MXPA01003738A - Non-endogenous, constitutively activated human g protein-coupled receptors - Google Patents

Abstract

Disclosed herein are constitutively activated, non-endogenous versions of endogenous human G protein-coupled receptors comprising (a) the following amino acid sequence region (C-terminus to N-terminus orientation) and/or (b) the following nucleic acid sequence region (3'to 5'orientation) transversing the transmembrane-6 (TM6) and intracellular loop-3 (IC3) regions of the GPCR:(a) P1 AA15 X and/or (b) Pcodon (AA-codon)15 Xcodon, respectively. In a most preferred embodiment, P1 and Pcodon are endogenous proline and an endogenous nucleic acid encoding region encoding proline, respectively, located within TM6 of the non-endogenous GPCR;AA15 and (AA-codon)15 are 15 endogenous amino acid residues and 15 codons encoding endogenous amino acid residues, respectively;and X and Xcodon are non-endogenous lysine and a non-endogenous nucleic acid encoding region encoding lysine, respectively, located within IC3 of the non-endogenous GPCR. Because it is most preferred that the non-endogenous human GPCRs which incorporate these mutations are incorporated into mammalian cells and utilized for the screening of the candidate compounds, the non-endogenous human GPCR incorporating the mutation need not be purified and isolated per se (i.e., these are incorporated within the cellular membrane of a mammalian cell), although such purified and isolated non-endogenous human GPCRs are well within the purview of this disclosure.

Description

RECEPTORS COUPLED TO HUMAN PROTEIN G. CONSTITUTIVELY ACTIVATED. NO ENDOGENOUS The benefits of the E.U.A. series No. 09 / 170,496, filed on October 13, 1998, patent of E.U.A. series No.08 / 839, 449, filed on April 14, 1997 (now abandoned), patent of E.U.A. series No. 09 / 060,188, filed on April 14, 1998; patent of E.U.A. Provisional Series No. 60/90/783, filed on June 26, 1998; and patent of E.U.A. Provisional No. 60 / 095,677, filed on August 7, 1998, are hereby claimed. Each of the above applications is incorporated herein by reference in its entirety.

FIELD OF THE INVENTION The invention described in this patent document refers to transmembrane receptors, and more particularly to human G protein coupled receptors (GPCRs) which have been altered so that the altered GPCRs receptors are constitutively activated. Most preferably, altered human GPCR receptors are used for the classification of therapeutic compounds.

BACKGROUND OF THE INVENTION Although a number of receptor classes exist in humans, the most abundant and therapeutically important is represented by the class of G-protein coupled receptors (GPCRs or GPCRs). It is estimated that there are some 100,000 genes within the human genome, and of these, approximately 2% or 2,000 genes are estimated to encode GPCRs. Of these, approximately 100 GPCRs receptors for which the endogenous ligand that binds to the GPCR receptor have been identified. Due to the significant time lag that exists between the discovery of an endogenous GPCR receptor and its endogenous ligand, it can be presumed that the 1,900 remaining GPCR receptors will be identified and characterized long before the endogenous ligands for these receptors are identified. In fact, the speed with which the Human Genome Project is sequencing the 100,000 human genes indicates that the remaining human GPCRs will be completely sequenced within the next few years. However, and despite efforts to sequence the human genome, it remains unclear how scientists will be able to quickly, effectively and efficiently exploit this information to improve and augment the human condition. The present invention is molded towards this important object. The receptors, including GPCRs, for which the endogenous ligand has been identified, are referred to as "known" receptors, whereas the receptors for which endogenous ligand has not been identified are referred to as "receptors". "Orphans". This distinction is not merely semantic, particularly in the case of GPCRs. GPCRs represent an important area for the development of pharmaceutical products: of approximately 20 of the 100 known GPCR receptors, 60% of all prescription pharmaceuticals have been developed. In this way the orphan GPCRs receivers are for the pharmaceutical industry what gold was for California at the end of the 19th century, an opportunity to direct growth, expansion, improvement and development. However, there is a very serious disadvantage with orphan receivers in relation to the discovery of novel therapeutics. This is because the traditional aspect of the discovery and development of pharmaceutical products has required access to both the receptor and its endogenous ligand. In this way, until now, orphan GPCRs have presented the technique with a tempting and rudimentary resource for the discovery of pharmaceutical products. Under the traditional aspect for the discovery of potential therapeutics, it is generally the case that the receptor is first identified. Before the discovery of drugs, efforts can be initiated, elaborate, time-consuming and costly procedures are typically put in place in order to identify, isolate and generate the endogenous receptor ligand, this process may require between 3 and 10 years per receiver, at a cost of approximately 5'000,000 (E.U.A.) per recipient. These time and financial resources must be spent before the traditional aspect for drug discovery begins. This is why traditional drug discovery techniques are based on so-called "competitive binding assays," by which putative therapeutic agents are "sorted" against the receptor in an effort to discover compounds that both block the endogenous ligand of receptor binding ("antagonist"), as they improve or resemble the effects of ligand binding to the receptor ("agonists"). The overall object is to identify compounds that prevent cellular activation when the ligand binds to the receptor (the antagonists), or that improves or increases cellular activity that might otherwise occur if the ligand was appropriately bound to the receptor (the agonists) . Since the endogenous ligands for orphan GPCRs are by definition unidentified, the ability to discover novel and unique therapeutics for these receptors using traditional drug discovery techniques is not possible. The present invention, as will be presented in great detail below, overcomes these and other severe limitations created by such traditional drug discovery techniques. The GPCRs receptors share a common structural motif All these receptors have 7 sequences of 22 to 24 hydrophobic amino acids that form 7 alpha helices each of which extends the membrane (each extension is identified by number), ie, transmembrane-1 ( TM-1), transmembrane-2 (TM-2), etc.). The transmembrane helices are bound through strands of amino acids between transmembrane-2 and transmembrane-3, transmembrane-4 and transmembrane-5, and transmembrane-6 and transmembrane-7 on the outside, or "extracellular" side, of the membrane cellular (these are referred to as "extracellular" 1, 2, and 3 regions (EC-1, EC-2, and EC-3, respectively.) Transmembrane helices also bind through strands of amino acids between transmembrane-1 and transmembrane-2, transmembrane-3 and transmembrane-4 and transmembrane-5 and transmembrane-6 on the interior or "intracellular" side of the cell membrane (referred to as "intracellular" 1, 2 and 3 regions (IC-1, IC -2 and IC-3), respectively.) The term "carboxy" ("C") of the receptor lies between the intracellular space within the cell, and the term "amino" ("N") the receptor lies in space The general structure of G protein-coupled receptors is illustrated in Figure 1. In general, When an endogenous ligand binds with the receptor (usually referred to as the "activation" of the receptor), there is a conformation channel of the intracellular region that allows for coupling between the intracellular region and an intracellular "G protein". Although other G proteins exist, currently, Gq, Gs, Gi and Go are G proteins that have been identified. The coupling of the endogenous ligand-activated GPCR receptor with the G protein initiates a signaling cascade process (referred to as "signal transduction"). Under normal conditions, signal transduction eventually results in cellular activation or cellular inhibition. It is believed that the IC-3 loop as well as the carboxy terminus of the receptor interact with the G protein. A major point of this invention is directed to the transmembrane-6 (TM6) region and the intracellular-3 (IC3) region of the receptor GPCR. Under physiological conditions, GPCRs receptors exist in the cell membrane in equilibrium between two different conformations: an "inactive" state and an "active" state. As shown schematically in Figure 2, a receptor in an inactive state is unable to bind to the transduction and intracellular signaling path to produce a biological response. The change of the receptor conformation to the active state allows the binding to the transduction path (through the G protein) and produces a biological response. A receptor can be stabilized in an active state through an endogenous ligand or a compound such as a drug. Recent discoveries, including but not limited to modifications to the amino acid sequence of the receptor provide means other than endogenous ligands to promote and stabilize the receptor in the conformation of active state. These means effectively stabilize the receptor in an active state by simulating the effect of an endogenous ligand binding to the receptor. The stabilization through said independent means of the ligand is called "constitutive receptor activation". As noted above, the use of an orphan receiver for classification purposes has not been possible. This is because the traditional "dogma" with respect to the classification of compounds mandates that the ligand for the receptor be known. By definition, then, this aspect has no applicability with respect to orphan receivers. In this way, adding to this dogmatic aspect the discovery of therapeutics, the technique has in essence taught and been taught to abandon the use of orphan receptors unless and until the endogenous ligand is discovered for the receptor. Given that there are an estimated 2,000 receptors coupled to G protein, most of which are orphan receptors, such dogma punishes a creative aspect, unique and different for the discovery of therapeutics. The information regarding the nucleic acid and / or amino acid sequence of a variety of GPCRs is summarized below in Table A. Since an important point of the invention described herein is directed towards orphan GPCRs, many of the references cited below are related to orphan GPCRs. However, this list is not intended to imply, nor is this list constructed, legally or otherwise, that allows the invention described herein to be applicable only to orphan GPCR receivers or the specific GPCRs receivers listed below. In addition, certain receptors that have been isolated are not the subject of publications per se, for example, reference is made to a database of G protein-coupled receptors on the "global web" (neither the named inventors nor the transferee have any affiliation with this site) that lists GPCRs receivers. Other GPCR receivers are the subject of patent applications belonging to the assignee herein and these are not listed below (including GPR3, GPR6 and GPR12).; see provisional application of E.U.A. No. 60/094879) - Table A As established and described in detail below, the use of a mutation cassette to modify the endogenous sequence of a human GPCR receptor leads to a constitutively activated version of the human GPCR receptor. These constitutively activated, non-endogenous versions of human GPCR receptors can be used, among others, for the classification of candidate compounds to directly identify compounds of, for example, therapeutic importance.

COMPENDIUM OF THE INVENTION Herein is described a non-endogenous human G protein-coupled receptor, comprising, (a) as a highly preferred amino acid sequence region (C-terminus orientation).

^ - MlÉfillÉtildÉ to term N) and / or (b) as a highly preferred nucleic acid sequence region (3 'to 5' orientation) traversing the regions of transmembrane-6 (TM6) and intracellular spira-3 (IC3 ) of the GPCR receptor: (a) P1AA15X wherein: (1) P1 is an amino acid residue located within the TM6 region of the GPCR receptor, wherein P1 is selected from the group consisting of (i) the proline residue of the endogenous GPCR receptor and (ii) a non-endogenous amino acid residue other than proline; (2) AA15 are 15 amino acids selected from the group consisting of: (a) the amino acids of the endogenous GPCR receptor (b) non-endogenous amino acid residues, and (c) a combination of the amino acids of the endogenous GPCR receptor and non-endogenous amino acids, except that none of the endogenous amino acid residues that are placed within the TM6 region of the GPCR receptor is proline; and (3) X is a non-endogenous amino acid residue located within the IC3 region of said GPCR receptor, preferably selected from the group consisting of lysine, histidine and arginine, and most preferably lysine, except that when the amino acid is endogenous at the position X is lysine, then X is an amino acid other than Usin, preferably alanine, and / or (b) Pcodon (AA-codon) X-codon where: (1) pcodon is a nucleic acid sequence within the TM6 region of the GPCR receptor , wherein an amino acid selected from the group consisting of (i) the proline residue of the endogenous GPCR receptor and (ii) a non-endogenous amino acid residue other than proline; (2) (AA-codon)? are 15 codons that encode 15 amino acids selected from the group consisting of (a) the amino acids of the endogenous GPCR receptor, (b) non-endogenous amino acid residues and (c) a combination of the endogenous GPCR receptor amino acids and non-endogenous amino acids, except that none of the 15 endogenous codons within the TM6 region of the GPCR receptor encodes a proline amino acid residue; (3) Xcodon is a nucleic acid encoding a region residue located within the IC3 region of said GPCR receptor, wherein XCOdon encodes a non-endogenous amino acid, preferably selected from the group consisting of lysine, histidine, arginine and most preferably lysine , except that when the endogenous coding region in the position XCO on encodes the amino acid lysine, then XCOdon encodes an amino acid other than lysine, preferably alanine. The terms endogenous and non-endogenous in reference to these sequence cassettes are relative to the endogenous GPCR receptor. For example, once the endogenous proline residue is located within the TM6 region of a particular GPCR receptor, the amino acid 16 thereof is identified for the mutation to constitutively activate the receptor, it is also possible to mutate the endogenous proline residue (ie, once the marker is localized and amino acid 16 is to be mutated it is identified, one can mutate the same marker), although it is highly preferred that the proline residue is not mutated. Similarly, and although it is highly preferred that AA15 be maintained in its endogenous forms, these amino acids can also be mutated. The only amino acid that must be mutated in the non-endogenous version of the human GPCR receptor is X, that is, the endogenous amino acid that is 16 residues from P1 can not be maintained in its endogenous form and must be permuted, as described herein. Established again, while it is preferred that in the non-endogenous version of the human GPCR receptor, P1 and AA15 remain in their endogenous forms (ie identical to their wild type forms), once X is identified and mutated, either y / or all P1 and AA15. This applies to the nucleic acid sequences as well. In those cases where the endogenous amino acid in the X position is lysine, then in the non-endogenous version of said GPCR receptor, X is an amino acid other than sine, preferably alanine. Accordingly, and as a hypothetical example, if the endogenous GPCR receptor has the following endogenous amino acid sequence at the positions previously observed. ^^^^ ^? ^ g? g P-AACCTTGGRRRDDDE-Q then any of the following illustrative and hypothetical cassettes could fall within the scope of the description of the invention (non-endogenous amino acids are set in bold): P-AACCTTGGRRRDDDE-K P-AACCTTHIGRRDDDE-K P-ADEETTGGRRRDDDE-A P-LLKFMASTWZLVAAPQ-K A-LLKFMSTWZLVAAPQ-K It is also possible to add amino acid residues within AA15 but that aspect is not particularly advanced. In fact, in highly preferred embodiments, the only amino acid that differs in the non-endogenous version of the GPCR receptor, human as compared to the endogenous version of that GPCR receptor, is the amino acid at the X position; the mutation of this same amino acid leads to the constitutive activation of the receptor. Thus, in particularly preferred embodiments, P1 and Xcodon are endogenous proline and an endogenous nucleic acid coding region encoding proline, respectively; and X and CCOdon with non-endogenous lysine or alanine and a non-endogenous nucleic acid coding region encoding lysine or alanine, respectively, with lysine being very preferred. Since it is highly preferred that the non-endogenous versions of the human GPCRs receptors, which incorporate these mutations, are incorporated into mammalian cells and used for the classification of candidate compounds, The non-endogenous human GPCR receptor incorporating the mutation does not need to be purified and isolated per se (ie, these are incorporated within the cell membrane of a mammalian cell), although said non-endogenous human GPCR receptors are purified and isolated are also within the vision of this description. Mammals that are not human with target gene and transgenic (preferably rats and mice) that incorporate non-endogenous human GPCR receptors are also within the scope of this invention; in particular, the target gene mammals are very preferred since these animals incorporate the non-endogenous versions of the human GPCRs receptors instead of the region encoding the mammalian endogenous GPCR receptor that is not a human (the teachings for generating said mammals that are not human beings to replace the protein coding region of the non-human mammal as a human coding region are well known, see for example, U.S. Patent No. 5,777,194.) It has been found that these changes to an endogenous human GPCR receptor makes the GPCR receptor constitutively active so that, as will be explained later herein, the constitutively activated, non-endogenous version of the human GPCR receptor can be used for, among other things, the direct classification of candidate compounds Without the need for endogenous ligand In this way, the methods to use these materials and products identified by these methods also m ?? l ß? ? ^^ are within the scope of the following description.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows a generalized structure of a receptor coupled to the G protein with the numbers assigned to the transmembrane helices, intracellular turns and extracellular coils. Figure 2 schematically illustrates the two states, active and inactive, for a receptor coupled to the typical G protein and the link from the active state to the second messenger transduction path. Figure 3 is a sequence diagram of the preferred vector pCMV, including restriction enzyme site locations. Figure 4 is a diagrammatic representation of the measured signal comparing pCMV, the inhibition of the non-endogenous constitutively active GPC30 receptor of the GPR6 mediated activation of the CRE-Luc report with the inhibition of endogenous GPR30 of the activation measured by GPR6 of the CRE- report. Luc. Figure 5 is a diagrammatic representation of the signal measured by comparing pCMV, the inhibition of the constitutively activated GP17 receptor, not endogenous of GPR3-mediated activation of the CRE-Luc report with endogenous GPR17 inhibition of GPR3-mediated activation of the CRE-Luc report Figure 6 provides the diag rammatic results of the measured signal by comparing control pCMV, endogenous APJ and non-endogenous APJ. Figure 7 provides an illustration of the production of IP3 from the non-endogenous human 5-HT2A receptor, as compared to the endogenous version of this receptor. Figure 8 are results of spot staining format for GPR1 (8A), GPR30 (8B) and APJ (8C).

DETAILED DESCRIPTION The scientific literature that has developed around receptors has adopted a number of terms to refer to ligand that have various effects on receptors. For clarity and consistency, the following definitions will be used throughout this patent document. To the extent that these definitions conflict with other definitions for these terms, the following definitions should control: AGONISTS mean compounds that activate the intracellular response when they bind to the receptor, or improve the binding of GTP to membranes. THE ABBREVIATIONS FOR AMINO ACIDS used herein are set forth below: ALANINA ALA A ARGININA ARG R ASPARAGINE ASN N ACIDO ASPARTICO ASP D CISTEINA CYS C GLUTAMIC ACID GLU E GLUTAMINE GLN Q GLICINA GLY G HISTIDINA HIS H ISOLEUCINE ILE 1 LEUCINE LEU L LISINA LYS K METIONINA MET M FENILALANINA PHE F PROLINA PRO P SERINA SER S TREONINE THR T TRIPTOPHAN TRP w TYROSINE TYR AND VALINA VAL N PARTIAL AGONISTS must represent compounds that activate the intracellular response when they bind to the receptor to a much lesser degree than do agonists, or improve GTP binding to membranes to a lesser extent / extent than do agonists ANTAGONIST must represent compounds that competitively they bind to the receptor in the same place as the agonists, but which do not activate the intracellular response initiated by the active form of the receptor, and in this way they can inhibit the intracellular responses by agonists or partial agonists. ANTAGONISTS do not decrease the intracellular baseline response in the absence of an agonist or partial agonist. COMPOSITE CANDIDATE must mean a molecule (for example, and without limitation, a chemical compound) that is manageable for a classification technique. Preferably, the phrase "candidate compound" does not include compounds that are publicly known as compounds selected from the group consisting of inverse agonist, agonist or antagonist for a receptor, as previously determined through an indirect identification process ("indirectly identified compounds"). "); most preferably, not including an indirectly identified compound that has previously been determined to have therapeutic efficacy in at least one mammal; and most preferably, not including an indirectly identified compound that has previously been determined to have therapeutic utility in humans. CODON must represent a grouping of three nucleotides (or nucleotide equivalents) that generally comprise a nucleoside (adenosine (A), guanosine (G), histidine (C), uridine (U) and thymidine (T)) coupled to a phosphate group and which, when translated, encodes an amino acid.

COMPOUND EFFICACY should mean a measurement of a compound's ability to inhibit or stimulate receptor functionality, as opposed to receptor binding affinity. A preferred means for detecting the effectiveness of the compound is through the measurement of, for example, the binding of [35S] GTPγS, as described below in the example section of this patent document. RECEPTOR CONSTITUTIVELY ACTIVATED must mean a receiver subject to activation of constituent receiver. According to the invention described herein, a non-endogenous constitutively activated human protein G-coupled receptor is one that has been mutated to include the amino acid cassette P1AA15X, as set forth in greater detail below. ACTIVATION CONSTITUTIVE OF RECEIVER should represent the stabilization of a receptor in the active state through another type of receptor binding with its endogenous ligand or a chemical equivalent thereof. Preferably, a G protein coupled receptor subjected to constitutive receptor activation according to the invention described herein, evidences at least a 10% difference in response (increase or reduction, as the case may be) to the measured signal for constitutive activation as compared to the endogenous form of that GPCR receptor, most preferably, about a 25% difference in said comparative response, and most preferably about 50% difference in said comparative response When used for For the purposes of directly identifying candidate compounds, it is highly preferred that the signal difference be at least about 50%, so that there is a sufficient difference between the endogenous signal and the non-endogenous signal to differentiate between candidate compounds selected. In many cases, the "difference" will be an increase in signal; however, with respect to GPCRS receiver coupled to Gs, the "difference" measured preferably is a decrease, as set forth in more detail below. 10 CONTACT OR CONTACT should represent the union of at least 2 portions together, either in an in vitro system or in an in vivo system. IDENTIFY DIRECTLY OR DIRECTLY IDENTIFIED, is related to the phrase "candidate compound", must represent the classification of a candidate compound against a constitutively activated protein G-coupled receptor, and determine the efficacy of the compound of said compound. This phrase, under no circumstances, must be interpreted or understood to be encompassed by or to encompass the phrase "indirectly identify" or "indirectly identified". ENDOGEN must represent a material that is naturally produced by the genome of the species. ENDOGEN in reference to, for example and without limitation, GPCR receptor, must represent that it is naturally produced by a human being, an insect, a plant, a bacterium or a virus In contrast, the term NON-ENDOGEN in This context must represent that which is not naturally produced by the genome of a species. For example, and without limitation, a receptor that is not constitutively active in its endogenous form, but when mutated using the cassettes described herein and then becomes constitutively active, is most preferably referred to herein as a "constitutively activated receptor". not endogenous ". Both terms can be used to describe both "in vivo" and "in vitro" systems. For example, and without limitation, in a classification aspect, the endogenous or non-endogenous receptor may be in reference to an in vitro classification system whereby the receptor is expressed on the cell surface of a mammalian cell. As a further example and without limitation, when the genome of a mammal has been engineered to include a constitutively activated, non-endogenous receptor, the classification of a candidate compound through an in vivo system is feasible. HOST CELL must represent a cell capable of having a plasmid and / or vector incorporated in it. In the case of a prokaryotic host cell, a plasmid is typically replicated as an autonomous molecule as the host cell replicates (generally, the plasmid is then isolated for introduction into a eukaryotic host cell); in the case of a eukaryotic host cell, a plasmid is integrated into the cellular DNA of the host cell, so that when the eukaryotic host cell replicates, the plasmid replicates ^^^^^^^^^^^^^^^^^^^^^^^^ | ^^^ | ^^^^^^^^^^^^^^^^^ Preferably, for the purposes of the invention described herein, the host cell is eukaryotic, most preferably, mammalian, and is preferably selected from the group consisting of 293 cells, 293T and COS-7. IDENTIFY INDIRECTLY OR INDIRECTLY IDENTIFIED represents the traditional aspect for the drug discovery process that involves the identification of an endogenous ligand specific for an endogenous receptor, the classification of candidate compounds against the receptor for the determination of those that interfere and / or compete with the ligand interaction -receptor, and determining the effectiveness of the compound to affect at least a second messenger path associated with the activated receptor. INHIBIT OR INHIBITION, in relation to the term "response" must represent that a response is diminished or avoided in the presence of a compound, as opposed to the absence of compound INVERSE AGONISTS should represent compounds that bind either the endogenous form of the receptor or the constitutively active form of the receptor, and which inhibit the intracellular baseline response initiated by the active form of the receptor below the normal base level of activity, which is observed in the absence of agonists or partial agonists, or reduces the binding of GTP to membranes Preferably, the intracellular baseline response is inhibited in the presence of the agonist inverse by at least 30%, preferably at least 50%, and most preferably at least 75% as compared to the baseline response in the absence of the inverse agonist. A KNOWN RECEIVER must represent an endogenous receptor for which the endogenous ligand specific for that receptor has been identified. LIGANDO must represent a molecule of natural existence, endogenous specific for a receptor of natural, endogenous existence. MUTANT OR MUTATION in reference to a nucleic acid and / or amino acid sequence of the endogenous receptor must represent a specific change or changes for said endogenous sequences, such that a mutated form of a non-constitutively activated, endogenous receptor demonstrates the constitutive activation of the receptor . In terms of equivalents to specific sequences, a subsequent mutated form of a human receptor is considered to be equivalent to a first mutation of the human receptor if, (a) the level of constitutive activation of the subsequent mutated form of the receptor is substantially equal to that evidenced by the first mutation of the receiver; and (b) the percentage of sequence homology (amino acid and / or nucleic acid) between the subsequent mutated form of the receptor and the first mutation of the receptor is at least about 80%, preferably at least about 90% and very preferably at least 95% Ideally, and in relation to "-,,.? The fact that the highly preferred cassettes described herein to achieve constitutive activation include a single amino acid change and / or codon between the endogenous and non-endogenous forms of the GPCR receptor say, X or XCOdon) > the percentage of sequence homology must be at least 98%. ORPHANE RECEPTOR must represent an endogenous receptor for which the endogenous ligand specific for that receptor has not been identified or is not known. PHARMACEUTICAL COMPOSITION must mean a A composition comprising at least one active ingredient, whereby the composition is manageable for the investigation of an effective, mammal-specific, effective result (eg, and without limitation, a human being). Those skilled in the art will understand and appreciate the appropriate techniques to determine if An active ingredient has a desired effective result based on the needs of the skilled person. PLASMIDO should represent the combination of a Vector and cDNA. Generally, a plasmid is introduced into a host cell for the purpose of replication and / or expression of the cDNA as a protein. STIMULATE OR STIMULATION in relation to the term "response" must represent that a response is increased in the presence of a compound as opposed to the absence of the compound. 25 TRANSVERSAL OR TRANSVERSE, in reference to either a ^^ fe ^^^^; ^^^ _ = ^ __ ^ __ ^ = ¿^^^^^^ - ^ v ~ * '? < ** & amp; amp. * & - ^? - > »~ '. £ & amp; amp; & amp; &; defined nucleic acid sequence or a defined amino acid sequence, must represent that the sequence is located within at least 2 different and defined regions. For example, in an amino acid sequence having a length of 10 amino acid portions, wherein 3 of the 10 portions are in the TM6 region of a GPCR receiver and the remaining 7 portions are in the IC3 region of the GPCR receptor, the 10 amino acid portions can be described as traversing the TM6 and IC3 regions of the GPCR receptor. VECTOR in reference the cDNA must represent a circular DNA capable of incorporating at least one cDNA and capable of being incorporated into a host cell. The order of the following sections is established for presentation efficiency and is not intended, nor should it be constructed as a limitation of the description or the claims that follow A. Introduction The traditional study of receptors has always proceeded from a (historically based) assumption that the ligand The endogenous first must be identified before the discovery can proceed to find antagonists or other molecules that may affect the receptor. Even in cases where an antagonist might have been known first, the search was immediately extended to look for the endogenous ligand. way of thinking has persisted in the investigation into receptor even - «" * - - - - "** & ¡! S? Tátk- ~. ,," - ^, .. .. .. tjflig ^^^:] IL_ _ ^ _-_ ^^ ^ _ ^ after the discovery of constitutively activated receptors What has not been recognized until now is that it is the active state of the receptor that is most useful for discovering agonists, partial agonists and inverse receptor agonists. of an excessively active receptor or a subactive receptor, what is desired in a therapeutic drug is a compound that acts to decrease the active state of a receptor or enhance the activity of the receptor, respectively, not necessarily a drug that is an antagonist for the ligand endogenous. This is because a compound that reduces or improves the activity of the active receptor state does not need to bind in the same site as the endogenous ligand. Thus, as seen through the method of this invention, any search for therapeutic compounds must begin by classifying compounds against the active state independent of the ligand. The classification of candidate compounds against constitutively activated, non-endogenous GPCRs allows the direct identification of candidate compounds that act on these cell surface receptors, without requiring any knowledge above or use of the endogenous receptor ligand The determination of areas within the body where the endogenous version of said GPCRs receptors are expressed and / or over expressed, it is possible to determine disease states / related disorders that are associated with expression and / or about expression of these receptors, said aspect is described in this patent document - ** a'- '- ".- ^ .. ^' MÜA ^, '.ABA.,., _, ^ .. ^. ^.», * & £ aéá¡ß ¿¡¡Hx¡¡ Se -: w .. «a» &- ..

B. Identification and / or selection of disease / disorder Most preferably, inverse agonists for constitutively activated, non-endogenous GPCRs can be identified using the materials of this invention. Such inverse agonists are ideal candidates as major compounds in drug discovery programs to treat diseases related to these receptors. Due to the ability to directly identify inverse agonists, partial agonists or agonists for these receptors, thus allowing the development of pharmaceutical compositions, a search is possible given diseases and disorders associated with these receptors. For example, the screening of both diseased and diseased tissue samples. Normal for the presence of these receptors has now become more than an academic exercise or one that may be in accordance with the identification path, in the case of an orphan receptor, an endogenous ligand. Tissue scans can be conducted across a wide range of healthy and diseased tissues. Such tissue scans provide a preferred first step in the association of a specific receptor with a disease and / or disorder. Preferably, the DNA sequence of the endogenous GPCR receptor is used to make a probe for both the identification of radiolabelled cDNA and for RT-PCR of GPCR receptor expression in tissue samples. The presence of a receptor in a diseased tissue, or the presence of the receiver .alBtete *. ».m ~ ^,. *. . ^^^ • ^^ < J ^ ^ r ^ - ^ t ^ s ^ í ^^^^^ s¡l ^^ r ".,., -," ^ *? ^ H ** .- + J *.

High or reduced concentrations in diseased tissue compared to a normal tissue, can be preferably used to identify a correlation with that disease. The receptors can also be well localized to organ regions through this technique. Based on the known functions of the specific tissues in which the receptor is located, the putative functional role of the receptor can be deduced.

C. An algorithm of "Human GPCR Receptor Proline Marker" and the Creation of Human, Constitutively Active, Non-Endogenous GPCRs Receptors Among many challenges confronting the biotechnology technique is the incalculable ability to collect genetic information of a species and correlate that information with another species, nowhere in this technique does this evidence of problem become a more annoying exacerbation than in the genetic sequences that encode nucleic acids and protein. Thus, for consistency and due to the highly incalculable nature of this technique the following invention is limited, in terms of mammals, to human GPCR receptors, the applicability of this invention to other mammalian species, although a potential possibility is considered beyond a mere application In general, when trying to apply common "rules" of a protein sequence related to another or from one species to another, the technique has typically made use of sequence alignment, ie the sequences are linearized and then attempts are made to find regions of community between two or more sequences. Although useful, this aspect does not always prove to result in important information. In the case of GPCRs, although the general structural motif is identical for all GPCRs, the variations in lengths of the TMs, ECs and ICs makes these aspects of alignment of one GPCR receiver to another very difficult. In this way, although it may be desirable to apply a consistent aspect, for example, to the constitutive activation of one GPCR receiver to another, due to the great diversity in sequence length, fidelity, etc., of one GPCR receiver to the next, in In essence, an aspect of mutational alignment that is generally applicable and easily successful is not possible. In an analogy, this aspect is similar by having a traveler start on a tour at point A giving the dozens of travelers from different maps to point B, without any scale or distance markers on any of the maps, and then Ask the traveler to find the shortest and most efficient route to destination B only using the maps. In such a situation, the task can be easily scientified by having, (a) a common "place marker" on each map, and (b) the ability to measure the distance from the place marker to destination B, then, this will allow the traveler selecting the most efficient point from the match point A and the destination B In essence, one aspect of the invention is to provide said coordinates within human GPCRs that easily allow the creation of a constitutively active form of human GPCRs receptors. As those in the art will appreciate, the transmembrane region of a cell is highly hydrophobic; in this way, by using standard hydrophobic graphics techniques, those aspects in the art will easily be able to determine the TM regions of a GPCR receiver, and specifically TM6 (this same aspect is also applicable to determine the EC and IC regions). of the GPCR receiver). It has been discovered that within the TM6 region of the human GPCRs receptors, a common proline residue (generally about half of TM6) acts as a "marker" of constitutive activation. Counting 15 amino acids from the proline marker, amino acid 16 (which is located in loop IC3), when it is mutated from its endogenous form to a non-endogenous form, leads to the constitutive activation of the receptor. For convenience, this is referred to as the "Proline Marker of the Human GPCR Receiver" algorithm. Although the non-endogenous amino acid in this position can be any of the amino acids, most preferably the The non-endogenous amino acid is lysine. Although not intended to be bound by any theory, it is believed that this position by itself is unique and that the mutation in this location intact to the receptor to allow constitutive activation It is observed that, for example, when the endogenous amino acid in position 16 is already hsina (as is the case with GPR4 and GPR32), ^^^^^^^^^^^^^^^^^^^^ i ^^^^^^ ^^^^ * ^^^^^^^^^ afterwards so that X is a non-endogenous amino acid, this must be different from lysine; thus, in those situations where the endogenous GPCR receptor has an endogenous lysine residue at position 16, the non-endogenous version of that 5 GPCR receptor preferably incorporates an amino acid other than lysine, preferably alanine, histidine and arginine, in that position. In addition, it has been determined that GPR4 appears to be linked to Gs and is active in its endogenous form (data not shown). Since there are only 20 naturally occurring amino acids (although the use of non-natural amino acids is also viable), the selection of a particular non-endogenous amino acid for substitution at this position 16 is feasible and allows efficient selection of a non-endogenous amino acid that conforms to the researcher's needs . However, as noted, the non-endogenous non-preferred amino acids at position 16 are lysine, histidine arginine, and alanine, with lysine being most preferred. Those skilled in the art are credited with the ability to easily determine expert methods to sequence the codon to achieve a desired mutation. It has also been found that occasionally, but not always, the proline residue marker will be preceded in TM6 by W2 (ie, W2P1AA15X) where W is a tpptophan and the number 2 is any amino acid residue This discovery, among others things, denies the need for aspects of complicated and not incalculable sequence alignment commonly used in the art. In fact, the strength of this discovery, although an algorithm in nature, is that it can be applied in an easy way to human GPCRs, with the skillful simplicity of those skilled in the art to achieve a unique and highly useful end product. say, a constitutively activated version of a human GPCR receptor. Since many years and significant amounts of money will be required to determine the endogenous ligands for the human GPCRs receptors that the Human Genome project is revealing, the The mentioned statement not only reduces the time needed to positively exploit this sequence information, but significant savings in cost. This aspect really validates the importance of the Human Genome project since it allows the use of genetic information not only to understand the role of GPCRs receptors in, for example, diseases, but can also propiciOna the opportunity to improve the human condition.

D. Classification of candidate compounds 20 1. Generic GPCR receptor classification assay techniques. When a G protein receptor becomes constitutively active, it is coupled to a G protein (eg, Gq, Gs, Gi, Go) and stimulates the release and subsequent binding of GTP to the protein G Protein G then acts as a GTPase and slowly What is the% £ -? * ^? ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ and hydrolyzes GTP to GDP, so that the receiver, under normal conditions, is deactivated. However, constitutively activated receptors, including the non-endogenous, constitutively active human GPCR receptors of the present invention, continue to exchange GDP for GTP. A non-hydrolysable GTP analog, [35S] GTP? S, can be used to verify the enhanced binding to G proteins present in membranes expressing constitutively activated receptors. It was reported that [35S] GTP? S can be used to verify coupling, ... of G protein a membranes in the absence and presence of the ligand. An example of this verification, among other examples well known and available to those skilled in the art was reported by Traynor and Nahorski in 1995. The preferred use of this test system is for the initial classification of candidate compounds that that system is generically applicable to all G-protein coupled receptors, without considering the particular G protein that interacts with the intracellular domain of the receptor.

B 2. GPCR C receptor-specific classification assay techniques Once the candidate compounds are identified using the G protein-coupled receptor assay "Generic", (ie, an assay to select compounds that are agonists, partial agonists or inverse agonists), is preferred an additional classification to confirm that the compounds have S &jysbeiía ». -"' -Y. ~ JS? & - ££ &&Jti É & i .. ** & amp; *} interacted on the recipient's site. For example, a compound identified by the "generic" assay may not bind to the receptor, but rather merely "decouples" the G protein from the intracellular domain. to. Gs and Gi Gs stimulates the enzyme adenylyl cyclase. Gi (and Go), on the other hand, inhibits this enzyme. The adenylyl cyclase catalyzes the conversion of ATP to cAMP; in this way, GPCRs receptors constitutively activated Gs-coupled proteins are associated with elevated cellular levels of cAMP. On the other hand, constitutively activated GPCRs that couple the Gi (Go) protein are associated with reduced cellular levels of cAMP. See, in general, "Indirect Mechanisms of Synaptic Tr-ansmission," Cap. 8, From Neuron To Brain (3rd Ed.) Nichols, J.G. and other eds. Sinauer Associates, Inc. (1992). In this manner, assays that detect cAMP can be used to determine whether a candidate compound is, for example, an inverse agonist to the receptor (ie, said compound can reduce cAMP levels). You can use a A variety of aspects known in the art for measuring cAMP; A very preferred aspect is based on the use of anti-cAMP antibodies in the ELISA-based format. Another type of assay that can be used is the whole cell secondary messenger report system assay. The promoters in the genes direct the expression of the proteins that a particular gene codes for AMP Cyclic directs gene expression by promoting the binding of a DNA-sensitive cAMP binding protein or transcription factor (CREB), which then binds to the promoter at specific sites called cAMP response elements and directs gene expression. Reporting systems having a promoter containing multiple cAMP response elements can be constructed, for example, β-galactosidase or luciferase. In this way, a receptor bound to constitutively activated Gs causes the accumulation of cAMP that then activates the gene and the expression of the report protein. The reporter protein, such as β-galactosidase or luciferase, can then be detected using standard biochemical assays (Chen et al., 1995). With respect to the GPCRs that bind to Gi (or Go) and thus reduce the levels of cAMP, one aspect is described for the classification of, for example, inverse agonists, based on the use of receptors that bind to Gs (and thus increase cAMP levels) in the examples section with respect to GPR17 and GPR30 b. Go and Gq Gq and Go are associated with the activation of the enzyme phospholipase C, which in turn hydrolyses the phospholipid PIP2 by releasing two intracellular messengers diacylloglycerol (DAG) and an osito I |, 4,5-tpfosfato (IP3) Increased accumulation of IP3 is associated with the activation of receptors associated with Gq- and Go-Ver, in General, "Indirect Mechanisms of Synaptic Transmission," Cap. 8, From Neuron To Brain (3rd ed.) Nichols, J.G. and other eds. Sinauer Associates, Inc. (1992). Assays for detecting IP3 accumulation can be used to determine whether a candidate compound is, for example, an inverse agonist for a Gq- or Go- associated receptor (ie, said compound can reduce IP3 levels). Gq-bound receptors can also be examined using an AP1 report assay since Gq-dependent phospholipase C causes the activation of genes that contain the elements AP1; in this way the activated Gq-associated receptors will show an increase in the expression of said genes, so the inverse agonists to them will show a reduction in said expression, and the agonists will show an increase in said expression. Tests are available commercially available for said detection.

E. Medical Chemistry Generally, but not always, direct identification of candidate compounds is preferably conducted in conjunction with compounds generated through chemistry techniques. of combination, so that thousands of compounds are randomly prepared for such analysis. In general, the results of such classification will be compounds that have unique core structures; then these compounds are preferably subjected to additional modification around a core structure (s) «A ^^^^^^. ^. ^. ,. fflri fc || fraj «tt.J .., Í» ^^ A¿A. ~ ^ ',. preferred to further improve its medicinal properties. Such techniques are known to those skilled in the art and will not be discussed in detail in this patent document.

F. Pharmaceutical Compositions Candidate compounds selected for further development can be formulated into pharmaceutical compositions, using techniques well known to those skilled in the art. The pharmaceutically acceptable carriers, suitable are available to those skilled in the art; for example, see Remington's Pharmaceutical Sciences, 16th. Edition, 1980, Mack Publishing Co., (Oslo et al., Eds.).

G. Other Utilities 15 Although a preferred use of the non-endogenous versions of the described human GPCR receptors is for the direct identification of candidate compounds as inverse agonists, agonists or partial agonists (preferably for use as a pharmaceutical agent), these receptors may also be used in aspects of search. For example, in vitro and in vivo systems can be used incorporating these receptors to further produce and understand the roles of the receptors in the human condition, both normal and diseased, as well as to understand the role of constitutive activation as it is applied. understanding of the signaling cascade A value in these '^^^^^^^^^^^^^^^ non-endogenous receptors is that their usefulness as a search tool is improved, since, due to their unique aspects, the described receptors can be used to understand the role of a particular receptor in the body of the human being before the endogenous ligand is identified. Other uses of the disclosed receptors will be apparent to those skilled in the art based on, in other things, a review of this patent document.

EXAMPLES 10 The following examples are presented for purposes of clarifying, and not limiting, the present invention. After the teaching of this patent document a mutational cassette can be used in the coil and C3 of human GPCRs receptors based on a position relative to a proline residue in TM6 to constitutively activate the receptor, and although the specific nucleic acid and amino acid sequences are described herein, those skilled in the art are credited with the ability to make minor modifications to these sequences while HE achieve the same results, or substantially similar results reported later. The particular aspects for sequence mutations are within the experience of the technicians based on the particular needs of the experts asife & a ^^ - - ^ ,,, .. "- ..,. ^ - ^ ¡S ^^ m ^^^^^^^^^^. ^^^ Example 1 Preparation of Endogenous Human GPCR Receptors A variety of GPCRs receptors were used in the following 5 examples. Some endogenous human GPCRs receptors were cordivily provided in expression vectors (as recognized below) and other endogenous human GPCR receptors were synthesized again using publicly available sequence information. 10 1. GPT1 (GenBank accession number: U13666) The human cDNA sequence for GPR1 was provided in pRcCMV by Brian O'Dowd (University of Toronto). The GPR1 cDNA (1.4kB fragment) was separated from the pRcCMV vector as an Ndel-Xbal fragment and subcloned into the NdelXbal site of the pCMV vector (see Figure 3). The nucleic acid (SEQ ID NO: 1) and amino acid (SEQ ID NO: 2) sequences for human GPR1 were then determined and verified. 2. GPR4 (GenBank Accession Numbers: L36148.U35399, U21051) 20 The human cDNA sequence for GPR4 was provided in pRcCMV by Brian O'Dowd (University of Toronto). The GPR1 cDNA (1.4kB fragment) was separated from the vector pRcCMV as an Apal fragment (shaved end) -Xbal and was subcloned (with most of the 5 'untranslated region removed) to the site H? Nd? (Shaved end) -Xbal of the vector pCMV The sequences of ^^ ¡^^ ^^^^^^^^^^^^^^^^^^^^^ ^^^ nucleic acid (SEQ ID NO: 3) and amino acid (SEQ ID NO: 4) for human GPR were then determined and verified. 3. GPR5 (GenBank Accession Number: L36149) The cDNA for human GPR5 was generated and cloned into the pMCV expression vector as follows: PCR was performed using template genomic DNA and rTth-polymerase (Perkin Elmer) with the pH regulator system provided by the manufacturer, 0.25 μM of each primer, and 0.2 μM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 64 ° C for 1 minutes; and 72 ° C for 1.5 minutes. The 5 'PCR primer contained an EcoRI site with the sequence: 5'-TATGAATTCAGATGCTCTAAACGTCCCTGC-3' (SEQ ID NO: 5) and the 3 'primer contained the BamHI site with the sequence: 5, -TCCGGATCCACCTGCACCTGCGCCTGCACC- 3, (SEQ ID NO: 6) 15 The 1.1 kb PCR fragment was digested with EcoRI and BamHI and cloned into the EcoRI-BamHI site of the PCMV expression vector. The nucleic acid (SEQ ID NO: 7) and the amino acid (SEQ ID NO: 8) sequences for human GPR5 were then determined and verified 20 4. GPR7 (GenBank Accession Number: U22491 ) The cDNA for GPR7 was generated and cloned into the expression vector pCMV as follows the PCR-PCR condition using DNA as template and rTth polymerase (Perkm Elmer) with the pH regulator system provided by the manufacturer, 0.25 μM of each initiator and 0 2 mM of each of the 4 nucleotides The condition < »» IAe * ~ ~~, f L s ^ £ of the cycle was 30 cycles of: 94 ° C for 1 minute; 62 ° C for 1 minute; and 72 ° C for 1 minute and 20 seconds. The 5 'PCR primer contained a Hindlll site with the sequence: 5'GCAAGGCTTGGGGGACGCCAGGTCGCCGGCT-3' (SEQ ID NO: 9) and the 3 'primer contained a BamHI site with the sequence: 5'-GCCGATCCGGACGCTGGGGGAGTCAGGCTGC-3' ( SEC. I D. NO .: 10) The 1.1 kb PCR fragment was digested with Hindllll and BamHI and cloned into the HlndlH-BamHI site of the pCMV expression vector. The nucleic acid (SEQ ID NO: 11) and the amino acid (SEQ ID NO: 12) sequences for human GPR7 were then determined and verified. 5. GPR8 (GenBank Accession Number: U22492) The cDNA for human GPR8 was generated and cloned into the pCMV expression vector as follows: PCR was performed using genomic DNA as a template and rTth polymerase (Perkin Elmer) with the regulatory system of pH provided by the manufacturer, 0.25 μM of each primer and 0.2 mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 62 ° C for 1 minute; and 72 ° C for 1 minute and 20 seconds. The 5 'PCR primer contained an EcoRI site with the sequence: 5'-CGGAATTCGTCAACGGTCCCAGCTAACAATC-3' (SEQ ID NO. 13) and the 3 'primer contained a BamHI site with the sequence. 5'-ATGGATCCCAGGCCCTTCAGCACCGCAATAT-3 '(SEQ ID NO 14) The 1.1 kb PCR fragment was digested with EcoRI and BamHI and cloned into the EcoRI I-BamHI site of the pCMV expression vector , ^^^^^^ l ^ ^ ^ The 4 sequenced cDNA clones contained a possible polymorphism involving a change of amino acid 206 from Arg to Gln. In addition to this difference, the nucleic acid (SEC.ID.NO.:15) and amino acid (SEQ ID NO: 16) sequences for human GPR8 were then determined and verified. 6. GPR9 (GenBank accession number: X95876) The cDNA for human GPR9 was generated and cloned into the pCMV expression vector as follows: PCR was performed using a clone (provided by Brian O'Dowd) as template and pfu polymerase (Stratagene) with the pH regulator system provided by the manufacturer supplemented with 10% DMSO, 0.25 μM of each primer and 0.2 mM of each of the 4 nucleotides. The condition of the cycle was 25 cycles of: 94 ° C for 1 minute; 56 ° C for 1 minute; and 72 ° C for 2.5 minutes. The 5 'PCR primer contained an EcoRI site with the sequence: 5'-ACGAATTCAGCCATGGTCCTTGAGGTGAGTGACCACCAAGTGCTAAAT -3' (SEC.ID.NO.:17) and the 3 'primer contained a BamHI site with the sequence. 5'-GAGGATCCTGGAATGCGGGGAAGTCAG-3 '(SEQ ID NO: 18) The 1.2kb PCR fragment was digested with EcoRI and cloned into the EcoRI-Smal site of the PCMV expression vector. The nucleic acid (SEQ ID NO: 19) and amino acid (SEQ ID NO: 20) sequences for human GPR9 were then determined and verified 7. GPR9-6 (GenBank accession number: U45982) CDNA for human GPR9-6 was generated and cloned into the pCMV expression vector as follows: PCR was performed using genomic DNA as a template and rTth polymerase (Perkin Elmer) with the pH regulator system provided by the manufacturer, 0.25 μM of each primer and 0.2 mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 62 ° C for 1 minute; and 72 ° C for 1 minute and 20 seconds. The 5 'PCR primer was treated with a kinase with the sequence: 10 5'-TTAAGCTTGACCTAATGCCATCTTGTGTCC-3' (SEQ ID NO: 21) and the 3 'primer contained a BamHI site with the sequence: 5'-TTGGATCCAAAAGACCATGCACCTCAGAG-3 '(SEQ ID NO: 22) The 1.2 KB PCR fragment was digested with BamHI and cloned into the EcoRV-BamHI site of the pCMV expression vector. The Nucleic acid (SEQ ID NO: 23) and amino acid (SEC.ID.NO.:24) sequences for human GPR9-6 were then determined and verified. 8. GPR10 (GenBank accession number: U32672) The cDNA sequence for GPR10 was provided in pRcCMV 20 by Brian O'Dowd (University of Toronto) The GPR10 cDNA (1.3kB fragment) was separated from the vector pRcCMV as a EcoRI-Xbal fragment and was subcloned into the EcoRI-Xbal site of the pCMV vector The nucleic acid (SEQ ID NO: 25) and amino acid (SEQ ID NO: 26) sequences for human GPR10 were then determined and verified * i?? J ~~! ** x * ^. ^ .. ^. ^^. ^ S ^ a ^, ^. | | , ^ .. ,, ^^ and ^ ß ^ r ^^ - ^^ a ^ iái ^^ 9. GPR15 (GenBank accession number: U34806) The human cDNA sequence for GPR15 was provided in pCDNA3 by Brian O ' Dowd (University of Toronto). The GPR15 cDNA (1.5 kB fragment) was separated from the pCDNA3 vector as a fragment of HindIII-Bam and subcloned into the HindIII-Bam site of the pCMV vector. The nucleic acid (SEC.ID.NO.:27) and amino acid (SEC.ID.NO.:28) sequences for human GPR15 were then determined and verified 10. GPR17 (GenBank accession number: Z94154) 10 Human cDNA sequence for GPR17 was generated and cloned into the pCMV expression vector as follows: PCR was performed using genomic DNA as template and rTth polymerase (Perkm Elmer) with the pH regulator system supplied by the manufacturer, 0.25μM of each primer , and 0.2 mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 56 ° C for 1 minute and 72 ° C for 1 minute 20 seconds. The 5 'PCR primer contained an EcoRI site with the sequence: 5'-CTAGGATTCTGACTCCAGCCAAAGCATGAAT-3' (SECC.ID NO 29) and the 3 'primer contained a BamHI site with the sequence: 5'-GCTGGATCCTAAACAGTCTGCGCTCGGCCT-3' (SEQ ID NO, 30) The 1 1 kb PCR fragment was digested with EcoRI and BamHI and cloned into the EcoRI-BamHI site of the pCMV expression vector The nucleic acid (SEQ ID NO: 31) and amino acid sequence (SEQ ID NO 32) for human GPR17 were then determined and verified. 11. GPR18 (GenBank Accession Number: L42324) The cDNA for human GPR18 was generated and cloned into the pCMV expression vector as follows: PCR was performed using 5 in genomic DNA as template and rTth-polymerase (Perkin Elmer) with the pH regulator system provided by the manufacturer, 025μM of each initiator and 0.2mM for each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 54 ° C for 1 minute and 72 ° C for 1 minute and 20 seconds. The 0 primer of 5 'PCR was treated with a kinase with the sequence: 5'-ATTAGATGATCACCCTGAACAATCAAGAT-3' (SEQ ID NO: 33) and the 3 'primer contained an EcoRI site with the sequence: 5'-TCCGAATTCATAACATTTCACTHTTTATATTGC- 3 '(SEC.I D. NO .: 34). The 1.0 kb PCR fragment was digested with EcoRI and 5 cloned into the shaved EcoRI site of the pCMV expression vector. The 8 sequenced cDNA clones contained 4 possible polymorphisms involving changes of amino acid 12 from Thr to Pro, amino acid 86 of Ala Glu, amino acid 97 from He to Leu and amino acid 310 from Leu to Met In addition to these changes, the sequences of 0 nucleic acid (SEQ ID NO..35) and of amino acid (SEQ ID NO.36) for GPR18 human were then determined and verified 12. GPR20 (GenBank accession number: U66579) The ANDc for human GPR20 was generated and cloned into the pCMV expression vector as follows the PCR was performed using 5 genomic DNA as a template and rTth-polymerase ( Perkin Elmer) with the níJkn? á & náii, «^^ * | yss? ^^^ & ^! 4 pH regulator system provided by the manufacturer, o.25μmM of each initiator, and 0.2 mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 62 ° C for 1 minute; and 72 ° C for 1 minute and 20 seconds. The 5 'PCR primer was treated with a kinase with the sequence: 5'-CCAAGCTTCCAGGCCTGGGGTGTGCTGG-3' (SEQ ID NO: 37) and the 3 'primer contained a BamHI site with the sequence: 5'-ATGGATCCYGACCTTCGGCCCCTGGCAGA-3' (SEQ ID NO: 38). The 1.2 kb PCR fragment was digested with BamHI and cloned into the EcoRV-BamHI site of the PCMV expression vector. The nucleic acid (SEQ ID NO: 39) and amino acid (SEQ ID NO: 40) sequences for human GPR20 were then determined and verified 13. GPR21 (GenBank accession number: U66580) The cDNA for Human GPR21 was generated and cloned into the pCMV expression vector as follows: PCR was performed using genomic DNA as template and rTth-polymerase (Perkin Elmer) with the regulatory system provided by the manufacturer, 0.25 μM of each primer and 0 2 mM of each of the 4 nucleotides. The cycle condition was 30 cycles of 94 ° C for 1 minute; 62 ° C for 1 minute and 72 ° C for 1 minute and 20 seconds The 5 'PCR primer was treated with a kinase with the sequence 5'-GAGAATTCACTCCTGAGCTCAAGATGAACT-3' (SEQ ID NO 41) and the 3 'primer contained a site BamHI with the sequence 5'-CGGGATCCCCGTAACTGAGCCACTTCAGAT-3 '(SEQ ID NO 42) jjj ^ g ^ Híglg &gg The 1. kb PCR fragment was digested with BamHI and cloned into the EcoRV-BamHI site of the pCMV expression vector. The nucleic acid (SEC.ID.NO.:43) and amino acid (SEC.ID.NO.:44) sequences for human GPR21 were then determined and verified. 14. GPR 22 (GenBank accession number: U66581) The cDNA for human GPR22 was generated and cloned into the pCMV expression vector as follows: PCR was performed using genomic DNA as template and rTth-polymerase (Perkin Elmer) with the pH regulator system provided by the manufacturer, 0.25μM of each initiator, and 0.2mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 50 ° C for 1 minute and 72 ° C for 1.5 minutes. The 5 'PCR primer was treated with a kinase with the sequence: 15 5'-TCCCCCGGGAAAAAAACCAACTGCTCCAAA-3' (SEQ ID NO: 45) and the 3 'primer contained a BamHI site with the sequence: 5'-TAGGATCCATTTGAATGTGGATTTGGTGAAA -3 '(SEC.I D. NO .: 46). The 1 38kb PCR fragment was digested with BamHI and cloned into the EcoRV-BamHI site of the pCMV expression vector The nucleic acid (SEQ.ID.NO..47) and amino acid (SEQ.ID.N048) sequences for human GPR22 were then determined and verified. 15. GPR24 (GenBank accession number: U71092) The cDNA for human GPR24 was generated and cloned into the pCMV expression vector as follows the PCR was performed using Genomic DNA as template and rTth-polymerase (Perkin Elmer) with the pH regulator system provided by the manufacturer, 0.25μM of each primer, and 0.2mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 56 ° C 5 for 1 minute and 72 ° C for Iminuto and 20 seconds. The 5 'PCR primer contains a Hindlll site with the sequence: d'-GTGAAGCTTGCCTCTGGTGCCTGCAGGAGG-S' (SEQ ID NO: 49) and the 3 'primer contains an EcoRI site with the sequence: 5'-GCAGAATTCCCGGTGGCGTGTTGTGGTGCCC-3 '(SEQ ID NO: 50). The 1.3 kb PCR fragment was digested with Hindlll and EcoRI and cloned into the HindIII-EcoRI site of the pCMV expression vector. The nucleic acid (SEC.ID.NO.:51) and amino acid sequences (SEC.ID.NO:52 for human GPR24 were then determined and verified.) 16. 16. GPR30 (GenBank accession number: U63917) The cDNA for human GPR30 was generated and cloned as follows: the GPR30 coding sequence (length 1128bp) was amplified from genomic DNA using the primers: 5'-GGCGGATCCATGGATGTGACTTCCCAA-3 '(SEQ ID NO: 53) and 20 5'-GGCGGATCCCTACACGGCACTGCTGAA-3 '(SEC.ID.NO.:54) The amplified product was then cloned into a commercially available vector, pCR2.1 (Invitrogen), using a "TOPO-TA Cloning Kit" cloning kit. (Invitrogen, # K4500-01), following the manufacturer's instructions In GPR30 insert of full length was released through digestion with BamHI, ? t? ^ ját¿¿í * > Separated from the vector through agarose gel electrophoresis and purified using a Sephaglas Bandprep ™ Kit kit (Pharmacia, # 27-9285-01) following the manufacturer's instructions. The nucleic acid (SEC.ID.NO.:55) and amino acid 5 (SEC.ID.NO.:56) sequences for human GPR30 were then determined and verified. 17. GPR31 (GenBank accession number: U65402) The cDNA for human GPR24 was generated and cloned into the pCMV expression vector as follows: PCR was performed using genomic DNA as a template and rTth-polymerase (Perkin Elmer) with the pH regulator system provided by the manufacturer, 0.25μM of each initiator, and 0.2mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 58 ° C for 1 minute and 72 ° C for 2 minutes. The 5 'PCR primer 15 contains an EcoRI site with the sequence: 5'-AAGGAATTCACGGCCGGGTGATGCCATTCCC-3' (SEQ ID NO: 57) and the 3 'initiator contains a BamHI site with the sequence: 5'-GGTGGATCCATAAACACGGGCGTTGAGGAC- 3 '(SEQ ID NO: 58). The 1.0 kb PCR fragment was digested with EcoRI and BamHI 20 and cloned into the EcoRI-BamHI site of the pCMV expression vector. The nucleic acid (SEC.ID.NO.:59) and amino acid (SEQ ID NO.60) sequences for human GPR31 were then determined and verified 18. GPR32 (GenBank accession number: AF045764) 25 The cDNA for human GPR32 was generated and cloned in the -Guy & aa ^^ ^ ^^^^^ & Sp ^ S ^ -r ^ S ^^ JÉSa ^^ ^. > ^^, -, ..J A.

I pCMV expression vector as follows: PCR was performed using genomic DNA as template and rTth-polymerase (Perkin Elmer) with the pH regulator system provided by the manufacturer, 0.25μM of each primer, and 0.2mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 56 ° C for 1 minute and 72 ° C for 1 minute and 20 seconds. The 5 'PCR primer contains an EcoRI site with the sequence: 5'-TAAGAATTCCATAAAAATTATGGAATGG-3' (SEC.ID.NO.:243) and the 3 'primer contained a BamHI site with the sequence: 10 5'-CCAGGATCCAGCTGAAGTCTTCCATCATTC- 3 '(SEC.I D.NO.:244). The 1.1 kb PCR fragment was digested with EcoRI and BamHI and cloned into the EcoRI-BamHI site of the pCMV expression vector. The sequences of acid (SEC.ID.NO.:245) and amino acid (SEC.ID.NO.:246) for human GPR32 were then detned and verified. 19. GPR40 (GenBank accession number: AF024687) The cDNA for human GPR40 was generated and cloned into the pCMV expression vector as follows: PCR was performed using genomic DNA as template and rTth-polymerase (Perkin Elmer) with the pH regulator system provided by the manufacturer, 0 25μM of each primer, and 0.2mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute, 65 ° C for 1 minute and 72 ° C for 1 minute and 10 seconds The 5 'PCR primer contains an EcoRI site with the sequence 25 5'- GCAGAATTCGGCGGCCCCATGGACCTGCCCCC-3 ' (SEC.ID.NO.; 247) and the 3 'primer contained a BamHI site with the sequence: d'-GCTGGATCCCCCGAGCAGTGOCGTTACTTC-S' (SEQ ID NO: 248). W The 1 kb PCR fragment was digested with EcoRI and BamHI and cloned into the EcoRI-BamHI site of the pCMV expression vector. The nucleic acid (SEC.ID.NO.:249) and amino acid sequences (SEC.ID.NO.:250) for the human GPR40 were then detned and verified. 20. GPR41 (GenBank accession number: AF024688) The cDNA for human GPR41 was generated and cloned into the pCMV expression vector as follows: PCR was performed using genomic DNA as a template and rTth-polymerase (Perkin Elmer) with the system pH regulator provided by the manufacturer, 0.25μM of each primer, and 0.2mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 65 ° C for 1 minute and 72 ° C for 1 minute and 10 seconds. The 5 'PCR primer contains a Hindlll site with the sequence: 5'-CTCAAGCTTACTCTCTCTCACCAGTGGCCAC-3' (SEQ ID NO: 251) and the 3 'primer was treated with a kinase with the sequence: 5'-CCCTCCTCCCCCGGAGGACCTAGC-3' (SEQ ID NO.:252). The 1 kb PCR fragment was digested with HindIII and cloned into the HindIII-shaved site of the expression vector pCMV. The nucleic acid (SEQ ID NO: 253) and amino acid (SEQ ID NO 254) sequences for human GPR41 then detned and verified - • *** ^ v &! ^. 21. GPR43 (GenBank accession number: AÍ024690) The cDNA for human GPR43 was generated and cloned into the pCMV expression vector as follows: PCR was performed using genomic DNA as template and rTth-polymerase (Perkin Elmer) with 5 regulatory system of pH provided by the manufacturer, 0.25μM of each initiator, and 0.2mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 65 ° C for 1 minute and 72 ° C for 1 minute and 10 seconds. The 5 * PCR primer contains an EcoRI site with the sequence: 0 5'-TTTAAGCTTCCCCTCCAGGATGCTGCCGGAC-3 '(SEQ ID NO: 255) and the 3"primer contained an EcoRI site with the sequence: 5'-GGCGAATTCTGAAGGTCCAGGGAACTGCTA- 3 '(SEQ ID NO: 256) The 1 kb PCR fragment was digested with Hindlll and EcoRI and cloned into the HindIII-EcoRI site of the pCMV expression vector, the 5 nucleic acid sequences (SEC.ID. .NO .:: 257) and amino acid (SEC.ID.NO.:258) for human GPR43 were then detned and verified 22. APJ (GenBank Accession Number: U03642) The human APJ cDNA (in the vector pRcCMV ) was provided by Brian O'Dowd (University of Toronto) The APJ cDNA was separated from the pRcCMV vector as an EcoRI-Xbal fragment (shaved) and subcloned into the EcoRI-Smal site of the pCMV vector. Nucleic acid (SEQ ID NO: 61) and amino acid (SEQ ID NO: 62) for human APJ were then detned and 5 verified. sg ^ ^^^^ j ^^^ g ^^^^^^^^^^^^ f | j¡j ^ Ü ^? BLR1 (GenBank accession number: X68149) The cDNA for human BLR1 was generated and cloned into the pCMV expression vector as follows: PCR was performed using genomic DNA as template and rTth-polymerase (Perkin Elmer) with 5 regulatory system of pH provided by the manufacturer, 0.25μM of each initiator, and 0.2mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 62 ° C for 1 minute and 72 ° C for 1 minute and 20 seconds. The 5 'PCR primer contains an EcoRI site with the sequence: 10 5'-TGAGAATTCTGGTGACTCACAGCCGGCACAG-3' (SEQ ID NO: 63): and the 3 'primer contained a BamHI site with the sequence: 5'-GCCGGATCCAAGGAAAAGCAGCAATAAAAGG -3 (SEQ ID NO: 64). The 1.2 kb PCR fragment was digested with EcoRI and BamHI and cloned into the EcoRI-BamHI site of the pCMV expression vector. The nucleic acid (SEC.ID.NO.:65) and amino acid (SEC.ID.NO.:66) sequences for human BLR1 were then determined and verified. 24. CEPR (GenBank Accession Number: U77827) The cDNA for human CEPR was generated and cloned into the pCMV expression vector as follows: PCR was performed using genomic DNA as template and rTth-polymerase (Perkin Elmer) with the pH regulator system provided by the manufacturer, 0.25μM of each initiator, and 0.2mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 65 ° C 25 for 1 minute and 72 ° C for 1 minute and 20 seconds The initiator ^ "S. **. ^^ * ....." ^ ,,. ,, V. UÉ SS &? AA * »* -,% * ¡n. -fff 5 'PCR was treated with a kinase with the sequence: 5'-CAAAGCTTGAAAGCTGCACGGTGCAGAGAC-3' (SEQ ID NO: 67) and the 3 'primer contained a BamHI site with the sequence: 5'-GGGGATCCCGAGTCACACCCTGGCTGGGCC-3 '(SEC, I D. NO.; 68). 5 The 1.2 kb PCR fragment was digested with BamHI and cloned into the EcoRV-BamHI site of the pCMV expression vector. The nucleic acid (SEC.ID.NO.:69) and amino acid (SEC.ID.NO.:70) sequences for human CEPR were then determined and verified. 10 25. EBI1 (GenBank accession number: L31581) The cDNA for human EBI1 was generated and cloned into the pCMV expression vector as follows the PCR was performed using thymus cDNA as template and rTth-polymerase (Perkin Elmer) with the pH regulator system provided by the manufacturer, 0.25μM of each initiator, and 0.2 mM of each of the 4 nucleotides. The condition of the cycle was 30 cycles of. 94 ° C for 1 minute; 62 ° C for 1 minute and 72 ° C for 1 minute and 20 seconds The 5 'PCR primer contains an EcoRI site with the sequence. 5'-ACAGAATTCCTGTGTGGTTTTACCGCCCAG-3 '(SEQ ID NO 71) and the 3 'primer contained a BamHI site with the sequence 5'-CTCGGATCCAGGCAGAAGAGTCGCCTATGG-3' (SEQ ID NO 72) The 1 kb PCR fragment was digested with EcoRI and BamHI and cloned into the EcoRI-BamHI site of the PCMV expression Nucleic acid (SEQ ID NO: 73) and amino acid sequences (SEQ ID NO. 74) for EBM were then determined and , ^^^^ ^. ^^ ....? iflifflMr? liffl? ftr rtifif - - «~ t verified. 26. EBI2 (GenBank accession number: L08177) The cDNA for human EBI2 was generated and cloned into the pCMV expression vector as follows: PCR was performed using clone 5 cDNA (complacently provided by Kevin Lynch, University of Virgina Health Sciences Center, the vector used was not identified by the sources), template and pfu-polymerase (Stratagene) with the pH regulator system provided by the manufacturer, supplemented with 10% DMSO, 0.25μM of each primer, and 0.25 mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 60 ° C for 1 minute and 72 ° C for 1 minute and 20 seconds. The 5 'PCR primer contains an EcoRI site with the sequence: 5'-CTGGAATTCACCTGGACCACCACCAATGGATA-3' (SEQ ID NO: 75) and the 3 'primer contained a BamHI site with the sequence: 5'-CTCGGATCCTGCAAAGTTTGTCATACAGTT-3' (SEQ ID NO: 76). The 1.2 kb PCR fragment was digested with EcoRI and BamHI and cloned into the EcoRI-BamHI site of the pCMV expression vector. The nucleic acid (SEC.ID.NO.:77) and amino acid sequences (SEQ ID NO.78) for EBI2 were then determined and verified. 27. ETBR-LP2 (GenBank accession number: D38449) The cDNA for human ETBR-LP2 was generated and cloned into the pCMV expression vector as the PCR was followed using Brain cDNA as template and rTth-polymerase (Perkin Elmer) with the pH regulator system provided by the manufacturer, 0.25μM of each primer, and 0.2mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 65 ° C for 1 minute and 72 ° C for 1.5 minutes. The 5 'PCR primer contains an EcoRI site with the sequence: 5'-CTGGAATTCTCCTGCTCASTCDAGCCATGCGG-3' (SEQ ID NO: 79) and the 3 'primer contained the BamHI site with the sequence: 5'-CCTGGATCCCCACCCCTACTGGGGCCTCAG-3 '(SEQ ID NO: 80). The 1.5 kb PCR fragment was digested with EcoRI and BamHI and cloned into the EcoRI-BamHI site of the pCMV expression vector. The nucleic acid (SEC.ID.NO.:81) and amino acid sequences (SEQ ID NO: 82) for human ETBR-LP2 were then determined and verified ..}. 28. GHSR (GenBank accession number: U60179) The cDNA for human GHSR was generated and cloned into the pCMV expression vector as follows: PCR was performed using hippocampal cDNA as template and TaqPlus precision polymerase (Stratagene) with the pH regulator system provided by the manufacturer, 025μM of each primer, and 0.2mM of each of the 4 nucleotides The cycle condition was 30 cycles of: 94 ° C for 1 minute, 68 ° C for 1 minute and 72 ° C C for 1 minute 10 seconds For the first round of PCR the primer sequence 5 'PCR was 5'-ATGTGGAACGCGACGCCCAGCG-3' (SEQ ID NO 83) and the sequence of 3 'primer was '-TCATGTATTAATACTAGATTCT-3 '(SEQ ID NO: 84). Two microliters of the first round of PCR was used as a template for the second round of PCR, where the 5 'primer was treated with a kinase with the sequence: 5'-TACCATGTGGAACGCGACGCCCAGCGAAGAGCCGGGGT-3' (SEC.ID.NO.:85) and the 3 'primer contained an EcoRI site with the sequence: 5'-CGGAATTCATGTATTAATACTAGATTCTGTCCAGGCCCG-3' (SEC.ID.NO.:86). The 1.1 kb PCR fragment was digested with EcoRI and cloned into the EcoRI-shaved site of the expression vector pCMV. The nucleic acid (SEC.ID.NO.:87) and amino acid (SEC.ID.NO.:88) sequences for human GHSR were then determined and verified. 29. GPCR-CNS (GenBank accession number: AF017262) The cDNA for human GPCR-CNS was generated and cloned into the pCMV expression vector as follows: PCR was performed using Brain cDNA as template and rTth-polymerase (Perkin Elmer) with the pH regulator system provided by the manufacturer, 0.25μM of each primer, and 0.2mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 65 ° C for 1 minute and 72 ° C for 2 minutes. The 5 'PCR primer contained a Hindlll site with the sequence: 5'-GCAAGCTTGTGCCCTCACCAAGCCATGCGAGCC-3' (SEC.ID.NO.:89) and the 3 'primer contained an EcoRI site with the sequence: 5'-CGGAATTCAGCAATGAGTTCCGACAGAAGC-3 '(SEC, I D.NO.:90). The 1.9 kb PCR fragment was digested with Hindlll and EcoRI and cloned into the HindMI-EcoRI site of the pCMV expression vector. 5 The 9 sequenced clones contained a potential polymorphism involving a S284C change. In addition to this difference, the nucleic acid (SEC.ID.NO.:91) and amino acid (SEC.ID.NO.:92) sequences for human GPCR-CNS were then determined and verified. 10 30. PGR-NGA (GenBank accession number: U55312) The cDNA for human GPR-NGA was generated and cloned into the pCMV expression vector as follows: PCR was performed using genomic DNA as template and rTth-polymerase (Perkin Elmer) with the pH regulator system provided by the manufacturer, 0.25μM each primer, and 0.2 mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 56 ° C for 1 minute and 72 ° C for 1.5 minutes. The 5 'PCR primer contained an EcoRI site with the sequence: 5'-CAGAATCAGAGAAAAAAGTGAATATGGTTTTT-3 * (SEQ ID NO: 93) and the 3 'primer contained a BamHI site with. the sequence: 5'-TTGGATCCCTGGTGCATAACAATTGAAAGAAT-3 '(SEQ ID NO: 94). The 1.3 kb PCR fragment was digested with EcoRI and BamHI and cloned into the EcoRI-BamHI site of the pCMV expression vector. The nucleic acid (SEC.ID.NO.:95) and amino acid sequences (SEQ ID NO 96) for human GPR-NGA afterwards were t¡ S * iSttái ^ .Áí ^? «tí? ^ & ^ 3S > v ^ determined and verified. 31. H9 (GenBank Accession Number: U52219) The cDNA for human HB954 was generated and cloned into the pCMV expression vector as follows: PCR was performed using 5 pituitary cDNAs as template and rTth-polymerase (Perkin Elmer) with the pH regulator system provided by the manufacturer, 0.25μM of each initiator, and 0.2mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 62 ° C for 1 minute and 72 ° C for 2 minutes. The 5 'PCR primer contains a Hindllll site with the sequence: 5'-GGAAAGCTTAACGATCCCCAGGAGACACAT-3 '(SEQ ID NO.:97) and the 3' initiator contains a BamHI site with the sequence: 5'-CTGGGATCCTACGAGAGCATTTTTCACACAG-3 '(SEQ ID NO .: 98). The 1.9 kb PCR fragment was digested with HindIII and BamHI and cloned into the HindIII-BamHI site of the pCMV expression vector When compared to the published sequences, a different isoform was also identified with 112 bp in frame insertion at the cytoplasmic end or tail and designated "H9b". Both isoforms contain two potential polymorphisms that involve changes of the amino acid P320S and the amino acid G448A The isoform H9a contained another potential polymorphism of the amino acid S493N, while the isoform H9b contained two additional potential polymorphisms involving changes of the amino acid I502T and the amino acid A523T (corresponding to amino acid 528 of the isoform H9a) Nucleic acid sequences (SEQ ID NO 99) and amino acid (SEC.ID.NO.:100) for human H9 were then determined and verified (in the section that follows, both isoforms were mutated according to the human GPCR proline marker algorithm). 32. HB954 (GenBank accession number: D38449) The cDNA for human HB954 was generated and cloned into the pCMV expression vector as follows: PCR was performed using brain cDNA as template and rTth-polymerase (Perkin Elmer) with the pH regulator system provided by the manufacturer, 0.25μM of each initiator, and 0.2mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 58 ° C for 1 minute and 72 ° C for 2 minutes. The 5 'PCR primer contains a Hindlll site with the sequence: 5'-TCCAAGCTTCGCCATGGGGACATSAACGGGAGCT-3' (SEQ ID NO: 101) and the 3 'primer contains an EcoRI site with the sequence: 5'-CGTGAATTCCAAGAATTTACAATCCTTGCT-3 '(SEQ ID NO: 102). The 1.6 kb PCR fragment was digested with Hindlll and EcoRI and cloned into the HindIII-EcoRI site of the pCMV expression vector. The nucleic acid (SEQ ID NO: 103) and amino acid sequences (SEQ ID NO .: 104) for human HP954 were then determined and verified. 33. HG38 (GenBank accession number: AF062006) The cDNA for human HG38 was generated and cloned into the expression vector pCMV as follows the PCR using brain cDNA as template and rTth-polymerase (Perkin Elmer) with the system pH regulator provided by the manufacturer, 0.25μM of each primer, and 0.2mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 56 ° C for 1 minute and 72 ° C for 1 minute 30 seconds. Two PCR reactions were performed to separately obtain the 5 'and 3"fragment.For the 5' fragment, the 5 'PCR primer contained a Hindlll site with the sequence: 5'-CCCAAGCTTCGGGCACCATGGACACCTCCC-3' (SEQ ID. NO .: 259) and the 3 'primer contained a BamHI site with the sequence: 5'-ACAGGATCCAAATGCACAGCACTGGTAAGC-3' (SEQ ID NO: 260) ..} This 1.5 kb PCR fragment was digested with HindIII Y BamHI and cloned into a HindIII-BamHI site of pCMV. For the 3 'fragment, the 5' PCR primer was treated with a kinase with the sequence: 5'-CTATAAXRGGGTTACATGGTTTAAC-3 '(SEC.I D.NO.:261) and the 3' primer contained an EcoRI site with the sequence : 5'-TTTGAATTCACATATTAAATTAGAGACATGG-3 '(SEQ ID NO: 262). The 3 'PCR fragment of 1.4 kb was digested with EcoRI and subcloned into a shaved EcoRI site of the pCMV vector. The 5 'and 3' fragments were then ligated together through a common EcoRV site to generate a full-length cDNA clone. Nucleic acid (SEQ ID NO: 263) and amino acid (SEQ ID NO, 264) sequences for HG38 human after they were determined and verified I- (aaaiÍÍÍÉÉ? | Í? * ^ Aaate * «? Sfltfte« _. ¿, «.... * T * t, ^^^? ¿,,« &3a * ~ ¿34. HM74 (GenBank Accession Number: D10923) The cDNA for human HM74 was generated and cloned into the pCMV expression vector as follows: PCR was performed using either genomic DNA or thymus cDNA (combined) as template and rTth-polymerase (Perkin Elmer) with the pH regulator system provided by the manufacturer, 0.25μM of each primer, and 0.2mM of each of the 4 nucleotides.The cycle condition was 30 cycles of: 94 ° C for 1 minute; C for 1 minute and 72 ° C for 1 minute and 20 seconds The 5 'PCR primer contained an EcoRI site with the sequence: 5'-GGAGAATTCACTAGGCGAGGCGCTCCATC-3' (SEQ ID NO: 105) and the primer 3 'was treated with kinase with the sequence: 5'-GGAGGATCCAGGAAACCTTAGGCCGAGTCC-3' (SEQ ID NO: 106) The 1.3 kb PCR fragment was digested with EcoRI and cloned into the EcoRI-Smal site of the vector of expression pCMV.The sequence clones Ados revealed a potency polymorphism involving a change of N94K. In addition to this difference, the nucleic acid (SEQ ID NO: 107) and amino acid (SEQ.ID.NO.:108) sequences for human HM74 were then determined and verified. 35. MIG (GenBank Accession Number: AFO44600 and AFO44601) The cDNA for human MIG was generated and cloned into the expression vector pCMV as follows the PCR using genomic DNA as template and precision polymerase (Stratagene) for the first round of PCR or pfu polymerase (Stratagene) for the second round of PCR, with the pH regulator system provided by the manufacturer, 0.25μM of each primer, and 0.2mM of (TaqPlus Precision) or 0.5mM (pfu) of each of the 4 nucleotides. When 5 pfu was used, 10% DMSO was included in the pH regulator. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 65 ° C for 1 minute and 72 ° C during: (a) 1 minute for the first round of PCR; and (b) 2 minutes for the second round of PCR. Since there is an intron in the coding region, they were used by Separated two groups of initiators to generate overlapping 5 'and 3' fragments. The PCR primers of the 5 'fragment were: 5'-ACCATGGCTTGCAATGGCAGTGCGGCCAGGGGGCACT-3' (external sense) (SEQ ID NO: 109) and 5'-CGACCAGGACAAACAGCATCTTGGTCACTTGTCTCCGGC-3 '15 (internal antisense) (SEQ ID NO. .: 110). The PCR primers 3 'of the fragment were: 5'-GACCAAGATGCTGTTTGTCCTGGTCGTGGTGTTTGGCAT-3' (internal sense) (SEQ ID NO: 111) and 5'-CGGAATTCAGGATGGATCGGTCTCTTGCTGCGCCT-3 '(antisense External with an EcoRI site) (SEQ ID NO: 112). The 5 'and 3' fragments were ligated together using the first round of PCR as template and the outer sense primer treated with kinase and the external antisense primer to perform the second round of PCR. The 1 kb PCR fragment was digested with EcoRI and cloned into the shaved EcoRI site of the pC'MV expression vector. The nucleic acid (SEC.ID.NO.:113) and amino acid (SEQ ID NO: 114) sequences for human MIG were then determined and verified. 36. OGR1 (GenBank Accession Number: U48405) 5 The cDNA for human OGR1 was generated and cloned into the pCMV expression vector as follows: PCR was performed using genomic DNA as template and rTth-polymerase (Perkin Elmer) with the pH regulator system provided by the manufacturer, 0.25μM of each initiator, and 0.2mM of each of the 4 nucleotides. The cycle condition was 30 cycles of: 94 ° C for 1 minute; 65 ° C for 1 minute and 72 ° C for 1 minute and 20 seconds. The 5 'PCR primer was treated with a kinase with the sequence: 5'-GGAAGCTTCAGGCCCAAAGATGGGGAACAT-3' (SEQ ID NO: 115): and the 3 'primer contained the BamHI site with the sequence: 15 5'-GTGGATCCACCCGCGGAGGACCCAGGCTAG -3 '(SEQ ID NO: 116). The 1.1 kb PCR fragment was digested with BamHI and cloned into the EcoRV-BamHI site of the pCMV expression vector. The nucleic acid (SEQ ID NO: 117) and amino acid (SEQ ID NO: 118) sequences for human OGR1 were then determined and verified. 37. Serotonin 5HT2A The ANDc encoding the endogenous human 5HT2A receptor was obtained through RT-PCR using brain pol? -A + RNA, a 5 'primer from the 5' untranslated region with a restriction site Xho I '-GACCTCFGAGTCCTCTACACCTCATC-3 '(SEQ ID NO: 119) and a 3' primer from the 3 'untranslated region containing an Xba I site: 5'-TGCTCTAGATTCCAGATAGGTGAAAACTTG-3' (SEQ ID NO. : 120). PCR was performed using TaqPlus ™ precision polymerase (Stratagene) or rTth ™ polymerase (Perkin Elmer) with the pH regulator system supplied by the manufacturer, 0.25μM of each primer, and 0.2mM of each of the 4 nucleotides. The cyclic condition was 30 cycles of: 94 ° C for one minute; 57 ° C for 1 minute; and 72 ° VC for 2 minutes. The 1.5 kb PCR fragment was digested with Xba I and subcloned into the EcoRV-Xba site of pBluescript. The resulting cDNA clones were fully sequenced and found to encode two amino acid changes from the published sequences. The first was a T25N mutation in the N-terminal extracellular domain; the second is a H452Y mutation. Since the cDNA clones derived from two dependent PCR regions using Taq polymerase from two different commercial sources (TaqPlus ™ from Strategene and rTth ™ Perkin Elmer) contained the same two mutations, these mutations are likely to represent sequence polymorphisms instead of PCR errors. With these exceptions, the nucleic acid (SEC.ID.NO:121) and amino acid (SEQ ID NO: 122) sequences for 5HT2A were then determined and verified. 38. Serotonin 5HT2c The cDNA encoding the endogenous human 5HT2C receptor was obtained from brain poly-A * RNA through RT-PCR. The £ •••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••••• 'and 3' primers were derived from the 5"and 3 'untranslated regions and contained the following sequences: 5'-GACCTCGAGGTTGCTTAAGACTGAAGC-3' (SEC.ID.NO .: 123) 5'-ATTTCTAGACATATGTAGCTTGTACCG-3 '(SEC ID NO: 124) The nucleic acid (SEC.ID.NO.:125) and amino acid (SEC.ID.NO.:126) sequences for 5HT2C were then determined and verified. GenBank Access: U20350) The cDNA for human V28 was generated and cloned into the pCMV expression vector as follows: PCR was performed using brain cDNA as template and rTth-polymerase (Perkin Elmer) with the pH regulator system provided by the manufacturer, 0.25μM of each primer, and 0 2mM of each of the 4 nucleotides.The cycle condition was 30 cycles of: 94 ° C for 1 minute, 65 ° C for 1 minute and 72 ° C for 1 Minute and 20 seconds The 5 'PCR primer contained a Hindlll site with the sequence: 5'-GGTAAGCTTGGCAGTCCACGCCAGGCCTTC-3' (SEC.ID.NO.:127) and the initiation 3 'host contained the EcoRI site with the sequence: 5'-TCCGAATTCTCTGTAGACACAAGGCTTTGG-3' (SEQ. ID. DO NOT. : 128) The 1.1 kb PCR fragment was digested with Hindlll and EcoRI and cloned into the HindIII-EcoRI site of the pCMV expression vector. The nucleic acid (SEQ ID NO: 129) and amino acid (SEQ ID NO 130) sequences for human V28 were then determined and verified Example 2 Preparation of Receptors Non-endogenous human GPCRs 1. Site-directed mutagenesis The mutagenesis based on the aspect of Proline Marker of the human GPCR Receptor described herein was performed on the previous endogenous human GPCRs receptor using a site-directed mutagenesis kit (Clontech) according to the manufacturer's instructions. For this aspect of mutagenesis, a mutation probe and a selection marker probe were used (unless otherwise indicated, the SEQ ID NO: 132 probe was the same throughout the entire study), and the sequences of these for the specified sequences are listed below in Table B (the number in parentheses is SEC. ID. DO NOT.). For convenience, the codon mutation incorporated in the GPCR receiver is also denoted, in standard form GCCAAGAAGCGGGTGAAGT GPR7 CCTGGTGGTGGCA CTCCTTCGGTCCTCCTATCGT (T250K) (135) TGTCAGAAGT Non-endogenous GPCRs were then sequenced and the derived and verified nucleic acid and amino acid are listed in the "Sequence List" annex attached to this patent document, as summarized in Table C below TABLE C 2. Aspects of Alternative Mutation for the Use of the Proline Algorithm: APJ; Serotonin 5HT2c; and GPR30 Although the aspect of site-directed mutagenesis of the above site is particularly preferred, other aspects may be used to create said mutations; those skilled in the art are easily credited with selecting aspects to mutate a GPCR receiver that fits within the particular needs of the skilled artisan. to. APJ 10 The preparation of the non-endogenous human APJ receptor was achieved through the mutation of L247K. Two oligonucleotides containing this mutation were synthesized: 5'-GGCTTAAGAGCATCATCGTGGTGCTGGTG-3 '(SEC.ID.NO.:233) 5'-GTCACCACCAGCACCACGATGATGCTCTTAAGCC-3' 15 (SEC.ID.NO.:234) The two oligonucleotides were subjected to heating and then to cooling and were used to replace the Nael-BstEII fragment of human, endogenous APJ to generate a non-endogenous version of human APJ. 20 b. Serotonin 5HT2A cDNA containing the C322K point mutation was constructed using the restriction enzyme site Sphl which spans amino acid 322. An initiator containing the C322K mutation: 5'-CAAGAAGTACTGGGCATCGTCTTCTTCCT-3 '(SEQ ID NO: 235 ) was used together with the primer of the 3 'untranslated region of the receptor ^ a ^ tf ^^, ¿^ a¡. & B ^^. '^. a ^ & ^^ f. ^^^^. ^, .-, ^ .. ,,, ^, ^. , 5'-TGCTCTAGATTCCAGATAGGTGAAAACTTG-3 '(SEQ ID NO: 236) to perform the PCR (under the conditions described above). The resulting PCR fragment was then used to replace the 3 'end of endogenous 5HT2A cDNA through the Sphl 5 site shaved at its end with T4 polymerase. c. Serotonin 5HT2c The cDNA containing an S310K mutation was constructed by replacing the restriction fragment Styl containing the amino acid 310 with synthetic double-stranded structure oligonucleotides encoding the desired mutation. The sense chain structure sequence used had the following sequence: 5'- CTAGGGGCACCATGCAGGTATCAACAATGAAGAAAAGTAAGAAAAGTC 15 -3 '(SEC.ID.NO.:237), and the antisense strand structure sequence used had the following sequence: 5'- CAAGAACTTTCTTAGCTTTTCTTTCATTGTTGATAGCCTGCATGGTGCC C-3 '(SEC.ID.NO.:238). 20 d. GPR 30 Before generating non-endogenous GPR30, several independent pCR2.1 / GPR30 isolates were sequenced in their entirety in order to identify clones with mutations generated without PCR. One clone without having mutations was digested with EcoRI and the cDNA fragment was analyzed. Endogenous GPR30 was transferred to the activated expression plasmid by CMV pCI-neo (Promega), through digestion of pCI-Neo with EcoRI and subcloning of the GPR30 fragment released with EcoRI from pCR2.1 / GPR30, to generate pCI / GPR30. Then, the leucine at codon 258 was mutated to a lysine using a site-directed mutagenesis kit Change ™ (Strategene, # 200518), according to the manufacturer's instructions, and the following primers: 5'-CGGCGGCAGAAGGCGAAACGCATGATCCTCGCGGT-3 '(SEC.ID.NO.:239) and 5'-ACCGCGAGGATCATGCGTTTCGCCTTCTGC CGCCG-3' (SEC.ID.NO.:240).

Example 3 Expression of Receptor (endogenous and mutated.

Although a variety of cells are available in the art for the expression of proteins, it is preferred that mammalian cells are used. The main reason for this is predicted in the practice capabilities, that is, the use of, for example, yeast cells for the expression of a GPCR receptor, when possible, introduces into the protocol a non-mammalian cell, which may not include (actually, in the case of yeast that does not include) the receptor coupling, genetic mechanism and secretion trajectories that have been developed for mammalian systems, in this way, the results obtained in non-mammalian cells, although of potential use, they are not as preferred as those obtained from mammalian cells. Of the mammalian cells, COS-7, 293 and 293T cells are particularly preferred, although the specific mammalian cell used can be predicted according to the particular needs of the person skilled in the art. Unless otherwise noted herein, the following protocol was used for the expression of endogenous and non-endogenous human GPCR receptors. Table D lists the mammalian cell and the number used (by 150mm plates) for the expression of the GPCR receptor.

Table D On day 1, the mammalian cells were placed in plates. On day 2, two reaction tubes were prepared (the portions to follow each tube are per plate): tube A was prepared by mixing 20μg of DNA (eg, the pCMV vector, the pCMV vector with endogenous receptor cDNA and the pCMV vector with non-endogenous receptor cDNA) in 1.2 ml of DMEM-free serum (Irvine Scientific, Irvine, CA); Tube B was prepared by mixing 120 μl of lipofectamine (Gibco BRL) in 1.2 ml of DMEM-free serum. Tubes A and B were then mixed by inversions (several times), followed by incubation at room temperature for 30-45 minutes. The mixture is referred to as the "transfection mixture". The cells in the plates were washed with 1XPBS, followed by the addition of 10ml of DMEM-free serum. Then 2.4ml of the transfection mixture was added to the cells, followed by incubation for 4 hours at 37 ° C / 5% C02 The transfection mixture was then removed by aspiration, followed by addition of 25ml of DMEM / serum of fetal bovine at 10%. Afterwards, the cells were incubated at 37 ° C / 5% C02. After 72 hours of incubation, the cells were then harvested and used for analysis. 1. Receptors coupled to Gi: Co-transfection with receptors coupled to Gs In the case of GPR30, it was determined that this receptor couples the protein G, Gi It is known that Gi inhibits the enzyme ad in i 111 cyclase, which is necessary for catalyze the conversion of ATP to cAMP In this way, one would expect a constitutively If it is activated, not endogenous to GPR30, it can be associated with reduced levels of cAMP. The assay conformation of a constitutively activated, non-endogenous form of GPR30 directly through the measurement of reduced levels of cAMP, while viable, can be preferably measured through cooperative use of a Gs-coupled receptor. For example, a receptor that is coupled to Gs will stimulate adenylyl cyclase, and in this way will be associated with an increase in cAMP. The assignee of the present application has discovered that the orphan GPR6 receptor is a constitutively activated, endogenous GPCR receptor. GPR6 is coupled to the Gs protein. In this way, when it is co-transfected, it can easily be verified that a putative GPR30 mutation leads to its constitutive activation; that is, a constitutively activated, endogenous / non-constitutively activated, endogenous GPR6 will evidence a high level of cAMP when compared to an endogenous constitutively active GPR6 / constitutively active, non-endogenous GPR30 (the latter evidencing a comparatively lower level of cAMP) . Assays detecting cAMP can be used to determine whether a candidate compound is, for example, an inverse agonist to a Gs-associated receptor (ie, said compound can reduce cAMP levels) or a receptor associated with Gi (or a receptor associated with Go) (ie, said candidate compounds can increase cAMP levels) A variety of aspects known in the art for measuring cAMP can be used, an aspect A &? Ak a? Ííß¡JttjUHiitit ¿adri) ábiiiiíid ^ H & preferred is based on the use of anti-cAMP antibodies. Another aspect, and the very preferred one, uses a whole cell secondary messenger report system assay. Promoters in genes activate the expression of the proteins that a particular gene encodes. 5 Cyclic AMP directs gene expression by promoting the binding of a DNA binding protein that responds to cAMP or transcription factor (CREB) which then binds to the promoter at specific sites called cAMP response elements and directs expression of the gene. You can build reporting systems, the Which have a promoter containing multiple cAMP response elements before the report gene, eg, β-galactosidase or luciferase. In this way, an activated receptor such as GPR6 causes the accumulation of cAMP, which then activates the gene and expression of the report protein. Most preferably, 293 cells are co-transfected with plasmids GPR6 (or other Gs-linked receptor) and GPR30 (or other Gi-linked receptor), preferably in a ratio of 1: 1, most preferably in a ratio of 1: 4. Since GPR6 is a constitutively active, endogenous receptor that stimulates the production of cAMP, GPR6 strongly activates the report gene and its expression. The reporter protein, such as β-galactosidase or luciferase, can then be detected using standard biochemical assays (Chen et al., 1995). The co-transfection of constitutively active GPR6, endogenous with non-constitutively active GPR30, endogenous shows an increase in the luciferase report protein In • - '- * "' - ••• * -ffllMffrf *" go it * ~ * '"i' f ^ g ^^^^ - ^? ^^ ¡^^^^^. - *. - *to*- .

In reverse form, the co-transfection of constitutively active, endogenous GPR6 gene with constitutively active, non-endogenous GPR30 evidences a drastic decrease in luciferase expression. Several report plasmids are known and available in the technique for measuring a secondary messenger assay. It is considered within the experience of those skilled in the art to determine an appropriate reporter plasmid for a particular gene expression based primarily on the particular need of the person skilled in the art. Although a variety of cells is available for Expression, mammalian cells are most preferred and of these types, 293 cells are preferred. The 293 cells were transfected with the reporter plasmid pCRE-Luc / GPR6 and GPR30 constitutively activated, non-endogenous using a mammalian transfection kit Mammalian Transfection ™ Kit (Stratagene, # 200285) CaP04 precipitation protocol according to the manufacturer's instructions (see, 28 Genomics 347 (1995) for the published endogenous GPR6 sequence). The pellet contained 400ng report, 80ng CMV expression plasmid (having a 1: 4 ratio of GPR6 to endogenous GPR30 or non-endogenous GPR30) and 20ng of CMV-SEAP (a transfection control plasmid encoding secreted alkaline phosphatase). 50% of the precipitate was divided into 3 cavities of a tissue culture dish of 96 cavities (containing 4 x 104 cells / well), the remaining 50% was discarded The next morning, the medium was changed 48 hours after the start of transfection, the cells were lysed and *? LÍL + ± * ^ .- ^. ..Jt? ** ¿¿¿¿¿¿Mí *,. ^^ J »^ * - .. .- ... *? a¡límb É *? a * Am * tí * u * M *. *. . ^ ai »^ examined for luciferase activity using a Liclite ™ equipment (Packard, Cat. # 6016911) and a Trilux 1450 Microbeta ™ and luminescence liquid scintillation counter (Wallac) according to the vendor's instructions. The data was analyzed using 5 GraphPad Prism 2.0a (GraphPad Software Inc.). With respect to GPR17, which had also been determined as linked Gi, a modification of the previous aspect was used, based on, among other things, the use of another endogenous receptor linked to Gs, GPR3 (see 23 Genomics 609 (1994) and 24 Genomics 391 (1994)). Most preferably, 293 cells were used. These cells were plated on 96-well plates at a density of 2 x 104 cells per well and were transfected using the lipofectamine reagent (BRL) the next day according to the manufacturer's instructions. A mixture was prepared DNA / lipid for each 6-well transfection as follows 260ng of plasmid DNA in 100μl of DMEM were modestly mixed with 2μl of lipid in 1OOμl of DMEM (the 260ng of the plasmid DNA consisted of 200 ng of a report plasmid) 8xCRE-Luc (see below), 50ng of pCMV comprising endogenous receptor or non-endogenous receptor or only pCMV, and 10 ng of a GPRS expression plasmid (GPRS in pcADn3 (Invitrogen)). The report plasmid 8XCRE-Luc was prepared as follows the SRIF-β-gal vector was obtained by cloning the rat somatostatma promoter (-71 / + 51) in the BgIV-HindIII site in the basic vector pßgal (Clontech) 8 copies of the 8 * response element of cAMP through PCR from an adenovirus template AdpCFI 26CCRE8 (see, 7 Human Gene Therapy 1883 (1996)) and cloned into the SRIF-β-gal vector at the Kpn-BglV site, resulting in the 8xCRE-β-gal report vector. The 8xCRE-Luc report plasmid was generated by deferring the β-galactosidase gene in the 8xCRE-β-gal report vector with the luciferase gene obtained from the pGL3 core vector (Promega) at the HindIII-BamHI site. After 30 minutes of incubation at room temperature, the DNA / lipid mixture was diluted with 400μl of DMEM and 100μl of the diluted mixture was added to each well. 10Oμl of DMEM with 10% FCS was added to each well after a 4 hour incubation in a cell culture incubator. The next morning, the transfected cells were changed with 200μl / DMEM cavity with 10% FCS. Eight hours later, the cavities were changed to 10Oμl / DMEM cavity without phenol red, after a wash with PBS. Luciferase activity was measured the next day using the LucLite ™ report gene assay kit (Packard) following the manufacturer's instructions and reading on a 1450 MIcroBeta ™ (Wallac) scintillation and luminescence counter. Figure 4 demonstrates that GPR30 constitutively inhibits GPR6-mediated activation of the CRE-Luc report in 293 cells. Luciferase was measured at approximately 4 1 relative light units in the pCMV expression vector. The endogenous GPR30 expressed luciferase at approximately 8.5 units. of relative light, while GPR30 (L258K), non-endogenous constitutively active expressed luciferase at approximately 3.8 and 3.1 relative light units, respectively. The co-transfection of endogenous GPR6 with endogenous GPR 30, at a ratio of 1: 4, drastically increased the expression of luciferase at about 104.1 units of relative light. The co-transfection of endogenous GPR6 with non-endogenous GPR30 (L258K), at the same ratio, drastically decreased expression, which is evident at approximately 18.2 and 29.5 relative light units, respectively. Results were observed similar with respect to GPR17 with respect to co-transfection with GPR3 as set forth in Figure 5.

Example 3 Assays for determinations of constitutive activity of non-endogenous GPCRs receptors A. Membrane Binding Assays 1. [35 S] TP? S Assay When a G protein coupled receptor is in its active state, either as a result of ligand binding or constitutive activation, the receptor is coupled to a G protein and stimulates the release of GDP and subsequent binding to GTP to the G protein The alpha subunit of the G protein-receptor complex acts as a GTPase and slowly hydrolyzes the GTP to GDP, at which point the receptor is normally deactivated. receivers constitutively activated continue to exchange GDP for GTP. The non-hydrolysable GTP analog, [35S] TP? S, can be used to demonstrate enhanced binding of [35S] TP? S to membranes by expressing constitutively activated receptors. The advantage of using the binding of [35S] TP? S to measure constitutive activation is that: (a) it is generically applicable to all G protein-coupled receptors; (b) it is close to the membrane surface making it less likely to pick up molecules that affect the intracellular cascade The assay uses the ability of G-protein coupled receptors to stimulate the binding of [35S] TP? S to membranes that Express the relevant receivers. Therefore, the assay can be used in the direct identification method to classify candidate compounds for constitutively activated protein G-coupled receptors, such as known and orphan. The assay is generic and has application to drug discovery in all G-protein coupled receptors. The [35S] TP? S assay was incubated in 20 mM HEPES and from 1 to approximately 20 mM MgCl2 (this amount can be be adjusted for the optimization of results, although it is preferred that it be 20 mM), pH 7.4, binding pH regulator with between about 0 3 and about 1 2 mM of [35S] TP? S (this amount can be adjusted for the optimization of results, although it is preferred that it be 1 2) and 12 5 to 75 μg membrane protein (e.g., COS-7 cells expressing the receptor, ^^^^ g ^^^ IB ^ fS? "*? * Ff * tft this amount can be adjusted for optimization, although 75 μg is preferred, and 1 μM GDP (this amount can be changed for optimization) during 1 hour . Then wheat germ agglutinin beads * (25μl, Amersham) were added and the mixture was incubated for 30 more at room temperature. The tubes were then centrifuged at 1,500 x g for 5 minutes at room temperature and then compared in a scintillation counter. A less expensive but equally applicable alternative has been identified, which also meets the needs of large-scale classification. Flash Plates ™ and Wallac ™ webbing strips can be used to format a high production [35S] TP? S binding assay. In addition, using this technique, the assay can be used for known GPCR receptors to simultaneously verify the binding of titrated ligand to the receptor at the same time that efficacy is verified through the binding of [35S] TP? S. This is possible since the Wallac beta counter can switch power windows to see both probes labeled with tritium and marked with 35S. This test can also be used to detect other types of activation events of membrane resulting in receptor activation, for example, the assay can be used to verify the phosphorylation of 32P of a variety of receptors (both G protein and tyrosine kinase coupled receptors) When the membranes are centrifuged in the background of the cavity, [35S] TP? S attached or the 25P-phosphate receptor will activate the scintillation product, which It is like cover in the cavities. Strips of Scinti® (Wallac) have been used to demonstrate this principle. In addition, the assay is also useful for measuring ligand binding to receptors using radioactively labeled ligands. In a similar manner, when the radiolabeled ligand bound is centrifuged at the bottom of the cavity, the label of the scintillation strip is close to the radiolabelled ligand resulting in activation and detection. Representative graph results comparing control (pCMV), endogenous APJ and non-endogenous APJ based on the above protocol are set forth in Figure 6. 2. Adenilyl Cyclase A team of Adenilyl Cyclase Flash Plate ™ (New England, Cat. No. SMP004A), designed for cell-based assays, was modified for use with raw plasma membranes. Flash Pit cavities contain a scintillation coating, which also has a specific antibody that recognizes cAMP. The cAMP generated in the cavities was quantified through direct competition for binding of the radioactive cAMP tracer to the cAMP antibody. The following serves as a short protocol for the measurement of changes in cAMP levels in membranes that express the receptors. Transfected cells were harvested about 3 days after transfection. Membranes were prepared through homogenization of suspended cells in pH buffer containing 20 mM HEPES, pH7 4 and 10 mM MgCl2.

The homogenization was performed on ice using a Brinkman Polytron ™ apparatus for approximately 10 seconds. The resulting honogenate was centrifuged at 49,000 X g for 15 minutes at 4 ° C. The resulting pellet was then resuspended in pH buffer containing 20 mM HEPES, pH 7.4 and 0.1 mM EDTA, homogenized for 10 seconds, followed by centrifugation at 49,000 Xg for 15 minutes at 4 ° C. The resulting pellet can be stored at -80 ° C until used. On the day of measurement, the membrane pellet was slowly thawed at room temperature, resuspended in regular pH containing 20mMM of HEPES, pH 7.4 and 10mM of MgCl2 (these quantities can be optimized, although the values listed here are preferred), to produce a final protein concentration of 0.60 mg / ml (membranes that were resuspended were placed on ice until used). CAMP standards and detection pH regulator were prepared (comprising 2μCi of the tracer [25l cAMP (100μl) for 11ml of detection buffer), and was maintained in accordance with the manufacturer's instructions. Fresh pH assay buffer was prepared to classify and contained 20mM of HEPES, pH 7.4, 10mM 20mM MgCI2 ATP (Sigma), 0.2 units / ml creatine phosphokinase (Sigma), 50 μM GTP (Sigma), and 0.2mM ATP (Sigma); The test pH regulator can be stored on ice until used. The assay was initiated through the addition of 50 ul of assay pH regulator followed by the addition of 50 ul of ^^^^^^^^^^^^^^^ ¡¡^^^^^^^^^^^^^^^^^^^^^^^^^^^ membrane suspension to the NEN Flash Plate plate. The resulting test mixture was incubated for 60 minutes at room temperature followed by the addition of 100 ul of detection buffer. Then, the plates were incubated for an additional 2-4 hours, by counting in a Wallac MicroBeta scintillation counter. The cAMP / cavity values were extrapolated from a standard cAMP curve, which is contained within each assay plate. The previous test was used with respect to the MIG analysis. B. Report-Based Assays 1. CREB Reporting Assay (Gs-Associated Receptors) One method to detect Gs stimulation depends on the known property of the CREB transcription factor, which is activated in a cAMP-dependent manner. A TransDetect CREB trans-Reporting System trans-report system (Stratagene, Catalog # 219010) was used to analyze the activity coupled to Gs in 293 cells or 293 T cells. The cells were transfected with the plasmid components of this previous system and the indicated expression plasmid encoding the endogenous or mutant receptor using a mammalian transfection kit Mammalian Transfection Kit (Stratagene, Catalog # 200285) according to the manufacturer's instructions. Briefly, 400nng pFR-Luc (luciferase reporter plasmid containing Gal4 recognition sequences), 40 ngg of pFR-Luc (Gal4-CREB fusion protein containing the Gal4 DNA binding domain), 80 ng of the expression plasmid of the CMV receptor (comprising the receptor) and 20 ng CMV-SEAP (secreted alkaline phosphatase expression plasmid, alkaline phosphatase activity was measured in the medium of transfected cells to control variations in transfection efficiency between samples) were combined in a calcium phosphate precipitate according to the equipment instructions. Half of the precipitate was also distributed over 3 cavities in a 96-well plate, maintained in the cells overnight, and replaced with a fresh medium the next morning. 48 hours after the start of transfection, cells treated and analyzed for luciferase activities as established above with respect to the above GPR30 system. This test was used with respect to GHSR. 2. AP1 report assay (Gq-associated receptors) The method for detecting Gq stimulation depends on the known property of Gq-dependent phospholipase C to cause activation of genes containing AP1 elements in its promoter. A cis-Pathdetect AP-1 cis-Reporting System report system (Stratagene, Catalog # 219073) was used following the protocol established above with respect to the CREB report assay, except that the calcium phosphate precipitate components were 410 ng of pAP1 -Luc, 80 ng of plasmid of expression of receptor and 20 ng of CMV-SEAP. This test was used with respect to ETBR-LP2.

C. Intracellular IP3 Accumulation Test On day 1, cells comprising the serotonin receptors (endogenous and mutated), usually 1 x 105 / well, were placed in 24-well plates. On day 2, the cells were transfected by first mixing 0.25ug of DNA in 50 ul of DMEM-free serum / well and 2 ul of lipfectamin in 50 μl of DMEM-free serum / well. The solutions were mixed moderately and incubated for 15-30 minutes at room temperature. The cells were washed with 0.5 ml of PBS and 400 μl of the serum-free medium was mixed with the transfection medium and added to the cell. Afterwards, the cells were incubated for 3-4 hours at 37 ° C / 5% CO2 and then the transfection medium was removed and replaced with 1 ml / cavity of the regular growth medium. On day 3, the cells were labeled with 3H-m? O-inositol. In summary, the medium was removed, the cells were washed with 0.5 ml of PBS. After, 0.5 ml of an inositol-free / serum-free medium (GIBCO BRL) / well with 0.25 μCi of 3 H-m? o-inositol / well was added and the cells were incubated for 16-18 hours at 37 ° C / 5 % CO2. On day 4, the cells were washed with 0.5 ml of PBS and 0.45 ml of the test medium containing inositol-free / serum-free medium, 10 μM of pargyline, 10 mM of lithium chloride or 0.4 ml of the test medium and 0.45 ml were added. 50 ul of 10x cetanserin (ket) at a final concentration of 10μM The cells were then incubated for 30 minutes at 37 ° C. The cells were then washed with 0 5 ml of PBS and 200ul of an ice cold stop / cool solution was added. .1 -% * "and 3 ^ er ^ ¿3 ^ (1M of KOH, 18 mM of Na borate, 3.8 mM of EDTA) per cavity. The solution was kept on ice for 5-10 minutes or until the cells were used and then neutralized through 200 ul of a fresh / ice-cold neutralization solution (7.5% 5 HCl). The lysate was then transfected into 1.5 ml of eppendorf tubes and 1 ml of chloroform / methanol (1: 2) was added per tube. The solution was swirled for 15 seconds and the upper phase was applied to an anion exchange resin Biorad AG1-X8 (100-200 mesh). First, the resin was washed with water at 1: 1.25 W / V and loaded 0.9 ml of the upper phase onto the column. The column was washed with 10 ml of 5 mM myo-inositol and 10 ml of 5 mM Na borate / 60 mM Na formeate. The inositol trisphosphates were eluted in vials containing 10 ml of scintillation cocktail with 2 ml of 0.1 M formic acid / 1 M ammonium formate. The columns were regenerated by washing with 10 ml of 0.1 M of formic acid / 13 M of ammonium permeate and rinsed twice with H20 and stored at 4 ° C in water. Figure 7 provides an illustration of the production of IP3 from the 5-HT2A receptor that incorporates the C322K mutation.

Although these results show that the aspect of Proline Mutation Algorithm constitutively activates this receptor, for the purpose of using said receptor for the identification of potential therapeutics, a more robust difference may be preferred. However, since the receiver activated to be used to understand and produce the role of constitutive activation and for In addition to identifying compounds that can also be examined, it is believed that this difference by itself is useful for differentiating between endogenous and non-endogenous versions of the human 5-HT2A receptor. 5 D. Summary of Results The results for the GPCRs receivers tested are set out in Table E, where the percentage increase indicates the percentage difference in results observed for the non-endogenous GPCR receiver, as compared to the GPCR receiver. endogenous; these values are followed by indications that are in parentheses as the type of test used. In addition, the test system used is listed in parentheses, (and, in cases where different host cells are used, both are listed). As these results indicate, a variety of trials can be used to determine constitutive activation of non-endogenous versions of human GPCRs. Those skilled in the art, based on the foregoing and with reference to information available in the art, are accredited with the ability to select / maximize an aspect of particular essay that fits the particular needs of the researcher Table E Example 6 - Distribution of endogenous orphan GPCRs receptor tissue Using a commercially available human tissue spot staining format, probes were applied to identify endogenous orphan GPRCs for a determination of the areas where said receptors are located Except as indicated below , all receptor cDNA (radiolabelled) was used as the probe the radiolabeled probe was generated using naaiat -üKüta a > < »I¡t? S > . 'afjhaC.j. -. .At * £ & the complete receptor cDNA (separated from the vector) using a Prime-lt II ™ Random Primer Labeling Kit (Stratagene, # 300385), according to the manufacturer's instructions. A Master Blot ™ stain of human RNA was hybridized with the radiolabelled GPCR receptor and washed under severe conditions according to the manufacturer's instructions. The staining was exposed to a Kodak BioMax autoradiography film overnight at -80 ° C. The representative results of the spot staining format are presented in Figure 8 for GPR1 (8A), GRPR30 (8B), and APJ (8C), with the results being summarized for all receivers in Table F. Table F ass ^ ife »» - * £ »vu Based on the above information, it can be seen that human GPCRs can also be analyzed for distribution in diseased tissue; then comparative determinations between "normal" and diseased tissue can be used to determine the potential for overexpression or underexpression of a particular receptor in a diseased state. In those circumstances where it is desirable to use non-endogenous versions of human GPCRs for the purpose of classifying to directly identify candidate compounds of potential therapeutic importance, it is observed that inverse agonists are useful in the treatment of diseases and disorders wherein a Particular human GPCR receptor is over expressed, whereas agonists or partial agonists are useful in the treatment of diseases and disorders where a human GPCR receptor particular is under-expressed. As desired, in more detail, the cellular localization of the receptors can be utilized, using techniques well known to those skilled in the art (e.g., in-situ hybridization) to identify particular cells within these tissues where the receptor of interest is expressed. It is intended that each of the patents, applications and printed publications mentioned in this patent document are hereby incorporated by reference in their entirety. As those skilled in the art will appreciate, they can be make numerous changes and modifications to the modalities of the invention without departing from the spirit thereof. It is intended that all these variations fall within the scope of the invention. Although a variety of expression vectors are available to those skilled in the art, for the purpose of using both endogenous and non-endogenous human GPCR receptors, it is highly preferred that the vector used be pCMV. This vector has been deposited in the American Type Culture Collection (ATCC) on October 13, 1998, (10801 University Blvd., Manassas, VA 20110-2209 USA) under the provisions of the Budapest Treaty for the International Recognition of Deposit of Microorganisms with the Purpose of Procedure of Patent. The vector was tested by the ATCC on, 1998 and determined as workable on 1998. The ATCC has assigned the following deposit number for pCMV:.

LIST OF SEQUENCES < 110 > Arena Pharmaceuticals, Inc. < 120 > Receptor Coupled to Protein G Human, Constitutively Activated, Not Endogenous < 130 > AREN0049 < 140 > PCT / US99 / 2393E < 141 > 1999-10-12 < 150 > 09 / 170,496 < 151 > 1998-10-13 < 160 > 280 < 170 > Patentln Ver. 2.1 < 210 > 1 < 211 > 1068 < 212 > DNA < 213 > Homo sapiens < 400 > 1 atggaagatt tggaggaaac attatttgaa gaatttgaaa actattccta tgacctagac 60 tattactctc tggagtctga tttggaggag aaagtccagc tgggagttgt ncactgggtc 120 tccctggtgt tatattgttt ggcttttgtt ctgggaattc caggaaatgc catcgtcatc 180 ^ ^ ¡K £ ^^^ §g ^ < ^ Tggttcacgg ggctcaagtg gaagaagaca gtcaccactc tgtggttcct caatctagcc 240 attgcggatt tcatttttct tctctttctg cccctgtaca tctcctatgt ggccatgaat 300 ttccactggc cctttggcat ctggctgtgc aaagccaatt ccttcactgc ccagttgaac 360 atgtttgcca gtgttttttt cctgacagtg atcagcctgg accactatat ccacttgatc 420 catcctgtct tatctcatcg gcatcgaacc ctcaagaact ctctgattgt cattatattc 480 atctggcttt tggcttctct aattggcggt cctgccctgt acttccggga cactgtggag 540 ttcaataatc atactctttg ctataacaat tttcagaagc atgatcctga cctcactttg 600 atcaggcacc atgttctgac ttgggtgaaa tttatcattg gctatctctt ccctttgcta 660 acaatgagta tttgctactt gtgtctcatc ttcaaggtga agaagcgaac agtcctgatc 720 tccagtaggc atttctggac aattctggtt gtggttgtgg cctttgtggt ttgctggact 780 JQ ccttatcacc tgtttagcat ttgggagctc accattcacc acaatagcta ttcccaccat 840 gtgatgcagg ctggaatccc cctctccact ggtttggcat tcctcaatag ttgcttgaac 900 cccatccttt atgtcctaat tagtaagaag ttccaagctc gcttccggtc ctcagttgct 960 gagatactca agtacacact gtgggaagtc agctgttctg gcacagtgag tgaacagctc 1020 aggaactcag aaaccaagaa tctgtgtctc ctggaaacag ctcaataa 1068 < 210 > 2 < 211 > 355 < 212 > PRT < 213 > Homo sapiens < 400 > 2 20 Met Glu Asp Leu Glu Glu Thr Leu Phe Glu Glu Phe Glu Asn Tyr Ser 1 5 10 15 Tyr Asp Leu Asp Tyr Tyr Ser Leu Glu Ser Asp Leu Glu Glu Lys Val 20 25 30 25 Gln Leu Gly Val Val His Trp Val Ser Leu Val Leu Tyr Cys Leu Ala 35 40 45 Phe Val Leu Gly lie Pro Gly Asn Ala lie Val lie Trp Phe Thr Gly 50 55 60 5 Leu Lys Trp Lys Lys Thr Val Thr Thr Leu Trp Phe Leu Asn Leu Wing 65 70 75 80 lie Wing Asp Phe lie Phe Leu Leu Phe Leu Pro Leu Tyr lie Ser Tyr 10 85 90 95 Val Ala Met Asn Phe His Trp Pro Phe Gly lie Trp Leu Cys Lys Wing 100 105 110 Asn Ser Phe Thr Ala Gln Leu Asn Met Phe Ala Ser Val Phe Phe Leu 115 120 125 Thr Val lie Ser Leu Asp His Tyr lie His Leu lie His Pro Val Leu 130 135 140 Ser His Arg His Arg Thr Leu Lys Asn Ser Leu lie Val lie lie Phe 145 150 155 160 lie Trp Leu Leu Wing Ser Leu lie Gly Gly Pro Wing Leu Tyr Phe Arg 165 170 175 Asp Thr Val Glu Phe Asn Lsn His Thr Leu Cys Tyr Asn Asn Phe Gln i «B« tefa- «fegsB.¿i &fa * .- A ^? ^! a ?? is¿s ^ uSm ^ itsSS¿.ti. .-? J ^ AA ?? íí¿ ..,, 180 185 190 Lys His Asp Pro Asp Leu Thr Leu lie Arg His His Val Leu Thr Trp 195 200 205 Val Lys Phe lie lie Gly Tyr Leu Phe Pro Leu Leu Thr Met Ser lie 210 215 220 Cys Tyr Leu Cys Leu lie Phe Lys Val Lys Lys Arg Thr Val Leu lie 225 230 235 240 Being Ser Arg His Phe Trp Thr lie Leu Val Val Val Val Ala Phe Val 245 250 255 Val Cys Trp Thr Pro Tyr His Leu Phe Ser lie Trp Glu Leu Thr lie 260 265 270 His His Asn Ser Tyr Ser His His Val Met Gln Ala Gly lie Pro Leu 275 280 285 Be Thr Gly Leu Wing Phe Leu Asn Ser Cys Leu Asn Pro lie Leu Tyr 290 295 300 Val Leu lie Ser Lys Lys Phe Gln Ala Arg Phe Arg Ser Ser Val Ala 305 310 315 320 Glu Lie Leu Lys Tyr Thr Leu Trp Glu Val Ser Cys Ser Gly Tnr Val 325 330 335 Ser Glu Gln Leu Arg Asn Ser Glu Thr Lys Asn Leu Cys Leu Leu Glu 340 345 350 Thr Ala Gln 355 < 210 > 3 < 211 > 1089 < 212 > DNA 10 < 213 > Homo sapiens < 400 > 3 atgggcaacc acacgtggga gggctgccac gtggactcgc gcgtggacca cctctttccg 60 ccatccctct acatctttgt catcggcgtg gggctgccca ccaactgcct ggctctgtgg 120 gcggcctacc gccaggtgca acagcgcaac gagctgggcg tctacctgat gaacctcagc 180 15 atcgccgacc tgctgtacat ctgcacgctg ccgctgtggg tggactactt cctgcaccac 240 gacaactgga tccacggccc cgggtcctgc aagctctttg ggttcatctt ctacaccaat 300 atctacatca gcatcgcctt cctgtgctgc atctcggtgg accgctacct ggctgtggcc 360 cacccactcc gcttcgcccg cctgcgccgc gtcaagaccg ccgtggccgt gagctccgtg 420 gtctgggcca cggagctggg cgccaactcg gcgcccctgt tccatgacga gctcttccga 480 gaccgctaca accacacctt ctgctttgag aagttcccca tggaaggctg ggtggcctgg 540 atgaacctct atcgggtgtt cgtgggcttc ctcttcccgt gggcgctcat gctgctgtcg 600 tcctgcgggc taccggggca agcgtgtcca cgtgcggggc ccgagcgcca ggagaaggcc 660 aagatcaagc ggctggccct cagcctcatc gccatcgtgc tggtctgctt tgcgccctat 720 cacgtgctct tgctgtcccg cagcgccatc tacctgggcc gcccctggga ctgcggcttc 780 gaggagcgcg tcttttctgc ataccacagc tcactggctt tcaccagcct caactgtgtg --1 840 gcggacccca tcctctactg cctggtcaac gagggcgccc gcagcgatgt ggccaaggcc 900 a * as »? ** i ^^ ^ Jt ^^ < ^^ ... ^ .. ctgcacaacc tgctccgctt tctggccagc gacaagcccc aggagatggc caatgcctcg 960 ctcaccctgg agaccccact cacctccaag aggaacagca cagccaaagc catgactggc 1020 agctgggcgg ccactccgcc ttcccagggg gaccaggtgc agctgaagat gctgccgcca 1080 gcacaatga 1089 < 210 > 4 < 211 > 362 < 212 > PRT < 213 > Homo sapiens < 400 > 4 Met Gly Asn His Thr Trp Glu Gly Cys His Val Asp Ser Arg Val Asp 1 5 10 15 His Leu Phe Pro Pro Ser Leu Tyr lie Phe Val lie Gly Val Gly Leu 20 25 30 Pro Thr Asn Cys Leu Wing Leu Trp Wing Wing Tyr Arg Gln Val Gln Gln 35 40 45 Arg Asn Glu Leu Gly Val Tyr Leu Met Asn Leu Ser lie Wing Asp Leu 50 55 60 Leu Tyr He Cys Thr Leu Pro Leu Trp Val Asp Tyr Pbe Leu His His 65 70 75 80 Asp »sn Trp He His Gly Pro Gly Ser Cys Lys Leu P" e Gly Phe He 85 90 95 Phe Tyr Thr Asn He Tyr He Ser Be He Wing Phe Leu Cys Cys He Ser 100 105 110 Val Asp Arg Tyr Leu Wing Val Wing His Pro Leu Arg Phe Wing Arg Leu 115 120 125 5 Arg Arg Val Lys Thr Ala Val Ala Val Ser Ser Val Val Trp Ala Thr 130 135 140 Glu Leu Gly Wing Asn Being Wing Pro Leu Phe His Asp Glu Leu Phe Arg 10 145 150 155 160 Asp Arg Tyr Asn His Thr Phe Cys Phe Glu Lys Phe Pro Met Glu Gly 165 170 175 Trp Val Wing Trp Met Asn Leu Tyr Arg Val Phe Val Gly Phe Leu Phe 180 185 190 Pro Trp Ala Leu Met Leu Leu Ser Tyr Arg Gly He Leu Arg Ala Val 195 200 205 2Q Arg Gly Ser Val Ser Thr Glu Arg Gln Glu Lys Wing Lys He Lys Arg 210 215 220 Leu Ala Leu Ser Leu He Ala He Val Leu Val Cys Phe Ala Pro Tyr 225 230 235 240 His Val Leu Leu Leu Ser Arg Be Ala He Tyr Leu Gly Arg Pro Trp 245 250 255 Asp Cys Gly Phe Glu Glu Arg Val Phe Ser Ala Tyr His Ser Ser Leu 260 265 270 Wing Phe Thr Ser Leu Asn Cys Val Wing Asp Pro He Leu Tyr Cys Leu 275 280 285 Val Asn Glu Gly Wing Arg Ser Asp Val Wing Lys Wing Leu His Asn Leu 290 295 300 10 Leu Arg Phe Leu Wing Being Asp Lys Pro Gln Glu Met Wing Asn Wing Ser 305 310 315 320 Leu Thr Leu Glu Thr Pro Leu Thr Ser Lys Arg Asn Ser Thr Ala Lys 325 330 335 15 Wing Met Thr Gly Ser Trp Wing Wing Thr Pro Pro Ser Gln Gly Asp Gln 340 345 350 Val Gln Leu Lys Met Leu Pro Pro Ala Gln 20 355 360 < 210 > 5 < 211 > 30 < 212 > DNA < 213 > Homo sapiens 25 < 400 > 5 tatgaattca gatgctctaa acgtccctgc 30 < 210 > 6 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 6 tccggatcca cctgcacctg cgcctgcacc 30 10 < 210 > 7 < 211 > 1002 < 212 > DNA < 213 > Homo sapiens < 400 > 7 atggagtcct caggcaaccc agagagcacc accttttttt actatgacct tcagagccag 60 ccgtgtgaga accaggcctg ggtctttgct accctcgcca ccactgtcct gtactgcctg 120 gtgtttctcc tcagcctagt gggcaacagc ctggtcctgt gggtcctggt gaagtatgag 180 agcctggagt ccctcaccaa catcttcatc ctcaacctgt gcctctcaga cctggtgttc 240 20 gcctgcttgt tgcctgtgtg gatctcccca taccactggg gctgggtgct gggagacttc 300 ctctgcaaac tcctcaatat gatcttctcc atcagcctct acagcagcat cttcttcctg 360 accatcatga ccatccaccg ctacctgtcg gtagtgagcc ccctctccac cctgcgcgtc 420 cccaccctcc gctgccgggt gctggtgacc atggctgtgt gggtagccag catcctgtcc 480 tccatcctcg acaccatctt ccacaaggrg ctttcttcgg gctgtgatta ttccgaactc 540 acgtggtacc tcacctccgt ctaccagcac aacctcttct tcctgctgtc cctggggatt 600 25 atcctgttct gctacgtgga gatcctca ¿q accctsttcc gctcacgctc caagcggcgc 660 ^ - ^^ ^,.! s * é -.3¡s & g¿s iEafei jisáa £ ^^^ E 10 * 8 'caccgcacgg tcaagctcat cttcgccatc gtggtggcct acttcctcag ctggggtccc 720 tacaacttca ccctgtttct gcagacgctg tttcggaccc agatcatccg gagctgcgag 780 agctagaata gccaaacagc cgccctgctc atctgccgca acctcgcctt ctcccactgc 840 tgctttaacc cggtgctcta tgtcttcgtg ggggtcaagt tccgcacaca cctgaaacat 900 gttctccggc agttctggtt ctgccggctg caggcaccca gcccagcctc gatcccccac 960 tcccctggtg ccttcgccta tgagggcgcc tccttctact ga 1002 < 210 > 8 < 211 > 333 < 212 > PRT < 213 > Homo sapiens < 400 > 8 Met Glu Be Ser Gly Asn Pro Glu Be Thr Thr Phe Phe Tyr Tyr Asp 1 5 10 15 Leu Gln Ser Gln Pro Cys Glu Asn Gln Wing Trp Val Phe Wing Thr Leu 20 25 30 Wing Thr Thr Val Leu Tyr Cys Leu Val Phe Leu Leu Ser Leu Val Gly 35 40 45 Asn Ser Leu Val Leu Trp Val Leu Val Lys Tyr Glu Ser Leu Glu Ser 50 55 60 Leu Thr Asn He Phe He Leu Asn Leu Cys Leu Ser Asp Lea Val Phe 65 70 75 80 ^^! Sá & iim¡! i ^ á¡lt? i £? xa Ala Cys Leu Leu Pro Val Trp He Ser Pro Tyr His Trp Gly Trp Val 85 90 95 Leu Gly Asp Phe Leu Cys Lys Leu Leu Asn Met lie Phe Ser He Ser 100 105 110 5 Leu Tyr Being Ser He Phe Phe Leu Thr He Met Thr lie His Arg Tyr 115 120 125 Leu Ser Val Val Pro Pro Leu Ser Thr Leu Arg Val Pro Thr Leu Arg 10 130 135 140 Cys Arg Val Leu Val Thr Met Wing Val Trp Val Wing Ser He Leu Ser 145 150 155 160 Ser He Leu Asp Thr He Phe His Lys Val Leu Ser Ser Gly Cys Asp 165 170 175 Tyr Ser Glu Leu Thr Trp Tyr Leu Thr Ser Val Tyr Gln His Asn Leu 180 185 190 2 Phe Phe Leu Leu Ser Leu Gly He lie Leu Phe Cys Tyr Val Glu He 195 200 205 Leu Arg Thr Leu Phe Arg Ser Arg Ser Lys Arg Arg His Arg Thr Val 210 215 220 - > Lys Lea He Phe Wing He Val Val -the Tyr Phe Leu Ser Trp Gly Pro 0 225 230 235 240 Tyr Asn Phe Thr Leu Phe Leu Gln Thr Leu Phe Arg Thr Gln lie He 245 250 255 Arg Ser Cys Glu Wing Lys Gln Gln Leu Glu Tyr Wing Leu Leu He Cys 260 265 270 Arg Asn Leu Ala Phe Ser His Cys Cys Phe Asn Pro Val Leu Tyr Val 275 280 285 Phe Val Gly Val Lys Phe Arg Thr His Leu Lys His Val Leu Arg Gln 290 295 300 Phe Trp Phe Cys Arg Leu Gln Ala Pro Ser Pro Ala Ser He Pro His 305 310 315 320 Ser Pro Gly Ala Phe Ala Tyr Glu Gly Ala Ser Phe Tyr 325 330 < 210 > 9 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 9 gcaagcttqg gggacgccag gtcgccggct 30 < 210 > 10 < 211 > 31 < 212 > DNA < 213 > Homo sapiens < 400 > 10 gcggatccgg acgctggggg agtcaggctg c 31 < 210 > 11 < 211 > 987 < 212 > DNA < 213 > Homo sapiens < 400 > 11 atggacaacg cctcgttctc ggagccctgg cccgccaacg catcgggccc ggacccggcg 60 ctgagctgct ccaacgcgtc gactctggcg ccgctgccgg cgccgctggc ggtggctgta 120 ccagttgtct acgcggtgat ctgcgccgtg ggtctggcgg gcaactccgc cgtgctgtac 180 gtgttgctgc gggcgccccg catgaagacc gtcaccaacc tgttcatcct caacctggcc 240 atcgccgacg agctcttcac gctggtgctg cccatcaaca tcgccgactt cctgctgcgg 300 cagtggccct tcggggagct catgtgcaag ctcatcgtgg ctatcgacca gtacaacacc 360 ttctccagcc tctacttcct caccgtcatg agcgccgacc gctacctggt ggtgttggcc 420 actgcggagt cgcgccgggt ggccggccgc acctacagcg ccgcgcgcgc ggtgagcctg 480 gccgtgtggg ggatcgtcac actcgtcgtg ctgcccttcg cagtcttcgc ccggctagac 540 gccggcgcca gacgagcagg gtgcgtgcta gtctttccgc agcccgaggc cttctggtgg 600 cgcgcgagcc gcctctacac gctcgtgctg ggcttcgcca tccccgtgtc caccatctgt 660 gtcctctata ccaccctgct gtgccggctg catgccatgc ggctggacag ccacgccaag 720 gccctggagc gcgccaagaa gcgggtgacc ttcctggtgg tggcaatcct ggcggtgtgc 780 ctcctctgct ggacgcccta ccacctgagc accgtggtgg cgctcaccac cgacctcccg 840 cagacgccgc tggtcat cgc tatctcctac ttcatcacca gcctgacgta cgccaacagc 900 tgcctcaacc ccttcctcta cgccttcctg gacgccagct tccgcaggaa cctccgccag 960 ctgataactt gccgcgcggc agcctga 987 < 210 > 12 < 211 > 328 < 212 > PRT < 213 > Homo sapiens < 400 > 12 Met Asp Asn Wing Ser Phe Ser Glu Pro Trp Pro Wing Asn Wing Ser Gly 1 5 10 15 Pro Asp Pro Wing Leu Ser Cys Ser Asn Wing Ser Thr Leu Wing Pro Leu 20 25 30 Pro Ala Pro Leu Ala Val Ala Val Pro Val Val Tyr Ala Val He Cys 35 40 45 Wing Val Gly Leu Wing Gly Asn Ser Wing Val Leu Tyr Val Leu Leu Arg 50 55 60 Wing Pro Arg Met Lys Thr Val Thr Asn Leu Phe He Leu Asn Leu Wing 65 70 75 80 He Wing Asp Glu Leu Phe Thr Leu Val Leu Pro He Asn He Wing Asp 85 90 95 Phe Leu Leu Arg Gln Trp Pro Phe Gly Glu Leu Met Cys Lys Leu He 100 105 110 Val Ala He Asp Gln Tyr Asn Thr Phe Ser Ser Leu Tyr Phe Leu Thr 115 120 125 Val Met Ser Wing Asp Arg Tyr Leu Val Val Leu Wing Thr Wing Glu Ser 130 135 140 Arg Arg Val Wing Gly Arg Thr Tyr Wing Wing Wing Arg Wing Val Ser Leu 145 150 155 160 Wing Val Trp Gly He Val Val Leu Val Val Leu Pro Val Val Phe W 165 170 175 Wing Arg Leu Asp Asp Glu Gln Gly Arg Arg Gln Cys Val Leu Val Phe 180 185 190 Pro Gln Pro Glu Wing Phe Trp Trp Arg Wing Ser Arg Leu Tyr Thr Leu 195 200 205 Val Leu Gly Phe Ala He Pro Val Ser Thr He Cys Val Leu Tyr Thr 210 215 220 Thr Leu Leu Cys Arg Leu His Wing Met Arg Leu Asp Ser His Wing Lys 225 230 235 2¿0 Ala Leu Glu Arg wing Lvs Lys Arg Val Thr Phe Leu Va] Vai Ala He 245 250 255 Leu Ala Val Cys Leu Leu Cys Trp Thr Pro Tyr His Leu Ser Thr Val 260 265 270 Val Ala Leu Thr Thr Asp Leu Pro Gln Thr Pro Leu Val He Ala He 275 280 285 Ser Tyr Phe He Thr Ser Leu Thr Tyr Wing Asn Ser Cys Leu Asn Pro 290 295 300 Phe Leu Tyr Ala Phe Leu Asp Ala Ser Phe Arg Arg Asn Leu Arg Gln 305 310 315 320 Leu He Thr Cys Arg Ala Ala Wing 325 < 210 > 13 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 13 cggaattcgt caacggtccc agctacaatg 30 < 210 > 14 < 211 > 31 < 212 ^ ^ DN ¡É < 213 > Homo sapiens < 400 > 14 atggatccca ggcccttcag caccgcaata t 31 < 210 > 15 < 211 > 1002 < 212 > DNA < 213 > Homo sapiens < 400 > 15 atgcaggccg ctgggcaccc agagcccctt gacagcaggg gctccttctc cctccccacg 60 acgtctctca atgggtgcca actggccaca ggacaatggc ctccgagcca atgccacctt 120 ctgccgttcc tctatgtgct cctgcccgcc gtgtactccg ggatctgtgc tgtggggctg 180 actggcaaca cggccgtcat ccttgtaatc ctaagggcgc ccaagatgaa gacggtgacc 240 aacgtgttca tcctgaacct ggccgtcgcc gacgggctct tcacgctggt actgcccgtc 300 aacatcgcgg agcacctgct gcagtactgg cccttcgggg agctgctctg caagctggtg 360 ctggccgtcg accactacaa catcttctcc agcatctact tcctagccgt gatgagcgtg 420 gaccgatacc tggtggtgct ggccaccgtg aggtcccgcc acatgccctg gcgcacctac 480 cggggggcga aggtcgccag cctgtgtgtc tggctgggcg tcacggtcct ggttctgccc 540 ttcttctctt tcgctggcgt ctacagcaac gagctgcagg tcccaagctg tgggctgagc 600 ttcccgtggc ccgagcgggt ctggttcaag gccagccgtg tctacacttt ggtcctgggc 660 ttcgtgctgc ccgtgtgcac catctgtgtg ctctacacag acctcctgcg caggctgcgg 720 gccgtgcggc tccgctctgg agccaaggct ctaggcaagg ccaggcggaa ggtgaccgtc 780 ctggtcctcg tcgtgctggc cgtgtgcctc ctctgctgga cgcccttcca cctggcctct 840 gtc gtggccc tgaccacgga cctgccccag accccactgg tcatcagtat gtcctacgtc 900 atcaccagcc tcacgtacgc caactcgtgc ctgaacccct tcctctacgc ctttctagat 960 gacaacttcc ggaagaactt ccgcagcata ttgcggtgct ga 1002 < 210 > 16 < 211 > 333 < 212 > PRT < 213 > Homo sapiens < 400 > 16 Met Gln Ala Ala Gly His Pro Glu Pro Leu Asp Ser Arg Gly Ser Phe 1 5 10 15 Be Leu Pro Thr Met Gly Wing Asn Val Ser Gln Asp Asn Gly Thr Gly 10 20 25 30 His Asn Ala Thr Phe Ser Glu Pro Leu Pro Phe Leu Tyr Val Leu Leu 35 40 45 Pro Wing Val Tyr Ser Gly He Cys Wing Val Gly Leu Thr Gly Asn Thr 50 55 60 Wing Val He Leu Val lie Leu Arg Wing Pro Lys Met Lys Thr Val Thr 65 70 75 80 Asn Val Phe He Leu Asn Leu Wing Val Wing Asp Gly Leu Phe Thr Leu 85 90 95 Val Leu Pro Val Asn He Wing Glu His Leu Leu Gln Tyr Trp Pro Phe 100 105 110 Gly Glu Leu Leu Cys Lys Leu Val Lea Wing Val Asp His Tyr Asn He 115 120 125 Phe Ser Ser He Tyr Phe Leu Wing Val Met Ser Val Asp Arg Tyr Leu 130 135 140 Val Val Leu Ala Thr Val Arg Ser Arg His Met Pro Trp Arg Thr Tyr 145 150 155 160 Arg Gly Ala Lys Val Ala Ser Leu Cys Val Trp Leu Gly Val Thr Val 165 170 175 Leu Val Leu Pro Phe Phe Ser Phe Wing Gly Val Tyr Ser Asn Glu Leu 180 185 190 Gln Val Pro Ser Cys Gly Leu Ser Phe Pro Trp Pro Glu Arg Val Trp 195 200 205 Phe Lys Wing Ser Arg Val Tyr Thr Leu Val Leu Gly Phe Val Leu Pro 210 215 220 Val Cys Thr He Cys Val Leu Tyr Thr Asp Leu Leu Arg Arg Leu Arg 225 230 235 240 Wing Val Arg Leu Arg Ser Gly Wing Lys Wing Leu Gly Lys Wing Arg Arg 245 250 255 Lys Val Thr Val Leu Val Leu Val Val Leu Val Val Cys Leu Leu Cys 260 265 270 Trp Thr Pro Phe His Leu Ala Ser Val Val Ala Leu Thr Thr Asp Leu 275 280 285 Pro Gln Thr Pro Leu Val He Ser Met Ser Tyr Val He Thr Ser Leu 290 295 300 Thr Tyr Wing Asn Ser Cys Leu Asn Pro Phe Leu Tyr Wing Phe Leu Asp 305 310 315 320 Asp Asn Phe Arg Lys Asn Phe Arg Ser He Leu Arg Cys 10 325 330 < 210 > 17 < 211 > 48 < 212 > DNA < 213 > Homo sapiens 15 < 400 > 17 acgaattcag ccatggtcct tgaggtgagt gaccaccaag tgctaaat 48 < 210 > 18 20 < 211 > 27 < 212 > DNA < 213 > Homo sapiens < 400 > 18 gaggatcctg gaatgcgggg aagtcag 27 ? $ j ~ & - £ «. ? ^ - $ ae $ £££ & -® < 210 > 19 < 211 > 1107 < 212 > DNA < 213 > Homo sapiens < 400 > 19 atggtccttg aggtgagtga ccaccaagtg ctaaatgacg ccgaggttgc cgccctcctg 60 gctcttccta gagaacttca tgactatgga gaaaacgaga gtgactcgtg ctgtacctcc 120 ccgccctgcc cacaggactt cagcctgaac ttcgaccggg ccttcctgcc agccctctac 180 agcctcctct ttctgctggg gctgctgggc aacggcgcgg tggcagccgt gctgctgagc 240 cggcggacag ccctgagcag caccgacacc ttcctgctcc acctagctgt agcagacacg 300 ctgctggtgc tgacactgcc gctctgggca gtggacgctg ccgtccagtg ggtctttggc 360 tctggcctct gcaaagtggc aggtgccctc ttcaacatca acttctacgc aggagccctc 420 ctgctggcct gcatcagctt tgaccgctac ctgaacatag ttcatgccac ccagctctac 480 cgccgggggc ccccggcccg cgtgaccctc acctgcctgg ctgtctgggg gctctgcctg 540 cttttcgccc tcccagactt catcttcctg tcggcccacc acgacgagcg cctcaacgcc 600 acccactgcc aatacaactt cccacaggtg ggccgcacgg ctctgcgggt gctgcagctg 660 gtggctggct ttctgctgcc cctgctggtc atggcctact gctatgccca catcctggcc 720 gtgctgctgg tttccagggg ccagcggcgc ctgcgggcca tgcggctggt ggtggtggtc 780 gtggtggcct ttgccctctg ctggaccccc tatcacctgg tggtgctggt ggacatcctc 840 atggacctgg gcgctttggc ccgcaactgt ggccgagaaa gcagggtaga cgtggccaag 900 tcggtcacct caggcctggg ctacatgcac tgctgcctca acccgctgct ctatgccttt 960 gtaggggtca agttccggga gcggatgtgg atgctgctct tgcgcctggg ctgccccaac 1020 cagagagggc tccagaggca gccatcgtct tcccgccggg attcatcctg gtctgagacc 1080 tcagaggcct cctactcggg cttgtga 1107 < 2i0 > 20 25 < 2-l > £ 36 • - * ÍS aa > W 'r «fi & aaJfca < 212 > PRT < 213 > Homo sapiens < 400 > 20 Met Val Leu Glu Val Ser Asp His Gln Val Leu Asn Asp Ala Glu Val 10 15 Wing Ala Leu Leu Glu Asn Phe Being Being Tyr Asp Tyr Gly Glu Asn 20 25 30 Glu Ser Asp Ser Cys Cys Thr Ser Pro Pro Cys Pro Gln Asp Phe Ser 35 40 45 Leu Asn Phe Asp Arg Ala Phe Leu Pro Ala Leu Tyr Ser Leu Leu Phe 50 55 60 Leu Leu Gly Leu Leu Gly Asn Gly Ala Val Ala Ala Val Leu Leu Ser 65 70 75 80 Arg Arg Thr Ala Leu Ser Ser Thr Asp Thr Phe Leu Leu His Leu Wing 85 90 95 Val Ala Asp Thr Leu Leu Val Leu Thr Leu Pro Leu Trp Wing Val Asp 100 105 110 Ala Ala Val Gln Trp Val Phe Gly Ser Gly Leu Cys Lys Val Ala Gly 115 120 125 Ala Leu Phe Asn He Asn Phe Tyr Ala Gly Ala Leu Leu Leu Ala Cys 130 135 140 He Be Phe Asp Arg Tyr Leu Asn He Val His Wing Thr Gln Leu Tyr 145 150 155 160 Arg Arg Gly Pro Pro Wing Arg Val Thr Leu Thr Cys Leu Wing Val Trp 165 170 175 Gly Leu Cys Leu Leu Phe Wing Leu Pro Asp Phe He Phe Leu Ser Wing 10 180 185 190 His His Asp Glu Arg Leu Asn Wing Thr His Cys Gln Tyr Asn Phe Pro 195 200 205 Gln Val Gly Arg Thr Ala Leu Arg Val Leu Gln Leu Val Ala Gly Phe 210 215 220 Leu Leu Pro Leu Leu Val Met Ala Tyr Cys Tyr Ala His He Leu Ala 225 230 235 240 ^ z-. Val Leu Leu Val Ser Arg Gly Gln Arg Arg Leu Arg Ala Met Arg Leu 245 250 255 Val Val Val Val Val Val Ala Phe Ala Leu Cys Trp Thr Pro Tyr His 260 265 270 Leu Val Val Leu Val Asp He Leu Met Asp Leu Gly Ala Leu Ala Arg 275 280 285 Asn Cys Gly Arg Glu Ser Arg Val Asp Val Wing Lys Ser Val Thr Ser 290 295 300 Gly Leu Gly Tyr Met His Cys Cys Leu Asn Pro Leu Leu Tyr Ala Phe 305 310 315 320 Val Gly Val Lys Phe Arg Glu Arg Met Trp Met Leu Leu Leu Arg Leu 325 330 335 Gly Cys Pro Asn Gln Arg Gly Leu Gln Arg Gln Pro Ser Ser Ser Arg 340 345 350 Arg Asp Ser Ser Trp Ser Glu Thr Ser Glu Wing Ser Tyr Ser Gly Leu 355 360 365 < 210 > 21 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 21 ttaagcttga cctaatgcca tcttgtgtcc 30 < 210 > 22 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 22 ttggatccaa aagaaccatg cacctcagag 30 < 210 > 23 < 211 > 1074 < 212 > DNA < 213 > Homo sapiens < 400 > 23 atggctgatg actatggctc tgaatccaca tcttccatgg aagactacgt taacttcaac 60 ttcactgact tctactgtga gaaaaacaat gtcaggcagt ttgcgagcca tttcctccca 120 cccttgtact ggctcgtgtt catcgtgggt gccttgggca acagtcttgt tatccttgtc 180 tactggtact gcacaagagt gaagaccatg accgacatgt tccttttgaa tttggcaatt 240 gctgacctcc tctttcttgt cactcttccc ttctgggcca ttgctgctgc tgaccagtgg 300 aagttccaga ccttcatgtg caaggtggtc aacagcatgt acaagatgaa cttctacagc 360 tgtgtgttgc tgatcatgtg catcagcgtg gacaggtaca ttgccattgc ccaggccatg 420 cttggaggga agagcacata gaaaaggctt ttgtacagca aaatggtttg ctttaccatc 480 tgggtattgg cagctgctct ctgcatccca gaaatcttat acagccaaat caaggaggaa 540 tccggcattg ctatctgcac catggtttac cctagcgatg agagcaccaa actgaagtca 600 gctgtcttga ccctgaaggt cattctgggg ttcttccttc ccttcgtggt catggcttgc 660 tcatcattca tgctatacca caagccaaga caccctgata agtcttccaa gcacaaagcc 720 ctaaaagtga ccatcactgt cctgaccgtc tttgtcttgt ctcagtttcc ctacaactgc 780 attttgttgg tgcagaccat tgacgcctat gccatgttca tctccaactg tgccgtttcc 840 accaacattg acatctgctt ccaggtcacc cagaccatcg ccttcttcca cagttgcctg 900 aaccctgttc tctatgtttt tgtgggtgag agattccgcc gggatctcgt gaaaaccctg 960 aagaacttgg gttgcatcag ccaggcccag tgggtttcat ttacaaggag agagggaagc 1020 ^^^ s ^^ i¡St ^ ^^^^^^ ttgaagctgt cgtctatgtt gctggagaca acctcaggag cactctccct ctga 1074 < 210 > 24 < 211 > 357 < 212 > PRT < 213 > Homo sapiens < 400 > 24 Met Wing Asp Asp Tyr Gly Ser Glu Ser Thr Ser Met Met Glu Asp Tyr 1 5 10 15 Val Asn Phe Asn Phe Thr Asp Phe Tyr Cys Glu Lys Asn Asn Val Arg 20 25 30 Gln Phe Ala Ser His Phe Leu Pro Pro Leu Tyr Trp Leu Val Phe He 35 40 45 Val Gly Ala Leu Gly Asn Ser Leu Val He Leu Val Tyr Trp Tyr Cys 50 55 60 Thr Arg Val Lys Thr Met Thr Asp Met Phe Leu Leu Asn Leu Ala He 65 70 75 80 Wing Asp Leu Leu Phe Leu Val Thr Leu Pro Phe Trp Wing Wing Wing 85 90 95 Wing Asp Gln Trp Lys Foot Gln Thr Phe Met Cys Lys Val Val Asn Se: 100 105 110 Met Tyr Lys Met Asn Phe Tyr Ser Cys Val Leu Leu He Met Cys He 115 120 125 Ser Val Asp Arg Tyr He Wing Wing Wing Gln Wing Met Arg Wing His Thr 130 135 140 5 Trp Arg Glu Lys Arg Leu Leu Tyr Ser Lys Met Val Cys Phe Thr He 145 150 155 160 Trp Val Leu Ala Ala Ala Leu Cys He Pro Glu He Leu Tyr Ser Gln 10 165 170 175 He Lys Glu Glu Be Gly He Wing He Cys Thr Met Val Tyr Pro Ser 180 185 190 Asp Glu Be Thr Lys Leu Lys Be Wing Val Leu Thr Leu Lys Val He 195 200 205 Leu Gly Phe Phe Leu Pro Phe Val Val Met Wing Cys Cys Tyr Thr He 210 215 220 He He His Thr Leu He Gln Wing Lys Lys Ser Ser Lys His Lys Wing 225 230 235 240 Leu Lys Val Thr He Thr Val Leu Thr Val Phe Val Leu Ser Gln Phe 245 250 255 Pro Tyr Asn Cys He Leu Leu Val Gln Thr He Asp Wing T ^ _ r Ala Met 260 265 270 Phe He Ser Asn Cys Wing Val Ser Thr Asn He Asp He Cys Phe Gln 275 280 285 Val Thr Gln Thr He Ala Phe Phe His Ser Cys Leu Asn Pro Val Leu 290 295 300 Tyr Val Phe Val Gly Glu Arg Phe Arg Arg Asp Leu Val Lys Thr Leu 305 310 315 320 Lys Asn Leu Gly Cys He Ser Gln Ala Gln Trp Val Ser Phe Thr Arg 325 330 335 Arg Glu Gly Ser Leu Lys Leu Ser Ser Met Leu Leu Glu Thr Thr Ser 340 345 350 Gly Ala Leu Ser Leu 355 < 210 > 25 < 211 > 1 < 212 > DNA < 213 > Homo sapiens < 400 > 25 a & * SS? £ 28 &alSk > i. j * &?, ~ ß £ s -? «Ah.-, J -w-. - - ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ ? ÉKríZ &iúásíátm, - < 210 > 26 < 211 > 369 < 212 > PRT < 213 > Homo sapiens < 400 > 26 Met Wing Being Thr Thr Arg Gly Pro Arg Val Being Asp Leu Phe Ser 1 5 10 15 Gly Leu Pro Pro Wing Val Thr Thr Pro Wing Asn Gln Ser Wing Glu Wing 20 25 30 Be Ala Gly Asn Gly Ser Val Ala Gly Ala Asp Ala Pro Ala Val Thr 35 40 45 Pro Phe Gln Ser Leu Gln Leu Val His Gln Leu Lys Gly Leu He Val 50 55 60 Leu Leu Tyr Ser Val Val Val Val Val Gly Leu Val Gly Asn Cys Leu 65 70 75 80 Leu Val Leu Val He Ala Arg Val Pro Arg Leu His Asn Val Thr Asn 85 90 95 Phe Leu He Gly Asn Leu Ala Leu Ser Asp Val Leu Met Cys Thr Ala 100 105 110 Cys Val Pro Leu Thr Leu Wing Tyr Wing Phe Olu Pro »rg Gl Trp Val 115 120 125 Phe Gly Gly Gly Leu Cys His Leu Val Phe Phe Leu Gln Pro Val Thr 130 135 140 Val Tyr Val Ser Val Phe Thr Leu Thr Thr He Ala Val Asp Arg Tyr 145 150 155 160 Val Val Leu Val His Pro Leu Arg Arg Ala Ser Arg Cys Ala Ser Ala 165 170 175 Tyr Ala Val Leu Ala He Trp Ala Leu Ser Ala Val Leu Ala Leu Pro 180 185 190 Pro Ala Val His Thr Tyr His Val Glu Leu Lys Pro His Asp Val Arg 195 200 205 Leu Cys Glu Glu Phe Trp Gly Ser Gln Glu Arg Gln Arg Gln Leu Tyr 210 215 220 Wing Trp Gly Leu Leu Leu Val Thr Tyr Leu Leu Pro Leu Leu Val He 225 230 235 240 Leu Leu Ser Tyr Val Arg Val Ser Val Lys Leu Arg Asn Arg Val Val 245 250 255 Pro Giy Cys Val Thr Gln Ser Gln Wing Asp Trp Asp Arg Wing Arg Arg ! 60 265 270 Arg Arg Thr Phe Cys Leu Leu Val Val Val Val Val Val Phe Ala Val 275 280 285 Cys Trp Leu Pro Leu His Val Phe Asn Leu Leu Arg Asp Leu Asp Pro 290 295 300 5 His Wing He Asp Pro Tyr Wing Phe Gly Leu Val Gln Leu Leu Cys His 305 310 315 320 Trp Leu Ala Met Ser Be Ala Cys Tyr Asn Pro Phe He Tyr Ala Trp 10 325 330 335 Read His Asp Ser Phe Arg Glu Glu Leu Arg Lys Leu Leu Val Wing Trp 340 345 350 Pro Arg Lys He Wing Pro His Gly Gln Asn Met Thr Val Val Ser Val 15 355 360 365 I have < 210 > 27 20 < 211 > 1083 < 212 > DNA < _13 > Homo sapiens < --0 > 27"^ aacccag aagaaacttc agtttatttg gattattact atgctacgag cccaaactct 60 * ccatgttcct tacacctctg tt-ttccttcc agtcttttac 120 acagctgtgt tcctgactgg agtgctgggg aaccttgttc tcatgggagc gttgcatttc 180 aaacccggca gccgaagact gatcgacatc tttatcatca atctggctgc ctctgacttc 240 atttttcttg tcacattgcc tctctgggtg gataaagaag catctctagg actgtggagg 300 acgggctcct tcctgtgcaa agggagctcc tacatgatct ccgtcaatat gcactgcagt 360 gtcctcctgc tcacttgcat gagtgttgac cgctacctgg ccattgtgtg gccagtcgta 420 5 tccaggaaat tcagaaggac agactgtgca tatgtagtct gtgccagcat ctggtttatc 480 tcctgcctgc tggggttgcc tactcttctg tccagggagc tcacgctgat tgatgataag 540 ccatactgtg ggcaactcca cagagaaaaa attaaactca tatggtccct ggtggcctta 600 attttcacct tttttgtccc tttgttgagc attgtgacct gctactgttg cattgcaagg 660 cccattacca aagctgtgtg gcaatcagga aagcacaaca aaaagctgaa gaaatctata 720 10 aagatcatct ttattgtcgt ggcagccttt cttgtctcct ggctgccctt caatactttc 780 aagttcctgg ccattgtctc tgggttgcgg caagaacact atttaccctc agctattctt 840 cagcttggta tggaggtgag tggacccttg gcatttgcca acagctgtgt caaccctttc 900 atttactata tcttcgacag ctacatccgc cgggccattg tccactgctt gtgcccttgc 960 ctgaaaaact atg actttgg gagtagcact gagacatcag atagtcacct cactaaggct 1020 ctctccacct tcattcatgc agaagatttt gccaggagga ggaagaggtc tgtgtcactc 1080 taa 1083 < 210 > 28 < 211 > 360 < 212 > PRT ^ < 213 > Homo sapiens < 400 > 28 Met Asp Pro Glu Glu Thr Ser Val Tyr Leu Asp Tyr Tyr Tyr Ala Thr 1 5 10 15 Ser Pro Asn Ser Asp He Arg Glu Thr His Ser His Val Pro Tyr Thr ~ J 20 25 30 Ser Val Phe Leu Pro Val Phe Tyr Thr Ala Val Phe Leu Thr Gly Val 35 40 45 Leu Gly Asn Leu Val Leu Met Gly Ala Leu His Phe Lys Pro Gly Ser 50 55 60 5 Arg Arg Leu He Asp He Phe He He Asn Leu Ala Wing Ser Asp Phe 65 70 75 80 He Phe Leu Val Thr Leu Pro Leu Trp Val Asp Lys Glu Ala Ser Leu 10 85 90 95 Gly Leu Trp Arg Thr Gly Ser Phe Leu Cys Lys Gly Ser Ser Tyr Met 100 105 110 He Ser Val Asn Met His Cys Ser Val Leu Leu Leu Thr Cys Met Ser 115 120 125 Val Asp Arg Tyr Leu Wing He Val Val Val Val Ser Ser Pg Arp Lys Phe 130 135 140 Arg Arg Thr Asp Cys Wing Tyr Val Val Cys Wing Being He Trp Phe He 145 150 155 160 Be Cys Leu Leu Gly Leu Pro Thr Leu Leu Be Arg Glu Leu Thr Leu 165 1"O 175 He Asp Aso Lys Pro Tyr Cys Ala Glu Lvs Lys Ala T Pro He Lys 180 185 190 Leu He Trp Ser Leu Val Ala Leu He Phe Thr Phe Phe Val Pro Leu 195 200 205 Leu Ser He Val Thr Cys Tyr Cys Cys He Ala Arg Lys Leu Cys Ala 210 215 220 His Tyr Gln Gln Ser Gly Lys His Asn Lys Lys Leu Lys Lys Ser He 225 230 235 240 Lys He He Phe He Val Val Wing Ala Phe Leu Val Ser Trp Leu Pro 245 250 255 Phe Asn Thr Phe Lys Phe Leu Wing He Val Ser Gly Leu Arg Gln Glu 260 265 270 15 His Tyr Leu Pro Be Ala He Leu Gln Leu Gly Met Glu Val Ser Gly 275 280 285 Pro Leu Ala Phe Ala Asn Ser Cys Val Asn Pro Phe He Tyr Tyr He 290 295 300 20 Phe Asp Ser Tyr He Arg Arg Wing He Val His Cys Leu Cys Pro Cys 305 310 315 320 Leu Lys Asn Tyr Asp Phe Gly Ser Ser Thr Glu Thr Ser Asp Ser His 3 ^ 25 ^ 330 335 ? t «M« fei ¿¿A > -M- «> »» »»?!? »«. BíBfcSt, Leu Thr Lys Ala Leu Ser Thr Phe He His Wing Glu Asp Phe Wing Arg 340 345 350 Arg Arg Lys Arg Ser Val Ser Leu 355 360 < 210 > 29 < 211 > 31 < 212 > DNA < 213 > Homo sapiens < 400 > 29 ctagaattct gactccagcc aaagcatgaa t 31 < 210 > 30 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 30 gctggatcct aaacagtctg cgctcggcct 30 < 210 > 31 < 211 > 1020 < 212 > DNA < 213 > Homo sapiens < 400 > 31 ! §t '^ t S & tf * je * ilJk * &? &! * UdSfci Siti »atgaatggcc ttgaagtggc tcccccaggt ctgatcacca acttctccct ggccacggca 60 gagcaatgtg gccaggagac gccactggag aacatgctgt tcgcctcctt ctaccttctg 120 gattttatcc tggctttagt tggcaatacc ctggctctgt ggcttttcat ccgagaccac 180 aagtccggga ccccggccaa cgtgttcctg atgcatctgg ccgtggccga cttgtcgtgc 240 gtgctggtcc tgcccacccg cctggtctac cacttctctg ggaaccactg gccatttggg 300 gaaatcgcat gccgtctcac cggcttcctc ttctacctca acatgtacgc cagcatctac 360 ttcctcacct gcatcagcgc cgaccgtttc ctggccattg tgcacccggt caagtccctc 420 ggcccctcta aagctccgca cgcacacctg gcctgtgcct tcctgtgggt ggtggtggct 480 gtggccatgg ccccgctgct ggtgagccca agaccaacca cagaccgtgc cacggtggtc 540 tgcctgcagc tgtaccggga gaaggcctcc caccatgccc tggtgtccct ggcagtggcc 600 ttcaccttcc cgttcatcac cacggtcacc tgctacctgc tgatcatccg cagcctgcgg 660 cagggcctgc gtgtggagaa gcgcctcaag accaaggcag tgcgcatgat cgccatagtg 720 ctggccatct tcctggtctg cttcgtgccc taccacgtca accgctccgt ctacgtgctg 780 cactaccgca gccatggggc ctcctgcgcc acccagcgca tcctggccct ggcaaaccgc 840 atcacctcct gcctcaccag cctcaacggg gcactcgacc ccatcatgta tttcttcgtg 900 gctgagaagt tccgccacgc cctgtgcaac ttgctctgtg gcaaaaggct caagggcccg 960 tcgaagggaa ccccccagct aaccaacgag agctcgctga agagctgtga gtgccaagtc 1020 < 210 > 32 < 211 > 339 < 212 > PRT < 213 > Homo sapiens < 400 > 32 Met Asn Gly Leu Glu Val Wing Pro Pro Gly Leu He Thr Asn Phe Ser 1 5 10 15 Ma Thr Ala Glu Gln Cys Gly Gln Glu Thr Pro Le- Glu Asn Met 20 25 30 Leu Phe Wing Being Phe Tyr Leu Leu Asp Phe He Leu Wing Leu Val Gly 35 40 45 Asn Thr Leu Ala Leu Trp Leu Phe He Arg Asp His Lys Ser Gly Thr 50 55 60 Pro Ala Asn Val Phe Leu Met His Leu Ala Val Ala Asp Leu Ser Cys 65 70 75 80 Val Leu Val Leu Pro Thr Arg Leu Val Tyr His Phe Ser Gly Asn His 85 90 95 Trp Pro Phe Gly Glu He Wing Cys Arg Leu Thr Gly Phe Leu Phe Tyr 100 105 110 15 Leu Asn Met Tyr Wing Ser He Tyr Phe Leu Thr Cys He Ser Wing Asp 115 120 125 Arg Phe Leu Wing He Val His Pro Val Lys Ser Leu Lys Leu Arg Arg 130 135 140 Pro Leu Tyr Ala His Leu Ala Cys Ala Phe Leu Trp Val Val Val Ala 145 150 155 160 Val Ala Met Ala Pro Leu Leu Val Ser Pro Gln Thr Val Gln Thr Asn ¿65 170 175 ^^ S ^^^ Í - £ & His Thr Val Val Cys Leu Gln Leu Tyr Arg Glu Lys Ala Ser His His 180 185 190 Ala Leu Val Ser Leu Ala Val Ala Phe Thr Phe Pro Phe He Thr Thr 195 200 205 Val Thr Cys Tyr Leu Leu He He Arg Ser Leu Arg Gln Gly Leu Arg 210 215 220 Val Glu Lys Arg Leu Lys Thr Lys Wing Val Arg Met He Wing He Val 225 230 235 240 Leu Ala He Phe Leu Val Cys Phe Val Pro Tyr His Val Asn Arg Ser 245 250 255 Val Tyr Val Leu His Tyr Arg Ser His Gly Wing Ser Cys Wing Thr Gln 260 265 270 Arg He Leu Ala Leu Ala Asn Arg He Thr Ser Cys Leu Thr Ser Leu 275 280 285 Asn Gly Ala Leu Asp Pro He Met Tyr Phe Phe Val Ala Glu Lys Phe 290 295 300 Arg His Wing Leu Cys Asn Leu Leu Cys Gly Lys Arg Leu Lys Gly Pro 305 310 315 320 Pro Pro Ser Phe Glu Gly Lys Thr Asn Glu Ser Ser Leu Ser Ala Lys 325 330 335 Ser Glu Leu < 210 > 33 < 211 > 29 < 212 > DNA < 213 > Homo sapiens < 400 > 33 ataagatgat caccctgaac aatcaagat 29 < 210 > 34 < 211 > 33 < 212 > DNA < 213 > Homo sapiens < 400 > 34 tccgaattca taacatttca ctgtttatat tgc 33 < 210 > 35 < 211 > 996 < 212 > DNA < 213 > Homo sapiens < 400 > 35 atgatcaccc tgaacaatca agatcaacct gtcactttta acagctcaca tccagatgaa 60 tacaaaattg cagcccttgt cttctatagc tgtatcttca taattggatt atttgttaac 120 asgHte Aáasa ^^ ^ aa atcactgcat tatgggtttt cagttgtacc accaagaaga gaaccacggt aaccatctat 180 atgatgaatg tggcattagt ggacttgata tttataatga ctttaccctt tcgaatgttt 240 tattatgcaa aagatgcatg gccatttgga gagtacttct gccagattat tggagctctc 300 acagtgtttt acccaagcat tgctttatgg cttcttgcct ttattagtgc tgacagatac 360 tacagccgaa atggccattg gtacgccaaa gaacttaaaa acacgtgcaa agccgtgctg 420 gcgtgtgtgg gagtctggat aatgaccctg accacgacca cccctctgct actgctctat 480 aaagacccag ataaagactc cactcccgcc acctgcctca agatttctga catcatctat 540 ctaaaagctg tgaacgtgct gaacctcact cgactgacat tttttttctt gattcctttg 600 ttgggtgcta ttcatcatga cttggtcatt attcataatc tccttcacgg caggacgtct 660 aagctgaaac ccaaagtcaa ggagaagtcc ataaggatca tcatcacgct gctggtgcag 720 gtgctcgtct gctttatgcc cttccacatc tgtttcgctt tcctgatgct gggaacgggg 780 gagaacagtt acaatccctg gggagccttt accaccttcc tcatgaacct cagcacgtgt 840 ttctctacta ctggatgtga catcgtttca aaacaatttc aggctcgagt cattagtgtc 900 atgctatacc gtaattacct tcgaagcctg cgcagaaaaa gtttccgatc tggtagtcta 960 ag gtcactaa gcaatataaa cagtgaaatg ttatga 996 < 210 > 36 < 211 > 331 < 212 > PRT < 213 > Homo sapiens < 400 > 36 Met He Thr Leu Asn Asn Gln Asp Gln Pro Val Thr Phe Asn Ser Ser 1 5 10 15 His Pro Asp Glu Tyr Lys He Ala Wing Leu Val Phe Tyr Ser Cys He 20 25 3C a ^ aae ^ ^ a ^ - ^^^^ s ^ fey ^ Phe He He Gly Leu Phe Vai Asn He Thr Ala Leu Trp Val Phe Ser 35 40 45 Cys Thr Thr Lys Lys Arg Thr Thr Val Thr He Tyr Met Met Asn Val 50 55 60 5 Wing Leu Val Asp Leu He Phe He Met Thr Leu Pro Phe Arg Met Phe 65 70 75 80 Tyr Tyr Wing Lys Asp Wing Trp Pro Phe Gly Glu Tyr Phe Cys Gln He 10 85 90 95 He Gly Ala Leu Thr Val Phe Tyr Pro Ser He Ala Leu Trp Leu Leu 100 105 110 Wing Phe He Wing Wing Asp Arg Tyr Met Wing He Val Val Gln Pro Lys Tyr 115 120 125 Wing Lys Glu Leu Lys Asn Thr Cys Lys Wing Val Leu Wing Cys Val Gly 130 135 140 Val Trp He Met Thr Leu Thr Thr Thr Pro Leu Leu Leu Leu Tyr 145 150 155 160 Lys Asp Pro Asp Lys Asp Ser Thr Pro Wing Thr Cys Leu Lys He Ser 165 170 175 Asp He He Tyr Leu L_ / S Wing Val Asn Val Leu Asn Leu Thr? Rg Leu Thr Phe Phe Phe Leu He Pro Leu Phe He Met He Gly Cys Tyr Leu 195 200 205 Val He He His Asn Leu Leu His Gly Arg Thr Ser Lys Leu Lys Pro 210 215 220 Lys Val Lys Glu Lys Ser He Arg He He He Thr Leu Leu Val Gln 225 230 235 240 Val Leu Val Cys Phe Met Pro Phe His He Cys Phe Ala Phe Leu Met 245 250 255 Leu Gly Thr Gly Glu Asn Ser Tyr Asn Pro Trp Gly Wing Phe Thr Thr 260 265 270 Phe Leu Met Asn Leu Ser Thr Cys Leu Asp Val He Leu Tyr Tyr He 275 280 285 Val Ser Lys Gln Phe Gln Wing Arg Val He Ser Val Val Leu Tyr Arg 290 295 300 Asn Tyr Leu Arg Ser Leu Arg Arg Lys Ser Phe Arg Ser Gly Ser Leu 305 310 315 320 Arg Ser Leu Ser Asn He Asn Ser Glu Met Leu 325 330 < 210 > 37 < 211 > 28 < 212 > DNA < 213 > Homo sapiens < 400 > 37 ccaagcttcg aggcctgggg tgtgctgg 28 < 210 > 38 < 211 > 29 < 212 > DNA < 213 > Homo sapiens < 400 > 38 atggatcctg accttcggcc cctggcaga 29 < 210 > 39 < 211 > 1077 < 212 > DNA < 213 > Homo sapiens < 400 > 39 atgccctctg tgtctccagc ggggccctcg gccggggcag tccccaatgc caccgcagtg 60 acaacagtgc ggaccaatgc cagcgggctg gaggtgcccc tgttccacct gtttgcccgg 120 ctggacgagg agctgcatgg caccttccca ggcctgtgcg tggcgctgat ggcggtgcac 180 ggagccatct tcctggcagg gctggtgctc aacgggctgg cgctgtacgt cttctgctgc 240 cgcacccggg ccaagacacc ctcagtcatc tacaccatca acctggtggt gaccgatcta 300 ctggtagggc tgtccctgcc cacgcgcttc gctgtgtact acggcgccag gggctgcctg 360 Bá k & & iß¡bmt cgctgtgcct tcccgcacgt cctcggttac ttcctcaaca tgcactgctc catcctcttc 420 tctgcgtgga ctcacctgca ccgctacctg gccatcgtgc ggcccgaagg ctcccgccgc 480 tgccgccagc ctgcctgtgc cagggccgtg tgcgccttcg tgtggctggc cgccggtgcc 540 gtcaccctgt cggtgctggg cgtgacaggc agccggccct gctgccgtgt ctttgcgctg 600 actgtcctgg agttcctgct gcccctgctg gtcatcagcg tgtttaccgg ccgcatcatg 660 tgtgcactgt cgcggccggg tctgctccac cagggtcgcc agcgccgcgt gcgggccatg 720 cagctcctgc tcacggtgct catcatcttt ctcgtctgct tcacgccctt ccacgcccgc 780 caagtggccg tggcgctgtg gcccgacatg ccacaccaca cgagcctcgt ggtctaccac 840 gtggccgtga ccctcagcag cctcaacagc tgcatggacc ccatcgtcta ctgcttcgtc 900 accagtggct tccaggccac cgtccgaggc ctcttcggcc agcacggaga gcgtgagccc 960 agcagcggtg acgtggtcag catgcacagg agctccaagg gctcaggccg tcatcacatc 1020 ctcagtgccg gccctcacgc cctcacccag gccctggcta atgggcccga ggcttag 1077 < 210 > 40 < 211 > 358 < 212 > PRT < 213 > Homo sapiens < 400 > 40 Met Pro Ser Val Ser Pro Wing Gly Pro Wing Ala Gly Wing Val Pro Asn 1 5 10 15 Ala Thr Ala Val Thr Thr Val Arg Thr Asn Ala Ser Gly Leu Glu Val 20 25 30 Pro Leu Phe His Leu Phe Ala Arg Leu Asp Glu Glu Leu His Gly Thr 35 40 45 . SMJSlÉ ^^ Phe Pro Gly Leu Cys Val Wing Leu Met Wing Val His Gly Wing He Phe 50 55 60 Leu Ala Gly Leu Val Leu Asn Gly Leu Ala Leu Tyr Val Phe Cys Cys 65 70 75 80 Arg Thr Arg Ala Lys Thr Pro Ser Val He Tyr Thr He Asn Leu Val 85 90 95 Val Thr Asp Leu Leu Val Gly Leu Ser Leu Pro Thr Arg Phe Ala Val 100 105 110 Tyr Tyr Gly Wing Arg Gly Cys Leu Arg Cys Wing Phe Pro His Val Leu 115 120 125 Gly Tyr Phe Leu Asn Met His Cys Ser He Leu Phe Leu Thr Cys He 130 135 140 Cys Val Asp Arg Tyr Leu Wing He Val Arg Pro Glu Wing Pro Wing Ala 145 150 155 160 Cys Arg Gln Pro Wing Cys Wing Arg Wing Val Cys Wing Phe Val Trp Leu 165 170 175 Ala Ala Gly Ala Val Thr Leu Ser Val Leu Gly Val Thr Gly Ser Arg 180 185 190 Pro Cys Cys Arg Val Phe Ala Leu Thr Val Leu Glu Phe Leu Leu Pro £ i &i! * Jtff * $ ila¡ »A tl? L3 195 200 205 Leu Leu Val He Ser Val Phe Thr Gly Arg He Met Cys Ala Leu Ser 210 215 220 Arg Pro Gly Leu Leu His Gln Gly Arg Gln Arg Arg Val Arg Ala Met 225 230 235 240 Gln Leu Leu Leu Thr Val Leu He He Phe Leu Val Cys Phe Thr Pro 245 250 255 Phe His Wing Arg Gln Val Wing Val Wing Leu Trp Pro Asp Met Pro His 260 265 270 His Thr Ser Leu Val Val Tyr His Val Ala Val Thr Leu Ser Ser Leu 275 280 285 Asn Ser Cys Met Asp Pro He Val Tyr Cys Phe Val Thr Ser Gly Phe 290 295 300 Gln Ala Thr Val Arg Gly Leu Phe Gly Gln His Gly Glu Arg Glu Pro 305 310 315 320 Be Ser Gly Asp Val Val Ser Met His Arg Ser Ser Lys Gly Ser Gly 325 330 335 Arg His His He Leu Ser Ala Gly? O His Ala Leu Thr Gln Ala Leu 3J0 3¿5 35C Ala Asn Gly Pro Glu Ala 355 < 210 > 41 < 211 > 30 5 < 212 > DNA < 213 > Homo sapiens < 400 > 41 gagaattcac tcctgagctc aagatgaact 30 < 210 > 42 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 42 cgggatcccc gtaactgagc cacttcagat 30 < 210 > 43 < 211 > 1050 20 < 212 > DNA < 213 > Homo sapiens < 400 > 43 atgaactcca ccttggatgg taatcagagc agccaccctt tttgcctctt ggcatttggc 60 tatttggaaa ctgtcaattt ttgccttttg gaagtattga ttattgtctt tctaactgta 120 ttgattattt ctggcaacat cattgtgatt tttgtatttc actgtccacc tttattgaac 180 catcacacta caagttattt tatccagact atggcatatg ctgacctttt tgttggggtg 240 agctgcgtgg tcccttcttt atcactcctc catcaccccc ttccagtaga ggagtccttg 300 acttgccaga tatttggttt tgtagtatca gttctgaaga gcgtctccat ggcttctctg 360 gcctgtatca gcattgatag atacattgcc attactaaac ctttaaccta taatactctg 420 gttacaccct ggagactacg cctgtgtatt ttcctgattt ggctatactc gaccctggtc 480 5 ttcctgcctt cctttttcca ctggggcaaa cctggatatc atggagatgt gtttcagtgg 540 tgtgcggagt cctggcacac cgactcctac ttcaccctgt tcatcgtgat gatgttatat 600 gccccagcag cccttattgt ctgcttcacc tatttcaaca tcttccgcat ctgccaacag 660 cacacaaagg atatcagcga aaggcaagcc cgcttcagca gccagagtgg ggagactggg 720 gaagtgcagg cctgtcctga taagcgctat gccatggtcc tgtttcgaat cactagtgta 780 ttttacatcc tctggttgcc atatatcatc tacttcttgt tggaaagctc cactggccac 840 agcaaccgct tcgcatcctt cttgaccacc tggcttgcta ttagtaacag tttctgcaac 900 tgtgtaattt atagtctctc caacagtgta ttccaaagag gactaaagcg cctctcaggg 960 gctatgtgta cttcttgtgc aagtcagact acagccaacg acccttacac agttagaagc 1020 1050 aaaggccctc ttaatggatg tcatatctga < 210 > 44 < 211 > 349 < 212 > PRT < 213 > Homo sapiens < 400 > 44 Met Asn Ser Thr Leu Asp Gly Asn Gln Ser Ser His Pro Phe Cys Leu 1 5 10 15 Leu Ala Phe Gly Tyr Leu Glu Thr Val Asn Phe Cys Leu Leu Glu Val 20 25 30 25 Leu He He Val Phe Leu Thr Val Leu He He Ser Gly Asn He He 35 40 45 Val He Phe Val Phe His Cys Ala Pro Leu Leu Asn His His Thr Thr 50 55 60 Ser Tyr Phe He Gln Thr Met Wing Tyr Wing Asp Leu Phe Val Gly Val 65 70 75 80 Ser Cys Val Val Pro Ser Leu Ser Leu Leu His Pro Pro Leu Pro Val 85 90 95 Glu Glu Ser Leu Thr Cys Gln He Phe Gly Phe Val Val Ser Val Leu 100 105 110 Lys Ser Val Ser Met Wing Ser Leu Wing Cys He Ser He Asp Arg Tyr 115 120 125 He Wing He Thr Lys Pro Leu Thr Tyr Asn Thr Leu Val Thr Pro Trp 130 135 140 Arg Leu Arg Leu Cys He Phe Leu He Trp Leu Tyr Ser Thr Leu Val 145 150 155 160 Phe Leu Pro Ser Phe Phe His Trp Gly Lys Pro Gly Tyr His Gly Asp 165 170 175 Val Phe Gln Trp Cys Wing Glu Ser Trp His Thr Asp Ser Tyr Phe Thr 180 185 190 Leu Phe He Val Met Met Leu Tyr Ala Pro Ala Ala Leu He Val Cys 195 200 205 Phe Thr Tyr Phe Asn He Phe Arg He Cys Gln Gln His Thr Lys Asp 210 215 220 He Is Glu Arg Gln Wing Arg Phe Being Ser Gln Ser Gly Glu Thr Gly 225 230 235 240 Glu Val Gln Ala Cys Pro Asp Lys Arg Tyr Ala Met Val Leu Phe Arg 245 250 255 He Thr Ser Val Phe Tyr He Leu Trp Leu Pro Tyr He He Tyr Phe 260 265 270 Leu Leu Glu Be Ser Thr Gly His Ser Asn Arg Phe Ala Ser Phe Leu 275 280 285 Thr Thr Trp Leu Wing He Being Asn Being Phe Cys Asn Cys Val He Tyr 290 295 300 Ser Leu Ser Asn Ser Val Phe Gln Arg Gly Leu Lys Arg Leu Ser Gly 305 310 315 320 Wing Met Cys Thr Ser Cys Wing Ser Gln Thr Thr Wing Asn Aso Pro Tyr 325 330 335 , ^^? * ^ * & Thr Val Arg Ser Lys Gly Pro Leu Asn Gly Cys His He 340 345 < 210 > 45 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 45 tcccccggga aaaaaaccaa ctgctccaaa 30 < 210 > 46 < 211 > 31 < 212 > DNA < 213 > Homo sapiens < 400 > 46 taggatccat ttgaatgtgg atttggtgaa at 31 < 210 > 47 < 211 > 1413 20 < 212 > DNA < 213 > Homo sapiens < 400 > 47 wchtrvhgnr awcanmwrwm mwdnmahmgs bdrvwnnymk ddwbhhrtan gkgbbkdwmh 60 atmwnwwnnn wmhasrthht msnwrmanrg artmsnwrma nrgarabac satgtgtttt 120 tctcccattc tggaaatcaa catgcagtct gaatctaaca ttacagtccc agatgacatt 180 < h? a > -gatgacatca acaccaatat gtaccaacca ctatcatatc cgttaagctt tcaagtgtct 240 ctcaccggat ttcttatgtt agaaattgtg ttgggacttg gcagcaacct cactgtattg 300 gtactttact gcatgaaatc caacttaatc aactctgtca gtaacattat tacaatgaat 360 cttcatgtac ttgatgtaat aatttgtgtg ggatgtattc ctctaactat agttatcctt 420 ctgctttcac tggagagtaa cactgctctc atttgctgtt tccatgaggc ttgtgtatct 480 tttgcaagtg tctcaacagc aatcaacgtt tttgctatca ctttggacag atatgacatc 540 tctgtaaaac ctgcaaaccg aattctgaca atgggcagag ctgtaatgtt aatgatatcc 600 atttggattt tttctttttt ctctttcctg attcctttta ttgaggtaaa ttttttcagt 660 cttcaaagtg gaaatacctg ggaaaacaag acacttttat gtgtcagtac aaatgaatac 720 tacactgaac tgggaatgta ttatcacctg ttagtacaga tcccaatatt ctttttcact 780 gttgtagtaa tgttaatcac atacaccaaa atacttcagg ctcttaatat tcgaataggc 840 caacagggca acaagatttt gcaagaaaga gaagaagaaa aaaagacaat ttctctaacc 900 aggctacaga acacaacatg catgtcacaa agcagtggtg ggagaaatgt agtctttggt 960 gtaagaactt cagtttctgt aataattgcc ctccggcgag ctgtgaaacg acaccgtgaa 1020 cgacgagaaa gacaaaa gag agtcttcagg atgtctttat tgattatttc tacatttctt 1080 ctctgctgga caccaatttc tgttttaaat accaccattt tatgtttagg cccaagtgac 1140 cttttagtaa aattaagatt gtgtttttta gtcatggctt atggaacaac tatatttcac 1200 cctctattat atgcattcac tagacaaaaa tttcaaaagg tcttgaaaag taaaatgaaa 1260 aagcgagttg tttctatagt agaagctgat cccctgccta ataatgctgt aatacacaac 1320 tcttggatag atcccaaaag aaacaaaaaa attacctttg aagatagtga aataagagaa 1380 aaacgtttag tgcctcaggt tgtcacagac tag 1413 < 210 > 48 < 211 > 433 < 212 > PRT < 213 > Homo sapiens < 400 > 48 Met Cys Phe Ser Pro He Leu Glu He Asn Met Gln Ser Glu Ser Asn 1 5 10 15 He Thr Val Arg Asp Asp He Asp Asp He Asn Thr Asn Met Tyr Gln 20 25 30 5 Pro Leu Ser Tyr Pro Leu Ser Phe Gln Val Ser Leu Thr Gly Phe Leu 35 40 45 Met Leu Glu He Val Leu Gly Leu Gly Ser Asn Leu Thr Val Leu Val 10 50 55 60 Leu Tyr Cys Met Lys Ser Asn Leu He Asn Ser Val Ser Asn He He 65 70 75 80 Thr Met Asn Leu His Val Leu Asp Val He He Cys Val Gly Cys He 15 85 90 95 Pro Leu Thr He Val Le Leu Leu Leu Ser Leu Glu Ser Asn Thr Ala 100 105 110 Leu He Cys Cys Phe His Glu Wing Cys Val Ser Phe Wing Ser Val Ser 20 115 120 125 Thr Ala He Asn Val Phe Wing He Thr Leu Asp Arg Tyr Asp He Ser 130 135 140 Val Lys Pro Wing Asn Arg He Leu Thr Met Gly Arg Wing Val Met Leu 145 150 155 160 Met He Ser He Trp He Phe Ser Phe Phe Ser Phe Leu He Pro Phe 165 170 175 He Glu Val Asn Phe Phe Ser Leu Gln Ser Gly Asn Thr Trp Glu Asn 180 185 190 Lys Thr Leu Leu Cys Val Ser Thr Asn Glu Tyr Tyr Thr Glu Leu Gly 195 200 205 10 Met Tyr Tyr His Leu Leu Val Gln He Pro He Phe Phe Phe Thr Val 210 215 220 Val Val Met Leu He Thr Tyr Thr Lys He Leu Gln Ala Leu Asn He 225 230 235 240 fifteen Arg He Gly Thr Arg Phe Ser Thr Gly Gln Lys Lys Lys Wing Arg Lys 245 250 255 Lys Lys Thr He Ser Leu Thr Thr Gln His Glu Wing Thr Asp Met Ser 260 265 270 Gln Ser Ser Gly Gly Arg Asn Val Val Phe Gly Val Arg Thr Ser Val 275 280 285 Ser Val He He Ala Ala Arg Arg Ala Val Lys Arg His Arg Glu Arg 290 295 300 rj ^ 153 Arg Glu Arg Gln Lys Arg Val Phe Arg Met Ser Leu Leu He He Ser 305 310 315 320 Thr Phe Leu Leu Cys Trp Thr Pro He Ser Val Leu Asn Thr Thr He 325 330 335 5 Leu Cys Leu Gly Pro Ser Asp Leu Leu Val Lys Leu Arg Leu Cys Phe 340 345 350 Leu Val Met Ala Tyr Gly Thr Thr He Phe His Pro Leu Leu Tyr Ala 10 355 360 365 Phe Thr Arg Gln Lys Phe Gln Lys Val Leu Lys Ser Lys Met Lys Lys 370 375 380 Arg Val Val Ser He Val Val Glu Ala Asp Pro Leu Pro Asn Asn Ala Val 385 390 395 400 He His Asn Ser Trp He Asp Pro Lys Arg Asn Lys Lys He Thr Phe 405 410 415 Glu Asp Ser Glu He Arg Glu Lys Arg Leu Val Pro Gln Val Val Thr 420 425 430 Asp < 210 > 49 < 211 30 s ^^^^^^^^ * ^^ j ^^ »fc ^ aia¿¿ ^ fc¿B ^ i5- ^" - ^ £ *:. JÉErfl88HMftfÉÉSÍ ^^? ^ "*%» * ~ 154 <212> ADN <213> Homo sapiens < 400 > 49 gtgaagcttg cctctggtgc ctgcaggagg 30 < 210 > 50 < 211 > 31 < 212 > DNA < 213 > Homo sapiens 10 < 400 > 50 gcagaattcc cggtggcgtg ttgtggtgcc c 31 < 210 > 51 < 211 > 1209 15 < 212 > DNA < 213 > Homo sapiens < 400 > 51 atgttgtgtc cttccaagac agatggctca gggcactctg gtaggattca ccaggaaact 60 catggagaag ggaaaaggga caagattagc aacagtgaag ggagggagaa tggtgggaga 120 ggattccaga tgaacggtgg gtcgctggag gctgagcatg ccagcaggat gtcagttctc 180 agagcaaagc ccatgtcaaa cagccaacgc ttgctccttc tgtccccagg atcacctcct 240 gcatctccta cgcacgggga catcaacatc atcatgcctt cggtgttcgg caccatctgc 300 tcatcgggaa ctcctgggca ctccacggtc atcttcgcgg tcgtgaagaa gtccaagctg 360 cactggtgca acaacgtccc cgacatcttc atcatcaacc tctcggtagt agatctcctc 420 tttctcctgg gcatgccctt catgatccac cagctcatgg gcaatggggt gtggcacu t 480 $ B & ^ k ^ ® & amp ^^ £ g £ ^^^^^ te ^^! D ^ S ^. 155 ggggagacca tgtgcaccct catcacggcc atggatgcca atagtcagtt caccagcacc 540 tacatcctga ccgccatggc cattgaccgc tacctggcca ctgtccaccc catctcttcc 600 acgaagttcc ggaagccctc tgtggccacc ctggtgatct gcctcctgtg ggccctctcc 660 ttcatcagca tcacccctgt gtggctgtat gccagactca tccccttccc aggaggtgca 720 gtgggctgcg gcatacgcct gcccaaccca gacactgacc tctactggtt caccctgtac 780 5 cagtttttcc tggcctttgc cctgcctttt gtggtcatca cagccgcata cgtgaggatc 840 ctgcagcgca tgacgtcctc agtggccccc gcctcccagc gcagcatccg gctgcggaca 900 aagagggtga cccgcacagc catcgccatc tgtctggtct tctttgtgtg ctgggcaccc 960 tactatgtgc tacagctgac ccagttgtcc atcagccgcc cgaccctcac ctttgtctac 1020 ttatacaatg cggccatcag cttgggctat gccaacagct gcctcaaccc ctttgtgtac 1080 atcgtgctct gtgagacgtt ccgcaaacgc ttggtcctgt cggtgaagcc tgcagcccag 1140 gggcagcttc gcgctgtcag caacgctcag acggctgacg aggagaggac agaaagcaaa 1200 ggcacctga 1209 < 210 > 52 < 211 > 402 15 < 212 > PRT < 213 > Homo sapiens < 400 > 52 Met Leu Cys Pro Ser Lys Thr Asp Gly Ser Gly His Ser Gly Arg He 20 1 5 10 15 His Gln Glu Thr His Gly Glu Gly Lys Arg Asp Lys He Ser Asn Ser 20 25 30 Glu Gly Arg Giu Asn Gly Glv Arg Gly Phe Gln Met Asn Gly Glv Ser 25 35 40 45 ... s £ sa £ m ?? i * 'á2S *****, *? aj¡¿a? 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J ^ ^ ^ m k & amp; * sa »*, 156 Leu Glu Ala Glu His Ala Ser Arg Met Ser Val Leu Arg Ala Lys Pro 50 55 60 Met Ser Asn Ser Gln Arg Leu Leu Leu Leu Ser Pro Gly Ser Pro Pro 65 70 75 80 Arg Thr Gly Be He Be Tyr He Asn He He Met Met Pro Ser Val Phe 85 90 95 Gly Thr He Cys Leu Leu Gly He He Gly Asn Ser Thr Val He Phe 100 105 110 Wing Val Val Lys Lys Ser Lys Leu His Trp Cys Asn Asn Val Pro Asp 115 120 125 He Phe He He Asn Leu Ser Val Val Asp Leu Leu Phe Leu Leu Gly 130 135 140 Met Pro Phe Met He His Gln Leu Met Gly Asn Gly Val Trp His Phe 145 150 155 160 Gly Glu Thr Met Cys Thr Leu He Thr Wing Met Asp Wing Asn Ser Gln 165 170 175 Pne Thr Ser Thr Tyr He Leu Thr Wing Met Wing He Asp Arg Tyr Leu 180 185 190 25 ? - * 157 Thr Val His Pro Wing Being Ser Thr Lys Phe Arg Lys Pro Ser Val 195 200 205 Wing Thr Leu Val He Cys Leu Leu Trp Wing Leu Ser Phe He Ser He 210 215 220 5 Thr Pro Val Trp Leu Tyr Wing Arg Leu He Pro Phe Pro Gly Gly Wing 225 230 235 240 Val Gly Cys Gly He Arg Leu Pro Asn Pro Asp Thr Asp Leu Tyr Trp (0 245 250 255 Phe Thr Leu Tyr Gln Phe Phe Leu Wing Phe Wing Leu Pro Phe Val Val 260 265 270 He Thr Ala Ala Tyr Val Arg He Leu Gln Arg Met Thr Ser Ser Val 275 280 285 Wing Pro Wing Being Gln Arg Being He Arg Leu Arg Thr Lys Arg Val Thr 290 295 300 Arg Thr Ala He Ala He Cys Leu Val Phe Phe Val Cys Trp Ala Pro 305 310 315 320 Tyr Tyr Val Leu Gln Leu Thr Gln Leu Ser He Be Arg Pro Thr Leu 325 330 335 Thr Phe Val Tyr Leu Tyr Asn Ala Ala Be Ser Leu Gly Tyr Ala Asn ? ^ ** 158 340 345 350 Ser Cys Leu Asn Pro Phe Val Tyr He Val Leu Cys Glu Thr Phe Arg 355 360 365 Lys Arg Leu Val Leu Ser Val Lys Pro Wing Ala Gln Gly Gln Leu Arg 370 375 380 Wing Val Ser Asn Wing Gln Thr Wing Asp Glu Glu Arg Thr Glu Ser Lys 385 390 395 400 10 Gly Thr < 210 > 53 < 211 > 27 < 212 > DNA 15 < 213 > Homo sapiens < 400 > 53 ggcggatcca tggatgtgac ttcccaa 27 < 210 > 54 < 211 > 27 < 212 > DNA < 213 > Homo sapiens < 400 > 54 25 ggcggatccc tacacggcac tgctgaa 27 ^^^ M ^^^ & étt? 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L ^ '^^ ít? ? ^ ~ & i'i ~ ~ K < 210 > 55 < 211 > 1128 < 212 > DNA < 213 > Homo sapiens < 400 > 55 atggatgtga cttcccaagc ccggggcgtg ggcctggaga tgtacccagg caccgcgcac 60 gctgcggccc ccaacaccac ctcccccgag ctcaacctgt cccacccgct cctgggcacc 120 gccctggcca atgggacagg tgagctctcg gagcaccagc agtacgtgat cggcctgttc 180 ctctcgtgcc tctacaccat cttcctcttc cccatcggct ttgtgggcaa catcctgatc 240 ctggtggtga acatcagctt ccgcgagaag atgaccatcc ccgacctgta cttcatcaac 300 ctggcggtgg cggacctcat cctggtggcc gactccctca ttgaggtgtt caacctgcac 360 gagcggtact acgacatcgc cgtcctgtgc accttcatgt cgctcttcct gcaggtcaac 420 atgtacagca gcgtcttctt cctcacctgg atgagcttcg accgctacat cgccctggcc 480 agggccatgc gctgcagcct gttccgcacc aagcaccacg cccggctgag ctgtggcctc 540 atctggatgg catccgtgtc agccacgctg ccgccgtgca gtgcccttca cctgcagcac 600 accgacgagg cctgcttctg tttcgcggat gtccgggagg tgcagtggct cgaggtcacg 660 ctgggcttca tcgtgccctt cgccatcatc ggcctgtgct actccctcat tgtccgggtg 720 ctggtcaggg cgcaccggca ccgtgggctg cggccccggc ggcagaaggc gctccgcatg 780 atcctcgcgg tggtgctggt cttcttcgtc tgctggctgc cggagaacgt cttcatcagc 840 gtgcacc aka tgcagcggac gcagcctggg gccgctccct gcaagcagtc tttccgccat 900 gcccaccccc tcacgggcca cattgtcaac ctcgccgcct tctccaacag ctgcctaaac 960 cccctcatct acagctttct cggggagacc ttcagggaca agctgaggct gtacattgag 1020 cagaaaacaa atttgccggc cctgaaccgc ttctgtcacg ctgccctgaa ggccgtcatt 1080 ccagacagca ccgagcagtc ggatgtgagg ttcagcagtg ccgtgtga 1128 < 210 > 56 < 211 > 375 < 212 > PRT < 213 > Homo sapiens < 400 > 56 Met Asp Val Thr Ser Gln Ala Arg Gly Val Gly Leu Glu Met Tyr Pro 10 15 Gly Thr Ala His Wing Ala Wing Pro Asn Thr Thr Ser Pro Glu Leu Asn 20 25 30 Leu Ser His Pro Leu Leu Gly Thr Ala Leu Wing Asn Gly Thr Gly Glu 35 40 45 Leu Ser Glu His Gln Gln Tyr Val He Gly Leu Phe Leu Ser Cys Leu 50 55 60 Tyr Thr He Phe Leu Phe Pro He Gly Phe Val Gly Asn He Leu He 65 70 75 80 Leu Val Val Asn He Be Phe Arg Glu Lys Met Thr He Pro Asp Leu 85 90 95 Tyr Phe He Asn Leu Wing Val Wing Asp Leu He Leu Val Wing Asp Ser 100 105 110 Leu Cys Thr Phe Met Ser. Leu Phe Leu Gln Val Asn Met Tyr Ser Ser 130 135 140 Val Phe Phe Leu Thr Trp Met Ser Phe Asp Arg Tyr He Ala Leu Ala 145 150 155 160 Arg Ala Met Arg Cys Ser Leu Phe Arg Thr Lys His His Wing Arg Leu 165 170 175 Ser Cys Gly Leu He Trp Met Wing Ser Val Be Wing Thr Leu Val Pro 180 185 190 Phe Thr Ala Val His Leu Gln His Thr Asp Glu Ala Cys Phe Cys Phe 195 200 205 Wing Asp Val Arg Glu Val Gln Trp Leu Glu Val Thr Leu Gly Phe He 210 215 220 Val Pro Phe Wing He He Gly Leu Cys Tyr Ser Leu He Val Arg Val 225 230 235 240 Leu Val Arg Ala His Arg His Arg Gly Leu Arg Pro Arg Arg Gln Lys 245 250 255 Ala Leu Arg Met He Leu Ala Val Val Leu Val Phe Phe Val Cys Trp 260 265 270 Leu PLO Glu Asn Val Phe He Ser Val His Leu Leu Gl- > Arg Thr Gln 275 280 285 Pro Gly Wing Wing Pro Cys Lys Gln Ser Phe Arg His Wing His Pro Leu 290 295 300 Thr Gly His He Val Asn Leu Ala Wing Phe Ser Asn Ser Cys Leu Asn 305 310 315 320 Pro Leu He Tyr Ser Phe Leu Gly Glu Thr Phe Arg Asp Lys Leu Arg 325 330 335 Leu Tyr He Glu Gln Lys Thr Asn Leu Pro Ala Leu Asn Arg Phe Cys 340 345 350 His Wing Wing Leu Lys Wing Val He Pro Asp Being Thr Glu Gln Being Asp 355 360 365 Val Arg Phe Ser Ser Ala Val 370 375 < 210 > 57 < 211 > 31 < 212 > DNA < 213 > Homo sapiens < 400 > 57 aaggaattca cggccgggtg atgccattcc c 31 fcf? S 1 63 < 210 > 58 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 58 ggtggatcca taaacacggg cgttgaggac 30 < 210 > 59 < 211 > 960 10 < 212 > DNA < 213 > Homo sapiens < 400 > 59 atgccattcc caaactgctc agcccccagc actgtggtgg ccacagctgt gggtgtcttg 60 ctggggctgg agtgtgggct gggtctgctg ggcaacgcgg tggcgctgtg gaccttcctg 120 ttccgggtca gggtgtggaa gccgtacgct gtctacctgc tcaacctggc cctggctgac 180 ctgctgttgg ctgcgtgcct gcctttcctg gccgccttct acctgagcct ccaggcttgg 240 catctgggcc gtgtgggctg ctgggccctg cgcttcctgc tggacctcag ccgcagcgtg 300 gggatggcct tcctggccgc cgtggctttg gaccggtacc tccgtgtggt ccaccctcgg 360 cttaaggtca acctgctgtc tcctcaggcg gccctggggg tctcgggcct cgtctggctc 420 ctgatggtcg ccctcacctg cccgggcttg ctcatctctg aggccgccca gaactccacc 480 aggtgccaca gtttctactc cagggcagac ggctccttca gcatcatctg gcaggaagca 540 ctctcctgcc ttcagtttgt cctccccttt ggcctcatcg tgttctgcaa tgcaggcatc 600 atcagggctc tccagaaaag actccgggag cctgagaaac agcccaagct tcagcgggcc 660 caggcactgg tcaccttggt ggtggtgctg tttgctctgt gctttctgcc ctgcttcctg 720 gccagagtcc tgatgcacat cttccagaat ctggggagct gcagggccct ttgtgcagtg 780 gctcatacct cggatgtcac gggcagcctc acctacctgc acagtgtcgt caaccccgtg 840 gtatactgct tctccagccc caccttcagg agctcctatc ggagggtctt ccacaccctc 900 cgaggcaaag ggcaggcagc agagccccca gatttcaacc ccagagactc ctattcctga 960 < 210 > 60 < 211 > 319 < 212 > PRT < 213 > Homo sapiens < 400 > 60 Met Pro Phe Pro Asn Cys Ser Ala Pro Ser Thr Val Val Ala Thr Ala 1 5 10 15 Val Gly Val Leu Leu Gly Leu Glu Cys Gly Leu Gly Leu Leu Gly Asn 20 25 30 Wing Val Ala Leu Trp Thr Phe Leu Phe Arg Val Arg Val Trp Lys Pro 35 40 45 Tyr Ala Val Tyr Leu Leu Asn Leu Ala Leu Ala Asp Leu Leu Leu Ala 50 55 60 Ala Cys Leu Pro Phe Leu Wing Wing Phe Tyr Leu Ser Leu Gln Wing Trp 65 70 75 80 His Leu Gly Arg Val Gly Cys Trp Ala Leu Arg Phe Leu Leu Asp Leu 85 90 95 Ser Arg Ser Val Gly Met Ala Phe Leu Ala Ala Val Ala Leu Asp Arg a ^ fefeji 100 105 110 Tyr Leu Arg Val Val His Pro Arg Leu Lys Val Asn Leu Leu Ser Pro 115 120 125 Gln Ala Ala Leu Gly Val Ser Gly Leu Val Trp Leu Leu Met Val Wing 130 135 140 Leu Thr Cys Pro Gly Leu Leu He Ser Glu Ala Wing Gln Asn Ser Thr 145 150 155 160 Arg Cys His Ser Phe Tyr Ser Arg Wing Asp Gly Ser Phe Ser He He 165 170 175 Trp Gln Glu Ala Leu Ser Cys Leu Gln Phe Val Leu Pro Phe Gly Leu 180 185 190 He Val Phe Cys Asn Wing Gly He He Arg Wing Leu Gln Lys Arg Leu 195 200 205 Arg Glu Pro Glu Lys Gln Pro Lys Leu Gln Arg Ala Gln Ala Leu Val 210 215 220 Thr Leu Val Val Val Leu Phe Ala Leu Cys Phe Leu Pro Cys Phe Leu 225 230 235 240 Ala Arg Val Leu Met His He Phe Gln Asn Leu Gly Ser Cys Arg Ala 5 250 255 Leu Cys Ala Val Ala His Thr Ser Asp Val Thr Gly Ser Leu Thr Tyr 260 265 270 Leu His Ser Val Val Asn Pro Val Val Tyr Cys Phe Ser Ser Pro Thr 275 280 285 5 Phe Arg Ser Ser Tyr Arg Arg Val Phe His Thr Leu Arg Gly Lys Gly 290 295 300 Gln Ala Ala Glu Pro Pro Asp Phe Asn Pro Arg Asp Ser Tyr Ser 10 305 310 315 < 210 > 61 < 211 > 1143 < 212 > DNA < 213 > Homo sapiens 15 < 400 > 61 atggaggaag gtggtgattt tgacaactac tatggggcag acaaccagtc tgagtgtgag 60 tacacagact ggaaatcctc gggggccctc atccctgcca tctacatgtt ggtcttcctc 120 ctgggcacca cgggaaacgg tctggtgctc tggaccgtgt ttcggagcag ccgggagaag 180 aggcgctcag ctgatatctt cattgctagc ctggcggtgg ctgacctgac cttcgtggtg 240 acgctgcccc tgtgggctac ctacacgtac cgggactatg actggccctt tgggaccttc 300 ttctgcaagc tcagcagcta cctcatcttc gtcaacatgt acgccagcgt cttctgcctc 360 accggcctca gcttcgaccg ctacctggcc atcgtgaggc cagtggccaa tgctcggctg 420 aggctgcggg tcagcggggc cgtggccacg gcagttcttt gggtgctggc cgccctcctg 480 gccatgcctg tcatggtgtt acgcaccacc ggggacttgg agaacaccac taaggtgcag 540 tactacatqg actactccat ggtggccact gtgagctcag agtgggcctg ggaggtgggc 600 tei ^ -Sj < ^ a ^ «, ^ - A¡« ^ M? £ ^^ g & £ 167 cttggggtct cgtccaccac cgtgggcttt gtggtgccct tcaccatcat gctgacctgt 660 tacttcttca tcgcccaaac catcgctggc cacttccgca aggaacgcat cgagggcctg 720 cggaagcggc gccggctgct cagcatcatc gtggtgctgg tggtgacctt tgccctgtgc 780 tggatgccct accacctggt gaagacgctg tacatgctgg gcagcctgct gcactggccc 840 tgtgactttg acctcttcct catgaacatc ttcccctact gcacctgcat cagctacgtc 900 aacagctgcc tcaacccctt cctctatgcc tttttcgacc cccgcttccg ccaggcctgc 960 acctccatgc tctgctgtgg ccagagcagg tgcgcaggca cctcccacag cagcagtggg 1020 gagaagtcag ccagctactc ttcggggcac agccaggggc ccggccccaa catgggcaag 1080 ggtggagaac agatgcacga gaaatccatc ccctacagcc aggagaccct tgtggttgac 1140 tag 1143 < 210 > 62 < 211 > 380 < 212 > PRT < 213 > Homo sapiens < 400 > 62 Met Glu Glu Gly Gly Asp Phe Asp Asn Tyr Tyr Gly Wing Asp Asn Gln 1 5 10 15 Ser Glu Cys Glu Tyr Thr Asp Trp Lys Ser Ser Gly Ala Leu He Pro 20 25 30 Ala He Tyr Met Leu Val Phe Leu Leu Gly Thr Thr Gly Asn Gly Leu 35 40 45 Val Leu Trp Thr Val Phe Arg Ser Ser Arg Glu Lys Arg Arg Ser Ala 50 55 60 »A **« ate * lfe Asp He Phe He Wing Ser Leu Wing Val Wing Asp Leu Thr Phe Val Val 65 70 75 80 Thr Leu Pro Leu Trp Wing Thr Tyr Thr Tyr Arg Asp Tyr Asp Trp Pro 85 90 95 Phe Gly Thr Phe Phe Cys Lys Leu Ser Ser Tyr Leu He Phe Val Asn 100 105 110 Met Tyr Ala Ser Val Phe Cys Leu Thr Gly Leu Ser Phe Asp Arg Tyr H5 120 125 Leu Ala He Val Arg Pro Val Ala Asn Ala Arg Leu Arg Leu Arg Val 130 135 140 Ser Gly Ala Val Ala Thr Ala Val Leu Trp Val Leu Ala Ala Leu Leu 145 150 155 160 Wing Met Pro Val Met Val Leu Arg Thr Thr Gly Asp Leu Glu Asn Thr 165 170 175 Thr Lys Val Gln Cys Tyr Met Asp Tyr Ser Met Val Wing Thr Val Ser 180 185 190 Ser Glu Trp Wing Trp Glu Val Gly Leu Gly Val Ser Ser Thr Thr Val 195 200 205 Gly Phe Val Val Pro Phe Thr He Met Leu Thr Cys Tyr Phe Phe He 210 215 220 Wing Gln Thr He Wing Gly His Phe Arg Lys Glu Arg He Glu Gly Leu 225 230 235 240 Arg Lys Arg Arg Arg Leu Leu Ser He He Val Val Leu Val Val Thr 245 250 255 Phe Ala Leu Cys Trp Met Pro Tyr His Leu Val Lys Thr Leu Tyr Met 260 265 270 Leu Gly Ser Leu Leu His Trp Pro Cys Asp Phe Asp Leu Phe Leu Met 275 280 285 Asn He Phe Pro Tyr Cys Thr Cys He Ser Tyr Val Asn Ser Cys Leu 290 295 300 Asn Pro Phe Leu Tyr Ala Phe Phe Asp Pro Arg Phe Arg Gln Ala Cys 305 310 315 320 Thr Ser Met Leu Cys Cys Gly Gln Ser Arg Cys Wing Gly Thr Ser His 325 330 335 Being Being Gly Glu Lys Being Wing Being Tyr Being Being Gly His Being Gln 340 345 350 Gly Pro Gly Pro Asn Met Gly Lys Gly Gly Glu Gln Met His Glu Lys 355 360 365 Ser He Pro Tyr Ser Gln Glu Thr Leu Val Val Asp 370 375 380 < 210 > 63 < 211 > 31 < 212 > DNA < 213 > Homo sapiens < 400 > 63 tgagaattct ggtgactcac agccggcaca g 31 < 210 > 64 < 211 > 31 < 212 > DNA < 213 > Homo sapiens < 400 > 64 gccggatcca aggaaaagca gcaataaaag g 31 < 210 > 65 < 211 > 1119 < 212 > DNA < 213 > Homo sapiens < 400 > 65 atgaactacc cgctaacgct ggaaatggac ctcgagaacc tggaggacct gttctgggaa 60 ctggacagat tggacaacta taacgacacc tccctggtgg aaaatcatct ctgccctgcc 120 acagagggtc ccctcatggc ctccttcoag gccstgttcg tgcccgtgg ^ ctacagccuc 180 atcttcctcc tgggcgtgat cggcaacgtc ctggtgctgg tgatcctgga gcggcaccgg 240 gttccacgga cagacacgca gaccttcctg ttccacctgg ccgtggccga cctcctgctg 300 gtcttcatct tgccctttgc cgtggccgag ggctctgtgg gctgggtcct ggggaccttc 360 ctctgcaaaa ctgtgattgc cctgcacaaa gtcaacttct actgcagcag cctgctcctg 420 gcctgcatcg ccgtggaccg ctacctggcc attgtccacg ccgtccatgc ctaccgccac 480 cgccgcctcc tctccatcca catcacctgt gggaccatct ggctggtggg cttcctcctt 540 gccttgccag agattctctt cgccaaagtc agccaaggcc atcacaacaa ctccctgcca 600 tctcccaaga cgttgcacct gaaccaagca gaaacgcatg cctggttcac ctcccgattc 660 ctctaccatg tggcgggatt cctgctgccc atgctggtga tgggctggtg ctacgtgggg 720 ggttgcgcca gtagtgcaca ggcccagcgg cgccctcagc ggcagaaggc agtcagggtg 780 gccatcctgg tgacaagcat cttcttcctc tgctggtcac cctaccacat cgtcatcttc 840 ctggacaccc tggcga GWOT gaaggccgtg gacaatacct gcaagctgaa tggctctctc 900 cccgtggcca tcaccatgtg tgagttcctg ggcctggccc actgctgcct caaccccatg 960 ctctacactt tcgccggcgt gaagttccgc agtgacctgt cgcggctcct gaccaagctg 1020 ggctgtaccg gccctgcctc cctgtgccag ctcttcccta gctggcgcag gagcagtctc 1080 tctgagtcag agaatgccac ctctctcacc acgttctag 1119 < 210 > 66 < 211 > 372 < 212 > PRT < 213 > Homo sapiens < 400 > 66 Met Asn Tyr Pro Leu Thr Leu Glu Met Asp Leu Glu Asn Leu Glu Asp 1 5 10 15 Leu Phe Trp Glu Leu Asp Arg Leu Asp Asn Tyr Asn Asp TT Ser Leu 20 25 33 Val Glu Asn His Leu Cys Pro Wing Thr Glu Gly Pro Leu Met Wing Ser 35 40 45 Phe Lys Wing Val Phe Val Pro Val Wing Tyr Ser Leu He Phe Leu Leu 50 55 60 Gly Val He Gly Asn Val Leu Val Leu Val He Leu Glu Arg His Arg 65 70 75 80 Gln Thr Arg Ser Ser Thr Glu Thr Phe Leu Phe His Leu Wing Val Wing 85 90 95 Asp Leu Leu Leu Val Phe He Leu Pro Phe Wing Val Wing Glu Gly Ser 100 105 110 Val Gly Trp Val Leu Gly Thr Phe Leu Cys Lys Thr Val He Ala Leu 115 120 125 His Lys Val Asn Phe Tyr Cys Ser Ser Leu Leu Leu Ala Cys He Ala 130 135 140 Val Asp Arg Tyr Leu Wing He Val His Wing Val His Wing Tyr Arg His 145 150 155 160 Arg Arg Leu Leu Ser He His He Thr Cys Gly Thr He Trp Leu Val 165 170 175 Gly Phe Leu u ° u Wing Leu Pro Glu He Leu Phe Wing Lys Val Ser Gln ^ a ^ am ^ m ^ a ^^ Gly His His Asn Asn Ser Leu Pro Arg Cys Thr Phe Ser Gln Glu Asn 195 200 205 Gln Ala Glu Thr His Wing Trp Phe Thr Ser Arg Phe Leu Tyr His Val 210 215 220 Wing Gly Phe Leu Leu Pro Met Leu Val Met Gly Trp Cys Tyr Val Gly 225 230 235 240 Val Val His Arg Leu Arg Gln Wing Gln Arg Arg Pro Gln Arg Gln Lys 245 250 255 Wing Val Arg Val Wing He Leu Val Thr Ser He Phe Phe Leu Cys Trp 260 265 270 Ser Pro Tyr His He Val He Phe Leu Asp Thr Leu Ala Arg Leu Lys 275 280 285 Wing Val Asp Asn Thr Cys Lys Leu Asn Gly Ser Leu Pro Val Wing He 290 295 300 Thr Met Cys Glu Phe Leu Gly Leu Wing His Cys Cys Leu Asn Pro Met í? Leu Thr Lys Leu Phe Pro Ser Trp Arg Arg Ser Ser Leu Ser Of? Ü Ser Glu Asn Ala Thr Ser 355 360 365 Leu Thr Thr Phe 370 < 210 > 67 10 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 67 caaagcttga aagctgcacg gtgcagagac 30 < 210 > 68 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 68 gcggatcccg agtcacaccc tggctgggcc 30 < 213 > Homo sapiens < 400 > 69 atggatgtga cttcccaagc ccggggcgtg ggcctggaga tgtacccagg caccgcgcag 60 cctgcggccc ccaacaccac ctcccccgag ctcaacctgt cccacccgct cctgggcacc 120 gccctggcca atgggacagg tgagctctcg gagcaccagc agtacgtgat cggcctgttc 180 ctctcgtgcc tctacaccat cttcctcttc cccatcggct ttgtgggcaa catcctgatc 240 ctggtggtga acatcagctt ccgcgagaag atgaccatcc ccgacctgta cttcatcaac 300 ctggcggtgg cggacctcat cctggtggcc gactccctca ttgaggtgtt caacctgcac 360 gagcggtact acgacatcgc cgtcctgtgc accttcatgt cgctcttcct gcaggtcaac 420 atgtacagca gcgtcttctt cctcacctgg atgagcttcg accgctacat cgccctggcc 480 agggccatgc gctgcagcct gttccgcacc aagcaccacg cccggctgag ctgtggcctc 540 atctggatgg catccgtgtc agccacgctg ccgccgtgca gtgcccttca cctgcagcac 600 accgacgagg cctgcttctg tttcgcggat gtccgggagg tgcagtggct cgaggtcacg 660 ctgggcttca tcgtgccctt cgccatcatc ggcctgtgct actccctcat tgtccgggtg 720 ctggtcaggg cgcaccggca ccgtgggctg cggccccggc ggcagaaggc gctccgcatg 780 atcctcgcgg tggtgctggt cttcttcgtc tgctggctgc cggagaacgt cttcatcagc 840 gtgcacctcc tgcagcg gac gcagcctggg gccgctccct gcaagcagtc tttccgccat 900 gcccaccccc tcacgggcca cattgtcaac ctcaccgcct tctccaacag ctgcctaaac 960 cccctcatct acagctttct cggggagacc ttcagggaca agctgaggct gtacattgag 1020 cagaaaacaa atttgccggc cctgaaccgc ttctgtcacg ctgccctgaa ggccgtcatt 1080 ccagacagca ccgagcagtc ggatgtgagg ttcagcagtg ccgtgtag 1128 < 210 > 70 < 211 > 375 < 212 > PRT < 213 > Homo sapiens < 400 > 70 Met Asp Val Thr Ser Gln Wing Gly Val Gly Leu Glu Met Tyr Pro 1 5 10 15 Gly Thr Ala Gln Pro Ala Ala Pro Asn Thr Thr Ser Pro Glu Leu Asn 25 30 Leu Ser His Pro Leu Leu Gly Thr Ala Leu Wing Asn Gly Thr Gly Glu 35 40 45 Leu Ser Glu His Gln Gln Tyr Val He Gly Leu Phe Leu Ser Cys Leu 50 55 60 Tyr Thr He Phe Leu Phe Pro He Gly Phe Val Gly Asn He Leu He 65 70 75 80 Leu Val Val Asn He Be Phe Arg Glu Lys Met Thr He Pro Asp Leu 85 90 95 Tyr Phe He Asn Leu Wing Val Wing Asp Leu He Leu Val Wing Asp Ser 100 105 110 Leu He Glu Val Phe Asn Leu His Glu Arg Tyr Tyr Asp He Ala Val 115 120 125 Leu Cys Thr Phe Met Ser Leu Phe Leu Gln Val Asn Met Tyr Ser Ser 130 135 1-iO Val Phe Phe Leu Thr Trp Met Ser Phe Asp Arg Tyr He Ala Leu Ala 145 150 155 160 Arg Ala Met Arg Cys Ser Leu Phe Arg Thr Lys His His Wing Arg Leu 165 170 175 Ser Cys Gly Leu He Trp Met Wing Ser Val Be Wing Thr Leu Val Pro 180 185 190 Phe Thr Ala Val His Leu Gln His Thr Asp Glu Ala Cys Phe Cys Phe 195 200 205 Wing Asp Val Arg Glu Val Gln Trp Leu Glu Val Thr Leu Gly Phe He 210 215 220 Val Pro Phe Wing He He Gly Leu Cys Tyr Ser Leu He Val Arg Val 225 230 235 240 Leu Val Arg Ala His Arg His Arg Gly Leu Arg Pro Arg Arg Gln Lys 245 250 255 Ala Leu Arg Met He Leu Ala Val Val Leu Val Phe Phe Val Cys Trp 260 265 270 Leu Pro Glu Asn Val Phe He Ser Val His Leu Leu Gln Arg Thr Gln 275 280 285 Pro Gly Ala Wing Pro Cys Lys Gln Ser Phe Arg His Wing H? _ Pro Leu 290 295 300 Thr Gly His He Val Asn Leu Thr Ala Phe Ser Asn Ser Cys Leu Asn 305 310 315 320 Pro Leu He Tyr Ser Phe Leu Gly Glu Thr Phe Arg Asp Lys Leu Arg 325 330 335 Leu Tyr He Glu Gln Lys Thr Asn Leu Pro Ala Leu Asn Arg Phe Cys 340 345 350 His Wing Wing Leu Lys Wing Val He Pro Asp Being Thr Glu Gln Being Asp 355 360 365 Val Arg Phe Ser Ser Ala Val 370 375 < 210 > 71 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 71 acagaattcc tgtgtggttt taccgcccag 30 v210 > 72 < 211 > 30? 212 > DNA < 213 > Homo sapiens < 400 > 72 ctcggatcca ggcagaagag tcgcctatgg 30 < 210 > 73 < 211 > 1137 < 212 > DNA < 213 > Homo sapiens < 400 > 73 atggacctgg ggaaaccaat gaaaagcgtg ctggtggtgg ctctccttgt cattttccag 60 gtatgcctgt gtcaagatga ggtcacggac gattacatcg gagacaacac cacagtggac 120 tacactttgt tcgagtcttt gtgctccaag aaggacgtgc ggaactttaa agcctggttc 180 ctccctatca tgtactccat catttgtttc gtgggcctac tgggcaatgg gctggtcgtg 240 tctatttcaa ttgacctata gaggctcaag accatgaccg atacctacct gctcaacctg 300 gcggtggcag acatcctctt cctcctgacc cttcccttct gggcctacag cgcggccaag 360 tcctgggtct tcggtgtcca cttttgcaag ctcatctttg ccatctacaa gatgagcttc 420 ttcagtggca tgctcctact tctttgcatc agcattgacc gctacgtggc catcgtccag 480 gctgtctcag ctcaccgcca gtccttctca ccgtgcccgc tcagcaagct gtcctgtgtg 540 ggcatctgga tactagccac agtgctctcc atcccagagc tcctgtacag tgacctccag 600 aggagcagca gtgagcaagc gatgcgatgc tctctcatca cagagcatgt ggaggccttt 660 atcaccatcc aggtggccca gatggtgatc ggctttctgg tccccctgct ggccatgagc 720 ttctgttacc ttgtcatcat ccgcaccctg ctccaggcac gcaactttga gcgcaacaag 780 gccatcaagg tgatcatcgc tgtggtcgtg gtcttcatag tcttccagct gccctacaat 840 ggggtggtcc tggccca gac ggtggccaac ttcaacatca ccagtagcac ctgtgagctc 900 agtaagcaac tcaacatcgc ctacgacgtc acctacagcc tggcctgcgt ccgctgctgc 960 gtcaaccctt tcttgtacgc cttca-cggc gtcaagttcc gcaacgatct cttcaagctc 1020 ttr < | aaggacc tgggctgcct cagccaggag cagctccggc agtggtcttc ctgtcggcac 1080 atccggcgct cctccatgag tgtggaggcc gagaccacca ccaccttctc ccatag 1137 < 210 > 74 < 211 > 378 < 212 > PRT < 213 > Homo sapiens < 400 > 74 Met Asp Leu Gly Lys Pro Met Lys Ser Val Leu Val Val Ala Leu Leu 1 5 10 15 Val He Phe Gln Val Cys Leu Cys Gln Asp Glu Val Thr Asp Asp Tyr 20 25 30 He Gly Asp Asn Thr Thr Val Asp Tyr Thr Leu Phe Glu Ser Leu Cys 35 45 Ser Lys Lys Asp Val Arg Asn Phe Lys Wing Trp Phe Leu Pro He Met 50 55 60 Tyr Ser He He Cys Phe Val Gly Leu Leu Gly Asn Gly Leu Val Val 65 70 75 80 Leu Thr Tyr He Tyr Phe Lys Arg Leu Lys Thr Met Thr Asp Thr Tyr 85 90 95 Leu Leu ^ sn Leu Ala Val Ala Asp He Leu Phe Leu Leu rhr Leu Pro t. 181 100 105 110 Phe Trp Ala Tyr Ser Ala Ala Lys Ser Trp Val Phe Gly Val His Phe 115 120 125 Cys Lys Leu He Phe Wing He Tyr Lys Met Ser Phe Phe Ser Gly Met 130 135 140 Leu Leu Leu Leu Cys He Ser He Asp Arg Tyr Val Wing He Val Val 145 150 155 160 Wing Val Ser Wing His Arg His Arg Wing Arg Val Leu Leu He Ser Lys 165 170 175 Leu Ser Cys Val Gly He Trp He Leu Wing Thr Val Leu Ser He Pro 180 185 190 15 Glu Leu Leu Tyr Being Asp Leu Gln Arg Being Ser Glu Gln Ala Met 195 200 205 Arg Cys Ser Leu He Thr Glu His Val Glu Wing Phe He Thr He Gln 210 215 220 Val Ala Gln Met Val He Gly Phe Leu Val Pro Leu Leu Ala Met Ser 225 230 235 240 Phe Cys Tyr Leu Val He He Arg Thr Leu Leu Gln Ala Arg Asn Phe 2J5 250 255 Glu Arg Asn Lys Wing He L; J | Val He He Ala Val Val Val Val Phe 260 * '265 270 He Val Phe Gln Leu Pro Tyr Asn Gly Val Val Leu Ala Gln Thr Val 275 280 285 Wing Asn Phe Asn He Thr Ser Ser Thr Cys Glu Leu Ser Lys Gln Leu 290 295 300 Asn He Ala Tyr Asp Val Thr Tyr Ser Leu Ala Cys Val Arg Cys Cys 305 310 315 320 Val Asn Pro Phe Leu Tyr Wing Phe He Gly Val Lys Phe Arg Asn Asp 325 330 335 Leu Phe Lys Leu Phe Lys Asp Leu Gly Cys Leu Ser Gln Glu Gln Leu 340 345 350 Arg Gln Trp Be Ser Cys Arg His He Arg Arg Ser Ser Met Ser Val 355 360 365 Glu Ala Glu Thr Thr Thr Thr Phe Ser Pro 370 375 < 210 > 75 < 211 > 32 < 212 > DNA < 213 > Homo sapiens < 400 > 75, c ctggaattca cctggaccac caccaatgga ta 32 < 210 > 76 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 76 ctcggatcct gcaaagtttg tcatacagtt 30 < 210 > 77 < 211 > 1086 < 212 > DNA < 213 > Homo sapiens < 400 > 77 atggatatac aaatggcaaa caattttact ccgccctctg caactcctca gggaaatgac 60 tgtgacctct atgcacatca cagcacggcc aggatagtaa tgcctctgca ttacagcctc 120 gtcttcatca ttgggctcgt gggaaactta ctagccttgg tcgtcattgt tcaaaacagg 180 aaaaaaatca actctaccac cctctattca acaaatttgg tgatttctga tatacttttt 240 accacggctt tgcctacacg aatagcctac tatgcaatgg gctttgactg gagaatcgga 300 gatgccttgt gtaggataac tgcgctagtg ttttacatca acacatatgc aggtgtgaac 360 tttatgacct gcctgagtat tgaccgcttc attgctgtgg tgcaccctct acgctacaac 420 aagataaaaa ggattgaaca tgcaaaaggc gtgtgcatat ttgtctggat tctagtattt 480 gctcagacac tcccactcct catcaaccct atgtcaaagc aaggattaca aggaggctga 540 tgcatggagt atccaaactt tgaagaaact aaatctcttc cctggattct gcttggggca 600 tgtttcatag gatatgtact tccacttata atcattctca tctgctattc tcagatctgc 660 tgcaaactct tcagaactgc caaacaaaac ccactcactg agaaatctgg tgtaaacaaa 720 aaggctctca acacaattat tcttattatt gttgtgtttg ttctctgttt cacaccttac 780 ttattcaaca catgttgcaa tatgattaag aagcttcgtt tctctaattt cctggaatgt 840 agccaaagac attcgtt cca gatttctctg cactttacag tatgcctgat gaacttcaat 900 tgctgcatgg acccttttat ctacttcttt gcatgtaaag ggtataagag aaaggttatg 960 aggatgctga aacggcaagt cagtgtatcg atttctagtg ctgtgaagtc agcccctgaa 1020 gaaaattcac gtgaaatgac agaaacgcag atgatgatac attccaagtc ttcaaatgga 1080 aagtga 1086 < 210 > 78 < 211 > 361 < 212 > PRT < 213 > Homo sapiens < 400 > 78 Met Asp He Gln Met Wing Asn Asn Phe Thr Pro Pro Be Wing Thr Pro 1 5 10 15 Gln Gly Asn Asp Cys Asp Leu Tyr Wing His His Ser Thr Wing Arg He 20 25 30 Val Met Pro Leu His Tyr Ser Leu Val Phe He He Gly Leu Val Gly 35 40 45 Asn Leu Leu Ala Leu Val Val He Val Gln Asn Arg Lys Lys He Asn 50 55 60 Being Thr Thr Leu Tyr Being Thr Asn Leu Val He Being -sp He Leu Phe asá 85 Thr Thr Ala Leu Pro Thr Arg He Wing Tyr Tyr Wing Met Gly Phe Asp 85 S 95 Trp Arg He Gly Asp Ala Leu Cys Arg He Thr Ala Leu Val Phe Tyr 100 105 110 He Asn Thr Tyr Wing Gly Val Asn Phe Met Thr Cys Leu Ser He Asp 115 120 125 Arg Phe He Wing Val Val His Pro Leu Arg Tyr Asn Lys He Lys Arg 130 135 140 He Glu His Wing Lys Gly Val Cys He Phe Val Trp He Leu Val Phe 145 150 155 160 Wing Gln Thr Leu Pro Leu Leu He Asn Pro Met Ser Lys Gln Glu Wing 165 170 175 Glu Arg He Thr Cys Met Glu Tyr Pro Asn Phe Glu Glu Thr Lys Ser 180 185 190 Leu Pro Trp He Leu Leu Gly Ala Cys Phe He Gly Tyr Val Leu Pro 195 200 205 Leu He He He Leu He Cys Tyr Ser Gln He Cys Cys Lys Leu Phe 2i0 215 220 á t t t t t ¡¡¡¡¡S S Ar Ar Ar Arg Thr Ala Lys Gln Asn Pro Leu Thr Glu Lys Ser Gly Val Asn Lys 225 230 235 240 Lys Ala Leu Asn Thr He He Leu He He Val Val Phe Val Leu Cys 245 250 255 Phe Thr Pro Tyr His Val Wing He He Gln His Met He Lys Lys Leu 260 265 270 Arg Phe Ser Asn Phe Leu Glu Cys Ser Gln Arg His Ser Phe Gln He 275 280 285 Ser Leu His Phe Thr Val Cys Leu Met Asn Phe Asn Cys Cys Met Asp 290 295 300 Pro Phe He Tyr Phe Phe Wing Cys Lys Gly Tyr Lys Arg Lys Val Met 305 310 315 320 Arg Met Leu Lys Arg Gln Val Ser Val Ser He Ser Ser Ala Ala Lys 325 330 335 Be Wing Pro Glu Glu Asn Be Arg Glu Met Thr Glu Thr Gln Met Met 340 345 350 He His Ser Lys Ser Ser Asn Gly Lys 355 360 < 210 > 79 4 ^^ 1 * 87 < 213 > Homo sapiens < 400 > 79 ctggaattct cctgctcatc cagccatgcg g 31 < 210 > 80 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 80 cctggatccc cacccctact ggggcctcag 30 < 210 > 81 < 211 > 1446 < 212 > DNA < 213 > Homo sapiens < 400 > 81 atgcggtggc tgtggcccct ggctgtctct cttgctgtga ttttggctgt ggggctaagc 60 agggtctctg ggggtgcccc cctgcacctg ggcaggcaca gagccgagac ccaggagcag 120 cagagccgat ccaagagggg caccgaggat gaggaggcca agggcgtgca gcagtatgtg 180 cctgaggagt gggcggagta cccccggccc attcaccctg ctggcctgca gccaaccaag 240 cccttggtgg ccaccagccc taaccccgac aaggatgggg gcaccccaga cagtgggcag 300 gaactgaggg gcaatctgac aggggcacca gggcagaggc tacagatcca gaaccccctg 360 tatccggtga ccgagagctc ctacagtgcc tatgccatca tgcttctggc gctggtggtg 420 tttgcggtgg gcattgtggg caacctgtcg gtcatgtgca tcgtgtggca cagctactac 480 ctgaagagcg cctggaactc catcctlígcs agcctggccc tctgggattt tctggtcctc 540 tttttctgcc tccctattgt catcttcaac gagatcacca agcagaggct actgggtgac 600 gtttcttgtc gtgccgtgcc cttcatggag gtctcctctc tgggagtcac gactttcagc 660 tgggcattga ctctgtgccc ccgcttccac gtggccacca gcaccctgcc caaggtgagg 720 cccatcgagc ggtgccaatc catcctggcc aagttggctg tcatctgggt gggctccatg 780 acgctggctg tgcctgagct cctgctgtgg cagctggcac aggagcctgc ccccaccatg 840 ggcaccctgg actca tgcat catgaaaccc tcagccagcc tgcccgagtc cctgtattca 900 cctaccagaa ctggtgatga cgcccgcatg tggtggtact ttggctgcta cttctgcctg 960 cccatcctct tcacagtcac ctgccagctg gtgacatggc gggtgcgagg ccctccaggg 1020 aggaagtcag agtgcagggc cagcaagcac gagcagtgtg agagccagct caacagcacc 1080 gtggtgggcc tgaccgtggt ctacgccttc tgcaccctcc cagagaacgt ctgcaacatc 1140 gtggtggcct acctctccac cgagctgacc cgccagaccc tggacctcct gggcctcatc 1200 aaccagttct ccaccttctt caagggcgcc atcaccccag tgctgctcct ttgcatctgc 1260 aggccgctgg gccaggcctt cctggactgc tgctgctgct gctgctgtga ggagtgcggc 1320 ggggcttcgg aggcctctgc tgccaatggg tcggacaaca agctcaagac cgaggtgtcc 1380 tcttccatct acttccacaa gcccagggag tcacccccac tcctgcccct gggcacacct 1440 tgctga 1446 < 210 > 82 < 211 > 481 < 212 > PRT < 213 > Homo sapiens < 400 > 82 Met Arg Trp Leu Trp Pro Leu Wing Val Ser Leu Wing Val He Leu Wing 1 5 10 15 Val Gly Leu Ser Arg Val Ser Gly Gly Wing Pro Leu His Leu Gly Arg 20 25 30 His Arg Ala Glu Thr Gln Glu Gln Gln Ser Arg Ser Lys Arg Gly Thr 40 45 Glu Asp Glu Glu Ala Lys Gly Val Gln Gln Tyr Val Pro Glu Glu Trp 50 55 60 Wing Glu Tyr Pro Arg Pro He His Pro Wing Gly Leu Gln Pro Thr Lys 65 70 75 80 Pro Leu Val Wing Thr Ser Pro Asn Pro Asp Lys Asp Gly Gly Thr Pro 85 90 95 Asp Ser Gly Gln Glu Leu Arg Gly Asn Leu Thr Gly Wing Pro Gly Gln 100 105 110 Arg Leu Gln He Gln Asn Pro Leu Tyr Pro Val Thr Glu Ser Ser Tyr 115 120 125 Being Ala Tyr Ala He Met Leu Leu Ala Leu Val Val Phe Ala Val Gly 130 135 140 He Val Gly Asn Leu Ser Val Met Cys He Val Trp His Ser Tyr Tyr 145 150 155 160 Leu Lys Ser Wing Trp Asn Ser He Leu Wing Ser Leu Wing Leu Trp Asp 165 170 175 Phe Leu Val Leu Phe Phe Cys Leu Pro He Val He Phe Asn Glu He 180 185 190 Thr Lys Gln Arg Leu Leu Gly Asp Val Ser Cys Arg Ala Val Pro Phe 195 200 205 Met Glu Val Ser Ser Leu Gly Val Thr Thr Phe Ser Leu Cys Ala Leu 210 215 220 Gly He Asp Arg Phe His Val Wing Thr Ser Thr Leu Pro Lys Val Arg 225 230 235 240 Pro He Glu Arg Cys Gln Ser He Leu Ala Lys Leu Ala Val He Trp 245 250 255 Val Gly Ser Met Thr Leu Ala Val Pro Glu Leu Leu Leu Trp Gln Leu 260 265 270 Wing Gln Glu Pro Wing Pro Thr Met Gly Thr Leu Asp Ser Cys He Met 275 280 285 Lys Pro Ser Ala Ser Leu Pro Glu Ser Leu Tyr Ser Leu Val Met Thr 290 295 300 Tyr Gln Asn Wing Arg Met Trp Trp Tyr Phe Gly Cys Tyr Phe Cys Leu 305 310 315 320 Pro He Leu Phe Thr Val Thr Cys Gln Leu Val Thr Trp Arg Val Arg 325 330 335 Gly Pro Pro Gly Arg Lys Ser Glu Cys Arg Ala Ser Lys His Glu Gln 340 345 350 Cys Glu Ser Gln Leu Asn Ser Thr Val Val Gly Leu Thr Val Val Tyr 355 360 365 Wing Phe Cys Thr Leu Pro Glu Asn Val Cys Asn He Val Val Wing Tyr 370 375 380 Leu Ser Thr Glu Leu Thr Arg Gln Thr Leu Asp Leu Leu Gly Leu He 385 390 395 400 Asn Gln Phe Ser Thr Phe Phe Lys Gly Wing He Thr Pro Val Leu Leu 405 410 415 Leu Cys He Cys Arg Pro Leu Gly Gln Wing Phe Leu Asp Cys Cys Cys 420 425 430 Cys Cys Cys Cys Glu Glu Cys Gly Gly Wing Ser Glu Wing Be Ala Wing 435 440 445 Asn Gly Ser Asp Asn Lys Leu Lys Thr Glu Val Ser SeL Ser He Tyr 450 455 460 Phe His Lys Pro Arg Glu Pro Pro Pro Leu Leu Pro Leu Gly Thr Pro 465 470 475 480 Cys < 210 > 83 < 211 > 22 < 212 > DNA < 213 > Homo sapiens < 400 > 83 atgtggaacg cgacgcccag cg 22 < 210 > 84 < 211 > 22 < 212 > DNA < 213 > Homo sapiens < 400 > 84 tcatgtatta atactagatt ct 22 < 210 > 85 < 211 > 38 < 212 > DNA < 213 > Homo sapiens < 400 > 85 taccatgtgg aacgcgacgc ccagcgaaga gccggggt < 210 > 86 < 211 > 39 < 212 > DNA < 213 > Homo sapiens < 400 > 86 cggaattcat gtattaatac tagattctgt ccaggcccg 39 < 210 > 87 < 211 > 1101 < 212 > DNA < 213 > Homo sapiens < 400 > 87 atgtggaacg cgacgcccag cgaagagccg gggttcaacc tcacactggc cgacctggac 60 tgggatgctt cccccggcaa cgactcgctg ggcgacgagc tgctgcagct cttccccgcg 120 ccgctgctgg cgggcgtcac agccacctgc gtggcactct tcgtggtggg tatcgctggc 180 aacctgctca ccatgctggt ggtgtcgcgc ttccgcgagc tgcgcaccac caccaacctc 240 tacctgtcca gcatggcctt ctccgatctg ctcatcttcc tctgcatgcc cctggacctc 300 gttcgcctct ggcagtaccg gccctggaac ttcggcgacc tcctctgcaa actcttccaa 360 ttcgtcagtg agagctgcac ctacgccacg gtgctcacca tcacagcgct gagcgtcgag 420 cgctacttcg ccatctgctt cccactccgg gccaaggtgg tggtcaccaa ggggcgggtg 480 aagctggtca tcttcgtcat ctgggccgtg gccttctgca gcgccgggcc catcttcgtg 540 ctagtcgggg tggagcacga gaacggcacc gacccttggg acaccaacga gtgccgcccc 600 accgagtttg cggtgcgctc tggactgctc acggtcatgg tgtgggtgtc cagcatcttc 660 ttcttccttc ctgtcttctg tctcacggtc ctctacagtc tcatcggcag gaagctgtgg 720 cggaggaggc gcggcgatgc tgtcgtgggt gggaccagaa gcctcgctca ccacaagcaa 780 accgtgaaaa tgctggctgt agtggtgttt gccttcatcc tctgctggct ccccttccac 840 gtagggcgat atttatt ttc caaatccttt gfeíg'cctggct ccttggagat tgctcagatc 900 agccagtact gcaacctcgt gtcctttgtc ctcttctacc tcagtgctgc catcaacccc 960 attctgtaca acatcatgtc caagaagtac cgggtggcag tgttcagact tctgggattc 1020 gaacccttct cccagagaaa gctctccact ctgaaagatg aaagttctcg ggcctggaca gaatctagta 1080 to 1101 ttaatacatg < 210 > 88 < 211 > 366 < 212 > PRT < 213 > Homo sapiens < 400 > 88 Met Trp Asn Wing Thr Pro Ser Glu Glu Pro Gly Phe Asn Leu Thr Leu 1 5 10 15 Wing Asp Leu Asp Trp Asp Wing Ser Pro Gly Asn Asp Ser Leu Gly Asp 20 25 30 Glu Leu Leu Gln Leu Phe Pro Pro Wing Leu Leu Wing Gly Val Thr Wing 35 40 45 Thr Cys Val Wing Leu Phe Val Val Gly He Wing Gly Asn Leu Leu Thr 50 55 60 Met Leu Val Val Ser Arg Phe Arg Glu Leu Arg Thr Thr Thr Asn Leu 65 70 75 80 Tyr Leu Ser Ser Met Wing Pne Ser Asp Leu Leu He Phe Leu Cys Met «^^^^^^^ ^^^ 85 90 95 Pro Leu Asp Leu Val Arg Leu Trp Gln Tyr Arg Pro Trp Asn Phe Gly 100 105 110 Asp Leu Leu Cys Lys Leu Phe Gln Phe Val Ser Glu Ser Cys Thr Tyr 115 120 125 Wing Thr Val Leu Thr He Thr Wing Leu Ser Val Glu Arg Tyr Phe Wing 130 135 140 He Cys Phe Pro Leu Arg Wing Lys Val Val Val Thr Lys Gly Arg Val 145 150 155 160 Lys Leu Val He Phe Val He Trp Wing Val Wing Phe Cys Ser Wing Gly 165 170 175 Pro He Phe Val Leu Val Gly Val Glu His Glu Asn Gly Thr Asp Pro 180 185 190 Trp Asp Thr Asn Glu Cys Arg Pro Thr Glu Phe Wing Val Arg Ser Gly 195 200 205 Leu Leu Thr Val Met Val Trp Val Ser Ser He Phe Phe Phe Leu Pro 210 215 220 'to Phe Cys Leu Thr to Leu Leu s T Tro ^? É í > s & ^ ni! m: -Arg Arg Arg Arg Gly Asp Ala Val Val Gly Ala Ser Leu Arg Asp Gln 245 250 255 Asn His Lys Gln Thr Val Lys Met Leu Wing Val Val Val Phe Wing Phe 260 265 270 He Leu Cys Trp Leu Pro Phe His Val Gly Arg Tyr Leu Phe Ser Lys 275 280 285 Being Phe Glu Pro Gly Being Leu Glu He Wing Gln He Being Gln Tyr Cys 290 295 300 Asn Leu Val Ser Phe Val Leu Phe Tyr Leu Ser Ala Ala He Asn Pro 305 310 315 320 He Leu Tyr Asn He Met Ser Lys Lys Tyr Arg Val Wing Val Phe Arg 325 330 335 Leu Leu Gly Phe Glu Pro Phe Ser Gln Arg Lys Leu Ser Thr Leu Lys 340 345 350 Asp Glu Be Ser Arg Ala Trp Thr Glu Be Ser He Asn Thr 355 360 365 < 210 > 89 < 211 > 33 v2l2 > DNA 3 ^ -o or < 400 > 89 gcaagcttgt gccctcacca agccatgcga gcc 33 < 210 > 90 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 90 cggaattcag caatgagttc cgacagaagc 30 < 210 > 91 < 211 > 1842 < 212 > DNA < 213 > Homo sapiens < 400 > 91 atgcgagccc cgggcgcgct tctcgcccgc atgtcgcggc tactgcttct gctactgctc 60 aaggtgtctg cctcttctgc cctcggggtc gcccctgcgt ccagaaacga aacttgtctg 120 ggggagagct gtgcacctac agtgatccag cgccgcggca gggacgcctg gggaccggga 180 aattctgcaa gagacgttct gcgagcccga gcacccaggg aggagcaggg ggcagcgttt 240 cttgcgggac cctcctggga cctgccggcg gccccgggcc gtgacccggc tgcaggcaga 300 ggggcggagg cgtcggcagc cggacccccg ggacctccaa ccaggccacc tggcccctgg 360 aggtggaaag gtgctcgggg tcaggagcct tctgaaactt tggggagagg gaaccccacg 420 gccctccagc tcttccttca gatctcagag gaggaagaga agggtcccag aggcgctggc 480 atttccgggc gtagccagga gcagagtgtg aagacagtcc ccggagccag cgatcttttt 540 tactggccaa ggagagccgg gaaactccag ggttcccacc ctccaagacg 600 tggcggggca cgaagggtgg ACAA 11GC T'cgctggcc z 660 cagaatggat ccttgggtga aggaatccat gagcctgggg gtccccgccg gggaaacagc 720 acgaaccggc gtgtgagact gaagaacccc ttctacccgc tgacccagga gtcctatgga 780 gcctacgcgg tcatgtgtct gtccgtggtg atcttcggga ccggcatcat tggcaacctg 840 gcggtgatga gcatcgtgtg ccacaactac tacatgcgga gcatct ccaa ctccctcttg 900 gccaacctgg ccttctggga ctttctcatc atcttcttct gccttccgct ggtcatcttc 960 cacgagctga ccaagaagtg gctgctggag gacttctcct gcaagatcgt gccctatata 1020 gaggtcgctt ctctgggagt caccactttc accttatgtg ctctgtgcat agaccgcttc 1080 ccaacgtaca cgtgctgcca gatgtactac gaaatgatcg aaaactgttc ctcaacaact 1140 gccaaacttg ctgttatatg ggtgggagct ctattgttag cacttccaga agttgttctc 1200 gcaaggagga cgccagctga tttggggttt agtggccgag ctccggcaga aaggtgcatt 1260 attaagatct ctcctgattt accagacacc atctatgttc tagccctcac ctacgacagt 1320 gcgagactgt ggtggtattt tggctgttac ttttgtttgc ccacgctttt caccatcacc 1380 tgctctctag tgactgcgag gaaaatccgc aaagcagaga aagcctgtac ccgagggaat 1440 ttcaactaga aaacggcaga gagtcagatg aactgtacag tagtggcact gaccatttta 1500 tatggatttt gcattattcc tgaaaatatc tgcaacattg ttactgccta catggctaca 1560 ggggtttcac agcagacaat ggacctcctt aatatcatca gccagttcct tttgttcttt 1620 aagtcctgtg tcaccccagt cctccttttc tgtctctgca aacccttcag tcgggccttc 1680 atggagtgct gctgctgttg ctgtgaggaa tgcattcaga agtcttcaac ggt gaccagt 1740 gatgacaatg acaacgagta caccacggaa ctcgaactct cgcctttcag taccatacgc 1800 cgtgaaatgt ccacttttgc ttctgtcgga actcattgct ga 1842 < 210 > 92 < 211 > 613 < 212 > PRT < 213 > Homo sapiens J00 ^ > 'ro < ty 10 15 Leu Leu Leu Leu Lys Val Be Ala Be Ser Ala Leu Gly Val Ala Pro 20 25 30 Ala Ser Arg Asn Glu Thr Cys Leu Gly Glu Ser Cys Ala Pro Thr Val 35 40 45 He Gln Arg Arg Gly Arg Asp Wing Trp Gly Pro Gly Asn Ser Wing Arg 50 55 60 Asp Val Leu Arg Wing Arg Wing Pro Arg Glu Glu Gln Gly Wing Wing Phe 65 70 75 80 Leu Wing Gly Pro Ser Trp Asp Leu Pro Wing Wing Pro Gly Arg Asp Pro 85 90 95 15 Ala Ala Gly Arg Gly Ala Glu Ala Be Ala Ala Gly Pro Pro Gly Pro 100 105 110 Pro Thr Arg Pro Pro Gly Pro Trp Arg Trp Lys Gly Wing Arg Gly Gln 115 120 125 Glu Pro Ser Glu Thr Leu Gly Arg Gly Asn Pro Thr Ala Leu Gln Leu 130 135 140 Ppe Leu Gin Ser Glu Glu Glu Gl; i and Dro Ar Gly Ala 1 -: 150 ^^ É tSá & ^ ii ^ ^ He Ser Gly Arg Ser Gln Glu Gln Ser Val Lys Thr Val Pro Gly Wing 165 170 175 Being Asp Leu Phe Tyr Trp Pro Arg Arg Wing Gly Lys Leu Gln Gly Ser 180 185 190 5 His His Lys Pro Leu Ser Lys Thr Wing Asn Gly Leu Wing Gly His Glu 195 200 205 Gly Trp Thr He Wing Leu Pro Gly Arg Wing Leu Wing Gln Asn Gly Ser [0 210 215 220 Leu Gly Glu Gly He His Glu Pro Gly Gly Pro Arg Arg Gly Asn Ser 225 230 235 240 Thr Asn Arg Arg Val Arg Leu Lys Asn Pro Phe Tyr Pro Leu Thr Gln 245 250 255 Glu Ser Tyr Gly Ala Tyr Ala Val Met Cys Leu Ser Val Val He Phe 260 265 270 Gly Thr Gly He He Gly Asn Leu Wing Val Met Ser He Val Cys His 275 280 285 Asn Tyr Tyr Met Arg Ser He Ser Asn Ser Leu Leu Ala Asn Leu Ala 290 295 300 2 Aso P- ^ e Leu He He Dhc Poe yes & & amp; 305 310 315 320 His Glu Leu Thr Lys Lys Trp Leu Leu Glu Asp Phe Ser Cys Lys He 325 330 335 Val Pro Tyr He Glu Val Wing Ser Leu Gly Val Thr Thr Phe Thr Leu 340 345 350 Cys Ala Leu Cys He Asp Arg Phe Arg Ala Wing Thr Asn Val Gln Met 355 360 365 Tyr Tyr Glu Met He Glu Asn Cys Ser Ser Thr Thr Ala Lys Leu Ala 370 375 380 Val He Trp Val Gly Ala Leu Leu Leu Ala Leu Pro Glu Val Val Leu 385 390 395 400 Arg Gln Leu Ser Lys Glu Asp Leu Gly Phe Ser Gly Arg Wing Pro Wing 405 410 415 Glu Arg Cys He He Lys He Ser Pro Asp Leu Pro Asp Thr He Tyr 420 425 430 Val Leu Ala Leu Thr Tyr Asp Ser Wing Arg Leu Trp Trp Tyr Phe Gly 435 440 445 c \ 3 i y: Le _ Dro TT Lea - ^ e "i: I have your Val oO Thr Ala Arg Lys He Arg Lys Ala Glu Lys Ala Cys Thr Arg Gly Asn 465 470 475 480 Lys Arg Gln He Gln Leu Glu Be Gln Met Asn Cys Thr Val Val Wing 485 490 495 Leu Thr He Leu Tyr Gly Phe Cys He He Pro Glu Asn He Cys Asn 500 505 510 He Val Thr Ala Tyr Met Ala Thr Gly Val Ser Gln Gln Thr Met Asp 515 520 525 Leu Leu Asn He He Ser Gln Phe Leu Leu Phe Phe Lys Ser Cys Val 530 535 540 Thr Pro Val Leu Leu Phe Cys Leu Cys Lys Pro Phe Ser Arg Ala Phe 545 550 555 560 Met Glu Cys Cys Cys Cys Cys Cys Glu Glu Cys He Gln Lys Ser Ser 565 570 575 Thr Val Thr Ser Asp Asp Asn Asp Asn Glu Tyr Thr Thr Glu Leu Glu 580 585 590 Leu Ser Pro Phe Ser Thr He Arg Arg Glu Met Ser Thr Phe Ala Ser 595 600 605 : ± v Thr -is r 610 < 210 > 93 < 211 > 34 < 212 > DNA < 213 > Homo sapiens < 400 > 93 cagaattcag agaaaaaaag tgaatatggt tttt 34 < 210 > 94 < 211 > 32 < 212 > DNA < 213 > Homo sapiens < 400 > 94 ttggatccct ggtgcataac aattgaaaga at 32 < 210 > 95 < 211 > 1248 < 212 > DNA < 213 > Homo sapiens < 400 > 95 atggtttttg ctcacagaat ggataacagc aagccacatt tgattattcc tacacttctg 60 gtgcccctcc aaaaccgcag ctgcactgaa acagccacac ctctgccaag ccaatacctg atggaattaa 120 g gaggagca cagttggatg agcaaccaaa ca ^ accttca ctatgtgctg 180 aaaTcaggg agccagcatc tct: tg3 ~ - '-gt gtt tctaLc 2-10 ttcggcaatt ccctggtttg tttggtcatc cataggagta ggaggactca gtctaccacc 300 aactactttg tggtctccat ggcatgtgct gaccttctca tcagcgttgc cagcacgcct 360 ttcgtcctgc tccagttcac cactggaagg tggacgctgg gtagtgcaac gtgcaaggtt 420 gtgcgatatt ttcaatatct cactccaggt gtccagatct acgttctcct ctccatctgc 480 atagaccggt tctacaccat cgtctatcct ctgagcttca aggtgtccag agaaaaagcc 540 aagaaaatga ttgcggcatc gtggatcttt gatgcaggct ttgtgacccc tgtgctcttt 600 ttctatggct ccaactggga cagtcattgt aactatttcc tcccctcctc ttgggaaggc 660 ctgtcatcca actgcctaca cttcttggtg ggctttgtga ttccatctgt cctcataatt 720 ttattttacc aaaaggtcat aaaatatatt tggagaatag gcacagatgg ccgaacggtg 780 aggaggacaa tgaacattgt ccctcggaca aaagtgaaaa ctatcaagat gttcctcatt 840 ttaaatctgt tgtttttgct ctcctgg ctg ccttttcatg tagctcagct atggcacccc 900 catgaacaag actataagaa aagttccctt gttttcacag ctatcacatg gatatccttt 960 agttcttcag cctctaaacc tactctgtat tcaatttata atgccaattt tcggagaggg 1020 atgaaagaga ctttttgcat gtcctctatg aaatgttacc gaagcaatgc ctatactatc 1080 acaacaagtt caaggatggc caaaaaaaac tacgttggca tttcagaaat cccttccatg 1140 ttaccaaaga gccaaaacta ctcgatctat gactcatttg acagagaagc caaggaaaaa 1200 ggcccattaa aagcttgctt ctcaaatcca ccaaatactt ttgtctaa 1248 < 210 > 96 < 211 > 415 < 212 > PRT < 213 > Homo sapiens < 400 > 96 Met Val Phe Ala His g Met Osp Asp Ser Lys Pro His Leu He He 5"O _5 Or r- > ~ - C K S t? ***** *. * J * ** which US 20 25 30 Thr Pro Leu Pro Ser Gln Tyr Leu Met Glu Leu Ser Glu Glu His Ser 35 40 45 Trp Met Ser Asn Gln Thr Asp Leu His Tyr Val Leu Lys Pro Gly Glu 50 55 60 Val Ala Thr Ala Ser He Phe Phe Gly He Leu Trp Leu Phe Ser He 65 70 75 80 Phe Gly Asn Ser Leu Val Cys Leu Val He His Arg Ser Arg Arg Thr 85 90 95 Gln Ser Thr Thr Asn Tyr Phe Val Val Ser Met Wing Cys Wing Asp Leu 100 105 110 Leu He Ser Val Ala Ser Thr Pro Phe Val Leu _, eu Gln Phe Thr Thr 115 120 125 Gly Arg Trp Thr Leu Gly Be Wing Thr Cys Lys Val Val Arg Tyr Phe 130 135 140 Gln Tyr Leu Thr Pro Gly Val Gln He Tyr Val Leu Leu Ser He Cys 145 150 155 160 He -so Arg Phe Tyr Thr He Val Tyr Pro Le_ Se: ^ e Lys Val Ser .65 .70 H5 ^ ^? ^ ^^^ s = ^^^^ Arg Glu Lys Wing Lys Lys Met Wing Wing Ser Trp He Phe Asp Wing 180 185 190 Gly Phe Val Thr Pro Val Leu Phe Phe Tyr Gly Ser Asn Trp Asp Ser 195 200 205 His Cys Asn Tyr Phe Leu Pro Being Ser Trp Glu Gly Thr Wing Tyr Thr 210 215 220 Val He His Phe Leu Val Gly Phe Val He Pro Ser Val Leu He He 225 230 235 240 Leu Phe Tyr Gln Lys Val He Lys Tyr He Trp Arg He Gly Thr Asp 245 250 255 Gly Arg Thr Val Arg Arg Thr Met Asn He Val Pro Arg Thr Lys Val 260 265 270 Lys Thr He Lys Met Phe Leu He Leu Asn Leu Leu Phe Leu Leu Ser 275 280 285 Trp Leu Pro Phe His Val Wing Gln Leu Trp His Pro His Glu Gln Asp 290 295 300 Tyr Lys Lys Ser Ser Leu Val Phe Thr Wing He Thr Trp He Ser Phe 305 3 0 315 32C Ser STL bí Pro "\ r Ser He ^ - A3 -.? L? .- 325 330 335 Phe Arg Arg Gly Met Lys Glu Thr Phe Cys Met Ser Ser Met Lys Cys 340 345 350 Tyr Arg Ser Asn Ala Tyr Thr He Thr Thr Ser Ser Arg Met Ala Lys 355 360 365 Lys Asn Tyr Val Gly He Ser Glu He Pro Ser Met Wing Lys Thr He 370 375 380 Thr Lys Asp Ser He Tyr Asp Ser Phe Asp Arg Glu Wing Lys Glu Lys 385 390 395 400 Lys Leu Wing Trp Pro He Asn Ser Asn Pro Pro Asn Thr Phe Val 405 410 415 < 210 > 97 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 97 ggaaagctta acgatcccca ggagcaacat 30 < 210 > 98 < 211 > 31 < 212 > DNA < 213 > Homo sapiens < 400 > 98 ctgggatcct acgagagcat ttttcacaca g 31 < 210 > 99 < 211 > 1842 < 212 > DNA < 213 > Homo sapiens < 400 > 99 atggggccca ccctagcggt tcccaccccc tatggctgta ttggctgtaa gctaccccag 60 ccagaatacc caccggctct aatcatcttt atgttctgcg cgatggttat caccatcgtt 120 gtagacctaa tcggcaactc catggtcatt ttggctgtga cgaagaacaa gaagctccgg 180 aattctggca acatcttcgt ggtcagtctc tctgtggccg atatgctggt ggccatctac 240 tgatgctgca ccataccctt tgccatgtcc attgggggct gggatctgag ccagttacag 300 tgccagatgg tcgggttcat cacagggctg agtgtggtcg gctccatctt caacatcgtg 360 tcaaccgtta gcaatcgcta ctgctacatc tgccacagcc tccagtacga acggatcttc 420 agtgtgcgca atacctgcat ctacctggtc atcacctgga tcatgaccgt cctggctgtc 480 ctgcccaaca tgtacattgg caccatcgag tacgatcctc gcacctacac ctgcatcttc 540 aactatctga acaaccctgt cttcactgtt accatcgtct gcatccactt cgtcctccct 600 ctcctcatcg tgggtttctg ctacgtgagg atctggacca aagtgctggc ggcccgtgac 660 cctgcagggc agaatcctga caaccaactt gctgaggttc gcaattttct aaccatgttt 720 gtgatcttcc tcctctttgc agtgtgctgg tgccctatca acgtgctcac tgtcttggtg 780 gctgtcagtc cgaaggagat ggcaggcaag atccccaact ggctttatct tgcagcctac 840 ttcatagcct acttcaa cag ctgcctcaac gctgtgatct acgggctcct caatgagaat 900 ttccgaagag aatac'ggac catcttccat gctatgcggc accctatcat attcttccct 960 ggcctcatca gtgatattcg tgagatgcag gaggcccgta ccctggcccg cgcccgtgcc 1020 * SSS? ?? u? ~ J * a *? e3 1i ** ~. ' ,, catgctcgcg accaagctcg tgaacaagac cgtgcccatg cctgtcctgc tgtggaggaa 1080 atgtccggaa accccgatga tgttccatta cctggtgatg ctgcagctgg ccaccccgac 1140 cgtgcctctg gccaccctaa gccccattcc agatcctcct ctgcctatcg caaatctgcc 1200 tctacccacc acaagtctgt ctttagccac tccaaggctg cctctggtca cctcaagcct 1260 gtctctggcc actccaagcc tgcctctggt caccccaagt ctgccactgt ctaccctaag 1320 cctgcctctg tccatttcaa gggtgactct gtccatttca agggtgactc tgtccatttc 1380 aagcctgact ctgttcattt caagcctgct tccagcaacc ccaagcccat cactggccac 1440 catgtctctg ctggcagcca ctccaagtct gccttcagtg ctgccaccag ccaccctaaa 1500 cccatcaagc cagctaccag ccatgctgag cccaccactg ctgactatcc caagcctgcc 1560 actaccagcc accctaagcc cgctgctgct gacaaccctg agctctctgc ctcccattgc 1620 cccgagatcc ctgccattgc ccaccctgtg tctgacgaca gtgacctccc tgagtcggcc 1680 tctagccctg ccgctgggcc caccaagcct gctgccagcc agctggagtc tgacaccatc 1740 gctgaccttc ctgaccctac tgtagtcact accagtacca atgattacca tgatgtcgtg 1800 gttgttgatg ttgaagatga tcctgatgaa atggctgtgt ga 1842 < 210 > 100 < 211 > 613 < 212 > PRT < 213 > Homo sapiens < 400 > 100 Met Gly Pro Thr Leu Wing Val Pro Thr Pro Tyr Gly Cys He Gly Cys 10 15 Lys Leu Pro Gln Pro Glu Tyr Pro Pro Wing Leu He He Phe Met Phe 20 25 30 Cys Ala Met Val He Tnr lie Val Val Asp L a He -sn Ser Met 40 45 35 Val He Leu Ala Val Thr Lys Asn Lys Lys Leu Arg Asn Ser Gly Asn 50 55 60 He Phe Val Val Ser Leu Ser Val Ala Asp Met Leu Val Ala He Tyr 75 80 65 70 Pro Tyr Pro Leu Met Leu His Wing Met Be He Gly Gly Trp Asp Leu «^ 90 95 Be Gln Leu Gln Cys Gln Met Val Gly Phe He Thr Gly Leu Ser Val 100 105 H ° Val Gly Ser He Phe Asn He Val Wing He Wing He Asn Arg Tyr Cys 115 120 125 Tyr He Cys His Ser Leu Gln Tyr Glu Arg He Phe Ser Val Arg Asn 130 135 140 Thr Cys He Tyr Leu Val He Thr Trp He Met Thr Val Leu Wing Val 145 150 155 160 Leu Pro Asn Met Tyr He Gly Thr He Glu Tyr Asp Pro Arg Thr Tyr 165 170 175 Thr Cys He Phe Asn Tyr Leu Asn ñsn Pro Val Phe Thr Val Thr He 180 185 190 a? ^ ¿Val Cys He His Phe Val Leu Pro Leu Leu He Val Gly Phe Cys Tyr 195 200 205 Val Arg He Trp Thr Lys Val Leu Ala Wing Arg Asp Pro Wing Gly Gln 210 215 220 Asn Pro Asp Asn Gln Leu Wing Glu Val Arg Asn Phe Leu Thr Met Phe 225 230 235 240 Val He Phe Leu Leu Phe Wing Val Cys Trp Cys Pro He Asn Val Leu 245 250 255 Thr Val Leu Val Wing Val Ser Pro Lys Glu Met Wing Gly Lys He Pro 260 265 270 Asn Trp Leu Tyr Leu Wing Ala Tyr Phe He Wing Tyr Phe Asn Ser Cys 275 280 285 Leu Asn Ala Val He Tyr Gly Leu Leu Asn Glu Asn Phe Arg Arg Glu 290 295 300 Tyr Trp Thr He Phe His Wing Met Arg His Pro He He Phe Phe Pro 305 310 315 320 Gly Leu He Ser Asp He Arg Glu Met Gln Glu Ala Arg Thr Leu Ala 325 330 335 -rg Ta Arg Ala His -_a Arg Aso Gln Wing Arg Glu Gln Aso Arg Wing 340 345 350 His Wing Cys Pro Wing Val Glu Glu Thr Pro Met Asn Val Arg Asn Val 355 360 365 Pro Leu Pro Gly Asp Ala Ala Ala Gly His Pro Asp Arg Ala Ser Gly 370 375 380 His Pro Lys Pro His Ser Arg Ser Ser Ser Ala Tyr Arg Lys Ser Ala 385 390 395 400 Ser Thr His His Lys Ser Val Phe Ser His Ser Lys Ala Ala Ser Gly 405 410 415 His Leu Lys Pro Val Ser Gly His Ser Lys Pro Wing Ser Gly His Pro 420 425 430 Lys Ser Wing Thr Val Tyr Pro Lys Pro Wing Ser Val His Phe Lys Gly 435 440 445 Asp Ser Val His Phe Lys Gly Asp Ser Val His Phe Lys Pro Asp Ser 450 455 460 Val His Phe Lys Pro Wing Ser Ser Asn Pro Lys Pro He Thr Gly His 465 470 475 480 His Val Ser Ala Gly Ser His Ser Lys Ser Ala Phe Ser Ala Ala Thr 485 490 495 Pro Lys Pro He Lys Pro Ala Thr Ser His Ala Glu Pro Thr Ser His 500 505 510 Thr Wing Asp Tyr Pro Lys Pro Wing Thr Thr Ser His Pro Lys Pro Wing 515 520 525 Ala Ala Asp Asn Pro Glu Leu Ser Ala Be His Cys Pro Glu He Pro 530 535 540 Ala He Ala His Pro Val Ser Asp Asp Ser Asp Leu Pro Glu Ser Ala 545 550 555 560 Be Ser Pro Ala Ala Gly Pro Thr Lys Pro Ala Ala Ser Gln Leu Glu 565 570 575 Be Asp Thr He Wing Asp Leu Pro Asp Pro Thr Val Val Thr Thr Ser 585 590 580 Thr Asn Asp Tyr His Asp Val Val Val Val Asp Val Glu Asp Asp Pro 595 600 605 Asp Glu Met Wing Val 610 < 210 > 101 < 211 > 32 < 212 > DNA < 213 > Homo sapiens < 400 > 101 tccaagcttc gccatgggac ataacgggag ct 32 < 210 > 102 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 102 cgtgaattcc aagaatttac aatccttgct 30 < 210 > 103 < 211 > 1548 < 212 > DNA < 213 > Homo sapiens < 400 > 103 atgggacata acgggagctg gatctctcca aatgccagcg agccgcacaa cgcgtccggc 60 gccgaggctg cgggtgtgaa ccgcagcgcg ctcggggagt tcggcgaggc gcagctgtac 120 cgccagttca ccaccaccgt gcaggtcgtc atcttcatag gctcgctgct cggaaacttc 180 atggtgttat ggtcaacttg ccgcacaacc gtgttcaaat ctgtcaccaa caggttcatt 240 aaaaacctgg cctgctcggg gatttgtgcc agcctggtct gtgtgccctt cgacatcatc 300 ctcagcacca gtcctcactg ttgctggtgg atctacacca tgctcttctg caaggtcgtc 360 aaatttttgc acaaagtatt ctgctctgtg accatcctca gcttccctgc tattgctttg 420 gacaggtact actcagtcct ctatccactg gagaggaaaa tatctgatgc caagtcccgt 480 gaactggtga tgtacatctg ggcccatgca gtggtggcca gtgtccctgt gtttgcagta 540 accaatgtgg ctgacatcta tgccacgtcc acctgcacgg aagtctggag caactccttg 600 ggccacctgg tgtacgttct ggtgta aac atcaccacgg tcattgtgcc tgtggtggtg 660 gtgttcctct tcttgatact gatccgacgg gccctgagtg ccagccagaa gaagaaggtc 720 atcatagcag cgctccggac cccacagaac accatctcta ttccctatgc ctcccagcgg 780 gaggccgagc tgcacgccac cctgctctcc atggtgatgg tcttcatctt gtgtagcgtg 840 ccctatgcca ccctggtcgt ctaccagact gtgctcaatg tccctgacac ttccgtcttc 900 ttgctgctca ctgctgtttg gctgcccaaa gtctccctgc tggcaaaccc tgttctcttt 960 acaaatctgt cttactgtga ccgcaagtgc ttgataggga ccctggtgca actacaccac 1020 gccgtaatgt cggtacagtc ggtcagtaca gggagtggca tggctgaggc cagcctggaa 1080 cccagcatac gctcgggtag ccagctcctg gagatgttcc acattgggca gcagcagatc 1140 cagaggatga tttaagccca ggaagagagt gaggccaagt acattggctc agctgacttc 1200 caggccaagg agatatttag cacctgcctg gagggagagc aggggccaca gtttgcgccc 1260 tctgccccac ccctgagcac agtggactct gtatcccagg tggcaccggc agcccctgtg 1320 cattccctga gaacctgaaa taagtattcc ctgcagtttg gctttgggcc ttttgagttg 1380 cctcctcag t ggctctcaga gacccgaaac agcaagaagc ggctgcttcc ccccttgggc 1440 aacaccccag aagagctgat ccagacaaag gtgcccaagg taggcagggt ggagcggaag 1500 atgagcagaa acaataaagt gagcattttt ccaaaggtgg attcctag 1548 < 210 > 104 < 211 > 515 < 212 > PRT < 213 > Homo sapiens < 400 > 104 Met Gly His Asn Gly Ser Trp He Ser Pro Asn Ala Ser Glu Pro His 1 5 10 15 Asn Ala Ser Gly Ala Glu To the Aia Cly Val Asn Arg Se- ^ the Leu Gly 20 25 30 ftfe ^ a ^ SISM ^ faitejgg ÉilÉ'f Glu Phe Gly Glu Wing Gln Leu Tyr Arg Gln Phe Thr Thr Thr Val Gln 35 40 45 Val Val He Phe He Gly Ser Leu Leu Gly Asn Phe Met Val Leu Trp 50 55 60 Be Thr Cys Arg Thr Thr Val Phe Lys Ser Val Thr Asn Arg Phe He 65 70 75 80 Lys Asn Leu Wing Cys Ser Gly He Cys Wing Ser Leu Val Cys Val Pro 85 90 95 Phe Asp He He Leu Ser Thr Ser Pro His Cys Cys Trp Trp He Tyr 100 105 110 Thr Met Leu Phe Cys Lys Val Val Lys Phe Leu His Lys Val Phe Cys 115 120 125 Being Val Thr He Leu Being Phe Pro Wing He Wing Leu Asp Arg Tyr Tyr 130 135 140 Ser Val Leu Tyr Pro Leu Glu Arg Lys He Ser Asp Ala Lys Ser Arg 145 150 155 160 Glu Leu Val Met Tyr He Trp Wing Hrs Wing Val Val Wing Ser Val Pro 165 170 175 Val Phe Wing Val Thr Asn Val Wing Asp He Tyr Wing Thr Ser Thr Cys 180 185 190 Thr Glu Val Trp Ser Asn Ser Leu Gly His Leu Val Tyr Val Leu Val 195 200 205 Tyr Asn He Thr Thr Val He Val Val Val Val Val Phe Leu Phe 210 215 220 Leu He Leu He Arg Arg Ala Leu Ser Ala Be Gln Lys Lys Lys Val 225 230 235 240 He He Ala Ala Leu Arg Thr Pro Gln Asn Thr He Ser He Pro Tyr 245 250 255 Ala Ser Gln Arg Glu Ala Glu Leu His Ala Thr Leu Leu Ser Met Val 260 265 270 Met Val Phe He Leu Cys Ser Val Pro Tyr Ala Thr Leu Val Val Tyr 275 280 285 Gln Thr Val Leu Asn Val Pro Asp Thr Ser Val Phe Leu Leu Leu Thr 290 295 300 Wing Val Trp Leu Pro Lys Val Ser Leu Leu Wing Asn Pro Val Leu Phe 305 310 315 320 Leu Th- Val 3n Lys Ser Val Arg Lys Cys Leu He Gly Tn Leu Val 325 330 335 Gln Leu His His Arg Tyr Ser Arg Arg Asn Val Val Ser Thr Gly Ser 340 345 350 Gly Met Wing Glu Wing Being Leu Glu Pro Being He Arg Being Gly Being Gln 355 360 365 Leu Leu Glu Met Phe His He Gly Gln Gln Gln He Phe Lys Pro Thr 370 375 380 Glu Asp Glu Glu Glu Ser Glu Wing Lys Tyr He Gly Ser Wing Asp Phe 385 390 395 400 Gln Ala Lys Glu He Phe Ser Thr Cys Leu Glu Gly Glu Gln Gly Pro 405 410 415 Gln Phe Ala Pro Ser Ala Pro Pro Leu Ser Thr Val Asp Ser Val Ser 420 425 430 Gln Val Ala Pro Ala Ala Pro Val Glu Pro Glu Thr Phe Pro Asp Lys 435 '440 445 Tyr Ser Leu Gln Phe Gly Phe Gly Pro Phe Glu Leu Pro Pro Gln Trp 450 455 460 Leu Ser Glu Thr Arg Asn Ser Lys Lys Arg Leu Leu Pro Pro Leu Gly 465 470 475 480 Asn Thr Pro Glu Gla _eu He Gln Thr Lvs Val Pro Lys Va_ Gly Arg 485 490 495 Val Glu Arg Lys Met Ser Arg Asn Asn Lys Val Ser He Phe Pro Lys 500 505 510 Val Asp Ser 515 < 210 > 105 < 211 > 29 < 212 > DNA < 213 > Homo sapiens < 400 > 105 ggagaattca ctaggcgagg cgctccatc 29 < 210 > 106 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 106 ggaggatcca ggaaacctta ggccgagtcc 30 < 210 > 107 < 211 > 1164 < 212 > DNA < 213 > Homo sapiens í ^? ^ kil? ^, < 400 > 107 atgaatcggc accatctgca ggatcacttt ctggaaatag acaagaagaa ctgctgtgtg 60 ttccgagatg acttcattgc caaggtgttg ccgccggtgt tggggctgga gtttatcttt 120 gggcttctgg gcaatggcct tgccctgtgg attttctgtt tccacctcaa gtcctggaaa 180 tccagccgga ttttcctgtt caacctggca gtagctgact ttctactgat catctgcctg 240 tggactacta ccgttcgtga tgtgcggcgt tcagactgga actttgggga catcccttgc 300 cggctggtgc tcttcatgtt tgccatgaac cgccagggca gcatcatctt cctcacggtg 360 gtggcggtag acaggtattt ccgggtggtc catccccacc acgccctgaa caagatctcc 420 aattggacag cagccatcat ctcttgcctt ctgtggggca tcactgttgg cctaacagtc 480 cacctcctga agaagaagtt gctgatccag aatggccctg caaatgtgtg catcagcttc 540 agcatctgcc ataccttccg gtggcacgaa gctatgttcc tcctggagtt cctcctgccc 600 tcctgttctg ctgggcatca attatctgga ctcagccaga gcctgcggca gagacaaatg 660 gaccggcatg ccaagatcaa gagagccatc accttcatca tggtggtggc catcgtcttt 720 gtcatctgct tccttcccag cgtggttgtg cggatccgca tcttctggct cctgcacact 780 tcgggcacgc agaattgtga agtgtaccgc tcggtggacc tggcgttctt tatcactctc 840 agcttcacct acatga ACAG catgctggac cccgtggtgt actacttctc cagcccatcc 900 tttcccaact tcttctccac tttgatcaac cgctgcctcc agaggaagat gacaggtgag 960 ccagataata accgcagcac gagcgtcgag ctcacagggg accccaacaa aaccagaggc 1020 gctccagagg cgttaatggc caactccggt gcccctctta gagccatgga tctgggccca 1080 accattccaa acctcaaata gaagggacat tgtcaccaag aaccagcatc tctggagaaa 1140 gttgcatcga cagttgggct GTAA 1164 < 210 > 108 < 211 > 387 < 212 > PRT < 213 > Homo sapiens < 400 > 108 - *** «fcs eaaL ^ diaés Met Asn Arg His His Leu Gln Asp His Phe Leu Glu He Asp Lys Lys 1 5 10 15 Asn Cys Cys Val Phe Arg Asp Asp Phe He Wing Lys Val Leu Pro Pro 20 25 30 Val Leu Gly Leu Glu Phe He Phe Gly Leu Leu Gly Asn Gly Leu Ala 35 40 45 Leu Trp He Phe Cys Phe His Leu Lys Ser Trp Lys Ser Ser Arg He 50 55 60 Phe Leu Phe Asn Leu Wing Val Wing Asp Phe Leu Leu He He Cys Leu 65 70 75 80 Pro Phe Val Met Asp Tyr Tyr Val Arg Arg As Asp Trp Asn Phe Gly 85 90 95 Asp He Pro Cys Arg Leu Val Leu Phe Met Phe Ala Met Asn Arg Gln 100 105 110 Gly Ser He He Phe Leu Thr Val Val Wing Val Asp Arg Tyr Phe Arg 115 120 125 Val Val His Pro His His Wing Leu Asn Lys He Ser Asn Trp Thr Wing 130 135 140 Wing He He Ser Cys Leu Leu tro Gly He Thr Val Gly Leu Thr Val 145 150 155 160 His Leu Leu Lys Lys Lys Leu He Gln Asn Gly Pro Wing Asn Val 165 170 175 Cys He Ser Phe Ser He Cys His Thr Phe Arg Trp His Glu Ala Met 180 185 190 Phe Leu Leu Glu Phe Leu Leu Pro Leu Gly He He Leu Phe Cys Ser 195 200 205 Wing Arg He He Trp Ser Leu Arg Gln Arg Gln Met Asp Arg His Wing 210 215 220 Lys He Lys Arg Wing He Thr Phe He Met Val Val Wing He Val Phe 225 230 235 240 Val He Cys Phe Leu Pro Ser Val Val Val Arg He Arg He Phe Trp 245 250 255 Leu Leu His Thr Ser Gly Thr Gln Asn Cys Glu Val Tyr Arg Ser Val 260 265 270 Asp Leu Ala Phe Phe He Thr Leu Ser Phe Thr Tyr Met Asn Ser Met 275 280 285 Leu Asp Pro Val Val Tyr Tyr Phe Ser Ser Pro Pro Phe Pro Asn Pns 290 295 300 Phe Ser Thr Leu He Asn Arg Cys Arg Lys Met Thr Gly Glu 305 310 315 320 Pro Asp Asn Asn Arg Ser Thr Ser Val Glu Leu Thr Gly Asp Pro Asn 325 330 335 Lys Thr Arg Gly Ala Pro Glu Ala Leu Met Ala Asn Ser Gly Glu Pro 340 345 350 Trp Ser Pro Ser Tyr Leu Gly Pro Thr Ser Asn Asn His Ser Lys Lys 355 360 365 Gly His Cys His Gln Glu Pro Wing Ser Leu Glu Lys Gln Leu Gly Cys 370 375 380 Cys He Glu 385 < 210 > 109 < 211 > 37 < 212 > DNA < 213 > Homo sapiens < 400 > 109 accatggctt gcaatggcag tgcggccagg gggcact 37 ^ .210 > 110 < 211 > 39 < 212 > DNA < 213 > Homo sapiens < 400 > 110 cgaccaggac aaacagcatc ttggtcactt gtctccggc 39 < 210 > 111 < 211 > 39 < 212 > DNA < 213 > Homo sapiens < 400 > 111 gaccaagatg ctgtttgtcc tggtcgtggt gtttggcat 39 < 210 > 112 < 211 > 35 < 212 > DNA < 213 > Homo sapiens < 400 > 112 cggaattcag gatggatcgg tctcttgctg cgcct 35 < 210 > 113 < 211 > 1212 < 212 > DNA < 213 > Homo sapiens < 400 > 113 atggcttgca atggcagtgc ggccaggggg cactttgacc ctgaggactt gaacctgact 60 gacgaggcac tgagactcaa gtacctgggg ccccagcaga cagagctgtt catgcccatc 120 tgtgccacat acctgctgat cttcgtggtg ggcgctgtgg gcaatgggct gacctgtctg 180 gtcatcctgc gccacaaggc catgcgcacg cctaccaact actacctctt cagcctggcc 240 gtgtcggacc tgctggtgct gctggtgggc ctgcccctgg agctctatga gatgtggcac 300 aactacccct tcctgctggg cgttggtggc tgctatttcc gcacgctact gtttgagatg 360 gtctgcctgg cctcagtgct caacgtcact gccctgagcg tggaacgcta tgtggccgtg 420 gtgcacccac tccaggccag gtccatggtg acgcgggccc atgtgcgccg agtgcttggg 480 gccgtctggg gtcttgccat gctctgctcc ctgcccaaca ccagcctgca cggcatccgg 540 cagctgcacg tgccctgccg gggcccagtg ccagactcag ctgtttgcat gctggtccgc 600 ccacgggccc tctacaacat ggtagtgcag accaccgcgc tgctcttctt ctgcctgccc 660 atggccatca tgagcgtgct ctacctgctc attgggctgc gactgcggcg ggagaggctg 720 ctgctcatgc aggaggccaa gggcaggggc tctgcagcag ccaggtccag atacacctgc 780 aggctccagc agcacgatcg caagtgacca gggccggaga agatgctgtt tgtcctggtc 840 gtggtgtttg gcatct gctg ggccccgttc cacgccgacc gcgtcatgtg gagcgtcgtg 900 tcacagtgga cagatggcct gcacctggcc ttccagcacg tgcacgtcat ctccggcatc 960 ttcttctacc tgggctcggc ggccaacccc gtgctctata gcctcatgtc cagccgcttc 1020 cgagagacct tccaggaggc cctgtgcctc ggggcctgct gccatcgcct cagaccccgc 1080 cacagctccc acagcctcag caggatgacc acaggcagca ccctgtgtga tgtgggctcc 1140 ctgggcagct gggtccaccc cctggctggg aacgatggcc cagaggcgca gcaagagacc gatccatcct 1200 ga 1212 < 210 > 114 < 211 > 403 < 212 > PRT < 213 > Ho or sapiens < 00 > ll? < J 1 *, 22 'go? - Met Wing Cys Asn Gly Wing Wing Wing Arg Gly His Phe Asp Pro Glu Asp 1 5 10 15 Leu Asn Leu Thr Asp Glu Ala Leu Arg Leu Lys Tyr Leu Gly Pro Gln 25 30 Gln Thr Glu Leu Phe Met Pro He Cys Wing Thr Tyr Leu Leu He Phe 35 40 45 Val Val Gly Ala Val Gly Asn Gly Leu Thr Cys Leu Val He Leu Arg 50 55 60 His Lys Wing Met Arg Thr Pro Thr Asn Tyr Tyr Leu Phe Ser Leu Wing 65 70 75 80 Val Ser Asp Leu Leu Val Leu Leu Val Gly Leu Pro Leu Glu Leu Tyr 90 95 Glu Met Trp His Asn Tyr Pro Phe Leu Leu Gly Val Gly Gly Cys Tyr 100 105 110 Phe Arg Thr Leu Leu Phe Glu Met Val Cys Leu Ala Ser Val Leu Asn 115 120 125 Val Thr Ala Leu Ser Val Glu Arg Tyr Val Val Val Val His Pro Leu 130 135 140 Gln Ala Arg Ser Met Val Thr Arg Ala His Val Arg Arg Va_ Leu Gly 145 150 155 160 Wing Val Trp Gly Leu Wing Met Leu Cys Ser Leu Pro Asn Thr Ser Leu 165 170 175 His Gly He Arg Gln Leu His Val Pro Cys Arg Gly Pro Val Pro Asp 180 185 190 Be Wing Val Cys Met Leu Val Arg Pro Arg Wing Leu Tyr Asn Met Val 195 200 205 Val Gln Thr Thr Ala Leu Leu Phe Phe Cys Leu Pro Met Ala He Met 210 215 220 Ser Val Leu Tyr Leu Leu He Gly Leu Arg Leu Arg Arg Glu Arg Leu 225 230 235 240 Leu Leu Met Gln Glu Ala Lys Gly Arg Gly Ser Ala Ala Ala Arg Ser 245 250 255 Arg Tyr Thr Cys Arg Leu Gln Gln His Asp Arg Gly Arg Arg Gln Val 260 265 270 Thr Lys Met Leu Phe Val Leu Val Val Val Phe Gly He Cys Trp Wing 275 280 285 Pro Phe His Wing Asp Arg Val Met Trp Ser Val Val: r C_n Trp Thr 290 295 300 Asp Gly Leu His Leu Wing Phe Gln His Val His Val He Ser Gly He 305 310 315 320 Phe Phe Tyr Leu Gly Ser Ala Ala Asn Pro Val Leu Tyr Ser Leu Met 325 330 335 Being Ser Arg Phe Arg Glu Thr Phe Gln Glu Wing Leu Cys Leu Gly Wing 340 345 350 Cys Cys His Arg Leu Arg Pro Arg His Ser Ser His Ser Leu Ser Arg 355 360 365 Met Thr Thr Gly Ser Thr Leu Cys Asp Val Gly Ser Leu Gly Ser Trp 370 375 380 Val His Pro Leu Wing Gly Asn Asp Gly Pro Glu Wing Gln Gln Glu Thr 385 390 395 400 Asp Pro Ser < 210 > 115 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 115 ggaagcttca ggcccaaaga tggggaacat 30 < 210 > 116 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 116 gtggatccac ccgcggagga cccaggctag 30 < 210 > 117 < 211 > 1098 < 212 > DNA < 213 > Homo sapiens < 400 > 117 tcactgcaga atggggaaca caactcctcg atgagctgta ccatcgacca taccatccac 60 cagacgctgg ccccggtggt ctatgttacc gtgctggtgg tgggcttccc ggccaactgc 120 acttcggcta ctgtccctct cctgcagatc aaggcccgga acgagctggg cgtgtacctg 180 tgcaacctga cggtggccga cctcttctac atctgctcgc tgcccttctg gctgcagtac 240 gtgctgcagc acgacaactg gtctcacggc gacctgtcct gccaggtgtg cggcatcctc 300 ctgtacgaga acatctacat cagcgtgggc ttcctctgct gcatctccgt ggaccgctac 360 ctggctgtgg cccatccctt ccgcttccac cagttccgga ccctgaaggc ggccgtcggc 420 gtcagcgtgg tcatctgggc caaggagctg ctgaccagca tctacttcct gatgcacgag 480 gaggtcatcg aggacgagaa ccagcaccgc gtgtgctttg agcactaccc catccaggca 540 tggcagcgcg ccatcaacta ctaccgcttc ctggtgggct tcctcttccc catctgcctg 600 ctgctggcgt cctaccaggg catcctgcgc gccgtgcgcc ggagccacgg cacccagaag 660 agccgcaagg accagatcca gcggctggtg ctcagcaccg tggtcatctt cctggcctgc 720 ttcctgccct accacgtgtt gctgctggtg cgcagcgtct gggaggccag ctgcgacttc 780 gccaagggcg ttttcaacgc ctaccacttc tccctcctgc tcaccagctt caactgcgtc 840 gccgaccccg tctctct ACTG 900 cttcgtcagc gagaccaccc accgggacct ggcccgcctc cgcggggcct gcctggcctt cctcacctgc tccaggaccg gccgggccag ggaggcctac 960 ccgctgggtg cccccgaggc ctccgggaaa agcggggccc agggtgagga gcccgagctg 1020 ttgaccaagc tccacccggc cttccagacc cctaactcgc cagggtcggg cgggttcccc 1080 acgggcaggt tggcctag 1098 < 210 > 118 < 211 > 365 < 212 > PRT < 213 > Homo sapiens < 400 > 118 Met Gly Asn He Thr Wing Asp Asn Ser Ser Met Ser Cys Thr He Asp 1 5 10 15 His Thr He His Gln Thr Leu Wing Pro Val Val Tyr Val Thr Val Leu 20 25 30 Val Val Gly Phe Pro Wing Asn Cys Leu Ser Leu Tyr Phe Gly Tyr Leu 35 40 45 Gln He Lys Wing Arg Asn Glu Leu Gly Val Tyr Leu Cys Asn Leu Thr 50 55 60 Val Ala Asp Leu Phe Tyr He Cys Ser Leu Pro Phe Trp Leu Gln Tyr 65 70 75 80 Val Leu Gln His Asp Asn Trp Ser His Gly Asp Leu Ser Cys Gln Val ná = saa 85 90 95 Cys Gly He Leu Leu Tyr Glu Asn He Tyr He Ser Val Gly Phe Leu 100 105 110 Cys Cys He Ser Val Asp Arg Tyr Leu Wing Val Wing His Pro Phe Arg 115 120 125 Phe His Gln Phe Arg Thr Leu Lys Wing Wing Val Gly Val Ser Val Val 130 135 140 10 He Trp Wing Lys Glu Leu Leu Thr Ser He Tyr Phe Leu Met His Glu 145 150 155 160 Glu Val He Glu Asp Glu Asn Gln His Arg Val Cys Phe Glu His Tyr 165 170 175 15 Pro He Gln Wing Trp Gln Arg Wing He Asn Tyr Tyr Arg Phe Leu Val 180 185 190 Gly Phe Leu Phe Pro He Cys Leu Leu Leu Wing Ser Tyr Gln Gly He 20 195 200 205 Leu Arg Ala Val Arg Arg Ser His Gly Thr Gln Lys Ser Arg Lys Asp 210 215 220 Gln He Gln Arg Leu Val Leu Ser Thr Val Val He Phe Leu Ala Cys 225 230 235 240 Phe Leu Pro Tyr His Val Leu Leu Leu Val Arg Ser Val Trp Glu Wing 245 250 255 Ser Cys Asp Phe Wing Lys Gly Val Phe Asn Wing Tyr His Phe Ser Leu 260 265 270 Leu Leu Thr Ser Phe Asn Cys Val Wing Asp Pro Val Leu Tyr Cys Phe 275 280 285 Val Ser Glu Thr Thr His Arg Asp Leu Wing Arg Leu Arg Gly Wing Cys 290 295 300 Leu Ala Phe Leu Thr Cys Ser Arg Thr Gly Arg Ala Arg Glu Ala Tyr 305 310 315 320 Pro Leu Gly Pro Wing Glu Wing Ser Gly Lys Ser Gly Wing Gln Gly Glu 325 330 335 Glu Pro Glu Leu Leu Thr Lys Leu His Pro Wing Phe Gln Thr Pro Asn 340 345 350 Be Pro Gly Be Gly Gly Phe Pro Thr Gly Arg Leu Ala 355 360 365 < 210 > 119 < 211 > 26 < 212 > »DN < 213 > homo saoiens ^ ^ ^ ^^^^^ Mü ^^^ < 400 > 119 gacctcgagt ccttctacac ctcatc 26 < 210 > 120 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 120 tgctctagat tccagatagg tgaaaacttg 30 < 210 > 121 < 211 > 1416 < 212 > DNA < 213 > Homo sapiens < 400 > 121 atggatattc tttgtgaaga aaatacttct ttgagctcaa ctacgaactc cctaatgcaa 60 ttáaatgatg acaacaggct ctacagtaat gactttaact ccggagaagc taacacttct 120 actggacagt gatgcattta cgactctgaa aatcgaacca acctttcctg tgaagggtgc 180 ctctcaccgt cgtgtctctc cttacttcat ctccaggaaa aaaactggtc tgctttactg 240 acagccgtag tgattattct aactattgct ggaaacatac tcgtcatcat ggcagtgtcc 300 agctgcagaa ctagagaaaa tgccaccaac tatttcctga tgtcacttgc catagctgat 360 atgctgctgg gtttccttgt catgcccgtg tccatgttaa ccatcctgta tgggtaccgg 420 tggcctctgc cgagcaagct ttgtgcagtc tggatttacc tggacgtgct cttctccacg 480 gcctccatca tgcacctctg cgccatctcg ctggaccgct acgtcgccat ccagaatccc 540 gccgcttcaa atccaccaca ctccagaact aaggcatttc tgaaaa cat tgctgtttgg 600 accatatcag taggtatatc catgccaata ccagtctttg ggctacagga cgattcgaag 660 S ^ ajfeJ¿ & ^ A ^^ e..fftfeg gtctttaagg aggggagttg cttactcgcc gatgataact ttgtcctgat cggctctttt 720 gtgtcatttt tcattccctt aaccatcatg gtgatcacct actttctaac tatcaagtca 780 ctccagaaag aagctacttt gtgtgtaagt gatcttggca attagcttct cacgggccaa 840 ttcagcttcc tccctcagag ttctttgtct tcagaaaagc tcttccagcg gtcgatccat 900 agggagccag ggtcctacac aggcaggagg actatgcagt ccatcagcaa tgagcaaaag 960 gcatgcaagg tgctgggcat cgtcttcttc ctgtttgtgg tgatgtggtg ccctttcttc 1020 tcatggccgt atcacaaaca catctgcaaa gagtcctgca atgaggatgt cattggggcc 1080 ctgctcaatg tgtttgtttg gatcggttat ctctcttcag cagtcaaccc actagtctac 1140 acaagaccta acactgttca taggtcagcc ttttcacggt atattcagtg tcagtacaag 1200 aaccattgca gaaaacaaaa gttaatttta gtgaacacaa taccggcttt ggcctacaag 1260 tctagccaac ttcaaatggg acaaaaaaag aattcaaagc aagatgccaa gacaacagat 1320 aatgactgct caatggttgc tctaggaaag cagtattctg aagaggcttc taaagacaat 1380 agcgacggag tgaatgaaaa ggtgagctgt gtgtga 1416 < 210 > 122 < 211 > 471 < 212 > PRT < 213 > Homo sapiens < 400 > 122 Met Asp He Leu Cys Glu Glu Asn Thr Ser Leu Ser Ser Thr Thr Asn 1 5 10 15 Be Leu Met Gln Leu Asn Asp Asp Asn Arg Leu Tyr Be Asn Asp Phe 20 25 30 Asn Ser Gly Glu Wing Asn Thr Ser Asp Wing Phe Asn Trp Thr Val Asp 35 40 45 Ser Glu Asn Arg Thr Asn Leu Ser Cys Glu Gly Cys Leu Ser Pro Ser 50 55 60 Cys Leu Ser Leu Leu His Leu Gln Glu Lys Asn Trp Ser Ala Leu Leu 65 70 75 80 Thr Ala Val Val He He Leu Thr He Ala Gly Asn He Leu Val He 85 90 95 Met Wing Val Ser Leu Glu Lys Lys Leu Gln Asn Wing Thr Asn Tyr Phe 100 105 110 Leu Met Ser Leu Wing He Wing Asp Met Leu Leu Gly Phe Leu Val Met 115 120 125 Pro Val Met Met Leu Thr He Leu Tyr Gly Tyr Arg Trp Pro Leu Pro 130 135 140 Ser Lys Leu Cys Wing Val Trp He Tyr Leu Asp Val Leu Phe Ser Thr 145 150 155 160 Ala Ser He Met His Leu Cys Ala He Ser Leu Asp Arg Tyr Val Ala 165 '170 175 He Gln Asn Pro He His His Being Arg Phe Asn Being Arg Thr Lys Wing 180 185 190 Phe Leu Lys He He ^ a Val Trp Thr He Ser Val Glv He Ser Met 195 200 205 Pro He Pro Val Phe Gly Leu Gln Asp Asp Ser Lys Val Phe Lys Glu 210 215 220 Gly Ser Cys Leu Leu Wing Asp Asp Asn Phe Val Leu He Gly Ser Phe 225 230 235 240 Val Ser Phe Phe He Pro Leu Thr He Met Val He Thr Tyr Phe Leu 245 250 255 Thr He Lys Ser Leu Gln Lys Glu Wing Thr Leu Cys Val Ser Asp Leu 260 265 270 Gly Thr Arg Ala Lys Leu Ala Ser Phe Ser Phe Leu Pro Gln Ser Ser 275 280 285 Leu Ser Ser Glu Lys Leu Phe Gln Arg Ser He His Arg Glu Pro Gly 290 295 300 Being Tyr Thr Gly Arg Arg Thr Met Gln Ser He Being Asn Glu Gln Lys 305 310 315 320 Wing Cys Lys Val Leu Gly He Val Phe Phe Leu Phe Val Val Met Trp 325 330 335 Cys Pro Phe Phe He Thr Asn He Met Wing Val He Cys L s Glu Ser 340 345 Itélhlte Cys Asn Glu Asp Val He Gly Ala Leu Leu Asn Val Phe Val Trp He 355 360 365 Gly Tyr Leu Ser Ser Wing Val Asn Pro Leu Val Tyr Thr Leu Phe Asn 370 375 380 Lys Thr Tyr Arg Ser Wing Phe Ser Arg Tyr He Gln Cys Gln Tyr Lys 385 390 395 400 Glu Asn Lys Lys Pro Leu Gln Leu He Leu Val Asn Thr He Pro Wing 405 410 415 Leu Ala Tyr Lys Ser Ser Gln Leu Gln Met Gly Gln Lys Lys Asn Ser 420 425 430 Lys Gln Asp Ala Lys Thr Thr Asp Asn Asp Cys Ser Met Val Ala Leu 435 440 445 Gly Lys Gln Tyr Ser Glu Glu Wing Ser Lys Asp Asn Ser Asp Gly Val 450 455 460 Asn Glu Lys Val Ser Cys Val 465 470 < 210 > 123 < 211 > 27 < 212 > DNA < 213 > Homo saoiens < 400 > 123 gacctcgagg ttgcttaaga ctgaagc 27 < 210 > 124 < 211 > 27 < 212 > DNA < 213 > Homo sapiens < 400 > 124 atttctagac atatgtagct tgtaccg 27 < 210 > 125 < 211 > 1377 < 212 > DNA < 213 > Homo sapiens < 400 > 125 atggtgaacc tgaggaatgc ggtgcattca ttccttgtgc acctaattgg cctattggtt 60 tggcaatgtg atatttctgt gagcccagta gcagctatag taactgacat tttcaatacc 120 tccgatggtg gacgcttcaa attcccagac ggggtacaaa actggccagc actttcaatc 180 gtcatcataa taatcatgac aataggtggc aacatccttg tgatcatggc agtaagcatg 240 gaaaagaaac tgcacaatgc caccaattac ttcttaatgt ccctagccat tgctgatatg 300 ctagtgggac tacttgtcat gcccctgtct ctcctggcaa tcctttatga ttatgtctgg 360 ccactaccta gatatttgtg ccccgtctgg atttctttag atgttttatt ttcaacagcg 420 tccatcatgc acctctgcgc tatatcgctg gatcggtatg tagcaatacg taatcctatt 480 gagcatagcc gtttcaattc gcggactaag gccatcatga agattgctat tgtttgggca 540 atttctatag gtgtatcagt tcctatccct gtgattggac tgagggacga agaaaaggtg 600 ttcgtgaaca acacgacgtg cgtgctcaac gacccaaatt tcgttcttat tgggtccttc 660 gtagctttct tcataccgct gacgattatg gtgattacgt attgcctgac catctacgtt 720 ctgcgccgac aagctttgat gttactgcac ggccacaccg aggaaccgcc tggactaagt 780 ctggatttcc tgaagtgctg caagaggaat acggccgagg aagagaactc tgcaaaccct 840 aaccaagacc agaacg cacg ccgaagaaag aagaaggaga gacgtcctag gggcaccatg 900 caggctatca acaatgaaag aaaagcttcg aaagtccttg ggattgtttt ctttgtgttt 960 ctgatcatgt ggtgcccatt tttcattacc aatattctgt ctgttctttg tgagaagtcc 1020 agctcatgga tgtaaccaaa aaagcttctg aatgtgtttg tttggattgg ctatgtttgt 1080 tcaggaatca atcctctggt gtatactctg ttcaacaaaa tttaccgaag ggcattctcc 1140 aactatttgc gttgcaatta taaggtagag aaaaagcctc ctgtcaggca gattccaaga 1200 gttgccgcca ctgctttgtc tgggagggag cttaatgtta acatttatcg gcataccaat 1260 gaaccggtga tcgagaaagc cagtgacaat gagcccggta tagagatgca agttgagaat 1320 ttagagttac cagtaaatcc ctccagtgtg gttagcgaaa ggattagcag tgtgtga 1377 < 210 > 126 < 211 > 458 < 212 > PRT < 213 > Homo sapiens < 400 > 126 Met Val Asn Leu Arg Asn Ala Val His Ser Phe Leu Val His Leu He 1 5 10 15 Gly Leu Leu Val Trp Gln Cys Asp He Ser Val Ser Pro Val Ala Wing 20 25 30 He Val Thr Asp He Phe Asn Thr Ser Asp Gly Gly Arg Phe Lys Phe 35 40 45 Pro Asp Gly Val Gln Asn Trp Pro Ala Leu Ser He Val He He He 50 55 60 I Met Thr He Gly Gly Asn He Leu Val I Met Met Wing Val Ser Met 65 70 75 80 Glu Lys Lys Leu His Asn Wing Thr Asn Tyr Phe Leu Met Ser Leu Wing 85 90 95 He Wing Asp Met Leu Val Gly Leu Leu Val Met Pro Leu Ser Leu Leu 100 105 110 Wing He Leu Tyr Asp Tyr Val Trp Pro Leu Pro Arg Tyr Leu Cys Pro 115 120 125 Val Trp He Ser Leu Asp Val Leu Phe Ser Thr Ala Ser He Met His 130 135 140 Leu Cys Ala He Ser Leu Asp Arg Tyr Val Ala He Arg Asn Pro He 145 150 155 160 Glu His Ser Arg Phe Asn Ser Arg Thr Lys Wing He Met Lys He Wing 165 170 175 He Val Trp Wing He Ser He Gly Val Ser Val Pro He Pro Val He 180 185 190 Gly Leu Arg Asp Glu Glu Lys Val Phe Val Asn Asn Thr Thr Cys Val to aggi j 195 200 205 Leu Asn Asp Pro Asn Phe Val Leu He Gly Be Phe Val Wing Phe Phe 210 215 220 He Pro Leu Thr He Met Val He Thr Tyr Cys Leu Thr He Tyr Val 225 230 235 240 Leu Arg Arg Gln Ala Leu Met Leu Leu His Gly His Thr Glu Glu Pro 245 250 255 Pro Gly Leu Ser Leu Asp Phe Leu Lys Cys Cys Lys Arg Asn Thr Ala 260 265 270 Glu Glu Glu Asn Be Wing Asn Pro Asn Gln Asp Gln Asn Wing Arg Arg 275 280 285 Arg Lys Lys Lys Glu Arg Arg Pro Arg Gly Thr Met Gln Ala He Asn 290 295 300 Asn Glu Arg Lys Wing Ser Lys Val Leu Gly He Val Phe Phe Val Phe 305 310 315 320 Leu He Met Trp Cys Pro Phe Phe He Thr Asn He Leu Ser Val Leu 325 330 335 Cys Glu Lys Ser Cys Asn Gln Lys Leu Met Glu Lys Leu Le ^. Asn V_t 340 345 35L Phe Val Trp He Gly Tyr Val Cys Ser Gly He Asn Pro Leu Val Tyr 355 360 365 Thr Leu Phe Asn Lys He Tyr Arg Arg Wing Phe Ser Asn Tyr Leu Arg 370 375 380 Cys Asn Tyr Lys Val Glu Lys Lys Pro Pro Val Arg Gln He Pro Arg 385 390 395 400 Val Ala Ala Thr Ala Leu Ser Gly Arg Glu Leu Asn Val Asn He Tyr 405 410 415 Arg His Thr Asn Glu Pro Val He Glu Lys Ala Ser Asp Asn Glu Pro 420 425 430 Gly He Glu Met Gln Val Glu Asn Leu Glu Leu Pro Val Asn Pro Ser 435 440 445 Ser Val Val Ser Glu Arg Ser Ser Ser Val 450 455 < 210 > 127 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 127 ggtaagcttg gcagtccacg ccaggccttc 30 < 210 > 128 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 128 tccgaattct ctgtagacac aaggctttgg 30 < 210 > 129 < 211 > 1068 < 212 > DNA < 213 > Homo sapiens < 400 > 129 atggatcagt tccctgaatc agtgacagaa aactttgagt acgatgattt ggctgaggcc 60 tgttatattg gggacatcgt ggtctttggg actgtgttcc tgtccatatt ctactccgtc 120 atctttgcca ttggcctggt gggaaatttg ttggtagtgt ttgccctcac caacagcaag 180 aagcccaaga gtgtcaccga catttacctc ctgaacctgg ccttgtctga tctgctgttt 240 gtagccactt tgcccttctg gactcactat ttgataaatg aaaagggcct ccacaatgcc 300 atgtgcaaat tcactaccgc cttcttcttc atcggctttt ttggaagcat attcttcatc 360 accgtcatca gcattgatag gtacctggcc atcgtcctgg ccgccaactc catgaacaac 420 cggaccgtgc agcatggcgt caccatcagc ctaggcgtct gggcagcagc cattttggtg 480 gcagcacccc agttcatgtt cacaaagcag aaagaaaatg aatgccttgg tgactacccc 540 gaggtcctcc aggaaatctg gcccgtgctc cgcaatgtgg aaacaaattt tcttggcttc 600 ctactccccc tgctcattat gagttattgc tacttcagaa tcatccagac gctgttttcc 660 tgcaagaacc acaagaaagc caaagccatt aaactgatcc ttctggtggt catcgtgttt 720 ttcctcttct ggacacccta caacgttatg attttcctgg agacgcttaa gctctatgac 780 ttctttccca gttgtqacat saggaaggat ctgaggctgg ccctcagt? t gaclgagacg 8 iC ? '? You & ® á¡tá * &!? J £ j iSO * '' gttgcattta gccattgttg cctgaatcct ctcatctatg catttgctgg ggagaagttc 900 agaagatacc tttaccacct gtatgggaaa tgcctggctg tcctgtgtgg gcgctcagtc 960 cacgttgatt tctcctcatc tgaatcacaa aggagcaggc atggaagtgt tctgagcagc 1020 aattttactt accacacgag tgatggagat gcattgctcc ttctctga 1068 < 210 > 130 < 211 > 355 < 212 > PRT < 213 > Homo sapiens < 400 > 130 Met Asp Gln Phe Pro Glu Ser Val Thr Glu Asn Phe Glu Tyr Asp Asp 1 5 10 15 Leu Ala Glu Ala Cys Tyr He Gly Asp He Val Val Phe Gly Thr Val 20 25 30 Phe Leu Ser He Phe Tyr Ser Val He Phe Wing He Gly Leu Val Gly 35 40 45 Asn Leu Leu Val Val Phe Ala Leu Thr Asn Ser Lys Lys Pro Lys Ser 50 55 60 Val Thr Asp He Tyr Leu Leu Asn Leu Ala Leu Ser Asp Leu Leu Phe 65 70 75 80 Val Ala Thr Leu Pro Phe Trp Thr His Tyr Leu He Asn Glu Lys Gly 85 90 95 Leu His Asn Wing Met Cys Lys Phe Thr Thr Wing Phe Phe Phe He Gly 100 105 110 Phe Phe Gly Ser He Phe Phe He Thr Val He Ser He Asp Arg Tyr 115 120 125 Leu Ala He Val Leu Ala Ala Asn Ser Met Asn Asn Arg Thr Val Gln 130 135 140 His Gly Val Thr He Ser Leu Gly Val Trp Ala Ala Ala He Leu Val 145 150 155 160 Ala Ala Pro Gln Phe Met Phe Thr Lys Gln Lys Glu Asn Glu Cys Leu 165 170 175 Gly Asp Tyr Pro Glu Val Leu Gln Glu He Trp Pro Val Leu Arg Asn 180 185 190 Val Glu Thr Asn Phe Leu Gly Phe Leu Leu Pro Leu Leu He Met Ser 195 200 205 yr Cys Tyr Phe Arg He He Gln Thr Leu Phe Ser Cys Lys Asn His 210 215 220 Lys Lys Ala Lys Ala He Lys Leu He Leu Leu Val Val He Val Phe 225 230 235 240 Pne Leu Phe Trp Thr Pro Tyr Asn Val Met Tle Foot e- Glu Thr Leu 245 250 255 Lys Leu Tyr Asp Phe Phe Pro Ser Cys Asp Met Arg Lys Asp Leu Arg 260 265 270 Leu Ala Leu Ser Val Thr Glu Thr Val Ala Phe Ser His Cys Cys Leu 275 280 285 Asn Pro Leu He Tyr Wing Phe Wing Gly Glu Lys Phe Arg Arg Tyr Leu 290 295 300 Tyr His Leu Tyr Gly Lys Cys Leu Wing Val Leu Cys Gly Arg Ser Val 305 310 315 320 His Val Asp Phe Ser Ser Ser Glu Ser Gln Arg Ser Arg His Gly Ser 325 330 335 Val Leu Ser Ser Asn Phe Thr Tyr His Thr Ser Asp Gly Asp Ala Leu 340 345 350 Leu Leu Leu 355 < 210 > 131 < 211 > 32 < 212 > DNA < 213 > Homo sapiens < 400 > 131 gatctccagt aggcataagt ggacaattct gg 32 < 210 > 132 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 132 ctccttcggt cctcctatcg ttgtcagaag 30 < 210 > 133 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 133 agaaggccaa gatcgcgcgg ctggccctca 30 < 210 > 134 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 134 cggcgccacc gcacgaaaaa gctcatcttc 30 < 210 > 135 < 211 > 33 < 212 > DNA < 213 > Homo sapiens < 400 > 135 gccaagaagc gggtgaagtt cctggtggtg gca 33 < 210 > 136 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 136 caggcggaag gtgaaagtcc tggtcctcgt 30 < 210 > 137 < 211 > 33 < 212 > DNA < 213 > Homo sapiens < 400 > 137 cggcgcctgc gggccaagcg gctggtggtg gtg 33 < 210 > 138 < 211 > 31 < 212 > DNA < 213 > Homo sapiens < 400 > 138 ccaagcacaa agccaagaaa gtgaccatca c 31 < 210 > 139 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 139 gcgccggcgc accaaatgct tgctggtggt 30 < 210 > 140 < 211 > 41 < 212 > DNA < 213 > Homo sapiens < 400 > 140 caaaaagctg aagaaatcta agaagatcat ctttattgtc g 41 < 210 > 141 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 141 caagaccaag gcaaaacgca tgatcgccat 30 S5tae ^ aa ^ aafc i? ^^ - ¿£. < 210 > 142 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 142 gtcaaggaga agtccaaaag gatcatcatc 30 < 210 > 143 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 143 cgccgcgtgc gggccaagca gctcctgctc 30 < 210 > 144 < 211 > 33 < 212 > DNA < 213 > Homo sapiens < 400 > 144 cctgataagc gctataaaat ggtcctgttt cga 33 < 210 > 145 < 211 > 36 < 212 > DNA < 213 > Homo sapiens < 400 > 145 gaaagacaaa agagagtcaa gaggatgtct ttattg 36 < 210 > 146 < 211 > 33 < 212 > DNA < 213 > Homo sapiens < 400 > 146 cggagaaaga gggtgaaacg cacagccatc gcc 33 < 210 > 147 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 147 aagcttcagc gggccaaggc actggtcacc 30 < 210 > 148 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 148 cagcggcaga aggcaaaaag ggtggccatc 30 < 210 > 149 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 149 cggcagaagg cgaagcgcat gatcctcgcg 30 < 210 > 150 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 150 gagcgcaaca aggccaaaaa ggtgatcatc 30 < 210 > 151 < 211 > 39 < 212 > DNA < 213 > Homo sapiens < 400 > 151 ggtgtaaaca aaaaggctaa aaacacaatt attcttatt 39 < 210 > 152 < 211 > 27 < 212 > DNA < 213 > Homo sapiens < 400 > 152 gagagccagc tcaagagcac cgtggtg 27 < 210 > 153 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 153 ccacaagcaa accaagaaaa tgctggctgt 30 < 210 > 154 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 154 catcaagtgt atcatgtgcc aagtacgccc 30 < 210 > 155 < 211 > 34 < 212 > DNA < 213 > Homo sapiens < 400 > 155 ctagagagtc agatgaagtg tacagtagtg gcac 34 < 210 > 156 < 211 > 34 < 212 > DNA < 213 > Homo sapiens < 400 > 156 ctagagagtc agatgaagtg tacagtagtg gcac 34 < 210 > 157 < 211 > 33 < 212 > DNA < 213 > Homo sapiens < 400 > 157 gctgaggttc gcaataaact aaccatgttt gtg 33 < 210 > 158 < 211 > 29 < 212 > DNA < 213 > Homo sapiens < 400 > 158 gggaggccga gctgaaagcc accctgctc 29 < 210 > 159 < 211 > 31 < 212 > DNA < 213 > Homo sapiens < 400 > 159 caagatcaag agagccaaaa ccttcatcat g 31 < 210 > 160 < 211 > 31 < 212 > DNA < 213 > Homo sapiens < 400 > 160 ccggagacaa gtgaagaaga tgctgtttgt c 31 < 210 > 161 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 161 gcaaggacca gatcaagcgg ctggtgctca 30 < 210 > 162 < 211 > 34 < 212 > DNA < 213 > Homo sapiens < 400 > 162 caagaaagcc aaagccaaga aactgatcct tctg 34 '& amp; s & ^^ & ? A ^ ?? X ^ M < 210 > 163 < 211 > 1068 < 212 > DNA < 213 > Homo sapiens < 400 > 163 atggaagatt tggaggaaac attatttgaa gaatttgaaa actattccta tgacctagac 60 tattactctc tggagtctga tttggaggag aaagtccagc tgggagttgt tcactgggtc 120 tccctggtgt tatattgttt ggcttttgtt ctgggaattc caggaaatgc catcgtcatt 180 tggttcacgg ggctcaagtg gaagaagaca gtcaccactc tgtggttcct caatctagcc 240 attgcggatt tcatttttct tctctttctg cccctgtaca tctcctatgt ggccatgaat 300 ttccactggc cctttggcat ctggctgtgc aaagccaatt ccttcactgc ccagttgaac 360 atgtttgcca gtgttttttt cctgacagtg atcagcctgg accactatat ccacttgatc 420 catcctgtct tatctcatcg gcatcgaacc ctcaagaact ctctgattgt cattatattc 480 atctggcttt tggcttctct aattggcggt cctgccctgt acttccggga cactgtggag 540 ttcaataatc atactctttg ctataacaat tttcagaagc atgatcctga cctcactttg 600 atcaggcacc atgttctgac ttgggtgaaa tttatcattg gctatctctt ccctttgcta 660 acaatgagta tttgctactt gtgtctcatc ttcaaggtga agaagcgaac agtcctgatc 720 tccagtaggc ataagtggac aattctggtt gtggttgtgg cctttgtggt ttgctggact 780 ccttatcacc tgtttagcat ttgggagctc accattcacc acaatagcta ttcccaccat 840 gtgatgcagg ctggaa tccc cctctccact ggtttggcat tcctcaatag ttgcttgaac 900 cccatccttt atgtcctaat tagtaagaag ttccaagctc gcttccggtc ctcagttgct 960 gagatactca agtacacact gtgggaagtc agctgttctg gcacagtgag tgaacagctc 1020 aggaactcag aaaccaagaa tctgtgtctc ctggaaacag ctcaataa 1068 < 210 > 164 < 211 > 355 < 212 > PRT < 213 > Homo sapiens < 400 > 164 Met Glu Asp Leu Glu Glu Thr Leu Phe Glu Glu Phe Glu Asn Tyr Ser 1 5 10 15 Tyr Asp Leu Asp Tyr Tyr Ser Leu Glu Ser Asp Leu Glu Glu Lys Val 20 25 30 Gln Leu Gly Val Val His Trp Val Ser Leu Val Leu Tyr Cys Leu Ala 35 40 45 Phe Val Leu Gly He Pro Gly Asn Wing He Val He Trp Phe Thr Gly 50 55 60 Leu Lys Trp Lys Lys Thr Val Thr Thr Leu Trp Phe Leu Asn Leu Ala 65 70 75 He Wing Asp Phe He Phe Leu Leu Phe Leu Pro Leu Tyr He Ser Tyr 85 90 95 Val Ala Met Asn Phe His Trp Pro Phe Gly He Trp Leu Cys Lys Wing 100 105 110 Asn Ser Phe Thr Ala Gln Leu Asn Met Phe Ala Ser Val Phe Phe Leu 115 120 125 Thr Val He Ser Leu Asp His Tyr He His Leu He His Pro Val Leu 130 135 140 Ser His Arg His Arg Thr Leu Lys Asn Ser Leu He Val He He Phe 145 150 155 160 He Trp Leu Leu Wing Ser Leu He Gly Gly Pro Wing Leu Tyr Phe Arg 165 170 175 Asp Thr Val Glu Phe Asn Asn His Thr Leu Cys Tyr Asn Asn Phe Gln 180 185 190 Lys His Asp Pro Asp Leu Thr Leu He Arg His His Val Leu Thr Trp 195 200 205 Val Lys Phe He He Gly Tyr Leu Phe Pro Leu Leu Thr Met Ser He 210 215 220 Cys Tyr Leu Cys Leu He Phe Lys Val Lys Lys Arg Thr Val Leu He 225 230 235 240 Being Ser Arg His Lys Trp Thr He Leu Val Val Val Val Ala Phe Val 245 250 255 Val Cys Trp Thr Pro Tyr His Leu Phe Ser He Trp Glu Leu Thr He 260 265 270 His His Asn Ser Tyr Ser His His Val Val Met Gln Ala Gly He Pro Leu 275 280 28o i ^ mi & ^? »s ^ á ^ í Ser Thr Gly Leu Ala Phe Leu Asn Ser Cys Leu Asn Pro He Leu Tyr 290 295 300 Val Leu He Ser Lys Lys Phe Gln Ala Arg Phe Arg Ser Ser Val Ala 305 310 315 320 Glu He Leu Lys Tyr Thr Leu Trp Glu Val Ser Cys Ser Gly Thr Val 325 330 335 Ser Glu Gln Leu Arg Asn Ser Glu Thr Lys Asn Leu Cys Leu Leu Glu 340 345 350 Tnr Ala Gln 355 < 210 > 165 < 211 > 1089 < 212 > DNA < 213 > Homo sapiens < 400 > 165 atgggcaacc acacgtggga gggctgccac gtggactcgc gcgtggacca cctctttccg 60 ccatccctct acatctttgt catcggcgtg gggctgccca ccaactgcct ggctctgtgg 120 gcggcctacc gccaggtgca acagcgcaac gagctgggcg tctacctgat gaacctcagc 180 atcgccgacc tgctgtacat ctgcacgctg ccgctgtggg tggactactt cctgcaccac 240 sacaactgga tccacggccc cgggtcctgc aagctctttg ggttcatctt ctacaccaat 300 atctacatca gcatcgcctt cctgtgctgc atctcggtgg accgctacct ggctgtggcc 360 Cscccactcc gcttcgcccg cctgcgccgc gtcaagaccg ccgtggccgt gagctccgtg 420 iasa & or gtctgggcca cggagctggg cgccaactcg gcgcccctgt tccatgacga gctcttccga 480 gaccgctaca accacacctt ctgctttgag aagttcccca tggaaggctg ggtggcctgg 540 atgaacctct atcgggtgtt cgtgggcttc ctcttcccgt gggcgctcat gctgctgtcg 600 tcctgcgggc taccggggca cgtgcggggc agcgtgtcca ccgagcgcca ggagaaggcc 660 aagatcgcgc ggctggccct cagcctcatc gccatcgtgc tggtctgctt tgcgccctat 720 cacgtgctct tgctgtcccg cagcgccatc tacctgggcc gcccctggga ctgcggcttc 780 gaggagcgcg tcttttctgc ataccacagc tcactggctt tcaccagcct caactgtgtg 840 gcgga CCCCA tcctctactg cctggtcaac gagggcgccc gcagcgatgt ggccaaggcc 900 ctgcacaacc tgctccgctt tctggccagc gacaagcccc aggagatggc caatgcctcg 960 ctcaccctgg agaccccact cacctccaag aggaacagca cagccaaagc catgactggc 1020 agctgggcgg ccactccgcc ttcccagggg gaccaggtgc agctgaagat gctgccgcca gcacaatga 1080 1089 < 210 > 166 < 211 > 362 < 212 > PRT < 213 > Homo sapiens < 400 > 166 Met Gly Asn His Thr Trp Glu Gly Cys His Val Asp Ser Arg Val Asp 1 5 10 15 His Leu Phe Pro Pro Ser Leu Tyr He Phe Val He Gly Val Gly Leu 20 25 30 Pro Thr Asn Cys Leu Wing Leu Trp Wing Wing Tyr Arg Gln Val Gln Gln 35 40 45 Arg Asn Glu Leu Gly Val Tyr Leu Met Asn Leu Ser He Wing Asp Leu 50 55 60 Leu Tyr He Cys Thr Leu Pro Leu Trp Val Asp Tyr Phe Leu His His 65 70 75 80 Asp Asn Trp He His Gly Pro Gly Ser Cys Lys Leu Phe Gly Phe He 85 90 95 Phe Tyr Thr Asn He Tyr He Ser Be He Wing Phe Leu Cys Cys He Ser 100 105 110 Val Asp Arg Tyr Leu Wing Val Wing His Pro Leu Arg Phe Wing Arg Leu 115 120 125 Arg Arg Val Lys Thr Ala Val Ala Val Ser Ser Val Val Trp Ala Thr 130 135 140 Glu Leu Gly Wing Asn Being Wing Pro Leu Phe His Asp Glu Leu Phe Arg 145 150 155 160 Asp Arg Tyr Asn His Thr Phe Cys Phe Glu Lys Phe Pro Met Glu Gly 165 170 175 Trp Val Wing Trp Met Asn Leu Tyr Arg Val Phe Val Gly Phe Leu Phe 180 185 190 Pro Tro Ala Leu Met Leu Leu Ser Tyr Arg Gly He Leu Arg Ala Val 195 200 205 Arg Gly Ser Val Ser Thr Glu Arg Gln Glu Lys Wing Lys He Wing Arg 210 215 220 Leu Ala Leu Ser Leu He Ala He Val Leu Val Cys Phe Ala Pro Tyr 225 230 235 240 His Val Leu Leu Leu Ser Arg Ser Wing He Tyr Leu Gly Arg Pro Trp 245 250 255 Asp Cys Gly Phe Glu Glu Arg Val Phe Ser Ala Tyr His Ser Ser Leu 260 265 270 Wing Phe Thr Ser Leu Asn Cys Val Wing Asp Pro He Leu Tyr Cys Leu 275 280 285 Val Asn Glu Gly Ala Arg Ser Asp Val Ala Lys Ala Leu His Asn Leu 290 295 300 Leu Arg Phe Leu Wing Being Asp Lys Pro Gln Glu Met Wing Asn Wing Ser 305 310 315 320 Leu Thr Leu Glu Thr Pro Leu Thr Ser Lys Arg Asn Ser Thr Ala Lys 325 330 335 Wing Met Thr Cly Se: Trp Wing Wing Thr Pro Pro Ser Gln Cly Asp Gln 3-0 345 JOJ «^ feafa ^ f.

Val Gln Leu Lys Met Leu Pro Pro Ala Gln 355 360 < 210 > 167 5 < 211 > 1002 < 212 > DNA < 213 > Homo sapiens < 400 > 167 10 atggagtcct caggcaaccc agagagcacc accttttttt actatgacct tcagagccag 60 ccgtgtgaga accaggcctg ggtctttgct accctcgcca ccactgtcct gtactgcctg 120 gtgtttctcc tcagcctagt gggcaacagc ctggtcctgt gggtcctggt gaagtatgag 180 agcctggagt ccctcaccaa catcttcatc ctcaacctgt gcctctcaga cctggtgttc 240 gcctgcttgt tgcctgtgtg gatctcccca taccactggg gctgggtgct gggagacttc 300 ctctgcaaac tcctcaatat gatcttctcc atcagcctct acagcagcat cttcttcctg 360 accatcatga ccatccaccg ctacctgtcg gtagtgagcc ccctctccac cctgcgcgtc 420 cccaccctcc gctgccgggt gctggtgacc atggctgtgt gggtagccag catcctgtcc 480 tccatcctcg acaccatctt ccacaaggtg ctttcttcgg gctgtgatta ttccgaactc 540 acgtggtacc tcacctccgt ctaccagcac aacctcttct tcctgctgtc cctggggatt 600 atcctgttct gctacgtgga gatcctcagg accctgttcc gctcacgctc caagcggcgc 660 caccgcacga aaaagctcat cttcgccatc gtggtggcct acttcctcag ctggggtccc 720 tacaacttca ccctgtttct gcagacgctg tttcggaccc agatcatccg gagctgcgag 780 agctagaata gccaaacagc cgccctgctc atctgccgca acctcgcctt ctcccactgc 840 tgctttaacc cggtgctcta tgtcttcgtg ggggtcaagt tccgcacaca cctgaaacat 900 gttctccggc agttctggtt ctgccggctg caggcaccca gcccagcctc gatcccccac 960 tcccctggtg ccttcgccta tgagggcgcc tccttctact ga 1002 < 210 > 168 < 211 > 333 < 212 > PRT < 213 > Homo sapiens < 400 > 168 Met Glu Be Ser Gly Asn Pro Glu Be Thr Thr Phe Phe Tyr Tyr Asp 1 5 10 15 Leu Gln Ser Gln Pro Cys Glu Asn Gln Wing Trp Val Phe Wing Thr Leu 20 25 30 Wing Thr Thr Val Leu Tyr Cys Leu Val Phe Leu Leu Ser Leu Val Gly 35 40 45 Asn Ser Leu Val Leu Trp Val Leu Val Lys Tyr Glu Ser Leu Glu Ser 50 55 60 Leu Thr Asn He Phe He Leu Asn Leu Cys Leu Ser Asp Leu Val Phe 65 70 75 80 Ala Cys Leu Leu Pro Val Trp He Ser Pro Tyr His Trp Gly Trp Val 85 90 95 Leu Gly Asp Phe Leu Cys Lys Leu Leu Asn Met He Phe Ser Be Ser 100 105 110 Leu yr Being Being He Phe Phe Leu Thr He Met Thr He h ^ .s Arg Tyr 115 120 125 Leu Ser Val Val Pro Pro Leu Ser Thr Leu Arg Val Pro Thr Leu Arg 130 135 140 Cys Arg Val Leu Val Thr Met Wing Val Trp Val Wing Ser He Leu Ser 145 150 155 160 Ser He Leu Asp Thr He Phe His Lys Val Leu Ser Ser Gly Cys Asp 165 170 175 Tyr Ser Glu Leu Thr Trp Tyr Leu Thr Ser Val Tyr Gln His Asn Leu 180 185 190 Phe Phe Leu Leu Ser Leu Gly He He Leu Phe Cys Tyr Val Glu He 195 200 205 Leu Arg Thr Leu Phe Arg Ser Arg Ser Lys Arg Arg His Arg Thr Lys 210 215 220 Lys Leu He Phe Wing He Val Val Wing Tyr Phe Leu Ser Trp Gly Pro 225 230 235 240 Tyr Asn Phe Thr Leu Phe Leu Gln Thr Leu Phe Arg Thr Gln He He 245 250 255 Arg Ser Cys Glu Wing Lys Gln Glr Leu Glu Tyr Wing Leu Leu He Cys 260 265 270 •• -, --.- Á -., ^^ _, - »» ~ -Arg Asn Leu Ala Phe Ser His Cys Cys Phe Asn Pro Val Leu Tyr Val 275 280 285 Phe Val Gly Val Lys Phe Arg Thr His Leu Lys His Val Leu Arg Gln 290 295 300 Phe Trp Phe Cys Arg Leu Gln Ala Pro Ser Pro Ala Ser He Pro His 305 310 315 320 Ser Pro Gly Ala Phe Ala Tyr Glu Gly Ala Ser Phe Tyr 325 330 < 210 > 169 < 211 > 987 < 212 > DNA < 213 > Homo sapiens < 400 > 169 atggacaacg cctcgttctc ggagccctgg cccgccaacg catcgggccc ggacccggcg 60 ctgagctgct ccaacgcgtc gactctggcg ccgctgccgg cgccgctggc ggtggctgta 120 ccagttgtct acgcggtgat ctgcgccgtg ggtctggcgg gcaactccgc cgtgctgtac 180 gtgttgctgc gggcgccccg catgaagacc gtcaccaacc tgttcatcct caacctggcc 240 atcgccgacg agctcttcac gctggtgctg cccatcaaca tcgccgactt cctgctgcgg 300 cagtggccct tcggggagct catgtgcaag ctcatcgtgg ctatcgacca gtacaacacc 360 ttctccagcc tctacttcct caccgtcatg agcgccgacc gctacctggt ggtgttggcc 420 actgcggagt cgcgccgggt ggccggccgc acctacagcg ccgcgcgcgc ggtgagcctg 480 gccgtgtggg ggatcgtcac actcgtcgtg ctgcccttcg cagtcttcgc ccggctagac 540 gacgagcagg gccggcgcca gtgcgtgcta gtctttccgc agccccaggc cttctggtgg 600 ? S & > t &? &? v * j¡¿ # i cgcgcgagcc gcctctacac gctcgtgctg ggcttcgcca tccccgtgtc caccatctgt 660 gtcctctata ccaccctgct gtgccggctg catgccatgc ggctggacag ccacgccaag 720 gccctggagc gcgccaagaa gcgggtgaag ttcctggtgg tggcaatcct ggcggtgtgc 780 ctcctctgct ggacgcccta ccacctgagc accgtggtgg cgctcaccac cgacctcccg 840 cagacgccgc tggtcatcgc tatctcctac ttcatcacca gcctgacgta cgccaacagc 900 tgcctcaacc ccttcctcta cgccttcctg gacgccagct tccgcaggaa cctccgccag 960 ctgataactt gccgcgcggc agcctga 987 < 210 > 170 < 211 > 328 < 212 > PRT < 213 > Homo sapiens < 400 > 170 Met Asp Asn Wing Ser Phe Ser Glu Pro Trp Pro Wing Asn Wing Ser Gly 1 5 10 15 Pro Asp Pro Wing Leu Ser Cys Ser Asn Wing Ser Thr Leu Wing Pro Leu 20 25 30 Pro Ala Pro Leu Ala Val Ala Val Pro Val Val Tyr Ala Val He Cys 35 40 45 Wing Val Gly Leu Wing Gly Asn Ser Wing Val Leu Tyr Val Leu Leu Arg 50 55 60 Wing Pro Arg Met Lys Thr Val Thr Asn Leu Phe He Leu Asn Leu Wing 65 70 75 80 He Wing Asp Glu Leu Phe Thr Leu Val Leu Pro He Asn He Wing Asp 85 90 95 Phe Leu Leu Arg Gln Trp Pro Phe Gly Glu Leu Met Cys Lys Leu He 100 105 110 Val Ala He Asp Gln Tyr Asn Thr Phe Ser Ser Leu Tyr Phe Leu Thr 115 120 125 Val Met Ser Wing Asp Arg Tyr Leu Val Val Leu Wing Thr Wing Glu Ser 30 135 140 Arg Arg Val Wing Gly Arg Thr Tyr Wing Wing Wing Arg Wing Val Ser Leu 145 150 155 160 Wing Val Trp Gly He Val Val Leu Val Val Leu Pro Val Val Phe W 165 170 175 Wing Arg Leu Asp Asp Glu Gln Gly Arg Arg Gln Cys Val Leu Val Phe 180 185 190 Pro Gln Pro Glu Wing Phe Trp Trp Arg Wing Ser Arg Leu Tyr Thr Leu 195 200 205 Val Leu Gly Phe Ala He Pro Val Ser Thr He Cys Val Leu Tyr Thr 210 215 220 Thr Leu Leu C s Arg Leu His Wing Met Arg Leu Asp Ser His Wing Lys 225 230 235 240 Ala Leu Glu Arg Ala Lys Lys Arg Val Lys Phe Leu Val Val Ala Wing 245 250 255 Leu Ala Val Cys Leu Leu Cys Trp Thr Pro Tyr His Leu Ser Thr Val 260 265 270 Val Ala Leu Thr Thr Asp Leu Pro Gln Thr Pro Leu Val He Ala He 275 280 285 Ser Tyr Phe He Thr Ser Leu Thr Tyr Wing Asn Ser Cys Leu Asn Pro 290 295 300 Phe Leu Tyr Ala Phe Leu Asp Ala Ser Phe Arg Arg Asn Leu Arg Gln 305 310 315 320 Leu He Thr Cys Arg Ala Ala Wing 325 < 210 > 171 < 211 > 1002 < 212 > DNA < 213 > Homo sapiens < 400 > 171 atgcaggccg ctgggcaccc agagcccctt gacagcaggg gctccttctc cctccccacg 60 atgggtgcca acgtctctca ggacaatggc actggccaca atgccacct "ctccgagcca 120 - < • - 2F- & * '' ctgccgttcc tctatgtgct cctgcccgcc gtgtactccg ggatctgtgc tgtggggctg 180 actggcaaca cggccgtcat ccttgtaatc ctaagggcgc ccaagatgaa gacggtgacc 240 aacgtgttca tcctgaacct ggccgtcgcc gacgggctct tcacgctggt actgcctgtc 300 aacatcgcgg agcacctgct gcagtactgg cccttcgggg agctgctctg caagctggtg 360 ctggccgtcg accactacaa catcttctcc agcatctact tcctagccgt gatgagcgtg 420 gaccgatacc tggtggtgct ggccaccgtg aggtcccgcc acatgccctg gcgcacctac 480 cggggggcga aggtcgccag cctgtgtgtc tggctgggcg tcacggtcct ggttctgccc 540 ttcttctctt tcgctggcgt ctacagcaac gagctgcagg tcccaagctg tgggctgagc 600 ttcccgtggc ccgagcaggt ctggttcaag gccagccgtg tctacacgtt ggtcctgggc 660 ttcgtgctgc ccgtgtgcac catctgtgtg ctctacacag acctcctgcg caggctgcgg 720 gccgtgcggc tccgctctgg agccaaggct ctaggcaagg ccaggcggaa ggtgaaagtc 780 ctggtcctcg tcgtgctggc cgtgtgcctc cgcccttcca ctctgctgga cctggcctct 840 gtcgtggccc tgaccacgga cctgccccag accccactgg tcatcagtat gtcctacgtc 900 atcaccagcc tcacgtacgc caactcgtgc ctgaacccct tcctctacgc ctt tctagat 960 gacaacttcc ggaagaactt ccgcagcata ttgcggtgct ga 1002 < 210 > 172 < 211 > 333 < 212 > PRT < 213 > Homo sapiens < 400 > 172 Met Gln Ala Ala Gly His Pro Glu Pro Leu Asp Ser Arg Gly Ser Phe 1 5 10 15 Be Leu Pro Thr Met Gly Wing Asn Val Ser Gln Asp Asn Gly Thr Gly 20 25 30 His Asn Ala Thr Phe Ser Glu Pro Leu Pro Phe Leu Tyr Val Leu Leu 35 40 45 Pro Wing Val Tyr Ser Gly He Cys Wing Val Gly Leu Thr Gly Asn Thr 50 55 60 Ala Val He Leu Val He Leu Arg Ala Pro Lys Met Lys Thr Val Thr 65 70 75 80 Asn Val Phe He Leu Asn Leu Wing Val Wing Asp Gly Leu Phe Thr Leu 85 90 95 Val Leu Pro Val Asn He Wing Glu His Leu Leu Gln Tyr Trp Pro Phe 100 105 110 Gly Glu Leu Leu Cys Lys Leu Val Leu Wing Val Asp His Tyr Asn He 115 120 125 Phe Ser Ser He Tyr Phe Leu Wing Val Met Ser Val Asp Arg Tyr Leu 130 135 140 Val Val Leu Ala Thr Val Arg Ser Arg His Met Pro Trp Arg Thr Tyr 145 150 155 160 Arg Gly Ala Lys Val Ala Ser Leu Cys Val Trp Leu Gly Val Thr Val 165 170 175 Leu Val Leu Pro Phe Phe Ser P-e Wing Gly Val Tyr Ser Asn Glu Leu fiftio * 272 180 185 190 Gln Val Pro Ser Cys Gly Leu Ser Phe Pro Trp Pro Glu Gln Val Trp 195 200 205 Phe Lys Wing Ser Arg Val Tyr Thr Leu Val Leu Gly Phe Val Leu Pro 210 215 220 Val Cys Thr He Cys Val Leu Tyr Thr Asp Leu Leu Arg Arg Leu Arg 225 230 235 240 Wing Val Arg Leu. Arg Ser Gly Wing Lys Wing Leu Gly Lys Wing Arg Arg 245 250 255 Lys Val Lys Val Leu Val Leu Val Val Leu Ala Val Cys Leu Leu Cys 260 265 270 Trp Thr Pro Phe His Leu Wing Ser Val Val Wing Leu Thr Thr Asp Leu 275 280 285 Pro Gln Thr Pro Leu Val He Ser Met Ser Tyr Val He Thr Ser Leu 290 295 300 Thr Tyr Wing Asn Ser Cys Leu Asn Pro Phe Leu Tyr Wing Phe Leu Asp 305 310 315 320 sp Asn Phe Arg Lys Asn Phe Arg Ser He Leu Arg Cys 325 330 < 210 > 173 < 211 > 1107 < 212 > DNA < 213 > Homo sapiens < 400 > 173 atggtccttg aggtgagtga ccaccaagtg ctaaatgacg ccgaggttgc cgccctcctg 60 gctcttccta gagaacttca tgactatgga gaaaacgaga gtgactcgtg ctgtacctcc 120 ccgccctgcc cacaggactt cagcctgaac ttcgaccggg ccttcctgcc agccctctac 180 agcctcctct ttctgctggg gctgctgggc aacggcgcgg tggcagccgt gctgctgagc 240 cggcggacag ccctgagcag caccgacacc ttcctgctcc acctagctgt agcagacacg 300 ctgctggtgc tgacactgcc gctctgggca gtggacgctg ccgtccagtg ggtctttggc 360 tctggcctct gcaaagtggc aggtgccctc ttcaacatca acttctacgc aggagccctc 420 ctgctggcct gcatcagctt tgaccgctac ctgaacatag ttcatgccac ccagctctac 480 cgccgggggc ccccggcccg cgtgaccctc acctgcctgg ctgtctgggg gctctgcctg 540 cttttcgccc tcccagactt catcttcctg tcggcccacc acgacgagcg cctcaacgcc 600 acccactgcc aatacaactt cccacaggtg ggccgcacgg ctctgcgggt gctgcagctg 660 gtggctggct ttctgctgcc cctgctggtc atggcctact gctatgccca catcctggcc 720 gtgctgctgg tttccagggg ccagcggcgc ctgcgggcca agcggctggt ggtggtggtc 780 gtggtggcct ttgccctctg ctggaccccc tatcacctgg tggtgctggt ggacatcctc 840 atggacctgg gcgctt tggc ccgcaactgt ggccgagaaa gcagggtaga cgtggccaag 900 tcggtcacct caggcctggg ctacatgcac tgctgcctca acccgctgct ctatgccttt 960 agttccggga gtaggggtca gcggatgtgg atgctgctct tgcgcctggg ctgccccaac 1020 tccagaggca cagagagggc gccatcgtct tcccgccggg attcatcctg gtctgagacc 1080 tcagaggcct cctactcggg cttgtga 1107 < 210 > 174 < 211 > 368 < 212 > PRT < 213 > Homo sapiens < 400 > 174 Met Val Leu Glu Val Ser Asp His Gln Val Leu Asn Asp Ala Glu Val 10 15 Wing Ala Leu Leu Glu Asn Phe Being Being Tyr Asp Tyr Gly Glu Asn 20 25 30 Glu Ser Asp Ser Cys Cys Thr Ser Pro Pro Cys Pro Gln Asp Phe Ser 35 40 45 Leu Asn Phe Asp Arg Ala Phe Leu Pro Ala Leu Tyr Ser Leu Leu Phe 50 55 60 Leu Leu Gly Leu Leu Gly Asn Gly Ala Val Ala Ala Val Leu Leu Ser 65 70 75 80 Arg Arg Thr Ala Leu Ser Ser Thr Asp Thr Phe Leu Leu His Leu Wing 85 90 95 Val Ala Asp Thr Leu Leu Val Leu Thr Leu Pro Leu Trp Wing Val Asp 100 105 110 Ala Ala Val Gln Trp Val Phe Gly Ser Gly Leu Cys Lys Val Ala Gly 115 120 125 Ala Leu Phe Asn He Asn Phe Tyr Ala Gly Ala Leu Leu Leu Ala Cys 130 135 140 He Ser Phe Asp Arg Tyr Leu Asn lie Val His Wing Thr Gln Leu Tyr 145 150 155 160 Arg Arg Gly Pro Pro Wing Arg Val Thr Leu Thr Cys Leu Wing Val Trp 165 170 175 Gly Leu Cys Leu Leu Phe Wing Leu Pro Asp Phe He Phe Leu Ser Wing 10 180 185 190 His His Asp Glu Arg Leu Asn Wing Thr His Cys Gln Tyr Asn Phe Pro 195 200 205 Gln Val Gly Arg Thr Ala Leu Arg Val Leu Gln Leu Val Ala Gly Phe 210 215 220 Leu Leu Pro Leu Leu Val Met Ala Tyr Cys Tyr Ala His He Leu Ala 225 230 235 240 2nd Val Leu Leu Val Ser Arg Gly Gln Arg Arg Leu Arg Ala Lys Arg Leu 245 250 255 Val Val Val Val Val Val Ala Phe Ala Leu Cys Trp Thr Pro Tyr His 260 265 270 Leu Val Val Leu Val Asp He Leu Met Asp Leu Gly Ala Leu Ala Arg 275 280 285 Asn Cys Gly Arg Glu Ser Arg Val Asp Val Wing Lys Ser Val Thr Ser 290 295 300 Gly Leu Gly Tyr Met His Cys Cys Leu Asn Pro Leu Leu Tyr Ala Phe 305 310 315 320 Val Gly Val Lys Phe Arg Glu Arg Met Trp Met Leu Leu Leu Arg Leu 325 330 335 Gly Cys Pro Asn Gln Arg Gly Leu Gln Arg Gln Pro Ser Ser Ser Arg 340 345 350 Arg Asp Ser Ser Trp Ser Glu Thr Ser Glu Wing Ser Tyr Ser Gly Leu 355 360 365 < 210 > 175 < 211 > 1074 < 212 > DNA < 213 > Homo sapiens < 400 > 175 atggctgatg actatggctc tgaatccaca tcttccatgg aagactacgt taacttcaac 60 ttcactgact tctactgtga gaaaaacaat gtcaggcagt ttgcgagcca tttcctccca 120 cccttgtact ggctcgtgtt catcgtgggt gccttgggca acagtcttgt tatccttgtc 180 tactggtact gcacaagagt gaagaccatg accgacatgt tcc'tttgaa tttggcaatt 240 gctgacctcc tctttcttgt cactcttccc ttctgggcca ttgctgctgc tgaccagtgg 300 aagttccaga ccttcatgtg caaggtggtc aacagcatgt acaagatgaa cttctacagc 360 tgtgtgttgc tgatcatgtg catcagcgtg gacaggtaca ttgccattgc ccaggccatg 420 cttggaggga agagcacata gaaaaggctt ttgtacagca aaatggtttg ctttaccatc 480 tgggtattgg cagctgctct ctgcatccca gaaatcttat acagccaaat caaggaggaa 540 tccggcattg ctatctgcac catggtttac cctagcgatg agagcaccaa actgaagtca 600 gctgtcttga ccctgaaggt cattctgggg ttcttccttc ccttcgtggt catggcttgc 660 tcatcattca tgctatacca caccctgata caagccaaga agtcttccaa gcacaaagcc 720 aagaaagtga ccatcactgt cctgaccgtc tttgtcttgt ctcagtttcc ctacaactgc 780 attttgttgg tgcagaccat tgacgcctat gccatgttca tctccaactg tgccgtttcc 840 accaacattg acatctgctt ccaggtcacc cagaccatcg ccttcttcca cagttgcctg 900 aaccctgttc tctatgtttt tgtgggtgag agattccgcc gggatctcgt gaaaaccctg 960 aagaacttgg gttgcatcag ccaggcccag tgggtttcat ttacaaggag agagggaagc 1020 ttgaagctgt cgtctatgtt gctggagaca acctcaggag cactctccct ctga 1074 < 210 > 176 < 211 > 357 15 < 212 > PRT < 213 > Homo sapiens < 400 > 176 Met Wing Asp Asp Tyr Gly Ser Glu Ser Thr Ser Ser Met Glu Asp Tyr 20 1 5 10 15 Val Asn Phe Asn Phe Thr Asp Phe Tyr Cys Glu Lys Asn Asn Val Arg 20 25 30 Gln Phe Ala Ser His Phe Leu Pro Pro Leu Tyr Trp Leu Val Phe He 25 35 40 45 & a Val Gly Ala Leu Gly Asn Ser Leu Val He Leu Val Tyr Trp Tyr Cys 50 55 60 Thr Arg Val Lys Thr Met Thr Asp Met Phe Leu Leu Asn Leu Ala He 65 70 75 80 Wing Asp Leu Leu Phe Leu Val Thr Leu Pro Phe Trp Wing Wing Wing 85 90 95 - Wing Asp Gln Trp Lys Phe Gln Thr Phe Met Cys Lys Val Val Asn Ser 100 105 110 Met Tyr Lys Met Asn Phe Tyr Ser Cys Val Leu Leu He Met Cys He 115 120 125 Ser Val Asp Arg Tyr He Wing Wing Wing Gln Wing Met Arg Wing His Thr 130 135 140 Trp Arg Glu Lys Arg Leu Leu Tyr Ser Lys Met Val Cys Phe Thr He 145 150 155 160 Trp Val Leu Ala Ala Ala Leu Cys He Pro Glu He Leu Tyr Ser Gln 165 170 175 He Lys Glu Glu Be Gly He Wing He Cys Thr Met Val Tyr Pro Ser 180 185 190 Asp Glu Be Thr Lys Leu Lys Be Wing Val Leu Thr Leu Lys Val He 195 200 205 Leu Gly Phe Phe Leu Pro Phe Val Val Met Wing Cys Cys Tyr Thr He 210 215 220 He He His Thr Leu He Gln Wing Lys Lys Ser Ser Lys His Lys Wing 225 230 235 240 Lys Lys Val Thr He Thr Val Leu Thr Val Phe Val Leu Ser Gln Phe 245 250 255 Pro Tyr Asn Cys He Leu Leu Val Gln Thr He Asp Ala Tyr Ala Met 260 265 270 Phe He Ser Asn Cys Wing Val Ser Thr Asn He Asp He Cys Phe Gln 275 280 285 Val Thr Gln Thr He Ala Phe Phe His Ser Cys Leu Asn Pro Val Leu 290 295 300 Tyr Val Phe Val Gly Glu Arg Phe Arg Arg Asp Leu Val Lys Thr Leu 305 310 315 320 Lys Asn Leu Gly Cys He Ser Gln Ala Gln Trp Val Ser Phe Thr Arg 325 330 335 Arg Glu Gly Ser Leu Lys Leu Ser Ser Met Leu Leu Glu Thr Thr Yes 3-0 3J5 350 355 < 210 > 177 < 211 > 1110 < 212 > DNA < 213 > Homo sapiens < 400 > 177 atggcctcat cgaccactcg gggccccagg gtttctgact tattttctgg gctgccgccg 60 ctcccgccaa gcggtcacaa ccagagcgca gaggcctcgg cgggcaacgg gtcggtggct 120 ggcgcggacg ctccagccgt cacgcccttc cagagcctgc agctggtgca tcagctgaag 180 gggctgatcg tgctgctcta cagcgtcgtg gtggtcgtgg ggctggtggg caactgcctg 240 ctggtgctgg tgatcgcgcg ggtgccgcgg ctgcacaacg tgacgaactt cctcatcggc 300 aacctggcct tgtccgacgt gctcatgtgc accgcctgcg tgccgctcac gctggcctat 360 gccttcgagc cacgcggctg ggtgttcggc ggcggcctgt gccacctggt cttcttcctg 420 cagccggtca ccgtctatgt gtcggtgttc acgctcacca ccatcgcagt ggaccgctac 480 gtcgtgctgg tgcacccgct gaggcgcgca tctcgctgcg cctcagccta cgctgtgctg 540 gccatctggg cgctgtccgc ggtgctggcg ctgccgcccg ccgtgcacac ctatcacgtg 600 gagctcaagc cgcacgacgt gcgcctctgc gaggagttct ggggctccca ggagcgccag 660 cgccagctct acgcctgggg gctgctgctg gtcacctacc tgctccctct gctggtcatc 720 ctcctgtctt acgtccgggt gtcagtgaag ctccgcaacc gcgtggtgcc gggctgcgtg 780 acccagagcc aggccgactg ggaccgcgct cggcgccggc gcaccaaatg cttgctggtg 840 gtggtcgtgg tggtgttcgc cgtctgctgg ctgccgctgc acgtcttcaa cctgctgcgg 900 gacctcgacc cccacgccat cgacccttac gcctttgggc tggtgcagct gctctgccac 960 tggctcgcca tgagttcggc ctgctacaac cccttcatct acgcctggct gcacgacagc 1020 ttccgcgagg agctgcgcaa actgttggtc gcttggcccc gcaagata gc cccccatggc 1080 ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^ ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ < 210 > 178 < 211 > 369 < 212 > PRT < 213 > Homo sapiens < 400 > 178 Met Wing Being Thr Thr Arg Gly Pro Arg Val Ser Asp Leu Phe Ser 1 5 10 15 10 Gly Leu Pro Pro Wing Val Thr Thr Pro Wing Asn Gln Ser Wing Glu Wing 20 25 30 Be Wing Gly Asn Gly Ser Val Wing Gly Wing Asp Wing Pro Wing Val Thr 35 40 45 15 Pro Phe Gln Ser Leu Gln Leu Val His Gln Leu Lys Gly Leu He Val 50 55 60 Leu Leu Tyr Ser Val Val Val Val Val Gly Leu Val Gly Asn Cys Leu 20 65 70 75 80 Leu Val Leu Val He Ala Arg Val Pro Arg Leu His Asn Val Thr Asn 85 90 95 Phe Leu He Gly Asn Leu Ala Leu Ser Asp Val Leu Met Cys Thr Ala 25 100 105 110 0 «- 282 Cys Val Pro Leu Thr Leu Wing Tyr Wing Phe Glu Pro Arg Gly Trp Val 115 120 125 Phe Gly Gly Gly Leu Cys His Leu Val Phe Phe Leu Gln Pro Val Thr 130 135 140 Val Tyr Val Ser Val Phe Thr Leu Thr Thr He Ala Val Asp Arg Tyr 145 150 155 160 Val Val Leu Val His Pro Leu Arg Arg Ala Ser Arg Cys Ala Ser Ala 165 170 175 Tyr Ala Val Leu Ala He Trp Ala Leu Ser Ala Val Leu Ala Leu Pro 180 185 190 Pro Ala Val His Thr Tyr His Val Glu Leu Lys Pro His Asp Val Arg 195 200 205 Leu Cys Glu Glu Phe Trp Gly Ser Gln Glu Arg Gln Arg Gln Leu Tyr 210 215 220 Wing Trp Gly Leu Leu Leu Val Thr Tyr Leu Leu Pro Leu Leu Val He 225 230 235 240 Leu Leu Ser Tyr Val Arg Val Ser Val Lys Leu Arg Asn Arg Val Val 245 250 255 Pro Gly Cys Val Thr Gln Ser Gln Wing Asp Trp Asp Arg Wing Arg Arg 260 265 270 Arg Arg Thr Lys Cys Leu Leu Val Val Val Val Val Val Phe Ala Val 275 280 285 Cys Trp Leu Pro Leu His Val Phe Asn Leu Leu Arg Asp Leu Asp Pro 290 295 300 His Wing He Asp Pro Tyr Wing Phe Gly Leu Val Gln Leu Leu Cys His 305 310 315 320 Trp Leu Ala Met Ser Be Ala Cys Tyr Asn Pro Phe He Tyr Wing Trp 325 330 335 Leu His Asp Ser Phe Arg Glu Glu Leu Arg Lys Leu Leu Val Wing Trp 340 345 350 Pro Arg Lys He Wing Pro His Gly Gln Asn Met Thr Val Ser Val Val 355 360 365 I have < 210 > 179 < 211 > 1083 < 212 > DNA < 213 > Homo saoiens < 400 > 179 WiJ8 »^ iirt ^ á- ^ Ma ^ -8 * ^ atefeA ^ B, 6 &, > atggacccag aagaaacttc agtttatttg gattattact atgctacgag cccaaactct 60 gacatcaggg agacccactc ccatgttcct tacacctctg tcttccttcc agtcttttac 120 acagctgtgt tcctgactgg agtgctgggg aaccttgttc tcatgggagc gttgcatttc 180 aaacccggca gccgaagact gatcgacatc tttatcatca atctggctgc ctctgacttc 240 atttttcttg tcacattgcc tctctgggtg gataaagaag catctctagg actgtggagg 300 acgggctcct tcctgtgcaa agggagctcc tacatgatct ccgtcaatat gcactgcagt 360 gtcctcctgc tcacttgcat gagtgttgac cgctacctgg ccattgtgtg gccagtcgta 420 tccaggaaat tcagaaggac agactgtgca tatgtagtct gtgccagcat ctggtttatc 480 tcctgcctgc tggggttgcc tactcttctg tccagggagc tcacgctgat tgatgataag 540 cagagaaaaa ccatactgtg ggcaactcca attaaactca tatggtccct ggtggcctta 600 attttcacct tttttgtccc tttgttgagc attgtgacct gctactgttg cattgcaagg 660 cccattacca aagctgtgtg aagcacaaca gcaatcagga aaaagctgaa gaaatctaag 720 aagatcatct ttattgtcgt ggcagccttt cttgtctcct ggctgccctt caatactttc 780 aagttcctgg ccattgtctc tgggttgcgg caagaacact atttaccctc agctattctt 840 cagcttggta tggaggtgag tggacccttg gcatttgcca acagctgtgt caaccctttc 900 atttactata tcttcgacag ctacatccgc cgggccattg tccactgctt gtgcccttgc 960 ctgaaaaact atgactttgg gagtagcact gagacatcag atagtcacct cactaaggct 1020 ctctccacct tcattcatgc agaagatttt gccaggagga ggaagaggtc tgtgtcactc 1080 taa 1083 < 210 > 180 < 211 > 360 < 212 > PRT < 213 > Homo sapiens < 400 > 180 Met Asp Pro Glu Glu Thr Ser Val Tyr Leu Asp Tyr Tyr Tyr Ala Thr 1 5 10 Ser Pro Asn Ser Asp He Arg Glu Thr His Ser His Val Pro Tyr Thr 20 25 30 Ser Val Phe Leu Pro Val Phe Tyr Thr Ala Val Phe Leu Thr Gly Val 40 45 Leu Gly Asn Leu Val Leu Met Gly Ala Leu His Phe Lys Pro Gly Ser 50 55 60 Arg Arg Leu He Asp He Phe He He Asn Leu Ala Wing Ser Asp Phe 65 70 75 80 He Phe Leu Val Thr Leu Pro Leu Trp Val Asp Lys Glu Ala Ser Leu 85 90 95 Gly Leu Trp Arg Thr Gly Ser Phe Leu Cys Lys Gly Ser Ser Tyr Met 100 105 110 He Ser Val Asn Met His Cys Ser Val Leu Leu Leu Thr Cys Met Ser 115 120 125 Val Asp Arg Tyr Leu Wing He Val Trp Pro Val Val Ser Arg Lys Phe 130 135 140 Arg Arg Thr Asp Cys Wing Tyr Val Val Cys Wing Being He Trp Phe He 145 150 155 160 Ser Cys Leu Leu Gly Leu Pro Thr Leu Leu Ser Arg Glu Leu Thr Leu 165 170 175 He Asp Asp Lys Pro Tyr Cys Wing Glu Lys Lys Wing Thr Pro He Lys 180 185 190 Leu He Trp Ser Leu Val Ala Leu He Phe Thr Phe Phe Val Pro Leu 195 200 205 Leu Ser He Val Thr Cys Tyr Cys Cys He Ala Arg Lys Leu Cys Ala 210 215 220 His Tyr Gln Gln Ser Gly Lys His Asn Lys Lys Leu Lys Lys Ser Lys 225 230 235 240 Lys He He Phe He Val Val Wing Ala Phe Leu Val Ser Trp Leu Pro 245 250 255 Phe Asn Thr Phe Lys Phe Leu Wing He Val Ser Gly Leu Arg Gln Glu 260 265 270 His Tyr Leu Pro Be Ala He Leu Gln Leu Gly Met Glu Val Ser Gly 275 280 285 Pro Leu Ala Phe Ala Asn Ser Cys Val Asn Pro Phe He Tyr Tyr He 290 295 300 Phe Asp Ser Tyr He Arg Arg Wing He Val His Cys Leu Cys Pro Cys 305 310 315 320 Leu Lys Asn Tyr Asp Phe Gly Ser Ser Thr Glu Thr Ser Asp Ser His 325 330 335 Leu Thr Lys Ala Leu Ser Thr Phe He His Wing Glu Asp Phe Wing Arg 340 345 350 Arg Arg Lys Arg Ser Val Ser Leu 355 360 < 210 > 181 < 211 > 1020 < 212 > DNA < 213 > Homo sapiens < 400 > 181 atgaatggcc ttgaagtggc tcccccaggt ctgatcacca acttctccct ggccacggca 60 gagcaatgtg gccaggagac gccactggag aacatgctgt tcgcctcctt ctaccttctg 120 gattttatcc tggctttagt tggcaatacc ctggctctgt ggcttttcat ccgagaccac 180 aagtccggga ccccggccaa cgtgttcctg atgcatctgg ccgtggccga cttgtcgtgc 240 gtgctggtcc tgcccacccg cctggtctac cacttctctg ggaaccactg gccatttggg 300 gaaatcgcat gccgtctcac cggcttcctc ttctacctca acatgtacgc cagcatctac 360 ttcctcacct gcatcagcgc cgaccgtttc ctggccattg tgcacccggt caagtccctc 420 aagctccgca ggcccctcta cgcacacctg gcctgtgcct tcctgtgggt ggtggtggct 480 gtggccatgg ccccgctgct ggtgagccca agaccaacca cagaccgtgc cacggtggtc 540 tgcctgcagc tgtaccggga gaaggcctcc caccatgccc tggtgtccct ggcagtggcc 600 ttcaccttcc cgttcatcac cacggtcacc tgctacctgc tgatcatccg cagcctgcgg 660 cagggcctgc gtc-ggagaa gcgcctcaag accaaggcaa cacgcaLgat cgccatagtg 720 ctggccatct tcctggtctg cttcgtgccc t "accacgLca accgctccgt ctacgtgctg 780 cactaccgca gccatggggc ctcctgcgcc acccagcgca tcctggccct ggcaaaccgc 840 atcacctcct gcctc accag cctcaacggg gcactcgacc ccatcatgta tttcttcgtg 900 gctgagaagt tccgccacgc cctgtgcaac ttgctctgtg gcaaaaggct caagggcccg 960 ccccccagct tcgaagggaa aaccaacgag agctcgctga gtgccaagtc agagctgtga 1020 < 210 > 182 < 211 > 339 < 212 > PRT < 213 > Homo sapiens < 400 > 182 Met Asn Gly Leu Glu Val Wing Pro Pro Gly Leu He Thr Asn Phe Ser 1 5 10 15 Leu Ala Thr Ala Glu Gln Cys Gly Gln Glu Thr Pro Leu Glu Asn Met 20 25 30 Leu Phe Wing Being Phe Tyr Leu Leu Asp Phe He Leu Wing Leu Val Gly 35 40 45 Asn Thr Leu Ala Leu Trp Leu Phe He Arg Asp His Lys Ser Gly Thr 50 55 60 Pro Ala Asn Val Phe Leu Met His Leu Ala Val Ala Asp Leu Ser Cys 65 70 75 80 Val Leu Val Leu Pro Thr Arg Leu Val Tyr His Phe Ser Gly Asn His 90 9th Trp Pro Phe Gly Glu He Wing Cys Arg Leu Thr Gly Phe Leu Phe Tyr 100 105 110 Leu Asn Met Tyr Wing Being He Tyr Phe Leu Thr Cys He Being Wing Asp 115 120 125 Arg Phe Leu Wing He Val His Pro Val Lys Ser Leu Lys Leu Arg Arg 130 135 140 Pro Leu Tyr Ala His Leu Ala Cys Ala Phe Leu Trp Val Val Val Ala 45 150 155 160 Val Ala Met Ala Pro Leu Leu Val Ser Pro Gln Thr Val Gln Thr Asn 165 170 175 His Thr Val Val Cys Leu Gln Leu Tyr Arg Glu Lys Ala Ser His His 180 185 190 Ala Leu Val Ser Leu Ala Val Ala Phe Thr Phe Pro Phe He Thr Thr 195 200 205 Val Thr Cys Tyr Leu Leu He He Arg Ser Leu Arg Gln Gly Leu Arg 210 215 220 Val Glu Lys Arg Leu Lys Thr Lys Wing Lys Arg Met He Wing He Val 225 230 235 240 Leu Ala He Phe Leu Val Cys Phe Val Pro Tyr His Val Asn Arg Sei • o ^^ s ^^ ßß ^ é¿ ¡^, 245 250 255 Val Tyr Val Leu His Tyr Arg Ser His Gly Wing Ser Cys Wing Thr Gln 260 265 270 Arg He Leu Ala Leu Ala Asn Arg He Thr Ser Cys Leu Thr Ser Leu 275 280 285 Asn Gly Ala Leu Asp Pro He Met Tyr Phe Phe Val Ala Glu Lys Phe 290 295 300 Arg His Wing Leu Cys Asn Leu Leu Cys Gly Lys Arg Leu Lys Gly Pro 305 310 315 320 Pro Pro Ser Phe Glu Gly Lys Thr Asn Glu Ser Ser Leu Ser Ala Lys 325 330 335 Ser Glu Leu < 210 > 183 < 211 > 996 < 212 > DNA < 213 > Homo sapiens < 400 > 183 tgaacaatca atgatcaccc gtccctttta agatcaacct tccagatgaa acagctcaca 60 tacaaaattg cagcccttgt cttctatagc tgtatcttca taattggatt atttgttaac 120 atcactgcat tatgggtttt cagttgtacc accaagaaga gaaccacggt aaccatctat 180 atgatgaatg tggcattagt ggacttgata tttataatga ctttaccctt tcgaatgttt 240 tattatgcaa aagatgaatg gccatttgga gagtacttct gccagattct tggagctctc 300 acagtgtttt acccaagcat tgctttatgg cttcttgcct ttattagtgc tgacagatac 360 tacagccgaa atggccattg gtacgccaaa gaacttaaaa acacgtgcaa agccgtgctg 420 gcgtgtgtgg gagtctggat aatgaccctg accacgacca cccctctgct actgctctat 480 aaagacccag ataaagactc cactcccgcc acctgcctca agatttctga catcatctat 540 ctaaaagctg tgaacgtgct gaacctcact cgactgacat tttttttctt gattcctttg 600 ttgggtgcta ttcatcatga cttggtcatt attcataatc tccttcacgg caggacgtct 660 aagctgaaac ccaaagtcaa ggagaagtcc aaaaggatca tcatcacgct gctggtgcag 720 gtgctcgtct gctttatgcc cttccacatc tgtttcgctt tcctgatgct gggaacgggg 780 gagaatagtt acaatccctg gggagccttt accaccttcc tcatgaacct cagcacgtgt 840 ctggatgtga tctctct acta catcgtttca aaacaatttc aggctcgagt cattagtgtc 900 atgctatacc gtaattacct tcgaagcatg cgcagaaaaa gtttccgatc tggtagtcta 960 aggtcactaa gcaatataaa cagtgaaatg ttatga 996 < 210 > 184 < 211 > 331 < 212 > PRT < 213 > Homo sapiens < 400 > 184 I've Thr Leu Asn Asn Gln Asp Gln Pro Val Pro Phe Asn Be Ser 1 5 10 15 His Pro Asp Glu Tyr Lys He Ala Wing Leu Val Phe Tyr Ser Cys He 20 25 30 Pne He He Gly Leu Phe Val Asn He Thr Ala Leu Tro Val? He Ser 35 40 45 Cys Thr Thr Lys Lys Arg Thr Thr Val Thr He Tyr Met Met Asn Val 50 55., 60 Wing Leu Val Asp Leu He Phe He Met Thr Leu Pro Phe Arg Met Phe 65 70 75 80 Tyr Tyr Ala Lys Asp Glu Trp Pro Phe Gly Glu Tyr Phe Cys Gln He 85 90. 95 Leu Gly Ala Leu Thr Val Phe Tyr Pro Ser He Ala Leu Trp Leu Leu 100 105 110 Wing Phe He Wing Wing Asp Arg Tyr Met Wing He Val Gln Pro Lys Tyr 115 120 125 Wing Lys Glu Leu Lys Asn Thr Cys Lys Wing Val Leu Wing Cys Val Gly 130 135 140 Val Trp He Met Thr Leu Thr Thr Thr Pro Leu Leu Leu Leu Tyr 145 150 155 160 Lys Asp Pro Asp Lys Asp Ser Thr Pro Wing Thr Cys Leu Lys He Ser 165 170 175 Asp He He Tyr Leu Lys Ala Val Asn Val Leu Asn Leu Thr Arg Leu 180 185 190 Thr Phe Phe Phe Leu He Pro Leu Phe He Met He Gly Cys Tyr Leu 195 200 205 Val He He His Asn Leu Leu His Gly Arg Thr Ser Lys Leu Lys Pro 210 215 220 Lys Val Lys Glu Lys Ser Lys Arg He He He Thr Leu Leu Val Gln 225 230 235 240 Val Leu Val Cys Phe Met Pro Phe His He Cys Phe Ala Phe Leu Met 245 250 255 Leu Gly Thr Gly Glu Asn Ser Tyr Asn Pro Trp Gly Wing Phe Thr Thr 260 265 270 Phe Leu Met Asn Leu Ser Thr Cys Leu Asp Val He Leu Tyr Tyr He 275 280 285 Val Ser Lys Gln Phe Gln Wing Arg Val He Ser Val Val Leu Tyr Arg 290 295 300 Asn Tyr Leu Arg Ser Met Arg Arg Lys Ser Phe Arg Ser Gly Ser Leu 305 310 315 320 Arg Ser Leu Ser Asn He Asn Ser Glu Met Leu 325 330 < 210 > 185 < 211 > 1077 < 212 > DNA < 213 > Homo sapiens < 400 > 185 atgccctctg tgtctccagc ggggccctcg gccggggcag tccccaatgc caccgcagtg 60 acaacagtgc ggaccaatgc cagcgggctg gaggtgcccc tgttccacct gtttgcccgg 120 ctggacgagg agctgcatgg caccttccca ggcctgtgcg tggcgctgat ggcggtgcac 180 ggagccatct tcctggcagg gctggtgctc aacgggctgg cgctgtacgt cttctgctgc 240 cgcacccggg ccaagacacc ctcagtcatc tacaccatca acctggtggt gaccgatcta 300 ctggtagggc tgtccctgcc cacgcgcttc gctgtgtact acggcgccag gggctgcctg 360 cgctgtgcct tcccgcacgt cctcggttac ttcctcaaca tgcactgctc catcctcttc 420 ctcacctgca tctgcgtgga ccgctacctg gccatcgtgc ggcccgaagg ctcccgccgc 480 tgccgccagc ctgcctgtgc cagggccgtg tgcgccttcg tgtggctggc cgccggtgcc 540 gtcaccctgt cggtgctggg cgtgacaggc agccggccct gctgccgtgt ctttgcgctg 600 actgtcctgg agttcctgct gcccctgctg gtcatcagcg tgtttaccgg ccgcatcatg 660 tgtgcactgt cgcggccggg tctgctccac cagggtcgcc agcgccgcgt gcgggccaag 720 cagctcctgc tcacggtgct catcatcttt ctcgtctgct tcacgccctt ccacgcccgc 780 caagtggccg tggcgctgtg gcccgacatg ccacaccaca cgagcctcgt ggtctaccac 840 gtggccgtga ccctcagcag cctcaacagc tgcatggacc ccatcgtcta ctgcttcgtc 900 accagtggct tccaggccac cgtccgaggc ctcttcggcc agcacggaga gcgtgagccc 960 agcagcggtg acgtggtcag catgcacagg agctccaagg gctcaggccg tcatcacatc 1020 ctcagtgccg gccctcacgc cctcacccag gccctggcta atgggcccga ggcttag 1077 < 210 > 186 < 211 > 358 < 212 > PRT < 213 > Homo sapiens < 400 > 186 Met Pro Ser Val Pro Pro Wing Gly Pro Wing Ala Gly Wing Val Pro Asn 1 5 10 15 Ala Thr Ala Val Thr Thr Val Arg Thr Asn Ala Ser Gly Leu Glu Val 20 25 30 Pro Leu Phe His Leu Phe Ala Arg Leu Asp Glu Glu Leu His Gly Thr 35 40 45 Phe Pro Gly Leu Cys Val Wing Leu Met Wing Val His Gly Wing He Phe 50 55 60 Leu Ala Gly Leu Val Leu Asn Gly Leu Ala Leu Tyr Val Phe Cys Cys 65 70 75 Arg Thr Arg Ala Lys Thr Pro Ser Val He Tyr Thr He Asn Leu Val 85 90 95 Val Thr Asp Leu Leu Val Gly Leu Ser Leu Pro Thr Arg Phe Ala Val 100 105 110 Tyr Tyr Gly Wing Arg Gly Cys Leu Arg Cys Wing Phe Pro His Val Leu 115 120 125 Gly Tyr Pne Leu Asn Met His Cys Ser He Leu Phe Le _ Thr Cys IIc 130 135 140 Cys Val Asp Arg Tyr Leu Wing He Val Arg Pro Glu Gly Ser Arg Wing 145 150 155 160 Cys Arg Gln Pro Wing Cys Wing Arg Wing Val Cys Wing Phe Val Trp Leu 165 170 175 Ala Ala Gly Ala Val Thr Leu Ser Val Leu Gly Val Thr Gly Ser Arg 180 185 190 Pro Cys Cys Arg Val Phe Ala Leu Thr Val Leu Glu Phe Leu Leu Pro 195 200 205 Leu Leu Val He Ser Val Phe Thr Gly Arg He Met Cys Ala Leu Ser 210 215 220 Arg Pro Gly Leu Leu His Gln Gly Arg Gln Arg Arg Val Arg Ala Lys 225 230 235 240 Gln Leu Leu Leu Thr Val Leu He He Phe Leu Val Cys Phe Thr Pro 245 250 255 Phe His Wing Arg Gln Val Wing Val Wing Leu Trp Pro Asp Met Pro His 260 265 270 His Thr Ser Leu Val Val Tyr His Val Wing Val Thr Leu Ser Ser Leu 275 280 285 Asn Ser Cys Met Asp Pro He Val Tyr Cys Phe Val Thr Ser Gly Phe 290 295 300 Gln Ala Thr Val Arg Gly Leu Phe Gly Gln His Gly Glu Arg Glu Pro 305 310 315 320 Be Ser Gly Asp Val Val Ser Met His Arg Ser Ser Lys Gly Ser Gly 325 330 335 Arg His His He Leu Ser Wing Gly Pro His Wing Leu Thr Gln Wing Leu 340 345 350 Wing Asn Gly Pro Glu Wing 355 < 210 > 187 < 211 > 1050 < 212 > DNA < 213 > Homo sapiens < 400 > 187 atgaactcca ccttggatgg taatcagagc agccaccctt tttgcctctt ggcatttggc 60 tatttggaaa ctgtcaattt ttgccttttg gaagtattga ttattgtctt tctaactgta 120 ttgattattt ctggcaacat cattgtgatt tttgtatttc actgtgcacc tttgttgaac 180 catcacacta caagttattt tatccagact atggcatatg ctgacctttt tgttggggtg 240 agctgcgtgg tcccttcttt atcactcctc catcaccccc ttccagtaga ggagtccttg 300 acttgccaga tatttggttt tgtagtatca gttctgaaga gcgtctccat ggcttctctg 360 gcctgtatca gcattgatag atacattgcc attactaaac ctttaaccta taatactctg 420 gttacaccct ggagactacg cctgtgtatt ttcctgattt ggctatactc gaccctggtc 480 ttcctgcctt cctttttcca ctggggcaaa cctggatatc atggagatgt gtttcagtgg 540 tgtgcggagt cctggcacac cgactcctac ttcaccctgt tcatcgtgat gatgttatat 600 gccccagcag cccttattgt ctgcttcacc tatttcaaca tcttccgcat ctgccaacag 660 atatcagcga cacacaaagg aaggcaagcc cgcttcagca gccagagtgg ggagactggg 720 gaagtgcagg cctgtcctga taagcgctat aaaatggtcc tgtttcgaat cactagtgta 780 ttttacatcc tctggttgcc atatatcatc tacttcttgt tggaaagctc cactggccac 840 agcaaccgct tcgcat cctt cttgaccacc tggcttgcta ttagtaacag tttctgcaac 900 tgtgtaattt atagtctctc caacagtgta ttccaaagag gactaaagcg cctctcaggg 960 gctatgtgta cttcttgtgc aagtcagact acagccaacg acccttacac agttagaagc 1020 aaaggccctc ttaatggatg tcatatctga 1050 < 210 > 188 < 211 > 349 < 212 > PRT < 213 > Homo sapiens < 400 > 188 Met Asn Ser Thr Leu Asp Gly Asn Gln Ser Ser His Pro Phe Cys Leu 1 5 10 15 Leu Ala Phe Gly Tyr Leu Glu Thr Val Asn Phe Cys Leu Leu Glu Val 20 25 30 Leu He He Val Phe Leu Thr Val Leu He He Ser Gly Asn He He 35 40 45 Val He Pbe Val Phe His Cys Ala Pro Leu Leu Asn His H s Thr Th] riwsa > i ^ &Sa8aa »aiaia? fea ^ iifa? i.« «. *, ^^^^^^^ & t, 50 55 60 Ser Tyr Phe He Gln Thr Met Wing Tyr Wing Asp Leu Phe Val Gly Val 65 70 75 80 Ser Cys Val Val Pro Ser Leu Ser Leu Leu His Pro Pro Leu Pro Val 85 90 95 Glu Glu Ser Leu Thr Cys Gln He Phe Gly Phe Val Val Ser Val Leu 100 105 110 Lys Ser Val Ser Met Wing Ser Leu Wing Cys He Ser He Asp Arg Tyr 115 120 125 He Wing He Thr Lys Pro Leu Thr Tyr Asn Thr Leu Val Thr Pro Trp 130 135 140 Arg Leu Arg Leu Cys He Phe Leu He Trp Leu Tyr Ser Thr Leu Val 145 150 155 160 Phe Leu Pro Ser Phe Phe His Trp Gly Lys Pro Gly Tyr His Gly Asp 165 170 175 Val Phe Gln Trp Cys Wing Glu Ser Trp His Thr Asp Ser Tyr Phe Thr 180 185 190 Leu Phe He Val Met Met Leu Tyr Ala Pro Ala Ala Leu He Val Cys 195 200 205 Phe Thr Tyr Phe Asn He Phe Arg He Cys Gln Gln His Thr Lys Asp 210 215 220 He Is Glu Arg Gln Wing Arg Phe Being Ser Gln Ser Gly Glu Thr Gly 225 230 235 240 Glu Val Gln Ala Cys Pro Asp Lys Arg Tyr Lys Met Val Leu Phe Arg 245 250 255 He Thr Ser Val Phe Tyr He Leu Trp Leu Pro Tyr He He Tyr Phe 260 265 270 Leu Leu Glu Be Ser Thr Gly His Ser Asn Arg Phe Ala Ser Phe Leu 275 280 285 Thr Thr Trp Leu Wing He Being Asn Being Phe Cys Asn Cys Val He Tyr 290 295 300 Ser Leu Ser Asn Ser Val Phe Gln Arg Gly Leu Lys Arg Leu Ser Gly 305 310 315 320 Wing Met Cys Thr Ser Cys Wing Ser Gln Thr Thr Wing Asn Asp Pro Tyr 325 330 335 Thr Val Arg Ser Lys Gly Pro Leu Asn Gly Cys His He 340 345 < 210 > 189 < 211 > 1302 < 212 > DNA < 213 > Homo sapiens < 400 > 189 atgtgttttt ctcccattct ggaaatcaac atgcagtctg aatctaacat tacagtgcga 60 gatgacattg atgacatcaa caccaatatg taccaaccac tatcatatcc gttaagcttt 120 caagtgtctc tcaccggatt tcttatgtta gaaattgtgt tgggacttgg cagcaacctc 180 actgtattgg tactttactg catgaaatcc aacttaatca actctgtcag taacattatt 240 acaatgaatc ttcatgtact tgatgtaata atttgtgtgg gatgtattcc tctaactata 300 gttatccttc tgctttcact ggagagtaac actgctctca tttgctgttt ccatgaggct 360 tgtgtatctt ttgcaagtgt ctcaacagca atcaacgttt ttgctatcac tttggacaga 420 tatgacatct ctgtaaaacc tgcaaaccga attctgacaa tgggcagagc tgtaatgtta 480 atgatatcca tttggatttt ttcttttttc tctttcctga ttccttttat tgaggtaaat 540 tttttcagtc ttcaaagtgg aaatacctgg gaaaacaaga tgtcagtaca cacttttatg 600 aatgaatact acactgaact gggaatgtat tatcacctgt tagtacagat cccaatattc 660 tttttcactg ttgtagtaat gttaatcaca tacaccaaaa tacttcaggc tcttaatatt 720 cgaataggca caagattttc aacagggcag aagaagaaag caagaaagaa aaagacaatt 780 cacaacatga tctctaacca atgtcacaaa ggctacagac gagaaatgta gcagtggtgg 840 gtctttggtg taagaa CTTC agtttctgta ataattgccc tccggcgagc tgtgaaacga 900 gacgagaaag caccgtgaac acaaaagaga gtcaagagga tgtctttatt gattatttct 960 acatttcttc tctgctggac accaatttct gttttaaata ccaccatttt atgtttaggc 1020 ccaagtgacc ttttagtaaa attaagattg tgttttttag tcatggctta tggaacaact 1080 atatttcacc ctctattata tgcattcact agacaaaaat ttcaaaaggt cttgaaaagt 1140 agcgagttgt aaaatgaaaa gaagctgatc ttctatagta ccctgcctaa taatgctgta 1200 cttggataga atacacaact tcccaaaaga aacaaaaaaa ttacctttga agatagtgaa 1260 ataagagaaa aacgtttagt gcctcaggtt gtcacagact ag 1302 * & amp; < 210 > 190 < 211 > 433 < 212 > PRT < 213 > Homo sapiens < 400 > 190 Met Cys Phe Ser Pro He Leu Glu He Asn Met Gln Ser Glu Ser Asn 1 5 10 15 He Thr Val Arg Asp Asp He Asp Asp He Asn Thr Asn Met Tyr Gln 20 25 30 Pro Leu Ser Tyr Pro Leu Ser Phe Gln Val Ser Leu Thr Gly Phe Leu 35 40 45 Met Leu Glu He Val Leu Gly Leu Gly Ser Asn Leu Thr Val Leu Val 50 55 60 Leu Tyr Cys Met Lys Ser Asn Leu He Asn Ser Val Ser Asn He He 65 70 75 80 Thr Met Asn Leu His Val Leu Asp Val He He Cys Val Gly Cys He 85 90 95 Pro Leu Thr He Val Leu Leu Leu Ser Leu Glu Ser Asn Thr Ala 100 105 110 Leu He Cys Cys Phe His Glu Wing Cys Val Ser Phe Ala Ser Val Ser 115 120 125 Thr Ala He Asn Val Phe Wing He Thr Leu Asp Arg Tyr Asp He Ser 130 135 140 Val Lys Pro Wing Asn Arg He Leu Thr Met Gly Arg Wing Val Met Leu 145 150 155 160 Met He Ser He Trp He Phe Ser Phe Phe Ser Phe Leu He Pro Phe 165 170 175 He Glu Val Asn Phe Phe Ser Leu Gln Ser Gly Asn Thr Trp Glu Asn 180 185 190 Lys Thr Leu Leu Cys Val Ser Thr Asn Glu Tyr Tyr Thr Glu Leu Gly 195 200 205 Met Tyr Tyr His Leu Leu Val Gln He Pro He Phe Phe Phe Thr Val 210 215 220 Val Val Met Leu He Thr Tyr Thr Lys He Leu Gln Ala Leu Asn He 225 230 235 240 Arg He Gly Thr Arg Phe Ser Thr Gly Gln Lys Lys Lys Wing Arg Lys 245 250 255 Lys Lys Thr He Ser Leu Thr Thr Gln His Glu Wing Thr Asp Met Ser 260 265 270 Gln Ser Ser Gly Gly Arg Asn Val Val Phe Gly Val Arg Thr Ser Val 275 280 285 Ser Val He He Ala Ala Arg Arg Ala Val Lys Arg His Arg Glu Arg 290 295 300 Arg Glu Arg Gln Lys Arg Val Lys Arg Met Ser Leu Leu He He Ser 305 310 315 320 Thr Phe Leu Leu Cys Trp Thr Pro He Ser Val Leu Asn Thr Thr He 325 330 335 Leu Cys Leu Gly Pro Ser Asp Leu Leu Val Lys Leu Arg Leu Cys Phe 340 345 350 Leu Val Met Ala Tyr Gly Thr Thr He Phe His Pro Leu Leu Tyr Ala 355 360 365 Phe Thr Arg Gln Lys Phe Gln Lys Val Leu Lys Ser Lys Met Lys Lys 370 375 380 Arg Val Val Ser He Val Val Glu Ala Asp Pro Leu Pro Asn Asn Ala Val 385 390 395 400 He His Asn Ser Trp He Asp Pro Lys Arg Asn Lys Lys He Thr Phe 405 410 415 Glu Asp Ser Glu He Arg Glu Lys Arg Leu Val Pro Gln Val Val Thr 420 425 430 Asp < 210 > 191 < 211 > 1209 < 212 > DNA < 213 > Homo sapiens < 400 > 191 atgttgtgtc cttccaagac agatggctca gggcactctg gtaggattca ccaggaaact 60 catggagaag ggaaaaggga caagattagc aacagtgaag ggagggagaa tggtgggaga 120 ggattccaga tgaacggtgg gtcgctggag gctgagcatg ccagcaggat gtcagttctc 180 agagcaaagc ccatgtcaaa cagccaacgc ttgctccttc tgtccccagg atcacctcct 240 gcatctccta cgcacgggga catcaacatc atcatgcctt cggtgttcgg caccatctgc 300 tcatcgggaa ctcctgggca ctccacggtc atcttcgcgg tcgtgaagaa gtccaagctg 360 cactggtgca acaacgtccc cgacatcttc atcatcaacc tctcggtagt agatctcctc 420 tttctcctgg gcatgccctt catgatccac cagctcatgg gcaatggggt gtggcacttt 480 ggggagacca tgtgcaccct catcacggcc atggatgcca atagtcagtt caccagcacc 540 tacatcctga ccgccatggc cattgaccgc tacctggcca ctgtccaccc catctcttcc 600 acgaagttcc ggaagccctc tgtggccacc ctggtgatct gcctcctgtg ggccctctcc 660 ttcatcagca tcacccctgt gtggctgtat gccagactca tccccttccc aggaggtgca 720 gtgggctgcg gcatacgcct gcccaaccca gacactgacc tctactggtt caccctgtac 780 cagtttttcc tggcctttgc cctgcctttt gtggtcatca cagccgcata cgtgaggatc 840 ctgcagcgca tgacgt CCTC agtggccccc gcctcccagc gcagcatccg gctgcggaca 900 aagagggtga aacgcacagc catcgccatc tgtctggtct tctttgtgtg ctgggcaccc 960 tactatgtgc tacagctgac ccagttgtcc atcagccgcc cgaccctcac ctttgtctac 1020 ttatacaatg cggccatcag cttgggc-at gccaacagct gcctcaaccc ctttgtgtac 1080 af F * # & 306 atcgtgctct gtgagacgtt ccgcaaacgc ttggtcctgt cggtgaagcc tgcagcccag 1140 gggcagcttc gcgctgtcag caacgctcag acggctgacg aggagaggac agaaagcaaa 1200 ggcacctga 1209 < 210 > 192 5 < 211 > 402 < 212 > PRT < 213 > Homo sapiens < 400 > 192 JO Met Leu Cys Pro Ser Lys Thr Asp Gly Ser Gly His Ser Gly Arg He 1 5 10 15 His Gln Glu Thr His Gly Glu Gly Lys Arg Asp Lys He Ser Asn Ser 20 25 30 Glu Gly Arg Glu Asn Gly Gly Arg Gly Phe Gln Met Asn Gly Gly Ser 35 40 45 Leu Glu Ala Glu His Ala Ser Arg Met Ser Val Leu Arg Ala Lys Pro 50 55 60 Met Ser Asn Ser Gln Arg Leu Leu Leu Leu Ser Pro Gly Ser Pro Pro 65 70 75 80 Arg Thr Gly Be He Be Tyr He Asn He He Met Met Pro Ser Val Phe 85 90 95 25 Gly Thr He Cys Leu Leu Gly He He Gly Asn Ser Thr Val He Phe 100 105 110 Wing Val Val Lys Lys Ser Lys Leu His Trp Cys Asn Asn Val Pro Asp 115 120 125 5 He Phe He He Asn Leu Ser Val Val Asp Leu Leu Phe Leu Leu Gly 130 135 140 Met Pro Phe Met He His Gln Leu Met Gly Asn Gly Val Trp His Phe 10 145 150 155 160 Gly Glu Thr Met Cys Thr Leu He Thr Wing Met Asp Wing Asn Ser Gln 165 170 175 Phe Thr Ser Thr Tyr He Leu Thr Ala Met Wing He Asp Arg Tyr Leu 180 185 190 Ala Thr Val His Pro Be Ser Thr Lys Phe Arg Lys Pro Ser Val 195 200 205 Wing Thr Leu Val He Cys Leu Leu Trp Wing Leu Ser Phe He Ser He 210 215 220 Thr Pro Val Trp Leu Tyr Wing Arg Leu He Pro Phe Pro Gly Gly Wing 225 230 235 240 Val Gly Cys Gly He Arg Leu Pro Asn Pro Asp Thr Asp Leu Tyr Trp 245 250 255 Phe Thr Leu Tyr Gln Phe Phe Leu Wing Phe Wing Leu Pro Phe Val Val 260 265 270 He Thr Ala Ala Tyr Val Arg He Leu Gln Arg Met Thr Ser Ser Val 275 280 285 Wing Pro Wing Being Gln Arg Being He Arg Leu Arg Thr Lys Arg Val Lys 290 295 300 Arg Thr Ala He Ala He Cys Leu Val Phe Phe Val Cys Trp Ala Pro 305 310 315 320 Tyr Tyr Val Leu Gln Leu Thr Gln Leu Ser He Be Arg Pro Thr Leu 325 330 335 Thr Phe Val Tyr Leu Tyr Asn Wing Wing He Ser Leu Gly Tyr Wing Asn 340 345 350 Ser Cys Leu Asn Pro Phe Val Tyr He Val Leu Cys Glu Thr Phe Arg 355 360 365 Lys Arg Leu Val Leu Ser Val Lys Pro Wing Ala Gln Gly Gln Leu Arg 370 375 380 Wing Val Ser Asn Wing Gln Thr Wing Asp Glu Glu Arg Thr Glu Ser Lys 385 390 395 400 Gly Thr < 210 > 193 < 211 > 1128 < 212 > DNA < 213 > Homo sapiens < 400 > 193 atggatgtga cttcccaagc ccggggcgtg ggcctggaga tgtacccagg caccgcgcac 60 gctgcggccc ccaacaccac ctcccccgag ctcaacctgt cccacccgct cctgggcacc 120 gccctggcca atgggacagg tgagctctcg gagcaccagc agtacgtgat cggcctgttc 180 ctctcgtgcc tctacaccat cttcctcttc cccatcggct ttgtgggcaa catcctgatc 240 ctggtggtga acatcagctt ccgcgagaag atgaccatcc ccgacctgta cttcatcaac 300 ctggcggtgg cggacctcat cctggtggcc gactccctca ttgaggtgtt caacctgcac 360 gagcggtact acgacatcgc cgtcctgtgc accttcatgt cgctcttcct gcaggtcaac 420 atgtacagca gcgtcttctt cctcacctgg atgagcttcg accgctacat cgccctggcc 480 agggccatgc gctgcagcct gttccgcacc aagcaccacg cccggctgag ctgtggcctc 540 atctggatgg catccgtgtc agccacgctg ccgccgtgca gtgcccttca cctgcagcac 600 accgacgagg cctgcttctg tttcgcggat gtccgggagg tgcagtggct cgaggtcacg 660 ctgggcttca tcgtgccctt cgccatcatc ggcctgtgct actccctcat tgtccgggtg 720 ctggtcaggg cgcaccggca ccgtgggctg cggccccggc ggcagaaggc gaaacgcatg 780 atcctcgcgg tggtgctggt cttcttcgtc tgctggctgc cggagaacgt cttcatcagc 840 gtgcacctcc tgcagc GGAC gcagcctggg gccgctccct gcaagcagtc tttccgccat 900 gcccaccccc tcacgggcca cattgtcaac ctcgccgcct tctccaacag ctgcctaaac 960 cccctcatct acagctttct cggggagacc ttcagggaca agctgaggct gtacattgag 1020 cagaaaacaa atttgccggc cctgaaccgc ttctgtcacg ctgccctgaa ggccgtcatt 1080 ccagacagca ccgagcagtc ggatgtgagg ttcagcagtg ccgtgtga 1128 ÍKlsSÍÍBSa ^^ ft¿Sáfc < 210 > 194 < 211 > 375 < 212 > PRT < 213 > Homo sapiens < 400 > 194 Met Asp Val Thr Ser Gln Ala Arg Gly Val Gly Leu Glu Met Tyr Pro 1 5 10 15 Gly Thr Ala His Wing Ala Wing Pro Asn Thr Thr Ser Pro Glu Leu Asn 20 25 30 Leu Ser His Pro Leu Leu Gly Thr Ala Leu Wing Asn Gly Thr Gly Glu 35 40 45 Leu Ser Glu His Gln Gln Tyr Val He Gly Leu Phe Leu Ser Cys Leu 50 55 60 Tyr Thr He Phe Leu Phe Pro He Gly Phe Val Gly Asn He Leu He 65 70 75 80 Leu Val Val Asn He Be Phe Arg Glu Lys Met Thr He Pro Asp Leu 85 90 95 Tyr Phe He Asn Leu Wing Val Wing Asp Leu He Leu Val Wing Asp Ser 100 105 110 Leu He Glu Val Phe Asn Leu His Glu Arg Tyr Tyr Asp He Ala Val 311 115 120 125 Leu Cys Thr Phe Met Ser Leu Phe Leu Gln Val Asn Met Tyr Ser Ser 130 135 140 Val Phe Phe Leu Thr Trp Met Ser Phe Asp Arg Tyr He Ala Leu Ala 145 150 155 160 Arg Ala Met Arg Cys Ser Leu Phe Arg Thr Lys His His Wing Arg Leu 165 170 175 Ser Cys Gly Leu He Trp Met Wing Ser Val Ser Wing Thr Leu Val Pro 180 185 190 Phe Thr Ala Val His Leu Gln His Thr Asp Glu Ala Cys Phe Cys Phe 195 200 205 15 Wing Asp Val Arg Glu Val Gln Trp Leu Glu Val Thr Leu Gly Phe He 210 215 220 Val Pro Phe Wing He He Gly Leu Cys Tyr Ser Leu He Val Arg Val 225 230 235 240 Leu Val Arg Ala His Arg His Arg Gly Leu Arg Pro Arg Arg Gln Lys 245 250 255 Ala Lys Arg Met He Leu Ala Val Val Leu Val Phe Phe Val Cys Trp 260 265 270 -taWiafcifinteifeaoiJ? éaaw, - .. • ..-.:,. ^. ..

Leu Pro Glu Asn Val Phe He Ser Val His Leu Leu Gln Arg Thr Gln 275 280 285 Pro Gly Wing Wing Pro Cys Lys Gln Ser Phe Arg His Wing His Pro Leu 290 295 300 Thr Gly His He Val Asn Leu Ala Wing Phe Ser Asn Ser Cys Leu Asn 305 310 315 320 Pro Leu He Tyr Ser Phe Leu Gly Glu Thr Phe Arg Asp Lys Leu Arg 325 330 335 Leu Tyr He Glu Gln Lys Thr Asn Leu Pro Ala Leu Asn Arg Phe Cys 340 345 350 His Wing Wing Leu Lys Wing Val He Pro Asp Being Thr Glu Gln Being Asp 355 360 365 Val Arg Phe Ser Ser Ala Val 370 375 < 210 > 195 < 211 > 960 < 212 > DNA < 213 > Homo sapiens < 400 > 195 atgccattcc caaactgctc agcccccagc actgtggtgg ccacagctgt gggtgtcttg 60 &? 313 ctggggctgg agtgtgggct gggtctgctg ggcaacgcgg tggcgctgtg gaccttcctg 120 ttccgggtca gggtgtggaa gccgtacgct gtctacctgc tcaacctggc cctggctgac 180 ctgctgttgg ctgcgtgcct gcctttcctg gccgccttct acctgagcct ccaggcttgg 240 catctgggcc gtgtgggctg ctgggccctg cgcttcctgc tggacctcag ccgcagcgtg 300 gggatggcct tcctggccgc cgtggctttg gaccggtacc tccgtgtggt ccaccctcgg 360 cttaaggtca acctgctgtc tcctcaggcg gccctggggg tctcgggcct cgtctggctc 420 ctgatggtcg ccctcacctg cccgggcttg ctcatctctg aggccgccca gaactccacc 480 gtttctactc aggtgccaca ggctccttca cagggcagac gcaggaagca gcatcatctg 540 ctctcctgcc ttcagtttgt cctccccttt ggcctcatcg tgttctgcaa tgcaggcatc 600 atcagggctc tccagaaaag actccgggag cctgagaaac agcccaagct tcagcgggcc 660 aaggcactgg tcaccttggt ggtggtgctg tttgctctgt gctttctgcc ctgcttcctg 720 gccagagtcc tgatgcacat cttccagaat ctggggagct gcagggccct ttgtgcagtg 780 gctcatacct cggatgtcac gggcagcctc acctacctgc acagtgtcgt caaccccgtg 840 gtatactgct tctccagccc caccttcagg agctcctatc ggagggtctt ccacaccctc 900 cgaggcaaag ggcaggcagc agagccccca gatttcaacc ccagagactc ctattcctga 960 < 210 > 196 < 211 > 319 < 212 > PRT < 213 > Homo sapiens < 400 > 196 Met Pro Phe Pro Asn Cys Ser Wing Pro Ser Thr Val Val Wing Ala Thr 1 5 10 15 Val Gly Val Leu Leu Gly Leu Glu Cys Gly Leu Gly Leu Leu Gly Asn 20 25 30 25 Wing Val Ala Leu Trp Thr Phe Leu Phe Arg Val Arg Val Trp Lys Pro 35 40 45 Tyr Ala Val Tyr Leu Leu Asn Leu Ala Leu Ala Asp Leu Leu Leu Ala 50 55 60 Ala Cys Leu Pro Phe Leu Wing Wing Phe Tyr Leu Ser Leu Gln Wing Trp 65 70 75 80 His Leu Gly Arg Val Gly Cys Trp Ala Leu Arg Phe Leu Leu Asp Leu 85 90 95 Ser Arg Ser Val Gly Met Wing Phe Leu Wing Wing Val Wing Leu Asp Arg 100 105 110 Tyr Leu Arg Val Val His Pro Arg Leu Lys Val Asn Leu Leu Ser Pro 115 120 125 Gln Ala Ala Leu Gly Val Ser Gly Leu Val Trp Leu Leu Met Val Wing 130 135 140 Leu Thr Cys Pro Gly Leu Leu He Ser Glu Ala Wing Gln Asn Ser Thr 145 150 155 160 Arg Cys His Ser Phe Tyr Ser Arg Wing Asp Gly Ser Phe Ser He He 165 170 175 Trp Gln Glu Ala Leu Ser Cys Leu Gln Phe Val Leu Pro Phe Gly Leu 85? * 315 180 185 190 He Val Phe Cys Asn Wing Gly He He Arg Wing Leu Gln Lys Arg Leu 195 200 205 Arg Glu Pro Glu Lys Gln Pro Lys Leu Gln Arg Ala Lys Ala Leu Val 210 215 220 Thr Leu Val Val Val Leu Phe Ala Leu Cys Phe Leu Pro Cys Phe Leu 225 230 235 240 Wing Arg Val Leu Met His He Phe Gln Asn Leu Gly Ser Cys Arg Wing 245 250 255 Leu Cys Ala Val Ala His Thr Ser Asp Val Thr Gly Ser Leu Thr Tyr 260 265 270 15 Leu His Ser Val Val Asn Pro Val Val Tyr Cys Phe Ser Ser Pro Thr 275 280 285 Phe Arg Ser Ser Tyr Arg Arg Val Phe His Thr Leu Arg Gly Lys Gly 290 295 300 Gln Ala Ala Glu Pro Pro Asp Phe Asn Pro Arg Asp Ser Tyr Ser 305 310 315 < 210 > 197 25 < 211 > 1143 < 212 > DNA < 213 > Homo sapiens < 400 > 197 atggaggaag gtggtgattt tgacaactac tatggggcag acaaccagtc tgagtgtgag 60 tacacagact ggaaatcctc gggggccctc atccctgcca tctacatgtt ggtcttcctc 120 ctgggcacca cgggaaacgg tctggtgctc tggaccgtgt ttcggagcag ccgggagaag 180 aggcgctcag ctgatatctt cattgctagc ctggcggtgg ctgacctgac cttcgtggtg 240 acgctgcccc tgtgggctac ctacacgtac cgggactatg actggccctt tgggaccttc 300 ttctgcaagc tcagcagcta cctcatcttc gtcaacatgt acgccagcgt cttctgcctc 360 accggcctca gcttcgaccg ctacctggcc atcgtgaggc cagtggccaa tgctcggctg 420 aggctgcggg tcagcggggc cgtggccacg gcagttcttt gggtgctggc cgccctcctg 480 gccatgcctg tcatggtgtt acgcaccacc ggggacttgg agaacaccac taaggtgcag 540 tgctacatgg actactccat ggtggccact gtgagctcag agtgggcctg ggaggtgggc 600 cttggggtct cgtccaccac cgtgggcttt gtggtgccct tcaccatcat gctgacctgt 660 tacttcttca tcgcccaaac catcgctggc cacttccgca aggaacgcat cgagggcctg 720 cggaagcggc gccggcttaa gagcatcatc gtggtgctgg tggtgacctt tgccctgtgc 780 tggatgccct accacctggt gaagacgctg tacatgctgg gcagcctgct gcactggccc 840 tgtgactttg acct cttcct catgaacatc ttcccctact gcacctgcat cagctacgtc 900 aacagctgcc tcaacccctt cctctatgcc tttttcgacc cccgcttccg ccaggcctgc 960 acctccatgc tctgctgtgg ccagagcagg tgcgcaggca cctcccacag cagcagtggg 1020 gagaagtcag ccagctactc ttcggggcac agccaggggc ccggccccaa catgggcaag 1080 ggtggagaac agatgcacga gaaatccatc ccctacagcc aggagaccct tgtggttgac tag 1140 1143 < 210 > 198 < 211 > 380 < 212 > PRT < 213 > Homo sapiens < 400 > 198 Met Glu Glu Gly Gly Asp Phe Asp Asn Tyr Tyr Gly Wing Asp Asn Gln 1 5 10 15 5 Ser Glu Cys Glu Tyr Thr Asp Trp Lys Ser Ser Gly Ala Leu He Pro 20 25 30 Ala He Tyr Met Leu Val Phe Leu Leu Gly Thr Thr Gly Asn Gly Leu 10 35 40 45 Val Leu Trp Thr Val Phe Arg Ser Ser Arg Glu Lys Arg Arg Ser Wing 50 55 60 Asp He Phe He Wing Ser Leu Wing Val Wing Asp Leu Thr Phe Val Val 65 70 75 Thr Leu Pro Leu Trp Wing Thr Tyr Thr Tyr Arg Asp Tyr Asp Trp Pro 85 90 95 Phe Gly Thr Phe Phe Cys Lys Leu Ser Ser Tyr Leu He Phe Val Asn 100 105 110 Met Tyr Ala Ser Val Phe Cys Leu Thr Gly Leu Ser Phe Asp Arg Tyr 115 120 125 Leu Ala He val Arg Pro Val Ala Asn Ala Arg Leu Arg Leu Arg Val 130 135 140 Ser Gly Ala Val Ala Thr Ala Val Leu Trp Val Leu Ala Ala Leu Leu 145 150 155 160 Wing Met Pro Val Met Val Leu Arg Thr Thr Gly Asp Leu Glu Asn Thr 165 170 175 Thr Lys Val Gln Cys Tyr Met Asp Tyr Ser Met Val Wing Thr Val Ser 180 185 190 Ser Glu Trp Wing Trp Glu Val Gly Leu Gly Val Ser Ser Thr Thr Val 195 200 205 Gly Phe Val Val Pro Phe Thr He Met Leu Thr Cys Tyr Phe Phe He 210 215 220 Wing Gln Thr He Wing Gly His Phe Arg Lys Glu Arg He Glu Gly Leu 225 230 235 240 Arg Lys Arg Arg Arg Leu Lys Ser He He Val Val Leu Val Val Thr 245 250 255 Phe Ala Leu Cys Trp Met Pro Tyr His Leu Val Lys Thr Leu Tyr Met 260 265 270 Leu Gly Ser Leu Leu His Trp Pro Cys Asp Phe Asp Leu Phe Leu Met 275 280 285 Asn He Phe Pro Tyr Cys Thr Cys He Ser Tyr Val Asn Ser Cys Leu 290 295 300 Asn Pro Phe Leu Tyr Wing Phe Phe Asp Pro Arg Phe Arg Gln Wing Cys 305 310 315 320 Thr Ser Met Leu Cys Cys Gly Gln Ser Arg Cys Wing Gly Thr Ser His 325 330 335 Being Being Gly Glu Lys Being Wing Being Tyr Being Being Gly His Being Gln 340 345 350 Gly Pro Gly Pro Asn Met Gly Lys Gly Gly Glu Gln Met His Glu Lys 355 360 365 Ser He Pro Tyr Ser Gln Glu Thr Leu Val Val Asp 370 375 380 < 210 > 199 < 211 > 1119 < 212 > DNA < 213 > Homo sapiens < 400 > 199 atgaactacc cgctaacgct ggaaatggac ctcgagaacc tggaggacct gttctgggaa 60 ctggacagat tggacaacta taacgacacc tccctggtgg aaaatcatct ctgccctgcc 120 acagagggtc ccctcatggc ctccttcaag gccgtgttcg tgcccgtggc ctacagcctc 180 atcttcctcc tgggcgtgat cggcaacgtc ctggtgctgg tgatcctgga gcggcaccgg 240 mÉ $ Mi iJÉÉ »á? í cagacacgca gttccacgga gaccttcctg ttccacctgg ccgtggccga cctcctgctg 300 gtcttcatct tgccctttgc cgtggccgag ggctctgtgg gctgggtcct ggggaccttc 360 ctctgcaaaa ctgtgattgc cctgcacaaa gtcaacttct actgcagcag cctgctcctg 420 gcctgcatcg ccgtggaccg ctacctggcc attgtccacg ccgtccatgc ctaccgccac 480 tctccatcca cgccgcctcc catcacctgt gggaccatct ggctggtggg cttcctcctt 540 gccttgccag agattctctt cgccaaagtc agccaaggcc atcacaacaa ctccctgcca 600 tctcccaaga cgttgcacct gaaccaagca gaaacgcatg cctggttcac ctcccgattc 660 ctctaccatg tggcgggatt cctgctgccc atgctggtga tgggctggtg ctacgtgggg 720 ggttgcgcca gtagtgcaca ggcccagcgg cgccctcagc ggcagaaggc aaaaagggtg 780 gccatcctgg tgacaagcat cttcttcctc tgctggtcac cctaccacat cgtcatcttc 840 ctggacaccc tggcgaggct gaaggccgtg gacaatacct gcaagctgaa tggctctctc 900 cccgtggcca tcaccatgtg tgagttcctg ggcctggccc actgctgcct caaccccatg 960 ctctacactt tcgccggcgt gaagttccgc agtgacctgt cgcggctcct gaccaagctg 1020 ggctgtaccg gccctgcctc cctgtgccag ctcttcccta gctggcgcag gagcagtctc 1080 tctgagtcag agaa tgccac ctctctcacc acgttctag 1119 < 210 > 200 < 211 > 372 < 212 > PRT < 213 > Homo sapiens < 400 > 200 Met Asn Tyr Pro Leu Thr Leu Glu Met Asp Leu Glu Asn Leu Glu Asp 1 5 10 15 Leu Phe Trp Glu Leu Asp Arg Leu Asp Asn Tyr Asn Asp Thr Ser Leu 20 25 30 I mMMÜ iiqf ^ iati &? Jbk * Val Glu Asn His Leu Cys Pro Wing Thr Glu Gly Pro Leu Met Wing Ser 35 40 45 Phe Lys Wing Val Phe Val Pro Val Wing Tyr Ser Leu He Phe Leu Leu 50 55 60 Gly Val He Gly Asn Val Leu Val Leu Val He Leu Glu Arg His Arg 65 70 75 80 Gln Thr Arg Ser Ser Thr Glu Thr Phe Leu Phe His Leu Wing Val Wing 85 90 95 Asp Leu Leu Leu Val Phe He Leu Pro Phe Wing Val Wing Glu Gly Ser 100 105 110 Val Gly Trp Val Leu Gly Thr Phe Leu Cys Lys Thr Val He Ala Leu 115 120 125 His Lys Val Asn Phe Tyr Cys Ser Ser Leu Leu Leu Ala Cys He Ala 130 135 140 Val Asp Arg Tyr Leu Wing He Val His Wing Val His Wing Tyr Arg His 145 150 155 160 Arg Arg Leu Leu Ser He His He Thr Cys Gly Thr He Trp Leu Val 165 170 175 G] and Phe Leu Leu Ala Leu Pro Glu He Leu Phe Ala Lys Val Ser Gln 180 185 190 Gly His His Asn Asn Ser Leu Pro Arg Cys Thr Phe Ser Gln Glu Asn 195 200 205 Gln Ala Glu Thr His Wing Trp Phe Thr Ser Arg Phe Leu Tyr His Val 210 215 220 Wing Gly Phe Leu Leu Pro Met Leu Val Met Gly Trp Cys Tyr Val Gly 225 230 235 240 Val Val His Arg Leu Arg Gln Wing Gln Arg Arg Pro Gln Arg Gln Lys 245 250 255 Ala Lys Arg Val Ala He Leu Val Thr Ser He Phe Phe Leu Cys Trp 260 265 270 Ser Pro Tyr His He Val He Phe Leu Asp Thr Leu Ala Arg Leu Lys 275 280 285 Wing Val Asp Asn Thr Cys Lys Leu Asn Gly Ser Leu Pro Val Wing He 290 295 300 Thr Met Cys Glu Phe Leu Gly Leu Wing His Cys Cys Leu Asn Pro Met 305 310 315 320 Leu Tyr Thr Phe Wing Gly Val Lys Phe Arg Ser Asp Leu Ser Arg Leu 325 330 335 ^ • l ^ ¡& ¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡¡Leu Thr Lys Leu Gly Cys Thr Gly Pro Wing Ser Leu Cys Gln Leu Phe 340 345 350 Pro Ser Trp Arg Arg Ser Ser Leu Ser Glu Ser Glu Asn Ala Thr Ser 355 360 365 Leu Thr Thr Phe 370 < 210 > 201 < 211 > 1128 < 212 > DNA < 213 > Homo sapiens < 400 > 201 atggatgtga cttcccaagc ccggggcgtg ggcctggaga tgtacccagg caccgcgcag 60 cctgcggccc ccaacaccac ctcccccgag ctcaacctgt cccacccgct cctgggcacc 120 gccctggcca atgggacagg tgagctctcg gagcaccagc agtacgtgat cggcctgttc 180 ctctcgtgcc tctacaccat cttcctcttc cccatcggct ttgtgggcaa catcctgatc 240 ctggtggtga acatcagctt ccgcgagaag atgaccatcc ccgacctgta cttcatcaac 300 ctggcggtgg cggacctcat cctggtggcc gactccctca ttgaggtgtt caacctgcac 360 gagcggtact acgacatcgc cgtcctgtgc accttcatgt cgctcttcct gcaggtcaac 420 atgtacagca gcgtcttctt cctcacctgg atgagcttcg accgctacat cgccctggcc 480 agggccatgc gctgcagcct gttccgcacc aagcaccacg cccggctgag ctgtggcctc 540 atctggatgg catccgtgtc agccacgctg ccgccgtgca gtgcccttca cctgcagcac 600 accgacgagg cctgcttctg tttcgcggat gtccgggagg tgcagtggct cgaggtcacg 660 ctgggcttca tcgtgccctt cgccatcatc ggcctgtgct actccctcat tgtccgggtg 720 ctggtcaggg cgcaccggca ccgtgggctg cggccccggc ggcagaaggc gaagcgcatg 780 atcctcgcgg tggtgctggt cttcttcgtc tgctggctgc cggagaacgt cttcatcagc 840 gtgcacctcc tgcagc GGAC gcagcctggg gccgctccct gcaagcagtc tttccgccat 900 gcccaccccc tcacgggcca cattgtcaac ctcaccgcct tctccaacag ctgcctaaac 960 cccctcatct acagctttct cggggagacc ttcagggaca agctgaggct gtacattgag 1020 cagaaaacaa atttgccggc cctgaaccgc ttctgtcacg ctgccctgaa ggccgtcatt 1080 ccagacagca ccgagcagtc ggatgtgagg ttcagcagtg ccgtgtag 1128 < 210 > 202 < 211 > 375 < 212 > PRT < 213 > Homo sapiens < 400 > 202 Met Asp Val Thr Ser Gln Ala Arg Gly Val Gly Leu Glu Met Tyr Pro 1 5 10 15 Gly Thr Ala Gln Pro Ala Ala Pro Asn Thr Thr Ser Pro Glu Leu Asn 20 25 30 Leu Ser His Pro Leu Leu Gly Thr Ala Leu Wing Asn Gly Thr Gly Glu 35 40 45 Leu Ser Glu His Gln Gln Tyr Val He Gly Leu Phe Leu Ser Cys Leu 50 55 60 Tyr Thr He Phe Leu Phe Pro He Gly Phe Val Gly Asn He Leu He 65 70 75 80 a-ga? ¿^.? ^, ^ ^ ^ ^ ^ ^, Leu Val Val Asn He Be Phe Arg Glu Lys Met Thr He Pro Asp Leu 85 90 95 Tyr Phe He Asn Leu Wing Val Wing Asp Leu He Leu Val Wing Asp Being 100 105 110 Leu He Glu Val Phe Asn Leu His Glu Arg Tyr Tyr Asp He Ala Val 115 120 125 Leu Cys Thr Phe Met Ser Leu Phe Leu Gln Val Asn Met Tyr Ser Ser 130 135 140 Val Phe Phe Leu Thr Trp Met Ser Phe Asp Arg Tyr He Ala Leu Ala 145 150 155 160 Arg Ala Met Arg Cys Ser Leu Phe Arg Thr Lys His His Wing Arg Leu 165 170 175 Ser Cys Gly Leu He Trp Met Wing Ser Val Be Wing Thr Leu Val Pro 180 185 190 Phe Thr Ala Val His Leu Gln His Thr Asp Glu Ala Cys Phe Cys Phe 195 200 205 Wing Asp Val Arg Glu Val Gln Trp Leu Glu Val Thr Leu Gly Pie He 210 215 220 Val Pro Phe Ala He He Gly Leu Cys Tyr Ser Leu He al _g Val 225 230 235 240 Leu Val Arg Ala His Arg His Arg Gly Leu Arg Pro Arg Arg Gln Lys 245 250 255 Ala Lys Arg Met He Leu Ala Val Val Leu Val Phe Phe Val Cys Trp 260 265 270 Leu Pro Glu Asn Val Phe He Ser Val His Leu Leu Gln Arg Thr Gln 275 280 285 Pro Gly Wing Wing Pro Cys Lys Gln Ser Phe Arg His Wing His Pro Leu 290 295 300 Thr Gly His He Val Asn Leu Thr Ala Phe Ser Asn Ser Cys Leu Asn 305 310 315 320 Pro Leu He Tyr Ser Phe Leu Gly Glu Thr Phe Arg Asp Lys Leu Arg 325 330 335 Leu Tyr He Glu Gln Lys Thr Asn Leu Pro Ala Leu Asn Arg Phe Cys 340 345 350 His Wing Wing Leu Lys Wing Val He Pro Asp Being Thr Glu Gln Being Asp 355 360 365 Val Arg Phe Ser Ser Ala Val 370 375 < 210 > 203 < 211 > 1137 < 212 > DNA < 213 > Homo sapiens < 400 > 203 atggacctgg ggaaaccaat gaaaagcgtg ctggtggtgg ctctccttgt cattttccag 60 gtatgcctgt gtcaagatga ggtcacggac gattacatcg gagacaacac cacagtggac 120 tacactttgt tcgagtcttt gtgctccaag aaggacgtgc ggaactttaa agcctggttc 180 ctccctatca tgtactccat catttgtttc gtgggcctac tgggcaatgg gctggtcgtg 240 tctatttcaa ttgacctata gaggctcaag accatgaccg atacctacct gctcaacctg 300 gcggtggcag acatcctctt cctcctgacc cttcccttct gggcctacag cgcggccaag 360 tcctgggtct tcggtgtcca cttttgcaag ctcatctttg ccatctacaa gatgagcttc 420 ttcagtggca tgctcctact tctttgcatc agcattgacc gctacgtggc catcgtccag 480 gctgtctcag ctcaccgcca gtccttctca ccgtgcccgc tcagcaagct gtcctgtgtg 540 ggcatctgga tactagccac agtgctctcc atcccagagc tcctgtacag tgacctccag 600 aggagcagca gtgagcaagc gatgcgatgc tctctcatca cagagcatgt ggaggccttt 660 atcaccatcc aggtggccca gatggtgatc ggctttctgg tccccctgct ggccatgagc 720 ttctgttacc ttgtcatcat ccgcaccctg ctccaggcac gcaactttga gcgcaacaag 780 gccaaaaagg tgatcatcgc tgtggtcgtg gtcttcatag tcttccagct gccctacaat 840 ggggtggtcc tggc ccagac ggtggccaac ttcaacatca ccagtagcac ctgtgagctc 900 agtaagcaac tcaacatcgc ctacgacgtc acctacagcc tggcctgcgt ccgctgctgc 960 gtcaaccctt tcttgtacgc cttcatcggc gtcaagttcc gcaacgatct cttcaagctc 1020 ttcaaggacc tgggctgcct cagccaggag cagctccggc agtggtcttc ctgtcggcac 1080 atccggcgct cctccatgag tgtggaggcc gagaccacca ccaccttctc cccatag 1137 < 210 > 204 < 211 > 37Í < 212 > PRT < 213 > Homo sapiens < 400 > 204 Met Asp Leu Gly Lys Pro Met Lys Ser Val Leu Val Val Ala Leu Leu 10 15 Val He Phe Gln Val Cys Leu Cys Gln Asp Glu Val Thr Asp Asp Tyr 20 25 30 He Gly Asp Asn Thr Thr Val Asp Tyr Thr Leu Phe Glu Ser Leu Cys 35 40 45 Ser Lys Lys Asp Val Arg Asn Phe Lys Wing Trp Phe Leu Pro He Met 50 55 60 Tyr Ser He He Cys Phe Val Gly Leu Leu Gly Asn Gly Leu Val Val 65 70 75 80 Leu Thr Tyr He Tyr Phe Lys Arg Leu Lys Thr Met Thr Asp Thr Tyr 85 90 95 Leu Leu Asn Leu Ala Val Ala Asp He Leu Phe Leu Leu Thr Leu Pro 100 105 110 Phe Trp Wing Tyr Wing Wing Lys Ser Trp Val Phe Gly Val his Phe 115 120 125 Cys Lys Leu He Phe Wing He Tyr Lys Met Ser Phe Phe Ser Gly Met 130 135 140 Leu Leu Leu Leu Cys He Ser He Asp Arg Tyr Val Ala He Val Gln 145 150 155 160 Ala Val Ser Ala His Arg His Arg Ala Arg Val Leu Leu IIe Ser Lys 165 170 175 Leu Ser Cys Val Gly He Trp He Leu Wing Thr Val Leu Ser He Pro 180 185 190 Glu Leu Leu Tyr Being Asp Leu Gln Arg Being Being Glu Gln Ala Met 195 200 205 Arg Cys Ser Leu He Thr Glu His Val Glu Wing Phe II e Thr He Gln 210 215 220 Val Ala Gln Met Val He Gly Phe Leu Val Pro Leu Leu Ala Met Ser 225 230 235 240 Phe Cys Tyr Leu Val He He Arg Thr Leu Leu Gln Ala Arg Asn Phe 245 250 255 Glu Arg Asn Lys Wing Lys Lys Val He He Wing Val Val Val Val Phí 260 265 270 He Val Val Gln Leu Pro "yr Asn Gly Val Val Leu Ala Gln Thr Val A. 3 J0 275 ^ or 285 Wing Asn Phe Asn He Thr Ser Ser Thr Cys Glu Leu Ser Lys Gln Leu 290 295 300 Asn He Ala Tyr Asp Val Thr Tyr Ser Leu Ala Cys Val Arg Cys Cys 305 310 315 320 Val Asn Pro Phe Leu Tyr Wing Phe He Gly Val Lys Phe Arg Asn Asp 325 330 335 10 Leu Phe Lys Leu Phe Lys Asp Leu Gly Cys Leu Ser Gln Glu Gln Leu 340 345 350 Arg Gln Trp Be Ser Cys Arg His He Arg Arg Ser Ser Met Ser Val 355 360 365 15 Glu Ala Glu Thr Thr Thr Thr Phe Ser Pro 370 375 < 210 > 205 20 < 211 > 1086 < 212 > DNA < 213 > Homo sapiens < 400 > 205 atggatatac aaatggcaaa caattttact ccgccctctg caactcctca gggaaatgac 60 atgcacatca tgtgacctct aggatagtaa cagcacggcc tgcctctgca ttacagcctc 120 gtcttcatca ttgggctcgt gggaaactta ctagccttgg tcgtcattgt tcaaaacagg 180 aaaaaaatca actctaccac cctctattca acaaatttgg tgatttctga tatacttttt 240 accacggctt tgcctacacg aatagcctac tatgcaatgg gctttgactg gagaatcgga 300 gatgccttgt gtaggataac tgcgctagtg tttíftacatca acacatatgc aggtgtgaac 360 tttatgacct gcctgagtat tgaccgcttc attgctgtgg tgcaccctct acgctacaac 420 ggattgaaca aagataaaaa tgcaaaaggc gtgtgcatat ttgtctggat tctagtattt 480 gctcagacac tcccactcct catcaaccct atgtcaaagc aaggattaca aggaggctga 540 tgcatggagt atccaaactt tgaagaaact aaatctcttc cctggattct gcttggggca 600 tgtttcatag gatatgtact tccacttata atcattctca tctgctattc tcagatctgc 660 tgcaaactct tcagaactgc caaacaaaac ccactcactg agaaatctgg tgtaaacaaa 720 aaggctaaaa acacaattat tcttattatt gttgtgtttg ttctctgttt cacaccttac 780 ttattcaaca catgttgcaa tatgattaag aagcttcgtt tctctaattt cctggaatgt 840 agccaaagac attcgttcca gatttctctg cactttacag tatgcctgat gaacttcaat 900 tgctgcatgg acccttttat ctacttcttt gcatgtaaag ggtataagag aaaggttatg 960 aggatgctga aacggcaagt cagtgtatcg atttctagtg ctgtgaagtc agcccctgaa 1020 gaaaattcac gtgaaatgac agaaacgcag atgatgatac attccaagtc ttcaaatgga AAGTGA 1080 1086 < 210 > 206 < 211 > 361 < 212 > PRT < 213 > Homo sapiens < 400 > 206 Met Asp He Gln Met Wing Asn Asn Phe Thr Pro Pro Be Wing Thr Pro 1 5 10 15 Gln Gly Asn Asp Cys Asp Leu Tyr Wing His His Ser Thr Wing Arg He 20 25 30 Val Met Pro Leu His Tyr Ser Leu Val Phe He He Gly Leu Val Gly 35 40 45 Asn Leu Leu Ala Leu Val Val He Val Gln Asn Arg Lys Lys He Asn 50 55 60 Being Thr Thr Leu Tyr Being Thr Asn Leu Val He Being Asp He Leu Phe 65 70 75 80 Thr Thr Ala Leu Pro Thr Arg He Wing Tyr Tyr Wing Met Gly Phe Asp 85 90 95 Trp Arg He Gly Asp Ala Leu Cys Arg He Thr Ala Leu Val Phe Tyr 100 105 110 He Asn Thr Tyr Wing Gly Val Asn Phe Met Thr Cys Leu Ser He Asp 115 120 125 Arg Phe He Wing Val Val His Pro Leu Arg Tyr Asn Lys He Lys Arg 130 135 140 He Glu His Wing Lys Gly Val Cys He Phe Val Trp He Leu Val Phe 145 150 155 160 Wing Gln Thr Leu Pro Leu Leu He Asn Pro Met Ser Lys Cm Glu Wing 165 170 175 Glu Arg He Thr Cys Met Glu Tyr Pro Asn Phe Glu Glu Thr Lys Ser 180 185 190 Leu Pro Trp He Leu Leu Gly Ala Cys Phe He Gly Tyr Val Leu Pro 195 200 205 Leu He He He Leu He Cys Tyr Ser Gln He Cys Cys Lys Leu Phe 210 215 220 Arg Thr Ala Lys Gln Asn Pro Leu Thr Glu Lys Ser Gly Val Asn Lys 225 230 235 240 Lys Ala Lys Asn Thr He He Leu He He Val Val Phe Val Leu Cys 245 250 255 Phe Thr Pro Tyr His Val Wing He He Gln His Met He Lys Lys Leu 260 265 270 Arg Phe Ser Asn Phe Leu Glu Cys Ser Gln Arg His Ser Phe Gln He 275 280 285 Ser Leu His Phe Thr Val Cys Leu Met Asn Phe Asn Cys Cys Met Asp 290 295 300 Pro Phe He Tyr Phe Phe Wing Cys Lys Gly Tyr Lys Arg Lys Val Met 305 310 315 320 Arg Met Leu Lys Arg Gln Val Ser Val Ser He Ser Ser Ala Ala Lys 325 330 335 Be Wing Pro Glu Glu Asn Be Arg Glu Met Thr Glu Thr Gln Met Met 340 345 350 He His Ser Lys Ser Ser Asn Gly Lys 355 360 < 210 > 207 < 211 > 1446 < 212 > DNA < 213 > Homo sapiens < 400 > 207 atgcggtggc tgtggcccct ggctgtctct cttgctgtga ttttggctgt ggggctaagc 60 agggtctctg ggggtgcccc cctgcacctg ggcaggcaca gagccgagac ccaggagcag 120 cagagccgat ccaagagggg caccgaggat gaggaggcca agggcgtgca gcagtatgtg 180 cctgaggagt gggcggagta cccccggccc attcaccctg ctggcctgca gccaaccaag 240 cccttggtgg ccaccagccc taaccccgac aaggatgggg gcaccccaga cagtgggcag 300 gaactgaggg gcaatctgac aggggcacca gggcagaggc tacagatcca gaaccccctg 360 tatccggtga ccgagagctc ctacagtgcc tatgccatca tgcttctggc gctggtggtg 420 tttgcggtgg gcattgtggg caacctgtcg tcgtgtggca gtcatgtgca cagctactac 480 ctgaagagcg cctggaactc catccttgcc agcctggccc tctgggattt tctggtcctc 540 tttttctgcc tccctattgt catcttcaac gagatcacca agcagaggct actgggtgac 600 gtttcttgtc gtgccgtgcc cttcatggag gtctcctctc tgggagtcac gactttcagc 660 tgggcattga ctctgtgccc ccgcttccac gtggccacca gcaccctgcc caaggtgagg 720 cccatcgagc gstgccaatc catcctggcc aagttggctg tcatctgggt gggctccatg 780 acgctggctg tgcctgagct cctgcfcgtgg cagctggcac aggagcctgc ccccaccatg 840 ggcaccctgg actcatgcat catgaaaccc tcagccagcc tgcccgagtc cctgtattca 900 cctaccagaa ctggtgatga cgcccgcatg tggtggtact ttggctgcta cttctgcctg 960 cccatcctct tcacagtcac ctgccagctg gtgacatggc gggtgcgagg ccctccaggg 1020 aggaagtcag agtgcagggc cagcaagcac gagcagtgtg agagccagct caagagcacc 1080 gtggtgggcc tgaccgtggt ctacgccttc tgcaccctcc cagagaacgt ctgcaacatc 1140 gtggtggcct acctctccac cgagctgacc cgccagaccc tggacctcct gggcctcatc 1200 aaccagttct ccaccttctt caagggcgcc atcaccccag tgctgctcct ttgcatctgc 1260 aggccgctgg gccaggcctt cctggactgc tgctgctgct gctgctgtga ggagtgcggc 1320 ggggcttcgg aggcctctgc tgccaatggg tcggacaaca agctcaagac cgaggtgtcc 1380 tcttccatct acttccacaa gcccagggag tcacccccac tcctgcccct gggcacacct tgctga 1440 1446 < 210 > 208 < 211 > 481 < 212 > PRT < 213 > Homo sapiens < 400 > 208 Met Arg Trp Leu Trp Pro Leu Ala Val Ser Leu Ala Val He Leu Ala 1 5 10 15 Val Gly Leu Ser Arg Val Ser Gly Gly Ala Pro Leu His Leu Gly Arg 20 25 30 His Arg Ala Glu Thr Gln Glu Gln Gln Ser Arg Ser Lys Arg Gly Thr 35 3 3 45 Glu Asp Glu Glu Ala Lys Gly Val Gln Gln Tyr Val Pro Glu Glu Trp 50 55 60 Wing Glu Tyr Pro Arg Pro He His Pro Wing Gly Leu Gln Pro Thr Lys 65 70 75 80 Pro Leu Val Wing Thr Ser Pro Asn Pro Asp Lys Asp Gly Gly Thr Pro 85 90 95 Asp Ser Gly Gln Glu Leu Arg Gly Asn Leu Thr Gly Wing Pro Gly Gln 100 105 110 Arg Leu Gln He Gln Asn Pro Leu Tyr Pro Val Thr Glu Ser Ser Tyr 115 120 125 Being Ala Tyr Ala He Met Leu Leu Ala Leu Val Val Phe Ala Val Gly 130 135 140 He Val Gly Asn Leu Ser Val Met Cys He Val Trp His Ser Tyr Tyr 145 150 155 160 Leu Lys Ser Wing Trp Asn Ser He Leu Wing Ser Leu Wing Leu Trp Asp 165 170 175 Phe Leu Val Leu Phe Phe Cys Leu Pro He Val He Phe Asn Glu He 180 185 190 Thr Lys Gln Arg Leu Leu Gly Asp Val Ser Cys Arg Ala Val Pro Pie 331 195 200 205 Met Glu Val Ser Ser Leu Gly Val Thr Thr Phe Ser Leu Cys Ala Leu 21? ' 215 t > [220 Gly He Asp Arg Phe His Val Wing Thr Ser Thr Leu Pro Lys Val Arg 225 230 235 240 Pro He Glu Arg Cys Gln Ser He Leu Ala Lys Leu Ala Val He Trp 245 250 255 Val Gly Ser Met Thr Leu Ala Val Pro Glu Leu Leu Leu Trp Gln Leu 260 265 270 Wing Gln Glu Pro Wing Pro Thr Met Gly Thr Leu Asp Ser Cys He Met 275 280 285 Lys Pro Ser Ala Ser Leu Pro Glu Ser Leu Tyr Ser Leu Val Met Thr 290 295 300 Tyr Gln Asn Ala Arg Met Trp Trp Tyr Phe Gly Cys Tyr Phe Cys Leu 305 310 315 320 Pro He Leu Phe Thr Val Thr Cys Gln Leu Val Thr Trp Arg Val Arg 325 330 335 Gly Pro Pro Gly Arg Lys Ser Glu Cys Arg Wing Ser Lys His Glu Gln 340 345 350 Cys Glu Ser Gln Leu Lys Ser Thr Val Val Gly Leu Thr Val Val Tyr 355 360 365 Wing Phe Cys Thr Leu Pro Glu Asn Val Cys Asn He Val Val Wing Tyr 370 375 380 Leu Ser Thr Glu Leu Thr Arg Gln Thr Leu Asp Leu Leu Gly Leu He 385 390 395 400 Asn Gln Phe Ser Thr Phe Phe Lys Gly Wing He Thr Pro Val Leu Leu 405 410 415 Leu Cys He Cys Arg Pro Leu Gly Gln Wing Phe Leu Asp Cys Cys Cys 420 425 430 Cys Cys Cys Cys Glu Glu Cys Gly Gly Wing Ser Glu Wing Be Ala Wing 435 440 445 Asn Gly Ser Asp Asn Lys Leu Lys Thr Glu Val Ser Ser Ser He Tyr 450 455 460 Phe His Lys Pro Arg Glu Pro Pro Pro Leu Leu Pro Leu Gly Thr Pro 465 470 475 480 Cys < 210 > 209 < 211 > 1101 < 212 > DNA < 213 > Homo sapiens < 400 > 209 atgtggaacg cgacgcccag cgaagagccg gggttcaacc tcacactggc cgacctggac 60 tgggatgctt cccccggcaa cgactcgctg ggcgacgagc tgctgcagct cttccccgcg 120 ccgctgctgg cgggcgtcac agccacctgc gtggcactct tcgtggtggg tatcgctggc 180 aacctgctca ccatgctggt ggtgtcgcgc ttccgcgagc tgcgcaccac caccaacctc 240 tacctgtcca gcatggcctt ctccgatctg ctcatcttcc tctgcatgcc cctggacctc 300 gttcgcctct ggcagtaccg gccctggaac ttcggcgacc tcctctgcaa actcttccaa 360 ttcgtcagtg agagctgcac ctacgccacg gtgctcacca tcacagcgct gagcgtcgag 420 cgctacttcg ccatctgctt cccactccgg gccaaggtgg tggtcaccaa ggggcgggtg 480 aagctggtca tcttcgtcat ctgggccgtg gccttctgca gcgccgggcc catcttcgtg 540 ctagtcgggg tggagcacga gaacggcacc gacccttggg acaccaacga gtgccgcccc 600 accgagtttg cggtgcgctc tggactgctc acggtcatgg tgtgggtgtc cagcatcttc 660 ttcttccttc ctgtcttctg tctcacggtc ctctacagtc tcatcggcag gaagctgtgg 720 cggaggaggc gcggcgatgc tgtcgtgggt gggaccagaa gcctcgctca ccacaagcaa 780 accaagaaaa tgctggctgt agtggtgttt gccttcatcc tctgctggct ccccttccac 840 gtagggcgat atttat TTTC caaatccttt gagcctggct ccttggagat tgctcagatc 900 agccagtact gcaacctcgt gtcctttgtc ctcttctacc tcagtgctgc catcaacccc 960 attctgtaca acatcatgtc caagaagtac cgggtggcag tgttcagact tctgggattc 1020 gaacccttct cccagagaaa gctctccact ctgaaagatg aaagttctcg ggcctggaca gaatctagta 1080 to 1101 ttaatacatg < 210 > 210 < 211 > 366 < 212 > PRT < 213 > Homo sapiens < 400 > 210 Met Trp Asn Wing Thr Pro Ser Glu Glu Pro Gly Phe Asn Leu Thr Leu 10 15 Wing Asp Leu Asp Trp Asp Wing Ser Pro Gly Asn Asp Ser Leu Gly Asp 25 30 Glu Leu Leu Gln Leu Phe Pro Pro Wing Leu Leu Wing Gly Val Thr Ala 40 45 Thr Cys Val Wing Leu Phe Val Val Gly He Wing Gly Asn Leu Leu Thr 50 55 60 Met Leu Val Val Ser Arg Phe Arg Glu Leu Arg Thr Thr Thr Asn Leu 65 70 75 80 Tyr Leu Ser Ser Met Wing Phe Ser Asp Leu Leu He Phe Leu Cys Met 85 90 95 Pro Leu Asp Leu Val Arg Leu Trp Gln Tyr Arg Pro Trp Asn Phe Gly 100 105 110 Asp Leu Leu Cys Lys Leu Phe Gln Phe Val Ser Glu Ser Cys Thr Tyr 115 120 125 Wing Thr Val Leu Thr He Thr Wing Leu Ser Val Glu Arg Tyr Phe Wing 130 135 140 He Cys Phe Pro Leu Arg Wing Lys Val Val Val Thr Lys Gly Arg Val 145 150 155 160 Lys Leu Val He Phe Val He Trp Wing Val Wing Phe Cys Ser Wing Gly 165 170 175 Pro He Phe Val Leu Val Gly Val Glu His Glu Asn Gly Thr Asp Pro 180 185 190 Trp Asp Thr Asn Glu Cys Arg Pro Thr Glu Phe Wing Val Arg Ser Gly 195 200 205 Leu Leu Thr Val Met Val Trp Val Ser Ser He Phe Phe Phe Leu Pro 210 215 220 Val Phe Cys Leu Thr Val Leu Tyr Ser Leu He Gly Arg Lys Leu Trp 225 230 235 240 Arg Arg Arg Arg Gly Asp Wing Val Val Gly Wing Ser Leu Arg Asp Gln 245 250 255 Asn His Lys Gln Thr Lys Lys Met Leu Wing Val Val Val Phe Wing Phe 260 265 270 He Leu Cys Trp Leu Pro Phe His Val Gly Arg Tyr Leu Phe Ser Lys 275 280 285 Being Phe Glu Pro Gly Being Leu Glu He Wing Gln He Being Gl- > Tyr Cys 290 295 300 Asn Leu Val Ser Phe Val Leu Phe Tyr Leu Ser Ala Ala He Asn Pro 305 310 315 320 He Leu Tyr Asn He Met Ser Lys Lys Tyr Arg Val Wing Val Phe Arg 325 330 335 Leu Leu Gly Phe Glu Pro Phe Ser Gln Arg Lys Leu Ser Thr Leu Lys 340 345 350 Asp Glu Be Ser Arg Ala Trp Thr Glu Be Ser He Asn Thr 355 360 365 < 210 > 211 < 211 > 1842 < 212 > DNA < 213 > Homo sapiens < 400 > 211 atgcgagccc cgggcgcgct tctcgcccgc atgtcgcggc tactgcttct gctactgctc 60 aaggtgtctg cctcttctgc cctcggggtc gcccctgcgt ccagaaacga aacttgtctg 120 ggggagagct gtgcacctac agtgatccag cgccgcggca gggacgcctg gggaccggga 180 aattctgcaa gagacgttct gcgagcccga gcacccaggg aggagcaggg ggcagcgttt 240 cttgcgggac cctcctggga cctgccggcg gccccgggcc gtgacccggc tgcaggcaga 300 ggggcggagg cgtcggcagc cggacccccg ggacctccaa ccaggccacc tggcccctgg 360 aggtggaaag gtgctcgggg tcaggagcct tctgaaactt tggggagagg gaaccccacg 420 gccctccagc tcttccttca gatctcagag gaggaagaga agggtcccag aggcgctggc 480 atttccgggc gtagccagga gcagagtgtg aagacagtcc ccggagccag cgatcttttt 540 tactggccaa ggagagccgg gaaactccag ggttcccacc acaagcccct gtccaagacg 600 tggcggggca gccaatggac cgaagggtgg acaattgcac tcccgggccg ggcgctggcc 660 ccttgggtga cagaatggat aggaatccat gagcctgggg gtccccgccg gggaaacagc 720 acgaaccggc gtgtgagact gaagaacccc ttctacccgc tgacccagga gtcctatgga 780 gcctacgcgg tcatgtgtct gtccgtggtg atcttcggga ccggcatcat tggcaacctg 840 gcggtgatgt gcatcg tgtg ccacaactac tacatgcgga gcatctccaa ctccctcttg 900 gccaacctgg ccttctggga ctttctcatc atcttcttct gccttccgct ggtcatcttc 960 cacgagctga ccaagaagtg gctgctggag gacttctcct gcaagatcgt gccctatata 1020 gaggtcgcct ctctgggagt caccactttc accttatgtg ctctgtgcat agaccgcttc 1080 ccaacgtaca cgtgctgcca gatgtactac gaaatgatcg aaaattgttc ctcaacaact 1140 gccaaacttg ctgttatatg ggtgggagct ctattgttag cacttccaga agttgttctc 1200 gcaaggagga cgccagctga tttggggttt agtggccgag ctccggcaga aaggtgcatt 1260 attaagatct ctcctgattt accagacacc atctatgttc tagccctcac ctacgacagt 1320 gcgagactgt ggtggtattt tggctgttac ttttgtttgc ccacgctttt caccatcacc 1380 tgctctctag tgactgcgag gaaaatccgc aaagcagaga aagcctgtac ccgagggaat 1440 ttcaactaga aaacggcaga gagtcagatg aagtgtacag tagtggcact gaccatttta 1500 tatggatttt gcattattcc tgaaaatatc tgcaacattg ttactgccta catggctaca 1560 ggggtttcac agcagacaat ggacctcctt aatatcatca gccagttcct tttgttcttt 1620 aagtcctgtg tcaccccagt cctccttttc tgtctctgca aacccttcag tcgggccttc 1680 atggagtgct gctgctgttg ctg tgaggaa tgcattcaga agtcttcaac ggtgaccagt 1740 gatgacaatg acaacgagta caccacggaa ctcgaactct cgcctttcag taccatacgc 1800 cgtgaaatgt ccacttttgc ttctgtcgga actcattgct ga 1842 < 210 > 212 < 211 > 613 < 212 > PRT < 213 > Homo sapiens g «« gu¿ »se ^^? ^ í ^ Ut í llbíám ^^ li & Sí < 400 > 212 Met Arg Ala Pro Gly Ala Leu Leu Ala Arg Met Ser Arg Leu Leu Leu 1 5 10 15 Leu Leu Leu Leu Lys Val Be Ala Be Ser Ala Leu Gly Val Ala Pro 25 30 Ala Ser Arg Asn Glu Thr Cys Leu Gly Glu Ser Cys Ala Pro Thr Val 35 40 45 He Gln Arg Arg Gly Arg Asp Wing Trp Gly Pro Gly Asn Ser Wing Arg 50 55 60 Asp Val Leu Arg Wing Arg Wing Pro Arg Glu Glu Gln Gly Wing Wing Phe 65 70 75 80 Leu Wing Gly Pro Ser Trp Asp Leu Pro Wing Wing Pro Gly Arg Asp Pro 85 90 95 Ala Ala Gly Arg Gly Ala Glu Ala Be Ala Ala Gly Pro Pro Gly Pro 100 105 110 Pro Thr Arg Pro Pro Gly Pro Trp Arg Trp Lys Gly Wing Arg Gly Gln 115 120 125 Glu Pro Ser Glu Thr Leu Gly Arg Gly Asn Pro Thr Ala Leu Gln Leu 130 135 140 Phe Leu Gln He Ser Glu Glu Glu Glu Gly Lys Gly Pro Arg Gly Gly Wing 145 150 155 160 He Be Gly Arg Be Gln Glu Gln Ser Val Lys Thr Val Pro Gly Wing 165 170 175 Being Asp Leu Phe Tyr Trp Pro Arg Arg Wing Gly Lys Leu Gln Gly Ser 180 185 190 His His Lys Pro Leu Ser Lys Thr Wing Asn Gly Leu Wing Gly His Glu 195 200 205 Gly Trp Thr He Wing Leu Pro Gly Arg Wing Leu Wing Gln Asn Gly Ser 210 215 220 Leu Gly Glu Gly He His Glu Pro Gly Gly Pro Arg Arg Gly Asn Ser 225 230 235 240 Thr Asn Arg Arg Val Arg Leu Lys Asn Pro Phe Tyr Pro Leu Thr Gln 245 250 255 Glu Ser Tyr Gly Ala Tyr Ala Val Met Cys Leu Ser Val Val He Phe 260 265 270 Gly Thr Gly He He Gly Asn Leu Wing Val Met Cys He Val Cys His 275 280 285 Asn Tyr Tyr Met Arg Ser He Ser Asn Ser Leu Leu Ala Asi Leu Ala 290 295 300 Phe Trp Asp Phe Leu He He Phe Phe Cys Leu Pro Leu Val He Phe 305 310 315 320 His Glu Leu Thr Lys Lys Trp Leu Leu Glu Asp Phe Ser Cys Lys He 325 330 335 Val Pro Tyr He Glu Val Wing Ser Leu Gly Val Thr Thr Phe Thr Leu 340 345 350 Cys Ala Leu Cys He Asp Arg Phe Arg Ala Wing Thr Asn Val Gln Met 355 360 365 Tyr Tyr Glu Met He Glu Asn Cys Ser Ser Thr Thr Ala Lys Leu Ala 370 375 380 Val He Trp Val Gly Ala Leu Leu Leu Ala Leu Pro Glu Val Val Leu 385 390 395 400 Arg Gln Leu Ser Lys Glu Asp Leu Gly Phe Ser Gly Arg Wing Pro Wing 405 410 415 Glu Arg Cys He He Lys He Ser Pro Asp Leu Pro Asp Thr He Tyr 420 425 430 Val Leu Ala Leu Thr Tyr Asp Ser Ala Arg Leu Trp Tro Tyr Phe Gly 435 440 4 < -5 Cys Tyr Phe Cys Leu Pro Thr Leu Phe Thr He Thr Cys Ser Leu Val 450 455 460 Thr Ala Arg Lys He Arg Lys Ala Glu Lys Ala Cys Thr Arg Gly Asn 465 470 475 480 Lys Arg Gln He Gln Leu Glu Ser Gln Met Lys Cys Thr Val Val Wing 485 490 495 Leu Thr He Leu Tyr Gly Phe Cys He He Pro Glu Asn He Cys Asn 500 505 510 He Val Thr Ala Tyr Met Ala Thr Gly Val Ser Gln Gln Thr Met Asp 515 520 525 Leu Leu Asn He He Ser Gln Phe Leu Leu Phe Phe Lys Ser Cys Val 530 535 540 Thr Pro Val Leu Leu Phe Cys Leu Cys Lys Pro Phe Ser Arg Ala Phe 545 550 555 560 Met Glu Cys Cys Cys Cys Cys Cys Glu Glu Cys lie Gln Lys Ser Ser 565 570 575 Thr Val Thr Ser Asp Asp Asn Asp Asn Glu Tyr Thr Thr Glu Leu Glu 580 585 590 Leu Ser Pro Phe Ser Thr He Arg Arg Glu Met Ser Thr Phe Ala Ser 595 600 605 Val Gly Thr His Cys 610 < 210 > 213 < 211 > 1248 < 212 > DNA < 213 > Homo sapiens < 400 > 213 atggtttttg ctcacagaat ggataacagc aagccacatt tgattattcc tacacttctg 60 gtgcccctcc aaaaccgcag ctgcactgaa acagccacac ctctgccaag ccaatacctg 120 gtgaggagca atggaattaá cagttggatg agcaaccaaa cagaccttca ctatgtgctg 180 aaacccgggg aagtggccac agccagcatc ttctttggga ttctgtggtt gttttctatc 240 ttcggcaatt ccctggtttg tttggtcatc cataggagta ggaggactca gtctaccacc 300 aactactttg tggtctccat ggcatgtgct gaccttctca tcagcgttgc cagcacgcct 360 ttcgtcctgc tccagttcac cactggaagg tggacgctgg gtagtgcaac gtgcaaggtt 420 gtgcgatatt ttcaatatct cactccaggt gtccagatct acgttctcct ctccatctgc 480 atagaccggt tctacaccat cgtctatcct ctgagcttca aggtgtccag agaaaaagcc 540 aagaaaatga ttgcggcatc gtggatcttt gatgcaggct ttgtgacccc tgtgctcttt 600 ttctatggct ccaactggga cagtcattgt aactatttcc tcccctcctc ttgggaaggc 660 ctgtcatcca actgcctaca cttcttggtg ggctttgtga ttccatctgt cctcataatt 720 ttattttacc aaaaggtcat aaaatatatt tggagaatag gcacagatgg ccgaacggtg 780 tgaacattgt aggaggacaa ccctcggaca aaagtgaaaa ctaaaaagat gttcctcatt 840 ttaaatctgt tgttt ttgct ctcctggctg ccttttcatg tagctcagct atggcacccc 900 catgaacaag actataagaa aagttccctt gttttcacag ctatcacatg gatatccttt 960 agttcttcag cctctaaacc tactctgtat tcaatttata atgccaattt tcggagaggg 1020 atgaaagaga ctttttgcat gtcctctatg aaatgttacc gaagcaatgc ctatactatc 1080 acaacaagtt caaggatggc caaaaaaaac tacgttggca tttcagaaat cccttccatg 1140 ttaccaaaga gccaaaacta ctcgatctat gactcatttg acagagaagc caaggaaaaa 1200 ggcccattaa aagcttgctt ctcaaatcca ccaaatactt ttgtctaa 1248 < 210 > 214 < 211 > 415 < 212 > PRT < 213 > Homo sapiens < 400 > 214 Met Val Phe Ala His Arg Met Asp Asn Ser Lys Pro His Leu He He 1 5 10 15 Pro Thr Leu Leu Val Pro Leu Gln Asn Arg Ser Cys Thr Glu Thr Wing 20 25 30 Thr Pro Leu Pro Ser Gln Tyr Leu Met Glu Leu Ser Glu Glu His Ser 35 40 45 Trp Met Ser Asn Gln Thr Asp Leu His Tyr Val Leu Lys Pro Gly Glu 50 55 60 Val Ala Thr Ala Ser He Phe Phe Gly He Leu Trp Leu Phe Ser He 65 70 75 80 Phe Gly Asn Ser Leu Val Cys Leu Val He His Arg Ser Arg Arg Thr 85 90 95 Gln Ser Thr Thr Asn Tyr Phe Val Val Ser Met Wing Cys Wing Asp Leu 100 105 110 Leu He Ser Val Ala Ser Thr Pro Phe Val Leu Leu Gln Phe Thr Thr 115 120 125 Gly Arg Trp Thr Leu Gly Be Wing Thr Cys Lys Val Val Arg Tyr Phe 130 135 140 Gln Tyr Leu Thr Pro Gly Val Gln He Tyr Val Leu Leu Ser He Cys 145 150 155 160 He Asp Arg Phe Tyr Thr He Val Tyr Pro Leu Ser Phe Lys Val Ser 165 170 175 Arg Glu Lys Wing Lys Lys Met He Wing Wing Ser Trp He Phe Asp Wing 180 185 190 Gly Phe Val Thr Pro Val Leu Phe Phe Tyr Gly Ser Asn Trp Asp Ser 195 200 205 His Cys Asn Tyr Phe Leu Pro Being Ser Trp Glu Gly Thr Wing Tyr Thr 210 215 220 Val He His Phe Leu Val Gly Phe Val He Pro Ser Val Leu He He 225 230 235 240 Leu Phe Tyr Gln Lys Val He Lys Tyr He Trp Arg He Gly Thr Asp 245 250 255 Gly Arg Thr Val Arg Arg Thr Met Asn He Val Pro Arg Thr Lys Val 260 265 270 Lys Thr Lys Lys Met Phe Leu He Leu Asn Leu Leu Phe Leu Leu Ser 275 280 285 Trp Leu Pro Phe His Val Wing Gln Leu Trp His Pro His Glu Gln Asp 0 290 295 300 Tyr Lys Lys Ser Ser Leu Val Phe Thr Wing He Thr Trp He Ser Phe 305 310 315 320 Being Being Wing Being Lys Pro Thr Leu Tyr Being He Tyr Asn Wing Asn 5 325 330 335 Phe Arg Arg Gly Met Lys Glu Thr Phe Cys Met Ser Ser Met Lys Cys 340 345 350 0 tYr Ar9 Ser Asn Ala Tyr Thr He Thr Thr Ser Ser Arg Met Ala Lys 355 360 365 Lys Asn Tyr Val Gly He Ser Glu He Pro Ser Met Wing Lys Thr He 370 375 380 Thr Lys Asp Ser He Tyr Asp Ser Phe Asp Arg Glu Wing Lys Glu Lys 385 390 395 400 Lys Leu Wing Trp Pro He Asn Ser Asn Pro Pro Asn Thr Phe Val 405 410 415 < 210 > 215 < 211 > 1842 < 212 > DNA < 213 > Homo sapiens < 400 > 215 atggggccca ccctagcggt tcccaccccc tatggctgta ttggctgtaa gctaccccag 60 ccagaatacc caccggctct aatcatcttt atgttctgcg cgatggttat caccatcgtt 120 gtagacctaa tcggcaactc catggtcatt ttggctgtga cgaagaacaa gaagctccgg 180 aattctggca acatcttcgt ggtcagtctc tctgtggccg atatgctggt ggccatctac 240 tgatgctgca ccataccctt tgccatgtcc attgggggct gggatctgag ccagttacag 300 tgccagatgg tcgggttcat cacagggctg agtgtggtcg gctccatctt caacatcgtg 360 tcaaccgtta gcaatcgcta ctgctacatc tgccacagcc tccagtacga acggatcttc 420 agtgtgcgca atacctgcat ctacctggtc atcacctgga tcatgaccgt cctggctgtc 480 ctgcccaaca tgtacattgg caccatcgag tacgatcctc gcacctacac ctgcatcttc 540 aactatctga acaaccctgt cttcactgtt accatcgtct gcatccactt cgtcctccct 600 ctcctcatcg tgggtttctg ctacgtgagg atctggacca aagtgctggc ggcccgtgac 660 cctgcagggc agaatcctga caaccaactt gctgaggttc gcaataaact aaccatgttt 720 gtgatcttcc tcctctttgc agtgtgctgg tgccctatca acgtgctcac tgtcttggtg 780 gctgtcagtc cgaaggagat ggcaggcaag atccccaact ggctttatct tgcagcctac 840 tt catagcct acttcaacag ctgcctcaac gctgtgatct acgggctcct caatgagaat 900 ttccgaagag aatactggac catcttccat gctatgcggc accctatcat attcttctct 960 ggcctcatca gtgatattcg tgagatgcag gaggcccgta ccctggcccg cgcccgtgcc 1020 catgctcgcg accaagctcg tgaacaagac cgtgcccatg cctgtcctgc tgtggaggaa 1080 atgtccggaa accccgatga tgttccatta cctggtgatg ctgcagctgg ccaccccgac 1140 cgtgcctctg gccaccctaa gccccattcc agatcctcct ctgcctatcg caaatctgcc 1200 tctacccacc acaagtctgt ctttagccac tccaaggctg cctctggtca cctcaagcct 1260 gtctctggcc actccaagcc tgcctctggt caccccaagt ctgccactgt ctaccctaag 1320 cctgcctctg tccatttcaa ggctgactct gtccatttca agggtgactc tgtccatttc 1380 aagcctgact ctgttcattt caagcctgct tccagcaacc ccaagcccat cactggccac 1440 catgtctctg ctggcagcca ctccaagtct gccttcaatg ctgccaccag ccaccctaaa 1500 cccatcaagc cagctaccag ccatgctgag cccaccactg ctgactatcc caagcctgcc 1560 actaccagcc accctaagcc cgctgctgct gacaaccctg agctctctgc ctcccattgc 1620 cccgagatcc ctgccattgc ccaccctgtg tctgacgaca gtgacctccc tgagtcggcc 1680 tctagccctg ccgctgggcc caccaagcct gctgccagcc agctggagtc tgacaccatc 1740 gctgaccttc ctgaccctac tgtagtcact accagtacca atgattacca tgatgtcgtg 1800 gttgttgatg ttgaagatga tcctgatgaa atggctgtgt ga 1842 < 210 > 216 < 211 > 613 < 212 > PRT < 213 > Homo sapiens < 400 > 216 et Gly Pro Thr Leu Wing Val Pro Thr Pro Tyr Gly Cys He Gly Cys 10 15 Lys Leu Pro Gln Pro Glu Tyr Pro Pro Wing Leu He He Phe Met Phe 20 25 30 Cys Ala Met Val He Thr He Val Val Asp Leu He Gly Asn Ser Met t &iji £ lSÜIki ^ ¿3ßH * ¿?? * i 35 40 45 Val He Leu Ala Val Thr Lys Asn Lys Lys Leu Arg Asn Ser Gly Asn 50 55 60 He Phe Val Val Ser Leu Ser Val Wing Asp Met Leu Val Wing He Tyr 65 70 75 80 Pro Tyr Pro Leu Met Leu His Wing Met Be He Gly Gly Trp Asp Leu 85 90 95 Being Gln Leu Gln Cys Gln Met Val Gly Phe He Thr Gly Leu Ser Val 100 105 110 Val Gly Ser He Phe Asn He Val Wing He Wing He Asn Arg Tyr Cys 115 120 125 Tyr He Cys His Ser Leu Gln Tyr Glu Arg He Phe Ser Val Arg Asn 130 135 140 Thr Cys He Tyr Leu Val He Thr Trp He Met Thr Val Leu Wing Val 145 150 155 160 Leu Pro Asn Met Tyr He Gly Thr He Glu Tyr Asp Pro Arg Thr Tyr 165 170 175 Thr Cys He Phe Asn Tyr Leu Asn Asn Pro Val Phe Thr Val Thr He 180 185 190 Val Cys He His Phe Val Leu Pro Leu Leu He Val Gly Phe Cys Tyr 195 200 205 Val Arg He Trp Thr Lys Val Leu Wing Wing Arg Asp Pro Wing Gly Gln 210 215 220 Asn Pro Asp Asn Gln Leu Wing Glu Val Arg Asn Lys Leu Thr Met Phe 225 230 235 240 Val He Phe Leu Leu Phe Wing Val Cys Trp Cys Pro He Asn Val Leu 245 250 255 Thr Val Leu Val Wing Val Ser Pro Lys Glu Met Wing Gly Lys He Pro 260 265 270 Asn Trp Leu Tyr Leu Wing Wing Tyr Phe He Wing Tyr Phe Asn Ser Cys 275 280 285 Leu Asn Ala Val He Tyr Gly Leu Leu Asn Glu Asn Phe Arg Arg Glu 290 295 300 Tyr Trp Thr He Phe His Wing Met Arg His Pro He He Phe Phe Ser 305 310 315 320 Gly Leu He Ser Asp He Arg Glu Met Gln Glu Ala Arg Thr Leu Ala 325 330 335 Arg Ala Arg Ala His Ala Arg Asp Gln Ala Arg Glu Gln Asp Arg Ala ~ «* ^. $ & ^% Z ¿¿340 345 350 His Wing Cys Pro Wing Val Glu Glu Thr Pro Met Asn Val Arg Asn Val 355 360 365 Pro Leu Pro Gly Asp Ala Ala Ala Gly His Pro Asp Arg Ala Ser Gly 370 375 380 His Pro Lys Pro His Ser Arg Ser Ser Ser Ala Tyr Arg Lys Ser Ala 385 390 395 400 Ser Thr His His Lys Ser Val Phe Ser His Ser Lys Ala Ala Ser Gly 405 410 415 His Leu Lys Pro Val Ser Gly His Ser Lys Pro Wing Ser Gly His Pro 420 425 430 Lys Ser Wing Thr Val Tyr Pro Lys Pro Wing Ser Val His Phe Lys Wing 435 440 445 Asp Ser Val His Phe Lys Gly Asp Ser Val His Phe Lys Pro Asp Ser 450 455 460 Val His Phe Lys Pro Wing Ser Ser Asn Pro Lys Pro He Thr Gly His 465 470 475 480 His Val Ser Ala Gly Ser His Ser Lys Ser Ala Phe Asn Ala Ala Thr 485 490 495 ^^^ OguaH Ser His Pro Lys Pro He Lys Pro Wing Thr Ser His Wing Glu Pro Thr 500 505 510 Thr Wing Asp Tyr Pro Lys Pro Wing Thr Thr Ser His Pro Lys Pro Wing 515 520 525 Ala Ala Asp Asn Pro Glu Leu Ser Ala Ser His Cys Pro Glu He Pro 530 535 540 Ala He Ala His Pro Val Ser Asp Asp Ser Asp Leu Pro Glu Ser Ala 545 550 555 560 Be Ser Pro Ala Ala Gly Pro Thr Lys Pro Ala Ala Ser Gln Leu Glu 565 570 575 Be Asp Thr He Wing Asp Leu Pro Asp Pro Thr Val Val Thr Thr Ser 580 585 590 Thr Asn Asp Tyr His Asp Val Val Val Val Asp Val Glu Asp Asp Pro 595 600 605 Asp Glu Met Wing Val 610 < 210 > 217 < 211 > 1854 < 212 > DNA < 213 > Homo sapiens * - b ^ ^ ^ ^ ^ m A ís ^^? Ém ^^^^^^ i &l ^ ¿^^^^ iil ^ t < 400 > 217 atggggccca ccctagcggt tcccaccccc tatggctgta ttggctgtaa gctaccccag 60 ccagaatacc caccggctct aatcatcttt atgttctgcg cgatggttat caccatcgtt 120 gtagacctaa tcggcaactc catggtcatt ttggctgtga cgaagaacaa gaagctccgg 180 aattctggca acatcttcgt ggtcagtctc tctgtggccg atatgctggt ggccatctac 240 tgatgctgca ccataccctt tgccatgtcc attgggggct gggatctgag ccagttacag 300 tgccagatgg tcgggttcat cacagggctg agtgtggtcg gctccatctt caacatcgtg 360 tcaaccgtta gcaatcgcta ctgctacatc tgccacagcc tccagtacga acggatcttc 420 agtgtgcgca atacctgcat ctacctggtc atcacctgga tcatgaccgt cctggctgtc 480 ctgcccaaca tgtacattgg caccatcgag tacgatcctc gcacctacac ctgcatcttc 540 aactatctga acaaccctgt cttcactgtt accatcgtct gcatccactt cgtcctccct 600 ctcctcatcg tgggtttctg ctacgtgagg atctggacca aagtgctggc ggcccgtgac 660 cctgcagggc agaatcctga caaccaactt gctgaggttc gcaataaact aaccatgttt 720 gtgatcttcc tcctctttgc agtgtgctgg tgccctatca acgtgctcac tgtcttggtg 780 gctgtcagtc cgaaggagat ggcaggcaag atccccaact ggctttatct tgcagcctac 840 ttcatagcct acttcaacag ctgcctcaac gctgtgatct acgggctcct caatgagaat 900 ttccgaagag aatactggac catcttccat gctatgcggc accctatcat attcttctct 960 ggcctcatca gtgatattcg tgagatgcag gaggcccgta ccctggcccg cgcccgtgcc 1020 catgctcgcg accaagctcg tgaacaagac cgtgcccatg cctgtcctgc tgtggaggaa 1080 atgtccggaa accccgatga tgttccatta cctggtgatg ctgcagctgg ccaccccgac 1140 cgtgcctctg gccaccctaa gccccattcc agatcctcct ctgcctatcg caaatctgcc 1200 tctacccacc acaagtctgt ctttagccac tccaaggctg cctctggtca cctcaagcct 1260 gtctctggcc actccaagcc tgcctctggt caccccaagt ctgccactgt ctaccctaag 1320 cctgcctctg tccatttcaa ggctgactct gtccatttca agggtgactc tgtccatttc 1380 aagcctgact ctgttcattt caagcctgct tccagcaacc ccaagcccat cactggccac 1440 catgtctctg ctggcagcca ctccaagtct gccttcagtg c tgccaccag ccaccctaaa 1500 cccaccactg gccacatcaa gccagctacc agccatgctg agcccaccac tgctgactat 1560 cccaagcctg ccactaccag ccaccctaag cccactgctg ctgacaaccc tgagctctct 1620 gcctcccatt gccccgagat ccctgccatt gcccaccctg tgtctgacga cagtgacctc 1680 cctgagtcgg cctctagccc tgccgctggg cccaccaagc ctgctgccag ccagctggag 1740 tctgacacca tcgctgacct tcctgaccct actgtagtca ctaccagtac caatgattac 1800 catgatgtcg tggttgttga tgttgaagat gatcctgatg aaatggctgt GTGA 1854 < 210 > 218 < 211 > 617 < 212 > PRT < 213 > Homo sapiens < 400 > 218 Met Gly Pro Thr Leu Wing Val Pro Thr Pro Tyr Gly Cys He Gly Cys 1 5 10 15 Lys Leu Pro Gln Pro Glu Tyr Pro Pro Wing Leu He He Phe Met Phe 20 25 30 Cys Ala Met Val He Thr He Val Val Asp Leu He Gly Asn Ser Met 35 40 45 Val He Leu Ala Val Thr Lys Asn Lys Lys Leu Arg Asn Ser Gly Asn 50 55 60 He Phe Val Val Ser Leu Ser Val Wing Asp Met Leu Val Wing He Tyr 65 70 75 80 Pro Tyr Pro Leu Met Leu His Wing Met Be He Gly Gly Trp Asp Leu 85 90 95 Being Gln Leu Gln Cys Gln Met Val Gly Phe He Thr Gly Leu Ser Val 100 105 110 Val Gly Ser He Phe Asn He Val Wing He Wing He Asn Arg Tyr Cys 115 120 125 Tyr He Cys His Ser Leu Gln Tyr Glu Arg He Phe Ser Val Arg Asn 130 135 140 Thr Cys He Tyr Leu Val He Thr Trp He Met Thr Val Leu Wing Val 145 150 155 160 Leu Pro Asn Met Tyr He Gly Thr He Glu Tyr Asp Pro Arg Thr Tyr 165 170 175 Thr Cys He Phe Asn Tyr Leu Asn Asn Pro Val Phe Thr Val Thr He 180 185 190 Val Cys He His Phe Val Leu Pro Leu Leu He Val Gly Phe Cys Tyr 195 200 205 l Arg He Trp Thr Lys Val Leu Wing Wing Arg Asp Pro Wing Gly Gln 210 215 220 Asn Pro Asp Asn Gln Leu Wing Glu Val Arg Asn Lys Leu Thr Met Phe 225 230 235 240 Val He Phe Leu Leu Phe Wing Val Cys Trp Cys Pro He Asn Val Leu jStfHMa &tiz 'ffißn Í tt! 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"? 245 250 255 Thr Val Leu Val Wing Val Ser Pro Lys Glu Met Wing Gly Lys He Pro 260 265 270 Asn Trp Leu Tyr Leu Wing Wing Tyr Phe He Wing Tyr Phe Asn Ser Cys 275 280 285 Leu Asn Ala Val He Tyr Gly Leu Leu Asn Glu Asn Phe Arg Arg Glu 290 295 300 Tyr Trp Thr He Phe His Wing Met Arg His Pro He He Phe Phe Ser 305 310 315 320 Gly Leu He Ser Asp He Arg Glu Met Gln Glu Ala Arg Thr Leu Ala 325 330 335 Arg Ala Arg Ala His Ala Arg Asp Gln Ala Arg Glu Gln Asp Arg Ala 340 345 350 His Wing Cys Pro Wing Val Glu Glu Thr Pro Met Asn Val Arg Asn Val 355 360 365 Pro Leu Pro Gly Asp Ala Ala Ala Gly His Pro Asp Arg Ala Ser Gly 370 375 380 His Pro Lys Pro His Ser Arg Ser Ser Ser Ala Tyr Arg Lys Ser Ala 385 390 395 400 ^^^^ ^^^ te ^ .. ^^^^ te Ser Thr His His Lys Ser Val Phe Ser His Ser Lys Ala Ala Ser Gly 405 410 415 His Leu Lys Pro Val Ser Gly His Ser Lys Pro Wing Ser Gly His Pro 420 425 430 Lys Ser Wing Thr Val Tyr Pro Lys Pro Wing Ser Val His Phe Lys Wing 435 440 445 Asp Ser Val His Phe Lys Gly Asp Ser Val His Phe Lys Pro Asp Ser 450 455 460 Val His Phe Lys Pro Wing Ser Ser Asn Pro Lys Pro He Thr Gly His 465 470 475 480 His Val Ser Ala Gly Ser His Ser Lys Ser Ala Phe Ser Ala Ala Thr 485 490 495 Ser His Pro Lys Pro Thr Thr Gly His He Lys Pro Wing Thr Ser His 500 505 510 Wing Glu Pro Thr Thr Wing Asp Tyr Pro Lys Pro Wing Thr Thr Ser His 515 520 525 Pro Lys Pro Thr Wing Wing Asp Asn Pro Glu Leu Ser Wing Ser His Cys 530 535 540 Pro Glu He Pro Wing He Wing His Pro Val Ser Asp Asp Ser Asp Leu a¿ ^ ¿g¿ü ^^ É | Í | sj? & £ ^ SÉÉI 545 550 555 560 Pro Glu Be Ala Be Ser Pro Ala Ala Gly Pro Thr Lys Pro Ala Ala 565 570 575 Being Gln Leu Glu Being Asp Thr He Wing Asp Leu Pro Asp Pro Thr Val 580 585 590 Val Thr Thr Ser Thr Asn Asp Tyr His Asp Val Val Val Val Asp Val 595 600 605 10 Glu Asp Asp Pro Asp Glu Met Wing Val 610 615 < 210 > 219 < 211 > 1548 15 < 212 > DNA < 213 > Homo sapiens < 400 > 219 atgggacata acgggagctg gatctctcca aatgccagcg agccgcacaa cgcgtccggc 60 gccgaggctg cgggtgtgaa ccgcagcgcg ctcggggagt tcggcgaggc gcagctgtac 120 cgccagttca ccaccaccgt gcaggtcgtc atcttcatag gctcgctgct cggaaacttc 180 atggtgttat ggtcaacttg ccgcacaacc gtgttcaaat ctgtcaccaa caggttcatt 240 aaaaacctgg cctgctcggg gatttgtgcc agcctggtct gtgtgccctt cgacatcatc 300 ctcagcacca gtcctcactg ttgctggtgg atctacacca tgctcttctg caaggtcgtc 360 aaa ttttgc acaaagtatt ctgctctgtg accatcctca gcttccctgc tattgctttg 420 gacaggtact actcagtcct ctatccactg gagaggaaaa tatctgatgc caagtcccgt 480 gaactggtga tgtacatctg ggcccatgca gtggtggcca gtgtccctgt gtttgcagta 540 accaatgtgg ctgacatcta tgccacgtcc acctgcacgg aagtctggag caactccttg 600 ggccacctgg tgtacgttct ggtgtataac atcaccacgg tcattgtgcc tgtggtggtg 660 gtgttcctct tcttgatact gatccgacgg gccctgagtg ccagccagaa gaagaaggtc 720 atcatagcag cgctccggac cccacagaac accatctcta ttccctatgc ctcccagcgg 780 gaggccgagc tgaaagccac cctgctctcc atggtgatgg tcttcatctt gtgtagcgtg 840 ccctatgcca ccctggtcgt ctaccagact gtgctcaatg tccctgacac ttccgtcttc 900 ttgctgctca ctgctgtttg gctgcccaaa gtctccctgc tggcaaaccc tgttctcttt 960 acaaatctgt cttactgtga ccgcaagtgc ttgataggga ccctggtgca actacaccac 1020 cggtacagtc gccgtaatgt gggagtggca ggtcagtaca tggctgaggc cagcctggaa 1080 cccagcatac gctcgggtag ccagctcctg gagatgttcc acattgggca gcagcagatc 1140 cagaggatga tttaagccca ggaagagagt gaggccaagt acattggctc agctgacttc 1200 caggccaagg agatatttag cacctgcctg gagggagagc aggggccaca gtttgcgccc 1260 tctgccccac ccctgagcac agtggactct gtatcccagg tggcaccggc agcccctgtg 1320 cattccctga gaacctgaaa taagtattcc ctgcagtttg gctttgggcc ttttgagttg 1380 cctcctcagt ggctctcaga gacccgaaac agcaagaagc ggctgcttcc ccccttgggc 1440 aacaccccag to agagctgat ccagacaaag gtgcccaagg taggcagggt ggagcggaag 1500 atgagcagaa acaataaagt gagcattttt ccaaaggtgg attcctag 1548 < 210 > 220 < 211 > 515 < 212 > PRT < 213 > Homo sapiens < 400 > 220 Met Gly His Asn Gly Ser Trp He Ser Pro Asn Ala Ser Gl »_ Pro His 1 5 10 15 «. ? "Asn Ala Ser Gly Ala Glu Ala Ala Gly Val Asn Arg Ser Ala Leu Gly 20 25 30 Glu Phe Gly Glu Wing Gln Leu Tyr Arg Gln Phe Thr Thr Thr Val Gln 35 40 45 Val Val He Phe He Gly Ser Leu Leu Gly Asn Phe Met Val Leu Trp 50 55 60 Be Thr Cys Arg Thr Thr Val Phe Lys Ser Val Thr Asn Arg Phe He 65 70 75 Lys Asn Leu Wing Cys Ser Gly He Cys Wing Ser Leu Val Cys Val Pro 85 90 95 Phe Asp He He Leu Ser Thr Ser Pro His Cys Cys Trp Trp He Tyr 100 105 110 Thr Met Leu Phe Cys Lys Val Val Lys Phe Leu His Lys Val Phe Cys 115 120 125 Being Val Thr He Leu Being Phe Pro Wing He Wing Leu Asp Arg Tyr Tyr 130 135 140 Ser Val Leu Tyr Pro Leu Glu Arg Lys He Ser Asp Ala Lys Ser Arg 145 150 155 160 Glu Leu Val Met Tyr He Trp Wing His Wing Val Val Wing Ser Val Val ^^? 3 & 165 170 175 Val Phe Wing Val Thr Asn Val Wing Asp He Tyr Wing Thr Ser Thr Cys 180 185 190 Thr Glu Val Trp Ser Asn Ser Leu Gly His Leu Val Tyr Val Leu Val 195 200 205 Tyr Asn He Thr Thr Val He Val Val Val Val Val Phe Leu Phe 210 215 220 Leu He Leu He Arg Arg Ala Leu Ser Ala Be Gln Lys Lys Lys Val 225 230 235 240 He He Ala Ala Leu Arg Thr Pro Gln Asn Thr He Ser He Pro Tyr 245 250 255 Wing Being Gln Arg Glu Wing Glu Leu Lys Wing Thr Leu Leu Ser Met Val 260 265 270 Met Val Phe He Leu Cys Ser Val Pro Tyr Ala Thr Leu Val Val Tyr 275 280 285 Gln Thr Val Leu Asn Val Pro Asp Thr Ser Val Phe Leu Leu Leu Thr 290 295 300 Wing Val Trp Leu Pro Lys Val Ser Leu Leu Wing Asn Pro Val Leu Phe 305 310 315 320 4 | < Leu Thr Val Asn Lys Ser Val Arg Lys Cys Leu He Gly Thr Leu Val 325 330 335 Gln Leu His His Arg Tyr Ser Arg Arg Asn Val Val Ser Thr Gly Ser 340 345 350 Gly Met Ala Glu Ala Ser Leu Glu Pro Ser He Arg Ser Gly Ser Gln 355 360 365 Leu Leu Glu Met Phe His He Gly Gln Gln Gln He Phe Lys Pro Thr 370 375 380 Glu Asp Glu Glu Glu Ser Glu Wing Lys Tyr He Gly Ser Wing Asp Phe 385 390 395 400 Gln Ala Lys Glu He Phe Ser Thr Cys Leu Glu Gly Glu Gln Gly Pro 405 410 415 Gln Phe Pro Wing Pro Wing Pro Pro Leu Ser Thr Val Asp Ser Val Ser 420 425 430 Gln Val Ala Pro Ala Ala Pro Val Glu Pro Glu Thr Phe Pro Asp Lys 435 440 445 Tyr Ser Leu Gln Phe Gly Phe Gly Pro Phe Glu Leu Pro Pro Gln Trp 450 455 460 Leu Ser Glu Tnr Arg Asn Ser Lys Lys Arg Leu Leu Pro Pro Leu Gly S-SHÜSK. 465 470 475 480 Asn Thr Pro Glu Glu Leu He Gln Thr Lys Val Pro Lys Val Gly Arg 485 490 495 Val Glu Arg Lys Met Ser Arg Asn Asn Lys Val Ser He Phe Pro Lys 500 505 510 Val Asp Ser 515 < 210 > 221 < 211 > 1164 < 212 > DNA < 213 > Homo sapiens < 400 > 221 atgaatcggc accatctgca ggatcacttt ctggaaatag acaagaagaa ctgctgtgtg 60 ttccgagatg acttcattgc caaggtgttg ccgccggtgt tggggctgga gtttatcttt 120 gggcttctgg gcaatggcct tgccctgtgg attttctgtt tccacctcaa gtcctggaaa 180 tccagccgga ttttcctgtt caacctggca gtagctgact ttctactgat catctgcctg 240 tggactacta ccgttcgtga tgtgcggcgt tcagactgga agtttgggga catcccttgc 300 cggctggtgc tcttcatgtt tgccatgaac cgccagggca gcatcatctt cctcacggtg 360 gtggcggtag acaggtattt ccgggtggtc catccccacc acgccctgaa caagatctcc 420 aattggacag cagccatcat ctcttgcctt ctgtggggca tcactgttgg cctaacagtc 480 cacctcctga agaagaagtt gctgatccag aatggccctg caaatgtgtg catcagcttc 540 agcatctgcc ataccttccg gtggcacgaa gctatgttcc tcctggagtt cctcctgccc 600 tcctgttctg ctgggcatca ctcagccaga attatctcqa gcctgcggca gagacaaatg 660 a ^ sa IIHA &? Aj &? "gaccggcatg ccaagatcaa gagagccaaa accttcatca tggtggtggc catcgtcttt 720 gtcatctgct tccttcccag cgtggttgtg cggatccgca tcttctggct cctgcacact 780 tcgggcacgc agaattgtga agtgtaccgc tcggtggacc tggcgttctt tatcactctc 840 agcttcacct acatgaacag catgctggac cccgtggtgt actacttctc cagcccatcc 900 tttcccaact tcttctccac tttgatcaac cgctgcctcc agaggaagat gacaggtgag 960 ccagataata accgcagcac gagcgtcgag ctcacagggg accccaacaa aaccagaggc 1020 gctccagagg cgttaatggc caactccggt gagccatgga gcccctctta tctgggccca 1080 acctcaaata accattccaa gaagggacat tgtcaccaag aaccagcatc tctggagaaa 1140 cagttgggct gttgcatcga gtaa 1164 < 210 > 222 < 211 > 387 < 212 > PRT < 213 > Homo sapiens < 400 > 222 15 Met Asn Arg His His Leu Gln Asp His Phe Leu Glu He Asp Lys Lys 1 5 10 15 Asn Cys Cys Val Phe Arg Asp Asp Phe He Wing Lys Val Leu Pro Pro 20 25 30 20 Val Leu Gly Leu Glu Phe He Phe Gly Leu Leu Gly Asn Gly Leu Wing 35 40 45 Leu Trp He Phe Cys Phe His Leu Lys Ser Trp Lys Ser Ser Arg He 50 55 60 25 aaái! ^^^^? Ml ^? 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A »* - i Phe Leu Phe Asn Leu Wing Val Wing Asp Phe Leu Leu He He Cys Leu 65 70 75 80 Pro Phe Val Met Asp Tyr Tyr Val Arg Arg As Asp Trp Lys Phe Gly 85 90 95 Asp He Pro Cys Arg Leu Val Leu Phe Met Phe Ala Met Asn Arg Gln 100 105 110 Gly Ser He He Phe Leu Thr Val Val Wing Val Asp Arg Tyr Phe Arg H5 120 125 Val Val His Pro His His Wing Leu Asn Lys He Ser Asn Trp Thr Wing 130 135 140 Ala He He Ser Cys Leu Leu Trp Gly He Thr Val Gly Leu Thr Val 145 150 155 160 His Leu Leu Lys Lys Lys Leu He Gln Asn Gly Pro Wing Asn Val 165 170 175 Cys He Ser Phe Ser He Cys His Thr Phe Arg Trp His Glu Ala Met 180 185 190 Phe Leu Leu Glu Phe Leu Leu Pro Leu Gly He He Leu Phe Cys Ser 195 200 205 Wing Arg He He Trp Ser Leu Arg Gln Arg Gln Met Asp Arg His Wing 210 215 220 Lys He Lys Arg Wing Lys Thr Phe He Met Val Val Wing He Val Phe 225 230 235 240 Val He Cys Phe Leu Pro Ser Val Val Val Arg He Arg He Phe Trp 245 250 255 Leu Leu His Thr Ser Gly Thr Gln Asn Cys Glu Val Tyr Arg Ser Val 260 265 270 Asp Leu Ala Phe Phe He Thr Leu Ser Phe Thr Tyr Met Asn Ser Met 275 280 285 Leu Asp Pro Val Val Tyr Tyr Phe Be Ser Pro Pro Phe Pro Asn Phe 290 295 300 Phe Ser Thr Leu He Asn Arg Cys Leu Gln Arg Lys Met Thr Gly Glu 305 310 315 320 Pro Asp Asn Asn Arg Ser Thr Ser Val Glu Leu Thr Gly Asp Pro Asn 325 330 335 Lys Thr Arg Gly Ala Pro Glu Ala Leu Met Ala Asn Ser Gly Glu Pro 340 345 350 Trp Ser Pro Ser Tyr Leu Gly Pro Thr Ser Asn Asn His Ser Lys Lys 355 360 365 Gly His Cys His Gln Glu Pro Wing Ser Leu Glu Lys Gln Leu Gly Cys 370 375 380 Cys He Glu 385 < 210 > 223 < 211 > 1212 < 212 > DNA < 213 > Homo sapiens < 400 > 223 atggcttgca atggcagtgc ggccaggggg cactttgacc ctgaggactt gaacctgact 60 gacgaggcac tgagactcaa gtacctgggg ccccagcaga cagagctgtt catgcccatc 120 tgtgccacat acctgctgat cttcgtggtg ggcgctgtgg gcaatgggct gacctgtctg 180 gtcatcctgc gccacaaggc catgcgcacg cctaccaact actacctctt cagcctggcc 240 gtgtcggacc tgctggtgct gctggtgggc ctgcccctgg agctctatga gatgtggcac 300 aactacccct tcctgctggg cgttggtggc tgctatttcc gcacgctact gtttgagatg 360 gtctgcctgg cctcagtgct caacgtcact gccctgagcg tggaacgcta tgtggccgtg 420 gtgcacccac tccaggccag gtccatggtg acgcgggccc atgtgcgccg agtgcttggg 480 gccgtctggg gtcttgccat gctctgctcc ctgcccaaca ccagcctgca cggcatccgg 540 cagctgcacg tgccctgccg gggcccagtg ccagactcag ctgtttgcat gctggtccgc 600 ccacgggccc tctacaacat ggtagtgcag accaccgcgc tgctcttctt ctgcctgccc 660 atggccatca tgagcgtgct ctacctgctc attgggctgc gactgcggcg ggagaggctg 720 ctgctcatgc aggaggccaa gggcaggggc tctgcagcag ccaggtccag atacacctgc 780 aggctccagc agcacgatcg gggccggaga caagtgaaga agatgctgtt tgtcctggtc 840 gtggtgtttg gcatct gctg ggccccgttc cacgccgacc gcgtcatgtg gagcgtcgtg 900 tcacagtgga cagatggcct gcacctggcc ttccagcacg tgcacgtcat ctccggcatc 960 . * Arfa -ttcttctacc tgggctcggc ggccaacccc gtgctctata gcctcatgtc cagccgcttc 1020 cgagagacct tccaggaggc cctgtgcctc ggggcctgct gccatcgcct cagaccccgc 1080 cacagctccc acagcctcag caggatgacc acaggcagca ccctgtgtga tgtgggctcc 1140 ctgggcagct gggtccaccc cctggctggg aacgatggcc cagaggcgca gcaagagacc 1200 gatccatcct ga 1212 < 210 > 224 < 211 > 403 < 212 > PRT < 213 > Homo sapiens < 400 > 224 Met Wing Cys Asn Gly Wing Wing Wing Arg Gly His Phe Asp Pro Glu Asp 1 5 10 15 Leu Asn Leu Thr Asp Glu Ala Leu Arg Leu Lys Tyr Leu Gly Pro Gln 20 25 30 Gln Thr Glu Leu Phe Met Pro He Cys Wing Thr Tyr Leu Leu He Phe 35 40 45 Val Val Gly Ala Val Gly Asn Gly Leu Thr Cys Leu Val He Leu Arg 50 55 60 His Lys Wing Met Arg Thr Pro Thr Asn Tyr Tyr Leu Phe Ser Leu Wing 65 70 75 80 Val Ser Asp Leu Leu Val Leu Leu Val Gly Leu Pro leu Glu Leu Tyr 90 95 Glu Met Trp His Asn Tyr Pro Phe Leu Leu Gly Val Gly Gly Cys Tyr 100 105 110 Phe Arg Thr Leu Leu Phe Glu Met Val Cys Leu Ala Ser Val Leu Asn 115 120 125 Val Thr Ala Leu Ser Val Glu Arg Tyr Val Val Val Val His Pro Leu 130 135 140 Gln Ala Arg Ser Met Val Thr Arg Ala His Val Arg Arg Val Leu Gly 145 150 155 160 Wing Val Trp Gly Leu Wing Met Leu Cys Ser Leu Pro Asn Thr Ser Leu 165 170 175 His Gly He Arg Gln Leu His Val Pro Cys Arg Gly Pro Val Pro Asp 180 185 190 Be Wing Val Cys Met Leu Val Arg Pro Arg Wing Leu Tyr Asn Met Val 195 200 205 Val Gln Thr Thr Ala Leu Leu Phe Phe Cys Leu Pro Met Ala He Met 210 215 220 Ser Val Leu Tyr Leu Leu He Gly Leu Arg Leu Arg Arg Glu Arg Leu 225 230 235 240 Leu Leu Met Gln Glu Ala Lys Gly J3 Gly Ser Ala Ala Ala Arg Ser 245 250 255 Arg Tyr Thr Cys Arg Leu Gln Gln His Asp Arg Gly Arg Arg Gln Val 260 265 270 Lys Lys Met Leu Phe Val Leu Val Val Val Phe Gly He Cys Trp Wing 275 280 285 Pro Phe His Wing Asp Arg Val Met Trp Ser Val Val Ser Gln Trp Thr 290 295 300 Asp Gly Leu His Leu Wing Phe Gln His Val His Val He Ser Gly He 305 310 315 320 Phe Phe Tyr Leu Gly Ser Ala Ala Asn Pro Val Leu Tyr Ser Leu Met 325 330 335 Being Ser Arg Phe Arg Glu Thr Phe Gln Glu Wing Leu Cys Leu Gly Wing 340 345 350 Cys Cys His Arg Leu Arg Pro Arg His Ser Ser His Ser Leu Ser Arg 355 360 365 Met Thr Thr Gly Ser Thr Leu Cys Asp Val Gly Ser Leu Gly Ser Trp 370 375 380 'al His Pro Leu Wing Gly Asn Asp Gly Pro Glu Wing Gln Glr Glu Thr "^ safei ^^ 385 390 395 400 Asp Pro Ser < 210 > 225 < 211 > 1098 < 212 > DNA < 213 > Homo sapiens < 400 > 225 tcactgcaga atggggaaca caactcctcg atgagctgta ccatcgacca taccatccac 60 cagacgctgg ccccggtggt ctatgttacc gtgctggtgg tgggcttccc ggccaactgc 120 acttcggcta ctgtccctct cctgcagatc aaggcccgga acgagctggg cgtgtacctg 180 tgcaacctga cggtggccga cctcttctac atctgctcgc tgcccttctg gctgcagtac 240 gtgctgcagc acgacaactg gtctcacggc gacctgtcct gccaggtgtg cggcatcctc 300 ctgtacgaga acatctacat cagcgtgggc ttcctctgct gcatctccgt ggaccgctac 360 ctggctgtgg cccatccctt ccgcttccac cagttccgga ccctgaaggc ggccgtcggc 420 gtcagcgtgg tcatctgggc caaggagctg ctgaccagca tctacttcct gatgcacgag 480 gaggtcatcg aggacgagaa ccagcaccgc gtgtgctttg agcactaccc catccaggca 540 tggcagcgcg ccatcaacta ctaccgcttc ctggtgggct tcctcttccc catctgcctg 600 ctgctggcgt cctaccaggg catcctgcgc gccgtgcgcc ggagccacgg cacccagaag 660 agccgcaagg accagatcaa gcggctggtg ctcagcaccg tggtcatctt cctggcctgc 720 ttcctgccct accacgtgtt gctgctggtg cgcagcgtct gggaggccag ctgcgacttc 780 gccaagggcg ttttcaacgc ctaccacttc tccctcctgc tcaccagctt caactgcgtc 840 gccgaccccg tctctct actg cttcgtcagc gagaccaccc accgggacct ggcccgcctc 900 cgcggggcct gcctggcctt cctcacctgc tccaggaccg gccgggccag ggaggcctac 960 ccgctgggtg cccccgaggc ctccgggaaa agcggggccc agggtgagga gcccgagctg 1020 ttgaccaagc tccacccggc cttccagacc cctaactcgc caggs-cggg cgggttcccc 1080 m? amüa ^ -st ^ S ^ ÉM acgggcaggt tggcctag 1098 < 210 > 226 < 211 > 365 < 212 > PRT < 213 > Homo sapiens < 400 > 226 Met Gly Asn He Thr Wing Asp Asn Ser Ser Met Ser Cys Thr He Asp 1 5 10 15 His Thr He His Gln Thr Leu Wing Pro Val Val Tyr Val Thr Val Leu 20 25 30 Val Val Gly Phe Pro Wing Asn Cys Leu Ser Leu Tyr Phe Gly Tyr Leu 35 40 45 Gln He Lys Wing Arg Asn Glu Leu Gly Val Tyr Leu Cys Asn Leu Thr 50 55 60 Val Ala Asp Leu Phe Tyr He Cys Ser Leu Pro Phe Trp Leu Gln Tyr 65 70 75 80 Val Leu Gln His Asp Asn Trp Ser His Gly Asp Leu Ser Cys Gln Val 85 90 95 Cys Gly He Leu Leu Tyr Glu Asn He Tyr He Ser Val Gly Phe Leu 100 105 110 '^^ f ^^ ití & ^^ & ^ t ^^ t ^^^^^^^^^^ i Cys Cys He Ser Val Asp Arg Tyr Leu Ala Val Ala His Pro Phe Arg 115 120 125 Phe His Gln Phe Arg Thr Leu Lys Ala Wing Val Gly Val Ser Val Val 130 135 140 He Trp Ala Lys Glu Leu Leu Thr Ser He Tyr Phe Leu Met His Glu 145 150 155 160 Glu Val He Glu Asp Glu Asn Gln His Arg Val Cys Phe Glu His Tyr 165 170 175 Pro He Gln Wing Trp Gln Arg Wing He Asn Tyr Tyr Arg Phe Leu Val 180 185 190 Gly Phe Leu Phe Pro He Cys Leu Leu Leu Wing Ser Tyr Gln Gly He 195 200 205 Leu Arg Ala Val Arg Arg Ser His Gly Thr Gln Lys Ser Arg Lys Asp 210 215 220 Gln He Lys Arg Leu Val Leu Ser Thr Val Val He Phe Leu Ala Cys 225 230 235 240 Phe Leu Pro Tyr His Val Leu Leu Leu Val Arg Ser Val Trp Glu Wing 245 250 255 Ser Cys Asp Phe Wing Lys Gly Val Phe Asn Wing Tyr P_s Phe Ser Leu 260 265 270 Leu Leu Thr Ser Phe Asn Cys Val Wing Asp Pro Val Leu Tyr Cys Phe 275 280 285 Val Ser Glu Thr Thr His Arg Asp Leu Wing Arg Leu Arg Gly Wing Cys 290 295 300 Leu Ala Phe Leu Thr Cys Ser Arg Thr Gly Arg Ala Arg Glu Ala Tyr 305 310 315 320 Pro Leu Gly Pro Wing Glu Wing Ser Gly Lys Ser Gly Wing Gln Gly Glu 325 330 335 Glu Pro Glu Leu Leu Thr Lys Leu His Pro Wing Phe Gln Thr Pro Asn 340 345 350 Be Pro Gly Be Gly Gly Phe Pro Thr Gly Arg Leu Ala 355 360 365 < 210 > 227 < 211 > 1416 < 212 > DNA < 213 > Homo sapiens < 400 > 227 atggatattc tttgtgaaga aaatacttct ttgagctcaa ctacgaactc cctaatgcaa 60 ttaaatgatg acaacaggct ctacagtaat STAP ~ ttaact ccggagaagc taacacttct 120 actggacagt gatgcattta cgactctgaa aatcgaacca acctttcctg tgaagggtgc 180 ctctcaccgt cgtgtctctc cttacttcat ctccaggaaa aaaactggtc tgctttactg 240 acagccgtag tgattattct aactattgct ggaaacatac tcgtcatcat ggcagtgtcc 300 agctgcagaa ctagagaaaa tgccaccaac tatttcctga tgtcacttgc catagctgat 360 atgctgctgg gtttccttgt catgcccgtg tccatgttaa ccatcctgta tgggtaccgg 420 tggcctctgc cgagcaagct ttgtgcagtc tggatttacc tggacgtgct cttctccacg 480 gcctccatca tgcacctctg cgccatctcg ctggaccgct acgtcgccat ccagaatccc 540 gccgcttcaa atccaccaca ctccagaact aaggcatttc tgaaaatcat tgctgtttgg 600 accatatcag taggtatatc catgccaata ccagtctttg ggctacagga cgattcgaag 660 gtctttaagg aggggagttg cttactcgcc gatgataact ttgtcctgat cggctctttt 720 gtgtcatttt tcattccctt aaccatcatg gtgatcacct actttctaac tatcaagtca 780 ctccagaaag aagctacttt gtgtgtaagt gatcttggca cacgggccaa attagcttct 840 ttcagcttcc tccct cagag ttctttgtct tcagaaaagc tcttccagcg gtcgatccat 900 agggagccag ggtcctacac aggcaggagg actatgcagt ccatcagcaa tgagcaaaag 960 gcaaagaagg tgctgggcat cgtcttcttc ctgtttgtgg tgatgtggtg ccctttcttc 1020 atcacaaaca tcatggccgt catctgcaaa gagtcctgca atgaggatgt cattggggcc 1080 ctgctcaatg tgtttgtttg gatcggttat ctctcttcag cagtcaaccc actagtctac 1140 acaagaccta acactgttca taggtcagcc ttttcacggt atattcagtg tcagtacaag 1200 aaccattgca gaaaacaaaa gttaatttta gtgaacacaa taccggcttt ggcctacaag 1260 tctagccaac ttcaaatggg acaaaaaaag aattcaaagc aagatgccaa gacaacagat 1320 aatgactgct caatggttgc tctaggaaag cagtattctg aagaggcttc taaagacaat 1380 agcgacggag tgaatgaaaa ggtgagctgt gtgtga 1416 < 210 > 228 < 211 > 471 < 212 > PRT < 213 > Homo sapiens < 400 > 228 Met Asp He Leu Cys Glu Glu Asn Thr Ser Leu Ser Ser Thr Thr Asn 1 5 10 15 Be Leu Met Gln Leu Asn Asp Asp Asn Arg Leu Tyr Be Asn Asp Phe 20 25 30 Asn Ser Gly Glu Wing Asn Thr Ser Asp Wing Phe Asn Trp Thr Val Asp 40 45 Ser Glu Asn Arg Thr Asn Leu Ser Cys Glu Gly Cys Leu Ser Pro 50 55 60 Cys Leu Ser Leu Leu His Leu Gln Glu Lys Asn Trp Ser Ala Leu Leu 65 70 75 80 Thr Ala Val Val He He Leu Thr He Ala Gly Asn He Leu Val He 85 90 95 Met Wing Val Ser Leu Glu Lys Lys Leu Gln Asn Wing Thr Asn Tyr Phe 100 105 110 Leu Met Ser Leu Wing He Wing Asp Met Leu Leu Gly Phe Leu Val Met 115 120 125 Pro Val Met Met Leu Thr He Leu Tyr Gly Tyr Arg Trp Pro Leu Pro 130 135 140 Ser Lys Leu Cys Wing Val Trp He Tyr Leu Asp Val Leu Phe Ser Thr 145 150 155 160 Ala Ser He Met His Leu Cys Ala He Ser Leu Asp Arg Tyr Val Ala 165 170 175 He Gln Asn Pro He His His Being Arg Phe Asn Being Arg Thr Lys Wing 180 185 190 Phe Leu Lys He He Wing Val Trp Thr He Ser Val Gly He Ser Met 195 200 205 Pro He Pro Val Phe Gly Leu Gln Asp Asp Ser Lys Val Phe Lys Glu 210 215 220 Gly Ser Cys Leu Leu Wing Asp Asp Asn Phe Val Leu He Gly Ser Phe 225 230 235 240 Val Ser Phe Phe He Pro Leu Thr He Met Val He Thr Tyr Phe Leu 245 250 255 T r He Lys Ser Leu Gln Lys Glu Wing Thr Leu Cys Val Ser Asp Leu 260 265 270 Gly Thr Arg Ala Lys Leu Ala Ser Phe Ser Phe Leu Pro Gln Ser Ser 275 280 285 Leu Be Ser Glu Lys Leu Phe Gln Arg Be He His Are Glu Pro Gly .jg-a i 290 295 300 Being Tyr Thr Gly Arg Thr Met Met Gln Being Ser Asn Glu Gln Lys 305 310 315 320 Wing Lys Lys Val Leu Gly He Val Phe Phe Leu Phe Val Val Met Trp 325 330 335 Cys Pro Phe Phe He Thr Asn He Met Wing Val He Cys Lys Glu Ser 340 345 350 Cys Asn Glu Asp Val He Gly Wing Leu Leu Asn Val Phe Val Trp He 355 360 * 365 Gly Tyr Leu Ser Ser Wing Val Asn Pro Leu Val Tyr Thr Leu Phe Asn 370 375 380 Lys Thr Tyr Arg Ser Wing Phe Ser Arg Tyr He Gln Cys Gln Tyr Lys 385 390 395 400 Glu Asn Lys Lys Pro Leu Gln Leu He Leu Val Asn Thr He Pro Wing 405 410 415 Leu Ala Tyr Lys Ser Ser Gln Leu Gln Met Gly Gln Lys Lys Asn Ser 420 425 430 Lys Gln Asp Ala Lys Thr Thr Asp Asn Asp Cys Ser Met Val Ala Leu 435 440 445 .M ^^^^. ^^^^ n ^ yfi. -iTia.fg Gly Lys Gln Tyr Ser Glu Glu Wing Ser Lys Asp Asn Ser Asp Gly Val 450 455. 460 Asn Glu Lys Val Ser Cys Val 465 470 < 210 > 229 < 211 > 1377 < 212 > DNA < 213 > Homo sapiens < 400 > 229 atggtgaacc tgaggaatgc ggtgcattca ttccttgtgc acctaattgg cctattggtt 60 tggcaatgtg atatttctgt gagcccagta gcagctatag taactgacat tttcaatacc 120 tccgatggtg gacgcttcaa attcccagac ggggtacaaa actggccagc actttcaatc 180 gtcatcataa taatcatgac aataggtggc aacatccttg tgatcatggc agtaagcatg 240 gaaaagaaac tgcacaatgc caccaattac ttcttaatgt ccctagccat tgctgatatg 300 ctagtgggac tacttgtcat gcccctgtct ctcctggcaa tcctttatga ttatgtctgg 360 ccactaccta gatatttgtg ccccgtctgg atttctttag atgttttatt ttcaacagcg 420 tccatcatgc acctctgcgc tatatcgctg gatcggtatg tagcaatacg taatcctatt 480 gagcatagcc gtttcaattc gcggactaag gccatcatga agattgctat tgtttgggca 540 atttctatag gtgtatcagt tcctatccct gtgattggac tgagggacga agaaaaggtg 600 ttcgtgaaca acacgacgtg cgtgctcaac gacccaaatt tcgttcttat tgggtccttc 660 gtagctttct tcataccgct gacgattatg gtgattacgt attgcctgac catctacgtt 720 ctgcgccgac aagctttgat gttactgcac ggccacaccg aggaaccgcc tggactaagt 780 ctggatttcc tgaagtgctg caagaggaat acggccgagg aagagaactc tgcaaaccct 840 aaccaagacc agaacg cacg ccgaagaaag aagaaggaga gacgtcctag gggcaccatg 900 caggctatca acaatgaaag aaaagctaag aaagtccttg ggattgtttt ctttgtgttt 960 ctgatcatgt ggtgcccatt tttcattacc aatattctgt ctgttctttg tgagaagtcc 1020 agctcatgga tgtaaccaaa aaagcttctg aatgtgtttg tttggattgg ctatgtttgt 1080 tcaggaatca atcctctggt gtatactctg ttcaacaaaa tttaccgaag ggcattctcc 1140 aactatttgc gttgcaatta taaggtagag aaaaagcctc ctgtcaggca gattccaaga 1200 gttgccgcca ctgctttgtc tgggagggag cttaatgtta acatttatcg gcataccaat 1260 gaaccggtga tcgagaaagc cagtgacaat gagcccggta tagagatgca agttgagaat 1320 ttagagttac cagtaaatcc ctccagtgtg gttagcgaaa ggattagcag tgtgtga 1377 < 210 > 230 < 211 > 458 < 212 > PRT < 213 > Homo sapiens < 400 > 230 Met Val Asn Leu Arg Asn Ala Val His Ser Phe Leu Val His Leu He 1 5 10 15 Gly Leu Leu Val Trp Gln Cys Asp He Ser Val Ser Pro Val Ala Wing 20 25 30 He Val Thr Asp He Phe Asn Thr Ser Asp Gly Gly Arg Phe Lys Phe 35 40 45 Pro Asp Gly Val Gln Asn Trp Pro Ala Leu Ser He Val He He He 50 55 60 He Met Thr He Gly Gly Asn He Leu Val He Met Wing Val Ser Met 65 70 75 80 Glu Lys Lys Leu His Asn Wing Thr Asn Tyr Phe Leu Met Ser Leu Wing 85 90 95 He Wing Asp Met Leu Val Gly Leu Leu Val Met Pro Leu Ser Leu Leu 100 105 110 Wing He Leu Tyr Asp Tyr Val Trp Pro Leu Pro Arg Tyr Leu Cys Pro 115 120 125 Val Trp He Ser Leu Asp Val Leu Phe Ser Thr Ala Ser He Met His 130 135 130 Leu Cys Ala He Ser Leu Asp Arg Tyr Val Ala He Arg Asn Pro He 145 150 155 160 Glu His Ser Arg Phe Asn Ser Arg Thr Lys Wing He Met Lys He Wing 165 170 175 He Val Trp Wing He Ser He Gly Val Ser Val Pro He Pro Val He 180 185 190 Gly Leu Arg Asp Glu Glu Lys Val Phe Val Asn Asn Thr Thr Cys Val 195 200 205 Leu Asn Asp Pro Asn Phe Val Leu He Gly Be Phe Val Wing Phe Phe 210 215 220 He Pro Leu Thr He Met Val He Thr T \ r Cys ueu "go He Tyr Val 225 230 235 240 Leu Arg Arg Gln Ala Leu Met Leu Leu His Gly His Thr Glu Glu Pro 245 250 255 Pro Gly Leu Ser Leu Asp Phe Leu Lys Cys Cys Lys Arg Asn Thr Ala 260 265 270 Glu Glu Glu Asn Be Wing Asn Pro Asn Gln Asp Gln Asn Wing Arg Arg 275 280 285 Arg Lys Lys Lys Glu Arg Arg Pro Arg Gly Thr Met Gln Ala He Asn 290 295 300 Asn Glu Arg Lys Wing Lys Lys Val Leu Gly He Val Phe Phe Val Phe 305 310 315 320 Leu He Met Trp Cys Pro Phe Phe He Thr Asn He Leu Ser Val Leu 325 330 335 Cys Glu Lys Ser Cys Asn Gln Lys Leu Met Glu Lys Leu Leu Asn Val 340 345 350 Phe Val Trp He Gly Tyr Val Cys Ser Gly He Asn Pro Leu Val Tyr 355 360 365 Thr Leu Phe Asn Lys He Tyr Arg Arg Wing Phe Ser Asn Tyr Leu Arg 370 375 380 Cys Asn Tyr Lys Val Glu Lys ** X, ys Pro Pro Val Arg Gln He Pro Arg 385 390 395 400 Val Ala Ala Thr Ala Leu Ser Gly Arg Glu Leu Asn Val Asn He Tyr 405 410 415 Arg His Thr Asn Glu Pro Val He Glu Lys Ala Ser Asp Asn Glu Pro 420 425 430 Gly He Glu Met Gln Val Glu Asn Leu Glu Leu Pro Val Asn Pro Ser 435 440 445 Ser Val Val Ser Glu Arg Ser Ser Ser Val 450 455 < 210 > 231 < 211 > 1068 < 212 > DNA < 213 > Homo sapiens < 400 > 231 atggatcagt tccctgaatc agtgacagaa aactttgagt acgatgattt ggctgaggcc 60 tgttatattg gggacatcgt ggtctttggg actgtgttcc tgtccatatt ctactccgtc 120 atctttgcca ttggcctggt gggaaatttg ttggtagtgt ttgccctcac caacagcaag 180 aagcccaaga gtgtcaccga catttacctc ctgaacctgg ccttgtctga tctgctgttt 240 gtagccactt tgcccttctg gactcactat ttgataaatg aaaagggcct ccacaatgcc 300 atgtgcaaat tcactaccgc cttcttcttc atcgactttt ttggaagcat attcttcatc 360 accgtcatca g ^ attgatag gtacctggcc atcgtcctgg ccgccaactc catgaacaac 420 cggaccgtgc agcatggcgt caccatcagc ctaggcgtct gggcagcagc cattttggtg 480 gcagcacccc agttcatgtt cacaaagcag aaagaaaatg aatgccttgg tgactacccc 540 gaggtcctcc aggaaatctg gcccgtgctc cgcaatgtgg aaacaaattt tcttggcttc 600 ctactccccc tgctcattat gagttattgc tacttcagaa tcatccagac gctgttttcc 660 tgcaagaacc acaagaaagc caaagccaag aaactgatcc ttctggtggt catcgtgttt 720 ttcctcttct ggacacccta caacgttatg attttcctgg agacgcttaa gctctatgac 780 ttctttccca gttgtgacat gaggaaggat ctgaggctgg ccctcagtgt gactgagacg 840 gttgcattta gccatt gttg cctgaatcct ctcatctatg catttgctgg ggagaagttc 900 agaagatacc tttaccacct gtatgggaaa tgcctggctg tcctgtgtgg gcgctcagtc 960 cacgttgatt tctcctcatc tgaatcacaa aggagcaggc atggaagtgt tctgagcagc 1020 aattttactt accacacgag tgatggagat gcattgctcc ttctctga 1068 < 210 > 232 < 211 > 355 < 212 > PRT < 213 > Homo sapiens < 400 > 232 Met Asp Gln Phe Pro Glu Ser Val Thr Glu Asn Phe Glu Tyr Asp Asp 1 5 10 15 Leu Ala Glu Ala Cys Tyr He Gly Asp He Val Val Phe Gly Thr Val 20 25 30 Phe Leu Ser He Phe Tyr Ser Val He Phe Wing He Gly Leu Val Gly 35 40 J5 Asn Leu Leu Val Val Phe Ala Leu Thr Asn Ser Lys 0 * s Pro Lys Ser 50 55 60 Val Thr Asp He Tyr Leu Leu Asn Leu Ala Leu Ser Asp Leu Leu Phe 65 70 75 80 Val Ala Thr Leu Pro Phe Trp Thr His Tyr Leu He Asn Glu Lys Gly 85 90 95 Leu His Asn Wing Met Cys Lys Phe Thr Thr Wing Phe Phe Phe He Gly 100 105 110 Phe Phe Gly Ser He Phe Phe He Thr Val He Ser He Asp Arg Tyr 115 120 125 Leu Ala He Val Leu Ala Ala Asn Ser Met Asn Asn Arg Thr Val Gln 130 135 140 His Gly Val Thr He Ser Leu Gly Val Trp Ala Ala Ala He Leu Val 145 150 155 160 Ala Ala Pro Gln Phe Met Phe Thr Lys Gln Lys Glu Asn Glu Cys Leu 165 170 175 Gly Asp Tyr Pro Glu Val Leu Gln Glu He Trp Pro Val Leu Arg Asn 180 185 190 Val Glu Thr Asn Phe Leu Glv Phe Leu Leu Pro Leu Leu He Met Ser 195 200 205 * »IB &amp * afc * a? Uc».,. 3, 1 Tyr Cys Tyr Phe Arg He Ilé '«jL? Thr Leu Phe Ser Cys Lys Asn His 210 215 220 Lys Lys Wing Lys Wing Lys Lys Leu He Leu Leu Val Val He Val Phe 225 230 235 240 Phe Leu Phe Trp Thr Pro Tyr Asn Val Met He Phe Leu Glu Thr Leu 245 250 255 Lys Leu Tyr Asp Phe Phe Pro Ser Cys Asp Met Arg Lys Asp Leu Arg 260 265 270 Leu Ala Leu Ser Val Thr Glu Thr Val Ala Phe Ser His Cys Cys Leu 275 280 285 Asn Pro Leu He Tyr Wing Phe Wing Gly Glu Lys Phe Arg Arg Tyr Leu 290 295 300 Tyr His Leu Tyr Gly Lys Cys Leu Wing Val Leu Cys Gly Arg Ser Val 305 310 315 320 His Val Asp Phe Ser Ser Ser Glu Ser Gln Arg Ser Arg His Gly Ser 325 330 335 Val Leu Ser Ser Asn Phe Thr Tyr His Thr Ser Asp Gly Asp Ala Leu 340 345 350 Leu Leu Leu 355 < 210 > 233 < 211 > 29 < 212 > DNA < 213 > Homo sapiens < 400 > 233 ggcttaagag catcatcgtg gtgctggtg 29 < 210 > 234 < 211 > 34 < 212 > DNA < 213 > Homo sapiens < 400 > 234 gtcaccacca gcaccacgat gatgctctta agcc 34 < 210 > 235 < 211 > 31 < 212 > DNA < 213 > Homo sapiens < 400 > 235 caaagaaagt actgggcatc gtcttcttcc t 31 < 210 > 236 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 236 tgctctagat tccagatagg tgaaaacttg 30 < 210 > 237 < 211 > 50 < 212 > DNA < 213 > Homo sapiens < 400 > 237 ctaggggcac catgcaggct atcaacaatg aaagaaaagc taagaaagtc 50 < 210 > 238 < 211 > 50 < 212 > DNA < 213 > Homo sapiens < 400 > 238 caaggacttt cttagctttt ctttcattgt tgatagcctg catggtgccc 50 < 210 > 239 < 211 > 35 < 212 > DNA < 213 > Homo sapiens 3S < 400 > 239 cggcggcaga aggcgaaacg catgatcctc gcggt 35 < 210 > 240 < 211 > 35 < 212 > DNA < 213 > Homo sapiens < 400 > 240 accgcgagga tcatgcgttt cgccttctgc cgccg 35 < 210 > 241 < 211 > 24 < 212 > DNA < 213 > Homo sapiens < 400 > 241 gagacatatt atctgccacg gagg 24 < 210 > 242 < 211 > 24 < 212 > DNA < 213 > Homo sapiens < 400 > 242 ttggcataga aaccggaccc aagg 24 < 210 > 243 < 211 > 28 < 212 > DNA < 213 > Homo sapiens < 400 > 243 taagaattcc ataaaaatta tggaatgg 28 < 210 > 244 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 244 ccaggatcca gctgaagtct tccatcattc 30 < 210 > 245 < 211 > 1071 < 212 > DNA < 213 > Homo sapiens < 400 > 245 atgaatgggg tctcggaggg gaccagaggc tgcagtgaca ggcaacctgg ggtcctgaca 60 cgtgatcgct cttgttccag gaagatgaac tcttccggat gcctgtctga ggaggtgggg 120 tccctccgcc cactgactgt ggttatcctg tctgcgtcca ttgtcgtcgg agtgctgggc 180 aatgggctgg tgctgtggat gactgtcttc cgtatggcac gcacggtctc caccgtctgc 240 ttcttccacc tggcccttgc cgatttcatg ctctcactgt ctctgcccat tgccatgtac 300 tatattgtct ccaggcagtg gctcctcgga gagtgggcct gcaaactcta catcaccttt 360 gtgttcctca gctactttgc cagtaactgc ctccttgtct tcatctctgt ggaccgttgc 420 atctctgtcc tctaccccgt ctgggccctg aaccaccgca ctgtgcagcg ggcgagctgg 480 ctggcctttg gggtgtggct cctggccgcc gccttgtgct ctgcgcacct gaaattccgg 540 acaaccagaa aatggaatqg ctgtacgcac tgctacttgg cgttcaactc tgacaatgag 600 tttggattga actgcccaga aggggtcgtg gagggacaca ttatagggac cattggccac 660 ttcctgctgg gcttcctggg gcccttagca atcataggca cctgcgccca cctcatccgg 720 gccaagctct tgcgggaggg ctgggtccat gccaaccggc ccgcgaggct gctgctggtg 780 ctggtgagcg ctttctttat cttctggtcc ccgtttaacg tggtgctgtt ggtccatctg 840 tggcgacggg tgatgc tcaa ggaaatctac cacccccgga tgctgctcat cctccaggct 900 agctttgcct tgggctgtgt caacagcagc ctcaacccct tcctctacgt cttcgttggc 960 agagatttcc aagaaaagtt tttgagtct ttgacttctg ccctggcgag ggcgtttgga 1020 gaggaggagt ttctgtcatc ctgtccccgt ggcaacgccc cccgggaatg a 1071 < 210 > 246 < 211 > 356 < 212 > PRT < 213 > Homo sapiens < 400 > 246 Met Asn Gly Val Ser Glu Gly Thr Arg Gly Cys Ser Asp Arg Gln Pro 1 5 10 15 Gly Val Leu Thr Arg Asp Arg Ser Cys Ser Arg Lys Met Asn Ser Ser 20 25 30 Gly Cys Leu Ser Glu Glu Val Gly Ser Leu Arg Pro Leu Thr Val Val 35 40 45 ah ^ éaatetfarf », ... fM1 He Leu Ser Wing Being He Val Val ély Val Leu Gly Asn Gly Leu Val 50 55 60 Leu Trp Met Thr Val Phe Arg Met Wing Arg Thr Val Ser Thr Val Cys 65 70 75 80 Phe Phe His Leu Wing Leu Wing Asp Phe Met Leu Ser Leu Ser Leu Pro 85 90 95 He Wing Met Tyr Tyr He Val Ser Arg Gln Trp Leu Leu Gly Glu Trp 100 105 110 Wing Cys Lys Leu Tyr He Thr Phe Val Phe Leu Ser Tyr Phe Wing Ser 115 120 125 Asn Cys Leu Leu Val Phe He Ser Val Asp Arg Cys He Ser Val Leu 130 135 140 Tyr Pro Val Trp Ala Leu Asn His Arg Thr Val Gln Arg Ala Ser Trp 145 150 155 160 Leu Ala Phe Gly VaL Trp Leu Leu Ala Ala Ala Leu Cys Ser Ala His 165 170 175 Leu Lys Phe Arg Thr Thr Arg Lys Trp Asn Gly Cys Thr His Cys Ty: 180 185 190 Leu Ala Phe Asn Ser Aso Asn Glu Thr Ala Gln He Trp l e Glu Gi 195 200 205 Val Val Glu Gly His He He Gly Thr He Gly His Phe Leu Leu Gly 210 215 220 Phe Leu Gly Pro Leu Wing He He Gly Thr Cys Wing His Leu He Arg 225 230 235 240 Wing Lys Leu Leu Arg Glu Gly Trp Val His Wing Asn Arg Pro Wing Arg 245 250 255 Leu Leu Leu Val Leu Val Ser Wing Phe Phe He Phe Trp Ser Pro Phe 260 265 270 Asn Val Val Leu Leu Val His Leu Trp Arg Arg Val Met Leu Lys Glu 275 280 285 He Tyr His Pro Arg Met Leu Leu He Leu Gln Ala Ser Phe Ala Leu 290 295 300 Gly Cys Val Asn Being Ser Leu Asn Pro Phe Leu Tyr Val Phe Val Gly 305 310 315 320 Arg Asp Phe Gln Glu Lys Phe Phe Gln Ser Leu Thr Ser Ala Leu Ala 325 330 335 Arg Ala Phe Gly Glu Glu Glu Pne Leu Ser Ser Cys Pa_o Arg Gly Asn 340 345 350 Wing Pro Arg Glu 355 < 210 > 247 < 211 > 32 < 212 > DNA < 213 > Homo sapiens < 400 > 247 gcagaattcg gcggccccat ggacctgccc ce 32 < 210 > 248 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 248 gctggatccc cegageagtg gcgttacttc 30 < 210 > 249 < 211 > 903 < 212 > DNA < 213 > Homo sapiens < 400 > 249 atggacctgc ccccgcagct ctccttcggc ctctatgtgg ccgcctttgc gctgggcttc 60 ccgctcaacg tcctggccat ccgaggcgcg acggcccacg cccggctccg tctcacccct 120 agcctggtct acgccctgaa cctgggctgc tccgacctgc tgctaacagt ctctctgccc 180 yí ± ß'Á? .i 4 | O < 210 > 250 < 211 > 300 < 212 > PRT < 213 > Homo sapiens < 400 > 250 Met Asp Leu Pro Pro Gln Leu Ser Phe Gly Leu Tyr Val Ala Wing Phe 10 15 Wing Leu Gly Phe Pro Leu Asn Val Leu Wing He Arg Gly Wing Thr Wing 20 25 30 His Wing Arg Leu Arg Leu Thr Pro Ser Leu Val Tyr Wing Leu Asn Leu 35 40 45 Gly Cys Ser Asp Leu Leu Leu Thr Val Ser Leu Pro Leu Lys Wing Val 55 55 60 Glu Ala Leu Ala Ser Gly Ala Trp Pro Leu Pro Ala Ser Leu Cys Pro 65 70 75 80 Val Phe Wing Val Wing His Phe Phe Pro Leu Tyr Wing Gly Gly Gly Phe 85 90 95 Leu Ala Ala Leu Ser Ala Gly Arg Tyr Leu Gly Ala Ala Phe Pro Leu 100 105 110 Gly Tyr Gln Ala Phe Arg Arg Pro Cys Tyr Ser Trp Gly Val Cys Ala 115 120 125 Ala He Trp Ala Leu Val Leu Cys His Leu Gly Leu Val Phe Gly Leu 130 135 140 Glu Pro Wing Gly Gly Trp Leu Asp His Ser Asn Thr Ser Leu Gly He 145 150 155 160 Asn Thr Pro Val Asn Gly Pro Pro Val Cys Leu Glu Ala Trp Asp Pro 165 170 175 Wing Being Wing Gly Pro Wing Arg Phe Being Leu Being Leu Leu Leu Phe Phe 180 185 190 Leu Pro Leu flla He Thr Wing Phe Cys Tyr Val Gly Cys Leu Arg Wing 195 200 205 Leu Ala Arg Ser Gly Leu Thr His Arg Arg Lys Leu Arg Ala Wing Trp 210 215 220 Val Ala Gly Gly Ala Leu Leu Thr Leu Leu Leu Cys Val Gly Pro Tyr 225 230 235 240 Asn Ala Ser Asn Val Ala Ser Phe Leu Tyr Pro Asn Leu Gly Gly Ser 245 250 255 Trp Arg Lys Leu Gly Leu He Thr Gly Wing Trp Ser Val Val Leu Asn 260 265 270 Pro Leu Val Thr Gly Tyr Leu Gly Arg Gly Pro Gly Leu Lys Thr Val 275 280 285 Cys Ala Ala Arg Thr Gln Gly Gly Lys Ser Gln Lys 290 295 300 < 210 > 251 < 211 > 31 < 212 > DNA < 213 > Homo sapiens < 400 > 251 ctcaagctta ctctctctca ccagtggcca c 31 < 210 > 252 < 211 > 24 < 212 > DNA < 213 > Homo sapiens < 400 > 252 ccctcctccc ccggaggacc tagc 24 < 210 > 253 < 211 > 1041 < 212 > DNA < 213 > Homo sapiens < 400 > 253 atggatacag gccccgacca gtcctacttc tccggcaatc actggttcgt cttctcggtg 60 taccttctca ctttcctggt ggggctcccc ctcaacctgc tggccctggt ggtcttcgtg 120 ggcaagctgc agcgccgccc ggtggccgtg gacgtgctcc tgctcaacct gaccgcctcg 180 gacctgctcc tgctgctgtt cctgcctttc cgcatggtgg aggcagccaa tggcatgcac 240 tggcccctgc ccttcatcct ctgcccactc tctggattca tcttcttcac caccatctat 300 ctcaccgccc tcttcctggc agctgtgagc attgaacgct tcctgagtgt ggcccaccca 360 ctgtggtaca agacccggcc gaggctgggg caggcaggtc tggtgagtgt ggcctgctgg 420 ctgttggcct ctgctcactg cagcgtggtc tacgtcatag aattctcagg ggacatctcc 480 cacagccagg gcaccaatgg gacctgctac ctggagttcc ggaaggacca gctagccatc 540 ctcctgcccg tgcggctgga gatggctgtg gtcctctttg tggtcccgct gatcatcacc 600 agctactgct acagccgcct ggtgtggatc ctcggcagag ggggcagcca ccgccggcag 660 aggagggtgg cggggctgtt ggcggccacg ctgctcaact tccttgtctg ctttgggccc 720 tacaacgtgt cccatgtcgt gggctatatc tgcggtgaaa gcccggcatg gaggatctac 780 gtgacgcttc tcagcaccct gaactcctgt gtcgacccct ttgtctacta cttctcctcc 840 i-te »a§ < & áSéata ^ .jZai tccgggttcc aagccgactt tcatgagctg ctgaggaggt tgtgtgggct ctggggccag 900 tggcagcagg agagcagcat ggagctgaag gagcagaagg gaggggagga gcagagagcg 960 gaccgaccag ctgaaagaaa gaccagtgaa cactcacagg gctgtggaac tggtggccag 1020 gtggcctgtg ctgaaagcta g 1041 < 210 > 254 < 211 > 346 < 212 > PRT < 213 > Homo sapiens < 400 > 254 Met Asp Thr Gly Pro Asp Gln Ser Tyr Phe Ser Gly Asn His Trp Phe 1 5 10 15 Val Phe Ser Val Tyr Leu Leu Thr Phe Leu Val Gly Leu Pro Leu Asn 20 25 30 Leu Leu Ala Leu Val Val Phe Val Gly Lys Leu Gln Arg Arg Pro Val 35 40 45 Ala Val Asp Val Leu Leu Leu Asn Leu Thr Ala Ser Asp Leu Leu Leu 50 55 60 Leu Leu Phe Leu Pro Phe Arg Met Val Glu Ala Wing Asn Gly Met His 65 70 75 80 Trp Pro Leu Pro P "e He Leu C ^ s Pro Leu Ser Gly Phe He Phe Phe 85 90 95 aM &afe? j? a? afe? JBÍ £ § Thr Thr He Tyr Leu Thr Ala Leu Phe Leu Ala Ala Val Ser He Glu 100 105 110 Arg Phe Leu Ser Val Ala Pro His Leu Trp Tyr Lys Thr Arg Pro Arg 115 120 125 Leu Gly Gln Wing Gly Leu Val Ser Val Wing Cys Trp Leu Leu Wing Ser 130 135 140 Ala His Cys Ser Val Val Tyr Val He Glu Phe Ser Gly Asp He Ser 145 150 155 160 His Ser Gln Gly Thr Asn Gly Thr Cys Tyr Leu Glu Phe Arg Lys Asp 165 170 175 Gln Leu Ala He Leu Leu Pro Val Arg Leu Glu Met Ala Val Val Leu 180 185 190 Phe Val Val Pro Leu He He Thr Ser Tyr Cys Tyr Ser Arg Leu Val 195 200 205 Trp He Leu Gly Arg Gly Gly Ser His Arg Arg Gln Arg Arg Val Ala 210 215 220 Gly Leu Leu Ala Ala Thr Leu Leu Asn Phe Leu Val Cys Phe Gly Pro 225 230 235 240 Tyr Asn Val Ser His Val Val Gly Tyr He Cys Gly Glu Ser Pro Wing 245 250 255 Trp Arg He Tyr Val Thr Leu Leu Ser Thr Leu Asn Ser Cys Val Asp 260 265 270 Pro Phe Val Tyr Tyr Phe Ser Ser Gly Phe Gln Wing Asp Phe His 275 280 285 Glu Leu Leu Arg Arg Leu Cys Gly Leu Trp Gly Gln Trp Gln Gln Glu 290 295 300 Being Ser Met Glu Leu Lys Glu Gln Lys Gly Gly Glu Glu Gln Arg Ala 305 310 315 320 Asp Arg Pro Wing Glu Arg Lys Thr Ser Glu His Ser Gln Gly Cys Gly 325 330 335 Thr Gly Gly Gln Val Wing Cys Wing Glu Ser 340 345 < 210 > 255 < 211 > 31 < 212 > DNA < 213 > Homo sapiens < 400 > 255 tttaagcttc ccctccagga tgctgccgga c 31 < 210 > 256 < 211 > 31 < 212 > DNA < 213 > Homo sapiens < 400 > 256 ggcgaattct gaaggtccag ggaaactgct to 31 < 210 > 257 < 211 > 993 < 212 > DNA < 213 > Homo sapiens < 400 > 257 atgctgccgg actggaagag ctccttgatc ctcatggctt acatcatcat cttcctcact 60 ggcctccctg ccaacctcct ggccctgcgg gcctttgtgg ggcggatccg ccagccccag 120 cctgcacctg tgcacatcct cctgctgagc ctgacgctgg ccgacctcct cctgctgctg 180 ctgctgccct tcaagatcat cgaggctgcg tcgaacttcc gctggtacct gcccaaggtc 240 gtctgcgccc tcacgagttt tggcttctac agcagcatct actgcagcac gtggctcctg 300 gcgggcatca gcatcgagcg ctacctggga gtggctttcc ccgtgcagta caagctctcc 360 cgccggcctc tgtatggagt gattgcagct ctggtggcct gggttatgtc ctttggtcac 420 tgcaccatcg tgatcatcgt tcaatacttg aacacgactg agcaggtcag aagtggcaat 480 gaaattacct gctacgagaa cttcaccgat aaccagttgg acgtggtgct gcccgtgcgg 540 ctggagctgt gcctggtgct cttcttcatc cccatggcag tcaccatctt ctgctactgg 600 cgttttgtgt ggatcatgct ctcccagccc cttgtggggg cccagaggcg gcgccgagcc 660 gtggggctgg ctgtggtgac gctgctcaat ttcctggtgt gcttcggacc ttacaacgtg 720 tggggtatca tcccacctgg ccagagaaaa agcccctggt ggcggtcaat agccgtcjgtg 78C ttcagttcac tcaacgccag tctggacccc ctgctcttct atttctcttc ttcagtggtg 8¿ 1 r J «faÍ« a &M »¿.mt £» < Cgcagggcat ttgggagagg gctgcaggtg ctgcggaatc agggctcctc cctgttggga 900 cgcagaggca aagacacagc agaggggaca aatgaggaca ggggtgtggg tcaaggagaa 960 gggatgccaa gttcggactt cactacagag tag 993 < 210 > 258 < 211 > 330 < 212 > PRT < 213 > Homo sapiens < 400 > 258 Met Leu Pro Asp Trp Lys Be Ser Leu He Leu Met Wing Tyr He He 1 5 10 15 He Phe Leu Thr Gly Leu Pro Wing Asn Leu Leu Wing Leu Arg Wing Phe 20 25 30 Val Gly Arg He Arg Gln Pro Pro Gln Pro Pro Val His He Leu Leu 35 40 45 Leu Ser Leu Thr Leu Wing Asp Leu Leu Leu Leu Leu Leu Leu Pro Phe 50 55 60 Lys He He Glu Wing Wing Being Asn Phe Arg Trp Tyr Leu Pro Lys Val 65 70 75 80 Val Cys Ala Leu Thr Ser Phe Gly Phe Tyr Ser Ser He Tyr Cys Ser 85 90 95 Thr Trp Leu Leu Wing Gly He Ser He Glu Arg Tyr Leu Gly Val Wing 100 105 110 Phe Pro Val Gln Tyr Lys Leu Ser Arg Arg Pro Leu Tyr Gly Val He 115 120 125 Ala Ala Leu Val Ala Trp Val Met Ser Phe Gly His Cys Thr He Val 130 135 140 He He Val Gln Tyr Leu Asn Thr Thr Glu Gln Val Arg Ser Gly Asn 145 150 155 160 Glu He Thr Cys Tyr Glu Asn Phe Thr Asp Asn Gln Leu Asp Val Val 165 170 175 Leu Pro Val Arg Leu Glu Leu Cys Leu Val Leu Phe Phe He Pro Met 180 185 190 Wing Val Thr He Phe Cys Tyr Trp Arg Phe Val Trp He Met Leu Ser 195 200 205 Gln Pro Leu Val Gly Ala Gln Arg Arg Arg Arg Ala Val Gly Leu Ala 210 215 220 Val Val Thr Leu Leu Asn Phe Leu Val Cys Phe Gly Pro Tyr Asn Val 225 230 235 240 Ser His Leu Val Gly Tyr His Gln Arg Lys Ser Pro Trp Trp Arg Ser feWgfa = SStJiSi. 245 250 255 He Ala Val Val Phe Ser Ser Leu Asn Ala Ser Leu Asp Pro Leu Leu 260 265 270 Phe Tyr Phe Ser Ser Val Val Arg Arg Ala Phe Gly Arg Gly Leu 275 280 285 Gln Val Leu Arg Asn Gln Gly Be Ser Leu Leu Gly Arg Arg Gly Lys 290 295 300 Asp Thr Ala Glu Gly Thr Asn Glu Asp Arg Gly Val Gly Gln Gly Glu 305 310 315 320 Gly Met Pro Ser Being Asp Phe Thr Thr Glu 325 330 < 210 > 259 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 259 cccaagcttc gggcaccatg gacacctccc 30 < 210 > 260 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 260 acaggatcca aatgcacagc actggtaagc 30 < 210 > 261 < 211 > 25 < 212 > DNA < 213 > Homo sapiens < 400 > 261 ctataactgg gttacatggt ttaac 25 < 210 > 262 < 211 > 30 < 212 > DNA 15 < 213 > Homo sapiens < 400 > 262 tttgaattca catattaatt agagacatgg 30 < 210 > 263 < 211 > 2724 < 212 > DNA < 213 > Homo sapiens < 400 > 263? O atggacacct cccggctcgg tgtgctcctg tccttgcctg tgctgctgca gctggcgacc 60 ^^^ ^^ s ^^^^ m ^^^^^ gggggcagct ctcccaggtc tggtgtgttg ctgaggggct gccccacaca ctgtcattgc 120 gagcccgacg gcaggatgtt gctcagggtg gactgctccg acctggggct ctcggagctg 180 ccttccaacc tcagcgtctt cacctcctac ctagacctca gtatgaacaa catcagtcag 240 ctgctcccga atcccctgcc cagtctccgc ttcctggagg agttacgtct tgcgggaaac 300 gctctgacat acattcccaa gggagcattc actggccttt acagtcttaa agttcttatg 360 ctgcagaata atcagctaag acacgtaccc acagaagctc tgcagaattt gcgaagcctt 420 caatccctgc gtctggatgc taaccacatc agctatgtgc ccccaagctg tttcagtggc 480 ctgcattccc tgaggcacct gtggctggat gacaatgcgt taacagaaat ccccgtccag 540 gcttttagaa gtttatcggc attgcaagcc atgaccttgg ccctgaacaa aatacaccac 600 ataccagact atgcctttgg aaacctctcc agcttggtag ttctacatct ccataacaat 660 agaatccact ccctgggaaa gaaatgcttt gatgggctcc acagcctaga gactttagat 720 ataaccttga ttaaattaca tgaattcccc actgcaatta ggacactctc caaccttaaa 780 gaactaggat ttcatagcaa caatatcagg tcgatacctg agaaagcatt tgtaggcaac 840 ccttctctta ttacaataca tttctatgac aatcccatcc aatttgttgg gagatctgct 900 t ttcaacatt tacctgaact aagaacactg actctgaatg gtgcctcaca aataactgaa 960 tttcctgatt taactggaac tgcaaacctg gagagtctga ctttaactgg agcacagatc 1020 tcatctcttc ctcaaaccgt ctgcaatcag ttacctaatc tccaagtgct agatctgtct 1080 tacaacctat tagaagattt acccagtttt tcagtctgcc aaaagcttca gaaaattgac 1140 atgaaatcta ctaagacata cgaaattaaa gttgacactt tccagcagtt gcttagcctc 1200 cgatcgctga atttggcttg gaacaaaatt gctattattc accccaatgc attttccact 1260 ttgccatccc taataaagct ggacctatcg tccaacctcc tgtcgtcttt tcctataact 1320 gggttacatg gtttaactca cttaaaatta acaggaaatc atgccttaca gagcttgata 1380 actttccaga tcatctgaaa actcaaggtt atagaaatgc cttatgctta ccagtgctgt 1440 gcatttggag tgtgtgagaa tgcctataag atttctaatc aatggaataa aggtgacaac 1500 agcagtatgg acgaccttca taagaaagat gctggaatgt ttcaggctca agatgaacgt 1560 gaccttgaag atttcctgct tgactttgag aagcccttca gaagacctga ttcagtgcag 1620 tgttcacctt ccccaggccc cttcaaaccc tgtgaacacc tgcttgatgg ctggctgatc 1680 agaattggag tgtggaccat agcagttctg gcacttactt gtaatgcttt ggtgacttca 1740 acagttttca gatcccctct gtacatttcc cccattaaac tgttaattgg ggtcatcgca 1800 gcagtgaaca tgctcacggg agtctccagt gccgtgctgg ctggtgtgga tgcgttcact 1860 tttggcagct ttgcacgaca tggtgcctgg tgggagaatg gggttggttg ccatgtcatt 1920 ggttttttgt ccatttttgc ttcagaatca tctgttttcc tgcttactct ggcagccctg 1980 tctctgtgaa gagcgtgggt atattctgca aaatttgaaa cgaaagctcc attttctagc 2040 ctgaaagtaa tcattttgct ctgtgccctg ctggccttga ccatggccgc agttcccctg 2100 ctgggtggca gcaagtatgg cgcctcccct ctctgcctgc ctttgccttt tggggagccc 2160 agcaccatgg gctacatggt cgctctcatc ttgctcaatt ccctttgctt cctcatgatg 2220 accattgcct acaccaagct ctactgcaat ttggacaagg gagacctgga gaatatttgg 2280 tggtaaaaca gactgctcta cattgccctg ttgctcttca ccaactgcat cctaaactgc 2340 cctgtggctt tcttgtcctt ctcctcttta ataaacctta catttatcag tcctgaagta 2400 attaagttta tccttctggt ggtagtccca cttcctgcat gtctcaatcc ccttctctac 2460 atcttgttca atcctcactt taaggaggat ctggtgagcc tgagaaagca aacctacgtc 2520 tggacaagat caaaacaccc aagcttgatg tcaattaact ctgatgatgt cgaaaaacag 2580 t cctgtgact caactcaagc cttggtaacc tttaccagct ccagcatcac ttatgacctg 2640 cctcccagtt ccgtgccatc accagcttat ccagtgactg agagctgcca tctttcctct 2700 gtggcatttg tcccatgtct ctaa 2724 < 210 > 264 < 211 > 907 < 212 > PRT < 213 > Homo sapiens < 400 > 264 Met Asp Thr Ser Arg Leu Gly Val Leu Leu Ser Leu Pro Val Leu Leu 1 5 10 15 Gln Leu Ala Thr Gly Gly Ser Ser Arg Ser Gly Val Leu Leu Arg 20 25 30 Gly Cys Pro Thr His Cys His Cys Glu Pro Asp Gly Arg Met Leu Leu 35 40 45 Arg Val Asp Cys Ser Asp Leu Gly Leu Ser Glu Leu Pro Ser Asn Leu 50 55 60 Ser Val Phe Thr Ser Tyr Leu Asp Leu Ser Met Asn Asn He Ser Gln 65 70 75 80 Leu Leu Pro Asn Pro Leu Pro Ser Leu Arg Phe Leu Glu Glu Leu Arg 85 90 95 Leu Ala Gly Asn Ala Leu Thr Tyr He Pro Lys Gly Ala Phe Thr Gly 100 105 110 Leu Tyr Ser Leu Lys Val Leu Met Leu Gln Asn Asn Gin Leu Arg His 115 120 125 Val Pro Thr Glu Ala Leu Gln Asn Leu Arg Ser Leu Gln Ser Leu Arg 130 135 140 Leu Asp Ala Asn His He Ser Tyr Val Pro Pro Ser Cys Phe Ser Gly 145 150 155 160 Leu His Ser Leu Arg His Leu Trp Leu Asp Asp Asn A_a Leu Thr Glu 165 170 175 He Pro Val Gln Wing Phe Arg Ser Leu Ser Wing Leu Gln Wing Met Thr 180 185 190 Leu Ala Leu Asn Lys He His His He Pro Asp Tyr Ala Phe Gly Asn 195 200 205 Leu Ser Ser Leu Val Val Leu His Leu His Asn Asn Arg He His Ser 210 215 220 Leu Gly Lys Lys Cys Phe Asp Gly Leu His Ser Leu Glu Thr Leu Asp 225 230 235 240 Leu Asn Tyr Asn Asn Leu Asp Glu Phe Pro Thr Wing He Arg Thr Leu 245 250 255 Being Asn Leu Lys Glu Leu Gly Phe His Being Asn Asn He Arg Being He 260 265 270 Pro Glu Lys Wing Phe Val Gly Asn Pro Ser Leu He Thr He His Phe 275 280 285 Tyr Asp Asn Pro He Gln Phe Val Gly Arg Ser Wing Phe Gln His Leu 290 295 300 Pro Glu Leu Arg Thr Leu Thr Leu Asn Gly Wing Ser Gln He Thr Glu 305 310 315 320 Phe Pro Asp Leu Thr Gl and Thr Ala Asn Leu Glu Ser Leu Thr Leu Thr Fegfe fen »» > ^ aaa «^ áa-áf '- iM-3fe'¿3 325 330 335 Gly Ala Gln He Ser Ser Leu Pro Gln Thr Val Cys Asn Gln Leu Pro 340 345 350 Asn Leu Gln Val Leu Asp Leu Ser Tyr Asn Leu Leu Glu Asp Leu Pro 355 360 365 Ser Phe Ser Val Cys Gln Lys Leu Gln Lys He Asp Leu Arg His Asn 370 375 380 Glu He Tyr Glu He Lys Val Asp Thr Phe Gln Gln Leu Leu Ser Leu 385 390 395 400 Arg Ser Leu Asn Leu Wing Trp Asn Lys He Wing He He His Pro Asn 405 410 415 Wing Phe Ser Thr Leu Pro Ser Leu He Lys Leu Asp Leu Ser Ser Asn 420 425 430 Leu Leu Ser Ser Phe Pro He Thr Gly Leu His Gly Leu Thr His Leu 435 440 445 Lys Leu Thr Gly Asn His Wing Leu Gln Ser Leu He Ser Ser Glu Asn 450 455 460 Phe Pro Glu ^ eu Lys Val He Glu Met Pro Tyr Ala Tyr Gln Cys Cys 465 470 475 180 Wing Phe Gly Val Cys Glu Asn Wing Tyr Lys He Ser Asn Gln Trp Asn 485 490 495 Lys Gly Asp Asn Being Ser Met Asp Asp Leu His Lys Lys Asp Wing Gly 500 505 510 Met Phe Gln Wing Gln Asp Glu Arg Asp Leu Glu Asp Phe Leu Leu Asp 515 520 525 Phe Glu Glu Asp Leu Lys Ala Leu His Ser Val Gln Cys Ser Pro Ser 530 535 540 Pro Gly Pro Phe Lys Pro Cys Glu His Leu Leu Asp Gly Trp Leu He 545 550 555 560 Arg He Gly Val Trp Thr He Ala Val Leu Ala Leu Thr Cys Asn Ala 565 570 575 Leu Val Thr Ser Thr Val Phe Arg Ser Pro Leu Tyr He Ser Pro He 580 585 590 Lys Leu Leu He Gly Val He Ala Wing Val Asn Met Leu Thr Gly Val 595 600 605 Be Ser Wing Val Leu Wing Gly Val Asp Wing Phe Thr Phe Gly Ser Phe 610 615 620 Wing Arg H S Gly Wing Tro Trp Glu Asn Gly Val Gly Cys Pis Vc_ He 8 625 630 635 640 Gly Phe Leu Ser He Phe Wing Ser Glu Ser Ser Val Phe Leu Leu Thr 645 650 655 Leu Ala Ala Leu Glu Arg Gly Phe Ser Val Lys Tyr Ser Ala Lys Phe 660 665 670 Glu Thr Lys Wing Pro Phe Ser Ser Leu Lys Val He He Leu Leu Cys 675 680 685 Wing Leu Leu Wing Leu Thr Met Wing Wing Val Pro Leu Leu Gly Gly Ser 690 695 700 Lys Tyr Gly Ala Ser Pro Leu Cys Leu Pro Leu Pro Phe Gly Glu Pro 705 710 715 720 Being Thr Met Gly Tyr Met Val Wing Leu He Leu Leu Asn Being Leu Cys 725 730 735 Phe Leu Met Met Thr He Ala Tyr Thr Lys Leu Tyr Cys Asn Leu Asp 740 745 750 Lys Gly Asp Leu Glu Asn He Trp Asp Cys Ser Met Val Lys His He 755 760 765 Wing Leu Leu Leu Phe Thr Asn Cys He Leu Asn Cys Pro Val Wing Phe 770 775 780 Leu Ser Phe Ser Ser Leu He Asn Leu Thr Phe He Ser Pro Glu Val 785 790 795 800 He Lys Phe He Leu Leu Val Val Val Pro Leu Pro Ala Cys Leu Asn 805 810 815 Pro Leu Leu Tyr He Leu Phe Asn Pro His Phe Lys Glu Asp Leu Val 820 825 830 Ser Leu Arg Lys Gln Thr Tyr Val Trp Thr Arg Ser Lys His Pro Ser 835 840 845 Leu Met Ser He Asn Ser Asp Asp Val Glu Lys Gln Ser Cys Asp Ser 850 855 860 Thr Gln Ala Leu Val Thr Phe Thr Ser Ser Ser He Thr Tyr Asp Leu 865 870 875 Pro Pro Ser Ser Val Pro Pro Pro Ala Tyr Pro Val Thr Glu Ser Cys 885 890 895 His Leu Ser Ser Val Val Phe Val Pro Cys Leu 900 905 < 210 > 265 < 211 > 30 < 212 > DNA < 213 ^ Homo sapiens "^^ Miftn? Ri tft? < 400 > 265 cggaagctgc gggccaaatg ggtgqccggc 30 < 210 > 266 < 211 > 27 < 212 > DNA < 213 > Homo sapiens < 400 > 266 cagaggaggg tgaaggggct gttggcg 27 < 210 > 267 < 211 > 30 < 212 > DNA < 213 > Homo sapiens < 400 > 267 ggcggcgccg agccaagggg ctggctgtgg 30 < 210 > 268 < 211 > 32 < 212 > DNA < 213 > Homo sapiens < 400 > 268 gggactgctc tatgaaaaaa cacattgccc tg 32 < 210 > 269 < 211 > 1071 < 212 > DNA < 213 > Homo sapiens < 400 > 269 atgaatgggg tctcggaggg gaccagaggc tgcagtgaca ggcaacctgg ggtcctgaca 60 cgtgatcgct cttgttccag gaagatgaac tcttccggat gcctgtctga ggaggtgggg 120 tccctccgcc cactgactgt ggttatcctg tctgcgtcca ttgtcgtcgg agtgctgggc 180 aatgggctgg tgctgtggat gactgtcttc cgtatggcac gcacggtctc caccgtctgc 240 ttcttccacc tggcccttgc cgatttcatg ctctcactgt ctctgcccat tgccatgtac 300 tatattgtct ccaggcagtg gctcctcgga gagtgggcct gcaaactcta catcaccttt 360 gtgttcctca gctactttgc cagtaactgc ctccttgtct tcatctctgt ggaccgttgc 420 atctctgtcc tctaccccgt ctgggccctg aaccaccgca ctgtgcagcg ggcgagctgg 480 ctggcctttg gggtgtggct cctggccgcc gccttgtgct ctgcgcacct gaaattccgg 540 acaaccagaa aatggaatgg ctgtacgcac tgctacttgg cgttcaactc tgacaatgag 600 tttggattga actgcccaga aggggtcgtg gagggacaca ttatagggac cattggccac 660 ttcctgctgg gcttcctggg gcccttagca atcataggca cctgcgccca cctcatccgg 720 gccaagctct tgcgggaggg ctgggtccat gccaaccggc ccaagaggct gctgctggtg 780 ctggtgagcg ctttctttat cttctggtcc ccgtttaacg tggtgctgtt ggtccatctg 840 tggcgacggg tgatgc tcaa ggaaatctac cacccccgga tgctgctcat cctccaggct 900 agctttgcct tgggctgtgt caacagcagc ctcaacccct tcctctacgt cttcgttggc 960 agagatttcc aagaaaagtt tttgagtct ttgacttctg ccctggcgag ggcgtttgga 1020 gaggaggagt ttctgtcatc ctgtccccgt ggcaacgccc cccgggaatg a 1071 < 210 > 270 < 211 > 356 < 212 > PRT < 213 > Homo sapiens < 400 > 270 Met Asn Gly Val Ser Glu Gly Thr Arg Gly Cys Ser Asp Arg Gln Pro 1 5 10 15 Gly Val Leu Thr Arg Asp Arg Ser Cys Ser Arg Lys Met Asn Ser Ser 20 25 30 Gly Cys Leu Ser Glu Glu Val Gly Ser Leu Arg Pro Leu Thr Val Val 35 40 45 He Leu Ser Ala Be He Val Val Gly Val Leu Gly Asn Gly Leu Val 50 55 60 Leu Trp Met Thr Val Phe Arg Met Wing Arg Thr Val Ser Thr Val Cys 65 70 75 80 Phe Phe His Leu Wing Leu Wing Asp Phe Met Leu Ser Leu Ser Leu Pro 85 90 95 He Wing Met Tyr Tyr He Val Ser Arg Gln Trp Leu Leu Gly Glu Trp 100 105 110 Wing Cys Lys Leu Tyr He Thr Phe Val Phe Leu Ser Tyr Phe Wing Ser 115 120 125 Asn Cys Leu Leu Val Phe He Ser Val Asp Arg Cys He Ser Val I read 130 135 140 Tyr Pro Val Trp Ala Leu Asn His Arg Thr Val Gln Arg Ala Ser Trp 145 150 155 160 Leu Ala Phe Gly Val Trp Leu Leu Ala Ala Ala Leu Cys Ser Ala His 165 170 175 Leu Lys Phe Arg Thr Thr Arg Lys Trp Asn Gly Cys Thr His Cys Tyr 180 185 190 Leu Ala Phe Asn Ser Asp Asn Glu Thr Ala Gln He Trp He Glu Gly 195 200 205 Val Val Glu Gly His He He Gly Thr He Gly His Phe Leu Leu Gly 210 215 220 Phe Leu Gly Pro Leu Wing He He Gly Thr Cys Wing His Leu He Arg 225 230 235 240 Ala Lys Leu Leu Arg Glu Gly Trp Val His Wing Asn Arg Pro Lys Arg 245 250 255 Leu Leu Leu Val Leu Val Ser Wing Phe Phe He Phe Trp Ser Pro Phe 260 265 270 Asn Val Val Leu Leu Val His Leu Tro Arg Arg Val Met Leu Lys Glu 275 280 285 s, -; jujjs », ^ a £ ftA.) & fa He Tyr His Pro Arg Met Leu Leu He Leu Gln Ala Ser Phe Ala Leu 290 295 300 Gly Cys Val Asn Being Ser Leu Asn Pro Phe Leu Tyr Val Phe Val Gly 305 310 315 320 Arg Asp Phe Gln Glu Lys Phe Phe Gln Ser Leu Thr Ser Ala Leu Ala 325 330 335 Arg Ala Phe Gly Glu Glu Glu Phe Leu Ser Ser Cys Pro Arg Gly Asn 340 345 350 Ala Pro Arg Glu 355 < 210 > 271 < 211 > 903 < 212 > DNA < 213 > Homo sapiens < 400 > 271 atggacctgc ccccgcagct ctccttcggc ctctatgtgg ccgcctttgc gctgggcttc 60 ccgctcaacg tcctggccat ccgaggcgcg acggcccacg cccggctccg tctcacccct 120 agcctggtct acgccctgaa cctgggctgc tccgacctgc tgctgacagt ctctctgccc 180 ctgaaggcgg tggaggcgct agcctccggg gcctggcctc tgccggcctc gctgtgcccc 240 gtcttcgcgg tggcccactt cttcccactc tatgccggcg ggggcttcct ggccgccctg 300 agtgcaggcc gctacctggg agcagccttc cccttgggct accaagcctt ccggaggccg 360 tgctattcct ggggggtgtg cgcggccatc tgggccctcg tcctgtgtca cctgggtctg 420 gtctttgggt tggaggctcc aggaggctgg ctggaccaca gcaacacctc cctgggcatc 480 aacacaccgg tcaacggctc tccggtctgc ctggaggcct gggacccggc ctctgccggc 540 ccggcccgct tcagcctctc tctcctgctc ttttttctgc ccttggccat cacagccttc 600 tgctacgtgg gctgcctccg ggcactggcc cgctccggcc tgacgcacag gcggaagctg 660 cgggccaaat gggtggccgg cggggccctc ctcacgctgc tgctctgcgt aggaccctac 720 aacgcctcca acgtggccag cttcctgtac cccaatctag gaggctcctg gcggaagctg 780 gggctcatca cgggtgcctg gagtgtggtg cttaatccgc tggtgaccgg ttacttggga 840 aggggtcctg gcctg aagac agtgtgtgcg gcaagaacgc aagggggcaa gtcccagaag 900 taa 903 < 210 > 272 < 211 > 300 < 212 > PRT < 213 > Homo sapiens < 400 > 272 Met Asp Leu Pro Pro Gln Leu Ser Phe Gly Leu Tyr Val Ala Wing Phe 1 5 10 15 Wing Leu Gly Phe Pro Leu Asn Val Leu Wing He Arg Gly Wing Thr Wing 20 25 30 His Wing Arg Leu Arg Leu Thr Pro Ser Leu Val Tyr Wing Leu Asn Leu 35 40 45 Gly Cys Ser Asp Leu Leu Leu Thr Val Ser Leu Pro Leu Lys Ala Val 50 55 60 Glu Ala Leu Ala Se- Ciy Ala Trp Pro Leu Pro Ala Ser Leu Cys Pro 65 70 75 80 Val Phe Wing Val Wing His Phe Phe Pro Leu Tyr Wing Gly Gly Gly Phe 85 90 95 Leu Ala Ala Leu Ser Ala Gly Arg Tyr Leu Gly Ala Ala Phe Pro Leu 100 105 110 Gly Tyr Gln Ala Phe Arg Arg Pro Cys Tyr Ser Trp Gly Val Cys Ala 115 120 125 Ala He Trp Ala Leu Val Leu Cys His Leu Gly Leu Val Phe Gly Leu 130 135 140 Glu Pro Wing Gly Gly Trp Leu Asp His Ser Asn Thr Ser Leu Gly He 145 150 155 160 Asn Thr Pro Val Asn Gly Pro Pro Val Cys Leu Glu Ala Trp Asp Pro 165 170 175 Wing Being Wing Gly Pro Wing Arg Phe Being Leu Being Leu Leu Leu Phe Phe 180 185 190 Leu Pro Leu Wing He Thr Wing Phe Cys Tyr Val Gly Cys Leu Arg Wing 195 200 205 Leu Ala Arg Ser Gly Leu Thr His Arg Arg Lys Leu Arg Ala Lys Trp 210 215 220 Val Ala Gly Gly Ala Leu Leu Thr Leu Leu Leu Cys Val Gly Pro Tyr 225 230 235 240 Asn Ala Ser Asn Val Ala Ser Phe Leu Tyr Pro Asn Leu Gly Gly Ser 245 250 255 Trp Arg Lys Leu Gly Leu He Thr Gly Wing Trp Ser Val Val Leu Asn 260 265 270 Pro Leu Val Thr Gly Tyr Leu Gly Arg Gly Pro Gly Leu Lys Thr Val 275 280 285 Cys Ala Ala Arg Thr Gln Gly Gly Lys Ser Gln Lys 290 295 300 < 210 > 273 < 211 > 1041 < 212 > DNA < 213 > Homo sapiens < 400 > 273 atggatacag gccccgacca gtcctacttc tccggcaatc actggttcgt cttctcggtg 60 taccttctca ctttcctggt ggggctcccc ctcaacctgc tggccctggt ggtcttcgtg 120 ggcaagctgc agcgccgccc ggtggccgtg gacgtgctcc tgctcaacct gaccgcctcg 180 gacctgctcc tgctgctgtt cctgcctttc cgcatggtgg aggcagccaa tggcatgcac 240 tggcccctgc ccttcatcct ctgcccactc tctggattca tcttcttcac caccatctat 300 ctcaccgccc tcttcctggc agctgtgagc attgaacgct tcctgagtgt ggcccaccca 360 ctgtggtaca agacccggcc gaggctggsg caggcaggtc tggtgagtgt ggcctgctgg 420 ctgttggcct ctgctcactg cagcsglggtc tacgtcatag aattctcagg ggacatctcc 480 cacagccagg gcaccaatgg gacctgctac ctggagttcc ggaaggacca gctagccatc 540 ctcctgcccg tgcggctgga gatggctgtg gtcctctttg tggtcccgct gatcatcacc 600 agctactgct acagccgcct ggtgtggatc ctcggcagag ggggcagcca ccgccggcag 660 aggagggtga aggggctgtt ggcggccacg ctgctcaact tccttgtctg ctttgggccc 720 tacaacgtgt cccatgtcgt gggctatatc tgcggtgaaa gcccggcatg gaggatctac 780 gtgacgcttc tcagcaccct gaactcctgt gtcgacccct ttgtctacta cttctcctcc 840 tccgggttcc aagcc gactt tcatgagctg ctgaggaggt tgtgtgggct ctggggccag 900 tggcagcagg agagcagcat ggagctgaag gagcagaagg gaggggagga gcagagagcg 960 gaccgaccag ctgaaagaaa gaccagtgaa cactcacagg gctgtggaac tggtggccag 1020 gtggcctgtg ctgaaagcta g 1041 < 210 > 274 < 211 > 346 < 212 > PRT < 213 > Homo sapiens < 400 > 274 Met Asp Thr Gly Pro Asp Gln Ser Tyr Phe Ser Gly Asn His Trp Phe 1 5 10 15 Val Phe Ser Val Tyr Leu Leu Thr Phe Leu Val Gly Leu Pro Leu Asn 20 25 30 Leu Leu Ala Leu Val Val Phe Val Gly Lys Leu Gln Arg Arg Pro Val 35 40 45 Ala Val Asp l to Leu Leu Leu Asn Leu l ^ r Ala Ser Asp Leu Leu Leí 50 55 60 Leu Leu Phe Leu Pro Phe Arg Met Val Glu Ala Wing Asn Gly Met His 65 70 75 80 Trp Pro Leu Pro Phe He Leu Cys Pro Leu Ser Gly Phe He Phe Phe 85 90 95 Thr Thr He Tyr Leu Thr Ala Leu Phe Leu Ala Wing Val Ser He Glu 100 105 110 Arg Phe Leu Ser Val Ala Pro His Leu Trp Tyr Lys Thr Arg Pro Arg 115 120 125 Leu Gly Gln Wing Gly Leu Val Ser Val Wing Cys Trp Leu Leu Wing Ser 130 135 140 Ala His Cys Ser Val Val Tyr Val He Glu Phe Ser Gly Asp He Ser 145 150 155 160 His Ser Gln Gly Thr Asn Gly Thr Cys Tyr Leu Glu Phe Arg Lys Asp 165 170 175 Gln Leu Wing He Leu Leu Pro Val Arg Leu Glu Met Wing Val Val Leu 180 185 190 Phe Val Val Pro Leu He He Thr Ser Tyr Cys Tyr Ser Arg Leu Val 195 200 205 Trp He Leu Gly Arg Gly Gly Ser His Arg Arg Gln Arg Arg Val Lys 210 215 220 Gly Leu Leu Ala Ala Thr Leu Leu Asn Phe Leu Val Cys Phe Gly Pro 225 230 235 240 Tyr Asn Val Ser His Val Val Gly Tyr He Cys Gly Glu Ser Pro Wing 245 250 255 Trp Arg He Tyr Val Thr Leu Leu Ser Thr Leu Asn Ser Cys Val Asp 260 265 270 Pro Phe Val Tyr Tyr Phe Ser Ser Gly Phe Gln Wing Asp Phe His 275 280 285 Glu Leu Leu Arg Arg Leu Cys Gly Leu Trp Gly Gln Trp Gln Gln Glu 290 295 300 Being Ser Met Glu Leu Lys Glu Gln Lys Gly Gly Glu Glu Gln Arg Ala 305 310 315 320 Asp Arg Pro Wing Glu Arg Lys Thr Ser Glu His Ser Gln Gly Cys Gly 325 330 335 Thr Gly Gly Gln Val Wing Cys Wing Glu Ser 340 345 < 210 > 275 a = ^ ^ S ^ ato ^ "^^^ afetoa» ^^ < 211 > 993 < 212 > DNA < 213 > Homo sapiens < 400 > 275 atgctgccgg actggaagag ctccttgatc ctcatggctt acatcatcat cttcctcact 60 ggcctccctg ccaacctcct ggccctgcgg gcctttgtgg ggcggatccg ccagccccag 120 cctgcacctg tgcacatcct cctgctgagc ctgacgctgg ccgacctcct cctgctgctg 180 ctgctgccct tcaagatcat cgaggctgcg tcgaacttcc gctggtacct gcccaaggtc 240 gtctgcgccc tcacgagttt tggcttctac agcagcatct actgcagcac gtggctcctg 300 gcgggcatca gcatcgagcg ctacctggga gtggctttcc ccgtgcagta caagctctcc 360 cgccggcctc tgtatggagt gattgcagct ctggtggcct gggttatgtc ctttggtcac 420 tgcaccatcg tgatcatcgt tcaatacttg aacacgactg agcaggtcag aagtggcaat 480 gaaattacct gctacgagaa cttcaccgat aaccagttgg acgtggtgct gcccgtgcgg 540 ctggagctgt gcctggtgct cttcttcatc cccatggcag tcaccatctt ctgctactgg 600 cgttttgtgt ggatcatgct ctcccagccc cttgtggggg cccagaggcg gcgccgagcc 660 aaggggctgg ctgtggtgac gctgctcaat ttcctggtgt gcttcggacc ttacaacgtg 720 tcccacctgg tggggtatca ccagagaaaa agcccctggt ggcggtcaat agccgtggtg 780 ttcagttcac tcaacgccag tctggacccc ctgctcttct atttctcttc ttcagtggtg 840 cgcagggcat ttggg agagg gctgcaggtg ctgcggaatc agggctcctc cctgttggga 900 cgcagaggca aagacacagc agaggggaca aatgaggaca ggggtgtggg tcaaggagaa 960 gggatgccaa gttcggactt cactacagag tag 993 < 210 > 276 < 211 > 330 < 212 > PRT < 213 > Homo sapiens < 400 > 276 Met Leu Pro Asp Trp Lys Be Ser Leu He Leu Met Wing Tyr He He 1 5 10 15 He Phe Leu Thr Gly Leu Pro Wing Asn Leu Leu Wing Leu Arg Wing Phe 20 25 30 Val Gly Arg He Arg Gln Pro Pro Gln Pro Pro Val His He Leu Leu 40 45 Leu Ser Leu Thr Leu Wing Asp Leu Leu Leu Leu Leu Leu Leu Pro Phe 50 55 60 Lys He He Glu Wing Wing Being Asn Phe Arg Trp Tyr Leu Pro Lys Val 65 70 75 80 Val Cys Ala Leu Thr Ser Phe Gly Phe Tyr Ser Ser He Tyr Cys Ser 85 90 95 Thr Trp Leu Leu Wing Gly He Ser He Glu Arg Tyr Leu Gly Val Wing 100 105 110 Phe Pro Val Gln Tyr Lys Leu Ser Arg Arg Pro Leu Tyr Gly Val He 115 120 125 Ala Ala Leu Val Ala Trp Val Met Ser Phe Gly His Cv5 Thr He Val 130 135 140 rma & £ &g- ^ »ásS ^ S¡j? 3¡? I ^ He He Val Gln Tyr Leu Asn Thr Thr Glu Gln Val Arg Ser Gly Asn 145 150 155 160 Glu He Thr Cys Tyr Glu Asn Phe Thr Asp Asn Gln Leu Asp Val Val 165 170 175 Leu Pro Val Arg Leu Glu Leu Cys Leu Val Leu Phe Phe He Pro Met 180 185 190 Wing Val Thr He Phe Cys Tyr Trp Arg Phe Val Trp He Met Leu Ser 195 200 205 Gln Pro Leu Val Gly Wing Gln Arg Arg Arg Arg Wing Lys Gly Leu Wing 210 215 220 Val Val Thr Leu Leu Asn Phe Leu Val Cys Phe Gly Pro Tyr Asn Val 225 230 235 240 Ser His Leu Val Gly Tyr His Gln Arg Lys Ser Pro Trp Trp Arg Ser 245 250 255 H Ala Val Val Phe Ser Ser Leu Asn Ala Ser Leu Asp Pro Leu Leu 260 265 270 Phe Tyr Phe Ser Ser Val Val Arg Arg Ala Phe Gly Arg Gly Leu 275 280 285 Gln Val Leu Arg Asn Gln Gly Ser Ser Leu Leu Gly Arg Arg Gly Lys ESSIFILfi 'J * ~ ";? 2 &3yrí -" í "~ - __? Í'" * ÍG.Í,? ÍJK > , * ífe * »» **. 290 295 300 Asp Thr Ala Glu Gly Thr Asn Glu Asp Arg Gly Val Gly Gln Gly Glu 305 310 315 320 Gly Met Pro Ser Being Asp Phe Thr Thr Glu 325 330 < 210 > 277 < 211 > 2724 < 212 > DNA < 213 > Homo sapiens < 400 > 277 atggacacct cccggctcgg tgtgctcctg tccttgcctg tgctgctgca gctggcgacc 60 gggggcagct ctcccaggtc tggtgtgttg ctgaggggct gccccacaca ctgtcattgc 120 gagcccgacg gcaggatgtt gctcagggtg gactgctccg acctggggct ctcggagctg 180 ccttccaacc tcagcgtctt cacctcctac ctagacctca gtatgaacaa catcagtcag 240 ctgctcccga atcccctgcc cagtctccgc ttcctggagg agttacgtct tgcgggaaac 300 gctctgacat acattcccaa gggagcattc actggccttt acagtcttaa agttcttatg 360 ctgcagaata atcagctaag acacgtaccc acagaagctc tgcagaattt gcgaagcctt 420 caatccctgc gtctggatgc taaccacatc agctatgtgc ccccaagctg tttcagtggc 480 ctgcattccc tgaggcacct gtggctggat gacaatgcgt taacagaaat ccccgtccag 540 gcttttagaa gtttatcggc attgcaagcc atgaccttgg ccctgaacaa aatacaccac 600 ataccagact atgcctttgg aaacctctcc agcttggtag ttctacatct ccataacaat 660 agaatccact ccctgggaaa gaaatgcttt gatgggctcc acagcctaga gactttagat 720 ataaccttga ttaaattaca actgcaatta tgaattcccc caaccttaaa ggacactctc 780 gaactaggat ttcatagcaa caatatcagg tcgatacctg agaaagcatt tgtaggcaac 840 - ItíÚt? itsIx? MSSL LJI IIHI? .. J 43.5 ttacaataca ccttctctta tttctatgac aatcccatcc aatttgttgg gagatctgct 900 tttcaacatt tacctgaact aagaacactg actctgaatg gtgcctcaca aataactgaa 960 tttcctgatt taactggaac tgcaaacctg gagagtctga ctttaactgg agcacagatc 1020 tcatctcttc ctcaaaccgt ctgcaatcag ttacctaatc tccaagtgct agatctgtct 1080 tacaacctat tagaagattt acccagtttt tcagtctgcc aaaagcttca gaaaattgac 1140 5 ctaagacata atgaaatcta cgaaattaaa gttgacactt tccagcagtt gcttagcctc 1200 cgatcgctga atttggcttg gaacaaaatt gctattattc accccaatgc attttccact 1260 ttgccatccc taataaagct ggacctatcg tccaacctcc tgtcgtcttt tcctataact 1320 gtttaactca gggttacatg cttaaaatta atgccttaca acaggaaatc gagcttgata 1380 actttccaga tcatctgaaa actcaaggtt atagaaatgc cttatgctta ccagtgctgt 1440 0 gcatttggag tgtgtgagaa tgcctataag atttctaatc aatggaataa aggtgacaac 1500 agcagtatgg acgaccttca taagaaagat gctggaatgt ttcaggctca agatgaacgt 1560 gaccttgaag atttcctgct tgactttgag gaagacctga aagcccttca ttcagtgcag 1620 tgttcacctt ccccaggccc cttcaaaccc tgtgaacac c tgcttgatgg ctggctgatc 1680 agaattggag tgtggaccat agcagttctg gcacttactt gtaatgcttt ggtgacttca 1740 acagttttca gatcccctct gtacatttcc cccattaaac tgttaattgg ggtcatcgca 1800 5 gcagtgaaca tgctcacggg agtctccagt gccgtgctgg ctggtgtgga tgcgttcact 1860 tttggcagct ttgcacgaca tggtgcctgg tgggagaatg gggttggttg ccatgtcatt 1920 ggttttttgt ccatttttgc ttcagaatca tctgttttcc tgcttactct ggcagccctg 1980 tctctgtgaa gagcgtgggt atattctgca aaatttgaaa cgaaagctcc attttctagc 2040 ctgaaagtaa tcattttgct ctgtgccctg ctggccttga ccatggccgc agttcccctg 2100 0 ctgggtggca gcaagtatgg cgcctcccct ctctgcctgc ctttgccttt tggggagccc 2160 agcaccatgg gctacatggt cgctctcatc ttgctcaatt ccctttgctt cctcatgatg 2220 accattgcct acaccaagct ctactgcaat ttggacaagg gagacctgga gaatatttgg 2280 tgaaaaaaca gactgctcta cattgccctg ttgctcttca ccaactgcat cctaaactgc 2340 cctgtggctt tcttgtcctt ctcctcttta ataaacctta catttatcag tcctgaagta 2400 attaagttta tccttctggt ggtagtccca cttcctgcat gtctcaatcc ccttctctac 2460 5 atcttgttca atcctcactt taaggaggat ctggtgag cc tgagaaagca aacctacgtc 2o20 * & ^ ^^ s.i¿a¿aiI¿¿Ba tggacaagat caaaacaccc aagcttgatg tcaattaact ctgatgatgt cgaaaaacag 2580 tcctgtgact caactcaagc cttggtaacc tttaccagct ccagcatcac ttatgacctg 2640 cctcccagtt ccgtgccatc accagcttat ccagtgactg agagctgcca tctttcctct gtggcatttg tcccatgtct 2700 CTAA 2724 < 210 > 278 < 211 > 907 < 212 > PRT < 213 > Homo sapiens < 400 > 278 Met Asp Thr Ser Arg Leu Gly Val Leu Leu Ser Leu Pro Val Leu Leu 1 5 10 15 Gln Leu Ala Thr Gly Gly Ser Ser Pro Arg Ser Gly Val Leu Leu Arg 20 25 30 Gly Cys Pro Thr His Cys Hs Cys Glu Pro Asp Gly Arg Met Leu Leu 35 40 45 Arg Val Asp Cys Ser Asp Leu Gly Leu Ser Glu Leu Pro Ser Asn Leu 50 55 60 Ser Val Phe Thr Ser Tyr Leu Asp Leu Ser Met Asn Asn He Ser Gln 65 70 75 80 Leu Leu Pro Asn Pro Leu Pro Ser Leu Arg Phe Leu Glu Glu Leu Arg 85 90 95 Leu Wing Gly Asn Wing Leu Thr Tyr He Pro Lys Gly Wing Phe Thr Gly 100 105 110 Leu Tyr Ser Leu Lys Val Leu Met Leu Gln Asn Asn Gln Leu Arg His 115 120 125 Val Pro Thr Glu Ala Leu Gln Asn Leu Arg Ser Leu Gln Ser Leu Arg 130 135 140 Leu Asp Ala Asn His He Ser Tyr Val Pro Pro Ser Cys Phe Ser Gly 145 150 155 160 Leu His Ser Leu Arg His Leu Trp Leu Asp Asp Asn Ala Leu Thr Glu 165 170 175 He Pro Val Gln Ala Phe Arg Ser Leu Ser Ala Leu Gln Ala Met Thr 180 185 190 Leu Ala Leu Asn Lys He His His He Pro Asp Tyr Ala Phe Gly Asn 195 200 205 Leu Ser Ser Leu Val Val Leu His Leu His Asn Asn Arg He His Ser 210 215 220 Leu Gly Lys Lys Cys Phe Asp Cly Leu His Ser Leu Glu Thr Leu Asp 225 230 235 240 g ^ - ^^^^^^^ g ^^^ itej ^^^^^ j ^.

Leu Asn Tyr Asn Asn Leu Asp Glu Phe Pro Thr Wing He Arg Thr Leu 245 250 255 Being Asn Leu Lys Glu Leu Gly Phe His Being Asn Asn He Arg Being He 260 265 270 Pro Glu Lys Wing Phe Val Gly Asn Pro Ser Leu He Thr He His Phe 275 280 285 Tyr Asp Asn Pro He Gln Phe Val Gly Arg Ser Wing Phe Gln His Leu 290 295 300 Pro Glu Leu Arg Thr Leu Thr Leu Asn Gly Wing Ser Gln He Thr Glu 305 310 315 320 Phe Pro Asp Leu Thr Gly Thr Wing Asn Leu Glu Ser Leu Thr Leu Thr 325 330 335 Gly Ala Gln He Ser Ser Leu Pro Gln Thr Val Cys Asn Gln Leu Pro 340 345 350 Asn Leu Gln Val Leu Asp Leu Ser Tyr Asn Leu Leu Glu Asp Leu Pro 355 360 365 Ser Phe Ser Val Cys Gln Lys Leu Gln Lys He Asp Leu Arg His Asn 370 375 380 Glu He Tyr Glu He Lys Val Asp Thr Phe Gln Gln Leu Leu Ser Leu 385 390 395 400 Arg Ser Leu Asn Leu Wing Trp Asn Lys He Wing He He His Pro Asn 405 410 415 Wing Phe Ser Thr Leu Pro Ser Leu He Lys Leu Asp Leu Ser Ser Asn 420 425 430 Leu Leu Ser Ser Phe Pro He Thr Gly Leu His Gly Leu Thr His Leu 435 440 445 Lys Leu Thr Gly Asn His Wing Leu Gln Ser Leu He Ser Ser Glu Asn 450 455 460 Phe Pro Glu Leu Lys Val He Glu Met Pro Tyr Ala Tyr Gln Cys Cys 465 470 475 480 Wing Phe Gly Val Cys Glu Asn Wing Tyr Lys He Ser Asn Gln Trp Asn 485 490 495 Lys Gly Asp Asn Being Ser Met Asp Asp Leu His Lys Lys Asp Wing Gly 500 505 510 Met Phe Gln Wing Gln Asp Glu Arg Asp Leu Glu Asp Phe Leu Leu Asp 515 520 525 Phe Glu Glu Asp Leu Lys Ala Leu His Ser Val Gln Cys Ser Pro Ser 530 535 540 Pro Gly Pro Phe Lys Pro Cys Glu His Leu Leu Asp Gly Trp Leu He 545 550 555 560 Arg He Gly Val Trp Thr He Ala Val Leu Ala Leu Thr Cys Asn Ala 565 570 575 Leu Val Thr Ser Thr Val Phe Arg Ser Pro Leu Tyr He Ser Pro He 580 585 590 Lys Leu Leu He Gly Val He Ala Wing Val Asn Met Leu Thr Gly Val 595 600 605 Be Ser Wing Val Leu Wing Gly Val Asp Wing Phe Thr Phe Gly Ser Phe 610 615 620 Wing Arg His Gly Wing Trp Trp Glu Asn Gly Val Gly Cys His Val He 625 630 635 640 Gly Phe Leu Ser He Phe Wing Ser Glu Ser Ser Val Phe Leu Leu Thr 645 650 655 Leu Ala Ala Leu Glu Arg Gly Phe Ser Val Lys Tyr Ser Ala Lys Phe 660 665 670 Glu Thr Lys Wing Pro Phe Ser Ser Leu Lys Val He He Leu Leu Cys 675 680 685 Wing Leu Leu Wing Leu Thr Met Wing Wing Val Pro Leu Leu Gl \ Gly Ser - ^^ f ^^^ s ^^^^ M? f ^^ j ^ ^ a ^^ tí ^ m ^ & 690 695. 700 Lys Tyr Gly Wing Pro Pro Leu Cys Leu Pro Leu Pro Phe Gly Glu Pro 705 710 it- 715 720 Being Thr Met Gly Tyr Met Val Wing Leu He Leu Leu Asn Being Leu Cys 725 730 735 Phe Leu Met Met Thr He Ala Tyr Thr Lys Leu Tyr Cys Asn Leu Asp 740 745 750 Lys Gly Asp Leu Glu Asn He Trp Asp Cys Ser Met Lys Lys His He 755 760 765 Ala Leu Leu Leu Phe Thr Asn Cys He Leu Asn Cys Pro Val Ala Phe 770 775 780 Leu Ser Phe Be Ser Leu He Asn Leu Thr Phe He Ser Pro Glu Val 785 790 795 800 He Lys Phe He Leu Leu Val Val Val Pro Leu Pro Ala Cys Leu Asn 805 810 815 Pro Leu Leu Tyr He Leu Phe Asn Pro His Phe Lys Glu Asp Leu Val 820 825 830 Ser Leu Arg Lys Gln Thr Tyr Val Trp Thr Arg Ser His Pro Ser 840 8J5 Leu Met Ser He Asn Ser Asp í Val Glu Lys Gln Ser Cys Asp Ser 850 855 860 Thr Gln Ala Leu Val Thr Phe Thr 865 870 Pro Pro Ser Ser Val Pro Pro Pro Ala Tyr Pro Val Thr Glu Ser Cys 885 890 895 His Leu Ser Ser Val Val Phe Val Pro Cys Leu 900 905 < 210 > 279 < 211 > 32 < 212 > DNA < 213 > Homo sapiens < 400 > 279 catgccaacc ggcccgcgag gctgctgctg gt 32 < 210 > 280 < 211 > 32 < 212 > DNA < 213 > Homo sapiens < 400 > 280 accagcagca gcctcgcggg ccggttggca tg 32

Claims (24)

1. A non-endogenous constitutively active version of an endogenous human orphan G protein (GPCR) coupled receptor comprising the following amino acid residues (carboxy terminus to amino terminus) traversing transmembrane-6 (TM6) and intracellular spira-3 regions (IC3) of the non-endogenous GPCR receptor: term carboxy-P1AA15X-amino terminus, wherein: (1) P1 is an amino acid residue located within the TM6 region of the non-endogenous GPCR receptor, wherein P1 is selected from the group consisting of of, (i) the proline residue of the endogenous orphan GPCR receptor and (ii) a non-endogenous amino acid residue other than proline; (2) AA15 are 15 amino acid residues selected from the group consisting of (a) the endogenous 15 amino acid residues of the orphan GPCR receptor, (b) 15 non-endogenous amino acid residues, and (c) a combination of 15 amino acid residues. amino acid residues, the combination comprising at least one endogenous amino acid residue of the endogenous orphan GPCR receptor and at least one non-endogenous amino acid residue, except that none of the endogenous amino acid residues that is located within the TM6 region of the amino acid GPCR receptor is proline, and (2) X is a non-endogenous amino acid residue located É ^ ilg ^ Sti ^ ii ^ jK ^ t within the IC3 region of the non-endogenous GPCR receptor.

2. The non-endogenous human GPCR receptor according to claim 1, is where P1 is the endogenous proline residue.

3. The non-endogenous human GPCR receptor according to claim 1, wherein P1 is a non-endogenous amino acid residue other than a proline residue.

4. The non-endogenous human GPCR receptor according to claim 1, wherein AA15 is the endogenous 15 amino acid residues of the endogenous GPCR receptor.

The non-endogenous human GPCR receptor according to claim 1, wherein X is selected from the group consisting of the lysine, histidine, arginine and alanine residues, except that when the endogenous amino acid in the X position of said human GPCR receptor endogenous is lysine, X is selected from the group consisting of histidine, arginine and alanine.

6. The non-endogenous human GPCR receptor according to claim 1, wherein X is a lysine residue, except that when the endogenous amino acid at the X position of the endogenous human GPCR receptor is lysine, X is an amino acid other than lysine.

The non-endogenous human GPCR receptor according to claim 4, wherein X is a lysine residue, except that when the endogenous amino acid at the X position of the endogenous human GPCR receptor is lysine, X is an amino acid other than Usin.

The non-endogenous human GPCR receptor according to claim 1, wherein P1 is a proline residue and X is a lysine residue, except that when the endogenous amino acid at the X position of the endogenous human GPCR is lysine, X is an amino acid other than lysine.

9. A host cell comprising the non-endogenous human GPCR receptor of claim 1.

10. The material according to claim 9 wherein the host cell is of mammalian origin.

11. The non-endogenous human GPCR receptor according to claim 1, in a purified and isolated form.

12. A nucleic acid sequence encoding a non-endogenous, constitutively active version of an endogenous orphan human G protein-coupled receptor (GPCR) comprising the following nucleic acid sequence region encoding an amino acid sequence region that it traverses the transmembrane-6 (TM6) and the intracellular turn-3 regions (IC3) of the orphan GPCR receptor: 3, -Pcodon (AA-COdÓnhsXcodón-S1) where: (1) pcodon is a nucleic acid that encodes a region within of the TM6 region of the non-endogenous GPCR receptor, wherein pcodon encodes an amino acid selected from the group consisting of (i) the proline residue of the endogenous GPCR receptor, and (ii) a non-endogenous amino acid residue other than proline; (2) (AA-codon) 15 are 15 codons encoding 15 amino acid residues selected from the group consisting of (a) the endogenous 15 amino acid residues of the endogenous orphan GPCR receptor, (b) 15 non-endogenous amino acid residues and (c) a combination of 15 amino acid residues, the combination comprising at least one endogenous amino acid residue of the endogenous orphan GPCR receptor and at least one non-endogenous amino acid residue, except that none of the 15 endogenous amino acid residues that are placed within the TM6 region of the orphan GPCR receptor is proline; and (3) Xcoon is a nucleic acid encoding a region residue located within the IC3 region of the non-endogenous human GPCR receptor, wherein XCO encodes a non-endogenous amino acid.

13. The nucleic acid sequence according to claim 12, wherein pcodon encodes an endogenous proline residue.

14. The nucleic acid sequence according to claim 12, wherein pcodon encodes a non-endogenous amino acid residue different from a proline residue.

15. The nucleic acid sequence according to claim 12, wherein Xcodon encodes a non-endogenous amino acid selected from the group consisting of lysine, histidine, arginine and alanine, except that when the endogenous amino acid in the X position of said GPCR receptor Endogenous human is lysine, Xcodon. encodes an amino acid selected from the group consisting of histidine, arginine and alanine.

16. The nucleic acid sequence according to claim 13, wherein Xcoon encodes a non-endogenous lysine amino acid, except that when the endogenous amino acid at the X position of said endogenous human GPCR receptor is lysine, codon encodes a selected amino acid. of the group consisting of 5 histidine, arginine and alanine.

17. The nucleic acid sequence according to claim 12, wherein XCOdon is selected from the group consisting of AAA, AAG, GCA, GCG, GCC and GCU.

18. The nucleic acid sequence according to claim 12, wherein XCOdon is selected from the group consisting of AAA and AAG.

19. The nucleic acid sequence according to claim 12, wherein pcodon is selected from the group consisting of CCA, CCC, CCG and CCU, and XCodon is selected from the group 15 which consists of AAA and AAG 20. A vector comprising the nucleic acid sequence of claim 12. 21. A plasmid comprising the nucleic acid sequence of claim 12. 20 22. A host cell comprising acid sequence The nucleic acid sequence of claim 12, in a purified and isolated form. A method for selecting an alteration of an endogenous amino acid residue within the third intracellular turn of a &tg3t ~ &d '«t > a human G protein coupled receptor ("GPCR"), said receptor comprises a region of transmembrane-6 and an intracellular turn region 3, said endogenous amino acid, when altered to a non-endogenous amino acid, constitutively active to the human GPCR receptor, the method comprises the steps of: (a) identifying an endogenous proline residue within the transmembrane region 6 of a GPCR receptor; (b) identifying the amino acid residue 16, endogenous from the proline residue of step (a), in a carboxy terminus to amino terminus; (c) altering the endogenous residue from step (b) to a non-endogenous amino acid residue to create a non-endogenous version of an endogenous human GPCR receptor; and (d) determining whether the non-endogenous human GPCR receptor of step (c) is constitutively active. 25. The method according to claim 24, wherein the amino acid residue that is two residues of the proline residue in the transmembrane region 6, in a carboxy terminus to amino terminus, is tryptophan. 26. A human, non-endogenous, constitutively active GPCR receptor produced through the process of claim 24. 27. A constitutively active, non-endogenous, human GPCR receptor produced through the process of claim 25 28. An algorithmic aspect to create a non-endogenous constitutively active version of an endogenous human G protein-coupled receptor (GPCR), the endogenous GPCR receptor comprising a transmembrane 6 region and an intracellular coil 3 region, the algorithmic aspect comprises the steps of: (a) selecting an endogenous human GPCR receptor comprising a proline residue in the transmembrane-6 region; (b) identifying, counting 16 amino acid residues from the proline residue of step (a), in a carboxy terminus to amino terminus, an endogenous amino acid residue; (c) altering the amino acid residue identified from step (b) to a non-endogenous amino acid residue to create a non-endogenous version of the endogenous human GPCR receptor; and (d) determining whether the non-endogenous version of the endogenous human GPCR receptor of step (c) is constitutively active. 29. The algorithmic aspect according to claim 28, wherein the amino acid residue that is two residues from the proline residue in the transmembrane region 6, in a carboxy terminus to amino terminus, is tryptophan. 30. A constitutively active, non-endogenous human GPCR receptor, produced through the algorithmic aspect of claim 28. 31. A constitutively active non-endogenous human GPCR receptor, produced through the algorithmic aspect of claim 29 32. A method for directly identify a compound faith & amp; SM & amp; > I selected from the group consisting of inverse agonists, agonists and partial agonists for a receptor coupled to the human G protein, constitutively activated non-endogenous, the receptor comprises a region of transmembrane-6 and an intracellular spira-3 region, the method comprises the steps of: (a) selecting an endogenous human GPCR receptor; (b) identifying a proline residue within the transmembrane-6 region of the GPCR receptor of step (a); (c) identifying, in a carboxy terminus to amino terminus, the amino acid residue 16, endogenous from the proline residue of step (b); (d) altering the endogenous amino acid from step (c) to a non-endogenous amino acid; (e) confirming that the non-endogenous GPCR receptor of step (d) is constitutively active; (f) contacting a candidate compound with the constitutively activated, non-endogenous GPCR receptor of step (e); and (g) determining, by measuring the effectiveness of the compound in the contacted receptor, whether the compound is an inverse agonist, agonist or partial agonist of said receptor. 33. The method according to claim 32, wherein the non-endogenous amino acid of step (d) is lysine. A compound directly identified by the method of claim 32. The method according to claim 32, wherein the directly identified compound is an inverse agonist. 36. The method according to claim 32, wherein the directly identified compound is an agonist. 37. The method according to claim 32, wherein the compound is directly identified in a partial agonist. 38. A composition comprising the inverse agonist of claim 35. 39. A composition comprising an agonist of claim 36. 40. A composition comprising the partial agonist of claim 37. 41. A method for directly identifying an agonist. Inverse to a non-endogenously activated, constitutively activated, human G protein receptor ("GPCR"), the GPCR receptor comprising a transmembrane-6 region and an intracellular coil-3 region, comprising the steps of: ) select the endogenous human GPCR receptor; (b) identifying a proline residue with the transmembrane-6 region of the GPCR receptor of step (a); (c) identifying, in a carboxy terminus to amino terminus, the amino acid residue 16, endogenous, from the proline residue of step (b), (d) altering the endogenous amino acid from step (c) to a residue of non-endogenous lysine, (e) confirming that the non-endogenous GPCR receptor of step (d) t ^ Mia is constitutively active; *** (f) contacting a candidate compound with the constitutively activated, non-endogenous GPCR receptor of step (e); and (g) determining, by measuring the effectiveness of the compound in the contacted receptor, whether the compound is an inverse agonist, of said receptor. 42. An inverse agonist directly identified through the method of claim 37. 43. A composition comprising an inverse agonist according to claim 38. SUMMARY Described herein are non-endogenous, constitutively activated versions of endogenous human G protein coupled receptors, comprising (a) the following amino acid sequence region (C-terminus targeting to N-terminus) and / or (b) the region of nucleic acid sequence following (3 'to 5' orientation) traversing the transmembrane-6 (TM6) and the intracellular turn-3 regions (IC3) of the GPCR receptor; (a) P1AA15X and / or (b) pcodon (AA-codon)? 5Xcoon, respectively. In a highly preferred embodiment, P1 and pcodop are endogenous proline and an endogenous nucleic acid coding region encoding proline, respectively, located within TM6 of the non-endogenous GPCR receptor; AA15 and (AA-codon) 15 are 15 endogenous amino acid residues and 15 codons encoding endogenous amino acid residues, respectively; and X and Xcodon are non-endogenous lysine and a non-endogenous nucleic acid coding region encoding lysine, respectively, located within IC3 of the non-endogenous GPCR receptor. Since it is highly preferred that human, non-endogenous GPCRs, which they incorporate into these notations, be incorporated into mammalian cells and used for the classification of candidate compounds, the non-endogenous human GPCR receptor incorporating the mutation does not need to be purified and isolated per se (that is, these are incorporated within the cell membrane of a mammalian cell), although said Non-endogenous, isolated human GPCR receptors are within the scope of this disclosure.