G protein-coupled receptor-like receptors and modulators thereof

This application claims benefit of U.S. Provisional Application No. 60/167,523, filed Nov. 24, 1999.

The present invention relates generally to G-protein, seven-transmembrane-receptor-like polynucleotides and polypeptides, as well as modulators of the interaction between the polypeptides and their ligand(s) that are useful for inhibiting the neurological activity of organisms, e.g., invertebrates.

It has been estimated that as many as one in three humans is infected by one or more species of parasitic helminth (flatworms and roundworms). Helminths also represent a chronic and continuing threat to the health of livestock and companion animals; their abundance and resistance to anthelmintic drugs effectively prevents animal agriculture in certain environments. Despite the prevalence of helminth-caused disease, little is known of helminth physiology. This ignorance, in turn, hampers efforts to identify agents capable of controlling these pathogens.

Flatworms (platyhelminths) are evolutionarily quite distinct from the roundworms (nematodes) and differ markedly in neuromuscular anatomy and physiology. Only a subset of one class of drugs (some of the benzimidazoles) shows activity against both flatworms and roundworms. The diversity among the animal species that threaten the health of man, livestock, crops, and sensitive environmental niches, presents a challenge to efforts to mount broad-based attacks on the pest organisms.

G protein-coupled receptors (i.e., GPCRs) form a vast superfamily of cell surface receptors which are present in virtually all animal cells and are characterized by an amino-terminal extracellular domain, a carboxy-terminal intracellular domain, and a serpentine structure that passes through the cell membrane seven times. Hence, such receptors are sometimes also referred to as seven transmembrane (7TM) receptors. These seven transmembrane domains define three extracellular loops and three intracellular loops, in addition to the amino- and carboxy-terminal domains. The extracellular portions of the receptor have a role in recognizing and binding one or more extracellular binding partners (e.g., ligands), whereas the intracellular portions have a role in recognizing and communicating with downstream effector molecules.

The G protein-coupled receptors bind a variety of ligands including calcium ions, hormones, chemokines, neuropeptides, neurotransmitters, nucleotides, lipids, odorants, and even photons. Not surprisingly, the GPCRs are important in the normal (and sometimes the aberrant) function of many cell types. [See generally Strosberg, Eur. J. Biochem., 196: 1-10 (1991) and Bohm et al., Biochem J., 322: 1-18 (1997).] When a specific ligand binds to its corresponding receptor, the ligand typically stimulates the receptor to activate a specific heterotrimeric guanine nucleotide-binding regulatory protein (G protein) that is coupled to the intracellular portion or region of the receptor. The G protein, in turn, transmits a signal to an effector molecule within the cell by either stimulating or inhibiting the activity of that effector molecule. These effector molecules include adenylate cyclase, phospholipases and ion channels. Adenylate cyclase and phospholipases are enzymes that are involved in the production of the second messenger molecules cAMP, inositol triphosphate and diacyglycerol. It is through this sequence of events that an extracellular ligand stimulus exerts intracellular changes through a G protein-coupled receptor. Each such receptor has its own characteristic primary structure, expression pattern, ligand binding profile, and intracellular effector system.

Because of the vital role of G protein-coupled receptors in the communication between cells and their environment, such receptors are attractive targets for therapeutic intervention, and drugs that activate or antagonize the activation of such receptors are known. For receptors having a known ligand, the identification of agonists or antagonists may be sought specifically for mimicking, enhancing or inhibiting the action of the ligand. Thus, GPCRs show promise as potential targets of methods for treating infestations and/or infections caused by a variety of invertebrate pests, including both ecto- and endo-parasites. However, such methods must be able to discriminate the GPCRs of the invertebrate pest organisms from the GPCRs found in those species of plants and vertebrate animals upon whom the pests prey.

A large family of peptides (typically 4-15 amino acids in length) that is largely, if not exclusively, found in invertebrate animals such as helminths is a class of neuropeptides known as FMRFamide related peptides (i.e., FaRPs). The prototypical FMRFamide peptides are so named because of the “FMRF” amino acid sequence, including the consensus “RF” sequence, at their C-termini. As neuropeptides, these molecules are involved in vital biological processes requiring controlled neuromuscular activity. Although some neurotransmitters and neuromodulators (including neuropeptides) have been shown to function as ligands for receptors, to date there has been no identification of a FaRP neuropeptide as a ligand of a GPCR.

Because of the toxic potential of broad-spectrum chemical parasiticides, there exists a need in the art for targeted biologicals capable of selectively interfering with the life cycle of harmful invertebrates such as helminths and insects without harming host plant and animal species, as well as the environment.

The present invention generally relates to materials and methods for the targeted interference with vital biological processes of pest invertebrates. By providing materials and methods for modulating the activity of invertebrate GPCRs involved in neuromuscular activity, the invention provides a biological approach to invertebrate pest control that can minimize the deleterious consequences to non-pest species of animals, including man, as well as plants and the environment in general.

One aspect of the invention is a screening method for identifying candidate anti-invertebrate modulators that affect one or more activities of an invertebrate GPCR-like receptor involved in neuromuscular functioning including, e.g., binding of a GPCR-like receptor to a ligand, typically a peptide ligand, and signal transduction. The method comprises the steps of: (a) contacting a test compound with a composition, wherein the composition contains a GPCR-like receptor encoded by a polynucleotide having a sequence selected from the group consisting of SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 104, 106, 108, 110, 112, 114, 116, 176 and 178, or a polynucleotide hybridizing to the GPCR-like receptor under stringent conditions of hybridizing at 42° C. in a solution comprising 50% formamide, 1% SDS, 1 M NaCl, 10% dextran sulfate, and washing twice for 30 minutes at 60° C. in a wash solution comprising 0.1×SSC and 1% SDS; and (b) measuring the activity of the GPCR-like receptor in the presence and absence of the test compound. In preferred embodiments, the screening method includes a receptor, or fragment, variant or derivative thereof, having a sequence set forth in SEQ ID NOS: 7, 21, 25, 35, 43, 45, 105, 107, 109, 111, 113, 115, 117, 177 and 179.

As one of ordinary skill in the art would recognize, the above-described method can be practiced with a variety of GPCR-like receptors. For example, the GPCR-like receptor used in the screening method may be encoded by a polynucleotide having a sequence set forth in any one of SEQ ID NOS:43, 21, 45, 35, 7, 106, and 104. As noted above, such GPCR-like receptors may be used in screening assays designed to measure a GPCR-like receptor activity, including binding activity. Expressly contemplated are embodiments of the screening method comprising a GPCR-like receptor encoded by a polynucleotide comprising a sequence set forth in SEQ ID NO:43 and a peptide comprising a sequence selected from the group consisting of SEQ ID NOS:85, 86, 88, 89, and 118, wherein the peptide binds to the GPCR-like receptor. encoded by a polynucleotide having the sequence set forth in SEQ ID NO:43 is provided. In an alternative embodiment, the GPCR-like receptor comprises a sequence set forth in SEQ ID NO:21 and the peptide comprises a sequence selected from the group consisting of SEQ ID NOS:78, 79, 80, 84, 87, 92, 98, 100, 120, 171, 143, 122, 123, 97, 85, 83, 101, 102, 93, 88, 91, 94, 93, 90, 152, 153, 154, 155, 156, 157, 80, 158, 119, 159, 160, 161, 162, 163 and 164. Another embodiment involves a GPCR-like receptor comprising a sequence set forth in SEQ ID NO:45 and a peptide comprising a sequence selected from the group consisting of SEQ ID NOS:86, 118, 125, 88, 126, 127, 128, 129, 102, 131, 100, 133, 92, 135, 136, 137, 87, 139, 91, 141 and 83. In yet another embodiment, the GPCR-like receptor comprises a sequence set forth in SEQ ID NO:35 and a peptide comprising a sequence selected from the group consisting of SEQ ID NOS:99, 97, 96, 77, 82, 81, 87, 100, 92, 80, 98, 120, 121, 79 and 84. In still another embodiment, the GPCR-like receptor comprises a sequence set forth in SEQ ID NO:7 and a peptide comprising a sequence selected from the group consisting of SEQ ID NOS:94, 103, 95, 101, 85, 79, 84, 87, 86, 80, 92, 100, and 180. Yet another embodiment involves a GPCR-like receptor comprising a sequence selected from the group consisting of SEQ ID NO:106 and a peptide comprising a sequence selected from the group consisting of SEQ ID NOS:80, 92, 98, 100, 120, 121, 79, 84, 136, 87 and 86. Still another one of the many embodiments of this aspect of the invention involves a GPCR-like receptor comprising a sequence set forth in SEQ ID NO:104 and a peptide comprising a sequence selected from the group consisting of SEQ ID NOS:80, 92, 98, 100, 120, 121, 79, 84, 136, 87, 86, 150, 151, 133, 165, 91, 166, 131 and 167.

Another aspect of the invention is a method of identifying an anti-invertebrate modulator of an activity of an invertebrate GPCR-like receptor comprising the following steps: (a) contacting a test compound and a composition, wherein the composition contains a GPCR-like receptor selected from the group consisting of polypeptides encoded by a polynucleotide having a sequence selected from the group consisting of SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 104, 106, 108, 110, 112, 114, 116, 176 and 178, or a polynucleotide hybridizing to the GPCR-like receptor under stringent conditions of hybridizing at 42° C. in a solution comprising 50% formamide, 1% SDS, 1 M NaCl, 10% Dextran sulfate, and washing twice for 30 minutes at 60° C. in a wash solution comprising 0.1×SSC and 1% SDS, optionally in the presence of a peptide or other ligand of the receptor; and (b) measuring the activity of the GPCR-like receptor in the presence and absence of the test compound. Modulators are identified as test compounds that alter (i.e., increase or decrease) a GPCR-like receptor function, such as a binding property of a receptor or an activity such as G protein-mediated signal transduction or membrane localization. The composition may contain an isolated GPCR-like receptor; alternatively, the composition may contain a GPCR-like receptor in association with, e.g., an intact cell or cell portion, such as a membrane. Presently preferred embodiments of the method use a GPCR-like receptor having an amino acid sequence set forth in SEQ ID NOS: 8, 22, 26, 36, 44, 105, 107, 109, 111, 113, 115, 117, 177 or 179. Preferred peptides are neuropeptides derived from invertebrates and include the FaRP family of neuropeptides. Particularly preferred are invertebrate neuropeptides having an amino acid sequence selected from the group consisting of SEQ ID NOS: 77-103 and 118-151. The methods of the invention embrace neuropeptides that are attached to a label, such as a radiolabel (e.g., 125 I, 35 S, 32 P, 33 P, 3 H), a fluorescence label, a chemiluminescence label, an enzymic label and an immunogenic label.

In various embodiments of the method, the assay may take the form of an ion flux assay, a yeast growth assay, a non-hydrolyzable GTP assay such as a [ 35 S]-GTPγS assay, a cAMP assay, an inositol triphosphate assay, a diacylglycerol assay, an Aequorin assay, a Luciferase assay, a FLIPR assay for intracellular Ca 2+ concentration, a mitogenesis assay, a MAP Kinase activity assay, an arachidonic acid release assay (e.g., using [ 3 H]-arachidonic acid), and an assay for extracellular acidification rates, as well as other binding or function-based assays of GPCR activity that are generally known in the art. In several of these embodiments, the invention comprehends the inclusion of any of the G proteins known in the art, such as G α16 , G α15 , or chimeric G qi5 , G qs5 , G qo5 , or G qz5 .

In another aspect of the invention, a method of identifying a candidate anti-invertebrate modulator is provided. The method comprises the steps of: (a) contacting a test compound and a composition, wherein the composition contains a GPCR-like receptor encoded by a polynucleotide selected from the group consisting of receptor polyucleotides having a sequence set forth in SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 104, 106, 108, 110, 112, 114, 116, 176 and 178, and polynucleotides hybridizing to the receptor polynucleotides under stringent conditions of hybridizing at 42° C. in a solution comprising 50% formamide, 1% SDS, 1 M NaCl, 10% dextran sulfate, and washing twice for 30 minutes at 60° C. in a wash solution comprising 0.1×SSC and 1% SDS; and (b) identifying a test compound that binds to or interacts with the composition as a candidate anti-invertebrate modulator. In a preferred embodiment, the polynucleotide encoding the GPCR-like receptor comprises a sequence selected from the group consisting of SEQ ID NOS: 7, 21, 25, 35, 43, 45, 105, 107, 109, 111, 113, 115, 117, 177 and 179.

Another aspect of the invention is a method of identifying an anti-invertebrate agent comprising the following steps: (a) identifying a modulator using the method described above; (b) contacting the modulator and an invertebrate tissue; and (c) measuring the response of the invertebrate tissue, e.g. neural signaling or neuromuscular activity, thereby identifying the modulator as an anti-invertebrate agent. Although any invertebrate tissue may be used in the method, presently preferred tissue sources are helminths and insects. An exemplary type of suitable invertebrate tissue is neuromuscular tissue, e.g. in isolated form or remaining in association with part, or all, of an invertebrate organism. The anti-invertebrate agents, and compositions comprising one of those agents, identified by this method constitute yet another aspect of the invention.

In a related aspect, the invention provides a method for treating an invertebrate comprising the step of contacting the invertebrate with a biologically effective amount of a modulator identified by the methods described herein. A biologically effective amount of a modulator is an amount that is sufficient to induce a desired response in the treated invertebrate. Thus, a biologically effective amount of a modulator may be the amount that interferes with physiological activity of the treated invertebrate in a non-lethal manner (i.e., a biostatic effect) or in a lethal manner (i.e., a biocidal effect). A preferred modulator for use in the treatment methods is an inhibitor of GPCR-like receptor activity. The invention is not limited to particular means for delivering the modulator to an invertebrate, nor is the invention limited as to the compositions comprising the modulator which may be delivered.

Another aspect of the invention is drawn to methods of producing an invertebrate GPCR-like receptor comprising the following steps:(a) incubating a source cell at a temperature of at least about 35° C.; (b) lowering the temperature to at most about 26° C.; and (c) detecting the GPCR-like receptor. In various embodiments, the temperatures may be varied to optimize production using no more than routine experimentation. For example, the cells may be incubated at temperatures higher than about 35° C., e.g., a temperature of at least about 37° C.; the temperature also may be lowered beyond 30° C., for example to at most 29° C., at most 28° C., at most 27° C., at most 26° C., at most 25° C. or at most 24° C. In some embodiments, both the incubation temperature may be raised above 35° C. and the temperature lowering may extend beyond 30° C. The method of producing an invertebrate GPCR-like receptor may further comprise recovering the GPCR-like receptor, which may be native or recombinant in origin. The receptor may be recovered in intact cells, cell portions (e.g., membranes) obtained as a result of cell lysis, or in isolated form. Any of a wide variety of cells may be used as source cells, such as cells derived from mammals, amphibians, arthropods (e.g., insects), mollusks, helminths, and others. It is anticipated that this method of producing a GPCR-like receptor is particularly suited to the recombinant production of GPCR-like receptors using non-invertebrate cells, such as mammalian cells.

The invention also comprehends compositions of matter, such as a modulator of an activity of the GPCR-like receptors identified by the methods described herein. The modulators of the invention exhibit a variety of chemical structures, which can be generally grouped into non-peptide mimetics of natural GPCR-like receptor ligands, peptide and non-peptide allosteric effectors of GPCR-like receptors, and peptides and non-peptide compounds that function as activators or inhibitors (competitive, uncompetitive and non-competitive) (e.g., antibody products) of an ultimate GPCR-like receptor activity. For example, such modulators may be compounds or compositions that are agonists or antagonists of ligand binding to a GPCR-like receptor, allosteric effectors thereof, or compounds (or compositions) that affect the ultimate activity of GPCR-like receptors through direct action on the receptor or an effect introduced downstream of the receptor in, e.g., a signal cascade. In addition, modulators according to the invention may be compounds or compositions that interfere with the expression of a GPCR-like receptor, either through inhibiting transcription of the DNA or translation of the corresponding mRNA. Expression of the GPCR-like receptor can be monitored by any methods known in the art, including Western blot analysis using polyclonal or monoclonal antibodies to the GPCR-like receptor or Northern blot analysis or quantitative polymerase chain reaction (PCR) using suitable probes or primers based on the sequence of the GPCR-like receptor gene. In particular, modulators that interfere with the expression of gene products include anti-sense polynucleotides and ribozymes that are complementary to the gene sequences. The invention further embraces modulators that affect the transcription of gene products of the invention through the formation of oligonucleotide-directed triplet helix formation. The invention does not restrict the sources for suitable modulators, which may be obtained from natural sources such as plant, animal or mineral extracts, or non-natural sources such as small molecule libraries, including the products of combinatorial chemical approaches to library construction, and peptide libraries. Preferred peptide receptors have an amino acid sequence selected from the group consisting of SEQ ID NOS: 8, 22, 26, 36, 44, 105, 107, 109, 111, 113, 115, 117, 177 or 179.

Another aspect of the invention is drawn to an isolated GPCR-like receptor comprising a sequence selected from the group consisting of SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 105, 107, 109, 111, 113, 115, 117, 177, and 179, and variants and fragments thereof. Preferred receptors have sequences set forth in SEQ ID NOS: 8, 22, 26, 36, 44, 105, 107, 109, 111, 113, 115, 117, 177 and 179. Variants and fragments of GPCR-like receptors retain at least one biological or immunological property of the cognate GPCR-like receptor, and are at least 10, at least 15, at least 20, at least 25, at least 30, at least 40, at least 50, at least 60, at least 70, at least 225, 80, at least 90, at least 100, at least 125, at least 150, at least 175, at least 200, at least 225, at least 250, at least 275, at least 300, at least 325, at least 350, at least 375, at least 400, at least 425, or at least 450 amino acids in length. Fragments specifically include GPCR domains of the receptors. Biological activities of GPCR-like receptors according to the invention include, but are not limited to, the binding of a natural or an unnatural ligand, as well as any one of the functional activities of GPCRs known in the art. Other non-limiting examples of GPCR activities include transmembrane signaling of various forms, which may involve G protein association and/or the exertion of an influence over G protein binding of various guanidylate nucleotides; transmembrane localization; or binding of accessory proteins or polypeptides unrelated to known G proteins.

The invention also provides an isolated polynucleotide encoding a GPCR-like receptor. Such polynucleotides may be selected from the group consisting of: (a) a polynucleotide comprising a nucleotide sequence encoding any one of the amino acid sequences set forth in SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 105, 107, 109, 111, 113, 115 117, 177, and 179 (including the nucleotide sequences set forth in SEQ ID NOS: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 104, 106, 108, 110, 112, 114, 116, 176, and 178); and (b) a polynucleotide which hybridizes under conditions of high stringency to the complement of the polynucleotide of (a). Exemplary conditions of high stringency are provided below. Such polynucleotides also include polynucleotides that exhibit at least 90%, at least 95%, at least 98%, at least 99% or at least 99.9% sequence identity to either a polynucleotide sequence disclosed in the sequence listing (i.e., SEQ ID NOS: 1, 3, 5, 7, 9, 11, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 104, 106, 108, 110, 112, 114, 116, 176 and 178) or to a polynucleotide encoding a GPCR-like receptor comprising one of the sequences disclosed in the sequence listing (i.e., SEQ ID NOS: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 105, 107, 109, 111, 113, 115, 117, 177, and 179). Any one of the publicly available algorithms (e.g., the BLAST1 program of GCG) for comparing sequences may be used in determining the degree of sequence similarity (including appropriate penalties for gap introductions). A preferred algorithm is the BLAST algorithm implemented at the GenBank website under the auspices of the National Center for Biotechnology Information A on the World Wide Web at ncbi.nlm.nih.gov/BLAST/ using default parameters. A polynucleotide of the invention may be partially or wholly chemically synthesized and embraces an anti-sense polynucleotide which specifically hybridizes to the complement of one or more of the above-described polynucleotides. In related aspects, the invention comprehends vectors comprising these polynucleotides preferably operably linked to expression control sequences, including expression vectors, as well as non-native host cells transformed or transfected with a polynucleotide in accordance with the invention or a host cell transformed or transfected with a vector of the invention. All suitable native and non-native host cells are embraced by the invention, including mammalian cells (e.g., COS cells, CHO cells, HEK293 cells), insect cells (e.g., Drosophila melanogaster S2 cells, Spodoptera frugiperda Sf9 cells, High-5 cells), yeast cells, bacterial cells (e.g., E. coli ) and helminthic cells. The suitability of a particular cell for use as a host cell in accordance with the invention will depend on the ability to introduce a polynucleotide of the invention into the cell by any known means of transformation or transfection. Preferred host cells will also be capable of stably maintaining the introduced polynucleotide and will present a minimum of obstacles to propagation.

Another aspect of the invention is directed to a genetically modified invertebrate comprising a polynucleotide encoding a heterologous GPCR-like receptor (e.g., transgene) as described above or comprising a modification in a native gene encoding a GPCR-like receptor (e.g., an insertional disruption or deletion of the gene). The GPCR-like receptor encoding gene may be expressed at normal levels for that gene or may be overexpressed or underexpressed. A preferred invertebrate for generation of genetically modified organisms is a member of the helminths.

Yet another aspect of the invention is drawn to diagnostic methods for determining neurological abnormalities associated with aberrant GPCR-like receptor activity. Such methods specifically measure the presence, and optionally quantity, of a GPCR-like receptor polynucleotide according to the invention or the presence, and optionally quantity or activity, of a GPCR-like receptor. Any method known in the art may be used to measure the specific polynucleotides or polypeptides of the invention, and measurements may be performed on intact organisms, isolated tissues, or cell cultures. In a related aspect, the invention contemplates methods for diagnosing invertebrate infestation of an organism (e.g., mammals such as humans, mammalian livestock, other vertebrates such as fish, and non-pest invertebrates such as molluscs) or an environment using a specific measurement of a polynucleotide or polypeptide according to the invention.

Another aspect of the invention is directed to treatment methods. The invention contemplates methods of killing or inhibiting the viability of invertebrates using the modulators described above or identified as described above, including antibodies and antisense polynucleotides. Such methods include methods for treating infestations and/or infections caused by a variety of invertebrate pests, including both ecto- and endo-parasites. A variety of human and other animal ailments, particularly those ailments relating to aberrant neurological functioning, are treated by administering a biologically effective amount of a modulator, GPCR-like receptor polynucleotide or GPCR-like receptor to a cell, tissue, organism, or environment using techniques known in the art.

Use of such modulators in the preparation of a medicament for treating parasitic infection is also contemplated. A variety of administration regimens known in the art are available to deliver a therapeutically effective (i.e., a level of activity capable of deleteriously affecting at least one biological process of a parasite, or more generally, of a pest organism) activity level of a modulator, directly or indirectly, to a parasite or pest, or to an environment associated with the parasite or pest.

Numerous additional aspects and advantages of the invention will become apparent to those skilled in the art upon consideration of the following detailed description of the preferred embodiments of the invention.

The present invention has several aspects, one of which is modulating the activity of invertebrate G protein-coupled receptors, which is useful in controlling a wide variety of pest organisms that affect the health of humans and other animals such as domestic pets and livestock, as well as plants. The G protein-coupled receptors typically transduce signals involved in the neurophysiological functioning of the target invertebrates and interference with that functioning frequently proves fatal to the target organism. Moreover, these receptors are found only in invertebrates, so that specific modulators are safe for use around humans, as well as their pets, livestock, and crops.

A “GPCR-like receptor” is a polypeptide receptor exhibiting the structural characteristics of G protein-coupled receptors (GPCRs), i.e., an N-terminal extracellular region, comprising several loop-like domains (typically three), a transmembrane region comprising seven transmembrane domains arranged in a typical serpentine disposition, and an intracellular region comprising several loop-like domains (typically three).

Invertebrate neuropeptides show profound neuromuscular effects and FaRPs represent the largest family of such neuropeptides known to date. A “FaRP” is a “FMRFamide-related peptide.” A “FMRFamide,” in turn, is a relatively small peptide, typically having 4-15 amino acids, that matches at least three of the four listed amino acids (FMRF) at its C-terminus. Generally, FaRPs exhibit neurophysiological effects and are therefore properly grouped in a class of neuropeptides that frequently function as ligands of GPCR-like receptors. A “modulator” is an effector of a GPCR-like receptor function, which include the binding of one or more ligands, localization to a membrane, and signal transduction. Signal transduction may involve a change in the relative affinities of a GPCR-associated G protein for various guanidylate nucleotides. With respect to polynucleotides and polypeptides of the invention, “synthesized,” as used herein and understood in the art, refers to polynucleotides or polypeptides produced by purely chemical, as opposed to enzymatic, methods. “Wholly” synthesized sequences are therefore produced entirely by chemical means, and “partially” synthesized sequences embrace those wherein only portions of the resulting polynucleotide or polypeptide were produced by chemical means.

The present invention provides purified and isolated polynucleotides (e.g., DNA sequences and RNA transcripts, both sense and complementary antisense strands, including splice variants thereof) encoding invertebrate G protein-coupled receptors. DNA polynucleotides of the invention include genomic DNA, cDNA, and DNA that has been chemically synthesized in whole or in part.

Genomic DNA of the invention comprises the protein coding region for a polypeptide of the invention and includes allelic variants thereof. It is widely understood that, for many genes, genomic DNA is transcribed into RNA transcripts that undergo one or more splicing events wherein intron (i.e., non-coding regions) of the transcripts are removed, or “spliced out.” RNA transcripts that can be spliced by alternative mechanisms, and therefore be subject to removal of different RNA sequences but still encode the same polypeptide, are referred to in the art as splice variants. Splice variants therefore are encoded by the same original genomic DNA sequences but arise from distinct mRNA transcripts found in at least one cell. By way of non-limiting example, several embodiments of the invention are characterized by one of the particular splice variants identified in Table 1, below.

Allelic variants are modified forms of a wild-type gene sequence, the modification resulting from recombination during chromosomal segregation or exposure to conditions which give rise to genetic mutation. Allelic variants, like wild type genes, are naturally occurring sequences (as opposed to non-naturally occurring variants which arise from in vitro manipulation), and are also comprehended by the invention.

The invention also comprehends cDNA that is obtained through reverse transcription of an RNA polynucleotide encoding invertebrate GPCR-like receptors (conventionally followed by second strand synthesis of a complementary strand to provide a double-stranded DNA). In addition to cDNA forms of the polynucleotides identified in Table 1 as splice variants, preferred cDNAs according to the invention include those polynucleotides having sequences selected from the group consisting of SEQ ID NOS: 13, 15 and 21. These sequences differ from sequences in the Wormpep database that exhibit some similarity thereto, as shown in Table 2.

Preferred DNA sequences encoding invertebrate GPCR-like receptor polypeptides are set out in SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 104, 106, 108, 110, 112, 114, 116, 176 and 178. A preferred DNA of the invention comprises a double stranded molecule (for example, the molecule having one of the sequences set forth in the above-referenced SEQ ID NOs, along with the complementary molecule (the “non-coding strand” or “complement”) having a sequence unambiguously deducible from one of those sequences, according to Watson-Crick base-pairing rules for DNA). Also preferred are other polynucleotides encoding one of the invertebrate GPCR-like receptor polypeptides of SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 105, 107, 109, 111, 113, 115, 117, 177, and 179 which may differ in sequence from the corresponding polynucleotides of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 104, 106, 108, 110, 112, 114, 116, 176 and 178 by virtue of the well-known degeneracy of the universal genetic code.

The invention further embraces invertebrate species (preferably helminth and insect) homologs of the disclosed GPCR-like DNAs. Species homologs, sometimes referred to as “orthologs,” in general share at least 35%, at least 40%, at least 45%, at least 50%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% similarity with the DNA sequences disclosed herein. Percent sequence “similarity” with respect to polynucleotides of the invention is defined herein as the percentage of nucleotide bases in the candidate sequence that are identical to nucleotides in the relevant sequences set forth in the sequence listing below, after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity. Preferred for comparative sequence analyses is the BLAST program available from GCG, implemented with default parameters. Also preferred is the Blastall program available from NCBI.

The polynucleotide sequence information provided by the invention makes possible large scale expression of an encoded polypeptide by techniques well known and routinely practiced in the art. Polynucleotides of the invention also permit identification and isolation of polynucleotides encoding related GPCR-like polypeptides, such as the aforementioned allelic variants and species homologs, by well known techniques including Southern and/or Northern hybridization, and by polymerase chain reaction (PCR). Examples of related polynucleotides include polynucleotides encoding polypeptides homologous to the invertebrate GPCRs and structurally related polypeptides sharing one or more biological, immunological, and/or physical properties of those GPCRs. Invertebrate genes encoding proteins homologous to the disclosed GPCRs can also be identified by Southern and/or PCR analysis and are useful in methods of the invention described below. Knowledge of the sequence of the disclosed GPCR-encoding DNAs also makes possible, through use of Southern hybridization, polymerase chain reaction (PCR), and other known techniques, the identification of genomic DNA sequences encoding GPCR expression control regulatory sequences such as promoters, operators, enhancers, repressors, and other regulatory sequences known in the art. Polynucleotides of the invention are also useful in hybridization assays to detect the capacity of cells to express an invertebrate GPCR.

The disclosure herein of a full-length polynucleotide encoding invertebrate GPCR-like polypeptides makes readily available to the worker of ordinary skill in the art every possible fragment of the full-length polynucleotides. The invention therefore provides fragments of invertebrate GPCR-encoding polynucleotides comprising at least 14-15, and preferably at least 18, 20, 25, 50, or 75 consecutive nucleotides of a polynucleotide encoding an invertebrate GPCR.

Fragment polynucleotides contemplated by the invention encode immunologically active peptides capable of interacting with specific anti-GPCR antibodies, as well as domains of GPCRs. The GPCR domains (i.e., the N-terminal extracellular domain, one or more of the three extracellular loop domains, one or more of the seven transmembrane domains, one or more of the three intracellular loop domains, or the C-terminal intracellular domain) of invertebrate GPCRs disclosed herein are characterized in Example 2 and Table 6, below. Full length or fragment polynulcleotides can be linked to polynucleotides encoding heterologous polypeptides, e.g., for producing variants that are fusion proteins.

Preferably, fragment polynucleotides of the invention comprise sequences unique to one of the disclosed GPCR-encoding sequences, and therefore hybridize under highly stringent or moderately stringent conditions only (i.e., “specifically”) to polynucleotides encoding a disclosed invertebrate GPCR (or fragments thereof) and not to polynucleotides encoding other GPCRs. Polynucleotide fragments of genomic sequences of the invention comprise not only sequences unique to the coding region, but also fragments of the full-length sequence derived from introns, regulatory regions, and/or other non-translated sequences. Sequences unique to polynucleotides of the invention are recognizable through sequence comparison to other known polynucleotides, and can be identified through use of alignment programs routinely utilized in the art, e.g., those made available in public sequence databases. Such sequences also are recognizable from Southern hybridization analyses to determine the number of fragments of genomic DNA to which a polynucleotide will hybridize. Polynucleotides of the invention can be labeled in a manner that permits their detection, including radioactive, fluorescent, and enzymatic labeling.

Fragment polynucleotides are particularly useful as probes for detection of full-length invertebrate GPCR-like polynucleotides, or other polynucleotide fragments thereof. One or more fragment polynucleotides can be included in kits that are used to detect the presence of a polynucleotide encoding an invertebrate GPCR-like receptor polypeptide, or used to detect variations in a polynucleotide sequence encoding such a polypeptide.

The invention also embraces DNAs encoding invertebrate GPCR-like polypeptides that hybridize under conditions of moderate or high stringency to the non-coding strand, or complement, of a polynucleotide comprising one of the sequences set forth in SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 104, 106, 108, 110, 112, 114, 116, 176 and 178.

Exemplary conditions of high stringency are as follows: hybridization at 42° C. in a solution (i.e., a hybridization solution) comprising 50% formamide, 1% SDS, 1 M NaCl, 10% Dextran sulfate, and washing twice for 30 minutes at 60° C. in a wash solution comprising 0.1×SSC and 1% SDS. It is understood in the art that conditions of equivalent stringency can be achieved through variation of temperature and buffer, or salt concentration, as described in Ausubel, et al. (Eds.), Protocols in Molecular Biology , John Wiley & Sons (1994), pp.6.0.3 to 6.4.10. Modifications in hybridization conditions can be empirically determined or precisely calculated based on the length and the percentage of guanosine/cytosine (GC) base pairing of the probe. The hybridization conditions can be calculated as described in Sambrook, et al., (Eds.), Molecular Cloning: A Laboratory Manual , Cold Spring Harbor Laboratory Press: Cold Spring Harbor, N.Y. (1989), pp. 9.47 to 9.51.

The invention also provides a purified and isolated invertebrate GPCR-like polypeptide encoded by a polynucleotide of the invention. Presently preferred is a polypeptide comprising one of the amino acid sequences set out in SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 105, 107, 109, 111, 113, 115, 117, 177, and 179, and species homologs thereof. The invention also embraces a GPCR-like polypeptide encoded by a DNA selected from the group consisting of: (a) the DNA sequence set out in any one of SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 104, 106, 108, 110, 112, 114, 116, 176 and 178 and species homologs thereof, and (b) a DNA molecule encoding a GPCR-like gene product that hybridizes under conditions of moderate or high stringency to the DNA of (a). The invention further embraces polypeptides that have at least about 99%, at least about 95%, at least about 90%, at least about 85%, at least about 80%, at least about 75%, at least about 70%, at least about 65%, at least about 60%, at least about 55%, and at least about 50% identity and/or homology to the preferred polypeptides of the invention. Percent amino acid sequence “identity” with respect to the preferred polypeptides of the invention is defined herein as the percentage of amino acid residues in the candidate sequence that are identical with the residues in the GPCR-like gene product sequence after aligning both sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and not considering any conservative substitutions as part of the sequence identity. Percent sequence “homology” with respect to the preferred polypeptides of the invention is defined herein as the percentage of amino acid residues in the candidate sequence that are identical with the residues in one of the GPCR-like receptor polypeptide sequences after aligning the sequences and introducing gaps, if necessary, to achieve the maximum percent sequence identity, and also considering any conservative substitutions as part of the sequence identity. Conservative substitutions are defined as set out in Tables 3 and 4.

GPCR polypeptides of the invention may be isolated from natural invertebrate cell sources or may be chemically synthesized, but are preferably produced by recombinant procedures involving host cells of the invention. GPCR-like gene products of the invention may be full-length polypeptides, biologically active fragments, or variants thereof which retain specific biological or immunological activity. Variants may comprise GPCR-like polypeptide analogs wherein one or more of the specified (i.e., naturally encoded) amino acids is deleted or replaced or wherein one or more non-specified amino acids are added: (1) without loss of one or more of the biological activities or immunological characteristics specific for the GPCR-like receptor; or (2) with specific disablement of a particular biological activity of the GPCR-like polypeptide. Contemplated deletion variants also include fragments lacking portions of a GPCR-like polypeptide not essential for biological activity, and insertion variants include fusion polypeptides in which the wild-type GPCR-like polypeptide or fragment thereof has been fused to another polypeptide.

Variant GPCR-like polypeptides include those wherein conservative substitutions have been introduced by modification of polynucleotides encoding polypeptides of the invention. Conservative substitutions are recognized in the art to classify amino acids according to their related physical properties and can be defined as set out in Table 3. (See, WO 97/09433, page 10, published Mar. 13, 1997 (PCT/GB96/02197, filed Sep. 6, 1996).) Alternatively, conservative amino acids can be grouped as defined in Lehninger, [ Biochemistry , Second Edition; Worth Publishers, Inc. NY:NY (1975), pp.71-77] as set out in Table 4.

Variant GPCR-like polypeptides of the invention include mature GPCR-like gene products, i.e., wherein leader or signal sequences are removed, having additional amino terminal residues. GPCR-like gene products having an additional methionine residue at position-1 are contemplated, as are GPCR-like receptors having additional methionine and lysine residues at positions-2 and -1. Variants of these types are particularly useful for recombinant protein production in bacterial cell types. Variants of the invention also include gene products wherein amino terminal sequences derived from other proteins have been introduced, as well as variants comprising amino terminal sequences that are not found in naturally occurring proteins.

Another component useful in some methods for identifying modulators of GPCR-like receptor activity, described below, is a class of neuropeptides that includes FaRPs. The FaRPs comprise a large family of peptides that typically function as neurotransmitters in the invertebrate nervous system. The FaRPs that are associated with these neurophysiological functions generally are about four to about nine amino acid residues in length and include a C-terminal amino acid sequence motif of (aromatic)-X-R-Famide, where X is typically M, L, I or V. Day et al., Peptides 20:999-1019 (1999), which is incorporated by reference in its entirety. However, peptides that are exceptions to this rule are also contemplated by the invention, particularly those that are co-encoded on FaRP precursor genes or those that share the characteristics of conforming peptides. Also contemplated by the invention are neuropeptide variants, including FaRP variants, peptides exhibiting an RYamide motif, and other peptides such as retro-inverso neuropeptides (e.g., FaRPs comprising the D stereoisomers of amino acids in a sequence that is reversed from a reference FaRP). For example a retro-inverso variant of A L -F L -M L -R L -F L would be F D -R D -M D -F D -A D .

Neuropeptides such as FaRPs have been found in a wide variety of invertebrates, including arthropods such as insects (e.g., locusts and flies such as Drosophila) and lobsters, mollusks such as the snail Lymnaea stagnalis , and helminths such as nematodes (e.g., C. elegans, A. suum, Haemonchus contortus ), trematodes (e.g., Schistosoma mansoni ) and cestodes, among others, including Manduca. Information relating to the structure, function, and structure-function relationships ofthese neuropeptides is known in the art [Day et al. (1999)]. Table 5 below provides a classification of several known C. elegans FaRPs, which are examples of the class of neuropeptides useful in practicing the invention.

Further characterization of the structure-function relationships of neuropeptides, such as FaRPs, that are embraced by the invention may be readily accomplished by one of ordinary skill in the art. For example, amino acid-scan modifications (e.g., alanine-scan), in which each residue is sequentially replaced with another amino acid such as alanine are available. Additionally, given the knowledge in the art (see generally, Geary et al., 1999), such modifications to known neuropeptides (e.g., FaRPs) as the internal or terminal deletion of one or more amino acids, as well as the internal or terminal addition of residues, involves no more than routine experimentation. Such “variants” of FaRPs and related neuropeptides are among the neuropeptides contemplated for use in the methods of the invention.

The GPCR-like receptor polypeptides and neuropeptides produced by the methods described above are useful in assays for modulators of GPCR-like receptor activities, including binding partner (e.g., ligand) binding. Assays contemplated by the invention include both binding assays and activity assays; these assays may be performed in conventional or high throughput formats. GPCR-like receptor activity is defined as including the binding of any binding partner, such as a ligand, as well as the propagation of any transmembrane signal (e.g., stimulation of a G protein or influence on the flux of an ion across a membrane). Modulator screens are designed to identify stimulatory and/or inhibitory agents. The sources for potential agents to be screened include natural sources, such as a cell extract (e.g., invertebrate cells including, but not limited to, bacterial, fungal, algal, and plant cells) and synthetic sources, such as chemical compound libraries. For proteins with known activity, function assays are established based on the activity, and a large number of potential agents are screened for the ability to either stimulate or inhibit the activity. Binding assays are used to detect GPCR-like receptor binding activity to neuropeptide or non-peptide ligands. Both functional and binding assays of GPCR-like receptor activity are readily adapted to screens for modulators such as inhibitory compounds.

The invention contemplates a multitude of assays to screen and identify inhibitors of ligand binding to GPCR-like receptors. In one example, the GPCR-like receptor is immobilized and interaction with a binding partner is assessed in the presence and absence of a candidate modulator such as an inhibitor compound. In another example, interaction between the GPCR-like receptor and its binding partner is assessed in a solution assay, both in the presence and absence of a candidate inhibitor compound. In either assay, an inhibitor is identified as a compound that decreases binding between the GPCR-like receptor and its binding partner. Another contemplated assay involves a variation of the di-hybrid assay wherein an inhibitor of protein/protein interactions is identified by detection of a positive signal in a transformed or transfected host cell.

Candidate modulators contemplated by the invention include any chemical compounds, including libraries of chemical compounds. There are a number of different libraries used for the identification of small molecule modulators, including: (1) chemical libraries, (2) natural product libraries, and (3) combinatorial libraries comprised of random peptides, oligonucleotides or organic molecules. Chemical libraries consist of random chemical structures, or analogs of known compounds, or analogs of compounds that have been identified as “hits” or “leads” in prior drug discovery screens, some of which may be derived from natural products or from non-directed synthetic organic chemistry. Natural product libraries are collections of microorganisms, animals, plants, or marine organisms which are used to create mixtures for screening by: (1) fermentation and extraction of broths from soil, plant or marine microorganisms or (2) extraction of plants or marine organisms. Natural product libraries include polyketides, non-ribosomal peptides, and variants (non-naturally occurring) thereof. For a review, see Science 282:63-68 (1998). Combinatorial libraries are composed of large numbers of peptides, oligonucleotides, or organic compounds as a mixture. These libraries are relatively easy to prepare by traditional automated synthesis methods, PCR, cloning, or synthetic methods. Of particular interest are non-peptide combinatorial libraries. Still other libraries of interest include peptide, protein, peptidomimetic, multiparallel synthetic collection, recombinatorial, and polypeptide libraries. For a review of combinatorial chemistry and libraries created therefrom, see Myers, Curr. Opin. Biotechnol . 8:701-707 (1997). Identification of modulators through use of the various libraries described herein permits modification of the candidate “hit” (or “lead”) to optimize the capacity of the “hit” to modulate activity.

Candidate modulators contemplated by the invention can be designed and include soluble forms of binding partners, as well as chimeric, or fusion, proteins thereof. A “binding partner” as used herein broadly encompasses non-peptide modulators, peptide modulators (e.g., neuropeptide variants), antibodies (including monoclonal and polyclonal antibodies, single chain antibodies, chimeric antibodies, biftinctional/bispecific antibodies, humlianized antibodies, human antibodies, and complementary determining region (CDR)-grafted antibodies, including compounds which include CDR and/or antigen-binding sequences, which specifically recognize a polypeptide of the invention), antibody fragments, and modified compounds comprising antibody domains that are immunospecific for the expression product of the identified GPCR-like gene.

A number of assays are known in the art that can identify chemical compounds that bind to or interact with a GPCR-like receptor. Such assays are useful, for example, in methods of identifying candidate modulators described herein, or in methods for identifying specific neuropeptide ligands of a GPCR-like receptor. Assays that measure binding or interaction of compounds with target proteins include assays that identify compounds that inhibit unfolding or denaturation of a target protein, assays that separate compounds that bind to target proteins through affinity ultrafiltration followed by ion spray mass spectroscopy/HPLC methods or other physical and analytical methods, capillary electrophoresis assays and two-hybrid assays.

One such screening method to identify direct binding of test ligands to a target protein is described in U.S. Pat. No. 5,585,277, incorporated herein by reference. This method relies on the principle that proteins generally exist as a mixture of folded and unfolded states, and continually alternate between the two states. When a test ligand binds to the folded form of a target protein (i.e., when the test ligand is a ligand of the target protein), the target protein molecule bound by the ligand remains in its folded state. Thus, the folded target protein is present to a greater extent in the presence of a test ligand which binds the target protein, than in the absence of a ligand. Binding of the ligand to the target protein can be determined by any method which distinguishes between the folded and unfolded states of the target protein. The function of the target protein need not be known in order for this assay to be performed. Virtually any agent can be assessed by this method as a test ligand, including, but not limited to, metals, polypeptides, proteins, lipids, polysaccharides, polynucleotides and small organic molecules.

Another method for identifying ligands of a target protein is described in Wieboldt et al., Anal. Chem., 69:1683-1691 (1997), incorporated herein by reference. This technique screens combinatorial libraries of 20-30 agents at a time in solution phase for binding, to the target protein. Agents that bind to the target protein are separated from other library components by simple membrane washing. The specifically selected molecules that are retained on the filter are subsequently liberated from the target protein and analyzed by HPLC and pneumatically assisted electrospray (ion spray) ionization mass spectroscopy. This procedure selects library components with the greatest affinity for the target protein, and is particularly useful for small molecule libraries.

Alternatively, such binding interactions are evaluated indirectly using the yeast two-hybrid system described in Fields et al., Nature, 340:245-246 (1989), and Fields et al., Trends in Genetics, 10:286-292 (1994), both of which are incorporated herein by reference. The two-hybrid system is a genetic assay for detecting interactions between two proteins or polypeptides. It can be used to identify proteins that bind to a known protein of interest, or to delineate domains or residues critical for an interaction. Variations on this methodology have been developed to clone genes that encode DNA binding proteins, to identify peptides that bind to a protein, and to screen for drugs. The two-hybrid system exploits the ability of a pair of interacting proteins to bring a transcription activation domain into close proximity with a DNA binding domain that binds to an upstream activation sequence (UAS) of a reporter gene, and is generally performed in yeast. The assay requires the construction of two hybrid genes encoding (1) a DNA-binding domain that is fused to a first protein and (2) an activation domain fused to a second protein. The DNA-binding domain targets the first hybrid protein to the UAS of the reporter gene; however, because most proteins lack an activation domain, this DNA-binding hybrid protein does not activate transcription of the reporter gene. The second hybrid protein, which contains the activation domain, cannot by itself activate expression of the reporter gene because it does not bind the UAS. However, when both hybrid proteins are present, the noncovalent interaction of the first and second proteins tethers the activation domain to the UAS, activating transcription of the reporter gene.

When the function of the GPCR-like receptor is unknown and no ligands are known to bind the gene product, the yeast two-hybrid assay can be used to identify proteins that bind to the receptor. In an assay to identify proteins that bind to a GPCR-like receptor, or fragment thereof, a fusion polynucleotide encoding both a GPCR-like receptor or fragment (i.e., a first protein) and a UAS binding domain may be used. In addition, a large number of hybrid genes each encoding a different second protein fused to an activation domain are produced and screened in the assay. Typically, the second protein is encoded by one or more members of a total cDNA or genomic DNA fusion library, with each second protein coding region being fused to the activation domain. This system is applicable to a wide variety of proteins, and it is not even necessary to know the identity or function of the second binding protein. The system is highly sensitive and can detect interactions not revealed by other methods; even transient interactions may trigger transcription to produce a stable mRNA that can be repeatedly translated to yield the reporter protein.

In addition, when the GPCR-like receptor or fragment thereof is known to interact with another protein or nucleic acid, the two-hybrid assay can be used to detect agents that interfere with the binding interaction. Expression of the reporter gene is monitored as different test agents are added to the system. The presence of an inhibitory agent, for example, results in lack of or reduction in a reporter signal.

The candidate modulators identified by the initial screens are evaluated for their effect on neuromuscular function using in vivo or ex vivo systems. A preferred evaluation method exposes the candidate modulators to A. suum neuromuscular strips and records neuromuscular activity relative to control strips exposed to compounds other than the candidate modulator under investigation. Other methods of screening for modulators are described in the following examples, and still other screening methods are well known in the art. Other aspects and advantages of the present invention will be understood upon consideration of the following illustrative examples. Example 1 describes the cloning of GPCR-like receptors; Example 2 provides an analysis of the polynucleotide sequences encoding those receptors in the context of their structural features such as regions and domains; Example 3 discloses GPCR-like receptor expression studies; Example 4 describes antibodies to GPCR-like receptors; Example 5 provides a variety of assays to identify modulators of GPCR-like receptor activity; and Example 6 describes approaches to the identification of candidate GPCR-like receptors, as well as the cloning and characterization of such receptors.

Homo sapiens

2

Met Asn Phe Ser Ala Thr Asp Ser Ile Leu Ala Ser Thr Ile Thr Thr

1 5 10 15

Val Ile Gly Gly Ala Gly Val Leu Ala Glu Ala Gly Glu Ala Glu Leu

20 25 30

Ser Gly Asp Asp Asp Phe Tyr Glu Leu Thr Pro Val Glu Leu Ile Ile

35 40 45

Trp Cys Met Leu Tyr Ala Ile Ile Ala Phe Met Ala Val Val Gly Asn

50 55 60

Leu Leu Val Leu Tyr Ile Thr Leu Phe Arg Leu Arg Val Arg Ser Ile

65 70 75 80

Thr Thr Tyr Phe Ile Leu Asn Leu Gly Phe Ala Asp Leu Phe Thr Gly

85 90 95

Ile Phe Ala Ile Pro Phe Lys Phe Gln Ala Ala Leu Phe Gln Glu Trp

100 105 110

Phe Leu Pro Arg Ser Leu Cys Arg Ile Val Pro Tyr Val Glu Thr Val

115 120 125

Ala Leu Thr Val Ser Val Phe Thr Leu Val Thr Ser Ala Val His Glu

130 135 140

Phe Arg Thr Met Phe Phe Ser Lys Cys Ser Gln Met Ser Pro Arg Ser

145 150 155 160

Ala Lys Arg Cys Val Leu Leu Ile Trp Ile Met Ala Val Leu Val Ser

165 170 175

Leu Pro His Gly Leu Phe His Asn Thr Tyr Glu Phe Pro Asp Asp Asn

180 185 190

Asn Thr Ser Ile Val Gln Cys Leu Pro Val Tyr Pro Asp Ala Gly Trp

195 200 205

Trp Lys Thr Tyr Asn Val Tyr Leu Val Ile Ile Gln Tyr Phe Val Pro

210 215 220

Met Ile Ile Leu Asp Thr Ala Tyr Thr Met Ile Ala Val Lys Ile Trp

225 230 235 240

Ser Leu Ser Gln Ser Arg Val Glu Leu Asp Glu Thr Lys Met Ala Thr

245 250 255

Gln Lys Leu Met Arg Thr Leu Ile Ile Val Val Ala Cys Phe Ser Leu

260 265 270

Cys Trp Phe Pro Leu Glu Thr Tyr Leu Leu Leu Asn Glu Leu Lys Pro

275 280 285

Glu Ile Asn Gly Trp Lys Tyr Ile Asn Leu Val Phe Phe Phe Ser His

290 295 300

Trp Leu Ala Met Ser Asn Ser Cys Leu Asn Pro Ile Ile Tyr Gly Leu

305 310 315 320

Tyr Asn Thr Lys Tyr Asn Glu Glu Tyr Arg Arg Leu Phe Arg Gln Ile

325 330 335

Gly Cys Ile Trp Gln Arg Gln Lys Ser Leu Asp Asp Ser Met Lys Pro

340 345 350

Glu Arg Arg Trp Asn Ser Ser Asn Asp Cys Gln Asp Gln Gln Glu Ile

355 360 365

Asp Gln Ile Val Asp Ile Pro Pro Val Ile Ser Thr Asn Asn Leu Ser

370 375 380

Pro

385

3

atg aac ttt tcg gcc acc gat tcg ata ttg gca tca acg ata aca acg 48

Met Asn Phe Ser Ala Thr Asp Ser Ile Leu Ala Ser Thr Ile Thr Thr

1 5 10 15

gtg att ggt gga gct gga gtt ttg gca gaa gca ggc gaa gct gaa cta 96

Val Ile Gly Gly Ala Gly Val Leu Ala Glu Ala Gly Glu Ala Glu Leu

20 25 30

tct ggt gat gat gat ttt tat gag ctg act cct gta gaa ttg ata ata 144

Ser Gly Asp Asp Asp Phe Tyr Glu Leu Thr Pro Val Glu Leu Ile Ile

35 40 45

tgg tgc atg ctg tat gca att ata gcc ttc atg gca gtt gtt gga aat 192

Trp Cys Met Leu Tyr Ala Ile Ile Ala Phe Met Ala Val Val Gly Asn

50 55 60

ctt ctg gtt ctc tac ata aca ctg ttc aga tta aga gtc cgt tcc atc 240

Leu Leu Val Leu Tyr Ile Thr Leu Phe Arg Leu Arg Val Arg Ser Ile

65 70 75 80

aca acc tac ttc att ctg aac ctc gga ttt gct gac ctc ttc act ggt 288

Thr Thr Tyr Phe Ile Leu Asn Leu Gly Phe Ala Asp Leu Phe Thr Gly

85 90 95

att ttt gcg att ccc ttc aag ttt cag gct gct ctt ttt caa gaa tgg 336

Ile Phe Ala Ile Pro Phe Lys Phe Gln Ala Ala Leu Phe Gln Glu Trp

100 105 110

ttc ctg ccg cga tca ctc tgc cgg ata gtt cca tac gtg gaa aca gtt 384

Phe Leu Pro Arg Ser Leu Cys Arg Ile Val Pro Tyr Val Glu Thr Val

115 120 125

gct ctg aca gtt tca gtc ttc aca ctt gtg acg tca gca gtt cat gaa 432

Ala Leu Thr Val Ser Val Phe Thr Leu Val Thr Ser Ala Val His Glu

130 135 140

ttc cgt aca atg ttc ttc tcg aaa tgc tca caa atg agc cca aga tct 480

Phe Arg Thr Met Phe Phe Ser Lys Cys Ser Gln Met Ser Pro Arg Ser

145 150 155 160

gca aaa cga tgt gta ctt ttg ata tgg ata atg gcg gtt ctt gtg tct 528

Ala Lys Arg Cys Val Leu Leu Ile Trp Ile Met Ala Val Leu Val Ser

165 170 175

cta cca cat gga ttg ttc cat aat aca tac gaa ttt cca gat gac aat 576

Leu Pro His Gly Leu Phe His Asn Thr Tyr Glu Phe Pro Asp Asp Asn

180 185 190

aat act tca att gta cag tgt ctc cca gta tat cct gat gct ggt tgg 624

Asn Thr Ser Ile Val Gln Cys Leu Pro Val Tyr Pro Asp Ala Gly Trp

195 200 205

tgg aaa aca tac aat gtc tac ctt gtc ata atc caa tat ttt gtt cca 672

Trp Lys Thr Tyr Asn Val Tyr Leu Val Ile Ile Gln Tyr Phe Val Pro

210 215 220

atg att att ctt gac act gcg tac aca atg att gct gtt aaa ata tgg 720

Met Ile Ile Leu Asp Thr Ala Tyr Thr Met Ile Ala Val Lys Ile Trp

225 230 235 240

tca ttg agt cag tca aga gtt gaa ctt gat gaa aca aaa atg gca acc 768

Ser Leu Ser Gln Ser Arg Val Glu Leu Asp Glu Thr Lys Met Ala Thr

245 250 255

cag aag ata tca gtg gta tca atg gtt tca cca aac act caa tta tcg 816

Gln Lys Ile Ser Val Val Ser Met Val Ser Pro Asn Thr Gln Leu Ser

260 265 270

cag ctt atg cgt act ctc atc att gtc gtt gcc tgt ttc tca ttg tgt 864

Gln Leu Met Arg Thr Leu Ile Ile Val Val Ala Cys Phe Ser Leu Cys

275 280 285

tgg ttt cca ttg gag acg tat cta ctt ttg aat gaa ttg aaa ccg gaa 912

Trp Phe Pro Leu Glu Thr Tyr Leu Leu Leu Asn Glu Leu Lys Pro Glu

290 295 300

att aat gga tgg aaa tac atc aat ttg gtg ttc ttc ttt tca cat tgg 960

Ile Asn Gly Trp Lys Tyr Ile Asn Leu Val Phe Phe Phe Ser His Trp

305 310 315 320

ctg gcg atg agc aat tct tgt ctt aat cca att att tat gga ctt tac 1008

Leu Ala Met Ser Asn Ser Cys Leu Asn Pro Ile Ile Tyr Gly Leu Tyr

325 330 335

aat aca aaa tac aac gag gaa tat cgt cgt ttg ttt cgc caa att gga 1056

Asn Thr Lys Tyr Asn Glu Glu Tyr Arg Arg Leu Phe Arg Gln Ile Gly

340 345 350

tgc att tgg caa cgg cag aaa agt ttg gac gat tcg atg aaa ccg gag 1104

Cys Ile Trp Gln Arg Gln Lys Ser Leu Asp Asp Ser Met Lys Pro Glu

355 360 365

cgt cgt tgg aat tct tca aat gat tgt caa gat caa cag gaa att gat 1152

Arg Arg Trp Asn Ser Ser Asn Asp Cys Gln Asp Gln Gln Glu Ile Asp

370 375 380

caa att gtt gat att cca cca gtt att tct aca aat aat ctt tct ccc 1200

Gln Ile Val Asp Ile Pro Pro Val Ile Ser Thr Asn Asn Leu Ser Pro

385 390 395 400

tg 1202

4

400

Homo sapiens

4

Met Asn Phe Ser Ala Thr Asp Ser Ile Leu Ala Ser Thr Ile Thr Thr

1 5 10 15

Val Ile Gly Gly Ala Gly Val Leu Ala Glu Ala Gly Glu Ala Glu Leu

20 25 30

Ser Gly Asp Asp Asp Phe Tyr Glu Leu Thr Pro Val Glu Leu Ile Ile

35 40 45

Trp Cys Met Leu Tyr Ala Ile Ile Ala Phe Met Ala Val Val Gly Asn

50 55 60

Leu Leu Val Leu Tyr Ile Thr Leu Phe Arg Leu Arg Val Arg Ser Ile

65 70 75 80

Thr Thr Tyr Phe Ile Leu Asn Leu Gly Phe Ala Asp Leu Phe Thr Gly

85 90 95

Ile Phe Ala Ile Pro Phe Lys Phe Gln Ala Ala Leu Phe Gln Glu Trp

100 105 110

Phe Leu Pro Arg Ser Leu Cys Arg Ile Val Pro Tyr Val Glu Thr Val

115 120 125

Ala Leu Thr Val Ser Val Phe Thr Leu Val Thr Ser Ala Val His Glu

130 135 140

Phe Arg Thr Met Phe Phe Ser Lys Cys Ser Gln Met Ser Pro Arg Ser

145 150 155 160

Ala Lys Arg Cys Val Leu Leu Ile Trp Ile Met Ala Val Leu Val Ser

165 170 175

Leu Pro His Gly Leu Phe His Asn Thr Tyr Glu Phe Pro Asp Asp Asn

180 185 190

Asn Thr Ser Ile Val Gln Cys Leu Pro Val Tyr Pro Asp Ala Gly Trp

195 200 205

Trp Lys Thr Tyr Asn Val Tyr Leu Val Ile Ile Gln Tyr Phe Val Pro

210 215 220

Met Ile Ile Leu Asp Thr Ala Tyr Thr Met Ile Ala Val Lys Ile Trp

225 230 235 240

Ser Leu Ser Gln Ser Arg Val Glu Leu Asp Glu Thr Lys Met Ala Thr

245 250 255

Gln Lys Ile Ser Val Val Ser Met Val Ser Pro Asn Thr Gln Leu Ser

260 265 270

Gln Leu Met Arg Thr Leu Ile Ile Val Val Ala Cys Phe Ser Leu Cys

275 280 285

Trp Phe Pro Leu Glu Thr Tyr Leu Leu Leu Asn Glu Leu Lys Pro Glu

290 295 300

Ile Asn Gly Trp Lys Tyr Ile Asn Leu Val Phe Phe Phe Ser His Trp

305 310 315 320

Leu Ala Met Ser Asn Ser Cys Leu Asn Pro Ile Ile Tyr Gly Leu Tyr

325 330 335

Asn Thr Lys Tyr Asn Glu Glu Tyr Arg Arg Leu Phe Arg Gln Ile Gly

340 345 350

Cys Ile Trp Gln Arg Gln Lys Ser Leu Asp Asp Ser Met Lys Pro Glu

355 360 365

Arg Arg Trp Asn Ser Ser Asn Asp Cys Gln Asp Gln Gln Glu Ile Asp

370 375 380

Gln Ile Val Asp Ile Pro Pro Val Ile Ser Thr Asn Asn Leu Ser Pro

385 390 395 400

5

atg tcg aat gat ctc gtg cct tca gtg tct tct ata cta aat gaa aca 48

Met Ser Asn Asp Leu Val Pro Ser Val Ser Ser Ile Leu Asn Glu Thr

1 5 10 15

aca cct tca tat caa agt aca tgt aaa atc aaa aac aac ccc atg gaa 96

Thr Pro Ser Tyr Gln Ser Thr Cys Lys Ile Lys Asn Asn Pro Met Glu

20 25 30

atg gaa tat ttc cgc cca ttc ttt att tct atg tat tgt gct gtt ttt 144

Met Glu Tyr Phe Arg Pro Phe Phe Ile Ser Met Tyr Cys Ala Val Phe

35 40 45

ttg gtt gct agt tcc ggt aat ttt ttg gtg gtg tac gtt gtg atg acg 192

Leu Val Ala Ser Ser Gly Asn Phe Leu Val Val Tyr Val Val Met Thr

50 55 60

aac aag cga atg cag acg atc acc aac att ttt att aca aat ctc gca 240

Asn Lys Arg Met Gln Thr Ile Thr Asn Ile Phe Ile Thr Asn Leu Ala

65 70 75 80

gtt tct gat ata atg gtt aac ttt aca tcg ttg tgg ctt aca cca aca 288

Val Ser Asp Ile Met Val Asn Phe Thr Ser Leu Trp Leu Thr Pro Thr

85 90 95

tac acc tca ata gga cat tgg ata ttc gga ggt gga ttg tgt cat ggt 336

Tyr Thr Ser Ile Gly His Trp Ile Phe Gly Gly Gly Leu Cys His Gly

100 105 110

tta ccc ctg ttc caa ggt aca agt atc ttc atc agt acg tgg aca ctt 384

Leu Pro Leu Phe Gln Gly Thr Ser Ile Phe Ile Ser Thr Trp Thr Leu

115 120 125

acg gct ata gcc ata gat cga tac ata gtg atc gtg cac aac tca tca 432

Thr Ala Ile Ala Ile Asp Arg Tyr Ile Val Ile Val His Asn Ser Ser

130 135 140

aat atc aat ata aat gat aga atg tcc atg aga tct tgc ctt tcg ttc 480

Asn Ile Asn Ile Asn Asp Arg Met Ser Met Arg Ser Cys Leu Ser Phe

145 150 155 160

att gtc ctc att tgg cta tgc tca ttg ctt ctg gtc act ccg tat gcc 528

Ile Val Leu Ile Trp Leu Cys Ser Leu Leu Leu Val Thr Pro Tyr Ala

165 170 175

atc aac atg aag ctc aac tac att cat gaa cca tgt gat ttt ctg ata 576

Ile Asn Met Lys Leu Asn Tyr Ile His Glu Pro Cys Asp Phe Leu Ile

180 185 190

tgt agt gag gac tgg agc aat gcc gaa ttt cga tct att ttt gga att 624

Cys Ser Glu Asp Trp Ser Asn Ala Glu Phe Arg Ser Ile Phe Gly Ile

195 200 205

gtg gtg atg att ctt caa ttc att ttg cca ttt gta ctc att gcc att 672

Val Val Met Ile Leu Gln Phe Ile Leu Pro Phe Val Leu Ile Ala Ile

210 215 220

agt tac ata aaa ata tgg ttg ttc cta aat agc cgt caa agt atg acc 720

Ser Tyr Ile Lys Ile Trp Leu Phe Leu Asn Ser Arg Gln Ser Met Thr

225 230 235 240

gag aga aaa tcc gat atc aag cgc aaa aag cgt tta cta cgg atg ttg 768

Glu Arg Lys Ser Asp Ile Lys Arg Lys Lys Arg Leu Leu Arg Met Leu

245 250 255

att gtc atg gtg gtc atc ttc gca att tgc tgg ttc cca ttc aac ctc 816

Ile Val Met Val Val Ile Phe Ala Ile Cys Trp Phe Pro Phe Asn Leu

260 265 270

tta aac tgt ctc cga gat ctc aag ttg gat aat ttc atg cgt ggc tac 864

Leu Asn Cys Leu Arg Asp Leu Lys Leu Asp Asn Phe Met Arg Gly Tyr

275 280 285

ttc agt ttt gtt ttc ctt tcc gtg cat ttg atg agt atg aca gct acc 912

Phe Ser Phe Val Phe Leu Ser Val His Leu Met Ser Met Thr Ala Thr

290 295 300

gcc tgg aat cca atc ctc tac gca ttc atg aat gag acc ttc cgt gag 960

Ala Trp Asn Pro Ile Leu Tyr Ala Phe Met Asn Glu Thr Phe Arg Glu

305 310 315 320

gag ttc gca aaa gtt gtt ccc tgc ttg ttt gcg cgt cgt cct gga act 1008

Glu Phe Ala Lys Val Val Pro Cys Leu Phe Ala Arg Arg Pro Gly Thr

325 330 335

ggt cca att cgc gtc atc act gaa cgc acc gct atg ata act aac ccg 1056

Gly Pro Ile Arg Val Ile Thr Glu Arg Thr Ala Met Ile Thr Asn Pro

340 345 350

ttt cga cgt gca aac cga aaa aaa aaa gtg gag gaa cag cct gtt acg 1104

Phe Arg Arg Ala Asn Arg Lys Lys Lys Val Glu Glu Gln Pro Val Thr

355 360 365

gtg att tct gat tca gag agt cca ctt caa act gca gtg gag ccg cag 1152

Val Ile Ser Asp Ser Glu Ser Pro Leu Gln Thr Ala Val Glu Pro Gln

370 375 380

cgc agt atc gtg tat ctc gat gag cct gag aac gga tca agt tgt cag 1200

Arg Ser Ile Val Tyr Leu Asp Glu Pro Glu Asn Gly Ser Ser Cys Gln

385 390 395 400

acg ctt ctg ctt ta 1214

Thr Leu Leu Leu

6

404

Homo sapiens

6

Met Ser Asn Asp Leu Val Pro Ser Val Ser Ser Ile Leu Asn Glu Thr

1 5 10 15

Thr Pro Ser Tyr Gln Ser Thr Cys Lys Ile Lys Asn Asn Pro Met Glu

20 25 30

Met Glu Tyr Phe Arg Pro Phe Phe Ile Ser Met Tyr Cys Ala Val Phe

35 40 45

Leu Val Ala Ser Ser Gly Asn Phe Leu Val Val Tyr Val Val Met Thr

50 55 60

Asn Lys Arg Met Gln Thr Ile Thr Asn Ile Phe Ile Thr Asn Leu Ala

65 70 75 80

Val Ser Asp Ile Met Val Asn Phe Thr Ser Leu Trp Leu Thr Pro Thr

85 90 95

Tyr Thr Ser Ile Gly His Trp Ile Phe Gly Gly Gly Leu Cys His Gly

100 105 110

Leu Pro Leu Phe Gln Gly Thr Ser Ile Phe Ile Ser Thr Trp Thr Leu

115 120 125

Thr Ala Ile Ala Ile Asp Arg Tyr Ile Val Ile Val His Asn Ser Ser

130 135 140

Asn Ile Asn Ile Asn Asp Arg Met Ser Met Arg Ser Cys Leu Ser Phe

145 150 155 160

Ile Val Leu Ile Trp Leu Cys Ser Leu Leu Leu Val Thr Pro Tyr Ala

165 170 175

Ile Asn Met Lys Leu Asn Tyr Ile His Glu Pro Cys Asp Phe Leu Ile

180 185 190

Cys Ser Glu Asp Trp Ser Asn Ala Glu Phe Arg Ser Ile Phe Gly Ile

195 200 205

Val Val Met Ile Leu Gln Phe Ile Leu Pro Phe Val Leu Ile Ala Ile

210 215 220

Ser Tyr Ile Lys Ile Trp Leu Phe Leu Asn Ser Arg Gln Ser Met Thr

225 230 235 240

Glu Arg Lys Ser Asp Ile Lys Arg Lys Lys Arg Leu Leu Arg Met Leu

245 250 255

Ile Val Met Val Val Ile Phe Ala Ile Cys Trp Phe Pro Phe Asn Leu

260 265 270

Leu Asn Cys Leu Arg Asp Leu Lys Leu Asp Asn Phe Met Arg Gly Tyr

275 280 285

Phe Ser Phe Val Phe Leu Ser Val His Leu Met Ser Met Thr Ala Thr

290 295 300

Ala Trp Asn Pro Ile Leu Tyr Ala Phe Met Asn Glu Thr Phe Arg Glu

305 310 315 320

Glu Phe Ala Lys Val Val Pro Cys Leu Phe Ala Arg Arg Pro Gly Thr

325 330 335

Gly Pro Ile Arg Val Ile Thr Glu Arg Thr Ala Met Ile Thr Asn Pro

340 345 350

Phe Arg Arg Ala Asn Arg Lys Lys Lys Val Glu Glu Gln Pro Val Thr

355 360 365

Val Ile Ser Asp Ser Glu Ser Pro Leu Gln Thr Ala Val Glu Pro Gln

370 375 380

Arg Ser Ile Val Tyr Leu Asp Glu Pro Glu Asn Gly Ser Ser Cys Gln

385 390 395 400

Thr Leu Leu Leu

7

atg tcg aat gat ctc gtg cct tca gtg tct tct ata cta aat gaa aca 48

Met Ser Asn Asp Leu Val Pro Ser Val Ser Ser Ile Leu Asn Glu Thr

1 5 10 15

aca cct tca tat caa agt aca tgt aaa atc aaa aac aac ccc atg gaa 96

Thr Pro Ser Tyr Gln Ser Thr Cys Lys Ile Lys Asn Asn Pro Met Glu

20 25 30

atg gaa tat ttc cgc cca ttc ttt att tct atg tat tgt gct gtt ttt 144

Met Glu Tyr Phe Arg Pro Phe Phe Ile Ser Met Tyr Cys Ala Val Phe

35 40 45

ttg gtt gct agt tcc ggt aat ttt ttg gtg gtg tac gtt gtg atg acg 192

Leu Val Ala Ser Ser Gly Asn Phe Leu Val Val Tyr Val Val Met Thr

50 55 60

aac aag cga atg cag acg atc acc aac att ttt att aca aat ctc gca 240

Asn Lys Arg Met Gln Thr Ile Thr Asn Ile Phe Ile Thr Asn Leu Ala

65 70 75 80

gtt tct gat ata atg gtt aac ttt aca tcg ttg tgg ctt aca cca aca 288

Val Ser Asp Ile Met Val Asn Phe Thr Ser Leu Trp Leu Thr Pro Thr

85 90 95

tac acc tca ata gga cat tgg ata ttc gga ggt gga ttg tgt cat ggt 336

Tyr Thr Ser Ile Gly His Trp Ile Phe Gly Gly Gly Leu Cys His Gly

100 105 110

tta ccc ctg ttc caa ggt aca agt atc ttc atc agt acg tgg aca ctt 384

Leu Pro Leu Phe Gln Gly Thr Ser Ile Phe Ile Ser Thr Trp Thr Leu

115 120 125

acg gct ata gcc ata gat cga tac ata gtg atc gtg cac aac tca tca 432

Thr Ala Ile Ala Ile Asp Arg Tyr Ile Val Ile Val His Asn Ser Ser

130 135 140

aat atc aat ata aat gat aga atg tcc atg aga tct tgc ctt tcg ttc 480

Asn Ile Asn Ile Asn Asp Arg Met Ser Met Arg Ser Cys Leu Ser Phe

145 150 155 160

att gtc ctc att tgg cta tgc tca ttg ctt ctg gtc act ccg tat gcc 528

Ile Val Leu Ile Trp Leu Cys Ser Leu Leu Leu Val Thr Pro Tyr Ala

165 170 175

atc aac atg aag ctc aac tac att cat gaa cca tgt gat ttt ctg ata 576

Ile Asn Met Lys Leu Asn Tyr Ile His Glu Pro Cys Asp Phe Leu Ile

180 185 190

tgt agt gag gac tgg agc aat gcc gaa ttt cga tct att ttt gga att 624

Cys Ser Glu Asp Trp Ser Asn Ala Glu Phe Arg Ser Ile Phe Gly Ile

195 200 205

gtg gtg atg att ctt caa ttc att ttg cca ttt gta ctc att gcc att 672

Val Val Met Ile Leu Gln Phe Ile Leu Pro Phe Val Leu Ile Ala Ile

210 215 220

agt tac ata aaa ata tgg ttg ttc cta aat agc cgt caa agt atg acc 720

Ser Tyr Ile Lys Ile Trp Leu Phe Leu Asn Ser Arg Gln Ser Met Thr

225 230 235 240

gag aga aaa tcc gat atc aag cgc aaa aag cgt tta cta cgg atg ttg 768

Glu Arg Lys Ser Asp Ile Lys Arg Lys Lys Arg Leu Leu Arg Met Leu

245 250 255

att gtc atg gtg gtc atc ttc gca att tgc tgg ttc cca ttc aac ctc 816

Ile Val Met Val Val Ile Phe Ala Ile Cys Trp Phe Pro Phe Asn Leu

260 265 270

tta aac tgt ctc cga gat ctc aag ttg gat aat ttc atg cgt ggc tac 864

Leu Asn Cys Leu Arg Asp Leu Lys Leu Asp Asn Phe Met Arg Gly Tyr

275 280 285

ttc agt ttt gtt ttc ctt tcc gtg cat ttg atg agt atg aca gct acc 912

Phe Ser Phe Val Phe Leu Ser Val His Leu Met Ser Met Thr Ala Thr

290 295 300

gcc tgg aat cca atc ctc tac gca ttc atg aat gag acc ttc cgt gag 960

Ala Trp Asn Pro Ile Leu Tyr Ala Phe Met Asn Glu Thr Phe Arg Glu

305 310 315 320

gag ttc gca aaa gtt gtt ccc tgc ttg ttt gcg cgt cgt cct gga act 1008

Glu Phe Ala Lys Val Val Pro Cys Leu Phe Ala Arg Arg Pro Gly Thr

325 330 335

ggt cca att cgc gtc atc act gaa cgc acc gct atg ata act aac ccg 1056

Gly Pro Ile Arg Val Ile Thr Glu Arg Thr Ala Met Ile Thr Asn Pro

340 345 350

ttt cga cgt gca aac cga aaa aaa aaa gtg gag gaa cag cct gtt acg 1104

Phe Arg Arg Ala Asn Arg Lys Lys Lys Val Glu Glu Gln Pro Val Thr

355 360 365

gtg att tct gag agt cca ctt caa act gca gtg gag ccg cag cgc agt 1152

Val Ile Ser Glu Ser Pro Leu Gln Thr Ala Val Glu Pro Gln Arg Ser

370 375 380

atc gtg tat ctc gat gag cct gag aac gga tca agt tgt cag acg ctt 1200

Ile Val Tyr Leu Asp Glu Pro Glu Asn Gly Ser Ser Cys Gln Thr Leu

385 390 395 400

ctg ctt ta 1208

Leu Leu

8

402

Homo sapiens

8

Met Ser Asn Asp Leu Val Pro Ser Val Ser Ser Ile Leu Asn Glu Thr

1 5 10 15

Thr Pro Ser Tyr Gln Ser Thr Cys Lys Ile Lys Asn Asn Pro Met Glu

20 25 30

Met Glu Tyr Phe Arg Pro Phe Phe Ile Ser Met Tyr Cys Ala Val Phe

35 40 45

Leu Val Ala Ser Ser Gly Asn Phe Leu Val Val Tyr Val Val Met Thr

50 55 60

Asn Lys Arg Met Gln Thr Ile Thr Asn Ile Phe Ile Thr Asn Leu Ala

65 70 75 80

Val Ser Asp Ile Met Val Asn Phe Thr Ser Leu Trp Leu Thr Pro Thr

85 90 95

Tyr Thr Ser Ile Gly His Trp Ile Phe Gly Gly Gly Leu Cys His Gly

100 105 110

Leu Pro Leu Phe Gln Gly Thr Ser Ile Phe Ile Ser Thr Trp Thr Leu

115 120 125

Thr Ala Ile Ala Ile Asp Arg Tyr Ile Val Ile Val His Asn Ser Ser

130 135 140

Asn Ile Asn Ile Asn Asp Arg Met Ser Met Arg Ser Cys Leu Ser Phe

145 150 155 160

Ile Val Leu Ile Trp Leu Cys Ser Leu Leu Leu Val Thr Pro Tyr Ala

165 170 175

Ile Asn Met Lys Leu Asn Tyr Ile His Glu Pro Cys Asp Phe Leu Ile

180 185 190

Cys Ser Glu Asp Trp Ser Asn Ala Glu Phe Arg Ser Ile Phe Gly Ile

195 200 205

Val Val Met Ile Leu Gln Phe Ile Leu Pro Phe Val Leu Ile Ala Ile

210 215 220

Ser Tyr Ile Lys Ile Trp Leu Phe Leu Asn Ser Arg Gln Ser Met Thr

225 230 235 240

Glu Arg Lys Ser Asp Ile Lys Arg Lys Lys Arg Leu Leu Arg Met Leu

245 250 255

Ile Val Met Val Val Ile Phe Ala Ile Cys Trp Phe Pro Phe Asn Leu

260 265 270

Leu Asn Cys Leu Arg Asp Leu Lys Leu Asp Asn Phe Met Arg Gly Tyr

275 280 285

Phe Ser Phe Val Phe Leu Ser Val His Leu Met Ser Met Thr Ala Thr

290 295 300

Ala Trp Asn Pro Ile Leu Tyr Ala Phe Met Asn Glu Thr Phe Arg Glu

305 310 315 320

Glu Phe Ala Lys Val Val Pro Cys Leu Phe Ala Arg Arg Pro Gly Thr

325 330 335

Gly Pro Ile Arg Val Ile Thr Glu Arg Thr Ala Met Ile Thr Asn Pro

340 345 350

Phe Arg Arg Ala Asn Arg Lys Lys Lys Val Glu Glu Gln Pro Val Thr

355 360 365

Val Ile Ser Glu Ser Pro Leu Gln Thr Ala Val Glu Pro Gln Arg Ser

370 375 380

Ile Val Tyr Leu Asp Glu Pro Glu Asn Gly Ser Ser Cys Gln Thr Leu

385 390 395 400

Leu Leu

9

atg tcg aat gat ctc gtg cct tca gtg tct tct ata cta aat gaa aca 48

Met Ser Asn Asp Leu Val Pro Ser Val Ser Ser Ile Leu Asn Glu Thr

1 5 10 15

aca cct tca tat caa agt aca tgt aaa atc aaa aac aac ccc atg gaa 96

Thr Pro Ser Tyr Gln Ser Thr Cys Lys Ile Lys Asn Asn Pro Met Glu

20 25 30

atg gaa tat ttc cgc cca ttc ttt att tct atg tat tgt gct gtt ttt 144

Met Glu Tyr Phe Arg Pro Phe Phe Ile Ser Met Tyr Cys Ala Val Phe

35 40 45

ttg gtt gct agt tcc ggt aat ttt ttg gtg gtg tac gtt gtg atg acg 192

Leu Val Ala Ser Ser Gly Asn Phe Leu Val Val Tyr Val Val Met Thr

50 55 60

aac aag cga atg cag acg atc acc aac att ttt att aca aat ctc gca 240

Asn Lys Arg Met Gln Thr Ile Thr Asn Ile Phe Ile Thr Asn Leu Ala

65 70 75 80

gtt tct gat ata atg gtt aac ttt aca tcg ttg tgg ctt aca cca aca 288

Val Ser Asp Ile Met Val Asn Phe Thr Ser Leu Trp Leu Thr Pro Thr

85 90 95

tac acc tca ata gga cat tgg ata ttc gga ggt gga ttg tgt cat ggt 336

Tyr Thr Ser Ile Gly His Trp Ile Phe Gly Gly Gly Leu Cys His Gly

100 105 110

tta ccc ctg ttc caa ggt aca agt atc ttc atc agt acg tgg aca ctt 384

Leu Pro Leu Phe Gln Gly Thr Ser Ile Phe Ile Ser Thr Trp Thr Leu

115 120 125

acg gct ata gcc ata gat cga tac ata gtg atc gtg cac aac tca tca 432

Thr Ala Ile Ala Ile Asp Arg Tyr Ile Val Ile Val His Asn Ser Ser

130 135 140

aat atc aat ata aat gat aga atg tcc atg aga tct tgc ctt tcg ttc 480

Asn Ile Asn Ile Asn Asp Arg Met Ser Met Arg Ser Cys Leu Ser Phe

145 150 155 160

att gtc ctc att tgg cta tgc tca ttg ctt ctg gtc act ccg tat gcc 528

Ile Val Leu Ile Trp Leu Cys Ser Leu Leu Leu Val Thr Pro Tyr Ala

165 170 175

atc aac atg aag ctc aac tac att cat gaa cca tgt gat ttt ctg ata 576

Ile Asn Met Lys Leu Asn Tyr Ile His Glu Pro Cys Asp Phe Leu Ile

180 185 190

tgt agt gag gac tgg agc aat gcc gaa ttt cga tct att ttt gga att 624

Cys Ser Glu Asp Trp Ser Asn Ala Glu Phe Arg Ser Ile Phe Gly Ile

195 200 205

gtg gtg atg att ctt caa ttc att ttg cca ttt gta ctc att gcc att 672

Val Val Met Ile Leu Gln Phe Ile Leu Pro Phe Val Leu Ile Ala Ile

210 215 220

agt tac ata aaa ata tgg ttg ttc cta aat agc cgt caa agt atg acc 720

Ser Tyr Ile Lys Ile Trp Leu Phe Leu Asn Ser Arg Gln Ser Met Thr

225 230 235 240

gag aga aaa tcc gat atc aag cgc aaa aag cgt tta cta cgg atg ttg 768

Glu Arg Lys Ser Asp Ile Lys Arg Lys Lys Arg Leu Leu Arg Met Leu

245 250 255

att gtc atg gtg gtc atc ttc gca att tgc tgg ttc cca ttc aac ctc 816

Ile Val Met Val Val Ile Phe Ala Ile Cys Trp Phe Pro Phe Asn Leu

260 265 270

tta aac tgt ctc cga gat ctc aag ttg gat aat ttc atg cgt ggc tac 864

Leu Asn Cys Leu Arg Asp Leu Lys Leu Asp Asn Phe Met Arg Gly Tyr

275 280 285

ttc agt ttt gtt ttc ctt tcc gtg cat ttg atg agt atg aca gct acc 912

Phe Ser Phe Val Phe Leu Ser Val His Leu Met Ser Met Thr Ala Thr

290 295 300

gcc tgg aat cca atc ctc tac gca ttc atg aat gag acc ttc cgt gag 960

Ala Trp Asn Pro Ile Leu Tyr Ala Phe Met Asn Glu Thr Phe Arg Glu

305 310 315 320

gag ttc gca aaa gtt gtt ccc tgc ttg ttt gcg cgt cgt cct gga act 1008

Glu Phe Ala Lys Val Val Pro Cys Leu Phe Ala Arg Arg Pro Gly Thr

325 330 335

ggt cca att cgc gtc atc act gaa cgc acc gct atg ata act aac ccg 1056

Gly Pro Ile Arg Val Ile Thr Glu Arg Thr Ala Met Ile Thr Asn Pro

340 345 350

ttt cga cgt gca aac cga aaa aaa aaa gtg gag gaa cag cct gtt acg 1104

Phe Arg Arg Ala Asn Arg Lys Lys Lys Val Glu Glu Gln Pro Val Thr

355 360 365

gtg att tct gaa aca gat tca gag agt cca ctt caa act gca gtg gag 1152

Val Ile Ser Glu Thr Asp Ser Glu Ser Pro Leu Gln Thr Ala Val Glu

370 375 380

ccg cag cgc agt atc gtg tat ctc gat gag cct gag aac gga tca agt 1200

Pro Gln Arg Ser Ile Val Tyr Leu Asp Glu Pro Glu Asn Gly Ser Ser

385 390 395 400

tgt cag acg ctt ctg ctt ta 1220

Cys Gln Thr Leu Leu Leu

405

10

406

Homo sapiens

10

Met Ser Asn Asp Leu Val Pro Ser Val Ser Ser Ile Leu Asn Glu Thr

1 5 10 15

Thr Pro Ser Tyr Gln Ser Thr Cys Lys Ile Lys Asn Asn Pro Met Glu

20 25 30

Met Glu Tyr Phe Arg Pro Phe Phe Ile Ser Met Tyr Cys Ala Val Phe

35 40 45

Leu Val Ala Ser Ser Gly Asn Phe Leu Val Val Tyr Val Val Met Thr

50 55 60

Asn Lys Arg Met Gln Thr Ile Thr Asn Ile Phe Ile Thr Asn Leu Ala

65 70 75 80

Val Ser Asp Ile Met Val Asn Phe Thr Ser Leu Trp Leu Thr Pro Thr

85 90 95

Tyr Thr Ser Ile Gly His Trp Ile Phe Gly Gly Gly Leu Cys His Gly

100 105 110

Leu Pro Leu Phe Gln Gly Thr Ser Ile Phe Ile Ser Thr Trp Thr Leu

115 120 125

Thr Ala Ile Ala Ile Asp Arg Tyr Ile Val Ile Val His Asn Ser Ser

130 135 140

Asn Ile Asn Ile Asn Asp Arg Met Ser Met Arg Ser Cys Leu Ser Phe

145 150 155 160

Ile Val Leu Ile Trp Leu Cys Ser Leu Leu Leu Val Thr Pro Tyr Ala

165 170 175

Ile Asn Met Lys Leu Asn Tyr Ile His Glu Pro Cys Asp Phe Leu Ile

180 185 190

Cys Ser Glu Asp Trp Ser Asn Ala Glu Phe Arg Ser Ile Phe Gly Ile

195 200 205

Val Val Met Ile Leu Gln Phe Ile Leu Pro Phe Val Leu Ile Ala Ile

210 215 220

Ser Tyr Ile Lys Ile Trp Leu Phe Leu Asn Ser Arg Gln Ser Met Thr

225 230 235 240

Glu Arg Lys Ser Asp Ile Lys Arg Lys Lys Arg Leu Leu Arg Met Leu

245 250 255

Ile Val Met Val Val Ile Phe Ala Ile Cys Trp Phe Pro Phe Asn Leu

260 265 270

Leu Asn Cys Leu Arg Asp Leu Lys Leu Asp Asn Phe Met Arg Gly Tyr

275 280 285

Phe Ser Phe Val Phe Leu Ser Val His Leu Met Ser Met Thr Ala Thr

290 295 300

Ala Trp Asn Pro Ile Leu Tyr Ala Phe Met Asn Glu Thr Phe Arg Glu

305 310 315 320

Glu Phe Ala Lys Val Val Pro Cys Leu Phe Ala Arg Arg Pro Gly Thr

325 330 335

Gly Pro Ile Arg Val Ile Thr Glu Arg Thr Ala Met Ile Thr Asn Pro

340 345 350

Phe Arg Arg Ala Asn Arg Lys Lys Lys Val Glu Glu Gln Pro Val Thr

355 360 365

Val Ile Ser Glu Thr Asp Ser Glu Ser Pro Leu Gln Thr Ala Val Glu

370 375 380

Pro Gln Arg Ser Ile Val Tyr Leu Asp Glu Pro Glu Asn Gly Ser Ser

385 390 395 400

Cys Gln Thr Leu Leu Leu

11

atg tcg aat gat ctc gtg cct tca gtg tct tct ata cta aat gaa aca 48

Met Ser Asn Asp Leu Val Pro Ser Val Ser Ser Ile Leu Asn Glu Thr

1 5 10 15

aca cct tca tat caa agt aca tgt aaa atc aaa aac aac ccc atg gaa 96

Thr Pro Ser Tyr Gln Ser Thr Cys Lys Ile Lys Asn Asn Pro Met Glu

20 25 30

atg gaa tat ttc cgc cca ttc ttt att tct atg tat tgt gct gtt ttt 144

Met Glu Tyr Phe Arg Pro Phe Phe Ile Ser Met Tyr Cys Ala Val Phe

35 40 45

ttg gtt gct agt tcc ggt aat ttt ttg gtg gtg tac gtt gtg atg acg 192

Leu Val Ala Ser Ser Gly Asn Phe Leu Val Val Tyr Val Val Met Thr

50 55 60

aac aag cga atg cag acg atc acc aac att ttt att aca aat ctc gca 240

Asn Lys Arg Met Gln Thr Ile Thr Asn Ile Phe Ile Thr Asn Leu Ala

65 70 75 80

gtt tct gat ata atg gtt aac ttt aca tcg ttg tgg ctt aca cca aca 288

Val Ser Asp Ile Met Val Asn Phe Thr Ser Leu Trp Leu Thr Pro Thr

85 90 95

tac acc tca ata gga cat tgg ata ttc gga ggt gga ttg tgt cat ggt 336

Tyr Thr Ser Ile Gly His Trp Ile Phe Gly Gly Gly Leu Cys His Gly

100 105 110

tta ccc ctg ttc caa ggt aca agt atc ttc atc agt acg tgg aca ctt 384

Leu Pro Leu Phe Gln Gly Thr Ser Ile Phe Ile Ser Thr Trp Thr Leu

115 120 125

acg gct ata gcc ata gat cga tac ata gtg atc gtg cac aac tca tca 432

Thr Ala Ile Ala Ile Asp Arg Tyr Ile Val Ile Val His Asn Ser Ser

130 135 140

aat atc aat ata aat gat aga atg tcc atg aga tct tgc ctt tcg ttc 480

Asn Ile Asn Ile Asn Asp Arg Met Ser Met Arg Ser Cys Leu Ser Phe

145 150 155 160

att gtc ctc att tgg cta tgc tca ttg ctt ctg gtc act ccg tat gcc 528

Ile Val Leu Ile Trp Leu Cys Ser Leu Leu Leu Val Thr Pro Tyr Ala

165 170 175

atc aac atg aag ctc aac tac att cat gaa cca tgt gat ttt ctg ata 576

Ile Asn Met Lys Leu Asn Tyr Ile His Glu Pro Cys Asp Phe Leu Ile

180 185 190

tgt agt gag gac tgg agc aat gcc gaa ttt cga tct att ttt gga att 624

Cys Ser Glu Asp Trp Ser Asn Ala Glu Phe Arg Ser Ile Phe Gly Ile

195 200 205

gtg gtg atg att ctt caa ttc att ttg cca ttt gta ctc att gcc att 672

Val Val Met Ile Leu Gln Phe Ile Leu Pro Phe Val Leu Ile Ala Ile

210 215 220

agt tac ata aaa ata tgg ttg ttc cta aat agc cgt caa agt atg acc 720

Ser Tyr Ile Lys Ile Trp Leu Phe Leu Asn Ser Arg Gln Ser Met Thr

225 230 235 240

gag aga aaa tcc gat atc aag cgc aaa aag cgt tta cta cgg atg ttg 768

Glu Arg Lys Ser Asp Ile Lys Arg Lys Lys Arg Leu Leu Arg Met Leu

245 250 255

att gtc atg gtg gtc atc ttc gca att tgc tgg ttc cca ttc aac ctc 816

Ile Val Met Val Val Ile Phe Ala Ile Cys Trp Phe Pro Phe Asn Leu

260 265 270

tta aac tgt ctc cga gat ctc aag ttg gat aat ttc atg cgt ggc tac 864

Leu Asn Cys Leu Arg Asp Leu Lys Leu Asp Asn Phe Met Arg Gly Tyr

275 280 285

ttc agt ttt gtt ttc ctt tcc gtg cat ttg atg agt atg aca gct acc 912

Phe Ser Phe Val Phe Leu Ser Val His Leu Met Ser Met Thr Ala Thr

290 295 300

gcc tgg aat cca atc ctc tac gca ttc atg aat gag acc ttc cgt gag 960

Ala Trp Asn Pro Ile Leu Tyr Ala Phe Met Asn Glu Thr Phe Arg Glu

305 310 315 320

gag ttc gca aaa gtt gtt ccc tgc ttg ttt gcg cgt cgt cct gga act 1008

Glu Phe Ala Lys Val Val Pro Cys Leu Phe Ala Arg Arg Pro Gly Thr

325 330 335

ggt cca att cgc gtc atc act gaa cgc acc gct atg ata act aac ccg 1056

Gly Pro Ile Arg Val Ile Thr Glu Arg Thr Ala Met Ile Thr Asn Pro

340 345 350

ttt cga cgt gca aac cga aaa aaa aaa gtg gag gaa cag cct gtt acg 1104

Phe Arg Arg Ala Asn Arg Lys Lys Lys Val Glu Glu Gln Pro Val Thr

355 360 365

gtg att tct gaa ctt tta cac ccg aca tcc aac gaa gaa taggaagcca 1153

Val Ile Ser Glu Leu Leu His Pro Thr Ser Asn Glu Glu

370 375 380

ttcattccct gcatgcactc gttgtcagtg aacttttcaa caaaccagca atctttagaa 1213

acagattcag agagtccact tcaaactgca gtggagccgc agcgcagtat cgtgtatctc 1273

gatgagcctg agaacggatc aagttgtcag acgcttctgc tttaa 1318

12

381

Homo sapiens

12

Met Ser Asn Asp Leu Val Pro Ser Val Ser Ser Ile Leu Asn Glu Thr

1 5 10 15

Thr Pro Ser Tyr Gln Ser Thr Cys Lys Ile Lys Asn Asn Pro Met Glu

20 25 30

Met Glu Tyr Phe Arg Pro Phe Phe Ile Ser Met Tyr Cys Ala Val Phe

35 40 45

Leu Val Ala Ser Ser Gly Asn Phe Leu Val Val Tyr Val Val Met Thr

50 55 60

Asn Lys Arg Met Gln Thr Ile Thr Asn Ile Phe Ile Thr Asn Leu Ala

65 70 75 80

Val Ser Asp Ile Met Val Asn Phe Thr Ser Leu Trp Leu Thr Pro Thr

85 90 95

Tyr Thr Ser Ile Gly His Trp Ile Phe Gly Gly Gly Leu Cys His Gly

100 105 110

Leu Pro Leu Phe Gln Gly Thr Ser Ile Phe Ile Ser Thr Trp Thr Leu

115 120 125

Thr Ala Ile Ala Ile Asp Arg Tyr Ile Val Ile Val His Asn Ser Ser

130 135 140

Asn Ile Asn Ile Asn Asp Arg Met Ser Met Arg Ser Cys Leu Ser Phe

145 150 155 160

Ile Val Leu Ile Trp Leu Cys Ser Leu Leu Leu Val Thr Pro Tyr Ala

165 170 175

Ile Asn Met Lys Leu Asn Tyr Ile His Glu Pro Cys Asp Phe Leu Ile

180 185 190

Cys Ser Glu Asp Trp Ser Asn Ala Glu Phe Arg Ser Ile Phe Gly Ile

195 200 205

Val Val Met Ile Leu Gln Phe Ile Leu Pro Phe Val Leu Ile Ala Ile

210 215 220

Ser Tyr Ile Lys Ile Trp Leu Phe Leu Asn Ser Arg Gln Ser Met Thr

225 230 235 240

Glu Arg Lys Ser Asp Ile Lys Arg Lys Lys Arg Leu Leu Arg Met Leu

245 250 255

Ile Val Met Val Val Ile Phe Ala Ile Cys Trp Phe Pro Phe Asn Leu

260 265 270

Leu Asn Cys Leu Arg Asp Leu Lys Leu Asp Asn Phe Met Arg Gly Tyr

275 280 285

Phe Ser Phe Val Phe Leu Ser Val His Leu Met Ser Met Thr Ala Thr

290 295 300

Ala Trp Asn Pro Ile Leu Tyr Ala Phe Met Asn Glu Thr Phe Arg Glu

305 310 315 320

Glu Phe Ala Lys Val Val Pro Cys Leu Phe Ala Arg Arg Pro Gly Thr

325 330 335

Gly Pro Ile Arg Val Ile Thr Glu Arg Thr Ala Met Ile Thr Asn Pro

340 345 350

Phe Arg Arg Ala Asn Arg Lys Lys Lys Val Glu Glu Gln Pro Val Thr

355 360 365

Val Ile Ser Glu Leu Leu His Pro Thr Ser Asn Glu Glu

370 375 380

13

atg atc aac gaa aca gaa gag aca tgt gat cga tat ata gac aag cat 48

Met Ile Asn Glu Thr Glu Glu Thr Cys Asp Arg Tyr Ile Asp Lys His

1 5 10 15

cca gat atg aca aat gaa cca aca gtc ctt gtc aca ttc tcc ctg ctt 96

Pro Asp Met Thr Asn Glu Pro Thr Val Leu Val Thr Phe Ser Leu Leu

20 25 30

tat ctt cat att ttt ctt ctt gga atc cta gga aat tcg gct gtt cta 144

Tyr Leu His Ile Phe Leu Leu Gly Ile Leu Gly Asn Ser Ala Val Leu

35 40 45

tat ctt aca atg aaa cat cgt caa tta caa act gtt caa aat ata ttt 192

Tyr Leu Thr Met Lys His Arg Gln Leu Gln Thr Val Gln Asn Ile Phe

50 55 60

att ttg aac tta tgc gca tcg aat gtt tta atg tgc ttg acg agt ctt 240

Ile Leu Asn Leu Cys Ala Ser Asn Val Leu Met Cys Leu Thr Ser Leu

65 70 75 80

cca atc aca ttt atc aca aat gtc tac aaa caa tgg ttc ttc tca tcg 288

Pro Ile Thr Phe Ile Thr Asn Val Tyr Lys Gln Trp Phe Phe Ser Ser

85 90 95

cct gtt tgt aaa ctt att cca ttg gtt cag gga gct tca atc ttt gtc 336

Pro Val Cys Lys Leu Ile Pro Leu Val Gln Gly Ala Ser Ile Phe Val

100 105 110

tcc act ttc tcc ctt tcc gcc att gca ctt gac cga tac aac ctc gtg 384

Ser Thr Phe Ser Leu Ser Ala Ile Ala Leu Asp Arg Tyr Asn Leu Val

115 120 125

gtt cgt cct cat aaa caa aaa ctc agt tca cga agt gca atg atg att 432

Val Arg Pro His Lys Gln Lys Leu Ser Ser Arg Ser Ala Met Met Ile

130 135 140

gct ctt ctc att tgg gtt att agt gta gtt gtt tgt atg cca tat gga 480

Ala Leu Leu Ile Trp Val Ile Ser Val Val Val Cys Met Pro Tyr Gly

145 150 155 160

tgg tac atg gat gtg gag aag ctc aat gga tta tgt gga gag tac tgt 528

Trp Tyr Met Asp Val Glu Lys Leu Asn Gly Leu Cys Gly Glu Tyr Cys

165 170 175

tct gag cac tgg cca tta gca gaa gta cga aag gga tat act ttt ttg 576

Ser Glu His Trp Pro Leu Ala Glu Val Arg Lys Gly Tyr Thr Phe Leu

180 185 190

gtg tta atc act caa ttt ttg ttt cct ttt gct acg atg gct ttt tgc 624

Val Leu Ile Thr Gln Phe Leu Phe Pro Phe Ala Thr Met Ala Phe Cys

195 200 205

tat tat aat att ttt tca aga ctc aga caa cga gtg gaa acg aaa ctg 672

Tyr Tyr Asn Ile Phe Ser Arg Leu Arg Gln Arg Val Glu Thr Lys Leu

210 215 220

aag aaa tta tca gaa aga tct caa ctt ttg gag aat agt aca aca tgt 720

Lys Lys Leu Ser Glu Arg Ser Gln Leu Leu Glu Asn Ser Thr Thr Cys

225 230 235 240

gga acc act aac cac att gtt agc att aac gcg gaa gca gtt caa aat 768

Gly Thr Thr Asn His Ile Val Ser Ile Asn Ala Glu Ala Val Gln Asn

245 250 255

ggt ctg gaa aac aaa caa aga tta gct gtt ctt gct caa caa aga agg 816

Gly Leu Glu Asn Lys Gln Arg Leu Ala Val Leu Ala Gln Gln Arg Arg

260 265 270

aca act act att tta tcg tgc atg gtt ctt ctt ttt gca ttt aca tgg 864

Thr Thr Thr Ile Leu Ser Cys Met Val Leu Leu Phe Ala Phe Thr Trp

275 280 285

ctt cca cat aat gtt gtc act ttg atg ata gaa tac gat gga ttc ttt 912

Leu Pro His Asn Val Val Thr Leu Met Ile Glu Tyr Asp Gly Phe Phe

290 295 300

ttt cat tct gat gag aca tcg gca acc agt acc gat cat aca tat att 960

Phe His Ser Asp Glu Thr Ser Ala Thr Ser Thr Asp His Thr Tyr Ile

305 310 315 320

gtt tca atg act gct cat tta ata tcc atg tta aca aat gta acc aac 1008

Val Ser Met Thr Ala His Leu Ile Ser Met Leu Thr Asn Val Thr Asn

325 330 335

cca ttt ctg tat gct tgg ctt aac cca atg ttc aaa gaa atg ctt att 1056

Pro Phe Leu Tyr Ala Trp Leu Asn Pro Met Phe Lys Glu Met Leu Ile

340 345 350

aaa act ctc aga ggt gga agt aaa tcc ccg aaa cca gct gac atc aag 1104

Lys Thr Leu Arg Gly Gly Ser Lys Ser Pro Lys Pro Ala Asp Ile Lys

355 360 365

caa act tca ttc att cga atg ccg aat agt ggt gcg cca agt caa tct 1152

Gln Thr Ser Phe Ile Arg Met Pro Asn Ser Gly Ala Pro Ser Gln Ser

370 375 380

tcc tac ctg tg 1163

Ser Tyr Leu

385

14

387

Homo sapiens

14

Met Ile Asn Glu Thr Glu Glu Thr Cys Asp Arg Tyr Ile Asp Lys His

1 5 10 15

Pro Asp Met Thr Asn Glu Pro Thr Val Leu Val Thr Phe Ser Leu Leu

20 25 30

Tyr Leu His Ile Phe Leu Leu Gly Ile Leu Gly Asn Ser Ala Val Leu

35 40 45

Tyr Leu Thr Met Lys His Arg Gln Leu Gln Thr Val Gln Asn Ile Phe

50 55 60

Ile Leu Asn Leu Cys Ala Ser Asn Val Leu Met Cys Leu Thr Ser Leu

65 70 75 80

Pro Ile Thr Phe Ile Thr Asn Val Tyr Lys Gln Trp Phe Phe Ser Ser

85 90 95

Pro Val Cys Lys Leu Ile Pro Leu Val Gln Gly Ala Ser Ile Phe Val

100 105 110

Ser Thr Phe Ser Leu Ser Ala Ile Ala Leu Asp Arg Tyr Asn Leu Val

115 120 125

Val Arg Pro His Lys Gln Lys Leu Ser Ser Arg Ser Ala Met Met Ile

130 135 140

Ala Leu Leu Ile Trp Val Ile Ser Val Val Val Cys Met Pro Tyr Gly

145 150 155 160

Trp Tyr Met Asp Val Glu Lys Leu Asn Gly Leu Cys Gly Glu Tyr Cys

165 170 175

Ser Glu His Trp Pro Leu Ala Glu Val Arg Lys Gly Tyr Thr Phe Leu

180 185 190

Val Leu Ile Thr Gln Phe Leu Phe Pro Phe Ala Thr Met Ala Phe Cys

195 200 205

Tyr Tyr Asn Ile Phe Ser Arg Leu Arg Gln Arg Val Glu Thr Lys Leu

210 215 220

Lys Lys Leu Ser Glu Arg Ser Gln Leu Leu Glu Asn Ser Thr Thr Cys

225 230 235 240

Gly Thr Thr Asn His Ile Val Ser Ile Asn Ala Glu Ala Val Gln Asn

245 250 255

Gly Leu Glu Asn Lys Gln Arg Leu Ala Val Leu Ala Gln Gln Arg Arg

260 265 270

Thr Thr Thr Ile Leu Ser Cys Met Val Leu Leu Phe Ala Phe Thr Trp

275 280 285

Leu Pro His Asn Val Val Thr Leu Met Ile Glu Tyr Asp Gly Phe Phe

290 295 300

Phe His Ser Asp Glu Thr Ser Ala Thr Ser Thr Asp His Thr Tyr Ile

305 310 315 320

Val Ser Met Thr Ala His Leu Ile Ser Met Leu Thr Asn Val Thr Asn

325 330 335

Pro Phe Leu Tyr Ala Trp Leu Asn Pro Met Phe Lys Glu Met Leu Ile

340 345 350

Lys Thr Leu Arg Gly Gly Ser Lys Ser Pro Lys Pro Ala Asp Ile Lys

355 360 365

Gln Thr Ser Phe Ile Arg Met Pro Asn Ser Gly Ala Pro Ser Gln Ser

370 375 380

Ser Tyr Leu

385

15

atg ggt gat gct gaa tct cat cat tgt ata gat gtg aac gcc att ctt 48

Met Gly Asp Ala Glu Ser His His Cys Ile Asp Val Asn Ala Ile Leu

1 5 10 15

cag cag ttc aat gat tgg aca gtc ctc ttt gaa gtt cgg ctt gga tat 96

Gln Gln Phe Asn Asp Trp Thr Val Leu Phe Glu Val Arg Leu Gly Tyr

20 25 30

tca gta cta tac ttt ctc ata tta ata atc gga ttg gtt gga aat ggg 144

Ser Val Leu Tyr Phe Leu Ile Leu Ile Ile Gly Leu Val Gly Asn Gly

35 40 45

cta ttg atc act tca att tta atg cga aag aaa ctt tcc gtg gca aac 192

Leu Leu Ile Thr Ser Ile Leu Met Arg Lys Lys Leu Ser Val Ala Asn

50 55 60

ata ttc ttg ata aac ctg gca gtt tct gat ttg ctt ctt tgc atc acg 240

Ile Phe Leu Ile Asn Leu Ala Val Ser Asp Leu Leu Leu Cys Ile Thr

65 70 75 80

gcg gtg ccg atc act cca gta ttg gcg ttt atg aag cga tgg ata ttt 288

Ala Val Pro Ile Thr Pro Val Leu Ala Phe Met Lys Arg Trp Ile Phe

85 90 95

gga ata att atg tgt aaa ttg gtt cca act tgt cag gcg ttt tcg gtg 336

Gly Ile Ile Met Cys Lys Leu Val Pro Thr Cys Gln Ala Phe Ser Val

100 105 110

ctc att tct tca tgg tct ttg tgt tac atc gca att gat aga tat cga 384

Leu Ile Ser Ser Trp Ser Leu Cys Tyr Ile Ala Ile Asp Arg Tyr Arg

115 120 125

agt att gtg acg cca ctc cgg gaa cca tgg tct gat agg cat gca agg 432

Ser Ile Val Thr Pro Leu Arg Glu Pro Trp Ser Asp Arg His Ala Arg

130 135 140

tgg ctt ctg atg ttc aca tgg gtg gtc gcc ttc ctt gct agt tat cct 480

Trp Leu Leu Met Phe Thr Trp Val Val Ala Phe Leu Ala Ser Tyr Pro

145 150 155 160

cta tat tac tca cag aac ttg aaa aca atg gtt att gaa aat gtg aca 528

Leu Tyr Tyr Ser Gln Asn Leu Lys Thr Met Val Ile Glu Asn Val Thr

165 170 175

tta tgt gga gat ttt tgc ggc gag ttc aat tgg cag tcg gat gaa ata 576

Leu Cys Gly Asp Phe Cys Gly Glu Phe Asn Trp Gln Ser Asp Glu Ile

180 185 190

tcc aag ttg aca tat act acg agt tta ttg att att cag ctg att att 624

Ser Lys Leu Thr Tyr Thr Thr Ser Leu Leu Ile Ile Gln Leu Ile Ile

195 200 205

cca gca att atc atg tct ttt tgt tat tta atg att cta caa aag gta 672

Pro Ala Ile Ile Met Ser Phe Cys Tyr Leu Met Ile Leu Gln Lys Val

210 215 220

caa acc gac tgg ctt gtc gac gag gga tcc atg ttg act gcc gca caa 720

Gln Thr Asp Trp Leu Val Asp Glu Gly Ser Met Leu Thr Ala Ala Gln

225 230 235 240

cag gct caa aca gca gtt cga aag cga cga gtg atg tac gtg ttg att 768

Gln Ala Gln Thr Ala Val Arg Lys Arg Arg Val Met Tyr Val Leu Ile

245 250 255

cta atg gtt att gtt ttt atg gct tgc tgg ttc ccg ttg tcc gcc gtg 816

Leu Met Val Ile Val Phe Met Ala Cys Trp Phe Pro Leu Ser Ala Val

260 265 270

aat ttg ttc aga gat ctc gga atg cga ttc gag ttc tgt caa act gtt 864

Asn Leu Phe Arg Asp Leu Gly Met Arg Phe Glu Phe Cys Gln Thr Val

275 280 285

tac aag gtt tta atg atg gac caa atg tat ttc aag ttg ctc aat gtg 912

Tyr Lys Val Leu Met Met Asp Gln Met Tyr Phe Lys Leu Leu Asn Val

290 295 300

cac gtc atc gcg atg act tcg atc gta tgg aat ccg gtg ctc tat ttc 960

His Val Ile Ala Met Thr Ser Ile Val Trp Asn Pro Val Leu Tyr Phe

305 310 315 320

tgg atg agc aag cgt cat cga cga gcc ctg aaa gac gac atg acg tgg 1008

Trp Met Ser Lys Arg His Arg Arg Ala Leu Lys Asp Asp Met Thr Trp

325 330 335

ctc acc aat gct cgc cgt cat aca aac gtc ggc gtt ctg tct cgc ttc 1056

Leu Thr Asn Ala Arg Arg His Thr Asn Val Gly Val Leu Ser Arg Phe

340 345 350

aca cct tct cca tca gtt tca gtg gtt tac aga cga act ctg gag cga 1104

Thr Pro Ser Pro Ser Val Ser Val Val Tyr Arg Arg Thr Leu Glu Arg

355 360 365

cat cta ggt gtc aat cat ttc cgc cgt ggc aca ctt gcg gac ccg aca 1152

His Leu Gly Val Asn His Phe Arg Arg Gly Thr Leu Ala Asp Pro Thr

370 375 380

tgc act tca cgt gaa cga agt ctt ccg cga gaa ctt caa tca aat tgt 1200

Cys Thr Ser Arg Glu Arg Ser Leu Pro Arg Glu Leu Gln Ser Asn Cys

385 390 395 400

ttc ctt ctt gtt ccg ctt atg cca tta tgt caa tct gtg acg agg aag 1248

Phe Leu Leu Val Pro Leu Met Pro Leu Cys Gln Ser Val Thr Arg Lys

405 410 415

aat agt cat cta gca atc aat cga gac ggg atc gtc att cca caa gcc 1296

Asn Ser His Leu Ala Ile Asn Arg Asp Gly Ile Val Ile Pro Gln Ala

420 425 430

aat ggc tca agt cgt cgg ccg agc agc gtg aat acc aat tca act cga 1344

Asn Gly Ser Ser Arg Arg Pro Ser Ser Val Asn Thr Asn Ser Thr Arg

435 440 445

gac tgg tg 1352

Asp Trp

450

16

450

Homo sapiens

16

Met Gly Asp Ala Glu Ser His His Cys Ile Asp Val Asn Ala Ile Leu

1 5 10 15

Gln Gln Phe Asn Asp Trp Thr Val Leu Phe Glu Val Arg Leu Gly Tyr

20 25 30

Ser Val Leu Tyr Phe Leu Ile Leu Ile Ile Gly Leu Val Gly Asn Gly

35 40 45

Leu Leu Ile Thr Ser Ile Leu Met Arg Lys Lys Leu Ser Val Ala Asn

50 55 60

Ile Phe Leu Ile Asn Leu Ala Val Ser Asp Leu Leu Leu Cys Ile Thr

65 70 75 80

Ala Val Pro Ile Thr Pro Val Leu Ala Phe Met Lys Arg Trp Ile Phe

85 90 95

Gly Ile Ile Met Cys Lys Leu Val Pro Thr Cys Gln Ala Phe Ser Val

100 105 110

Leu Ile Ser Ser Trp Ser Leu Cys Tyr Ile Ala Ile Asp Arg Tyr Arg

115 120 125

Ser Ile Val Thr Pro Leu Arg Glu Pro Trp Ser Asp Arg His Ala Arg

130 135 140

Trp Leu Leu Met Phe Thr Trp Val Val Ala Phe Leu Ala Ser Tyr Pro

145 150 155 160

Leu Tyr Tyr Ser Gln Asn Leu Lys Thr Met Val Ile Glu Asn Val Thr

165 170 175

Leu Cys Gly Asp Phe Cys Gly Glu Phe Asn Trp Gln Ser Asp Glu Ile

180 185 190

Ser Lys Leu Thr Tyr Thr Thr Ser Leu Leu Ile Ile Gln Leu Ile Ile

195 200 205

Pro Ala Ile Ile Met Ser Phe Cys Tyr Leu Met Ile Leu Gln Lys Val

210 215 220

Gln Thr Asp Trp Leu Val Asp Glu Gly Ser Met Leu Thr Ala Ala Gln

225 230 235 240

Gln Ala Gln Thr Ala Val Arg Lys Arg Arg Val Met Tyr Val Leu Ile

245 250 255

Leu Met Val Ile Val Phe Met Ala Cys Trp Phe Pro Leu Ser Ala Val

260 265 270

Asn Leu Phe Arg Asp Leu Gly Met Arg Phe Glu Phe Cys Gln Thr Val

275 280 285

Tyr Lys Val Leu Met Met Asp Gln Met Tyr Phe Lys Leu Leu Asn Val

290 295 300

His Val Ile Ala Met Thr Ser Ile Val Trp Asn Pro Val Leu Tyr Phe

305 310 315 320

Trp Met Ser Lys Arg His Arg Arg Ala Leu Lys Asp Asp Met Thr Trp

325 330 335

Leu Thr Asn Ala Arg Arg His Thr Asn Val Gly Val Leu Ser Arg Phe

340 345 350

Thr Pro Ser Pro Ser Val Ser Val Val Tyr Arg Arg Thr Leu Glu Arg

355 360 365

His Leu Gly Val Asn His Phe Arg Arg Gly Thr Leu Ala Asp Pro Thr

370 375 380

Cys Thr Ser Arg Glu Arg Ser Leu Pro Arg Glu Leu Gln Ser Asn Cys

385 390 395 400

Phe Leu Leu Val Pro Leu Met Pro Leu Cys Gln Ser Val Thr Arg Lys

405 410 415

Asn Ser His Leu Ala Ile Asn Arg Asp Gly Ile Val Ile Pro Gln Ala

420 425 430

Asn Gly Ser Ser Arg Arg Pro Ser Ser Val Asn Thr Asn Ser Thr Arg

435 440 445

Asp Trp

450

17

atg acc gac gag gag ttg ttc gag atc gct ctt ccc ggc ttc tta tat 48

Met Thr Asp Glu Glu Leu Phe Glu Ile Ala Leu Pro Gly Phe Leu Tyr

1 5 10 15

ctc act gtt ttt cta gtt gga act att gga aac tct atg gta ata ttt 96

Leu Thr Val Phe Leu Val Gly Thr Ile Gly Asn Ser Met Val Ile Phe

20 25 30

gtt gta aac cga ttc aaa cga atg cgc aac gta acg aac atc ttt ctc 144

Val Val Asn Arg Phe Lys Arg Met Arg Asn Val Thr Asn Ile Phe Leu

35 40 45

gcc tcg ctc agc acc gcc gac ttg tgc ctt atc tgg ttt tgt gtg cct 192

Ala Ser Leu Ser Thr Ala Asp Leu Cys Leu Ile Trp Phe Cys Val Pro

50 55 60

ata atg ttc atg aag tat atg tcg cat acg tgg tcg atg ggc agg ttt 240

Ile Met Phe Met Lys Tyr Met Ser His Thr Trp Ser Met Gly Arg Phe

65 70 75 80

gcg tgc tat tct gtg cac tac att caa cag ttt aca tgc ttc tgc tcg 288

Ala Cys Tyr Ser Val His Tyr Ile Gln Gln Phe Thr Cys Phe Cys Ser

85 90 95

gtg ctc acg atg act atg att agt ttt gag agg ttt ctt gca ata gca 336

Val Leu Thr Met Thr Met Ile Ser Phe Glu Arg Phe Leu Ala Ile Ala

100 105 110

tat cct atg cga aat atc tgg ttt tca tcc ata gga cga gct aaa aaa 384

Tyr Pro Met Arg Asn Ile Trp Phe Ser Ser Ile Gly Arg Ala Lys Lys

115 120 125

gta atc cta ctc atc tgg atg tca tcc gcg gta ctg gcc gtc cca acc 432

Val Ile Leu Leu Ile Trp Met Ser Ser Ala Val Leu Ala Val Pro Thr

130 135 140

gct gtt cgg atg gat tat gag acc aat ctt tca ttg tcc ggg cag agg 480

Ala Val Arg Met Asp Tyr Glu Thr Asn Leu Ser Leu Ser Gly Gln Arg

145 150 155 160

gtg cat tgg tgt cga aga cgg ttt ccc gcg caa ttt tta gga tat cct 528

Val His Trp Cys Arg Arg Arg Phe Pro Ala Gln Phe Leu Gly Tyr Pro

165 170 175

agg aca tcg ttg aat aaa gca tat gcc atg tat cag ttg ttg cta ctt 576

Arg Thr Ser Leu Asn Lys Ala Tyr Ala Met Tyr Gln Leu Leu Leu Leu

180 185 190

atc ata ttc ccg gtg ctc aca atg tcc ata tgt tat gct cgt gta tct 624

Ile Ile Phe Pro Val Leu Thr Met Ser Ile Cys Tyr Ala Arg Val Ser

195 200 205

gca ata gtg tac aag tcg tcg aaa gat cgt gta ata ctt tcc caa gct 672

Ala Ile Val Tyr Lys Ser Ser Lys Asp Arg Val Ile Leu Ser Gln Ala

210 215 220

atg gtc gca ttt tca aag gcc gcc act gac gcc gtt acc ttc tcc ggc 720

Met Val Ala Phe Ser Lys Ala Ala Thr Asp Ala Val Thr Phe Ser Gly

225 230 235 240

tac tct gca atc ccc atg att aca act tcc cgg aac ttg aaa acc gcc 768

Tyr Ser Ala Ile Pro Met Ile Thr Thr Ser Arg Asn Leu Lys Thr Ala

245 250 255

aac acg acc atc aag tcc tac agt aat cac aga aat aat cgc gtg gca 816

Asn Thr Thr Ile Lys Ser Tyr Ser Asn His Arg Asn Asn Arg Val Ala

260 265 270

gag gcg aat aag aaa cag ata gtt caa atg tta atc tcc atc gtc tgc 864

Glu Ala Asn Lys Lys Gln Ile Val Gln Met Leu Ile Ser Ile Val Cys

275 280 285

atg tac acg gtt tgc tgg ctc cca acg atc gtc gac gag ctt ctg acg 912

Met Tyr Thr Val Cys Trp Leu Pro Thr Ile Val Asp Glu Leu Leu Thr

290 295 300

tcc ttc ggg tac att tgt cga aca tca aat acg cag aca ttg aag cat 960

Ser Phe Gly Tyr Ile Cys Arg Thr Ser Asn Thr Gln Thr Leu Lys His

305 310 315 320

atg cgg atg gga ttt aat gcg ctg acc tat tgc caa tca tgc att aat 1008

Met Arg Met Gly Phe Asn Ala Leu Thr Tyr Cys Gln Ser Cys Ile Asn

325 330 335

cct atc ctg tat gcc ttc att tct cag aat ttc cgg tcc acg ttc aag 1056

Pro Ile Leu Tyr Ala Phe Ile Ser Gln Asn Phe Arg Ser Thr Phe Lys

340 345 350

acc gcc tat tcg aga atg aaa agt cgt ctt cag ggc gtg gaa gaa atg 1104

Thr Ala Tyr Ser Arg Met Lys Ser Arg Leu Gln Gly Val Glu Glu Met

355 360 365

cgc tct cgt atg gga tcg tgc tct tcg gcg agc atg atg tcg acc cgc 1152

Arg Ser Arg Met Gly Ser Cys Ser Ser Ala Ser Met Met Ser Thr Arg

370 375 380

aac cag cac cga atc tac ggg tcc agc ttc aac aca ctc aca gtg ccc 1200

Asn Gln His Arg Ile Tyr Gly Ser Ser Phe Asn Thr Leu Thr Val Pro

385 390 395 400

ggt cgc tcc atg atc act ccg aac atg tca cgc gac gtc tca cag ttg 1248

Gly Arg Ser Met Ile Thr Pro Asn Met Ser Arg Asp Val Ser Gln Leu

405 410 415

tca ttg tgc agg ccg acg tcg caa atg tcg ttc tgc cga ccg aag agt 1296

Ser Leu Cys Arg Pro Thr Ser Gln Met Ser Phe Cys Arg Pro Lys Ser

420 425 430

cca atg gcc gga gac tct ccg tcg act ttc atg aga cat cgt cct aga 1344

Pro Met Ala Gly Asp Ser Pro Ser Thr Phe Met Arg His Arg Pro Arg

435 440 445

tcg cca acc gac gtg tcc cat gat tcc gga aga cca cgt agc ccc acg 1392

Ser Pro Thr Asp Val Ser His Asp Ser Gly Arg Pro Arg Ser Pro Thr

450 455 460

gat ctt tcg cag tcg aca aag cct tcg cga cga tcc tcc tct ata aga 1440

Asp Leu Ser Gln Ser Thr Lys Pro Ser Arg Arg Ser Ser Ser Ile Arg

465 470 475 480

ccc cgt agc cca aca tcg aca tct caa atg tct acc ata gtc cga tcg 1488

Pro Arg Ser Pro Thr Ser Thr Ser Gln Met Ser Thr Ile Val Arg Ser

485 490 495

aga agt cct aca ggc gca tcg gac acc tct tca ttg ttc cca tca aga 1536

Arg Ser Pro Thr Gly Ala Ser Asp Thr Ser Ser Leu Phe Pro Ser Arg

500 505 510

aca aga agt cca act ctc caa tca aac aca tct ggt caa tcc atg gaa 1584

Thr Arg Ser Pro Thr Leu Gln Ser Asn Thr Ser Gly Gln Ser Met Glu

515 520 525

cga acc acg gac cga ctg agt gtc cgt gac gct gtc cga cca aaa aca 1632

Arg Thr Thr Asp Arg Leu Ser Val Arg Asp Ala Val Arg Pro Lys Thr

530 535 540

ccg cca gca gtg gtt gtc ta 1652

Pro Pro Ala Val Val Val

545 550

18

550

Homo sapiens

18

Met Thr Asp Glu Glu Leu Phe Glu Ile Ala Leu Pro Gly Phe Leu Tyr

1 5 10 15

Leu Thr Val Phe Leu Val Gly Thr Ile Gly Asn Ser Met Val Ile Phe

20 25 30

Val Val Asn Arg Phe Lys Arg Met Arg Asn Val Thr Asn Ile Phe Leu

35 40 45

Ala Ser Leu Ser Thr Ala Asp Leu Cys Leu Ile Trp Phe Cys Val Pro

50 55 60

Ile Met Phe Met Lys Tyr Met Ser His Thr Trp Ser Met Gly Arg Phe

65 70 75 80

Ala Cys Tyr Ser Val His Tyr Ile Gln Gln Phe Thr Cys Phe Cys Ser

85 90 95

Val Leu Thr Met Thr Met Ile Ser Phe Glu Arg Phe Leu Ala Ile Ala

100 105 110

Tyr Pro Met Arg Asn Ile Trp Phe Ser Ser Ile Gly Arg Ala Lys Lys

115 120 125

Val Ile Leu Leu Ile Trp Met Ser Ser Ala Val Leu Ala Val Pro Thr

130 135 140

Ala Val Arg Met Asp Tyr Glu Thr Asn Leu Ser Leu Ser Gly Gln Arg

145 150 155 160

Val His Trp Cys Arg Arg Arg Phe Pro Ala Gln Phe Leu Gly Tyr Pro

165 170 175

Arg Thr Ser Leu Asn Lys Ala Tyr Ala Met Tyr Gln Leu Leu Leu Leu

180 185 190

Ile Ile Phe Pro Val Leu Thr Met Ser Ile Cys Tyr Ala Arg Val Ser

195 200 205

Ala Ile Val Tyr Lys Ser Ser Lys Asp Arg Val Ile Leu Ser Gln Ala

210 215 220

Met Val Ala Phe Ser Lys Ala Ala Thr Asp Ala Val Thr Phe Ser Gly

225 230 235 240

Tyr Ser Ala Ile Pro Met Ile Thr Thr Ser Arg Asn Leu Lys Thr Ala

245 250 255

Asn Thr Thr Ile Lys Ser Tyr Ser Asn His Arg Asn Asn Arg Val Ala

260 265 270

Glu Ala Asn Lys Lys Gln Ile Val Gln Met Leu Ile Ser Ile Val Cys

275 280 285

Met Tyr Thr Val Cys Trp Leu Pro Thr Ile Val Asp Glu Leu Leu Thr

290 295 300

Ser Phe Gly Tyr Ile Cys Arg Thr Ser Asn Thr Gln Thr Leu Lys His

305 310 315 320

Met Arg Met Gly Phe Asn Ala Leu Thr Tyr Cys Gln Ser Cys Ile Asn

325 330 335

Pro Ile Leu Tyr Ala Phe Ile Ser Gln Asn Phe Arg Ser Thr Phe Lys

340 345 350

Thr Ala Tyr Ser Arg Met Lys Ser Arg Leu Gln Gly Val Glu Glu Met

355 360 365

Arg Ser Arg Met Gly Ser Cys Ser Ser Ala Ser Met Met Ser Thr Arg

370 375 380

Asn Gln His Arg Ile Tyr Gly Ser Ser Phe Asn Thr Leu Thr Val Pro

385 390 395 400

Gly Arg Ser Met Ile Thr Pro Asn Met Ser Arg Asp Val Ser Gln Leu

405 410 415

Ser Leu Cys Arg Pro Thr Ser Gln Met Ser Phe Cys Arg Pro Lys Ser

420 425 430

Pro Met Ala Gly Asp Ser Pro Ser Thr Phe Met Arg His Arg Pro Arg

435 440 445

Ser Pro Thr Asp Val Ser His Asp Ser Gly Arg Pro Arg Ser Pro Thr

450 455 460

Asp Leu Ser Gln Ser Thr Lys Pro Ser Arg Arg Ser Ser Ser Ile Arg

465 470 475 480

Pro Arg Ser Pro Thr Ser Thr Ser Gln Met Ser Thr Ile Val Arg Ser

485 490 495

Arg Ser Pro Thr Gly Ala Ser Asp Thr Ser Ser Leu Phe Pro Ser Arg

500 505 510

Thr Arg Ser Pro Thr Leu Gln Ser Asn Thr Ser Gly Gln Ser Met Glu

515 520 525

Arg Thr Thr Asp Arg Leu Ser Val Arg Asp Ala Val Arg Pro Lys Thr

530 535 540

Pro Pro Ala Val Val Val

545 550

19

0

synthetic

19

000

20

0

synthetic

20

000

21

atg aat ggc tcc gat tgt ctg aat ctc aac tca gaa tta tgg ttg tat 48

Met Asn Gly Ser Asp Cys Leu Asn Leu Asn Ser Glu Leu Trp Leu Tyr

1 5 10 15

cga gaa gat ttg tca tca agg tgg tac ata atg tta gtg ttt gca ttt 96

Arg Glu Asp Leu Ser Ser Arg Trp Tyr Ile Met Leu Val Phe Ala Phe

20 25 30

ctc tac ctg ata atc att gcc gcc gga ata att gga aac tca tgt gtg 144

Leu Tyr Leu Ile Ile Ile Ala Ala Gly Ile Ile Gly Asn Ser Cys Val

35 40 45

att ttg gca atc aca agg aac aaa tca ctt caa act gtt ccg aat ctg 192

Ile Leu Ala Ile Thr Arg Asn Lys Ser Leu Gln Thr Val Pro Asn Leu

50 55 60

ttt att ctt tct tta tca tgt tct gat att gtg gta tgc tgc aca tct 240

Phe Ile Leu Ser Leu Ser Cys Ser Asp Ile Val Val Cys Cys Thr Ser

65 70 75 80

gca aca atc act ccg att act gca ttc aag aaa gaa tgg atc ttt gga 288

Ala Thr Ile Thr Pro Ile Thr Ala Phe Lys Lys Glu Trp Ile Phe Gly

85 90 95

gag gct tta tgc cga att gca cca ttc att gct ggt atc agc ctt tgt 336

Glu Ala Leu Cys Arg Ile Ala Pro Phe Ile Ala Gly Ile Ser Leu Cys

100 105 110

ttc tca act ttc aca ttg act gca atc tcc atc gac aga tac atc ctg 384

Phe Ser Thr Phe Thr Leu Thr Ala Ile Ser Ile Asp Arg Tyr Ile Leu

115 120 125

att cga ttt ccg atg agg aaa cct att acg cat tat caa gcg gtt gga 432

Ile Arg Phe Pro Met Arg Lys Pro Ile Thr His Tyr Gln Ala Val Gly

130 135 140

gtg att gct att att tgc gct ttt gct gca acc atc aca tcc cca ata 480

Val Ile Ala Ile Ile Cys Ala Phe Ala Ala Thr Ile Thr Ser Pro Ile

145 150 155 160

atg ttc aag caa aag ctg gga gag ttt gag aat ttt tgt ggg cag tac 528

Met Phe Lys Gln Lys Leu Gly Glu Phe Glu Asn Phe Cys Gly Gln Tyr

165 170 175

tgc acg gaa aac tgg gga gcc aat gaa agc cag aga aaa att tat ggt 576

Cys Thr Glu Asn Trp Gly Ala Asn Glu Ser Gln Arg Lys Ile Tyr Gly

180 185 190

gca gct ctg atg ttt ctt cag ctc gtc att ccg ctt acc atc atc atc 624

Ala Ala Leu Met Phe Leu Gln Leu Val Ile Pro Leu Thr Ile Ile Ile

195 200 205

ata tcc tac act gcg att tct ttg aag atc gga caa agc atg att ctc 672

Ile Ser Tyr Thr Ala Ile Ser Leu Lys Ile Gly Gln Ser Met Ile Leu

210 215 220

aaa ggg gcg aaa aag caa aaa aca gac aat tgg gaa atg gaa tta agt 720

Lys Gly Ala Lys Lys Gln Lys Thr Asp Asn Trp Glu Met Glu Leu Ser

225 230 235 240

gat caa caa aga atc gct gtg aag aga aga caa aga act aat aga atg 768

Asp Gln Gln Arg Ile Ala Val Lys Arg Arg Gln Arg Thr Asn Arg Met

245 250 255

ctt att ggt atg gta gtc gca ttc gct tgc agc tgg att tgg tca gtg 816

Leu Ile Gly Met Val Val Ala Phe Ala Cys Ser Trp Ile Trp Ser Val

260 265 270

acg ttc aac att ctg agg gac tat gaa tat ttg cca gag ctc atc aaa 864

Thr Phe Asn Ile Leu Arg Asp Tyr Glu Tyr Leu Pro Glu Leu Ile Lys

275 280 285

act caa gaa tat atc ttt gga att gct aca cat tgc att gca atg acc 912

Thr Gln Glu Tyr Ile Phe Gly Ile Ala Thr His Cys Ile Ala Met Thr

290 295 300

tca acg gta tgg aac ccg tta ctc tac gca gtg ctc aac ctc caa ctg 960

Ser Thr Val Trp Asn Pro Leu Leu Tyr Ala Val Leu Asn Leu Gln Leu

305 310 315 320

cgt gca gca ttc att gac ctg atg cct cac tgg ctt cgt cgt cat tta 1008

Arg Ala Ala Phe Ile Asp Leu Met Pro His Trp Leu Arg Arg His Leu

325 330 335

aac ctg gaa gga gac aac agc tct cca ttg ctc aac cat ccg acg atg 1056

Asn Leu Glu Gly Asp Asn Ser Ser Pro Leu Leu Asn His Pro Thr Met

340 345 350

aca att aca aac aaa ccg tca aag caa cat aca tta ata cca gca atg 1104

Thr Ile Thr Asn Lys Pro Ser Lys Gln His Thr Leu Ile Pro Ala Met

355 360 365

gac aac cat acg tgt caa caa gtt ta 1130

Asp Asn His Thr Cys Gln Gln Val

370 375

22

376

Homo sapiens

22

Met Asn Gly Ser Asp Cys Leu Asn Leu Asn Ser Glu Leu Trp Leu Tyr

1 5 10 15

Arg Glu Asp Leu Ser Ser Arg Trp Tyr Ile Met Leu Val Phe Ala Phe

20 25 30

Leu Tyr Leu Ile Ile Ile Ala Ala Gly Ile Ile Gly Asn Ser Cys Val

35 40 45

Ile Leu Ala Ile Thr Arg Asn Lys Ser Leu Gln Thr Val Pro Asn Leu

50 55 60

Phe Ile Leu Ser Leu Ser Cys Ser Asp Ile Val Val Cys Cys Thr Ser

65 70 75 80

Ala Thr Ile Thr Pro Ile Thr Ala Phe Lys Lys Glu Trp Ile Phe Gly

85 90 95

Glu Ala Leu Cys Arg Ile Ala Pro Phe Ile Ala Gly Ile Ser Leu Cys

100 105 110

Phe Ser Thr Phe Thr Leu Thr Ala Ile Ser Ile Asp Arg Tyr Ile Leu

115 120 125

Ile Arg Phe Pro Met Arg Lys Pro Ile Thr His Tyr Gln Ala Val Gly

130 135 140

Val Ile Ala Ile Ile Cys Ala Phe Ala Ala Thr Ile Thr Ser Pro Ile

145 150 155 160

Met Phe Lys Gln Lys Leu Gly Glu Phe Glu Asn Phe Cys Gly Gln Tyr

165 170 175

Cys Thr Glu Asn Trp Gly Ala Asn Glu Ser Gln Arg Lys Ile Tyr Gly

180 185 190

Ala Ala Leu Met Phe Leu Gln Leu Val Ile Pro Leu Thr Ile Ile Ile

195 200 205

Ile Ser Tyr Thr Ala Ile Ser Leu Lys Ile Gly Gln Ser Met Ile Leu

210 215 220

Lys Gly Ala Lys Lys Gln Lys Thr Asp Asn Trp Glu Met Glu Leu Ser

225 230 235 240

Asp Gln Gln Arg Ile Ala Val Lys Arg Arg Gln Arg Thr Asn Arg Met

245 250 255

Leu Ile Gly Met Val Val Ala Phe Ala Cys Ser Trp Ile Trp Ser Val

260 265 270

Thr Phe Asn Ile Leu Arg Asp Tyr Glu Tyr Leu Pro Glu Leu Ile Lys

275 280 285

Thr Gln Glu Tyr Ile Phe Gly Ile Ala Thr His Cys Ile Ala Met Thr

290 295 300

Ser Thr Val Trp Asn Pro Leu Leu Tyr Ala Val Leu Asn Leu Gln Leu

305 310 315 320

Arg Ala Ala Phe Ile Asp Leu Met Pro His Trp Leu Arg Arg His Leu

325 330 335

Asn Leu Glu Gly Asp Asn Ser Ser Pro Leu Leu Asn His Pro Thr Met

340 345 350

Thr Ile Thr Asn Lys Pro Ser Lys Gln His Thr Leu Ile Pro Ala Met

355 360 365

Asp Asn His Thr Cys Gln Gln Val

370 375

23

atg att att ttt tat ctt tac gta gca act caa gta ttt gtg gca att 48

Met Ile Ile Phe Tyr Leu Tyr Val Ala Thr Gln Val Phe Val Ala Ile

1 5 10 15

gca ttt gtc ctt ctg atg gca act gca ata att gga aac tct gtc gtg 96

Ala Phe Val Leu Leu Met Ala Thr Ala Ile Ile Gly Asn Ser Val Val

20 25 30

atg tgg ata att tat caa cac aaa gta atg cac tac ggc ttc aac tat 144

Met Trp Ile Ile Tyr Gln His Lys Val Met His Tyr Gly Phe Asn Tyr

35 40 45

ttt ctt ttc aat atg gca ttc gct gat ctt ttg att gct ctc ttc aat 192

Phe Leu Phe Asn Met Ala Phe Ala Asp Leu Leu Ile Ala Leu Phe Asn

50 55 60

gtt ggt act tca tgg acc tat aat tta tac tat gac tgg tgg tat ggt 240

Val Gly Thr Ser Trp Thr Tyr Asn Leu Tyr Tyr Asp Trp Trp Tyr Gly

65 70 75 80

gat cta tgt aca ctt act tcc ttc ttc ggt att gca cca act acc gta 288

Asp Leu Cys Thr Leu Thr Ser Phe Phe Gly Ile Ala Pro Thr Thr Val

85 90 95

tcc gtg tgc tca atg atg gct ctc agc tgg gat aga tgt caa gca gtc 336

Ser Val Cys Ser Met Met Ala Leu Ser Trp Asp Arg Cys Gln Ala Val

100 105 110

gtg aat cct cta caa aaa cgt cca cta tct cga aaa aga tcc gtc att 384

Val Asn Pro Leu Gln Lys Arg Pro Leu Ser Arg Lys Arg Ser Val Ile

115 120 125

gct att ctc atc att tgg gtt gtt tca acg gtt act gca ctt ccg ttt 432

Ala Ile Leu Ile Ile Trp Val Val Ser Thr Val Thr Ala Leu Pro Phe

130 135 140

gca att gct gca tct gtc aac tct ctc tac aca tat gac gtg gtt aca 480

Ala Ile Ala Ala Ser Val Asn Ser Leu Tyr Thr Tyr Asp Val Val Thr

145 150 155 160

tca act gtt tca aaa gct cac gtt tgt tca gca cca gtt aat act ttc 528

Ser Thr Val Ser Lys Ala His Val Cys Ser Ala Pro Val Asn Thr Phe

165 170 175

ttt gaa aaa gtg ctc ttt ggg att caa tat gct cta cct ata atc att 576

Phe Glu Lys Val Leu Phe Gly Ile Gln Tyr Ala Leu Pro Ile Ile Ile

180 185 190

ttg gga tca acg ttc aca cgg att gcc gtt gca ttt cga gca aca aat 624

Leu Gly Ser Thr Phe Thr Arg Ile Ala Val Ala Phe Arg Ala Thr Asn

195 200 205

gaa gcc act gac agt agt ctg aag aac aat cac aca cgc gca aag agc 672

Glu Ala Thr Asp Ser Ser Leu Lys Asn Asn His Thr Arg Ala Lys Ser

210 215 220

aag gca gta aaa atg ctc ttc cta atg gtc gtt gca ttc gtt gtc tgc 720

Lys Ala Val Lys Met Leu Phe Leu Met Val Val Ala Phe Val Val Cys

225 230 235 240

tgg ctt cca tac cac att tat cac gca ttc gct ctt gaa gaa ttc ttc 768

Trp Leu Pro Tyr His Ile Tyr His Ala Phe Ala Leu Glu Glu Phe Phe

245 250 255

gat gca gct cgt gga aaa tat gcg tat ttg ttg att tac tgg att gca 816

Asp Ala Ala Arg Gly Lys Tyr Ala Tyr Leu Leu Ile Tyr Trp Ile Ala

260 265 270

atg tct agt tgt gca tac aat cca att att tat tgt ttt gcc aac gaa 864

Met Ser Ser Cys Ala Tyr Asn Pro Ile Ile Tyr Cys Phe Ala Asn Glu

275 280 285

aga ttc cgc att ggc ttc cgg tac gtc ttc cga tgg att cca gtg att 912

Arg Phe Arg Ile Gly Phe Arg Tyr Val Phe Arg Trp Ile Pro Val Ile

290 295 300

gac tgc aaa aag gaa caa tat gaa tat tca caa tta ttc ccg gat aaa 960

Asp Cys Lys Lys Glu Gln Tyr Glu Tyr Ser Gln Leu Phe Pro Asp Lys

305 310 315 320

atg aga agt atg gct att tct ttg caa aaa gga aga gtg aac tct tcc 1008

Met Arg Ser Met Ala Ile Ser Leu Gln Lys Gly Arg Val Asn Ser Ser

325 330 335

tgt ttg gat aaa aaa gtc aaa gag aat tct tct caa gat ttg gtt tgt 1056

Cys Leu Asp Lys Lys Val Lys Glu Asn Ser Ser Gln Asp Leu Val Cys

340 345 350

gtg atg cat tcc gag aaa aat acg aag aaa tat tca aaa gta cat ctt 1104

Val Met His Ser Glu Lys Asn Thr Lys Lys Tyr Ser Lys Val His Leu

355 360 365

ctg agt tgc cat gaa cgg tga 1125

Leu Ser Cys His Glu Arg

370

24

374

Homo sapiens

24

Met Ile Ile Phe Tyr Leu Tyr Val Ala Thr Gln Val Phe Val Ala Ile

1 5 10 15

Ala Phe Val Leu Leu Met Ala Thr Ala Ile Ile Gly Asn Ser Val Val

20 25 30

Met Trp Ile Ile Tyr Gln His Lys Val Met His Tyr Gly Phe Asn Tyr

35 40 45

Phe Leu Phe Asn Met Ala Phe Ala Asp Leu Leu Ile Ala Leu Phe Asn

50 55 60

Val Gly Thr Ser Trp Thr Tyr Asn Leu Tyr Tyr Asp Trp Trp Tyr Gly

65 70 75 80

Asp Leu Cys Thr Leu Thr Ser Phe Phe Gly Ile Ala Pro Thr Thr Val

85 90 95

Ser Val Cys Ser Met Met Ala Leu Ser Trp Asp Arg Cys Gln Ala Val

100 105 110

Val Asn Pro Leu Gln Lys Arg Pro Leu Ser Arg Lys Arg Ser Val Ile

115 120 125

Ala Ile Leu Ile Ile Trp Val Val Ser Thr Val Thr Ala Leu Pro Phe

130 135 140

Ala Ile Ala Ala Ser Val Asn Ser Leu Tyr Thr Tyr Asp Val Val Thr

145 150 155 160

Ser Thr Val Ser Lys Ala His Val Cys Ser Ala Pro Val Asn Thr Phe

165 170 175

Phe Glu Lys Val Leu Phe Gly Ile Gln Tyr Ala Leu Pro Ile Ile Ile

180 185 190

Leu Gly Ser Thr Phe Thr Arg Ile Ala Val Ala Phe Arg Ala Thr Asn

195 200 205

Glu Ala Thr Asp Ser Ser Leu Lys Asn Asn His Thr Arg Ala Lys Ser

210 215 220

Lys Ala Val Lys Met Leu Phe Leu Met Val Val Ala Phe Val Val Cys

225 230 235 240

Trp Leu Pro Tyr His Ile Tyr His Ala Phe Ala Leu Glu Glu Phe Phe

245 250 255

Asp Ala Ala Arg Gly Lys Tyr Ala Tyr Leu Leu Ile Tyr Trp Ile Ala

260 265 270

Met Ser Ser Cys Ala Tyr Asn Pro Ile Ile Tyr Cys Phe Ala Asn Glu

275 280 285

Arg Phe Arg Ile Gly Phe Arg Tyr Val Phe Arg Trp Ile Pro Val Ile

290 295 300

Asp Cys Lys Lys Glu Gln Tyr Glu Tyr Ser Gln Leu Phe Pro Asp Lys

305 310 315 320

Met Arg Ser Met Ala Ile Ser Leu Gln Lys Gly Arg Val Asn Ser Ser

325 330 335

Cys Leu Asp Lys Lys Val Lys Glu Asn Ser Ser Gln Asp Leu Val Cys

340 345 350

Val Met His Ser Glu Lys Asn Thr Lys Lys Tyr Ser Lys Val His Leu

355 360 365

Leu Ser Cys His Glu Arg

370

25

atg gaa gtt gaa aat ttt acc gac tgt caa gta tat tgg aaa gtg tat 48

Met Glu Val Glu Asn Phe Thr Asp Cys Gln Val Tyr Trp Lys Val Tyr

1 5 10 15

cca gat cct tct caa agt ata tat gcg ata gtg cca ttt ctg acc gtg 96

Pro Asp Pro Ser Gln Ser Ile Tyr Ala Ile Val Pro Phe Leu Thr Val

20 25 30

tac ctt ttt ctc ttt ttt ctt gga ctc ttt gga aat gtg acc ttg att 144

Tyr Leu Phe Leu Phe Phe Leu Gly Leu Phe Gly Asn Val Thr Leu Ile

35 40 45

tac gta act tgc agc cat aaa gct tta ctg agc gtt caa aac ata ttc 192

Tyr Val Thr Cys Ser His Lys Ala Leu Leu Ser Val Gln Asn Ile Phe

50 55 60

att ctg aac ctg gcg gcg agc gat tgc atg atg tgc ata tta tcg ctt 240

Ile Leu Asn Leu Ala Ala Ser Asp Cys Met Met Cys Ile Leu Ser Leu

65 70 75 80

cca atc act cca atc aca aat gtg tac aaa aac tgg tac ttt gga aat 288

Pro Ile Thr Pro Ile Thr Asn Val Tyr Lys Asn Trp Tyr Phe Gly Asn

85 90 95

cta ctc tgc cat ttg ata cca tgc att caa ggt atc agc att ttc gta 336

Leu Leu Cys His Leu Ile Pro Cys Ile Gln Gly Ile Ser Ile Phe Val

100 105 110

tgc aca ttc agt ctc ggt gcg att gct ttg gat cgg tat atc ctt gta 384

Cys Thr Phe Ser Leu Gly Ala Ile Ala Leu Asp Arg Tyr Ile Leu Val

115 120 125

gta aga cca cat tct aca cca cta tcc caa aga gga gca ttt ctt act 432

Val Arg Pro His Ser Thr Pro Leu Ser Gln Arg Gly Ala Phe Leu Thr

130 135 140

act gtt cta ttg tgg atc ctc tct ttt gtt gta act cta ccc tat gcg 480

Thr Val Leu Leu Trp Ile Leu Ser Phe Val Val Thr Leu Pro Tyr Ala

145 150 155 160

ttc aat atg caa atg att gaa tac aca gaa gag aga ata tgc ggc tac 528

Phe Asn Met Gln Met Ile Glu Tyr Thr Glu Glu Arg Ile Cys Gly Tyr

165 170 175

ttt tgc act gaa aag tgg gaa tct gcc aag tct aga aga gcc tac aca 576

Phe Cys Thr Glu Lys Trp Glu Ser Ala Lys Ser Arg Arg Ala Tyr Thr

180 185 190

atg atc gtg atg ctc gcc caa ttc gtg gtc cca ttc gct gtc atg gcc 624

Met Ile Val Met Leu Ala Gln Phe Val Val Pro Phe Ala Val Met Ala

195 200 205

ttc tgc tat gca aat att gtt tcg gtg ctc agc aag cgt gct cag aca 672

Phe Cys Tyr Ala Asn Ile Val Ser Val Leu Ser Lys Arg Ala Gln Thr

210 215 220

aag ata cgc aaa atg gtg gag aga aca agc gcg ttg gag agc tct tgc 720

Lys Ile Arg Lys Met Val Glu Arg Thr Ser Ala Leu Glu Ser Ser Cys

225 230 235 240

gca ttc ccg tcg cat ggt ctt gaa cag tat gaa aat gag ttg aac gaa 768

Ala Phe Pro Ser His Gly Leu Glu Gln Tyr Glu Asn Glu Leu Asn Glu

245 250 255

ttt cta gac aaa cag gaa aag gag aaa caa cga gtt gta ctt cag aac 816

Phe Leu Asp Lys Gln Glu Lys Glu Lys Gln Arg Val Val Leu Gln Asn

260 265 270

aga aga aca acg tca atc cta gtt acc atg gtt gtc tgg ttt ggg ata 864

Arg Arg Thr Thr Ser Ile Leu Val Thr Met Val Val Trp Phe Gly Ile

275 280 285

act tgg ctg cca cat aac gtc att tct ttg att att gaa tat gat gac 912

Thr Trp Leu Pro His Asn Val Ile Ser Leu Ile Ile Glu Tyr Asp Asp

290 295 300

aca caa tcg ttt ttc cga ctt tat ggc aga gat gat tac gat atc agt 960

Thr Gln Ser Phe Phe Arg Leu Tyr Gly Arg Asp Asp Tyr Asp Ile Ser

305 310 315 320

tat tta ctg aac ctt ttc act cac agt att gcc atg tcg aac aat gtt 1008

Tyr Leu Leu Asn Leu Phe Thr His Ser Ile Ala Met Ser Asn Asn Val

325 330 335

tta aac ccg gta ctc tat gcg tgg ctg aac cca agt ttc cgt caa ctg 1056

Leu Asn Pro Val Leu Tyr Ala Trp Leu Asn Pro Ser Phe Arg Gln Leu

340 345 350

gtc ata aag aca tat ttt gga gac cgg cgt aaa agt gac aga ata atc 1104

Val Ile Lys Thr Tyr Phe Gly Asp Arg Arg Lys Ser Asp Arg Ile Ile

355 360 365

aat caa aca tca gtt tac aaa aca aag atc gtg cat gat acg aag cac 1152

Asn Gln Thr Ser Val Tyr Lys Thr Lys Ile Val His Asp Thr Lys His

370 375 380

ttg aat gga aga gcc aaa att ggc ggt ggt ggt agc cac gag gcg ttg 1200

Leu Asn Gly Arg Ala Lys Ile Gly Gly Gly Gly Ser His Glu Ala Leu

385 390 395 400

aag gag agg gag ctg aac tcg tgt tcg gaa aat tta agc tat cat gtg 1248

Lys Glu Arg Glu Leu Asn Ser Cys Ser Glu Asn Leu Ser Tyr His Val

405 410 415

aac ggt cat acg agg act cct aca ccg gaa gtt cag ttg aat gaa gtt 1296

Asn Gly His Thr Arg Thr Pro Thr Pro Glu Val Gln Leu Asn Glu Val

420 425 430

tca agt cct gaa ata agt aaa ctt gtt gct gag ccg gaa gaa ttg atc 1344

Ser Ser Pro Glu Ile Ser Lys Leu Val Ala Glu Pro Glu Glu Leu Ile

435 440 445

gag ttc agc gtc aac gac acg cta gtc tga 1374

Glu Phe Ser Val Asn Asp Thr Leu Val

450 455

26

457

Homo sapiens

26

Met Glu Val Glu Asn Phe Thr Asp Cys Gln Val Tyr Trp Lys Val Tyr

1 5 10 15

Pro Asp Pro Ser Gln Ser Ile Tyr Ala Ile Val Pro Phe Leu Thr Val

20 25 30

Tyr Leu Phe Leu Phe Phe Leu Gly Leu Phe Gly Asn Val Thr Leu Ile

35 40 45

Tyr Val Thr Cys Ser His Lys Ala Leu Leu Ser Val Gln Asn Ile Phe

50 55 60

Ile Leu Asn Leu Ala Ala Ser Asp Cys Met Met Cys Ile Leu Ser Leu

65 70 75 80

Pro Ile Thr Pro Ile Thr Asn Val Tyr Lys Asn Trp Tyr Phe Gly Asn

85 90 95

Leu Leu Cys His Leu Ile Pro Cys Ile Gln Gly Ile Ser Ile Phe Val

100 105 110

Cys Thr Phe Ser Leu Gly Ala Ile Ala Leu Asp Arg Tyr Ile Leu Val

115 120 125

Val Arg Pro His Ser Thr Pro Leu Ser Gln Arg Gly Ala Phe Leu Thr

130 135 140

Thr Val Leu Leu Trp Ile Leu Ser Phe Val Val Thr Leu Pro Tyr Ala

145 150 155 160

Phe Asn Met Gln Met Ile Glu Tyr Thr Glu Glu Arg Ile Cys Gly Tyr

165 170 175

Phe Cys Thr Glu Lys Trp Glu Ser Ala Lys Ser Arg Arg Ala Tyr Thr

180 185 190

Met Ile Val Met Leu Ala Gln Phe Val Val Pro Phe Ala Val Met Ala

195 200 205

Phe Cys Tyr Ala Asn Ile Val Ser Val Leu Ser Lys Arg Ala Gln Thr

210 215 220

Lys Ile Arg Lys Met Val Glu Arg Thr Ser Ala Leu Glu Ser Ser Cys

225 230 235 240

Ala Phe Pro Ser His Gly Leu Glu Gln Tyr Glu Asn Glu Leu Asn Glu

245 250 255

Phe Leu Asp Lys Gln Glu Lys Glu Lys Gln Arg Val Val Leu Gln Asn

260 265 270

Arg Arg Thr Thr Ser Ile Leu Val Thr Met Val Val Trp Phe Gly Ile

275 280 285

Thr Trp Leu Pro His Asn Val Ile Ser Leu Ile Ile Glu Tyr Asp Asp

290 295 300

Thr Gln Ser Phe Phe Arg Leu Tyr Gly Arg Asp Asp Tyr Asp Ile Ser

305 310 315 320

Tyr Leu Leu Asn Leu Phe Thr His Ser Ile Ala Met Ser Asn Asn Val

325 330 335

Leu Asn Pro Val Leu Tyr Ala Trp Leu Asn Pro Ser Phe Arg Gln Leu

340 345 350

Val Ile Lys Thr Tyr Phe Gly Asp Arg Arg Lys Ser Asp Arg Ile Ile

355 360 365

Asn Gln Thr Ser Val Tyr Lys Thr Lys Ile Val His Asp Thr Lys His

370 375 380

Leu Asn Gly Arg Ala Lys Ile Gly Gly Gly Gly Ser His Glu Ala Leu

385 390 395 400

Lys Glu Arg Glu Leu Asn Ser Cys Ser Glu Asn Leu Ser Tyr His Val

405 410 415

Asn Gly His Thr Arg Thr Pro Thr Pro Glu Val Gln Leu Asn Glu Val

420 425 430

Ser Ser Pro Glu Ile Ser Lys Leu Val Ala Glu Pro Glu Glu Leu Ile

435 440 445

Glu Phe Ser Val Asn Asp Thr Leu Val

450 455

27

atg aat acg tca ttt gta gag cca tta tat gca gat gtt gaa caa ctt 48

Met Asn Thr Ser Phe Val Glu Pro Leu Tyr Ala Asp Val Glu Gln Leu

1 5 10 15

gaa cca gtc cct cta ctt aga cat tca tat caa cta act gtt ctt tat 96

Glu Pro Val Pro Leu Leu Arg His Ser Tyr Gln Leu Thr Val Leu Tyr

20 25 30

aca gtt gca tat gga gct gta ttc ttc act ggt gta ctt gga aac acg 144

Thr Val Ala Tyr Gly Ala Val Phe Phe Thr Gly Val Leu Gly Asn Thr

35 40 45

ttt gtt gtc tta gcg gtt tgg gct cat aag aat tta aat ata acc acg 192

Phe Val Val Leu Ala Val Trp Ala His Lys Asn Leu Asn Ile Thr Thr

50 55 60

gat tat cta att ttg tct ctt gca ctt gct gat ctg ttt att tta tgg 240

Asp Tyr Leu Ile Leu Ser Leu Ala Leu Ala Asp Leu Phe Ile Leu Trp

65 70 75 80

att tgt ctg cca act acg ttg att aat agc att ttc aca gaa tgg ctt 288

Ile Cys Leu Pro Thr Thr Leu Ile Asn Ser Ile Phe Thr Glu Trp Leu

85 90 95

tgg ggt caa ttt ttc tgc cga ttg tcc aca tgg gct aac gca tct acg 336

Trp Gly Gln Phe Phe Cys Arg Leu Ser Thr Trp Ala Asn Ala Ser Thr

100 105 110

tca ttt gca tca gtt tac acc ttg gtt gca gtg acg gct gat cgt tat 384

Ser Phe Ala Ser Val Tyr Thr Leu Val Ala Val Thr Ala Asp Arg Tyr

115 120 125

cta gct att tgc cat acg ttg aaa tac aac act agc tgg gat cga gaa 432

Leu Ala Ile Cys His Thr Leu Lys Tyr Asn Thr Ser Trp Asp Arg Glu

130 135 140

tat aca aaa tat gtt ata ttt gct gtt tgg cta gta gct gca ata ttc 480

Tyr Thr Lys Tyr Val Ile Phe Ala Val Trp Leu Val Ala Ala Ile Phe

145 150 155 160

gga ata cct aat tgg tat aac tat gat ttg ata gta tgg caa gaa ggc 528

Gly Ile Pro Asn Trp Tyr Asn Tyr Asp Leu Ile Val Trp Gln Glu Gly

165 170 175

agt tat ggt tac cga tta tgt acg tca caa acg gat caa aaa tta tat 576

Ser Tyr Gly Tyr Arg Leu Cys Thr Ser Gln Thr Asp Gln Lys Leu Tyr

180 185 190

ttt tta ttt gtt aac tta ttg ctg gct ttc ata gtt cca ttt ggt ttg 624

Phe Leu Phe Val Asn Leu Leu Leu Ala Phe Ile Val Pro Phe Gly Leu

195 200 205

att tcg ggt cta tac acg aga ata ttt atc act gta tca aca cat aga 672

Ile Ser Gly Leu Tyr Thr Arg Ile Phe Ile Thr Val Ser Thr His Arg

210 215 220

agt ctg gca gtt gat gca aga gcc cga gaa gat cga gta aaa cta cga 720

Ser Leu Ala Val Asp Ala Arg Ala Arg Glu Asp Arg Val Lys Leu Arg

225 230 235 240

gtt gcc aca atg atg tta aca gta ata att gta ttt gct tgt tgc tgg 768

Val Ala Thr Met Met Leu Thr Val Ile Ile Val Phe Ala Cys Cys Trp

245 250 255

tta cct ctc tat tgc atc ttc aca tat ttt ttc ttc ttt gct gat cag 816

Leu Pro Leu Tyr Cys Ile Phe Thr Tyr Phe Phe Phe Phe Ala Asp Gln

260 265 270

cga tcg gat ctt ttt caa att act tca atg ttg att cgg cca ata ttc 864

Arg Ser Asp Leu Phe Gln Ile Thr Ser Met Leu Ile Arg Pro Ile Phe

275 280 285

caa tgg atg tca tta cta tcg agt tct tta aat cca ata att tat att 912

Gln Trp Met Ser Leu Leu Ser Ser Ser Leu Asn Pro Ile Ile Tyr Ile

290 295 300

gca tac agt cac aag tac aga aga gct ttc aaa agt ata tta ctg atg 960

Ala Tyr Ser His Lys Tyr Arg Arg Ala Phe Lys Ser Ile Leu Leu Met

305 310 315 320

cca tgt aag aca aga tac gaa aga gtc cga agc aca ata ctc cgt cgt 1008

Pro Cys Lys Thr Arg Tyr Glu Arg Val Arg Ser Thr Ile Leu Arg Arg

325 330 335

cac tct cgt ggc ttc aaa tca act gca aca att tca atg tct aat ttt 1056

His Ser Arg Gly Phe Lys Ser Thr Ala Thr Ile Ser Met Ser Asn Phe

340 345 350

gga act gaa cca aca aat tta ggt gga gca tct agt tta ctt att gaa 1104

Gly Thr Glu Pro Thr Asn Leu Gly Gly Ala Ser Ser Leu Leu Ile Glu

355 360 365

cta gat gga aaa cag gtg gaa aga tct act tct gat tgt taa 1146

Leu Asp Gly Lys Gln Val Glu Arg Ser Thr Ser Asp Cys

370 375 380

28

381

Homo sapiens

28

Met Asn Thr Ser Phe Val Glu Pro Leu Tyr Ala Asp Val Glu Gln Leu

1 5 10 15

Glu Pro Val Pro Leu Leu Arg His Ser Tyr Gln Leu Thr Val Leu Tyr

20 25 30

Thr Val Ala Tyr Gly Ala Val Phe Phe Thr Gly Val Leu Gly Asn Thr

35 40 45

Phe Val Val Leu Ala Val Trp Ala His Lys Asn Leu Asn Ile Thr Thr

50 55 60

Asp Tyr Leu Ile Leu Ser Leu Ala Leu Ala Asp Leu Phe Ile Leu Trp

65 70 75 80

Ile Cys Leu Pro Thr Thr Leu Ile Asn Ser Ile Phe Thr Glu Trp Leu

85 90 95

Trp Gly Gln Phe Phe Cys Arg Leu Ser Thr Trp Ala Asn Ala Ser Thr

100 105 110

Ser Phe Ala Ser Val Tyr Thr Leu Val Ala Val Thr Ala Asp Arg Tyr

115 120 125

Leu Ala Ile Cys His Thr Leu Lys Tyr Asn Thr Ser Trp Asp Arg Glu

130 135 140

Tyr Thr Lys Tyr Val Ile Phe Ala Val Trp Leu Val Ala Ala Ile Phe

145 150 155 160

Gly Ile Pro Asn Trp Tyr Asn Tyr Asp Leu Ile Val Trp Gln Glu Gly

165 170 175

Ser Tyr Gly Tyr Arg Leu Cys Thr Ser Gln Thr Asp Gln Lys Leu Tyr

180 185 190

Phe Leu Phe Val Asn Leu Leu Leu Ala Phe Ile Val Pro Phe Gly Leu

195 200 205

Ile Ser Gly Leu Tyr Thr Arg Ile Phe Ile Thr Val Ser Thr His Arg

210 215 220

Ser Leu Ala Val Asp Ala Arg Ala Arg Glu Asp Arg Val Lys Leu Arg

225 230 235 240

Val Ala Thr Met Met Leu Thr Val Ile Ile Val Phe Ala Cys Cys Trp

245 250 255

Leu Pro Leu Tyr Cys Ile Phe Thr Tyr Phe Phe Phe Phe Ala Asp Gln

260 265 270

Arg Ser Asp Leu Phe Gln Ile Thr Ser Met Leu Ile Arg Pro Ile Phe

275 280 285

Gln Trp Met Ser Leu Leu Ser Ser Ser Leu Asn Pro Ile Ile Tyr Ile

290 295 300

Ala Tyr Ser His Lys Tyr Arg Arg Ala Phe Lys Ser Ile Leu Leu Met

305 310 315 320

Pro Cys Lys Thr Arg Tyr Glu Arg Val Arg Ser Thr Ile Leu Arg Arg

325 330 335

His Ser Arg Gly Phe Lys Ser Thr Ala Thr Ile Ser Met Ser Asn Phe

340 345 350

Gly Thr Glu Pro Thr Asn Leu Gly Gly Ala Ser Ser Leu Leu Ile Glu

355 360 365

Leu Asp Gly Lys Gln Val Glu Arg Ser Thr Ser Asp Cys

370 375 380

29

atg gaa gtg aaa gat ata gat aac tac tgt gat cgt gga atc agt ccg 48

Met Glu Val Lys Asp Ile Asp Asn Tyr Cys Asp Arg Gly Ile Ser Pro

1 5 10 15

aat gca tcc aat tat ctc acg tac cca ttt gac ggg ctc tgt cta cag 96

Asn Ala Ser Asn Tyr Leu Thr Tyr Pro Phe Asp Gly Leu Cys Leu Gln

20 25 30

aaa ttt ttt tat caa ctc caa act tct ttg cga agg ttc act cct tac 144

Lys Phe Phe Tyr Gln Leu Gln Thr Ser Leu Arg Arg Phe Thr Pro Tyr

35 40 45

gaa gaa atc att tac aca aca gtt tac atc att atc tct gta gca gct 192

Glu Glu Ile Ile Tyr Thr Thr Val Tyr Ile Ile Ile Ser Val Ala Ala

50 55 60

gtt att gga aat gga ttg gtg ata atg gct gta gta cgg aaa aag aca 240

Val Ile Gly Asn Gly Leu Val Ile Met Ala Val Val Arg Lys Lys Thr

65 70 75 80

atg aga aca aac aga aat gtt ttg att tta aat ctc gcg ctt tca aac 288

Met Arg Thr Asn Arg Asn Val Leu Ile Leu Asn Leu Ala Leu Ser Asn

85 90 95

ttg ata ctc gcc atc acc aac atc cca ttt cta tgg ctt ccg tca att 336

Leu Ile Leu Ala Ile Thr Asn Ile Pro Phe Leu Trp Leu Pro Ser Ile

100 105 110

gat ttc gaa ttt ccg tac tct cga ttt ttc tgc aaa ttt gcc aat gtg 384

Asp Phe Glu Phe Pro Tyr Ser Arg Phe Phe Cys Lys Phe Ala Asn Val

115 120 125

ctt ccg ggt agt aat atc tac tgc tca act tta acc atc tcg gtg atg 432

Leu Pro Gly Ser Asn Ile Tyr Cys Ser Thr Leu Thr Ile Ser Val Met

130 135 140

gca att gat aga tat tat tcg gtg aag aaa ttg aaa att gca tca aat 480

Ala Ile Asp Arg Tyr Tyr Ser Val Lys Lys Leu Lys Ile Ala Ser Asn

145 150 155 160

cgt aaa caa tgt ttc cat gct gtt ttg gtt tca ttg gct att tgg att 528

Arg Lys Gln Cys Phe His Ala Val Leu Val Ser Leu Ala Ile Trp Ile

165 170 175

gtg tca ttc atc ctc tcg tta cct ctg ctc ttg tac tat gaa acc tca 576

Val Ser Phe Ile Leu Ser Leu Pro Leu Leu Leu Tyr Tyr Glu Thr Ser

180 185 190

atg ctc tac gtc atg aga gaa att cga gtt gtt gat caa agc ggt cag 624

Met Leu Tyr Val Met Arg Glu Ile Arg Val Val Asp Gln Ser Gly Gln

195 200 205

gaa gtc atc cga agc tac gga tgg aga cag tgc cgt cta gtt tct gcc 672

Glu Val Ile Arg Ser Tyr Gly Trp Arg Gln Cys Arg Leu Val Ser Ala

210 215 220

gga cga tta ccg gac atc acc caa agc atc cag ttg ctc atg tct att 720

Gly Arg Leu Pro Asp Ile Thr Gln Ser Ile Gln Leu Leu Met Ser Ile

225 230 235 240

ctt caa gtc gct ttc cta tac atc gtt cca ctc ttt gtt ctt tca atc 768

Leu Gln Val Ala Phe Leu Tyr Ile Val Pro Leu Phe Val Leu Ser Ile

245 250 255

ttc aac gtg aaa ctc acc cgg ttt tta aaa aca aat gcc aac aaa atg 816

Phe Asn Val Lys Leu Thr Arg Phe Leu Lys Thr Asn Ala Asn Lys Met

260 265 270

agc aaa act cgt gct ccg cca aaa cga ttt gac aga tcc gat agc cac 864

Ser Lys Thr Arg Ala Pro Pro Lys Arg Phe Asp Arg Ser Asp Ser His

275 280 285

cat aat tcg ttg aaa aat aac aac aac cac acg tct tct cta cgt tcg 912

His Asn Ser Leu Lys Asn Asn Asn Asn His Thr Ser Ser Leu Arg Ser

290 295 300

cca tca atg ccc tca atc aga agt tcg ata acg gag aga aac aag acg 960

Pro Ser Met Pro Ser Ile Arg Ser Ser Ile Thr Glu Arg Asn Lys Thr

305 310 315 320

aat cag aga aca aac aga act act tcg tta ctg att gca atg gcc gga 1008

Asn Gln Arg Thr Asn Arg Thr Thr Ser Leu Leu Ile Ala Met Ala Gly

325 330 335

agc tat gcg gct ctt tgg ttt cca ttc act ctc atc act ttt ttg ata 1056

Ser Tyr Ala Ala Leu Trp Phe Pro Phe Thr Leu Ile Thr Phe Leu Ile

340 345 350

gac ttc gag ttg atc atc aat caa gac tac gtg aac ttg gta gaa cga 1104

Asp Phe Glu Leu Ile Ile Asn Gln Asp Tyr Val Asn Leu Val Glu Arg

355 360 365

att gac caa acc tgc aaa atg gta tcc atg ctg tcc att tgt gtg aac 1152

Ile Asp Gln Thr Cys Lys Met Val Ser Met Leu Ser Ile Cys Val Asn

370 375 380

cca ttt ctc tac gga ttc cta aat acc aat ttt cga cac gaa ttt tcc 1200

Pro Phe Leu Tyr Gly Phe Leu Asn Thr Asn Phe Arg His Glu Phe Ser

385 390 395 400

gac atc tac tac cga tac att cgc tgt gaa aca aag agt cag cca gcc 1248

Asp Ile Tyr Tyr Arg Tyr Ile Arg Cys Glu Thr Lys Ser Gln Pro Ala

405 410 415

ggc cga ttc cat cat gat gta tca tca atc gct cac cat aga caa gac 1296

Gly Arg Phe His His Asp Val Ser Ser Ile Ala His His Arg Gln Asp

420 425 430

tct gtt tac aat gat gag gca aca ctt ttg act aca ggg cgt cag agt 1344

Ser Val Tyr Asn Asp Glu Ala Thr Leu Leu Thr Thr Gly Arg Gln Ser

435 440 445

aat ggt aaa gat ggg agc tcg tct cca ata gga ttc cgc tct agc gtc 1392

Asn Gly Lys Asp Gly Ser Ser Ser Pro Ile Gly Phe Arg Ser Ser Val

450 455 460

cgt gtt tgc tcg ggt caa aca aaa atg att gga gat cgc att gta ttg 1440

Arg Val Cys Ser Gly Gln Thr Lys Met Ile Gly Asp Arg Ile Val Leu

465 470 475 480

gac gat gat atc gag aaa gat agt ttt gtc taa 1473

Asp Asp Asp Ile Glu Lys Asp Ser Phe Val

485 490

30

490

Homo sapiens

30

Met Glu Val Lys Asp Ile Asp Asn Tyr Cys Asp Arg Gly Ile Ser Pro

1 5 10 15

Asn Ala Ser Asn Tyr Leu Thr Tyr Pro Phe Asp Gly Leu Cys Leu Gln

20 25 30

Lys Phe Phe Tyr Gln Leu Gln Thr Ser Leu Arg Arg Phe Thr Pro Tyr

35 40 45

Glu Glu Ile Ile Tyr Thr Thr Val Tyr Ile Ile Ile Ser Val Ala Ala

50 55 60

Val Ile Gly Asn Gly Leu Val Ile Met Ala Val Val Arg Lys Lys Thr

65 70 75 80

Met Arg Thr Asn Arg Asn Val Leu Ile Leu Asn Leu Ala Leu Ser Asn

85 90 95

Leu Ile Leu Ala Ile Thr Asn Ile Pro Phe Leu Trp Leu Pro Ser Ile

100 105 110

Asp Phe Glu Phe Pro Tyr Ser Arg Phe Phe Cys Lys Phe Ala Asn Val

115 120 125

Leu Pro Gly Ser Asn Ile Tyr Cys Ser Thr Leu Thr Ile Ser Val Met

130 135 140

Ala Ile Asp Arg Tyr Tyr Ser Val Lys Lys Leu Lys Ile Ala Ser Asn

145 150 155 160

Arg Lys Gln Cys Phe His Ala Val Leu Val Ser Leu Ala Ile Trp Ile

165 170 175

Val Ser Phe Ile Leu Ser Leu Pro Leu Leu Leu Tyr Tyr Glu Thr Ser

180 185 190

Met Leu Tyr Val Met Arg Glu Ile Arg Val Val Asp Gln Ser Gly Gln

195 200 205

Glu Val Ile Arg Ser Tyr Gly Trp Arg Gln Cys Arg Leu Val Ser Ala

210 215 220

Gly Arg Leu Pro Asp Ile Thr Gln Ser Ile Gln Leu Leu Met Ser Ile

225 230 235 240

Leu Gln Val Ala Phe Leu Tyr Ile Val Pro Leu Phe Val Leu Ser Ile

245 250 255

Phe Asn Val Lys Leu Thr Arg Phe Leu Lys Thr Asn Ala Asn Lys Met

260 265 270

Ser Lys Thr Arg Ala Pro Pro Lys Arg Phe Asp Arg Ser Asp Ser His

275 280 285

His Asn Ser Leu Lys Asn Asn Asn Asn His Thr Ser Ser Leu Arg Ser

290 295 300

Pro Ser Met Pro Ser Ile Arg Ser Ser Ile Thr Glu Arg Asn Lys Thr

305 310 315 320

Asn Gln Arg Thr Asn Arg Thr Thr Ser Leu Leu Ile Ala Met Ala Gly

325 330 335

Ser Tyr Ala Ala Leu Trp Phe Pro Phe Thr Leu Ile Thr Phe Leu Ile

340 345 350

Asp Phe Glu Leu Ile Ile Asn Gln Asp Tyr Val Asn Leu Val Glu Arg

355 360 365

Ile Asp Gln Thr Cys Lys Met Val Ser Met Leu Ser Ile Cys Val Asn

370 375 380

Pro Phe Leu Tyr Gly Phe Leu Asn Thr Asn Phe Arg His Glu Phe Ser

385 390 395 400

Asp Ile Tyr Tyr Arg Tyr Ile Arg Cys Glu Thr Lys Ser Gln Pro Ala

405 410 415

Gly Arg Phe His His Asp Val Ser Ser Ile Ala His His Arg Gln Asp

420 425 430

Ser Val Tyr Asn Asp Glu Ala Thr Leu Leu Thr Thr Gly Arg Gln Ser

435 440 445

Asn Gly Lys Asp Gly Ser Ser Ser Pro Ile Gly Phe Arg Ser Ser Val

450 455 460

Arg Val Cys Ser Gly Gln Thr Lys Met Ile Gly Asp Arg Ile Val Leu

465 470 475 480

Asp Asp Asp Ile Glu Lys Asp Ser Phe Val

485 490

31

1130

Homo sapiens

CeGPCR11 (F35G8.1)

31

atg aat atc gac tcg aat tta aca gat ttt caa tgc gag tac ccg gcg 48

Met Asn Ile Asp Ser Asn Leu Thr Asp Phe Gln Cys Glu Tyr Pro Ala

1 5 10 15

att gac ata gga att cat atg aaa acc ttg tta gca gtc ggg tat ggt 96

Ile Asp Ile Gly Ile His Met Lys Thr Leu Leu Ala Val Gly Tyr Gly

20 25 30

ttg gtg gga gcc ctg agc tta gtt gga aat ctt gct gta ttg ctc att 144

Leu Val Gly Ala Leu Ser Leu Val Gly Asn Leu Ala Val Leu Leu Ile

35 40 45

gtg ata tgc agg aga gaa atg caa aca gtc acc aac att ttt ata agt 192

Val Ile Cys Arg Arg Glu Met Gln Thr Val Thr Asn Ile Phe Ile Ser

50 55 60

agc gtc tcc gcg gct gac ttg gta ata aca agt ttc tcc tta tgg gcg 240

Ser Val Ser Ala Ala Asp Leu Val Ile Thr Ser Phe Ser Leu Trp Ala

65 70 75 80

acc cca tta gcc tat tat caa cgg gta tgg cat ttc gga aag tat atg 288

Thr Pro Leu Ala Tyr Tyr Gln Arg Val Trp His Phe Gly Lys Tyr Met

85 90 95

tgc tat atg gtt tcc atc ata caa ggc tta tcc ctc atg tgg gta cca 336

Cys Tyr Met Val Ser Ile Ile Gln Gly Leu Ser Leu Met Trp Val Pro

100 105 110

ctg acc cta gca gca gtt gca tta gat cgc tac tct cta gtt gct tct 384

Leu Thr Leu Ala Ala Val Ala Leu Asp Arg Tyr Ser Leu Val Ala Ser

115 120 125

ccg ttc cgt cag cca atg tct aaa aag act tgc ttg ctg atc atc gct 432

Pro Phe Arg Gln Pro Met Ser Lys Lys Thr Cys Leu Leu Ile Ile Ala

130 135 140

gga atc tgg atg gga ggg ttt gca gtt ttg tcg cca atg att cgg atg 480

Gly Ile Trp Met Gly Gly Phe Ala Val Leu Ser Pro Met Ile Arg Met

145 150 155 160

gta gat ttt gtt gac agc tat gga cca tgc cat ttt tgc ctg gaa tcc 528

Val Asp Phe Val Asp Ser Tyr Gly Pro Cys His Phe Cys Leu Glu Ser

165 170 175

tgg gac cac gac aaa caa cac tac cga ctt ttc tac gga ctc tcg gtg 576

Trp Asp His Asp Lys Gln His Tyr Arg Leu Phe Tyr Gly Leu Ser Val

180 185 190

ctc gtg atc cgc tcc gca att cca ctt gtt ctc att tcc ctg tgc cac 624

Leu Val Ile Arg Ser Ala Ile Pro Leu Val Leu Ile Ser Leu Cys His

195 200 205

tgg aga atc gca gtt att ttg aac acg cag acg gag aaa ttc caa aca 672

Trp Arg Ile Ala Val Ile Leu Asn Thr Gln Thr Glu Lys Phe Gln Thr

210 215 220

tta cgt agt gcc agc aca gtc acc caa tcg act gac atc cgc cgt aaa 720

Leu Arg Ser Ala Ser Thr Val Thr Gln Ser Thr Asp Ile Arg Arg Lys

225 230 235 240

caa cgt ctt cag act ctc tta ttg gca atg gtg gtc ata ttt gcc gtg 768

Gln Arg Leu Gln Thr Leu Leu Leu Ala Met Val Val Ile Phe Ala Val

245 250 255

tcc agt ctc cca ctg gac ctt tca aat gtt ctt caa gat ttg atc gta 816

Ser Ser Leu Pro Leu Asp Leu Ser Asn Val Leu Gln Asp Leu Ile Val

260 265 270

gtg tac cag gtt cga cct gtc ccc gac aac gtt cgc cat ttt atc ttc 864

Val Tyr Gln Val Arg Pro Val Pro Asp Asn Val Arg His Phe Ile Phe

275 280 285

ttc ttt tgc cat tgg acc gca atg gca gga aca ctt ctc aac ccg tta 912

Phe Phe Cys His Trp Thr Ala Met Ala Gly Thr Leu Leu Asn Pro Leu

290 295 300

gtc tac gcg tac tac aac gaa aac ttc cgg cgt cag att caa aca tgc 960

Val Tyr Ala Tyr Tyr Asn Glu Asn Phe Arg Arg Gln Ile Gln Thr Cys

305 310 315 320

ttt gga gaa atg cgt gga cag gga gag ttc aag cgg ggg cta tac tct 1008

Phe Gly Glu Met Arg Gly Gln Gly Glu Phe Lys Arg Gly Leu Tyr Ser

325 330 335

att gtc tcc ggc aga tac tcc tac cga gca gac gac gag gaa aat cat 1056

Ile Val Ser Gly Arg Tyr Ser Tyr Arg Ala Asp Asp Glu Glu Asn His

340 345 350

cac aga caa aac aca cgt atc gaa ctg gct aac aat caa act ggt gat 1104

His Arg Gln Asn Thr Arg Ile Glu Leu Ala Asn Asn Gln Thr Gly Asp

355 360 365

atc gaa gtt ctc aga acg gat ctt ta 1130

Ile Glu Val Leu Arg Thr Asp Leu

370 375

32

376

Homo sapiens

32

Met Asn Ile Asp Ser Asn Leu Thr Asp Phe Gln Cys Glu Tyr Pro Ala

1 5 10 15

Ile Asp Ile Gly Ile His Met Lys Thr Leu Leu Ala Val Gly Tyr Gly

20 25 30

Leu Val Gly Ala Leu Ser Leu Val Gly Asn Leu Ala Val Leu Leu Ile

35 40 45

Val Ile Cys Arg Arg Glu Met Gln Thr Val Thr Asn Ile Phe Ile Ser

50 55 60

Ser Val Ser Ala Ala Asp Leu Val Ile Thr Ser Phe Ser Leu Trp Ala

65 70 75 80

Thr Pro Leu Ala Tyr Tyr Gln Arg Val Trp His Phe Gly Lys Tyr Met

85 90 95

Cys Tyr Met Val Ser Ile Ile Gln Gly Leu Ser Leu Met Trp Val Pro

100 105 110

Leu Thr Leu Ala Ala Val Ala Leu Asp Arg Tyr Ser Leu Val Ala Ser

115 120 125

Pro Phe Arg Gln Pro Met Ser Lys Lys Thr Cys Leu Leu Ile Ile Ala

130 135 140

Gly Ile Trp Met Gly Gly Phe Ala Val Leu Ser Pro Met Ile Arg Met

145 150 155 160

Val Asp Phe Val Asp Ser Tyr Gly Pro Cys His Phe Cys Leu Glu Ser

165 170 175

Trp Asp His Asp Lys Gln His Tyr Arg Leu Phe Tyr Gly Leu Ser Val

180 185 190

Leu Val Ile Arg Ser Ala Ile Pro Leu Val Leu Ile Ser Leu Cys His

195 200 205

Trp Arg Ile Ala Val Ile Leu Asn Thr Gln Thr Glu Lys Phe Gln Thr

210 215 220

Leu Arg Ser Ala Ser Thr Val Thr Gln Ser Thr Asp Ile Arg Arg Lys

225 230 235 240

Gln Arg Leu Gln Thr Leu Leu Leu Ala Met Val Val Ile Phe Ala Val

245 250 255

Ser Ser Leu Pro Leu Asp Leu Ser Asn Val Leu Gln Asp Leu Ile Val

260 265 270

Val Tyr Gln Val Arg Pro Val Pro Asp Asn Val Arg His Phe Ile Phe

275 280 285

Phe Phe Cys His Trp Thr Ala Met Ala Gly Thr Leu Leu Asn Pro Leu

290 295 300

Val Tyr Ala Tyr Tyr Asn Glu Asn Phe Arg Arg Gln Ile Gln Thr Cys

305 310 315 320

Phe Gly Glu Met Arg Gly Gln Gly Glu Phe Lys Arg Gly Leu Tyr Ser

325 330 335

Ile Val Ser Gly Arg Tyr Ser Tyr Arg Ala Asp Asp Glu Glu Asn His

340 345 350

His Arg Gln Asn Thr Arg Ile Glu Leu Ala Asn Asn Gln Thr Gly Asp

355 360 365

Ile Glu Val Leu Arg Thr Asp Leu

370 375

33

atg aca acg tgt ccc cta cca ccc agt tta gac gaa atg gat ctg cga 48

Met Thr Thr Cys Pro Leu Pro Pro Ser Leu Asp Glu Met Asp Leu Arg

1 5 10 15

tta gct gcc gat aaa gtt cta aac ggt tca ctg atc aac tgt aca ttc 96

Leu Ala Ala Asp Lys Val Leu Asn Gly Ser Leu Ile Asn Cys Thr Phe

20 25 30

caa tcg ttt tac gat caa atg tat caa aca cac gga gta tac ttc ata 144

Gln Ser Phe Tyr Asp Gln Met Tyr Gln Thr His Gly Val Tyr Phe Ile

35 40 45

ttt gaa cca act ccg ttc gtt cat cca att gtt tca cag att ttc tat 192

Phe Glu Pro Thr Pro Phe Val His Pro Ile Val Ser Gln Ile Phe Tyr

50 55 60

gga atc ctg ttc aca cta aca ata ttt ctg gcg tta atg ggc aat ttt 240

Gly Ile Leu Phe Thr Leu Thr Ile Phe Leu Ala Leu Met Gly Asn Phe

65 70 75 80

aca gtg atg tgg ata atc ctg tac cac cgt caa atg cga agc gtc aca 288

Thr Val Met Trp Ile Ile Leu Tyr His Arg Gln Met Arg Ser Val Thr

85 90 95

aat tac tat ctg ttc aac ttg gca gtg gcg gat gcc tcg att tca gtg 336

Asn Tyr Tyr Leu Phe Asn Leu Ala Val Ala Asp Ala Ser Ile Ser Val

100 105 110

ttc aac acg gga ttc tca tgg tct tat aat tat tat tat gtt tgg aaa 384

Phe Asn Thr Gly Phe Ser Trp Ser Tyr Asn Tyr Tyr Tyr Val Trp Lys

115 120 125

ttc gga agc ttt tac tgt cga ata aac aat ttg atg gga ata act ccg 432

Phe Gly Ser Phe Tyr Cys Arg Ile Asn Asn Leu Met Gly Ile Thr Pro

130 135 140

att tgt gca agt gta ttc aca atg att gtc atg agc att gaa aga tat 480

Ile Cys Ala Ser Val Phe Thr Met Ile Val Met Ser Ile Glu Arg Tyr

145 150 155 160

tat gcc ata atc cat cca ttg aaa aag cgt cca gga cga cga tca act 528

Tyr Ala Ile Ile His Pro Leu Lys Lys Arg Pro Gly Arg Arg Ser Thr

165 170 175

gtt acc atc atc ata atg att tgg ttc atg gca ttt ttg ttc ggg gtt 576

Val Thr Ile Ile Ile Met Ile Trp Phe Met Ala Phe Leu Phe Gly Val

180 185 190

cca gca ttt ctt gcg tca aag gtt gat gtc tat tac ttc tac gat ggt 624

Pro Ala Phe Leu Ala Ser Lys Val Asp Val Tyr Tyr Phe Tyr Asp Gly

195 200 205

tac aca tta tac gag aat cca ctg tgc ctt gca gac aat tat ccc ggt 672

Tyr Thr Leu Tyr Glu Asn Pro Leu Cys Leu Ala Asp Asn Tyr Pro Gly

210 215 220

gga aat gaa tca cta ctt gga cag gta tac aac aac gga ctg ata act 720

Gly Asn Glu Ser Leu Leu Gly Gln Val Tyr Asn Asn Gly Leu Ile Thr

225 230 235 240

gtt caa tac att ctt cca cta tgc att tta tca gct gct tat tat cga 768

Val Gln Tyr Ile Leu Pro Leu Cys Ile Leu Ser Ala Ala Tyr Tyr Arg

245 250 255

gtt ggt gtt gag ctg aga aag gat aaa acc gtc ggt gac gtg aga cat 816

Val Gly Val Glu Leu Arg Lys Asp Lys Thr Val Gly Asp Val Arg His

260 265 270

gca aaa tca gtg gcc gca aag aag aag gcg tca atc atg ttg gca gtg 864

Ala Lys Ser Val Ala Ala Lys Lys Lys Ala Ser Ile Met Leu Ala Val

275 280 285

gtt gtg ttc att ttc atg att gtc tgg ttc cca tac aat gcc tac tat 912

Val Val Phe Ile Phe Met Ile Val Trp Phe Pro Tyr Asn Ala Tyr Tyr

290 295 300

ctc aca ttg cat tta gtt gag cca att ggg aat aaa atg ttg agt ctg 960

Leu Thr Leu His Leu Val Glu Pro Ile Gly Asn Lys Met Leu Ser Leu

305 310 315 320

tac att tat atc aac atc tat tgg ttg gga atg tcg tca act gtc ttc 1008

Tyr Ile Tyr Ile Asn Ile Tyr Trp Leu Gly Met Ser Ser Thr Val Phe

325 330 335

aat cct gtc atc tat tat ttt atg aac aaa cga ttc cgt gtc gga ttc 1056

Asn Pro Val Ile Tyr Tyr Phe Met Asn Lys Arg Phe Arg Val Gly Phe

340 345 350

cat cac gca ttc cgt tgg ctt cca ttc gtt cgt tcc gat aaa gat gaa 1104

His His Ala Phe Arg Trp Leu Pro Phe Val Arg Ser Asp Lys Asp Glu

355 360 365

tat caa aca att ctt tca cag aca cgt cca tct ctg atg cca ccc aca 1152

Tyr Gln Thr Ile Leu Ser Gln Thr Arg Pro Ser Leu Met Pro Pro Thr

370 375 380

acg atg gcg cat acg gat ttc tga 1176

Thr Met Ala His Thr Asp Phe

385 390

34

391

Homo sapiens

34

Met Thr Thr Cys Pro Leu Pro Pro Ser Leu Asp Glu Met Asp Leu Arg

1 5 10 15

Leu Ala Ala Asp Lys Val Leu Asn Gly Ser Leu Ile Asn Cys Thr Phe

20 25 30

Gln Ser Phe Tyr Asp Gln Met Tyr Gln Thr His Gly Val Tyr Phe Ile

35 40 45

Phe Glu Pro Thr Pro Phe Val His Pro Ile Val Ser Gln Ile Phe Tyr

50 55 60

Gly Ile Leu Phe Thr Leu Thr Ile Phe Leu Ala Leu Met Gly Asn Phe

65 70 75 80

Thr Val Met Trp Ile Ile Leu Tyr His Arg Gln Met Arg Ser Val Thr

85 90 95

Asn Tyr Tyr Leu Phe Asn Leu Ala Val Ala Asp Ala Ser Ile Ser Val

100 105 110

Phe Asn Thr Gly Phe Ser Trp Ser Tyr Asn Tyr Tyr Tyr Val Trp Lys

115 120 125

Phe Gly Ser Phe Tyr Cys Arg Ile Asn Asn Leu Met Gly Ile Thr Pro

130 135 140

Ile Cys Ala Ser Val Phe Thr Met Ile Val Met Ser Ile Glu Arg Tyr

145 150 155 160

Tyr Ala Ile Ile His Pro Leu Lys Lys Arg Pro Gly Arg Arg Ser Thr

165 170 175

Val Thr Ile Ile Ile Met Ile Trp Phe Met Ala Phe Leu Phe Gly Val

180 185 190

Pro Ala Phe Leu Ala Ser Lys Val Asp Val Tyr Tyr Phe Tyr Asp Gly

195 200 205

Tyr Thr Leu Tyr Glu Asn Pro Leu Cys Leu Ala Asp Asn Tyr Pro Gly

210 215 220

Gly Asn Glu Ser Leu Leu Gly Gln Val Tyr Asn Asn Gly Leu Ile Thr

225 230 235 240

Val Gln Tyr Ile Leu Pro Leu Cys Ile Leu Ser Ala Ala Tyr Tyr Arg

245 250 255

Val Gly Val Glu Leu Arg Lys Asp Lys Thr Val Gly Asp Val Arg His

260 265 270

Ala Lys Ser Val Ala Ala Lys Lys Lys Ala Ser Ile Met Leu Ala Val

275 280 285

Val Val Phe Ile Phe Met Ile Val Trp Phe Pro Tyr Asn Ala Tyr Tyr

290 295 300

Leu Thr Leu His Leu Val Glu Pro Ile Gly Asn Lys Met Leu Ser Leu

305 310 315 320

Tyr Ile Tyr Ile Asn Ile Tyr Trp Leu Gly Met Ser Ser Thr Val Phe

325 330 335

Asn Pro Val Ile Tyr Tyr Phe Met Asn Lys Arg Phe Arg Val Gly Phe

340 345 350

His His Ala Phe Arg Trp Leu Pro Phe Val Arg Ser Asp Lys Asp Glu

355 360 365

Tyr Gln Thr Ile Leu Ser Gln Thr Arg Pro Ser Leu Met Pro Pro Thr

370 375 380

Thr Met Ala His Thr Asp Phe

385 390

35

atg agt tct tcg aat cac tgc atc gac atc cgt gca tac ttg tgg cag 48

Met Ser Ser Ser Asn His Cys Ile Asp Ile Arg Ala Tyr Leu Trp Gln

1 5 10 15

aca aag cat gac ctg acg ctc cac ccg att ccc atc gcg att ctt gca 96

Thr Lys His Asp Leu Thr Leu His Pro Ile Pro Ile Ala Ile Leu Ala

20 25 30

acc atc tac act ata att gtc gta gtt ggc gta acc ggc aat ttg tta 144

Thr Ile Tyr Thr Ile Ile Val Val Val Gly Val Thr Gly Asn Leu Leu

35 40 45

gta gtg atg tcg gtg atg agg ttc aaa gtt ctt caa tca gtc agg aac 192

Val Val Met Ser Val Met Arg Phe Lys Val Leu Gln Ser Val Arg Asn

50 55 60

atg ttc atc gta tct ttg tca gtt tct gac att ttt gtg gcg att gtt 240

Met Phe Ile Val Ser Leu Ser Val Ser Asp Ile Phe Val Ala Ile Val

65 70 75 80

agt ggt tca gta acg ccg ata acc gca ttc tct aaa gtt tgg tta ttt 288

Ser Gly Ser Val Thr Pro Ile Thr Ala Phe Ser Lys Val Trp Leu Phe

85 90 95

ggt gga cca ttg tgt cat tta cta cct ttg tta cag ggt acc gcg ttg 336

Gly Gly Pro Leu Cys His Leu Leu Pro Leu Leu Gln Gly Thr Ala Leu

100 105 110

agt ttt tcc acg tta acg ctc acc gca att gca att gac aga tat att 384

Ser Phe Ser Thr Leu Thr Leu Thr Ala Ile Ala Ile Asp Arg Tyr Ile

115 120 125

ctc atc tgt cat ccg acg aaa gaa ccg ata cgc aaa gat caa gca ttg 432

Leu Ile Cys His Pro Thr Lys Glu Pro Ile Arg Lys Asp Gln Ala Leu

130 135 140

aaa atg ata agt ttc aac agc gcc atc tca gtt ggg ctt tcg gta cca 480

Lys Met Ile Ser Phe Asn Ser Ala Ile Ser Val Gly Leu Ser Val Pro

145 150 155 160

tta ttc atg aaa cag gaa ctt atg caa ttc cga aac tat tgc gga gaa 528

Leu Phe Met Lys Gln Glu Leu Met Gln Phe Arg Asn Tyr Cys Gly Glu

165 170 175

tat tgc tca gaa aac tgg gga cca gat gct tat ttg aga agc gtt tat 576

Tyr Cys Ser Glu Asn Trp Gly Pro Asp Ala Tyr Leu Arg Ser Val Tyr

180 185 190

gga aca gtg gtg ttc att att caa ttc gtg ttt cca ttg atc acc atc 624

Gly Thr Val Val Phe Ile Ile Gln Phe Val Phe Pro Leu Ile Thr Ile

195 200 205

aca ttt tgc tat gca tct att tct atc aaa cta cga cgt ggt gtc ttt 672

Thr Phe Cys Tyr Ala Ser Ile Ser Ile Lys Leu Arg Arg Gly Val Phe

210 215 220

gtg aga gga agc caa aaa gag ctg atg tct gag gca cgt cgt caa ttg 720

Val Arg Gly Ser Gln Lys Glu Leu Met Ser Glu Ala Arg Arg Gln Leu

225 230 235 240

acg caa cgt cga ctt cgc aca aat cgg atg ctt att atc atg aca gtc 768

Thr Gln Arg Arg Leu Arg Thr Asn Arg Met Leu Ile Ile Met Thr Val

245 250 255

aca ttc gct ctc tca tgg ctg cca tct gtt ggc ttc aac ttt ctc cgg 816

Thr Phe Ala Leu Ser Trp Leu Pro Ser Val Gly Phe Asn Phe Leu Arg

260 265 270

gat tac tca gcg ctt ccc ggc att att gat tca caa gat tac cta ttc 864

Asp Tyr Ser Ala Leu Pro Gly Ile Ile Asp Ser Gln Asp Tyr Leu Phe

275 280 285

gga att att ttc cat tgc att tca atg aca tcg gtg att gtg aat ccc 912

Gly Ile Ile Phe His Cys Ile Ser Met Thr Ser Val Ile Val Asn Pro

290 295 300

ttc ctt tac ggt tac tgt aat gaa cac ttt cgt gct gca ttt gcg gct 960

Phe Leu Tyr Gly Tyr Cys Asn Glu His Phe Arg Ala Ala Phe Ala Ala

305 310 315 320

ctt ctt gac acg gtg aag gca gct tgt gga atg aga cga gtg agt ccg 1008

Leu Leu Asp Thr Val Lys Ala Ala Cys Gly Met Arg Arg Val Ser Pro

325 330 335

ggc aat cca gcg tgc tcc cag cta ctc agt act cac ttt gaa agc acc 1056

Gly Asn Pro Ala Cys Ser Gln Leu Leu Ser Thr His Phe Glu Ser Thr

340 345 350

aca aga cga tcc gtg act acc acg att cca agt tca att taa 1098

Thr Arg Arg Ser Val Thr Thr Thr Ile Pro Ser Ser Ile

355 360 365

36

365

Homo sapiens

36

Met Ser Ser Ser Asn His Cys Ile Asp Ile Arg Ala Tyr Leu Trp Gln

1 5 10 15

Thr Lys His Asp Leu Thr Leu His Pro Ile Pro Ile Ala Ile Leu Ala

20 25 30

Thr Ile Tyr Thr Ile Ile Val Val Val Gly Val Thr Gly Asn Leu Leu

35 40 45

Val Val Met Ser Val Met Arg Phe Lys Val Leu Gln Ser Val Arg Asn

50 55 60

Met Phe Ile Val Ser Leu Ser Val Ser Asp Ile Phe Val Ala Ile Val

65 70 75 80

Ser Gly Ser Val Thr Pro Ile Thr Ala Phe Ser Lys Val Trp Leu Phe

85 90 95

Gly Gly Pro Leu Cys His Leu Leu Pro Leu Leu Gln Gly Thr Ala Leu

100 105 110

Ser Phe Ser Thr Leu Thr Leu Thr Ala Ile Ala Ile Asp Arg Tyr Ile

115 120 125

Leu Ile Cys His Pro Thr Lys Glu Pro Ile Arg Lys Asp Gln Ala Leu

130 135 140

Lys Met Ile Ser Phe Asn Ser Ala Ile Ser Val Gly Leu Ser Val Pro

145 150 155 160

Leu Phe Met Lys Gln Glu Leu Met Gln Phe Arg Asn Tyr Cys Gly Glu

165 170 175

Tyr Cys Ser Glu Asn Trp Gly Pro Asp Ala Tyr Leu Arg Ser Val Tyr

180 185 190

Gly Thr Val Val Phe Ile Ile Gln Phe Val Phe Pro Leu Ile Thr Ile

195 200 205

Thr Phe Cys Tyr Ala Ser Ile Ser Ile Lys Leu Arg Arg Gly Val Phe

210 215 220

Val Arg Gly Ser Gln Lys Glu Leu Met Ser Glu Ala Arg Arg Gln Leu

225 230 235 240

Thr Gln Arg Arg Leu Arg Thr Asn Arg Met Leu Ile Ile Met Thr Val

245 250 255

Thr Phe Ala Leu Ser Trp Leu Pro Ser Val Gly Phe Asn Phe Leu Arg

260 265 270

Asp Tyr Ser Ala Leu Pro Gly Ile Ile Asp Ser Gln Asp Tyr Leu Phe

275 280 285

Gly Ile Ile Phe His Cys Ile Ser Met Thr Ser Val Ile Val Asn Pro

290 295 300

Phe Leu Tyr Gly Tyr Cys Asn Glu His Phe Arg Ala Ala Phe Ala Ala

305 310 315 320

Leu Leu Asp Thr Val Lys Ala Ala Cys Gly Met Arg Arg Val Ser Pro

325 330 335

Gly Asn Pro Ala Cys Ser Gln Leu Leu Ser Thr His Phe Glu Ser Thr

340 345 350

Thr Arg Arg Ser Val Thr Thr Thr Ile Pro Ser Ser Ile

355 360 365

37

atg caa ccg cca aac tct acg gga caa tgg aca gaa att cac tgc gat 48

Met Gln Pro Pro Asn Ser Thr Gly Gln Trp Thr Glu Ile His Cys Asp

1 5 10 15

tgg ttt gca gaa atg caa aat tat cag aac agt ctc tac aaa ata aat 96

Trp Phe Ala Glu Met Gln Asn Tyr Gln Asn Ser Leu Tyr Lys Ile Asn

20 25 30

ttt gat gga tcc cca ata gtg cca atg tat ggg ttg gtg tgc tca ttc 144

Phe Asp Gly Ser Pro Ile Val Pro Met Tyr Gly Leu Val Cys Ser Phe

35 40 45

gga gct ctt gcc aac ttt atc gtt ctc ctc gca ttt gtc aga act gca 192

Gly Ala Leu Ala Asn Phe Ile Val Leu Leu Ala Phe Val Arg Thr Ala

50 55 60

aat ctt cga aac ttg aga aac agt ttc att gtg aat ttg gca ttt tcc 240

Asn Leu Arg Asn Leu Arg Asn Ser Phe Ile Val Asn Leu Ala Phe Ser

65 70 75 80

gat ttg att ctg tgt gtg gtc aca gcg cca gtc act ctc tat acg agt 288

Asp Leu Ile Leu Cys Val Val Thr Ala Pro Val Thr Leu Tyr Thr Ser

85 90 95

tta aat tta ttt tgg cca ttc gga gat tgg tcg tgc aag ttt ctc gct 336

Leu Asn Leu Phe Trp Pro Phe Gly Asp Trp Ser Cys Lys Phe Leu Ala

100 105 110

ggt gtt caa gca gtg aac aca ttt gtt tca tca ctt act ctt gca ttc 384

Gly Val Gln Ala Val Asn Thr Phe Val Ser Ser Leu Thr Leu Ala Phe

115 120 125

att gca atg gat cgt gtt ctt cta aca ctt tgt cca gtt cga tgg aga 432

Ile Ala Met Asp Arg Val Leu Leu Thr Leu Cys Pro Val Arg Trp Arg

130 135 140

tta gca gca act gca cca ctt tta tgc tat ggt gtc gta tgg atc att 480

Leu Ala Ala Thr Ala Pro Leu Leu Cys Tyr Gly Val Val Trp Ile Ile

145 150 155 160

tcg atc ata gtt gct ctt cca tat gca ttg gca gta agc tca aag ttg 528

Ser Ile Ile Val Ala Leu Pro Tyr Ala Leu Ala Val Ser Ser Lys Leu

165 170 175

gct cca ttt gat cca tgg agt gat aga gca act ccc aaa atg cta acc 576

Ala Pro Phe Asp Pro Trp Ser Asp Arg Ala Thr Pro Lys Met Leu Thr

180 185 190

tat tgc aac cgt caa gtg cca gaa ata tgt gca gag atg caa gaa gcc 624

Tyr Cys Asn Arg Gln Val Pro Glu Ile Cys Ala Glu Met Gln Glu Ala

195 200 205

tgg gat aat gca att gtc tca aaa acc acg tac aca ttt gta gta ctt 672

Trp Asp Asn Ala Ile Val Ser Lys Thr Thr Tyr Thr Phe Val Val Leu

210 215 220

ggt att caa tat att cta cca ctt gct gcc ttg gca tat gca tat ttc 720

Gly Ile Gln Tyr Ile Leu Pro Leu Ala Ala Leu Ala Tyr Ala Tyr Phe

225 230 235 240

caa atc ggg tca aca att caa aaa cga tca aaa gta tca cgt aca gtg 768

Gln Ile Gly Ser Thr Ile Gln Lys Arg Ser Lys Val Ser Arg Thr Val

245 250 255

gat aca aca aga aga atg caa atg caa aat aga aat cga aga gct ctt 816

Asp Thr Thr Arg Arg Met Gln Met Gln Asn Arg Asn Arg Arg Ala Leu

260 265 270

ttg ttg ctc ttt ttg tta gta ctc aca tat gcc gtg tgt tgg gct cca 864

Leu Leu Leu Phe Leu Leu Val Leu Thr Tyr Ala Val Cys Trp Ala Pro

275 280 285

atg aat att tat cat gtt ttg aat ggt ctc gag att att aac tat tca 912

Met Asn Ile Tyr His Val Leu Asn Gly Leu Glu Ile Ile Asn Tyr Ser

290 295 300

caa aat atg tac atc ttc tgt cat ttg gtc gga atc tct tca acg tgt 960

Gln Asn Met Tyr Ile Phe Cys His Leu Val Gly Ile Ser Ser Thr Cys

305 310 315 320

gtt aat cca ata gta tat gca ctg gtc aat gaa tca ttt aga aat gct 1008

Val Asn Pro Ile Val Tyr Ala Leu Val Asn Glu Ser Phe Arg Asn Ala

325 330 335

tta caa tca atg att ctt caa ttc cgc ccg tgt tac gtc aca act acc 1056

Leu Gln Ser Met Ile Leu Gln Phe Arg Pro Cys Tyr Val Thr Thr Thr

340 345 350

ggt aca gca gcc acc aac gtg tat gca tat tct gcg act tcg aag gcg 1104

Gly Thr Ala Ala Thr Asn Val Tyr Ala Tyr Ser Ala Thr Ser Lys Ala

355 360 365

gaa aat gtc act ttg atg cgt gat cct ttc tca aca act cct cgt cca 1152

Glu Asn Val Thr Leu Met Arg Asp Pro Phe Ser Thr Thr Pro Arg Pro

370 375 380

aat gaa cgc cca gac agt gtt tga 1176

Asn Glu Arg Pro Asp Ser Val

385 390

38

391

Homo sapiens

38

Met Gln Pro Pro Asn Ser Thr Gly Gln Trp Thr Glu Ile His Cys Asp

1 5 10 15

Trp Phe Ala Glu Met Gln Asn Tyr Gln Asn Ser Leu Tyr Lys Ile Asn

20 25 30

Phe Asp Gly Ser Pro Ile Val Pro Met Tyr Gly Leu Val Cys Ser Phe

35 40 45

Gly Ala Leu Ala Asn Phe Ile Val Leu Leu Ala Phe Val Arg Thr Ala

50 55 60

Asn Leu Arg Asn Leu Arg Asn Ser Phe Ile Val Asn Leu Ala Phe Ser

65 70 75 80

Asp Leu Ile Leu Cys Val Val Thr Ala Pro Val Thr Leu Tyr Thr Ser

85 90 95

Leu Asn Leu Phe Trp Pro Phe Gly Asp Trp Ser Cys Lys Phe Leu Ala

100 105 110

Gly Val Gln Ala Val Asn Thr Phe Val Ser Ser Leu Thr Leu Ala Phe

115 120 125

Ile Ala Met Asp Arg Val Leu Leu Thr Leu Cys Pro Val Arg Trp Arg

130 135 140

Leu Ala Ala Thr Ala Pro Leu Leu Cys Tyr Gly Val Val Trp Ile Ile

145 150 155 160

Ser Ile Ile Val Ala Leu Pro Tyr Ala Leu Ala Val Ser Ser Lys Leu

165 170 175

Ala Pro Phe Asp Pro Trp Ser Asp Arg Ala Thr Pro Lys Met Leu Thr

180 185 190

Tyr Cys Asn Arg Gln Val Pro Glu Ile Cys Ala Glu Met Gln Glu Ala

195 200 205

Trp Asp Asn Ala Ile Val Ser Lys Thr Thr Tyr Thr Phe Val Val Leu

210 215 220

Gly Ile Gln Tyr Ile Leu Pro Leu Ala Ala Leu Ala Tyr Ala Tyr Phe

225 230 235 240

Gln Ile Gly Ser Thr Ile Gln Lys Arg Ser Lys Val Ser Arg Thr Val

245 250 255

Asp Thr Thr Arg Arg Met Gln Met Gln Asn Arg Asn Arg Arg Ala Leu

260 265 270

Leu Leu Leu Phe Leu Leu Val Leu Thr Tyr Ala Val Cys Trp Ala Pro

275 280 285

Met Asn Ile Tyr His Val Leu Asn Gly Leu Glu Ile Ile Asn Tyr Ser

290 295 300

Gln Asn Met Tyr Ile Phe Cys His Leu Val Gly Ile Ser Ser Thr Cys

305 310 315 320

Val Asn Pro Ile Val Tyr Ala Leu Val Asn Glu Ser Phe Arg Asn Ala

325 330 335

Leu Gln Ser Met Ile Leu Gln Phe Arg Pro Cys Tyr Val Thr Thr Thr

340 345 350

Gly Thr Ala Ala Thr Asn Val Tyr Ala Tyr Ser Ala Thr Ser Lys Ala

355 360 365

Glu Asn Val Thr Leu Met Arg Asp Pro Phe Ser Thr Thr Pro Arg Pro

370 375 380

Asn Glu Arg Pro Asp Ser Val

385 390

39

atg gag att att ctt tgt ttt ttg aac tac ctg gca cat ttt aaa gcg 48

Met Glu Ile Ile Leu Cys Phe Leu Asn Tyr Leu Ala His Phe Lys Ala

1 5 10 15

ggt ttc gag att gat tta ttt aac ttc att aac ata aca att tat aag 96

Gly Phe Glu Ile Asp Leu Phe Asn Phe Ile Asn Ile Thr Ile Tyr Lys

20 25 30

aaa ttt cct ttt ttt ttt cat cga ctg aaa ttt gat aga aaa ttg gat 144

Lys Phe Pro Phe Phe Phe His Arg Leu Lys Phe Asp Arg Lys Leu Asp

35 40 45

ttt atg att aat ttc cag aac acg ctt ttc gat ttt ccc att tta gaa 192

Phe Met Ile Asn Phe Gln Asn Thr Leu Phe Asp Phe Pro Ile Leu Glu

50 55 60

aaa aac att ttt cga ttt tcg aat tta aaa aat tta aaa act cta aaa 240

Lys Asn Ile Phe Arg Phe Ser Asn Leu Lys Asn Leu Lys Thr Leu Lys

65 70 75 80

ttt tca acg ata ttt tta ttt tat gga ttt tat gca tgt aat ttt ctt 288

Phe Ser Thr Ile Phe Leu Phe Tyr Gly Phe Tyr Ala Cys Asn Phe Leu

85 90 95

caa aac aac ctt cga tgc atg gtt agt tcg gcg gcc acc att tcg acc 336

Gln Asn Asn Leu Arg Cys Met Val Ser Ser Ala Ala Thr Ile Ser Thr

100 105 110

att tca acc aca acg act ccc tcc acc atc agc aac gtt atc aca agt 384

Ile Ser Thr Thr Thr Thr Pro Ser Thr Ile Ser Asn Val Ile Thr Ser

115 120 125

cat tcg aac aat ggc tcg tgc att cag atc gct gag gcg att gcg gca 432

His Ser Asn Asn Gly Ser Cys Ile Gln Ile Ala Glu Ala Ile Ala Ala

130 135 140

caa ggc atc gat gat att act gta gac ttt tac atc cga tca atc ttc 480

Gln Gly Ile Asp Asp Ile Thr Val Asp Phe Tyr Ile Arg Ser Ile Phe

145 150 155 160

aca ttc ctc tac ggg ttc ctg ttt gta tta ggc att ttt gga aac ggc 528

Thr Phe Leu Tyr Gly Phe Leu Phe Val Leu Gly Ile Phe Gly Asn Gly

165 170 175

ggc gta cta tgg gcg gtg gcg aga aac aag cgg ctc caa tcg gct cgc 576

Gly Val Leu Trp Ala Val Ala Arg Asn Lys Arg Leu Gln Ser Ala Arg

180 185 190

aac gta ttt ctg ctc aac ttg atc ttc acc gat ttg ata ttg gtg ttc 624

Asn Val Phe Leu Leu Asn Leu Ile Phe Thr Asp Leu Ile Leu Val Phe

195 200 205

aca gcg att cca gtc aca cca tgg tac gcg atg acc aaa gac tgg gca 672

Thr Ala Ile Pro Val Thr Pro Trp Tyr Ala Met Thr Lys Asp Trp Ala

210 215 220

ttc ggg tca gtg atg tgc cat tta gtt cct ttg tca aat tcg tgt tcg 720

Phe Gly Ser Val Met Cys His Leu Val Pro Leu Ser Asn Ser Cys Ser

225 230 235 240

gtg ttt gtg acg agt tgg agc ctc act gca atc tcc tta gat aaa ttt 768

Val Phe Val Thr Ser Trp Ser Leu Thr Ala Ile Ser Leu Asp Lys Phe

245 250 255

ctg cat atc aac gat ccc acc aaa caa cca gtt tct att cgt caa gcg 816

Leu His Ile Asn Asp Pro Thr Lys Gln Pro Val Ser Ile Arg Gln Ala

260 265 270

ttg gca ata aca ttt ctt atc tgg ata gtc tca aca ctg ata aat cta 864

Leu Ala Ile Thr Phe Leu Ile Trp Ile Val Ser Thr Leu Ile Asn Leu

275 280 285

ccg tat ctt atg tct ttc gag cac gtc gat gga agc ttt tac gtt cag 912

Pro Tyr Leu Met Ser Phe Glu His Val Asp Gly Ser Phe Tyr Val Gln

290 295 300

ccc gga gaa act cca tac tgc ggg cac ttt tgc gac gag gcg aat tgg 960

Pro Gly Glu Thr Pro Tyr Cys Gly His Phe Cys Asp Glu Ala Asn Trp

305 310 315 320

cag agc gaa aat agt cga aag att tac gga act acg gtt atg ttg tta 1008

Gln Ser Glu Asn Ser Arg Lys Ile Tyr Gly Thr Thr Val Met Leu Leu

325 330 335

cag ttc gtc gtg ccg atg gca gtg atc acg tat tgc tac ttc aaa atc 1056

Gln Phe Val Val Pro Met Ala Val Ile Thr Tyr Cys Tyr Phe Lys Ile

340 345 350

ttg caa aaa gtg tca aaa gac atg atc atc caa aat gct caa ttc tgt 1104

Leu Gln Lys Val Ser Lys Asp Met Ile Ile Gln Asn Ala Gln Phe Cys

355 360 365

caa tca ctg aca caa aag cag aga agt gat gcg acg tca cga aag aag 1152

Gln Ser Leu Thr Gln Lys Gln Arg Ser Asp Ala Thr Ser Arg Lys Lys

370 375 380

aaa gtg aat tat att cta att gca atg gtt gtc aca ttt atc ggg tgt 1200

Lys Val Asn Tyr Ile Leu Ile Ala Met Val Val Thr Phe Ile Gly Cys

385 390 395 400

tgg ttg cct tta aca tta ctc aat ttg gtc aaa gat ttt aaa aaa gag 1248

Trp Leu Pro Leu Thr Leu Leu Asn Leu Val Lys Asp Phe Lys Lys Glu

405 410 415

ccc gaa tgg cta aaa cgt cag ccg ttc ttc tgg gca ata aat gct cac 1296

Pro Glu Trp Leu Lys Arg Gln Pro Phe Phe Trp Ala Ile Asn Ala His

420 425 430

gtc ata gcc atg tcc tta gtc gtc tgg aac cct ctg cta ttc ttt tgg 1344

Val Ile Ala Met Ser Leu Val Val Trp Asn Pro Leu Leu Phe Phe Trp

435 440 445

ctg aca cga aaa caa aaa cgt tcc gga ctg tca aaa ata ctc aac tca 1392

Leu Thr Arg Lys Gln Lys Arg Ser Gly Leu Ser Lys Ile Leu Asn Ser

450 455 460

aca gag ggt tcg aaa aaa gca ggt ggt tct gga ttg cga ggg atc cag 1440

Thr Glu Gly Ser Lys Lys Ala Gly Gly Ser Gly Leu Arg Gly Ile Gln

465 470 475 480

cta cac gac ctc ctc ccg acc tct act cat tcg gac aga tgt gca ggc 1488

Leu His Asp Leu Leu Pro Thr Ser Thr His Ser Asp Arg Cys Ala Gly

485 490 495

aac tct ttc taa 1500

Asn Ser Phe

40

499

Homo sapiens

40

Met Glu Ile Ile Leu Cys Phe Leu Asn Tyr Leu Ala His Phe Lys Ala

1 5 10 15

Gly Phe Glu Ile Asp Leu Phe Asn Phe Ile Asn Ile Thr Ile Tyr Lys

20 25 30

Lys Phe Pro Phe Phe Phe His Arg Leu Lys Phe Asp Arg Lys Leu Asp

35 40 45

Phe Met Ile Asn Phe Gln Asn Thr Leu Phe Asp Phe Pro Ile Leu Glu

50 55 60

Lys Asn Ile Phe Arg Phe Ser Asn Leu Lys Asn Leu Lys Thr Leu Lys

65 70 75 80

Phe Ser Thr Ile Phe Leu Phe Tyr Gly Phe Tyr Ala Cys Asn Phe Leu

85 90 95

Gln Asn Asn Leu Arg Cys Met Val Ser Ser Ala Ala Thr Ile Ser Thr

100 105 110

Ile Ser Thr Thr Thr Thr Pro Ser Thr Ile Ser Asn Val Ile Thr Ser

115 120 125

His Ser Asn Asn Gly Ser Cys Ile Gln Ile Ala Glu Ala Ile Ala Ala

130 135 140

Gln Gly Ile Asp Asp Ile Thr Val Asp Phe Tyr Ile Arg Ser Ile Phe

145 150 155 160

Thr Phe Leu Tyr Gly Phe Leu Phe Val Leu Gly Ile Phe Gly Asn Gly

165 170 175

Gly Val Leu Trp Ala Val Ala Arg Asn Lys Arg Leu Gln Ser Ala Arg

180 185 190

Asn Val Phe Leu Leu Asn Leu Ile Phe Thr Asp Leu Ile Leu Val Phe

195 200 205

Thr Ala Ile Pro Val Thr Pro Trp Tyr Ala Met Thr Lys Asp Trp Ala

210 215 220

Phe Gly Ser Val Met Cys His Leu Val Pro Leu Ser Asn Ser Cys Ser

225 230 235 240

Val Phe Val Thr Ser Trp Ser Leu Thr Ala Ile Ser Leu Asp Lys Phe

245 250 255

Leu His Ile Asn Asp Pro Thr Lys Gln Pro Val Ser Ile Arg Gln Ala

260 265 270

Leu Ala Ile Thr Phe Leu Ile Trp Ile Val Ser Thr Leu Ile Asn Leu

275 280 285

Pro Tyr Leu Met Ser Phe Glu His Val Asp Gly Ser Phe Tyr Val Gln

290 295 300

Pro Gly Glu Thr Pro Tyr Cys Gly His Phe Cys Asp Glu Ala Asn Trp

305 310 315 320

Gln Ser Glu Asn Ser Arg Lys Ile Tyr Gly Thr Thr Val Met Leu Leu

325 330 335

Gln Phe Val Val Pro Met Ala Val Ile Thr Tyr Cys Tyr Phe Lys Ile

340 345 350

Leu Gln Lys Val Ser Lys Asp Met Ile Ile Gln Asn Ala Gln Phe Cys

355 360 365

Gln Ser Leu Thr Gln Lys Gln Arg Ser Asp Ala Thr Ser Arg Lys Lys

370 375 380

Lys Val Asn Tyr Ile Leu Ile Ala Met Val Val Thr Phe Ile Gly Cys

385 390 395 400

Trp Leu Pro Leu Thr Leu Leu Asn Leu Val Lys Asp Phe Lys Lys Glu

405 410 415

Pro Glu Trp Leu Lys Arg Gln Pro Phe Phe Trp Ala Ile Asn Ala His

420 425 430

Val Ile Ala Met Ser Leu Val Val Trp Asn Pro Leu Leu Phe Phe Trp

435 440 445

Leu Thr Arg Lys Gln Lys Arg Ser Gly Leu Ser Lys Ile Leu Asn Ser

450 455 460

Thr Glu Gly Ser Lys Lys Ala Gly Gly Ser Gly Leu Arg Gly Ile Gln

465 470 475 480

Leu His Asp Leu Leu Pro Thr Ser Thr His Ser Asp Arg Cys Ala Gly

485 490 495

Asn Ser Phe

41

atg tcg ttg gga aat gtc atc att gcc tct tca gta aat aca cgt tca 48

Met Ser Leu Gly Asn Val Ile Ile Ala Ser Ser Val Asn Thr Arg Ser

1 5 10 15

ccc ata gat tcc cac ttg ttt aga aaa att ttg tgt ttt aga att tat 96

Pro Ile Asp Ser His Leu Phe Arg Lys Ile Leu Cys Phe Arg Ile Tyr

20 25 30

gac gac act atc agt ttt gag aga aaa att gga ata atc att cca aca 144

Asp Asp Thr Ile Ser Phe Glu Arg Lys Ile Gly Ile Ile Ile Pro Thr

35 40 45

att ttt gcc gtt atc att ttg gtc gga ctt gtt ggt aat gct ctg gtg 192

Ile Phe Ala Val Ile Ile Leu Val Gly Leu Val Gly Asn Ala Leu Val

50 55 60

gtg att gtt gct ttt gga cga caa atg aga aat tca acc aac act ctt 240

Val Ile Val Ala Phe Gly Arg Gln Met Arg Asn Ser Thr Asn Thr Leu

65 70 75 80

att att gga ctt gcc ata tct gac ttg atg ttc ctt ttg ctt tgc gtt 288

Ile Ile Gly Leu Ala Ile Ser Asp Leu Met Phe Leu Leu Leu Cys Val

85 90 95

cct ttc aca gct gtg gat tac gca gct ccg aca tgg atc ttt ccc gag 336

Pro Phe Thr Ala Val Asp Tyr Ala Ala Pro Thr Trp Ile Phe Pro Glu

100 105 110

tgg aca tgc tct atg atc aat ttc ttc cag cat acg tct gca tac tgt 384

Trp Thr Cys Ser Met Ile Asn Phe Phe Gln His Thr Ser Ala Tyr Cys

115 120 125

agt gtt tgg aca ttg acc ctt atg gcc ctc gat aga tat cta gca gtt 432

Ser Val Trp Thr Leu Thr Leu Met Ala Leu Asp Arg Tyr Leu Ala Val

130 135 140

gta tat cca gtt gaa tca atg acg tta cga aca cca agg aac act gtg 480

Val Tyr Pro Val Glu Ser Met Thr Leu Arg Thr Pro Arg Asn Thr Val

145 150 155 160

att gcg tta tgc ttc att tac atc att atc att gct tct cag att cct 528

Ile Ala Leu Cys Phe Ile Tyr Ile Ile Ile Ile Ala Ser Gln Ile Pro

165 170 175

gtg gga cga atg cac ggg att tat gtg tat gac ttt att atg gaa aaa 576

Val Gly Arg Met His Gly Ile Tyr Val Tyr Asp Phe Ile Met Glu Lys

180 185 190

cgg tca acg tgc gca att ctg aca att gcc act gca gag gct act ccg 624

Arg Ser Thr Cys Ala Ile Leu Thr Ile Ala Thr Ala Glu Ala Thr Pro

195 200 205

acg atg gct cga aca tat ttt atg aca ttc aat gtg ttt ggt tac gtg 672

Thr Met Ala Arg Thr Tyr Phe Met Thr Phe Asn Val Phe Gly Tyr Val

210 215 220

ctt cca ctg ggc att tct gtt gtc ctg tat ggt ctt atg ttg aga aaa 720

Leu Pro Leu Gly Ile Ser Val Val Leu Tyr Gly Leu Met Leu Arg Lys

225 230 235 240

ctt tgg gac atg cca agg ccg ggt aac tct caa tct gtt ggt ggt aga 768

Leu Trp Asp Met Pro Arg Pro Gly Asn Ser Gln Ser Val Gly Gly Arg

245 250 255

aat ctt aca aat cgt gat agt ggt tca agt att cgt cgg agg ccg gaa 816

Asn Leu Thr Asn Arg Asp Ser Gly Ser Ser Ile Arg Arg Arg Pro Glu

260 265 270

gca act gct gcc aaa aga aaa gtt acc cgc ctt gta ctg tgt gtt ttg 864

Ala Thr Ala Ala Lys Arg Lys Val Thr Arg Leu Val Leu Cys Val Leu

275 280 285

atc acc tgg gca ctt tgc tgg ctt cca cta aac gtg tgc ttt ttc atg 912

Ile Thr Trp Ala Leu Cys Trp Leu Pro Leu Asn Val Cys Phe Phe Met

290 295 300

tct ggt ctc gcc tac ccg gaa cca ctt gtt ata tct cat ggt gtc atc 960

Ser Gly Leu Ala Tyr Pro Glu Pro Leu Val Ile Ser His Gly Val Ile

305 310 315 320

atg gta att gtt cag att gct agt caa gtt ctt gcc tac acc aat tcg 1008

Met Val Ile Val Gln Ile Ala Ser Gln Val Leu Ala Tyr Thr Asn Ser

325 330 335

tgt ctt aat cca att cta tac gct ttg atg tcg cag agt ttc cgg gaa 1056

Cys Leu Asn Pro Ile Leu Tyr Ala Leu Met Ser Gln Ser Phe Arg Glu

340 345 350

gga ttc att cga gtc atg aaa atg cta ata aat aag cta tcg cgt gga 1104

Gly Phe Ile Arg Val Met Lys Met Leu Ile Asn Lys Leu Ser Arg Gly

355 360 365

agg ttc tgc act aat tac cga cga agt gct ctt cgg aca gag ctc aca 1152

Arg Phe Cys Thr Asn Tyr Arg Arg Ser Ala Leu Arg Thr Glu Leu Thr

370 375 380

cac tat aac caa act cca gca cat cca gca aac act gtg gtt caa gtg 1200

His Tyr Asn Gln Thr Pro Ala His Pro Ala Asn Thr Val Val Gln Val

385 390 395 400

tca aac gga gaa cga tcc tcg ctt ctg aaa gat aac tcg agc tct gcg 1248

Ser Asn Gly Glu Arg Ser Ser Leu Leu Lys Asp Asn Ser Ser Ser Ala

405 410 415

acg tct gta caa cca ctt cgg acg tca att caa gcg aag aaa aca aag 1296

Thr Ser Val Gln Pro Leu Arg Thr Ser Ile Gln Ala Lys Lys Thr Lys

420 425 430

aat gtc tgt gat acg atg ctc ttt gtg tgt ttc ttc taa 1335

Asn Val Cys Asp Thr Met Leu Phe Val Cys Phe Phe

435 440

42

444

Homo sapiens

42

Met Ser Leu Gly Asn Val Ile Ile Ala Ser Ser Val Asn Thr Arg Ser

1 5 10 15

Pro Ile Asp Ser His Leu Phe Arg Lys Ile Leu Cys Phe Arg Ile Tyr

20 25 30

Asp Asp Thr Ile Ser Phe Glu Arg Lys Ile Gly Ile Ile Ile Pro Thr

35 40 45

Ile Phe Ala Val Ile Ile Leu Val Gly Leu Val Gly Asn Ala Leu Val

50 55 60

Val Ile Val Ala Phe Gly Arg Gln Met Arg Asn Ser Thr Asn Thr Leu

65 70 75 80

Ile Ile Gly Leu Ala Ile Ser Asp Leu Met Phe Leu Leu Leu Cys Val

85 90 95

Pro Phe Thr Ala Val Asp Tyr Ala Ala Pro Thr Trp Ile Phe Pro Glu

100 105 110

Trp Thr Cys Ser Met Ile Asn Phe Phe Gln His Thr Ser Ala Tyr Cys

115 120 125

Ser Val Trp Thr Leu Thr Leu Met Ala Leu Asp Arg Tyr Leu Ala Val

130 135 140

Val Tyr Pro Val Glu Ser Met Thr Leu Arg Thr Pro Arg Asn Thr Val

145 150 155 160

Ile Ala Leu Cys Phe Ile Tyr Ile Ile Ile Ile Ala Ser Gln Ile Pro

165 170 175

Val Gly Arg Met His Gly Ile Tyr Val Tyr Asp Phe Ile Met Glu Lys

180 185 190

Arg Ser Thr Cys Ala Ile Leu Thr Ile Ala Thr Ala Glu Ala Thr Pro

195 200 205

Thr Met Ala Arg Thr Tyr Phe Met Thr Phe Asn Val Phe Gly Tyr Val

210 215 220

Leu Pro Leu Gly Ile Ser Val Val Leu Tyr Gly Leu Met Leu Arg Lys

225 230 235 240

Leu Trp Asp Met Pro Arg Pro Gly Asn Ser Gln Ser Val Gly Gly Arg

245 250 255

Asn Leu Thr Asn Arg Asp Ser Gly Ser Ser Ile Arg Arg Arg Pro Glu

260 265 270

Ala Thr Ala Ala Lys Arg Lys Val Thr Arg Leu Val Leu Cys Val Leu

275 280 285

Ile Thr Trp Ala Leu Cys Trp Leu Pro Leu Asn Val Cys Phe Phe Met

290 295 300

Ser Gly Leu Ala Tyr Pro Glu Pro Leu Val Ile Ser His Gly Val Ile

305 310 315 320

Met Val Ile Val Gln Ile Ala Ser Gln Val Leu Ala Tyr Thr Asn Ser

325 330 335

Cys Leu Asn Pro Ile Leu Tyr Ala Leu Met Ser Gln Ser Phe Arg Glu

340 345 350

Gly Phe Ile Arg Val Met Lys Met Leu Ile Asn Lys Leu Ser Arg Gly

355 360 365

Arg Phe Cys Thr Asn Tyr Arg Arg Ser Ala Leu Arg Thr Glu Leu Thr

370 375 380

His Tyr Asn Gln Thr Pro Ala His Pro Ala Asn Thr Val Val Gln Val

385 390 395 400

Ser Asn Gly Glu Arg Ser Ser Leu Leu Lys Asp Asn Ser Ser Ser Ala

405 410 415

Thr Ser Val Gln Pro Leu Arg Thr Ser Ile Gln Ala Lys Lys Thr Lys

420 425 430

Asn Val Cys Asp Thr Met Leu Phe Val Cys Phe Phe

435 440

43

atg gag ggt ggt cga aac tgt gta atg aca gta caa cag tgg caa cct 48

Met Glu Gly Gly Arg Asn Cys Val Met Thr Val Gln Gln Trp Gln Pro

1 5 10 15

gaa tac aat gat atg aac cag ata aga gca ata ttc tcg tta ctg tac 96

Glu Tyr Asn Asp Met Asn Gln Ile Arg Ala Ile Phe Ser Leu Leu Tyr

20 25 30

ctt ctt gtt tgg gtt gga gct att gtt ggc aac act cta gta ctt tat 144

Leu Leu Val Trp Val Gly Ala Ile Val Gly Asn Thr Leu Val Leu Tyr

35 40 45

gta ctc act ttt aat cag gta tca ctg tca gtt agg acg gta ttt gtt 192

Val Leu Thr Phe Asn Gln Val Ser Leu Ser Val Arg Thr Val Phe Val

50 55 60

gga tgt cta gct ggt tca gac ctt cta atg tgc ctt ttc tcg ttg cca 240

Gly Cys Leu Ala Gly Ser Asp Leu Leu Met Cys Leu Phe Ser Leu Pro

65 70 75 80

att acc gcg att tct ata ttt tca aga gtt tgg gta ttt cct gct ata 288

Ile Thr Ala Ile Ser Ile Phe Ser Arg Val Trp Val Phe Pro Ala Ile

85 90 95

ttt tgc aag ttg atc gga gtt ttc cag ggc ggt acg att ttt gtc tca 336

Phe Cys Lys Leu Ile Gly Val Phe Gln Gly Gly Thr Ile Phe Val Ser

100 105 110

tca ttc aca tta aca gtt att gct ctg gac aga tgt gta cta att cta 384

Ser Phe Thr Leu Thr Val Ile Ala Leu Asp Arg Cys Val Leu Ile Leu

115 120 125

cgt cca aat cag gag ata gta aat ttc ccg aga gct gtc ttc att gtt 432

Arg Pro Asn Gln Glu Ile Val Asn Phe Pro Arg Ala Val Phe Ile Val

130 135 140

ttc tgc att tgg ctt ctc gga tac tct cta gca ctt cct gta ggc atc 480

Phe Cys Ile Trp Leu Leu Gly Tyr Ser Leu Ala Leu Pro Val Gly Ile

145 150 155 160

tac agc gac att gca gta tac gac gaa att tgc ggc aca ttc tgt gaa 528

Tyr Ser Asp Ile Ala Val Tyr Asp Glu Ile Cys Gly Thr Phe Cys Glu

165 170 175

gag aat tgg cct gat ttc aat ccg gat act gga aga tcg gga att cga 576

Glu Asn Trp Pro Asp Phe Asn Pro Asp Thr Gly Arg Ser Gly Ile Arg

180 185 190

aga gct tat gga ctt tct gtg ttg gta ctt caa ttt ggt att cct gca 624

Arg Ala Tyr Gly Leu Ser Val Leu Val Leu Gln Phe Gly Ile Pro Ala

195 200 205

ttg ata agt tca att tgt tac tgg atg att agt cga gtg atg tca gat 672

Leu Ile Ser Ser Ile Cys Tyr Trp Met Ile Ser Arg Val Met Ser Asp

210 215 220

caa tta gca aga aga aga ggg cac aat att cga ccg gaa tct gaa aca 720

Gln Leu Ala Arg Arg Arg Gly His Asn Ile Arg Pro Glu Ser Glu Thr

225 230 235 240

aag ctg gtg aat cga aag aca aga gct aat cga atg atg atc gta atg 768

Lys Leu Val Asn Arg Lys Thr Arg Ala Asn Arg Met Met Ile Val Met

245 250 255

gtt gtt gga ttc gtt ctc gcg tgg atg cca ttc aat gca gtc aat ctc 816

Val Val Gly Phe Val Leu Ala Trp Met Pro Phe Asn Ala Val Asn Leu

260 265 270

tac cgt gac cta ttt gga att tct aaa tgg tat tct aca gtc ttt gcg 864

Tyr Arg Asp Leu Phe Gly Ile Ser Lys Trp Tyr Ser Thr Val Phe Ala

275 280 285

ctt tgc cac gta tgc gca atg tgc tcc gct gtg ctc aac cca atc atc 912

Leu Cys His Val Cys Ala Met Cys Ser Ala Val Leu Asn Pro Ile Ile

290 295 300

tat tcc tgg ttc aat cct caa ttc cga caa agt atc acc act ttg ttc 960

Tyr Ser Trp Phe Asn Pro Gln Phe Arg Gln Ser Ile Thr Thr Leu Phe

305 310 315 320

aag ggt act gat gaa gct aga ttg atc aag aag aaa cca caa tct acc 1008

Lys Gly Thr Asp Glu Ala Arg Leu Ile Lys Lys Lys Pro Gln Ser Thr

325 330 335

agt aaa atg gtt tcg tat ccg act aat ttc tcc gag atc cga aaa gaa 1056

Ser Lys Met Val Ser Tyr Pro Thr Asn Phe Ser Glu Ile Arg Lys Glu

340 345 350

aca gaa att gca tcg aca aag aca aaa atc aca att gct gaa aac gac 1104

Thr Glu Ile Ala Ser Thr Lys Thr Lys Ile Thr Ile Ala Glu Asn Asp

355 360 365

tat cga gct gga gat caa ctt tta taa 1131

Tyr Arg Ala Gly Asp Gln Leu Leu

370 375

44

376

Homo sapiens

44

Met Glu Gly Gly Arg Asn Cys Val Met Thr Val Gln Gln Trp Gln Pro

1 5 10 15

Glu Tyr Asn Asp Met Asn Gln Ile Arg Ala Ile Phe Ser Leu Leu Tyr

20 25 30

Leu Leu Val Trp Val Gly Ala Ile Val Gly Asn Thr Leu Val Leu Tyr

35 40 45

Val Leu Thr Phe Asn Gln Val Ser Leu Ser Val Arg Thr Val Phe Val

50 55 60

Gly Cys Leu Ala Gly Ser Asp Leu Leu Met Cys Leu Phe Ser Leu Pro

65 70 75 80

Ile Thr Ala Ile Ser Ile Phe Ser Arg Val Trp Val Phe Pro Ala Ile

85 90 95

Phe Cys Lys Leu Ile Gly Val Phe Gln Gly Gly Thr Ile Phe Val Ser

100 105 110

Ser Phe Thr Leu Thr Val Ile Ala Leu Asp Arg Cys Val Leu Ile Leu

115 120 125

Arg Pro Asn Gln Glu Ile Val Asn Phe Pro Arg Ala Val Phe Ile Val

130 135 140

Phe Cys Ile Trp Leu Leu Gly Tyr Ser Leu Ala Leu Pro Val Gly Ile

145 150 155 160

Tyr Ser Asp Ile Ala Val Tyr Asp Glu Ile Cys Gly Thr Phe Cys Glu

165 170 175

Glu Asn Trp Pro Asp Phe Asn Pro Asp Thr Gly Arg Ser Gly Ile Arg

180 185 190

Arg Ala Tyr Gly Leu Ser Val Leu Val Leu Gln Phe Gly Ile Pro Ala

195 200 205

Leu Ile Ser Ser Ile Cys Tyr Trp Met Ile Ser Arg Val Met Ser Asp

210 215 220

Gln Leu Ala Arg Arg Arg Gly His Asn Ile Arg Pro Glu Ser Glu Thr

225 230 235 240

Lys Leu Val Asn Arg Lys Thr Arg Ala Asn Arg Met Met Ile Val Met

245 250 255

Val Val Gly Phe Val Leu Ala Trp Met Pro Phe Asn Ala Val Asn Leu

260 265 270

Tyr Arg Asp Leu Phe Gly Ile Ser Lys Trp Tyr Ser Thr Val Phe Ala

275 280 285

Leu Cys His Val Cys Ala Met Cys Ser Ala Val Leu Asn Pro Ile Ile

290 295 300

Tyr Ser Trp Phe Asn Pro Gln Phe Arg Gln Ser Ile Thr Thr Leu Phe

305 310 315 320

Lys Gly Thr Asp Glu Ala Arg Leu Ile Lys Lys Lys Pro Gln Ser Thr

325 330 335

Ser Lys Met Val Ser Tyr Pro Thr Asn Phe Ser Glu Ile Arg Lys Glu

340 345 350

Thr Glu Ile Ala Ser Thr Lys Thr Lys Ile Thr Ile Ala Glu Asn Asp

355 360 365

Tyr Arg Ala Gly Asp Gln Leu Leu

370 375

45

atg gga tcg gtg aat gaa tca tgt gac aat tat gta gaa att ttc aac 48

Met Gly Ser Val Asn Glu Ser Cys Asp Asn Tyr Val Glu Ile Phe Asn

1 5 10 15

aaa atc aac tac ttt ttt cga gat gat cag gtt atc aat ggg act gag 96

Lys Ile Asn Tyr Phe Phe Arg Asp Asp Gln Val Ile Asn Gly Thr Glu

20 25 30

tat tca cca aaa gag ttc gga tat ttc atc aca ttc gca tac atg ctg 144

Tyr Ser Pro Lys Glu Phe Gly Tyr Phe Ile Thr Phe Ala Tyr Met Leu

35 40 45

atc att ttg ttt gga gca ata ggc aac ttt ttg aca atc atc gta gtc 192

Ile Ile Leu Phe Gly Ala Ile Gly Asn Phe Leu Thr Ile Ile Val Val

50 55 60

ata ctc aac cca gca atg cgg aca aca agg aac ttt ttc att tta aac 240

Ile Leu Asn Pro Ala Met Arg Thr Thr Arg Asn Phe Phe Ile Leu Asn

65 70 75 80

ttg gcg ctg tcg gac ttt ttt gtt tgt att gtg aca gcg ccg acc aca 288

Leu Ala Leu Ser Asp Phe Phe Val Cys Ile Val Thr Ala Pro Thr Thr

85 90 95

tta tac acg gtt ctc tac atg ttc tgg cca ttt agc agg aca tta tgc 336

Leu Tyr Thr Val Leu Tyr Met Phe Trp Pro Phe Ser Arg Thr Leu Cys

100 105 110

aaa att gcg ggt tcg ctg caa ggc ttt aac ata ttt tta tcc aca ttc 384

Lys Ile Ala Gly Ser Leu Gln Gly Phe Asn Ile Phe Leu Ser Thr Phe

115 120 125

tcg ata gcc tca att gct gtt gat aga tac gtg ctc att atc ttc cca 432

Ser Ile Ala Ser Ile Ala Val Asp Arg Tyr Val Leu Ile Ile Phe Pro

130 135 140

acg aag cga gaa cga caa caa aat ctg tcg ttc tgc ttt ttt atc atg 480

Thr Lys Arg Glu Arg Gln Gln Asn Leu Ser Phe Cys Phe Phe Ile Met

145 150 155 160

atc tgg gtg att tcc cta atc ctt gcg gtt cca ctt ctg cag gct tct 528

Ile Trp Val Ile Ser Leu Ile Leu Ala Val Pro Leu Leu Gln Ala Ser

165 170 175

gat ttg aca ccg gtt ttc gtt gag cca tcg tgc gat ttg gct ctt tac 576

Asp Leu Thr Pro Val Phe Val Glu Pro Ser Cys Asp Leu Ala Leu Tyr

180 185 190

att tgc cat gag caa aat gag ata tgg gaa aag atg atc ata tca aaa 624

Ile Cys His Glu Gln Asn Glu Ile Trp Glu Lys Met Ile Ile Ser Lys

195 200 205

ggc acc tac acg ttg gca gtt ctt atc acc caa tac gca ttt ccc ctg 672

Gly Thr Tyr Thr Leu Ala Val Leu Ile Thr Gln Tyr Ala Phe Pro Leu

210 215 220

ttt tca cta gtc ttc gcc tac tcc cgg ata gca cat cgg atg aag ctg 720

Phe Ser Leu Val Phe Ala Tyr Ser Arg Ile Ala His Arg Met Lys Leu

225 230 235 240

aga ttt gca aac cga aat cag aat gtg aca aca aat acc aat acg agt 768

Arg Phe Ala Asn Arg Asn Gln Asn Val Thr Thr Asn Thr Asn Thr Ser

245 250 255

cag agg aga cga tcc gtc gtg gaa cgt caa cga cgc acc cac ctc ctt 816

Gln Arg Arg Arg Ser Val Val Glu Arg Gln Arg Arg Thr His Leu Leu

260 265 270

ctt gta tgc gtt gta gct gta ttc gcc gtc gcc tgg ctg cca ctc aac 864

Leu Val Cys Val Val Ala Val Phe Ala Val Ala Trp Leu Pro Leu Asn

275 280 285

gtt ttt cat atc ttc aac aca ttc gag ctg gtc aac agt ttt tcc gtt 912

Val Phe His Ile Phe Asn Thr Phe Glu Leu Val Asn Ser Phe Ser Val

290 295 300

aca acg ttc agc atc tgt cac tgc ttg gca atg tgc tcg gcg tgc ttg 960

Thr Thr Phe Ser Ile Cys His Cys Leu Ala Met Cys Ser Ala Cys Leu

305 310 315 320

aat ccg ctg atc tat gca ttt ttc aat cat aac ttc cgg atc gaa ttt 1008

Asn Pro Leu Ile Tyr Ala Phe Phe Asn His Asn Phe Arg Ile Glu Phe

325 330 335

atg cat ctt ttc gat aga gtt ggg ttg aga tcc ctt cga gtc gtg ata 1056

Met His Leu Phe Asp Arg Val Gly Leu Arg Ser Leu Arg Val Val Ile

340 345 350

ttt gga gag caa gag tcg ctc aag aaa agt atg cgc act gaa ttc aga 1104

Phe Gly Glu Gln Glu Ser Leu Lys Lys Ser Met Arg Thr Glu Phe Arg

355 360 365

agc cgt gga ggc tgt aag acg gta act act gca gag cca gca acc ttc 1152

Ser Arg Gly Gly Cys Lys Thr Val Thr Thr Ala Glu Pro Ala Thr Phe

370 375 380

cag aga atg aat gaa agt atg att ctg agt gcg atg gag caa gat gag 1200

Gln Arg Met Asn Glu Ser Met Ile Leu Ser Ala Met Glu Gln Asp Glu

385 390 395 400

cag ctg tga 1209

Gln Leu

46

402

Homo sapiens

46

Met Gly Ser Val Asn Glu Ser Cys Asp Asn Tyr Val Glu Ile Phe Asn

1 5 10 15

Lys Ile Asn Tyr Phe Phe Arg Asp Asp Gln Val Ile Asn Gly Thr Glu

20 25 30

Tyr Ser Pro Lys Glu Phe Gly Tyr Phe Ile Thr Phe Ala Tyr Met Leu

35 40 45

Ile Ile Leu Phe Gly Ala Ile Gly Asn Phe Leu Thr Ile Ile Val Val

50 55 60

Ile Leu Asn Pro Ala Met Arg Thr Thr Arg Asn Phe Phe Ile Leu Asn

65 70 75 80

Leu Ala Leu Ser Asp Phe Phe Val Cys Ile Val Thr Ala Pro Thr Thr

85 90 95

Leu Tyr Thr Val Leu Tyr Met Phe Trp Pro Phe Ser Arg Thr Leu Cys

100 105 110

Lys Ile Ala Gly Ser Leu Gln Gly Phe Asn Ile Phe Leu Ser Thr Phe

115 120 125

Ser Ile Ala Ser Ile Ala Val Asp Arg Tyr Val Leu Ile Ile Phe Pro

130 135 140

Thr Lys Arg Glu Arg Gln Gln Asn Leu Ser Phe Cys Phe Phe Ile Met

145 150 155 160

Ile Trp Val Ile Ser Leu Ile Leu Ala Val Pro Leu Leu Gln Ala Ser

165 170 175

Asp Leu Thr Pro Val Phe Val Glu Pro Ser Cys Asp Leu Ala Leu Tyr

180 185 190

Ile Cys His Glu Gln Asn Glu Ile Trp Glu Lys Met Ile Ile Ser Lys

195 200 205

Gly Thr Tyr Thr Leu Ala Val Leu Ile Thr Gln Tyr Ala Phe Pro Leu

210 215 220

Phe Ser Leu Val Phe Ala Tyr Ser Arg Ile Ala His Arg Met Lys Leu

225 230 235 240

Arg Phe Ala Asn Arg Asn Gln Asn Val Thr Thr Asn Thr Asn Thr Ser

245 250 255

Gln Arg Arg Arg Ser Val Val Glu Arg Gln Arg Arg Thr His Leu Leu

260 265 270

Leu Val Cys Val Val Ala Val Phe Ala Val Ala Trp Leu Pro Leu Asn

275 280 285

Val Phe His Ile Phe Asn Thr Phe Glu Leu Val Asn Ser Phe Ser Val

290 295 300

Thr Thr Phe Ser Ile Cys His Cys Leu Ala Met Cys Ser Ala Cys Leu

305 310 315 320

Asn Pro Leu Ile Tyr Ala Phe Phe Asn His Asn Phe Arg Ile Glu Phe

325 330 335

Met His Leu Phe Asp Arg Val Gly Leu Arg Ser Leu Arg Val Val Ile

340 345 350

Phe Gly Glu Gln Glu Ser Leu Lys Lys Ser Met Arg Thr Glu Phe Arg

355 360 365

Ser Arg Gly Gly Cys Lys Thr Val Thr Thr Ala Glu Pro Ala Thr Phe

370 375 380

Gln Arg Met Asn Glu Ser Met Ile Leu Ser Ala Met Glu Gln Asp Glu

385 390 395 400

Gln Leu

47

31

Homo sapiens

Description of Artificial Sequence PCR primer

47

gccgccatgc tgtatgcaat tatagccttc a 31

48

31

Homo sapiens

Description of Artificial Sequence PCR primer

48

tctagatcag ggagaaagat tatttgtaga a 31

49

31

Homo sapiens

Description of Artificial Sequence PCR primer

49

gccgccatgg cccgtgcagt caacatatct c 31

50

31

Artificial Sequence

Description of Artificial Sequence PCR primer

50

tctagattat gaataggtga aagtgttgaa t 31

51

31

Artificial Sequence

Description of Artificial Sequence PCR primer

51

gccgccatgg agggtggtcg aaactgtgta a 31

52

31

Artificial Sequence

Description of Artificial Sequence PCR primer

52

tctagattat aaaagttgat ctccagctcg a 31

53

31

Artificial Sequence

Description of Artificial Sequence PCR primer

53

gccgccatga atggctccga ttgtctgaat c 31

54

31

Artificial Sequence

Description of Artificial Sequence PCR primer

54

tctagatcac gtgcatagtg tcgtcgaacg g 31

55

31

Artificial Sequence

Description of Artificial Sequence PCR primer

55

gccgccatgg gatcggtgaa tgaatcatgt g 31

56

31

Artificial Sequence

Description of Artificial Sequence PCR primer

56

tctagatcaa ctcagtaccc cttcaactat a 31

57

31

Artificial Sequence

Description of Artificial Sequence PCR primer

57

gccgccatga ttatttttta tctttacgta g 31

58

31

Artificial Sequence

Description of Artificial Sequence PCR primer

58

tctagatcac cgttcatggc aactcagaag a 31

59

31

Artificial Sequence

Description of Artificial Sequence PCR primer

59

gccgccatgg aagttgaaaa ttttaccgac t 31

60

31

Artificial Sequence

Description of Artificial Sequence PCR primer

60

ctcgagtcag actagcgtgt cgttgacgct g 31

61

31

Artificial Sequence

Description of Artificial Sequence PCR primer

61

gccgccatga atacgtcatt tgtagagcca t 31

62

31

Artificial Sequence

Description of Artificial Sequence PCR primer

62

tctagattaa caatcagaag tagatctttc c 31

63

31

Artificial Sequence

Description of Artificial Sequence PCR primer

63

gccgccatgg aagtgaaaga tatagataac t 31

64

31

Artificial Sequence

Description of Artificial Sequence PCR primer

64

tctagattag acaaaactat ctttctcgat a 31

65

31

Artificial Sequence

Description of Artificial Sequence PCR primer

65

gccgccatgt gcttcgcaga aaaaggagaa g 31

66

31

Artificial Sequence

Description of Artificial Sequence PCR primer

66

tctagattag acacgagaag ttgagctggg t 31

67

31

Artificial Sequence

Description of Artificial Sequence PCR primer

67

gccgccatgg gactccaagg gcgtgcaatt a 31

68

31

Artificial Sequence

Description of Artificial Sequence PCR primer

68

tctagattaa agatccgttc tgagaacttc g 31

69

31

Artificial Sequence

Description of Artificial Sequence PCR primer

69

gccgccatgg aaatggaata tttccgccca t 31

70

31

Artificial Sequence

Description of Artificial Sequence PCR primer

70

tctagattaa agcagaagcg tctgacaact t 31

71

31

Artificial Sequence

Description of Artificial Sequence PCR primer

71

gccgccatga tcaacgaaac agaagagaca t 31

72

31

Artificial Sequence

Description of Artificial Sequence PCR primer

72

ctcgagtcat tggcaaacaa aataagtata a 31

73

31

Artificial Sequence

Description of Artificial Sequence PCR primer

73

gccgccatgg gtgatgctga atctcatcat t 31

74

31

Artificial Sequence

Description of Artificial Sequence PCR primer

74

tctagattat tgtttcgttt cgaaacagac a 31

75

31

Artificial Sequence

Description of Artificial Sequence PCR primer

75

gccgccatga caacgtgtcc cctaccaccc a 31

76

31

Artificial Sequence

Description of Artificial Sequence PCR primer

76

tctagatcag aaatccgtat gcgccatcgt t 31

77

Ala Ser Glu Asp Ala Leu Phe Gly Thr Met Arg Phe

1 5 10

78

Ala Ser Pro Ser Phe Ile Arg Phe

1 5

79

8

A. suum

AF3

79

Ala Val Pro Gly Val Leu Arg Phe

1 5

80

Asp Val Pro Gly Val Leu Arg Phe

1 5

81

Glu Ala Glu Glu Pro Leu Gly Thr Met Arg Phe

1 5 10

82

Glu Asp Gly Asn Ala Pro Phe Gly Thr Met Arg Phe

1 5 10

83

Glu Ile Val Phe His Gln Ile Ser Pro Ile Phe Phe Arg Phe

1 5 10

84

9

A. suum

AF4

84

Gly Asp Val Pro Gly Val Leu Arg Phe

1 5

85

Gly Gly Pro Gln Gly Pro Leu Arg Phe

1 5

86

9

A. suum/C.elegans (flp 21)

AF9

86

Gly Leu Gly Pro Arg Pro Leu Arg Phe

1 5

87

8

A. suum

AF20

87

Gly Met Pro Gly Val Leu Arg Phe

1 5

88

Gly Asn Ser Phe Leu Arg Phe

1 5

89

Gly Pro Ser Gly Pro Leu Arg Phe

1 5

90

Ile Leu Xaa Arg Phe

1 5

91

Lys Pro Asn Phe Leu Arg Phe

1 5

92

Lys Ser Val Pro Gly Val Leu Arg Phe

1 5

93

Asn Gly Ala Pro Gln Pro Phe Val Arg Phe

1 5 10

94

10

Locust

SchistoFLRFa

94

Pro Asp Val Asp His Val Phe Leu Arg Phe

1 5 10

95

11

Locust

leucomyosuppressin

95

Xaa Glu Asp Val Asp His Val Phe Leu Arg Phe

1 5 10

96

Ser Ala Asp Asp Ser Ala Pro Phe Gly Thr Met Arg Phe

1 5 10

97

Ser Ala Glu Pro Phe Gly Thr Met Arg Phe

1 5 10

98

Ser Glu Val Pro Gly Val Leu Arg Phe

1 5

99

Ser Pro Leu Gly Thr Met Arg Phe

1 5

100

Ser Val Pro Gly Val Leu Arg Phe

1 5

101

Thr Asp Val Asp His Val Phe Leu Arg Phe

1 5 10

102

8

lobster

Lobster peptide II

102

Thr Asn Arg Asn Phe Leu Arg Phe

1 5

103

Xaa Pro Asp Val Asp His Val Phe Leu Arg Phe

1 5 10

104

atg gtt agt tcg gcg gcc acc att tcg acc att tca acc aca acg act 48

Met Val Ser Ser Ala Ala Thr Ile Ser Thr Ile Ser Thr Thr Thr Thr

1 5 10 15

ccc tcc acc atc agc aac gtt atc aca agt cat tcg aac aat ggc tcg 96

Pro Ser Thr Ile Ser Asn Val Ile Thr Ser His Ser Asn Asn Gly Ser

20 25 30

tgc att cag atc gct gag gcg att gcg gca caa ggc atc gat gat att 144

Cys Ile Gln Ile Ala Glu Ala Ile Ala Ala Gln Gly Ile Asp Asp Ile

35 40 45

act gta gac ttt tac atc cga tca atc ttc aca ttc ctc tac ggg ttc 192

Thr Val Asp Phe Tyr Ile Arg Ser Ile Phe Thr Phe Leu Tyr Gly Phe

50 55 60

ctg ttt gta tta ggc att ttt gga aac ggc ggc gta cta tgg gcg gtg 240

Leu Phe Val Leu Gly Ile Phe Gly Asn Gly Gly Val Leu Trp Ala Val

65 70 75 80

gcg aga aac aag cgg ctc caa tcg gct cgc aac gta ttt ctg ctc aac 288

Ala Arg Asn Lys Arg Leu Gln Ser Ala Arg Asn Val Phe Leu Leu Asn

85 90 95

ttg atc ttc acc gat ttg ata ttg gtg ttc aca gcg att cca gtc aca 336

Leu Ile Phe Thr Asp Leu Ile Leu Val Phe Thr Ala Ile Pro Val Thr

100 105 110

cca tgg tac gcg atg acc aaa gac tgg gca ttc ggg tca gtg atg tgc 384

Pro Trp Tyr Ala Met Thr Lys Asp Trp Ala Phe Gly Ser Val Met Cys

115 120 125

cat tta gtt cct ttg tca aat tcg tgt tcg gtg ttt gtg acg agt tgg 432

His Leu Val Pro Leu Ser Asn Ser Cys Ser Val Phe Val Thr Ser Trp

130 135 140

agc ctc act gca atc tcc tta gat aaa ttt ctg cat atc aac gat ccc 480

Ser Leu Thr Ala Ile Ser Leu Asp Lys Phe Leu His Ile Asn Asp Pro

145 150 155 160

acc aaa caa cca gtt tct att cgt caa gcg ttg gca ata aca ttt ctt 528

Thr Lys Gln Pro Val Ser Ile Arg Gln Ala Leu Ala Ile Thr Phe Leu

165 170 175

atc tgg ata gtc tca aca ctg ata aat cta ccg tat ctt atg tct ttc 576

Ile Trp Ile Val Ser Thr Leu Ile Asn Leu Pro Tyr Leu Met Ser Phe

180 185 190

gag cac gtc gat gga agc ttt tac gtt cag ccc gga gaa act cca tac 624

Glu His Val Asp Gly Ser Phe Tyr Val Gln Pro Gly Glu Thr Pro Tyr

195 200 205

tgc ggg cac ttt tgc gac gag gcg aat tgg cag agc gaa aat agt cga 672

Cys Gly His Phe Cys Asp Glu Ala Asn Trp Gln Ser Glu Asn Ser Arg

210 215 220

aag att tac gga act acg gtt atg ttg tta cag ttc gtc gtg ccg atg 720

Lys Ile Tyr Gly Thr Thr Val Met Leu Leu Gln Phe Val Val Pro Met

225 230 235 240

gca gtg atc acg tat tgc tac ttc aaa atc ttg caa aaa gtg tca aaa 768

Ala Val Ile Thr Tyr Cys Tyr Phe Lys Ile Leu Gln Lys Val Ser Lys

245 250 255

gac atg atc atc caa aat gct caa ttc tgt caa tca ctg aca caa aag 816

Asp Met Ile Ile Gln Asn Ala Gln Phe Cys Gln Ser Leu Thr Gln Lys

260 265 270

cag aga agt gat gcg acg tca cga aag aag aaa gtg aat tat att cta 864

Gln Arg Ser Asp Ala Thr Ser Arg Lys Lys Lys Val Asn Tyr Ile Leu

275 280 285

att gca atg gtt gtc aca ttt atc ggg tgt tgg ttg cct tta aca tta 912

Ile Ala Met Val Val Thr Phe Ile Gly Cys Trp Leu Pro Leu Thr Leu

290 295 300

ctc aat ttg gtc aaa gat ttt aaa aaa gag ccc gaa tgg cta aaa cgt 960

Leu Asn Leu Val Lys Asp Phe Lys Lys Glu Pro Glu Trp Leu Lys Arg

305 310 315 320

cag ccg ttc ttc tgg gca ata aat gct cac gtc ata gcc atg tcc tta 1008

Gln Pro Phe Phe Trp Ala Ile Asn Ala His Val Ile Ala Met Ser Leu

325 330 335

gtc gtc tgg aac cct ctg cta ttc ttt tgg ctg aca cga aaa caa aaa 1056

Val Val Trp Asn Pro Leu Leu Phe Phe Trp Leu Thr Arg Lys Gln Lys

340 345 350

cgt tcc gga ctg tca aaa ata ctc aac tca aca gag ggt tcg aaa aaa 1104

Arg Ser Gly Leu Ser Lys Ile Leu Asn Ser Thr Glu Gly Ser Lys Lys

355 360 365

gca ggt ggt tct gga ttg cga ggg atc cag cta cac gac ctc ctc ccg 1152

Ala Gly Gly Ser Gly Leu Arg Gly Ile Gln Leu His Asp Leu Leu Pro

370 375 380

acc tct act cat tcg gac aga tgt gca ggc aac tct ttc ta 1193

Thr Ser Thr His Ser Asp Arg Cys Ala Gly Asn Ser Phe

385 390 395

105

397

Homo sapiens

105

Met Val Ser Ser Ala Ala Thr Ile Ser Thr Ile Ser Thr Thr Thr Thr

1 5 10 15

Pro Ser Thr Ile Ser Asn Val Ile Thr Ser His Ser Asn Asn Gly Ser

20 25 30

Cys Ile Gln Ile Ala Glu Ala Ile Ala Ala Gln Gly Ile Asp Asp Ile

35 40 45

Thr Val Asp Phe Tyr Ile Arg Ser Ile Phe Thr Phe Leu Tyr Gly Phe

50 55 60

Leu Phe Val Leu Gly Ile Phe Gly Asn Gly Gly Val Leu Trp Ala Val

65 70 75 80

Ala Arg Asn Lys Arg Leu Gln Ser Ala Arg Asn Val Phe Leu Leu Asn

85 90 95

Leu Ile Phe Thr Asp Leu Ile Leu Val Phe Thr Ala Ile Pro Val Thr

100 105 110

Pro Trp Tyr Ala Met Thr Lys Asp Trp Ala Phe Gly Ser Val Met Cys

115 120 125

His Leu Val Pro Leu Ser Asn Ser Cys Ser Val Phe Val Thr Ser Trp

130 135 140

Ser Leu Thr Ala Ile Ser Leu Asp Lys Phe Leu His Ile Asn Asp Pro

145 150 155 160

Thr Lys Gln Pro Val Ser Ile Arg Gln Ala Leu Ala Ile Thr Phe Leu

165 170 175

Ile Trp Ile Val Ser Thr Leu Ile Asn Leu Pro Tyr Leu Met Ser Phe

180 185 190

Glu His Val Asp Gly Ser Phe Tyr Val Gln Pro Gly Glu Thr Pro Tyr

195 200 205

Cys Gly His Phe Cys Asp Glu Ala Asn Trp Gln Ser Glu Asn Ser Arg

210 215 220

Lys Ile Tyr Gly Thr Thr Val Met Leu Leu Gln Phe Val Val Pro Met

225 230 235 240

Ala Val Ile Thr Tyr Cys Tyr Phe Lys Ile Leu Gln Lys Val Ser Lys

245 250 255

Asp Met Ile Ile Gln Asn Ala Gln Phe Cys Gln Ser Leu Thr Gln Lys

260 265 270

Gln Arg Ser Asp Ala Thr Ser Arg Lys Lys Lys Val Asn Tyr Ile Leu

275 280 285

Ile Ala Met Val Val Thr Phe Ile Gly Cys Trp Leu Pro Leu Thr Leu

290 295 300

Leu Asn Leu Val Lys Asp Phe Lys Lys Glu Pro Glu Trp Leu Lys Arg

305 310 315 320

Gln Pro Phe Phe Trp Ala Ile Asn Ala His Val Ile Ala Met Ser Leu

325 330 335

Val Val Trp Asn Pro Leu Leu Phe Phe Trp Leu Thr Arg Lys Gln Lys

340 345 350

Arg Ser Gly Leu Ser Lys Ile Leu Asn Ser Thr Glu Gly Ser Lys Lys

355 360 365

Ala Gly Gly Ser Gly Leu Arg Gly Ile Gln Leu His Asp Leu Leu Pro

370 375 380

Thr Ser Thr His Ser Asp Arg Cys Ala Gly Asn Ser Phe

385 390 395

106

atg gtt agt tcg gcg gcc acc att tcg acc att tca acc aca acg act 48

Met Val Ser Ser Ala Ala Thr Ile Ser Thr Ile Ser Thr Thr Thr Thr

1 5 10 15

ccc tcc acc atc agc aac gtt atc aca agt cat tcg aac aat ggc tcg 96

Pro Ser Thr Ile Ser Asn Val Ile Thr Ser His Ser Asn Asn Gly Ser

20 25 30

tgc att cag atc gct gag gcg att gcg gca caa ggc atc gat gat att 144

Cys Ile Gln Ile Ala Glu Ala Ile Ala Ala Gln Gly Ile Asp Asp Ile

35 40 45

act gta gac ttt tac atc cga tca atc ttc aca ttc ctc tac ggg ttc 192

Thr Val Asp Phe Tyr Ile Arg Ser Ile Phe Thr Phe Leu Tyr Gly Phe

50 55 60

ctg ttt gta tta ggc att ttt gga aac ggc ggc gta cta tgg gcg gtg 240

Leu Phe Val Leu Gly Ile Phe Gly Asn Gly Gly Val Leu Trp Ala Val

65 70 75 80

gcg aga aac aag cgg ctc caa tcg gct cgc aac gta ttt ctg ctc aac 288

Ala Arg Asn Lys Arg Leu Gln Ser Ala Arg Asn Val Phe Leu Leu Asn

85 90 95

ttg atc ttc acc gat ttg ata ttg gtg ttc aca gcg att cca gtc aca 336

Leu Ile Phe Thr Asp Leu Ile Leu Val Phe Thr Ala Ile Pro Val Thr

100 105 110

cca tgg tac gcg atg acc aaa gac tgg gca ttc ggg tca gtg atg tgc 384

Pro Trp Tyr Ala Met Thr Lys Asp Trp Ala Phe Gly Ser Val Met Cys

115 120 125

cat tta gtt cct ttg tca aat tcg tgt tcg gtg ttt gtg acg agt tgg 432

His Leu Val Pro Leu Ser Asn Ser Cys Ser Val Phe Val Thr Ser Trp

130 135 140

agc ctc act gca atc tcc tta gat aaa ttt ctg cat atc aac gat ccc 480

Ser Leu Thr Ala Ile Ser Leu Asp Lys Phe Leu His Ile Asn Asp Pro

145 150 155 160

acc aaa caa cca gtt tct att cgt caa gcg ttg gca ata aca ttt ctt 528

Thr Lys Gln Pro Val Ser Ile Arg Gln Ala Leu Ala Ile Thr Phe Leu

165 170 175

atc tgg ata gtc tca aca ctg ata aat cta ccg tat ctt atg tct ttc 576

Ile Trp Ile Val Ser Thr Leu Ile Asn Leu Pro Tyr Leu Met Ser Phe

180 185 190

gag cac gtc gat gga agc ttt tac gtt cag ccc gga gaa act cca tac 624

Glu His Val Asp Gly Ser Phe Tyr Val Gln Pro Gly Glu Thr Pro Tyr

195 200 205

tgc ggg cac ttt tgc gac gag gcg aat tgg cag agc gaa aat agt cga 672

Cys Gly His Phe Cys Asp Glu Ala Asn Trp Gln Ser Glu Asn Ser Arg

210 215 220

aag att tac gga act acg gtt atg ttg tta cag ttc gtc gtg ccg atg 720

Lys Ile Tyr Gly Thr Thr Val Met Leu Leu Gln Phe Val Val Pro Met

225 230 235 240

gca gtg atc acg tat tgc tac ttc aaa atc ttg caa aaa gtg tca aaa 768

Ala Val Ile Thr Tyr Cys Tyr Phe Lys Ile Leu Gln Lys Val Ser Lys

245 250 255

gac atg atc atc caa aat gct caa ttc tgt caa tca ctg aca caa aag 816

Asp Met Ile Ile Gln Asn Ala Gln Phe Cys Gln Ser Leu Thr Gln Lys

260 265 270

cag aga agt gat gcg acg tca cga aag aag aaa gtg aat tat att cta 864

Gln Arg Ser Asp Ala Thr Ser Arg Lys Lys Lys Val Asn Tyr Ile Leu

275 280 285

att gca atg gtt gtc aca ttt atc ggg tgt tgg ttg cct tta aca tta 912

Ile Ala Met Val Val Thr Phe Ile Gly Cys Trp Leu Pro Leu Thr Leu

290 295 300

ctc aat ttg gtc aaa gat ttt aaa aaa gag ccc gaa tgg cta aaa cgt 960

Leu Asn Leu Val Lys Asp Phe Lys Lys Glu Pro Glu Trp Leu Lys Arg

305 310 315 320

cag ccg ttc ttc tgg gca ata aat gct cac gtc ata gcc atg tcc tta 1008

Gln Pro Phe Phe Trp Ala Ile Asn Ala His Val Ile Ala Met Ser Leu

325 330 335

gtc gtc tgg aac cct ctg cta ttc ttt tgg ctg aca cga aaa caa aaa 1056

Val Val Trp Asn Pro Leu Leu Phe Phe Trp Leu Thr Arg Lys Gln Lys

340 345 350

cgt tcc gga ctg tca aaa ata ctc aac tca aca gag att gtg tcc tcg 1104

Arg Ser Gly Leu Ser Lys Ile Leu Asn Ser Thr Glu Ile Val Ser Ser

355 360 365

ttt gcc agt aga gtg agt aac tcg att cgg cgg tca acg ttt cgg aga 1152

Phe Ala Ser Arg Val Ser Asn Ser Ile Arg Arg Ser Thr Phe Arg Arg

370 375 380

aac aat att gac agg gtt cga aaa aag cag gtg gtt ctg gat tgc gag 1200

Asn Asn Ile Asp Arg Val Arg Lys Lys Gln Val Val Leu Asp Cys Glu

385 390 395 400

gga tcc agc tac acg acc tcc tcc cga cct cta ctc att cgg aca gat 1248

Gly Ser Ser Tyr Thr Thr Ser Ser Arg Pro Leu Leu Ile Arg Thr Asp

405 410 415

gtg cag gca act ctt tct aat ggc tcg acg agt act acc cgc gag atg 1296

Val Gln Ala Thr Leu Ser Asn Gly Ser Thr Ser Thr Thr Arg Glu Met

420 425 430

ctg ta 1301

Leu

107

433

Homo sapiens

107

Met Val Ser Ser Ala Ala Thr Ile Ser Thr Ile Ser Thr Thr Thr Thr

1 5 10 15

Pro Ser Thr Ile Ser Asn Val Ile Thr Ser His Ser Asn Asn Gly Ser

20 25 30

Cys Ile Gln Ile Ala Glu Ala Ile Ala Ala Gln Gly Ile Asp Asp Ile

35 40 45

Thr Val Asp Phe Tyr Ile Arg Ser Ile Phe Thr Phe Leu Tyr Gly Phe

50 55 60

Leu Phe Val Leu Gly Ile Phe Gly Asn Gly Gly Val Leu Trp Ala Val

65 70 75 80

Ala Arg Asn Lys Arg Leu Gln Ser Ala Arg Asn Val Phe Leu Leu Asn

85 90 95

Leu Ile Phe Thr Asp Leu Ile Leu Val Phe Thr Ala Ile Pro Val Thr

100 105 110

Pro Trp Tyr Ala Met Thr Lys Asp Trp Ala Phe Gly Ser Val Met Cys

115 120 125

His Leu Val Pro Leu Ser Asn Ser Cys Ser Val Phe Val Thr Ser Trp

130 135 140

Ser Leu Thr Ala Ile Ser Leu Asp Lys Phe Leu His Ile Asn Asp Pro

145 150 155 160

Thr Lys Gln Pro Val Ser Ile Arg Gln Ala Leu Ala Ile Thr Phe Leu

165 170 175

Ile Trp Ile Val Ser Thr Leu Ile Asn Leu Pro Tyr Leu Met Ser Phe

180 185 190

Glu His Val Asp Gly Ser Phe Tyr Val Gln Pro Gly Glu Thr Pro Tyr

195 200 205

Cys Gly His Phe Cys Asp Glu Ala Asn Trp Gln Ser Glu Asn Ser Arg

210 215 220

Lys Ile Tyr Gly Thr Thr Val Met Leu Leu Gln Phe Val Val Pro Met

225 230 235 240

Ala Val Ile Thr Tyr Cys Tyr Phe Lys Ile Leu Gln Lys Val Ser Lys

245 250 255

Asp Met Ile Ile Gln Asn Ala Gln Phe Cys Gln Ser Leu Thr Gln Lys

260 265 270

Gln Arg Ser Asp Ala Thr Ser Arg Lys Lys Lys Val Asn Tyr Ile Leu

275 280 285

Ile Ala Met Val Val Thr Phe Ile Gly Cys Trp Leu Pro Leu Thr Leu

290 295 300

Leu Asn Leu Val Lys Asp Phe Lys Lys Glu Pro Glu Trp Leu Lys Arg

305 310 315 320

Gln Pro Phe Phe Trp Ala Ile Asn Ala His Val Ile Ala Met Ser Leu

325 330 335

Val Val Trp Asn Pro Leu Leu Phe Phe Trp Leu Thr Arg Lys Gln Lys

340 345 350

Arg Ser Gly Leu Ser Lys Ile Leu Asn Ser Thr Glu Ile Val Ser Ser

355 360 365

Phe Ala Ser Arg Val Ser Asn Ser Ile Arg Arg Ser Thr Phe Arg Arg

370 375 380

Asn Asn Ile Asp Arg Val Arg Lys Lys Gln Val Val Leu Asp Cys Glu

385 390 395 400

Gly Ser Ser Tyr Thr Thr Ser Ser Arg Pro Leu Leu Ile Arg Thr Asp

405 410 415

Val Gln Ala Thr Leu Ser Asn Gly Ser Thr Ser Thr Thr Arg Glu Met

420 425 430

Leu

108

1277

Homo sapiens

Clone identifier CEGPCR21 (F02E8.2)

108

atg aca cat gac aat gaa tat caa tct gca ctt gta ttc gat aga att 48

Met Thr His Asp Asn Glu Tyr Gln Ser Ala Leu Val Phe Asp Arg Ile

1 5 10 15

aga cga tta atc tta aac aac tcg aat acc cca ata acg aca aaa gag 96

Arg Arg Leu Ile Leu Asn Asn Ser Asn Thr Pro Ile Thr Thr Lys Glu

20 25 30

ctt ata aag cat tgc ttt cat cca gat gtt cag ttt ctt gct cac atg 144

Leu Ile Lys His Cys Phe His Pro Asp Val Gln Phe Leu Ala His Met

35 40 45

acc ctg aaa tcg ttg gat cat ccc ggt gaa cag ttt aat aat tca tca 192

Thr Leu Lys Ser Leu Asp His Pro Gly Glu Gln Phe Asn Asn Ser Ser

50 55 60

aat caa ctt tta tta gat cgc gct ttt cta aac cca ata ctc aca ctc 240

Asn Gln Leu Leu Leu Asp Arg Ala Phe Leu Asn Pro Ile Leu Thr Leu

65 70 75 80

att ttt gtt ttt gtc ggg ctt gtg ggt ctc att ggc aat ttg ctc aca 288

Ile Phe Val Phe Val Gly Leu Val Gly Leu Ile Gly Asn Leu Leu Thr

85 90 95

gtt att gtg att ttc aag aca aat tcc ctg cac tcg cac aca aac tat 336

Val Ile Val Ile Phe Lys Thr Asn Ser Leu His Ser His Thr Asn Tyr

100 105 110

ttc ttg gca aat ctt gct acc ggc gac ttc tgt ctc atc gtt gtt gga 384

Phe Leu Ala Asn Leu Ala Thr Gly Asp Phe Cys Leu Ile Val Val Gly

115 120 125

gtt tcg ttt gac ttg gtg aat atc tgg aac gat gag gaa ccg ctg gac 432

Val Ser Phe Asp Leu Val Asn Ile Trp Asn Asp Glu Glu Pro Leu Asp

130 135 140

att ttt gga tat tgc tct ctt aca agc act ttt ata tct ctg ttc aca 480

Ile Phe Gly Tyr Cys Ser Leu Thr Ser Thr Phe Ile Ser Leu Phe Thr

145 150 155 160

ttt gct tca att ctc aca att gtt ctt ttg acg gca gaa aga ttt aca 528

Phe Ala Ser Ile Leu Thr Ile Val Leu Leu Thr Ala Glu Arg Phe Thr

165 170 175

gcg att tgt tat cct ttt tcc cat aga aca att ttc gac gag aag cgt 576

Ala Ile Cys Tyr Pro Phe Ser His Arg Thr Ile Phe Asp Glu Lys Arg

180 185 190

gtt aaa agg ttt ata ctg ctt att tgg ttc gta gca ctt ctt cca tca 624

Val Lys Arg Phe Ile Leu Leu Ile Trp Phe Val Ala Leu Leu Pro Ser

195 200 205

att ttc att ggc tct atg ttc aaa cga gtg tct caa gac ttt tgt ggc 672

Ile Phe Ile Gly Ser Met Phe Lys Arg Val Ser Gln Asp Phe Cys Gly

210 215 220

ttc aat cgc caa atg act tat atc ggt cga tgt gat ttg gtg aca tct 720

Phe Asn Arg Gln Met Thr Tyr Ile Gly Arg Cys Asp Leu Val Thr Ser

225 230 235 240

cca gat agt ttc ttc cgg tac cca ttt gaa tca gca ata acc atc act 768

Pro Asp Ser Phe Phe Arg Tyr Pro Phe Glu Ser Ala Ile Thr Ile Thr

245 250 255

ttt gta ctt ccc ttg ttc ttc att att tat tgt tac ttc cgg att cta 816

Phe Val Leu Pro Leu Phe Phe Ile Ile Tyr Cys Tyr Phe Arg Ile Leu

260 265 270

gtc aca ttg aac gag atg tcc aat tcg act cat gtg cac act cca gtc 864

Val Thr Leu Asn Glu Met Ser Asn Ser Thr His Val His Thr Pro Val

275 280 285

gga act gct cgt agt gat agt gga gct ttt cct ttt ccc cat aca tct 912

Gly Thr Ala Arg Ser Asp Ser Gly Ala Phe Pro Phe Pro His Thr Ser

290 295 300

aat aac tct aac act caa agt ttc ccg cta aca gtc cat act aaa aat 960

Asn Asn Ser Asn Thr Gln Ser Phe Pro Leu Thr Val His Thr Lys Asn

305 310 315 320

gtc caa ccg ccg cga agt caa caa gcc cag aaa atg gtc att aag atg 1008

Val Gln Pro Pro Arg Ser Gln Gln Ala Gln Lys Met Val Ile Lys Met

325 330 335

ctt gtt act gta acc gct gta ttt ttt gtc tgc tat ctt cca tat cac 1056

Leu Val Thr Val Thr Ala Val Phe Phe Val Cys Tyr Leu Pro Tyr His

340 345 350

gct caa cgt ctc atc gtc aaa tac aac agc aag gat tgt tcc aac tca 1104

Ala Gln Arg Leu Ile Val Lys Tyr Asn Ser Lys Asp Cys Ser Asn Ser

355 360 365

gac ttc tgc aag ctt ctc tac cca ata gca gga atc ctc caa tac atc 1152

Asp Phe Cys Lys Leu Leu Tyr Pro Ile Ala Gly Ile Leu Gln Tyr Ile

370 375 380

tcc gct tct ttg aat cca att ttc tac aac ctc atg tct gta cga ttt 1200

Ser Ala Ser Leu Asn Pro Ile Phe Tyr Asn Leu Met Ser Val Arg Phe

385 390 395 400

cgc aac gga ttc aag aag ctc atc aaa gac gtc tgg gca cat cga gcc 1248

Arg Asn Gly Phe Lys Lys Leu Ile Lys Asp Val Trp Ala His Arg Ala

405 410 415

cgt agt tac agc aat cta gct cgt gtc ta 1277

Arg Ser Tyr Ser Asn Leu Ala Arg Val

420 425

109

425

Homo sapiens

109

Met Thr His Asp Asn Glu Tyr Gln Ser Ala Leu Val Phe Asp Arg Ile

1 5 10 15

Arg Arg Leu Ile Leu Asn Asn Ser Asn Thr Pro Ile Thr Thr Lys Glu

20 25 30

Leu Ile Lys His Cys Phe His Pro Asp Val Gln Phe Leu Ala His Met

35 40 45

Thr Leu Lys Ser Leu Asp His Pro Gly Glu Gln Phe Asn Asn Ser Ser

50 55 60

Asn Gln Leu Leu Leu Asp Arg Ala Phe Leu Asn Pro Ile Leu Thr Leu

65 70 75 80

Ile Phe Val Phe Val Gly Leu Val Gly Leu Ile Gly Asn Leu Leu Thr

85 90 95

Val Ile Val Ile Phe Lys Thr Asn Ser Leu His Ser His Thr Asn Tyr

100 105 110

Phe Leu Ala Asn Leu Ala Thr Gly Asp Phe Cys Leu Ile Val Val Gly

115 120 125

Val Ser Phe Asp Leu Val Asn Ile Trp Asn Asp Glu Glu Pro Leu Asp

130 135 140

Ile Phe Gly Tyr Cys Ser Leu Thr Ser Thr Phe Ile Ser Leu Phe Thr

145 150 155 160

Phe Ala Ser Ile Leu Thr Ile Val Leu Leu Thr Ala Glu Arg Phe Thr

165 170 175

Ala Ile Cys Tyr Pro Phe Ser His Arg Thr Ile Phe Asp Glu Lys Arg

180 185 190

Val Lys Arg Phe Ile Leu Leu Ile Trp Phe Val Ala Leu Leu Pro Ser

195 200 205

Ile Phe Ile Gly Ser Met Phe Lys Arg Val Ser Gln Asp Phe Cys Gly

210 215 220

Phe Asn Arg Gln Met Thr Tyr Ile Gly Arg Cys Asp Leu Val Thr Ser

225 230 235 240

Pro Asp Ser Phe Phe Arg Tyr Pro Phe Glu Ser Ala Ile Thr Ile Thr

245 250 255

Phe Val Leu Pro Leu Phe Phe Ile Ile Tyr Cys Tyr Phe Arg Ile Leu

260 265 270

Val Thr Leu Asn Glu Met Ser Asn Ser Thr His Val His Thr Pro Val

275 280 285

Gly Thr Ala Arg Ser Asp Ser Gly Ala Phe Pro Phe Pro His Thr Ser

290 295 300

Asn Asn Ser Asn Thr Gln Ser Phe Pro Leu Thr Val His Thr Lys Asn

305 310 315 320

Val Gln Pro Pro Arg Ser Gln Gln Ala Gln Lys Met Val Ile Lys Met

325 330 335

Leu Val Thr Val Thr Ala Val Phe Phe Val Cys Tyr Leu Pro Tyr His

340 345 350

Ala Gln Arg Leu Ile Val Lys Tyr Asn Ser Lys Asp Cys Ser Asn Ser

355 360 365

Asp Phe Cys Lys Leu Leu Tyr Pro Ile Ala Gly Ile Leu Gln Tyr Ile

370 375 380

Ser Ala Ser Leu Asn Pro Ile Phe Tyr Asn Leu Met Ser Val Arg Phe

385 390 395 400

Arg Asn Gly Phe Lys Lys Leu Ile Lys Asp Val Trp Ala His Arg Ala

405 410 415

Arg Ser Tyr Ser Asn Leu Ala Arg Val

420 425

110

1310

Homo sapiens

Clone identifier CeGPCR22 (C06G4.5)

110

atg tct aca aat ttg gtg gac tat gtc gat gat tcg tat ttg aat caa 48

Met Ser Thr Asn Leu Val Asp Tyr Val Asp Asp Ser Tyr Leu Asn Gln

1 5 10 15

tca atg aat tca gaa aat gga ttg gat tca gtc aca cag att atg tat 96

Ser Met Asn Ser Glu Asn Gly Leu Asp Ser Val Thr Gln Ile Met Tyr

20 25 30

gat atg aaa aag tac aat ata gtg aat gat gtt cta cct cct ccc aat 144

Asp Met Lys Lys Tyr Asn Ile Val Asn Asp Val Leu Pro Pro Pro Asn

35 40 45

cac gaa gat cta cat gtt gta ata atg gca gtt tca tac ctt ctt tta 192

His Glu Asp Leu His Val Val Ile Met Ala Val Ser Tyr Leu Leu Leu

50 55 60

ttt tta tta ggt act tgt gga aat gtg gca gtg tta act aca ata tac 240

Phe Leu Leu Gly Thr Cys Gly Asn Val Ala Val Leu Thr Thr Ile Tyr

65 70 75 80

cat gtt att cga tcg tct cga gcc acg ttg gat aac aca tta ata tat 288

His Val Ile Arg Ser Ser Arg Ala Thr Leu Asp Asn Thr Leu Ile Tyr

85 90 95

gtc att gtg ctt tct tgt gtc gac ttc gga gtt tgt ttg tca ctt cca 336

Val Ile Val Leu Ser Cys Val Asp Phe Gly Val Cys Leu Ser Leu Pro

100 105 110

att acg gtt att gat cag att ctc ggt ttc tgg atg ttt ggc aaa ata 384

Ile Thr Val Ile Asp Gln Ile Leu Gly Phe Trp Met Phe Gly Lys Ile

115 120 125

cca tgt aaa ctt cat gca gta ttc gag aat ttc ggt aaa atc ctg agt 432

Pro Cys Lys Leu His Ala Val Phe Glu Asn Phe Gly Lys Ile Leu Ser

130 135 140

gct ctc att ctg acg gca atg agt ttt gat cgg tac gcc gga gtt tgc 480

Ala Leu Ile Leu Thr Ala Met Ser Phe Asp Arg Tyr Ala Gly Val Cys

145 150 155 160

cat cca cag cga aaa cgg ttg aga tca agg aat ttt gca att act ata 528

His Pro Gln Arg Lys Arg Leu Arg Ser Arg Asn Phe Ala Ile Thr Ile

165 170 175

ctt tta gtt ctt gcc gta tat gca ttc atc aca ctc tgc ccg tta tta 576

Leu Leu Val Leu Ala Val Tyr Ala Phe Ile Thr Leu Cys Pro Leu Leu

180 185 190

tgg tct ttt act gca cgg gaa att ata ctt tat gcg aag gaa aca gca 624

Trp Ser Phe Thr Ala Arg Glu Ile Ile Leu Tyr Ala Lys Glu Thr Ala

195 200 205

ccc gga atg ctg aca aga atg aaa att gag aaa tgc aca gtg gat atc 672

Pro Gly Met Leu Thr Arg Met Lys Ile Glu Lys Cys Thr Val Asp Ile

210 215 220

gac tca caa atg ttc aca gct ttc acg att tat cag ttc att ctc tgt 720

Asp Ser Gln Met Phe Thr Ala Phe Thr Ile Tyr Gln Phe Ile Leu Cys

225 230 235 240

tat tgt act cca ttg gtt ctc atc gcc ttt ttc tat acg aaa ctt ctc 768

Tyr Cys Thr Pro Leu Val Leu Ile Ala Phe Phe Tyr Thr Lys Leu Leu

245 250 255

agc aaa ctc cgt gaa cac aca agg acg ttt aag agc tct caa atc cca 816

Ser Lys Leu Arg Glu His Thr Arg Thr Phe Lys Ser Ser Gln Ile Pro

260 265 270

ttt ttg cac att tcg ttg tac act cta gca gtt gca tgt ttc tat ttt 864

Phe Leu His Ile Ser Leu Tyr Thr Leu Ala Val Ala Cys Phe Tyr Phe

275 280 285

tta tgc tgg acc cca ttc tgg atg gct aca tta ttc gca gtt tat ctc 912

Leu Cys Trp Thr Pro Phe Trp Met Ala Thr Leu Phe Ala Val Tyr Leu

290 295 300

gaa aac tca gca aat tcg agt agt gtt cca cca gtt ttt gta tat att 960

Glu Asn Ser Ala Asn Ser Ser Ser Val Pro Pro Val Phe Val Tyr Ile

305 310 315 320

atg tat ttt att cat gct cta ccg ttc acc aac tct gcc att aat tgg 1008

Met Tyr Phe Ile His Ala Leu Pro Phe Thr Asn Ser Ala Ile Asn Trp

325 330 335

att tta tac ggt gca cta aat ggc caa ctt caa caa aga tat cga tca 1056

Ile Leu Tyr Gly Ala Leu Asn Gly Gln Leu Gln Gln Arg Tyr Arg Ser

340 345 350

aat cgt tca aat tct aca aaa aag acg aca aca aca aca gct tca aca 1104

Asn Arg Ser Asn Ser Thr Lys Lys Thr Thr Thr Thr Thr Ala Ser Thr

355 360 365

gct tta ttg gaa aag aaa atc aca aat ttg aat act aac tct aat tat 1152

Ala Leu Leu Glu Lys Lys Ile Thr Asn Leu Asn Thr Asn Ser Asn Tyr

370 375 380

cag gta aat ggc tca atg aac tca ata gcc act gca gct cca aca aaa 1200

Gln Val Asn Gly Ser Met Asn Ser Ile Ala Thr Ala Ala Pro Thr Lys

385 390 395 400

acg att gga aat aat gaa gta ctt gtt gcc acg tca aca att gat gat 1248

Thr Ile Gly Asn Asn Glu Val Leu Val Ala Thr Ser Thr Ile Asp Asp

405 410 415

gat gtt gca act gat gtt gta gat gtt cga ctt ttg agt aat cat aat 1296

Asp Val Ala Thr Asp Val Val Asp Val Arg Leu Leu Ser Asn His Asn

420 425 430

cca act ttt ctt tg 1310

Pro Thr Phe Leu

435

111

436

Homo sapiens

111

Met Ser Thr Asn Leu Val Asp Tyr Val Asp Asp Ser Tyr Leu Asn Gln

1 5 10 15

Ser Met Asn Ser Glu Asn Gly Leu Asp Ser Val Thr Gln Ile Met Tyr

20 25 30

Asp Met Lys Lys Tyr Asn Ile Val Asn Asp Val Leu Pro Pro Pro Asn

35 40 45

His Glu Asp Leu His Val Val Ile Met Ala Val Ser Tyr Leu Leu Leu

50 55 60

Phe Leu Leu Gly Thr Cys Gly Asn Val Ala Val Leu Thr Thr Ile Tyr

65 70 75 80

His Val Ile Arg Ser Ser Arg Ala Thr Leu Asp Asn Thr Leu Ile Tyr

85 90 95

Val Ile Val Leu Ser Cys Val Asp Phe Gly Val Cys Leu Ser Leu Pro

100 105 110

Ile Thr Val Ile Asp Gln Ile Leu Gly Phe Trp Met Phe Gly Lys Ile

115 120 125

Pro Cys Lys Leu His Ala Val Phe Glu Asn Phe Gly Lys Ile Leu Ser

130 135 140

Ala Leu Ile Leu Thr Ala Met Ser Phe Asp Arg Tyr Ala Gly Val Cys

145 150 155 160

His Pro Gln Arg Lys Arg Leu Arg Ser Arg Asn Phe Ala Ile Thr Ile

165 170 175

Leu Leu Val Leu Ala Val Tyr Ala Phe Ile Thr Leu Cys Pro Leu Leu

180 185 190

Trp Ser Phe Thr Ala Arg Glu Ile Ile Leu Tyr Ala Lys Glu Thr Ala

195 200 205

Pro Gly Met Leu Thr Arg Met Lys Ile Glu Lys Cys Thr Val Asp Ile

210 215 220

Asp Ser Gln Met Phe Thr Ala Phe Thr Ile Tyr Gln Phe Ile Leu Cys

225 230 235 240

Tyr Cys Thr Pro Leu Val Leu Ile Ala Phe Phe Tyr Thr Lys Leu Leu

245 250 255

Ser Lys Leu Arg Glu His Thr Arg Thr Phe Lys Ser Ser Gln Ile Pro

260 265 270

Phe Leu His Ile Ser Leu Tyr Thr Leu Ala Val Ala Cys Phe Tyr Phe

275 280 285

Leu Cys Trp Thr Pro Phe Trp Met Ala Thr Leu Phe Ala Val Tyr Leu

290 295 300

Glu Asn Ser Ala Asn Ser Ser Ser Val Pro Pro Val Phe Val Tyr Ile

305 310 315 320

Met Tyr Phe Ile His Ala Leu Pro Phe Thr Asn Ser Ala Ile Asn Trp

325 330 335

Ile Leu Tyr Gly Ala Leu Asn Gly Gln Leu Gln Gln Arg Tyr Arg Ser

340 345 350

Asn Arg Ser Asn Ser Thr Lys Lys Thr Thr Thr Thr Thr Ala Ser Thr

355 360 365

Ala Leu Leu Glu Lys Lys Ile Thr Asn Leu Asn Thr Asn Ser Asn Tyr

370 375 380

Gln Val Asn Gly Ser Met Asn Ser Ile Ala Thr Ala Ala Pro Thr Lys

385 390 395 400

Thr Ile Gly Asn Asn Glu Val Leu Val Ala Thr Ser Thr Ile Asp Asp

405 410 415

Asp Val Ala Thr Asp Val Val Asp Val Arg Leu Leu Ser Asn His Asn

420 425 430

Pro Thr Phe Leu

435

112

1130

Homo sapiens

Clone identifier CEGPCR23 (T02E9.1)

112

atg aat atc aca aat tca agc atc ggg tac cca cct cca cca ctg gta 48

Met Asn Ile Thr Asn Ser Ser Ile Gly Tyr Pro Pro Pro Pro Leu Val

1 5 10 15

ggt gca tca ttt gca aaa aca gct ata cca tat tca ata tgt ttt gtt 96

Gly Ala Ser Phe Ala Lys Thr Ala Ile Pro Tyr Ser Ile Cys Phe Val

20 25 30

ttt gga act ctc ggc aac acg gcc gtt ctc tcc tac gtt ttc ttc att 144

Phe Gly Thr Leu Gly Asn Thr Ala Val Leu Ser Tyr Val Phe Phe Ile

35 40 45

aca cga tcc cta aaa tca tct gta act gca ctt ggg aac aca ttt att 192

Thr Arg Ser Leu Lys Ser Ser Val Thr Ala Leu Gly Asn Thr Phe Ile

50 55 60

tac atc gtt gca tta tgc gca gtc gat ctt ctt gtc acc gtt tcg att 240

Tyr Ile Val Ala Leu Cys Ala Val Asp Leu Leu Val Thr Val Ser Ile

65 70 75 80

cca ttc tcc cta tcg tac atg att ctc aac aac tgg gta ttc gga gag 288

Pro Phe Ser Leu Ser Tyr Met Ile Leu Asn Asn Trp Val Phe Gly Glu

85 90 95

ctg gtg tgc aag atc cac ttt atg ctt gag ctt tct aat aag atg tgc 336

Leu Val Cys Lys Ile His Phe Met Leu Glu Leu Ser Asn Lys Met Cys

100 105 110

tcc aca ttc att cta acc gca ctg gca ttt gat cgt tac atg gca ata 384

Ser Thr Phe Ile Leu Thr Ala Leu Ala Phe Asp Arg Tyr Met Ala Ile

115 120 125

tgt cat ccg gaa ata aaa cga atc cat gag atg cgt cac acg att tat 432

Cys His Pro Glu Ile Lys Arg Ile His Glu Met Arg His Thr Ile Tyr

130 135 140

atc acg aca att ctt gca aca ttg tca ctt ttt ctc ata tct cca gtc 480

Ile Thr Thr Ile Leu Ala Thr Leu Ser Leu Phe Leu Ile Ser Pro Val

145 150 155 160

gtt ttg tct gcc aga gtg acg agt ttc aaa agt gga caa tat ttt gtg 528

Val Leu Ser Ala Arg Val Thr Ser Phe Lys Ser Gly Gln Tyr Phe Val

165 170 175

agc gca aag aat gaa cgg cac gaa gtt atc cga caa atg tgt att gac 576

Ser Ala Lys Asn Glu Arg His Glu Val Ile Arg Gln Met Cys Ile Asp

180 185 190

gga atg gca tta gag tgg aag gtt tgg gtg tct gca ttt ctg atc ttc 624

Gly Met Ala Leu Glu Trp Lys Val Trp Val Ser Ala Phe Leu Ile Phe

195 200 205

ttt gca ttc tta ctt cca tgc act ctt cta acc tac ttt tac gcg aag 672

Phe Ala Phe Leu Leu Pro Cys Thr Leu Leu Thr Tyr Phe Tyr Ala Lys

210 215 220

atc gtc ctt cgt ctg agg aga caa aga aga aca atg ctc caa tct cga 720

Ile Val Leu Arg Leu Arg Arg Gln Arg Arg Thr Met Leu Gln Ser Arg

225 230 235 240

att ccc ctc cgc cgc att aca ata tac aca atg gca gcc acg ttc ttc 768

Ile Pro Leu Arg Arg Ile Thr Ile Tyr Thr Met Ala Ala Thr Phe Phe

245 250 255

tat ctt tcg tgt cat att cca ttt tgg ctc cca cag atc tac aac att 816

Tyr Leu Ser Cys His Ile Pro Phe Trp Leu Pro Gln Ile Tyr Asn Ile

260 265 270

ttc tcg aca gtt ctt ggg cac aaa atg aat cca aaa gtc atg aca ttc 864

Phe Ser Thr Val Leu Gly His Lys Met Asn Pro Lys Val Met Thr Phe

275 280 285

acc tat tat tca cat ctt ctt ccg ttc ata tcg gcg gca ttt aac tgg 912

Thr Tyr Tyr Ser His Leu Leu Pro Phe Ile Ser Ala Ala Phe Asn Trp

290 295 300

ata ttc tat gct cga ctt aat agt caa ttc aaa aaa gga ttg gtt cta 960

Ile Phe Tyr Ala Arg Leu Asn Ser Gln Phe Lys Lys Gly Leu Val Leu

305 310 315 320

gtt acg gaa aga atg atc aga aag cga aca aaa tcg atg cat gag aaa 1008

Val Thr Glu Arg Met Ile Arg Lys Arg Thr Lys Ser Met His Glu Lys

325 330 335

gga tac agt gag gca gct gtt gag ctt acg agc aag ttc gat gat gtc 1056

Gly Tyr Ser Glu Ala Ala Val Glu Leu Thr Ser Lys Phe Asp Asp Val

340 345 350

cca ttg atg tgt cca cac tgt gaa gct caa ctt tct att cgt tca agt 1104

Pro Leu Met Cys Pro His Cys Glu Ala Gln Leu Ser Ile Arg Ser Ser

355 360 365

agt aat gga aag aag aat tca aga ta 1130

Ser Asn Gly Lys Lys Asn Ser Arg

370 375

113

376

Homo sapiens

113

Met Asn Ile Thr Asn Ser Ser Ile Gly Tyr Pro Pro Pro Pro Leu Val

1 5 10 15

Gly Ala Ser Phe Ala Lys Thr Ala Ile Pro Tyr Ser Ile Cys Phe Val

20 25 30

Phe Gly Thr Leu Gly Asn Thr Ala Val Leu Ser Tyr Val Phe Phe Ile

35 40 45

Thr Arg Ser Leu Lys Ser Ser Val Thr Ala Leu Gly Asn Thr Phe Ile

50 55 60

Tyr Ile Val Ala Leu Cys Ala Val Asp Leu Leu Val Thr Val Ser Ile

65 70 75 80

Pro Phe Ser Leu Ser Tyr Met Ile Leu Asn Asn Trp Val Phe Gly Glu

85 90 95

Leu Val Cys Lys Ile His Phe Met Leu Glu Leu Ser Asn Lys Met Cys

100 105 110

Ser Thr Phe Ile Leu Thr Ala Leu Ala Phe Asp Arg Tyr Met Ala Ile

115 120 125

Cys His Pro Glu Ile Lys Arg Ile His Glu Met Arg His Thr Ile Tyr

130 135 140

Ile Thr Thr Ile Leu Ala Thr Leu Ser Leu Phe Leu Ile Ser Pro Val

145 150 155 160

Val Leu Ser Ala Arg Val Thr Ser Phe Lys Ser Gly Gln Tyr Phe Val

165 170 175

Ser Ala Lys Asn Glu Arg His Glu Val Ile Arg Gln Met Cys Ile Asp

180 185 190

Gly Met Ala Leu Glu Trp Lys Val Trp Val Ser Ala Phe Leu Ile Phe

195 200 205

Phe Ala Phe Leu Leu Pro Cys Thr Leu Leu Thr Tyr Phe Tyr Ala Lys

210 215 220

Ile Val Leu Arg Leu Arg Arg Gln Arg Arg Thr Met Leu Gln Ser Arg

225 230 235 240

Ile Pro Leu Arg Arg Ile Thr Ile Tyr Thr Met Ala Ala Thr Phe Phe

245 250 255

Tyr Leu Ser Cys His Ile Pro Phe Trp Leu Pro Gln Ile Tyr Asn Ile

260 265 270

Phe Ser Thr Val Leu Gly His Lys Met Asn Pro Lys Val Met Thr Phe

275 280 285

Thr Tyr Tyr Ser His Leu Leu Pro Phe Ile Ser Ala Ala Phe Asn Trp

290 295 300

Ile Phe Tyr Ala Arg Leu Asn Ser Gln Phe Lys Lys Gly Leu Val Leu

305 310 315 320

Val Thr Glu Arg Met Ile Arg Lys Arg Thr Lys Ser Met His Glu Lys

325 330 335

Gly Tyr Ser Glu Ala Ala Val Glu Leu Thr Ser Lys Phe Asp Asp Val

340 345 350

Pro Leu Met Cys Pro His Cys Glu Ala Gln Leu Ser Ile Arg Ser Ser

355 360 365

Ser Asn Gly Lys Lys Asn Ser Arg

370 375

114

1284

Homo sapiens

Clone identifier CEGPCR24a (Y59H11AL.a-01)

114

atg gac gaa gga ggg ggt att gga agc agt ttg ctc tcc aga atc acg 48

Met Asp Glu Gly Gly Gly Ile Gly Ser Ser Leu Leu Ser Arg Ile Thr

1 5 10 15

acg aca gcc tct gaa att atg atg cga aac gaa ccg acg aca act gaa 96

Thr Thr Ala Ser Glu Ile Met Met Arg Asn Glu Pro Thr Thr Thr Glu

20 25 30

aat cca gct gtt caa gaa atg aat cat att tat cat ttg aca cca agt 144

Asn Pro Ala Val Gln Glu Met Asn His Ile Tyr His Leu Thr Pro Ser

35 40 45

atg aag atg tta tgt att ctt ttc tat agt ata ctt tgc gta tgc tgt 192

Met Lys Met Leu Cys Ile Leu Phe Tyr Ser Ile Leu Cys Val Cys Cys

50 55 60

gtc tat gga aat gtg ctc gtt att ctg gtt att gtt tat ttt aaa cga 240

Val Tyr Gly Asn Val Leu Val Ile Leu Val Ile Val Tyr Phe Lys Arg

65 70 75 80

ctt cga acg gcg act aat att ttg ata ttg aac ttg gca gtt gct gat 288

Leu Arg Thr Ala Thr Asn Ile Leu Ile Leu Asn Leu Ala Val Ala Asp

85 90 95

ctt ctc ata tca gta ttc tgc att ccg ttc agc tat tgg caa gta ttg 336

Leu Leu Ile Ser Val Phe Cys Ile Pro Phe Ser Tyr Trp Gln Val Leu

100 105 110

att tat gat gat caa cgt tgg ctc ttc ggc tca atg atg tgc tct tta 384

Ile Tyr Asp Asp Gln Arg Trp Leu Phe Gly Ser Met Met Cys Ser Leu

115 120 125

tta gca ttc ctt caa gca atg gct gta ttt tta tca gct tgg aca ctt 432

Leu Ala Phe Leu Gln Ala Met Ala Val Phe Leu Ser Ala Trp Thr Leu

130 135 140

gtc gtt atc agt ttt gat cgg tgg atg gct ata atg ttc ctt tta act 480

Val Val Ile Ser Phe Asp Arg Trp Met Ala Ile Met Phe Leu Leu Thr

145 150 155 160

cca aat att cga att aca aga cga aga gct ctt tat ctg gta gct gcc 528

Pro Asn Ile Arg Ile Thr Arg Arg Arg Ala Leu Tyr Leu Val Ala Ala

165 170 175

acg tgg ata ttc agt atc cta atg gcg ttg ccg tta ctc ttc aca acg 576

Thr Trp Ile Phe Ser Ile Leu Met Ala Leu Pro Leu Leu Phe Thr Thr

180 185 190

aga ttt ttc gaa gac caa gac ggt tta ccg aat tgt gga gaa aat tgg 624

Arg Phe Phe Glu Asp Gln Asp Gly Leu Pro Asn Cys Gly Glu Asn Trp

195 200 205

acg tat ttt gga gat tct gga gaa caa gtg aga aaa gtg tat tct tca 672

Thr Tyr Phe Gly Asp Ser Gly Glu Gln Val Arg Lys Val Tyr Ser Ser

210 215 220

atg gtc tta att cta caa tat gtt gta cct caa gca gtt tta ata ata 720

Met Val Leu Ile Leu Gln Tyr Val Val Pro Gln Ala Val Leu Ile Ile

225 230 235 240

act tac aca cat att gga att aaa atg tgg aat agt cga gta cca gga 768

Thr Tyr Thr His Ile Gly Ile Lys Met Trp Asn Ser Arg Val Pro Gly

245 250 255

atg cag aat gga gca aca aag aaa atg atc gtt gat cga cat gaa agt 816

Met Gln Asn Gly Ala Thr Lys Lys Met Ile Val Asp Arg His Glu Ser

260 265 270

gtc aaa aag ctg gtc cca atg gtg att ctc att tcg gca ctc ttc gca 864

Val Lys Lys Leu Val Pro Met Val Ile Leu Ile Ser Ala Leu Phe Ala

275 280 285

ctt tgt tgg ctt cct tta ctt ata ctg atc aac gtc att cca gaa ttc 912

Leu Cys Trp Leu Pro Leu Leu Ile Leu Ile Asn Val Ile Pro Glu Phe

290 295 300

tat cca gat atc aac agt tgg gga tat att ctg tat ttg tgg tgg ttt 960

Tyr Pro Asp Ile Asn Ser Trp Gly Tyr Ile Leu Tyr Leu Trp Trp Phe

305 310 315 320

gct cat gga ctt gcc atg tct cat tca atg gtc aac cca att atc tat 1008

Ala His Gly Leu Ala Met Ser His Ser Met Val Asn Pro Ile Ile Tyr

325 330 335

ttc att cga aat gcc cgt ttc cgt gaa gga ttc tgt ttc ttc tct tca 1056

Phe Ile Arg Asn Ala Arg Phe Arg Glu Gly Phe Cys Phe Phe Ser Ser

340 345 350

aaa ctt ctt cca tgt ata tca ttt aaa gaa ctt cgt ctt tta act gat 1104

Lys Leu Leu Pro Cys Ile Ser Phe Lys Glu Leu Arg Leu Leu Thr Asp

355 360 365

aat act agc aga aga cat cgc tta cga gat att cac gaa gtg gag tcc 1152

Asn Thr Ser Arg Arg His Arg Leu Arg Asp Ile His Glu Val Glu Ser

370 375 380

ttg aca ggc aaa cat gtc gtt cgg cac gtt tct tcg aag ccc gac cac 1200

Leu Thr Gly Lys His Val Val Arg His Val Ser Ser Lys Pro Asp His

385 390 395 400

tcg tcg tcg tcc gaa aca act ctg cca att ctc tcg cgt agc ttt tcc 1248

Ser Ser Ser Ser Glu Thr Thr Leu Pro Ile Leu Ser Arg Ser Phe Ser

405 410 415

cgt atc att aag aaa att gat cta cca tgt act tga 1284

Arg Ile Ile Lys Lys Ile Asp Leu Pro Cys Thr

420 425

115

427

Homo sapiens

115

Met Asp Glu Gly Gly Gly Ile Gly Ser Ser Leu Leu Ser Arg Ile Thr

1 5 10 15

Thr Thr Ala Ser Glu Ile Met Met Arg Asn Glu Pro Thr Thr Thr Glu

20 25 30

Asn Pro Ala Val Gln Glu Met Asn His Ile Tyr His Leu Thr Pro Ser

35 40 45

Met Lys Met Leu Cys Ile Leu Phe Tyr Ser Ile Leu Cys Val Cys Cys

50 55 60

Val Tyr Gly Asn Val Leu Val Ile Leu Val Ile Val Tyr Phe Lys Arg

65 70 75 80

Leu Arg Thr Ala Thr Asn Ile Leu Ile Leu Asn Leu Ala Val Ala Asp

85 90 95

Leu Leu Ile Ser Val Phe Cys Ile Pro Phe Ser Tyr Trp Gln Val Leu

100 105 110

Ile Tyr Asp Asp Gln Arg Trp Leu Phe Gly Ser Met Met Cys Ser Leu

115 120 125

Leu Ala Phe Leu Gln Ala Met Ala Val Phe Leu Ser Ala Trp Thr Leu

130 135 140

Val Val Ile Ser Phe Asp Arg Trp Met Ala Ile Met Phe Leu Leu Thr

145 150 155 160

Pro Asn Ile Arg Ile Thr Arg Arg Arg Ala Leu Tyr Leu Val Ala Ala

165 170 175

Thr Trp Ile Phe Ser Ile Leu Met Ala Leu Pro Leu Leu Phe Thr Thr

180 185 190

Arg Phe Phe Glu Asp Gln Asp Gly Leu Pro Asn Cys Gly Glu Asn Trp

195 200 205

Thr Tyr Phe Gly Asp Ser Gly Glu Gln Val Arg Lys Val Tyr Ser Ser

210 215 220

Met Val Leu Ile Leu Gln Tyr Val Val Pro Gln Ala Val Leu Ile Ile

225 230 235 240

Thr Tyr Thr His Ile Gly Ile Lys Met Trp Asn Ser Arg Val Pro Gly

245 250 255

Met Gln Asn Gly Ala Thr Lys Lys Met Ile Val Asp Arg His Glu Ser

260 265 270

Val Lys Lys Leu Val Pro Met Val Ile Leu Ile Ser Ala Leu Phe Ala

275 280 285

Leu Cys Trp Leu Pro Leu Leu Ile Leu Ile Asn Val Ile Pro Glu Phe

290 295 300

Tyr Pro Asp Ile Asn Ser Trp Gly Tyr Ile Leu Tyr Leu Trp Trp Phe

305 310 315 320

Ala His Gly Leu Ala Met Ser His Ser Met Val Asn Pro Ile Ile Tyr

325 330 335

Phe Ile Arg Asn Ala Arg Phe Arg Glu Gly Phe Cys Phe Phe Ser Ser

340 345 350

Lys Leu Leu Pro Cys Ile Ser Phe Lys Glu Leu Arg Leu Leu Thr Asp

355 360 365

Asn Thr Ser Arg Arg His Arg Leu Arg Asp Ile His Glu Val Glu Ser

370 375 380

Leu Thr Gly Lys His Val Val Arg His Val Ser Ser Lys Pro Asp His

385 390 395 400

Ser Ser Ser Ser Glu Thr Thr Leu Pro Ile Leu Ser Arg Ser Phe Ser

405 410 415

Arg Ile Ile Lys Lys Ile Asp Leu Pro Cys Thr

420 425

116

1305

Homo sapiens

Clone identifier CEGPCR24b (Y59H11A1.a-02)

116

atg gac gaa gga ggg ggt att gga agc agt ttg ctc tcc aga atc acg 48

Met Asp Glu Gly Gly Gly Ile Gly Ser Ser Leu Leu Ser Arg Ile Thr

1 5 10 15

acg aca gcc tct gaa att atg atg cga aac gaa ccg acg aca act gaa 96

Thr Thr Ala Ser Glu Ile Met Met Arg Asn Glu Pro Thr Thr Thr Glu

20 25 30

aat cca gct gtt caa gaa atg aat cat att tat cat ttg aca cca agt 144

Asn Pro Ala Val Gln Glu Met Asn His Ile Tyr His Leu Thr Pro Ser

35 40 45

atg aag atg tta tgt att ctt ttc tat agt ata ctt tgc gta tgc tgt 192

Met Lys Met Leu Cys Ile Leu Phe Tyr Ser Ile Leu Cys Val Cys Cys

50 55 60

gtc tat gga aat gtg ctc gtt att ctg gtt att gtt tat ttt aaa cga 240

Val Tyr Gly Asn Val Leu Val Ile Leu Val Ile Val Tyr Phe Lys Arg

65 70 75 80

ctt cga acg gcg act aat att ttg ata ttg aac ttg gca gtt gct gat 288

Leu Arg Thr Ala Thr Asn Ile Leu Ile Leu Asn Leu Ala Val Ala Asp

85 90 95

ctt ctc ata tca gta ttc tgc att ccg ttc agc tat tgg caa gta ttg 336

Leu Leu Ile Ser Val Phe Cys Ile Pro Phe Ser Tyr Trp Gln Val Leu

100 105 110

att tat gat gat caa cgt tgg ctc ttc ggc tca atg atg tgc tct tta 384

Ile Tyr Asp Asp Gln Arg Trp Leu Phe Gly Ser Met Met Cys Ser Leu

115 120 125

tta gca ttc ctt caa gca atg gct gta ttt tta tca gct tgg aca ctt 432

Leu Ala Phe Leu Gln Ala Met Ala Val Phe Leu Ser Ala Trp Thr Leu

130 135 140

gtc gtt atc agt ttt gat cgg tgg atg gct ata atg ttc ctt tta act 480

Val Val Ile Ser Phe Asp Arg Trp Met Ala Ile Met Phe Leu Leu Thr

145 150 155 160

cca aat att cga att aca aga cga aga gct ctt tat ctg gta gct gcc 528

Pro Asn Ile Arg Ile Thr Arg Arg Arg Ala Leu Tyr Leu Val Ala Ala

165 170 175

acg tgg ata ttc agt atc cta atg gcg ttg ccg tta ctc ttc aca acg 576

Thr Trp Ile Phe Ser Ile Leu Met Ala Leu Pro Leu Leu Phe Thr Thr

180 185 190

aga ttt ttc gaa gac caa gac ggt tta ccg aat tgt gga gaa aat tgg 624

Arg Phe Phe Glu Asp Gln Asp Gly Leu Pro Asn Cys Gly Glu Asn Trp

195 200 205

acg tat ttt gga gat tct gga gaa caa gtg aga aaa gtg tat tct tca 672

Thr Tyr Phe Gly Asp Ser Gly Glu Gln Val Arg Lys Val Tyr Ser Ser

210 215 220

atg gtc tta att cta caa tat gtt gta cct caa gca gtt tta ata ata 720

Met Val Leu Ile Leu Gln Tyr Val Val Pro Gln Ala Val Leu Ile Ile

225 230 235 240

act tac aca cat att gga att aaa atg tgg aat agt cga gta cca gga 768

Thr Tyr Thr His Ile Gly Ile Lys Met Trp Asn Ser Arg Val Pro Gly

245 250 255

atg cag aat gga gca aca aag aaa atg atc gtt gat cga cat gaa agt 816

Met Gln Asn Gly Ala Thr Lys Lys Met Ile Val Asp Arg His Glu Ser

260 265 270

gtc aaa aag ctg gtc cca atg gtg att ctc att tcg gca ctc ttc gca 864

Val Lys Lys Leu Val Pro Met Val Ile Leu Ile Ser Ala Leu Phe Ala

275 280 285

ctt tgt tgg ctt cct tta ctt ata ctg atc aac gtc att cca gaa ttc 912

Leu Cys Trp Leu Pro Leu Leu Ile Leu Ile Asn Val Ile Pro Glu Phe

290 295 300

tat cca gat atc aac agt tgg gga tat att ctg tat ttg tgg tgg ttt 960

Tyr Pro Asp Ile Asn Ser Trp Gly Tyr Ile Leu Tyr Leu Trp Trp Phe

305 310 315 320

gct cat gga ctt gcc atg tct cat tca atg gtc aac cca att atc tat 1008

Ala His Gly Leu Ala Met Ser His Ser Met Val Asn Pro Ile Ile Tyr

325 330 335

ttc att cga aat gcc cgt ttc cgt gaa gga ttc tgt ttc ttc tct tca 1056

Phe Ile Arg Asn Ala Arg Phe Arg Glu Gly Phe Cys Phe Phe Ser Ser

340 345 350

aaa ctt ctt cca tgt ata tca ttt aaa gaa ctt cgt ctt tta act gat 1104

Lys Leu Leu Pro Cys Ile Ser Phe Lys Glu Leu Arg Leu Leu Thr Asp

355 360 365

aat act agc aga agt ttt cga aac cgt tca cgg ttt tct ggt gtc ata 1152

Asn Thr Ser Arg Ser Phe Arg Asn Arg Ser Arg Phe Ser Gly Val Ile

370 375 380

aat ccg act tca agc gat gaa aaa cct gct aca tcg ctt acg aga tat 1200

Asn Pro Thr Ser Ser Asp Glu Lys Pro Ala Thr Ser Leu Thr Arg Tyr

385 390 395 400

tca cga agt gga gtc ctt gac agg caa aca tgt cgt tcg gca cgt ttc 1248

Ser Arg Ser Gly Val Leu Asp Arg Gln Thr Cys Arg Ser Ala Arg Phe

405 410 415

ttc gaa gcc cga cca ctc gtc gtc gtc cga aac aac tct gcc aat tct 1296

Phe Glu Ala Arg Pro Leu Val Val Val Arg Asn Asn Ser Ala Asn Ser

420 425 430

ctc gcg tag 1305

Leu Ala

117

434

Homo sapiens

117

Met Asp Glu Gly Gly Gly Ile Gly Ser Ser Leu Leu Ser Arg Ile Thr

1 5 10 15

Thr Thr Ala Ser Glu Ile Met Met Arg Asn Glu Pro Thr Thr Thr Glu

20 25 30

Asn Pro Ala Val Gln Glu Met Asn His Ile Tyr His Leu Thr Pro Ser

35 40 45

Met Lys Met Leu Cys Ile Leu Phe Tyr Ser Ile Leu Cys Val Cys Cys

50 55 60

Val Tyr Gly Asn Val Leu Val Ile Leu Val Ile Val Tyr Phe Lys Arg

65 70 75 80

Leu Arg Thr Ala Thr Asn Ile Leu Ile Leu Asn Leu Ala Val Ala Asp

85 90 95

Leu Leu Ile Ser Val Phe Cys Ile Pro Phe Ser Tyr Trp Gln Val Leu

100 105 110

Ile Tyr Asp Asp Gln Arg Trp Leu Phe Gly Ser Met Met Cys Ser Leu

115 120 125

Leu Ala Phe Leu Gln Ala Met Ala Val Phe Leu Ser Ala Trp Thr Leu

130 135 140

Val Val Ile Ser Phe Asp Arg Trp Met Ala Ile Met Phe Leu Leu Thr

145 150 155 160

Pro Asn Ile Arg Ile Thr Arg Arg Arg Ala Leu Tyr Leu Val Ala Ala

165 170 175

Thr Trp Ile Phe Ser Ile Leu Met Ala Leu Pro Leu Leu Phe Thr Thr

180 185 190

Arg Phe Phe Glu Asp Gln Asp Gly Leu Pro Asn Cys Gly Glu Asn Trp

195 200 205

Thr Tyr Phe Gly Asp Ser Gly Glu Gln Val Arg Lys Val Tyr Ser Ser

210 215 220

Met Val Leu Ile Leu Gln Tyr Val Val Pro Gln Ala Val Leu Ile Ile

225 230 235 240

Thr Tyr Thr His Ile Gly Ile Lys Met Trp Asn Ser Arg Val Pro Gly

245 250 255

Met Gln Asn Gly Ala Thr Lys Lys Met Ile Val Asp Arg His Glu Ser

260 265 270

Val Lys Lys Leu Val Pro Met Val Ile Leu Ile Ser Ala Leu Phe Ala

275 280 285

Leu Cys Trp Leu Pro Leu Leu Ile Leu Ile Asn Val Ile Pro Glu Phe

290 295 300

Tyr Pro Asp Ile Asn Ser Trp Gly Tyr Ile Leu Tyr Leu Trp Trp Phe

305 310 315 320

Ala His Gly Leu Ala Met Ser His Ser Met Val Asn Pro Ile Ile Tyr

325 330 335

Phe Ile Arg Asn Ala Arg Phe Arg Glu Gly Phe Cys Phe Phe Ser Ser

340 345 350

Lys Leu Leu Pro Cys Ile Ser Phe Lys Glu Leu Arg Leu Leu Thr Asp

355 360 365

Asn Thr Ser Arg Ser Phe Arg Asn Arg Ser Arg Phe Ser Gly Val Ile

370 375 380

Asn Pro Thr Ser Ser Asp Glu Lys Pro Ala Thr Ser Leu Thr Arg Tyr

385 390 395 400

Ser Arg Ser Gly Val Leu Asp Arg Gln Thr Cys Arg Ser Ala Arg Phe

405 410 415

Phe Glu Ala Arg Pro Leu Val Val Val Arg Asn Asn Ser Ala Asn Ser

420 425 430

Leu Ala

118

Xaa Gly Leu Gly Pro Arg Pro Leu Arg Phe

1 5 10

119

9

Artificial Sequence

Description of Artificial Sequence Synthetic

analog

119

Xaa Asp Val Pro Gly Val Leu Arg Phe

1 5

120

Asp Phe Asp Gly Ala Met Pro Gly Val Leu Arg Phe

1 5 10

121

Glu Ile Pro Gly Val Leu Arg Phe

1 5

122

Ser Asp Asn Phe Met Arg Phe

1 5

123

Pro Asp Asn Phe Met Arg Phe

1 5

124

0

synthetic

124

000

125

Tyr Gly Leu Gly Pro Arg Pro Leu Arg Phe

1 5 10

126

Tyr Leu Arg Phe

1

127

Ser Asp Arg Asn Phe Leu Arg Phe

1 5

128

Phe Leu Arg Phe

1

129

Phe Met Arg Phe

1

130

0

synthetic

130

000

131

Asp Pro Ser Phe Leu Arg Phe

1 5

132

0

synthetic

132

000

133

Ala Gly Pro Arg Phe Ile Arg Phe

1 5

134

0

synthetic

134

000

135

Lys Pro Asn Phe Leu Arg Tyr

1 5

136

Ala Arg Gly Pro Gln Leu Arg Leu Arg Phe

1 5 10

137

Tyr Ile Arg Phe

1

138

0

synthetic

138

000

139

Ala Gly Ala Lys Phe Ile Arg Phe

1 5

140

0

synthetic

140

000

141

Lys His Glu Tyr Leu Arg Phe

1 5

142

0

synthetic

142

000

143

Ser Pro Leu Gly Thr Met Arg Phe

1 5

144

0

synthetic

144

000

145

0

synthetic

145

000

146

0

synthetic

146

000

147

0

synthetic

147

000

148

0

synthetic

148

000

149

0

synthetic

149

000

150

Ala Glu Gly Leu Ser Ser Pro Leu Ile Arg Phe

1 5 10

151

Phe Asp Arg Asp Phe Met His Phe

1 5

152

Val Leu Arg Phe

1

153

Gly Val Leu Arg Phe

1 5

154

Gly Val Leu Arg Phe

1 5

155

Pro Gly Val Leu Arg Phe

1 5

156

Val Pro Gly Val Leu Arg Phe

1 5

157

Val Pro Gly Val Leu Arg Phe

1 5

158

Tyr Asp Val Pro Gly Val Leu Arg Phe

1 5

159

Tyr Val Pro Gly Val Leu Arg Phe

1 5

160

Xaa Val Pro Gly Val Leu Arg Phe

1 5

161

Tyr Pro Gly Val Leu Arg Phe

1 5

162

Xaa Pro Gly Val Leu Arg Phe

1 5

163

Tyr Gly Val Leu Arg Phe

1 5

164

Xaa Gly Val Leu Arg Phe

1 5

165

Lys Pro Asn Phe Ile Arg Phe

1 5

166

Ser Gln Pro Asn Phe Leu Arg Phe

1 5

167

Leu Gln Pro Asn Phe Leu Arg Phe

1 5

168

0

Artificial Sequence

Description of Artificial Sequence synthetic

analog

168

000

169

0

Artificial Sequence

Description of Artificial Sequence synthetic

analog

169

000

170

0

Artificial Sequence

Description of Artificial Sequence synthetic

analog

170

000

171

25

Artificial Sequence

SCN162

171

acgtttaaga gctctcaaat cccat 25

172

25

Artificial Sequence

SCN160

172

ccagagctca tcaaaactca agaat 25

173

31

Artificial Sequence

DEL-1850 (CEGPCR12c_F.2)

173

gccgccatgt cgaatgatct cgtgccttca g 31

174

25

Artificial Sequence

SCN189

174

ttacaattta aaactaggtg cttct 25

175

31

Artificial Sequence

SCN199

175

gccgccatga acttttcggc caccgattcg a 31

176

atg gcc cgt gca gtc aac ata tct cca ttc gct tct tat aca gtc gta 48

Met Ala Arg Ala Val Asn Ile Ser Pro Phe Ala Ser Tyr Thr Val Val

1 5 10 15

cca att acc tcg gca tgg cca ccg gac gac ttg aaa gcc gat cga gtt 96

Pro Ile Thr Ser Ala Trp Pro Pro Asp Asp Leu Lys Ala Asp Arg Val

20 25 30

caa ctt gcc agt ttc acg act gga aaa gct ctg cta gcc att gcc att 144

Gln Leu Ala Ser Phe Thr Thr Gly Lys Ala Leu Leu Ala Ile Ala Ile

35 40 45

ctt gca atg att att atg aca acg gtc ggc aat gcg ctg gtt tgc tta 192

Leu Ala Met Ile Ile Met Thr Thr Val Gly Asn Ala Leu Val Cys Leu

50 55 60

gca gtt tta ctg gta cga aag ttg aaa cat cct caa aat ttt ctt ttg 240

Ala Val Leu Leu Val Arg Lys Leu Lys His Pro Gln Asn Phe Leu Leu

65 70 75 80

gtc tca ctg gca gtg gcg gac ttt ttc gtg ggg ctc gtt gtg atg cca 288

Val Ser Leu Ala Val Ala Asp Phe Phe Val Gly Leu Val Val Met Pro

85 90 95

ctt gca ctg att gac ctt ctc ttc gat aaa tgg cca ctt gga agc acc 336

Leu Ala Leu Ile Asp Leu Leu Phe Asp Lys Trp Pro Leu Gly Ser Thr

100 105 110

atg tgt tcg gtg tac aca aca tcc gac cta acg cta tgc act gct tca 384

Met Cys Ser Val Tyr Thr Thr Ser Asp Leu Thr Leu Cys Thr Ala Ser

115 120 125

att gtg aat ctg tgt gca ata tca gtt gat aga tat ctg gtg att tca 432

Ile Val Asn Leu Cys Ala Ile Ser Val Asp Arg Tyr Leu Val Ile Ser

130 135 140

agt cca ctt cgg tat tct gca aaa cga aca act aaa cgt atc atg atg 480

Ser Pro Leu Arg Tyr Ser Ala Lys Arg Thr Thr Lys Arg Ile Met Met

145 150 155 160

tat att gcc tgt gta tgg atc atc gct gcc att gtg agc att tcg tcg 528

Tyr Ile Ala Cys Val Trp Ile Ile Ala Ala Ile Val Ser Ile Ser Ser

165 170 175

cac att atc gca aat ctt ctg aac gac ggc act tat gtc gat gac acg 576

His Ile Ile Ala Asn Leu Leu Asn Asp Gly Thr Tyr Val Asp Asp Thr

180 185 190

gga act tgt cag gtc atc cct cat ttc atc tat caa agc tat gct aca 624

Gly Thr Cys Gln Val Ile Pro His Phe Ile Tyr Gln Ser Tyr Ala Thr

195 200 205

att atc tca ttc tat gcg cca aca ttt atc atg gtc atc ttg aac atc 672

Ile Ile Ser Phe Tyr Ala Pro Thr Phe Ile Met Val Ile Leu Asn Ile

210 215 220

aaa att tgg cga gca gca aaa cga ttg gca gct caa gac agg ttg atg 720

Lys Ile Trp Arg Ala Ala Lys Arg Leu Ala Ala Gln Asp Arg Leu Met

225 230 235 240

tct cac tgt aac tct gtg gat gcc tcc gaa cgg cca cga aat gga tca 768

Ser His Cys Asn Ser Val Asp Ala Ser Glu Arg Pro Arg Asn Gly Ser

245 250 255

gct gag aca aag gat ttc ctg aat gag aaa gaa aca att gat gtt ccg 816

Ala Glu Thr Lys Asp Phe Leu Asn Glu Lys Glu Thr Ile Asp Val Pro

260 265 270

aaa aaa gag cgg gcc aat tca aca aac tcg agg ctt ttc aag ttg gaa 864

Lys Lys Glu Arg Ala Asn Ser Thr Asn Ser Arg Leu Phe Lys Leu Glu

275 280 285

cgt aaa tat ctt cat cga ccc agt gca ttc ttt tcg gct gca aaa gga 912

Arg Lys Tyr Leu His Arg Pro Ser Ala Phe Phe Ser Ala Ala Lys Gly

290 295 300

cca ttg att cgg cag acg gag aaa agt gaa tgc aaa gcc cgg aaa aca 960

Pro Leu Ile Arg Gln Thr Glu Lys Ser Glu Cys Lys Ala Arg Lys Thr

305 310 315 320

ttg ggg gtc atc atg tca gtg ttc att att tgc tgg ctc cca ttc ttc 1008

Leu Gly Val Ile Met Ser Val Phe Ile Ile Cys Trp Leu Pro Phe Phe

325 330 335

att ctt gcc ata ttc aag tct ttc ggc atg tgg atc ccg gat tgg ttg 1056

Ile Leu Ala Ile Phe Lys Ser Phe Gly Met Trp Ile Pro Asp Trp Leu

340 345 350

gat ctg cta gca ctg tgg tta ggc tac tca aat agc aca tta aat cca 1104

Asp Leu Leu Ala Leu Trp Leu Gly Tyr Ser Asn Ser Thr Leu Asn Pro

355 360 365

ttg atc tac tgc aag tac aac aaa gag ttt cga ata cca ttc cgt gaa 1152

Leu Ile Tyr Cys Lys Tyr Asn Lys Glu Phe Arg Ile Pro Phe Arg Glu

370 375 380

atg ctt gct tgt cgc tgt gct act tta cag act gta atg cga caa caa 1200

Met Leu Ala Cys Arg Cys Ala Thr Leu Gln Thr Val Met Arg Gln Gln

385 390 395 400

agc ttc acc agc cgc tac gga cct cct gtg tga 1233

Ser Phe Thr Ser Arg Tyr Gly Pro Pro Val

405 410

177

410

C. elegans

177

Met Ala Arg Ala Val Asn Ile Ser Pro Phe Ala Ser Tyr Thr Val Val

1 5 10 15

Pro Ile Thr Ser Ala Trp Pro Pro Asp Asp Leu Lys Ala Asp Arg Val

20 25 30

Gln Leu Ala Ser Phe Thr Thr Gly Lys Ala Leu Leu Ala Ile Ala Ile

35 40 45

Leu Ala Met Ile Ile Met Thr Thr Val Gly Asn Ala Leu Val Cys Leu

50 55 60

Ala Val Leu Leu Val Arg Lys Leu Lys His Pro Gln Asn Phe Leu Leu

65 70 75 80

Val Ser Leu Ala Val Ala Asp Phe Phe Val Gly Leu Val Val Met Pro

85 90 95

Leu Ala Leu Ile Asp Leu Leu Phe Asp Lys Trp Pro Leu Gly Ser Thr

100 105 110

Met Cys Ser Val Tyr Thr Thr Ser Asp Leu Thr Leu Cys Thr Ala Ser

115 120 125

Ile Val Asn Leu Cys Ala Ile Ser Val Asp Arg Tyr Leu Val Ile Ser

130 135 140

Ser Pro Leu Arg Tyr Ser Ala Lys Arg Thr Thr Lys Arg Ile Met Met

145 150 155 160

Tyr Ile Ala Cys Val Trp Ile Ile Ala Ala Ile Val Ser Ile Ser Ser

165 170 175

His Ile Ile Ala Asn Leu Leu Asn Asp Gly Thr Tyr Val Asp Asp Thr

180 185 190

Gly Thr Cys Gln Val Ile Pro His Phe Ile Tyr Gln Ser Tyr Ala Thr

195 200 205

Ile Ile Ser Phe Tyr Ala Pro Thr Phe Ile Met Val Ile Leu Asn Ile

210 215 220

Lys Ile Trp Arg Ala Ala Lys Arg Leu Ala Ala Gln Asp Arg Leu Met

225 230 235 240

Ser His Cys Asn Ser Val Asp Ala Ser Glu Arg Pro Arg Asn Gly Ser

245 250 255

Ala Glu Thr Lys Asp Phe Leu Asn Glu Lys Glu Thr Ile Asp Val Pro

260 265 270

Lys Lys Glu Arg Ala Asn Ser Thr Asn Ser Arg Leu Phe Lys Leu Glu

275 280 285

Arg Lys Tyr Leu His Arg Pro Ser Ala Phe Phe Ser Ala Ala Lys Gly

290 295 300

Pro Leu Ile Arg Gln Thr Glu Lys Ser Glu Cys Lys Ala Arg Lys Thr

305 310 315 320

Leu Gly Val Ile Met Ser Val Phe Ile Ile Cys Trp Leu Pro Phe Phe

325 330 335

Ile Leu Ala Ile Phe Lys Ser Phe Gly Met Trp Ile Pro Asp Trp Leu

340 345 350

Asp Leu Leu Ala Leu Trp Leu Gly Tyr Ser Asn Ser Thr Leu Asn Pro

355 360 365

Leu Ile Tyr Cys Lys Tyr Asn Lys Glu Phe Arg Ile Pro Phe Arg Glu

370 375 380

Met Leu Ala Cys Arg Cys Ala Thr Leu Gln Thr Val Met Arg Gln Gln

385 390 395 400

Ser Phe Thr Ser Arg Tyr Gly Pro Pro Val

405 410

178

1749

C. elegans

CEGPCR25 (Y39A3B.5)

178

atg tca acg gta cat cag gag gaa ata tgc cgg ttt cgt ggt aca aca 48

Met Ser Thr Val His Gln Glu Glu Ile Cys Arg Phe Arg Gly Thr Thr

1 5 10 15

gaa aat tac aca atc gcc gtg acg ttt ttc atg att ttt ttg cta tca 96

Glu Asn Tyr Thr Ile Ala Val Thr Phe Phe Met Ile Phe Leu Leu Ser

20 25 30

gtc gtc gga aat tcg gtg gtt ttg ata gtg att att aag caa cgt gca 144

Val Val Gly Asn Ser Val Val Leu Ile Val Ile Ile Lys Gln Arg Ala

35 40 45

atg cga tca ata acc aat ata tat tta atg aat ctg gcg gca tcg gat 192

Met Arg Ser Ile Thr Asn Ile Tyr Leu Met Asn Leu Ala Ala Ser Asp

50 55 60

atg atg tta tca gtg gtt tgt atg ccg ccg aca ctt gtc tcc atg gtt 240

Met Met Leu Ser Val Val Cys Met Pro Pro Thr Leu Val Ser Met Val

65 70 75 80

atg aat tgt tgg atg ttc ggc aat tat atg tgc aaa att ttg gct tat 288

Met Asn Cys Trp Met Phe Gly Asn Tyr Met Cys Lys Ile Leu Ala Tyr

85 90 95

ttg caa ccc gta gta gtc act gct tca gcg tac acc cta gca gta atc 336

Leu Gln Pro Val Val Val Thr Ala Ser Ala Tyr Thr Leu Ala Val Ile

100 105 110

gca ttc gag agg tac ttt gca att tgc aag ccg ctt cac tca agg att 384

Ala Phe Glu Arg Tyr Phe Ala Ile Cys Lys Pro Leu His Ser Arg Ile

115 120 125

tgg caa acc aga tcc cac gcc tac gca atg atc aca ctt gtg tgg gtg 432

Trp Gln Thr Arg Ser His Ala Tyr Ala Met Ile Thr Leu Val Trp Val

130 135 140

atc gcc att gcc gcc aat att ctg atg ctt ttt atg tac gaa caa caa 480

Ile Ala Ile Ala Ala Asn Ile Leu Met Leu Phe Met Tyr Glu Gln Gln

145 150 155 160

acg tat agc tcg aat gga tac acg tgt gct cca att cat ccg ccg att 528

Thr Tyr Ser Ser Asn Gly Tyr Thr Cys Ala Pro Ile His Pro Pro Ile

165 170 175

tat cat ttt gct tat cag gaa aat cgg aaa ttt cac tta aaa tcg ata 576

Tyr His Phe Ala Tyr Gln Glu Asn Arg Lys Phe His Leu Lys Ser Ile

180 185 190

ata tat ttt cag gta tac atg acc gtc gtc cta ctt gta atc ccg cta 624

Ile Tyr Phe Gln Val Tyr Met Thr Val Val Leu Leu Val Ile Pro Leu

195 200 205

gtt gtg atg gcg ggt ttg tac ggc aac gtc att acc tcc cta aaa tcc 672

Val Val Met Ala Gly Leu Tyr Gly Asn Val Ile Thr Ser Leu Lys Ser

210 215 220

ggc atc aaa ctg gaa atc gcc tct gtg gat ccg ccg ctc gcc acc gcc 720

Gly Ile Lys Leu Glu Ile Ala Ser Val Asp Pro Pro Leu Ala Thr Ala

225 230 235 240

aca acc aca ggt gct aaa aat tta ggc tcc cac tct gac tcg gct cac 768

Thr Thr Thr Gly Ala Lys Asn Leu Gly Ser His Ser Asp Ser Ala His

245 250 255

ctt ttg ttg aac aat gtg ctc gtc ggt agc tcg caa tta gct cgt gcc 816

Leu Leu Leu Asn Asn Val Leu Val Gly Ser Ser Gln Leu Ala Arg Ala

260 265 270

acg tcg tgc atc gcg ttg aac acg ttt tcc tgc aac aac acc act aac 864

Thr Ser Cys Ile Ala Leu Asn Thr Phe Ser Cys Asn Asn Thr Thr Asn

275 280 285

ccc ttc agt acc ctg aca ccg ccg ccg ccg att cag cag aaa aat cga 912

Pro Phe Ser Thr Leu Thr Pro Pro Pro Pro Ile Gln Gln Lys Asn Arg

290 295 300

tcg aag ccg caa ctt ctg cag ctg ccc gga aaa atc gat aat ttc gaa 960

Ser Lys Pro Gln Leu Leu Gln Leu Pro Gly Lys Ile Asp Asn Phe Glu

305 310 315 320

gag ttc cgc ctt cag tgc ctg tcc gac tgt cgt agt gat gga gtg ttg 1008

Glu Phe Arg Leu Gln Cys Leu Ser Asp Cys Arg Ser Asp Gly Val Leu

325 330 335

ttt ccc ccg cca gca att gtt gcg tcg atg acc gac gag caa aag tta 1056

Phe Pro Pro Pro Ala Ile Val Ala Ser Met Thr Asp Glu Gln Lys Leu

340 345 350

tcg ttc tgg aat aag ctg tcg aac aag ctg act ttt agt cag caa gat 1104

Ser Phe Trp Asn Lys Leu Ser Asn Lys Leu Thr Phe Ser Gln Gln Asp

355 360 365

aaa acc gtg caa cac cca aac ttt ggg cat cgc aaa tcc gac aca tca 1152

Lys Thr Val Gln His Pro Asn Phe Gly His Arg Lys Ser Asp Thr Ser

370 375 380

att tgc ctc gaa aat cct agt tta agg tct acg cac act cag aaa agt 1200

Ile Cys Leu Glu Asn Pro Ser Leu Arg Ser Thr His Thr Gln Lys Ser

385 390 395 400

gca atg gca aag caa aga gtg att aaa atg ctc att gtt gtc gta att 1248

Ala Met Ala Lys Gln Arg Val Ile Lys Met Leu Ile Val Val Val Ile

405 410 415

atc ttt ttc tgt tgt tgg acg cct tcc tac atc tgg tgg ttg tta ttg 1296

Ile Phe Phe Cys Cys Trp Thr Pro Ser Tyr Ile Trp Trp Leu Leu Leu

420 425 430

atc gcg gga gac tcg ttt caa agc ctc aac tta tct gtc tgg aac agc 1344

Ile Ala Gly Asp Ser Phe Gln Ser Leu Asn Leu Ser Val Trp Asn Ser

435 440 445

gat atc aac aca ttc atc act ctt ctt acc tat att tct tca tgc acc 1392

Asp Ile Asn Thr Phe Ile Thr Leu Leu Thr Tyr Ile Ser Ser Cys Thr

450 455 460

aat ccc atc aca tat tgc ttc ctg aac aaa aaa ttt agg aat gcg gtg 1440

Asn Pro Ile Thr Tyr Cys Phe Leu Asn Lys Lys Phe Arg Asn Ala Val

465 470 475 480

tat gca aca ttt ggc agg aag aaa aat atg cga cat cat ttt cag aag 1488

Tyr Ala Thr Phe Gly Arg Lys Lys Asn Met Arg His His Phe Gln Lys

485 490 495

gta tat ttt gat att ttt gaa tta ttg ata ttt ttt aaa atc aat tat 1536

Val Tyr Phe Asp Ile Phe Glu Leu Leu Ile Phe Phe Lys Ile Asn Tyr

500 505 510

caa aaa tca ata aaa tct ccg gtt tca gtt ttt tct aac tat ctg ttt 1584

Gln Lys Ser Ile Lys Ser Pro Val Ser Val Phe Ser Asn Tyr Leu Phe

515 520 525

ttc ggc ttt tcg gcg ccg cta att tct gtt aac ctt agt ttg att ttg 1632

Phe Gly Phe Ser Ala Pro Leu Ile Ser Val Asn Leu Ser Leu Ile Leu

530 535 540

ttc agg tct aca ttc cgg tca acg gcg gaa cta att aca cta aca aag 1680

Phe Arg Ser Thr Phe Arg Ser Thr Ala Glu Leu Ile Thr Leu Thr Lys

545 550 555 560

gag agc cga gac aaa tta tta aca ggt act aac aca cac aaa ttt gta 1728

Glu Ser Arg Asp Lys Leu Leu Thr Gly Thr Asn Thr His Lys Phe Val

565 570 575

gtg att tcg ctt ttt gtc tag 1749

Val Ile Ser Leu Phe Val

580

179

582

C. elegans

179

Met Ser Thr Val His Gln Glu Glu Ile Cys Arg Phe Arg Gly Thr Thr

1 5 10 15

Glu Asn Tyr Thr Ile Ala Val Thr Phe Phe Met Ile Phe Leu Leu Ser

20 25 30

Val Val Gly Asn Ser Val Val Leu Ile Val Ile Ile Lys Gln Arg Ala

35 40 45

Met Arg Ser Ile Thr Asn Ile Tyr Leu Met Asn Leu Ala Ala Ser Asp

50 55 60

Met Met Leu Ser Val Val Cys Met Pro Pro Thr Leu Val Ser Met Val

65 70 75 80

Met Asn Cys Trp Met Phe Gly Asn Tyr Met Cys Lys Ile Leu Ala Tyr

85 90 95

Leu Gln Pro Val Val Val Thr Ala Ser Ala Tyr Thr Leu Ala Val Ile

100 105 110

Ala Phe Glu Arg Tyr Phe Ala Ile Cys Lys Pro Leu His Ser Arg Ile

115 120 125

Trp Gln Thr Arg Ser His Ala Tyr Ala Met Ile Thr Leu Val Trp Val

130 135 140

Ile Ala Ile Ala Ala Asn Ile Leu Met Leu Phe Met Tyr Glu Gln Gln

145 150 155 160

Thr Tyr Ser Ser Asn Gly Tyr Thr Cys Ala Pro Ile His Pro Pro Ile

165 170 175

Tyr His Phe Ala Tyr Gln Glu Asn Arg Lys Phe His Leu Lys Ser Ile

180 185 190

Ile Tyr Phe Gln Val Tyr Met Thr Val Val Leu Leu Val Ile Pro Leu

195 200 205

Val Val Met Ala Gly Leu Tyr Gly Asn Val Ile Thr Ser Leu Lys Ser

210 215 220

Gly Ile Lys Leu Glu Ile Ala Ser Val Asp Pro Pro Leu Ala Thr Ala

225 230 235 240

Thr Thr Thr Gly Ala Lys Asn Leu Gly Ser His Ser Asp Ser Ala His

245 250 255

Leu Leu Leu Asn Asn Val Leu Val Gly Ser Ser Gln Leu Ala Arg Ala

260 265 270

Thr Ser Cys Ile Ala Leu Asn Thr Phe Ser Cys Asn Asn Thr Thr Asn

275 280 285

Pro Phe Ser Thr Leu Thr Pro Pro Pro Pro Ile Gln Gln Lys Asn Arg

290 295 300

Ser Lys Pro Gln Leu Leu Gln Leu Pro Gly Lys Ile Asp Asn Phe Glu

305 310 315 320

Glu Phe Arg Leu Gln Cys Leu Ser Asp Cys Arg Ser Asp Gly Val Leu

325 330 335

Phe Pro Pro Pro Ala Ile Val Ala Ser Met Thr Asp Glu Gln Lys Leu

340 345 350

Ser Phe Trp Asn Lys Leu Ser Asn Lys Leu Thr Phe Ser Gln Gln Asp

355 360 365

Lys Thr Val Gln His Pro Asn Phe Gly His Arg Lys Ser Asp Thr Ser

370 375 380

Ile Cys Leu Glu Asn Pro Ser Leu Arg Ser Thr His Thr Gln Lys Ser

385 390 395 400

Ala Met Ala Lys Gln Arg Val Ile Lys Met Leu Ile Val Val Val Ile

405 410 415

Ile Phe Phe Cys Cys Trp Thr Pro Ser Tyr Ile Trp Trp Leu Leu Leu

420 425 430

Ile Ala Gly Asp Ser Phe Gln Ser Leu Asn Leu Ser Val Trp Asn Ser

435 440 445

Asp Ile Asn Thr Phe Ile Thr Leu Leu Thr Tyr Ile Ser Ser Cys Thr

450 455 460

Asn Pro Ile Thr Tyr Cys Phe Leu Asn Lys Lys Phe Arg Asn Ala Val

465 470 475 480

Tyr Ala Thr Phe Gly Arg Lys Lys Asn Met Arg His His Phe Gln Lys

485 490 495

Val Tyr Phe Asp Ile Phe Glu Leu Leu Ile Phe Phe Lys Ile Asn Tyr

500 505 510

Gln Lys Ser Ile Lys Ser Pro Val Ser Val Phe Ser Asn Tyr Leu Phe

515 520 525

Phe Gly Phe Ser Ala Pro Leu Ile Ser Val Asn Leu Ser Leu Ile Leu

530 535 540

Phe Arg Ser Thr Phe Arg Ser Thr Ala Glu Leu Ile Thr Leu Thr Lys

545 550 555 560

Glu Ser Arg Asp Lys Leu Leu Thr Gly Thr Asn Thr His Lys Phe Val

565 570 575

Val Ile Ser Leu Phe Val

580

180

9

Artificial Sequence

Description of Artificial Sequence synthetic

180

Phe Asp Asp Tyr Gly His Leu Arg Pro

1 5