Cys Gln Ala Gly Glu
100 105 110

Val Ser Cys Glu Glu Gln Glu Cys Pro Val Thr Pro Cys Ala Leu Pro
115 120 125

Ala Ser Gly Arg Gln Leu Cys Pro Ala Cys Glu Leu Asp Gly Glu Glu
130 135 140

Phe Ala Glu Gly Val Gln Trp Glu Pro Asp Gly Arg Pro Cys Thr Ala
145 150 155 160

Cys Val Cys Gln Asp Gly Val Pro Lys Cys Gly Ala Val Leu Cys Pro
165 170 175

Pro Ala Pro Cys Gln His Pro Thr Gln Pro Pro Gly Ala Cys Cys Pro
180 185 190

Ser Cys Asp Ser Cys Thr Tyr His Ser Gln Val Tyr Ala Asn Gly Gln
195 200 205

Asn Phe Thr Asp Ala Asp Ser Pro Cys His Ala Cys His Cys Gln Asp
210 215 220

Gly Thr Val Thr Cys Ser Leu Val Asp Cys Pro Pro Thr Thr Cys Ala
225 230 235 240

Arg Pro Gln Ser Gly Pro Gly Gln Cys Cys Pro Arg Cys Pro Asp Cys
245 250 255

Ile Leu Glu Glu Glu Val Phe Val Asp Gly Glu Ser Phe Ser His Pro
260 265 270

Arg Asp Pro Cys Gln Glu Cys Arg Cys Gln Glu Gly His Ala His Cys
275 280 285

Gln Pro Arg Pro Cys Pro Arg Ala Pro Cys Ala His Pro Leu Pro Gly
290 295 300

Thr Cys Cys Pro Asn Asp Cys Ser Gly Cys Ala Phe Gly Gly Lys Glu
305 310 315 320

Tyr Pro Ser Gly Ala Asp Phe Pro His Pro Ser Asp Pro Cys Arg Leu
325 330 335

Cys Arg Cys Leu Ser Gly Asn Val Gln Cys Leu Ala Arg Arg Cys Val
340 345 350

Pro Leu Pro Cys Pro Glu Pro Val Leu Leu Pro Gly Glu Cys Cys Pro
355 360 365

Gln Cys Pro Ala Ala Pro Ala Pro Ala Gly Cys Pro Arg Pro Gly Ala
370 375 380

Ala His Ala Arg His Gln Glu Tyr Phe Ser Pro Pro Gly Asp Pro Cys
385 390 395 400

Arg Arg Cys Leu Cys Leu Asp Gly Ser Val Ser Cys Gln Arg Leu Pro
405 410 415

Cys Pro Pro Ala Pro Cys Ala His Pro Arg Gln Gly Pro Cys Cys Pro
420 425 430

Ser Cys Asp Gly Cys Leu Tyr Gln Gly Lys Glu Phe Ala Ser Gly Glu
435 440 445

Arg Phe Pro Ser Pro Thr Ala Ala Cys His Leu Cys Leu Cys Trp Glu
450 455 460

Gly Ser Val Ser Cys Glu Pro Lys Ala Cys Ala Pro Ala Leu Cys Pro
465 470 475 480

Phe Pro Ala Arg Gly Asp Cys Cys Pro Asp Cys Asp Gly Cys Glu Tyr
485 490 495

Leu Gly Glu Ser Tyr Leu Ser Asn Gln Glu Phe Pro Asp Pro Arg Glu
500 505 510

Pro Cys Asn Leu Cys Thr Cys Leu Gly Gly Phe Val Thr Cys Gly Arg
515 520 525

Arg Pro Cys Glu Pro Pro Gly Cys Ser His Pro Leu Ile Pro Ser Gly
530 535 540

His Cys Cys Pro Thr Cys Gln Gly Cys Arg Tyr His Gly Val Thr Thr
545 550 555 560

Ala Ser Gly Glu Thr Leu Pro Asp Pro Leu Asp Pro Thr Cys Ser Leu
565 570 575

Cys Thr Cys Gln Glu Gly Ser Met Arg Cys Gln Lys Lys Pro Cys Ala
580 585 590

Pro Ala Leu Cys Pro His Pro Ser Pro Gly Pro Cys Phe Cys Pro Val
595 600 605

Cys His Ser Cys Leu Ser Gln Gly Arg Glu His Gln Asp Gly Glu Glu
610 615 620

Phe Glu Gly Pro Ala Gly Ser Cys Glu Trp Cys Arg Cys Gln Ala Gly
625 630 635 640

Gln Val Ser Cys Val Arg Leu Gln Cys Pro Pro Leu Pro Cys Lys Leu
645 650 655

Gln Val Thr Glu Arg Gly Ser Cys Cys Pro Arg Cys Arg Gly Cys Leu
660 665 670

Ala His Gly Glu Glu His Pro Glu Gly Ser Arg Trp Val Pro Pro Asp
675 680 685

Ser Ala Cys Ser Ser Cys Val Cys His Glu Gly Val Val Thr Cys Ala
690 695 700

Arg Ile Gln Cys Ile Ser Ser Cys Ala Gln Pro Arg Gln Gly Pro His
705 710 715 720

Asp Cys Cys Pro Gln Cys Ser Asp Cys Glu His Glu Gly Arg Lys Tyr
725 730 735

Glu Pro Gly Glu Ser Phe Gln Pro Gly Ala Asp Pro Cys Glu Val Cys
740 745 750

Ile Cys Glu Pro Gln Pro Glu Gly Pro Pro Ser Leu Arg Cys His Arg
755 760 765

Arg Gln Cys Pro Ser Leu Val Gly Cys Pro Pro Ser Gln Leu Leu Pro
770 775 780

Pro Gly Pro Gln His Cys Cys Pro Thr Cys Ala Glu Ala Leu Ser Asn
785 790 795 800

Cys Ser Glu Gly Leu Leu Gly Ser Glu Leu Ala Pro Pro Asp Pro Cys
805 810 815

Tyr Thr Cys Gln Cys Gln Asp Leu Thr Trp Leu Cys Ile His Gln Ala
820 825 830

Cys Pro Glu Leu Ser Cys Pro Leu Ser Glu Arg His Thr Pro Pro Gly
835 840 845

Ser Cys Cys Pro Val Cys Arg Glu Cys Val Val Glu Ala Glu Gly Arg
850 855 860

Arg Val Ala Asp Gly Glu Ser Trp Arg Asp Pro Ser Asn Ala Cys Ile
865 870 875 880

Ala Cys Thr Cys His Arg Gly His Val Glu Cys His Leu Glu Glu Cys
885 890 895

Gln Ala Leu Ser Cys Pro His Gly Trp Ala Lys Val Pro Gln Ala Asp
900 905 910

Ser Cys Cys Glu Arg Cys Gln Ala Pro Thr Gln Ser Cys Val His Gln
915 920 925

Gly Arg Glu Val Ala Ser Gly Glu Arg Trp Thr Val Asp Thr Cys Thr
930 935 940

Ser Cys Ser Cys Met Ala Gly Thr Val Arg Cys Gln Ser Gln Arg Cys
945 950 955 960

Ser Pro Leu Ser Cys Gly Pro Asp Lys Ala Pro Ala Leu Ser Pro Gly
965 970 975

Ser Cys Cys Pro Arg Cys Leu Pro Arg Pro Ala Ser Cys Met Ala Phe
980 985 990

Gly Asp Pro His Tyr Arg Thr Phe Asp Gly Arg Leu Leu His Phe Gln
995 1000 1005

Gly Ser Cys Ser Tyr Val Leu Ala Lys Asp Cys His Ser Gly Asp Phe
1010 1015 1020

Ser Val His Val Thr Asn Asp Asp Arg Gly Arg Ser Gly Val Ala Trp
1025 1030 1035 1040

Thr Gln Glu Val Ala Val Leu Leu Gly Asp Met Ala Val Arg Leu Leu
1045 1050 1055

Gln Asp Gly Ala Val Thr Val Asp Gly His Pro Val Ala Leu Pro Phe
1060 1065 1070

Leu Gln Glu Pro Leu Leu Tyr Val Glu Leu Arg Gly His Thr Val Ile
1075 1080 1085

Leu His Ala Gln Pro Gly Leu Gln Val Leu Trp Asp Gly Gln Ser Gln
1090 1095 1100

Val Glu Val Ser Val Pro Gly Ser Tyr Gln Gly Arg Thr Cys Gly Leu
1105 1110 1115 1120

Cys Gly Asn Phe Asn Gly Phe Ala Gln Asp Asp Leu Gln Gly Pro Glu
1125 1130 1135

Gly Leu Leu Leu Pro Ser Glu Ala Ala Phe Gly Asn Ser Trp Gln Val
1140 1145 1150

Ser Glu Gly Leu Trp Pro Gly Arg Pro Cys Ser Ala Gly Arg Glu Val
1155 1160 1165

Asp Pro Cys Arg Ala Ala Gly Tyr Arg Ala Arg Arg Glu Ala Asn Ala
1170 1175 1180

Arg Cys Gly Val Leu Lys Ser Ser Pro Phe Ser Arg Cys His Ala Val
1185 1190 1195 1200

Val Pro Pro Glu Pro Phe Phe Ala Ala Cys Val Tyr Asp Leu Cys Ala
1205 1210 1215

Cys Gly Pro Gly Ser Ser Ala Asp Ala Cys Leu Cys Asp Ala Leu Glu
1220 1225 1230

Ala Tyr Ala Ser His Cys Arg Gln Ala Gly Val Thr Pro Thr Trp Arg
1235 1240 1245

Gly Pro Thr Leu Cys Val Val Gly Cys Pro Leu Glu Arg Gly Phe Val
1250 1255 1260

Phe Asp Glu Cys Gly Pro Pro Cys Pro Arg Thr Cys Phe Asn Gln His
1265 1270 1275 1280

Ile Pro Leu Gly Glu Leu Ala Ala His Cys Val Arg Pro Cys Val Pro
1285 1290 1295

Gly Cys Gln Cys Pro Ala Gly Leu Val Glu His Glu Ala His Cys Ile
1300 1305 1310

Pro Pro Glu Ala Cys Pro Gln Val Leu Leu Thr Gly Asp Gln Pro Leu
1315 1320 1325

Gly Ala Arg Pro Ser Pro Ser Arg Glu Pro Gln Glu Thr Pro
1330 1335 1340



25
5776
DNA
homo sapiens

25

ctggctggcc ctggctttcc tctgtgacct cagctccagg cactgaggcc aggtcttagc 60

gtggcattgc agcctccctg ccccctgtgg caaaggctca ggtccactat gggcccagac 120

tctggggcag agaagctgcc gtctccttac tgaagcttta agcttggtgg agagtgggct 180

ggggagacct cagtccctgc ctggtctagg gggaggggtg gcttccgact tctggtcttt 240

atgacaggga gggagagctt tggaagggtt cacagctccg ccctcaatgt tcctttttgc 300

ctgtgagctt cgcctgtgag acccaaccct ctgcttccca gcttcaagga ggagtttccc 360

agcctgtggg cccacaggga cggctgtcct cacttcctcc ctttggcccc ctctgcctgc 420

tgagcccagg gcccagccct gccccctacc caggctcacc ccacagccag gcctgagctc 480

aggagtggga aatggggctg agaccagcca gtgaagggcg gccttggcat ttggggccaa 540

gcctgggact gctgggggtc tcctcctgga tcttaagcgg agacaaggcc tacacccccg 600

ttgggcttcc tgcgagctgg agctgctctc tgggcgcctg ctgagccgcg acgacagacg 660

gcgagccgag cgaggcggag ctagcatggc cggggtcggg gccgctgcgc tgtcccttct 720

cctgcacctc ggggccctgg cgctggccgc gggcgcggaa ggtggggctg tccccaggga 780

gccccctggg cagcagacaa ctgcccattc ctcagtcctt gctgggaact cccaggagca 840

gtggcacccc ctgcgagagt ggctggggcg actggaggct gcagtgatgg agctcagaga 900

acagaataag gacctgcaga cgagggtgag gcagctggag tcctgtgagt gccaccctgc 960

atctccccag tgctgggggc tggggcgtgc ctggcccgag ggggcacgct gggagcctga 1020

cgcctgcaca gcctgcgtct gccaggatgg ggccgctcac tgtggccccc aagcacacct 1080

gccccattgc aggggctgca gccaaaatgg ccagacctac ggcaacgggg agaccttctc 1140

cccagatgcc tgcaccacct gccgctgtct ggaaggtacc atcacttgca accagaagcc 1200

atgcccaaga ggaccctgcc ctgagccagg agcatgctgc ccgcactgta agccaggctg 1260

tgattatgag gggcagcttt atgaggaggg ggtcaccttc ctgtccagct ccaacccttg 1320

tctacagtgc acctgcctga ggagccgagt tcgctgcatg gccctgaagt gcccgcctag 1380

cccctgccca gagccagtgc tgaggcctgg gcactgctgc ccaacctgcc aaggctgcac 1440

agaaggtggc tctcactggg aacatggcca agagtggaca acacctgggg acccctgccg 1500

aatctgccgg tgcctggagg gtcacatcca gtgccgccag cgagaatgtg ccagcctgtg 1560

tccataccca gcccggcccc tcccaggcac ctgctgccct gtgtgtgatg gctgtttcct 1620

aaacgggcgg gagcaccgca gcggggagcc tgtgggctca ggggacccct gctcgcactg 1680

ccgctgtgct aatgggagtg tccagtgtga gcctctgccc tgcccgccag tgccctgcag 1740

acacccaggc aagatccctg ggcagtgctg ccctgtctgc gatggctgtg agtaccaggg 1800

acaccagtat cagagccagg agaccttcag actccaagag cggggcctct gtgtccgctg 1860

ctcctgccag gctggcgagg tctcctgtga ggagcaggag tgcccagtca ccccctgtgc 1920

cctgcctgcc tctggccgcc agctctgccc agcctgtgag ctggatggag aggagtttgc 1980

tgagggagtc cagtgggagc ctgatggtcg gccctgcacc gcctgcgtct gtcaagatgg 2040

ggtacccaag tgcggggctg tgctctgccc cccagccccc tgccagcacc ccacccagcc 2100

ccctggtgcc tgctgcccca gctgtgacag ctgcacctac cacagccaag tgtatgccaa 2160

tgggcagaac ttcacggatg cagacagccc ttgccatgcc tgccactgtc aggatggaac 2220

tgtgacatgc tccttggttg actgccctcc cacgacctgt gccaggcccc agagtggacc 2280

aggccagtgt tgccccaggt gcccagactg catcctggag gaagaggtgt ttgtggacgg 2340

cgagagcttc tcccaccccc gagacccctg ccaggagtgc cgatgccagg aaggccatgc 2400

ccactgccag cctcgcccct gccccagggc cccctgtgcc cacccgctgc ctgggacctg 2460

ctgcccgaac gactgcagcg gctgtgcctt tggcgggaaa gagtacccca gcggagcgga 2520

cttcccccac ccctctgacc cctgccgtct gtgtcgctgt ctgagcggca acgtgcagtg 2580

cctggcccgc cgctgcgtgc cgctgccctg tccagagcct gtcctgctgc cgggagagtg 2640

ctgcccgcag tgcccagccg ccccagcccc cgccggctgc ccacggcccg gcgcggccca 2700

cgcccgccac caggagtact tctccccgcc cggcgatccc tgccgccgct gcctctgcct 2760

cgacggctcc gtgtcctgcc agcggctgcc ctgcccgccc gcgccctgcg cgcacccgcg 2820

ccaggggcct tgctgcccct cctgcgacgg ctgcctgtac caggggaagg agtttgccag 2880

cggggagcgc ttcccatcgc ccactgctgc ctgccacctc tgcctttgct gggagggcag 2940

cgtgagctgc gagcccaagg catgtgcccc tgcactgtgc cccttccctg ccaggggcga 3000

ctgctgccct gactgtgatg gctgtgagta cctgggggag tcctacctga gtaaccagga 3060

gttcccagac ccccgagaac cctgcaacct gtgtacctgt cttggaggct tcgtgacctg 3120

cggccgccgg ccctgtgagc ctccgggctg cagccaccca ctcatcccct ctgggcactg 3180

ctgcccgacc tgccagggat gccgctacca tggcgtcact actgcctccg gagagaccct 3240

tcctgaccca cttgacccta cctgctccct ctgcacctgc caggaaggtt ccatgcgctg 3300

ccaaaagaag ccatgtgccc cagctctctg cccccacccc tctccaggcc cctgcttctg 3360

ccctgtttgc cacagttgtc tctctcaggg ccgggagcac caggatgggg aggagtttga 3420

gggaccagca ggcagctgtg agtggtgtcg ctgtcaggct ggccaggtca gctgtgtgcg 3480

gctgcagtgc ccaccccttc cctgcaagct ccaggtcacc gagcggggga gctgctgccc 3540

tcgctgcaga ggctgcctgg ctcatgggga agagcacccc gaaggcagta gatgggtgcc 3600

ccccgacagt gcctgctcct cctgtgtgtg tcacgagggc gtcgtcacct gtgcacgcat 3660

ccagtgcatc agctcttgcg cccagccccg ccaagggccc catgactgct gtcctcaatg 3720

ctctgactgt gagcatgagg gccggaagta cgagcctggg gagagcttcc agcctggggc 3780

agacccctgt gaagtgtgca tctgcgagcc acagcctgag gggcctccca gccttcgctg 3840

tcaccggcgg cagtgtccca gcctggtggg ctgccccccc agccagctcc tgccccctgg 3900

gccccagcac tgctgtccca cctgtgccga ggccttgagt aactgttcag agggcctgct 3960

gggatctgag ctagccccac cagacccctg ctacacgtgc cagtgccagg acctgacatg 4020

gctctgcatc caccaggctt gtcctgagct cagctgtccc ctctcagagc gccacactcc 4080

ccctgggagc tgctgccccg tatgccggga atgtgtggtg gaggccgagg gccggagagt 4140

ggcagatgga gagagctggc gggaccccag caatgcgtgc atcgcctgca cctgccatcg 4200

gggccatgtg gagtgccacc tcgaggagtg ccaggccctc tcctgccccc atggctgggc 4260

gaaggtgccc caggctgaca gctgctgtga gcgatgccaa gctcccaccc agtcctgcgt 4320

gcaccagggc cgtgaggtgg cctctggaga gcgctggact gtggacacct gcaccagctg 4380

ctcctgcatg gcgggcaccg tgcgttgcca gagccagcgc tgctcaccgc tctcgtgtgg 4440

ccccgacaag gcccctgccc tgagtcctgg cagctgctgc ccccgctgcc tgcctcggcc 4500

cgcttcctgc atggccttcg gagaccccca ttaccgcacc ttcgacggcc gcctgctgca 4560

cttccagggc agttgcagct atgtgctggc caaggactgc cacagcgggg acttcagtgt 4620

gcacgtgacc aatgatgacc ggggccggag cggtgtggcc tggacccagg aggtggcggt 4680

gctgctggga gacatggccg tgcggctgct gcaggacggg gcagtcacgg tggatgggca 4740

cccggtggcc ttgcccttcc tgcaggagcc gctgctgtat gtggagctgc gaggacacac 4800

tgtgatcctg cacgcccagc ccgggctcca ggtgctgtgg gatgggcagt cccaggtgga 4860

ggtgagcgta cctggctcct accagggccg gacttgtggg ctctgtggga acttcaatgg 4920

ctttgcccag gacgatctgc agggccctga ggggctgctc ctgccctcgg aggctgcgtt 4980

tgggaatagc tggcaggtct cagaggggct gtggcctggc cggccctgtt ctgcaggccg 5040

agaggtggat ccgtgccggg cagcaggtta ccgtgccagg cgtgaggcca atgcccggtg 5100

tggggtgctg aagtcctccc cattcagtcg ctgccatgct gtggtgccac cggagccctt 5160

ctttgccgcc tgtgtgtatg acctgtgtgc ctgtggccct ggctcctccg ctgatgcctg 5220

cctctgtgat gccctggaag cctacgccag tcactgtcgc caggcaggag tgacacctac 5280

ctggcgaggc cccacgctgt gtgtggtagg ctgccccctg gagcgtggct tcgtgtttga 5340

tgagtgcggc ccaccctgtc cccgcacctg cttcaatcag catatccccc tgggggagct 5400

ggcagcccac tgcgtgaggc cctgcgtgcc cggctgccag tgccctgcag gcctggtgga 5460

gcatgaggcc cactgcatcc cacccgaggc ctgcccccaa gtcctgctca ctggagacca 5520

gccacttggt gctcggccca gccccagccg ggagccccag gagacaccct gagccaggac 5580

agtgcctgat aagggttcat caggccagga gtctcccctt ggcgagcagt tcccaccctg 5640

gttagggcta tggagagaat gccctgcctg gacactggag cctgggcccc tgccctgcaa 5700

agacccccgc catgttgagt caccagcagt aaactctagg cctgcccgaa ggctaaaaaa 5760

aaaaaaaaaa aaaaaa 5776