Apparatus, Compositions, and Methods for Assessment of Chronic Obstructive Pulmonary Disease Progression Among Rapid and Slow Decline Conditions

Abstract

Methods are disclosed for generating and isolating an informative content repository of respiratory related biomarkers to accurately determine whether an individual has normal or abnormal pulmonary function. Specifically, methods are directed to determination of whether individuals have chronic obstructive pulmonary disease, and if so, whether the affected individuals experience rapid long decline or slow lung decline as a result of COPD. Also disclosed is an informative content repository of chronic obstructive pulmonary disease biomarkers, which when linked with other informative content provides a powerful tool for diagnosis, study, therapeutic discovery and development, condition management, health maintenance, and linking chronic obstructive pulmonary disease through pattern of life style, environmental exposure, and genetic susceptibility and inheritance. Disclosed herein is a chronic obstructive pulmonary disease biomarker informative content repository comprising at least one COPD biomarker, apparatus and methods to diagnose, assess, address, and ameliorate related conditions.

Description

RELATED APPLICATIONS

[0001] This application is a continuation of U.S. application Ser. No. 11/770,074 filed on Jun. 28, 2007 now U.S. Pat. No. 9,885,085, which claims the Paris Convention Priority and fully incorporates by reference U.S. Provisional Application No. 60/817,316 entitled "Apparatus, Compositions, and Methods for Assessment of Chronic Obstructive Pulmonary Disease Progression Among Rapid and Slow Decline Conditions" filed on 28 Jun. 2006, each of which applications is hereby incorporated by reference as if fully disclosed herein.

INCORPORATION OF SEQUENCE LISTING

[0002] This application contains a sequence listing submitted electronically via EFS-web, which serves as both the paper copy and the computer readable form (CRF) and consists of a file entitled "001881-8004US02_seqlist.txt", which was created on Apr. 30, 2018, which is 569,344 bytes in size, and which is herein incorporated by reference in its entirety.

GOVERNMENTAL INSPECTION

[0003] The present disclosure is subject to a right of inspection by the Department of Energy.

BACKGROUND

[0004] The present disclosure relates to the study of respiratory functions and conditions, specifically chronic obstructive pulmonary disease, biomarkers related to respiratory functions and conditions, specifically biomarkers related to chronic obstructive pulmonary disease, and the creation of an informative content repository of biomarkers related to chronic obstructive pulmonary disease (COPD).

SUMMARY

[0005] Methods are disclosed for generating and isolating biomarkers related to pulmonary functions and conditions, specifically biomarkers related to chronic obstructive pulmonary disease, and an informative content repository of respiratory related biomarkers to accurately determine whether an individual has normal or abnormal pulmonary function. Specifically, methods are directed to determination of whether individuals have chronic obstructive pulmonary disease, and if so, whether the affected individuals experience rapid lung decline or slow lung decline as a result of COPD. Also disclosed is an informative content repository of chronic obstructive pulmonary disease biomarkers, which when linked with other informative content provides a powerful tool for diagnosis, study, therapeutic discovery and development, condition management, health maintenance, and linking chronic obstructive pulmonary disease through pattern of life style, environmental exposure, and genetic susceptibility and inheritance. Disclosed herein are at least one biomarker related to COPD and a chronic obstructive pulmonary disease biomarker informative content repository comprising at least one COPD biomarker, apparatus and methods to diagnose, assess, address, and ameliorate related conditions.

[0006] According to a feature of the present disclosure, a respiratory condition informative content repository is disclosed comprising at least one respiratory condition-related biomarker.

[0007] According to a feature of the present disclosure, a process is disclosed comprising identification of a respiratory related condition to study, use of an informative content repository containing at least one first set of data useful in the selection of at least one individual having or predisposed to a respiratory related condition, identification of at least one biomarker from samples taken from the at least one individual; and populating a biomarker informative content repository with the at least one biomarker.

[0008] According to a feature of the present disclosure, a process is disclosed comprising, obtaining a sample from a patient, using a chronic obstructive pulmonary disease (COPD) biomarker diagnostic tool in conjunction the sample to obtain data, and using the data to decide whether the patient is a rapid decliner or a slow decliner.

[0009] According to a feature of the present disclosure, an informative content repository is disclosed comprising at least the amino acid sequences of SEQ ID NO:1 to SEQ ID NO:266.

[0010] According to a feature of the present disclosure, an informative content repository of proteins is disclosed comprising at least a set of data comprising the proteins of Table 2.

DRAWINGS

[0011] The above-mentioned features and objects of the present disclosure will become more apparent with reference to the following description taken in conjunction with the accompanying drawings wherein like reference numerals denote like elements and in which:

[0012] FIG. 1 is a graph illustrating the relative progression of the loss of pulmonary function between non-smokers, chronic pulmonary obstructive disorder (COPD) slow decliners, and COPD fast decliners;

[0013] FIG. 2A is a block diagram of an embodiment of an experimental design for determination of biomarkers contributing to COPD and biomarkers distinguishing between COPD rapid and slow decliners;

[0014] FIG. 2B is a graph illustrating how rapid decliner and slow decliner subjects are selected from a group of known COPD patients;

[0015] FIG. 3 is a block diagram of an embodiment of an experimental design for identification of the biomarkers of COPD using .mu.LC-MS/MS analysis and .mu.LC-FTICR-MS analysis to identify and correlate candidate proteins;

[0016] FIG. 4 is a block diagram of an embodiment of an experimental design illustrating a method for determining biomarkers from .mu.LC-MS/MS analysis; and

[0017] FIGS. 5A and 5B are graphs of an embodiment of an experimental design illustrating statistical analysis of identified proteins.

DETAILED DESCRIPTION

[0018] In the following detailed description of embodiments of the invention, reference is made to the accompanying drawings in which like references indicate similar elements, and in which is shown by way of illustration specific embodiments in which the invention may be practiced. These embodiments are described in sufficient detail to enable those skilled in the art to practice the invention, and it is to be understood that other embodiments may be utilized and that logical, mechanical, biological, electrical, functional, and other changes may be made without departing from the scope of the present invention. The following detailed description is, therefore, not to be taken in a limiting sense, and the scope of the present invention is defined only by the appended claims. As used in the present disclosure, the term "or" shall be understood to be defined as a logical disjunction and shall not indicate an exclusive disjunction unless expressly indicated as such or notated as "xor."

[0019] As used in this application, the term "biomarker" means any characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention, including biological measurements that provide information regarding progression, pharmacology, or safety of conditions that can be used as a basis for decision-making in drug development and therapeutic administration decisions.

[0020] As used in this application, the term "function" and "condition" means normal physiological and pathophysiological states, including diseases and disorders. As used herein, the terms "function" and "condition" include normal physiological as well as acute and chronic pathophysiological states, such as diseases and disorders.

[0021] As used in this application, the term "disease" or "disorder" means any condition in humans or animals deemed to be abnormal as compared to the majority of humans and animals respectively.

[0022] As used in this application, the term "informative content repository" means a collection of at least one set of respiratory condition related biomarker data, optionally indexed together with other ancillary data, and stored in a suitable data structure. Examples of suitable data structures include databases, gene chips, protein chips, and filing cabinets.

[0023] As used in this application, the term "decline" refers to the rate in which a condition or conditions worsens over time, and the term "decliner" refers to an individual affected with a respiratory condition in whom the condition worsens over time.

[0024] As used in this application, the term "related" refers to causing or being associated with a function or condition.

[0025] As used in this application, the terms "COPD related biomarker(s)" or "COPD biomarker(s)" refer to one or more biomarkers that are associated with COPD.

[0026] Mapping condition indicators by use of integrated phenotypic and genotypic data from humans is a longstanding need, which only serves to underscore or highlight prior attempts to effectively do so with significant informative condition end-points.

[0027] Harnessing the power of the computer to manage large volumes of data in conjunction with the volume of information contained in the human genome, proteome, metabalome, regulome, functome, phenome, and textome proved critical for projects such as the human genome project to high-throughput devices such as DNA and protein microarrays. Naturally, the scientific community recognized the brute force power of computers for management of otherwise impossibly large volumes of information. Since then numerous bioinformatic and computational biology applications now exist. However, in most cases, the data sets are created as byproducts of experimental protocols. Other databases grew as researchers obtained experimental data and populated the databases with their findings for later reference.

[0028] Functions and conditions of the respiratory system, including lung conditions may be suitable targets for study using the instant techniques. Despite advances in practice, lung conditions continue to afflict millions of people worldwide. Many lung conditions such as emphysema, asthma, and COPD develop, at least in part, due to genetic predispositions or are directly linked with life-style choices and environmental exposure. Still others are caused by infections, such as tuberculosis.

[0029] Nonmalignant respiratory conditions are typically characterized as obstructive, restrictive, infectious, or vascular in nature. Obstructive respiratory conditions are those that impede the rate that air can flow into and out of the respiratory system, including the lungs. They include emphysema, bronchitis, asthma, and COPD. Similarly, restrictive lung conditions are characterized by a reduction of the functional volume of the lungs. Examples of restrictive lung conditions are sarcoidosis, pleural effusion, fibrosis, and alveolar effusion. Infectious lung conditions include tuberculosis, pneumonia, upper respiratory tract infections, and lower respiratory tract infections. Vascular lung conditions include pulmonary edema, pulmonary embolism, and pulmonary hypertension. Lung cancer alone causes of 3 million deaths each year.

[0030] Of the respiratory conditions, COPD is a condition especially suited to the instant techniques. COPD is a condition of the respiratory tract characterized by permanent airway obstruction. It constitutes an abnormal inflammatory response triggered by foreign particles and gasses. COPD victims experience a chronic inflammation of the bronchi, which leads to airway obstruction. Other causes of COPD may include .alpha.1-antitrypsin deficiency, byssinosis, genetic susceptibility, and idiopathic disease.

[0031] Researchers currently believe that smoking is that main risk factor associated with the development of COPD. Indeed, nearly one-fifth of all smokers will develop the condition. Nevertheless, other risk factors exist such as the prolonged breathing of dust, for example in coal-mines. Women comprise the majority of non-smoking victims. Greater susceptibility in women appears to be related to decreased estrogen levels. Additionally, it is estimated that up to 15% to 20% of all COPD cases are non-smoking related, thus highlighting the heterogeneous nature and genetic susceptibility of COPD.

[0032] COPD is a progressive condition that worsens over time and with prolonged contact to smoke or other irritants. Spirometry changes, as illustrated in FIG. 1, and decreased diffusion capacity are commonly seen prior to diagnosis of COPD. As COPD progresses, patients experience shortness of breath, coughs, and recurrent respiratory infections. Progression of COPD is marked by increased severity and duration of symptoms, until, during advanced stages, the patient experiences constant wheezing and shortness of breath, with a severe cough even while at rest. COPD advances either rapidly or slowly; rapid decliners, as shown in FIG. 1, experience a more pronounced deterioration in lung capacity compared to slow decliners.

[0033] Currently, doctors diagnose COPD by observing a patient's symptoms. Doctors evaluate life-style choices, such as smoking and occupation, perform physical examinations on patients, and conduct spirometry tests to measure patient's airflow. Generally and turning again to FIG. 1, FEV.sub.1, to FVC ratio is decreased in a COPD patient. Often, the COPD patient cannot expire 80% of their vital capacity in one second, which is a measurement of normal airflow. Moreover, doctors may observe a residual volume or hyperinflation of lung capacity in COPD patients. Despite these indicia, no existing molecular factors or definitive tests currently exists to positively identify patients with COPD, nor are there existing molecular factors or definitive tests that can differentiate between affected patients that may experience rapid lung decline or slow lung decline as a result of COPD.

[0034] To that end, the present disclosure presents a novel way to discover or isolate respiratory system related biomarkers, specifically COPD related biomarkers. Once biomarkers are identified for a condition, diagnostic tools, for example genomic or protein chips, may be manufactured and used to positively determine whether a patient has developed the condition, and how a patient's condition may progress (i.e., rapid lung decline vs. slow lung decline). Moreover, isolating the biomarkers informs researchers as to the causative factors and pathways that eventually lead to COPD and how COPD progresses. Better understanding of the causes and pathways of COPD allow researchers to focus on discovering better treatments for COPD, including targeted therapeutics, combination of diagnostics and therapeutics, and holistic type treatments.

[0035] The present inventors have discovered embodiments of the present disclosure that contemplate COPD related biomarkers and repositories of biomarker content useful for diagnoses, treatment, research, and other uses suitable to such an informative content repository. Methods for the generation and use of informative content repositories are naturally contemplated as well. Specifically, the present disclosure relates to the development and use of COPD related biomarkers or an informative content repository of COPD biomarkers.

[0036] The COPD related biomarkers and the informative content repository disclosed in the present disclosure may be used for diagnosis or determination of predisposition of conditions in humans, plants, and animals or for the treatment of the condition. For example, the information contained in an informative content repository may be used to design personalized treatments. The informative content repository is also useful for basic research activities, health care decision-making, for forensic applications, or for genetic counseling.

[0037] The informative content repository contains at least one set of biomarkers. Biomarker informative content may include molecular factors comprising one or more sets of genes, proteins, or metabolites. In embodiments, the informative content is easily accessible, sortable, and indexed. Additionally, the informative content repository may be linked to other informative content repositories, which increases the correlative power of the informative content sets comprising the informative content repository.

[0038] In an embodiment, the data structure of the informative content repository is a computerized database, for example a MySQL or Oracle database. Informative content is easily accessible using MySQL or Oracle tables and may be manipulated in ways common to a person of ordinary skill in the art. Using computer databases as the data structure for the informative content repository is beneficial because it provides for easy searching, organization, and correlation to data in other informative content repositories.

[0039] Among the uses of COPD related biomarkers and the informative content repository are as diagnostic tools. An informative content repository with at least one respiratory related biomarker or at least one set of respiratory related biomarker informative content, for example, is useful in the diagnosis of respiratory related conditions. It is also useful for diagnosis of such conditions or predisposition to such conditions. As previously discussed, COPD diagnosis is accomplished by assessing symptoms because there does not exist definitive tests (blood-based or molecular-based) to diagnose COPD. Thus, COPD related biomarkers or an informative content repository of biomarkers that includes COPD biomarker informative content could be potentially used to positively diagnose whether an individual is affected with COPD and whether a COPD patient is a rapid decliner or a slow decliner. For example, for sets of protein biomarkers, protein chips may be used to screen a patient's blood (serum or plasma) for the presence of, or absence of, a pattern of proteins indicative of COPD or COPD progression.

[0040] Similarly, COPD related biomarkers or an informative content repository of respiratory related biomarkers are useful tools for prediction of predispositions to respiratory related conditions. Genes, proteins, metabolites, and other molecular or non-molecular indicia may give healthcare providers and researchers clues as to individuals or populations of individuals susceptible to specific respiratory related conditions. For example, in a subject with susceptibility to COPD, a healthcare provider (including pharmacists) could screen blood samples of each smoking subject using a diagnostic (i.e., genomic or proteomic) chip. Healthcare providers could then use the positive informative content as additional content in individualized healthcare regimens for their subjects.

[0041] COPD related biomarkers or an informative content repository of respiratory related biomarkers are also useful in the development of treatments for the conditions predicted by the biomarkers in the informative content repository. Using such an informative content repository, researchers can access sets of data useful in development of compounds for treatment of respiratory related conditions. For example, with COPD, COPD related biomarkers and informative content obtained from the informative content repository, such as proteins, genes, or metabolites can be used to target compounds against the specific proteins, genes, or metabolites. Compounds may also be used to induce or artificially introduce proteins, genes, or metabolites that characteristically are absent in rapid decline conditions. Consequently, the use of compound combinations based on clues provided by respiratory related biomarkers for a respiratory related condition gives researchers and healthcare providers the power to design optimized and personalized regimens of compounds targeted specifically towards maintaining or modulating the condition.

[0042] In addition to traditionally administered compounds, COPD related biomarkers or an informative content repository of related biomarkers are useful tools for creating or administering therapies. For example, contemplated in the present disclosure is use of an informative content repository of respiratory related biomarkers useful for the administration or development of inhaled substances including drug therapies.

[0043] An informative content repository of respiratory related biomarkers is also useful in developing more individualized or personalized drug treatments for patients. At doctor visits, patients may donate a sample to the doctor, which may then be analyzed and compared against informative content in the respiratory related informative content repository. Using the correlation between the informative content in the informative content repository and the patient's personal genetic, proteomic, and metabonomic make-up, the doctor can prescribe optimal drug regimens for each individual patient.

[0044] Naturally, the research applications of such COPD related biomarkers and informative content repositories are broader than simply for use in personalized medical applications. Researchers may also use the informative content repository of respiratory related biomarkers in the pursuit and development of compounds to treat respiratory related conditions in humans and animals. As previously discussed, COPD related biomarkers and biomarker informative content in informative content repositories gives researchers clues as to potential targets for newly developed compounds.

[0045] Moreover, the absence of healthy biomarkers in a condition may give healthcare providers clues about ways to induce resurgence of healthy proteins, genes, or metabolites that will restore normal function or eradicate a respiratory related condition. Similarly, information regarding healthy biomarkers gives healthcare providers health maintenance type tools. Healthcare providers may use these type of tools to help maintain and improve otherwise healthy states and lifestyles, in addition to helping patients prevent pathophysiological conditions. Indeed, the ability of healthcare providers to positively assert the presence of a healthy condition or an abnormal condition is a tool in the medical field that has utility in mapping lifestyles, habits, and genes that promote good health or healing.

[0046] Nevertheless, COPD related biomarkers or an informative content repository of respiratory related biomarkers are not only useful for research and development of new diagnostics, drugs, or medical devices. The COPD related biomarkers and informative content repository may also be used for more general research purposes. Using subject-specific informative content in an informative content repository, researchers can target individuals who may be susceptible to a particular condition for long-term studies before the condition develops to monitor physiological, phenotypic, and genetic changes in the subject. Similarly, COPD related biomarkers or an informative content repository gives researchers clues as to where they can find potential subjects for studies already expressing a respiratory related condition. Likewise, an informative content repository gives researchers another tool to study pathways, development, and expression of respiratory related conditions over time.

[0047] An informative content repository of respiratory related biomarkers may also be used in various decision-making processes. As previously alluded to, healthcare providers may use the correlation between informative content in the informative content repository and the biomarkers expressed in an individual to advise the patient regarding specific treatment decisions and lifestyle choices. Insurance companies, health maintenance organizations, pharmacies, pharmacy benefit managers, hospitals, and other healthcare related organizations may use such informative content to reduce costs by using information learned from correlation between patients and informative content repositories. For example, referencing a particular patient's informative content may reduce the need for expensive testing regimens by correlating with each patient profile with predispositions and other indicia useful in streamlining medical services. Moreover, informative content may be used to pre-approve patients for available treatments, visits to specialists with merely a phone call to a service center that correlates a set of symptoms, life-style choices, and predispositions with the informative content in an informative content repository.

[0048] Similarly, optimal prescriptions may be prescribed using COPD related biomarkers or an informative content repository of respiratory related biomarkers that will reduce costs for insurance companies, hospitals, pharmacy benefit managers, health management organizations, and other healthcare related organizations by accurate diagnoses, prescribing, dispensing, or administering optimal drugs for increased efficacy or for reducing the number of adverse reactions, for example. Finally, the correlation of patient information and information contained in an informative content repository of respiratory related biomarkers may be used for automated treatment decisions or insurance reimbursement decisions for both private insurance companies and for federal government insurance programs such as Medicare and Medicaid.

[0049] Furthermore, COPD related biomarkers or an informative content repository of respiratory related biomarkers may be used as a method of tracking family data over generations. In embodiments, conditions may be studied using genealogical correlations for each subject or tracked through generations to study condition evolution and inheritance in humans, plants, and animals. The informative content repository is also useful for tracking phenotypic data. Additionally, COPD related biomarkers or the informative content repository may be used for genetic analysis and counseling. The respiratory related data in an informative content repository is an invaluable tool for genetic counselors that allows them to streamline gathering, studying, and disseminating genetic information to clients. Clients could learn the consequences and risk factors for themselves and their children, now and in the foreseeable future.

[0050] According to an embodiment, an informative content repository contains data relevant to lung treatment and more broadly to the use of the respiratory system for treatment regimens, specifically inhalation-type conditions, and inhaled administration of therapeutic ingredients. The COPD related biomarkers and an informative content repository COPD related biomarkers and a set of biomarkers contained in the informative content repository would be specifically relevant to upper and lower respiratory system function and conditions. In an embodiment, the informative content repository contains biomarkers relevant to the progression of COPD. Specifically, the biomarkers would indicate differences between the progression of COPD rapid decline conditions and slow decline conditions. In another embodiment, the biomarker informative content would identify individuals with a greater or lesser degree of pulmonary function, thereby indicating or selecting individuals as candidates for inhaled drug therapy.

Example 1

[0051] An embodiment of the present disclosure describes the informative content repository of COPD markers. Clinical histories, pulmonary function tests, and related data were obtained from 100 subjects who had never smoked and unaffected with COPD, 100 smokers who were disease free, and 200 smokers with COPD, as illustrated in FIG. 2A. The COPD subjects were divided into quintiles depending on the decline rate, as shown in FIG. 2B. Subjects in the first quintile and fifth quintile representing the slowest decliners and the most rapid decliners were selected for the purposes of determining a set of biomarkers differentiating between slow and fast decliners. Plasma samples were taken from subjects and a subset of these samples were analyzed as a source of COPD biomarkers. The COPD informative content repository in an embodiment is designed to be a set of peptides or proteins. Approximately forty smokers with COPD were selected for the study herein disclosed.

[0052] The twelve top most abundant plasma proteins were depleted using GenWay Seppro 12 spin-columns (GenWay Biotech, Inc., San Diego, Calif., now ProteomeLab.TM. IgY-12, Beckman Coulter, Inc.). The removal of abundant proteins was monitored by SDS-PAGE.

[0053] Protein depletion has been used for some years to remove most of the albumin or IgG from biofluids such as plasma and serum prior to analysis, but it is clear that this alone is insufficient to enable progress to be made in biomarker discovery. The presence of highly abundant proteins significantly complicates the discovery process by masking the presence and limiting the detection of low abundance species. ProteomeLab IgY partitioning addresses this issue by reversibly capturing 12 of the more abundant proteins from human biofluids such as plasma and serum, yielding an enriched pool of low abundance proteins for further study. The captured proteins can also be easily recovered for investigation if required.

[0054] As shown in FIG. 3, after the abundant serum proteins were removed from the samples, the first series of mass spectrometry is .mu.LC-MS/MS mass spectrometry in operation 300. .mu.LC-MS-MS mass spectrometry was used to identify peptide fragments from trypsin-digested proteins. Proteins, after being run through the IgY-12 columns in operation 302 were trypsin digested in operation 304.

[0055] Trichloroacetic acid-precipitated protein from the depleted serum samples was denatured by addition of urea to 8 M, thiourea to 2 M, DTT to 5 mM, and heating to 60.degree. C. for 30 minutes. The sample was then diluted 4-fold with 100 mM ammonium bicarbonate and CaCl2 was added to a concentration 1 mM. Methylated, sequencing-grade tryp sin (Promega, Madison, Wis.) was added at a substrate-to-enzyme ratio of 50:1 (mass:mass) and incubated at 37.degree. C. for 15 hours. Sample cleanup was achieved using a 1-mL SPE C18 column (Supelco, Bellefonte, Pa.). The peptides were eluted from each column with 1 mL of methanol and concentrated via SpeedVac. The samples were reconstituted to 10 .mu.g/.mu.L with 25 mM ammonium bicarbonate and frozen at -20.degree. C. until analyzed.

[0056] Selected plasma samples (corresponding to experimental sample numbers: 54110, 54128, 54207, 54112, 54154, 54118) were depleted of abundant proteins, trypsin digested as detailed previously, and pooled. Strong cation exchange chromatography was performed on the pooled peptide sample utilizing a Synchropak S 300, 100.times.2 mm chromatographic column (Thermo Hypersil-Keystone, Bellefonte, Pa.). A 1 h gradient was utilized at a flow rate of 200 .mu.l/min with fractions collected every 2 minutes. The beginning solvent system was 25% acetonitrile, 75% water containing 10 mM HCOONH.sub.4, pH 3.0, adjusted with formic acid, and the ending solvent system was 25% acetonitrile, 75% water containing 200 mM HCOONH.sub.4, pH 8.0. The peptide mixture was resuspended in 25% acetonitrile, 75% water containing 10 mM HCOONH.sub.4, pH 3.0 with formic acid prior to injection. Fractions were lyophilized and stored at -20.degree. C. until mass spectrometer analysis.

[0057] The fractionated peptide samples were analyzed by tandem mass spectrometry to identify the peptides for a mass and time tag database in operation 306. Peptide samples were analyzed by reversed phase microcapillary LC coupled directly with electrospray tandem mass spectrometers (Thermo Finnigan, models LCQ Duo and DecaXP). Chromatography was performed on a 60-cm, 150 .mu.m i.d..times.360 .mu.m o.d capillary column (Polymicro Technologies, Phoenix, Ariz.) packed with Jupiter C18 5-um-diameter particles (Phenomenex, Torrance, Calif.). A solvent gradient was used to elute the peptides using 0.1% formic acid in water (Solvent A) and 0.1% formic acid in acetonitrile (Solvent B). The gradient was linear from 0 to 5% solvent B in 20 minutes, followed by 5 to 70% solvent B in 80 minutes, and then 70-85% solvent B in 45 minutes. Solvent flow rate was 1.8 .mu.l/min.

[0058] The capillary LC system was coupled to a LCQ ion trap mass spectrometer (Thermo Finnigan, San Jose, Calif.). The temperature of heated capillary and electrospray voltage was 200.degree. C. and 3.0 kV, respectively. Samples were analyzed using the data-dependent MS/MS mode over the m/z range of 300-2000. The three most abundant ions detected in each MS scan were selected for collision-induced dissociation.

[0059] Peptide sequences (see operation 309 in FIG. 4) were obtained by analysis of MS/MS spectra using the SEQUEST algorithm against the human.fasta from the National Center for Biotechnology Information (RefSeq release 10, March, 2005) in operation 308 of FIG. 3. Peptide identifications were accepted using a conservative criteria set developed by Yates and coworkers (Link et al, 1999; Washburn et al, 2001) in operation 316. Briefly, all accepted SEQUEST results had a delta Cn of 0.1 or greater. Peptides with a +1 charge state were accepted if they were fully tryptic and had a cross correlation (Xcorr) of at least 1.9. Peptides with a +2 charge state were accepted if they were fully tryptic or partially tryptic and had an Xcorr of at least 2.2. Peptides with +2 or +3 charge states with an Xcorr of at least 3.0 or 3.75, respectively, were accepted regardless of their tryptic state.

[0060] The peptide identifications and elution times from analysis of the pooled samples were used to establish the mass and time tag database and combined with identifications of plasma protein peptides from previous multidimensional analyses done previously (Qian et al, 2005) in operation 318. The raw LC-MS/MS data from the pooled sample described above and from the previous multidimensional analysis were reanalyzed to populate the PMT database that was subsequently used for generating the AMT tag results. The PMT database was derived using a PMT quality score of 1.0 (requires a minimum cross correlation score of 2) and a discriminant score of 0.5 (Stritmatter et al, 2005).

[0061] Turning still to FIG. 3 and according to embodiments, the second round of mass spectrometry was done using microcapillary liquid chromatography Fourier transform ion cyclotron resonance mass spectrometry (LC-FTICR-MS) in operation 310 after sample preparation in operation 312. A modified and enhanced Bruker Daltonics 9.4 tesla FTICR mass spectrometer was employed for the high-throughput proteomics as described by Belov et al (2004). Briefly, the FTICR mass spectrometer was combined with the capillary liquid chromatography system and modified for concurrent internal mass calibration and auto-sampling in operation 314. Tryptic peptides were resuspended in mobile phase A (0.1% TFA) and analyzed using reversed phase capillary LC coupled to an electrospray ionization interface with a FTICR mass spectrometer as described by Smith et al.

[0062] Analysis of the LC-FTICR experiments was performed using in-house software tools (Kiebel et al. 2006) to identify MS features, deisotope, normalize elution times, and match features to peptides. These tools are incorporated into the Proteomics Research Information Storage and Management system (PRISM). The result yielded a set of peptides.

[0063] A discriminant program was used to determine peptide confidence probabilities. The results of an exemplary embodiment are shown in FIGS. 5A and 5B. The discriminant score takes advantage of elution time information and tryptic cleavage information, which enhances peptide confidence. Protein identifications from the list of peptides (see operation 318 in FIG. 4) were accomplished by using the ProteinProphet program and only peptides having a discriminant score greater than 0.5 were considered. The result was a set of proteins in operation 320.

[0064] Abundances of the individual peptides were computed by summing the intensity of the ions from a single scan or multiple scans that matched each peptide. Peptides from each protein that were in the top 66% in peak abundance for that protein were averaged to compute protein abundance. In general the integrated, averaged peptide intensities correlate with the relative protein mass.

[0065] Missing values were replaced using approximately one-half the minimum detectable peak (0.004). Data was preprocessed using a log.sub.10 transformation and quantile normalization to make the distribution of ion currents for each mass spectrometry run in the experiment the same. Normalized technical replicates were averaged for each subject. For each of the over 525 proteins identified, a separate linear model accounting for phenotype and gender were used to assess the ion current values. A large-scale simultaneous testing approach was then used for the statistical analysis of the normalized data.

[0066] Once the proteins were identified between the sets of subjects with rapid declining pulmonary function versus slow declining pulmonary function, a statistical analysis was used to determine the relevant biomarkers. The statistical analysis compared the biomarkers of rapid decline condition subjects against the biomarkers of slow decline condition subjects to determine proteins either present or absent in rapid decline conditions versus slow decline conditions. Several statistical methods were used to determine the absence or presence of proteins in the rapid decline condition, including QC, filtering the data, transformation of the data, and normalization of the data, as would be common to a person of ordinary skill in the art.

[0067] As demonstrated in the current study of COPD biomarkers, 267 peptides leading to 78 proteins distinguished slow decline conditions from rapid decline conditions. Table 1 lists the proteins determined to distinguish slow decline conditions from rapid decline conditions:

TABLE-US-00001 TABLE 1 Number of Unique Present in SEQ. ID. Peptides/ PLS analysis Reference NO. Protein Description Protein of Proteins gi|4501987|ref|NP_001124.1| 267 afamin precursor; alpha-albumin 1 [Homo sapiens] gi|4502027|ref|NP_000468.1| 268 albumin precursor; PRO0883 protein 8 [Homo sapiens] gi|21071030|ref|NP_570602.2| 269 alpha 1B-glycoprotein [Homo 6 sapiens] gi|4501843|ref|NP_001076.1| 270 alpha-1-antichymotrypsin, precursor; 2 alpha-1-antichymotrypsin; antichymotrypsin [Homo sapiens] gi|4557225|ref|NP_000005.1| 271 alpha-2-macroglobulin precursor 6 [Homo sapiens] gi|11386143|ref|NP_000925.1| 272 alpha-2-plasmin inhibitor; alpha-2- 7 antiplasmin [Homo sapiens] gi|4557287|ref|NP_000020.1| 273 angiotensinogen precursor; 1 angiotensin II precursor; pre- angiotensinogen; angiotensin I [Homo sapiens] gi|4557321|ref|NP000030.1| 274 apolipoprotein A-I precursor [Homo 2 sapiens] gi|4502149|ref|NP001634.1| 275 apolipoprotein A-II precursor 2 [Homo sapiens] gi|4502151|ref|NP000473.1| 276 apolipoprotein A-IV precursor 7 [Homo sapiens] gi|4502153|ref|NP_000375.1| 277 apolipoprotein B precursor; apoB- 25 100; apoB-48 [Homo sapiens] gi|4502157|ref|NP_001636.1| 278 apolipoprotein C-I precursor [Homo 1 sapiens] gi|4557325|ref|NP_000032.1| 279 apolipoprotein E precursor; 1 apolipoprotein E3 [Homo sapiens] gi|4557327|ref|NP_000033.1| 280 beta-2-glycoprotein I precursor 1 [Homo sapiens] gi|4557373|ref|NP_000051.1| 281 biotinidase precursor [Homo sapiens] 1 gi|4502517|ref|NP_001729.1| 282 carbonic anhydrase I; carbonic 1 dehydratase [Homo sapiens] gi|4503011|ref|NP_001299.1| 283 carboxypeptidase N, polypeptide 1, 2 50 kD precursor [Homo sapiens] gi|4557485|ref|NP_000087.1| 284 ceruloplasmin (ferroxidase); 6 Ceruloplasmin [Homo sapiens] gi|42716297|ref|NP_001822.2| 285 clusterin isoform 1; complement- 1 associated protein SP-40 [Homo sapiens] gi|4503635|ref|NP_000497.1| 286 coagulation factor II precursor; 4 prothrombin [Homo sapiens] gi|4503625|ref|NP_000495.1| 287 coagulation factor X precursor; 1 prothrombinase; factor Xa [Homo sapiens] gi|4557379|ref|NP_000053.1| 288 complement component 1 inhibitor 2 precursor [Homo sapiens] gi|4502493|ref|NP_001724.1| 289 complement component 1, r 1 subcomponent [Homo sapiens] gi|7706083|ref|NP_057630.1| 290 complement component 1, r 1 subcomponent-like precursor; complement C1r-like proteinase; C1r- like serine protease analog [Homo sapiens] gi|4502495|ref|NP_001725.1| 291 complement component 1, s 1 subcomponent [Homo sapiens] gi|14550407|ref|NP_000054.2| 292 complement component 2 precursor; 2 C3/C5 convertase [Homo sapiens] gi|4557385|ref|NP_000055.1| 293 complement component 3 precursor; 21 acylation-stimulating protein cleavage product [Homo sapiens] gi|4502503|ref|NP_000706.1| 294 complement component 4 binding 1 yes protein, alpha; Complement component 4-binding protein, alpha polypeptide; complement component 4-binding protein, alpha [Homo sapiens] gi|50345296|ref|NP_001002029.1| 295 complement component 4B 12 preproprotein; Chido form of C4; basic C4; C4A anaphylatoxin [Homo sapiens] gi|38016947|ref|NP_001726.2| 296 complement component 5 [Homo 4 sapiens] gi|4559406|ref|NP_000056.1| 297 Complement component 6 precursor 3 [Homo sapiens] gi|45580688|ref|NP_000578.2| 298 complement component 7 precursor 2 [Homo sapiens] gi|4557389|ref|NP_000553.1| 299 complement component 8, alpha 1 polypeptide precursor [Homo sapiens] gi|4502511|ref|NP_001728.1| 300 complement component 9 [Homo 2 sapiens] gi|4502397|ref|NP_001701.1| 301 complement factor B preproprotein; 7 C3 proactivator; C3 proaccelerator; glycine-rich beta-glycoprotein; C3/C5 convertase [Homo sapiens] gi|4504375|ref|NP_000177.1| 302 complement factor H; H factor-1 3 (complement); factor H-like 1; H factor 2 (complement); H factor 1 (complement) [Homo sapiens] gi|11761629|ref|NP_068657.1| 303 fibrinogen, alpha chain isoform alpha 7 preproprotein [Homo sapiens] gi|11761631|ref|NP_005132.1| 304 fibrinogen, beta chain preproprotein 9 [Homo sapiens] gi|4503715|ref|NP_000500.1| 305 fibrinogen, gamma chain isoform 5 gamma-A precursor [Homo sapiens] gi|47132557|ref|NP_997647.1| 306 fibronectin 1 isoform 1 3 preproprotein; cold-insoluble globulin; migration-stimulating factor [Homo sapiens] gi|4504165|ref|NP_000168.1| 307 gelsolin isoform a [Homo sapiens] 7 gi|11321561|ref|NP_000604.1| 308 hemopexin [Homo sapiens] 4 gi|4504355|ref|NP_000176.1| 309 heparin cofactor II [Homo sapiens] 3 gi|4504579|ref|NP_000195.1| 310 I factor (complement) [Homo 1 sapiens] gi|21489959|ref|NP_653247.1| 311 immunoglobulin J chain [Homo 1 sapiens] gi|4504781|ref|NP_002206.1| 312 inter-alpha (globulin) inhibitor H1; 6 inter-alpha (globulin) inhibitor, H1 polypeptide [Homo sapiens] gi|4504783|ref|NP_002207.1| 313 inter-alpha (globulin) inhibitor H2; 10 inter-alpha (globulin) inhibitor, H2 polypeptide [Homo sapiens] gi|10092579|ref|NP_002208.1| 314 inter-alpha (globulin) inhibitor H3; 2 Inter-alpha (globulin) inhibitor, H3 polypeptide; pre-alpha (globulin) inhibitor, H3 polypeptide [Homo sapiens] gi|31542984|ref|NP_002209.2| 315 inter-alpha (globulin) inhibitor H4 11 (plasma Kallikrein-sensitive glycoprotein); Inter-alpha (globulin) inhibitor, H4 polypeptide; inter-alpha (globulin) inhibitor, H polypeptide- like 1 [Homo sapiens] gi|10835141|ref|NP_000563.1| 316 interleukin 10 precursor; cytokine 2 synthesis inhibitory factor [Homo sapiens] gi|4504893|ref|NP_000884.1| 317 kininogen 1; alpha-2-thiol proteinase 2 inhibitor; bradykinin [Homo sapiens] gi|4505047|ref|NP_002336.1| 318 lumican [Homo sapiens] 2 gi|33188445|ref|NP_036222.3| 319 microfilament and actin filament 1 cross-linker protein isoform a; actin cross-linking factor; 620 kDa actin binding protein; macrophin 1; trabeculin-alpha; actin cross-linking family protein 7 [Homo sapiens] gi|19923106|ref|NP_000437.3| 320 paraoxonase 1; Paraoxonase [Homo 1 sapiens] gi|21361845|ref|NP_443122.2| 321 peptidoglycan recognition protein L 2 precursor [Homo sapiens] gi|4504877|ref|NP_000883.1| 322 plasma kallikrein B1 precursor; 1 kallikrein 3, plasma; Kallikrein, plasma; kallikrein B plasma; Fletcher factor [Homo sapiens] gi|4505881|ref|NP_000292.1| 323 plasminogen [Homo sapiens] 2 gi|151465432|ref|XP_376519.2| 324 PREDICTED: ankyrin repeat 1 yes domain 6 [Homo sapiens] gi|42662334|ref|XP_375941.1| 325 PREDICTED: FLJ45139 protein 1 [Homo sapiens] gi|42656986|ref|XP_098238.8| 326 PREDICTED: SH3 domain protein 1 D19 [Homo sapiens] gi|51464068|ref|XP_209550.4| 327 PREDICTED: similar to 1 Carboxypeptidase N 83 kDa chain (Carboxypeptidase N regulatory subunit) [Homo sapiens] gi|51458647|ref|XP_497680.1| 328 PREDICTED: similar to prohibitin 1 [Homo sapiens] gi|51460685|ref|XP_497833.1| 329 PREDICTED: similar to SULT6B1 1 [Homo sapiens] gi|4506117|ref|NP_000304.1| 330 protein S (alpha); Protein S, alpha 2 [Homo sapiens] gi|13325075|ref|NP_002817.2| 331 quiescin Q6 [Homo sapiens] 1 gi|5803139|ref|NP_006735.1| 332 RBP4 gene product [Homo sapiens] 1 gi|21361198|ref|NP_000286.2| 333 serine (or cysteine) proteinase 4 inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 1; protease inhibitor 1 (anti-elastase), alpha-1-antitrypsin [Homo sapiens] gi|4507377|ref|NP_000345.1| 334 serine (or cysteine) proteinase 1 inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 7; thyroxine-binding globulin; thyroxin-binding globulin [Homo sapiens] gi|4502261|ref|NP_000479.1| 335 serine (or cysteine) proteinase 7 inhibitor, clade C (antithrombin), member 1; antithrombin III [Homo sapiens] gi|39725934|ref|NP_002606.3| 336 serine (or cysteine) proteinase 2 inhibitor, Glade F (alpha-2 antiplasmin, pigment epithelium derived factor), member 1; pigment epithelium-derived factor [Homo sapiens] gi|4502133|ref|NP_001630.1| 337 serum amyloid P component 2 precursor; pentaxin-related; 9.5S alpha-1-glycoprotein [Homo sapiens] gi|7382460|ref|NP_001031.2| 338 sex hormone-binding globulin; Sex 1 yes hormone-binding globulin (androgen binding protein) [Homo sapiens] gi|4557739|ref|NP_000233.1| 339 soluble mannose-binding lectin 1 precursor; Mannose-binding lectin 2, soluble (opsonic defect); mannose binding protein [Homo sapiens] gi|4507659|ref|NP_003283.1| 340 translocated promoter region (to 1 activated MET oncogene); Tumor potentiating region (translocated promoter region) [Homo sapiens] gi|46195765|ref|NP_954712.1| 341 unc-13 homolog D [Homo sapiens] 1 yes gi|32483410|ref|NP_000574.2| 342 vitamin D-binding protein precursor; 2 vitamin D-binding alpha-globulin [Homo sapiens] gi|18201911|ref|NP_000629.2| 343 vitronectin precursor; serum 4 spreading factor; somatomedin B; complement S-protein; epibolin [Homo sapiens]

[0068] Data was determined using partial least squares-discriminant analysis (PLS-DA). Individual protein abundances were compared between slow decline condition and rapid decline condition populations to assess which proteins are differentially abundant between the two populations. If the protein was not identified in all the samples, an abundance value of 0.004 was assigned to those samples in which the protein was not detected. The value of 0.004 represents one-half of the minimum ion current or abundance value observed. The abundances from each peptide identified from slow decline conditions or rapid decline conditions were then averaged. The ratio between the two populations for each protein was then determined. Table 2 shows those proteins having a two-fold or greater difference in abundance between slow decline conditions and rapid decline conditions:

TABLE-US-00002 TABLE 2 Anti-Log Average Rapid (Rapid decline decline conditions Number of NCBI SEQ. conditions vs. Slow to Slow decline Standard Significant Reference ID. NO. Protein Description decline conditions conditions Ratio Deviation Peptides 4501843 270 Antichymotrypsin 0.87 0.83 0.05 2 4557225 271 Alpha-2-macroglobulin 0.88 1.05 0.48 4 4502153 277 Apolipoprotein B 1.48 1.22 0.21 17 4557485 284 Ceruloplasmin 0.97 0.82 0.34 5 4557385 293 Complement component 3 0.64 0.71 0.22 15 11761629 303 Fibrogen, alpha chain isoform 1.24 1.29 0.37 6 11761631 304 Fibrogen, beta chain 1.41 1.23 0.30 5 4503715 305 Fibrogen, gamma chain isoform 1.21 1.24 0.50 5 47132557 306 Fibronectin 1 isoform 1 0.75 0.63 0.17 2 4504165 307 Gelsolin isoform a 0.76 0.85 0.30 4 4504893 317 Kininogen 1; bradykinin 1.20 1.27 0.10 2 4504877 322 Plasma kallikrein B1; kallikrein 0.46 1 3, plasma 21361198 333 Serine (or cysteine) proteinase 1.60 1.37 0.15 4 inhibitor; alpha-1-antitrypsin 4502133 337 Serum amyloid P component 1.26 1.23 0.04 2 32483410 342 Vitamin D-binding protein 0.86 1

[0069] The results of the mass spectrometry experiments yielded an average of 1,407 peptide fragments per subject, leading to 207 identified proteins per subject. Of the proteins identified in aggregate, 532 proteins occurred in more than 10 subjects. Of those 532 proteins, 21 were proteases, 16 were cytokines and chemokines, 26 were hypothetical proteins, and one was cytochrome P450.

[0070] According to embodiments and referring again to FIG. 3, the biomarker informative content repository 330 was created using data sets generated from the COPD protein study. According to embodiments, the COPD informative content repository is a MySQL database populated with protein, peptide, and metabolite data. The COPD informative content repository database resides on a server, according to embodiments, and may be accessed using various protocols such as http, ssh, ftp, and odbc.

[0071] The COPD informative content repository MySQL tables are organized and sortable by subject, sample name, peptide sequence, demographic information, and protein. Various tables are used to link the data, as well as to link other informative content repositories with the COPD informative content repository. The COPD informative content repository is linked to other databases for correlation of clinical data, genealogical data, and demographic data. The informative content repositories are maintained independently of each other and a firewall is employed to maintain independence of each respective informative content repository.

[0072] According to embodiments, the informative content repository of the present disclosure comprises high throughput screening devices, such as gene and protein chips, for rapid determination of predisposition to rapid COPD decline or slow COPD decline.

[0073] While the apparatus and method have been described in terms of what are presently considered to be the most practical and preferred embodiments, it is to be understood that the disclosure need not be limited to the disclosed embodiments. It is intended to cover various modifications and similar arrangements included within the spirit and scope of the claims, the scope of which should be accorded the broadest interpretation so as to encompass all such modifications and similar structures. The present disclosure includes any and all embodiments of the following claims.

REFERENCES

[0074] The following references are hereby incorporated by reference as if fully disclosed herein.

[0075] Belov, M. E., Anderson, G. A., Wingerd, M. A., Udseth, H. R., Tang, K., Prior, D. C., Swanson, K. R. et al., 2004. J. Am Soc. Mass Spectrom. 15, 212-232.

[0076] Bolstad, B. M., Irizarry, R. A., Astrand, M. and Speed, T. A. (2003) A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics, 19(2), pp. 185-193.

[0077] Efron, B. (2004) Large-scale simultaneous hypothesis testing: The choice of a null hypothesis. J. Am. Stat. Assoc., 99(465), pp. 96-104.

[0078] Eng, J. K., McCormack, A. L., Yates, J. R. 1994. J. Am Soc. Mass Spectrom. 5: 976-989.

[0079] Gary R. Kiebel, Ken J. Auberry, Navdeep Jaitly, David A. Clark, Matthew E. Monroe, Elena S. Peterson, Nikola Toli, Gordon A. Anderson, Richard D. Smith. PROTEOMICS. 6:1783-1790. 2006.

[0080] Link, A. J., Eng, J., Schieltz, D. M., Carmack, E., Mize, G. J., Morris, D. R., Garvik, B. M., Yates III, J. R. 1999. Nat. Biotechnol. 17: 676-682.

[0081] Smith, R. D., Anderson, G. A., Lipton, M. S., Pasa-Tolic, L., Shen, Y., Conrads, T. P., Veenstra, T. D., and H. R. Udseth. 2002. Proteomics 2, 513-523.

[0082] Smith, R. D., Anderson, G. A., Lipton, M. S., Pasa-Tolic, L., Shen, Y., Conrads, T. P., Veenstra, T. D., and H. R. Udseth. 2002. Proteomics 2, 513-523.

[0083] Tang, H.; Wang, Y; Nicholson, J; and Lindon, J. "Use of relaxation-edited one-dimensional and two dimensional nuclear magnetic resonance spectroscopy to improve detection of small metabolites in blood plasma." Analytical Biochemistry 325:260-272. 2004.

[0084] Washburn, M. P., Wolters, D., Yates III, J. R. 2001. Nat. Biotechnol. 19: 242-247.

[0085] Wei-Jun Qian, Jon M. Jacobi, David G. Camp III, Matthew E. Monroe, Ronald J. Moore, Marina A. Gritsenko, Steve E. Calvano, Stephen F. Lowry, Wenzhong Xiao, Lyle L. Moldawer, Ronald W. Davis, Ronald G. Tompkins and Richard D. Smith, 2005. Proteomics 5:572-584.

Sequence CWU 1

1

343122PRTHomo sapiens 1Arg Asn Pro Phe Val Phe Ala Pro Thr Leu Leu Thr Val Ala Val His 1 5 10 15 Phe Glu Glu Val Ala Lys 20 28PRTHomo sapiens 2Asp Asp Asn Pro Asn Leu Pro Arg 1 5 37PRTHomo sapiens 3Glu Phe Ala Glu Val Ser Lys 1 5 49PRTHomo sapiens 4Lys Asp Leu Gly Glu Glu Asn Phe Lys 1 5 57PRTHomo sapiens 5Leu Ser Gln Arg Phe Pro Lys 1 5 611PRTHomo sapiens 6Leu Val Ala Ala Ser Gln Ala Ala Leu Gly Leu 1 5 10 710PRTHomo sapiens 7Leu Val Asn Glu Val Thr Glu Phe Ala Lys 1 5 10 819PRTHomo sapiens 8Asn Tyr Ala Glu Ala Lys Asp Val Phe Leu Gly Met Phe Leu Tyr Glu 1 5 10 15 Tyr Ala Arg 98PRTHomo sapiens 9Thr Tyr Glu Thr Thr Leu Glu Lys 1 5 1020PRTHomo sapiens 10Gly Ala Ala Ala Asn Leu Glu Leu Ile Phe Val Gly Pro Gln His Ala 1 5 10 15 Gly Asn Tyr Arg 20 119PRTHomo sapiens 11Gly Glu Lys Glu Leu Leu Val Pro Arg 1 5 1237PRTHomo sapiens 12Leu His Asp Asn Gln Asn Gly Trp Ser Gly Asp Ser Ala Pro Val Glu 1 5 10 15 Leu Ile Leu Ser Asp Glu Thr Leu Pro Ala Pro Glu Phe Ser Pro Glu 20 25 30 Pro Glu Ser Gly Arg 35 1312PRTHomo sapiens 13Ser Gly Leu Ser Thr Gly Trp Thr Gln Leu Ser Lys 1 5 10 1420PRTHomo sapiens 14Ser Leu Pro Ala Pro Trp Leu Ser Met Ala Pro Val Ser Trp Ile Thr 1 5 10 15 Pro Gly Leu Lys 20 1517PRTHomo sapiens 15Val Thr Leu Thr Cys Val Ala Pro Leu Ser Gly Val Asp Phe Gln Leu 1 5 10 15 Arg 1618PRTHomo sapiens 16Leu Tyr Gly Ser Glu Ala Phe Ala Thr Asp Phe Gln Asp Ser Ala Ala 1 5 10 15 Ala Lys 1714PRTHomo sapiens 17Trp Glu Met Pro Phe Asp Pro Gln Asp Thr His Gln Ser Arg 1 5 10 1819PRTHomo sapiens 18Ala Ser Val Ser Val Leu Gly Asp Ile Leu Gly Ser Ala Met Gln Asn 1 5 10 15 Thr Gln Asn 1930PRTHomo sapiens 19Gly Gly Val Glu Asp Glu Val Thr Leu Ser Ala Tyr Ile Thr Ile Ala 1 5 10 15 Leu Leu Glu Ile Pro Leu Thr Val Thr His Pro Val Val Arg 20 25 30 208PRTHomo sapiens 20Gly Pro Thr Gln Glu Phe Lys Lys 1 5 2118PRTHomo sapiens 21Leu Leu Leu Gln Gln Val Ser Leu Pro Glu Leu Pro Gly Glu Tyr Ser 1 5 10 15 Met Lys 2212PRTHomo sapiens 22Gln Glu Gly Asp His Gly Ser His Val Tyr Thr Lys 1 5 10 2311PRTHomo sapiens 23Val Gly Phe Tyr Glu Ser Asp Val Met Gly Arg 1 5 10 2419PRTHomo sapiens 24Asp Ser Phe His Leu Asp Glu Gln Phe Thr Val Pro Val Glu Met Met 1 5 10 15 Gln Ala Arg 2533PRTHomo sapiens 25Glu Ala Thr Glu Gly Lys Ile Gln Glu Phe Leu Ser Gly Leu Pro Glu 1 5 10 15 Asp Thr Val Leu Leu Leu Leu Asn Ala Ile His Phe Gln Gly Phe Trp 20 25 30 Arg 2623PRTHomo sapiens 26Glu Leu Lys Glu Gln Gln Asp Ser Pro Gly Asn Lys Asp Phe Leu Gln 1 5 10 15 Ser Leu Lys Gly Phe Pro Arg 20 2739PRTHomo sapiens 27Gly Phe Pro Ile Lys Glu Asp Phe Leu Glu Gln Ser Glu Gln Leu Phe 1 5 10 15 Gly Ala Lys Pro Val Ser Leu Thr Gly Lys Gln Glu Asp Asp Leu Ala 20 25 30 Asn Ile Asn Gln Trp Val Lys 35 2827PRTHomo sapiens 28Ile Gln Glu Phe Leu Ser Gly Leu Pro Glu Asp Thr Val Leu Leu Leu 1 5 10 15 Leu Asn Ala Ile His Phe Gln Gly Phe Trp Arg 20 25 298PRTHomo sapiens 29Asn Pro Asn Pro Ser Ala Pro Arg 1 5 3014PRTHomo sapiens 30Pro Pro Met Glu Glu Asp Tyr Pro Gln Phe Gly Ser Pro Lys 1 5 10 3114PRTHomo sapiens 31Pro Lys Asp Pro Thr Phe Ile Pro Ala Pro Ile Gln Ala Lys 1 5 10 3220PRTHomo sapiens 32Gln Lys Leu His Glu Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu 1 5 10 15 Met Arg Asp Arg 20 3316PRTHomo sapiens 33Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys 1 5 10 15 3421PRTHomo sapiens 34Ala Gly Thr Glu Leu Val Asn Phe Leu Ser Tyr Phe Val Glu Leu Gly 1 5 10 15 Thr Gln Pro Ala Thr 20 3522PRTHomo sapiens 35Ala Gly Thr Glu Leu Val Asn Phe Leu Ser Tyr Phe Val Glu Leu Gly 1 5 10 15 Thr Gln Pro Ala Thr Gln 20 3611PRTHomo sapiens 36Ile Asp Gln Asn Val Glu Glu Leu Lys Gly Arg 1 5 10 3712PRTHomo sapiens 37Lys Leu Val Pro Phe Ala Thr Glu Leu His Glu Arg 1 5 10 3821PRTHomo sapiens 38Leu Thr Pro Tyr Ala Asp Glu Phe Lys Val Lys Ile Asp Gln Thr Val 1 5 10 15 Glu Glu Leu Arg Arg 20 399PRTHomo sapiens 39Pro Phe Ala Thr Glu Leu His Glu Arg 1 5 407PRTHomo sapiens 40Pro Tyr Ala Asp Glu Phe Lys 1 5 4117PRTHomo sapiens 41Ser Leu Ala Glu Leu Gly Gly His Leu Asp Gln Gln Val Glu Glu Phe 1 5 10 15 Arg 4218PRTHomo sapiens 42Ser Leu Ala Glu Leu Gly Gly His Leu Asp Gln Gln Val Glu Glu Phe 1 5 10 15 Arg Arg 4315PRTHomo sapiens 43Ala Leu Tyr Trp Val Asn Gly Gln Val Pro Asp Gly Val Ser Lys 1 5 10 15 4411PRTHomo sapiens 44Asp Leu Lys Val Glu Asp Ile Pro Leu Ala Arg 1 5 10 4511PRTHomo sapiens 45Glu Phe Gln Val Pro Thr Phe Thr Ile Pro Lys 1 5 10 467PRTHomo sapiens 46Phe Ile Ile Pro Ser Pro Lys 1 5 4713PRTHomo sapiens 47Phe Leu Asp Ser Asn Ile Lys Phe Ser His Val Glu Lys 1 5 10 4818PRTHomo sapiens 48Phe Ser Val Pro Ala Gly Ile Val Ile Pro Ser Phe Gln Ala Leu Thr 1 5 10 15 Ala Arg 4913PRTHomo sapiens 49Ile Ala Glu Leu Ser Ala Thr Ala Gln Glu Ile Ile Lys 1 5 10 5010PRTHomo sapiens 50Ile Glu Ile Pro Leu Pro Phe Gly Gly Lys 1 5 10 5118PRTHomo sapiens 51Ile His Ser Gly Ser Phe Gln Ser Gln Val Glu Leu Ser Asn Asp Gln 1 5 10 15 Glu Lys 5220PRTHomo sapiens 52Ile Thr Glu Asn Asp Ile Gln Ile Ala Leu Asp Asp Ala Lys Ile Asn 1 5 10 15 Phe Asn Glu Lys 20 5319PRTHomo sapiens 53Leu Leu Leu Gln Met Asp Ser Ser Ala Thr Ala Tyr Gly Ser Thr Val 1 5 10 15 Ser Lys Arg 549PRTHomo sapiens 54Leu Thr Ile Phe Lys Thr Glu Leu Arg 1 5 558PRTHomo sapiens 55Leu Thr Leu Asp Ile Gln Asn Lys 1 5 5612PRTHomo sapiens 56Met Asn Phe Lys Gln Glu Leu Asn Gly Asn Thr Lys 1 5 10 5715PRTHomo sapiens 57Asn Leu Gln Asn Asn Ala Glu Trp Val Tyr Gln Gly Ala Ile Arg 1 5 10 15 5823PRTHomo sapiens 58Asn Ser Leu Phe Phe Ser Ala Gln Pro Phe Glu Ile Thr Ala Ser Thr 1 5 10 15 Asn Asn Glu Gly Asn Leu Lys 20 5910PRTHomo sapiens 59Gln Gly Phe Phe Pro Asp Ser Val Asn Lys 1 5 10 6019PRTHomo sapiens 60Gln Val Phe Leu Tyr Pro Glu Lys Asp Glu Pro Thr Tyr Ile Leu Asn 1 5 10 15 Ile Lys Arg 6116PRTHomo sapiens 61Arg Asn Leu Gln Asn Asn Ala Glu Trp Val Tyr Gln Gly Ala Ile Arg 1 5 10 15 627PRTHomo sapiens 62Ser Gln Ala Ile Ala Thr Lys 1 5 6313PRTHomo sapiens 63Ser Val Ser Leu Pro Ser Leu Asp Pro Ala Ser Ala Lys 1 5 10 6413PRTHomo sapiens 64Thr Lys Asn Ser Glu Glu Phe Ala Ala Ala Met Ser Arg 1 5 10 6514PRTHomo sapiens 65Val Leu Leu Asp Gln Leu Gly Thr Thr Ile Ser Phe Glu Arg 1 5 10 6611PRTHomo sapiens 66Val Arg Glu Ser Asp Glu Glu Thr Gln Ile Lys 1 5 10 679PRTHomo sapiens 67Val Ser Thr Ala Phe Val Tyr Thr Lys 1 5 6821PRTHomo sapiens 68Asp Val Ser Ser Ala Leu Asp Lys Leu Lys Glu Phe Gly Asn Thr Leu 1 5 10 15 Glu Asp Lys Ala Arg 20 699PRTHomo sapiens 69Leu Gln Ala Glu Ala Phe Gln Ala Arg 1 5 7010PRTHomo sapiens 70Lys Ala Thr Val Val Tyr Gln Gly Glu Arg 1 5 10 7117PRTHomo sapiens 71Thr Ser Ile Tyr Pro Phe Leu Asp Phe Met Pro Ser Pro Gln Val Val 1 5 10 15 Arg 7210PRTHomo sapiens 72Val Gly Glu Ala Asn Pro Lys Leu Gln Lys 1 5 10 7315PRTHomo sapiens 73Glu Ala Leu Ile Gln Phe Leu Glu Gln Val His Gln Gly Ile Lys 1 5 10 15 7422PRTHomo sapiens 74His Leu Tyr Val Leu Glu Phe Ser Asp His Pro Gly Ile His Glu Pro 1 5 10 15 Leu Glu Pro Glu Val Lys 20 7520PRTHomo sapiens 75Lys Leu Ile Ser Val Asp Thr Glu His Ser Asn Ile Tyr Leu Gln Asn 1 5 10 15 Gly Pro Asp Arg 20 7642PRTHomo sapiens 76Met Phe Gly Asn Leu Gln Gly Leu Thr Met His Val Gly Asp Glu Val 1 5 10 15 Asn Trp Tyr Leu Met Gly Met Gly Asn Glu Ile Asp Leu His Thr Val 20 25 30 His Phe His Gly His Ser Phe Gln Tyr Lys 35 40 7721PRTHomo sapiens 77Met Tyr Tyr Ser Ala Val Asp Pro Thr Lys Asp Ile Phe Thr Gly Leu 1 5 10 15 Ile Gly Pro Met Lys 20 7810PRTHomo sapiens 78Pro Leu Ser Ile Glu Pro Ile Gly Val Arg 1 5 10 7913PRTHomo sapiens 79Gln Tyr Thr Asp Ser Thr Phe Arg Val Pro Val Glu Arg 1 5 10 8017PRTHomo sapiens 80Thr Thr Ile Glu Lys Pro Val Trp Leu Gly Phe Leu Gly Pro Ile Ile 1 5 10 15 Lys 8110PRTHomo sapiens 81Thr Leu Leu Ser Asn Leu Glu Glu Ala Lys 1 5 10 8220PRTHomo sapiens 82Ile Val Glu Gly Ser Asp Ala Glu Ile Gly Met Ser Pro Trp Gln Val 1 5 10 15 Met Leu Phe Arg 20 8313PRTHomo sapiens 83Thr Ala Thr Ser Glu Tyr Gln Thr Phe Phe Asn Pro Arg 1 5 10 8417PRTHomo sapiens 84Val Thr Gly Trp Gly Asn Leu Lys Glu Thr Trp Thr Ala Asn Val Gly 1 5 10 15 Lys 8511PRTHomo sapiens 85Trp Ile Gln Lys Val Ile Asp Gln Phe Gly Glu 1 5 10 869PRTHomo sapiens 86Thr Gly Ile Val Ser Gly Phe Gly Arg 1 5 8710PRTHomo sapiens 87Phe Gln Pro Thr Leu Leu Thr Leu Pro Arg 1 5 10 888PRTHomo sapiens 88Pro Thr Leu Leu Thr Leu Pro Arg 1 5 8915PRTHomo sapiens 89Met Gly Asn Phe Pro Trp Gln Val Phe Thr Asn Ile His Gly Arg 1 5 10 15 9040PRTHomo sapiens 90Ser Val Leu Leu Ala Gln Glu Leu Pro Gln Gln Leu Thr Ser Pro Gly 1 5 10 15 Tyr Pro Glu Pro Tyr Gly Lys Gly Gln Glu Ser Ser Thr Asp Ile Lys 20 25 30 Ala Pro Glu Gly Phe Ala Val Arg 35 40 9119PRTHomo sapiens 91Ser Ser Asn Asn Pro His Ser Pro Ile Val Glu Glu Phe Gln Val Pro 1 5 10 15 Tyr Asn Lys 9214PRTHomo sapiens 92Ala Leu His Gln Val Phe Glu His Met Leu Asp Val Ser Lys 1 5 10 9312PRTHomo sapiens 93Gln His Leu Gly Asp Val Leu Asn Phe Leu Pro Leu 1 5 10 9414PRTHomo sapiens 94Ala Gly Asp Phe Leu Glu Ala Asn Tyr Met Asn Leu Gln Arg 1 5 10 957PRTHomo sapiens 95Ala Val Leu Tyr Asn Tyr Arg 1 5 9618PRTHomo sapiens 96Ala Tyr Tyr Glu Asn Ser Pro Gln Gln Val Phe Ser Thr Glu Phe Glu 1 5 10 15 Val Lys 9732PRTHomo sapiens 97His Gln Gln Thr Val Thr Ile Pro Pro Lys Ser Ser Leu Ser Val Pro 1 5 10 15 Tyr Val Ile Val Pro Leu Lys Thr Gly Leu Gln Glu Val Glu Val Lys 20 25 30 9814PRTHomo sapiens 98Ile Pro Ile Glu Asp Gly Ser Gly Glu Val Val Leu Ser Arg 1 5 10 997PRTHomo sapiens 99Leu Met Asn Ile Phe Leu Lys 1 5 10024PRTHomo sapiens 100Leu Met Asn Ile Phe Leu Lys Asp Ser Ile Thr Thr Trp Glu Ile Leu 1 5 10 15 Ala Val Ser Met Ser Asp Lys Lys 20 1018PRTHomo sapiens 101Pro Gly Gln Gln Met Thr Leu Lys 1 5 10216PRTHomo sapiens 102Pro Leu Ser Trp Asp Ile Pro Glu Leu Val Asn Met Gly Gln Trp Lys 1 5 10 15 10311PRTHomo sapiens 103Gln Glu Leu Ser Glu Ala Glu Gln Ala Thr Arg 1 5 10 1048PRTHomo sapiens 104Gln Gly Ala Leu Glu Leu Ile Lys 1 5 10523PRTHomo sapiens 105Gln Lys Pro Asp Gly Val Phe Gln Glu Asp Ala Pro Val Ile His Gln 1 5 10 15 Glu Met Ile Gly Gly Leu Arg 20 10629PRTHomo sapiens 106Gln Leu Tyr Asn Val Glu Ala Thr Ser Tyr Ala Leu Leu Ala Leu Leu 1 5 10 15 Gln Leu Lys Asp Phe Asp Phe Val Pro Pro Val Val Arg 20 25 10710PRTHomo sapiens 107Ser Asp Asp Lys Val Thr Leu Glu Glu Arg 1 5 10 10813PRTHomo sapiens 108Ser Asp Asp Lys Val Thr Leu Glu Glu Arg Leu Asp Lys 1 5 10 10918PRTHomo sapiens 109Ser Gly Gln Ser Glu Asp Arg Gln Pro Val Pro Gly Gln Gln Met Thr 1 5 10 15 Leu Lys 11010PRTHomo sapiens 110Ser Leu Lys Val Val Pro Glu Gly Ile Arg 1 5 10 11116PRTHomo sapiens 111Ser Asn Leu Asp Glu Asp Ile Ile Ala Glu Glu Asn Ile Val Ser Arg 1 5 10 15 11213PRTHomo sapiens 112Ser Pro Met Tyr Ser Ile Ile Thr Pro Asn Ile Leu Arg 1 5 10 11316PRTHomo sapiens 113Ser Tyr Thr Val Ala Ile Ala Gly Tyr Ala Leu Ala Gln Met Gly Arg 1 5 10 15 11416PRTHomo sapiens 114Val His Gln Tyr Phe Asn Val Glu Leu Ile Gln Pro Gly Ala Val Lys 1 5 10 15 11510PRTHomo sapiens 115Leu Asn Asn Gly Glu Ile Thr Gln His Arg 1 5 10 1169PRTHomo sapiens 116Asp His Ala Val Asp Leu Ile Gln Lys 1 5 11710PRTHomo sapiens 117Phe Gly Leu Leu Asp Glu Asp Gly Lys Lys 1 5 10 11838PRTHomo sapiens 118Gly Ser Phe Glu Phe Pro Val Gly Asp Ala Val Ser Lys Val Leu Gln 1 5 10 15 Ile Glu Lys Glu Gly Ala Ile His Arg Glu Glu Leu Val Tyr Glu Leu 20 25 30 Asn Pro Leu Asp His Arg 35 11927PRTHomo sapiens 119Lys Lys Glu Val Tyr Met Pro Ser Ser Ile Phe Gln Asp Asp Phe Val 1 5 10 15 Ile Pro Asp Ile Ser Glu Pro Gly Thr Trp Lys 20 25 12036PRTHomo sapiens 120Leu Tyr Val Ala Ala Ala Ile Ile Glu Ser Pro Gly Gly Glu Met Glu 1 5 10 15 Glu Ala Glu Leu Thr Ser Trp Tyr Phe Val Ser Ser Pro Phe Ser Leu 20 25 30 Asp Leu Ser Lys 35 12141PRTHomo sapiens 121Ser Met Gln Gly Gly Leu Val Gly Asn Asp Glu Thr Val Ala Leu Thr 1 5 10 15 Ala Phe Val Thr Ile Ala Leu His His Gly Leu Ala Val Phe Gln Asp 20 25 30 Glu Gly Ala Glu Pro Leu Lys Gln Arg 35 40 12223PRTHomo sapiens 122Thr Leu Glu Ile Pro Gly Asn Ser Asp Pro Asn Met Ile Pro Asp Gly 1 5 10 15 Asp Phe Asn Ser Tyr Val Arg 20

12310PRTHomo sapiens 123Val Gly Asp Thr Leu Asn Leu Asn Leu Arg 1 5 10 12425PRTHomo sapiens 124Val Leu Gln Ile Glu Lys Glu Gly Ala Ile His Arg Glu Glu Leu Val 1 5 10 15 Tyr Glu Leu Asn Pro Leu Asp His Arg 20 25 12526PRTHomo sapiens 125Val Thr Ala Ser Asp Pro Leu Asp Thr Leu Gly Ser Glu Gly Ala Leu 1 5 10 15 Ser Pro Gly Gly Val Ala Ser Leu Leu Arg 20 25 1269PRTHomo sapiens 126Tyr Arg Val Phe Ala Leu Asp Gln Lys 1 5 1279PRTHomo sapiens 127Tyr Val Leu Pro Asn Phe Glu Val Lys 1 5 12824PRTHomo sapiens 128Glu Lys Phe Ser Asp Ala Ser Tyr Gln Ser Ile Asn Ile Pro Val Thr 1 5 10 15 Gln Asn Met Val Pro Ser Ser Arg 20 12922PRTHomo sapiens 129Phe Ser Asp Ala Ser Tyr Gln Ser Ile Asn Ile Pro Val Thr Gln Asn 1 5 10 15 Met Val Pro Ser Ser Arg 20 13014PRTHomo sapiens 130Lys Gln Thr Ala Cys Lys Pro Glu Ile Ala Tyr Ala Tyr Lys 1 5 10 13111PRTHomo sapiens 131Thr Leu Leu Pro Val Ser Lys Pro Glu Ile Arg 1 5 10 13212PRTHomo sapiens 132Ala Lys Asp Leu His Leu Ser Asp Val Phe Leu Lys 1 5 10 13315PRTHomo sapiens 133Leu Ser Glu Lys His Glu Gly Ser Phe Ile Gln Gly Ala Glu Lys 1 5 10 15 13428PRTHomo sapiens 134Thr Phe Ser Glu Trp Leu Glu Ser Val Lys Glu Asn Pro Ala Val Ile 1 5 10 15 Asp Phe Glu Leu Ala Pro Ile Val Asp Leu Val Arg 20 25 13514PRTHomo sapiens 135Ser Arg Glu Cys Asn Asn Pro Pro Pro Ser Gly Gly Gly Arg 1 5 10 13616PRTHomo sapiens 136Tyr Ser Ala Trp Ala Glu Ser Val Thr Asn Leu Pro Gln Val Ile Lys 1 5 10 15 13710PRTHomo sapiens 137Ala Met Ala Val Glu Asp Ile Ile Ser Arg 1 5 10 13815PRTHomo sapiens 138Gln Lys Ile Ser Glu Gly Leu Pro Ala Leu Glu Phe Pro Asn Glu 1 5 10 15 1398PRTHomo sapiens 139Tyr Ala Phe Glu Leu Lys Glu Lys 1 5 14010PRTHomo sapiens 140Ala Leu Phe Val Ser Glu Glu Glu Lys Lys 1 5 10 1419PRTHomo sapiens 141Asp Ile Ser Glu Val Val Thr Pro Arg 1 5 14211PRTHomo sapiens 142Glu Lys Leu Gln Asp Glu Asp Leu Gly Phe Leu 1 5 10 14332PRTHomo sapiens 143His Val Ile Ile Leu Met Thr Asp Gly Leu His Asn Met Gly Gly Asp 1 5 10 15 Pro Ile Thr Val Ile Asp Glu Ile Arg Asp Leu Leu Tyr Ile Gly Lys 20 25 30 14414PRTHomo sapiens 144Val Ser Glu Ala Asp Ser Ser Asn Ala Asp Trp Val Thr Lys 1 5 10 14534PRTHomo sapiens 145Val Ser Glu Ala Asp Ser Ser Asn Ala Asp Trp Val Thr Lys Gln Leu 1 5 10 15 Asn Glu Ile Asn Tyr Glu Asp His Lys Leu Lys Ser Gly Thr Asn Thr 20 25 30 Lys Lys 1468PRTHomo sapiens 146Val Ser Val Gly Gly Glu Lys Arg 1 5 1479PRTHomo sapiens 147Glu Phe Asp His Asn Ser Asn Ile Arg 1 5 1489PRTHomo sapiens 148Ile Asp Val His Leu Val Pro Asp Arg 1 5 1497PRTHomo sapiens 149Asn Asp Phe Thr Trp Phe Lys 1 5 15019PRTHomo sapiens 150Ala Asp Ser Gly Glu Gly Asp Phe Leu Ala Glu Gly Gly Gly Val Arg 1 5 10 15 Gly Pro Arg 15120PRTHomo sapiens 151Glu Val Asp Leu Lys Asp Tyr Glu Asp Gln Gln Lys Gln Leu Glu Gln 1 5 10 15 Val Ile Ala Lys 20 15216PRTHomo sapiens 152Gly Leu Ile Asp Glu Val Asn Gln Asp Phe Thr Asn Arg Ile Asn Lys 1 5 10 15 15313PRTHomo sapiens 153Met Glu Leu Glu Arg Pro Gly Gly Asn Glu Ile Thr Arg 1 5 10 15413PRTHomo sapiens 154Met Lys Pro Val Pro Asp Leu Val Pro Gly Asn Phe Lys 1 5 10 15511PRTHomo sapiens 155Pro Val Pro Asp Leu Val Pro Gly Asn Phe Lys 1 5 10 15610PRTHomo sapiens 156Val Thr Ser Gly Ser Thr Thr Thr Thr Arg 1 5 10 15720PRTHomo sapiens 157Gly Gly Glu Thr Ser Glu Met Tyr Leu Ile Gln Pro Asp Ser Ser Val 1 5 10 15 Lys Pro Tyr Arg 20 1588PRTHomo sapiens 158Ile Arg Pro Phe Phe Pro Gln Gln 1 5 15921PRTHomo sapiens 159Lys Gly Gly Glu Thr Ser Glu Met Tyr Leu Ile Gln Pro Asp Ser Ser 1 5 10 15 Val Lys Pro Tyr Arg 20 16019PRTHomo sapiens 160Lys Trp Asp Pro Tyr Lys Gln Gly Phe Gly Asn Val Ala Thr Asn Thr 1 5 10 15 Asp Gly Lys 1617PRTHomo sapiens 161Ser Ile Leu Glu Asn Leu Arg 1 5 16226PRTHomo sapiens 162Thr Met Thr Ile His Asn Gly Met Phe Phe Ser Thr Tyr Asp Arg Asp 1 5 10 15 Asn Asp Gly Trp Leu Thr Ser Asp Pro Arg 20 25 16327PRTHomo sapiens 163Thr Met Thr Ile His Asn Gly Met Phe Phe Ser Thr Tyr Asp Arg Asp 1 5 10 15 Asn Asp Gly Trp Leu Thr Ser Asp Pro Arg Lys 20 25 16418PRTHomo sapiens 164Trp Asp Pro Tyr Lys Gln Gly Phe Gly Asn Val Ala Thr Asn Thr Asp 1 5 10 15 Gly Lys 16513PRTHomo sapiens 165Tyr Tyr Trp Gly Gly Gln Tyr Thr Trp Asp Met Ala Lys 1 5 10 16615PRTHomo sapiens 166Ile His Leu Ile Ser Thr Gln Ser Ala Ile Pro Tyr Ala Leu Arg 1 5 10 15 16710PRTHomo sapiens 167Pro Asn Met Ile Asp Ala Ala Thr Leu Lys 1 5 10 1688PRTHomo sapiens 168Thr Ala Asp Tyr Ala Met Phe Lys 1 5 16919PRTHomo sapiens 169Thr Tyr Asn Pro Asp Glu Ser Ser Lys Pro Asn Met Ile Asp Ala Ala 1 5 10 15 Thr Leu Lys 17018PRTHomo sapiens 170Tyr Asn Pro Asp Glu Ser Ser Lys Pro Asn Met Ile Asp Ala Ala Thr 1 5 10 15 Leu Lys 17116PRTHomo sapiens 171Gly Ala Thr Tyr Asn Ile Ile Val Glu Ala Leu Lys Asp Gln Gln Arg 1 5 10 15 17222PRTHomo sapiens 172Thr Glu Ile Asp Lys Pro Ser Gln Met Gln Val Thr Asp Val Gln Asp 1 5 10 15 Asn Ser Ile Ser Val Lys 20 17340PRTHomo sapiens 173Thr Pro Phe Val Thr His Pro Gly Tyr Asp Thr Gly Asn Gly Ile Gln 1 5 10 15 Leu Pro Gly Thr Ser Gly Gln Gln Pro Ser Val Gly Gln Gln Met Ile 20 25 30 Phe Glu Glu His Gly Phe Arg Arg 35 40 17413PRTHomo sapiens 174Ala Gly Ala Leu Asn Ser Asn Asp Ala Phe Val Leu Lys 1 5 10 17522PRTHomo sapiens 175Ala Gln Pro Val Gln Val Ala Glu Gly Ser Glu Pro Asp Gly Phe Trp 1 5 10 15 Glu Ala Leu Gly Gly Lys 20 17630PRTHomo sapiens 176Ile Glu Gly Ser Asn Lys Val Pro Val Asp Pro Ala Thr Tyr Gly Gln 1 5 10 15 Phe Tyr Gly Gly Asp Ser Tyr Ile Ile Leu Tyr Asn Tyr Arg 20 25 30 17720PRTHomo sapiens 177Pro Val Gln Val Ala Glu Gly Ser Glu Pro Asp Gly Phe Trp Glu Ala 1 5 10 15 Leu Gly Gly Lys 20 17817PRTHomo sapiens 178Gln Thr Gln Val Ser Val Leu Pro Glu Gly Gly Glu Thr Pro Leu Phe 1 5 10 15 Lys 1798PRTHomo sapiens 179Arg Thr Pro Ile Thr Val Val Lys 1 5 1808PRTHomo sapiens 180Thr Ala Ser Asp Phe Ile Thr Lys 1 5 18128PRTHomo sapiens 181Cys Ser Pro His Leu Val Leu Ser Ala Leu Thr Ser Asp Asn His Gly 1 5 10 15 Ala Thr Tyr Ala Phe Ser Gly Thr His Tyr Trp Arg 20 25 18212PRTHomo sapiens 182Asp Val Arg Asp Tyr Phe Met Pro Cys Pro Gly Arg 1 5 10 1836PRTHomo sapiens 183Glu Lys Gly Tyr Pro Lys 1 5 1849PRTHomo sapiens 184Val Trp Val Tyr Pro Pro Glu Lys Lys 1 5 18515PRTHomo sapiens 185Phe Thr Val Asp Arg Pro Phe Leu Phe Leu Ile Tyr Glu His Arg 1 5 10 15 1867PRTHomo sapiens 186Leu Asn Ile Leu Asn Ala Lys 1 5 1878PRTHomo sapiens 187Thr Arg Glu Val Leu Leu Pro Lys 1 5 18810PRTHomo sapiens 188Val Phe Ser Leu Gln Trp Gly Glu Val Lys 1 5 10 1897PRTHomo sapiens 189His Leu Ser Asp Leu Cys Lys 1 5 19012PRTHomo sapiens 190Ala Ala Ile Ser Gly Glu Asn Ala Gly Leu Val Arg 1 5 10 19118PRTHomo sapiens 191Phe Ala His Tyr Val Val Thr Ser Gln Val Val Asn Thr Ala Asn Glu 1 5 10 15 Ala Arg 19228PRTHomo sapiens 192Gly Met Ala Asp Gln Asp Gly Leu Lys Pro Thr Ile Asp Lys Pro Ser 1 5 10 15 Glu Asp Ser Pro Pro Leu Glu Met Leu Gly Pro Arg 20 25 19313PRTHomo sapiens 193Lys Ala Ala Ile Ser Gly Glu Asn Ala Gly Leu Val Arg 1 5 10 19410PRTHomo sapiens 194Leu Asp Ala Gln Ala Ser Phe Leu Pro Lys 1 5 10 19513PRTHomo sapiens 195Gln Ala Val Asp Thr Ala Val Asp Gly Val Phe Ile Arg 1 5 10 1968PRTHomo sapiens 196Ala Thr Thr Met Ile Gln Ser Lys 1 5 19710PRTHomo sapiens 197Asp Lys His Ala Asp Pro Asp Phe Thr Arg 1 5 10 19815PRTHomo sapiens 198Ile Gln Pro Ser Gly Gly Thr Asn Ile Asn Glu Ala Leu Leu Arg 1 5 10 15 19912PRTHomo sapiens 199Ile Tyr Gly Asn Gln Asp Thr Ser Ser Gln Leu Lys 1 5 10 20013PRTHomo sapiens 200Ile Tyr Gly Asn Gln Asp Thr Ser Ser Gln Leu Lys Lys 1 5 10 2017PRTHomo sapiens 201Ile Tyr Leu Gln Pro Gly Arg 1 5 20214PRTHomo sapiens 202Leu Trp Ala Tyr Leu Thr Ile Asn Gln Leu Leu Ala Glu Arg 1 5 10 2039PRTHomo sapiens 203Met Lys Gln Thr Val Glu Ala Met Lys 1 5 2047PRTHomo sapiens 204Gln Thr Val Glu Ala Met Lys 1 5 20522PRTHomo sapiens 205Thr Ile Leu Asp Asp Leu Arg Ala Glu Asp His Phe Ser Val Ile Asp 1 5 10 15 Phe Asn Gln Asn Ile Arg 20 20635PRTHomo sapiens 206His Phe Glu Ile Glu Val Asp Ile Phe Glu Pro Gln Gly Ile Ser Met 1 5 10 15 Leu Asp Ala Glu Ala Ser Phe Ile Thr Asn Asp Leu Leu Gly Ser Ala 20 25 30 Leu Thr Lys 35 20715PRTHomo sapiens 207Ala Asn Thr Val Gln Glu Ala Thr Phe Gln Met Glu Leu Pro Lys 1 5 10 15 2089PRTHomo sapiens 208Leu Gly Val Tyr Glu Leu Leu Leu Lys 1 5 20916PRTHomo sapiens 209Leu Gln Asp Arg Gly Pro Asp Val Leu Thr Ala Thr Val Ser Gly Lys 1 5 10 15 21016PRTHomo sapiens 210Asn Met Glu Gln Phe Gln Val Ser Val Ser Val Ala Pro Asn Ala Lys 1 5 10 15 21124PRTHomo sapiens 211Gln Gly Pro Val Asn Leu Leu Ser Asp Pro Glu Gln Gly Val Glu Val 1 5 10 15 Thr Gly Gln Tyr Glu Arg Glu Lys 20 21220PRTHomo sapiens 212Gln Leu Gly Leu Pro Gly Pro Pro Asp Val Pro Asp His Ala Ala Tyr 1 5 10 15 His Pro Phe Arg 20 21321PRTHomo sapiens 213Gln Leu Gly Leu Pro Gly Pro Pro Asp Val Pro Asp His Ala Ala Tyr 1 5 10 15 His Pro Phe Arg Arg 20 21410PRTHomo sapiens 214Arg Leu Gly Val Tyr Glu Leu Leu Leu Lys 1 5 10 21510PRTHomo sapiens 215Val Gln Gly Asn Asp His Ser Ala Thr Arg 1 5 10 2169PRTHomo sapiens 216Tyr Ile Phe His Asn Phe Met Glu Arg 1 5 2177PRTHomo sapiens 217Tyr Tyr Leu Gln Gly Ala Lys 1 5 21811PRTHomo sapiens 218Ala Val Glu Gln Val Lys Asn Ala Phe Asn Lys 1 5 10 21932PRTHomo sapiens 219Asn Ala Phe Asn Lys Leu Gln Glu Lys Gly Ile Tyr Lys Ala Met Ser 1 5 10 15 Glu Phe Asp Ile Phe Ile Asn Tyr Ile Glu Ala Tyr Met Thr Met Lys 20 25 30 2209PRTHomo sapiens 220Gln Val Val Ala Gly Leu Asn Phe Arg 1 5 2217PRTHomo sapiens 221Val Gln Val Val Ala Gly Lys 1 5 2228PRTHomo sapiens 222Phe Asn Ala Leu Gln Tyr Leu Arg 1 5 22311PRTHomo sapiens 223Leu Lys Glu Asp Ala Val Ser Ala Ala Phe Lys 1 5 10 2247PRTHomo sapiens 224Ile Ala Leu Asp Phe Leu Lys 1 5 22529PRTHomo sapiens 225Gly Ile Glu Thr Gly Ser Glu Asp Leu Glu Ile Leu Pro Asn Gly Leu 1 5 10 15 Ala Phe Ile Ser Ser Gly Leu Lys Tyr Pro Gly Ile Lys 20 25 22617PRTHomo sapiens 226Pro Ser Leu Ser His Leu Leu Ser Gln Tyr Tyr Gly Ala Gly Val Ala 1 5 10 15 Arg 22724PRTHomo sapiens 227Ser Leu Pro Leu Leu Met Asp Ser Val Ile Gln Ala Leu Ala Glu Leu 1 5 10 15 Glu Gln Lys Val Pro Ala Ala Lys 20 2289PRTHomo sapiens 228Glu Ile Ile Ile His Gln Asn Tyr Lys 1 5 22919PRTHomo sapiens 229Glu Pro Leu Asp Asp Tyr Val Asn Thr Gln Gly Ala Ser Leu Phe Ser 1 5 10 15 Val Thr Lys 23010PRTHomo sapiens 230Met Arg Asp Val Val Leu Phe Glu Lys Lys 1 5 10 23110PRTHomo sapiens 231Ala Gly Ala Asn Val Leu Ala Lys Asn Lys 1 5 10 2326PRTHomo sapiens 232Thr Val Ser Ile Pro Arg 1 5 23317PRTHomo sapiens 233Glu Gly Ile Phe Pro Ala Val Phe Val Arg Pro Cys Pro Ala Glu Ala 1 5 10 15 Lys 23416PRTHomo sapiens 234Leu Ser Asn Asn Ala Leu Ser Gly Leu Pro Gln Gly Val Phe Gly Lys 1 5 10 15 2359PRTHomo sapiens 235Asp Phe Thr Glu Ala Val Gly Ala Lys 1 5 23615PRTHomo sapiens 236Ser Gln Asp Thr His Gly Ala Val Gly Pro Phe Leu Phe Arg Lys 1 5 10 15 23728PRTHomo sapiens 237Ile Thr Thr Gly Gly Asp Val Ile Asn Asn Gly Leu Trp Asn Met Val 1 5 10 15 Ser Val Glu Glu Leu Glu His Ser Ile Ser Ile Lys 20 25 2388PRTHomo sapiens 238Val Tyr Phe Ala Gly Phe Pro Arg 1 5 23919PRTHomo sapiens 239Asn Asn Glu Glu Tyr Leu Ala Leu Ile Phe Glu Lys Gly Gly Ser Tyr 1 5 10 15 Leu Gly Arg 24010PRTHomo sapiens 240Gln Arg Gln Glu Glu Leu Cys Leu Ala Arg 1 5 10 24110PRTHomo sapiens 241Leu Ser Ile Thr Gly Thr Tyr Asp Leu Lys 1 5 10 2429PRTHomo sapiens 242Leu Ser Ser Trp Val Leu Leu Met Lys 1 5 24310PRTHomo sapiens 243Ser Val Leu Gly Gln Leu Gly Ile Thr Lys 1 5 10 24431PRTHomo sapiens 244Ser Val Leu Gly Gln Leu Gly Ile Thr Lys Val Phe Ser Asn Gly Ala 1 5 10 15 Asp Leu Ser Gly Val Thr Glu Glu Ala Pro Leu Lys Leu Ser Lys 20 25 30 2457PRTHomo sapiens 245Ser Ile Leu Phe Leu Gly Lys 1 5 24612PRTHomo sapiens 246Glu Val Pro Leu Asn Thr Ile Ile Phe Met Gly Arg 1 5 10 24734PRTHomo sapiens 247Phe Ala Thr Thr Phe Tyr Gln His Leu Ala Asp Ser Lys Asn Asp Asn 1 5 10 15 Asp Asn Ile Phe Leu Ser Pro Leu Ser Ile Ser Thr Ala Phe Ala Met 20 25 30 Thr Lys 24812PRTHomo sapiens 248Pro Leu Asp Phe Lys Glu Asn Ala Glu Gln Ser Arg 1 5 10 24929PRTHomo sapiens 249Arg Val Ala Glu Gly Thr Gln Val Leu Glu Leu Pro Phe Lys Gly Asp 1 5 10 15 Asp Ile Thr Met Val Leu Ile Leu Pro Lys Pro Glu Lys

20 25 25022PRTHomo sapiens 250Ser Lys Leu Pro Gly Ile Val Ala Glu Gly Arg Asp Asp Leu Tyr Val 1 5 10 15 Ser Asp Ala Phe His Lys 20 25132PRTHomo sapiens 251Ser Leu Ala Lys Val Glu Lys Glu Leu Thr Pro Glu Val Leu Gln Glu 1 5 10 15 Trp Leu Asp Glu Leu Glu Glu Met Met Leu Val Val His Met Pro Arg 20 25 30 25228PRTHomo sapiens 252Val Ala Glu Gly Thr Gln Val Leu Glu Leu Pro Phe Lys Gly Asp Asp 1 5 10 15 Ile Thr Met Val Leu Ile Leu Pro Lys Pro Glu Lys 20 25 25313PRTHomo sapiens 253Lys Thr Ser Leu Glu Asp Phe Tyr Leu Asp Glu Glu Arg 1 5 10 2548PRTHomo sapiens 254Val Pro Met Met Ser Asp Pro Lys 1 5 25510PRTHomo sapiens 255Asp Asn Glu Leu Leu Val Tyr Lys Glu Arg 1 5 10 25610PRTHomo sapiens 256Val Gly Glu Tyr Ser Leu Tyr Ile Gly Arg 1 5 10 25724PRTHomo sapiens 257Val Val Leu Ser Ser Gly Ser Gly Pro Gly Leu Asp Leu Pro Leu Val 1 5 10 15 Leu Gly Leu Pro Leu Gln Leu Lys 20 2589PRTHomo sapiens 258Lys Ala Leu Gln Thr Glu Met Ala Arg 1 5 2598PRTHomo sapiens 259Asn Asp Leu Leu Ser Ala Thr Lys 1 5 26018PRTHomo sapiens 260Gly Ile Leu Gly Lys Asp Val Ser Gly Phe Ser Asp Pro Tyr Cys Leu 1 5 10 15 Leu Gly 2618PRTHomo sapiens 261Leu Pro Glu Val Phe Leu Ser Lys 1 5 26211PRTHomo sapiens 262Val Met Asp Lys Tyr Thr Phe Glu Leu Ser Arg 1 5 10 26316PRTHomo sapiens 263Asp Trp His Gly Val Pro Gly Gln Val Asp Ala Ala Met Ala Gly Arg 1 5 10 15 26411PRTHomo sapiens 264Pro Gly Gln Val Asp Ala Ala Met Ala Gly Arg 1 5 10 26511PRTHomo sapiens 265Arg Val Asp Thr Val Asp Pro Pro Tyr Pro Arg 1 5 10 26613PRTHomo sapiens 266Thr Ser Ala Gly Thr Arg Gln Pro Gln Phe Ile Ser Arg 1 5 10 267599PRTHomo sapiens 267Met Lys Leu Leu Lys Leu Thr Gly Phe Ile Phe Phe Leu Phe Phe Leu 1 5 10 15 Thr Glu Ser Leu Thr Leu Pro Thr Gln Pro Arg Asp Ile Glu Asn Phe 20 25 30 Asn Ser Thr Gln Lys Phe Ile Glu Asp Asn Ile Glu Tyr Ile Thr Ile 35 40 45 Ile Ala Phe Ala Gln Tyr Val Gln Glu Ala Thr Phe Glu Glu Met Glu 50 55 60 Lys Leu Val Lys Asp Met Val Glu Tyr Lys Asp Arg Cys Met Ala Asp 65 70 75 80 Lys Thr Leu Pro Glu Cys Ser Lys Leu Pro Asn Asn Val Leu Gln Glu 85 90 95 Lys Ile Cys Ala Met Glu Gly Leu Pro Gln Lys His Asn Phe Ser His 100 105 110 Cys Cys Ser Lys Val Asp Ala Gln Arg Arg Leu Cys Phe Phe Tyr Asn 115 120 125 Lys Lys Ser Asp Val Gly Phe Leu Pro Pro Phe Pro Thr Leu Asp Pro 130 135 140 Glu Glu Lys Cys Gln Ala Tyr Glu Ser Asn Arg Glu Ser Leu Leu Asn 145 150 155 160 His Phe Leu Tyr Glu Val Ala Arg Arg Asn Pro Phe Val Phe Ala Pro 165 170 175 Thr Leu Leu Thr Val Ala Val His Phe Glu Glu Val Ala Lys Ser Cys 180 185 190 Cys Glu Glu Gln Asn Lys Val Asn Cys Leu Gln Thr Arg Ala Ile Pro 195 200 205 Val Thr Gln Tyr Leu Lys Ala Phe Ser Ser Tyr Gln Lys His Val Cys 210 215 220 Gly Ala Leu Leu Lys Phe Gly Thr Lys Val Val His Phe Ile Tyr Ile 225 230 235 240 Ala Ile Leu Ser Gln Lys Phe Pro Lys Ile Glu Phe Lys Glu Leu Ile 245 250 255 Ser Leu Val Glu Asp Val Ser Ser Asn Tyr Asp Gly Cys Cys Glu Gly 260 265 270 Asp Val Val Gln Cys Ile Arg Asp Thr Ser Lys Val Met Asn His Ile 275 280 285 Cys Ser Lys Gln Asp Ser Ile Ser Ser Lys Ile Lys Glu Cys Cys Glu 290 295 300 Lys Lys Ile Pro Glu Arg Gly Gln Cys Ile Ile Asn Ser Asn Lys Asp 305 310 315 320 Asp Arg Pro Lys Asp Leu Ser Leu Arg Glu Gly Lys Phe Thr Asp Ser 325 330 335 Glu Asn Val Cys Gln Glu Arg Asp Ala Asp Pro Asp Thr Phe Phe Ala 340 345 350 Lys Phe Thr Phe Glu Tyr Ser Arg Arg His Pro Asp Leu Ser Ile Pro 355 360 365 Glu Leu Leu Arg Ile Val Gln Ile Tyr Lys Asp Leu Leu Arg Asn Cys 370 375 380 Cys Asn Thr Glu Asn Pro Pro Gly Cys Tyr Arg Tyr Ala Glu Asp Lys 385 390 395 400 Phe Asn Glu Thr Thr Glu Lys Ser Leu Lys Met Val Gln Gln Glu Cys 405 410 415 Lys His Phe Gln Asn Leu Gly Lys Asp Gly Leu Lys Tyr His Tyr Leu 420 425 430 Ile Arg Leu Thr Lys Ile Ala Pro Gln Leu Ser Thr Glu Glu Leu Val 435 440 445 Ser Leu Gly Glu Lys Met Val Thr Ala Phe Thr Thr Cys Cys Thr Leu 450 455 460 Ser Glu Glu Phe Ala Cys Val Asp Asn Leu Ala Asp Leu Val Phe Gly 465 470 475 480 Glu Leu Cys Gly Val Asn Glu Asn Arg Thr Ile Asn Pro Ala Val Asp 485 490 495 His Cys Cys Lys Thr Asn Phe Ala Phe Arg Arg Pro Cys Phe Glu Ser 500 505 510 Leu Lys Ala Asp Lys Thr Tyr Val Pro Pro Pro Phe Ser Gln Asp Leu 515 520 525 Phe Thr Phe His Ala Asp Met Cys Gln Ser Gln Asn Glu Glu Leu Gln 530 535 540 Arg Lys Thr Asp Arg Phe Leu Val Asn Leu Val Lys Leu Lys His Glu 545 550 555 560 Leu Thr Asp Glu Glu Leu Gln Ser Leu Phe Thr Asn Phe Ala Asn Val 565 570 575 Val Asp Lys Cys Cys Lys Ala Glu Ser Pro Glu Val Cys Phe Asn Glu 580 585 590 Glu Ser Pro Lys Ile Gly Asn 595 268609PRTHomo sapiens 268Met Lys Trp Val Thr Phe Ile Ser Leu Leu Phe Leu Phe Ser Ser Ala 1 5 10 15 Tyr Ser Arg Gly Val Phe Arg Arg Asp Ala His Lys Ser Glu Val Ala 20 25 30 His Arg Phe Lys Asp Leu Gly Glu Glu Asn Phe Lys Ala Leu Val Leu 35 40 45 Ile Ala Phe Ala Gln Tyr Leu Gln Gln Cys Pro Phe Glu Asp His Val 50 55 60 Lys Leu Val Asn Glu Val Thr Glu Phe Ala Lys Thr Cys Val Ala Asp 65 70 75 80 Glu Ser Ala Glu Asn Cys Asp Lys Ser Leu His Thr Leu Phe Gly Asp 85 90 95 Lys Leu Cys Thr Val Ala Thr Leu Arg Glu Thr Tyr Gly Glu Met Ala 100 105 110 Asp Cys Cys Ala Lys Gln Glu Pro Glu Arg Asn Glu Cys Phe Leu Gln 115 120 125 His Lys Asp Asp Asn Pro Asn Leu Pro Arg Leu Val Arg Pro Glu Val 130 135 140 Asp Val Met Cys Thr Ala Phe His Asp Asn Glu Glu Thr Phe Leu Lys 145 150 155 160 Lys Tyr Leu Tyr Glu Ile Ala Arg Arg His Pro Tyr Phe Tyr Ala Pro 165 170 175 Glu Leu Leu Phe Phe Ala Lys Arg Tyr Lys Ala Ala Phe Thr Glu Cys 180 185 190 Cys Gln Ala Ala Asp Lys Ala Ala Cys Leu Leu Pro Lys Leu Asp Glu 195 200 205 Leu Arg Asp Glu Gly Lys Ala Ser Ser Ala Lys Gln Arg Leu Lys Cys 210 215 220 Ala Ser Leu Gln Lys Phe Gly Glu Arg Ala Phe Lys Ala Trp Ala Val 225 230 235 240 Ala Arg Leu Ser Gln Arg Phe Pro Lys Ala Glu Phe Ala Glu Val Ser 245 250 255 Lys Leu Val Thr Asp Leu Thr Lys Val His Thr Glu Cys Cys His Gly 260 265 270 Asp Leu Leu Glu Cys Ala Asp Asp Arg Ala Asp Leu Ala Lys Tyr Ile 275 280 285 Cys Glu Asn Gln Asp Ser Ile Ser Ser Lys Leu Lys Glu Cys Cys Glu 290 295 300 Lys Pro Leu Leu Glu Lys Ser His Cys Ile Ala Glu Val Glu Asn Asp 305 310 315 320 Glu Met Pro Ala Asp Leu Pro Ser Leu Ala Ala Asp Phe Val Glu Ser 325 330 335 Lys Asp Val Cys Lys Asn Tyr Ala Glu Ala Lys Asp Val Phe Leu Gly 340 345 350 Met Phe Leu Tyr Glu Tyr Ala Arg Arg His Pro Asp Tyr Ser Val Val 355 360 365 Leu Leu Leu Arg Leu Ala Lys Thr Tyr Glu Thr Thr Leu Glu Lys Cys 370 375 380 Cys Ala Ala Ala Asp Pro His Glu Cys Tyr Ala Lys Val Phe Asp Glu 385 390 395 400 Phe Lys Pro Leu Val Glu Glu Pro Gln Asn Leu Ile Lys Gln Asn Cys 405 410 415 Glu Leu Phe Glu Gln Leu Gly Glu Tyr Lys Phe Gln Asn Ala Leu Leu 420 425 430 Val Arg Tyr Thr Lys Lys Val Pro Gln Val Ser Thr Pro Thr Leu Val 435 440 445 Glu Val Ser Arg Asn Leu Gly Lys Val Gly Ser Lys Cys Cys Lys His 450 455 460 Pro Glu Ala Lys Arg Met Pro Cys Ala Glu Asp Tyr Leu Ser Val Val 465 470 475 480 Leu Asn Gln Leu Cys Val Leu His Glu Lys Thr Pro Val Ser Asp Arg 485 490 495 Val Thr Lys Cys Cys Thr Glu Ser Leu Val Asn Arg Arg Pro Cys Phe 500 505 510 Ser Ala Leu Glu Val Asp Glu Thr Tyr Val Pro Lys Glu Phe Asn Ala 515 520 525 Glu Thr Phe Thr Phe His Ala Asp Ile Cys Thr Leu Ser Glu Lys Glu 530 535 540 Arg Gln Ile Lys Lys Gln Thr Ala Leu Val Glu Leu Val Lys His Lys 545 550 555 560 Pro Lys Ala Thr Lys Glu Gln Leu Lys Ala Val Met Asp Asp Phe Ala 565 570 575 Ala Phe Val Glu Lys Cys Cys Lys Ala Asp Asp Lys Glu Thr Cys Phe 580 585 590 Ala Glu Glu Gly Lys Lys Leu Val Ala Ala Ser Gln Ala Ala Leu Gly 595 600 605 Leu 269495PRTHomo sapiens 269Met Ser Met Leu Val Val Phe Leu Leu Leu Trp Gly Val Thr Trp Gly 1 5 10 15 Pro Val Thr Glu Ala Ala Ile Phe Tyr Glu Thr Gln Pro Ser Leu Trp 20 25 30 Ala Glu Ser Glu Ser Leu Leu Lys Pro Leu Ala Asn Val Thr Leu Thr 35 40 45 Cys Gln Ala His Leu Glu Thr Pro Asp Phe Gln Leu Phe Lys Asn Gly 50 55 60 Val Ala Gln Glu Pro Val His Leu Asp Ser Pro Ala Ile Lys His Gln 65 70 75 80 Phe Leu Leu Thr Gly Asp Thr Gln Gly Arg Tyr Arg Cys Arg Ser Gly 85 90 95 Leu Ser Thr Gly Trp Thr Gln Leu Ser Lys Leu Leu Glu Leu Thr Gly 100 105 110 Pro Lys Ser Leu Pro Ala Pro Trp Leu Ser Met Ala Pro Val Ser Trp 115 120 125 Ile Thr Pro Gly Leu Lys Thr Thr Ala Val Cys Arg Gly Val Leu Arg 130 135 140 Gly Val Thr Phe Leu Leu Arg Arg Glu Gly Asp His Glu Phe Leu Glu 145 150 155 160 Val Pro Glu Ala Gln Glu Asp Val Glu Ala Thr Phe Pro Val His Gln 165 170 175 Pro Gly Asn Tyr Ser Cys Ser Tyr Arg Thr Asp Gly Glu Gly Ala Leu 180 185 190 Ser Glu Pro Ser Ala Thr Val Thr Ile Glu Glu Leu Ala Ala Pro Pro 195 200 205 Pro Pro Val Leu Met His His Gly Glu Ser Ser Gln Val Leu His Pro 210 215 220 Gly Asn Lys Val Thr Leu Thr Cys Val Ala Pro Leu Ser Gly Val Asp 225 230 235 240 Phe Gln Leu Arg Arg Gly Glu Lys Glu Leu Leu Val Pro Arg Ser Ser 245 250 255 Thr Ser Pro Asp Arg Ile Phe Phe His Leu Asn Ala Val Ala Leu Gly 260 265 270 Asp Gly Gly His Tyr Thr Cys Arg Tyr Arg Leu His Asp Asn Gln Asn 275 280 285 Gly Trp Ser Gly Asp Ser Ala Pro Val Glu Leu Ile Leu Ser Asp Glu 290 295 300 Thr Leu Pro Ala Pro Glu Phe Ser Pro Glu Pro Glu Ser Gly Arg Ala 305 310 315 320 Leu Arg Leu Arg Cys Leu Ala Pro Leu Glu Gly Ala Arg Phe Ala Leu 325 330 335 Val Arg Glu Asp Arg Gly Gly Arg Arg Val His Arg Phe Gln Ser Pro 340 345 350 Ala Gly Thr Glu Ala Leu Phe Glu Leu His Asn Ile Ser Val Ala Asp 355 360 365 Ser Ala Asn Tyr Ser Cys Val Tyr Val Asp Leu Lys Pro Pro Phe Gly 370 375 380 Gly Ser Ala Pro Ser Glu Arg Leu Glu Leu His Val Asp Gly Pro Pro 385 390 395 400 Pro Arg Pro Gln Leu Arg Ala Thr Trp Ser Gly Ala Val Leu Ala Gly 405 410 415 Arg Asp Ala Val Leu Arg Cys Glu Gly Pro Ile Pro Asp Val Thr Phe 420 425 430 Glu Leu Leu Arg Glu Gly Glu Thr Lys Ala Val Lys Thr Val Arg Thr 435 440 445 Pro Gly Ala Ala Ala Asn Leu Glu Leu Ile Phe Val Gly Pro Gln His 450 455 460 Ala Gly Asn Tyr Arg Cys Arg Tyr Arg Ser Trp Val Pro His Thr Phe 465 470 475 480 Glu Ser Glu Leu Ser Asp Pro Val Glu Leu Leu Val Ala Glu Ser 485 490 495 270433PRTHomo sapiens 270Met Glu Arg Met Leu Pro Leu Leu Ala Leu Gly Leu Leu Ala Ala Gly 1 5 10 15 Phe Cys Pro Ala Val Leu Cys His Pro Asn Ser Pro Leu Asp Glu Glu 20 25 30 Asn Leu Thr Gln Glu Asn Gln Asp Arg Gly Thr His Val Asp Leu Gly 35 40 45 Leu Ala Ser Ala Asn Val Asp Phe Ala Phe Ser Leu Tyr Lys Gln Leu 50 55 60 Val Leu Lys Ala Leu Asp Lys Asn Val Ile Phe Ser Pro Leu Ser Ile 65 70 75 80 Ser Thr Ala Leu Ala Phe Leu Ser Leu Gly Ala His Asn Thr Thr Leu 85 90 95 Thr Glu Ile Leu Lys Ala Ser Ser Ser Pro His Gly Asp Leu Leu Arg 100 105 110 Gln Lys Phe Thr Gln Ser Phe Gln His Leu Arg Ala Pro Ser Ile Ser 115 120 125 Ser Ser Asp Glu Leu Gln Leu Ser Met Gly Asn Ala Met Phe Val Lys 130 135 140 Glu Gln Leu Ser Leu Leu Asp Arg Phe Thr Glu Asp Ala Lys Arg Leu 145 150 155 160 Tyr Gly Ser Glu Ala Phe Ala Thr Asp Phe Gln Asp Ser Ala Ala Ala 165 170 175 Lys Lys Leu Ile Asn Asp Tyr Val Lys Asn Gly Thr Arg Gly Lys Ile 180 185 190 Thr Asp Leu Ile Lys Asp Pro Asp Ser Gln Thr Met Met Val Leu Val 195 200 205 Asn Tyr Ile Phe Phe Lys Ala Lys Trp Glu Met Pro Phe Asp Pro Gln 210 215 220 Asp Thr His Gln Ser Arg Phe Tyr Leu Ser Lys Lys Lys Trp Val Met 225 230 235 240 Val Pro Met Met Ser Leu His His Leu Thr Ile Pro Tyr Phe Arg Asp 245 250 255 Glu Glu Leu Ser Cys Thr Val Val Glu Leu Lys Tyr Thr Gly Asn Ala 260 265 270 Ser Ala Leu Phe Ile Leu Pro Asp Gln Asp Lys Met Glu Glu Val Glu

275 280 285 Ala Met Leu Leu Pro Glu Thr Leu Lys Arg Trp Arg Asp Ser Leu Glu 290 295 300 Phe Arg Glu Ile Gly Glu Leu Tyr Leu Pro Lys Phe Ser Ile Ser Arg 305 310 315 320 Asp Tyr Asn Leu Asn Asp Ile Leu Leu Gln Leu Gly Ile Glu Glu Ala 325 330 335 Phe Thr Ser Lys Ala Asp Leu Ser Gly Ile Thr Gly Ala Arg Asn Leu 340 345 350 Ala Val Ser Gln Val Val His Lys Val Val Ser Asp Val Phe Glu Glu 355 360 365 Gly Thr Glu Ala Ser Ala Ala Thr Ala Val Lys Ile Thr Leu Leu Ser 370 375 380 Ala Leu Val Glu Thr Arg Thr Ile Val Arg Phe Asn Arg Pro Phe Leu 385 390 395 400 Met Ile Ile Val Pro Thr Asp Thr Gln Asn Ile Phe Phe Met Ser Lys 405 410 415 Val Thr Asn Pro Ser Lys Pro Arg Ala Cys Ile Lys Gln Trp Gly Ser 420 425 430 Gln 2711474PRTHomo sapiens 271Met Gly Lys Asn Lys Leu Leu His Pro Ser Leu Val Leu Leu Leu Leu 1 5 10 15 Val Leu Leu Pro Thr Asp Ala Ser Val Ser Gly Lys Pro Gln Tyr Met 20 25 30 Val Leu Val Pro Ser Leu Leu His Thr Glu Thr Thr Glu Lys Gly Cys 35 40 45 Val Leu Leu Ser Tyr Leu Asn Glu Thr Val Thr Val Ser Ala Ser Leu 50 55 60 Glu Ser Val Arg Gly Asn Arg Ser Leu Phe Thr Asp Leu Glu Ala Glu 65 70 75 80 Asn Asp Val Leu His Cys Val Ala Phe Ala Val Pro Lys Ser Ser Ser 85 90 95 Asn Glu Glu Val Met Phe Leu Thr Val Gln Val Lys Gly Pro Thr Gln 100 105 110 Glu Phe Lys Lys Arg Thr Thr Val Met Val Lys Asn Glu Asp Ser Leu 115 120 125 Val Phe Val Gln Thr Asp Lys Ser Ile Tyr Lys Pro Gly Gln Thr Val 130 135 140 Lys Phe Arg Val Val Ser Met Asp Glu Asn Phe His Pro Leu Asn Glu 145 150 155 160 Leu Ile Pro Leu Val Tyr Ile Gln Asp Pro Lys Gly Asn Arg Ile Ala 165 170 175 Gln Trp Gln Ser Phe Gln Leu Glu Gly Gly Leu Lys Gln Phe Ser Phe 180 185 190 Pro Leu Ser Ser Glu Pro Phe Gln Gly Ser Tyr Lys Val Val Val Gln 195 200 205 Lys Lys Ser Gly Gly Arg Thr Glu His Pro Phe Thr Val Glu Glu Phe 210 215 220 Val Leu Pro Lys Phe Glu Val Gln Val Thr Val Pro Lys Ile Ile Thr 225 230 235 240 Ile Leu Glu Glu Glu Met Asn Val Ser Val Cys Gly Leu Tyr Thr Tyr 245 250 255 Gly Lys Pro Val Pro Gly His Val Thr Val Ser Ile Cys Arg Lys Tyr 260 265 270 Ser Asp Ala Ser Asp Cys His Gly Glu Asp Ser Gln Ala Phe Cys Glu 275 280 285 Lys Phe Ser Gly Gln Leu Asn Ser His Gly Cys Phe Tyr Gln Gln Val 290 295 300 Lys Thr Lys Val Phe Gln Leu Lys Arg Lys Glu Tyr Glu Met Lys Leu 305 310 315 320 His Thr Glu Ala Gln Ile Gln Glu Glu Gly Thr Val Val Glu Leu Thr 325 330 335 Gly Arg Gln Ser Ser Glu Ile Thr Arg Thr Ile Thr Lys Leu Ser Phe 340 345 350 Val Lys Val Asp Ser His Phe Arg Gln Gly Ile Pro Phe Phe Gly Gln 355 360 365 Val Arg Leu Val Asp Gly Lys Gly Val Pro Ile Pro Asn Lys Val Ile 370 375 380 Phe Ile Arg Gly Asn Glu Ala Asn Tyr Tyr Ser Asn Ala Thr Thr Asp 385 390 395 400 Glu His Gly Leu Val Gln Phe Ser Ile Asn Thr Thr Asn Val Met Gly 405 410 415 Thr Ser Leu Thr Val Arg Val Asn Tyr Lys Asp Arg Ser Pro Cys Tyr 420 425 430 Gly Tyr Gln Trp Val Ser Glu Glu His Glu Glu Ala His His Thr Ala 435 440 445 Tyr Leu Val Phe Ser Pro Ser Lys Ser Phe Val His Leu Glu Pro Met 450 455 460 Ser His Glu Leu Pro Cys Gly His Thr Gln Thr Val Gln Ala His Tyr 465 470 475 480 Ile Leu Asn Gly Gly Thr Leu Leu Gly Leu Lys Lys Leu Ser Phe Tyr 485 490 495 Tyr Leu Ile Met Ala Lys Gly Gly Ile Val Arg Thr Gly Thr His Gly 500 505 510 Leu Leu Val Lys Gln Glu Asp Met Lys Gly His Phe Ser Ile Ser Ile 515 520 525 Pro Val Lys Ser Asp Ile Ala Pro Val Ala Arg Leu Leu Ile Tyr Ala 530 535 540 Val Leu Pro Thr Gly Asp Val Ile Gly Asp Ser Ala Lys Tyr Asp Val 545 550 555 560 Glu Asn Cys Leu Ala Asn Lys Val Asp Leu Ser Phe Ser Pro Ser Gln 565 570 575 Ser Leu Pro Ala Ser His Ala His Leu Arg Val Thr Ala Ala Pro Gln 580 585 590 Ser Val Cys Ala Leu Arg Ala Val Asp Gln Ser Val Leu Leu Met Lys 595 600 605 Pro Asp Ala Glu Leu Ser Ala Ser Ser Val Tyr Asn Leu Leu Pro Glu 610 615 620 Lys Asp Leu Thr Gly Phe Pro Gly Pro Leu Asn Asp Gln Asp Asp Glu 625 630 635 640 Asp Cys Ile Asn Arg His Asn Val Tyr Ile Asn Gly Ile Thr Tyr Thr 645 650 655 Pro Val Ser Ser Thr Asn Glu Lys Asp Met Tyr Ser Phe Leu Glu Asp 660 665 670 Met Gly Leu Lys Ala Phe Thr Asn Ser Lys Ile Arg Lys Pro Lys Met 675 680 685 Cys Pro Gln Leu Gln Gln Tyr Glu Met His Gly Pro Glu Gly Leu Arg 690 695 700 Val Gly Phe Tyr Glu Ser Asp Val Met Gly Arg Gly His Ala Arg Leu 705 710 715 720 Val His Val Glu Glu Pro His Thr Glu Thr Val Arg Lys Tyr Phe Pro 725 730 735 Glu Thr Trp Ile Trp Asp Leu Val Val Val Asn Ser Ala Gly Val Ala 740 745 750 Glu Val Gly Val Thr Val Pro Asp Thr Ile Thr Glu Trp Lys Ala Gly 755 760 765 Ala Phe Cys Leu Ser Glu Asp Ala Gly Leu Gly Ile Ser Ser Thr Ala 770 775 780 Ser Leu Arg Ala Phe Gln Pro Phe Phe Val Glu Leu Thr Met Pro Tyr 785 790 795 800 Ser Val Ile Arg Gly Glu Ala Phe Thr Leu Lys Ala Thr Val Leu Asn 805 810 815 Tyr Leu Pro Lys Cys Ile Arg Val Ser Val Gln Leu Glu Ala Ser Pro 820 825 830 Ala Phe Leu Ala Val Pro Val Glu Lys Glu Gln Ala Pro His Cys Ile 835 840 845 Cys Ala Asn Gly Arg Gln Thr Val Ser Trp Ala Val Thr Pro Lys Ser 850 855 860 Leu Gly Asn Val Asn Phe Thr Val Ser Ala Glu Ala Leu Glu Ser Gln 865 870 875 880 Glu Leu Cys Gly Thr Glu Val Pro Ser Val Pro Glu His Gly Arg Lys 885 890 895 Asp Thr Val Ile Lys Pro Leu Leu Val Glu Pro Glu Gly Leu Glu Lys 900 905 910 Glu Thr Thr Phe Asn Ser Leu Leu Cys Pro Ser Gly Gly Glu Val Ser 915 920 925 Glu Glu Leu Ser Leu Lys Leu Pro Pro Asn Val Val Glu Glu Ser Ala 930 935 940 Arg Ala Ser Val Ser Val Leu Gly Asp Ile Leu Gly Ser Ala Met Gln 945 950 955 960 Asn Thr Gln Asn Leu Leu Gln Met Pro Tyr Gly Cys Gly Glu Gln Asn 965 970 975 Met Val Leu Phe Ala Pro Asn Ile Tyr Val Leu Asp Tyr Leu Asn Glu 980 985 990 Thr Gln Gln Leu Thr Pro Glu Val Lys Ser Lys Ala Ile Gly Tyr Leu 995 1000 1005 Asn Thr Gly Tyr Gln Arg Gln Leu Asn Tyr Lys His Tyr Asp Gly 1010 1015 1020 Ser Tyr Ser Thr Phe Gly Glu Arg Tyr Gly Arg Asn Gln Gly Asn 1025 1030 1035 Thr Trp Leu Thr Ala Phe Val Leu Lys Thr Phe Ala Gln Ala Arg 1040 1045 1050 Ala Tyr Ile Phe Ile Asp Glu Ala His Ile Thr Gln Ala Leu Ile 1055 1060 1065 Trp Leu Ser Gln Arg Gln Lys Asp Asn Gly Cys Phe Arg Ser Ser 1070 1075 1080 Gly Ser Leu Leu Asn Asn Ala Ile Lys Gly Gly Val Glu Asp Glu 1085 1090 1095 Val Thr Leu Ser Ala Tyr Ile Thr Ile Ala Leu Leu Glu Ile Pro 1100 1105 1110 Leu Thr Val Thr His Pro Val Val Arg Asn Ala Leu Phe Cys Leu 1115 1120 1125 Glu Ser Ala Trp Lys Thr Ala Gln Glu Gly Asp His Gly Ser His 1130 1135 1140 Val Tyr Thr Lys Ala Leu Leu Ala Tyr Ala Phe Ala Leu Ala Gly 1145 1150 1155 Asn Gln Asp Lys Arg Lys Glu Val Leu Lys Ser Leu Asn Glu Glu 1160 1165 1170 Ala Val Lys Lys Asp Asn Ser Val His Trp Glu Arg Pro Gln Lys 1175 1180 1185 Pro Lys Ala Pro Val Gly His Phe Tyr Glu Pro Gln Ala Pro Ser 1190 1195 1200 Ala Glu Val Glu Met Thr Ser Tyr Val Leu Leu Ala Tyr Leu Thr 1205 1210 1215 Ala Gln Pro Ala Pro Thr Ser Glu Asp Leu Thr Ser Ala Thr Asn 1220 1225 1230 Ile Val Lys Trp Ile Thr Lys Gln Gln Asn Ala Gln Gly Gly Phe 1235 1240 1245 Ser Ser Thr Gln Asp Thr Val Val Ala Leu His Ala Leu Ser Lys 1250 1255 1260 Tyr Gly Ala Ala Thr Phe Thr Arg Thr Gly Lys Ala Ala Gln Val 1265 1270 1275 Thr Ile Gln Ser Ser Gly Thr Phe Ser Ser Lys Phe Gln Val Asp 1280 1285 1290 Asn Asn Asn Arg Leu Leu Leu Gln Gln Val Ser Leu Pro Glu Leu 1295 1300 1305 Pro Gly Glu Tyr Ser Met Lys Val Thr Gly Glu Gly Cys Val Tyr 1310 1315 1320 Leu Gln Thr Ser Leu Lys Tyr Asn Ile Leu Pro Glu Lys Glu Glu 1325 1330 1335 Phe Pro Phe Ala Leu Gly Val Gln Thr Leu Pro Gln Thr Cys Asp 1340 1345 1350 Glu Pro Lys Ala His Thr Ser Phe Gln Ile Ser Leu Ser Val Ser 1355 1360 1365 Tyr Thr Gly Ser Arg Ser Ala Ser Asn Met Ala Ile Val Asp Val 1370 1375 1380 Lys Met Val Ser Gly Phe Ile Pro Leu Lys Pro Thr Val Lys Met 1385 1390 1395 Leu Glu Arg Ser Asn His Val Ser Arg Thr Glu Val Ser Ser Asn 1400 1405 1410 His Val Leu Ile Tyr Leu Asp Lys Val Ser Asn Gln Thr Leu Ser 1415 1420 1425 Leu Phe Phe Thr Val Leu Gln Asp Val Pro Val Arg Asp Leu Lys 1430 1435 1440 Pro Ala Ile Val Lys Val Tyr Asp Tyr Tyr Glu Thr Asp Glu Phe 1445 1450 1455 Ala Ile Ala Glu Tyr Asn Ala Pro Cys Ser Lys Asp Leu Gly Asn 1460 1465 1470 Ala 272491PRTHomo sapiens 272Met Ala Leu Leu Trp Gly Leu Leu Val Leu Ser Trp Ser Cys Leu Gln 1 5 10 15 Gly Pro Cys Ser Val Phe Ser Pro Val Ser Ala Met Glu Pro Leu Gly 20 25 30 Trp Gln Leu Thr Ser Gly Pro Asn Gln Glu Gln Val Ser Pro Leu Thr 35 40 45 Leu Leu Lys Leu Gly Asn Gln Glu Pro Gly Gly Gln Thr Ala Leu Lys 50 55 60 Ser Pro Pro Gly Val Cys Ser Arg Asp Pro Thr Pro Glu Gln Thr His 65 70 75 80 Arg Leu Ala Arg Ala Met Met Ala Phe Thr Ala Asp Leu Phe Ser Leu 85 90 95 Val Ala Gln Thr Ser Thr Cys Pro Asn Leu Ile Leu Ser Pro Leu Ser 100 105 110 Val Ala Leu Ala Leu Ser His Leu Ala Leu Gly Ala Gln Asn His Thr 115 120 125 Leu Gln Arg Leu Gln Gln Val Leu His Ala Gly Ser Gly Pro Cys Leu 130 135 140 Pro His Leu Leu Ser Arg Leu Cys Gln Asp Leu Gly Pro Gly Ala Phe 145 150 155 160 Arg Leu Ala Ala Arg Met Tyr Leu Gln Lys Gly Phe Pro Ile Lys Glu 165 170 175 Asp Phe Leu Glu Gln Ser Glu Gln Leu Phe Gly Ala Lys Pro Val Ser 180 185 190 Leu Thr Gly Lys Gln Glu Asp Asp Leu Ala Asn Ile Asn Gln Trp Val 195 200 205 Lys Glu Ala Thr Glu Gly Lys Ile Gln Glu Phe Leu Ser Gly Leu Pro 210 215 220 Glu Asp Thr Val Leu Leu Leu Leu Asn Ala Ile His Phe Gln Gly Phe 225 230 235 240 Trp Arg Asn Lys Phe Asp Pro Ser Leu Thr Gln Arg Asp Ser Phe His 245 250 255 Leu Asp Glu Gln Phe Thr Val Pro Val Glu Met Met Gln Ala Arg Thr 260 265 270 Tyr Pro Leu Arg Trp Phe Leu Leu Glu Gln Pro Glu Ile Gln Val Ala 275 280 285 His Phe Pro Phe Lys Asn Asn Met Ser Phe Val Val Leu Val Pro Thr 290 295 300 His Phe Glu Trp Asn Val Ser Gln Val Leu Ala Asn Leu Ser Trp Asp 305 310 315 320 Thr Leu His Pro Pro Leu Val Trp Glu Arg Pro Thr Lys Val Arg Leu 325 330 335 Pro Lys Leu Tyr Leu Lys His Gln Met Asp Leu Val Ala Thr Leu Ser 340 345 350 Gln Leu Gly Leu Gln Glu Leu Phe Gln Ala Pro Asp Leu Arg Gly Ile 355 360 365 Ser Glu Gln Ser Leu Val Val Ser Gly Val Gln His Gln Ser Thr Leu 370 375 380 Glu Leu Ser Glu Val Gly Val Glu Ala Ala Ala Ala Thr Ser Ile Ala 385 390 395 400 Met Ser Arg Met Ser Leu Ser Ser Phe Ser Val Asn Arg Pro Phe Leu 405 410 415 Phe Phe Ile Phe Glu Asp Thr Thr Gly Leu Pro Leu Phe Val Gly Ser 420 425 430 Val Arg Asn Pro Asn Pro Ser Ala Pro Arg Glu Leu Lys Glu Gln Gln 435 440 445 Asp Ser Pro Gly Asn Lys Asp Phe Leu Gln Ser Leu Lys Gly Phe Pro 450 455 460 Arg Gly Asp Lys Leu Phe Gly Pro Asp Leu Lys Leu Val Pro Pro Met 465 470 475 480 Glu Glu Asp Tyr Pro Gln Phe Gly Ser Pro Lys 485 490 273485PRTHomo sapiens 273Met Arg Lys Arg Ala Pro Gln Ser Glu Met Ala Pro Ala Gly Val Ser 1 5 10 15 Leu Arg Ala Thr Ile Leu Cys Leu Leu Ala Trp Ala Gly Leu Ala Ala 20 25 30 Gly Asp Arg Val Tyr Ile His Pro Phe His Leu Val Ile His Asn Glu 35 40 45 Ser Thr Cys Glu Gln Leu Ala Lys Ala Asn Ala Gly Lys Pro Lys Asp 50 55 60 Pro Thr Phe Ile Pro Ala Pro Ile Gln Ala Lys Thr Ser Pro Val Asp 65 70 75 80 Glu Lys Ala Leu Gln Asp Gln Leu Val Leu Val Ala Ala Lys Leu Asp 85 90 95 Thr Glu Asp Lys Leu Arg Ala Ala Met Val Gly Met Leu Ala Asn Phe 100 105 110 Leu Gly Phe Arg Ile Tyr Gly Met His Ser Glu Leu Trp Gly Val Val 115 120 125 His Gly Ala Thr Val Leu Ser Pro Thr Ala Val Phe Gly Thr Leu Ala 130 135 140 Ser Leu Tyr Leu Gly Ala Leu Asp His Thr Ala Asp Arg Leu Gln Ala 145 150

155 160 Ile Leu Gly Val Pro Trp Lys Asp Lys Asn Cys Thr Ser Arg Leu Asp 165 170 175 Ala His Lys Val Leu Ser Ala Leu Gln Ala Val Gln Gly Leu Leu Val 180 185 190 Ala Gln Gly Arg Ala Asp Ser Gln Ala Gln Leu Leu Leu Ser Thr Val 195 200 205 Val Gly Val Phe Thr Ala Pro Gly Leu His Leu Lys Gln Pro Phe Val 210 215 220 Gln Gly Leu Ala Leu Tyr Thr Pro Val Val Leu Pro Arg Ser Leu Asp 225 230 235 240 Phe Thr Glu Leu Asp Val Ala Ala Glu Lys Ile Asp Arg Phe Met Gln 245 250 255 Ala Val Thr Gly Trp Lys Thr Gly Cys Ser Leu Met Gly Ala Ser Val 260 265 270 Asp Ser Thr Leu Ala Phe Asn Thr Tyr Val His Phe Gln Gly Lys Met 275 280 285 Lys Gly Phe Ser Leu Leu Ala Glu Pro Gln Glu Phe Trp Val Asp Asn 290 295 300 Ser Thr Ser Val Ser Val Pro Met Leu Ser Gly Met Gly Thr Phe Gln 305 310 315 320 His Trp Ser Asp Ile Gln Asp Asn Phe Ser Val Thr Gln Val Pro Phe 325 330 335 Thr Glu Ser Ala Cys Leu Leu Leu Ile Gln Pro His Tyr Ala Ser Asp 340 345 350 Leu Asp Lys Val Glu Gly Leu Thr Phe Gln Gln Asn Ser Leu Asn Trp 355 360 365 Met Lys Lys Leu Ser Pro Arg Thr Ile His Leu Thr Met Pro Gln Leu 370 375 380 Val Leu Gln Gly Ser Tyr Asp Leu Gln Asp Leu Leu Ala Gln Ala Glu 385 390 395 400 Leu Pro Ala Ile Leu His Thr Glu Leu Asn Leu Gln Lys Leu Ser Asn 405 410 415 Asp Arg Ile Arg Val Gly Glu Val Leu Asn Ser Ile Phe Phe Glu Leu 420 425 430 Glu Ala Asp Glu Arg Glu Pro Thr Glu Ser Thr Gln Gln Leu Asn Lys 435 440 445 Pro Glu Val Leu Glu Val Thr Leu Asn Arg Pro Phe Leu Phe Ala Val 450 455 460 Tyr Asp Gln Ser Ala Thr Ala Leu His Phe Leu Gly Arg Val Ala Asn 465 470 475 480 Pro Leu Ser Thr Ala 485 274267PRTHomo sapiens 274Met Lys Ala Ala Val Leu Thr Leu Ala Val Leu Phe Leu Thr Gly Ser 1 5 10 15 Gln Ala Arg His Phe Trp Gln Gln Asp Glu Pro Pro Gln Ser Pro Trp 20 25 30 Asp Arg Val Lys Asp Leu Ala Thr Val Tyr Val Asp Val Leu Lys Asp 35 40 45 Ser Gly Arg Asp Tyr Val Ser Gln Phe Glu Gly Ser Ala Leu Gly Lys 50 55 60 Gln Leu Asn Leu Lys Leu Leu Asp Asn Trp Asp Ser Val Thr Ser Thr 65 70 75 80 Phe Ser Lys Leu Arg Glu Gln Leu Gly Pro Val Thr Gln Glu Phe Trp 85 90 95 Asp Asn Leu Glu Lys Glu Thr Glu Gly Leu Arg Gln Glu Met Ser Lys 100 105 110 Asp Leu Glu Glu Val Lys Ala Lys Val Gln Pro Tyr Leu Asp Asp Phe 115 120 125 Gln Lys Lys Trp Gln Glu Glu Met Glu Leu Tyr Arg Gln Lys Val Glu 130 135 140 Pro Leu Arg Ala Glu Leu Gln Glu Gly Ala Arg Gln Lys Leu His Glu 145 150 155 160 Leu Gln Glu Lys Leu Ser Pro Leu Gly Glu Glu Met Arg Asp Arg Ala 165 170 175 Arg Ala His Val Asp Ala Leu Arg Thr His Leu Ala Pro Tyr Ser Asp 180 185 190 Glu Leu Arg Gln Arg Leu Ala Ala Arg Leu Glu Ala Leu Lys Glu Asn 195 200 205 Gly Gly Ala Arg Leu Ala Glu Tyr His Ala Lys Ala Thr Glu His Leu 210 215 220 Ser Thr Leu Ser Glu Lys Ala Lys Pro Ala Leu Glu Asp Leu Arg Gln 225 230 235 240 Gly Leu Leu Pro Val Leu Glu Ser Phe Lys Val Ser Phe Leu Ser Ala 245 250 255 Leu Glu Glu Tyr Thr Lys Lys Leu Asn Thr Gln 260 265 275100PRTHomo sapiens 275Met Lys Leu Leu Ala Ala Thr Val Leu Leu Leu Thr Ile Cys Ser Leu 1 5 10 15 Glu Gly Ala Leu Val Arg Arg Gln Ala Lys Glu Pro Cys Val Glu Ser 20 25 30 Leu Val Ser Gln Tyr Phe Gln Thr Val Thr Asp Tyr Gly Lys Asp Leu 35 40 45 Met Glu Lys Val Lys Ser Pro Glu Leu Gln Ala Glu Ala Lys Ser Tyr 50 55 60 Phe Glu Lys Ser Lys Glu Gln Leu Thr Pro Leu Ile Lys Lys Ala Gly 65 70 75 80 Thr Glu Leu Val Asn Phe Leu Ser Tyr Phe Val Glu Leu Gly Thr Gln 85 90 95 Pro Ala Thr Gln 100 276396PRTHomo sapiens 276Met Phe Leu Lys Ala Val Val Leu Thr Leu Ala Leu Val Ala Val Ala 1 5 10 15 Gly Ala Arg Ala Glu Val Ser Ala Asp Gln Val Ala Thr Val Met Trp 20 25 30 Asp Tyr Phe Ser Gln Leu Ser Asn Asn Ala Lys Glu Ala Val Glu His 35 40 45 Leu Gln Lys Ser Glu Leu Thr Gln Gln Leu Asn Ala Leu Phe Gln Asp 50 55 60 Lys Leu Gly Glu Val Asn Thr Tyr Ala Gly Asp Leu Gln Lys Lys Leu 65 70 75 80 Val Pro Phe Ala Thr Glu Leu His Glu Arg Leu Ala Lys Asp Ser Glu 85 90 95 Lys Leu Lys Glu Glu Ile Gly Lys Glu Leu Glu Glu Leu Arg Ala Arg 100 105 110 Leu Leu Pro His Ala Asn Glu Val Ser Gln Lys Ile Gly Asp Asn Leu 115 120 125 Arg Glu Leu Gln Gln Arg Leu Glu Pro Tyr Ala Asp Gln Leu Arg Thr 130 135 140 Gln Val Asn Thr Gln Ala Glu Gln Leu Arg Arg Gln Leu Thr Pro Tyr 145 150 155 160 Ala Gln Arg Met Glu Arg Val Leu Arg Glu Asn Ala Asp Ser Leu Gln 165 170 175 Ala Ser Leu Arg Pro His Ala Asp Glu Leu Lys Ala Lys Ile Asp Gln 180 185 190 Asn Val Glu Glu Leu Lys Gly Arg Leu Thr Pro Tyr Ala Asp Glu Phe 195 200 205 Lys Val Lys Ile Asp Gln Thr Val Glu Glu Leu Arg Arg Ser Leu Ala 210 215 220 Pro Tyr Ala Gln Asp Thr Gln Glu Lys Leu Asn His Gln Leu Glu Gly 225 230 235 240 Leu Thr Phe Gln Met Lys Lys Asn Ala Glu Glu Leu Lys Ala Arg Ile 245 250 255 Ser Ala Ser Ala Glu Glu Leu Arg Gln Arg Leu Ala Pro Leu Ala Glu 260 265 270 Asp Val Arg Gly Asn Leu Arg Gly Asn Thr Glu Gly Leu Gln Lys Ser 275 280 285 Leu Ala Glu Leu Gly Gly His Leu Asp Gln Gln Val Glu Glu Phe Arg 290 295 300 Arg Arg Val Glu Pro Tyr Gly Glu Asn Phe Asn Lys Ala Leu Val Gln 305 310 315 320 Gln Met Glu Gln Leu Arg Thr Lys Leu Gly Pro His Ala Gly Asp Val 325 330 335 Glu Gly His Leu Ser Phe Leu Glu Lys Asp Leu Arg Asp Lys Val Asn 340 345 350 Ser Phe Phe Ser Thr Phe Lys Glu Lys Glu Ser Gln Asp Lys Thr Leu 355 360 365 Ser Leu Pro Glu Leu Glu Gln Gln Gln Glu Gln His Gln Glu Gln Gln 370 375 380 Gln Glu Gln Val Gln Met Leu Ala Pro Leu Glu Ser 385 390 395 2774563PRTHomo sapiens 277Met Asp Pro Pro Arg Pro Ala Leu Leu Ala Leu Leu Ala Leu Pro Ala 1 5 10 15 Leu Leu Leu Leu Leu Leu Ala Gly Ala Arg Ala Glu Glu Glu Met Leu 20 25 30 Glu Asn Val Ser Leu Val Cys Pro Lys Asp Ala Thr Arg Phe Lys His 35 40 45 Leu Arg Lys Tyr Thr Tyr Asn Tyr Glu Ala Glu Ser Ser Ser Gly Val 50 55 60 Pro Gly Thr Ala Asp Ser Arg Ser Ala Thr Arg Ile Asn Cys Lys Val 65 70 75 80 Glu Leu Glu Val Pro Gln Leu Cys Ser Phe Ile Leu Lys Thr Ser Gln 85 90 95 Cys Thr Leu Lys Glu Val Tyr Gly Phe Asn Pro Glu Gly Lys Ala Leu 100 105 110 Leu Lys Lys Thr Lys Asn Ser Glu Glu Phe Ala Ala Ala Met Ser Arg 115 120 125 Tyr Glu Leu Lys Leu Ala Ile Pro Glu Gly Lys Gln Val Phe Leu Tyr 130 135 140 Pro Glu Lys Asp Glu Pro Thr Tyr Ile Leu Asn Ile Lys Arg Gly Ile 145 150 155 160 Ile Ser Ala Leu Leu Val Pro Pro Glu Thr Glu Glu Ala Lys Gln Val 165 170 175 Leu Phe Leu Asp Thr Val Tyr Gly Asn Cys Ser Thr His Phe Thr Val 180 185 190 Lys Thr Arg Lys Gly Asn Val Ala Thr Glu Ile Ser Thr Glu Arg Asp 195 200 205 Leu Gly Gln Cys Asp Arg Phe Lys Pro Ile Arg Thr Gly Ile Ser Pro 210 215 220 Leu Ala Leu Ile Lys Gly Met Thr Arg Pro Leu Ser Thr Leu Ile Ser 225 230 235 240 Ser Ser Gln Ser Cys Gln Tyr Thr Leu Asp Ala Lys Arg Lys His Val 245 250 255 Ala Glu Ala Ile Cys Lys Glu Gln His Leu Phe Leu Pro Phe Ser Tyr 260 265 270 Asn Asn Lys Tyr Gly Met Val Ala Gln Val Thr Gln Thr Leu Lys Leu 275 280 285 Glu Asp Thr Pro Lys Ile Asn Ser Arg Phe Phe Gly Glu Gly Thr Lys 290 295 300 Lys Met Gly Leu Ala Phe Glu Ser Thr Lys Ser Thr Ser Pro Pro Lys 305 310 315 320 Gln Ala Glu Ala Val Leu Lys Thr Leu Gln Glu Leu Lys Lys Leu Thr 325 330 335 Ile Ser Glu Gln Asn Ile Gln Arg Ala Asn Leu Phe Asn Lys Leu Val 340 345 350 Thr Glu Leu Arg Gly Leu Ser Asp Glu Ala Val Thr Ser Leu Leu Pro 355 360 365 Gln Leu Ile Glu Val Ser Ser Pro Ile Thr Leu Gln Ala Leu Val Gln 370 375 380 Cys Gly Gln Pro Gln Cys Ser Thr His Ile Leu Gln Trp Leu Lys Arg 385 390 395 400 Val His Ala Asn Pro Leu Leu Ile Asp Val Val Thr Tyr Leu Val Ala 405 410 415 Leu Ile Pro Glu Pro Ser Ala Gln Gln Leu Arg Glu Ile Phe Asn Met 420 425 430 Ala Arg Asp Gln Arg Ser Arg Ala Thr Leu Tyr Ala Leu Ser His Ala 435 440 445 Val Asn Asn Tyr His Lys Thr Asn Pro Thr Gly Thr Gln Glu Leu Leu 450 455 460 Asp Ile Ala Asn Tyr Leu Met Glu Gln Ile Gln Asp Asp Cys Thr Gly 465 470 475 480 Asp Glu Asp Tyr Thr Tyr Leu Ile Leu Arg Val Ile Gly Asn Met Gly 485 490 495 Gln Thr Met Glu Gln Leu Thr Pro Glu Leu Lys Ser Ser Ile Leu Lys 500 505 510 Cys Val Gln Ser Thr Lys Pro Ser Leu Met Ile Gln Lys Ala Ala Ile 515 520 525 Gln Ala Leu Arg Lys Met Glu Pro Lys Asp Lys Asp Gln Glu Val Leu 530 535 540 Leu Gln Thr Phe Leu Asp Asp Ala Ser Pro Gly Asp Lys Arg Leu Ala 545 550 555 560 Ala Tyr Leu Met Leu Met Arg Ser Pro Ser Gln Ala Asp Ile Asn Lys 565 570 575 Ile Val Gln Ile Leu Pro Trp Glu Gln Asn Glu Gln Val Lys Asn Phe 580 585 590 Val Ala Ser His Ile Ala Asn Ile Leu Asn Ser Glu Glu Leu Asp Ile 595 600 605 Gln Asp Leu Lys Lys Leu Val Lys Glu Ala Leu Lys Glu Ser Gln Leu 610 615 620 Pro Thr Val Met Asp Phe Arg Lys Phe Ser Arg Asn Tyr Gln Leu Tyr 625 630 635 640 Lys Ser Val Ser Leu Pro Ser Leu Asp Pro Ala Ser Ala Lys Ile Glu 645 650 655 Gly Asn Leu Ile Phe Asp Pro Asn Asn Tyr Leu Pro Lys Glu Ser Met 660 665 670 Leu Lys Thr Thr Leu Thr Ala Phe Gly Phe Ala Ser Ala Asp Leu Ile 675 680 685 Glu Ile Gly Leu Glu Gly Lys Gly Phe Glu Pro Thr Leu Glu Ala Leu 690 695 700 Phe Gly Lys Gln Gly Phe Phe Pro Asp Ser Val Asn Lys Ala Leu Tyr 705 710 715 720 Trp Val Asn Gly Gln Val Pro Asp Gly Val Ser Lys Val Leu Val Asp 725 730 735 His Phe Gly Tyr Thr Lys Asp Asp Lys His Glu Gln Asp Met Val Asn 740 745 750 Gly Ile Met Leu Ser Val Glu Lys Leu Ile Lys Asp Leu Lys Ser Lys 755 760 765 Glu Val Pro Glu Ala Arg Ala Tyr Leu Arg Ile Leu Gly Glu Glu Leu 770 775 780 Gly Phe Ala Ser Leu His Asp Leu Gln Leu Leu Gly Lys Leu Leu Leu 785 790 795 800 Met Gly Ala Arg Thr Leu Gln Gly Ile Pro Gln Met Ile Gly Glu Val 805 810 815 Ile Arg Lys Gly Ser Lys Asn Asp Phe Phe Leu His Tyr Ile Phe Met 820 825 830 Glu Asn Ala Phe Glu Leu Pro Thr Gly Ala Gly Leu Gln Leu Gln Ile 835 840 845 Ser Ser Ser Gly Val Ile Ala Pro Gly Ala Lys Ala Gly Val Lys Leu 850 855 860 Glu Val Ala Asn Met Gln Ala Glu Leu Val Ala Lys Pro Ser Val Ser 865 870 875 880 Val Glu Phe Val Thr Asn Met Gly Ile Ile Ile Pro Asp Phe Ala Arg 885 890 895 Ser Gly Val Gln Met Asn Thr Asn Phe Phe His Glu Ser Gly Leu Glu 900 905 910 Ala His Val Ala Leu Lys Ala Gly Lys Leu Lys Phe Ile Ile Pro Ser 915 920 925 Pro Lys Arg Pro Val Lys Leu Leu Ser Gly Gly Asn Thr Leu His Leu 930 935 940 Val Ser Thr Thr Lys Thr Glu Val Ile Pro Pro Leu Ile Glu Asn Arg 945 950 955 960 Gln Ser Trp Ser Val Cys Lys Gln Val Phe Pro Gly Leu Asn Tyr Cys 965 970 975 Thr Ser Gly Ala Tyr Ser Asn Ala Ser Ser Thr Asp Ser Ala Ser Tyr 980 985 990 Tyr Pro Leu Thr Gly Asp Thr Arg Leu Glu Leu Glu Leu Arg Pro Thr 995 1000 1005 Gly Glu Ile Glu Gln Tyr Ser Val Ser Ala Thr Tyr Glu Leu Gln 1010 1015 1020 Arg Glu Asp Arg Ala Leu Val Asp Thr Leu Lys Phe Val Thr Gln 1025 1030 1035 Ala Glu Gly Ala Lys Gln Thr Glu Ala Thr Met Thr Phe Lys Tyr 1040 1045 1050 Asn Arg Gln Ser Met Thr Leu Ser Ser Glu Val Gln Ile Pro Asp 1055 1060 1065 Phe Asp Val Asp Leu Gly Thr Ile Leu Arg Val Asn Asp Glu Ser 1070 1075 1080 Thr Glu Gly Lys Thr Ser Tyr Arg Leu Thr Leu Asp Ile Gln Asn 1085 1090 1095 Lys Lys Ile Thr Glu Val Ala Leu Met Gly His Leu Ser Cys Asp 1100 1105 1110 Thr Lys Glu Glu Arg Lys Ile Lys Gly Val Ile Ser Ile Pro Arg 1115 1120 1125 Leu Gln Ala Glu Ala Arg Ser Glu Ile Leu Ala His Trp Ser Pro 1130 1135 1140 Ala Lys Leu Leu Leu Gln Met Asp Ser Ser Ala Thr Ala Tyr Gly 1145 1150 1155 Ser Thr Val Ser Lys Arg Val Ala Trp His Tyr Asp Glu Glu Lys 1160 1165 1170 Ile Glu Phe Glu Trp Asn Thr Gly Thr Asn Val Asp Thr Lys Lys 1175 1180 1185 Met Thr Ser Asn Phe Pro Val

Asp Leu Ser Asp Tyr Pro Lys Ser 1190 1195 1200 Leu His Met Tyr Ala Asn Arg Leu Leu Asp His Arg Val Pro Glu 1205 1210 1215 Thr Asp Met Thr Phe Arg His Val Gly Ser Lys Leu Ile Val Ala 1220 1225 1230 Met Ser Ser Trp Leu Gln Lys Ala Ser Gly Ser Leu Pro Tyr Thr 1235 1240 1245 Gln Thr Leu Gln Asp His Leu Asn Ser Leu Lys Glu Phe Asn Leu 1250 1255 1260 Gln Asn Met Gly Leu Pro Asp Phe His Ile Pro Glu Asn Leu Phe 1265 1270 1275 Leu Lys Ser Asp Gly Arg Val Lys Tyr Thr Leu Asn Lys Asn Ser 1280 1285 1290 Leu Lys Ile Glu Ile Pro Leu Pro Phe Gly Gly Lys Ser Ser Arg 1295 1300 1305 Asp Leu Lys Met Leu Glu Thr Val Arg Thr Pro Ala Leu His Phe 1310 1315 1320 Lys Ser Val Gly Phe His Leu Pro Ser Arg Glu Phe Gln Val Pro 1325 1330 1335 Thr Phe Thr Ile Pro Lys Leu Tyr Gln Leu Gln Val Pro Leu Leu 1340 1345 1350 Gly Val Leu Asp Leu Ser Thr Asn Val Tyr Ser Asn Leu Tyr Asn 1355 1360 1365 Trp Ser Ala Ser Tyr Ser Gly Gly Asn Thr Ser Thr Asp His Phe 1370 1375 1380 Ser Leu Arg Ala Arg Tyr His Met Lys Ala Asp Ser Val Val Asp 1385 1390 1395 Leu Leu Ser Tyr Asn Val Gln Gly Ser Gly Glu Thr Thr Tyr Asp 1400 1405 1410 His Lys Asn Thr Phe Thr Leu Ser Cys Asp Gly Ser Leu Arg His 1415 1420 1425 Lys Phe Leu Asp Ser Asn Ile Lys Phe Ser His Val Glu Lys Leu 1430 1435 1440 Gly Asn Asn Pro Val Ser Lys Gly Leu Leu Ile Phe Asp Ala Ser 1445 1450 1455 Ser Ser Trp Gly Pro Gln Met Ser Ala Ser Val His Leu Asp Ser 1460 1465 1470 Lys Lys Lys Gln His Leu Phe Val Lys Glu Val Lys Ile Asp Gly 1475 1480 1485 Gln Phe Arg Val Ser Ser Phe Tyr Ala Lys Gly Thr Tyr Gly Leu 1490 1495 1500 Ser Cys Gln Arg Asp Pro Asn Thr Gly Arg Leu Asn Gly Glu Ser 1505 1510 1515 Asn Leu Arg Phe Asn Ser Ser Tyr Leu Gln Gly Thr Asn Gln Ile 1520 1525 1530 Thr Gly Arg Tyr Glu Asp Gly Thr Leu Ser Leu Thr Ser Thr Ser 1535 1540 1545 Asp Leu Gln Ser Gly Ile Ile Lys Asn Thr Ala Ser Leu Lys Tyr 1550 1555 1560 Glu Asn Tyr Glu Leu Thr Leu Lys Ser Asp Thr Asn Gly Lys Tyr 1565 1570 1575 Lys Asn Phe Ala Thr Ser Asn Lys Met Asp Met Thr Phe Ser Lys 1580 1585 1590 Gln Asn Ala Leu Leu Arg Ser Glu Tyr Gln Ala Asp Tyr Glu Ser 1595 1600 1605 Leu Arg Phe Phe Ser Leu Leu Ser Gly Ser Leu Asn Ser His Gly 1610 1615 1620 Leu Glu Leu Asn Ala Asp Ile Leu Gly Thr Asp Lys Ile Asn Ser 1625 1630 1635 Gly Ala His Lys Ala Thr Leu Arg Ile Gly Gln Asp Gly Ile Ser 1640 1645 1650 Thr Ser Ala Thr Thr Asn Leu Lys Cys Ser Leu Leu Val Leu Glu 1655 1660 1665 Asn Glu Leu Asn Ala Glu Leu Gly Leu Ser Gly Ala Ser Met Lys 1670 1675 1680 Leu Thr Thr Asn Gly Arg Phe Arg Glu His Asn Ala Lys Phe Ser 1685 1690 1695 Leu Asp Gly Lys Ala Ala Leu Thr Glu Leu Ser Leu Gly Ser Ala 1700 1705 1710 Tyr Gln Ala Met Ile Leu Gly Val Asp Ser Lys Asn Ile Phe Asn 1715 1720 1725 Phe Lys Val Ser Gln Glu Gly Leu Lys Leu Ser Asn Asp Met Met 1730 1735 1740 Gly Ser Tyr Ala Glu Met Lys Phe Asp His Thr Asn Ser Leu Asn 1745 1750 1755 Ile Ala Gly Leu Ser Leu Asp Phe Ser Ser Lys Leu Asp Asn Ile 1760 1765 1770 Tyr Ser Ser Asp Lys Phe Tyr Lys Gln Thr Val Asn Leu Gln Leu 1775 1780 1785 Gln Pro Tyr Ser Leu Val Thr Thr Leu Asn Ser Asp Leu Lys Tyr 1790 1795 1800 Asn Ala Leu Asp Leu Thr Asn Asn Gly Lys Leu Arg Leu Glu Pro 1805 1810 1815 Leu Lys Leu His Val Ala Gly Asn Leu Lys Gly Ala Tyr Gln Asn 1820 1825 1830 Asn Glu Ile Lys His Ile Tyr Ala Ile Ser Ser Ala Ala Leu Ser 1835 1840 1845 Ala Ser Tyr Lys Ala Asp Thr Val Ala Lys Val Gln Gly Val Glu 1850 1855 1860 Phe Ser His Arg Leu Asn Thr Asp Ile Ala Gly Leu Ala Ser Ala 1865 1870 1875 Ile Asp Met Ser Thr Asn Tyr Asn Ser Asp Ser Leu His Phe Ser 1880 1885 1890 Asn Val Phe Arg Ser Val Met Ala Pro Phe Thr Met Thr Ile Asp 1895 1900 1905 Ala His Thr Asn Gly Asn Gly Lys Leu Ala Leu Trp Gly Glu His 1910 1915 1920 Thr Gly Gln Leu Tyr Ser Lys Phe Leu Leu Lys Ala Glu Pro Leu 1925 1930 1935 Ala Phe Thr Phe Ser His Asp Tyr Lys Gly Ser Thr Ser His His 1940 1945 1950 Leu Val Ser Arg Lys Ser Ile Ser Ala Ala Leu Glu His Lys Val 1955 1960 1965 Ser Ala Leu Leu Thr Pro Ala Glu Gln Thr Gly Thr Trp Lys Leu 1970 1975 1980 Lys Thr Gln Phe Asn Asn Asn Glu Tyr Ser Gln Asp Leu Asp Ala 1985 1990 1995 Tyr Asn Thr Lys Asp Lys Ile Gly Val Glu Leu Thr Gly Arg Thr 2000 2005 2010 Leu Ala Asp Leu Thr Leu Leu Asp Ser Pro Ile Lys Val Pro Leu 2015 2020 2025 Leu Leu Ser Glu Pro Ile Asn Ile Ile Asp Ala Leu Glu Met Arg 2030 2035 2040 Asp Ala Val Glu Lys Pro Gln Glu Phe Thr Ile Val Ala Phe Val 2045 2050 2055 Lys Tyr Asp Lys Asn Gln Asp Val His Ser Ile Asn Leu Pro Phe 2060 2065 2070 Phe Glu Thr Leu Gln Glu Tyr Phe Glu Arg Asn Arg Gln Thr Ile 2075 2080 2085 Ile Val Val Val Glu Asn Val Gln Arg Asn Leu Lys His Ile Asn 2090 2095 2100 Ile Asp Gln Phe Val Arg Lys Tyr Arg Ala Ala Leu Gly Lys Leu 2105 2110 2115 Pro Gln Gln Ala Asn Asp Tyr Leu Asn Ser Phe Asn Trp Glu Arg 2120 2125 2130 Gln Val Ser His Ala Lys Glu Lys Leu Thr Ala Leu Thr Lys Lys 2135 2140 2145 Tyr Arg Ile Thr Glu Asn Asp Ile Gln Ile Ala Leu Asp Asp Ala 2150 2155 2160 Lys Ile Asn Phe Asn Glu Lys Leu Ser Gln Leu Gln Thr Tyr Met 2165 2170 2175 Ile Gln Phe Asp Gln Tyr Ile Lys Asp Ser Tyr Asp Leu His Asp 2180 2185 2190 Leu Lys Ile Ala Ile Ala Asn Ile Ile Asp Glu Ile Ile Glu Lys 2195 2200 2205 Leu Lys Ser Leu Asp Glu His Tyr His Ile Arg Val Asn Leu Val 2210 2215 2220 Lys Thr Ile His Asp Leu His Leu Phe Ile Glu Asn Ile Asp Phe 2225 2230 2235 Asn Lys Ser Gly Ser Ser Thr Ala Ser Trp Ile Gln Asn Val Asp 2240 2245 2250 Thr Lys Tyr Gln Ile Arg Ile Gln Ile Gln Glu Lys Leu Gln Gln 2255 2260 2265 Leu Lys Arg His Ile Gln Asn Ile Asp Ile Gln His Leu Ala Gly 2270 2275 2280 Lys Leu Lys Gln His Ile Glu Ala Ile Asp Val Arg Val Leu Leu 2285 2290 2295 Asp Gln Leu Gly Thr Thr Ile Ser Phe Glu Arg Ile Asn Asp Val 2300 2305 2310 Leu Glu His Val Lys His Phe Val Ile Asn Leu Ile Gly Asp Phe 2315 2320 2325 Glu Val Ala Glu Lys Ile Asn Ala Phe Arg Ala Lys Val His Glu 2330 2335 2340 Leu Ile Glu Arg Tyr Glu Val Asp Gln Gln Ile Gln Val Leu Met 2345 2350 2355 Asp Lys Leu Val Glu Leu Thr His Gln Tyr Lys Leu Lys Glu Thr 2360 2365 2370 Ile Gln Lys Leu Ser Asn Val Leu Gln Gln Val Lys Ile Lys Asp 2375 2380 2385 Tyr Phe Glu Lys Leu Val Gly Phe Ile Asp Asp Ala Val Lys Lys 2390 2395 2400 Leu Asn Glu Leu Ser Phe Lys Thr Phe Ile Glu Asp Val Asn Lys 2405 2410 2415 Phe Leu Asp Met Leu Ile Lys Lys Leu Lys Ser Phe Asp Tyr His 2420 2425 2430 Gln Phe Val Asp Glu Thr Asn Asp Lys Ile Arg Glu Val Thr Gln 2435 2440 2445 Arg Leu Asn Gly Glu Ile Gln Ala Leu Glu Leu Pro Gln Lys Ala 2450 2455 2460 Glu Ala Leu Lys Leu Phe Leu Glu Glu Thr Lys Ala Thr Val Ala 2465 2470 2475 Val Tyr Leu Glu Ser Leu Gln Asp Thr Lys Ile Thr Leu Ile Ile 2480 2485 2490 Asn Trp Leu Gln Glu Ala Leu Ser Ser Ala Ser Leu Ala His Met 2495 2500 2505 Lys Ala Lys Phe Arg Glu Thr Leu Glu Asp Thr Arg Asp Arg Met 2510 2515 2520 Tyr Gln Met Asp Ile Gln Gln Glu Leu Gln Arg Tyr Leu Ser Leu 2525 2530 2535 Val Gly Gln Val Tyr Ser Thr Leu Val Thr Tyr Ile Ser Asp Trp 2540 2545 2550 Trp Thr Leu Ala Ala Lys Asn Leu Thr Asp Phe Ala Glu Gln Tyr 2555 2560 2565 Ser Ile Gln Asp Trp Ala Lys Arg Met Lys Ala Leu Val Glu Gln 2570 2575 2580 Gly Phe Thr Val Pro Glu Ile Lys Thr Ile Leu Gly Thr Met Pro 2585 2590 2595 Ala Phe Glu Val Ser Leu Gln Ala Leu Gln Lys Ala Thr Phe Gln 2600 2605 2610 Thr Pro Asp Phe Ile Val Pro Leu Thr Asp Leu Arg Ile Pro Ser 2615 2620 2625 Val Gln Ile Asn Phe Lys Asp Leu Lys Asn Ile Lys Ile Pro Ser 2630 2635 2640 Arg Phe Ser Thr Pro Glu Phe Thr Ile Leu Asn Thr Phe His Ile 2645 2650 2655 Pro Ser Phe Thr Ile Asp Phe Val Glu Met Lys Val Lys Ile Ile 2660 2665 2670 Arg Thr Ile Asp Gln Met Gln Asn Ser Glu Leu Gln Trp Pro Val 2675 2680 2685 Pro Asp Ile Tyr Leu Arg Asp Leu Lys Val Glu Asp Ile Pro Leu 2690 2695 2700 Ala Arg Ile Thr Leu Pro Asp Phe Arg Leu Pro Glu Ile Ala Ile 2705 2710 2715 Pro Glu Phe Ile Ile Pro Thr Leu Asn Leu Asn Asp Phe Gln Val 2720 2725 2730 Pro Asp Leu His Ile Pro Glu Phe Gln Leu Pro His Ile Ser His 2735 2740 2745 Thr Ile Glu Val Pro Thr Phe Gly Lys Leu Tyr Ser Ile Leu Lys 2750 2755 2760 Ile Gln Ser Pro Leu Phe Thr Leu Asp Ala Asn Ala Asp Ile Gly 2765 2770 2775 Asn Gly Thr Thr Ser Ala Asn Glu Ala Gly Ile Ala Ala Ser Ile 2780 2785 2790 Thr Ala Lys Gly Glu Ser Lys Leu Glu Val Leu Asn Phe Asp Phe 2795 2800 2805 Gln Ala Asn Ala Gln Leu Ser Asn Pro Lys Ile Asn Pro Leu Ala 2810 2815 2820 Leu Lys Glu Ser Val Lys Phe Ser Ser Lys Tyr Leu Arg Thr Glu 2825 2830 2835 His Gly Ser Glu Met Leu Phe Phe Gly Asn Ala Ile Glu Gly Lys 2840 2845 2850 Ser Asn Thr Val Ala Ser Leu His Thr Glu Lys Asn Thr Leu Glu 2855 2860 2865 Leu Ser Asn Gly Val Ile Val Lys Ile Asn Asn Gln Leu Thr Leu 2870 2875 2880 Asp Ser Asn Thr Lys Tyr Phe His Lys Leu Asn Ile Pro Lys Leu 2885 2890 2895 Asp Phe Ser Ser Gln Ala Asp Leu Arg Asn Glu Ile Lys Thr Leu 2900 2905 2910 Leu Lys Ala Gly His Ile Ala Trp Thr Ser Ser Gly Lys Gly Ser 2915 2920 2925 Trp Lys Trp Ala Cys Pro Arg Phe Ser Asp Glu Gly Thr His Glu 2930 2935 2940 Ser Gln Ile Ser Phe Thr Ile Glu Gly Pro Leu Thr Ser Phe Gly 2945 2950 2955 Leu Ser Asn Lys Ile Asn Ser Lys His Leu Arg Val Asn Gln Asn 2960 2965 2970 Leu Val Tyr Glu Ser Gly Ser Leu Asn Phe Ser Lys Leu Glu Ile 2975 2980 2985 Gln Ser Gln Val Asp Ser Gln His Val Gly His Ser Val Leu Thr 2990 2995 3000 Ala Lys Gly Met Ala Leu Phe Gly Glu Gly Lys Ala Glu Phe Thr 3005 3010 3015 Gly Arg His Asp Ala His Leu Asn Gly Lys Val Ile Gly Thr Leu 3020 3025 3030 Lys Asn Ser Leu Phe Phe Ser Ala Gln Pro Phe Glu Ile Thr Ala 3035 3040 3045 Ser Thr Asn Asn Glu Gly Asn Leu Lys Val Arg Phe Pro Leu Arg 3050 3055 3060 Leu Thr Gly Lys Ile Asp Phe Leu Asn Asn Tyr Ala Leu Phe Leu 3065 3070 3075 Ser Pro Ser Ala Gln Gln Ala Ser Trp Gln Val Ser Ala Arg Phe 3080 3085 3090 Asn Gln Tyr Lys Tyr Asn Gln Asn Phe Ser Ala Gly Asn Asn Glu 3095 3100 3105 Asn Ile Met Glu Ala His Val Gly Ile Asn Gly Glu Ala Asn Leu 3110 3115 3120 Asp Phe Leu Asn Ile Pro Leu Thr Ile Pro Glu Met Arg Leu Pro 3125 3130 3135 Tyr Thr Ile Ile Thr Thr Pro Pro Leu Lys Asp Phe Ser Leu Trp 3140 3145 3150 Glu Lys Thr Gly Leu Lys Glu Phe Leu Lys Thr Thr Lys Gln Ser 3155 3160 3165 Phe Asp Leu Ser Val Lys Ala Gln Tyr Lys Lys Asn Lys His Arg 3170 3175 3180 His Ser Ile Thr Asn Pro Leu Ala Val Leu Cys Glu Phe Ile Ser 3185 3190 3195 Gln Ser Ile Lys Ser Phe Asp Arg His Phe Glu Lys Asn Arg Asn 3200 3205 3210 Asn Ala Leu Asp Phe Val Thr Lys Ser Tyr Asn Glu Thr Lys Ile 3215 3220 3225 Lys Phe Asp Lys Tyr Lys Ala Glu Lys Ser His Asp Glu Leu Pro 3230 3235 3240 Arg Thr Phe Gln Ile Pro Gly Tyr Thr Val Pro Val Val Asn Val 3245 3250 3255 Glu Val Ser Pro Phe Thr Ile Glu Met Ser Ala Phe Gly Tyr Val 3260 3265 3270 Phe Pro Lys Ala Val Ser Met Pro Ser Phe Ser Ile Leu Gly Ser 3275 3280 3285 Asp Val Arg Val Pro Ser Tyr Thr Leu Ile Leu Pro Ser Leu Glu 3290 3295 3300 Leu Pro Val Leu His Val Pro Arg Asn Leu Lys Leu Ser Leu Pro 3305 3310 3315 His Phe Lys Glu Leu Cys Thr Ile Ser His Ile Phe Ile Pro Ala 3320 3325 3330 Met Gly Asn Ile Thr Tyr Asp Phe Ser Phe Lys Ser Ser Val Ile 3335 3340 3345 Thr Leu Asn Thr Asn Ala Glu Leu Phe Asn Gln Ser Asp Ile Val 3350 3355 3360 Ala His Leu Leu Ser Ser Ser Ser Ser Val Ile Asp Ala Leu Gln 3365 3370 3375 Tyr Lys Leu Glu Gly Thr Thr Arg Leu Thr Arg Lys Arg Gly Leu 3380

3385 3390 Lys Leu Ala Thr Ala Leu Ser Leu Ser Asn Lys Phe Val Glu Gly 3395 3400 3405 Ser His Asn Ser Thr Val Ser Leu Thr Thr Lys Asn Met Glu Val 3410 3415 3420 Ser Val Ala Lys Thr Thr Lys Ala Glu Ile Pro Ile Leu Arg Met 3425 3430 3435 Asn Phe Lys Gln Glu Leu Asn Gly Asn Thr Lys Ser Lys Pro Thr 3440 3445 3450 Val Ser Ser Ser Met Glu Phe Lys Tyr Asp Phe Asn Ser Ser Met 3455 3460 3465 Leu Tyr Ser Thr Ala Lys Gly Ala Val Asp His Lys Leu Ser Leu 3470 3475 3480 Glu Ser Leu Thr Ser Tyr Phe Ser Ile Glu Ser Ser Thr Lys Gly 3485 3490 3495 Asp Val Lys Gly Ser Val Leu Ser Arg Glu Tyr Ser Gly Thr Ile 3500 3505 3510 Ala Ser Glu Ala Asn Thr Tyr Leu Asn Ser Lys Ser Thr Arg Ser 3515 3520 3525 Ser Val Lys Leu Gln Gly Thr Ser Lys Ile Asp Asp Ile Trp Asn 3530 3535 3540 Leu Glu Val Lys Glu Asn Phe Ala Gly Glu Ala Thr Leu Gln Arg 3545 3550 3555 Ile Tyr Ser Leu Trp Glu His Ser Thr Lys Asn His Leu Gln Leu 3560 3565 3570 Glu Gly Leu Phe Phe Thr Asn Gly Glu His Thr Ser Lys Ala Thr 3575 3580 3585 Leu Glu Leu Ser Pro Trp Gln Met Ser Ala Leu Val Gln Val His 3590 3595 3600 Ala Ser Gln Pro Ser Ser Phe His Asp Phe Pro Asp Leu Gly Gln 3605 3610 3615 Glu Val Ala Leu Asn Ala Asn Thr Lys Asn Gln Lys Ile Arg Trp 3620 3625 3630 Lys Asn Glu Val Arg Ile His Ser Gly Ser Phe Gln Ser Gln Val 3635 3640 3645 Glu Leu Ser Asn Asp Gln Glu Lys Ala His Leu Asp Ile Ala Gly 3650 3655 3660 Ser Leu Glu Gly His Leu Arg Phe Leu Lys Asn Ile Ile Leu Pro 3665 3670 3675 Val Tyr Asp Lys Ser Leu Trp Asp Phe Leu Lys Leu Asp Val Thr 3680 3685 3690 Thr Ser Ile Gly Arg Arg Gln His Leu Arg Val Ser Thr Ala Phe 3695 3700 3705 Val Tyr Thr Lys Asn Pro Asn Gly Tyr Ser Phe Ser Ile Pro Val 3710 3715 3720 Lys Val Leu Ala Asp Lys Phe Ile Thr Pro Gly Leu Lys Leu Asn 3725 3730 3735 Asp Leu Asn Ser Val Leu Val Met Pro Thr Phe His Val Pro Phe 3740 3745 3750 Thr Asp Leu Gln Val Pro Ser Cys Lys Leu Asp Phe Arg Glu Ile 3755 3760 3765 Gln Ile Tyr Lys Lys Leu Arg Thr Ser Ser Phe Ala Leu Asn Leu 3770 3775 3780 Pro Thr Leu Pro Glu Val Lys Phe Pro Glu Val Asp Val Leu Thr 3785 3790 3795 Lys Tyr Ser Gln Pro Glu Asp Ser Leu Ile Pro Phe Phe Glu Ile 3800 3805 3810 Thr Val Pro Glu Ser Gln Leu Thr Val Ser Gln Phe Thr Leu Pro 3815 3820 3825 Lys Ser Val Ser Asp Gly Ile Ala Ala Leu Asp Leu Asn Ala Val 3830 3835 3840 Ala Asn Lys Ile Ala Asp Phe Glu Leu Pro Thr Ile Ile Val Pro 3845 3850 3855 Glu Gln Thr Ile Glu Ile Pro Ser Ile Lys Phe Ser Val Pro Ala 3860 3865 3870 Gly Ile Val Ile Pro Ser Phe Gln Ala Leu Thr Ala Arg Phe Glu 3875 3880 3885 Val Asp Ser Pro Val Tyr Asn Ala Thr Trp Ser Ala Ser Leu Lys 3890 3895 3900 Asn Lys Ala Asp Tyr Val Glu Thr Val Leu Asp Ser Thr Cys Ser 3905 3910 3915 Ser Thr Val Gln Phe Leu Glu Tyr Glu Leu Asn Val Leu Gly Thr 3920 3925 3930 His Lys Ile Glu Asp Gly Thr Leu Ala Ser Lys Thr Lys Gly Thr 3935 3940 3945 Leu Ala His Arg Asp Phe Ser Ala Glu Tyr Glu Glu Asp Gly Lys 3950 3955 3960 Phe Glu Gly Leu Gln Glu Trp Glu Gly Lys Ala His Leu Asn Ile 3965 3970 3975 Lys Ser Pro Ala Phe Thr Asp Leu His Leu Arg Tyr Gln Lys Asp 3980 3985 3990 Lys Lys Gly Ile Ser Thr Ser Ala Ala Ser Pro Ala Val Gly Thr 3995 4000 4005 Val Gly Met Asp Met Asp Glu Asp Asp Asp Phe Ser Lys Trp Asn 4010 4015 4020 Phe Tyr Tyr Ser Pro Gln Ser Ser Pro Asp Lys Lys Leu Thr Ile 4025 4030 4035 Phe Lys Thr Glu Leu Arg Val Arg Glu Ser Asp Glu Glu Thr Gln 4040 4045 4050 Ile Lys Val Asn Trp Glu Glu Glu Ala Ala Ser Gly Leu Leu Thr 4055 4060 4065 Ser Leu Lys Asp Asn Val Pro Lys Ala Thr Gly Val Leu Tyr Asp 4070 4075 4080 Tyr Val Asn Lys Tyr His Trp Glu His Thr Gly Leu Thr Leu Arg 4085 4090 4095 Glu Val Ser Ser Lys Leu Arg Arg Asn Leu Gln Asn Asn Ala Glu 4100 4105 4110 Trp Val Tyr Gln Gly Ala Ile Arg Gln Ile Asp Asp Ile Asp Val 4115 4120 4125 Arg Phe Gln Lys Ala Ala Ser Gly Thr Thr Gly Thr Tyr Gln Glu 4130 4135 4140 Trp Lys Asp Lys Ala Gln Asn Leu Tyr Gln Glu Leu Leu Thr Gln 4145 4150 4155 Glu Gly Gln Ala Ser Phe Gln Gly Leu Lys Asp Asn Val Phe Asp 4160 4165 4170 Gly Leu Val Arg Val Thr Gln Lys Phe His Met Lys Val Lys His 4175 4180 4185 Leu Ile Asp Ser Leu Ile Asp Phe Leu Asn Phe Pro Arg Phe Gln 4190 4195 4200 Phe Pro Gly Lys Pro Gly Ile Tyr Thr Arg Glu Glu Leu Cys Thr 4205 4210 4215 Met Phe Ile Arg Glu Val Gly Thr Val Leu Ser Gln Val Tyr Ser 4220 4225 4230 Lys Val His Asn Gly Ser Glu Ile Leu Phe Ser Tyr Phe Gln Asp 4235 4240 4245 Leu Val Ile Thr Leu Pro Phe Glu Leu Arg Lys His Lys Leu Ile 4250 4255 4260 Asp Val Ile Ser Met Tyr Arg Glu Leu Leu Lys Asp Leu Ser Lys 4265 4270 4275 Glu Ala Gln Glu Val Phe Lys Ala Ile Gln Ser Leu Lys Thr Thr 4280 4285 4290 Glu Val Leu Arg Asn Leu Gln Asp Leu Leu Gln Phe Ile Phe Gln 4295 4300 4305 Leu Ile Glu Asp Asn Ile Lys Gln Leu Lys Glu Met Lys Phe Thr 4310 4315 4320 Tyr Leu Ile Asn Tyr Ile Gln Asp Glu Ile Asn Thr Ile Phe Asn 4325 4330 4335 Asp Tyr Ile Pro Tyr Val Phe Lys Leu Leu Lys Glu Asn Leu Cys 4340 4345 4350 Leu Asn Leu His Lys Phe Asn Glu Phe Ile Gln Asn Glu Leu Gln 4355 4360 4365 Glu Ala Ser Gln Glu Leu Gln Gln Ile His Gln Tyr Ile Met Ala 4370 4375 4380 Leu Arg Glu Glu Tyr Phe Asp Pro Ser Ile Val Gly Trp Thr Val 4385 4390 4395 Lys Tyr Tyr Glu Leu Glu Glu Lys Ile Val Ser Leu Ile Lys Asn 4400 4405 4410 Leu Leu Val Ala Leu Lys Asp Phe His Ser Glu Tyr Ile Val Ser 4415 4420 4425 Ala Ser Asn Phe Thr Ser Gln Leu Ser Ser Gln Val Glu Gln Phe 4430 4435 4440 Leu His Arg Asn Ile Gln Glu Tyr Leu Ser Ile Leu Thr Asp Pro 4445 4450 4455 Asp Gly Lys Gly Lys Glu Lys Ile Ala Glu Leu Ser Ala Thr Ala 4460 4465 4470 Gln Glu Ile Ile Lys Ser Gln Ala Ile Ala Thr Lys Lys Ile Ile 4475 4480 4485 Ser Asp Tyr His Gln Gln Phe Arg Tyr Lys Leu Gln Asp Phe Ser 4490 4495 4500 Asp Gln Leu Ser Asp Tyr Tyr Glu Lys Phe Ile Ala Glu Ser Lys 4505 4510 4515 Arg Leu Ile Asp Leu Ser Ile Gln Asn Tyr His Thr Phe Leu Ile 4520 4525 4530 Tyr Ile Thr Glu Leu Leu Lys Lys Leu Gln Ser Thr Thr Val Met 4535 4540 4545 Asn Pro Tyr Met Lys Leu Ala Pro Gly Glu Leu Thr Ile Ile Leu 4550 4555 4560 27883PRTHomo sapiens 278Met Arg Leu Phe Leu Ser Leu Pro Val Leu Val Val Val Leu Ser Ile 1 5 10 15 Val Leu Glu Gly Pro Ala Pro Ala Gln Gly Thr Pro Asp Val Ser Ser 20 25 30 Ala Leu Asp Lys Leu Lys Glu Phe Gly Asn Thr Leu Glu Asp Lys Ala 35 40 45 Arg Glu Leu Ile Ser Arg Ile Lys Gln Ser Glu Leu Ser Ala Lys Met 50 55 60 Arg Glu Trp Phe Ser Glu Thr Phe Gln Lys Val Lys Glu Lys Leu Lys 65 70 75 80 Ile Asp Ser 279317PRTHomo sapiens 279Met Lys Val Leu Trp Ala Ala Leu Leu Val Thr Phe Leu Ala Gly Cys 1 5 10 15 Gln Ala Lys Val Glu Gln Ala Val Glu Thr Glu Pro Glu Pro Glu Leu 20 25 30 Arg Gln Gln Thr Glu Trp Gln Ser Gly Gln Arg Trp Glu Leu Ala Leu 35 40 45 Gly Arg Phe Trp Asp Tyr Leu Arg Trp Val Gln Thr Leu Ser Glu Gln 50 55 60 Val Gln Glu Glu Leu Leu Ser Ser Gln Val Thr Gln Glu Leu Arg Ala 65 70 75 80 Leu Met Asp Glu Thr Met Lys Glu Leu Lys Ala Tyr Lys Ser Glu Leu 85 90 95 Glu Glu Gln Leu Thr Pro Val Ala Glu Glu Thr Arg Ala Arg Leu Ser 100 105 110 Lys Glu Leu Gln Ala Ala Gln Ala Arg Leu Gly Ala Asp Met Glu Asp 115 120 125 Val Cys Gly Arg Leu Val Gln Tyr Arg Gly Glu Val Gln Ala Met Leu 130 135 140 Gly Gln Ser Thr Glu Glu Leu Arg Val Arg Leu Ala Ser His Leu Arg 145 150 155 160 Lys Leu Arg Lys Arg Leu Leu Arg Asp Ala Asp Asp Leu Gln Lys Arg 165 170 175 Leu Ala Val Tyr Gln Ala Gly Ala Arg Glu Gly Ala Glu Arg Gly Leu 180 185 190 Ser Ala Ile Arg Glu Arg Leu Gly Pro Leu Val Glu Gln Gly Arg Val 195 200 205 Arg Ala Ala Thr Val Gly Ser Leu Ala Gly Gln Pro Leu Gln Glu Arg 210 215 220 Ala Gln Ala Trp Gly Glu Arg Leu Arg Ala Arg Met Glu Glu Met Gly 225 230 235 240 Ser Arg Thr Arg Asp Arg Leu Asp Glu Val Lys Glu Gln Val Ala Glu 245 250 255 Val Arg Ala Lys Leu Glu Glu Gln Ala Gln Gln Ile Arg Leu Gln Ala 260 265 270 Glu Ala Phe Gln Ala Arg Leu Lys Ser Trp Phe Glu Pro Leu Val Glu 275 280 285 Asp Met Gln Arg Gln Trp Ala Gly Leu Val Glu Lys Val Gln Ala Ala 290 295 300 Val Gly Thr Ser Ala Ala Pro Val Pro Ser Asp Asn His 305 310 315 280345PRTHomo sapiens 280Met Ile Ser Pro Val Leu Ile Leu Phe Ser Ser Phe Leu Cys His Val 1 5 10 15 Ala Ile Ala Gly Arg Thr Cys Pro Lys Pro Asp Asp Leu Pro Phe Ser 20 25 30 Thr Val Val Pro Leu Lys Thr Phe Tyr Glu Pro Gly Glu Glu Ile Thr 35 40 45 Tyr Ser Cys Lys Pro Gly Tyr Val Ser Arg Gly Gly Met Arg Lys Phe 50 55 60 Ile Cys Pro Leu Thr Gly Leu Trp Pro Ile Asn Thr Leu Lys Cys Thr 65 70 75 80 Pro Arg Val Cys Pro Phe Ala Gly Ile Leu Glu Asn Gly Ala Val Arg 85 90 95 Tyr Thr Thr Phe Glu Tyr Pro Asn Thr Ile Ser Phe Ser Cys Asn Thr 100 105 110 Gly Phe Tyr Leu Asn Gly Ala Asp Ser Ala Lys Cys Thr Glu Glu Gly 115 120 125 Lys Trp Ser Pro Glu Leu Pro Val Cys Ala Pro Ile Ile Cys Pro Pro 130 135 140 Pro Ser Ile Pro Thr Phe Ala Thr Leu Arg Val Tyr Lys Pro Ser Ala 145 150 155 160 Gly Asn Asn Ser Leu Tyr Arg Asp Thr Ala Val Phe Glu Cys Leu Pro 165 170 175 Gln His Ala Met Phe Gly Asn Asp Thr Ile Thr Cys Thr Thr His Gly 180 185 190 Asn Trp Thr Lys Leu Pro Glu Cys Arg Glu Val Lys Cys Pro Phe Pro 195 200 205 Ser Arg Pro Asp Asn Gly Phe Val Asn Tyr Pro Ala Lys Pro Thr Leu 210 215 220 Tyr Tyr Lys Asp Lys Ala Thr Phe Gly Cys His Asp Gly Tyr Ser Leu 225 230 235 240 Asp Gly Pro Glu Glu Ile Glu Cys Thr Lys Leu Gly Asn Trp Ser Ala 245 250 255 Met Pro Ser Cys Lys Ala Ser Cys Lys Leu Pro Val Lys Lys Ala Thr 260 265 270 Val Val Tyr Gln Gly Glu Arg Val Lys Ile Gln Glu Lys Phe Lys Asn 275 280 285 Gly Met Leu His Gly Asp Lys Val Ser Phe Phe Cys Lys Asn Lys Glu 290 295 300 Lys Lys Cys Ser Tyr Thr Glu Asp Ala Gln Cys Ile Asp Gly Thr Ile 305 310 315 320 Glu Val Pro Lys Cys Phe Lys Glu His Ser Ser Leu Ala Phe Trp Lys 325 330 335 Thr Asp Ala Ser Asp Val Lys Pro Cys 340 345 281543PRTHomo sapiens 281Met Ala His Ala His Ile Gln Gly Gly Arg Arg Ala Lys Ser Arg Phe 1 5 10 15 Val Val Cys Ile Met Ser Gly Ala Arg Ser Lys Leu Ala Leu Phe Leu 20 25 30 Cys Gly Cys Tyr Val Val Ala Leu Gly Ala His Thr Gly Glu Glu Ser 35 40 45 Val Ala Asp His His Glu Ala Glu Tyr Tyr Val Ala Ala Val Tyr Glu 50 55 60 His Pro Ser Ile Leu Ser Leu Asn Pro Leu Ala Leu Ile Ser Arg Gln 65 70 75 80 Glu Ala Leu Glu Leu Met Asn Gln Asn Leu Asp Ile Tyr Glu Gln Gln 85 90 95 Val Met Thr Ala Ala Gln Lys Asp Val Gln Ile Ile Val Phe Pro Glu 100 105 110 Asp Gly Ile His Gly Phe Asn Phe Thr Arg Thr Ser Ile Tyr Pro Phe 115 120 125 Leu Asp Phe Met Pro Ser Pro Gln Val Val Arg Trp Asn Pro Cys Leu 130 135 140 Glu Pro His Arg Phe Asn Asp Thr Glu Val Leu Gln Arg Leu Ser Cys 145 150 155 160 Met Ala Ile Arg Gly Asp Met Phe Leu Val Ala Asn Leu Gly Thr Lys 165 170 175 Glu Pro Cys His Ser Ser Asp Pro Arg Cys Pro Lys Asp Gly Arg Tyr 180 185 190 Gln Phe Asn Thr Asn Val Val Phe Ser Asn Asn Gly Thr Leu Val Asp 195 200 205 Arg Tyr Arg Lys His Asn Leu Tyr Phe Glu Ala Ala Phe Asp Val Pro 210 215 220 Leu Lys Val Asp Leu Ile Thr Phe Asp Thr Pro Phe Ala Gly Arg Phe 225 230 235 240 Gly Ile Phe Thr Cys Phe Asp Ile Leu Phe Phe Asp Pro Ala Ile Arg 245 250 255 Val Leu Arg Asp Tyr Lys Val Lys His Val Val Tyr Pro Thr Ala Trp 260 265 270 Met Asn Gln Leu Pro Leu Leu Ala Ala Ile Glu Ile Gln Lys Ala Phe 275 280 285 Ala Val Ala Phe Gly Ile Asn Val Leu Ala Ala Asn Val His His Pro 290 295 300 Val Leu Gly Met Thr Gly Ser Gly Ile His Thr Pro Leu Glu Ser Phe 305 310

315 320 Trp Tyr His Asp Met Glu Asn Pro Lys Ser His Leu Ile Ile Ala Gln 325 330 335 Val Ala Lys Asn Pro Val Gly Leu Ile Gly Ala Glu Asn Ala Thr Gly 340 345 350 Glu Thr Asp Pro Ser His Ser Lys Phe Leu Lys Ile Leu Ser Gly Asp 355 360 365 Pro Tyr Cys Glu Lys Asp Ala Gln Glu Val His Cys Asp Glu Ala Thr 370 375 380 Lys Trp Asn Val Asn Ala Pro Pro Thr Phe His Ser Glu Met Met Tyr 385 390 395 400 Asp Asn Phe Thr Leu Val Pro Val Trp Gly Lys Glu Gly Tyr Leu His 405 410 415 Val Cys Ser Asn Gly Leu Cys Cys Tyr Leu Leu Tyr Glu Arg Pro Thr 420 425 430 Leu Ser Lys Glu Leu Tyr Ala Leu Gly Val Phe Asp Gly Leu His Thr 435 440 445 Val His Gly Thr Tyr Tyr Ile Gln Val Cys Ala Leu Val Arg Cys Gly 450 455 460 Gly Leu Gly Phe Asp Thr Cys Gly Gln Glu Ile Thr Glu Ala Thr Gly 465 470 475 480 Ile Phe Glu Phe His Leu Trp Gly Asn Phe Ser Thr Ser Tyr Ile Phe 485 490 495 Pro Leu Phe Leu Thr Ser Gly Met Thr Leu Glu Val Pro Asp Gln Leu 500 505 510 Gly Trp Glu Asn Asp His Tyr Phe Leu Arg Lys Ser Arg Leu Ser Ser 515 520 525 Gly Leu Val Thr Ala Ala Leu Tyr Gly Arg Leu Tyr Glu Arg Asp 530 535 540 282261PRTHomo sapiens 282Met Ala Ser Pro Asp Trp Gly Tyr Asp Asp Lys Asn Gly Pro Glu Gln 1 5 10 15 Trp Ser Lys Leu Tyr Pro Ile Ala Asn Gly Asn Asn Gln Ser Pro Val 20 25 30 Asp Ile Lys Thr Ser Glu Thr Lys His Asp Thr Ser Leu Lys Pro Ile 35 40 45 Ser Val Ser Tyr Asn Pro Ala Thr Ala Lys Glu Ile Ile Asn Val Gly 50 55 60 His Ser Phe His Val Asn Phe Glu Asp Asn Asp Asn Arg Ser Val Leu 65 70 75 80 Lys Gly Gly Pro Phe Ser Asp Ser Tyr Arg Leu Phe Gln Phe His Phe 85 90 95 His Trp Gly Ser Thr Asn Glu His Gly Ser Glu His Thr Val Asp Gly 100 105 110 Val Lys Tyr Ser Ala Glu Leu His Val Ala His Trp Asn Ser Ala Lys 115 120 125 Tyr Ser Ser Leu Ala Glu Ala Ala Ser Lys Ala Asp Gly Leu Ala Val 130 135 140 Ile Gly Val Leu Met Lys Val Gly Glu Ala Asn Pro Lys Leu Gln Lys 145 150 155 160 Val Leu Asp Ala Leu Gln Ala Ile Lys Thr Lys Gly Lys Arg Ala Pro 165 170 175 Phe Thr Asn Phe Asp Pro Ser Thr Leu Leu Pro Ser Ser Leu Asp Phe 180 185 190 Trp Thr Tyr Pro Gly Ser Leu Thr His Pro Pro Leu Tyr Glu Ser Val 195 200 205 Thr Trp Ile Ile Cys Lys Glu Ser Ile Ser Val Ser Ser Glu Gln Leu 210 215 220 Ala Gln Phe Arg Ser Leu Leu Ser Asn Val Glu Gly Asp Asn Ala Val 225 230 235 240 Pro Met Gln His Asn Asn Arg Pro Thr Gln Pro Leu Lys Gly Arg Thr 245 250 255 Val Arg Ala Ser Phe 260 283458PRTHomo sapiens 283Met Ser Asp Leu Leu Ser Val Phe Leu His Leu Leu Leu Leu Phe Lys 1 5 10 15 Leu Val Ala Pro Val Thr Phe Arg His His Arg Tyr Asp Asp Leu Val 20 25 30 Arg Thr Leu Tyr Lys Val Gln Asn Glu Cys Pro Gly Ile Thr Arg Val 35 40 45 Tyr Ser Ile Gly Arg Ser Val Glu Gly Arg His Leu Tyr Val Leu Glu 50 55 60 Phe Ser Asp His Pro Gly Ile His Glu Pro Leu Glu Pro Glu Val Lys 65 70 75 80 Tyr Val Gly Asn Met His Gly Asn Glu Ala Leu Gly Arg Glu Leu Met 85 90 95 Leu Gln Leu Ser Glu Phe Leu Cys Glu Glu Phe Arg Asn Arg Asn Gln 100 105 110 Arg Ile Val Gln Leu Ile Gln Asp Thr Arg Ile His Ile Leu Pro Ser 115 120 125 Met Asn Pro Asp Gly Tyr Glu Val Ala Ala Ala Gln Gly Pro Asn Lys 130 135 140 Pro Gly Tyr Leu Val Gly Arg Asn Asn Ala Asn Gly Val Asp Leu Asn 145 150 155 160 Arg Asn Phe Pro Asp Leu Asn Thr Tyr Ile Tyr Tyr Asn Glu Lys Tyr 165 170 175 Gly Gly Pro Asn His His Leu Pro Leu Pro Asp Asn Trp Lys Ser Gln 180 185 190 Val Glu Pro Glu Thr Arg Ala Val Ile Arg Trp Met His Ser Phe Asn 195 200 205 Phe Val Leu Ser Ala Asn Leu His Gly Gly Ala Val Val Ala Asn Tyr 210 215 220 Pro Tyr Asp Lys Ser Phe Glu His Arg Val Arg Gly Val Arg Arg Thr 225 230 235 240 Ala Ser Thr Pro Thr Pro Asp Asp Lys Leu Phe Gln Lys Leu Ala Lys 245 250 255 Val Tyr Ser Tyr Ala His Gly Trp Met Phe Gln Gly Trp Asn Cys Gly 260 265 270 Asp Tyr Phe Pro Asp Gly Ile Thr Asn Gly Ala Ser Trp Tyr Ser Leu 275 280 285 Ser Lys Gly Met Gln Asp Phe Asn Tyr Leu His Thr Asn Cys Phe Glu 290 295 300 Ile Thr Leu Glu Leu Ser Cys Asp Lys Phe Pro Pro Glu Glu Glu Leu 305 310 315 320 Gln Arg Glu Trp Leu Gly Asn Arg Glu Ala Leu Ile Gln Phe Leu Glu 325 330 335 Gln Val His Gln Gly Ile Lys Gly Met Val Leu Asp Glu Asn Tyr Asn 340 345 350 Asn Leu Ala Asn Ala Val Ile Ser Val Ser Gly Ile Asn His Asp Val 355 360 365 Thr Ser Gly Asp His Gly Asp Tyr Phe Arg Leu Leu Leu Pro Gly Ile 370 375 380 Tyr Thr Val Ser Ala Thr Ala Pro Gly Tyr Asp Pro Glu Thr Val Thr 385 390 395 400 Val Thr Val Gly Pro Ala Glu Pro Thr Leu Val Asn Phe His Leu Lys 405 410 415 Arg Ser Ile Pro Gln Val Ser Pro Val Arg Arg Ala Pro Ser Arg Arg 420 425 430 His Gly Val Arg Ala Lys Val Gln Pro Gln Ala Arg Lys Lys Glu Met 435 440 445 Glu Met Arg Gln Leu Gln Arg Gly Pro Ala 450 455 2841065PRTHomo sapiens 284Met Lys Ile Leu Ile Leu Gly Ile Phe Leu Phe Leu Cys Ser Thr Pro 1 5 10 15 Ala Trp Ala Lys Glu Lys His Tyr Tyr Ile Gly Ile Ile Glu Thr Thr 20 25 30 Trp Asp Tyr Ala Ser Asp His Gly Glu Lys Lys Leu Ile Ser Val Asp 35 40 45 Thr Glu His Ser Asn Ile Tyr Leu Gln Asn Gly Pro Asp Arg Ile Gly 50 55 60 Arg Leu Tyr Lys Lys Ala Leu Tyr Leu Gln Tyr Thr Asp Glu Thr Phe 65 70 75 80 Arg Thr Thr Ile Glu Lys Pro Val Trp Leu Gly Phe Leu Gly Pro Ile 85 90 95 Ile Lys Ala Glu Thr Gly Asp Lys Val Tyr Val His Leu Lys Asn Leu 100 105 110 Ala Ser Arg Pro Tyr Thr Phe His Ser His Gly Ile Thr Tyr Tyr Lys 115 120 125 Glu His Glu Gly Ala Ile Tyr Pro Asp Asn Thr Thr Asp Phe Gln Arg 130 135 140 Ala Asp Asp Lys Val Tyr Pro Gly Glu Gln Tyr Thr Tyr Met Leu Leu 145 150 155 160 Ala Thr Glu Glu Gln Ser Pro Gly Glu Gly Asp Gly Asn Cys Val Thr 165 170 175 Arg Ile Tyr His Ser His Ile Asp Ala Pro Lys Asp Ile Ala Ser Gly 180 185 190 Leu Ile Gly Pro Leu Ile Ile Cys Lys Lys Asp Ser Leu Asp Lys Glu 195 200 205 Lys Glu Lys His Ile Asp Arg Glu Phe Val Val Met Phe Ser Val Val 210 215 220 Asp Glu Asn Phe Ser Trp Tyr Leu Glu Asp Asn Ile Lys Thr Tyr Cys 225 230 235 240 Ser Glu Pro Glu Lys Val Asp Lys Asp Asn Glu Asp Phe Gln Glu Ser 245 250 255 Asn Arg Met Tyr Ser Val Asn Gly Tyr Thr Phe Gly Ser Leu Pro Gly 260 265 270 Leu Ser Met Cys Ala Glu Asp Arg Val Lys Trp Tyr Leu Phe Gly Met 275 280 285 Gly Asn Glu Val Asp Val His Ala Ala Phe Phe His Gly Gln Ala Leu 290 295 300 Thr Asn Lys Asn Tyr Arg Ile Asp Thr Ile Asn Leu Phe Pro Ala Thr 305 310 315 320 Leu Phe Asp Ala Tyr Met Val Ala Gln Asn Pro Gly Glu Trp Met Leu 325 330 335 Ser Cys Gln Asn Leu Asn His Leu Lys Ala Gly Leu Gln Ala Phe Phe 340 345 350 Gln Val Gln Glu Cys Asn Lys Ser Ser Ser Lys Asp Asn Ile Arg Gly 355 360 365 Lys His Val Arg His Tyr Tyr Ile Ala Ala Glu Glu Ile Ile Trp Asn 370 375 380 Tyr Ala Pro Ser Gly Ile Asp Ile Phe Thr Lys Glu Asn Leu Thr Ala 385 390 395 400 Pro Gly Ser Asp Ser Ala Val Phe Phe Glu Gln Gly Thr Thr Arg Ile 405 410 415 Gly Gly Ser Tyr Lys Lys Leu Val Tyr Arg Glu Tyr Thr Asp Ala Ser 420 425 430 Phe Thr Asn Arg Lys Glu Arg Gly Pro Glu Glu Glu His Leu Gly Ile 435 440 445 Leu Gly Pro Val Ile Trp Ala Glu Val Gly Asp Thr Ile Arg Val Thr 450 455 460 Phe His Asn Lys Gly Ala Tyr Pro Leu Ser Ile Glu Pro Ile Gly Val 465 470 475 480 Arg Phe Asn Lys Asn Asn Glu Gly Thr Tyr Tyr Ser Pro Asn Tyr Asn 485 490 495 Pro Gln Ser Arg Ser Val Pro Pro Ser Ala Ser His Val Ala Pro Thr 500 505 510 Glu Thr Phe Thr Tyr Glu Trp Thr Val Pro Lys Glu Val Gly Pro Thr 515 520 525 Asn Ala Asp Pro Val Cys Leu Ala Lys Met Tyr Tyr Ser Ala Val Asp 530 535 540 Pro Thr Lys Asp Ile Phe Thr Gly Leu Ile Gly Pro Met Lys Ile Cys 545 550 555 560 Lys Lys Gly Ser Leu His Ala Asn Gly Arg Gln Lys Asp Val Asp Lys 565 570 575 Glu Phe Tyr Leu Phe Pro Thr Val Phe Asp Glu Asn Glu Ser Leu Leu 580 585 590 Leu Glu Asp Asn Ile Arg Met Phe Thr Thr Ala Pro Asp Gln Val Asp 595 600 605 Lys Glu Asp Glu Asp Phe Gln Glu Ser Asn Lys Met His Ser Met Asn 610 615 620 Gly Phe Met Tyr Gly Asn Gln Pro Gly Leu Thr Met Cys Lys Gly Asp 625 630 635 640 Ser Val Val Trp Tyr Leu Phe Ser Ala Gly Asn Glu Ala Asp Val His 645 650 655 Gly Ile Tyr Phe Ser Gly Asn Thr Tyr Leu Trp Arg Gly Glu Arg Arg 660 665 670 Asp Thr Ala Asn Leu Phe Pro Gln Thr Ser Leu Thr Leu His Met Trp 675 680 685 Pro Asp Thr Glu Gly Thr Phe Asn Val Glu Cys Leu Thr Thr Asp His 690 695 700 Tyr Thr Gly Gly Met Lys Gln Lys Tyr Thr Val Asn Gln Cys Arg Arg 705 710 715 720 Gln Ser Glu Asp Ser Thr Phe Tyr Leu Gly Glu Arg Thr Tyr Tyr Ile 725 730 735 Ala Ala Val Glu Val Glu Trp Asp Tyr Ser Pro Gln Arg Glu Trp Glu 740 745 750 Lys Glu Leu His His Leu Gln Glu Gln Asn Val Ser Asn Ala Phe Leu 755 760 765 Asp Lys Gly Glu Phe Tyr Ile Gly Ser Lys Tyr Lys Lys Val Val Tyr 770 775 780 Arg Gln Tyr Thr Asp Ser Thr Phe Arg Val Pro Val Glu Arg Lys Ala 785 790 795 800 Glu Glu Glu His Leu Gly Ile Leu Gly Pro Gln Leu His Ala Asp Val 805 810 815 Gly Asp Lys Val Lys Ile Ile Phe Lys Asn Met Ala Thr Arg Pro Tyr 820 825 830 Ser Ile His Ala His Gly Val Gln Thr Glu Ser Ser Thr Val Thr Pro 835 840 845 Thr Leu Pro Gly Glu Thr Leu Thr Tyr Val Trp Lys Ile Pro Glu Arg 850 855 860 Ser Gly Ala Gly Thr Glu Asp Ser Ala Cys Ile Pro Trp Ala Tyr Tyr 865 870 875 880 Ser Thr Val Asp Gln Val Lys Asp Leu Tyr Ser Gly Leu Ile Gly Pro 885 890 895 Leu Ile Val Cys Arg Arg Pro Tyr Leu Lys Val Phe Asn Pro Arg Arg 900 905 910 Lys Leu Glu Phe Ala Leu Leu Phe Leu Val Phe Asp Glu Asn Glu Ser 915 920 925 Trp Tyr Leu Asp Asp Asn Ile Lys Thr Tyr Ser Asp His Pro Glu Lys 930 935 940 Val Asn Lys Asp Asp Glu Glu Phe Ile Glu Ser Asn Lys Met His Ala 945 950 955 960 Ile Asn Gly Arg Met Phe Gly Asn Leu Gln Gly Leu Thr Met His Val 965 970 975 Gly Asp Glu Val Asn Trp Tyr Leu Met Gly Met Gly Asn Glu Ile Asp 980 985 990 Leu His Thr Val His Phe His Gly His Ser Phe Gln Tyr Lys His Arg 995 1000 1005 Gly Val Tyr Ser Ser Asp Val Phe Asp Ile Phe Pro Gly Thr Tyr 1010 1015 1020 Gln Thr Leu Glu Met Phe Pro Arg Thr Pro Gly Ile Trp Leu Leu 1025 1030 1035 His Cys His Val Thr Asp His Ile His Ala Gly Met Glu Thr Thr 1040 1045 1050 Tyr Thr Val Leu Gln Asn Glu Asp Thr Lys Ser Gly 1055 1060 1065 285501PRTHomo sapiens 285Met Gln Val Cys Ser Gln Pro Gln Arg Gly Cys Val Arg Glu Gln Ser 1 5 10 15 Ala Ile Asn Thr Ala Pro Pro Ser Ala His Asn Ala Ala Ser Pro Gly 20 25 30 Gly Ala Arg Gly His Arg Val Pro Leu Thr Glu Ala Cys Lys Asp Ser 35 40 45 Arg Ile Gly Gly Met Met Lys Thr Leu Leu Leu Phe Val Gly Leu Leu 50 55 60 Leu Thr Trp Glu Ser Gly Gln Val Leu Gly Asp Gln Thr Val Ser Asp 65 70 75 80 Asn Glu Leu Gln Glu Met Ser Asn Gln Gly Ser Lys Tyr Val Asn Lys 85 90 95 Glu Ile Gln Asn Ala Val Asn Gly Val Lys Gln Ile Lys Thr Leu Ile 100 105 110 Glu Lys Thr Asn Glu Glu Arg Lys Thr Leu Leu Ser Asn Leu Glu Glu 115 120 125 Ala Lys Lys Lys Lys Glu Asp Ala Leu Asn Glu Thr Arg Glu Ser Glu 130 135 140 Thr Lys Leu Lys Glu Leu Pro Gly Val Cys Asn Glu Thr Met Met Ala 145 150 155 160 Leu Trp Glu Glu Cys Lys Pro Cys Leu Lys Gln Thr Cys Met Lys Phe 165 170 175 Tyr Ala Arg Val Cys Arg Ser Gly Ser Gly Leu Val Gly Arg Gln Leu 180 185 190 Glu Glu Phe Leu Asn Gln Ser Ser Pro Phe Tyr Phe Trp Met Asn Gly 195 200 205 Asp Arg Ile Asp Ser Leu Leu Glu Asn Asp Arg Gln Gln Thr His Met 210 215 220 Leu Asp Val Met Gln Asp His Phe Ser Arg Ala Ser Ser Ile Ile Asp 225 230 235 240 Glu Leu Phe Gln Asp Arg Phe Phe Thr Arg Glu Pro Gln Asp Thr Tyr 245 250 255 His Tyr Leu Pro Phe Ser Leu Pro His Arg Arg Pro His Phe Phe Phe 260 265 270 Pro Lys Ser Arg Ile Val Arg Ser Leu Met Pro Phe Ser Pro Tyr Glu 275

280 285 Pro Leu Asn Phe His Ala Met Phe Gln Pro Phe Leu Glu Met Ile His 290 295 300 Glu Ala Gln Gln Ala Met Asp Ile His Phe His Ser Pro Ala Phe Gln 305 310 315 320 His Pro Pro Thr Glu Phe Ile Arg Glu Gly Asp Asp Asp Arg Thr Val 325 330 335 Cys Arg Glu Ile Arg His Asn Ser Thr Gly Cys Leu Arg Met Lys Asp 340 345 350 Gln Cys Asp Lys Cys Arg Glu Ile Leu Ser Val Asp Cys Ser Thr Asn 355 360 365 Asn Pro Ser Gln Ala Lys Leu Arg Arg Glu Leu Asp Glu Ser Leu Gln 370 375 380 Val Ala Glu Arg Leu Thr Arg Lys Tyr Asn Glu Leu Leu Lys Ser Tyr 385 390 395 400 Gln Trp Lys Met Leu Asn Thr Ser Ser Leu Leu Glu Gln Leu Asn Glu 405 410 415 Gln Phe Asn Trp Val Ser Arg Leu Ala Asn Leu Thr Gln Gly Glu Asp 420 425 430 Gln Tyr Tyr Leu Arg Val Thr Thr Val Ala Ser His Thr Ser Asp Ser 435 440 445 Asp Val Pro Ser Gly Val Thr Glu Val Val Val Lys Leu Phe Asp Ser 450 455 460 Asp Pro Ile Thr Val Thr Val Pro Val Glu Val Ser Arg Lys Asn Pro 465 470 475 480 Lys Phe Met Glu Thr Val Ala Glu Lys Ala Leu Gln Glu Tyr Arg Lys 485 490 495 Lys His Arg Glu Glu 500 286622PRTHomo sapiens 286Met Ala His Val Arg Gly Leu Gln Leu Pro Gly Cys Leu Ala Leu Ala 1 5 10 15 Ala Leu Cys Ser Leu Val His Ser Gln His Val Phe Leu Ala Pro Gln 20 25 30 Gln Ala Arg Ser Leu Leu Gln Arg Val Arg Arg Ala Asn Thr Phe Leu 35 40 45 Glu Glu Val Arg Lys Gly Asn Leu Glu Arg Glu Cys Val Glu Glu Thr 50 55 60 Cys Ser Tyr Glu Glu Ala Phe Glu Ala Leu Glu Ser Ser Thr Ala Thr 65 70 75 80 Asp Val Phe Trp Ala Lys Tyr Thr Ala Cys Glu Thr Ala Arg Thr Pro 85 90 95 Arg Asp Lys Leu Ala Ala Cys Leu Glu Gly Asn Cys Ala Glu Gly Leu 100 105 110 Gly Thr Asn Tyr Arg Gly His Val Asn Ile Thr Arg Ser Gly Ile Glu 115 120 125 Cys Gln Leu Trp Arg Ser Arg Tyr Pro His Lys Pro Glu Ile Asn Ser 130 135 140 Thr Thr His Pro Gly Ala Asp Leu Gln Glu Asn Phe Cys Arg Asn Pro 145 150 155 160 Asp Ser Ser Thr Thr Gly Pro Trp Cys Tyr Thr Thr Asp Pro Thr Val 165 170 175 Arg Arg Gln Glu Cys Ser Ile Pro Val Cys Gly Gln Asp Gln Val Thr 180 185 190 Val Ala Met Thr Pro Arg Ser Glu Gly Ser Ser Val Asn Leu Ser Pro 195 200 205 Pro Leu Glu Gln Cys Val Pro Asp Arg Gly Gln Gln Tyr Gln Gly Arg 210 215 220 Leu Ala Val Thr Thr His Gly Leu Pro Cys Leu Ala Trp Ala Ser Ala 225 230 235 240 Gln Ala Lys Ala Leu Ser Lys His Gln Asp Phe Asn Ser Ala Val Gln 245 250 255 Leu Val Glu Asn Phe Cys Arg Asn Pro Asp Gly Asp Glu Glu Gly Val 260 265 270 Trp Cys Tyr Val Ala Gly Lys Pro Gly Asp Phe Gly Tyr Cys Asp Leu 275 280 285 Asn Tyr Cys Glu Glu Ala Val Glu Glu Glu Thr Gly Asp Gly Leu Asp 290 295 300 Glu Asp Ser Asp Arg Ala Ile Glu Gly Arg Thr Ala Thr Ser Glu Tyr 305 310 315 320 Gln Thr Phe Phe Asn Pro Arg Thr Phe Gly Ser Gly Glu Ala Asp Cys 325 330 335 Gly Leu Arg Pro Leu Phe Glu Lys Lys Ser Leu Glu Asp Lys Thr Glu 340 345 350 Arg Glu Leu Leu Glu Ser Tyr Ile Asp Gly Arg Ile Val Glu Gly Ser 355 360 365 Asp Ala Glu Ile Gly Met Ser Pro Trp Gln Val Met Leu Phe Arg Lys 370 375 380 Ser Pro Gln Glu Leu Leu Cys Gly Ala Ser Leu Ile Ser Asp Arg Trp 385 390 395 400 Val Leu Thr Ala Ala His Cys Leu Leu Tyr Pro Pro Trp Asp Lys Asn 405 410 415 Phe Thr Glu Asn Asp Leu Leu Val Arg Ile Gly Lys His Ser Arg Thr 420 425 430 Arg Tyr Glu Arg Asn Ile Glu Lys Ile Ser Met Leu Glu Lys Ile Tyr 435 440 445 Ile His Pro Arg Tyr Asn Trp Arg Glu Asn Leu Asp Arg Asp Ile Ala 450 455 460 Leu Met Lys Leu Lys Lys Pro Val Ala Phe Ser Asp Tyr Ile His Pro 465 470 475 480 Val Cys Leu Pro Asp Arg Glu Thr Ala Ala Ser Leu Leu Gln Ala Gly 485 490 495 Tyr Lys Gly Arg Val Thr Gly Trp Gly Asn Leu Lys Glu Thr Trp Thr 500 505 510 Ala Asn Val Gly Lys Gly Gln Pro Ser Val Leu Gln Val Val Asn Leu 515 520 525 Pro Ile Val Glu Arg Pro Val Cys Lys Asp Ser Thr Arg Ile Arg Ile 530 535 540 Thr Asp Asn Met Phe Cys Ala Gly Tyr Lys Pro Asp Glu Gly Lys Arg 545 550 555 560 Gly Asp Ala Cys Glu Gly Asp Ser Gly Gly Pro Phe Val Met Lys Ser 565 570 575 Pro Phe Asn Asn Arg Trp Tyr Gln Met Gly Ile Val Ser Trp Gly Glu 580 585 590 Gly Cys Asp Arg Asp Gly Lys Tyr Gly Phe Tyr Thr His Val Phe Arg 595 600 605 Leu Lys Lys Trp Ile Gln Lys Val Ile Asp Gln Phe Gly Glu 610 615 620 287488PRTHomo sapiens 287Met Gly Arg Pro Leu His Leu Val Leu Leu Ser Ala Ser Leu Ala Gly 1 5 10 15 Leu Leu Leu Leu Gly Glu Ser Leu Phe Ile Arg Arg Glu Gln Ala Asn 20 25 30 Asn Ile Leu Ala Arg Val Thr Arg Ala Asn Ser Phe Leu Glu Glu Met 35 40 45 Lys Lys Gly His Leu Glu Arg Glu Cys Met Glu Glu Thr Cys Ser Tyr 50 55 60 Glu Glu Ala Arg Glu Val Phe Glu Asp Ser Asp Lys Thr Asn Glu Phe 65 70 75 80 Trp Asn Lys Tyr Lys Asp Gly Asp Gln Cys Glu Thr Ser Pro Cys Gln 85 90 95 Asn Gln Gly Lys Cys Lys Asp Gly Leu Gly Glu Tyr Thr Cys Thr Cys 100 105 110 Leu Glu Gly Phe Glu Gly Lys Asn Cys Glu Leu Phe Thr Arg Lys Leu 115 120 125 Cys Ser Leu Asp Asn Gly Asp Cys Asp Gln Phe Cys His Glu Glu Gln 130 135 140 Asn Ser Val Val Cys Ser Cys Ala Arg Gly Tyr Thr Leu Ala Asp Asn 145 150 155 160 Gly Lys Ala Cys Ile Pro Thr Gly Pro Tyr Pro Cys Gly Lys Gln Thr 165 170 175 Leu Glu Arg Arg Lys Arg Ser Val Ala Gln Ala Thr Ser Ser Ser Gly 180 185 190 Glu Ala Pro Asp Ser Ile Thr Trp Lys Pro Tyr Asp Ala Ala Asp Leu 195 200 205 Asp Pro Thr Glu Asn Pro Phe Asp Leu Leu Asp Phe Asn Gln Thr Gln 210 215 220 Pro Glu Arg Gly Asp Asn Asn Leu Thr Arg Ile Val Gly Gly Gln Glu 225 230 235 240 Cys Lys Asp Gly Glu Cys Pro Trp Gln Ala Leu Leu Ile Asn Glu Glu 245 250 255 Asn Glu Gly Phe Cys Gly Gly Thr Ile Leu Ser Glu Phe Tyr Ile Leu 260 265 270 Thr Ala Ala His Cys Leu Tyr Gln Ala Lys Arg Phe Lys Val Arg Val 275 280 285 Gly Asp Arg Asn Thr Glu Gln Glu Glu Gly Gly Glu Ala Val His Glu 290 295 300 Val Glu Val Val Ile Lys His Asn Arg Phe Thr Lys Glu Thr Tyr Asp 305 310 315 320 Phe Asp Ile Ala Val Leu Arg Leu Lys Thr Pro Ile Thr Phe Arg Met 325 330 335 Asn Val Ala Pro Ala Cys Leu Pro Glu Arg Asp Trp Ala Glu Ser Thr 340 345 350 Leu Met Thr Gln Lys Thr Gly Ile Val Ser Gly Phe Gly Arg Thr His 355 360 365 Glu Lys Gly Arg Gln Ser Thr Arg Leu Lys Met Leu Glu Val Pro Tyr 370 375 380 Val Asp Arg Asn Ser Cys Lys Leu Ser Ser Ser Phe Ile Ile Thr Gln 385 390 395 400 Asn Met Phe Cys Ala Gly Tyr Asp Thr Lys Gln Glu Asp Ala Cys Gln 405 410 415 Gly Asp Ser Gly Gly Pro His Val Thr Arg Phe Lys Asp Thr Tyr Phe 420 425 430 Val Thr Gly Ile Val Ser Trp Gly Glu Gly Cys Ala Arg Lys Gly Lys 435 440 445 Tyr Gly Ile Tyr Thr Lys Val Thr Ala Phe Leu Lys Trp Ile Asp Arg 450 455 460 Ser Met Lys Thr Arg Gly Leu Pro Lys Ala Lys Ser His Ala Pro Glu 465 470 475 480 Val Ile Thr Ser Ser Pro Leu Lys 485 288500PRTHomo sapiens 288Met Ala Ser Arg Leu Thr Leu Leu Thr Leu Leu Leu Leu Leu Leu Ala 1 5 10 15 Gly Asp Arg Ala Ser Ser Asn Pro Asn Ala Thr Ser Ser Ser Ser Gln 20 25 30 Asp Pro Glu Ser Leu Gln Asp Arg Gly Glu Gly Lys Val Ala Thr Thr 35 40 45 Val Ile Ser Lys Met Leu Phe Val Glu Pro Ile Leu Glu Val Ser Ser 50 55 60 Leu Pro Thr Thr Asn Ser Thr Thr Asn Ser Ala Thr Lys Ile Thr Ala 65 70 75 80 Asn Thr Thr Asp Glu Pro Thr Thr Gln Pro Thr Thr Glu Pro Thr Thr 85 90 95 Gln Pro Thr Ile Gln Pro Thr Gln Pro Thr Thr Gln Leu Pro Thr Asp 100 105 110 Ser Pro Thr Gln Pro Thr Thr Gly Ser Phe Cys Pro Gly Pro Val Thr 115 120 125 Leu Cys Ser Asp Leu Glu Ser His Ser Thr Glu Ala Val Leu Gly Asp 130 135 140 Ala Leu Val Asp Phe Ser Leu Lys Leu Tyr His Ala Phe Ser Ala Met 145 150 155 160 Lys Lys Val Glu Thr Asn Met Ala Phe Ser Pro Phe Ser Ile Ala Ser 165 170 175 Leu Leu Thr Gln Val Leu Leu Gly Ala Gly Gln Asn Thr Lys Thr Asn 180 185 190 Leu Glu Ser Ile Leu Ser Tyr Pro Lys Asp Phe Thr Cys Val His Gln 195 200 205 Ala Leu Lys Gly Phe Thr Thr Lys Gly Val Thr Ser Val Ser Gln Ile 210 215 220 Phe His Ser Pro Asp Leu Ala Ile Arg Asp Thr Phe Val Asn Ala Ser 225 230 235 240 Arg Thr Leu Tyr Ser Ser Ser Pro Arg Val Leu Ser Asn Asn Ser Asp 245 250 255 Ala Asn Leu Glu Leu Ile Asn Thr Trp Val Ala Lys Asn Thr Asn Asn 260 265 270 Lys Ile Ser Arg Leu Leu Asp Ser Leu Pro Ser Asp Thr Arg Leu Val 275 280 285 Leu Leu Asn Ala Ile Tyr Leu Ser Ala Lys Trp Lys Thr Thr Phe Asp 290 295 300 Pro Lys Lys Thr Arg Met Glu Pro Phe His Phe Lys Asn Ser Val Ile 305 310 315 320 Lys Val Pro Met Met Asn Ser Lys Lys Tyr Pro Val Ala His Phe Ile 325 330 335 Asp Gln Thr Leu Lys Ala Lys Val Gly Gln Leu Gln Leu Ser His Asn 340 345 350 Leu Ser Leu Val Ile Leu Val Pro Gln Asn Leu Lys His Arg Leu Glu 355 360 365 Asp Met Glu Gln Ala Leu Ser Pro Ser Val Phe Lys Ala Ile Met Glu 370 375 380 Lys Leu Glu Met Ser Lys Phe Gln Pro Thr Leu Leu Thr Leu Pro Arg 385 390 395 400 Ile Lys Val Thr Thr Ser Gln Asp Met Leu Ser Ile Met Glu Lys Leu 405 410 415 Glu Phe Phe Asp Phe Ser Tyr Asp Leu Asn Leu Cys Gly Leu Thr Glu 420 425 430 Asp Pro Asp Leu Gln Val Ser Ala Met Gln His Gln Thr Val Leu Glu 435 440 445 Leu Thr Glu Thr Gly Val Glu Ala Ala Ala Ala Ser Ala Ile Ser Val 450 455 460 Ala Arg Thr Leu Leu Val Phe Glu Val Gln Gln Pro Phe Leu Phe Val 465 470 475 480 Leu Trp Asp Gln Gln His Lys Phe Pro Val Phe Met Gly Arg Val Tyr 485 490 495 Asp Pro Arg Ala 500 289705PRTHomo sapiens 289Met Trp Leu Leu Tyr Leu Leu Val Pro Ala Leu Phe Cys Arg Ala Gly 1 5 10 15 Gly Ser Ile Pro Ile Pro Gln Lys Leu Phe Gly Glu Val Thr Ser Pro 20 25 30 Leu Phe Pro Lys Pro Tyr Pro Asn Asn Phe Glu Thr Thr Thr Val Ile 35 40 45 Thr Val Pro Thr Gly Tyr Arg Val Lys Leu Val Phe Gln Gln Phe Asp 50 55 60 Leu Glu Pro Ser Glu Gly Cys Phe Tyr Asp Tyr Val Lys Ile Ser Ala 65 70 75 80 Asp Lys Lys Ser Leu Gly Arg Phe Cys Gly Gln Leu Gly Ser Pro Leu 85 90 95 Gly Asn Pro Pro Gly Lys Lys Glu Phe Met Ser Gln Gly Asn Lys Met 100 105 110 Leu Leu Thr Phe His Thr Asp Phe Ser Asn Glu Glu Asn Gly Thr Ile 115 120 125 Met Phe Tyr Lys Gly Phe Leu Ala Tyr Tyr Gln Ala Val Asp Leu Asp 130 135 140 Glu Cys Ala Ser Arg Ser Lys Leu Gly Glu Glu Asp Pro Gln Pro Gln 145 150 155 160 Cys Gln His Leu Cys His Asn Tyr Val Gly Gly Tyr Phe Cys Ser Cys 165 170 175 Arg Pro Gly Tyr Glu Leu Gln Glu Asp Arg His Ser Cys Gln Ala Glu 180 185 190 Cys Ser Ser Glu Leu Tyr Thr Glu Ala Ser Gly Tyr Ile Ser Ser Leu 195 200 205 Glu Tyr Pro Arg Ser Tyr Pro Pro Asp Leu Arg Cys Asn Tyr Ser Ile 210 215 220 Arg Val Glu Arg Gly Leu Thr Leu His Leu Lys Phe Leu Glu Pro Phe 225 230 235 240 Asp Ile Asp Asp His Gln Gln Val His Cys Pro Tyr Asp Gln Leu Gln 245 250 255 Ile Tyr Ala Asn Gly Lys Asn Ile Gly Glu Phe Cys Gly Lys Gln Arg 260 265 270 Pro Pro Asp Leu Asp Thr Ser Ser Asn Ala Val Asp Leu Leu Phe Phe 275 280 285 Thr Asp Glu Ser Gly Asp Ser Arg Gly Trp Lys Leu Arg Tyr Thr Thr 290 295 300 Glu Ile Ile Lys Cys Pro Gln Pro Lys Thr Leu Asp Glu Phe Thr Ile 305 310 315 320 Ile Gln Asn Leu Gln Pro Gln Tyr Gln Phe Arg Asp Tyr Phe Ile Ala 325 330 335 Thr Cys Lys Gln Gly Tyr Gln Leu Ile Glu Gly Asn Gln Val Leu His 340 345 350 Ser Phe Thr Ala Val Cys Gln Asp Asp Gly Thr Trp His Arg Ala Met 355 360 365 Pro Arg Cys Lys Ile Lys Asp Cys Gly Gln Pro Arg Asn Leu Pro Asn 370 375 380 Gly Asp Phe Arg Tyr Thr Thr Thr Met Gly Val Asn Thr Tyr Lys Ala 385 390 395 400 Arg Ile Gln Tyr Tyr Cys His Glu Pro Tyr Tyr Lys Met Gln Thr Arg 405 410 415 Ala Gly Ser Arg Glu Ser Glu Gln Gly Val Tyr Thr Cys Thr Ala Gln 420 425 430 Gly Ile Trp Lys Asn Glu Gln Lys Gly Glu Lys Ile Pro Arg Cys Leu 435 440 445 Pro Val Cys Gly Lys Pro Val Asn Pro Val Glu Gln Arg Gln Arg Ile 450 455 460 Ile Gly Gly Gln Lys

Ala Lys Met Gly Asn Phe Pro Trp Gln Val Phe 465 470 475 480 Thr Asn Ile His Gly Arg Gly Gly Gly Ala Leu Leu Gly Asp Arg Trp 485 490 495 Ile Leu Thr Ala Ala His Thr Leu Tyr Pro Lys Glu His Glu Ala Gln 500 505 510 Ser Asn Ala Ser Leu Asp Val Phe Leu Gly His Thr Asn Val Glu Glu 515 520 525 Leu Met Lys Leu Gly Asn His Pro Ile Arg Arg Val Ser Val His Pro 530 535 540 Asp Tyr Arg Gln Asp Glu Ser Tyr Asn Phe Glu Gly Asp Ile Ala Leu 545 550 555 560 Leu Glu Leu Glu Asn Ser Val Thr Leu Gly Pro Asn Leu Leu Pro Ile 565 570 575 Cys Leu Pro Asp Asn Asp Thr Phe Tyr Asp Leu Gly Leu Met Gly Tyr 580 585 590 Val Ser Gly Phe Gly Val Met Glu Glu Lys Ile Ala His Asp Leu Arg 595 600 605 Phe Val Arg Leu Pro Val Ala Asn Pro Gln Ala Cys Glu Asn Trp Leu 610 615 620 Arg Gly Lys Asn Arg Met Asp Val Phe Ser Gln Asn Met Phe Cys Ala 625 630 635 640 Gly His Pro Ser Leu Lys Gln Asp Ala Cys Gln Gly Asp Ser Gly Gly 645 650 655 Val Phe Ala Val Arg Asp Pro Asn Thr Asp Arg Trp Val Ala Thr Gly 660 665 670 Ile Val Ser Trp Gly Ile Gly Cys Ser Arg Gly Tyr Gly Phe Tyr Thr 675 680 685 Lys Val Leu Asn Tyr Val Asp Trp Ile Lys Lys Glu Met Glu Glu Glu 690 695 700 Asp 705 290487PRTHomo sapiens 290Met Pro Gly Pro Arg Val Trp Gly Lys Tyr Leu Trp Arg Ser Pro His 1 5 10 15 Ser Lys Gly Cys Pro Gly Ala Met Trp Trp Leu Leu Leu Trp Gly Val 20 25 30 Leu Gln Ala Cys Pro Thr Arg Gly Ser Val Leu Leu Ala Gln Glu Leu 35 40 45 Pro Gln Gln Leu Thr Ser Pro Gly Tyr Pro Glu Pro Tyr Gly Lys Gly 50 55 60 Gln Glu Ser Ser Thr Asp Ile Lys Ala Pro Glu Gly Phe Ala Val Arg 65 70 75 80 Leu Val Phe Gln Asp Phe Asp Leu Glu Pro Ser Gln Asp Cys Ala Gly 85 90 95 Asp Ser Val Thr Ile Ser Phe Val Gly Ser Asp Pro Ser Gln Phe Cys 100 105 110 Gly Gln Gln Gly Ser Pro Leu Gly Arg Pro Pro Gly Gln Arg Glu Phe 115 120 125 Val Ser Ser Gly Arg Ser Leu Arg Leu Thr Phe Arg Thr Gln Pro Ser 130 135 140 Ser Glu Asn Lys Thr Ala His Leu His Lys Gly Phe Leu Ala Leu Tyr 145 150 155 160 Gln Thr Val Ala Val Asn Tyr Ser Gln Pro Ile Ser Glu Ala Ser Arg 165 170 175 Gly Ser Glu Ala Ile Asn Ala Pro Gly Asp Asn Pro Ala Lys Val Gln 180 185 190 Asn His Cys Gln Glu Pro Tyr Tyr Gln Ala Ala Ala Ala Gly Ala Leu 195 200 205 Thr Cys Ala Thr Pro Gly Thr Trp Lys Asp Arg Gln Asp Gly Glu Glu 210 215 220 Val Leu Gln Cys Met Pro Val Cys Gly Arg Pro Val Thr Pro Ile Ala 225 230 235 240 Gln Asn Gln Thr Thr Leu Gly Ser Ser Arg Ala Lys Leu Gly Asn Phe 245 250 255 Pro Trp Gln Ala Phe Thr Ser Ile His Gly Arg Gly Gly Gly Ala Leu 260 265 270 Leu Gly Asp Arg Trp Ile Leu Thr Ala Ala His Thr Val Tyr Pro Lys 275 280 285 Asp Ser Val Ser Leu Arg Lys Asn Gln Ser Val Asn Val Phe Leu Gly 290 295 300 His Thr Ala Ile Asp Glu Met Leu Lys Leu Gly Asn His Pro Val His 305 310 315 320 Arg Val Val Val His Pro Asp Tyr Arg Gln Asn Glu Ser His Asn Phe 325 330 335 Ser Gly Asp Ile Ala Leu Leu Glu Leu Gln His Ser Ile Pro Leu Gly 340 345 350 Pro Asn Val Leu Pro Val Cys Leu Pro Asp Asn Glu Thr Leu Tyr Arg 355 360 365 Ser Gly Leu Leu Gly Tyr Val Ser Gly Phe Gly Met Glu Met Gly Trp 370 375 380 Leu Thr Thr Glu Leu Lys Tyr Ser Arg Leu Pro Val Ala Pro Arg Glu 385 390 395 400 Ala Cys Asn Ala Trp Leu Gln Lys Arg Gln Arg Pro Glu Val Phe Ser 405 410 415 Asp Asn Met Phe Cys Val Gly Asp Glu Thr Gln Arg His Ser Val Cys 420 425 430 Gln Gly Asp Ser Gly Ser Val Tyr Val Val Trp Asp Asn His Ala His 435 440 445 His Trp Val Ala Thr Gly Ile Val Ser Trp Gly Ile Gly Cys Gly Glu 450 455 460 Gly Tyr Asp Phe Tyr Thr Lys Val Leu Ser Tyr Val Asp Trp Ile Lys 465 470 475 480 Gly Val Met Asn Gly Lys Asn 485 291688PRTHomo sapiens 291Met Trp Cys Ile Val Leu Phe Ser Leu Leu Ala Trp Val Tyr Ala Glu 1 5 10 15 Pro Thr Met Tyr Gly Glu Ile Leu Ser Pro Asn Tyr Pro Gln Ala Tyr 20 25 30 Pro Ser Glu Val Glu Lys Ser Trp Asp Ile Glu Val Pro Glu Gly Tyr 35 40 45 Gly Ile His Leu Tyr Phe Thr His Leu Asp Ile Glu Leu Ser Glu Asn 50 55 60 Cys Ala Tyr Asp Ser Val Gln Ile Ile Ser Gly Asp Thr Glu Glu Gly 65 70 75 80 Arg Leu Cys Gly Gln Arg Ser Ser Asn Asn Pro His Ser Pro Ile Val 85 90 95 Glu Glu Phe Gln Val Pro Tyr Asn Lys Leu Gln Val Ile Phe Lys Ser 100 105 110 Asp Phe Ser Asn Glu Glu Arg Phe Thr Gly Phe Ala Ala Tyr Tyr Val 115 120 125 Ala Thr Asp Ile Asn Glu Cys Thr Asp Phe Val Asp Val Pro Cys Ser 130 135 140 His Phe Cys Asn Asn Phe Ile Gly Gly Tyr Phe Cys Ser Cys Pro Pro 145 150 155 160 Glu Tyr Phe Leu His Asp Asp Met Lys Asn Cys Gly Val Asn Cys Ser 165 170 175 Gly Asp Val Phe Thr Ala Leu Ile Gly Glu Ile Ala Ser Pro Asn Tyr 180 185 190 Pro Lys Pro Tyr Pro Glu Asn Ser Arg Cys Glu Tyr Gln Ile Arg Leu 195 200 205 Glu Lys Gly Phe Gln Val Val Val Thr Leu Arg Arg Glu Asp Phe Asp 210 215 220 Val Glu Ala Ala Asp Ser Ala Gly Asn Cys Leu Asp Ser Leu Val Phe 225 230 235 240 Val Ala Gly Asp Arg Gln Phe Gly Pro Tyr Cys Gly His Gly Phe Pro 245 250 255 Gly Pro Leu Asn Ile Glu Thr Lys Ser Asn Ala Leu Asp Ile Ile Phe 260 265 270 Gln Thr Asp Leu Thr Gly Gln Lys Lys Gly Trp Lys Leu Arg Tyr His 275 280 285 Gly Asp Pro Met Pro Cys Pro Lys Glu Asp Thr Pro Asn Ser Val Trp 290 295 300 Glu Pro Ala Lys Ala Lys Tyr Val Phe Arg Asp Val Val Gln Ile Thr 305 310 315 320 Cys Leu Asp Gly Phe Glu Val Val Glu Gly Arg Val Gly Ala Thr Ser 325 330 335 Phe Tyr Ser Thr Cys Gln Ser Asn Gly Lys Trp Ser Asn Ser Lys Leu 340 345 350 Lys Cys Gln Pro Val Asp Cys Gly Ile Pro Glu Ser Ile Glu Asn Gly 355 360 365 Lys Val Glu Asp Pro Glu Ser Thr Leu Phe Gly Ser Val Ile Arg Tyr 370 375 380 Thr Cys Glu Glu Pro Tyr Tyr Tyr Met Glu Asn Gly Gly Gly Gly Glu 385 390 395 400 Tyr His Cys Ala Gly Asn Gly Ser Trp Val Asn Glu Val Leu Gly Pro 405 410 415 Glu Leu Pro Lys Cys Val Pro Val Cys Gly Val Pro Arg Glu Pro Phe 420 425 430 Glu Glu Lys Gln Arg Ile Ile Gly Gly Ser Asp Ala Asp Ile Lys Asn 435 440 445 Phe Pro Trp Gln Val Phe Phe Asp Asn Pro Trp Ala Gly Gly Ala Leu 450 455 460 Ile Asn Glu Tyr Trp Val Leu Thr Ala Ala His Val Val Glu Gly Asn 465 470 475 480 Arg Glu Pro Thr Met Tyr Val Gly Ser Thr Ser Val Gln Thr Ser Arg 485 490 495 Leu Ala Lys Ser Lys Met Leu Thr Pro Glu His Val Phe Ile His Pro 500 505 510 Gly Trp Lys Leu Leu Glu Val Pro Glu Gly Arg Thr Asn Phe Asp Asn 515 520 525 Asp Ile Ala Leu Val Arg Leu Lys Asp Pro Val Lys Met Gly Pro Thr 530 535 540 Val Ser Pro Ile Cys Leu Pro Gly Thr Ser Ser Asp Tyr Asn Leu Met 545 550 555 560 Asp Gly Asp Leu Gly Leu Ile Ser Gly Trp Gly Arg Thr Glu Lys Arg 565 570 575 Asp Arg Ala Val Arg Leu Lys Ala Ala Arg Leu Pro Val Ala Pro Leu 580 585 590 Arg Lys Cys Lys Glu Val Lys Val Glu Lys Pro Thr Ala Asp Ala Glu 595 600 605 Ala Tyr Val Phe Thr Pro Asn Met Ile Cys Ala Gly Gly Glu Lys Gly 610 615 620 Met Asp Ser Cys Lys Gly Asp Ser Gly Gly Ala Phe Ala Val Gln Asp 625 630 635 640 Pro Asn Asp Lys Thr Lys Phe Tyr Ala Ala Gly Leu Val Ser Trp Gly 645 650 655 Pro Gln Cys Gly Thr Tyr Gly Leu Tyr Thr Arg Val Lys Asn Tyr Val 660 665 670 Asp Trp Ile Met Lys Thr Met Gln Glu Asn Ser Thr Pro Arg Glu Asp 675 680 685 292752PRTHomo sapiens 292Met Gly Pro Leu Met Val Leu Phe Cys Leu Leu Phe Leu Tyr Pro Gly 1 5 10 15 Leu Ala Asp Ser Ala Pro Ser Cys Pro Gln Asn Val Asn Ile Ser Gly 20 25 30 Gly Thr Phe Thr Leu Ser His Gly Trp Ala Pro Gly Ser Leu Leu Thr 35 40 45 Tyr Ser Cys Pro Gln Gly Leu Tyr Pro Ser Pro Ala Ser Arg Leu Cys 50 55 60 Lys Ser Ser Gly Gln Trp Gln Thr Pro Gly Ala Thr Arg Ser Leu Ser 65 70 75 80 Lys Ala Val Cys Lys Pro Val Arg Cys Pro Ala Pro Val Ser Phe Glu 85 90 95 Asn Gly Ile Tyr Thr Pro Arg Leu Gly Ser Tyr Pro Val Gly Gly Asn 100 105 110 Val Ser Phe Glu Cys Glu Asp Gly Phe Ile Leu Arg Gly Ser Pro Val 115 120 125 Arg Gln Cys Arg Pro Asn Gly Met Trp Asp Gly Glu Thr Ala Val Cys 130 135 140 Asp Asn Gly Ala Gly His Cys Pro Asn Pro Gly Ile Ser Leu Gly Ala 145 150 155 160 Val Arg Thr Gly Phe Arg Phe Gly His Gly Asp Lys Val Arg Tyr Arg 165 170 175 Cys Ser Ser Asn Leu Val Leu Thr Gly Ser Ser Glu Arg Glu Cys Gln 180 185 190 Gly Asn Gly Val Trp Ser Gly Thr Glu Pro Ile Cys Arg Gln Pro Tyr 195 200 205 Ser Tyr Asp Phe Pro Glu Asp Val Ala Pro Ala Leu Gly Thr Ser Phe 210 215 220 Ser His Met Leu Gly Ala Thr Asn Pro Thr Gln Lys Thr Lys Glu Ser 225 230 235 240 Leu Gly Arg Lys Ile Gln Ile Gln Arg Ser Gly His Leu Asn Leu Tyr 245 250 255 Leu Leu Leu Asp Cys Ser Gln Ser Val Ser Glu Asn Asp Phe Leu Ile 260 265 270 Phe Lys Glu Ser Ala Ser Leu Met Val Asp Arg Ile Phe Ser Phe Glu 275 280 285 Ile Asn Val Ser Val Ala Ile Ile Thr Phe Ala Ser Glu Pro Lys Val 290 295 300 Leu Met Ser Val Leu Asn Asp Asn Ser Arg Asp Met Thr Glu Val Ile 305 310 315 320 Ser Ser Leu Glu Asn Ala Asn Tyr Lys Asp His Glu Asn Gly Thr Gly 325 330 335 Thr Asn Thr Tyr Ala Ala Leu Asn Ser Val Tyr Leu Met Met Asn Asn 340 345 350 Gln Met Arg Leu Leu Gly Met Glu Thr Met Ala Trp Gln Glu Ile Arg 355 360 365 His Ala Ile Ile Leu Leu Thr Asp Gly Lys Ser Asn Met Gly Gly Ser 370 375 380 Pro Lys Thr Ala Val Asp His Ile Arg Glu Ile Leu Asn Ile Asn Gln 385 390 395 400 Lys Arg Asn Asp Tyr Leu Asp Ile Tyr Ala Ile Gly Val Gly Lys Leu 405 410 415 Asp Val Asp Trp Arg Glu Leu Asn Glu Leu Gly Ser Lys Lys Asp Gly 420 425 430 Glu Arg His Ala Phe Ile Leu Gln Asp Thr Lys Ala Leu His Gln Val 435 440 445 Phe Glu His Met Leu Asp Val Ser Lys Leu Thr Asp Thr Ile Cys Gly 450 455 460 Val Gly Asn Met Ser Ala Asn Ala Ser Asp Gln Glu Arg Thr Pro Trp 465 470 475 480 His Val Thr Ile Lys Pro Lys Ser Gln Glu Thr Cys Arg Gly Ala Leu 485 490 495 Ile Ser Asp Gln Trp Val Leu Thr Ala Ala His Cys Phe Arg Asp Gly 500 505 510 Asn Asp His Ser Leu Trp Arg Val Asn Val Gly Asp Pro Lys Ser Gln 515 520 525 Trp Gly Lys Glu Phe Leu Ile Glu Lys Ala Val Ile Ser Pro Gly Phe 530 535 540 Asp Val Phe Ala Lys Lys Asn Gln Gly Ile Leu Glu Phe Tyr Gly Asp 545 550 555 560 Asp Ile Ala Leu Leu Lys Leu Ala Gln Lys Val Lys Met Ser Thr His 565 570 575 Ala Arg Pro Ile Cys Leu Pro Cys Thr Met Glu Ala Asn Leu Ala Leu 580 585 590 Arg Arg Pro Gln Gly Ser Thr Cys Arg Asp His Glu Asn Glu Leu Leu 595 600 605 Asn Lys Gln Ser Val Pro Ala His Phe Val Ala Leu Asn Gly Ser Lys 610 615 620 Leu Asn Ile Asn Leu Lys Met Gly Val Glu Trp Thr Ser Cys Ala Glu 625 630 635 640 Val Val Ser Gln Glu Lys Thr Met Phe Pro Asn Leu Thr Asp Val Arg 645 650 655 Glu Val Val Thr Asp Gln Phe Leu Cys Ser Gly Thr Gln Glu Asp Glu 660 665 670 Ser Pro Cys Lys Gly Glu Ser Gly Gly Ala Val Phe Leu Glu Arg Arg 675 680 685 Phe Arg Phe Phe Gln Val Gly Leu Val Ser Trp Gly Leu Tyr Asn Pro 690 695 700 Cys Leu Gly Ser Ala Asp Lys Asn Ser Arg Lys Arg Ala Pro Arg Ser 705 710 715 720 Lys Val Pro Pro Pro Arg Asp Phe His Ile Asn Leu Phe Arg Met Gln 725 730 735 Pro Trp Leu Arg Gln His Leu Gly Asp Val Leu Asn Phe Leu Pro Leu 740 745 750 2931663PRTHomo sapiens 293Met Gly Pro Thr Ser Gly Pro Ser Leu Leu Leu Leu Leu Leu Thr His 1 5 10 15 Leu Pro Leu Ala Leu Gly Ser Pro Met Tyr Ser Ile Ile Thr Pro Asn 20 25 30 Ile Leu Arg Leu Glu Ser Glu Glu Thr Met Val Leu Glu Ala His Asp 35 40 45 Ala Gln Gly Asp Val Pro Val Thr Val Thr Val His Asp Phe Pro Gly 50 55 60 Lys Lys Leu Val Leu Ser Ser Glu Lys Thr Val Leu Thr Pro Ala Thr 65 70 75 80 Asn His Met Gly Asn Val Thr Phe Thr Ile Pro Ala Asn Arg Glu Phe 85 90 95 Lys Ser Glu Lys Gly Arg Asn Lys Phe Val Thr Val Gln Ala Thr Phe 100 105 110 Gly Thr Gln Val Val Glu Lys Val Val Leu Val Ser Leu Gln Ser Gly 115 120 125 Tyr

Leu Phe Ile Gln Thr Asp Lys Thr Ile Tyr Thr Pro Gly Ser Thr 130 135 140 Val Leu Tyr Arg Ile Phe Thr Val Asn His Lys Leu Leu Pro Val Gly 145 150 155 160 Arg Thr Val Met Val Asn Ile Glu Asn Pro Glu Gly Ile Pro Val Lys 165 170 175 Gln Asp Ser Leu Ser Ser Gln Asn Gln Leu Gly Val Leu Pro Leu Ser 180 185 190 Trp Asp Ile Pro Glu Leu Val Asn Met Gly Gln Trp Lys Ile Arg Ala 195 200 205 Tyr Tyr Glu Asn Ser Pro Gln Gln Val Phe Ser Thr Glu Phe Glu Val 210 215 220 Lys Glu Tyr Val Leu Pro Ser Phe Glu Val Ile Val Glu Pro Thr Glu 225 230 235 240 Lys Phe Tyr Tyr Ile Tyr Asn Glu Lys Gly Leu Glu Val Thr Ile Thr 245 250 255 Ala Arg Phe Leu Tyr Gly Lys Lys Val Glu Gly Thr Ala Phe Val Ile 260 265 270 Phe Gly Ile Gln Asp Gly Glu Gln Arg Ile Ser Leu Pro Glu Ser Leu 275 280 285 Lys Arg Ile Pro Ile Glu Asp Gly Ser Gly Glu Val Val Leu Ser Arg 290 295 300 Lys Val Leu Leu Asp Gly Val Gln Asn Leu Arg Ala Glu Asp Leu Val 305 310 315 320 Gly Lys Ser Leu Tyr Val Ser Ala Thr Val Ile Leu His Ser Gly Ser 325 330 335 Asp Met Val Gln Ala Glu Arg Ser Gly Ile Pro Ile Val Thr Ser Pro 340 345 350 Tyr Gln Ile His Phe Thr Lys Thr Pro Lys Tyr Phe Lys Pro Gly Met 355 360 365 Pro Phe Asp Leu Met Val Phe Val Thr Asn Pro Asp Gly Ser Pro Ala 370 375 380 Tyr Arg Val Pro Val Ala Val Gln Gly Glu Asp Thr Val Gln Ser Leu 385 390 395 400 Thr Gln Gly Asp Gly Val Ala Lys Leu Ser Ile Asn Thr His Pro Ser 405 410 415 Gln Lys Pro Leu Ser Ile Thr Val Arg Thr Lys Lys Gln Glu Leu Ser 420 425 430 Glu Ala Glu Gln Ala Thr Arg Thr Met Gln Ala Leu Pro Tyr Ser Thr 435 440 445 Val Gly Asn Ser Asn Asn Tyr Leu His Leu Ser Val Leu Arg Thr Glu 450 455 460 Leu Arg Pro Gly Glu Thr Leu Asn Val Asn Phe Leu Leu Arg Met Asp 465 470 475 480 Arg Ala His Glu Ala Lys Ile Arg Tyr Tyr Thr Tyr Leu Ile Met Asn 485 490 495 Lys Gly Arg Leu Leu Lys Ala Gly Arg Gln Val Arg Glu Pro Gly Gln 500 505 510 Asp Leu Val Val Leu Pro Leu Ser Ile Thr Thr Asp Phe Ile Pro Ser 515 520 525 Phe Arg Leu Val Ala Tyr Tyr Thr Leu Ile Gly Ala Ser Gly Gln Arg 530 535 540 Glu Val Val Ala Asp Ser Val Trp Val Asp Val Lys Asp Ser Cys Val 545 550 555 560 Gly Ser Leu Val Val Lys Ser Gly Gln Ser Glu Asp Arg Gln Pro Val 565 570 575 Pro Gly Gln Gln Met Thr Leu Lys Ile Glu Gly Asp His Gly Ala Arg 580 585 590 Val Val Leu Val Ala Val Asp Lys Gly Val Phe Val Leu Asn Lys Lys 595 600 605 Asn Lys Leu Thr Gln Ser Lys Ile Trp Asp Val Val Glu Lys Ala Asp 610 615 620 Ile Gly Cys Thr Pro Gly Ser Gly Lys Asp Tyr Ala Gly Val Phe Ser 625 630 635 640 Asp Ala Gly Leu Thr Phe Thr Ser Ser Ser Gly Gln Gln Thr Ala Gln 645 650 655 Arg Ala Glu Leu Gln Cys Pro Gln Pro Ala Ala Arg Arg Arg Arg Ser 660 665 670 Val Gln Leu Thr Glu Lys Arg Met Asp Lys Val Gly Lys Tyr Pro Lys 675 680 685 Glu Leu Arg Lys Cys Cys Glu Asp Gly Met Arg Glu Asn Pro Met Arg 690 695 700 Phe Ser Cys Gln Arg Arg Thr Arg Phe Ile Ser Leu Gly Glu Ala Cys 705 710 715 720 Lys Lys Val Phe Leu Asp Cys Cys Asn Tyr Ile Thr Glu Leu Arg Arg 725 730 735 Gln His Ala Arg Ala Ser His Leu Gly Leu Ala Arg Ser Asn Leu Asp 740 745 750 Glu Asp Ile Ile Ala Glu Glu Asn Ile Val Ser Arg Ser Glu Phe Pro 755 760 765 Glu Ser Trp Leu Trp Asn Val Glu Asp Leu Lys Glu Pro Pro Lys Asn 770 775 780 Gly Ile Ser Thr Lys Leu Met Asn Ile Phe Leu Lys Asp Ser Ile Thr 785 790 795 800 Thr Trp Glu Ile Leu Ala Val Ser Met Ser Asp Lys Lys Gly Ile Cys 805 810 815 Val Ala Asp Pro Phe Glu Val Thr Val Met Gln Asp Phe Phe Ile Asp 820 825 830 Leu Arg Leu Pro Tyr Ser Val Val Arg Asn Glu Gln Val Glu Ile Arg 835 840 845 Ala Val Leu Tyr Asn Tyr Arg Gln Asn Gln Glu Leu Lys Val Arg Val 850 855 860 Glu Leu Leu His Asn Pro Ala Phe Cys Ser Leu Ala Thr Thr Lys Arg 865 870 875 880 Arg His Gln Gln Thr Val Thr Ile Pro Pro Lys Ser Ser Leu Ser Val 885 890 895 Pro Tyr Val Ile Val Pro Leu Lys Thr Gly Leu Gln Glu Val Glu Val 900 905 910 Lys Ala Ala Val Tyr His His Phe Ile Ser Asp Gly Val Arg Lys Ser 915 920 925 Leu Lys Val Val Pro Glu Gly Ile Arg Met Asn Lys Thr Val Ala Val 930 935 940 Arg Thr Leu Asp Pro Glu Arg Leu Gly Arg Glu Gly Val Gln Lys Glu 945 950 955 960 Asp Ile Pro Pro Ala Asp Leu Ser Asp Gln Val Pro Asp Thr Glu Ser 965 970 975 Glu Thr Arg Ile Leu Leu Gln Gly Thr Pro Val Ala Gln Met Thr Glu 980 985 990 Asp Ala Val Asp Ala Glu Arg Leu Lys His Leu Ile Val Thr Pro Ser 995 1000 1005 Gly Cys Gly Glu Gln Asn Met Ile Gly Met Thr Pro Thr Val Ile 1010 1015 1020 Ala Val His Tyr Leu Asp Glu Thr Glu Gln Trp Glu Lys Phe Gly 1025 1030 1035 Leu Glu Lys Arg Gln Gly Ala Leu Glu Leu Ile Lys Lys Gly Tyr 1040 1045 1050 Thr Gln Gln Leu Ala Phe Arg Gln Pro Ser Ser Ala Phe Ala Ala 1055 1060 1065 Phe Val Lys Arg Ala Pro Ser Thr Trp Leu Thr Ala Tyr Val Val 1070 1075 1080 Lys Val Phe Ser Leu Ala Val Asn Leu Ile Ala Ile Asp Ser Gln 1085 1090 1095 Val Leu Cys Gly Ala Val Lys Trp Leu Ile Leu Glu Lys Gln Lys 1100 1105 1110 Pro Asp Gly Val Phe Gln Glu Asp Ala Pro Val Ile His Gln Glu 1115 1120 1125 Met Ile Gly Gly Leu Arg Asn Asn Asn Glu Lys Asp Met Ala Leu 1130 1135 1140 Thr Ala Phe Val Leu Ile Ser Leu Gln Glu Ala Lys Asp Ile Cys 1145 1150 1155 Glu Glu Gln Val Asn Ser Leu Pro Gly Ser Ile Thr Lys Ala Gly 1160 1165 1170 Asp Phe Leu Glu Ala Asn Tyr Met Asn Leu Gln Arg Ser Tyr Thr 1175 1180 1185 Val Ala Ile Ala Gly Tyr Ala Leu Ala Gln Met Gly Arg Leu Lys 1190 1195 1200 Gly Pro Leu Leu Asn Lys Phe Leu Thr Thr Ala Lys Asp Lys Asn 1205 1210 1215 Arg Trp Glu Asp Pro Gly Lys Gln Leu Tyr Asn Val Glu Ala Thr 1220 1225 1230 Ser Tyr Ala Leu Leu Ala Leu Leu Gln Leu Lys Asp Phe Asp Phe 1235 1240 1245 Val Pro Pro Val Val Arg Trp Leu Asn Glu Gln Arg Tyr Tyr Gly 1250 1255 1260 Gly Gly Tyr Gly Ser Thr Gln Ala Thr Phe Met Val Phe Gln Ala 1265 1270 1275 Leu Ala Gln Tyr Gln Lys Asp Ala Pro Asp His Gln Glu Leu Asn 1280 1285 1290 Leu Asp Val Ser Leu Gln Leu Pro Ser Arg Ser Ser Lys Ile Thr 1295 1300 1305 His Arg Ile His Trp Glu Ser Ala Ser Leu Leu Arg Ser Glu Glu 1310 1315 1320 Thr Lys Glu Asn Glu Gly Phe Thr Val Thr Ala Glu Gly Lys Gly 1325 1330 1335 Gln Gly Thr Leu Ser Val Val Thr Met Tyr His Ala Lys Ala Lys 1340 1345 1350 Asp Gln Leu Thr Cys Asn Lys Phe Asp Leu Lys Val Thr Ile Lys 1355 1360 1365 Pro Ala Pro Glu Thr Glu Lys Arg Pro Gln Asp Ala Lys Asn Thr 1370 1375 1380 Met Ile Leu Glu Ile Cys Thr Arg Tyr Arg Gly Asp Gln Asp Ala 1385 1390 1395 Thr Met Ser Ile Leu Asp Ile Ser Met Met Thr Gly Phe Ala Pro 1400 1405 1410 Asp Thr Asp Asp Leu Lys Gln Leu Ala Asn Gly Val Asp Arg Tyr 1415 1420 1425 Ile Ser Lys Tyr Glu Leu Asp Lys Ala Phe Ser Asp Arg Asn Thr 1430 1435 1440 Leu Ile Ile Tyr Leu Asp Lys Val Ser His Ser Glu Asp Asp Cys 1445 1450 1455 Leu Ala Phe Lys Val His Gln Tyr Phe Asn Val Glu Leu Ile Gln 1460 1465 1470 Pro Gly Ala Val Lys Val Tyr Ala Tyr Tyr Asn Leu Glu Glu Ser 1475 1480 1485 Cys Thr Arg Phe Tyr His Pro Glu Lys Glu Asp Gly Lys Leu Asn 1490 1495 1500 Lys Leu Cys Arg Asp Glu Leu Cys Arg Cys Ala Glu Glu Asn Cys 1505 1510 1515 Phe Ile Gln Lys Ser Asp Asp Lys Val Thr Leu Glu Glu Arg Leu 1520 1525 1530 Asp Lys Ala Cys Glu Pro Gly Val Asp Tyr Val Tyr Lys Thr Arg 1535 1540 1545 Leu Val Lys Val Gln Leu Ser Asn Asp Phe Asp Glu Tyr Ile Met 1550 1555 1560 Ala Ile Glu Gln Thr Ile Lys Ser Gly Ser Asp Glu Val Gln Val 1565 1570 1575 Gly Gln Gln Arg Thr Phe Ile Ser Pro Ile Lys Cys Arg Glu Ala 1580 1585 1590 Leu Lys Leu Glu Glu Lys Lys His Tyr Leu Met Trp Gly Leu Ser 1595 1600 1605 Ser Asp Phe Trp Gly Glu Lys Pro Asn Leu Ser Tyr Ile Ile Gly 1610 1615 1620 Lys Asp Thr Trp Val Glu His Trp Pro Glu Glu Asp Glu Cys Gln 1625 1630 1635 Asp Glu Glu Asn Gln Lys Gln Cys Gln Asp Leu Gly Ala Phe Thr 1640 1645 1650 Glu Ser Met Val Val Phe Gly Cys Pro Asn 1655 1660 294597PRTHomo sapiens 294Met His Pro Pro Lys Thr Pro Ser Gly Ala Leu His Arg Lys Arg Lys 1 5 10 15 Met Ala Ala Trp Pro Phe Ser Arg Leu Trp Lys Val Ser Asp Pro Ile 20 25 30 Leu Phe Gln Met Thr Leu Ile Ala Ala Leu Leu Pro Ala Val Leu Gly 35 40 45 Asn Cys Gly Pro Pro Pro Thr Leu Ser Phe Ala Ala Pro Met Asp Ile 50 55 60 Thr Leu Thr Glu Thr Arg Phe Lys Thr Gly Thr Thr Leu Lys Tyr Thr 65 70 75 80 Cys Leu Pro Gly Tyr Val Arg Ser His Ser Thr Gln Thr Leu Thr Cys 85 90 95 Asn Ser Asp Gly Glu Trp Val Tyr Asn Thr Phe Cys Ile Tyr Lys Arg 100 105 110 Cys Arg His Pro Gly Glu Leu Arg Asn Gly Gln Val Glu Ile Lys Thr 115 120 125 Asp Leu Ser Phe Gly Ser Gln Ile Glu Phe Ser Cys Ser Glu Gly Phe 130 135 140 Phe Leu Ile Gly Ser Thr Thr Ser Arg Cys Glu Val Gln Asp Arg Gly 145 150 155 160 Val Gly Trp Ser His Pro Leu Pro Gln Cys Glu Ile Val Lys Cys Lys 165 170 175 Pro Pro Pro Asp Ile Arg Asn Gly Arg His Ser Gly Glu Glu Asn Phe 180 185 190 Tyr Ala Tyr Gly Phe Ser Val Thr Tyr Ser Cys Asp Pro Arg Phe Ser 195 200 205 Leu Leu Gly His Ala Ser Ile Ser Cys Thr Val Glu Asn Glu Thr Ile 210 215 220 Gly Val Trp Arg Pro Ser Pro Pro Thr Cys Glu Lys Ile Thr Cys Arg 225 230 235 240 Lys Pro Asp Val Ser His Gly Glu Met Val Ser Gly Phe Gly Pro Ile 245 250 255 Tyr Asn Tyr Lys Asp Thr Ile Val Phe Lys Cys Gln Lys Gly Phe Val 260 265 270 Leu Arg Gly Ser Ser Val Ile His Cys Asp Ala Asp Ser Lys Trp Asn 275 280 285 Pro Ser Pro Pro Ala Cys Glu Pro Asn Ser Cys Ile Asn Leu Pro Asp 290 295 300 Ile Pro His Ala Ser Trp Glu Thr Tyr Pro Arg Pro Thr Lys Glu Asp 305 310 315 320 Val Tyr Val Val Gly Thr Val Leu Arg Tyr Arg Cys His Pro Gly Tyr 325 330 335 Lys Pro Thr Thr Asp Glu Pro Thr Thr Val Ile Cys Gln Lys Asn Leu 340 345 350 Arg Trp Thr Pro Tyr Gln Gly Cys Glu Ala Leu Cys Cys Pro Glu Pro 355 360 365 Lys Leu Asn Asn Gly Glu Ile Thr Gln His Arg Lys Ser Arg Pro Ala 370 375 380 Asn His Cys Val Tyr Phe Tyr Gly Asp Glu Ile Ser Phe Ser Cys His 385 390 395 400 Glu Thr Ser Arg Phe Ser Ala Ile Cys Gln Gly Asp Gly Thr Trp Ser 405 410 415 Pro Arg Thr Pro Ser Cys Gly Asp Ile Cys Asn Phe Pro Pro Lys Ile 420 425 430 Ala His Gly His Tyr Lys Gln Ser Ser Ser Tyr Ser Phe Phe Lys Glu 435 440 445 Glu Ile Ile Tyr Glu Cys Asp Lys Gly Tyr Ile Leu Val Gly Gln Ala 450 455 460 Lys Leu Ser Cys Ser Tyr Ser His Trp Ser Ala Pro Ala Pro Gln Cys 465 470 475 480 Lys Ala Leu Cys Arg Lys Pro Glu Leu Val Asn Gly Arg Leu Ser Val 485 490 495 Asp Lys Asp Gln Tyr Val Glu Pro Glu Asn Val Thr Ile Gln Cys Asp 500 505 510 Ser Gly Tyr Gly Val Val Gly Pro Gln Ser Ile Thr Cys Ser Gly Asn 515 520 525 Arg Thr Trp Tyr Pro Glu Val Pro Lys Cys Glu Trp Glu Thr Pro Glu 530 535 540 Gly Cys Glu Gln Val Leu Thr Gly Lys Arg Leu Met Gln Cys Leu Pro 545 550 555 560 Asn Pro Glu Asp Val Lys Met Ala Leu Glu Val Tyr Lys Leu Ser Leu 565 570 575 Glu Ile Glu Gln Leu Glu Leu Gln Arg Asp Ser Ala Arg Gln Ser Thr 580 585 590 Leu Asp Lys Glu Leu 595 2951744PRTHomo sapiens 295Met Arg Leu Leu Trp Gly Leu Ile Trp Ala Ser Ser Phe Phe Thr Leu 1 5 10 15 Ser Leu Gln Lys Pro Arg Leu Leu Leu Phe Ser Pro Ser Val Val His 20 25 30 Leu Gly Val Pro Leu Ser Val Gly Val Gln Leu Gln Asp Val Pro Arg 35 40 45 Gly Gln Val Val Lys Gly Ser Val Phe Leu Arg Asn Pro Ser Arg Asn 50 55 60 Asn Val Pro Cys Ser Pro Lys Val Asp Phe Thr Leu Ser Ser Glu Arg 65 70 75 80 Asp Phe Ala Leu Leu Ser Leu Gln Val Pro Leu Lys Asp Ala Lys Ser 85 90 95 Cys Gly Leu His Gln Leu Leu Arg Gly Pro Glu Val Gln Leu Val Ala 100 105 110 His Ser Pro Trp Leu Lys Asp Ser Leu Ser Arg Thr Thr Asn Ile Gln 115 120 125 Gly Ile Asn Leu Leu Phe Ser Ser Arg Arg Gly His Leu Phe

Leu Gln 130 135 140 Thr Asp Gln Pro Ile Tyr Asn Pro Gly Gln Arg Val Arg Tyr Arg Val 145 150 155 160 Phe Ala Leu Asp Gln Lys Met Arg Pro Ser Thr Asp Thr Ile Thr Val 165 170 175 Met Val Glu Asn Ser His Gly Leu Arg Val Arg Lys Lys Glu Val Tyr 180 185 190 Met Pro Ser Ser Ile Phe Gln Asp Asp Phe Val Ile Pro Asp Ile Ser 195 200 205 Glu Pro Gly Thr Trp Lys Ile Ser Ala Arg Phe Ser Asp Gly Leu Glu 210 215 220 Ser Asn Ser Ser Thr Gln Phe Glu Val Lys Lys Tyr Val Leu Pro Asn 225 230 235 240 Phe Glu Val Lys Ile Thr Pro Gly Lys Pro Tyr Ile Leu Thr Val Pro 245 250 255 Gly His Leu Asp Glu Met Gln Leu Asp Ile Gln Ala Arg Tyr Ile Tyr 260 265 270 Gly Lys Pro Val Gln Gly Val Ala Tyr Val Arg Phe Gly Leu Leu Asp 275 280 285 Glu Asp Gly Lys Lys Thr Phe Phe Arg Gly Leu Glu Ser Gln Thr Lys 290 295 300 Leu Val Asn Gly Gln Ser His Ile Ser Leu Ser Lys Ala Glu Phe Gln 305 310 315 320 Asp Ala Leu Glu Lys Leu Asn Met Gly Ile Thr Asp Leu Gln Gly Leu 325 330 335 Arg Leu Tyr Val Ala Ala Ala Ile Ile Glu Ser Pro Gly Gly Glu Met 340 345 350 Glu Glu Ala Glu Leu Thr Ser Trp Tyr Phe Val Ser Ser Pro Phe Ser 355 360 365 Leu Asp Leu Ser Lys Thr Lys Arg His Leu Val Pro Gly Ala Pro Phe 370 375 380 Leu Leu Gln Ala Leu Val Arg Glu Met Ser Gly Ser Pro Ala Ser Gly 385 390 395 400 Ile Pro Val Lys Val Ser Ala Thr Val Ser Ser Pro Gly Ser Val Pro 405 410 415 Glu Val Gln Asp Ile Gln Gln Asn Thr Asp Gly Ser Gly Gln Val Ser 420 425 430 Ile Pro Ile Ile Ile Pro Gln Thr Ile Ser Glu Leu Gln Leu Ser Val 435 440 445 Ser Ala Gly Ser Pro His Pro Ala Ile Ala Arg Leu Thr Val Ala Ala 450 455 460 Pro Pro Ser Gly Gly Pro Gly Phe Leu Ser Ile Glu Arg Pro Asp Ser 465 470 475 480 Arg Pro Pro Arg Val Gly Asp Thr Leu Asn Leu Asn Leu Arg Ala Val 485 490 495 Gly Ser Gly Ala Thr Phe Ser His Tyr Tyr Tyr Met Ile Leu Ser Arg 500 505 510 Gly Gln Ile Val Phe Met Asn Arg Glu Pro Lys Arg Thr Leu Thr Ser 515 520 525 Val Ser Val Phe Val Asp His His Leu Ala Pro Ser Phe Tyr Phe Val 530 535 540 Ala Phe Tyr Tyr His Gly Asp His Pro Val Ala Asn Ser Leu Arg Val 545 550 555 560 Asp Val Gln Ala Gly Ala Cys Glu Gly Lys Leu Glu Leu Ser Val Asp 565 570 575 Gly Ala Lys Gln Tyr Arg Asn Gly Glu Ser Val Lys Leu His Leu Glu 580 585 590 Thr Asp Ser Leu Ala Leu Val Ala Leu Gly Ala Leu Asp Thr Ala Leu 595 600 605 Tyr Ala Ala Gly Ser Lys Ser His Lys Pro Leu Asn Met Gly Lys Val 610 615 620 Phe Glu Ala Met Asn Ser Tyr Asp Leu Gly Cys Gly Pro Gly Gly Gly 625 630 635 640 Asp Ser Ala Leu Gln Val Phe Gln Ala Ala Gly Leu Ala Phe Ser Asp 645 650 655 Gly Asp Gln Trp Thr Leu Ser Arg Lys Arg Leu Ser Cys Pro Lys Glu 660 665 670 Lys Thr Thr Arg Lys Lys Arg Asn Val Asn Phe Gln Lys Ala Ile Asn 675 680 685 Glu Lys Leu Gly Gln Tyr Ala Ser Pro Thr Ala Lys Arg Cys Cys Gln 690 695 700 Asp Gly Val Thr Arg Leu Pro Met Met Arg Ser Cys Glu Gln Arg Ala 705 710 715 720 Ala Arg Val Gln Gln Pro Asp Cys Arg Glu Pro Phe Leu Ser Cys Cys 725 730 735 Gln Phe Ala Glu Ser Leu Arg Lys Lys Ser Arg Asp Lys Gly Gln Ala 740 745 750 Gly Leu Gln Arg Ala Leu Glu Ile Leu Gln Glu Glu Asp Leu Ile Asp 755 760 765 Glu Asp Asp Ile Pro Val Arg Ser Phe Phe Pro Glu Asn Trp Leu Trp 770 775 780 Arg Val Glu Thr Val Asp Arg Phe Gln Ile Leu Thr Leu Trp Leu Pro 785 790 795 800 Asp Ser Leu Thr Thr Trp Glu Ile His Gly Leu Ser Leu Ser Lys Thr 805 810 815 Lys Gly Leu Cys Val Ala Thr Pro Val Gln Leu Arg Val Phe Arg Glu 820 825 830 Phe His Leu His Leu Arg Leu Pro Met Ser Val Arg Arg Phe Glu Gln 835 840 845 Leu Glu Leu Arg Pro Val Leu Tyr Asn Tyr Leu Asp Lys Asn Leu Thr 850 855 860 Val Ser Val His Val Ser Pro Val Glu Gly Leu Cys Leu Ala Gly Gly 865 870 875 880 Gly Gly Leu Ala Gln Gln Val Leu Val Pro Ala Gly Ser Ala Arg Pro 885 890 895 Val Ala Phe Ser Val Val Pro Thr Ala Ala Thr Ala Val Ser Leu Lys 900 905 910 Val Val Ala Arg Gly Ser Phe Glu Phe Pro Val Gly Asp Ala Val Ser 915 920 925 Lys Val Leu Gln Ile Glu Lys Glu Gly Ala Ile His Arg Glu Glu Leu 930 935 940 Val Tyr Glu Leu Asn Pro Leu Asp His Arg Gly Arg Thr Leu Glu Ile 945 950 955 960 Pro Gly Asn Ser Asp Pro Asn Met Ile Pro Asp Gly Asp Phe Asn Ser 965 970 975 Tyr Val Arg Val Thr Ala Ser Asp Pro Leu Asp Thr Leu Gly Ser Glu 980 985 990 Gly Ala Leu Ser Pro Gly Gly Val Ala Ser Leu Leu Arg Leu Pro Arg 995 1000 1005 Gly Cys Gly Glu Gln Thr Met Ile Tyr Leu Ala Pro Thr Leu Ala 1010 1015 1020 Ala Ser Arg Tyr Leu Asp Lys Thr Glu Gln Trp Ser Thr Leu Pro 1025 1030 1035 Pro Glu Thr Lys Asp His Ala Val Asp Leu Ile Gln Lys Gly Tyr 1040 1045 1050 Met Arg Ile Gln Gln Phe Arg Lys Ala Asp Gly Ser Tyr Ala Ala 1055 1060 1065 Trp Leu Ser Arg Gly Ser Ser Thr Trp Leu Thr Ala Phe Val Leu 1070 1075 1080 Lys Val Leu Ser Leu Ala Gln Glu Gln Val Gly Gly Ser Pro Glu 1085 1090 1095 Lys Leu Gln Glu Thr Ser Asn Trp Leu Leu Ser Gln Gln Gln Ala 1100 1105 1110 Asp Gly Ser Phe Gln Asp Leu Ser Pro Val Ile His Arg Ser Met 1115 1120 1125 Gln Gly Gly Leu Val Gly Asn Asp Glu Thr Val Ala Leu Thr Ala 1130 1135 1140 Phe Val Thr Ile Ala Leu His His Gly Leu Ala Val Phe Gln Asp 1145 1150 1155 Glu Gly Ala Glu Pro Leu Lys Gln Arg Val Glu Ala Ser Ile Ser 1160 1165 1170 Lys Ala Ser Ser Phe Leu Gly Glu Lys Ala Ser Ala Gly Leu Leu 1175 1180 1185 Gly Ala His Ala Ala Ala Ile Thr Ala Tyr Ala Leu Thr Leu Thr 1190 1195 1200 Lys Ala Pro Ala Asp Leu Arg Gly Val Ala His Asn Asn Leu Met 1205 1210 1215 Ala Met Ala Gln Glu Thr Gly Asp Asn Leu Tyr Trp Gly Ser Val 1220 1225 1230 Thr Gly Ser Gln Ser Asn Ala Val Ser Pro Thr Pro Ala Pro Arg 1235 1240 1245 Asn Pro Ser Asp Pro Met Pro Gln Ala Pro Ala Leu Trp Ile Glu 1250 1255 1260 Thr Thr Ala Tyr Ala Leu Leu His Leu Leu Leu His Glu Gly Lys 1265 1270 1275 Ala Glu Met Ala Asp Gln Ala Ala Ala Trp Leu Thr Arg Gln Gly 1280 1285 1290 Ser Phe Gln Gly Gly Phe Arg Ser Thr Gln Asp Thr Val Ile Ala 1295 1300 1305 Leu Asp Ala Leu Ser Ala Tyr Trp Ile Ala Ser His Thr Thr Glu 1310 1315 1320 Glu Arg Gly Leu Asn Val Thr Leu Ser Ser Thr Gly Arg Asn Gly 1325 1330 1335 Phe Lys Ser His Ala Leu Gln Leu Asn Asn Arg Gln Ile Arg Gly 1340 1345 1350 Leu Glu Glu Glu Leu Gln Phe Ser Leu Gly Ser Lys Ile Asn Val 1355 1360 1365 Lys Val Gly Gly Asn Ser Lys Gly Thr Leu Lys Val Leu Arg Thr 1370 1375 1380 Tyr Asn Val Leu Asp Met Lys Asn Thr Thr Cys Gln Asp Leu Gln 1385 1390 1395 Ile Glu Val Thr Val Lys Gly His Val Glu Tyr Thr Met Glu Ala 1400 1405 1410 Asn Glu Asp Tyr Glu Asp Tyr Glu Tyr Asp Glu Leu Pro Ala Lys 1415 1420 1425 Asp Asp Pro Asp Ala Pro Leu Gln Pro Val Thr Pro Leu Gln Leu 1430 1435 1440 Phe Glu Gly Arg Arg Asn Arg Arg Arg Arg Glu Ala Pro Lys Val 1445 1450 1455 Val Glu Glu Gln Glu Ser Arg Val His Tyr Thr Val Cys Ile Trp 1460 1465 1470 Arg Asn Gly Lys Val Gly Leu Ser Gly Met Ala Ile Ala Asp Val 1475 1480 1485 Thr Leu Leu Ser Gly Phe His Ala Leu Arg Ala Asp Leu Glu Lys 1490 1495 1500 Leu Thr Ser Leu Ser Asp Arg Tyr Val Ser His Phe Glu Thr Glu 1505 1510 1515 Gly Pro His Val Leu Leu Tyr Phe Asp Ser Val Pro Thr Ser Arg 1520 1525 1530 Glu Cys Val Gly Phe Glu Ala Val Gln Glu Val Pro Val Gly Leu 1535 1540 1545 Val Gln Pro Ala Ser Ala Thr Leu Tyr Asp Tyr Tyr Asn Pro Glu 1550 1555 1560 Arg Arg Cys Ser Val Phe Tyr Gly Ala Pro Ser Lys Ser Arg Leu 1565 1570 1575 Leu Ala Thr Leu Cys Ser Ala Glu Val Cys Gln Cys Ala Glu Gly 1580 1585 1590 Lys Cys Pro Arg Gln Arg Arg Ala Leu Glu Arg Gly Leu Gln Asp 1595 1600 1605 Glu Asp Gly Tyr Arg Met Lys Phe Ala Cys Tyr Tyr Pro Arg Val 1610 1615 1620 Glu Tyr Gly Phe Gln Val Lys Val Leu Arg Glu Asp Ser Arg Ala 1625 1630 1635 Ala Phe Arg Leu Phe Glu Thr Lys Ile Thr Gln Val Leu His Phe 1640 1645 1650 Thr Lys Asp Val Lys Ala Ala Ala Asn Gln Met Arg Asn Phe Leu 1655 1660 1665 Val Arg Ala Ser Cys Arg Leu Arg Leu Glu Pro Gly Lys Glu Tyr 1670 1675 1680 Leu Ile Met Gly Leu Asp Gly Ala Thr Tyr Asp Leu Glu Gly His 1685 1690 1695 Pro Gln Tyr Leu Leu Asp Ser Asn Ser Trp Ile Glu Glu Met Pro 1700 1705 1710 Ser Glu Arg Leu Cys Arg Ser Thr Arg Gln Arg Ala Ala Cys Ala 1715 1720 1725 Gln Leu Asn Asp Phe Leu Gln Glu Tyr Gly Thr Gln Gly Cys Gln 1730 1735 1740 Val 2961676PRTHomo sapiens 296Met Gly Leu Leu Gly Ile Leu Cys Phe Leu Ile Phe Leu Gly Lys Thr 1 5 10 15 Trp Gly Gln Glu Gln Thr Tyr Val Ile Ser Ala Pro Lys Ile Phe Arg 20 25 30 Val Gly Ala Ser Glu Asn Ile Val Ile Gln Val Tyr Gly Tyr Thr Glu 35 40 45 Ala Phe Asp Ala Thr Ile Ser Ile Lys Ser Tyr Pro Asp Lys Lys Phe 50 55 60 Ser Tyr Ser Ser Gly His Val His Leu Ser Ser Glu Asn Lys Phe Gln 65 70 75 80 Asn Ser Ala Ile Leu Thr Ile Gln Pro Lys Gln Leu Pro Gly Gly Gln 85 90 95 Asn Pro Val Ser Tyr Val Tyr Leu Glu Val Val Ser Lys His Phe Ser 100 105 110 Lys Ser Lys Arg Met Pro Ile Thr Tyr Asp Asn Gly Phe Leu Phe Ile 115 120 125 His Thr Asp Lys Pro Val Tyr Thr Pro Asp Gln Ser Val Lys Val Arg 130 135 140 Val Tyr Ser Leu Asn Asp Asp Leu Lys Pro Ala Lys Arg Glu Thr Val 145 150 155 160 Leu Thr Phe Ile Asp Pro Glu Gly Ser Glu Val Asp Met Val Glu Glu 165 170 175 Ile Asp His Ile Gly Ile Ile Ser Phe Pro Asp Phe Lys Ile Pro Ser 180 185 190 Asn Pro Arg Tyr Gly Met Trp Thr Ile Lys Ala Lys Tyr Lys Glu Asp 195 200 205 Phe Ser Thr Thr Gly Thr Ala Tyr Phe Glu Val Lys Glu Tyr Val Leu 210 215 220 Pro His Phe Ser Val Ser Ile Glu Pro Glu Tyr Asn Phe Ile Gly Tyr 225 230 235 240 Lys Asn Phe Lys Asn Phe Glu Ile Thr Ile Lys Ala Arg Tyr Phe Tyr 245 250 255 Asn Lys Val Val Thr Glu Ala Asp Val Tyr Ile Thr Phe Gly Ile Arg 260 265 270 Glu Asp Leu Lys Asp Asp Gln Lys Glu Met Met Gln Thr Ala Met Gln 275 280 285 Asn Thr Met Leu Ile Asn Gly Ile Ala Gln Val Thr Phe Asp Ser Glu 290 295 300 Thr Ala Val Lys Glu Leu Ser Tyr Tyr Ser Leu Glu Asp Leu Asn Asn 305 310 315 320 Lys Tyr Leu Tyr Ile Ala Val Thr Val Ile Glu Ser Thr Gly Gly Phe 325 330 335 Ser Glu Glu Ala Glu Ile Pro Gly Ile Lys Tyr Val Leu Ser Pro Tyr 340 345 350 Lys Leu Asn Leu Val Ala Thr Pro Leu Phe Leu Lys Pro Gly Ile Pro 355 360 365 Tyr Pro Ile Lys Val Gln Val Lys Asp Ser Leu Asp Gln Leu Val Gly 370 375 380 Gly Val Pro Val Thr Leu Asn Ala Gln Thr Ile Asp Val Asn Gln Glu 385 390 395 400 Thr Ser Asp Leu Asp Pro Ser Lys Ser Val Thr Arg Val Asp Asp Gly 405 410 415 Val Ala Ser Phe Val Leu Asn Leu Pro Ser Gly Val Thr Val Leu Glu 420 425 430 Phe Asn Val Lys Thr Asp Ala Pro Asp Leu Pro Glu Glu Asn Gln Ala 435 440 445 Arg Glu Gly Tyr Arg Ala Ile Ala Tyr Ser Ser Leu Ser Gln Ser Tyr 450 455 460 Leu Tyr Ile Asp Trp Thr Asp Asn His Lys Ala Leu Leu Val Gly Glu 465 470 475 480 His Leu Asn Ile Ile Val Thr Pro Lys Ser Pro Tyr Ile Asp Lys Ile 485 490 495 Thr His Tyr Asn Tyr Leu Ile Leu Ser Lys Gly Lys Ile Ile His Phe 500 505 510 Gly Thr Arg Glu Lys Phe Ser Asp Ala Ser Tyr Gln Ser Ile Asn Ile 515 520 525 Pro Val Thr Gln Asn Met Val Pro Ser Ser Arg Leu Leu Val Tyr Tyr 530 535 540 Ile Val Thr Gly Glu Gln Thr Ala Glu Leu Val Ser Asp Ser Val Trp 545 550 555 560 Leu Asn Ile Glu Glu Lys Cys Gly Asn Gln Leu Gln Val His Leu Ser 565 570 575 Pro Asp Ala Asp Ala Tyr Ser Pro Gly Gln Thr Val Ser Leu Asn Met 580 585 590 Ala Thr Gly Met Asp Ser Trp Val Ala Leu Ala Ala Val Asp Ser Ala 595 600 605 Val Tyr Gly Val Gln Arg Gly Ala Lys Lys Pro Leu Glu Arg Val Phe 610 615 620 Gln Phe Leu Glu Lys Ser Asp Leu Gly Cys Gly Ala Gly Gly Gly Leu 625 630 635 640 Asn Asn Ala Asn Val Phe His Leu Ala Gly Leu Thr Phe Leu Thr Asn 645 650 655 Ala Asn Ala

Asp Asp Ser Gln Glu Asn Asp Glu Pro Cys Lys Glu Ile 660 665 670 Leu Arg Pro Arg Arg Thr Leu Gln Lys Lys Ile Glu Glu Ile Ala Ala 675 680 685 Lys Tyr Lys His Ser Val Val Lys Lys Cys Cys Tyr Asp Gly Ala Cys 690 695 700 Val Asn Asn Asp Glu Thr Cys Glu Gln Arg Ala Ala Arg Ile Ser Leu 705 710 715 720 Gly Pro Arg Cys Ile Lys Ala Phe Thr Glu Cys Cys Val Val Ala Ser 725 730 735 Gln Leu Arg Ala Asn Ile Ser His Lys Asp Met Gln Leu Gly Arg Leu 740 745 750 His Met Lys Thr Leu Leu Pro Val Ser Lys Pro Glu Ile Arg Ser Tyr 755 760 765 Phe Pro Glu Ser Trp Leu Trp Glu Val His Leu Val Pro Arg Arg Lys 770 775 780 Gln Leu Gln Phe Ala Leu Pro Asp Ser Leu Thr Thr Trp Glu Ile Gln 785 790 795 800 Gly Val Gly Ile Ser Asn Thr Gly Ile Cys Val Ala Asp Thr Val Lys 805 810 815 Ala Lys Val Phe Lys Asp Val Phe Leu Glu Met Asn Ile Pro Tyr Ser 820 825 830 Val Val Arg Gly Glu Gln Ile Gln Leu Lys Gly Thr Val Tyr Asn Tyr 835 840 845 Arg Thr Ser Gly Met Gln Phe Cys Val Lys Met Ser Ala Val Glu Gly 850 855 860 Ile Cys Thr Ser Glu Ser Pro Val Ile Asp His Gln Gly Thr Lys Ser 865 870 875 880 Ser Lys Cys Val Arg Gln Lys Val Glu Gly Ser Ser Ser His Leu Val 885 890 895 Thr Phe Thr Val Leu Pro Leu Glu Ile Gly Leu His Asn Ile Asn Phe 900 905 910 Ser Leu Glu Thr Trp Phe Gly Lys Glu Ile Leu Val Lys Thr Leu Arg 915 920 925 Val Val Pro Glu Gly Val Lys Arg Glu Ser Tyr Ser Gly Val Thr Leu 930 935 940 Asp Pro Arg Gly Ile Tyr Gly Thr Ile Ser Arg Arg Lys Glu Phe Pro 945 950 955 960 Tyr Arg Ile Pro Leu Asp Leu Val Pro Lys Thr Glu Ile Lys Arg Ile 965 970 975 Leu Ser Val Lys Gly Leu Leu Val Gly Glu Ile Leu Ser Ala Val Leu 980 985 990 Ser Gln Glu Gly Ile Asn Ile Leu Thr His Leu Pro Lys Gly Ser Ala 995 1000 1005 Glu Ala Glu Leu Met Ser Val Val Pro Val Phe Tyr Val Phe His 1010 1015 1020 Tyr Leu Glu Thr Gly Asn His Trp Asn Ile Phe His Ser Asp Pro 1025 1030 1035 Leu Ile Glu Lys Gln Lys Leu Lys Lys Lys Leu Lys Glu Gly Met 1040 1045 1050 Leu Ser Ile Met Ser Tyr Arg Asn Ala Asp Tyr Ser Tyr Ser Val 1055 1060 1065 Trp Lys Gly Gly Ser Ala Ser Thr Trp Leu Thr Ala Phe Ala Leu 1070 1075 1080 Arg Val Leu Gly Gln Val Asn Lys Tyr Val Glu Gln Asn Gln Asn 1085 1090 1095 Ser Ile Cys Asn Ser Leu Leu Trp Leu Val Glu Asn Tyr Gln Leu 1100 1105 1110 Asp Asn Gly Ser Phe Lys Glu Asn Ser Gln Tyr Gln Pro Ile Lys 1115 1120 1125 Leu Gln Gly Thr Leu Pro Val Glu Ala Arg Glu Asn Ser Leu Tyr 1130 1135 1140 Leu Thr Ala Phe Thr Val Ile Gly Ile Arg Lys Ala Phe Asp Ile 1145 1150 1155 Cys Pro Leu Val Lys Ile Asp Thr Ala Leu Ile Lys Ala Asp Asn 1160 1165 1170 Phe Leu Leu Glu Asn Thr Leu Pro Ala Gln Ser Thr Phe Thr Leu 1175 1180 1185 Ala Ile Ser Ala Tyr Ala Leu Ser Leu Gly Asp Lys Thr His Pro 1190 1195 1200 Gln Phe Arg Ser Ile Val Ser Ala Leu Lys Arg Glu Ala Leu Val 1205 1210 1215 Lys Gly Asn Pro Pro Ile Tyr Arg Phe Trp Lys Asp Asn Leu Gln 1220 1225 1230 His Lys Asp Ser Ser Val Pro Asn Thr Gly Thr Ala Arg Met Val 1235 1240 1245 Glu Thr Thr Ala Tyr Ala Leu Leu Thr Ser Leu Asn Leu Lys Asp 1250 1255 1260 Ile Asn Tyr Val Asn Pro Val Ile Lys Trp Leu Ser Glu Glu Gln 1265 1270 1275 Arg Tyr Gly Gly Gly Phe Tyr Ser Thr Gln Asp Thr Ile Asn Ala 1280 1285 1290 Ile Glu Gly Leu Thr Glu Tyr Ser Leu Leu Val Lys Gln Leu Arg 1295 1300 1305 Leu Ser Met Asp Ile Asp Val Ser Tyr Lys His Lys Gly Ala Leu 1310 1315 1320 His Asn Tyr Lys Met Thr Asp Lys Asn Phe Leu Gly Arg Pro Val 1325 1330 1335 Glu Val Leu Leu Asn Asp Asp Leu Ile Val Ser Thr Gly Phe Gly 1340 1345 1350 Ser Gly Leu Ala Thr Val His Val Thr Thr Val Val His Lys Thr 1355 1360 1365 Ser Thr Ser Glu Glu Val Cys Ser Phe Tyr Leu Lys Ile Asp Thr 1370 1375 1380 Gln Asp Ile Glu Ala Ser His Tyr Arg Gly Tyr Gly Asn Ser Asp 1385 1390 1395 Tyr Lys Arg Ile Val Ala Cys Ala Ser Tyr Lys Pro Ser Arg Glu 1400 1405 1410 Glu Ser Ser Ser Gly Ser Ser His Ala Val Met Asp Ile Ser Leu 1415 1420 1425 Pro Thr Gly Ile Ser Ala Asn Glu Glu Asp Leu Lys Ala Leu Val 1430 1435 1440 Glu Gly Val Asp Gln Leu Phe Thr Asp Tyr Gln Ile Lys Asp Gly 1445 1450 1455 His Val Ile Leu Gln Leu Asn Ser Ile Pro Ser Ser Asp Phe Leu 1460 1465 1470 Cys Val Arg Phe Arg Ile Phe Glu Leu Phe Glu Val Gly Phe Leu 1475 1480 1485 Ser Pro Ala Thr Phe Thr Val Tyr Glu Tyr His Arg Pro Asp Lys 1490 1495 1500 Gln Cys Thr Met Phe Tyr Ser Thr Ser Asn Ile Lys Ile Gln Lys 1505 1510 1515 Val Cys Glu Gly Ala Ala Cys Lys Cys Val Glu Ala Asp Cys Gly 1520 1525 1530 Gln Met Gln Glu Glu Leu Asp Leu Thr Ile Ser Ala Glu Thr Arg 1535 1540 1545 Lys Gln Thr Ala Cys Lys Pro Glu Ile Ala Tyr Ala Tyr Lys Val 1550 1555 1560 Ser Ile Thr Ser Ile Thr Val Glu Asn Val Phe Val Lys Tyr Lys 1565 1570 1575 Ala Thr Leu Leu Asp Ile Tyr Lys Thr Gly Glu Ala Val Ala Glu 1580 1585 1590 Lys Asp Ser Glu Ile Thr Phe Ile Lys Lys Val Thr Cys Thr Asn 1595 1600 1605 Ala Glu Leu Val Lys Gly Arg Gln Tyr Leu Ile Met Gly Lys Glu 1610 1615 1620 Ala Leu Gln Ile Lys Tyr Asn Phe Ser Phe Arg Tyr Ile Tyr Pro 1625 1630 1635 Leu Asp Ser Leu Thr Trp Ile Glu Tyr Trp Pro Arg Asp Thr Thr 1640 1645 1650 Cys Ser Ser Cys Gln Ala Phe Leu Ala Asn Leu Asp Glu Phe Ala 1655 1660 1665 Glu Asp Ile Phe Leu Asn Gly Cys 1670 1675 297934PRTHomo sapiens 297Met Ala Arg Arg Ser Val Leu Tyr Phe Ile Leu Leu Asn Ala Leu Ile 1 5 10 15 Asn Lys Gly Gln Ala Cys Phe Cys Asp His Tyr Ala Trp Thr Gln Trp 20 25 30 Thr Ser Cys Ser Lys Thr Cys Asn Ser Gly Thr Gln Ser Arg His Arg 35 40 45 Gln Ile Val Val Asp Lys Tyr Tyr Gln Glu Asn Phe Cys Glu Gln Ile 50 55 60 Cys Ser Lys Gln Glu Thr Arg Glu Cys Asn Trp Gln Arg Cys Pro Ile 65 70 75 80 Asn Cys Leu Leu Gly Asp Phe Gly Pro Trp Ser Asp Cys Asp Pro Cys 85 90 95 Ile Glu Lys Gln Ser Lys Val Arg Ser Val Leu Arg Pro Ser Gln Phe 100 105 110 Gly Gly Gln Pro Cys Thr Glu Pro Leu Val Ala Phe Gln Pro Cys Ile 115 120 125 Pro Ser Lys Leu Cys Lys Ile Glu Glu Ala Asp Cys Lys Asn Lys Phe 130 135 140 Arg Cys Asp Ser Gly Arg Cys Ile Ala Arg Lys Leu Glu Cys Asn Gly 145 150 155 160 Glu Asn Asp Cys Gly Asp Asn Ser Asp Glu Arg Asp Cys Gly Arg Thr 165 170 175 Lys Ala Val Cys Thr Arg Lys Tyr Asn Pro Ile Pro Ser Val Gln Leu 180 185 190 Met Gly Asn Gly Phe His Phe Leu Ala Gly Glu Pro Arg Gly Glu Val 195 200 205 Leu Asp Asn Ser Phe Thr Gly Gly Ile Cys Lys Thr Val Lys Ser Ser 210 215 220 Arg Thr Ser Asn Pro Tyr Arg Val Pro Ala Asn Leu Glu Asn Val Gly 225 230 235 240 Phe Glu Val Gln Thr Ala Glu Asp Asp Leu Lys Thr Asp Phe Tyr Lys 245 250 255 Asp Leu Thr Ser Leu Gly His Asn Glu Asn Gln Gln Gly Ser Phe Ser 260 265 270 Ser Gln Gly Gly Ser Ser Phe Ser Val Pro Ile Phe Tyr Ser Ser Lys 275 280 285 Arg Ser Glu Asn Ile Asn His Asn Ser Ala Phe Lys Gln Ala Ile Gln 290 295 300 Ala Ser His Lys Lys Asp Ser Ser Phe Ile Arg Ile His Lys Val Met 305 310 315 320 Lys Val Leu Asn Phe Thr Thr Lys Ala Lys Asp Leu His Leu Ser Asp 325 330 335 Val Phe Leu Lys Ala Leu Asn His Leu Pro Leu Glu Tyr Asn Ser Ala 340 345 350 Leu Tyr Ser Arg Ile Phe Asp Asp Phe Gly Thr His Tyr Phe Thr Ser 355 360 365 Gly Ser Leu Gly Gly Val Tyr Asp Leu Leu Tyr Gln Phe Ser Ser Glu 370 375 380 Glu Leu Lys Asn Ser Gly Leu Thr Glu Glu Glu Ala Lys His Cys Val 385 390 395 400 Arg Ile Glu Thr Lys Lys Arg Val Leu Phe Ala Lys Lys Thr Lys Val 405 410 415 Glu His Arg Cys Thr Thr Asn Lys Leu Ser Glu Lys His Glu Gly Ser 420 425 430 Phe Ile Gln Gly Ala Glu Lys Ser Ile Ser Leu Ile Arg Gly Gly Arg 435 440 445 Ser Glu Tyr Gly Ala Ala Leu Ala Trp Glu Lys Gly Ser Ser Gly Leu 450 455 460 Glu Glu Lys Thr Phe Ser Glu Trp Leu Glu Ser Val Lys Glu Asn Pro 465 470 475 480 Ala Val Ile Asp Phe Glu Leu Ala Pro Ile Val Asp Leu Val Arg Asn 485 490 495 Ile Pro Cys Ala Val Thr Lys Arg Asn Asn Leu Arg Lys Ala Leu Gln 500 505 510 Glu Tyr Ala Ala Lys Phe Asp Pro Cys Gln Cys Ala Pro Cys Pro Asn 515 520 525 Asn Gly Arg Pro Thr Leu Ser Gly Thr Glu Cys Leu Cys Val Cys Gln 530 535 540 Ser Gly Thr Tyr Gly Glu Asn Cys Glu Lys Gln Ser Pro Asp Tyr Lys 545 550 555 560 Ser Asn Ala Val Asp Gly Gln Trp Gly Cys Trp Ser Ser Trp Ser Thr 565 570 575 Cys Asp Ala Thr Tyr Lys Arg Ser Arg Thr Arg Glu Cys Asn Asn Pro 580 585 590 Ala Pro Gln Arg Gly Gly Lys Arg Cys Glu Gly Glu Lys Arg Gln Glu 595 600 605 Glu Asp Cys Thr Phe Ser Ile Met Glu Asn Asn Gly Gln Pro Cys Ile 610 615 620 Asn Asp Asp Glu Glu Met Lys Glu Val Asp Leu Pro Glu Ile Glu Ala 625 630 635 640 Asp Ser Gly Cys Pro Gln Pro Val Pro Pro Glu Asn Gly Phe Ile Arg 645 650 655 Asn Glu Lys Gln Leu Tyr Leu Val Gly Glu Asp Val Glu Ile Ser Cys 660 665 670 Leu Thr Gly Phe Glu Thr Val Gly Tyr Gln Tyr Phe Arg Cys Leu Pro 675 680 685 Asp Gly Thr Trp Arg Gln Gly Asp Val Glu Cys Gln Arg Thr Glu Cys 690 695 700 Ile Lys Pro Val Val Gln Glu Val Leu Thr Ile Thr Pro Phe Gln Arg 705 710 715 720 Leu Tyr Arg Ile Gly Glu Ser Ile Glu Leu Thr Cys Pro Lys Gly Phe 725 730 735 Val Val Ala Gly Pro Ser Arg Tyr Thr Cys Gln Gly Asn Ser Trp Thr 740 745 750 Pro Pro Ile Ser Asn Ser Leu Thr Cys Glu Lys Asp Thr Leu Thr Lys 755 760 765 Leu Lys Gly His Cys Gln Leu Gly Gln Lys Gln Ser Gly Ser Glu Cys 770 775 780 Ile Cys Met Ser Pro Glu Glu Asp Cys Ser His His Ser Glu Asp Leu 785 790 795 800 Cys Val Phe Asp Thr Asp Ser Asn Asp Tyr Phe Thr Ser Pro Ala Cys 805 810 815 Lys Phe Leu Ala Glu Lys Cys Leu Asn Asn Gln Gln Leu His Phe Leu 820 825 830 His Ile Gly Ser Cys Gln Asp Gly Arg Gln Leu Glu Trp Gly Leu Glu 835 840 845 Arg Thr Arg Leu Ser Ser Asn Ser Thr Lys Lys Glu Ser Cys Gly Tyr 850 855 860 Asp Thr Cys Tyr Asp Trp Glu Lys Cys Ser Ala Ser Thr Ser Lys Cys 865 870 875 880 Val Cys Leu Leu Pro Pro Gln Cys Phe Lys Gly Gly Asn Gln Leu Tyr 885 890 895 Cys Val Lys Met Gly Ser Ser Thr Ser Glu Lys Thr Leu Asn Ile Cys 900 905 910 Glu Val Gly Thr Ile Arg Cys Ala Asn Arg Lys Met Glu Ile Leu His 915 920 925 Pro Gly Lys Cys Leu Ala 930 298843PRTHomo sapiens 298Met Lys Val Ile Ser Leu Phe Ile Leu Val Gly Phe Ile Gly Glu Phe 1 5 10 15 Gln Ser Phe Ser Ser Ala Ser Ser Pro Val Asn Cys Gln Trp Asp Phe 20 25 30 Tyr Ala Pro Trp Ser Glu Cys Asn Gly Cys Thr Lys Thr Gln Thr Arg 35 40 45 Arg Arg Ser Val Ala Val Tyr Gly Gln Tyr Gly Gly Gln Pro Cys Val 50 55 60 Gly Asn Ala Phe Glu Thr Gln Ser Cys Glu Pro Thr Arg Gly Cys Pro 65 70 75 80 Thr Glu Glu Gly Cys Gly Glu Arg Phe Arg Cys Phe Ser Gly Gln Cys 85 90 95 Ile Ser Lys Ser Leu Val Cys Asn Gly Asp Ser Asp Cys Asp Glu Asp 100 105 110 Ser Ala Asp Glu Asp Arg Cys Glu Asp Ser Glu Arg Arg Pro Ser Cys 115 120 125 Asp Ile Asp Lys Pro Pro Pro Asn Ile Glu Leu Thr Gly Asn Gly Tyr 130 135 140 Asn Glu Leu Thr Gly Gln Phe Arg Asn Arg Val Ile Asn Thr Lys Ser 145 150 155 160 Phe Gly Gly Gln Cys Arg Lys Val Phe Ser Gly Asp Gly Lys Asp Phe 165 170 175 Tyr Arg Leu Ser Gly Asn Val Leu Ser Tyr Thr Phe Gln Val Lys Ile 180 185 190 Asn Asn Asp Phe Asn Tyr Glu Phe Tyr Asn Ser Thr Trp Ser Tyr Val 195 200 205 Lys His Thr Ser Thr Glu His Thr Ser Ser Ser Arg Lys Arg Ser Phe 210 215 220 Phe Arg Ser Ser Ser Ser Ser Ser Arg Ser Tyr Thr Ser His Thr Asn 225 230 235 240 Glu Ile His Lys Gly Lys Ser Tyr Gln Leu Leu Val Val Glu Asn Thr 245 250 255 Val Glu Val Ala Gln Phe Ile Asn Asn Asn Pro Glu Phe Leu Gln Leu 260 265 270 Ala Glu Pro Phe Trp Lys Glu Leu Ser His Leu Pro Ser Leu Tyr Asp 275 280 285 Tyr Ser Ala Tyr Arg Arg Leu Ile Asp Gln Tyr Gly Thr His Tyr Leu 290 295 300 Gln Ser Gly Ser Leu Gly Gly Glu Tyr Arg Val Leu Phe Tyr Val Asp 305

310 315 320 Ser Glu Lys Leu Lys Gln Asn Asp Phe Asn Ser Val Glu Glu Lys Lys 325 330 335 Cys Lys Ser Ser Gly Trp His Phe Val Val Lys Phe Ser Ser His Gly 340 345 350 Cys Lys Glu Leu Glu Asn Ala Leu Lys Ala Ala Ser Gly Thr Gln Asn 355 360 365 Asn Val Leu Arg Gly Glu Pro Phe Ile Arg Gly Gly Gly Ala Gly Phe 370 375 380 Ile Ser Gly Leu Ser Tyr Leu Glu Leu Asp Asn Pro Ala Gly Asn Lys 385 390 395 400 Arg Arg Tyr Ser Ala Trp Ala Glu Ser Val Thr Asn Leu Pro Gln Val 405 410 415 Ile Lys Gln Lys Leu Thr Pro Leu Tyr Glu Leu Val Lys Glu Val Pro 420 425 430 Cys Ala Ser Val Lys Lys Leu Tyr Leu Lys Trp Ala Leu Glu Glu Tyr 435 440 445 Leu Asp Glu Phe Asp Pro Cys His Cys Arg Pro Cys Gln Asn Gly Gly 450 455 460 Leu Ala Thr Val Glu Gly Thr His Cys Leu Cys His Cys Lys Pro Tyr 465 470 475 480 Thr Phe Gly Ala Ala Cys Glu Gln Gly Val Leu Val Gly Asn Gln Ala 485 490 495 Gly Gly Val Asp Gly Gly Trp Ser Cys Trp Ser Ser Trp Ser Pro Cys 500 505 510 Val Gln Gly Lys Lys Thr Arg Ser Arg Glu Cys Asn Asn Pro Pro Pro 515 520 525 Ser Gly Gly Gly Arg Ser Cys Val Gly Glu Thr Thr Glu Ser Thr Gln 530 535 540 Cys Glu Asp Glu Glu Leu Glu His Leu Arg Leu Leu Glu Pro His Cys 545 550 555 560 Phe Pro Leu Ser Leu Val Pro Thr Glu Phe Cys Pro Ser Pro Pro Ala 565 570 575 Leu Lys Asp Gly Phe Val Gln Asp Glu Gly Thr Met Phe Pro Val Gly 580 585 590 Lys Asn Val Val Tyr Thr Cys Asn Glu Gly Tyr Ser Leu Ile Gly Asn 595 600 605 Pro Val Ala Arg Cys Gly Glu Asp Leu Arg Trp Leu Val Gly Glu Met 610 615 620 His Cys Gln Lys Ile Ala Cys Val Leu Pro Val Leu Met Asp Gly Ile 625 630 635 640 Gln Ser His Pro Gln Lys Pro Phe Tyr Thr Val Gly Glu Lys Val Thr 645 650 655 Val Ser Cys Ser Gly Gly Met Ser Leu Glu Gly Pro Ser Ala Phe Leu 660 665 670 Cys Gly Ser Ser Leu Lys Trp Ser Pro Glu Met Lys Asn Ala Arg Cys 675 680 685 Val Gln Lys Glu Asn Pro Leu Thr Gln Ala Val Pro Lys Cys Gln Arg 690 695 700 Trp Glu Lys Leu Gln Asn Ser Arg Cys Val Cys Lys Met Pro Tyr Glu 705 710 715 720 Cys Gly Pro Ser Leu Asp Val Cys Ala Gln Asp Glu Arg Ser Lys Arg 725 730 735 Ile Leu Pro Leu Thr Val Cys Lys Met His Val Leu His Cys Gln Gly 740 745 750 Arg Asn Tyr Thr Leu Thr Gly Arg Asp Ser Cys Thr Leu Pro Ala Ser 755 760 765 Ala Glu Lys Ala Cys Gly Ala Cys Pro Leu Trp Gly Lys Cys Asp Ala 770 775 780 Glu Ser Ser Lys Cys Val Cys Arg Glu Ala Ser Glu Cys Glu Glu Glu 785 790 795 800 Gly Phe Ser Ile Cys Val Glu Val Asn Gly Lys Glu Gln Thr Met Ser 805 810 815 Glu Cys Glu Ala Gly Ala Leu Arg Cys Arg Gly Gln Ser Ile Ser Val 820 825 830 Thr Ser Ile Arg Pro Cys Ala Ala Glu Thr Gln 835 840 299584PRTHomo sapiens 299Met Phe Ala Val Val Phe Phe Ile Leu Ser Leu Met Thr Cys Gln Pro 1 5 10 15 Gly Val Thr Ala Gln Glu Lys Val Asn Gln Arg Val Arg Arg Ala Ala 20 25 30 Thr Pro Ala Ala Val Thr Cys Gln Leu Ser Asn Trp Ser Glu Trp Thr 35 40 45 Asp Cys Phe Pro Cys Gln Asp Lys Lys Tyr Arg His Arg Ser Leu Leu 50 55 60 Gln Pro Asn Lys Phe Gly Gly Thr Ile Cys Ser Gly Asp Ile Trp Asp 65 70 75 80 Gln Ala Ser Cys Ser Ser Ser Thr Thr Cys Val Arg Gln Ala Gln Cys 85 90 95 Gly Gln Asp Phe Gln Cys Lys Glu Thr Gly Arg Cys Leu Lys Arg His 100 105 110 Leu Val Cys Asn Gly Asp Gln Asp Cys Leu Asp Gly Ser Asp Glu Asp 115 120 125 Asp Cys Glu Asp Val Arg Ala Ile Asp Glu Asp Cys Ser Gln Tyr Glu 130 135 140 Pro Ile Pro Gly Ser Gln Lys Ala Ala Leu Gly Tyr Asn Ile Leu Thr 145 150 155 160 Gln Glu Asp Ala Gln Ser Val Tyr Asp Ala Ser Tyr Tyr Gly Gly Gln 165 170 175 Cys Glu Thr Val Tyr Asn Gly Glu Trp Arg Glu Leu Arg Tyr Asp Ser 180 185 190 Thr Cys Glu Arg Leu Tyr Tyr Gly Asp Asp Glu Lys Tyr Phe Arg Lys 195 200 205 Pro Tyr Asn Phe Leu Lys Tyr His Phe Glu Ala Leu Ala Asp Thr Gly 210 215 220 Ile Ser Ser Glu Phe Tyr Asp Asn Ala Asn Asp Leu Leu Ser Lys Val 225 230 235 240 Lys Lys Asp Lys Ser Asp Ser Phe Gly Val Thr Ile Gly Ile Gly Pro 245 250 255 Ala Gly Ser Pro Leu Leu Val Gly Val Gly Val Ser His Ser Gln Asp 260 265 270 Thr Ser Phe Leu Asn Glu Leu Asn Lys Tyr Asn Glu Lys Lys Phe Ile 275 280 285 Phe Thr Arg Ile Phe Thr Lys Val Gln Thr Ala His Phe Lys Met Arg 290 295 300 Lys Asp Asp Ile Met Leu Asp Glu Gly Met Leu Gln Ser Leu Met Glu 305 310 315 320 Leu Pro Asp Gln Tyr Asn Tyr Gly Met Tyr Ala Lys Phe Ile Asn Asp 325 330 335 Tyr Gly Thr His Tyr Ile Thr Ser Gly Ser Met Gly Gly Ile Tyr Glu 340 345 350 Tyr Ile Leu Val Ile Asp Lys Ala Lys Met Glu Ser Leu Gly Ile Thr 355 360 365 Ser Arg Asp Ile Thr Thr Cys Phe Gly Gly Ser Leu Gly Ile Gln Tyr 370 375 380 Glu Asp Lys Ile Asn Val Gly Gly Gly Leu Ser Gly Asp His Cys Lys 385 390 395 400 Lys Phe Gly Gly Gly Lys Thr Glu Arg Ala Arg Lys Ala Met Ala Val 405 410 415 Glu Asp Ile Ile Ser Arg Val Arg Gly Gly Ser Ser Gly Trp Ser Gly 420 425 430 Gly Leu Ala Gln Asn Arg Ser Thr Ile Thr Tyr Arg Ser Trp Gly Arg 435 440 445 Ser Leu Lys Tyr Asn Pro Val Val Ile Asp Phe Glu Met Gln Pro Ile 450 455 460 His Glu Val Leu Arg His Thr Ser Leu Gly Pro Leu Glu Ala Lys Arg 465 470 475 480 Gln Asn Leu Arg Arg Ala Leu Asp Gln Tyr Leu Met Glu Phe Asn Ala 485 490 495 Cys Arg Cys Gly Pro Cys Phe Asn Asn Gly Val Pro Ile Leu Glu Gly 500 505 510 Thr Ser Cys Arg Cys Gln Cys Arg Leu Gly Ser Leu Gly Ala Ala Cys 515 520 525 Glu Gln Thr Gln Thr Glu Gly Ala Lys Ala Asp Gly Ser Trp Ser Cys 530 535 540 Trp Ser Ser Trp Ser Val Cys Arg Ala Gly Ile Gln Glu Arg Arg Arg 545 550 555 560 Glu Cys Asp Asn Pro Ala Pro Gln Asn Gly Gly Ala Ser Cys Pro Gly 565 570 575 Arg Lys Val Gln Thr Gln Ala Cys 580 300559PRTHomo sapiens 300Met Ser Ala Cys Arg Ser Phe Ala Val Ala Ile Cys Ile Leu Glu Ile 1 5 10 15 Ser Ile Leu Thr Ala Gln Tyr Thr Thr Ser Tyr Asp Pro Glu Leu Thr 20 25 30 Glu Ser Ser Gly Ser Ala Ser His Ile Asp Cys Arg Met Ser Pro Trp 35 40 45 Ser Glu Trp Ser Gln Cys Asp Pro Cys Leu Arg Gln Met Phe Arg Ser 50 55 60 Arg Ser Ile Glu Val Phe Gly Gln Phe Asn Gly Lys Arg Cys Thr Asp 65 70 75 80 Ala Val Gly Asp Arg Arg Gln Cys Val Pro Thr Glu Pro Cys Glu Asp 85 90 95 Ala Glu Asp Asp Cys Gly Asn Asp Phe Gln Cys Ser Thr Gly Arg Cys 100 105 110 Ile Lys Met Arg Leu Arg Cys Asn Gly Asp Asn Asp Cys Gly Asp Phe 115 120 125 Ser Asp Glu Asp Asp Cys Glu Ser Glu Pro Arg Pro Pro Cys Arg Asp 130 135 140 Arg Val Val Glu Glu Ser Glu Leu Ala Arg Thr Ala Gly Tyr Gly Ile 145 150 155 160 Asn Ile Leu Gly Met Asp Pro Leu Ser Thr Pro Phe Asp Asn Glu Phe 165 170 175 Tyr Asn Gly Leu Cys Asn Arg Asp Arg Asp Gly Asn Thr Leu Thr Tyr 180 185 190 Tyr Arg Arg Pro Trp Asn Val Ala Ser Leu Ile Tyr Glu Thr Lys Gly 195 200 205 Glu Lys Asn Phe Arg Thr Glu His Tyr Glu Glu Gln Ile Glu Ala Phe 210 215 220 Lys Ser Ile Ile Gln Glu Lys Thr Ser Asn Phe Asn Ala Ala Ile Ser 225 230 235 240 Leu Lys Phe Thr Pro Thr Glu Thr Asn Lys Ala Glu Gln Cys Cys Glu 245 250 255 Glu Thr Ala Ser Ser Ile Ser Leu His Gly Lys Gly Ser Phe Arg Phe 260 265 270 Ser Tyr Ser Lys Asn Glu Thr Tyr Gln Leu Phe Leu Ser Tyr Ser Ser 275 280 285 Lys Lys Glu Lys Met Phe Leu His Val Lys Gly Glu Ile His Leu Gly 290 295 300 Arg Phe Val Met Arg Asn Arg Asp Val Val Leu Thr Thr Thr Phe Val 305 310 315 320 Asp Asp Ile Lys Ala Leu Pro Thr Thr Tyr Glu Lys Gly Glu Tyr Phe 325 330 335 Ala Phe Leu Glu Thr Tyr Gly Thr His Tyr Ser Ser Ser Gly Ser Leu 340 345 350 Gly Gly Leu Tyr Glu Leu Ile Tyr Val Leu Asp Lys Ala Ser Met Lys 355 360 365 Arg Lys Gly Val Glu Leu Lys Asp Ile Lys Arg Cys Leu Gly Tyr His 370 375 380 Leu Asp Val Ser Leu Ala Phe Ser Glu Ile Ser Val Gly Ala Glu Phe 385 390 395 400 Asn Lys Asp Asp Cys Val Lys Arg Gly Glu Gly Arg Ala Val Asn Ile 405 410 415 Thr Ser Glu Asn Leu Ile Asp Asp Val Val Ser Leu Ile Arg Gly Gly 420 425 430 Thr Arg Lys Tyr Ala Phe Glu Leu Lys Glu Lys Leu Leu Arg Gly Thr 435 440 445 Val Ile Asp Val Thr Asp Phe Val Asn Trp Ala Ser Ser Ile Asn Asp 450 455 460 Ala Pro Val Leu Ile Ser Gln Lys Leu Ser Pro Ile Tyr Asn Leu Val 465 470 475 480 Pro Val Lys Met Lys Asn Ala His Leu Lys Lys Gln Asn Leu Glu Arg 485 490 495 Ala Ile Glu Asp Tyr Ile Asn Glu Phe Ser Val Arg Lys Cys His Thr 500 505 510 Cys Gln Asn Gly Gly Thr Val Ile Leu Met Asp Gly Lys Cys Leu Cys 515 520 525 Ala Cys Pro Phe Lys Phe Glu Gly Ile Ala Cys Glu Ile Ser Lys Gln 530 535 540 Lys Ile Ser Glu Gly Leu Pro Ala Leu Glu Phe Pro Asn Glu Lys 545 550 555 301764PRTHomo sapiens 301Met Gly Ser Asn Leu Ser Pro Gln Leu Cys Leu Met Pro Phe Ile Leu 1 5 10 15 Gly Leu Leu Ser Gly Gly Val Thr Thr Thr Pro Trp Ser Leu Ala Gln 20 25 30 Pro Gln Gly Ser Cys Ser Leu Glu Gly Val Glu Ile Lys Gly Gly Ser 35 40 45 Phe Arg Leu Leu Gln Glu Gly Gln Ala Leu Glu Tyr Val Cys Pro Ser 50 55 60 Gly Phe Tyr Pro Tyr Pro Val Gln Thr Arg Thr Cys Arg Ser Thr Gly 65 70 75 80 Ser Trp Ser Thr Leu Lys Thr Gln Asp Gln Lys Thr Val Arg Lys Ala 85 90 95 Glu Cys Arg Ala Ile His Cys Pro Arg Pro His Asp Phe Glu Asn Gly 100 105 110 Glu Tyr Trp Pro Arg Ser Pro Tyr Tyr Asn Val Ser Asp Glu Ile Ser 115 120 125 Phe His Cys Tyr Asp Gly Tyr Thr Leu Arg Gly Ser Ala Asn Arg Thr 130 135 140 Cys Gln Val Asn Gly Arg Trp Ser Gly Gln Thr Ala Ile Cys Asp Asn 145 150 155 160 Gly Ala Gly Tyr Cys Ser Asn Pro Gly Ile Pro Ile Gly Thr Arg Lys 165 170 175 Val Gly Ser Gln Tyr Arg Leu Glu Asp Ser Val Thr Tyr His Cys Ser 180 185 190 Arg Gly Leu Thr Leu Arg Gly Ser Gln Arg Arg Thr Cys Gln Glu Gly 195 200 205 Gly Ser Trp Ser Gly Thr Glu Pro Ser Cys Gln Asp Ser Phe Met Tyr 210 215 220 Asp Thr Pro Gln Glu Val Ala Glu Ala Phe Leu Ser Ser Leu Thr Glu 225 230 235 240 Thr Ile Glu Gly Val Asp Ala Glu Asp Gly His Gly Pro Gly Glu Gln 245 250 255 Gln Lys Arg Lys Ile Val Leu Asp Pro Ser Gly Ser Met Asn Ile Tyr 260 265 270 Leu Val Leu Asp Gly Ser Asp Ser Ile Gly Ala Ser Asn Phe Thr Gly 275 280 285 Ala Lys Lys Cys Leu Val Asn Leu Ile Glu Lys Val Ala Ser Tyr Gly 290 295 300 Val Lys Pro Arg Tyr Gly Leu Val Thr Tyr Ala Thr Tyr Pro Lys Ile 305 310 315 320 Trp Val Lys Val Ser Glu Ala Asp Ser Ser Asn Ala Asp Trp Val Thr 325 330 335 Lys Gln Leu Asn Glu Ile Asn Tyr Glu Asp His Lys Leu Lys Ser Gly 340 345 350 Thr Asn Thr Lys Lys Ala Leu Gln Ala Val Tyr Ser Met Met Ser Trp 355 360 365 Pro Asp Asp Val Pro Pro Glu Gly Trp Asn Arg Thr Arg His Val Ile 370 375 380 Ile Leu Met Thr Asp Gly Leu His Asn Met Gly Gly Asp Pro Ile Thr 385 390 395 400 Val Ile Asp Glu Ile Arg Asp Leu Leu Tyr Ile Gly Lys Asp Arg Lys 405 410 415 Asn Pro Arg Glu Asp Tyr Leu Asp Val Tyr Val Phe Gly Val Gly Pro 420 425 430 Leu Val Asn Gln Val Asn Ile Asn Ala Leu Ala Ser Lys Lys Asp Asn 435 440 445 Glu Gln His Val Phe Lys Val Lys Asp Met Glu Asn Leu Glu Asp Val 450 455 460 Phe Tyr Gln Met Ile Asp Glu Ser Gln Ser Leu Ser Leu Cys Gly Met 465 470 475 480 Val Trp Glu His Arg Lys Gly Thr Asp Tyr His Lys Gln Pro Trp Gln 485 490 495 Ala Lys Ile Ser Val Ile Arg Pro Ser Lys Gly His Glu Ser Cys Met 500 505 510 Gly Ala Val Val Ser Glu Tyr Phe Val Leu Thr Ala Ala His Cys Phe 515 520 525 Thr Val Asp Asp Lys Glu His Ser Ile Lys Val Ser Val Gly Gly Glu 530 535 540 Lys Arg Asp Leu Glu Ile Glu Val Val Leu Phe His Pro Asn Tyr Asn 545 550 555 560 Ile Asn Gly Lys Lys Glu Ala Gly Ile Pro Glu Phe Tyr Asp Tyr Asp 565 570 575 Val Ala Leu Ile Lys Leu Lys Asn Lys Leu Lys Tyr Gly Gln Thr Ile 580 585 590 Arg Pro Ile Cys Leu Pro Cys Thr Glu Gly Thr Thr Arg Ala Leu Arg 595 600 605 Leu Pro Pro Thr Thr Thr Cys Gln Gln Gln Lys Glu Glu Leu Leu Pro 610 615 620 Ala Gln Asp Ile

Lys Ala Leu Phe Val Ser Glu Glu Glu Lys Lys Leu 625 630 635 640 Thr Arg Lys Glu Val Tyr Ile Lys Asn Gly Asp Lys Lys Gly Ser Cys 645 650 655 Glu Arg Asp Ala Gln Tyr Ala Pro Gly Tyr Asp Lys Val Lys Asp Ile 660 665 670 Ser Glu Val Val Thr Pro Arg Phe Leu Cys Thr Gly Gly Val Ser Pro 675 680 685 Tyr Ala Asp Pro Asn Thr Cys Arg Gly Asp Ser Gly Gly Pro Leu Ile 690 695 700 Val His Lys Arg Ser Arg Phe Ile Gln Val Gly Val Ile Ser Trp Gly 705 710 715 720 Val Val Asp Val Cys Lys Asn Gln Lys Arg Gln Lys Gln Val Pro Ala 725 730 735 His Ala Arg Asp Phe His Ile Asn Leu Phe Gln Val Leu Pro Trp Leu 740 745 750 Lys Glu Lys Leu Gln Asp Glu Asp Leu Gly Phe Leu 755 760 3021231PRTHomo sapiens 302Met Arg Leu Leu Ala Lys Ile Ile Cys Leu Met Leu Trp Ala Ile Cys 1 5 10 15 Val Ala Glu Asp Cys Asn Glu Leu Pro Pro Arg Arg Asn Thr Glu Ile 20 25 30 Leu Thr Gly Ser Trp Ser Asp Gln Thr Tyr Pro Glu Gly Thr Gln Ala 35 40 45 Ile Tyr Lys Cys Arg Pro Gly Tyr Arg Ser Leu Gly Asn Val Ile Met 50 55 60 Val Cys Arg Lys Gly Glu Trp Val Ala Leu Asn Pro Leu Arg Lys Cys 65 70 75 80 Gln Lys Arg Pro Cys Gly His Pro Gly Asp Thr Pro Phe Gly Thr Phe 85 90 95 Thr Leu Thr Gly Gly Asn Val Phe Glu Tyr Gly Val Lys Ala Val Tyr 100 105 110 Thr Cys Asn Glu Gly Tyr Gln Leu Leu Gly Glu Ile Asn Tyr Arg Glu 115 120 125 Cys Asp Thr Asp Gly Trp Thr Asn Asp Ile Pro Ile Cys Glu Val Val 130 135 140 Lys Cys Leu Pro Val Thr Ala Pro Glu Asn Gly Lys Ile Val Ser Ser 145 150 155 160 Ala Met Glu Pro Asp Arg Glu Tyr His Phe Gly Gln Ala Val Arg Phe 165 170 175 Val Cys Asn Ser Gly Tyr Lys Ile Glu Gly Asp Glu Glu Met His Cys 180 185 190 Ser Asp Asp Gly Phe Trp Ser Lys Glu Lys Pro Lys Cys Val Glu Ile 195 200 205 Ser Cys Lys Ser Pro Asp Val Ile Asn Gly Ser Pro Ile Ser Gln Lys 210 215 220 Ile Ile Tyr Lys Glu Asn Glu Arg Phe Gln Tyr Lys Cys Asn Met Gly 225 230 235 240 Tyr Glu Tyr Ser Glu Arg Gly Asp Ala Val Cys Thr Glu Ser Gly Trp 245 250 255 Arg Pro Leu Pro Ser Cys Glu Glu Lys Ser Cys Asp Asn Pro Tyr Ile 260 265 270 Pro Asn Gly Asp Tyr Ser Pro Leu Arg Ile Lys His Arg Thr Gly Asp 275 280 285 Glu Ile Thr Tyr Gln Cys Arg Asn Gly Phe Tyr Pro Ala Thr Arg Gly 290 295 300 Asn Thr Ala Lys Cys Thr Ser Thr Gly Trp Ile Pro Ala Pro Arg Cys 305 310 315 320 Thr Leu Lys Pro Cys Asp Tyr Pro Asp Ile Lys His Gly Gly Leu Tyr 325 330 335 His Glu Asn Met Arg Arg Pro Tyr Phe Pro Val Ala Val Gly Lys Tyr 340 345 350 Tyr Ser Tyr Tyr Cys Asp Glu His Phe Glu Thr Pro Ser Gly Ser Tyr 355 360 365 Trp Asp His Ile His Cys Thr Gln Asp Gly Trp Ser Pro Ala Val Pro 370 375 380 Cys Leu Arg Lys Cys Tyr Phe Pro Tyr Leu Glu Asn Gly Tyr Asn Gln 385 390 395 400 Asn His Gly Arg Lys Phe Val Gln Gly Lys Ser Ile Asp Val Ala Cys 405 410 415 His Pro Gly Tyr Ala Leu Pro Lys Ala Gln Thr Thr Val Thr Cys Met 420 425 430 Glu Asn Gly Trp Ser Pro Thr Pro Arg Cys Ile Arg Val Lys Thr Cys 435 440 445 Ser Lys Ser Ser Ile Asp Ile Glu Asn Gly Phe Ile Ser Glu Ser Gln 450 455 460 Tyr Thr Tyr Ala Leu Lys Glu Lys Ala Lys Tyr Gln Cys Lys Leu Gly 465 470 475 480 Tyr Val Thr Ala Asp Gly Glu Thr Ser Gly Ser Ile Arg Cys Gly Lys 485 490 495 Asp Gly Trp Ser Ala Gln Pro Thr Cys Ile Lys Ser Cys Asp Ile Pro 500 505 510 Val Phe Met Asn Ala Arg Thr Lys Asn Asp Phe Thr Trp Phe Lys Leu 515 520 525 Asn Asp Thr Leu Asp Tyr Glu Cys His Asp Gly Tyr Glu Ser Asn Thr 530 535 540 Gly Ser Thr Thr Gly Ser Ile Val Cys Gly Tyr Asn Gly Trp Ser Asp 545 550 555 560 Leu Pro Ile Cys Tyr Glu Arg Glu Cys Glu Leu Pro Lys Ile Asp Val 565 570 575 His Leu Val Pro Asp Arg Lys Lys Asp Gln Tyr Lys Val Gly Glu Val 580 585 590 Leu Lys Phe Ser Cys Lys Pro Gly Phe Thr Ile Val Gly Pro Asn Ser 595 600 605 Val Gln Cys Tyr His Phe Gly Leu Ser Pro Asp Leu Pro Ile Cys Lys 610 615 620 Glu Gln Val Gln Ser Cys Gly Pro Pro Pro Glu Leu Leu Asn Gly Asn 625 630 635 640 Val Lys Glu Lys Thr Lys Glu Glu Tyr Gly His Ser Glu Val Val Glu 645 650 655 Tyr Tyr Cys Asn Pro Arg Phe Leu Met Lys Gly Pro Asn Lys Ile Gln 660 665 670 Cys Val Asp Gly Glu Trp Thr Thr Leu Pro Val Cys Ile Val Glu Glu 675 680 685 Ser Thr Cys Gly Asp Ile Pro Glu Leu Glu His Gly Trp Ala Gln Leu 690 695 700 Ser Ser Pro Pro Tyr Tyr Tyr Gly Asp Ser Val Glu Phe Asn Cys Ser 705 710 715 720 Glu Ser Phe Thr Met Ile Gly His Arg Ser Ile Thr Cys Ile His Gly 725 730 735 Val Trp Thr Gln Leu Pro Gln Cys Val Ala Ile Asp Lys Leu Lys Lys 740 745 750 Cys Lys Ser Ser Asn Leu Ile Ile Leu Glu Glu His Leu Lys Asn Lys 755 760 765 Lys Glu Phe Asp His Asn Ser Asn Ile Arg Tyr Arg Cys Arg Gly Lys 770 775 780 Glu Gly Trp Ile His Thr Val Cys Ile Asn Gly Arg Trp Asp Pro Glu 785 790 795 800 Val Asn Cys Ser Met Ala Gln Ile Gln Leu Cys Pro Pro Pro Pro Gln 805 810 815 Ile Pro Asn Ser His Asn Met Thr Thr Thr Leu Asn Tyr Arg Asp Gly 820 825 830 Glu Lys Val Ser Val Leu Cys Gln Glu Asn Tyr Leu Ile Gln Glu Gly 835 840 845 Glu Glu Ile Thr Cys Lys Asp Gly Arg Trp Gln Ser Ile Pro Leu Cys 850 855 860 Val Glu Lys Ile Pro Cys Ser Gln Pro Pro Gln Ile Glu His Gly Thr 865 870 875 880 Ile Asn Ser Ser Arg Ser Ser Gln Glu Ser Tyr Ala His Gly Thr Lys 885 890 895 Leu Ser Tyr Thr Cys Glu Gly Gly Phe Arg Ile Ser Glu Glu Asn Glu 900 905 910 Thr Thr Cys Tyr Met Gly Lys Trp Ser Ser Pro Pro Gln Cys Glu Gly 915 920 925 Leu Pro Cys Lys Ser Pro Pro Glu Ile Ser His Gly Val Val Ala His 930 935 940 Met Ser Asp Ser Tyr Gln Tyr Gly Glu Glu Val Thr Tyr Lys Cys Phe 945 950 955 960 Glu Gly Phe Gly Ile Asp Gly Pro Ala Ile Ala Lys Cys Leu Gly Glu 965 970 975 Lys Trp Ser His Pro Pro Ser Cys Ile Lys Thr Asp Cys Leu Ser Leu 980 985 990 Pro Ser Phe Glu Asn Ala Ile Pro Met Gly Glu Lys Lys Asp Val Tyr 995 1000 1005 Lys Ala Gly Glu Gln Val Thr Tyr Thr Cys Ala Thr Tyr Tyr Lys 1010 1015 1020 Met Asp Gly Ala Ser Asn Val Thr Cys Ile Asn Ser Arg Trp Thr 1025 1030 1035 Gly Arg Pro Thr Cys Arg Asp Thr Ser Cys Val Asn Pro Pro Thr 1040 1045 1050 Val Gln Asn Ala Tyr Ile Val Ser Arg Gln Met Ser Lys Tyr Pro 1055 1060 1065 Ser Gly Glu Arg Val Arg Tyr Gln Cys Arg Ser Pro Tyr Glu Met 1070 1075 1080 Phe Gly Asp Glu Glu Val Met Cys Leu Asn Gly Asn Trp Thr Glu 1085 1090 1095 Pro Pro Gln Cys Lys Asp Ser Thr Gly Lys Cys Gly Pro Pro Pro 1100 1105 1110 Pro Ile Asp Asn Gly Asp Ile Thr Ser Phe Pro Leu Ser Val Tyr 1115 1120 1125 Ala Pro Ala Ser Ser Val Glu Tyr Gln Cys Gln Asn Leu Tyr Gln 1130 1135 1140 Leu Glu Gly Asn Lys Arg Ile Thr Cys Arg Asn Gly Gln Trp Ser 1145 1150 1155 Glu Pro Pro Lys Cys Leu His Pro Cys Val Ile Ser Arg Glu Ile 1160 1165 1170 Met Glu Asn Tyr Asn Ile Ala Leu Arg Trp Thr Ala Lys Gln Lys 1175 1180 1185 Leu Tyr Ser Arg Thr Gly Glu Ser Val Glu Phe Val Cys Lys Arg 1190 1195 1200 Gly Tyr Arg Leu Ser Ser Arg Ser His Thr Leu Arg Thr Thr Cys 1205 1210 1215 Trp Asp Gly Lys Leu Glu Tyr Pro Thr Cys Ala Lys Arg 1220 1225 1230 303644PRTHomo sapiens 303Met Phe Ser Met Arg Ile Val Cys Leu Val Leu Ser Val Val Gly Thr 1 5 10 15 Ala Trp Thr Ala Asp Ser Gly Glu Gly Asp Phe Leu Ala Glu Gly Gly 20 25 30 Gly Val Arg Gly Pro Arg Val Val Glu Arg His Gln Ser Ala Cys Lys 35 40 45 Asp Ser Asp Trp Pro Phe Cys Ser Asp Glu Asp Trp Asn Tyr Lys Cys 50 55 60 Pro Ser Gly Cys Arg Met Lys Gly Leu Ile Asp Glu Val Asn Gln Asp 65 70 75 80 Phe Thr Asn Arg Ile Asn Lys Leu Lys Asn Ser Leu Phe Glu Tyr Gln 85 90 95 Lys Asn Asn Lys Asp Ser His Ser Leu Thr Thr Asn Ile Met Glu Ile 100 105 110 Leu Arg Gly Asp Phe Ser Ser Ala Asn Asn Arg Asp Asn Thr Tyr Asn 115 120 125 Arg Val Ser Glu Asp Leu Arg Ser Arg Ile Glu Val Leu Lys Arg Lys 130 135 140 Val Ile Glu Lys Val Gln His Ile Gln Leu Leu Gln Lys Asn Val Arg 145 150 155 160 Ala Gln Leu Val Asp Met Lys Arg Leu Glu Val Asp Ile Asp Ile Lys 165 170 175 Ile Arg Ser Cys Arg Gly Ser Cys Ser Arg Ala Leu Ala Arg Glu Val 180 185 190 Asp Leu Lys Asp Tyr Glu Asp Gln Gln Lys Gln Leu Glu Gln Val Ile 195 200 205 Ala Lys Asp Leu Leu Pro Ser Arg Asp Arg Gln His Leu Pro Leu Ile 210 215 220 Lys Met Lys Pro Val Pro Asp Leu Val Pro Gly Asn Phe Lys Ser Gln 225 230 235 240 Leu Gln Lys Val Pro Pro Glu Trp Lys Ala Leu Thr Asp Met Pro Gln 245 250 255 Met Arg Met Glu Leu Glu Arg Pro Gly Gly Asn Glu Ile Thr Arg Gly 260 265 270 Gly Ser Thr Ser Tyr Gly Thr Gly Ser Glu Thr Glu Ser Pro Arg Asn 275 280 285 Pro Ser Ser Ala Gly Ser Trp Asn Ser Gly Ser Ser Gly Pro Gly Ser 290 295 300 Thr Gly Asn Arg Asn Pro Gly Ser Ser Gly Thr Gly Gly Thr Ala Thr 305 310 315 320 Trp Lys Pro Gly Ser Ser Gly Pro Gly Ser Thr Gly Ser Trp Asn Ser 325 330 335 Gly Ser Ser Gly Thr Gly Ser Thr Gly Asn Gln Asn Pro Gly Ser Pro 340 345 350 Arg Pro Gly Ser Thr Gly Thr Trp Asn Pro Gly Ser Ser Glu Arg Gly 355 360 365 Ser Ala Gly His Trp Thr Ser Glu Ser Ser Val Ser Gly Ser Thr Gly 370 375 380 Gln Trp His Ser Glu Ser Gly Ser Phe Arg Pro Asp Ser Pro Gly Ser 385 390 395 400 Gly Asn Ala Arg Pro Asn Asn Pro Asp Trp Gly Thr Phe Glu Glu Val 405 410 415 Ser Gly Asn Val Ser Pro Gly Thr Arg Arg Glu Tyr His Thr Glu Lys 420 425 430 Leu Val Thr Ser Lys Gly Asp Lys Glu Leu Arg Thr Gly Lys Glu Lys 435 440 445 Val Thr Ser Gly Ser Thr Thr Thr Thr Arg Arg Ser Cys Ser Lys Thr 450 455 460 Val Thr Lys Thr Val Ile Gly Pro Asp Gly His Lys Glu Val Thr Lys 465 470 475 480 Glu Val Val Thr Ser Glu Asp Gly Ser Asp Cys Pro Glu Ala Met Asp 485 490 495 Leu Gly Thr Leu Ser Gly Ile Gly Thr Leu Asp Gly Phe Arg His Arg 500 505 510 His Pro Asp Glu Ala Ala Phe Phe Asp Thr Ala Ser Thr Gly Lys Thr 515 520 525 Phe Pro Gly Phe Phe Ser Pro Met Leu Gly Glu Phe Val Ser Glu Thr 530 535 540 Glu Ser Arg Gly Ser Glu Ser Gly Ile Phe Thr Asn Thr Lys Glu Ser 545 550 555 560 Ser Ser His His Pro Gly Ile Ala Glu Phe Pro Ser Arg Gly Lys Ser 565 570 575 Ser Ser Tyr Ser Lys Gln Phe Thr Ser Ser Thr Ser Tyr Asn Arg Gly 580 585 590 Asp Ser Thr Phe Glu Ser Lys Ser Tyr Lys Met Ala Asp Glu Ala Gly 595 600 605 Ser Glu Ala Asp His Glu Gly Thr His Ser Thr Lys Arg Gly His Ala 610 615 620 Lys Ser Arg Pro Val Arg Gly Ile His Thr Ser Pro Leu Gly Lys Pro 625 630 635 640 Ser Leu Ser Pro 304491PRTHomo sapiens 304Met Lys Arg Met Val Ser Trp Ser Phe His Lys Leu Lys Thr Met Lys 1 5 10 15 His Leu Leu Leu Leu Leu Leu Cys Val Phe Leu Val Lys Ser Gln Gly 20 25 30 Val Asn Asp Asn Glu Glu Gly Phe Phe Ser Ala Arg Gly His Arg Pro 35 40 45 Leu Asp Lys Lys Arg Glu Glu Ala Pro Ser Leu Arg Pro Ala Pro Pro 50 55 60 Pro Ile Ser Gly Gly Gly Tyr Arg Ala Arg Pro Ala Lys Ala Ala Ala 65 70 75 80 Thr Gln Lys Lys Val Glu Arg Lys Ala Pro Asp Ala Gly Gly Cys Leu 85 90 95 His Ala Asp Pro Asp Leu Gly Val Leu Cys Pro Thr Gly Cys Gln Leu 100 105 110 Gln Glu Ala Leu Leu Gln Gln Glu Arg Pro Ile Arg Asn Ser Val Asp 115 120 125 Glu Leu Asn Asn Asn Val Glu Ala Val Ser Gln Thr Ser Ser Ser Ser 130 135 140 Phe Gln Tyr Met Tyr Leu Leu Lys Asp Leu Trp Gln Lys Arg Gln Lys 145 150 155 160 Gln Val Lys Asp Asn Glu Asn Val Val Asn Glu Tyr Ser Ser Glu Leu 165 170 175 Glu Lys His Gln Leu Tyr Ile Asp Glu Thr Val Asn Ser Asn Ile Ala 180 185 190 Thr Asn Leu Arg Val Leu Arg Ser Ile Leu Glu Asn Leu Arg Ser Lys 195 200 205 Ile Gln Lys Leu Glu Ser Asp Val Ser Ala Gln Met Glu Tyr Cys Arg 210 215 220 Thr Pro Cys Thr Val Ser Cys Asn Ile Pro Val Val Ser Gly Lys Glu 225 230 235 240 Cys Glu Glu Ile Ile Arg Lys Gly Gly Glu Thr Ser Glu Met Tyr Leu 245 250 255 Ile Gln Pro Asp Ser Ser Val Lys Pro Tyr Arg Val Tyr Cys Asp Met 260 265 270 Asn

Thr Glu Asn Gly Gly Trp Thr Val Ile Gln Asn Arg Gln Asp Gly 275 280 285 Ser Val Asp Phe Gly Arg Lys Trp Asp Pro Tyr Lys Gln Gly Phe Gly 290 295 300 Asn Val Ala Thr Asn Thr Asp Gly Lys Asn Tyr Cys Gly Leu Pro Gly 305 310 315 320 Glu Tyr Trp Leu Gly Asn Asp Lys Ile Ser Gln Leu Thr Arg Met Gly 325 330 335 Pro Thr Glu Leu Leu Ile Glu Met Glu Asp Trp Lys Gly Asp Lys Val 340 345 350 Lys Ala His Tyr Gly Gly Phe Thr Val Gln Asn Glu Ala Asn Lys Tyr 355 360 365 Gln Ile Ser Val Asn Lys Tyr Arg Gly Thr Ala Gly Asn Ala Leu Met 370 375 380 Asp Gly Ala Ser Gln Leu Met Gly Glu Asn Arg Thr Met Thr Ile His 385 390 395 400 Asn Gly Met Phe Phe Ser Thr Tyr Asp Arg Asp Asn Asp Gly Trp Leu 405 410 415 Thr Ser Asp Pro Arg Lys Gln Cys Ser Lys Glu Asp Gly Gly Gly Trp 420 425 430 Trp Tyr Asn Arg Cys His Ala Ala Asn Pro Asn Gly Arg Tyr Tyr Trp 435 440 445 Gly Gly Gln Tyr Thr Trp Asp Met Ala Lys His Gly Thr Asp Asp Gly 450 455 460 Val Val Trp Met Asn Trp Lys Gly Ser Trp Tyr Ser Met Arg Lys Met 465 470 475 480 Ser Met Lys Ile Arg Pro Phe Phe Pro Gln Gln 485 490 305437PRTHomo sapiens 305Met Ser Trp Ser Leu His Pro Arg Asn Leu Ile Leu Tyr Phe Tyr Ala 1 5 10 15 Leu Leu Phe Leu Ser Ser Thr Cys Val Ala Tyr Val Ala Thr Arg Asp 20 25 30 Asn Cys Cys Ile Leu Asp Glu Arg Phe Gly Ser Tyr Cys Pro Thr Thr 35 40 45 Cys Gly Ile Ala Asp Phe Leu Ser Thr Tyr Gln Thr Lys Val Asp Lys 50 55 60 Asp Leu Gln Ser Leu Glu Asp Ile Leu His Gln Val Glu Asn Lys Thr 65 70 75 80 Ser Glu Val Lys Gln Leu Ile Lys Ala Ile Gln Leu Thr Tyr Asn Pro 85 90 95 Asp Glu Ser Ser Lys Pro Asn Met Ile Asp Ala Ala Thr Leu Lys Ser 100 105 110 Arg Ile Met Leu Glu Glu Ile Met Lys Tyr Glu Ala Ser Ile Leu Thr 115 120 125 His Asp Ser Ser Ile Arg Tyr Leu Gln Glu Ile Tyr Asn Ser Asn Asn 130 135 140 Gln Lys Ile Val Asn Leu Lys Glu Lys Val Ala Gln Leu Glu Ala Gln 145 150 155 160 Cys Gln Glu Pro Cys Lys Asp Thr Val Gln Ile His Asp Ile Thr Gly 165 170 175 Lys Asp Cys Gln Asp Ile Ala Asn Lys Gly Ala Lys Gln Ser Gly Leu 180 185 190 Tyr Phe Ile Lys Pro Leu Lys Ala Asn Gln Gln Phe Leu Val Tyr Cys 195 200 205 Glu Ile Asp Gly Ser Gly Asn Gly Trp Thr Val Phe Gln Lys Arg Leu 210 215 220 Asp Gly Ser Val Asp Phe Lys Lys Asn Trp Ile Gln Tyr Lys Glu Gly 225 230 235 240 Phe Gly His Leu Ser Pro Thr Gly Thr Thr Glu Phe Trp Leu Gly Asn 245 250 255 Glu Lys Ile His Leu Ile Ser Thr Gln Ser Ala Ile Pro Tyr Ala Leu 260 265 270 Arg Val Glu Leu Glu Asp Trp Asn Gly Arg Thr Ser Thr Ala Asp Tyr 275 280 285 Ala Met Phe Lys Val Gly Pro Glu Ala Asp Lys Tyr Arg Leu Thr Tyr 290 295 300 Ala Tyr Phe Ala Gly Gly Asp Ala Gly Asp Ala Phe Asp Gly Phe Asp 305 310 315 320 Phe Gly Asp Asp Pro Ser Asp Lys Phe Phe Thr Ser His Asn Gly Met 325 330 335 Gln Phe Ser Thr Trp Asp Asn Asp Asn Asp Lys Phe Glu Gly Asn Cys 340 345 350 Ala Glu Gln Asp Gly Ser Gly Trp Trp Met Asn Lys Cys His Ala Gly 355 360 365 His Leu Asn Gly Val Tyr Tyr Gln Gly Gly Thr Tyr Ser Lys Ala Ser 370 375 380 Thr Pro Asn Gly Tyr Asp Asn Gly Ile Ile Trp Ala Thr Trp Lys Thr 385 390 395 400 Arg Trp Tyr Ser Met Lys Lys Thr Thr Met Lys Ile Ile Pro Phe Asn 405 410 415 Arg Leu Thr Ile Gly Glu Gly Gln Gln His His Leu Gly Gly Ala Lys 420 425 430 Gln Ala Gly Asp Val 435 3062477PRTHomo sapiens 306Met Leu Arg Gly Pro Gly Pro Gly Leu Leu Leu Leu Ala Val Gln Cys 1 5 10 15 Leu Gly Thr Ala Val Pro Ser Thr Gly Ala Ser Lys Ser Lys Arg Gln 20 25 30 Ala Gln Gln Met Val Gln Pro Gln Ser Pro Val Ala Val Ser Gln Ser 35 40 45 Lys Pro Gly Cys Tyr Asp Asn Gly Lys His Tyr Gln Ile Asn Gln Gln 50 55 60 Trp Glu Arg Thr Tyr Leu Gly Asn Ala Leu Val Cys Thr Cys Tyr Gly 65 70 75 80 Gly Ser Arg Gly Phe Asn Cys Glu Ser Lys Pro Glu Ala Glu Glu Thr 85 90 95 Cys Phe Asp Lys Tyr Thr Gly Asn Thr Tyr Arg Val Gly Asp Thr Tyr 100 105 110 Glu Arg Pro Lys Asp Ser Met Ile Trp Asp Cys Thr Cys Ile Gly Ala 115 120 125 Gly Arg Gly Arg Ile Ser Cys Thr Ile Ala Asn Arg Cys His Glu Gly 130 135 140 Gly Gln Ser Tyr Lys Ile Gly Asp Thr Trp Arg Arg Pro His Glu Thr 145 150 155 160 Gly Gly Tyr Met Leu Glu Cys Val Cys Leu Gly Asn Gly Lys Gly Glu 165 170 175 Trp Thr Cys Lys Pro Ile Ala Glu Lys Cys Phe Asp His Ala Ala Gly 180 185 190 Thr Ser Tyr Val Val Gly Glu Thr Trp Glu Lys Pro Tyr Gln Gly Trp 195 200 205 Met Met Val Asp Cys Thr Cys Leu Gly Glu Gly Ser Gly Arg Ile Thr 210 215 220 Cys Thr Ser Arg Asn Arg Cys Asn Asp Gln Asp Thr Arg Thr Ser Tyr 225 230 235 240 Arg Ile Gly Asp Thr Trp Ser Lys Lys Asp Asn Arg Gly Asn Leu Leu 245 250 255 Gln Cys Ile Cys Thr Gly Asn Gly Arg Gly Glu Trp Lys Cys Glu Arg 260 265 270 His Thr Ser Val Gln Thr Thr Ser Ser Gly Ser Gly Pro Phe Thr Asp 275 280 285 Val Arg Ala Ala Val Tyr Gln Pro Gln Pro His Pro Gln Pro Pro Pro 290 295 300 Tyr Gly His Cys Val Thr Asp Ser Gly Val Val Tyr Ser Val Gly Met 305 310 315 320 Gln Trp Leu Lys Thr Gln Gly Asn Lys Gln Met Leu Cys Thr Cys Leu 325 330 335 Gly Asn Gly Val Ser Cys Gln Glu Thr Ala Val Thr Gln Thr Tyr Gly 340 345 350 Gly Asn Ser Asn Gly Glu Pro Cys Val Leu Pro Phe Thr Tyr Asn Gly 355 360 365 Arg Thr Phe Tyr Ser Cys Thr Thr Glu Gly Arg Gln Asp Gly His Leu 370 375 380 Trp Cys Ser Thr Thr Ser Asn Tyr Glu Gln Asp Gln Lys Tyr Ser Phe 385 390 395 400 Cys Thr Asp His Thr Val Leu Val Gln Thr Arg Gly Gly Asn Ser Asn 405 410 415 Gly Ala Leu Cys His Phe Pro Phe Leu Tyr Asn Asn His Asn Tyr Thr 420 425 430 Asp Cys Thr Ser Glu Gly Arg Arg Asp Asn Met Lys Trp Cys Gly Thr 435 440 445 Thr Gln Asn Tyr Asp Ala Asp Gln Lys Phe Gly Phe Cys Pro Met Ala 450 455 460 Ala His Glu Glu Ile Cys Thr Thr Asn Glu Gly Val Met Tyr Arg Ile 465 470 475 480 Gly Asp Gln Trp Asp Lys Gln His Asp Met Gly His Met Met Arg Cys 485 490 495 Thr Cys Val Gly Asn Gly Arg Gly Glu Trp Thr Cys Ile Ala Tyr Ser 500 505 510 Gln Leu Arg Asp Gln Cys Ile Val Asp Asp Ile Thr Tyr Asn Val Asn 515 520 525 Asp Thr Phe His Lys Arg His Glu Glu Gly His Met Leu Asn Cys Thr 530 535 540 Cys Phe Gly Gln Gly Arg Gly Arg Trp Lys Cys Asp Pro Val Asp Gln 545 550 555 560 Cys Gln Asp Ser Glu Thr Gly Thr Phe Tyr Gln Ile Gly Asp Ser Trp 565 570 575 Glu Lys Tyr Val His Gly Val Arg Tyr Gln Cys Tyr Cys Tyr Gly Arg 580 585 590 Gly Ile Gly Glu Trp His Cys Gln Pro Leu Gln Thr Tyr Pro Ser Ser 595 600 605 Ser Gly Pro Val Glu Val Phe Ile Thr Glu Thr Pro Ser Gln Pro Asn 610 615 620 Ser His Pro Ile Gln Trp Asn Ala Pro Gln Pro Ser His Ile Ser Lys 625 630 635 640 Tyr Ile Leu Arg Trp Arg Pro Lys Asn Ser Val Gly Arg Trp Lys Glu 645 650 655 Ala Thr Ile Pro Gly His Leu Asn Ser Tyr Thr Ile Lys Gly Leu Lys 660 665 670 Pro Gly Val Val Tyr Glu Gly Gln Leu Ile Ser Ile Gln Gln Tyr Gly 675 680 685 His Gln Glu Val Thr Arg Phe Asp Phe Thr Thr Thr Ser Thr Ser Thr 690 695 700 Pro Val Thr Ser Asn Thr Val Thr Gly Glu Thr Thr Pro Phe Ser Pro 705 710 715 720 Leu Val Ala Thr Ser Glu Ser Val Thr Glu Ile Thr Ala Ser Ser Phe 725 730 735 Val Val Ser Trp Val Ser Ala Ser Asp Thr Val Ser Gly Phe Arg Val 740 745 750 Glu Tyr Glu Leu Ser Glu Glu Gly Asp Glu Pro Gln Tyr Leu Asp Leu 755 760 765 Pro Ser Thr Ala Thr Ser Val Asn Ile Pro Asp Leu Leu Pro Gly Arg 770 775 780 Lys Tyr Ile Val Asn Val Tyr Gln Ile Ser Glu Asp Gly Glu Gln Ser 785 790 795 800 Leu Ile Leu Ser Thr Ser Gln Thr Thr Ala Pro Asp Ala Pro Pro Asp 805 810 815 Pro Thr Val Asp Gln Val Asp Asp Thr Ser Ile Val Val Arg Trp Ser 820 825 830 Arg Pro Gln Ala Pro Ile Thr Gly Tyr Arg Ile Val Tyr Ser Pro Ser 835 840 845 Val Glu Gly Ser Ser Thr Glu Leu Asn Leu Pro Glu Thr Ala Asn Ser 850 855 860 Val Thr Leu Ser Asp Leu Gln Pro Gly Val Gln Tyr Asn Ile Thr Ile 865 870 875 880 Tyr Ala Val Glu Glu Asn Gln Glu Ser Thr Pro Val Val Ile Gln Gln 885 890 895 Glu Thr Thr Gly Thr Pro Arg Ser Asp Thr Val Pro Ser Pro Arg Asp 900 905 910 Leu Gln Phe Val Glu Val Thr Asp Val Lys Val Thr Ile Met Trp Thr 915 920 925 Pro Pro Glu Ser Ala Val Thr Gly Tyr Arg Val Asp Val Ile Pro Val 930 935 940 Asn Leu Pro Gly Glu His Gly Gln Arg Leu Pro Ile Ser Arg Asn Thr 945 950 955 960 Phe Ala Glu Val Thr Gly Leu Ser Pro Gly Val Thr Tyr Tyr Phe Lys 965 970 975 Val Phe Ala Val Ser His Gly Arg Glu Ser Lys Pro Leu Thr Ala Gln 980 985 990 Gln Thr Thr Lys Leu Asp Ala Pro Thr Asn Leu Gln Phe Val Asn Glu 995 1000 1005 Thr Asp Ser Thr Val Leu Val Arg Trp Thr Pro Pro Arg Ala Gln 1010 1015 1020 Ile Thr Gly Tyr Arg Leu Thr Val Gly Leu Thr Arg Arg Gly Gln 1025 1030 1035 Pro Arg Gln Tyr Asn Val Gly Pro Ser Val Ser Lys Tyr Pro Leu 1040 1045 1050 Arg Asn Leu Gln Pro Ala Ser Glu Tyr Thr Val Ser Leu Val Ala 1055 1060 1065 Ile Lys Gly Asn Gln Glu Ser Pro Lys Ala Thr Gly Val Phe Thr 1070 1075 1080 Thr Leu Gln Pro Gly Ser Ser Ile Pro Pro Tyr Asn Thr Glu Val 1085 1090 1095 Thr Glu Thr Thr Ile Val Ile Thr Trp Thr Pro Ala Pro Arg Ile 1100 1105 1110 Gly Phe Lys Leu Gly Val Arg Pro Ser Gln Gly Gly Glu Ala Pro 1115 1120 1125 Arg Glu Val Thr Ser Asp Ser Gly Ser Ile Val Val Ser Gly Leu 1130 1135 1140 Thr Pro Gly Val Glu Tyr Val Tyr Thr Ile Gln Val Leu Arg Asp 1145 1150 1155 Gly Gln Glu Arg Asp Ala Pro Ile Val Asn Lys Val Val Thr Pro 1160 1165 1170 Leu Ser Pro Pro Thr Asn Leu His Leu Glu Ala Asn Pro Asp Thr 1175 1180 1185 Gly Val Leu Thr Val Ser Trp Glu Arg Ser Thr Thr Pro Asp Ile 1190 1195 1200 Thr Gly Tyr Arg Ile Thr Thr Thr Pro Thr Asn Gly Gln Gln Gly 1205 1210 1215 Asn Ser Leu Glu Glu Val Val His Ala Asp Gln Ser Ser Cys Thr 1220 1225 1230 Phe Asp Asn Leu Ser Pro Gly Leu Glu Tyr Asn Val Ser Val Tyr 1235 1240 1245 Thr Val Lys Asp Asp Lys Glu Ser Val Pro Ile Ser Asp Thr Ile 1250 1255 1260 Ile Pro Glu Val Pro Gln Leu Thr Asp Leu Ser Phe Val Asp Ile 1265 1270 1275 Thr Asp Ser Ser Ile Gly Leu Arg Trp Thr Pro Leu Asn Ser Ser 1280 1285 1290 Thr Ile Ile Gly Tyr Arg Ile Thr Val Val Ala Ala Gly Glu Gly 1295 1300 1305 Ile Pro Ile Phe Glu Asp Phe Val Asp Ser Ser Val Gly Tyr Tyr 1310 1315 1320 Thr Val Thr Gly Leu Glu Pro Gly Ile Asp Tyr Asp Ile Ser Val 1325 1330 1335 Ile Thr Leu Ile Asn Gly Gly Glu Ser Ala Pro Thr Thr Leu Thr 1340 1345 1350 Gln Gln Thr Ala Val Pro Pro Pro Thr Asp Leu Arg Phe Thr Asn 1355 1360 1365 Ile Gly Pro Asp Thr Met Arg Val Thr Trp Ala Pro Pro Pro Ser 1370 1375 1380 Ile Asp Leu Thr Asn Phe Leu Val Arg Tyr Ser Pro Val Lys Asn 1385 1390 1395 Glu Glu Asp Val Ala Glu Leu Ser Ile Ser Pro Ser Asp Asn Ala 1400 1405 1410 Val Val Leu Thr Asn Leu Leu Pro Gly Thr Glu Tyr Val Val Ser 1415 1420 1425 Val Ser Ser Val Tyr Glu Gln His Glu Ser Thr Pro Leu Arg Gly 1430 1435 1440 Arg Gln Lys Thr Gly Leu Asp Ser Pro Thr Gly Ile Asp Phe Ser 1445 1450 1455 Asp Ile Thr Ala Asn Ser Phe Thr Val His Trp Ile Ala Pro Arg 1460 1465 1470 Ala Thr Ile Thr Gly Tyr Arg Ile Arg His His Pro Glu His Phe 1475 1480 1485 Ser Gly Arg Pro Arg Glu Asp Arg Val Pro His Ser Arg Asn Ser 1490 1495 1500 Ile Thr Leu Thr Asn Leu Thr Pro Gly Thr Glu Tyr Val Val Ser 1505 1510 1515 Ile Val Ala Leu Asn Gly Arg Glu Glu Ser Pro Leu Leu Ile Gly 1520 1525 1530 Gln Gln Ser Thr Val Ser Asp Val Pro Arg Asp Leu Glu Val Val 1535 1540 1545 Ala Ala Thr Pro Thr Ser Leu Leu Ile Ser Trp Asp Ala Pro Ala 1550 1555 1560 Val Thr Val Arg Tyr Tyr Arg Ile Thr Tyr Gly Glu Thr Gly Gly 1565 1570 1575 Asn Ser Pro Val Gln Glu Phe Thr Val Pro Gly Ser Lys Ser Thr 1580 1585 1590 Ala Thr Ile Ser Gly Leu Lys Pro Gly Val Asp Tyr Thr Ile Thr 1595 1600 1605 Val Tyr Ala Val Thr Gly Arg Gly Asp Ser Pro Ala

Ser Ser Lys 1610 1615 1620 Pro Ile Ser Ile Asn Tyr Arg Thr Glu Ile Asp Lys Pro Ser Gln 1625 1630 1635 Met Gln Val Thr Asp Val Gln Asp Asn Ser Ile Ser Val Lys Trp 1640 1645 1650 Leu Pro Ser Ser Ser Pro Val Thr Gly Tyr Arg Val Thr Thr Thr 1655 1660 1665 Pro Lys Asn Gly Pro Gly Pro Thr Lys Thr Lys Thr Ala Gly Pro 1670 1675 1680 Asp Gln Thr Glu Met Thr Ile Glu Gly Leu Gln Pro Thr Val Glu 1685 1690 1695 Tyr Val Val Ser Val Tyr Ala Gln Asn Pro Ser Gly Glu Ser Gln 1700 1705 1710 Pro Leu Val Gln Thr Ala Val Thr Asn Ile Asp Arg Pro Lys Gly 1715 1720 1725 Leu Ala Phe Thr Asp Val Asp Val Asp Ser Ile Lys Ile Ala Trp 1730 1735 1740 Glu Ser Pro Gln Gly Gln Val Ser Arg Tyr Arg Val Thr Tyr Ser 1745 1750 1755 Ser Pro Glu Asp Gly Ile His Glu Leu Phe Pro Ala Pro Asp Gly 1760 1765 1770 Glu Glu Asp Thr Ala Glu Leu Gln Gly Leu Arg Pro Gly Ser Glu 1775 1780 1785 Tyr Thr Val Ser Val Val Ala Leu His Asp Asp Met Glu Ser Gln 1790 1795 1800 Pro Leu Ile Gly Thr Gln Ser Thr Ala Ile Pro Ala Pro Thr Asp 1805 1810 1815 Leu Lys Phe Thr Gln Val Thr Pro Thr Ser Leu Ser Ala Gln Trp 1820 1825 1830 Thr Pro Pro Asn Val Gln Leu Thr Gly Tyr Arg Val Arg Val Thr 1835 1840 1845 Pro Lys Glu Lys Thr Gly Pro Met Lys Glu Ile Asn Leu Ala Pro 1850 1855 1860 Asp Ser Ser Ser Val Val Val Ser Gly Leu Met Val Ala Thr Lys 1865 1870 1875 Tyr Glu Val Ser Val Tyr Ala Leu Lys Asp Thr Leu Thr Ser Arg 1880 1885 1890 Pro Ala Gln Gly Val Val Thr Thr Leu Glu Asn Val Ser Pro Pro 1895 1900 1905 Arg Arg Ala Arg Val Thr Asp Ala Thr Glu Thr Thr Ile Thr Ile 1910 1915 1920 Ser Trp Arg Thr Lys Thr Glu Thr Ile Thr Gly Phe Gln Val Asp 1925 1930 1935 Ala Val Pro Ala Asn Gly Gln Thr Pro Ile Gln Arg Thr Ile Lys 1940 1945 1950 Pro Asp Val Arg Ser Tyr Thr Ile Thr Gly Leu Gln Pro Gly Thr 1955 1960 1965 Asp Tyr Lys Ile Tyr Leu Tyr Thr Leu Asn Asp Asn Ala Arg Ser 1970 1975 1980 Ser Pro Val Val Ile Asp Ala Ser Thr Ala Ile Asp Ala Pro Ser 1985 1990 1995 Asn Leu Arg Phe Leu Ala Thr Thr Pro Asn Ser Leu Leu Val Ser 2000 2005 2010 Trp Gln Pro Pro Arg Ala Arg Ile Thr Gly Tyr Ile Ile Lys Tyr 2015 2020 2025 Glu Lys Pro Gly Ser Pro Pro Arg Glu Val Val Pro Arg Pro Arg 2030 2035 2040 Pro Gly Val Thr Glu Ala Thr Ile Thr Gly Leu Glu Pro Gly Thr 2045 2050 2055 Glu Tyr Thr Ile Tyr Val Ile Ala Leu Lys Asn Asn Gln Lys Ser 2060 2065 2070 Glu Pro Leu Ile Gly Arg Lys Lys Thr Asp Glu Leu Pro Gln Leu 2075 2080 2085 Val Thr Leu Pro His Pro Asn Leu His Gly Pro Glu Ile Leu Asp 2090 2095 2100 Val Pro Ser Thr Val Gln Lys Thr Pro Phe Val Thr His Pro Gly 2105 2110 2115 Tyr Asp Thr Gly Asn Gly Ile Gln Leu Pro Gly Thr Ser Gly Gln 2120 2125 2130 Gln Pro Ser Val Gly Gln Gln Met Ile Phe Glu Glu His Gly Phe 2135 2140 2145 Arg Arg Thr Thr Pro Pro Thr Thr Ala Thr Pro Ile Arg His Arg 2150 2155 2160 Pro Arg Pro Tyr Pro Pro Asn Val Gly Glu Glu Ile Gln Ile Gly 2165 2170 2175 His Ile Pro Arg Glu Asp Val Asp Tyr His Leu Tyr Pro His Gly 2180 2185 2190 Pro Gly Leu Asn Pro Asn Ala Ser Thr Gly Gln Glu Ala Leu Ser 2195 2200 2205 Gln Thr Thr Ile Ser Trp Ala Pro Phe Gln Asp Thr Ser Glu Tyr 2210 2215 2220 Ile Ile Ser Cys His Pro Val Gly Thr Asp Glu Glu Pro Leu Gln 2225 2230 2235 Phe Arg Val Pro Gly Thr Ser Thr Ser Ala Thr Leu Thr Gly Leu 2240 2245 2250 Thr Arg Gly Ala Thr Tyr Asn Ile Ile Val Glu Ala Leu Lys Asp 2255 2260 2265 Gln Gln Arg His Lys Val Arg Glu Glu Val Val Thr Val Gly Asn 2270 2275 2280 Ser Val Asn Glu Gly Leu Asn Gln Pro Thr Asp Asp Ser Cys Phe 2285 2290 2295 Asp Pro Tyr Thr Val Ser His Tyr Ala Val Gly Asp Glu Trp Glu 2300 2305 2310 Arg Met Ser Glu Ser Gly Phe Lys Leu Leu Cys Gln Cys Leu Gly 2315 2320 2325 Phe Gly Ser Gly His Phe Arg Cys Asp Ser Ser Arg Trp Cys His 2330 2335 2340 Asp Asn Gly Val Asn Tyr Lys Ile Gly Glu Lys Trp Asp Arg Gln 2345 2350 2355 Gly Glu Asn Gly Gln Met Met Ser Cys Thr Cys Leu Gly Asn Gly 2360 2365 2370 Lys Gly Glu Phe Lys Cys Asp Pro His Glu Ala Thr Cys Tyr Asp 2375 2380 2385 Asp Gly Lys Thr Tyr His Val Gly Glu Gln Trp Gln Lys Glu Tyr 2390 2395 2400 Leu Gly Ala Ile Cys Ser Cys Thr Cys Phe Gly Gly Gln Arg Gly 2405 2410 2415 Trp Arg Cys Asp Asn Cys Arg Arg Pro Gly Gly Glu Pro Ser Pro 2420 2425 2430 Glu Gly Thr Thr Gly Gln Ser Tyr Asn Gln Tyr Ser Gln Arg Tyr 2435 2440 2445 His Gln Arg Thr Asn Thr Asn Val Asn Cys Pro Ile Glu Cys Phe 2450 2455 2460 Met Pro Leu Asp Val Gln Ala Asp Arg Glu Asp Ser Arg Glu 2465 2470 2475 307782PRTHomo sapiens 307Met Ala Pro His Arg Pro Ala Pro Ala Leu Leu Cys Ala Leu Ser Leu 1 5 10 15 Ala Leu Cys Ala Leu Ser Leu Pro Val Arg Ala Ala Thr Ala Ser Arg 20 25 30 Gly Ala Ser Gln Ala Gly Ala Pro Gln Gly Arg Val Pro Glu Ala Arg 35 40 45 Pro Asn Ser Met Val Val Glu His Pro Glu Phe Leu Lys Ala Gly Lys 50 55 60 Glu Pro Gly Leu Gln Ile Trp Arg Val Glu Lys Phe Asp Leu Val Pro 65 70 75 80 Val Pro Thr Asn Leu Tyr Gly Asp Phe Phe Thr Gly Asp Ala Tyr Val 85 90 95 Ile Leu Lys Thr Val Gln Leu Arg Asn Gly Asn Leu Gln Tyr Asp Leu 100 105 110 His Tyr Trp Leu Gly Asn Glu Cys Ser Gln Asp Glu Ser Gly Ala Ala 115 120 125 Ala Ile Phe Thr Val Gln Leu Asp Asp Tyr Leu Asn Gly Arg Ala Val 130 135 140 Gln His Arg Glu Val Gln Gly Phe Glu Ser Ala Thr Phe Leu Gly Tyr 145 150 155 160 Phe Lys Ser Gly Leu Lys Tyr Lys Lys Gly Gly Val Ala Ser Gly Phe 165 170 175 Lys His Val Val Pro Asn Glu Val Val Val Gln Arg Leu Phe Gln Val 180 185 190 Lys Gly Arg Arg Val Val Arg Ala Thr Glu Val Pro Val Ser Trp Glu 195 200 205 Ser Phe Asn Asn Gly Asp Cys Phe Ile Leu Asp Leu Gly Asn Asn Ile 210 215 220 His Gln Trp Cys Gly Ser Asn Ser Asn Arg Tyr Glu Arg Leu Lys Ala 225 230 235 240 Thr Gln Val Ser Lys Gly Ile Arg Asp Asn Glu Arg Ser Gly Arg Ala 245 250 255 Arg Val His Val Ser Glu Glu Gly Thr Glu Pro Glu Ala Met Leu Gln 260 265 270 Val Leu Gly Pro Lys Pro Ala Leu Pro Ala Gly Thr Glu Asp Thr Ala 275 280 285 Lys Glu Asp Ala Ala Asn Arg Lys Leu Ala Lys Leu Tyr Lys Val Ser 290 295 300 Asn Gly Ala Gly Thr Met Ser Val Ser Leu Val Ala Asp Glu Asn Pro 305 310 315 320 Phe Ala Gln Gly Ala Leu Lys Ser Glu Asp Cys Phe Ile Leu Asp His 325 330 335 Gly Lys Asp Gly Lys Ile Phe Val Trp Lys Gly Lys Gln Ala Asn Thr 340 345 350 Glu Glu Arg Lys Ala Ala Leu Lys Thr Ala Ser Asp Phe Ile Thr Lys 355 360 365 Met Asp Tyr Pro Lys Gln Thr Gln Val Ser Val Leu Pro Glu Gly Gly 370 375 380 Glu Thr Pro Leu Phe Lys Gln Phe Phe Lys Asn Trp Arg Asp Pro Asp 385 390 395 400 Gln Thr Asp Gly Leu Gly Leu Ser Tyr Leu Ser Ser His Ile Ala Asn 405 410 415 Val Glu Arg Val Pro Phe Asp Ala Ala Thr Leu His Thr Ser Thr Ala 420 425 430 Met Ala Ala Gln His Gly Met Asp Asp Asp Gly Thr Gly Gln Lys Gln 435 440 445 Ile Trp Arg Ile Glu Gly Ser Asn Lys Val Pro Val Asp Pro Ala Thr 450 455 460 Tyr Gly Gln Phe Tyr Gly Gly Asp Ser Tyr Ile Ile Leu Tyr Asn Tyr 465 470 475 480 Arg His Gly Gly Arg Gln Gly Gln Ile Ile Tyr Asn Trp Gln Gly Ala 485 490 495 Gln Ser Thr Gln Asp Glu Val Ala Ala Ser Ala Ile Leu Thr Ala Gln 500 505 510 Leu Asp Glu Glu Leu Gly Gly Thr Pro Val Gln Ser Arg Val Val Gln 515 520 525 Gly Lys Glu Pro Ala His Leu Met Ser Leu Phe Gly Gly Lys Pro Met 530 535 540 Ile Ile Tyr Lys Gly Gly Thr Ser Arg Glu Gly Gly Gln Thr Ala Pro 545 550 555 560 Ala Ser Thr Arg Leu Phe Gln Val Arg Ala Asn Ser Ala Gly Ala Thr 565 570 575 Arg Ala Val Glu Val Leu Pro Lys Ala Gly Ala Leu Asn Ser Asn Asp 580 585 590 Ala Phe Val Leu Lys Thr Pro Ser Ala Ala Tyr Leu Trp Val Gly Thr 595 600 605 Gly Ala Ser Glu Ala Glu Lys Thr Gly Ala Gln Glu Leu Leu Arg Val 610 615 620 Leu Arg Ala Gln Pro Val Gln Val Ala Glu Gly Ser Glu Pro Asp Gly 625 630 635 640 Phe Trp Glu Ala Leu Gly Gly Lys Ala Ala Tyr Arg Thr Ser Pro Arg 645 650 655 Leu Lys Asp Lys Lys Met Asp Ala His Pro Pro Arg Leu Phe Ala Cys 660 665 670 Ser Asn Lys Ile Gly Arg Phe Val Ile Glu Glu Val Pro Gly Glu Leu 675 680 685 Met Gln Glu Asp Leu Ala Thr Asp Asp Val Met Leu Leu Asp Thr Trp 690 695 700 Asp Gln Val Phe Val Trp Val Gly Lys Asp Ser Gln Glu Glu Glu Lys 705 710 715 720 Thr Glu Ala Leu Thr Ser Ala Lys Arg Tyr Ile Glu Thr Asp Pro Ala 725 730 735 Asn Arg Asp Arg Arg Thr Pro Ile Thr Val Val Lys Gln Gly Phe Glu 740 745 750 Pro Pro Ser Phe Val Gly Trp Phe Leu Gly Trp Asp Asp Asp Tyr Trp 755 760 765 Ser Val Asp Pro Leu Asp Arg Ala Met Ala Glu Leu Ala Ala 770 775 780 308462PRTHomo sapiens 308Met Ala Arg Val Leu Gly Ala Pro Val Ala Leu Gly Leu Trp Ser Leu 1 5 10 15 Cys Trp Ser Leu Ala Ile Ala Thr Pro Leu Pro Pro Thr Ser Ala His 20 25 30 Gly Asn Val Ala Glu Gly Glu Thr Lys Pro Asp Pro Asp Val Thr Glu 35 40 45 Arg Cys Ser Asp Gly Trp Ser Phe Asp Ala Thr Thr Leu Asp Asp Asn 50 55 60 Gly Thr Met Leu Phe Phe Lys Gly Glu Phe Val Trp Lys Ser His Lys 65 70 75 80 Trp Asp Arg Glu Leu Ile Ser Glu Arg Trp Lys Asn Phe Pro Ser Pro 85 90 95 Val Asp Ala Ala Phe Arg Gln Gly His Asn Ser Val Phe Leu Ile Lys 100 105 110 Gly Asp Lys Val Trp Val Tyr Pro Pro Glu Lys Lys Glu Lys Gly Tyr 115 120 125 Pro Lys Leu Leu Gln Asp Glu Phe Pro Gly Ile Pro Ser Pro Leu Asp 130 135 140 Ala Ala Val Glu Cys His Arg Gly Glu Cys Gln Ala Glu Gly Val Leu 145 150 155 160 Phe Phe Gln Gly Asp Arg Glu Trp Phe Trp Asp Leu Ala Thr Gly Thr 165 170 175 Met Lys Glu Arg Ser Trp Pro Ala Val Gly Asn Cys Ser Ser Ala Leu 180 185 190 Arg Trp Leu Gly Arg Tyr Tyr Cys Phe Gln Gly Asn Gln Phe Leu Arg 195 200 205 Phe Asp Pro Val Arg Gly Glu Val Pro Pro Arg Tyr Pro Arg Asp Val 210 215 220 Arg Asp Tyr Phe Met Pro Cys Pro Gly Arg Gly His Gly His Arg Asn 225 230 235 240 Gly Thr Gly His Gly Asn Ser Thr His His Gly Pro Glu Tyr Met Arg 245 250 255 Cys Ser Pro His Leu Val Leu Ser Ala Leu Thr Ser Asp Asn His Gly 260 265 270 Ala Thr Tyr Ala Phe Ser Gly Thr His Tyr Trp Arg Leu Asp Thr Ser 275 280 285 Arg Asp Gly Trp His Ser Trp Pro Ile Ala His Gln Trp Pro Gln Gly 290 295 300 Pro Ser Ala Val Asp Ala Ala Phe Ser Trp Glu Glu Lys Leu Tyr Leu 305 310 315 320 Val Gln Gly Thr Gln Val Tyr Val Phe Leu Thr Lys Gly Gly Tyr Thr 325 330 335 Leu Val Ser Gly Tyr Pro Lys Arg Leu Glu Lys Glu Val Gly Thr Pro 340 345 350 His Gly Ile Ile Leu Asp Ser Val Asp Ala Ala Phe Ile Cys Pro Gly 355 360 365 Ser Ser Arg Leu His Ile Met Ala Gly Arg Arg Leu Trp Trp Leu Asp 370 375 380 Leu Lys Ser Gly Ala Gln Ala Thr Trp Thr Glu Leu Pro Trp Pro His 385 390 395 400 Glu Lys Val Asp Gly Ala Leu Cys Met Glu Lys Ser Leu Gly Pro Asn 405 410 415 Ser Cys Ser Ala Asn Gly Pro Gly Leu Tyr Leu Ile His Gly Pro Asn 420 425 430 Leu Tyr Cys Tyr Ser Asp Val Glu Lys Leu Asn Ala Ala Lys Ala Leu 435 440 445 Pro Gln Pro Gln Asn Val Thr Ser Leu Leu Gly Cys Thr His 450 455 460 309499PRTHomo sapiens 309Met Lys His Ser Leu Asn Ala Leu Leu Ile Phe Leu Ile Ile Thr Ser 1 5 10 15 Ala Trp Gly Gly Ser Lys Gly Pro Leu Asp Gln Leu Glu Lys Gly Gly 20 25 30 Glu Thr Ala Gln Ser Ala Asp Pro Gln Trp Glu Gln Leu Asn Asn Lys 35 40 45 Asn Leu Ser Met Pro Leu Leu Pro Ala Asp Phe His Lys Glu Asn Thr 50 55 60 Val Thr Asn Asp Trp Ile Pro Glu Gly Glu Glu Asp Asp Asp Tyr Leu 65 70 75 80 Asp Leu Glu Lys Ile Phe Ser Glu Asp Asp Asp Tyr Ile Asp Ile Val 85 90 95 Asp Ser Leu Ser Val Ser Pro Thr Asp Ser Asp Val Ser Ala Gly Asn 100 105 110 Ile Leu Gln Leu Phe His Gly Lys Ser Arg Ile Gln Arg Leu Asn Ile 115 120 125 Leu Asn Ala Lys Phe Ala Phe Asn Leu Tyr Arg Val Leu Lys Asp Gln 130 135 140

Val Asn Thr Phe Asp Asn Ile Phe Ile Ala Pro Val Gly Ile Ser Thr 145 150 155 160 Ala Met Gly Met Ile Ser Leu Gly Leu Lys Gly Glu Thr His Glu Gln 165 170 175 Val His Ser Ile Leu His Phe Lys Asp Phe Val Asn Ala Ser Ser Lys 180 185 190 Tyr Glu Ile Thr Thr Ile His Asn Leu Phe Arg Lys Leu Thr His Arg 195 200 205 Leu Phe Arg Arg Asn Phe Gly Tyr Thr Leu Arg Ser Val Asn Asp Leu 210 215 220 Tyr Ile Gln Lys Gln Phe Pro Ile Leu Leu Asp Phe Arg Thr Lys Val 225 230 235 240 Arg Glu Tyr Tyr Phe Ala Glu Ala Gln Ile Ala Asp Phe Ser Asp Pro 245 250 255 Ala Phe Ile Ser Lys Thr Asn Asn His Ile Met Lys Leu Thr Lys Gly 260 265 270 Leu Ile Lys Asp Ala Leu Glu Asn Ile Asp Pro Ala Thr Gln Met Met 275 280 285 Ile Leu Asn Cys Ile Tyr Phe Lys Gly Ser Trp Val Asn Lys Phe Pro 290 295 300 Val Glu Met Thr His Asn His Asn Phe Arg Leu Asn Glu Arg Glu Val 305 310 315 320 Val Lys Val Ser Met Met Gln Thr Lys Gly Asn Phe Leu Ala Ala Asn 325 330 335 Asp Gln Glu Leu Asp Cys Asp Ile Leu Gln Leu Glu Tyr Val Gly Gly 340 345 350 Ile Ser Met Leu Ile Val Val Pro His Lys Met Ser Gly Met Lys Thr 355 360 365 Leu Glu Ala Gln Leu Thr Pro Arg Val Val Glu Arg Trp Gln Lys Ser 370 375 380 Met Thr Asn Arg Thr Arg Glu Val Leu Leu Pro Lys Phe Lys Leu Glu 385 390 395 400 Lys Asn Tyr Asn Leu Val Glu Ser Leu Lys Leu Met Gly Ile Arg Met 405 410 415 Leu Phe Asp Lys Asn Gly Asn Met Ala Gly Ile Ser Asp Gln Arg Ile 420 425 430 Ala Ile Asp Leu Phe Lys His Gln Gly Thr Ile Thr Val Asn Glu Glu 435 440 445 Gly Thr Gln Ala Thr Thr Val Thr Thr Val Gly Phe Met Pro Leu Ser 450 455 460 Thr Gln Val Arg Phe Thr Val Asp Arg Pro Phe Leu Phe Leu Ile Tyr 465 470 475 480 Glu His Arg Thr Ser Cys Leu Leu Phe Met Gly Arg Val Ala Asn Pro 485 490 495 Ser Arg Ser 310583PRTHomo sapiens 310Met Lys Leu Leu His Val Phe Leu Leu Phe Leu Cys Phe His Leu Arg 1 5 10 15 Phe Cys Lys Val Thr Tyr Thr Ser Gln Glu Asp Leu Val Glu Lys Lys 20 25 30 Cys Leu Ala Lys Lys Tyr Thr His Leu Ser Cys Asp Lys Val Phe Cys 35 40 45 Gln Pro Trp Gln Arg Cys Ile Glu Gly Thr Cys Val Cys Lys Leu Pro 50 55 60 Tyr Gln Cys Pro Lys Asn Gly Thr Ala Val Cys Ala Thr Asn Arg Arg 65 70 75 80 Ser Phe Pro Thr Tyr Cys Gln Gln Lys Ser Leu Glu Cys Leu His Pro 85 90 95 Gly Thr Lys Phe Leu Asn Asn Gly Thr Cys Thr Ala Glu Gly Lys Phe 100 105 110 Ser Val Ser Leu Lys His Gly Asn Thr Asp Ser Glu Gly Ile Val Glu 115 120 125 Val Lys Leu Val Asp Gln Asp Lys Thr Met Phe Ile Cys Lys Ser Ser 130 135 140 Trp Ser Met Arg Glu Ala Asn Val Ala Cys Leu Asp Leu Gly Phe Gln 145 150 155 160 Gln Gly Ala Asp Thr Gln Arg Arg Phe Lys Leu Ser Asp Leu Ser Ile 165 170 175 Asn Ser Thr Glu Cys Leu His Val His Cys Arg Gly Leu Glu Thr Ser 180 185 190 Leu Ala Glu Cys Thr Phe Thr Lys Arg Arg Thr Met Gly Tyr Gln Asp 195 200 205 Phe Ala Asp Val Val Cys Tyr Thr Gln Lys Ala Asp Ser Pro Met Asp 210 215 220 Asp Phe Phe Gln Cys Val Asn Gly Lys Tyr Ile Ser Gln Met Lys Ala 225 230 235 240 Cys Asp Gly Ile Asn Asp Cys Gly Asp Gln Ser Asp Glu Leu Cys Cys 245 250 255 Lys Ala Cys Gln Gly Lys Gly Phe His Cys Lys Ser Gly Val Cys Ile 260 265 270 Pro Ser Gln Tyr Gln Cys Asn Gly Glu Val Asp Cys Ile Thr Gly Glu 275 280 285 Asp Glu Val Gly Cys Ala Gly Phe Ala Ser Val Ala Gln Glu Glu Thr 290 295 300 Glu Ile Leu Thr Ala Asp Met Asp Ala Glu Arg Arg Arg Ile Lys Ser 305 310 315 320 Leu Leu Pro Lys Leu Ser Cys Gly Val Lys Asn Arg Met His Ile Arg 325 330 335 Arg Lys Arg Ile Val Gly Gly Lys Arg Ala Gln Leu Gly Asp Leu Pro 340 345 350 Trp Gln Val Ala Ile Lys Asp Ala Ser Gly Ile Thr Cys Gly Gly Ile 355 360 365 Tyr Ile Gly Gly Cys Trp Ile Leu Thr Ala Ala His Cys Leu Arg Ala 370 375 380 Ser Lys Thr His Arg Tyr Gln Ile Trp Thr Thr Val Val Asp Trp Ile 385 390 395 400 His Pro Asp Leu Lys Arg Ile Val Ile Glu Tyr Val Asp Arg Ile Ile 405 410 415 Phe His Glu Asn Tyr Asn Ala Gly Thr Tyr Gln Asn Asp Ile Ala Leu 420 425 430 Ile Glu Met Lys Lys Asp Gly Asn Lys Lys Asp Cys Glu Leu Pro Arg 435 440 445 Ser Ile Pro Ala Cys Val Pro Trp Ser Pro Tyr Leu Phe Gln Pro Asn 450 455 460 Asp Thr Cys Ile Val Ser Gly Trp Gly Arg Glu Lys Asp Asn Glu Arg 465 470 475 480 Val Phe Ser Leu Gln Trp Gly Glu Val Lys Leu Ile Ser Asn Cys Ser 485 490 495 Lys Phe Tyr Gly Asn Arg Phe Tyr Glu Lys Glu Met Glu Cys Ala Gly 500 505 510 Thr Tyr Asp Gly Ser Ile Asp Ala Cys Lys Gly Asp Ser Gly Gly Pro 515 520 525 Leu Val Cys Met Asp Ala Asn Asn Val Thr Tyr Val Trp Gly Val Val 530 535 540 Ser Trp Gly Glu Asn Cys Gly Lys Pro Glu Phe Pro Gly Phe Tyr Thr 545 550 555 560 Lys Val Ala Asn Tyr Phe Asp Trp Ile Ser Tyr His Val Gly Arg Pro 565 570 575 Phe Ile Ser Gln Tyr Asn Val 580 311159PRTHomo sapiens 311Met Lys Asn His Leu Leu Phe Trp Gly Val Leu Ala Val Phe Ile Lys 1 5 10 15 Ala Val His Val Lys Ala Gln Glu Asp Glu Arg Ile Val Leu Val Asp 20 25 30 Asn Lys Cys Lys Cys Ala Arg Ile Thr Ser Arg Ile Ile Arg Ser Ser 35 40 45 Glu Asp Pro Asn Glu Asp Ile Val Glu Arg Asn Ile Arg Ile Ile Val 50 55 60 Pro Leu Asn Asn Arg Glu Asn Ile Ser Asp Pro Thr Ser Pro Leu Arg 65 70 75 80 Thr Arg Phe Val Tyr His Leu Ser Asp Leu Cys Lys Lys Cys Asp Pro 85 90 95 Thr Glu Val Glu Leu Asp Asn Gln Ile Val Thr Ala Thr Gln Ser Asn 100 105 110 Ile Cys Asp Glu Asp Ser Ala Thr Glu Thr Cys Tyr Thr Tyr Asp Arg 115 120 125 Asn Lys Cys Tyr Thr Ala Val Val Pro Leu Val Tyr Gly Gly Glu Thr 130 135 140 Lys Met Val Glu Thr Ala Leu Thr Pro Asp Ala Cys Tyr Pro Asp 145 150 155 312911PRTHomo sapiens 312Met Asp Gly Ala Met Gly Pro Arg Gly Leu Leu Leu Cys Met Tyr Leu 1 5 10 15 Val Ser Leu Leu Ile Leu Gln Ala Met Pro Ala Leu Gly Ser Ala Thr 20 25 30 Gly Arg Ser Lys Ser Ser Glu Lys Arg Gln Ala Val Asp Thr Ala Val 35 40 45 Asp Gly Val Phe Ile Arg Ser Leu Lys Val Asn Cys Lys Val Thr Ser 50 55 60 Arg Phe Ala His Tyr Val Val Thr Ser Gln Val Val Asn Thr Ala Asn 65 70 75 80 Glu Ala Arg Glu Val Ala Phe Asp Leu Glu Ile Pro Lys Thr Ala Phe 85 90 95 Ile Ser Asp Phe Ala Val Thr Ala Asp Gly Asn Ala Phe Ile Gly Asp 100 105 110 Ile Lys Asp Lys Val Thr Ala Trp Lys Gln Tyr Arg Lys Ala Ala Ile 115 120 125 Ser Gly Glu Asn Ala Gly Leu Val Arg Ala Ser Gly Arg Thr Met Glu 130 135 140 Gln Phe Thr Ile His Leu Thr Val Asn Pro Gln Ser Lys Val Thr Phe 145 150 155 160 Gln Leu Thr Tyr Glu Glu Val Leu Lys Arg Asn His Met Gln Tyr Glu 165 170 175 Ile Val Ile Lys Val Lys Pro Lys Gln Leu Val His His Phe Glu Ile 180 185 190 Asp Val Asp Ile Phe Glu Pro Gln Gly Ile Ser Lys Leu Asp Ala Gln 195 200 205 Ala Ser Phe Leu Pro Lys Glu Leu Ala Ala Gln Thr Ile Lys Lys Ser 210 215 220 Phe Ser Gly Lys Lys Gly His Val Leu Phe Arg Pro Thr Val Ser Gln 225 230 235 240 Gln Gln Ser Cys Pro Thr Cys Ser Thr Ser Leu Leu Asn Gly His Phe 245 250 255 Lys Val Thr Tyr Asp Val Thr Arg Asp Glu Ile Cys Asp Leu Leu Val 260 265 270 Ala Asn Asn His Phe Ala His Phe Phe Ala Pro Gln Asn Leu Thr Asn 275 280 285 Met Asn Lys Asn Val Val Phe Val Ile Asp Ile Ser Gly Ser Met Arg 290 295 300 Gly Gln Lys Val Lys Gln Thr Lys Glu Ala Leu Leu Lys Ile Leu Gly 305 310 315 320 Asp Met Gln Pro Gly Asp Tyr Phe Asp Leu Val Leu Phe Gly Thr Arg 325 330 335 Val Gln Ser Trp Lys Gly Ser Leu Val Gln Ala Ser Glu Ala Asn Leu 340 345 350 Gln Ala Ala Gln Asp Phe Val Arg Gly Phe Ser Leu Asp Glu Ala Thr 355 360 365 Asn Leu Asn Gly Gly Leu Leu Arg Gly Ile Glu Ile Leu Asn Gln Val 370 375 380 Gln Glu Ser Leu Pro Glu Leu Ser Asn His Ala Ser Ile Leu Ile Met 385 390 395 400 Leu Thr Asp Gly Asp Pro Thr Glu Gly Val Thr Asp Arg Ser Gln Ile 405 410 415 Leu Lys Asn Val Arg Asn Ala Ile Arg Gly Arg Phe Pro Leu Tyr Asn 420 425 430 Leu Gly Phe Gly His Asn Val Asp Phe Asn Phe Leu Glu Val Met Ser 435 440 445 Met Glu Asn Asn Gly Arg Ala Gln Arg Ile Tyr Glu Asp His Asp Ala 450 455 460 Thr Gln Gln Leu Gln Gly Phe Tyr Ser Gln Val Ala Lys Pro Leu Leu 465 470 475 480 Val Asp Val Asp Leu Gln Tyr Pro Gln Asp Ala Val Leu Ala Leu Thr 485 490 495 Gln Asn His His Lys Gln Tyr Tyr Glu Gly Ser Glu Ile Val Val Ala 500 505 510 Gly Arg Ile Ala Asp Asn Lys Gln Ser Ser Phe Lys Ala Asp Val Gln 515 520 525 Ala His Gly Glu Gly Gln Glu Phe Ser Ile Thr Cys Leu Val Asp Glu 530 535 540 Glu Glu Met Lys Lys Leu Leu Arg Glu Arg Gly His Met Leu Glu Asn 545 550 555 560 His Val Glu Arg Leu Trp Ala Tyr Leu Thr Ile Gln Glu Leu Leu Ala 565 570 575 Lys Arg Met Lys Val Asp Arg Glu Val Arg Ala Asn Leu Ser Ser Gln 580 585 590 Ala Leu Arg Met Ser Leu Asp Tyr Gly Phe Val Thr Pro Leu Thr Ser 595 600 605 Met Ser Ile Arg Gly Met Ala Asp Gln Asp Gly Leu Lys Pro Thr Ile 610 615 620 Asp Lys Pro Ser Glu Asp Ser Pro Pro Leu Glu Met Leu Gly Pro Arg 625 630 635 640 Arg Thr Phe Val Leu Ser Ala Leu Gln Pro Ser Pro Thr His Ser Ser 645 650 655 Ser Asn Thr Gln Arg Leu Pro Asp Arg Val Thr Gly Val Asp Thr Asp 660 665 670 Pro His Phe Ile Ile His Val Pro Gln Lys Glu Asp Thr Leu Cys Phe 675 680 685 Asn Ile Asn Glu Glu Pro Gly Val Ile Leu Ser Leu Val Gln Asp Pro 690 695 700 Asn Thr Gly Phe Ser Val Asn Gly Gln Leu Ile Gly Asn Lys Ala Arg 705 710 715 720 Ser Pro Gly Gln His Asp Gly Thr Tyr Phe Gly Arg Leu Gly Ile Ala 725 730 735 Asn Pro Ala Thr Asp Phe Gln Leu Glu Val Thr Pro Gln Asn Ile Thr 740 745 750 Leu Asn Pro Gly Phe Gly Gly Pro Val Phe Ser Trp Arg Asp Gln Ala 755 760 765 Val Leu Arg Gln Asp Gly Val Val Val Thr Ile Asn Lys Lys Arg Asn 770 775 780 Leu Val Val Ser Val Asp Asp Gly Gly Thr Phe Glu Val Val Leu His 785 790 795 800 Arg Val Trp Lys Gly Ser Ser Val His Gln Asp Phe Leu Gly Phe Tyr 805 810 815 Val Leu Asp Ser His Arg Met Ser Ala Arg Thr His Gly Leu Leu Gly 820 825 830 Gln Phe Phe His Pro Ile Gly Phe Glu Val Ser Asp Ile His Pro Gly 835 840 845 Ser Asp Pro Thr Lys Pro Asp Ala Thr Met Val Val Arg Asn Arg Arg 850 855 860 Leu Thr Val Thr Arg Gly Leu Gln Lys Asp Tyr Ser Lys Asp Pro Trp 865 870 875 880 His Gly Ala Glu Val Ser Cys Trp Phe Ile His Asn Asn Gly Ala Gly 885 890 895 Leu Ile Asp Gly Ala Tyr Thr Asp Tyr Ile Val Pro Asp Ile Phe 900 905 910 313946PRTHomo sapiens 313Met Lys Arg Leu Thr Cys Phe Phe Ile Cys Phe Phe Leu Ser Glu Val 1 5 10 15 Ser Gly Phe Glu Ile Pro Ile Asn Gly Leu Ser Glu Phe Val Asp Tyr 20 25 30 Glu Asp Leu Val Glu Leu Ala Pro Gly Lys Phe Gln Leu Val Ala Glu 35 40 45 Asn Arg Arg Tyr Gln Arg Ser Leu Pro Gly Glu Ser Glu Glu Met Met 50 55 60 Glu Glu Val Asp Gln Val Thr Leu Tyr Ser Tyr Lys Val Gln Ser Thr 65 70 75 80 Ile Thr Ser Arg Met Ala Thr Thr Met Ile Gln Ser Lys Val Val Asn 85 90 95 Asn Ser Pro Gln Pro Gln Asn Val Val Phe Asp Val Gln Ile Pro Lys 100 105 110 Gly Ala Phe Ile Ser Asn Phe Ser Met Thr Val Asp Gly Lys Thr Phe 115 120 125 Arg Ser Ser Ile Lys Glu Lys Thr Val Gly Arg Ala Leu Tyr Ala Gln 130 135 140 Ala Arg Ala Lys Gly Lys Thr Ala Gly Leu Val Arg Ser Ser Ala Leu 145 150 155 160 Asp Met Glu Asn Phe Arg Thr Glu Val Asn Val Leu Pro Gly Ala Lys 165 170 175 Val Gln Phe Glu Leu His Tyr Gln Glu Val Lys Trp Arg Lys Leu Gly 180 185 190 Ser Tyr Glu His Arg Ile Tyr Leu Gln Pro Gly Arg Leu Ala Lys His 195 200 205 Leu Glu Val Asp Val Trp Val Ile Glu Pro Gln Gly Leu Arg Phe Leu 210 215 220 His Val Pro Asp Thr Phe Glu Gly His Phe Asp Gly Val Pro Val Ile 225 230 235 240 Ser Lys Gly Gln Gln Lys Ala His Val Ser Phe Lys Pro Thr Val Ala 245 250 255 Gln Gln Arg Ile Cys Pro Ser Cys Arg Glu Thr Ala Val Asp Gly Glu 260 265 270 Leu Val Val Leu Tyr Asp Val Lys Arg Glu Glu Lys Ala Gly Glu Leu 275 280 285 Glu Val Phe Asn

Gly Tyr Phe Val His Phe Phe Ala Pro Asp Asn Leu 290 295 300 Asp Pro Ile Pro Lys Asn Ile Leu Phe Val Ile Asp Val Ser Gly Ser 305 310 315 320 Met Trp Gly Val Lys Met Lys Gln Thr Val Glu Ala Met Lys Thr Ile 325 330 335 Leu Asp Asp Leu Arg Ala Glu Asp His Phe Ser Val Ile Asp Phe Asn 340 345 350 Gln Asn Ile Arg Thr Trp Arg Asn Asp Leu Phe Gln Leu Gln Lys His 355 360 365 Arg Leu Gln Ile Ala Lys Arg Tyr Ile Glu Lys Ile Gln Pro Ser Gly 370 375 380 Gly Thr Asn Ile Asn Glu Ala Leu Leu Arg Ala Ile Phe Ile Leu Asn 385 390 395 400 Glu Ala Asn Asn Leu Gly Leu Leu Asp Pro Asn Ser Val Ser Leu Ile 405 410 415 Ile Leu Val Ser Asp Gly Asp Pro Thr Val Gly Glu Leu Lys Leu Ser 420 425 430 Lys Ile Gln Lys Asn Val Lys Glu Asn Ile Gln Asp Asn Ile Ser Leu 435 440 445 Phe Ser Leu Gly Met Gly Phe Asp Val Asp Tyr Asp Phe Leu Lys Arg 450 455 460 Leu Ser Asn Glu Asn His Gly Ile Ala Gln Arg Ile Tyr Gly Asn Gln 465 470 475 480 Asp Thr Ser Ser Gln Leu Lys Lys Phe Tyr Asn Gln Val Ser Thr Pro 485 490 495 Leu Leu Arg Asn Val Gln Phe Asn Tyr Pro His Thr Ser Val Thr Asp 500 505 510 Val Thr Gln Asn Asn Phe His Asn Tyr Phe Gly Gly Ser Glu Ile Val 515 520 525 Val Ala Gly Lys Phe Asp Pro Ala Lys Leu Asp Gln Ile Glu Ser Val 530 535 540 Ile Thr Ala Thr Ser Ala Asn Thr Gln Leu Val Leu Glu Thr Leu Ala 545 550 555 560 Gln Met Asp Asp Leu Gln Asp Phe Leu Ser Lys Asp Lys His Ala Asp 565 570 575 Pro Asp Phe Thr Arg Lys Leu Trp Ala Tyr Leu Thr Ile Asn Gln Leu 580 585 590 Leu Ala Glu Arg Ser Leu Ala Pro Thr Ala Ala Ala Lys Arg Arg Ile 595 600 605 Thr Arg Ser Ile Leu Gln Met Ser Leu Asp His His Ile Val Thr Pro 610 615 620 Leu Thr Ser Leu Val Ile Glu Asn Glu Ala Gly Asp Glu Arg Met Leu 625 630 635 640 Ala Asp Ala Pro Pro Gln Asp Pro Ser Cys Cys Ser Gly Ala Leu Tyr 645 650 655 Tyr Gly Ser Lys Val Val Pro Asp Ser Thr Pro Ser Trp Ala Asn Pro 660 665 670 Ser Pro Thr Pro Val Ile Ser Met Leu Ala Gln Gly Ser Gln Val Leu 675 680 685 Glu Ser Thr Pro Pro Pro His Val Met Arg Val Glu Asn Asp Pro His 690 695 700 Phe Ile Ile Tyr Leu Pro Lys Ser Gln Lys Asn Ile Cys Phe Asn Ile 705 710 715 720 Asp Ser Glu Pro Gly Lys Ile Leu Asn Leu Val Ser Asp Pro Glu Ser 725 730 735 Gly Ile Val Val Asn Gly Gln Leu Val Gly Ala Lys Lys Pro Asn Asn 740 745 750 Gly Lys Leu Ser Thr Tyr Phe Gly Lys Leu Gly Phe Tyr Phe Gln Ser 755 760 765 Glu Asp Ile Lys Ile Glu Ile Ser Thr Glu Thr Ile Thr Leu Ser His 770 775 780 Gly Ser Ser Thr Phe Ser Leu Ser Trp Ser Asp Thr Ala Gln Val Thr 785 790 795 800 Asn Gln Arg Val Gln Ile Ser Val Lys Lys Glu Lys Val Val Thr Ile 805 810 815 Thr Leu Asp Lys Glu Met Ser Phe Ser Val Leu Leu His Arg Val Trp 820 825 830 Lys Lys His Pro Val Asn Val Asp Phe Leu Gly Ile Tyr Ile Pro Pro 835 840 845 Thr Asn Lys Phe Ser Pro Lys Ala His Gly Leu Ile Gly Gln Phe Met 850 855 860 Gln Glu Pro Lys Ile His Ile Phe Asn Glu Arg Pro Gly Lys Asp Pro 865 870 875 880 Glu Lys Pro Glu Ala Ser Met Glu Val Lys Gly Gln Lys Leu Ile Ile 885 890 895 Thr Arg Gly Leu Gln Lys Asp Tyr Arg Thr Asp Leu Val Phe Gly Thr 900 905 910 Asp Val Thr Cys Trp Phe Val His Asn Ser Gly Lys Gly Phe Ile Asp 915 920 925 Gly His Tyr Lys Asp Tyr Phe Val Pro Gln Leu Tyr Ser Phe Leu Lys 930 935 940 Arg Pro 945 314885PRTHomo sapiens 314Met Val Ala Leu Ser His Leu Gly Ser Ala Leu Gln Leu Gly Ser Leu 1 5 10 15 Cys Phe Pro Arg Ser Pro Phe Arg Leu Leu Gly Lys Arg Ser Leu Pro 20 25 30 Glu Gly Val Ala Asn Gly Ile Glu Val Tyr Ser Thr Lys Ile Asn Ser 35 40 45 Lys Val Thr Ser Arg Phe Ala His Asn Val Val Thr Met Arg Ala Val 50 55 60 Asn Arg Ala Asp Thr Ala Lys Glu Val Ser Phe Asp Val Glu Leu Pro 65 70 75 80 Lys Thr Ala Phe Ile Thr Asn Phe Thr Leu Thr Ile Asp Gly Val Thr 85 90 95 Tyr Pro Gly Asn Val Lys Glu Lys Glu Val Ala Lys Lys Gln Tyr Glu 100 105 110 Lys Ala Val Ser Gln Gly Lys Thr Ala Gly Leu Val Lys Ala Ser Gly 115 120 125 Arg Lys Leu Glu Lys Phe Thr Val Ser Val Asn Val Ala Ala Gly Ser 130 135 140 Lys Val Thr Phe Glu Leu Thr Tyr Glu Glu Leu Leu Lys Arg His Lys 145 150 155 160 Gly Lys Tyr Glu Met Tyr Leu Lys Val Gln Pro Lys Gln Leu Val Lys 165 170 175 His Phe Glu Ile Glu Val Asp Ile Phe Glu Pro Gln Gly Ile Ser Met 180 185 190 Leu Asp Ala Glu Ala Ser Phe Ile Thr Asn Asp Leu Leu Gly Ser Ala 195 200 205 Leu Thr Lys Ser Phe Ser Gly Lys Lys Gly His Val Ser Phe Lys Pro 210 215 220 Ser Leu Asp Gln Gln Arg Ser Cys Pro Thr Cys Thr Asp Ser Leu Leu 225 230 235 240 Asn Gly Asp Phe Thr Ile Thr Tyr Asp Val Asn Arg Glu Ser Pro Gly 245 250 255 Asn Val Gln Ile Val Asn Gly Tyr Phe Val His Phe Phe Ala Pro Gln 260 265 270 Gly Leu Pro Val Val Pro Lys Asn Val Ala Phe Val Ile Asp Ile Ser 275 280 285 Gly Ser Met Ala Gly Arg Lys Leu Glu Gln Thr Lys Glu Ala Leu Leu 290 295 300 Arg Ile Leu Glu Asp Met Lys Glu Glu Asp Tyr Leu Asn Phe Ile Leu 305 310 315 320 Phe Ser Gly Asp Val Ser Thr Trp Lys Glu His Leu Val Gln Ala Thr 325 330 335 Pro Glu Asn Leu Gln Glu Ala Arg Thr Phe Val Lys Ser Met Glu Asp 340 345 350 Lys Gly Met Thr Asn Ile Asn Asp Gly Leu Leu Arg Gly Ile Ser Met 355 360 365 Leu Asn Lys Ala Arg Glu Glu His Arg Ile Pro Glu Arg Ser Thr Ser 370 375 380 Ile Val Ile Met Leu Thr Asp Gly Asp Ala Asn Val Gly Glu Ser Arg 385 390 395 400 Pro Glu Lys Ile Gln Glu Asn Val Arg Asn Ala Ile Gly Gly Lys Phe 405 410 415 Pro Leu Tyr Asn Leu Gly Phe Gly Asn Asn Leu Asn Tyr Asn Phe Leu 420 425 430 Glu Asn Met Ala Leu Glu Asn His Gly Phe Ala Arg Arg Ile Tyr Glu 435 440 445 Asp Ser Asp Ala Asp Leu Gln Leu Gln Gly Phe Tyr Glu Glu Val Ala 450 455 460 Asn Pro Leu Leu Thr Gly Val Glu Met Glu Tyr Pro Glu Asn Ala Ile 465 470 475 480 Leu Asp Leu Thr Gln Asn Thr Tyr Gln His Phe Tyr Asp Gly Ser Glu 485 490 495 Ile Val Val Ala Gly Arg Leu Val Asp Glu Asp Met Asn Ser Phe Lys 500 505 510 Ala Asp Val Lys Gly His Gly Ala Thr Asn Asp Leu Thr Phe Thr Glu 515 520 525 Glu Val Asp Met Lys Glu Met Glu Lys Ala Leu Gln Glu Arg Asp Tyr 530 535 540 Ile Phe Gly Asn Tyr Ile Glu Arg Leu Trp Ala Tyr Leu Thr Ile Glu 545 550 555 560 Gln Leu Leu Glu Lys Arg Lys Asn Ala His Gly Glu Glu Lys Glu Asn 565 570 575 Leu Thr Ala Arg Ala Leu Asp Leu Ser Leu Lys Tyr His Phe Val Thr 580 585 590 Pro Leu Thr Ser Met Val Val Thr Lys Pro Glu Asp Asn Glu Asp Glu 595 600 605 Arg Ala Ile Ala Asp Lys Pro Gly Glu Asp Ala Glu Ala Thr Pro Val 610 615 620 Ser Pro Ala Met Ser Tyr Leu Thr Ser Tyr Gln Pro Pro Gln Asn Pro 625 630 635 640 Tyr Tyr Tyr Val Asp Gly Asp Pro His Phe Ile Ile Gln Ile Pro Glu 645 650 655 Lys Asp Asp Ala Leu Cys Phe Asn Ile Asp Glu Ala Pro Gly Thr Val 660 665 670 Leu Arg Leu Ile Gln Asp Ala Val Thr Gly Leu Thr Val Asn Gly Gln 675 680 685 Ile Thr Gly Asp Lys Arg Gly Ser Pro Asp Ser Lys Thr Arg Lys Thr 690 695 700 Tyr Phe Gly Lys Leu Gly Ile Arg Asn Ala Gln Met Asp Phe Gln Val 705 710 715 720 Glu Val Thr Thr Glu Lys Ile Thr Cys Gly Thr Gly Arg Ala Ser Thr 725 730 735 Phe Ser Trp Leu Asp Thr Val Thr Val Thr Gln Asp Gly Leu Ser Met 740 745 750 Met Ile Asn Arg Lys Asn Met Val Val Ser Phe Gly Asp Gly Val Thr 755 760 765 Phe Val Val Val Leu His Gln Val Trp Lys Lys His Pro Val His Arg 770 775 780 Asp Phe Leu Gly Phe Tyr Val Val Asp Ser His Arg Met Ser Ala Gln 785 790 795 800 Thr His Gly Leu Leu Gly Gln Phe Phe Gln Pro Phe Asp Phe Lys Val 805 810 815 Ser Asp Ile Arg Pro Gly Ser Asp Pro Thr Lys Pro Asp Ala Thr Leu 820 825 830 Val Val Lys Asn His Gln Leu Ile Val Thr Arg Gly Ser Gln Lys Asp 835 840 845 Tyr Arg Lys Asp Ala Ser Ile Gly Thr Lys Val Val Cys Trp Phe Val 850 855 860 His Asn Asn Gly Glu Gly Leu Ile Asp Gly Val His Thr Asp Tyr Ile 865 870 875 880 Val Pro Asn Leu Phe 885 315930PRTHomo sapiens 315Met Lys Pro Pro Arg Pro Val Arg Thr Cys Ser Lys Val Leu Val Leu 1 5 10 15 Leu Ser Leu Leu Ala Ile His Gln Thr Thr Thr Ala Glu Lys Asn Gly 20 25 30 Ile Asp Ile Tyr Ser Leu Thr Val Asp Ser Arg Val Ser Ser Arg Phe 35 40 45 Ala His Thr Val Val Thr Ser Arg Val Val Asn Arg Ala Asn Thr Val 50 55 60 Gln Glu Ala Thr Phe Gln Met Glu Leu Pro Lys Lys Ala Phe Ile Thr 65 70 75 80 Asn Phe Ser Met Ile Ile Asp Gly Met Thr Tyr Pro Gly Ile Ile Lys 85 90 95 Glu Lys Ala Glu Ala Gln Ala Gln Tyr Ser Ala Ala Val Ala Lys Gly 100 105 110 Lys Ser Ala Gly Leu Val Lys Ala Thr Gly Arg Asn Met Glu Gln Phe 115 120 125 Gln Val Ser Val Ser Val Ala Pro Asn Ala Lys Ile Thr Phe Glu Leu 130 135 140 Val Tyr Glu Glu Leu Leu Lys Arg Arg Leu Gly Val Tyr Glu Leu Leu 145 150 155 160 Leu Lys Val Arg Pro Gln Gln Leu Val Lys His Leu Gln Met Asp Ile 165 170 175 His Ile Phe Glu Pro Gln Gly Ile Ser Phe Leu Glu Thr Glu Ser Thr 180 185 190 Phe Met Thr Asn Gln Leu Val Asp Ala Leu Thr Thr Trp Gln Asn Lys 195 200 205 Thr Lys Ala His Ile Arg Phe Lys Pro Thr Leu Ser Gln Gln Gln Lys 210 215 220 Ser Pro Glu Gln Gln Glu Thr Val Leu Asp Gly Asn Leu Ile Ile Arg 225 230 235 240 Tyr Asp Val Asp Arg Ala Ile Ser Gly Gly Ser Ile Gln Ile Glu Asn 245 250 255 Gly Tyr Phe Val His Tyr Phe Ala Pro Glu Gly Leu Thr Thr Met Pro 260 265 270 Lys Asn Val Val Phe Val Ile Asp Lys Ser Gly Ser Met Ser Gly Arg 275 280 285 Lys Ile Gln Gln Thr Arg Glu Ala Leu Ile Lys Ile Leu Asp Asp Leu 290 295 300 Ser Pro Arg Asp Gln Phe Asn Leu Ile Val Phe Ser Thr Glu Ala Thr 305 310 315 320 Gln Trp Arg Pro Ser Leu Val Pro Ala Ser Ala Glu Asn Val Asn Lys 325 330 335 Ala Arg Ser Phe Ala Ala Gly Ile Gln Ala Leu Gly Gly Thr Asn Ile 340 345 350 Asn Asp Ala Met Leu Met Ala Val Gln Leu Leu Asp Ser Ser Asn Gln 355 360 365 Glu Glu Arg Leu Pro Glu Gly Ser Val Ser Leu Ile Ile Leu Leu Thr 370 375 380 Asp Gly Asp Pro Thr Val Gly Glu Thr Asn Pro Arg Ser Ile Gln Asn 385 390 395 400 Asn Val Arg Glu Ala Val Ser Gly Arg Tyr Ser Leu Phe Cys Leu Gly 405 410 415 Phe Gly Phe Asp Val Ser Tyr Ala Phe Leu Glu Lys Leu Ala Leu Asp 420 425 430 Asn Gly Gly Leu Ala Arg Arg Ile His Glu Asp Ser Asp Ser Ala Leu 435 440 445 Gln Leu Gln Asp Phe Tyr Gln Glu Val Ala Asn Pro Leu Leu Thr Ala 450 455 460 Val Thr Phe Glu Tyr Pro Ser Asn Ala Val Glu Glu Val Thr Gln Asn 465 470 475 480 Asn Phe Arg Leu Leu Phe Lys Gly Ser Glu Met Val Val Ala Gly Lys 485 490 495 Leu Gln Asp Arg Gly Pro Asp Val Leu Thr Ala Thr Val Ser Gly Lys 500 505 510 Leu Pro Thr Gln Asn Ile Thr Phe Gln Thr Glu Ser Ser Val Ala Glu 515 520 525 Gln Glu Ala Glu Phe Gln Ser Pro Lys Tyr Ile Phe His Asn Phe Met 530 535 540 Glu Arg Leu Trp Ala Tyr Leu Thr Ile Gln Gln Leu Leu Glu Gln Thr 545 550 555 560 Val Ser Ala Ser Asp Ala Asp Gln Gln Ala Leu Arg Asn Gln Ala Leu 565 570 575 Asn Leu Ser Leu Ala Tyr Ser Phe Val Thr Pro Leu Thr Ser Met Val 580 585 590 Val Thr Lys Pro Asp Asp Gln Glu Gln Ser Gln Val Ala Glu Lys Pro 595 600 605 Met Glu Gly Glu Ser Arg Asn Arg Asn Val His Ser Gly Ser Thr Phe 610 615 620 Phe Lys Tyr Tyr Leu Gln Gly Ala Lys Ile Pro Lys Pro Glu Ala Ser 625 630 635 640 Phe Ser Pro Arg Arg Gly Trp Asn Arg Gln Ala Gly Ala Ala Gly Ser 645 650 655 Arg Met Asn Phe Arg Pro Gly Val Leu Ser Ser Arg Gln Leu Gly Leu 660 665 670 Pro Gly Pro Pro Asp Val Pro Asp His Ala Ala Tyr His Pro Phe Arg 675 680 685 Arg Leu Ala Ile Leu Pro Ala Ser Ala Pro Pro Ala Thr Ser Asn Pro 690 695 700 Asp Pro Ala Val Ser Arg Val Met Asn Met Lys Ile Glu Glu Thr Thr 705 710 715 720 Met Thr Thr Gln Thr Pro Ala Pro Ile Gln Ala Pro Ser Ala Ile Leu 725 730 735 Pro Leu Pro Gly Gln Ser Val Glu Arg Leu Cys Val Asp Pro Arg His 740 745 750 Arg Gln Gly Pro Val Asn Leu Leu Ser Asp Pro Glu Gln Gly Val Glu

755 760 765 Val Thr Gly Gln Tyr Glu Arg Glu Lys Ala Gly Phe Ser Trp Ile Glu 770 775 780 Val Thr Phe Lys Asn Pro Leu Val Trp Val His Ala Ser Pro Glu His 785 790 795 800 Val Val Val Thr Arg Asn Arg Arg Ser Ser Ala Tyr Lys Trp Lys Glu 805 810 815 Thr Leu Phe Ser Val Met Pro Gly Leu Lys Met Thr Met Asp Lys Thr 820 825 830 Gly Leu Leu Leu Leu Ser Asp Pro Asp Lys Val Thr Ile Gly Leu Leu 835 840 845 Phe Trp Asp Gly Arg Gly Glu Gly Leu Arg Leu Leu Leu Arg Asp Thr 850 855 860 Asp Arg Phe Ser Ser His Val Gly Gly Thr Leu Gly Gln Phe Tyr Gln 865 870 875 880 Glu Val Leu Trp Gly Ser Pro Ala Ala Ser Asp Asp Gly Arg Arg Thr 885 890 895 Leu Arg Val Gln Gly Asn Asp His Ser Ala Thr Arg Glu Arg Arg Leu 900 905 910 Asp Tyr Gln Glu Gly Pro Pro Gly Val Glu Ile Ser Cys Trp Ser Val 915 920 925 Glu Leu 930 316178PRTHomo sapiens 316Met His Ser Ser Ala Leu Leu Cys Cys Leu Val Leu Leu Thr Gly Val 1 5 10 15 Arg Ala Ser Pro Gly Gln Gly Thr Gln Ser Glu Asn Ser Cys Thr His 20 25 30 Phe Pro Gly Asn Leu Pro Asn Met Leu Arg Asp Leu Arg Asp Ala Phe 35 40 45 Ser Arg Val Lys Thr Phe Phe Gln Met Lys Asp Gln Leu Asp Asn Leu 50 55 60 Leu Leu Lys Glu Ser Leu Leu Glu Asp Phe Lys Gly Tyr Leu Gly Cys 65 70 75 80 Gln Ala Leu Ser Glu Met Ile Gln Phe Tyr Leu Glu Glu Val Met Pro 85 90 95 Gln Ala Glu Asn Gln Asp Pro Asp Ile Lys Ala His Val Asn Ser Leu 100 105 110 Gly Glu Asn Leu Lys Thr Leu Arg Leu Arg Leu Arg Arg Cys His Arg 115 120 125 Phe Leu Pro Cys Glu Asn Lys Ser Lys Ala Val Glu Gln Val Lys Asn 130 135 140 Ala Phe Asn Lys Leu Gln Glu Lys Gly Ile Tyr Lys Ala Met Ser Glu 145 150 155 160 Phe Asp Ile Phe Ile Asn Tyr Ile Glu Ala Tyr Met Thr Met Lys Ile 165 170 175 Arg Asn 317427PRTHomo sapiens 317Met Lys Leu Ile Thr Ile Leu Phe Leu Cys Ser Arg Leu Leu Leu Ser 1 5 10 15 Leu Thr Gln Glu Ser Gln Ser Glu Glu Ile Asp Cys Asn Asp Lys Asp 20 25 30 Leu Phe Lys Ala Val Asp Ala Ala Leu Lys Lys Tyr Asn Ser Gln Asn 35 40 45 Gln Ser Asn Asn Gln Phe Val Leu Tyr Arg Ile Thr Glu Ala Thr Lys 50 55 60 Thr Val Gly Ser Asp Thr Phe Tyr Ser Phe Lys Tyr Glu Ile Lys Glu 65 70 75 80 Gly Asp Cys Pro Val Gln Ser Gly Lys Thr Trp Gln Asp Cys Glu Tyr 85 90 95 Lys Asp Ala Ala Lys Ala Ala Thr Gly Glu Cys Thr Ala Thr Val Gly 100 105 110 Lys Arg Ser Ser Thr Lys Phe Ser Val Ala Thr Gln Thr Cys Gln Ile 115 120 125 Thr Pro Ala Glu Gly Pro Val Val Thr Ala Gln Tyr Asp Cys Leu Gly 130 135 140 Cys Val His Pro Ile Ser Thr Gln Ser Pro Asp Leu Glu Pro Ile Leu 145 150 155 160 Arg His Gly Ile Gln Tyr Phe Asn Asn Asn Thr Gln His Ser Ser Leu 165 170 175 Phe Met Leu Asn Glu Val Lys Arg Ala Gln Arg Gln Val Val Ala Gly 180 185 190 Leu Asn Phe Arg Ile Thr Tyr Ser Ile Val Gln Thr Asn Cys Ser Lys 195 200 205 Glu Asn Phe Leu Phe Leu Thr Pro Asp Cys Lys Ser Leu Trp Asn Gly 210 215 220 Asp Thr Gly Glu Cys Thr Asp Asn Ala Tyr Ile Asp Ile Gln Leu Arg 225 230 235 240 Ile Ala Ser Phe Ser Gln Asn Cys Asp Ile Tyr Pro Gly Lys Asp Phe 245 250 255 Val Gln Pro Pro Thr Lys Ile Cys Val Gly Cys Pro Arg Asp Ile Pro 260 265 270 Thr Asn Ser Pro Glu Leu Glu Glu Thr Leu Thr His Thr Ile Thr Lys 275 280 285 Leu Asn Ala Glu Asn Asn Ala Thr Phe Tyr Phe Lys Ile Asp Asn Val 290 295 300 Lys Lys Ala Arg Val Gln Val Val Ala Gly Lys Lys Tyr Phe Ile Asp 305 310 315 320 Phe Val Ala Arg Glu Thr Thr Cys Ser Lys Glu Ser Asn Glu Glu Leu 325 330 335 Thr Glu Ser Cys Glu Thr Lys Lys Leu Gly Gln Ser Leu Asp Cys Asn 340 345 350 Ala Glu Val Tyr Val Val Pro Trp Glu Lys Lys Ile Tyr Pro Thr Val 355 360 365 Asn Cys Gln Pro Leu Gly Met Ile Ser Leu Met Lys Arg Pro Pro Gly 370 375 380 Phe Ser Pro Phe Arg Ser Ser Arg Ile Gly Glu Ile Lys Glu Glu Thr 385 390 395 400 Thr Ser His Leu Arg Ser Cys Glu Tyr Lys Gly Arg Pro Pro Lys Ala 405 410 415 Gly Ala Glu Pro Ala Ser Glu Arg Glu Val Ser 420 425 318338PRTHomo sapiens 318Met Ser Leu Ser Ala Phe Thr Leu Phe Leu Ala Leu Ile Gly Gly Thr 1 5 10 15 Ser Gly Gln Tyr Tyr Asp Tyr Asp Phe Pro Leu Ser Ile Tyr Gly Gln 20 25 30 Ser Ser Pro Asn Cys Ala Pro Glu Cys Asn Cys Pro Glu Ser Tyr Pro 35 40 45 Ser Ala Met Tyr Cys Asp Glu Leu Lys Leu Lys Ser Val Pro Met Val 50 55 60 Pro Pro Gly Ile Lys Tyr Leu Tyr Leu Arg Asn Asn Gln Ile Asp His 65 70 75 80 Ile Asp Glu Lys Ala Phe Glu Asn Val Thr Asp Leu Gln Trp Leu Ile 85 90 95 Leu Asp His Asn Leu Leu Glu Asn Ser Lys Ile Lys Gly Arg Val Phe 100 105 110 Ser Lys Leu Lys Gln Leu Lys Lys Leu His Ile Asn His Asn Asn Leu 115 120 125 Thr Glu Ser Val Gly Pro Leu Pro Lys Ser Leu Glu Asp Leu Gln Leu 130 135 140 Thr His Asn Lys Ile Thr Lys Leu Gly Ser Phe Glu Gly Leu Val Asn 145 150 155 160 Leu Thr Phe Ile His Leu Gln His Asn Arg Leu Lys Glu Asp Ala Val 165 170 175 Ser Ala Ala Phe Lys Gly Leu Lys Ser Leu Glu Tyr Leu Asp Leu Ser 180 185 190 Phe Asn Gln Ile Ala Arg Leu Pro Ser Gly Leu Pro Val Ser Leu Leu 195 200 205 Thr Leu Tyr Leu Asp Asn Asn Lys Ile Ser Asn Ile Pro Asp Glu Tyr 210 215 220 Phe Lys Arg Phe Asn Ala Leu Gln Tyr Leu Arg Leu Ser His Asn Glu 225 230 235 240 Leu Ala Asp Ser Gly Ile Pro Gly Asn Ser Phe Asn Val Ser Ser Leu 245 250 255 Val Glu Leu Asp Leu Ser Tyr Asn Lys Leu Lys Asn Ile Pro Thr Val 260 265 270 Asn Glu Asn Leu Glu Asn Tyr Tyr Leu Glu Val Asn Gln Leu Glu Lys 275 280 285 Phe Asp Ile Lys Ser Phe Cys Lys Ile Leu Gly Pro Leu Ser Tyr Ser 290 295 300 Lys Ile Lys His Leu Arg Leu Asp Gly Asn Arg Ile Ser Glu Thr Ser 305 310 315 320 Leu Pro Pro Asp Met Tyr Glu Cys Leu Arg Val Ala Asn Glu Val Thr 325 330 335 Leu Asn 3195430PRTHomo sapiens 319Met Ser Ser Ser Asp Glu Glu Thr Leu Ser Glu Arg Ser Cys Arg Ser 1 5 10 15 Glu Arg Ser Cys Arg Ser Glu Arg Ser Tyr Arg Ser Glu Arg Ser Gly 20 25 30 Ser Leu Ser Pro Cys Pro Pro Gly Asp Thr Leu Pro Trp Asn Leu Pro 35 40 45 Leu His Glu Gln Lys Lys Arg Lys Ser Gln Asp Ser Val Leu Asp Pro 50 55 60 Ala Glu Arg Ala Val Val Arg Val Ala Asp Glu Arg Asp Arg Val Gln 65 70 75 80 Lys Lys Thr Phe Thr Lys Trp Val Asn Lys His Leu Met Lys Val Arg 85 90 95 Lys His Ile Asn Asp Leu Tyr Glu Asp Leu Arg Asp Gly His Asn Leu 100 105 110 Ile Ser Leu Leu Glu Val Leu Ser Gly Ile Lys Leu Pro Arg Glu Lys 115 120 125 Gly Arg Met Arg Phe His Arg Leu Gln Asn Val Gln Ile Ala Leu Asp 130 135 140 Phe Leu Lys Gln Arg Gln Val Lys Leu Val Asn Ile Arg Asn Asp Asp 145 150 155 160 Ile Thr Asp Gly Asn Pro Lys Leu Thr Leu Gly Leu Ile Trp Thr Ile 165 170 175 Ile Leu His Phe Gln Ile Ser Asp Ile Tyr Ile Ser Gly Glu Ser Gly 180 185 190 Asp Met Ser Ala Lys Glu Lys Leu Leu Leu Trp Thr Gln Lys Val Thr 195 200 205 Ala Gly Tyr Thr Gly Ile Lys Cys Thr Asn Phe Ser Ser Cys Trp Ser 210 215 220 Asp Gly Lys Met Phe Asn Ala Leu Ile His Arg Tyr Arg Pro Asp Leu 225 230 235 240 Val Asp Met Glu Arg Val Gln Ile Gln Ser Asn Arg Glu Asn Leu Glu 245 250 255 Gln Ala Phe Glu Val Ala Glu Arg Leu Gly Val Thr Arg Leu Leu Asp 260 265 270 Ala Glu Asp Val Asp Val Pro Ser Pro Asp Glu Lys Ser Val Ile Thr 275 280 285 Tyr Val Ser Ser Ile Tyr Asp Ala Phe Pro Lys Val Pro Glu Gly Gly 290 295 300 Glu Gly Ile Ser Ala Thr Glu Val Asp Ser Arg Trp Gln Glu Tyr Gln 305 310 315 320 Ser Arg Val Asp Ser Leu Ile Pro Trp Ile Lys Gln His Thr Ile Leu 325 330 335 Met Ser Asp Lys Thr Phe Pro Gln Asn Pro Val Glu Leu Lys Ala Leu 340 345 350 Tyr Asn Gln Tyr Ile His Phe Lys Glu Thr Glu Ile Leu Ala Lys Glu 355 360 365 Arg Glu Lys Gly Arg Ile Glu Glu Leu Tyr Lys Leu Leu Glu Val Trp 370 375 380 Ile Glu Phe Gly Arg Ile Lys Leu Pro Gln Gly Tyr His Pro Asn Asp 385 390 395 400 Val Glu Glu Glu Trp Gly Lys Leu Ile Ile Glu Met Leu Glu Arg Glu 405 410 415 Lys Ser Leu Arg Pro Ala Val Glu Arg Leu Glu Leu Leu Leu Gln Ile 420 425 430 Ala Asn Lys Ile Gln Asn Gly Ala Leu Asn Cys Glu Glu Lys Leu Thr 435 440 445 Leu Ala Lys Asn Thr Leu Gln Ala Asp Ala Ala His Leu Glu Ser Gly 450 455 460 Gln Pro Val Gln Cys Glu Ser Asp Val Ile Met Tyr Ile Gln Glu Cys 465 470 475 480 Glu Gly Leu Ile Arg Gln Leu Gln Val Asp Leu Gln Ile Leu Arg Asp 485 490 495 Glu Asn Tyr Tyr Gln Leu Glu Glu Leu Ala Phe Arg Val Met Arg Leu 500 505 510 Gln Asp Glu Leu Val Thr Leu Arg Leu Glu Cys Thr Asn Leu Tyr Arg 515 520 525 Lys Gly His Phe Thr Ser Leu Glu Leu Val Pro Pro Ser Thr Leu Thr 530 535 540 Thr Thr His Leu Lys Ala Glu Pro Leu Thr Lys Ala Thr His Ser Ser 545 550 555 560 Ser Thr Ser Trp Phe Arg Lys Pro Met Thr Arg Ala Glu Leu Val Ala 565 570 575 Ile Ser Ser Ser Glu Asp Glu Gly Asn Leu Arg Phe Val Tyr Glu Leu 580 585 590 Leu Ser Trp Val Glu Glu Met Gln Met Lys Leu Glu Arg Ala Glu Trp 595 600 605 Gly Asn Asp Leu Pro Ser Val Glu Leu Gln Leu Glu Thr Gln Gln His 610 615 620 Ile His Thr Ser Val Glu Glu Leu Gly Ser Ser Val Lys Glu Ala Arg 625 630 635 640 Leu Tyr Glu Gly Lys Met Ser Gln Asn Phe His Thr Ser Tyr Ala Glu 645 650 655 Thr Leu Gly Lys Leu Glu Thr Gln Tyr Cys Lys Leu Lys Glu Thr Ser 660 665 670 Ser Phe Arg Met Arg His Leu Gln Ser Leu His Lys Phe Val Ser Arg 675 680 685 Ala Thr Ala Glu Leu Ile Trp Leu Asn Glu Lys Glu Glu Glu Glu Leu 690 695 700 Ala Tyr Asp Trp Ser Asp Asn Asn Ser Asn Ile Ser Ala Lys Arg Asn 705 710 715 720 Tyr Phe Ser Glu Leu Thr Met Glu Leu Glu Glu Lys Gln Asp Val Phe 725 730 735 Arg Ser Leu Gln Asp Thr Ala Glu Leu Leu Ser Leu Glu Asn His Pro 740 745 750 Ala Lys Gln Thr Val Glu Ala Tyr Ser Ala Ala Val Gln Ser Gln Leu 755 760 765 Gln Trp Met Lys Gln Leu Cys Leu Cys Val Glu Gln His Val Lys Glu 770 775 780 Asn Thr Ala Tyr Phe Gln Phe Phe Ser Asp Ala Arg Glu Leu Glu Ser 785 790 795 800 Phe Leu Arg Asn Leu Gln Asp Ser Ile Lys Arg Lys Tyr Ser Cys Asp 805 810 815 His Asn Thr Ser Leu Ser Arg Leu Glu Asp Leu Leu Gln Asp Ser Met 820 825 830 Asp Glu Lys Glu Gln Leu Ile Gln Ser Lys Ser Ser Val Ala Ser Leu 835 840 845 Val Gly Arg Ser Lys Thr Ile Val Gln Leu Lys Pro Arg Ser Pro Asp 850 855 860 His Val Leu Lys Asn Thr Ile Ser Val Lys Ala Val Cys Asp Tyr Arg 865 870 875 880 Gln Ile Glu Ile Thr Ile Cys Lys Asn Asp Glu Cys Val Leu Glu Asp 885 890 895 Asn Ser Gln Arg Thr Lys Trp Lys Val Ile Ser Pro Thr Gly Asn Glu 900 905 910 Ala Met Val Pro Ser Val Cys Phe Leu Ile Pro Pro Pro Asn Lys Asp 915 920 925 Ala Ile Glu Met Ala Ser Arg Val Glu Gln Ser Tyr Gln Lys Val Met 930 935 940 Ala Leu Trp His Gln Leu His Val Asn Thr Lys Ser Leu Ile Ser Trp 945 950 955 960 Asn Tyr Leu Arg Lys Asp Leu Asp Leu Val Gln Thr Trp Asn Leu Glu 965 970 975 Lys Leu Arg Ser Ser Ala Pro Gly Glu Cys His Gln Ile Met Lys Asn 980 985 990 Leu Gln Ala His Tyr Glu Asp Phe Leu Gln Asp Ser Arg Asp Ser Val 995 1000 1005 Leu Phe Ser Val Ala Asp Arg Leu Arg Leu Glu Glu Glu Val Glu 1010 1015 1020 Ala Cys Lys Ala Arg Phe Gln His Leu Met Lys Ser Met Glu Asn 1025 1030 1035 Glu Asp Lys Glu Glu Thr Val Ala Lys Met Tyr Ile Ser Glu Leu 1040 1045 1050 Lys Asn Ile Arg Leu Arg Leu Glu Glu Tyr Glu Gln Arg Val Val 1055 1060 1065 Lys Arg Ile Gln Ser Leu Ala Ser Ser Arg Thr Asp Arg Asp Ala 1070 1075 1080 Trp Gln Asp Asn Ala Leu Arg Ile Ala Glu Gln Glu His Thr Gln 1085 1090 1095 Glu Asp Leu Gln Gln Leu Arg Ser Asp Leu Asp Ala Val Ser Met 1100 1105 1110 Lys Cys Asp Ser Phe Leu His Gln Ser Pro Ser Ser Ser Ser Val 1115 1120 1125 Pro Thr Leu Arg Ser Glu Leu Asn Leu Leu Val Glu Lys Met Asp 1130 1135 1140 His Val Tyr Gly Leu Ser Thr Val Tyr Leu Asn Lys Leu Lys Thr 1145 1150 1155 Val Asp Val Ile Val Arg Ser Ile Gln Asp Ala Glu Leu Leu Val 1160 1165 1170 Lys Gly

Tyr Glu Ile Lys Leu Ser Gln Glu Glu Val Val Leu Ala 1175 1180 1185 Asp Leu Ser Ala Leu Glu Ala His Trp Ser Thr Leu Arg His Trp 1190 1195 1200 Leu Ser Asp Val Lys Asp Lys Asn Ser Val Phe Ser Val Leu Asp 1205 1210 1215 Glu Glu Ile Ala Lys Ala Lys Val Val Ala Glu Gln Met Ser Arg 1220 1225 1230 Leu Thr Pro Glu Arg Asn Leu Asp Leu Glu Arg Tyr Gln Glu Lys 1235 1240 1245 Gly Ser Gln Leu Gln Glu Arg Trp His Arg Val Ile Ala Gln Leu 1250 1255 1260 Glu Ile Arg Gln Ser Glu Leu Glu Ser Ile Gln Glu Val Leu Gly 1265 1270 1275 Asp Tyr Arg Ala Cys His Gly Thr Leu Ile Lys Trp Ile Glu Glu 1280 1285 1290 Thr Thr Ala Gln Gln Glu Met Met Lys Pro Gly Gln Ala Glu Asp 1295 1300 1305 Ser Arg Val Leu Ser Glu Gln Leu Ser Gln Gln Thr Ala Leu Phe 1310 1315 1320 Ala Glu Ile Glu Arg Asn Gln Thr Lys Leu Asp Gln Cys Gln Lys 1325 1330 1335 Phe Ser Gln Gln Tyr Ser Thr Ile Val Lys Asp Tyr Glu Leu Gln 1340 1345 1350 Leu Met Thr Tyr Lys Ala Phe Val Glu Ser Gln Gln Lys Ser Pro 1355 1360 1365 Gly Lys Arg Arg Arg Met Leu Ser Ser Ser Asp Ala Ile Thr Gln 1370 1375 1380 Glu Phe Met Asp Leu Arg Thr Arg Tyr Thr Ala Leu Val Thr Leu 1385 1390 1395 Thr Thr Gln His Val Lys Tyr Ile Ser Asp Ala Leu Arg Arg Leu 1400 1405 1410 Glu Glu Glu Glu Lys Val Val Glu Glu Glu Lys Gln Glu His Val 1415 1420 1425 Glu Lys Val Lys Glu Leu Leu Gly Trp Val Ser Thr Leu Ala Arg 1430 1435 1440 Asn Thr Gln Gly Lys Ala Thr Ser Ser Glu Thr Lys Glu Ser Thr 1445 1450 1455 Asp Ile Glu Lys Ala Ile Leu Glu Gln Gln Val Leu Ser Glu Glu 1460 1465 1470 Leu Thr Thr Lys Lys Glu Gln Val Ser Glu Ala Ile Lys Thr Ser 1475 1480 1485 Gln Ile Phe Leu Ala Lys His Gly His Lys Leu Ser Glu Lys Glu 1490 1495 1500 Lys Lys Gln Ile Ser Glu Gln Leu Asn Ala Leu Asn Lys Ala Tyr 1505 1510 1515 His Asp Leu Cys Asp Gly Ser Ala Asn Gln Leu Gln Gln Leu Gln 1520 1525 1530 Ser Gln Leu Ala His Gln Thr Glu Gln Lys Thr Leu Gln Lys Gln 1535 1540 1545 Gln Asn Thr Cys His Gln Gln Leu Glu Asp Leu Cys Ser Trp Val 1550 1555 1560 Gly Gln Ala Glu Arg Ala Leu Ala Gly His Gln Gly Arg Thr Thr 1565 1570 1575 Gln Gln Asp Leu Ser Ala Leu Gln Lys Asn Gln Ser Asp Leu Lys 1580 1585 1590 Asp Leu Gln Asp Asp Ile Gln Asn Arg Ala Thr Ser Phe Ala Thr 1595 1600 1605 Val Val Lys Asp Ile Glu Gly Phe Met Glu Glu Asn Gln Thr Lys 1610 1615 1620 Leu Ser Pro Arg Glu Leu Thr Ala Leu Arg Glu Lys Leu His Gln 1625 1630 1635 Ala Lys Glu Gln Tyr Glu Ala Leu Gln Glu Glu Thr Arg Val Ala 1640 1645 1650 Gln Lys Glu Leu Glu Glu Ala Val Thr Ser Ala Leu Gln Gln Glu 1655 1660 1665 Thr Glu Lys Ser Lys Ala Ala Lys Glu Leu Ala Glu Asn Lys Lys 1670 1675 1680 Lys Ile Asp Ala Leu Leu Asp Trp Val Thr Ser Val Gly Ser Ser 1685 1690 1695 Gly Gly Gln Leu Leu Thr Asn Leu Pro Gly Met Glu Gln Leu Ser 1700 1705 1710 Gly Ala Ser Leu Glu Lys Gly Ala Leu Asp Thr Thr Asp Gly Tyr 1715 1720 1725 Met Gly Val Asn Gln Ala Pro Glu Lys Leu Asp Lys Gln Cys Glu 1730 1735 1740 Met Met Lys Ala Arg His Gln Glu Leu Leu Ser Gln Gln Gln Asn 1745 1750 1755 Phe Ile Leu Ala Thr Gln Ser Ala Gln Ala Phe Leu Asp Gln His 1760 1765 1770 Gly His Asn Leu Thr Pro Glu Glu Gln Gln Met Leu Gln Gln Lys 1775 1780 1785 Leu Gly Glu Leu Lys Glu Gln Tyr Ser Thr Ser Leu Ala Gln Ser 1790 1795 1800 Glu Ala Glu Leu Lys Gln Val Gln Thr Leu Gln Asp Glu Leu Gln 1805 1810 1815 Lys Phe Leu Gln Asp His Lys Glu Phe Glu Ser Trp Leu Glu Arg 1820 1825 1830 Ser Glu Lys Glu Leu Glu Asn Met His Lys Gly Gly Ser Ser Pro 1835 1840 1845 Glu Thr Leu Pro Ser Leu Leu Lys Arg Gln Gly Ser Phe Ser Glu 1850 1855 1860 Asp Val Ile Ser His Lys Gly Asp Leu Arg Phe Val Thr Ile Ser 1865 1870 1875 Gly Gln Lys Val Leu Asp Met Glu Asn Ser Phe Lys Glu Gly Lys 1880 1885 1890 Glu Pro Ser Glu Ile Gly Asn Leu Val Lys Asp Lys Leu Lys Asp 1895 1900 1905 Ala Thr Glu Arg Tyr Thr Ala Leu His Ser Lys Cys Thr Arg Leu 1910 1915 1920 Gly Ser His Leu Asn Met Leu Leu Gly Gln Tyr His Gln Phe Gln 1925 1930 1935 Asn Ser Ala Asp Ser Leu Gln Ala Trp Met Gln Ala Cys Glu Ala 1940 1945 1950 Asn Val Glu Lys Leu Leu Ser Asp Thr Val Ala Ser Asp Pro Gly 1955 1960 1965 Val Leu Gln Glu Gln Leu Ala Thr Thr Lys Gln Leu Gln Glu Glu 1970 1975 1980 Leu Ala Glu His Gln Val Pro Val Glu Lys Leu Gln Lys Val Ala 1985 1990 1995 Arg Asp Ile Met Glu Ile Glu Gly Glu Pro Ala Pro Asp His Arg 2000 2005 2010 His Val Gln Glu Thr Thr Asp Ser Ile Leu Ser His Phe Gln Ser 2015 2020 2025 Leu Ser Tyr Ser Leu Ala Glu Arg Ser Ser Leu Leu Gln Lys Ala 2030 2035 2040 Ile Ala Gln Ser Gln Ser Val Gln Glu Ser Leu Glu Ser Leu Leu 2045 2050 2055 Gln Ser Ile Gly Glu Val Glu Gln Asn Leu Glu Gly Lys Gln Val 2060 2065 2070 Ser Ser Leu Ser Ser Gly Val Ile Gln Glu Ala Leu Ala Thr Asn 2075 2080 2085 Met Lys Leu Lys Gln Asp Ile Ala Arg Gln Lys Ser Ser Leu Glu 2090 2095 2100 Ala Thr Arg Glu Met Val Thr Arg Phe Met Glu Thr Ala Asp Ser 2105 2110 2115 Thr Thr Ala Ala Val Leu Gln Gly Lys Leu Ala Glu Val Ser Gln 2120 2125 2130 Arg Phe Glu Gln Leu Cys Leu Gln Gln Gln Glu Lys Glu Ser Ser 2135 2140 2145 Leu Lys Lys Leu Leu Pro Gln Ala Glu Met Phe Glu His Leu Ser 2150 2155 2160 Gly Lys Leu Gln Gln Phe Met Glu Asn Lys Ser Arg Met Leu Ala 2165 2170 2175 Ser Gly Asn Gln Pro Asp Gln Asp Ile Thr His Phe Phe Gln Gln 2180 2185 2190 Ile Gln Glu Leu Asn Leu Glu Met Glu Asp Gln Gln Glu Asn Leu 2195 2200 2205 Asp Thr Leu Glu His Leu Val Thr Glu Leu Ser Ser Cys Gly Phe 2210 2215 2220 Ala Leu Asp Leu Cys Gln His Gln Asp Arg Val Gln Asn Leu Arg 2225 2230 2235 Lys Asp Phe Thr Glu Leu Gln Lys Thr Val Lys Glu Arg Glu Lys 2240 2245 2250 Asp Ala Ser Ser Cys Gln Glu Gln Leu Asp Glu Phe Arg Lys Leu 2255 2260 2265 Val Arg Thr Phe Gln Lys Trp Leu Lys Glu Thr Glu Gly Ser Ile 2270 2275 2280 Pro Pro Thr Glu Thr Ser Met Ser Ala Lys Glu Leu Glu Lys Gln 2285 2290 2295 Ile Glu His Leu Lys Ser Leu Leu Asp Asp Trp Ala Ser Lys Gly 2300 2305 2310 Thr Leu Val Glu Glu Ile Asn Cys Lys Gly Thr Ser Leu Glu Asn 2315 2320 2325 Leu Ile Met Glu Ile Thr Ala Pro Asp Ser Gln Gly Lys Thr Gly 2330 2335 2340 Ser Ile Leu Pro Ser Val Gly Ser Ser Val Gly Ser Val Asn Gly 2345 2350 2355 Tyr His Thr Cys Lys Asp Leu Thr Glu Ile Gln Cys Asp Met Ser 2360 2365 2370 Asp Val Asn Leu Lys Tyr Glu Lys Leu Gly Gly Val Leu His Glu 2375 2380 2385 Arg Gln Glu Ser Leu Gln Ala Ile Leu Asn Arg Met Glu Glu Val 2390 2395 2400 His Lys Glu Ala Asn Ser Val Leu Gln Trp Leu Glu Ser Lys Glu 2405 2410 2415 Glu Val Leu Lys Ser Met Asp Ala Met Ser Ser Pro Thr Lys Thr 2420 2425 2430 Glu Thr Val Lys Ala Gln Ala Glu Ser Asn Lys Ala Phe Leu Ala 2435 2440 2445 Glu Leu Glu Gln Asn Ser Pro Lys Ile Gln Lys Val Lys Glu Ala 2450 2455 2460 Leu Ala Gly Leu Leu Val Thr Tyr Pro Asn Ser Gln Glu Ala Glu 2465 2470 2475 Asn Trp Lys Lys Ile Gln Glu Glu Leu Asn Ser Arg Trp Glu Arg 2480 2485 2490 Ala Thr Glu Val Thr Val Ala Arg Gln Arg Gln Leu Glu Glu Ser 2495 2500 2505 Ala Ser His Leu Ala Cys Phe Gln Ala Ala Glu Ser Gln Leu Arg 2510 2515 2520 Pro Trp Leu Met Glu Lys Glu Leu Met Met Gly Val Leu Gly Pro 2525 2530 2535 Leu Ser Ile Asp Pro Asn Met Leu Asn Ala Gln Lys Gln Gln Val 2540 2545 2550 Gln Phe Met Leu Lys Glu Phe Glu Ala Arg Arg Gln Gln His Glu 2555 2560 2565 Gln Leu Asn Glu Ala Ala Gln Gly Ile Leu Thr Gly Pro Gly Asp 2570 2575 2580 Val Ser Leu Ser Thr Ser Gln Val Gln Lys Glu Leu Gln Ser Ile 2585 2590 2595 Asn Gln Lys Trp Val Glu Leu Thr Asp Lys Leu Asn Ser Arg Ser 2600 2605 2610 Ser Gln Ile Asp Gln Ala Ile Val Lys Ser Thr Gln Tyr Gln Glu 2615 2620 2625 Leu Leu Gln Asp Leu Ser Glu Lys Val Arg Ala Val Gly Gln Arg 2630 2635 2640 Leu Ser Val Gln Ser Ala Ile Ser Thr Gln Pro Glu Ala Val Lys 2645 2650 2655 Gln Gln Leu Glu Glu Thr Ser Glu Ile Arg Ser Asp Leu Glu Gln 2660 2665 2670 Leu Asp His Glu Val Lys Glu Ala Gln Thr Leu Cys Asp Glu Leu 2675 2680 2685 Ser Val Leu Ile Gly Glu Gln Tyr Leu Lys Asp Glu Leu Lys Lys 2690 2695 2700 Arg Leu Glu Thr Val Ala Leu Pro Leu Gln Gly Leu Glu Asp Leu 2705 2710 2715 Ala Ala Asp Arg Ile Asn Arg Leu Gln Ala Ala Leu Ala Ser Thr 2720 2725 2730 Gln Gln Phe Gln Gln Met Phe Asp Glu Leu Arg Thr Trp Leu Asp 2735 2740 2745 Asp Lys Gln Ser Gln Gln Ala Lys Asn Cys Pro Ile Ser Ala Lys 2750 2755 2760 Leu Glu Arg Leu Gln Ser Gln Leu Gln Glu Asn Glu Glu Phe Gln 2765 2770 2775 Lys Ser Leu Asn Gln His Ser Gly Ser Tyr Glu Val Ile Val Ala 2780 2785 2790 Glu Gly Glu Ser Leu Leu Leu Ser Val Pro Pro Gly Glu Glu Lys 2795 2800 2805 Arg Thr Leu Gln Asn Gln Leu Val Glu Leu Lys Asn His Trp Glu 2810 2815 2820 Glu Leu Ser Lys Lys Thr Ala Asp Arg Gln Ser Arg Leu Lys Asp 2825 2830 2835 Cys Met Gln Lys Ala Gln Lys Tyr Gln Trp His Val Glu Asp Leu 2840 2845 2850 Val Pro Trp Ile Glu Asp Cys Lys Ala Lys Met Ser Glu Leu Arg 2855 2860 2865 Val Thr Leu Asp Pro Val Gln Leu Glu Ser Ser Leu Leu Arg Ser 2870 2875 2880 Lys Ala Met Leu Asn Glu Val Glu Lys Arg Arg Ser Leu Leu Glu 2885 2890 2895 Ile Leu Asn Ser Ala Ala Asp Ile Leu Ile Asn Ser Ser Glu Ala 2900 2905 2910 Asp Glu Asp Gly Ile Arg Asp Glu Lys Ala Gly Ile Asn Gln Asn 2915 2920 2925 Met Asp Ala Val Thr Glu Glu Leu Gln Ala Lys Thr Gly Ser Leu 2930 2935 2940 Glu Glu Met Thr Gln Arg Leu Arg Glu Phe Gln Glu Ser Phe Lys 2945 2950 2955 Asn Ile Glu Lys Lys Val Glu Gly Ala Lys His Gln Leu Glu Ile 2960 2965 2970 Phe Asp Ala Leu Gly Ser Gln Ala Cys Ser Asn Lys Asn Leu Glu 2975 2980 2985 Lys Leu Arg Ala Gln Gln Glu Val Leu Gln Ala Leu Glu Pro Gln 2990 2995 3000 Val Asp Tyr Leu Arg Asn Phe Thr Gln Gly Leu Val Glu Asp Ala 3005 3010 3015 Pro Asp Gly Ser Asp Ala Ser Gln Leu Leu His Gln Ala Glu Val 3020 3025 3030 Ala Gln Gln Glu Phe Leu Glu Val Lys Gln Arg Val Asn Ser Gly 3035 3040 3045 Cys Val Met Met Glu Asn Lys Leu Glu Gly Ile Gly Gln Phe His 3050 3055 3060 Cys Arg Val Arg Glu Met Phe Ser Gln Leu Ala Asp Leu Asp Asp 3065 3070 3075 Glu Leu Asp Gly Met Gly Ala Ile Gly Arg Asp Thr Asp Ser Leu 3080 3085 3090 Gln Ser Gln Ile Glu Asp Val Arg Leu Phe Leu Asn Lys Ile His 3095 3100 3105 Val Leu Lys Leu Asp Ile Glu Ala Ser Glu Ala Glu Cys Arg His 3110 3115 3120 Met Leu Glu Glu Glu Gly Thr Leu Asp Leu Leu Gly Leu Lys Arg 3125 3130 3135 Glu Leu Glu Ala Leu Asn Lys Gln Cys Gly Lys Leu Thr Glu Arg 3140 3145 3150 Gly Lys Ala Arg Gln Glu Gln Leu Glu Leu Thr Leu Gly Arg Val 3155 3160 3165 Glu Asp Phe Tyr Arg Lys Leu Lys Gly Leu Asn Asp Ala Thr Thr 3170 3175 3180 Ala Ala Glu Glu Ala Glu Ala Leu Gln Trp Val Val Gly Thr Glu 3185 3190 3195 Val Glu Ile Ile Asn Gln Gln Leu Ala Asp Phe Lys Met Phe Gln 3200 3205 3210 Lys Glu Gln Val Asp Pro Leu Gln Met Lys Leu Gln Gln Val Asn 3215 3220 3225 Gly Leu Gly Gln Gly Leu Ile Gln Ser Ala Gly Lys Asp Cys Asp 3230 3235 3240 Val Gln Gly Leu Glu His Asp Met Glu Glu Ile Asn Ala Arg Trp 3245 3250 3255 Asn Thr Leu Asn Lys Lys Val Ala Gln Arg Ile Ala Gln Leu Gln 3260 3265 3270 Glu Ala Leu Leu His Cys Gly Lys Phe Gln Asp Ala Leu Glu Pro 3275 3280 3285 Leu Leu Ser Trp Leu Ala Asp Thr Glu Glu Leu Ile Ala Asn Gln 3290 3295 3300 Lys Pro Pro Ser Ala Glu Tyr Lys Val Val Lys Ala Gln Ile Gln 3305 3310 3315 Glu Gln Lys Leu Leu Gln Arg Leu Leu Asp Asp Arg Lys Ala Thr 3320 3325 3330 Val Asp Met Leu Gln Ala Glu Gly Gly Arg Ile Ala Gln Ser Ala 3335 3340 3345 Glu Leu Ala Asp Arg Glu Lys Ile Thr Gly Gln Leu Glu Ser Leu 3350 3355 3360 Glu Ser Arg Trp Thr Glu Leu Leu Ser Lys Ala Ala Ala Arg Gln

3365 3370 3375 Lys Gln Leu Glu Asp Ile Leu Val Leu Ala Lys Gln Phe His Glu 3380 3385 3390 Thr Ala Glu Pro Ile Ser Asp Phe Leu Ser Val Thr Glu Lys Lys 3395 3400 3405 Leu Ala Asn Ser Glu Pro Val Gly Thr Gln Thr Ala Lys Ile Gln 3410 3415 3420 Gln Gln Ile Ile Arg His Lys Ala Leu Glu Glu Asp Ile Glu Asn 3425 3430 3435 His Ala Thr Asp Val His Gln Ala Val Lys Ile Gly Gln Ser Leu 3440 3445 3450 Ser Ser Leu Thr Ser Pro Ala Glu Gln Gly Val Leu Ser Glu Lys 3455 3460 3465 Ile Asp Ser Leu Gln Ala Arg Tyr Ser Glu Ile Gln Asp Arg Cys 3470 3475 3480 Cys Arg Lys Ala Ala Leu Leu Asp Gln Ala Leu Ser Asn Ala Arg 3485 3490 3495 Leu Phe Gly Glu Asp Glu Val Glu Val Leu Asn Trp Leu Ala Glu 3500 3505 3510 Val Glu Asp Lys Leu Ser Ser Val Phe Val Lys Asp Phe Lys Gln 3515 3520 3525 Asp Val Leu His Arg Gln His Ala Asp His Leu Ala Leu Asn Glu 3530 3535 3540 Glu Ile Val Asn Arg Lys Lys Asn Val Asp Gln Ala Ile Lys Asn 3545 3550 3555 Gly Gln Ala Leu Leu Lys Gln Thr Thr Gly Glu Glu Val Leu Leu 3560 3565 3570 Ile Gln Glu Lys Leu Asp Gly Ile Lys Thr Arg Tyr Ala Asp Ile 3575 3580 3585 Thr Val Thr Ser Ser Lys Ala Leu Arg Thr Leu Glu Gln Ala Arg 3590 3595 3600 Gln Leu Ala Thr Lys Phe Gln Ser Thr Tyr Glu Glu Leu Thr Gly 3605 3610 3615 Trp Leu Arg Glu Val Glu Glu Glu Leu Ala Thr Ser Gly Gly Gln 3620 3625 3630 Ser Pro Thr Gly Glu Gln Ile Pro Gln Phe Gln Gln Arg Gln Lys 3635 3640 3645 Glu Leu Lys Lys Glu Val Met Glu His Arg Leu Val Leu Asp Thr 3650 3655 3660 Val Asn Glu Val Ser Arg Ala Leu Leu Glu Leu Val Pro Trp Arg 3665 3670 3675 Ala Arg Glu Gly Leu Asp Lys Leu Val Ser Asp Ala Asn Glu Gln 3680 3685 3690 Tyr Lys Leu Val Ser Asp Thr Ile Gly Gln Arg Val Asp Glu Ile 3695 3700 3705 Asp Ala Ala Ile Gln Arg Ser Gln Gln Tyr Glu Gln Ala Ala Asp 3710 3715 3720 Ala Glu Leu Ala Trp Val Ala Glu Thr Lys Arg Lys Leu Met Ala 3725 3730 3735 Leu Gly Pro Ile Arg Leu Glu Gln Asp Gln Thr Thr Ala Gln Leu 3740 3745 3750 Gln Val Gln Lys Ala Phe Ser Ile Asp Ile Ile Arg His Lys Asp 3755 3760 3765 Ser Met Asp Glu Leu Phe Ser His Arg Ser Glu Ile Phe Gly Thr 3770 3775 3780 Cys Gly Glu Glu Gln Lys Thr Val Leu Gln Glu Lys Thr Glu Ser 3785 3790 3795 Leu Ile Gln Gln Tyr Glu Ala Ile Ser Leu Leu Asn Ser Glu Arg 3800 3805 3810 Tyr Ala Arg Leu Glu Arg Ala Gln Val Leu Val Asn Gln Phe Trp 3815 3820 3825 Glu Thr Tyr Glu Glu Leu Ser Pro Trp Ile Glu Glu Thr Arg Ala 3830 3835 3840 Leu Ile Ala Gln Leu Pro Ser Pro Ala Ile Asp His Glu Gln Leu 3845 3850 3855 Arg Gln Gln Gln Glu Glu Met Arg Gln Leu Arg Glu Ser Ile Ala 3860 3865 3870 Glu His Lys Pro His Ile Asp Lys Leu Leu Lys Ile Gly Pro Gln 3875 3880 3885 Leu Lys Glu Leu Asn Pro Glu Glu Gly Glu Met Val Glu Glu Lys 3890 3895 3900 Tyr Gln Lys Ala Glu Asn Met Tyr Ala Gln Ile Lys Glu Glu Val 3905 3910 3915 Arg Gln Arg Ala Leu Ala Leu Asp Glu Ala Val Ser Gln Ser Thr 3920 3925 3930 Gln Ile Thr Glu Phe His Asp Lys Ile Glu Pro Met Leu Glu Thr 3935 3940 3945 Leu Glu Asn Leu Ser Ser Arg Leu Arg Met Pro Pro Leu Ile Pro 3950 3955 3960 Ala Glu Val Asp Lys Ile Arg Glu Cys Ile Ser Asp Asn Lys Ser 3965 3970 3975 Ala Thr Val Glu Leu Glu Lys Leu Gln Pro Ser Phe Glu Ala Leu 3980 3985 3990 Lys Arg Arg Gly Glu Glu Leu Ile Gly Arg Ser Gln Gly Ala Asp 3995 4000 4005 Lys Asp Leu Ala Ala Lys Glu Ile Gln Asp Lys Leu Asp Gln Met 4010 4015 4020 Val Phe Phe Trp Glu Asp Ile Lys Ala Arg Ala Glu Glu Arg Glu 4025 4030 4035 Ile Lys Phe Leu Asp Val Leu Glu Leu Ala Glu Lys Phe Trp Tyr 4040 4045 4050 Asp Met Ala Ala Leu Leu Thr Thr Ile Lys Asp Thr Gln Asp Ile 4055 4060 4065 Val His Asp Leu Glu Ser Pro Gly Ile Asp Pro Ser Ile Ile Lys 4070 4075 4080 Gln Gln Val Glu Ala Ala Glu Thr Ile Lys Glu Glu Thr Asp Gly 4085 4090 4095 Leu His Glu Glu Leu Glu Phe Ile Arg Ile Leu Gly Ala Asp Leu 4100 4105 4110 Ile Phe Ala Cys Gly Glu Thr Glu Lys Pro Glu Val Arg Lys Ser 4115 4120 4125 Ile Asp Glu Met Asn Asn Ala Trp Glu Asn Leu Asn Lys Thr Trp 4130 4135 4140 Lys Glu Arg Leu Glu Lys Leu Glu Asp Ala Met Gln Ala Ala Val 4145 4150 4155 Gln Tyr Gln Asp Thr Leu Gln Ala Met Phe Asp Trp Leu Asp Asn 4160 4165 4170 Thr Val Ile Lys Leu Cys Thr Met Pro Pro Val Gly Thr Asp Leu 4175 4180 4185 Asn Thr Val Lys Asp Gln Leu Asn Glu Met Lys Glu Phe Lys Val 4190 4195 4200 Glu Val Tyr Gln Gln Gln Ile Glu Met Glu Lys Leu Asn His Gln 4205 4210 4215 Gly Glu Leu Met Leu Lys Lys Ala Thr Asp Glu Thr Asp Arg Asp 4220 4225 4230 Ile Ile Arg Glu Pro Leu Thr Glu Leu Lys His Leu Trp Glu Asn 4235 4240 4245 Leu Gly Glu Lys Ile Ala His Arg Gln His Lys Leu Glu Gly Ala 4250 4255 4260 Leu Leu Ala Leu Gly Gln Phe Gln His Ala Leu Glu Glu Leu Met 4265 4270 4275 Ser Trp Leu Thr His Thr Glu Glu Leu Leu Asp Ala Gln Arg Pro 4280 4285 4290 Ile Ser Gly Asp Pro Lys Val Ile Glu Val Glu Leu Ala Lys His 4295 4300 4305 His Val Leu Lys Asn Asp Val Leu Ala His Gln Ala Thr Val Glu 4310 4315 4320 Thr Val Asn Lys Ala Gly Asn Glu Leu Leu Glu Ser Ser Ala Gly 4325 4330 4335 Asp Asp Ala Ser Ser Leu Arg Ser Arg Leu Glu Ala Met Asn Gln 4340 4345 4350 Cys Trp Glu Ser Val Leu Gln Lys Thr Glu Glu Arg Glu Gln Gln 4355 4360 4365 Leu Gln Ser Thr Leu Gln Gln Ala Gln Gly Phe His Ser Glu Ile 4370 4375 4380 Glu Asp Phe Leu Leu Glu Leu Thr Arg Met Glu Ser Gln Leu Ser 4385 4390 4395 Ala Ser Lys Pro Thr Gly Gly Leu Pro Glu Thr Ala Arg Glu Gln 4400 4405 4410 Leu Asp Thr His Met Glu Leu Tyr Ser Gln Leu Lys Ala Lys Glu 4415 4420 4425 Glu Thr Tyr Asn Gln Leu Leu Asp Lys Gly Arg Leu Met Leu Leu 4430 4435 4440 Ser Arg Asp Asp Ser Gly Ser Gly Ser Lys Thr Glu Gln Ser Val 4445 4450 4455 Ala Leu Leu Glu Gln Lys Trp His Val Val Ser Ser Lys Met Glu 4460 4465 4470 Glu Arg Lys Ser Lys Leu Glu Glu Ala Leu Asn Leu Ala Thr Glu 4475 4480 4485 Phe Gln Asn Ser Leu Gln Glu Phe Ile Asn Trp Leu Thr Leu Ala 4490 4495 4500 Glu Gln Ser Leu Asn Ile Ala Ser Pro Pro Ser Leu Ile Leu Asn 4505 4510 4515 Thr Val Leu Ser Gln Ile Glu Glu His Lys Val Phe Ala Asn Glu 4520 4525 4530 Val Asn Ala His Arg Asp Gln Ile Ile Glu Leu Asp Gln Thr Gly 4535 4540 4545 Asn Gln Leu Lys Phe Leu Ser Gln Lys Gln Asp Val Val Leu Ile 4550 4555 4560 Lys Asn Leu Leu Val Ser Val Gln Ser Arg Trp Glu Lys Val Val 4565 4570 4575 Gln Arg Ser Ile Glu Arg Gly Arg Ser Leu Asp Asp Ala Arg Lys 4580 4585 4590 Arg Ala Lys Gln Phe His Glu Ala Trp Lys Lys Leu Ile Asp Trp 4595 4600 4605 Leu Glu Asp Ala Glu Ser His Leu Asp Ser Glu Leu Glu Ile Ser 4610 4615 4620 Asn Asp Pro Asp Lys Ile Lys Leu Gln Leu Ser Lys His Lys Glu 4625 4630 4635 Phe Gln Lys Thr Leu Gly Gly Lys Gln Pro Val Tyr Asp Thr Thr 4640 4645 4650 Ile Arg Thr Gly Arg Ala Leu Lys Glu Lys Thr Leu Leu Pro Glu 4655 4660 4665 Asp Ser Gln Lys Leu Asp Asn Phe Leu Gly Glu Val Arg Asp Lys 4670 4675 4680 Trp Asp Thr Val Cys Gly Lys Ser Val Glu Arg Gln His Lys Leu 4685 4690 4695 Glu Glu Ala Leu Leu Phe Ser Gly Gln Phe Met Asp Ala Leu Gln 4700 4705 4710 Ala Leu Val Asp Trp Leu Tyr Lys Val Glu Pro Gln Leu Ala Glu 4715 4720 4725 Asp Gln Pro Val His Gly Asp Leu Asp Leu Val Met Asn Leu Met 4730 4735 4740 Asp Ala His Lys Val Phe Gln Lys Glu Leu Gly Lys Arg Thr Gly 4745 4750 4755 Thr Val Gln Val Leu Lys Arg Ser Gly Arg Glu Leu Ile Glu Asn 4760 4765 4770 Ser Arg Asp Asp Thr Thr Trp Val Lys Gly Gln Leu Gln Glu Leu 4775 4780 4785 Ser Thr Arg Trp Asp Thr Val Cys Lys Leu Ser Val Ser Lys Gln 4790 4795 4800 Ser Arg Leu Glu Gln Ala Leu Lys Gln Ala Glu Val Phe Arg Asp 4805 4810 4815 Thr Val His Met Leu Leu Glu Trp Leu Ser Glu Ala Glu Gln Thr 4820 4825 4830 Leu Arg Phe Arg Gly Ala Leu Pro Asp Asp Thr Glu Ala Leu Gln 4835 4840 4845 Ser Leu Ile Asp Thr His Lys Glu Phe Met Lys Lys Val Glu Glu 4850 4855 4860 Lys Arg Val Asp Val Asn Ser Ala Val Ala Met Gly Glu Val Ile 4865 4870 4875 Leu Ala Val Cys His Pro Asp Cys Ile Thr Thr Ile Lys His Trp 4880 4885 4890 Ile Thr Ile Ile Arg Ala Arg Phe Glu Glu Val Leu Thr Trp Ala 4895 4900 4905 Lys Gln His Gln Gln Arg Leu Glu Thr Ala Leu Ser Glu Leu Val 4910 4915 4920 Ala Asn Ala Glu Leu Leu Glu Glu Leu Leu Ala Trp Ile Gln Trp 4925 4930 4935 Ala Glu Thr Thr Leu Ile Gln Arg Asp Gln Glu Pro Ile Pro Gln 4940 4945 4950 Asn Ile Asp Arg Val Lys Ala Leu Ile Ala Glu His Gln Thr Phe 4955 4960 4965 Met Glu Glu Met Thr Arg Lys Gln Pro Asp Val Asp Arg Val Thr 4970 4975 4980 Lys Thr Tyr Lys Arg Lys Asn Ile Glu Pro Thr His Ala Pro Phe 4985 4990 4995 Ile Glu Lys Ser Arg Ser Gly Gly Arg Lys Ser Leu Ser Gln Pro 5000 5005 5010 Thr Pro Pro Pro Met Pro Ile Leu Ser Gln Ser Glu Ala Lys Asn 5015 5020 5025 Pro Arg Ile Asn Gln Leu Ser Ala Arg Trp Gln Gln Val Trp Leu 5030 5035 5040 Leu Ala Leu Glu Arg Gln Arg Lys Leu Asn Asp Ala Leu Asp Arg 5045 5050 5055 Leu Glu Glu Leu Lys Glu Phe Ala Asn Phe Asp Phe Asp Val Trp 5060 5065 5070 Arg Lys Lys Tyr Met Arg Trp Met Asn His Lys Lys Ser Arg Val 5075 5080 5085 Met Asp Phe Phe Arg Arg Ile Asp Lys Asp Gln Asp Gly Lys Ile 5090 5095 5100 Thr Arg Gln Glu Phe Ile Asp Gly Ile Leu Ala Ser Lys Phe Pro 5105 5110 5115 Thr Thr Lys Leu Glu Met Thr Ala Val Ala Asp Ile Phe Asp Arg 5120 5125 5130 Asp Gly Asp Gly Tyr Ile Asp Tyr Tyr Glu Phe Val Ala Ala Leu 5135 5140 5145 His Pro Asn Lys Asp Ala Tyr Arg Pro Thr Thr Asp Ala Asp Lys 5150 5155 5160 Ile Glu Asp Glu Val Thr Arg Gln Val Ala Gln Cys Lys Cys Ala 5165 5170 5175 Lys Arg Phe Gln Val Glu Gln Ile Gly Glu Asn Lys Tyr Arg Phe 5180 5185 5190 Gly Asp Ser Gln Gln Leu Arg Leu Val Arg Ile Leu Arg Ser Thr 5195 5200 5205 Val Met Val Arg Val Gly Gly Gly Trp Met Ala Leu Asp Glu Phe 5210 5215 5220 Leu Val Lys Asn Asp Pro Cys Arg Ala Arg Gly Arg Thr Asn Ile 5225 5230 5235 Glu Leu Arg Glu Lys Phe Ile Leu Pro Glu Gly Ala Ser Gln Gly 5240 5245 5250 Met Thr Pro Phe Arg Ser Arg Gly Arg Arg Ser Lys Pro Ser Ser 5255 5260 5265 Arg Ala Ala Ser Pro Thr Arg Ser Ser Ser Ser Ala Ser Gln Ser 5270 5275 5280 Asn His Ser Cys Thr Ser Met Pro Ser Ser Pro Ala Thr Pro Ala 5285 5290 5295 Ser Gly Thr Lys Val Ile Pro Ser Ser Gly Ser Lys Leu Lys Arg 5300 5305 5310 Pro Thr Pro Thr Phe His Ser Ser Arg Thr Ser Leu Ala Gly Asp 5315 5320 5325 Thr Ser Asn Ser Ser Ser Pro Ala Ser Thr Gly Ala Lys Thr Asn 5330 5335 5340 Arg Ala Asp Pro Lys Lys Ser Ala Ser Arg Pro Gly Ser Arg Ala 5345 5350 5355 Gly Ser Arg Ala Gly Ser Arg Ala Ser Ser Arg Arg Gly Ser Asp 5360 5365 5370 Ala Ser Asp Phe Asp Leu Leu Glu Thr Gln Ser Ala Cys Ser Asp 5375 5380 5385 Thr Ser Glu Ser Ser Ala Ala Gly Gly Gln Gly Asn Ser Arg Arg 5390 5395 5400 Gly Leu Asn Lys Pro Ser Lys Ile Pro Thr Met Ser Lys Lys Thr 5405 5410 5415 Thr Thr Ala Ser Pro Arg Thr Pro Gly Pro Lys Arg 5420 5425 5430 320355PRTHomo sapiens 320Met Ala Lys Leu Ile Ala Leu Thr Leu Leu Gly Met Gly Leu Ala Leu 1 5 10 15 Phe Arg Asn His Gln Ser Ser Tyr Gln Thr Arg Leu Asn Ala Leu Arg 20 25 30 Glu Val Gln Pro Val Glu Leu Pro Asn Cys Asn Leu Val Lys Gly Ile 35 40 45 Glu Thr Gly Ser Glu Asp Leu Glu Ile Leu Pro Asn Gly Leu Ala Phe 50 55 60 Ile Ser Ser Gly Leu Lys Tyr Pro Gly Ile Lys Ser Phe Asn Pro Asn 65 70 75 80 Ser Pro Gly Lys Ile Leu Leu Met Asp Leu Asn Glu Glu Asp Pro Thr 85 90 95 Val Leu Glu Leu Gly Ile Thr Gly Ser Lys Phe Asp Val Ser Ser Phe 100 105 110 Asn Pro His Gly Ile Ser Thr Phe Thr Asp Glu Asp Asn Ala Met Tyr 115 120 125 Leu Leu Val Val Asn His Pro Asp Ala Lys Ser Thr Val Glu Leu Phe 130 135

140 Lys Phe Gln Glu Glu Glu Lys Ser Leu Leu His Leu Lys Thr Ile Arg 145 150 155 160 His Lys Leu Leu Pro Asn Leu Asn Asp Ile Val Ala Val Gly Pro Glu 165 170 175 His Phe Tyr Gly Thr Asn Asp His Tyr Phe Leu Asp Pro Tyr Leu Gln 180 185 190 Ser Trp Glu Met Tyr Leu Gly Leu Ala Trp Ser Tyr Val Val Tyr Tyr 195 200 205 Ser Pro Ser Glu Val Arg Val Val Ala Glu Gly Phe Asp Phe Ala Asn 210 215 220 Gly Ile Asn Ile Ser Pro Asp Gly Lys Tyr Val Tyr Ile Ala Glu Leu 225 230 235 240 Leu Ala His Lys Ile His Val Tyr Glu Lys His Ala Asn Trp Thr Leu 245 250 255 Thr Pro Leu Lys Ser Leu Asp Phe Asn Thr Leu Val Asp Asn Ile Ser 260 265 270 Val Asp Pro Glu Thr Gly Asp Leu Trp Val Gly Cys His Pro Asn Gly 275 280 285 Met Lys Ile Phe Phe Tyr Asp Ser Glu Asn Pro Pro Ala Ser Glu Val 290 295 300 Leu Arg Ile Gln Asn Ile Leu Thr Glu Glu Pro Lys Val Thr Gln Val 305 310 315 320 Tyr Ala Glu Asn Gly Thr Val Leu Gln Gly Ser Thr Val Ala Ser Val 325 330 335 Tyr Lys Gly Lys Leu Leu Ile Gly Thr Val Phe His Lys Ala Leu Tyr 340 345 350 Cys Glu Leu 355 321634PRTHomo sapiens 321Met Ala Gln Gly Val Leu Trp Ile Leu Leu Gly Leu Leu Leu Trp Ser 1 5 10 15 Asp Pro Gly Thr Ala Ser Leu Pro Leu Leu Met Asp Ser Val Ile Gln 20 25 30 Ala Leu Ala Glu Leu Glu Gln Lys Val Pro Ala Ala Lys Thr Arg His 35 40 45 Thr Ala Ser Ala Trp Leu Met Ser Ala Pro Asn Ser Gly Pro His Asn 50 55 60 Arg Leu Tyr His Phe Leu Leu Gly Ala Trp Ser Leu Asn Ala Thr Glu 65 70 75 80 Leu Asp Pro Cys Pro Leu Ser Pro Glu Leu Leu Gly Leu Thr Lys Glu 85 90 95 Val Ala Arg His Asp Val Arg Glu Gly Lys Glu Tyr Gly Val Val Leu 100 105 110 Ala Pro Asp Gly Ser Thr Val Ala Val Glu Pro Leu Leu Ala Gly Leu 115 120 125 Glu Ala Gly Leu Gln Gly Arg Arg Val Ile Asn Leu Pro Leu Asp Ser 130 135 140 Met Ala Ala Pro Trp Glu Thr Gly Asp Thr Phe Pro Asp Val Val Ala 145 150 155 160 Ile Ala Pro Asp Val Arg Ala Thr Ser Ser Pro Gly Leu Arg Asp Gly 165 170 175 Ser Pro Asp Val Thr Thr Ala Asp Ile Gly Ala Asn Thr Pro Asp Ala 180 185 190 Thr Lys Gly Cys Pro Asp Val Gln Ala Ser Leu Pro Asp Ala Lys Ala 195 200 205 Lys Ser Pro Pro Thr Met Val Asp Ser Leu Leu Ala Val Thr Leu Ala 210 215 220 Gly Asn Leu Gly Leu Thr Phe Leu Arg Gly Ser Gln Thr Gln Ser His 225 230 235 240 Pro Asp Leu Gly Thr Glu Gly Cys Trp Asp Gln Leu Ser Ala Pro Arg 245 250 255 Thr Phe Thr Leu Leu Asp Pro Lys Ala Ser Leu Leu Thr Met Ala Phe 260 265 270 Leu Asn Gly Ala Leu Asp Gly Val Ile Leu Gly Asp Tyr Leu Ser Arg 275 280 285 Thr Pro Glu Pro Arg Pro Ser Leu Ser His Leu Leu Ser Gln Tyr Tyr 290 295 300 Gly Ala Gly Val Ala Arg Asp Pro Gly Phe Arg Ser Asn Phe Arg Arg 305 310 315 320 Gln Asn Gly Ala Ala Leu Thr Ser Ala Ser Ile Leu Ala Gln Gln Val 325 330 335 Trp Gly Thr Leu Val Leu Leu Gln Arg Leu Glu Pro Val His Leu Gln 340 345 350 Leu Gln Cys Met Ser Gln Glu Gln Leu Ala Gln Val Ala Ala Asn Ala 355 360 365 Thr Lys Glu Phe Thr Glu Ala Phe Leu Gly Cys Pro Ala Ile His Pro 370 375 380 Arg Cys Arg Trp Gly Ala Ala Pro Tyr Arg Gly Arg Pro Lys Leu Leu 385 390 395 400 Gln Leu Pro Leu Gly Phe Leu Tyr Val His His Thr Tyr Val Pro Ala 405 410 415 Pro Pro Cys Thr Asp Phe Thr Arg Cys Ala Ala Asn Met Arg Ser Met 420 425 430 Gln Arg Tyr His Gln Asp Thr Gln Gly Trp Gly Asp Ile Gly Tyr Gly 435 440 445 Phe Val Val Gly Ser Asp Gly Tyr Val Tyr Glu Gly Arg Gly Trp His 450 455 460 Trp Val Gly Ala His Thr Leu Gly His Asn Ser Arg Gly Phe Gly Val 465 470 475 480 Ala Ile Val Gly Asn Tyr Thr Ala Ala Leu Pro Thr Glu Ala Ala Leu 485 490 495 Arg Thr Val Arg Asp Thr Leu Pro Ser Cys Ala Val Arg Ala Gly Leu 500 505 510 Leu Arg Pro Asp Tyr Ala Leu Leu Gly His Arg Gln Leu Val Arg Thr 515 520 525 Asp Cys Pro Gly Asp Ala Leu Phe Asp Leu Leu Arg Thr Trp Pro His 530 535 540 Phe Thr Ala Val Ser Leu Arg Ser Leu His Tyr Thr Ala Arg Arg Pro 545 550 555 560 Ser Val Tyr Thr Ser Ser Thr Arg Pro Leu Pro Pro Ala Cys Asn Ser 565 570 575 Cys Ala Arg Thr Ala Ser Ala Arg Pro Pro Thr Ser Arg Arg His Val 580 585 590 Tyr Ser Gly Asn Leu Gly Pro Ala Phe Ala Gly His Ser Ala Gly Asn 595 600 605 Ile Pro Asp Pro Val Thr Ser Ala Tyr Ala Ala Ser Ala Gln Pro Gln 610 615 620 Thr Gln Pro Ala Cys Pro Phe Pro Ser Ser 625 630 322638PRTHomo sapiens 322Met Ile Leu Phe Lys Gln Ala Thr Tyr Phe Ile Ser Leu Phe Ala Thr 1 5 10 15 Val Ser Cys Gly Cys Leu Thr Gln Leu Tyr Glu Asn Ala Phe Phe Arg 20 25 30 Gly Gly Asp Val Ala Ser Met Tyr Thr Pro Asn Ala Gln Tyr Cys Gln 35 40 45 Met Arg Cys Thr Phe His Pro Arg Cys Leu Leu Phe Ser Phe Leu Pro 50 55 60 Ala Ser Ser Ile Asn Asp Met Glu Lys Arg Phe Gly Cys Phe Leu Lys 65 70 75 80 Asp Ser Val Thr Gly Thr Leu Pro Lys Val His Arg Thr Gly Ala Val 85 90 95 Ser Gly His Ser Leu Lys Gln Cys Gly His Gln Ile Ser Ala Cys His 100 105 110 Arg Asp Ile Tyr Lys Gly Val Asp Met Arg Gly Val Asn Phe Asn Val 115 120 125 Ser Lys Val Ser Ser Val Glu Glu Cys Gln Lys Arg Cys Thr Asn Asn 130 135 140 Ile Arg Cys Gln Phe Phe Ser Tyr Ala Thr Gln Thr Phe His Lys Ala 145 150 155 160 Glu Tyr Arg Asn Asn Cys Leu Leu Lys Tyr Ser Pro Gly Gly Thr Pro 165 170 175 Thr Ala Ile Lys Val Leu Ser Asn Val Glu Ser Gly Phe Ser Leu Lys 180 185 190 Pro Cys Ala Leu Ser Glu Ile Gly Cys His Met Asn Ile Phe Gln His 195 200 205 Leu Ala Phe Ser Asp Val Asp Val Ala Arg Val Leu Thr Pro Asp Ala 210 215 220 Phe Val Cys Arg Thr Ile Cys Thr Tyr His Pro Asn Cys Leu Phe Phe 225 230 235 240 Thr Phe Tyr Thr Asn Val Trp Lys Ile Glu Ser Gln Arg Asn Val Cys 245 250 255 Leu Leu Lys Thr Ser Glu Ser Gly Thr Pro Ser Ser Ser Thr Pro Gln 260 265 270 Glu Asn Thr Ile Ser Gly Tyr Ser Leu Leu Thr Cys Lys Arg Thr Leu 275 280 285 Pro Glu Pro Cys His Ser Lys Ile Tyr Pro Gly Val Asp Phe Gly Gly 290 295 300 Glu Glu Leu Asn Val Thr Phe Val Lys Gly Val Asn Val Cys Gln Glu 305 310 315 320 Thr Cys Thr Lys Met Ile Arg Cys Gln Phe Phe Thr Tyr Ser Leu Leu 325 330 335 Pro Glu Asp Cys Lys Glu Glu Lys Cys Lys Cys Phe Leu Arg Leu Ser 340 345 350 Met Asp Gly Ser Pro Thr Arg Ile Ala Tyr Gly Thr Gln Gly Ser Ser 355 360 365 Gly Tyr Ser Leu Arg Leu Cys Asn Thr Gly Asp Asn Ser Val Cys Thr 370 375 380 Thr Lys Thr Ser Thr Arg Ile Val Gly Gly Thr Asn Ser Ser Trp Gly 385 390 395 400 Glu Trp Pro Trp Gln Val Ser Leu Gln Val Lys Leu Thr Ala Gln Arg 405 410 415 His Leu Cys Gly Gly Ser Leu Ile Gly His Gln Trp Val Leu Thr Ala 420 425 430 Ala His Cys Phe Asp Gly Leu Pro Leu Gln Asp Val Trp Arg Ile Tyr 435 440 445 Ser Gly Ile Leu Asn Leu Ser Asp Ile Thr Lys Asp Thr Pro Phe Ser 450 455 460 Gln Ile Lys Glu Ile Ile Ile His Gln Asn Tyr Lys Val Ser Glu Gly 465 470 475 480 Asn His Asp Ile Ala Leu Ile Lys Leu Gln Ala Pro Leu Asn Tyr Thr 485 490 495 Glu Phe Gln Lys Pro Ile Cys Leu Pro Ser Lys Gly Asp Thr Ser Thr 500 505 510 Ile Tyr Thr Asn Cys Trp Val Thr Gly Trp Gly Phe Ser Lys Glu Lys 515 520 525 Gly Glu Ile Gln Asn Ile Leu Gln Lys Val Asn Ile Pro Leu Val Thr 530 535 540 Asn Glu Glu Cys Gln Lys Arg Tyr Gln Asp Tyr Lys Ile Thr Gln Arg 545 550 555 560 Met Val Cys Ala Gly Tyr Lys Glu Gly Gly Lys Asp Ala Cys Lys Gly 565 570 575 Asp Ser Gly Gly Pro Leu Val Cys Lys His Asn Gly Met Trp Arg Leu 580 585 590 Val Gly Ile Thr Ser Trp Gly Glu Gly Cys Ala Arg Arg Glu Gln Pro 595 600 605 Gly Val Tyr Thr Lys Val Ala Glu Tyr Met Asp Trp Ile Leu Glu Lys 610 615 620 Thr Gln Ser Ser Asp Gly Lys Ala Gln Met Gln Ser Pro Ala 625 630 635 323810PRTHomo sapiens 323Met Glu His Lys Glu Val Val Leu Leu Leu Leu Leu Phe Leu Lys Ser 1 5 10 15 Gly Gln Gly Glu Pro Leu Asp Asp Tyr Val Asn Thr Gln Gly Ala Ser 20 25 30 Leu Phe Ser Val Thr Lys Lys Gln Leu Gly Ala Gly Ser Ile Glu Glu 35 40 45 Cys Ala Ala Lys Cys Glu Glu Asp Glu Glu Phe Thr Cys Arg Ala Phe 50 55 60 Gln Tyr His Ser Lys Glu Gln Gln Cys Val Ile Met Ala Glu Asn Arg 65 70 75 80 Lys Ser Ser Ile Ile Ile Arg Met Arg Asp Val Val Leu Phe Glu Lys 85 90 95 Lys Val Tyr Leu Ser Glu Cys Lys Thr Gly Asn Gly Lys Asn Tyr Arg 100 105 110 Gly Thr Met Ser Lys Thr Lys Asn Gly Ile Thr Cys Gln Lys Trp Ser 115 120 125 Ser Thr Ser Pro His Arg Pro Arg Phe Ser Pro Ala Thr His Pro Ser 130 135 140 Glu Gly Leu Glu Glu Asn Tyr Cys Arg Asn Pro Asp Asn Asp Pro Gln 145 150 155 160 Gly Pro Trp Cys Tyr Thr Thr Asp Pro Glu Lys Arg Tyr Asp Tyr Cys 165 170 175 Asp Ile Leu Glu Cys Glu Glu Glu Cys Met His Cys Ser Gly Glu Asn 180 185 190 Tyr Asp Gly Lys Ile Ser Lys Thr Met Ser Gly Leu Glu Cys Gln Ala 195 200 205 Trp Asp Ser Gln Ser Pro His Ala His Gly Tyr Ile Pro Ser Lys Phe 210 215 220 Pro Asn Lys Asn Leu Lys Lys Asn Tyr Cys Arg Asn Pro Asp Arg Glu 225 230 235 240 Leu Arg Pro Trp Cys Phe Thr Thr Asp Pro Asn Lys Arg Trp Glu Leu 245 250 255 Cys Asp Ile Pro Arg Cys Thr Thr Pro Pro Pro Ser Ser Gly Pro Thr 260 265 270 Tyr Gln Cys Leu Lys Gly Thr Gly Glu Asn Tyr Arg Gly Asn Val Ala 275 280 285 Val Thr Val Ser Gly His Thr Cys Gln His Trp Ser Ala Gln Thr Pro 290 295 300 His Thr His Asn Arg Thr Pro Glu Asn Phe Pro Cys Lys Asn Leu Asp 305 310 315 320 Glu Asn Tyr Cys Arg Asn Pro Asp Gly Lys Arg Ala Pro Trp Cys His 325 330 335 Thr Thr Asn Ser Gln Val Arg Trp Glu Tyr Cys Lys Ile Pro Ser Cys 340 345 350 Asp Ser Ser Pro Val Ser Thr Glu Gln Leu Ala Pro Thr Ala Pro Pro 355 360 365 Glu Leu Thr Pro Val Val Gln Asp Cys Tyr His Gly Asp Gly Gln Ser 370 375 380 Tyr Arg Gly Thr Ser Ser Thr Thr Thr Thr Gly Lys Lys Cys Gln Ser 385 390 395 400 Trp Ser Ser Met Thr Pro His Arg His Gln Lys Thr Pro Glu Asn Tyr 405 410 415 Pro Asn Ala Gly Leu Thr Met Asn Tyr Cys Arg Asn Pro Asp Ala Asp 420 425 430 Lys Gly Pro Trp Cys Phe Thr Thr Asp Pro Ser Val Arg Trp Glu Tyr 435 440 445 Cys Asn Leu Lys Lys Cys Ser Gly Thr Glu Ala Ser Val Val Ala Pro 450 455 460 Pro Pro Val Val Leu Leu Pro Asp Val Glu Thr Pro Ser Glu Glu Asp 465 470 475 480 Cys Met Phe Gly Asn Gly Lys Gly Tyr Arg Gly Lys Arg Ala Thr Thr 485 490 495 Val Thr Gly Thr Pro Cys Gln Asp Trp Ala Ala Gln Glu Pro His Arg 500 505 510 His Ser Ile Phe Thr Pro Glu Thr Asn Pro Arg Ala Gly Leu Glu Lys 515 520 525 Asn Tyr Cys Arg Asn Pro Asp Gly Asp Val Gly Gly Pro Trp Cys Tyr 530 535 540 Thr Thr Asn Pro Arg Lys Leu Tyr Asp Tyr Cys Asp Val Pro Gln Cys 545 550 555 560 Ala Ala Pro Ser Phe Asp Cys Gly Lys Pro Gln Val Glu Pro Lys Lys 565 570 575 Cys Pro Gly Arg Val Val Gly Gly Cys Val Ala His Pro His Ser Trp 580 585 590 Pro Trp Gln Val Ser Leu Arg Thr Arg Phe Gly Met His Phe Cys Gly 595 600 605 Gly Thr Leu Ile Ser Pro Glu Trp Val Leu Thr Ala Ala His Cys Leu 610 615 620 Glu Lys Ser Pro Arg Pro Ser Ser Tyr Lys Val Ile Leu Gly Ala His 625 630 635 640 Gln Glu Val Asn Leu Glu Pro His Val Gln Glu Ile Glu Val Ser Arg 645 650 655 Leu Phe Leu Glu Pro Thr Arg Lys Asp Ile Ala Leu Leu Lys Leu Ser 660 665 670 Ser Pro Ala Val Ile Thr Asp Lys Val Ile Pro Ala Cys Leu Pro Ser 675 680 685 Pro Asn Tyr Val Val Ala Asp Arg Thr Glu Cys Phe Ile Thr Gly Trp 690 695 700 Gly Glu Thr Gln Gly Thr Phe Gly Ala Gly Leu Leu Lys Glu Ala Gln 705 710 715 720 Leu Pro Val Ile Glu Asn Lys Val Cys Asn Arg Tyr Glu Phe Leu Asn 725 730 735 Gly Arg Val Gln Ser Thr Glu Leu Cys Ala Gly His Leu Ala Gly Gly 740 745 750 Thr Asp Ser Cys Gln Gly Asp Ser Gly Gly Pro Leu Val Cys Phe Glu 755 760 765 Lys Asp Lys Tyr Ile Leu Gln Gly Val Thr Ser Trp Gly Leu Gly Cys 770 775 780 Ala Arg Pro Asn Lys Pro Gly Val Tyr Val Arg Val Ser Arg Phe Val 785 790 795 800 Thr Trp Ile Glu Gly Val Met Arg Asn Asn 805 810 324722PRTHomo

sapiens 324Met Ser Gln Gln Asp Ala Val Ala Ala Leu Ser Glu Arg Leu Leu Val 1 5 10 15 Ala Ala Tyr Lys Gly Gln Thr Glu Asn Val Val Gln Leu Ile Asn Lys 20 25 30 Gly Ala Arg Val Ala Val Thr Lys His Gly Arg Thr Pro Leu His Leu 35 40 45 Ala Ala Asn Lys Gly His Leu Pro Val Val Gln Ile Leu Leu Lys Ala 50 55 60 Gly Cys Asp Leu Asp Val Gln Asp Asp Gly Asp Gln Thr Ala Leu His 65 70 75 80 Arg Ala Thr Val Val Gly Asn Thr Glu Ile Ile Ala Ala Leu Ile His 85 90 95 Glu Gly Cys Ala Leu Asp Arg Gln Asp Lys Asp Gly Asn Thr Ala Leu 100 105 110 His Glu Ala Ser Trp His Gly Phe Ser Gln Ser Ala Lys Leu Leu Ile 115 120 125 Lys Ala Gly Ala Asn Val Leu Ala Lys Asn Lys Ala Gly Asn Thr Ala 130 135 140 Leu His Leu Ala Cys Gln Asn Ser His Ser Gln Ser Thr Arg Val Leu 145 150 155 160 Leu Leu Ala Gly Ser Arg Ala Asp Leu Lys Asn Asn Ala Gly Asp Thr 165 170 175 Cys Leu His Val Ala Ala Arg Tyr Asn His Leu Ser Ile Ile Arg Leu 180 185 190 Leu Leu Thr Ala Phe Cys Ser Val His Glu Lys Asn Gln Ala Gly Asp 195 200 205 Thr Ala Leu His Val Ala Ala Ala Leu Asn His Lys Lys Val Ala Lys 210 215 220 Ile Leu Leu Glu Ala Gly Ala Asp Thr Thr Ile Val Asn Asn Ala Gly 225 230 235 240 Gln Thr Pro Leu Glu Thr Ala Arg Tyr His Asn Asn Pro Glu Val Ala 245 250 255 Leu Leu Leu Thr Lys Ala Pro Gln Val Leu Arg Phe Ser Arg Gly Arg 260 265 270 Ser Leu Arg Lys Lys Arg Glu Arg Leu Lys Glu Glu Arg Arg Ala Gln 275 280 285 Ser Val Pro Arg Asp Glu Val Ala Gln Ser Lys Gly Ser Val Ser Ala 290 295 300 Gly Asp Thr Pro Ser Ser Glu Gln Ala Val Ala Arg Lys Glu Glu Ala 305 310 315 320 Arg Glu Glu Phe Leu Ser Ala Ser Pro Glu Pro Arg Ala Lys Asp Asp 325 330 335 Arg Arg Arg Lys Ser Arg Pro Lys Val Ser Ala Phe Ser Asp Pro Thr 340 345 350 Pro Pro Ala Asp Gln Gln Pro Gly His Gln Lys Asn Leu His Ala His 355 360 365 Asn His Pro Lys Lys Arg Asn Arg His Arg Cys Ser Ser Pro Pro Pro 370 375 380 Pro His Glu Phe Arg Ala Tyr Gln Leu Tyr Thr Leu Tyr Arg Gly Lys 385 390 395 400 Asp Gly Lys Val Met Gln Ala Pro Ile Asn Gly Cys Arg Cys Glu Pro 405 410 415 Leu Ile Asn Lys Leu Glu Asn Gln Leu Glu Ala Thr Val Glu Glu Ile 420 425 430 Lys Ala Glu Leu Gly Ser Val Gln Asp Lys Met Asn Thr Lys Leu Gly 435 440 445 Gln Met Glu Asn Lys Thr Gln His Gln Met Arg Val Leu Asp Lys Leu 450 455 460 Met Val Glu Arg Leu Ser Ala Glu Arg Thr Glu Cys Leu Asn Arg Leu 465 470 475 480 Gln Gln His Ser Asp Thr Glu Lys His Glu Gly Glu Lys Arg Gln Ile 485 490 495 Ser Leu Val Asp Glu Leu Lys Thr Trp Cys Met Leu Lys Ile Gln Asn 500 505 510 Leu Glu Gln Lys Leu Ser Gly Asp Ser Arg Ala Cys Arg Ala Lys Ser 515 520 525 Thr Pro Ser Thr Cys Val Asp Gln Leu Val Val Thr Ala Gly Pro Ala 530 535 540 Ala Ala Ser Asp Ser Ser Pro Pro Val Val Arg Pro Lys Glu Lys Ala 545 550 555 560 Leu Asn Ser Thr Ala Thr Gln Arg Leu Gln Gln Glu Leu Ser Ser Ser 565 570 575 Asp Cys Thr Gly Ser Arg Leu Arg Asn Val Lys Val Gln Thr Ala Leu 580 585 590 Leu Pro Met Asn Glu Ala Ala Arg Ser Asp Gln Gln Ala Gly Pro Cys 595 600 605 Val Asn Arg Gly Thr Gln Thr Lys Lys Ser Gly Lys Ser Gly Pro Thr 610 615 620 Arg His Arg Ala Gln Gln Pro Ala Ala Ser Ser Thr Cys Gly Gln Pro 625 630 635 640 Pro Pro Ala Thr Gly Ser Glu Gln Thr Gly Pro His Ile Arg Asp Thr 645 650 655 Ser Gln Ala Leu Glu Leu Thr Gln Tyr Phe Phe Glu Ala Val Ser Thr 660 665 670 Gln Met Glu Lys Trp Tyr Glu Arg Lys Ile Glu Glu Ala Arg Ser Gln 675 680 685 Ala Asn Gln Lys Ala Gln Gln Asp Lys Ala Thr Leu Lys Glu His Ile 690 695 700 Lys Ser Leu Glu Glu Glu Leu Ala Lys Leu Arg Thr Arg Val Gln Lys 705 710 715 720 Glu Asn 32594PRTHomo sapiens 325Met Glu Lys Glu Ser Leu Pro Arg Ser Leu Asn Phe Asp His His Gly 1 5 10 15 Ile Tyr Met Asn Trp Gln Thr Lys Phe Met Leu Leu Leu Lys Thr Val 20 25 30 Ser Ile Pro Arg Ser Gln Ala Ile Phe Thr Gln Pro Gly Leu Gly Ser 35 40 45 Gly Thr Pro Gln Gly Tyr Lys Gln Ser His Ser Ala Leu Gly Trp Ala 50 55 60 Ala Thr Leu Ser Cys Trp Gly Lys Asp Gly Ser Arg Gln Leu Ser Trp 65 70 75 80 Val Thr Ala Gly Ser Ser Phe His Lys Ser Asp Leu Ile Ser 85 90 326790PRTHomo sapiens 326Met Asn Ile Met Asn Thr Glu Gln Ser Gln Asn Ser Ile Val Ser Arg 1 5 10 15 Ile Lys Val Phe Glu Gly Gln Thr Asn Ile Glu Thr Ser Gly Leu Pro 20 25 30 Lys Lys Pro Glu Ile Thr Pro Arg Ser Leu Pro Pro Lys Pro Thr Val 35 40 45 Ser Ser Gly Lys Pro Ser Val Ala Pro Lys Pro Ala Ala Asn Arg Ala 50 55 60 Ser Gly Glu Trp Asp Ser Gly Thr Glu Asn Arg Leu Lys Val Thr Ser 65 70 75 80 Lys Glu Gly Leu Thr Pro Tyr Pro Pro Leu Gln Glu Ala Gly Ser Ile 85 90 95 Pro Val Thr Lys Pro Glu Leu Pro Lys Lys Pro Asn Pro Gly Leu Ile 100 105 110 Arg Ser Val Asn Pro Glu Ile Pro Gly Arg Gly Pro Leu Ala Glu Ser 115 120 125 Ser Asp Ser Gly Lys Lys Val Pro Thr Pro Ala Pro Arg Pro Leu Leu 130 135 140 Leu Lys Lys Ser Val Ser Ser Glu Asn Pro Thr Tyr Pro Ser Ala Pro 145 150 155 160 Leu Lys Pro Val Thr Val Pro Pro Arg Leu Ala Gly Ala Ser Gln Ala 165 170 175 Lys Ala Tyr Lys Ser Leu Gly Glu Gly Pro Pro Ala Asn Pro Pro Val 180 185 190 Pro Val Leu Gln Ser Lys Pro Leu Val Asp Ile Asp Leu Ile Ser Phe 195 200 205 Asp Asp Asp Val Leu Pro Thr Pro Ser Gly Asn Leu Ala Glu Glu Ser 210 215 220 Val Gly Ser Glu Met Val Leu Asp Pro Phe Gln Leu Pro Ala Lys Thr 225 230 235 240 Glu Pro Ile Lys Glu Arg Ala Val Gln Pro Ala Pro Thr Arg Lys Pro 245 250 255 Thr Val Ile Arg Ile Pro Ala Lys Pro Gly Lys Cys Leu His Glu Asp 260 265 270 Pro Gln Ser Pro Pro Pro Leu Pro Ala Glu Lys Pro Ile Gly Asn Thr 275 280 285 Phe Ser Thr Val Ser Gly Lys Leu Ser Asn Val Glu Arg Thr Arg Asn 290 295 300 Leu Glu Ser Asn His Pro Gly Gln Thr Gly Gly Phe Val Arg Val Pro 305 310 315 320 Pro Arg Leu Pro Pro Arg Pro Val Asn Gly Lys Thr Ile Pro Thr Gln 325 330 335 Gln Pro Pro Thr Lys Val Pro Pro Glu Arg Pro Pro Pro Pro Lys Leu 340 345 350 Ser Ala Thr Arg Arg Ser Asn Lys Lys Leu Pro Phe Asn Arg Ser Ser 355 360 365 Ser Asp Met Asp Leu Gln Lys Lys Gln Ser Asn Leu Ala Thr Gly Leu 370 375 380 Ser Lys Ala Lys Ser Gln Val Phe Lys Asn Gln Asp Pro Val Leu Pro 385 390 395 400 Pro Arg Pro Lys Pro Gly His Pro Leu Tyr Ser Lys Tyr Met Leu Ser 405 410 415 Val Pro His Gly Ile Ala Asn Glu Asp Ile Val Ser Gln Asn Pro Gly 420 425 430 Glu Leu Ser Cys Lys Arg Gly Asp Val Leu Val Met Leu Lys Gln Thr 435 440 445 Glu Asn Asn Tyr Leu Glu Cys Gln Lys Gly Glu Asp Thr Gly Arg Val 450 455 460 His Leu Ser Gln Met Lys Ile Ile Thr Pro Leu Asp Glu His Leu Arg 465 470 475 480 Ser Arg Pro Asn Asp Pro Ser His Ala Gln Lys Pro Val Asp Ser Gly 485 490 495 Ala Pro His Ala Val Val Leu His Asp Phe Pro Ala Glu Gln Val Asp 500 505 510 Asp Leu Asn Leu Thr Ser Gly Glu Ile Val Tyr Leu Leu Glu Lys Ile 515 520 525 Asp Thr Asp Trp Tyr Arg Gly Asn Cys Arg Asn Gln Ile Gly Ile Phe 530 535 540 Pro Ala Asn Tyr Val Lys Val Ile Ile Asp Ile Pro Glu Gly Gly Asn 545 550 555 560 Gly Lys Arg Glu Cys Val Ser Ser His Cys Val Lys Gly Ser Arg Cys 565 570 575 Val Ala Arg Phe Glu Tyr Ile Gly Glu Gln Lys Asp Glu Leu Ser Phe 580 585 590 Ser Glu Gly Glu Ile Ile Ile Leu Lys Glu Tyr Val Asn Glu Glu Trp 595 600 605 Ala Arg Gly Glu Val Arg Gly Arg Thr Gly Ile Phe Pro Leu Asn Phe 610 615 620 Val Glu Pro Val Glu Asp Tyr Pro Thr Ser Gly Ala Asn Val Leu Ser 625 630 635 640 Thr Lys Val Pro Leu Lys Thr Lys Lys Glu Asp Ser Gly Ser Asn Ser 645 650 655 Gln Val Asn Ser Leu Pro Ala Glu Trp Cys Glu Ala Leu His Ser Phe 660 665 670 Thr Ala Glu Thr Ser Asp Asp Leu Ser Phe Lys Arg Gly Asp Arg Ile 675 680 685 Gln Ile Leu Glu Arg Leu Asp Ser Asp Trp Cys Arg Gly Arg Leu Gln 690 695 700 Asp Arg Glu Gly Ile Phe Pro Ala Val Phe Val Arg Pro Cys Pro Ala 705 710 715 720 Glu Ala Lys Ser Met Leu Ala Ile Val Pro Lys Gly Arg Lys Ala Lys 725 730 735 Ala Leu Tyr Asp Phe Arg Gly Glu Asn Glu Asp Glu Leu Ser Phe Lys 740 745 750 Ala Gly Asp Ile Ile Thr Glu Leu Glu Ser Val Asp Asp Asp Trp Met 755 760 765 Ser Gly Glu Leu Met Gly Lys Ser Gly Ile Phe Pro Lys Asn Tyr Ile 770 775 780 Gln Phe Leu Gln Ile Ser 785 790 327593PRTHomo sapiens 327Met Gly Gly Val Gln Gly His Phe Val Ile Phe Arg Gly Leu Ala Lys 1 5 10 15 Ala Leu Ser Arg Pro Val Thr Leu Ala Thr Pro Asp Ser Ser Leu Leu 20 25 30 Leu Arg Lys Thr Gly Gln Pro Gly Ala Thr Arg Ser Ala Leu Thr Lys 35 40 45 Met Leu Pro Gly Ala Trp Leu Leu Trp Thr Ser Leu Leu Leu Leu Ala 50 55 60 Arg Pro Ala Gln Pro Cys Pro Met Gly Cys Asp Cys Phe Val Gln Glu 65 70 75 80 Val Phe Cys Ser Asp Glu Glu Leu Ala Thr Val Pro Leu Asp Ile Pro 85 90 95 Pro Tyr Thr Lys Asn Ile Ile Phe Val Glu Thr Ser Phe Thr Thr Leu 100 105 110 Glu Thr Arg Ala Phe Gly Ser Asn Pro Asn Leu Thr Lys Val Val Phe 115 120 125 Leu Asn Thr Gln Leu Cys Gln Phe Arg Pro Asp Ala Phe Gly Gly Leu 130 135 140 Pro Arg Leu Glu Asp Leu Glu Val Thr Gly Ser Ser Phe Leu Asn Leu 145 150 155 160 Ser Thr Asn Ile Phe Ser Asn Leu Thr Ser Leu Gly Lys Leu Thr Leu 165 170 175 Asn Phe Asn Met Leu Glu Ala Leu Pro Glu Gly Leu Phe Gln His Leu 180 185 190 Ala Ala Leu Glu Ser Leu His Leu Gln Gly Asn Gln Leu Gln Ala Leu 195 200 205 Pro Arg Arg Leu Phe Gln Pro Leu Thr His Leu Lys Thr Leu Asn Leu 210 215 220 Ala Gln Asn Leu Leu Ala Gln Leu Pro Glu Glu Leu Phe His Pro Leu 225 230 235 240 Thr Ser Leu Gln Thr Leu Lys Leu Ser Asn Asn Ala Leu Ser Gly Leu 245 250 255 Pro Gln Gly Val Phe Gly Lys Leu Gly Ser Leu Gln Glu Leu Phe Leu 260 265 270 Asp Ser Asn Asn Ile Ser Glu Leu Pro Pro Gln Val Phe Ser Gln Leu 275 280 285 Phe Cys Leu Glu Arg Leu Trp Leu Gln Arg Asn Ala Ile Thr His Leu 290 295 300 Pro Leu Ser Ile Phe Ala Ser Leu Gly Asn Leu Thr Phe Leu Ser Leu 305 310 315 320 Gln Trp Asn Met Leu Arg Val Leu Pro Ala Gly Leu Phe Ala His Thr 325 330 335 Pro Cys Leu Val Gly Leu Ser Leu Thr His Asn Gln Leu Glu Thr Val 340 345 350 Ala Glu Gly Thr Phe Ala His Leu Ser Asn Leu Arg Ser Leu Met Leu 355 360 365 Ser Tyr Asn Ala Ile Thr His Leu Pro Ala Gly Ile Phe Arg Asp Leu 370 375 380 Glu Glu Leu Val Lys Leu Tyr Leu Gly Ser Asn Asn Leu Thr Ala Leu 385 390 395 400 His Pro Ala Leu Phe Gln Asn Leu Ser Lys Leu Glu Leu Leu Ser Leu 405 410 415 Ser Lys Asn Gln Leu Thr Thr Leu Pro Glu Gly Ile Phe Asp Thr Asn 420 425 430 Tyr Asn Leu Phe Asn Leu Ala Leu His Gly Asn Pro Trp Gln Cys Asp 435 440 445 Cys His Leu Ala Tyr Leu Phe Asn Trp Leu Gln Gln Tyr Thr Asp Arg 450 455 460 Leu Leu Asn Ile Gln Thr Tyr Cys Ala Gly Pro Ala Tyr Leu Lys Gly 465 470 475 480 Gln Val Val Pro Ala Leu Asn Glu Lys Gln Leu Val Cys Pro Val Thr 485 490 495 Arg Asp His Leu Gly Phe Gln Val Thr Trp Pro Asp Glu Ser Lys Ala 500 505 510 Gly Gly Ser Trp Asp Leu Ala Val Gln Glu Arg Ala Ala Arg Ser Gln 515 520 525 Cys Thr Tyr Ser Asn Pro Glu Gly Thr Val Val Leu Ala Cys Asp Gln 530 535 540 Ala Gln Cys Arg Trp Leu Asn Val Gln Leu Ser Pro Trp Gln Gly Ser 545 550 555 560 Leu Gly Leu Gln Tyr Asn Ala Ser Gln Glu Trp Asp Leu Arg Ser Ser 565 570 575 Cys Gly Ser Leu Arg Leu Thr Val Ser Ile Glu Ala Arg Ala Ala Gly 580 585 590 Pro 328210PRTHomo sapiensmisc_feature(95)..(95)Xaa can be any naturally occurring amino acidmisc_feature(180)..(180)Xaa can be any naturally occurring amino acid 328Met Asp Asp Asp Asp Asn Lys Asp Asn Ala Ile Leu Glu Asn Asp Ser 1 5 10 15 Arg Thr Trp Ser Lys Asp Leu Gln Asn Val Asn Ile Thr Leu His Ile 20 25 30 Pro Phe Gln Pro Val Ala Ser Gln Leu Pro Arg Ile Phe Thr Ser Ile 35 40 45 Gly Glu Asp Tyr Asp Glu Pro Val Leu Pro Ser Ile Thr Thr Glu Met 50 55 60 Leu Lys Ser Val Val Val Cys Phe Asp Ala Gly Glu Leu Ile Thr Gln 65 70

75 80 Arg Glu Leu Val Ser Arg Gln Val Ser Asp Asn Leu Thr Glu Xaa Ala 85 90 95 Ala Thr Phe Arg Leu Ile Leu Asp Asp Val Ser Leu Thr Tyr Leu Thr 100 105 110 Phe Arg Lys Asp Phe Thr Glu Ala Val Gly Ala Lys Gln Val Ala Gln 115 120 125 Gln Glu Ala Glu Arg Ala Arg Phe Val Met Glu Lys Ala Lys Gln Gln 130 135 140 Lys Lys Ala Ala Ile Ile Ser Ala Glu Gly Asp Ser Lys Ala Ala Glu 145 150 155 160 Leu Ile Ala Asn Ser Leu Ala Thr Ala Gly Asp Gly Leu Ile Glu Leu 165 170 175 Arg Lys Leu Xaa Ala Ala Glu Asp Ile Ala Tyr Gln Leu Ser Arg Ser 180 185 190 Gln Asn Ile Thr Tyr Leu Pro Ala Gly Gln Ser Val Leu Leu Gln Leu 195 200 205 Pro Gln 210 329374PRTHomo sapiens 329Met Ala Pro Ala Lys Asn Ser Gly Lys Lys Lys Met Asp His Ser Ala 1 5 10 15 Ile Asn Glu Val Met Thr Gln Glu Tyr Thr Asn Ile His Lys His Ile 20 25 30 His Arg Val Gly Phe Lys Lys His Val Pro Gln Ala Leu Lys Glu Ile 35 40 45 Arg Lys Phe Cys Asn Glu Gly Asp Gly Asn Ser Arg Ser Thr Glu Gln 50 55 60 Val Leu Leu Gln Gly Ala Thr Met Ala Asp Lys Ser Lys Phe Ile Glu 65 70 75 80 Tyr Ile Asp Glu Ala Leu Glu Lys Ser Lys Glu Thr Ala Leu Ser His 85 90 95 Leu Phe Phe Thr Tyr Gln Gly Ile Pro Tyr Pro Ile Thr Met Cys Thr 100 105 110 Ser Glu Thr Phe Gln Ala Leu Asp Thr Phe Glu Ala Arg His Asp Asp 115 120 125 Ile Val Leu Ala Ser Tyr Pro Lys Cys Gly Ser Asn Trp Ile Leu His 130 135 140 Ile Val Ser Glu Leu Ile Tyr Ala Val Ser Lys Lys Lys Tyr Lys Tyr 145 150 155 160 Pro Glu Phe Pro Val Leu Glu Cys Gly Asp Ser Glu Lys Tyr Gln Arg 165 170 175 Met Lys Gly Phe Pro Ser Pro Arg Ile Leu Ala Thr His Leu His Tyr 180 185 190 Asp Lys Leu Pro Gly Ser Ile Phe Glu Asn Lys Ala Lys Ile Leu Val 195 200 205 Ile Phe Arg Asn Pro Lys Asp Thr Ala Val Ser Phe Leu His Phe His 210 215 220 Asn Asp Val Pro Asp Ile Pro Ser Tyr Gly Ser Trp Asp Glu Phe Phe 225 230 235 240 Arg Gln Phe Met Lys Gly Gln Val Ser Trp Gly Arg Tyr Phe Asp Phe 245 250 255 Ala Ile Asn Trp Asn Lys His Leu Asp Gly Asp Asn Val Lys Phe Ile 260 265 270 Leu Tyr Glu Asp Leu Lys Glu Asn Leu Ala Ala Gly Ile Lys Gln Ile 275 280 285 Ala Glu Phe Leu Gly Phe Phe Leu Thr Gly Glu Gln Ile Gln Thr Ile 290 295 300 Ser Val Gln Ser Thr Phe Gln Ala Met Arg Ala Lys Ser Gln Asp Thr 305 310 315 320 His Gly Ala Val Gly Pro Phe Leu Phe Arg Lys Gly Glu Val Gly Asp 325 330 335 Trp Lys Asn Leu Phe Ser Glu Ile Gln Asn Gln Glu Met Asp Glu Lys 340 345 350 Phe Lys Glu Cys Leu Ala Gly Thr Ser Leu Gly Ala Lys Leu Lys Tyr 355 360 365 Glu Ser Tyr Cys Gln Gly 370 330676PRTHomo sapiens 330Met Arg Val Leu Gly Gly Arg Cys Gly Ala Pro Leu Ala Cys Leu Leu 1 5 10 15 Leu Val Leu Pro Val Ser Glu Ala Asn Leu Leu Ser Lys Gln Gln Ala 20 25 30 Ser Gln Val Leu Val Arg Lys Arg Arg Ala Asn Ser Leu Leu Glu Glu 35 40 45 Thr Lys Gln Gly Asn Leu Glu Arg Glu Cys Ile Glu Glu Leu Cys Asn 50 55 60 Lys Glu Glu Ala Arg Glu Val Phe Glu Asn Asp Pro Glu Thr Asp Tyr 65 70 75 80 Phe Tyr Pro Lys Tyr Leu Val Cys Leu Arg Ser Phe Gln Thr Gly Leu 85 90 95 Phe Thr Ala Ala Arg Gln Ser Thr Asn Ala Tyr Pro Asp Leu Arg Ser 100 105 110 Cys Val Asn Ala Ile Pro Asp Gln Cys Ser Pro Leu Pro Cys Asn Glu 115 120 125 Asp Gly Tyr Met Ser Cys Lys Asp Gly Lys Ala Ser Phe Thr Cys Thr 130 135 140 Cys Lys Pro Gly Trp Gln Gly Glu Lys Cys Glu Phe Asp Ile Asn Glu 145 150 155 160 Cys Lys Asp Pro Ser Asn Ile Asn Gly Gly Cys Ser Gln Ile Cys Asp 165 170 175 Asn Thr Pro Gly Ser Tyr His Cys Ser Cys Lys Asn Gly Phe Val Met 180 185 190 Leu Ser Asn Lys Lys Asp Cys Lys Asp Val Asp Glu Cys Ser Leu Lys 195 200 205 Pro Ser Ile Cys Gly Thr Ala Val Cys Lys Asn Ile Pro Gly Asp Phe 210 215 220 Glu Cys Glu Cys Pro Glu Gly Tyr Arg Tyr Asn Leu Lys Ser Lys Ser 225 230 235 240 Cys Glu Asp Ile Asp Glu Cys Ser Glu Asn Met Cys Ala Gln Leu Cys 245 250 255 Val Asn Tyr Pro Gly Gly Tyr Thr Cys Tyr Cys Asp Gly Lys Lys Gly 260 265 270 Phe Lys Leu Ala Gln Asp Gln Lys Ser Cys Glu Val Val Ser Val Cys 275 280 285 Leu Pro Leu Asn Leu Asp Thr Lys Tyr Glu Leu Leu Tyr Leu Ala Glu 290 295 300 Gln Phe Ala Gly Val Val Leu Tyr Leu Lys Phe Arg Leu Pro Glu Ile 305 310 315 320 Ser Arg Phe Ser Ala Glu Phe Asp Phe Arg Thr Tyr Asp Ser Glu Gly 325 330 335 Val Ile Leu Tyr Ala Glu Ser Ile Asp His Ser Ala Trp Leu Leu Ile 340 345 350 Ala Leu Arg Gly Gly Lys Ile Glu Val Gln Leu Lys Asn Glu His Thr 355 360 365 Ser Lys Ile Thr Thr Gly Gly Asp Val Ile Asn Asn Gly Leu Trp Asn 370 375 380 Met Val Ser Val Glu Glu Leu Glu His Ser Ile Ser Ile Lys Ile Ala 385 390 395 400 Lys Glu Ala Val Met Asp Ile Asn Lys Pro Gly Pro Leu Phe Lys Pro 405 410 415 Glu Asn Gly Leu Leu Glu Thr Lys Val Tyr Phe Ala Gly Phe Pro Arg 420 425 430 Lys Val Glu Ser Glu Leu Ile Lys Pro Ile Asn Pro Arg Leu Asp Gly 435 440 445 Cys Ile Arg Ser Trp Asn Leu Met Lys Gln Gly Ala Ser Gly Ile Lys 450 455 460 Glu Ile Ile Gln Glu Lys Gln Asn Lys His Cys Leu Val Thr Val Glu 465 470 475 480 Lys Gly Ser Tyr Tyr Pro Gly Ser Gly Ile Ala Gln Phe His Ile Asp 485 490 495 Tyr Asn Asn Val Ser Ser Ala Glu Gly Trp His Val Asn Val Thr Leu 500 505 510 Asn Ile Arg Pro Ser Thr Gly Thr Gly Val Met Leu Ala Leu Val Ser 515 520 525 Gly Asn Asn Thr Val Pro Phe Ala Val Ser Leu Val Asp Ser Thr Ser 530 535 540 Glu Lys Ser Gln Asp Ile Leu Leu Ser Val Glu Asn Thr Val Ile Tyr 545 550 555 560 Arg Ile Gln Ala Leu Ser Leu Cys Ser Asp Gln Gln Ser His Leu Glu 565 570 575 Phe Arg Val Asn Arg Asn Asn Leu Glu Leu Ser Thr Pro Leu Lys Ile 580 585 590 Glu Thr Ile Ser His Glu Asp Leu Gln Arg Gln Leu Ala Val Leu Asp 595 600 605 Lys Ala Met Lys Ala Lys Val Ala Thr Tyr Leu Gly Gly Leu Pro Asp 610 615 620 Val Pro Phe Ser Ala Thr Pro Val Asn Ala Phe Tyr Asn Gly Cys Met 625 630 635 640 Glu Val Asn Ile Asn Gly Val Gln Leu Asp Leu Asp Glu Ala Ile Ser 645 650 655 Lys His Asn Asp Ile Arg Ala His Ser Cys Pro Ser Val Trp Lys Lys 660 665 670 Thr Lys Asn Ser 675 331747PRTHomo sapiens 331Met Arg Arg Cys Asn Ser Gly Ser Gly Pro Pro Pro Ser Leu Leu Leu 1 5 10 15 Leu Leu Leu Trp Leu Leu Ala Val Pro Gly Ala Asn Ala Ala Pro Arg 20 25 30 Ser Ala Leu Tyr Ser Pro Ser Asp Pro Leu Thr Leu Leu Gln Ala Asp 35 40 45 Thr Val Arg Gly Ala Val Leu Gly Ser Arg Ser Ala Trp Ala Val Glu 50 55 60 Phe Phe Ala Ser Trp Cys Gly His Cys Ile Ala Phe Ala Pro Thr Trp 65 70 75 80 Lys Ala Leu Ala Glu Asp Val Lys Ala Trp Arg Pro Ala Leu Tyr Leu 85 90 95 Ala Ala Leu Asp Cys Ala Glu Glu Thr Asn Ser Ala Val Cys Arg Asp 100 105 110 Phe Asn Ile Pro Gly Phe Pro Thr Val Arg Phe Phe Lys Ala Phe Thr 115 120 125 Lys Asn Gly Ser Gly Ala Val Phe Pro Val Ala Gly Ala Asp Val Gln 130 135 140 Thr Leu Arg Glu Arg Leu Ile Asp Ala Leu Glu Ser His His Asp Thr 145 150 155 160 Trp Pro Pro Ala Cys Pro Pro Leu Glu Pro Ala Lys Leu Glu Glu Ile 165 170 175 Asp Gly Phe Phe Ala Arg Asn Asn Glu Glu Tyr Leu Ala Leu Ile Phe 180 185 190 Glu Lys Gly Gly Ser Tyr Leu Gly Arg Glu Val Ala Leu Asp Leu Ser 195 200 205 Gln His Lys Gly Val Ala Val Arg Arg Val Leu Asn Thr Glu Ala Asn 210 215 220 Val Val Arg Lys Phe Gly Val Thr Asp Phe Pro Ser Cys Tyr Leu Leu 225 230 235 240 Phe Arg Asn Gly Ser Val Ser Arg Val Pro Val Leu Met Glu Ser Arg 245 250 255 Ser Phe Tyr Thr Ala Tyr Leu Gln Arg Leu Ser Gly Leu Thr Arg Glu 260 265 270 Ala Ala Gln Thr Thr Val Ala Pro Thr Thr Ala Asn Lys Ile Ala Pro 275 280 285 Thr Val Trp Lys Leu Ala Asp Arg Ser Lys Ile Tyr Met Ala Asp Leu 290 295 300 Glu Ser Ala Leu His Tyr Ile Leu Arg Ile Glu Val Gly Arg Phe Pro 305 310 315 320 Val Leu Glu Gly Gln Arg Leu Val Ala Leu Lys Lys Phe Val Ala Val 325 330 335 Leu Ala Lys Tyr Phe Pro Gly Arg Pro Leu Val Gln Asn Phe Leu His 340 345 350 Ser Val Asn Glu Trp Leu Lys Arg Gln Lys Arg Asn Lys Ile Pro Tyr 355 360 365 Ser Phe Phe Lys Thr Ala Leu Asp Asp Arg Lys Glu Gly Ala Val Leu 370 375 380 Ala Lys Lys Val Asn Trp Ile Gly Cys Gln Gly Ser Glu Pro His Phe 385 390 395 400 Arg Gly Phe Pro Cys Ser Leu Trp Val Leu Phe His Phe Leu Thr Val 405 410 415 Gln Ala Ala Arg Gln Asn Val Asp His Ser Gln Glu Ala Ala Lys Ala 420 425 430 Lys Glu Val Leu Pro Ala Ile Arg Gly Tyr Val His Tyr Phe Phe Gly 435 440 445 Cys Arg Asp Cys Ala Ser His Phe Glu Gln Met Ala Ala Ala Ser Met 450 455 460 His Arg Val Gly Ser Pro Asn Ala Ala Val Leu Trp Leu Trp Ser Ser 465 470 475 480 His Asn Arg Val Asn Ala Arg Leu Ala Gly Ala Pro Ser Glu Asp Pro 485 490 495 Gln Phe Pro Lys Val Gln Trp Pro Pro Arg Glu Leu Cys Ser Ala Cys 500 505 510 His Asn Glu Arg Leu Asp Val Pro Val Trp Asp Val Glu Ala Thr Leu 515 520 525 Asn Phe Leu Lys Ala His Phe Ser Pro Ser Asn Ile Ile Leu Asp Phe 530 535 540 Pro Ala Ala Gly Ser Ala Ala Arg Arg Asp Val Gln Asn Val Ala Ala 545 550 555 560 Ala Pro Glu Leu Ala Met Gly Ala Leu Glu Leu Glu Ser Arg Asn Ser 565 570 575 Thr Leu Asp Pro Gly Lys Pro Glu Met Met Lys Ser Pro Thr Asn Thr 580 585 590 Thr Pro His Val Pro Ala Glu Gly Pro Glu Ala Ser Arg Pro Pro Lys 595 600 605 Leu His Pro Gly Leu Arg Ala Ala Pro Gly Gln Glu Pro Pro Glu His 610 615 620 Met Ala Glu Leu Gln Arg Asn Glu Gln Glu Gln Pro Leu Gly Gln Trp 625 630 635 640 His Leu Ser Lys Arg Asp Thr Gly Ala Ala Leu Leu Ala Glu Ser Arg 645 650 655 Ala Glu Lys Asn Arg Leu Trp Gly Pro Leu Glu Val Arg Arg Val Gly 660 665 670 Arg Ser Ser Lys Gln Leu Val Asp Ile Pro Glu Gly Gln Leu Glu Ala 675 680 685 Arg Ala Gly Arg Gly Arg Gly Gln Trp Leu Gln Val Leu Gly Gly Gly 690 695 700 Phe Ser Tyr Leu Asp Ile Ser Leu Cys Val Gly Leu Tyr Ser Leu Ser 705 710 715 720 Phe Met Gly Leu Leu Ala Met Tyr Thr Tyr Phe Gln Ala Lys Ile Arg 725 730 735 Ala Leu Lys Gly His Ala Gly His Pro Ala Ala 740 745 332199PRTHomo sapiens 332Met Lys Trp Val Trp Ala Leu Leu Leu Leu Ala Ala Trp Ala Ala Ala 1 5 10 15 Glu Arg Asp Cys Arg Val Ser Ser Phe Arg Val Lys Glu Asn Phe Asp 20 25 30 Lys Ala Arg Phe Ser Gly Thr Trp Tyr Ala Met Ala Lys Lys Asp Pro 35 40 45 Glu Gly Leu Phe Leu Gln Asp Asn Ile Val Ala Glu Phe Ser Val Asp 50 55 60 Glu Thr Gly Gln Met Ser Ala Thr Ala Lys Gly Arg Val Arg Leu Leu 65 70 75 80 Asn Asn Trp Asp Val Cys Ala Asp Met Val Gly Thr Phe Thr Asp Thr 85 90 95 Glu Asp Pro Ala Lys Phe Lys Met Lys Tyr Trp Gly Val Ala Ser Phe 100 105 110 Leu Gln Lys Gly Asn Asp Asp His Trp Ile Val Asp Thr Asp Tyr Asp 115 120 125 Thr Tyr Ala Val Gln Tyr Ser Cys Arg Leu Leu Asn Leu Asp Gly Thr 130 135 140 Cys Ala Asp Ser Tyr Ser Phe Val Phe Ser Arg Asp Pro Asn Gly Leu 145 150 155 160 Pro Pro Glu Ala Gln Lys Ile Val Arg Gln Arg Gln Glu Glu Leu Cys 165 170 175 Leu Ala Arg Gln Tyr Arg Leu Ile Val His Asn Gly Tyr Cys Asp Gly 180 185 190 Arg Ser Glu Arg Asn Leu Leu 195 333418PRTHomo sapiens 333Met Pro Ser Ser Val Ser Trp Gly Ile Leu Leu Leu Ala Gly Leu Cys 1 5 10 15 Cys Leu Val Pro Val Ser Leu Ala Glu Asp Pro Gln Gly Asp Ala Ala 20 25 30 Gln Lys Thr Asp Thr Ser His His Asp Gln Asp His Pro Thr Phe Asn 35 40 45 Lys Ile Thr Pro Asn Leu Ala Glu Phe Ala Phe Ser Leu Tyr Arg Gln 50 55 60 Leu Ala His Gln Ser Asn Ser Thr Asn Ile Phe Phe Ser Pro Val Ser 65 70 75 80 Ile Ala Thr Ala Phe Ala Met Leu Ser Leu Gly Thr Lys Ala Asp Thr 85 90 95 His Asp Glu Ile Leu Glu Gly Leu Asn Phe Asn Leu Thr Glu Ile Pro 100 105 110 Glu Ala Gln Ile His Glu Gly Phe Gln Glu Leu Leu Arg Thr Leu Asn 115 120 125 Gln Pro Asp Ser Gln Leu Gln Leu Thr Thr Gly Asn Gly Leu Phe Leu 130 135 140 Ser Glu Gly Leu Lys Leu Val Asp Lys Phe Leu Glu Asp Val Lys Lys 145 150 155 160 Leu Tyr His Ser Glu

Ala Phe Thr Val Asn Phe Gly Asp Thr Glu Glu 165 170 175 Ala Lys Lys Gln Ile Asn Asp Tyr Val Glu Lys Gly Thr Gln Gly Lys 180 185 190 Ile Val Asp Leu Val Lys Glu Leu Asp Arg Asp Thr Val Phe Ala Leu 195 200 205 Val Asn Tyr Ile Phe Phe Lys Gly Lys Trp Glu Arg Pro Phe Glu Val 210 215 220 Lys Asp Thr Glu Glu Glu Asp Phe His Val Asp Gln Val Thr Thr Val 225 230 235 240 Lys Val Pro Met Met Lys Arg Leu Gly Met Phe Asn Ile Gln His Cys 245 250 255 Lys Lys Leu Ser Ser Trp Val Leu Leu Met Lys Tyr Leu Gly Asn Ala 260 265 270 Thr Ala Ile Phe Phe Leu Pro Asp Glu Gly Lys Leu Gln His Leu Glu 275 280 285 Asn Glu Leu Thr His Asp Ile Ile Thr Lys Phe Leu Glu Asn Glu Asp 290 295 300 Arg Arg Ser Ala Ser Leu His Leu Pro Lys Leu Ser Ile Thr Gly Thr 305 310 315 320 Tyr Asp Leu Lys Ser Val Leu Gly Gln Leu Gly Ile Thr Lys Val Phe 325 330 335 Ser Asn Gly Ala Asp Leu Ser Gly Val Thr Glu Glu Ala Pro Leu Lys 340 345 350 Leu Ser Lys Ala Val His Lys Ala Val Leu Thr Ile Asp Glu Lys Gly 355 360 365 Thr Glu Ala Ala Gly Ala Met Phe Leu Glu Ala Ile Pro Met Ser Ile 370 375 380 Pro Pro Glu Val Lys Phe Asn Lys Pro Phe Val Phe Leu Met Ile Asp 385 390 395 400 Gln Asn Thr Lys Ser Pro Leu Phe Met Gly Lys Val Val Asn Pro Thr 405 410 415 Gln Lys 334415PRTHomo sapiens 334Met Ser Pro Phe Leu Tyr Leu Val Leu Leu Val Leu Gly Leu His Ala 1 5 10 15 Thr Ile His Cys Ala Ser Pro Glu Gly Lys Val Thr Ala Cys His Ser 20 25 30 Ser Gln Pro Asn Ala Thr Leu Tyr Lys Met Ser Ser Ile Asn Ala Asp 35 40 45 Phe Ala Phe Asn Leu Tyr Arg Arg Phe Thr Val Glu Thr Pro Asp Lys 50 55 60 Asn Ile Phe Phe Ser Pro Val Ser Ile Ser Ala Ala Leu Val Met Leu 65 70 75 80 Ser Phe Gly Ala Cys Cys Ser Thr Gln Thr Glu Ile Val Glu Thr Leu 85 90 95 Gly Phe Asn Leu Thr Asp Thr Pro Met Val Glu Ile Gln His Gly Phe 100 105 110 Gln His Leu Ile Cys Ser Leu Asn Phe Pro Lys Lys Glu Leu Glu Leu 115 120 125 Gln Ile Gly Asn Ala Leu Phe Ile Gly Lys His Leu Lys Pro Leu Ala 130 135 140 Lys Phe Leu Asn Asp Val Lys Thr Leu Tyr Glu Thr Glu Val Phe Ser 145 150 155 160 Thr Asp Phe Ser Asn Ile Ser Ala Ala Lys Gln Glu Ile Asn Ser His 165 170 175 Val Glu Met Gln Thr Lys Gly Lys Val Val Gly Leu Ile Gln Asp Leu 180 185 190 Lys Pro Asn Thr Thr Met Val Leu Val Asn Tyr Ile His Phe Lys Ala 195 200 205 Gln Trp Ala Asn Pro Phe Asp Pro Ser Lys Thr Glu Asp Ser Ser Ser 210 215 220 Phe Leu Ile Asp Lys Thr Thr Thr Val Gln Val Pro Met Met His Gln 225 230 235 240 Met Glu Gln Tyr Tyr His Leu Val Asp Met Glu Leu Asn Cys Thr Val 245 250 255 Leu Gln Met Asp Tyr Ser Lys Asn Ala Leu Ala Leu Phe Val Leu Pro 260 265 270 Lys Glu Gly Gln Met Glu Ser Val Glu Ala Ala Met Ser Ser Lys Thr 275 280 285 Leu Lys Lys Trp Asn Arg Leu Leu Gln Lys Gly Trp Val Asp Leu Phe 290 295 300 Val Pro Lys Phe Ser Ile Ser Ala Thr Tyr Asp Leu Gly Ala Thr Leu 305 310 315 320 Leu Lys Met Gly Ile Gln His Ala Tyr Ser Glu Asn Ala Asp Phe Ser 325 330 335 Gly Leu Thr Glu Asp Asn Gly Leu Lys Leu Ser Asn Ala Ala His Lys 340 345 350 Ala Val Leu His Ile Gly Glu Lys Gly Thr Glu Ala Ala Ala Val Pro 355 360 365 Glu Val Glu Leu Ser Asp Gln Pro Glu Asn Thr Phe Leu His Pro Ile 370 375 380 Ile Gln Ile Asp Arg Ser Phe Met Leu Leu Ile Leu Glu Arg Ser Thr 385 390 395 400 Arg Ser Ile Leu Phe Leu Gly Lys Val Val Asn Pro Thr Glu Ala 405 410 415 335464PRTHomo sapiens 335Met Tyr Ser Asn Val Ile Gly Thr Val Thr Ser Gly Lys Arg Lys Val 1 5 10 15 Tyr Leu Leu Ser Leu Leu Leu Ile Gly Phe Trp Asp Cys Val Thr Cys 20 25 30 His Gly Ser Pro Val Asp Ile Cys Thr Ala Lys Pro Arg Asp Ile Pro 35 40 45 Met Asn Pro Met Cys Ile Tyr Arg Ser Pro Glu Lys Lys Ala Thr Glu 50 55 60 Asp Glu Gly Ser Glu Gln Lys Ile Pro Glu Ala Thr Asn Arg Arg Val 65 70 75 80 Trp Glu Leu Ser Lys Ala Asn Ser Arg Phe Ala Thr Thr Phe Tyr Gln 85 90 95 His Leu Ala Asp Ser Lys Asn Asp Asn Asp Asn Ile Phe Leu Ser Pro 100 105 110 Leu Ser Ile Ser Thr Ala Phe Ala Met Thr Lys Leu Gly Ala Cys Asn 115 120 125 Asp Thr Leu Gln Gln Leu Met Glu Val Phe Lys Phe Asp Thr Ile Ser 130 135 140 Glu Lys Thr Ser Asp Gln Ile His Phe Phe Phe Ala Lys Leu Asn Cys 145 150 155 160 Arg Leu Tyr Arg Lys Ala Asn Lys Ser Ser Lys Leu Val Ser Ala Asn 165 170 175 Arg Leu Phe Gly Asp Lys Ser Leu Thr Phe Asn Glu Thr Tyr Gln Asp 180 185 190 Ile Ser Glu Leu Val Tyr Gly Ala Lys Leu Gln Pro Leu Asp Phe Lys 195 200 205 Glu Asn Ala Glu Gln Ser Arg Ala Ala Ile Asn Lys Trp Val Ser Asn 210 215 220 Lys Thr Glu Gly Arg Ile Thr Asp Val Ile Pro Ser Glu Ala Ile Asn 225 230 235 240 Glu Leu Thr Val Leu Val Leu Val Asn Thr Ile Tyr Phe Lys Gly Leu 245 250 255 Trp Lys Ser Lys Phe Ser Pro Glu Asn Thr Arg Lys Glu Leu Phe Tyr 260 265 270 Lys Ala Asp Gly Glu Ser Cys Ser Ala Ser Met Met Tyr Gln Glu Gly 275 280 285 Lys Phe Arg Tyr Arg Arg Val Ala Glu Gly Thr Gln Val Leu Glu Leu 290 295 300 Pro Phe Lys Gly Asp Asp Ile Thr Met Val Leu Ile Leu Pro Lys Pro 305 310 315 320 Glu Lys Ser Leu Ala Lys Val Glu Lys Glu Leu Thr Pro Glu Val Leu 325 330 335 Gln Glu Trp Leu Asp Glu Leu Glu Glu Met Met Leu Val Val His Met 340 345 350 Pro Arg Phe Arg Ile Glu Asp Gly Phe Ser Leu Lys Glu Gln Leu Gln 355 360 365 Asp Met Gly Leu Val Asp Leu Phe Ser Pro Glu Lys Ser Lys Leu Pro 370 375 380 Gly Ile Val Ala Glu Gly Arg Asp Asp Leu Tyr Val Ser Asp Ala Phe 385 390 395 400 His Lys Ala Phe Leu Glu Val Asn Glu Glu Gly Ser Glu Ala Ala Ala 405 410 415 Ser Thr Ala Val Val Ile Ala Gly Arg Ser Leu Asn Pro Asn Arg Val 420 425 430 Thr Phe Lys Ala Asn Arg Pro Phe Leu Val Phe Ile Arg Glu Val Pro 435 440 445 Leu Asn Thr Ile Ile Phe Met Gly Arg Val Ala Asn Pro Cys Val Lys 450 455 460 336418PRTHomo sapiens 336Met Gln Ala Leu Val Leu Leu Leu Cys Ile Gly Ala Leu Leu Gly His 1 5 10 15 Ser Ser Cys Gln Asn Pro Ala Ser Pro Pro Glu Glu Gly Ser Pro Asp 20 25 30 Pro Asp Ser Thr Gly Ala Leu Val Glu Glu Glu Asp Pro Phe Phe Lys 35 40 45 Val Pro Val Asn Lys Leu Ala Ala Ala Val Ser Asn Phe Gly Tyr Asp 50 55 60 Leu Tyr Arg Val Arg Ser Ser Thr Ser Pro Thr Thr Asn Val Leu Leu 65 70 75 80 Ser Pro Leu Ser Val Ala Thr Ala Leu Ser Ala Leu Ser Leu Gly Ala 85 90 95 Glu Gln Arg Thr Glu Ser Ile Ile His Arg Ala Leu Tyr Tyr Asp Leu 100 105 110 Ile Ser Ser Pro Asp Ile His Gly Thr Tyr Lys Glu Leu Leu Asp Thr 115 120 125 Val Thr Ala Pro Gln Lys Asn Leu Lys Ser Ala Ser Arg Ile Val Phe 130 135 140 Glu Lys Lys Leu Arg Ile Lys Ser Ser Phe Val Ala Pro Leu Glu Lys 145 150 155 160 Ser Tyr Gly Thr Arg Pro Arg Val Leu Thr Gly Asn Pro Arg Leu Asp 165 170 175 Leu Gln Glu Ile Asn Asn Trp Val Gln Ala Gln Met Lys Gly Lys Leu 180 185 190 Ala Arg Ser Thr Lys Glu Ile Pro Asp Glu Ile Ser Ile Leu Leu Leu 195 200 205 Gly Val Ala His Phe Lys Gly Gln Trp Val Thr Lys Phe Asp Ser Arg 210 215 220 Lys Thr Ser Leu Glu Asp Phe Tyr Leu Asp Glu Glu Arg Thr Val Arg 225 230 235 240 Val Pro Met Met Ser Asp Pro Lys Ala Val Leu Arg Tyr Gly Leu Asp 245 250 255 Ser Asp Leu Ser Cys Lys Ile Ala Gln Leu Pro Leu Thr Gly Ser Met 260 265 270 Ser Ile Ile Phe Phe Leu Pro Leu Lys Val Thr Gln Asn Leu Thr Leu 275 280 285 Ile Glu Glu Ser Leu Thr Ser Glu Phe Ile His Asp Ile Asp Arg Glu 290 295 300 Leu Lys Thr Val Gln Ala Val Leu Thr Val Pro Lys Leu Lys Leu Ser 305 310 315 320 Tyr Glu Gly Glu Val Thr Lys Ser Leu Gln Glu Met Lys Leu Gln Ser 325 330 335 Leu Phe Asp Ser Pro Asp Phe Ser Lys Ile Thr Gly Lys Pro Ile Lys 340 345 350 Leu Thr Gln Val Glu His Arg Ala Gly Phe Glu Trp Asn Glu Asp Gly 355 360 365 Ala Gly Thr Thr Pro Ser Pro Gly Leu Gln Pro Ala His Leu Thr Phe 370 375 380 Pro Leu Asp Tyr His Leu Asn Gln Pro Phe Ile Phe Val Leu Arg Asp 385 390 395 400 Thr Asp Thr Gly Ala Leu Leu Phe Ile Gly Lys Ile Leu Asp Pro Arg 405 410 415 Gly Pro 337223PRTHomo sapiens 337Met Asn Lys Pro Leu Leu Trp Ile Ser Val Leu Thr Ser Leu Leu Glu 1 5 10 15 Ala Phe Ala His Thr Asp Leu Ser Gly Lys Val Phe Val Phe Pro Arg 20 25 30 Glu Ser Val Thr Asp His Val Asn Leu Ile Thr Pro Leu Glu Lys Pro 35 40 45 Leu Gln Asn Phe Thr Leu Cys Phe Arg Ala Tyr Ser Asp Leu Ser Arg 50 55 60 Ala Tyr Ser Leu Phe Ser Tyr Asn Thr Gln Gly Arg Asp Asn Glu Leu 65 70 75 80 Leu Val Tyr Lys Glu Arg Val Gly Glu Tyr Ser Leu Tyr Ile Gly Arg 85 90 95 His Lys Val Thr Ser Lys Val Ile Glu Lys Phe Pro Ala Pro Val His 100 105 110 Ile Cys Val Ser Trp Glu Ser Ser Ser Gly Ile Ala Glu Phe Trp Ile 115 120 125 Asn Gly Thr Pro Leu Val Lys Lys Gly Leu Arg Gln Gly Tyr Phe Val 130 135 140 Glu Ala Gln Pro Lys Ile Val Leu Gly Gln Glu Gln Asp Ser Tyr Gly 145 150 155 160 Gly Lys Phe Asp Arg Ser Gln Ser Phe Val Gly Glu Ile Gly Asp Leu 165 170 175 Tyr Met Trp Asp Ser Val Leu Pro Pro Glu Asn Ile Leu Ser Ala Tyr 180 185 190 Gln Gly Thr Pro Leu Pro Ala Asn Ile Leu Asp Trp Gln Ala Leu Asn 195 200 205 Tyr Glu Ile Arg Gly Tyr Val Ile Ile Lys Pro Leu Val Trp Val 210 215 220 338402PRTHomo sapiens 338Met Glu Ser Arg Gly Pro Leu Ala Thr Ser Arg Leu Leu Leu Leu Leu 1 5 10 15 Leu Leu Leu Leu Leu Arg His Thr Arg Gln Gly Trp Ala Leu Arg Pro 20 25 30 Val Leu Pro Thr Gln Ser Ala His Asp Pro Pro Ala Val His Leu Ser 35 40 45 Asn Gly Pro Gly Gln Glu Pro Ile Ala Val Met Thr Phe Asp Leu Thr 50 55 60 Lys Ile Thr Lys Thr Ser Ser Ser Phe Glu Val Arg Thr Trp Asp Pro 65 70 75 80 Glu Gly Val Ile Phe Tyr Gly Asp Thr Asn Pro Lys Asp Asp Trp Phe 85 90 95 Met Leu Gly Leu Arg Asp Gly Arg Pro Glu Ile Gln Leu His Asn His 100 105 110 Trp Ala Gln Leu Thr Val Gly Ala Gly Pro Arg Leu Asp Asp Gly Arg 115 120 125 Trp His Gln Val Glu Val Lys Met Glu Gly Asp Ser Val Leu Leu Glu 130 135 140 Val Asp Gly Glu Glu Val Leu Arg Leu Arg Gln Val Ser Gly Pro Leu 145 150 155 160 Thr Ser Lys Arg His Pro Ile Met Arg Ile Ala Leu Gly Gly Leu Leu 165 170 175 Phe Pro Ala Ser Asn Leu Arg Leu Pro Leu Val Pro Ala Leu Asp Gly 180 185 190 Cys Leu Arg Arg Asp Ser Trp Leu Asp Lys Gln Ala Glu Ile Ser Ala 195 200 205 Ser Ala Pro Thr Ser Leu Arg Ser Cys Asp Val Glu Ser Asn Pro Gly 210 215 220 Ile Phe Leu Pro Pro Gly Thr Gln Ala Glu Phe Asn Leu Arg Asp Ile 225 230 235 240 Pro Gln Pro His Ala Glu Pro Trp Ala Phe Ser Leu Asp Leu Gly Leu 245 250 255 Lys Gln Ala Ala Gly Ser Gly His Leu Leu Ala Leu Gly Thr Pro Glu 260 265 270 Asn Pro Ser Trp Leu Ser Leu His Leu Gln Asp Gln Lys Val Val Leu 275 280 285 Ser Ser Gly Ser Gly Pro Gly Leu Asp Leu Pro Leu Val Leu Gly Leu 290 295 300 Pro Leu Gln Leu Lys Leu Ser Met Ser Arg Val Val Leu Ser Gln Gly 305 310 315 320 Ser Lys Met Lys Ala Leu Ala Leu Pro Pro Leu Gly Leu Ala Pro Leu 325 330 335 Leu Asn Leu Trp Ala Lys Pro Gln Gly Arg Leu Phe Leu Gly Ala Leu 340 345 350 Pro Gly Glu Asp Ser Ser Thr Ser Phe Cys Leu Asn Gly Leu Trp Ala 355 360 365 Gln Gly Gln Arg Leu Asp Val Asp Gln Ala Leu Asn Arg Ser His Glu 370 375 380 Ile Trp Thr His Ser Cys Pro Gln Ser Pro Gly Asn Gly Thr Asp Ala 385 390 395 400 Ser His 339248PRTHomo sapiens 339Met Ser Leu Phe Pro Ser Leu Pro Leu Leu Leu Leu Ser Met Val Ala 1 5 10 15 Ala Ser Tyr Ser Glu Thr Val Thr Cys Glu Asp Ala Gln Lys Thr Cys 20 25 30 Pro Ala Val Ile Ala Cys Ser Ser Pro Gly Ile Asn Gly Phe Pro Gly 35 40 45 Lys Asp Gly Arg Asp Gly Thr Lys Gly Glu Lys Gly Glu Pro Gly Gln 50 55 60 Gly Leu Arg Gly Leu Gln Gly Pro Pro Gly Lys Leu Gly Pro Pro Gly 65 70 75 80 Asn Pro Gly Pro Ser Gly Ser Pro Gly Pro Lys Gly Gln Lys Gly Asp 85 90 95 Pro Gly Lys Ser Pro Asp Gly Asp Ser Ser Leu Ala Ala Ser Glu Arg 100 105 110 Lys Ala

Leu Gln Thr Glu Met Ala Arg Ile Lys Lys Trp Leu Thr Phe 115 120 125 Ser Leu Gly Lys Gln Val Gly Asn Lys Phe Phe Leu Thr Asn Gly Glu 130 135 140 Ile Met Thr Phe Glu Lys Val Lys Ala Leu Cys Val Lys Phe Gln Ala 145 150 155 160 Ser Val Ala Thr Pro Arg Asn Ala Ala Glu Asn Gly Ala Ile Gln Asn 165 170 175 Leu Ile Lys Glu Glu Ala Phe Leu Gly Ile Thr Asp Glu Lys Thr Glu 180 185 190 Gly Gln Phe Val Asp Leu Thr Gly Asn Arg Leu Thr Tyr Thr Asn Trp 195 200 205 Asn Glu Gly Glu Pro Asn Asn Ala Gly Ser Asp Glu Asp Cys Val Leu 210 215 220 Leu Leu Lys Asn Gly Gln Trp Asn Asp Val Pro Cys Ser Thr Ser His 225 230 235 240 Leu Ala Val Cys Glu Phe Pro Ile 245 3402349PRTHomo sapiens 340Met Ala Ala Val Leu Gln Gln Val Leu Glu Arg Thr Glu Leu Asn Lys 1 5 10 15 Leu Pro Lys Ser Val Gln Asn Lys Leu Glu Lys Phe Leu Ala Asp Gln 20 25 30 Gln Ser Glu Ile Asp Gly Leu Lys Gly Arg His Glu Lys Phe Lys Val 35 40 45 Glu Ser Glu Gln Gln Tyr Phe Glu Ile Glu Lys Arg Leu Ser His Ser 50 55 60 Gln Glu Arg Leu Val Asn Glu Thr Arg Glu Cys Gln Ser Leu Arg Leu 65 70 75 80 Glu Leu Glu Lys Leu Asn Asn Gln Leu Lys Ala Leu Thr Glu Lys Asn 85 90 95 Lys Glu Leu Glu Ile Ala Gln Asp Arg Asn Ile Ala Ile Gln Ser Gln 100 105 110 Phe Thr Arg Thr Lys Glu Glu Leu Glu Ala Glu Lys Arg Asp Leu Ile 115 120 125 Arg Thr Asn Glu Arg Leu Ser Gln Glu Leu Glu Tyr Leu Thr Glu Asp 130 135 140 Val Lys Arg Leu Asn Glu Lys Leu Lys Glu Ser Asn Thr Thr Lys Gly 145 150 155 160 Glu Leu Gln Leu Lys Leu Asp Glu Leu Gln Ala Ser Asp Val Ser Val 165 170 175 Lys Tyr Arg Glu Lys Arg Leu Glu Gln Glu Lys Glu Leu Leu His Ser 180 185 190 Gln Asn Thr Trp Leu Asn Thr Glu Leu Lys Thr Lys Thr Asp Glu Leu 195 200 205 Leu Ala Leu Gly Arg Glu Lys Gly Asn Glu Ile Leu Glu Leu Lys Cys 210 215 220 Asn Leu Glu Asn Lys Lys Glu Glu Val Ser Arg Leu Glu Glu Gln Met 225 230 235 240 Asn Gly Leu Lys Thr Ser Asn Glu His Leu Gln Lys His Val Glu Asp 245 250 255 Leu Leu Thr Lys Leu Lys Glu Ala Lys Glu Gln Gln Ala Ser Met Glu 260 265 270 Glu Lys Phe His Asn Glu Leu Asn Ala His Ile Lys Leu Ser Asn Leu 275 280 285 Tyr Lys Ser Ala Ala Asp Asp Ser Glu Ala Lys Ser Asn Glu Leu Thr 290 295 300 Arg Ala Val Glu Glu Leu His Lys Leu Leu Lys Glu Ala Gly Glu Ala 305 310 315 320 Asn Lys Ala Ile Gln Asp His Leu Leu Glu Val Glu Gln Ser Lys Asp 325 330 335 Gln Met Glu Lys Glu Met Leu Glu Lys Ile Gly Arg Leu Glu Lys Glu 340 345 350 Leu Glu Asn Ala Asn Asp Leu Leu Ser Ala Thr Lys Arg Lys Gly Ala 355 360 365 Ile Leu Ser Glu Glu Glu Leu Ala Ala Met Ser Pro Thr Ala Ala Ala 370 375 380 Val Ala Lys Ile Val Lys Pro Gly Met Lys Leu Thr Glu Leu Tyr Asn 385 390 395 400 Ala Tyr Val Glu Thr Gln Asp Gln Leu Leu Leu Glu Lys Leu Glu Asn 405 410 415 Lys Arg Ile Asn Lys Tyr Leu Asp Glu Ile Val Lys Glu Val Glu Ala 420 425 430 Lys Ala Pro Ile Leu Lys Arg Gln Arg Glu Glu Tyr Glu Arg Ala Gln 435 440 445 Lys Ala Val Ala Ser Leu Ser Val Lys Leu Glu Gln Ala Met Lys Glu 450 455 460 Ile Gln Arg Leu Gln Glu Asp Thr Asp Lys Ala Asn Lys Gln Ser Ser 465 470 475 480 Val Leu Glu Arg Asp Asn Arg Arg Met Glu Ile Gln Val Lys Asp Leu 485 490 495 Ser Gln Gln Ile Arg Val Leu Leu Met Glu Leu Glu Glu Ala Arg Gly 500 505 510 Asn His Val Ile Arg Asp Glu Glu Val Ser Ser Ala Asp Ile Ser Ser 515 520 525 Ser Ser Glu Val Ile Ser Gln His Leu Val Ser Tyr Arg Asn Ile Glu 530 535 540 Glu Leu Gln Gln Gln Asn Gln Arg Leu Leu Val Ala Leu Arg Glu Leu 545 550 555 560 Gly Glu Thr Arg Glu Arg Glu Glu Gln Glu Thr Thr Ser Ser Lys Ile 565 570 575 Thr Glu Leu Gln Leu Lys Leu Glu Ser Ala Leu Thr Glu Leu Glu Gln 580 585 590 Leu Arg Lys Ser Arg Gln His Gln Met Gln Leu Val Asp Ser Ile Val 595 600 605 Arg Gln Arg Asp Met Tyr Arg Ile Leu Leu Ser Gln Thr Thr Gly Val 610 615 620 Ala Ile Pro Leu His Ala Ser Ser Leu Asp Asp Val Ser Leu Ala Ser 625 630 635 640 Thr Pro Lys Arg Pro Ser Thr Ser Gln Thr Val Ser Thr Pro Ala Pro 645 650 655 Val Pro Val Ile Glu Ser Thr Glu Ala Ile Glu Ala Lys Ala Ala Leu 660 665 670 Lys Gln Leu Gln Glu Ile Phe Glu Asn Tyr Lys Lys Glu Lys Ala Glu 675 680 685 Asn Glu Lys Ile Gln Asn Glu Gln Leu Glu Lys Leu Gln Glu Gln Val 690 695 700 Thr Asp Leu Arg Ser Gln Asn Thr Lys Ile Ser Thr Gln Leu Asp Phe 705 710 715 720 Ala Ser Lys Arg Tyr Glu Met Leu Gln Asp Asn Val Glu Gly Tyr Arg 725 730 735 Arg Glu Ile Thr Ser Leu His Glu Arg Asn Gln Lys Leu Thr Ala Thr 740 745 750 Thr Gln Lys Gln Glu Gln Ile Ile Asn Thr Met Thr Gln Asp Leu Arg 755 760 765 Gly Ala Asn Glu Lys Leu Ala Val Ala Glu Val Arg Ala Glu Asn Leu 770 775 780 Lys Lys Glu Lys Glu Met Leu Lys Leu Ser Glu Val Arg Leu Ser Gln 785 790 795 800 Gln Arg Glu Ser Leu Leu Ala Glu Gln Arg Gly Gln Asn Leu Leu Leu 805 810 815 Thr Asn Leu Gln Thr Ile Gln Gly Ile Leu Glu Arg Ser Glu Thr Glu 820 825 830 Thr Lys Gln Arg Leu Ser Ser Gln Ile Glu Lys Leu Glu His Glu Ile 835 840 845 Ser His Leu Lys Lys Lys Leu Glu Asn Glu Val Glu Gln Arg His Thr 850 855 860 Leu Thr Arg Asn Leu Asp Val Gln Leu Leu Asp Thr Lys Arg Gln Leu 865 870 875 880 Asp Thr Glu Thr Asn Leu His Leu Asn Thr Lys Glu Leu Leu Lys Asn 885 890 895 Ala Gln Lys Glu Ile Ala Thr Leu Lys Gln His Leu Ser Asn Met Glu 900 905 910 Val Gln Val Ala Ser Gln Ser Ser Gln Arg Thr Gly Lys Gly Gln Pro 915 920 925 Ser Asn Lys Glu Asp Val Asp Asp Leu Val Ser Gln Leu Arg Gln Thr 930 935 940 Glu Glu Gln Val Asn Asp Leu Lys Glu Arg Leu Lys Thr Ser Thr Ser 945 950 955 960 Asn Val Glu Gln Tyr Gln Ala Met Val Thr Ser Leu Glu Glu Ser Leu 965 970 975 Asn Lys Glu Lys Gln Val Thr Glu Glu Val Arg Lys Asn Ile Glu Val 980 985 990 Arg Leu Lys Glu Ser Ala Glu Phe Gln Thr Gln Leu Glu Lys Lys Leu 995 1000 1005 Met Glu Val Glu Lys Glu Lys Gln Glu Leu Gln Asp Asp Lys Arg 1010 1015 1020 Arg Ala Ile Glu Ser Met Glu Gln Gln Leu Ser Glu Leu Lys Lys 1025 1030 1035 Thr Leu Ser Ser Val Gln Asn Glu Val Gln Glu Ala Leu Gln Arg 1040 1045 1050 Ala Ser Thr Ala Leu Ser Asn Glu Gln Gln Ala Arg Arg Asp Cys 1055 1060 1065 Gln Glu Gln Ala Lys Ile Ala Val Glu Ala Gln Asn Lys Tyr Glu 1070 1075 1080 Arg Glu Leu Met Leu His Ala Ala Asp Val Glu Ala Leu Gln Ala 1085 1090 1095 Ala Lys Glu Gln Val Ser Lys Met Ala Ser Val Arg Gln His Leu 1100 1105 1110 Glu Glu Thr Thr Gln Lys Ala Glu Ser Gln Leu Leu Glu Cys Lys 1115 1120 1125 Ala Ser Trp Glu Glu Arg Glu Arg Met Leu Lys Asp Glu Val Ser 1130 1135 1140 Lys Cys Val Cys Arg Cys Glu Asp Leu Glu Lys Gln Asn Arg Leu 1145 1150 1155 Leu His Asp Gln Ile Glu Lys Leu Ser Asp Lys Val Val Ala Ser 1160 1165 1170 Val Lys Glu Gly Val Gln Gly Pro Leu Asn Val Ser Leu Ser Glu 1175 1180 1185 Glu Gly Lys Ser Gln Glu Gln Ile Leu Glu Ile Leu Arg Phe Ile 1190 1195 1200 Arg Arg Glu Lys Glu Ile Ala Glu Thr Arg Phe Glu Val Ala Gln 1205 1210 1215 Val Glu Ser Leu Arg Tyr Arg Gln Arg Val Glu Leu Leu Glu Arg 1220 1225 1230 Glu Leu Gln Glu Leu Glu Asp Ser Leu Asn Ala Glu Arg Glu Lys 1235 1240 1245 Val Gln Val Thr Ala Lys Thr Met Ala Gln His Glu Glu Leu Met 1250 1255 1260 Lys Lys Thr Glu Thr Met Asn Val Val Met Glu Thr Asn Lys Met 1265 1270 1275 Leu Arg Glu Glu Lys Glu Arg Leu Glu Gln Asp Leu Gln Gln Met 1280 1285 1290 Gln Ala Lys Val Arg Lys Leu Glu Leu Asp Ile Leu Pro Leu Gln 1295 1300 1305 Glu Ala Asn Ala Glu Leu Ser Glu Lys Ser Gly Met Leu Gln Ala 1310 1315 1320 Glu Lys Lys Leu Leu Glu Glu Asp Val Lys Arg Trp Lys Ala Arg 1325 1330 1335 Asn Gln His Leu Val Ser Gln Gln Lys Asp Pro Asp Thr Glu Glu 1340 1345 1350 Tyr Arg Lys Leu Leu Ser Glu Lys Glu Val His Thr Lys Arg Ile 1355 1360 1365 Gln Gln Leu Thr Glu Glu Ile Gly Arg Leu Lys Ala Glu Ile Ala 1370 1375 1380 Arg Ser Asn Ala Ser Leu Thr Asn Asn Gln Asn Leu Ile Gln Ser 1385 1390 1395 Leu Lys Glu Asp Leu Asn Lys Val Arg Thr Glu Lys Glu Thr Ile 1400 1405 1410 Gln Lys Asp Leu Asp Ala Lys Ile Ile Asp Ile Gln Glu Lys Val 1415 1420 1425 Lys Thr Ile Thr Gln Val Lys Lys Ile Gly Arg Arg Tyr Lys Thr 1430 1435 1440 Gln Tyr Glu Glu Leu Lys Ala Gln Gln Asp Lys Val Met Glu Thr 1445 1450 1455 Ser Ala Gln Ser Ser Gly Asp His Gln Glu Gln His Val Ser Val 1460 1465 1470 Gln Glu Met Gln Glu Leu Lys Glu Thr Leu Asn Gln Ala Glu Thr 1475 1480 1485 Lys Ser Lys Ser Leu Glu Ser Gln Val Glu Asn Leu Gln Lys Thr 1490 1495 1500 Leu Ser Glu Lys Glu Thr Glu Ala Arg Asn Leu Gln Glu Gln Thr 1505 1510 1515 Val Gln Leu Gln Ser Glu Leu Ser Arg Leu Arg Gln Asp Leu Gln 1520 1525 1530 Asp Arg Thr Thr Gln Glu Glu Gln Leu Arg Gln Gln Ile Thr Glu 1535 1540 1545 Lys Glu Glu Lys Thr Arg Lys Ala Ile Val Ala Ala Lys Ser Lys 1550 1555 1560 Ile Ala His Leu Ala Gly Val Lys Asp Gln Leu Thr Lys Glu Asn 1565 1570 1575 Glu Glu Leu Lys Gln Arg Asn Gly Ala Leu Asp Gln Gln Lys Asp 1580 1585 1590 Glu Leu Asp Val Arg Ile Thr Ala Leu Lys Ser Gln Tyr Glu Gly 1595 1600 1605 Arg Ile Ser Arg Leu Glu Arg Glu Leu Arg Glu His Gln Glu Arg 1610 1615 1620 His Leu Glu Gln Arg Asp Glu Pro Gln Glu Pro Ser Asn Lys Val 1625 1630 1635 Pro Glu Gln Gln Arg Gln Ile Thr Leu Lys Thr Thr Pro Ala Ser 1640 1645 1650 Gly Glu Arg Gly Ile Ala Ser Thr Ser Asp Pro Pro Thr Ala Asn 1655 1660 1665 Ile Lys Pro Thr Pro Val Val Ser Thr Pro Ser Lys Val Thr Ala 1670 1675 1680 Ala Ala Met Ala Gly Asn Lys Ser Thr Pro Arg Ala Ser Ile Arg 1685 1690 1695 Pro Met Val Thr Pro Ala Thr Val Thr Asn Pro Thr Thr Thr Pro 1700 1705 1710 Thr Ala Thr Val Met Pro Thr Thr Gln Val Glu Ser Gln Glu Ala 1715 1720 1725 Met Gln Ser Glu Gly Pro Val Glu His Val Pro Val Phe Gly Ser 1730 1735 1740 Thr Ser Gly Ser Val Arg Ser Thr Ser Pro Asn Val Gln Pro Ser 1745 1750 1755 Ile Ser Gln Pro Ile Leu Thr Val Gln Gln Gln Thr Gln Ala Thr 1760 1765 1770 Ala Phe Val Gln Pro Thr Gln Gln Ser His Pro Gln Ile Glu Pro 1775 1780 1785 Ala Asn Gln Glu Leu Ser Ser Asn Ile Val Glu Val Val Gln Ser 1790 1795 1800 Ser Pro Val Glu Arg Pro Ser Thr Ser Thr Ala Val Phe Gly Thr 1805 1810 1815 Val Ser Ala Thr Pro Ser Ser Ser Leu Pro Lys Arg Thr Arg Glu 1820 1825 1830 Glu Glu Glu Asp Ser Thr Ile Glu Ala Ser Asp Gln Val Ser Asp 1835 1840 1845 Asp Thr Val Glu Met Pro Leu Pro Lys Lys Leu Lys Ser Val Thr 1850 1855 1860 Pro Val Gly Thr Glu Glu Glu Val Met Ala Glu Glu Ser Thr Asp 1865 1870 1875 Gly Glu Val Glu Thr Gln Val Tyr Asn Gln Asp Ser Gln Asp Ser 1880 1885 1890 Ile Gly Glu Gly Val Thr Gln Gly Asp Tyr Thr Pro Met Glu Asp 1895 1900 1905 Ser Glu Glu Thr Ser Gln Ser Leu Gln Ile Asp Leu Gly Pro Leu 1910 1915 1920 Gln Ser Asp Gln Gln Thr Thr Thr Ser Ser Gln Asp Gly Gln Gly 1925 1930 1935 Lys Gly Asp Asp Val Ile Val Ile Asp Ser Asp Asp Glu Glu Glu 1940 1945 1950 Asp Glu Glu Asp Asp Asp Asp Asp Glu Asp Asp Thr Gly Met Gly 1955 1960 1965 Asp Glu Gly Glu Asp Ser Asn Glu Gly Thr Gly Ser Ala Asp Gly 1970 1975 1980 Asn Asp Gly Tyr Glu Ala Asp Asp Ala Glu Gly Gly Asp Gly Thr 1985 1990 1995 Asp Pro Gly Thr Glu Thr Glu Glu Ser Met Gly Gly Gly Glu Gly 2000 2005 2010 Asn His Arg Ala Ala Asp Ser Gln Asn Ser Gly Glu Gly Asn Thr 2015 2020 2025 Gly Ala Ala Glu Ser Ser Phe Ser Gln Glu Val Ser Arg Glu Gln 2030 2035 2040 Gln Pro Ser Ser Ala Ser Glu Arg Gln Ala Pro Arg Ala Pro Gln 2045 2050 2055 Ser Pro Arg Arg Pro Pro His Pro Leu Pro Pro Arg Leu Thr Ile 2060 2065 2070 His Ala Pro Pro Gln Glu Leu Gly Pro Pro Val Gln Arg Ile Gln 2075 2080 2085 Met Thr Arg Arg Gln Ser Val Gly Arg Gly Leu Gln Leu Thr Pro 2090 2095 2100 Gly Ile Gly Gly Met Gln Gln His Phe Phe Asp Asp Glu Asp Arg 2105

2110 2115 Thr Val Pro Ser Thr Pro Thr Leu Val Val Pro His Arg Thr Asp 2120 2125 2130 Gly Phe Ala Glu Ala Ile His Ser Pro Gln Val Ala Gly Val Pro 2135 2140 2145 Arg Phe Arg Phe Gly Pro Pro Glu Asp Met Pro Gln Thr Ser Ser 2150 2155 2160 Ser His Ser Asp Leu Gly Gln Leu Ala Ser Gln Gly Gly Leu Gly 2165 2170 2175 Met Tyr Glu Thr Pro Leu Phe Leu Ala His Glu Glu Glu Ser Gly 2180 2185 2190 Gly Arg Ser Val Pro Thr Thr Pro Leu Gln Val Ala Ala Pro Val 2195 2200 2205 Thr Val Phe Thr Glu Ser Thr Thr Ser Asp Ala Ser Glu His Ala 2210 2215 2220 Ser Gln Ser Val Pro Met Val Thr Thr Ser Thr Gly Thr Leu Ser 2225 2230 2235 Thr Thr Asn Glu Thr Ala Thr Gly Asp Asp Gly Asp Glu Val Phe 2240 2245 2250 Val Glu Ala Glu Ser Glu Gly Ile Ser Ser Glu Ala Gly Leu Glu 2255 2260 2265 Ile Asp Ser Gln Gln Glu Glu Glu Pro Val Gln Ala Ser Asp Glu 2270 2275 2280 Ser Asp Leu Pro Ser Thr Ser Gln Asp Pro Pro Ser Ser Ser Ser 2285 2290 2295 Val Asp Thr Ser Ser Ser Gln Pro Lys Pro Phe Arg Arg Val Arg 2300 2305 2310 Leu Gln Thr Thr Leu Arg Gln Gly Val Arg Gly Arg Gln Phe Asn 2315 2320 2325 Arg Gln Arg Gly Val Ser His Ala Met Gly Gly Arg Gly Gly Ile 2330 2335 2340 Asn Arg Gly Asn Ile Asn 2345 3411090PRTHomo sapiens 341Met Ala Thr Leu Leu Ser His Pro Gln Gln Arg Pro Pro Phe Leu Arg 1 5 10 15 Gln Ala Ile Lys Ile Arg Arg Arg Arg Val Arg Asp Leu Gln Asp Pro 20 25 30 Pro Pro Gln Met Ala Pro Glu Ile Gln Pro Pro Ser His His Phe Ser 35 40 45 Pro Glu Gln Arg Ala Leu Leu Tyr Glu Asp Ala Leu Tyr Thr Val Leu 50 55 60 His Arg Leu Gly His Pro Glu Pro Asn His Val Thr Glu Ala Ser Glu 65 70 75 80 Leu Leu Arg Tyr Leu Gln Glu Ala Phe His Val Glu Pro Glu Glu His 85 90 95 Gln Gln Thr Leu Gln Arg Val Arg Glu Leu Glu Lys Pro Ile Phe Cys 100 105 110 Leu Lys Ala Thr Val Lys Gln Ala Lys Gly Ile Leu Gly Lys Asp Val 115 120 125 Ser Gly Phe Ser Asp Pro Tyr Cys Leu Leu Gly Ile Glu Gln Gly Val 130 135 140 Gly Val Pro Gly Gly Ser Pro Gly Ser Arg His Arg Gln Lys Ala Val 145 150 155 160 Val Arg His Thr Ile Pro Glu Glu Glu Thr His Arg Thr Gln Val Ile 165 170 175 Thr Gln Thr Leu Asn Pro Val Trp Asp Glu Thr Phe Ile Leu Glu Phe 180 185 190 Glu Asp Ile Thr Asn Ala Ser Phe His Leu Asp Met Trp Asp Leu Asp 195 200 205 Thr Val Glu Ser Val Arg Gln Lys Leu Gly Glu Leu Thr Asp Leu His 210 215 220 Gly Leu Arg Arg Ile Phe Lys Glu Ala Arg Lys Asp Lys Gly Gln Asp 225 230 235 240 Asp Phe Leu Gly Asn Val Val Leu Arg Leu Gln Asp Leu Arg Cys Arg 245 250 255 Glu Asp Gln Trp Tyr Pro Leu Glu Pro Arg Thr Glu Thr Tyr Pro Asp 260 265 270 Arg Gly Gln Cys His Leu Gln Phe Gln Leu Ile His Lys Arg Arg Ala 275 280 285 Thr Ser Ala Ser Arg Ser Gln Pro Ser Tyr Thr Val His Leu His Leu 290 295 300 Leu Gln Gln Leu Val Ser His Glu Val Thr Gln His Glu Ala Gly Ser 305 310 315 320 Thr Ser Trp Asp Gly Ser Leu Ser Pro Gln Ala Ala Thr Val Leu Phe 325 330 335 Leu His Ala Thr Gln Lys Asp Leu Ser Asp Phe His Gln Ser Met Ala 340 345 350 Gln Trp Leu Ala Tyr Ser Arg Leu Tyr Gln Ser Leu Glu Phe Pro Ser 355 360 365 Ser Cys Leu Leu His Pro Ile Thr Ser Ile Glu Tyr Gln Trp Ile Gln 370 375 380 Gly Arg Leu Lys Ala Glu Gln Gln Glu Glu Leu Ala Ala Ser Phe Ser 385 390 395 400 Ser Leu Leu Thr Tyr Gly Leu Ser Leu Ile Arg Arg Phe Arg Ser Val 405 410 415 Phe Pro Leu Ser Val Ser Asp Ser Pro Ala Arg Leu Gln Ser Leu Leu 420 425 430 Arg Val Leu Val Gln Met Cys Lys Met Lys Ala Phe Gly Glu Leu Cys 435 440 445 Pro Asn Thr Ala Pro Leu Pro Gln Leu Val Thr Glu Ala Leu Gln Thr 450 455 460 Gly Thr Thr Glu Trp Phe His Leu Lys Gln Gln His His Gln Pro Met 465 470 475 480 Val Gln Gly Ile Pro Glu Ala Gly Lys Ala Leu Leu Gly Leu Val Gln 485 490 495 Asp Val Ile Gly Asp Leu His Gln Cys Gln Arg Thr Trp Asp Lys Ile 500 505 510 Phe His Asn Thr Leu Lys Ile His Leu Phe Ser Met Ala Phe Arg Glu 515 520 525 Leu Gln Trp Leu Val Ala Lys Arg Val Gln Asp His Thr Thr Val Val 530 535 540 Gly Asp Val Val Ser Pro Glu Met Gly Glu Ser Leu Phe Gln Leu Tyr 545 550 555 560 Ile Ser Leu Lys Glu Leu Cys Gln Leu Arg Met Ser Ser Ser Glu Arg 565 570 575 Asp Gly Val Leu Ala Leu Asp Asn Phe His Arg Trp Phe Gln Pro Ala 580 585 590 Ile Pro Ser Trp Leu Gln Lys Thr Tyr Asn Glu Ala Leu Ala Arg Val 595 600 605 Gln Arg Ala Val Gln Met Asp Glu Leu Val Pro Leu Gly Glu Leu Thr 610 615 620 Lys His Ser Thr Ser Ala Val Asp Leu Ser Thr Cys Phe Ala Gln Ile 625 630 635 640 Ser His Thr Ala Arg Gln Leu Asp Trp Pro Asp Pro Glu Glu Ala Phe 645 650 655 Met Ile Thr Val Lys Phe Val Glu Asp Thr Cys Arg Leu Ala Leu Val 660 665 670 Tyr Cys Ser Leu Ile Lys Ala Arg Ala Arg Glu Leu Ser Ser Gly Gln 675 680 685 Lys Asp Gln Gly Gln Ala Ala Asn Met Leu Cys Val Val Val Asn Asp 690 695 700 Met Glu Gln Leu Arg Leu Val Ile Gly Lys Leu Pro Ala Gln Leu Ala 705 710 715 720 Trp Glu Ala Leu Glu Gln Arg Val Gly Ala Val Leu Glu Gln Gly Gln 725 730 735 Leu Gln Asn Thr Leu His Ala Gln Leu Gln Ser Ala Leu Ala Gly Leu 740 745 750 Gly His Glu Ile Arg Thr Gly Val Arg Thr Leu Ala Glu Gln Leu Glu 755 760 765 Val Gly Ile Ala Lys His Ile Gln Lys Leu Val Gly Val Arg Glu Ser 770 775 780 Val Leu Pro Glu Asp Ala Ile Leu Pro Leu Met Lys Phe Leu Glu Val 785 790 795 800 Glu Leu Cys Tyr Met Asn Thr Asn Leu Val Gln Glu Asn Phe Ser Ser 805 810 815 Leu Leu Thr Leu Leu Trp Thr His Thr Leu Thr Val Leu Val Glu Ala 820 825 830 Ala Ala Ser Gln Arg Ser Ser Ser Leu Ala Ser Asn Arg Leu Lys Ile 835 840 845 Ala Leu Gln Asn Leu Glu Ile Cys Phe His Ala Glu Gly Cys Gly Leu 850 855 860 Pro Pro Lys Ala Leu His Thr Ala Thr Phe Gln Ala Leu Gln Arg Asp 865 870 875 880 Leu Glu Leu Gln Ala Ala Ser Ser Arg Glu Leu Ile Arg Lys Tyr Phe 885 890 895 Cys Ser Arg Ile Gln Gln Gln Ala Glu Thr Thr Ser Glu Glu Leu Gly 900 905 910 Ala Val Thr Val Lys Ala Ser Tyr Arg Ala Ser Glu Gln Lys Leu Arg 915 920 925 Val Glu Leu Leu Ser Ala Ser Ser Leu Leu Pro Leu Asp Ser Asn Gly 930 935 940 Ser Ser Asp Pro Phe Val Gln Leu Thr Leu Glu Pro Arg His Glu Phe 945 950 955 960 Pro Glu Leu Ala Ala Arg Glu Thr Gln Lys His Lys Lys Asp Leu His 965 970 975 Pro Leu Phe Asp Glu Thr Phe Glu Phe Leu Val Pro Ala Glu Pro Cys 980 985 990 Arg Lys Ala Gly Ala Cys Leu Leu Leu Thr Val Leu Asp Tyr Asp Thr 995 1000 1005 Leu Gly Ala Asp Asp Leu Glu Gly Glu Ala Phe Leu Pro Leu Arg 1010 1015 1020 Glu Val Pro Gly Leu Ser Gly Ser Glu Glu Pro Gly Glu Val Pro 1025 1030 1035 Gln Thr Arg Leu Pro Leu Thr Tyr Pro Ala Pro Asn Gly Asp Pro 1040 1045 1050 Ile Leu Gln Leu Leu Glu Gly Arg Lys Gly Asp Arg Glu Ala Gln 1055 1060 1065 Val Phe Val Arg Leu Arg Arg His Arg Ala Lys Gln Ala Ser Gln 1070 1075 1080 His Ala Leu Arg Pro Ala Pro 1085 1090 342474PRTHomo sapiens 342Met Lys Arg Val Leu Val Leu Leu Leu Ala Val Ala Phe Gly His Ala 1 5 10 15 Leu Glu Arg Gly Arg Asp Tyr Glu Lys Asn Lys Val Cys Lys Glu Phe 20 25 30 Ser His Leu Gly Lys Glu Asp Phe Thr Ser Leu Ser Leu Val Leu Tyr 35 40 45 Ser Arg Lys Phe Pro Ser Gly Thr Phe Glu Gln Val Ser Gln Leu Val 50 55 60 Lys Glu Val Val Ser Leu Thr Glu Ala Cys Cys Ala Glu Gly Ala Asp 65 70 75 80 Pro Asp Cys Tyr Asp Thr Arg Thr Ser Ala Leu Ser Ala Lys Ser Cys 85 90 95 Glu Ser Asn Ser Pro Phe Pro Val His Pro Gly Thr Ala Glu Cys Cys 100 105 110 Thr Lys Glu Gly Leu Glu Arg Lys Leu Cys Met Ala Ala Leu Lys His 115 120 125 Gln Pro Gln Glu Phe Pro Thr Tyr Val Glu Pro Thr Asn Asp Glu Ile 130 135 140 Cys Glu Ala Phe Arg Lys Asp Pro Lys Glu Tyr Ala Asn Gln Phe Met 145 150 155 160 Trp Glu Tyr Ser Thr Asn Tyr Gly Gln Ala Pro Leu Ser Leu Leu Val 165 170 175 Ser Tyr Thr Lys Ser Tyr Leu Ser Met Val Gly Ser Cys Cys Thr Ser 180 185 190 Ala Ser Pro Thr Val Cys Phe Leu Lys Glu Arg Leu Gln Leu Lys His 195 200 205 Leu Ser Leu Leu Thr Thr Leu Ser Asn Arg Val Cys Ser Gln Tyr Ala 210 215 220 Ala Tyr Gly Glu Lys Lys Ser Arg Leu Ser Asn Leu Ile Lys Leu Ala 225 230 235 240 Gln Lys Val Pro Thr Ala Asp Leu Glu Asp Val Leu Pro Leu Ala Glu 245 250 255 Asp Ile Thr Asn Ile Leu Ser Lys Cys Cys Glu Ser Ala Ser Glu Asp 260 265 270 Cys Met Ala Lys Glu Leu Pro Glu His Thr Val Lys Leu Cys Asp Asn 275 280 285 Leu Ser Thr Lys Asn Ser Lys Phe Glu Asp Cys Cys Gln Glu Lys Thr 290 295 300 Ala Met Asp Val Phe Val Cys Thr Tyr Phe Met Pro Ala Ala Gln Leu 305 310 315 320 Pro Glu Leu Pro Asp Val Glu Leu Pro Thr Asn Lys Asp Val Cys Asp 325 330 335 Pro Gly Asn Thr Lys Val Met Asp Lys Tyr Thr Phe Glu Leu Ser Arg 340 345 350 Arg Thr His Leu Pro Glu Val Phe Leu Ser Lys Val Leu Glu Pro Thr 355 360 365 Leu Lys Ser Leu Gly Glu Cys Cys Asp Val Glu Asp Ser Thr Thr Cys 370 375 380 Phe Asn Ala Lys Gly Pro Leu Leu Lys Lys Glu Leu Ser Ser Phe Ile 385 390 395 400 Asp Lys Gly Gln Glu Leu Cys Ala Asp Tyr Ser Glu Asn Thr Phe Thr 405 410 415 Glu Tyr Lys Lys Lys Leu Ala Glu Arg Leu Lys Ala Lys Leu Pro Asp 420 425 430 Ala Thr Pro Thr Glu Leu Ala Lys Leu Val Asn Lys His Ser Asp Phe 435 440 445 Ala Ser Asn Cys Cys Ser Ile Asn Ser Pro Pro Leu Tyr Cys Asp Ser 450 455 460 Glu Ile Asp Ala Glu Leu Lys Asn Ile Leu 465 470 343478PRTHomo sapiens 343Met Ala Pro Leu Arg Pro Leu Leu Ile Leu Ala Leu Leu Ala Trp Val 1 5 10 15 Ala Leu Ala Asp Gln Glu Ser Cys Lys Gly Arg Cys Thr Glu Gly Phe 20 25 30 Asn Val Asp Lys Lys Cys Gln Cys Asp Glu Leu Cys Ser Tyr Tyr Gln 35 40 45 Ser Cys Cys Thr Asp Tyr Thr Ala Glu Cys Lys Pro Gln Val Thr Arg 50 55 60 Gly Asp Val Phe Thr Met Pro Glu Asp Glu Tyr Thr Val Tyr Asp Asp 65 70 75 80 Gly Glu Glu Lys Asn Asn Ala Thr Val His Glu Gln Val Gly Gly Pro 85 90 95 Ser Leu Thr Ser Asp Leu Gln Ala Gln Ser Lys Gly Asn Pro Glu Gln 100 105 110 Thr Pro Val Leu Lys Pro Glu Glu Glu Ala Pro Ala Pro Glu Val Gly 115 120 125 Ala Ser Lys Pro Glu Gly Ile Asp Ser Arg Pro Glu Thr Leu His Pro 130 135 140 Gly Arg Pro Gln Pro Pro Ala Glu Glu Glu Leu Cys Ser Gly Lys Pro 145 150 155 160 Phe Asp Ala Phe Thr Asp Leu Lys Asn Gly Ser Leu Phe Ala Phe Arg 165 170 175 Gly Gln Tyr Cys Tyr Glu Leu Asp Glu Lys Ala Val Arg Pro Gly Tyr 180 185 190 Pro Lys Leu Ile Arg Asp Val Trp Gly Ile Glu Gly Pro Ile Asp Ala 195 200 205 Ala Phe Thr Arg Ile Asn Cys Gln Gly Lys Thr Tyr Leu Phe Lys Gly 210 215 220 Ser Gln Tyr Trp Arg Phe Glu Asp Gly Val Leu Asp Pro Asp Tyr Pro 225 230 235 240 Arg Asn Ile Ser Asp Gly Phe Asp Gly Ile Pro Asp Asn Val Asp Ala 245 250 255 Ala Leu Ala Leu Pro Ala His Ser Tyr Ser Gly Arg Glu Arg Val Tyr 260 265 270 Phe Phe Lys Gly Lys Gln Tyr Trp Glu Tyr Gln Phe Gln His Gln Pro 275 280 285 Ser Gln Glu Glu Cys Glu Gly Ser Ser Leu Ser Ala Val Phe Glu His 290 295 300 Phe Ala Met Met Gln Arg Asp Ser Trp Glu Asp Ile Phe Glu Leu Leu 305 310 315 320 Phe Trp Gly Arg Thr Ser Ala Gly Thr Arg Gln Pro Gln Phe Ile Ser 325 330 335 Arg Asp Trp His Gly Val Pro Gly Gln Val Asp Ala Ala Met Ala Gly 340 345 350 Arg Ile Tyr Ile Ser Gly Met Ala Pro Arg Pro Ser Leu Ala Lys Lys 355 360 365 Gln Arg Phe Arg His Arg Asn Arg Lys Gly Tyr Arg Ser Gln Arg Gly 370 375 380 His Ser Arg Gly Arg Asn Gln Asn Ser Arg Arg Pro Ser Arg Ala Met 385 390 395 400 Trp Leu Ser Leu Phe Ser Ser Glu Glu Ser Asn Leu Gly Ala Asn Asn 405 410 415 Tyr Asp Asp Tyr Arg Met Asp Trp Leu Val Pro Ala Thr Cys Glu Pro 420 425 430 Ile Gln Ser Val Phe Phe Phe Ser Gly Asp Lys Tyr Tyr Arg Val Asn 435 440 445 Leu Arg Thr Arg Arg Val Asp Thr Val Asp Pro Pro Tyr Pro Arg Ser 450 455 460 Ile Ala Gln Tyr Trp Leu Gly Cys Pro Ala Pro Gly His Leu 465 470 475

Claims

1.-31. (canceled)

32. A diagnostic tool comprising: tryptic peptides of at least three of the respiratory condition biomarkers in Table 1, wherein the respiratory condition biomarkers are indexed with their abundance; with the proviso that the diagnostic tool does not comprise tryptic peptides of at least one of the proteins in Table 1.

33. The diagnostic tool of claim 32, comprising at least four of the respiratory condition biomarkers in Table 1.

34. The diagnostic tool of claim 33, further comprising a mass spectrometer, liquid chromatograph, size separation column, electrophoretic gel or protein chip.

35. The diagnostic tool of claim 32, comprising at least three of the respiratory condition biomarkers in Table 2.

36. The diagnostic tool of claim 32, comprising at least four of the respiratory condition biomarkers in Table 2.

37. The diagnostic tool of claim 36, further comprising a mass spectrometer, liquid chromatograph, size separation column, electrophoretic gel or protein chip.

38. The diagnostic tool of claim 32, wherein the diagnostic tool comprises a protein chip for determining three or more proteins, or peptides of three or more proteins, set forth in Table 1, wherein said proteins, or the peptides of the proteins, bind to the surface of the chip.

39. The diagnostic tool of claim 38, wherein the diagnostic tool comprises a protein chip for determining four or more proteins, or peptides of four or more proteins, set forth in Table 1, wherein said proteins, or the peptides of the proteins, bind to the surface of the chip.

40. The diagnostic tool of claim 38, wherein the diagnostic tool comprises a protein chip for determining five or more proteins, or peptides of five or more proteins, set forth in Table 1, wherein said proteins, or the peptides of the proteins, bind to the surface of the chip.

41. A diagnostic tool comprising: a gene chip that specifically binds expressed nucleic acids for the respiratory condition biomarkers of three or more proteins in Table 1; wherein the expressed nucleic acids for the respiratory condition biomarkers specifically bind to the surface of the gene chip; and wherein said gene chip does not specifically bind an expressed nucleic acid for each of the respiratory condition biomarkers set forth in Table 1.

42. A process comprising: obtaining a sample from a patient having or suspected of having a chronic obstructive pulmonary disease (COPD); analyzing the sample using the diagnostic tool of claim 32 to obtain data; and using the data to determine whether the patient will undergo a rapid or a slow decline in respiratory condition.