Patent Application: US-99800392-A

Abstract:
polynucleotide sequences encoding novel cadherin - related polypeptides , designated protocadherins , and variants thereof are provided by the invention as well as methods and materials for the recombinant production of the same . antibody substances specific for protocadherins are also disclosed as useful for modulating the natural binding and / or regulatory activities of the protocadherins .

Description:
the present invention is illustrated by the following examples wherein examples 1 , 2 and 3 describe the isolation by pcr of protocadherin polynucleotide sequences of the invention . example 4 presents the construction of expression plasmids including polynucleotides encoding protocadherin - 42 or protocadherin - 43 and the transfection of l cells with the plasmids . the generation of antibodies to protocadherin - 42 and protocadherin - 43 is described in example 5 . example 6 presents the results of immunoassays of transfected l cells for the expression of protocadherin - 42 or protocadherin - 43 . example 7 describes the cell aggregation properties of transfected l cells . the calcium - binding properties of pc43 are described in example 8 . the results of assays of various tissues and cell lines for the expression of protocadherin - 42 and protocadherin - 43 by northern blot , western blot and in situ hybridization are respectively presented in examples 9 , 10 and 11 . the polymerase chain reaction ( pcr ) was used to isolate novel rat cdna fragments encoding cadherin - related polypeptides . two regions of conserved amino acid sequence , one from the middle of the third cadherin extracellular subdomain ( ec - 3 ) and the other from the c - terminus of the fourth extracellular subdomain ( ec - 4 ), were identified by comparison of the published amino acid sequences for l - cam ( gallin et al ., supra ), e - cadherin ( nagafuchi et al ., supra ), mouse p - cadherin ( nose et al ., supra ), uvomorulin ( ringwald et al ., supra ), chicken n - cadherin ( hatta et al ., supra ), mouse n - cadherin [ miyatani et al ., science , 245 : 631 - 635 ( 1989 )] and human p - cadherin [ shimoyama et al ., j . cell . biol ., 109 : 1787 - 1794 ( 1989 )], and the corresponding degenerate oligonucleotides respectively set out below in iupac nomenclature were designed for use as pcr primers . the degenerate oligonucleotides were synthesized using an applied biosystems model 380b dna synthesizer ( foster city , calif .). pcr was carried out in a manner similar to that described in suzuki et al ., cell regulation , 2 : 261 - 270 ( 1991 ) on a rat brain cdna preparation . total rna was prepared from rat brain by the guanidium isothiocyanate / cesium chloride method described in maniatis et al ., pp . 196 in molecular cloning : a laboratory manual , cold spring harbor , n . y . : cold spring harbor laboratory ( 1982 ). brain poly ( a ) + rnas were then isolated using a fasttrack ® kit ( invitrogen , san diego , calif .) and cdna was prepared using a cdna synthesis kit ( boehringer mannheim biochemicals , indianapolis , ind .). the pcr reaction was initiated by adding 2 . 5 units of taq dna polymerase ( boehringer mannheim biochemicals ) to 100 ng template cdna and 10 μg of each primer , after which 35 reaction cycles of denaturation at 94 ° c . for 1 . 5 minutes , annealing at 45 ° c . for 2 minutes , and polymerization at 72 ° c . for 3 minutes were carried out . two major bands of about 450 base pairs ( bp ) and 130 bp in size were found when the products of the pcr reaction were subjected to agarose gel electrophoresis . the 450 bp band corresponded to the expected length between the two primer sites corresponding to the middle of the third cadherin extracellular subdomain ( ec - 3 ) and the carboxyl terminus of the fourth cadherin extracellular subdomain ( ec - 4 ), but the 130 bp band could not be predicted from any of the previously identified cadherin sequences . the 450 bp and 130 bp bands were extracted by a freezing and thawing method . the resulting fragments were phosphorylated at the 5 &# 39 ; end with t4 polynucleotide kinase and subcloned by a blunt - end ligation into the sma i site of m13mp18 ( boehringer mannheim biochemicals ) in a blunt end ligation for sequence analysis . sequencing of the fragments was carried out by the dideoxynucleotide chain termination method using a sequenase kit ( united states biochemicals , cleveland , ohio ). dna and amino acid sequence were analyzed using the beckman microgenie program ( fullerton , calif .). nineteen novel partial cdna clones were isolated . the dna and deduced amino acid sequences of the clones ( including sequences corresponding to the pcr primers ) are set out as follows : rat - 123 ( seq id nos : 3 and 4 , respectively ), rat - 212 ( seq id nos : 5 and 6 ), rat - 214 ( seq id nos : 7 and 8 ), rat - 216 ( seq id nos : 9 and 10 ), rat - 218 ( seq id nos : 11 and 12 ), rat - 224 ( seq id nos : 13 and 14 ), rat - 312 ( seq id nos : 15 and 16 ), rat - 313 ( seq id nos : 17 and 18 ), rat - 314 ( seq id nos : 19 and 20 ), rat - 315 ( seq id nos : 21 and 22 ), rat - 316 ( seq id nos : 23 and 24 ), rat - 317 ( seq id nos : 25 and 26 ), rat - 321 ( seq id nos : 27 and 28 ), rat - 323 ( seq id nos : 29 and 30 ), rat - 336 ( seq id nos : 31 and 32 ), rat - 352 ( seq id nos : 33 and 34 ), rat - 411 ( seq id nos : 35 and 36 ), rat - 413 ( seq id nos : 37 and 38 ), and rat - 551 ( seq id nos : 39 and 40 ). the deduced amino acid sequences of the cdna clones are homologous to , but distinct from the known cadherins . the cadherins described thus far have highly conserved , short amino acid sequences in the third extracellular subdomain ( ec - 3 ) including the consensus sequence d - y - e or d - f - e located at the middle region of the subdomain and the consensus sequence d - x - n - e - x - p - x - f ( seq id no : 41 ) or d - x - d - e - x - p - x - f ( seq id no : 42 ) at its end ( hatta et al ., supra ), while the corresponding sequences of other subdomains , except for the fifth extracellular subdomain ( ec - 5 ), are d - r - e and d - x - n - d - n - x - p - x - f ( seq id no : 43 ), respectively . in contrast , the deduced amino acid sequences of the new clones that correspond to cadherin extracellular subdomains include the sequence d - y - e or d - f - e at one end , but have the sequence d - x - n - d - n - x - p - x - f ( seq id no : 43 ) instead of d - x - n - e - x - p - x - f ( seq id no : 41 ) or d - x - d - e - x - p - x - f ( seq id no : 42 ), at the other end . the polypeptides encoded by the partial clones are homologous to previously identified cadherins but did not show significant homology to any other sequences in genbank . therefore , the partial cdnas appear to comprise a new subclass of cadherin - related molecules . various cdna fragments structurally similar to the rat cdnas described in example 1 were isolated from human , mouse , and xenopus brain cdna preparations and from drosophila and c . elegans whole body cdna preparations by pcr using primers 1 and 2 as described in example 1 . the dna and deduced amino acid sequences of the resulting pcr fragments ( including sequences corresponding to the pcr primers ) are set out as follows : mouse - 321 ( seq id nos : 44 and 45 ), mouse - 322 ( seq id nos : 46 and 47 ), mouse - 324 ( seq id nos : 48 and 49 ), mouse - 326 ( seq id nos : 50 and 51 ), human - 11 ( seq id nos : 52 and 53 ), human - 13 ( seq id nos : 54 and 55 ), human - 21 ( seq id nos : 56 and 57 ), human - 24 ( seq id nos : 58 and 59 ), human - 32 ( seq id nos : 60 and 61 ), human - 42 ( seq id nos : 62 and 63 ), human - 43 ( seq id nos : 64 and 65 ), human - 212 ( seq id nos : 66 and 67 ), human - 213 ( seq id nos : 68 and 69 ), human - 215 ( seq id nos : 70 and 71 ), human - 223 ( seq id nos : 72 and 73 ), human - 410 ( seq id nos : 74 and 75 ), human - 443 ( seq id nos : 76 and 77 ), xenopus - 21 ( seq id nos : 78 and 79 ), xenopus - 23 ( seq id nos : 80 and 81 ), xenopus - 25 ( seq id nos : 82 and 83 ), xenopus - 31 ( seq id nos : 84 and 85 ), drosophila - 12 ( seq id nos : 86 and 87 ), drosophila - 13 ( seq id nos : 88 and 89 ), drosophila - 14 ( seq id nos : 90 and 91 ) and c . elegans - 41 ( seq id nos : 92 and 93 ). comparison of the deduced amino acid sequences indicates significant similarity between sets of these clones . in particular , there are three sets of clones that appear to be cross - species homologues : rat - 218 , mouse - 322 and human - 43 ; rat - 314 , mouse - 321 and human - 11 ; and mouse - 326 and human - 42 . to ascertain the complete structure of the new proteins defined by the pcr products , two full length human cdnas corresponding to the partial cdnas human - 42 and human - 43 were isolated . a human fetal brain cdna library ( stratagene , la jolla , calif .) in the λzapii vector was screened by the plaque hybridization method [ described in ausubel et al ., eds ., current protocols in molecular biology , sections 6 . 1 . 1 to 6 . 1 . 4 and 6 . 2 . 1 to 6 . 2 . 3 , john wiley & amp ; sons , new york ( 1987 )] with 32 p - labelled human - 42 and human - 43 dna fragments . the positive clones were plaque - purified and , using a helper virus , the inserts were cut out by an in vivo excision method in the form of a bluescript sk (+) plasmid . the insert sequences were then subcloned into the m13 vector ( boehringer mannheim , biochemicals ) for sequencing . several overlapping cdna clones were isolated with each probe including two cdnas which contained the putative entire coding sequences of two novel proteins designated protocadherin - 42 ( pc42 ) and protocadherin - 43 ( pc43 ). the dna and deduced amino acid sequences of pc42 are set out in seq id nos : 94 and 95 , respectively , while the dna and deduced amino acid sequences of pc43 are set out in seq id nos : 96 and 97 , respectively . comparison of the full length cdna sequences of pc42 and pc43 to the sequences of the various dna fragments originally obtained by pcr reveals that mouse - 326 and human - 42 correspond to a portion of the fourth extracellular subdomain ( ec - 4 ) of pc42 , and rat - 314 , mouse - 321 , and human - 11 correspond to a portion of the third extracellular subdomain ( ec - 3 ) of pc43 and rat - 218 , mouse - 322 and human - 43 correspond to a portion of the fifth extracellular domain ( ec - 5 ) of pc43 . the overall structures of pc42 and pc43 are similar to that of typical cadherins but also have distinct features . both protocadherin cdna sequences contain putative translation initiation sites and translated amino acid sequences start with typical signal sequences , but the clones lack the prosequences that are present in all known cadherin precursors . the cdnas encode proteins having a large n - terminal extracellular domain and a relatively short c - terminal cytoplasmic domain connected by a transmembrane sequence . the extracellular domains of pc42 and pc43 are different in length and pc42 contains seven subdomains that closely resemble the typical cadherin extracellular subdomain while pc43 has six such subdomains . the sizes of the protocadherin cytoplasmic domains are similar to those of typical cadherins , but the sequences do not show any significant homology with those of known cadherins or cadherin - related proteins . amino acid identity determinations between extracellular subdomains of human pc42 and pc43 , and of mouse n - cadherin ( seq id no : 98 ) ( presented as an example of a &# 34 ; typical &# 34 ; cadherin ) and the eighteenth extracellular subdomain of drosophila fat tumor suppressor ( ec - 18 , seq id no : 99 ) ( the eighteenth extracellular subdomain of fat is a prototypical fat subdomain ) are presented in table 1 below , wherein , for example , &# 34 ; n - ec - 1 × pc42 &# 34 ; indicates that the first extracellular subdomain of n - cadherin was compared to the extracellular subdomain of pc42 indicated on the horizonal axis . table 1______________________________________ ec - 1 ec - 2 ec - 3 ec - 4 ec - 5 ec - 6 ec - 7______________________________________n - ec - 1 × pc42 20 27 26 26 31 29 17n - ec - 1 × pc43 31 23 23 26 31 24n - ec - 2 × pc42 28 30 32 30 37 31 19n - ec - 2 × pc43 30 28 30 36 29 30n - ec - 3 × pc42 21 26 30 29 31 30 22n - ec - 3 × pc43 25 18 26 28 28 25n - ec - 4 × pc42 28 28 26 25 29 27 17n - ec - 4 × pc43 21 25 28 28 29 24n - ec - 5 × pc42 24 21 25 24 24 19 12n - ec - 5 × pc43 15 21 20 20 25 16fat ec - 18 × pc42 22 35 32 34 42 35 19fat ec - 18 × pc43 32 30 36 36 33 29______________________________________ the amino acid identity values between the extracellular subdomains of pc42 and pc43 , and n - cadherin ec - 1 through ec - 5 and drosophila fat ec - 18 are mostly less than 40 %. these identity values are comparable to the values between the subdomains of other cadherin subclasses . however , higher identity values indicate that pc42 and pc43 are more closely related to fat than to n - cadherin . amino acid identity determinations between extracellular subdomains of human pc42 and pc43 are presented in table 2 below . table 2______________________________________pc42pc43 ec - 1 ec - 2 ec - 3 ec - 4 ec - 5 ec - 6 ec - 7______________________________________ec - 1 33 27 29 26 25 26 25ec - 2 26 38 29 33 34 28 21ec - 3 26 32 41 30 32 31 22ec - 4 25 34 30 41 39 31 18ec - 5 23 32 29 27 36 34 16ec - 6 25 25 26 25 28 23 26______________________________________ the identity values between respective ec - 1 , ec - 2 , ec - 3 , ec - 4 , ec - 5 subdomains and the last subdomains of pc42 and pc43 are generally higher values than values obtained for comparisons of the protocadherins to n - cadherin . these results suggest that pc42 and pc43 are more closely related to one another than they are to classic cadherins . fig1 a - c presents an alignment of the deduced amino acid sequences of the extracellular subdomains of pc42 ( ec - 1 through ec - 7 ) ( amino acids 42 - 818 of seq id no : 95 ), pc43 ( ec - 1 through ec - 6 ) ( amino acids 29 - 688 of seq id no : 97 ), mouse n - cadherin ( ec - 1 through ec - 5 ) ( amino acids 1 - 557 of seq id no : 98 ) and drosophila fat ec - 18 ( seq id no : 99 ). a sequence on a line in fig1 a continues on the same line in fig1 b and 1c . gaps were introduced to maximize homology . in fig1 a - 1c , the position at which an amino acid appears in a seq id no is indicated in parenthesis . for example , in fig1 a the first amino acid of ec1 of protocadherin - 43 is an alanine which appears at position 29 in seq id no : 97 and the last amino acid of the protocadherin - 43 ec1 appearing in fig1 a is an alanine which appears at position 63 in seq id no : 97 . the amino acid residues described by capital letters in the &# 34 ; motif &# 34 ; line are present in more than half of the subdomains of n - cadherin , pc42 , pc43 and drosophila fat . the amino acid residues described by small letters in the motif line are less well conserved in human pc42 , pc43 , and drosophila fat . fig1 a - c shows that many amino acids characteristic of other cadherin extracellular domain repeats are conserved in the pc42 and pc43 sequences , including the cadherin sequence motifs dxd , dre and dxndnxpxf ( seq id no : 43 ), two glycine residues , and one glutamic acid residue . additionally , pc42 and pc43 share unique features in comparison to n - cadherin . more amino acids at specific sites are conserved between pc42 and pc43 , such as the dxdxgxn ( seq id no : 100 ) protocadherin sequence motif near the amino terminus of the pc42 and pc43 subdomains and the axdxgxp ( seq id no : 101 ) sequence motif near the carboxyl terminus of the subdomains . additionally , both protocadherins share regions that do not show significant homology with the typical cadherin motif ( of n - cadherin ) near the carboxyl terminus of ec - 1 , in the middle of ec - 2 and ec - 4 , and at the carboxyl terminus of the last repeat . a cysteine residue is located at a similar position in the middle of ec - 4 of pc42 and pc43 . in general , the extracellular subdomains of pc42 and pc43 are more similar to ec - 18 of fat than the extracellular subdomains of n - cadherin . sequence analysis of various overlapping protocadherin cdna clones revealed that some clones contained unique sequences at the 3 &# 39 ; end , although the 5 &# 39 ; end sequences were identical to other clones . the sequences forming the boundaries of the 3 &# 39 ; end regions are consistent with the consensus sequence of mrna splicing , suggesting that these clones may correspond to alternatively spliced mrnas . the dna and deduced amino acid sequences of one possible product of alternative splicing of pc42 mrna are set out in seq id nos : 102 and 103 . the dna and deduced amino acid sequences of two possible products of alternative splicing of pc43 mrna are respectively presented in seq id no : 104 and 105 , and seq id nos : 106 and 107 . the full length human cdnas encoding pc42 and pc43 were expressed in l cells ( atcc ccl 1 ) using the prc / rsv expression vector ( invitrogen , san diego , calif .). the cdnas were isolated from the bluescript sk (+) clones described in example 2 by digestion with sspi followed by blunt - ending with dna polymerase and digestion with xbai ( for pc42 ), or by double digestion with spei and ecorv ( for pc43 ). the prc / rsv expression vector was digested with hindiii , followed by blunt - ending and re - digestion with xbai for insertion of pc42 sequences , or by digested with xbai followed by blunt - ending and re - digestion with spei for insertion of pc43 sequences . the isolated protocadherin dnas were ligated into the linearized prc / rsv vector . the resulting pc42 expression plasmid designated prc / rsv - pc42 ( atcc 69162 ) and pc43 expression plasmid designated prc / rsv - pc43 ( atcc 69163 ) were purified by csci gradient centrifugation and transfected into l cells by a ca - phosphate method . the pc42 and pc43 transfectants were morphologically similar to the parental cells . northern blot analysis of l cells transfected with pc42 or pc43 dna sequences showed that the transfected cells expressed mrnas of a size expected to encode the particular protocadherin . rabbit polyclonal antibodies specific for pc42 and pc43 were generated as well as a mouse monoclonal antibody specific for pc43 . dna sequences encoding portions of the extracellular domain of pc42 and pc43 were each fused to a maltose binding protein - encoding sequence and expressed in bacteria . specifically , dnas corresponding to ec - 4 through ec - 7 of pc42 and ec - 3 through ec - 5 of pc43 were prepared by pcr and subcloned in the correct reading frame into the multicloning site of the pmal expression vector ( new england biolabs , beverly , mass .) which contains sequences encoding maltose binding protein immediately upstream of the multicloning site . the resulting plasmids were then introduced into e . coli nm522 cells ( invitrogen , san diego , calif .) by a single step transformation method . expression of the fusion proteins was induced by the addition of iptg and the fusion proteins were purified from cell extracts by amylose resin affinity chromatography ( new england biolabs ) as described by the manufacturer . the fusion proteins were used for the immunization of rabbits without further purification . polyclonal antibodies were prepared in rabbits by immunization at four subcutaneous sites with 500 μg of purified fusion protein in freund &# 39 ; s complete adjuvant . subsequent immunizations with 100 μg of the fusion protein were in freund &# 39 ; s incomplete adjuvant . immune sera was passed through sepharose coupled to maltose binding protein ( new england biolabs ) and polyclonal antibodies were purified from immune sera using sepharose affinity columns prepared by reaction of the purified fusion protein with cnbr sepharose ( pharmacia ). reactivity of the polyclonal sera with purified pc42 fusion protein and pc42 transfected cell extracts ( described in example 4 ) was confirmed . the pc43 fusion protein ( containing the ec - 3 through ec - 5 subdomains of pc43 ) was used to generate monoclonal antibodies in mice according to the method of kennett , methods in enzymol ., 58 : 345 - 359 ( 1978 ). briefly , mice were immunized with the pc43 fusion protein ( 100 μg ) at two subcutaneous sites . the spleen from the highest titer mouse was fused to the ns1 myeloma cell line . the resulting hybridoma supernatants were screened in a elisa assay for reactivity with the pc43 fusion protein and with maltose binding protein . the fusion wells with the highest reactivity to the pc43 extracellular domains were subcloned . the hybridoma cell line designated 3812c ( atcc hb 11207 ) produced a igg 1 subtype monoclonal antibody specific for pc43 . reactivity of the monoclonal antibody produced by hybridoma cell line 3812c to pc43 was confirmed by immunoblotting the pc43 l cell transfectants described in example 4 . the 3812c monoclonal antibody is specific for human pc43 . l cells transfected with dna sequences encoding pc42 and pc43 as prepared in example 4 were assayed for expression of the protocadherins by immunoblot and by immunofluorescence microscopy . cell extracts of pc42 and pc43 transfectants were subjected to sds - page and then blotted electrophoretically onto a pvdf membrane ( millipore , bedford , mass .). the membranes were incubated with 5 % skim milk in tris - buffered saline ( tbs ) for two hours and then respectively with either pc42 polyclonal sera or pc43 monoclonal antibody for one hour . the membranes were washed three times ( for 5 minutes each wash ) with tbs containing 0 . 05 % tween 20 and respectively incubated with alkaline phosphatase - conjugated anti - rabbit igg antibody or anti - mouse igg antibody ( promega , madison , wis .) in the same buffer for one hour . after washing the membranes with tbs containing 0 . 05 % tween 20 , reactive bands were visualized by using western blue solution ( promega ). anti - pc42 polyclonal antibodies stained a band of about 170 kda molecular weight in pc42 transfected cells , but not parental l cells . the pc43 - specific monoclonal antibody ( 3812c ) and polyclonal antibodies stained two adjacent bands of about 150 kda molecular weight in pc43 transfected cells . the pc43 antibodies did not stain bands in parental l - cells . the molecular weights indicated by the staining of bands by the pc42 and pc43 antibodies are significantly larger than the molecular weights predicted from the deduced amino acid sequences . this discrepancy in molecular weight is common among various cadherin - related proteins and may be attributable to the glycosylation and / or cadherin specific structural properties . the pc42 antibody also stained smaller bands , which may be proteolytic degradation products . when transfected cells were trypsinized and cell extracts were prepared , run on sds / page and immunoblotted with the appropriate antibody , the pc42 and pc43 polypeptides expressed by the transfected cells were found to be highly sensitive to proteolysis and were easily digested by 0 . 01 % trypsin treatment . in contrast to the classic cadherins , however , these proteins were not protected from the digestion in the presence of 1 - 5 mm ca 2 + . transfected cells were grown on a cover slip precoated with fibronectin and were fixed with 4 % paraformaldehyde for 5 minutes at room temperature or with cold methanol on ice for 10 minutes followed by 4 % paraformaldehyde fixation . after washing with tbs , the cells were incubated with tbs containing 1 % bsa for 30 minutes and then with anti - pc42 polyclonal antibody or anti - pc43 monoclonal antibody in tbs containing 1 % bsa for 1 hour at room temperature . cover slips were then washed with tbs containing 0 . 01 % bsa and respectively incubated with fitc - conjugated anti - rabbit antibody or anti - mouse antibody ( cappel , durham , n . c .) for 60 minutes at room temperature . the cells were washed again with tbs containing 0 . 01 % bsa and subjected to fluorescence microscopy . both pc42 - specific and pc43 - specific polyclonal antibodies stained the cell periphery of transfected cells expressing the protocadherin proteins , mainly at the cell - cell contact sites . the antibodies did not stain the parent l cells , nor did rabbit preimmune sera stain the pc42 and pc43 transfectants . the cell aggregation properties of the transfected l cells expressing protocadherin proteins were examined . transfected l cells were cultured in dulbecco &# 39 ; s modified eagles medium ( dmem ) ( gibco , grand island , n . y .) supplemented with 10 % fetal bovine serum at 37 ° c . in 5 % co 2 . cells grown near confluence were treated with 0 . 01 % trypsin in the presence of 1 mm egta for 25 minutes on a rotary shaker at 37 ° c . and collected by centrifugation . the cells were washed three times with ca 2 + free hepes - buffered saline ( hbs ) after adding soybean trypsin inhibitor , and were resuspended in hbs containing 1 % bsa . the cell aggregation assay [ urushihara et al ., dev . biol ., 70 : 206 - 216 ( 1979 )] was performed by incubating the resuspended cells in a 1 : 1 mixture of dmem and hbs containing 1 % bsa , 2 mm cacl 2 and 20 μg / ml of deoxyribonucelease on a rotary shaker at 37 ° c . for 30 minutes to 6 hours . the pc42 and pc43 transfectants did not show any significant cell aggregation activity during periods of incubation less than 1 hour . this is in contrast to the cell aggregation that occurs with classic cadherins in similar experiments ( nagafuchi et al ., supra , and hatta et al ., supra ). however , prolonged incubation of transfected cells ( more than 1 - 2 hours ) resulted in gradual re - aggregation of the cells into small aggregates . similar results were obtained when single cell suspensions of transfected cells were prepared by trypsin treatment in the presence of ca 2 + . no re - aggregation was observed under the same conditions when untransfected l cells or l cells transfected with prc / rsv vector alone were tested . the procedures of maruyama et al ., j . biochem ., 95 : 511 - 519 ( 1984 ) were used to determine the calcium binding properties of pc43 by western blot analysis in the presence or absence of calcium - 45 . the pc43 fusion protein described in example 5 containing pc43 subdomains ec - 3 through ec - 5 was compared to the calcium binding protein calmodulin . samples of purified pc43 fusion protein were run on sds / page and electrophoretically transferred to pvdf membrane . binding of the 45 ca 2 + to the pc43 fusion protein was detected by autoradiography and was determined to be nearly as efficient as binding of 45 ca 2 + to calmodulin . in contrast , there was no binding of calcium to purified maltose binding protein lacking the pc43 extracellular domain . the pc43 subdomains ec - 3 through ec - 5 contain sequences highly homologous to the putative ca 2 ± binding motifs found in e - cadherin . [ see , ringwald et al ., embo j ., 6 : 3647 - 3653 .] the expression of mrna encoding pc42 and pc43 was assayed in various tissues and cell lines by northern blot . total rnas were prepared by the guanidium isothiocyanate method and poly ( a )+ rnas were isolated using a fasttrack kit ( invitrogen ). rna preparations were electrophoresed in a 0 . 8 % agarose gel under denaturing conditions and transferred onto a nitrocellulose filter using a capillary method . northern blot analyses were performed according to the method of thomas , proc . natl . acad . sci . usa , 77 : 5201 - 5205 ( 1980 ). the final wash was in 0 . 2 × standard saline titrate containing 0 . 1 % sodium dodecyl sulfate at 65 ° c . for 10 minutes . total mrna preparations of rat tissues including brain , heart , liver , lung , skin , kidney and muscle were separated electrophoretically under denaturing conditions ( 10 μg mrna / lane ) and transferred onto nitrocellulose filters . the filters were hybridized with 32 p - labelled cdna fragments mouse - 326 ( which corresponds to ec - 4 of human pc42 ) and rat - 218 ( which corresponds to ec - 5 of human pc43 ). the mrnas of both protocadherins were highly expressed in brain . the pc42 probe detected a major band of 7 kb and a minor band of 4 kb in size , possibly representing the products of alternative splicing . the pc43 probe hybridized to a major band of 5 kb in size and with minor bands of smaller sizes . to examine the developmental regulation of mrna expression of the protocadherins , brain mrna from rats at embryonic days 17 and 20 , neonatal days 5 and 11 and from adult rats was prepared and subjected to northern blot analysis as described above for other rat tissues . β - actin was used as an internal standard . mrna levels for pc42 and pc43 proteins increased during embryonic development of the brain as compared with β - actin expression . several neuronal and glial cell lines ( including human sk - n - sh neuroblastoma , human u251 glioma , and mouse neuro - 2a neuroblastoma cell lines ) were assayed by northern blot using 32 p - labelled for expression of pc42 and pc43 mrna . human cell lines were probed with human - 42 ( which corresponds to ec - 4 of human pc42 ) and human - 43 ( which corresponds to ec - 5 of human pc43 ) cdna fragments while the mouse cell line was probed with mouse - 326 ( which corresponds to ec - 4 of human pc42 ) and rat - 322 ( which corresponds to ec - 5 of human pc43 ) cdna fragments . sk - n - sh human neuroblastoma cells and u251 human glioma cells were found to express pc43 mrna and neuro - 2a mouse neuroblastoma cells were found to express pc42 mrna . expression of pc43 protein in various human and rat tissues was assayed by western blot . a rat heart non - ionic detergent extract was prepared by freezing a heart in liquid nitrogen after removal , powdering in a mortar and pestle , grinding briefly in a polytron in 0 . 5 % nonidet p40 in [ 10 mm pipes ( ph 6 . 8 ), 50 mm nacl , 250 mm nh 4 so 4 , 300 mm sucrose , 3 mm mgcl 2 ] and microfuging for 15 minutes . samples were separated by sds / page and electrophoretically transferred to nitrocellulose ( towbin et al ., pnas 76 : 4350 - 4354 , 1979 ). two pc43 protein bands with molecular weights of 150 kda and 140 kda were detected with rabbit polyclonal antibodies to pc43 by the immunoblot method described in example 6 . to determine the localization of the protocadherins in various tissues , human and rat adult tissues were removed , incubated in 30 % sucrose in pbs for 30 minutes at 4 ° c ., embedded in oct compound ( tissue - tek , elkhart , ind .) in cryomolds and quickly frozen . six micron sections were cut and placed on glass slides . the slides were washed with pbs and fixed in 3 % p - formaldehyde for 5 minutes . to permeablize the tissue sections , the slides were immersed in - 20 ° c . acetone for 10 minutes and air dried . the sections were blocked with 2 % goat serum and 1 % bsa in pbs for 30 minutes and then incubated with the rabbit anti - pc43 polyclonal antisera for 1 hour at room temperature . the sections were rinsed 3 times in pbs containing 0 . 1 % bsa and incubated with a biotinylated anti - rabbit ( vector laboratories , burlingame , calif .) in 1 % bsa in pbs for 30 minutes . after rinsing 3 times , strepavidin - conjugated with fitc ( vector laboratories ) was added for 30 minutes and again washed 3 times . for co - localization studies , an appropriate primary antibody was used with a tritc - conjugated secondary antibody . immunolocalization of pc43 in cardiac muscle shows that pc43 is localized in a repeating pattern which is consistent with pc43 being associated with the sarcomeres . sarcomeres are repetitive contractile units between the fascia adherens in skeletal and cardiac muscle . co - localization with cytoskeletal proteins shows that pc43 is present at the ends of the sarcomeres in the z lines which are associated with desmin and the actin - binding protein vinculin , and alpha - actinin . the thin microfilaments of f - actin are associated with the thick myosin filaments between the z lines . in contrast , n - cadherin is localized at the ends of cardiac myocytes at the fascia adherens junctions at sites of mycocyte : myocyte contact . the localization of pc43 in cardiac muscle suggests that pc43 may play a role in muscle contraction in the anchoring of the contractile apparatus to the plasma membrane . similar localization for pc43 was observed in rat skeletal muscle . ultrastructural studies have shown that dystrophin , the gene product lacking in duchenne muscular dystrophy , is a component of the sarcolemma [ porter et al ., j . cell . biol ., 117 : 997 - 1005 ( 1992 )]. the sarcolemma is connected to the contractile apparatus at the m and z lines where pc43 is localized . reactivity of anti - pc43 polyclonal antibody and monoclonal antibody 38i2c on frozen sections of rat and human cerebellum , respectively , shows that the major sites of pc43 expression are located in purkinje cells and the granule cell layer which contains numerous small neurons . immunocytochemical localization of pc43 in sk - n - sh neuroblastoma cells and uw28 astrocytoma cells using anti - pc43 antibodies reveals a punctate cell surface distribution of pc43 and in some cells there is a localization at the tips of extensions of neuronal foot processes . at sites of cell - cell contact of uw28 astrocytoma cells , pc43 is organized in a series of parallel lines . the lines start at the contact site and extend approximately 5 micron . f - actin microfilaments were identified with rhodamine - phalloidin ( molecular probes , eugene , oreg ., as described by the manufacturer ) showing that the microfilaments in the cell appear to end in the pc43 linear structures which extend from the edge of the cell at sites of cell contact . immunoblotting studies with pc43 specific antibodies show that a protein with a molecular weight of 140 kda is recognized in human sk - n - sh neuroblastoma cells and in uw28 astrocytoma cells . in situ hybridization experiments using protocadherin specific rna probes were preformed on cryosections of rat tissue . sense and antisense 35 s - riboprobes were made using the standard procedure described by promega ( madison , wis .). an approximately 400 bp ecori - xbal fragment of the mouse - 326 cdna clone was used as a pc42 specific probe . this fragment encodes the middle of ec - 3 to the end of ec - 4 of pc42 . an approximately 700 bp smal fragment of the rat - 218 cdna clone was used as a pc43 specific probe . the fragment encodes the end of ec - 3 to the end of ec - 5 of pc43 . rat adult tissues were harvested and immediately embedded with oct compound ( tissue - tek ) in cryomolds and quickly frozen in a bath of 95 % ethanol / dry ice . the frozen blocks were stored at - 80 ° c . until cut . six micron tissue sections were cut using a cryostat ( reichert - jung , model # 2800 frigocut n , leica , inc ., gilroy , calif .). cut tissue sections were stored at - 80 ° c . the in situ protocol used was a variation of that described by angerer et al ., methods in enzymology , 152 : 649 - 660 , 1987 . all solutions were treated with diethylpyrocarbonate ( depc , sigma , st . louis , mo .) to remove rnase contamination . the tissue sections were first fixed in 4 % paraformaldehyde at 4 ° c . for 20 minutes . to remove excess paraformaldehyde and stop the tissue fixation , the slides were washed in pbs ( phosphate buffered saline ), denatured in a graded series of alcohols ( 70 , 95 , 100 %) and then dried . to prevent the tissue from detaching from the glass slide during the in situ procedure , the tissue sections were treated in a poly - l - lysine solution ( sigma ) at room temperature for 10 minutes . to denature all rna in the tissue , the sections were placed in a solution of 70 % formamide / 2 × ssc [ 0 . 15m nacl / 0 . 3m na citrate , ph 7 . 0 ] at 70 ° c . for 2 minutes after which they were rinsed in chilled 2 × ssc , dehydrated in a graded series of alcohols and then dried . once dried , the sections were prehybridized in hybridization buffer ( 50 % formamide / 50 mm dtt ( dithiothrietol )/ 0 . 3m nacl / 20 mm tris , ph 8 . 0 / 5 mm edta / 1 × denhardt &# 39 ; s ( 0 . 02 % ficoll type 400 / 0 . 02 % polyvinylpyrrolidone / 0 . 02 % bsa )/ 10 % dextran sulfate ) at the final hybridization temperature for approximately 4 hours . after prehybridization , approximately 1 × 10 6 cpm of the appropriate riboprobe was added to each section . the sections were generally hybridized at 45 ° c . overnight ( 12 - 16 hours ). to insure that the hybridization seen was specific , in some experiments the hybridization stringency was increased by raising the hybridization temperature to 50 ° c . as both the 45 ° c . and 50 ° c . experiments gave comparable results , the standard hybridization temperature used was 45 ° c . to remove excess , nonhybridized probe , the sections were put through a series of washes . the sections were first rinsed in 4 × ssc to remove the bulk of the hybridization solution and probe . next a 15 minute wash in 4 × ssc / 50 mm dtt was carried out at room temperature . washes at increased stringencies were also utilized . a 40 minute wash in 50 % formamide / 2 × ssc / 50 mm dtt was performed at 60 ° c . four final room temperature washes were carried out for 10 minutes each : two in 2 × ssc and two in 0 . 1 × ssc . the washed slides were dehydrated in a graded series of alcohols and dried . to visualize the hybridized probe , the slides were dipped in kodak ntb2 nuclear emulsion ( international biotechnology , new haven , conn .) which had been diluted 1 : 1 in dh 2 o . once dry , the slides were stored at 4 ° c . in light - tight boxes for the appropriate exposure time . the in situ slides were independently viewed by two persons and scored positive or negative for hybridization signal . all in situ hybridization studies were performed on rat tissue . because results from northern blot experiments ( see example 9 ) indicated that both pc42 and pc43 are expressed in adult brain , in situ hybridization studies were carried out to localize the expression of these molecules to specific brain cell types . hybridization seen in the normal adult rat brian was specific ( no background hybridization was seen with the sense probes ) and was localized to specific regions in the brain . the overall pattern of expression seen for pc42 and pc43 was very similar , with the major difference being in the level of expression . pc43 appears to be expressed at a lower level than pc42 . both molecules are expressed in the germinal and pyramidal cells of the hippocampus , purkinje cells of the cerebellum and neurons in grey matter . in addition , pc42 is expressed in glial cells in the white matter but , in contrast to the expression of pc43 in glioma cell lines ( as described in example 9 ), expression of pc43 in normal glial cells was not observed . in the spinal chord , both protocadherins are expressed in the motor neurons in the gray matter and pc42 is expressed in the glial cells in the white matter . when expression of both protocadherin molecules was determined in brains and spinal chords from rats having eae ( experimental allergic encephaiomyelitis ) [ vandenbark et al ., cell . immunol ., 12 : 85 - 93 ( 1974 )], the same structures as described above were found to be positive . in addition , expression of pc42 was observed in the leukocytic infiltrates in the eae tissues . expression of pc42 in leukocytes was confirmed by in situ hybridization analysis of two leukocytic cell lines , rbl - 1 and y3 . while the present invention has been described in terms of specific methods and compositions , it is understood that variations and modifications will occur to those skilled in the art . therefore , only such limitations as appear in the claims should be placed on the invention . __________________________________________________________________________sequence listing ( 1 ) general information :( iii ) number of sequences : 107 ( 2 ) information for seq id no : 1 :( i ) sequence characteristics :( a ) length : 17 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : dna ( xi ) sequence description : seq id no : 1 : aarssnntngaytryga17 ( 2 ) information for seq id no : 2 :( i ) sequence characteristics :( a ) length : 17 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : dna ( xi ) sequence description : seq id no : 2 : ttrctrttrcgnggnnn17 ( 2 ) information for seq id no : 3 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 3 : aagggagtggactttgaggagcagcctgagcttagtctcatcctcacggctttggatgga60gggactccatccaggtctgggactgcattggttcaagtggaagtcatagatgccaatgac120aacgcaccgta131 ( 2 ) information for seq id no : 4 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 4 : lysglyvalasppheglugluglnprogluleuserleuileleuthr151015alaleuaspglyglythrproserargserglythralaleuvalgln202530valgluvalileaspalaasnaspasnalapro3540 ( 2 ) information for seq id no : 5 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 5 : aaacgcatggatttcgaggagtcttcctcctaccagatctatgtgcaagctactgaccgg60ggaccagtacccatggcgggtcattgcaaggtgttggtggacattatagatgtgaacgac120aacgcacctaa131 ( 2 ) information for seq id no : 6 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 6 : lysalametaspphegluglusersersertyrglniletyrvalgln151015alathraspargglyprovalprometalaglyhiscyslysvalleu202530valaspileileaspvalasnaspasnalapro3540 ( 2 ) information for seq id no : 7 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 7 : aagcgactggactttgagaccctgcagaccttcgagttcagcgtgggtgccacagaccat60ggctccccctcgctccgcagtcaggctctggtgcgcgtggtggtgctggaccacaatgac120aatgcccccaa131 ( 2 ) information for seq id no : 8 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 8 : lysargleuaspphegluthrleuglnthrpheglupheservalgly151015alathrasphisglyserproserleuargserglnalaleuvalarg202530valvalvalleuasphisasnaspasnalapro3540 ( 2 ) information for seq id no : 9 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 9 : aagggcctggattacgaggcactgcagtccttcgagttctacgtgggcgctacagatgga60ggctcacccgcgctcagcagccagactctggtgcggatggtggtgctggatgacaacgac120aacgcccctaa131 ( 2 ) information for seq id no : 10 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 10 : lysglyleuasptyrglualaleuglnserphegluphetyrvalgly151015alathraspglyglyserproalaleuserserglnthrleuvalarg202530metvalvalleuaspaspasnaspasnalapro3540 ( 2 ) information for seq id no : 11 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 11 : aaggcgtttgattttgaggatcagagagagttccagctaaccgctcatataaacgacgga60ggtaccccggttttggccaccaacatcagcgtgaacatatttgttactgaccgcaatgac120aacgccccgca131 ( 2 ) information for seq id no : 12 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 12 : lysalapheaspphegluaspglnargglupheglnleuthralahis151015ileasnaspglyglythrprovalleualathrasnileservalasn202530ilephevalthraspargasnaspasnalapro3540 ( 2 ) information for seq id no : 13 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 13 : aaggcggtggattacgaaatcaccaagtcctatgagatagatgttcaagcccaagatctg60ggtcccaattctattcctgctcattgcaaaattataattaaggtcgtggatgtcaacgac120aacgctcccaa131 ( 2 ) information for seq id no : 14 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 14 : lysalavalasptyrgluilethrlyssertyrgluileaspvalgln151015alaglnaspleuglyproasnserileproalahiscyslysileile202530ilelysvalvalaspvalasnaspasnalapro3540 ( 2 ) information for seq id no : 15 :( i ) sequence characteristics :( a ) length : 135 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 15 : tatgaccatgattacgagacaaccaaagaatatacactgcggatccgggcccaggatggt60ggccggactccactttccaacgtctccggtctagtaaccgtgcaggtcctagacatcaac120gacaatgccccccca135 ( 2 ) information for seq id no : 16 :( i ) sequence characteristics :( a ) length : 44 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 16 : tyrasphisasptyrgluthrthrlysglutyrthrleuargilearg151015alaglnaspglyglyargthrproleuserasnvalserglyleuval202530thrvalglnvalleuaspileasnaspasnalapro3540 ( 2 ) information for seq id no : 17 :( i ) sequence characteristics :( a ) length : 129 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 17 : ggggggtcgattacgaggagaacggcatgttagagatcgacgtgcaggccagagacctag60gacctaacccaattccagcccattgcaaggtcacagtcaagctcatcgaccgcaatgata120acgccccca129 ( 2 ) information for seq id no : 18 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 18 : argglyvalasptyrglugluasnglymetleugluileaspvalgln151015alaargaspleuglyproasnproileproalahiscyslysvalthr202530vallysleuileaspargasnaspasnalapro3540 ( 2 ) information for seq id no : 19 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 19 : aaggggttggactacgaagacaccaaactccatgagatttacatccaggccaaagacaaa60ggtgccaatccggaaggagcgcattgcaaagtactggtagaggttgtggacgttaacgac120aatgcccctca131 ( 2 ) information for seq id no : 20 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 20 : lysglyleuasptyrgluaspthrlysleuhisgluiletyrilegln151015alalysasplysglyalaasnprogluglyalahiscyslysvalleu202530valgluvalvalaspvalasnaspasnalapro3540 ( 2 ) information for seq id no : 21 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 21 : aagggtttggactttgagcaagtagatgtctacaaaatccgcgttgacgcgacggacaaa60ggacaccctccgatggcaggccattgcactgttttagtgagggtattggatgaaaacgac120aatgcgcctct131 ( 2 ) information for seq id no : 22 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 22 : lysglyleuaspphegluglnvalaspvaltyrlysileargvalasp151015alathrasplysglyhisproprometalaglyhiscysthrvalleu202530valargvalleuaspgluasnaspasnalapro3540 ( 2 ) information for seq id no : 23 :( i ) sequence characteristics :( a ) length : 134 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 23 : aagggtatagacttcgagcagatcaaggacttcagctttcaagtggaagcccgggacgcc60ggcagtccccaggcgctgtccggcaactgcactgtcaacatcttgatagtggatcagaac120gacaacgcccctaa134 ( 2 ) information for seq id no : 24 :( i ) sequence characteristics :( a ) length : 44 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 24 : lysglyileaspphegluglnilelysasppheserpheglnvalglu151015alaargaspalaglyserproglnalaleualaglyasnthrthrval202530asnileleuilevalaspglnasnaspasnalapro3540 ( 2 ) information for seq id no : 25 :( i ) sequence characteristics :( a ) length : 134 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 25 : aagccgttcgactatgagcaaaccgccaacacgctggcacagattgacgccgtgctggaa60aaacagggcagcaataaatcgagcattctggatgccaccattttcctggccgataaaaac120gacaatgcgccaga134 ( 2 ) information for seq id no : 26 :( i ) sequence characteristics :( a ) length : 44 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 26 : lyspropheasptyrgluglnthralaasnthrleualaglnileasp151015alavalleuglulysglnglyserasnlysserserileleuaspala202530thrilepheleualaasplysasnaspasnalapro3540 ( 2 ) information for seq id no : 27 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 27 : aagcggctggatttcgaacagttccagcagcacaagctgctcgtaagggctgttgatgga60ggaatgccgccactgagcagcgatgtggtcgtcactgtggatgtcaccgacctcaacgat120aacgcgcccta131 ( 2 ) information for seq id no : 28 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 28 : lysargleuaspphegluglnpheglnglnhislysleuleuvalarg151015alavalaspglyglymetproproleuserseraspvalvalvalthr202530valaspvalthraspleuasnaspasnalapro3540 ( 2 ) information for seq id no : 29 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 29 : aaggggatagactttgagagtgagaattactatgaatttgatgtgcgggctcgcgatggg60ggttctccagccatggagcaacattgcagccttcgagtggatctgctggacgtaaatgac120aacgccccact131 ( 2 ) information for seq id no : 30 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 30 : lysglyileasppheglusergluasntyrtyrglupheaspvalarg151015alaargaspglyglyserproalametgluglnhiscysserleuarg202530valaspleuleuaspvalasnaspasnalapro3540 ( 2 ) information for seq id no : 31 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 31 : aaggcattggactttgaggcccggcgactgtattcgctgacagttcaggccacggaccga60ggcgtgccctcgctcaccgggcgtgccgaagcgcttatccagctgctagatgtcaacgac120aacgcacccat131 ( 2 ) information for seq id no : 32 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 32 : lysalaleuasppheglualaargargleutyrserleuthrvalgln151015alathraspargglyvalproserleuthrglyargalaglualaleu202530ileglnleuleuaspvalasnaspasnalapro3540 ( 2 ) information for seq id no : 33 :( i ) sequence characteristics :( a ) length : 125 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 33 : aagccaattgattacgaggcaactccatactataacatggaaattgtagccacagacagc60ggaggtctttcgggaaaatgcactgtgtctatacaggtggtggatgtgaacgacaacgcc120cccaa125 ( 2 ) information for seq id no : 34 :( i ) sequence characteristics :( a ) length : 41 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 34 : lysproileasptyrglualathrprotyrtyrasnmetgluileval151015alathraspserglyglyleuserglylyscysthrvalserilegln202530valvalaspvalasnaspasnalapro3540 ( 2 ) information for seq id no : 35 :( i ) sequence characteristics :( a ) length : 446 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 35 : aagcgggtagacttcgaaatgtgcaaaagattttaccttgtggtggaagctaaagacgga60ggcaccccagccctcagcacggcagccactgtcagcatcgacctcacagatgtgaatgat120aaccctcctcggttcagccaagatgtctacagtgctgtcatcagtgaggatgccttagag180ggggactctgtcattctgctgatagcagaagatgtggatagcaagcctaatggacagatt240cggttttccatcgtgggtggagatagggacaatgaatttgctgtcgatccaatcttggga300cttgtgaaagttaagaagaaactggaccgggagcgggtgtcaggatactccctgctcatc360caggcagtagatagtggcattcctgcaatgtcctcaacgacaactgtcaacattgatatt420tctgatgtgaacgacaacgcccccct446 ( 2 ) information for seq id no : 36 :( i ) sequence characteristics :( a ) length : 148 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 36 : lysargvalasppheglumetcyslysargphetyrleuvalvalglu151015alalysaspglyglythrproalaleuserthralaalathrvalser202530ileaspleuthraspvalasnaspasnproproargpheserglnasp354045valtyraspalavalilesergluaspalaleugluglyaspserval505560ileleuleuilealagluaspvalaspserlysproasnglyglnile65707580argpheserilevalglyglyaspargaspasngluphealavalasp859095proileleuglyleuvallysvallyslyslysleuasparggluarg100105110valserglytyrserleuleuileglnalavalaspserglyilepro115120125alametserserthrthrthrvalasnileaspileseraspvalasn130135140aspasnalapro145 ( 2 ) information for seq id no : 37 :( i ) sequence characteristics :( a ) length : 440 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 37 : aagggggttgattatgagacaaacccacggctacgactggtgctacaggcagagagtgga60ggagcctttgctttctcggtgctgaccctgacccttcaagatgccaatgacaatgctccc120cgtttcctgcagcctcactacgtggctttcctgccagagtcccgacccttggaagggccc180ctgctgcaggtggaagcagacgacctggatcaaggctctggaggacagatctcctacagt240ctggctgcatcccagccagcacggggcttgttccatgtagacccagccacaggcactatc300actaccacagccatcctggaccgggaaatctgggctgaaacacggctggtactgatggcc360acagacagaggaagcccagcattggtgggctcagctaccctgacagtgatggtcatcgat420accaacgacaatgctcccct440 ( 2 ) information for seq id no : 38 :( i ) sequence characteristics :( a ) length : 146 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 38 : lysglyvalasptyrgluthrasnproargleuargleuvalleugln151015alagluserglyglyalaphealapheservalleuthrleuthrleu202530glnaspalaasnaspasnalaproargpheleuglnprohistyrval354045alapheleuprogluserargproleugluglyproleuleuglnval505560glualaasnaspleuaspglnglyserglyglyglnilesertyrser65707580leualaalaserglnproalaargglyleuphehisvalaspproala859095thrglythrilethrthrthralaileleuasparggluiletrpala100105110gluthrargleuvalleumetalathraspargglyserproalaleu115120125valglyseralathrleuthrvalmetvalileaspthrasnaspasn130135140alapro145 ( 2 ) information for seq id no : 39 :( i ) sequence characteristics :( a ) length : 124 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 39 : aaggtctcgattatgaggcaactccatattataacgtggaaattgtagccacagatggtg60ggggcctttcaggaaaatgcactgtggctatagaagtggtggatgtgaacgacggcgctc120caat124 ( 2 ) information for seq id no : 40 :( i ) sequence characteristics :( a ) length : 41 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 40 : lysglyleuasptyrglualathrprotyrtyrasnvalgluileval151015alathraspglyglyalapheaspgluasncysthrvalalaileglu202530valvalaspvalasnaspasnalapro3540 ( 2 ) information for seq id no : 41 :( i ) sequence characteristics :( a ) length : 8 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : dna ( xi ) sequence description : seq id no : 41 : aspxaaasngluxaaproxaaphe15 ( 2 ) information for seq id no : 42 :( i ) sequence characteristics :( a ) length : 8 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : dna ( xi ) sequence description : seq id no : 42 : aspxaaaspgluxaaproxaaphe15 ( 2 ) information for seq id no : 43 :( i ) sequence characteristics :( a ) length : 9 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : dna ( xi ) sequence description : seq id no : 43 : aspxaaasnaspasnxaaproxaaphe15 ( 2 ) information for seq id no : 44 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 44 : aagcggatggattttgaagacaccaaactccatgagatttacatccaggccaaagacaaa60ggtgccaatcccgaaggagcgcattgcaaagtacttgtagaggttgtagacgtaaacgac120aacgccccagt131 ( 2 ) information for seq id no : 45 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 45 : leuargmetaspphegluaspthrlysleuhisgluiletyrilegln151015alalysasplysglyalaasnprogluglyalahiscyslysvalleu202530valgluvalvalaspvalasnaspasnalapro3540 ( 2 ) information for seq id no : 46 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 46 : aaggctttggattacgaggatcagagagagttccaactaacagctcatataaacgacgga60ggtaccccagtcttagccaccaacatcagcgtgaacgtatttgttactgaccgcaatgat120aacgcccccta131 ( 2 ) information for seq id no : 47 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 47 : lysalaleuasptyrgluaspglnargglupheglnleuthralahis151015ileasnaspglyglythrprovalleualathrasnileservalasn202530valphevalthraspargasnaspasnalapro3540 ( 2 ) information for seq id no : 48 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 48 : aagcgcttggactacgaggagagtaacaattatgaaattcacgtggatgctacagataaa60ggatacccacctatggttgctcactgcaccgtactcgtgggaatcttggatgaaaatgac120aacgcacccat131 ( 2 ) information for seq id no : 49 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 49 : lysargleuasptyrglugluserasnasntyrgluilehisvalasp151015alathrasplysglytyrproprometvalalahiscysthrvalleu202530valglyileleuaspgluasnaspasnalapro3540 ( 2 ) information for seq id no : 50 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 50 : aaaccggtggactacgagaaagtcaaagactataccatcgagatcgtggctgtggattcc60ggcaaccctccactctctagcaccaactccctcaaggtgcaggtggtagacgtcaacgat120aacgcccctct131 ( 2 ) information for seq id no : 51 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 51 : lysprovalasptyrglulysvallysasptyrthrilegluileval151015alavalaspserglyasnproproleuserserthrasnserleulys202530valglnvalvalaspvalasnaspasnalapro3540 ( 2 ) information for seq id no : 52 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 52 : aagccttttgatttcgaggacaccaaactccatgagatttacatccaggccaaagacaag60ggcgccaatcccgaaggagcacattgcaaagtgttggtggaggttgtggatgtgaacgac120aatgcccctca131 ( 2 ) information for seq id no : 53 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 53 : lyspropheaspphegluaspthrlysleuhisgluiletyrilegln151015alalysasplysglyalaasnprogluglyalahiscyslysvalleu202530valgluvalvalaspvalasnaspasnalapro3540 ( 2 ) information for seq id no : 54 :( i ) sequence characteristics :( a ) length : 122 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 54 : aaaggtgtcgattacgaggtgagtccacggctgcgactggtgctgcaggcagagagtcga60ggagcctttgccttcactgtgctgaccctgaccctgcaagatgccaacgacaacgccccg120ag122 ( 2 ) information for seq id no : 55 :( i ) sequence characteristics :( a ) length : 40 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 55 : lysglyvalasptyrgluvalserproargleuargleuvalleugln151015alagluserargglyalaphealaphethrvalleuthrleuthrleu202530glnaspalaasnaspasnalapro3540 ( 2 ) information for seq id no : 56 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 56 : aaagggattgattacgagcagttgagagacctacagctgtgggtgacagccagcgacagc60ggggacccgcctcttagcagcaacgtgtcactgagcctgtttgtgctggaccagaacgac120aacgcccccct131 ( 2 ) information for seq id no : 57 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 57 : lysglyileasptyrgluglnleuargaspleuglnleutrpvalthr151015alaseraspserglyaspproproleuserserasnvalserleuser202530leuphevalleuaspglnasnaspasnalapro3540 ( 2 ) information for seq id no : 58 :( i ) sequence characteristics :( a ) length : 125 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 58 : aaggcggtcgattttgagcgcacatcctcttatcaactcatcattcaggccaccaatatg60gcaggaatggcttccaatgctacagtcaatattcagattgttgatgaaaacgacaacgcc120cccca125 ( 2 ) information for seq id no : 59 :( i ) sequence characteristics :( a ) length : 41 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 59 : lysalavalaspphegluargthrsersertyrglnleuileilegln151015alathrasnmetalaglymetalaserasnalathrvalasnilegln202530ilevalaspgluasnaspasnalapro3540 ( 2 ) information for seq id no : 60 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 60 : aaacggctagactttgaaaagatacaaaaatatgttgtatggatagaggccagagatggt60ggtttccctcctttctcctcttacgagaaacttgatataacagtattagatgtcaacgat120aacgcgcctaa131 ( 2 ) information for seq id no : 61 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 61 : lysargleuasppheglulysileglnlystyrvalvaltrpileglu151015alaargaspglyglypheproprophesersertyrglulysleuasp202530ilethrvalleuaspvalasnaspasnalapro3540 ( 2 ) information for seq id no : 62 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 62 : aaggggatcgattatgagaaggtcaaagactacaccattgagattgtggctgtggactct60ggcaaccccccactctccagcactaactccctcaaggtgcaggtggtggacgtcaatgac120aacgcaccgtg131 ( 2 ) information for seq id no : 63 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 63 : lysglyileasptyrglulysvallysasptyrthrilegluileval151015alavalaspserglyasnproproleuserserthrasnserleulys202530valglnvalvalaspvalasnaspasnalapro3540 ( 2 ) information for seq id no : 64 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 64 : aagggactcgactacgaggatcggcgggaatttgaattaacagctcatatcagcgatggg60ggcaccccggtcctagccaccaacatcagcgtgaacatatttgtcactgatcgcaacgat120aatgcccccgt131 ( 2 ) information for seq id no : 65 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 65 : lysglyleuasptyrgluaspargarggluphegluleuthralahis151015ileseraspglyglythrprovalleualathrasnileservalasn202530ilephevalthraspargasnaspasnalapro3540 ( 2 ) information for seq id no : 66 :( i ) sequence characteristics :( a ) length : 470 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 66 : aagggtttggactacgagaccacacaggcctaccagctcacggtcaacgccacagatcaa60gacaacaccaggcctctgtccaccctggccaacttggccatcatcatcacagatgtccag120gacatggaccccatcttcatcaacctgccttacagcaccaacatctacgagcattctcct180ccgggcacgacggtgcgcatcatcaccgccatagaccaggatcaaggacgtccccggggc240attggctacaccatcgtttcagggaataccaacagcatctttgccctggactacatcagc300ggagtgctgaccttgaatggcctgctggaccgggagaaccccctgtacagccatggcttc360atcctgactgtgaagggcacggagctgaacgatgaccgcaccccatctgacgctacagtc420accacgaccttcaatatcctggttattgacatcaacgacaacgccccact470 ( 2 ) information for seq id no : 67 :( i ) sequence characteristics :( a ) length : 156 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 67 : lysglyleuasptyrgluthrthrglnalatyrglnleuthrvalasn151015alathraspglnaspasnthrargproleuserthrleualaasnleu202530alaileileilethraspvalglnaspmetaspproilepheileasn354045leuprotyrserthrasniletyrgluhisserproproglythrthr505560valargileilethralaileaspglnaspglnglyargproarggly65707580ileglytyrthrilevalserglyasnthrasnserilephealaleu859095asptyrileserglyvalleuthrleuasnglyleuleuaspargglu100105110asnproleutyrserglyglypheileleuthrvallysglythrglu115120125leuasnaspaspargthrproseraspalathrvalthrthrthrphe130135140asnileleuvalileaspileasnaspasnalapro145150155 ( 2 ) information for seq id no : 68 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 68 : aagggggtcgattacgaggtactacaggcctttgagttccacgtgagcgccacagaccga60ggctcaccggggctcagcagccaggctctggtgcgcgtggtggtgctggacgacaatgac120aacgctcccgt131 ( 2 ) information for seq id no : 69 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 69 : lysglyvalasptyrgluvalleuglnalaphegluphehisvalser151015alathraspargglyserproglyleuserserglnalaleuvalarg202530valvalvalleuaspaspasnaspasnalapro3540 ( 2 ) information for seq id no : 70 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 70 : aaggggctggattatgagcagttccagaccctacaactgggagtgaccgctagtgacagt60ggaaacccaccattaagaagcaatatttcactgacccttttcgtgctggaccagaatgat120aacgccccaaa131 ( 2 ) information for seq id no : 71 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 71 : lysglyleuasptyrgluglnpheglnthrleuglnleuglyvalthr151015alaseraspserglyasnproproleuargserasnileserleuthr202530leuphevalleuaspglnasnaspasnalapro3540 ( 2 ) information for seq id no : 72 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 72 : aagcgggttgattacgaggatgtccagaaatactcgctgagcattaaggcccaggatggg60cggcccccgctcatcaattcttcaggggtggtgtctgtgcaggtgctggatgtcaacgac120aatgccccgga131 ( 2 ) information for seq id no : 73 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : peptide ( xi ) sequence description : seq id no : 73 : lysargvalasptyrgluaspvalglnlystyrserleuserilelys151015alaglnaspglyargproproleuileasnserserglyvalvalser202530valglnvalleuaspvalasnaspasnalapro3540 ( 2 ) information for seq id no : 74 :( i ) sequence characteristics :( a ) length : 125 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 74 : aaaccggtagactttgagctacagcagttctatgaagtagctgtggtggcttggaactct60gagggatttcatgtcaaaagggtcattaaagtgcaacttttagatgacaacgacaatgcc120ccgat125 ( 2 ) information for seq id no : 75 :( i ) sequence characteristics :( a ) length : 41 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 75 : lysprovalaspphegluleuglnglnphetyrgluvalalavalval151015alatrpasnsergluglyphehisvallysargvalilelysvalgln202530leuleuaspaspasnaspasnalapro3540 ( 2 ) information for seq id no : 76 :( i ) sequence characteristics :( a ) length : 125 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 76 : aagggattagattttgaaactttgcccatttacacattgataatacaaggaactaacatg60gctggtttgtccactaatacaacggttctagttcacttgcaggatgagaatgataacgcc120ccaaa125 ( 2 ) information for seq id no : 77 :( i ) sequence characteristics :( a ) length : 41 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 77 : lysglyleuaspphegluthrleuproiletyrthrleuileilegln151015glythrasnmetalaglyleuserthrasnthrthrvalleuvalhis202530leuglnaspgluasnaspasnalapro3540 ( 2 ) information for seq id no : 78 :( i ) sequence characteristics :( a ) length : 134 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 78 : aagcgggcggatttcgaggcgatccgggagtacagtctgaggatcaaagcgcaggacggg60gggcggcctcccctcagcaacaccacgggcatggtcacagtgcaggtcgtggacgtcaat120gacaacgcacccct134 ( 2 ) information for seq id no : 79 :( i ) sequence characteristics :( a ) length : 44 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 79 : lysargalaasppheglualaileargglutyrserleuargilelys151015alaglnaspglyglyargproproleuserasnthrthrglymetval202530thrvalglnvalvalaspvalasnaspasnalapro3540 ( 2 ) information for seq id no : 80 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 80 : aagcggttggattacgaaaaggcatcggaatatgaaatctatgttcaagccgctgacaaa60ggcgctgtccctatggctggccattgcaaagtgttgctggagatcgtggatgtcaacgac120aacgccccctt131 ( 2 ) information for seq id no : 81 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 81 : lysargleuasptyrglulysalaserglutyrgluiletyrvalgln151015alaalaasplysglyalavalprometalaglyhiscyslysvalleu202530leugluilevalaspvalasnaspasnalapro3540 ( 2 ) information for seq id no : 82 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 82 : aaggggatcgattatgaggatcaggtctcttacacattagcagtaacagcacatgactat60ggcatccctcaaaaatcagacactacctatttggaaatcttagtaattgatgttaacgac120aacgcgcccca131 ( 2 ) information for seq id no : 83 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 83 : lysglyileasptyrgluaspglnvalsertyrthrleualavalthr151015alahisasptyrglyileproglnlysseraspthrthrtyrleuglu202530ileleuvalileaspvalasnaspasnalapro3540 ( 2 ) information for seq id no : 84 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 84 : aaagggttagatttcgagggcactaaagattcagcgtttaaaatagtggcagctgacaca60gggaagcccagcctcaaccagacagccctggtgagagtagagctggaggatgagaacgac120aacgccccaat131 ( 2 ) information for seq id no : 85 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 85 : lysglyleuaspphegluglythrlysaspseralaphelysileval151015alaalaaspthrglylysproserleuasnglnthralaleuvalarg202530valgluleugluaspgluasnaspasnalapro3540 ( 2 ) information for seq id no : 86 :( i ) sequence characteristics :( a ) length : 130 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 86 : aagggtgtggattttgaaagtgtgcgtagctacaggctggttattcgtgctcaagatgga60ggcagcccctccagaagtaacaccacccagctcttggtcaacgtcatcgatcgaatgaca120atgcgccgct130 ( 2 ) information for seq id no : 87 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 87 : lysglyvalaspphegluservalargsertyrargleuvalilearg151015alaglnaspglyglyserproserargserasnthrthrglnleuleu202530valasnvalileaspvalasnaspasnalapro3540 ( 2 ) information for seq id no : 88 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 88 : aagggtgtggacttcgagctgacacatctgtatgagatttggattgaggctgccgatgga60gacacgccaagtctgcgtagtgtaactcttataacgctcaacgtaacggatgccaatgac120aatgctcccaa131 ( 2 ) information for seq id no : 89 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 89 : lysglyvalaspphegluleuthrhisleutyrgluiletrpileglu151015alaalaaspglyaspthrproserleuargservalthrleuilethr202530leuasnvalthraspalaasnaspasnalapro3540 ( 2 ) information for seq id no : 90 :( i ) sequence characteristics :( a ) length : 441 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 90 : caaggcgtttgattttgaagagacaagtagatatgtgttgagtgtggaagctaaggatgg60aggagtacacacagctcactgtaatgttcaaatagaaattgttgacgagaatgacaatgc120cccagaggtgacattcatgtccttctctaaccagattccagaggattcagaccttggaac180tgtaatagccctcataaaagtgcgagacaaggattctgggcaaaatggcatggtgacatg240ctatactcaggaagaagttcctttcaaattagaatccacctcgaagaattattacaagct300ggtgattgctggagccctaaaccgggagcagacagcagactacaacgtcacaatcatagc360caccgacaagggcaaaccagccctttcctccaggacaagcatcaccctgcacatctccga420catcaacgataatgcccccgt441 ( 2 ) information for seq id no : 91 :( i ) sequence characteristics :( a ) length : 146 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 91 : lysalapheasppheglugluthrserargtyrvalleuservalglu151015alalysaspglyglyvalhisthralahiscysasnvalglnileglu202530ilevalaspgluasnaspasnalaprogluvalthrphemetserphe354045serasnglnileprogluaspseraspleuglythrvalilealaleu505560ilelysvalargasplysaspserglyglnasnglymetvalthrcys65707580tyrthrglnglugluvalprophelysleugluserthrserlysasn859095tyrtyrlysleuvalilealaglyalaleuasnarggluglnthrala100105110asptyrasnvalthrileilealathrasplysglylysproalaleu115120125serserargthrserilethrleuhisileseraspileasnaspasn130135140alapro145 ( 2 ) information for seq id no : 92 :( i ) sequence characteristics :( a ) length : 131 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( xi ) sequence description : seq id no : 92 : aagcgagtggattacgaggccactcggaattataagctgagagttaaggctactgatctt60gggattccaccgagatcttctaacatgacactgttcattcatgtccttgatgttaacgac120aacgctccctt131 ( 2 ) information for seq id no : 93 :( i ) sequence characteristics :( a ) length : 43 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 93 : lysargvalasptyrglualathrargasntyrlysleuargvallys151015alathraspleuglyileproproargserserasnmetthrleuphe202530ilehisvalleuaspvalasnaspasnalapro3540 ( 2 ) information for seq id no : 94 :( i ) sequence characteristics :( a ) length : 4104 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( ix ) feature :( a ) name / key : cds ( b ) location : 495 .. 3572 ( xi ) sequence description : seq id no : 94 : cctctattcgacattctctttggattgttttgctataacttgaaatttgggatgtcacaa60acgaaactgtcatctgtttccgccaaactgtggttctgctaatctcccaggctggcagca120ttggagacttgctgacttctttcatcccccactcttttcacctgaaattcctttccttgg180ttttgctctaagtcctatgcttcagtcaggggccaaccaaatctcactgcctccttttta240tcatgaagcctttgatcactgatagttctttttatatcttgaaaaatcacccttcccagt300acagttaatatttagtatctctactcatcttggcacttactcacagctccataattcagt360cgttttcgtacctcttcatggtgatggggagccctttggaggtggtgactgtgctttata420ctcctcatgatgcttcacatgtggcaggcgtggagtgcccggaggcggccctcctgattc480tggggcctcccaggatggagcccctgaggcacagcccaggccctgggggg530metgluproleuarghisserproglyproglygly1510caacggctactgctgccctccatgctgctagcactgctgctcctgctg578glnargleuleuleuprosermetleuleualaleuleuleuleuleu152025gctccatccccaggccacgccactcgggtagtgtacaaggtgccggag626alaproserproglyhisalathrargvalvaltyrlysvalproglu303540gaacagccacccaacaccctcattgggagcctcgcagccgactatggt674gluglnproproasnthrleuileglyserleualaalaasptyrgly45505560tttccagatgtggggcacctgtacaagctagaggtgggtgccccgtac722pheproaspvalglyhisleutyrlysleugluvalglyalaprotyr657075cttcgcgtggatggcaagacaggtgacattttcaccaccgagacctcc770leuargvalaspglylysthrglyaspilephethrthrgluthrser808590atcgaccgtgaggggctccgtgaatgccagaaccagctccctggtgat818ileasparggluglyleuargglucysglnasnglnleuproglyasp95100105ccctgcatcctggagtttgaggtatctatcacagacctcgtgcagaat866procysileleugluphegluvalserilethraspleuvalglnasn110115120gcgagcccccggctgctagagggccagatagaagtacaagacatcaat914alaserproargleuleugluglyglnilegluvalglnaspileasn125130135140gacaacacacccaacttcgcctcaccagtcatcactctggccatccct962aspasnthrproasnphealaserprovalilethrleualailepro145150155gagaacaccaacatcggctcactcttccccatcccgctggcttcagac1010gluasnthrasnileglyserleupheproileproleualaserasp160165170cgtgatgctggtcccaacggtgtggcatcctatgagctgcaggtggca1058argaspalaglyproasnglyvalalasertyrgluleuglnvalala175180185gaggaccaggaggagaagcaaccacagctcattgtgatgggcaacctg1106gluaspglngluglulysglnproglnleuilevalmetglyasnleu190195200gaccgtgagcgctgggactcctatgacctcaccatcaaggtgcaggat1154asparggluargtrpaspsertyraspleuthrilelysvalglnasp205210215220ggcggcagccccccacgcgccacgagtgccctgctgcgtgtcaccgtg1202glyglyserproproargalathrseralaleuleuargvalthrval225230235cttgacaccaatgacaacgcccccaagtttgagcggccctcctatgag1250leuaspthrasnaspasnalaprolysphegluargprosertyrglu240245250gccgaactatctgagaatagccccataggccactcggtcatccaggtg1298alagluleusergluasnserproileglyhisservalileglnval255260265aaggccaatgactcagaccaaggtgccaatgcagaaatcgaatacaca1346lysalaasnaspseraspglnglyalaasnalagluileglutyrthr270275280ttccaccaggcgcccgaagttgtgaggcgtcttcttcgactggacagg1394phehisglnalaprogluvalvalargargleuleuargleuasparg285290295300aacactggacttatcactgttcagggcccggtggaccgtgaggaccta1442asnthrglyleuilethrvalglnglyprovalasparggluaspleu305310315agcaccctgcgcttctcagtgcttgctaaggaccgaggcaccaacccc1490serthrleuargpheservalleualalysaspargglythrasnpro320325330aagagtgcccgtgcccaggtggttgtgaccgtgaaggacatgaatgac1538lysseralaargalaglnvalvalvalthrvallysaspmetasnasp335340345aatgcccccaccattgagatccggggcatagggctagtgactcatcaa1586asnalaprothrilegluileargglyileglyleuvalthrhisgln350355360gatgggatggctaacatctcagaggatgtggcagaggagacagctgtg1634aspglymetalaasnilesergluaspvalalaglugluthralaval365370375380gccctggtgcaggtgtctgaccgagatgagggagagaatgcagctgtc1682alaleuvalglnvalseraspargaspgluglygluasnalaalaval385390395acctgtgtggtggcaggtgatgtgcccttccagctgcgccaggccagt1730thrcysvalvalalaglyaspvalpropheglnleuargglnalaser400405410gagacaggcagtgacagcaagaagaagtatttcctgcagactaccacc1778gluthrglyseraspserlyslyslystyrpheleuglnthrthrthr415420425ccgctagactacgagaaggtcaaagactacaccattgagattgtggct1826proleuasptyrglulysvallysasptyrthrilegluilevalala430435440gtggactctggcaaccccccactctccagcactaactccctcaaggtg1874valaspserglyasnproproleuserserthrasnserleulysval445450455460caggtggtggacgtcaatgacaacgcacctgtcttcactcagagtgtc1922glnvalvalaspvalasnaspasnalaprovalphethrglnserval465470475actgaggtcgccttcccggaaaacaacaagcctggtgaagtgattgct1970thrgluvalalapheprogluasnasnlysproglygluvalileala480485490gagatcactgccagtgatgctgactctggctctaatgctgagctggtt2018gluilethralaseraspalaaspserglyserasnalagluleuval495500505tactctctggagcctgagccggctgctaagggcctcttcaccatctca2066tyrserleugluprogluproalaalalysglyleuphethrileser510515520cccgagactggagagatccaggtgaagacatctctggatcgggaacag2114progluthrglygluileglnvallysthrserleuaspargglugln525530535540cgggagagctatgagttgaaggtggtggcagctgaccggggcagtcct2162argglusertyrgluleulysvalvalalaalaaspargglyserpro545550555agcctccagggcacagccactgtccttgtcaatgtgctggactgcaat2210serleuglnglythralathrvalleuvalasnvalleuaspcysasn560565570gacaatgaccccaaatttatgctgagtggctacaacttctcagtgatg2258aspasnaspprolysphemetleuserglytyrasnpheservalmet575580585gagaacatgccagcactgagtccagtgggcatggtgactgtcattgat2306gluasnmetproalaleuserprovalglymetvalthrvalileasp590595600ggagacaagggggagaatgcccaggtgcagctctcagtggagcaggac2354glyasplysglygluasnalaglnvalglnleuservalgluglnasp605610615620aacggtgactttgttatccagaatggcacaggcaccatcctatccagc2402asnglyaspphevalileglnasnglythrglythrileleuserser625630635ctgagctttgatcgagagcaacaaagcacctacaccttccagctgaag2450leuserpheasparggluglnglnserthrtyrthrpheglnleulys640645650gcagtggatggtggcgtcccacctcgctcagcttacgttggtgtca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( 2 ) information for seq id no : 95 :( i ) sequence characteristics :( a ) length : 1026 amino acids ( b ) type : amino acid ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 95 : metgluproleuarghisserproglyproglyglyglnargleuleu151015leuprosermetleuleualaleuleuleuleuleualaproserpro202530glyhisalathrargvalvaltyrlysvalproglugluglnpropro354045asnthrleuileglyserleualaalaasptyrglypheproaspval505560glyhisleutyrlysleugluvalglyalaprotyrleuargvalasp65707580glylysthrglyaspilephethrthrgluthrserileaspargglu859095glyleuargglucysglnasnglnleuproglyaspprocysileleu100105110gluphegluvalserilethraspleuvalglnasnalaserproarg115120125leuleugluglyglnilegluvalglnaspileasnaspasnthrpro130135140asnphealaserprovalilethrleualaileprogluasnthrasn145150155160ileglyserleupheproileproleualaseraspargaspalagly165170175proasnglyvalalasertyrgluleuglnvalalagluaspglnglu180185190glulysglnproglnleuilevalmetglyasnleuasparggluarg195200205trpaspsertyraspleuthrilelysvalglnaspglyglyserpro210215220proargalathrseralaleuleuargvalthrvalleuaspthrasn225230235240aspasnalaprolysphegluargprosertyrglualagluleuser245250255gluasnserproileglyhisservalileglnvallysalaasnasp260265270seraspglnglyalaasnalagluileglutyrthrphehisglnala275280285progluvalvalargargleuleuargleuaspargasnthrglyleu290295300ilethrvalglnglyprovalasparggluaspleuserthrleuarg305310315320pheservalleualalysaspargglythrasnprolysseralaarg325330335alaglnvalvalvalthrvallysaspmetasnaspasnalaprothr340345350ilegluileargglyileglyleuvalthrhisglnaspglymetala355360365asnilesergluaspvalalaglugluthralavalalaleuvalgln370375380valseraspargaspgluglygluasnalaalavalthrcysvalval385390395400alaglyaspvalpropheglnleuargglnalasergluthrglyser405410415aspserlyslyslystyrpheleuglnthrthrthrproleuasptyr420425430glulysvallysasptyrthrilegluilevalalavalaspsergly435440445asnproproleuserserthrasnserleulysvalglnvalvalasp450455460valasnaspasnalaprovalphethrglnservalthrgluvalala465470475480pheprogluasnasnlysproglygluvalilealagluilethrala485490495seraspalaaspserglyserasnalagluleuvaltyrserleuglu500505510progluproalaalalysglyleuphethrileserprogluthrgly515520525gluileglnvallysthrserleuasparggluglnargglusertyr530535540gluleulysvalvalalaalaaspargglyserproserleuglngly545550555560thralathrvalleuvalasnvalleuaspcysasnaspasnasppro565570575lysphemetleuserglytyrasnpheservalmetgluasnmetpro580585590alaleuserprovalglymetvalthrvalileaspglyasplysgly595600605gluasnalaglnvalglnleuservalgluglnaspasnglyaspphe610615620valileglnasnglythrglythrileleuserserleuserpheasp625630635640arggluglnglnserthrtyrthrpheglnleulysalavalaspgly645650655glyvalproproargseralatyrvalglyvalthrileasnvalleu660665670aspgluasnaspasnalaprotyrilethralaproserasnthrser675680685hislysleuleuthrproglnthrargleuglygluthrvalsergln690695700valalaalagluasppheaspserglyvalasnalagluleuiletyr705710715720serilealaglyglyasnprotyrglyleupheglnileglyserhis725730735serglyalailethrleuglulysgluilegluargarghishisgly740745750leuhisargleuvalvallysvalseraspargglylysproproarg755760765tyrglythralaleuvalhisleutyrvalasngluthrleualaasn770775780argthrleuleugluthrleuleuglyhisserleuaspthrproleu785790795800aspileaspilealaglyaspproglutyrgluargserlysglnarg805810815glyasnileleupheglyvalvalalaglyvalvalalavalalaleu820825830leuilealaleualavalleuvalargtyrcysargglnarggluala835840845lysserglytyrglnalaglylyslysgluthrlysaspleutyrala850855860prolysproserglylysalaserlysglyasnlysserlysglylys865870875880lysserlysserprolysprovallysprovalgluaspgluaspglu885890895alaglyleuglnlysserleulyspheasnleumetseraspalapro900905910glyaspserproargilehisleuproleuasntyrproproglyser915920925proaspleuglyarghistyrargserasnserproleuproserile930935940glnleuglnproglnserproseralaserlyslyshisglnvalval945950955960glnaspleuproproalaasnthrphevalglythrglyaspthrthr965970975serthrglysergluglntyrserasptyrsertyrargthrasnpro980985990prolystyrproserlysglnvalglyglnpropheglnleuserthr99510001005proglnproleuprohisprotyrhisglyalailetrpthrgluval101010151020trpglu1025 ( 2 ) information for seq id no : 96 :( i ) sequence characteristics :( a ) length : 4705 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( ix ) feature :( a ) name / key : cds ( b ) location : 115 .. 2827 ( xi ) sequence description : seq id no : 96 : 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( 2 ) information for seq id no : 97 :( i ) sequence characteristics :( a ) length : 904 amino acids ( b ) type : amino acid ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 97 : metvalproglualatrpargserglyleuvalserthrglyargval151015valglyvalleuleuleuleuglyalaleuasnlysalaserthrval202530ilehistyrgluileproglugluargglulysglyphealavalgly354045asnvalvalalaasnleuglyleuaspleuglyserleuseralaarg505560argpheprovalvalserglyalaserargargphephegluvalasn65707580arggluthrglyglumetphevalasnaspargleuasparggluglu859095leucysglythrleuprosercysthrvalthrleugluleuvalval100105110gluasnproleugluleupheservalgluvalvalileglnaspile115120125asnaspasnasnproalapheprothrglnglumetlysleugluile130135140serglualavalalaproglythrargpheproleugluseralahis145150155160aspproaspleuglyserasnserleuglnthrtyrgluleuserarg165170175asnglutyrphealaleuargvalglnthrarggluaspserthrlys180185190tyralagluleuvalleugluargalaleuasparggluargglupro195200205serleuglnleuvalleuthralaleuaspglyglythrproalaleu210215220seralaserleuproilehisilelysvalleuaspalaasnaspasn225230235240alaprovalpheasnglnserleutyrargalaargvalproglygly245250255cysthrserglythrargvalvalglnvalleualathraspleuasp260265270gluglyproasnglygluileiletyrserpheglyserhisasnarg275280285alaglyvalargglnleuphealaleuaspleuvalthrglymetleu290295300thrilelysglyargleuaspphegluaspthrlysleuhisgluile305310315320tyrileglnalalysasplysglyalaasnprogluglyalahiscys325330335lysvalleuvalgluvalvalaspvalasnaspasnalaprogluile340345350thrvalthrservaltyrserprovalprogluaspalaserglythr355360365valilealaleuleuservalthraspleuaspalaglygluasngly370375380leuvalthrcysgluvalproproglyleupropheserleuthrser385390395400serleulysasntyrphethrleulysthrseralaaspleuasparg405410415gluthrvalproglutyrasnleuserilethralaargaspalagly420425430thrproserleuseralaleuthrilevalargvalglnvalserasp435440445ileasnaspasnproproglnserserglnsersertyraspvaltyr450455460ileglugluasnasnleuproglyalaproileleuasnleuserval465470475480trpaspproaspalaproglnasnalaargleuserphepheleuleu485490495gluglnglyalagluthrglyleuvalglyargtyrphethrileasn500505510argaspasnglyilevalserserleuvalproleuasptyrgluasp515520525argarggluphegluleuthralahisileseraspglyglythrpro530535540valleualathrasnileservalasnilephevalthraspargasn545550555560aspasnalaproglnvalleutyrproargproglyglyserserval565570575glumetleuproargglythrseralaglyhisleuvalserargval580585590valglytrpaspalaaspalaglyhisasnalatrpleusertyrser595600605leupheglyserproasnglnserleuphealaileglyleuhisthr610615620glyglnileserthralaargprovalglnaspthraspserproarg625630635640glnthrleuthrvalleuilelysaspasnglygluproserleuser645650655thrthralathrleuthrvalservalthrgluaspserprogluala660665670argalaglupheproserglyseralaproarggluglnlyslysasn675680685leuthrphetyrleuleuleuserleuileleuvalservalglyphe690695700valvalthrvalpheglyvalileilephelysvaltyrlystrplys705710715720glnserargaspleutyrargalaprovalserserleutyrargthr725730735proglyproserleuhisalaaspalavalargglyglyleumetser740745750prohisleutyrhisglnvaltyrleuthrthraspserargargser755760765aspproleuleulyslysproglyalaalaserproleualaserarg770775780glnasnthrleuargsercysaspprovalphetyrargglnvalleu785790795800glyalagluseralaproproglyglnglnalaproproasnthrasp805810815trpargpheserglnalaglnargproglythrserglyserglnasn820825830glyaspaspthrglythrtrpproasnasnglnpheaspthrglumet835840845leuglnalametileleualaseralaserglualaalaaspglyser850855860serthrleuglyglyglyalaglythrmetglyleuseralaargtyr865870875880glyproglnphethrleuglnhisvalproasptyrargglnasnval885890895tyrileproglyserasnalahis900 ( 2 ) information for seq id no : 98 :( i ) sequence characteristics :( a ) length : 556 amino acids ( b ) type : amino acid ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 98 : 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( 2 ) information for seq id no : 99 :( i ) sequence characteristics :( a ) length : 105 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 99 : gluaspthrvaltyrserpheaspileprogluasnalaglnarggly151015tyrglnvalglyglnilevalalaargaspalaaspleuglyglnasn202530alaglnleusertyrglyvalvalserasptrpalaasnaspvalphe354045serleuasnproglnthrglymetleuthrleuthralaargleuasp505560tyrglugluvalglnhistyrileleuilevalglnalaglnaspasn65707580glyglnproserleuserthrthrilethrvaltyrcysasnvalleu859095aspleuasnaspasnalaproilephe100105 ( 2 ) information for seq id no : 100 :( i ) sequence characteristics :( a ) length : 7 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 100 : aspxaaaspxaaglyxaaasn15 ( 2 ) information for seq id no : 101 :( i ) sequence characteristics :( a ) length : 7 amino acids ( b ) type : amino acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 101 : alaxaaaspxaaglyxaapro15 ( 2 ) information for seq id no : 102 :( i ) sequence characteristics :( a ) length : 4650 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( ix ) feature :( a ) name / key : cds ( b ) location : 495 .. 4103 ( xi ) sequence description : seq id no : 102 : 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( 2 ) information for seq id no : 103 :( i ) sequence characteristics :( a ) length : 1203 amino acids ( b ) type : amino acid ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 103 : 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( 2 ) information for seq id no : 104 :( i ) sequence characteristics :( a ) length : 2789 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( ix ) feature :( a ) name / key : cds ( b ) location : 115 .. 2622 ( xi ) sequence description : seq id no : 104 : cgaaagccatgtcggactcgtcgcccagcgcccaagcgctaacccgctgaaagtttctca60gcgaaatctcagggacgatctggaccccgctgagaggaactgcttttgagtgagatg117met1gtcccagaggcctggaggagcggactggtaagcaccgggagggtagtg165valproglualatrpargserglyleuvalserthrglyargvalval51015ggagttttgcttctgcttggtgccttgaacaaggcttccacggtcatt213glyvalleuleuleuleuglyalaleuasnlysalaserthrvalile202530cactatgagatcccggaggaaagagagaagggtttcgctgtgggcaac261histyrgluileproglugluargglulysglyphealavalglyasn354045gtggtcgcgaaccttggtttggatctcggtagcctctcagcccgcagg309valvalalaasnleuglyleuaspleuglyserleuseralaargarg50556065ttcccggtggtgtctggagctagccgaagattctttgaggtgaaccgg357pheprovalvalserglyalaserargargphephegluvalasnarg707580gagaccggagagatgtttgtgaacgaccgtctggatcgagaggagctg405gluthrglyglumetphevalasnaspargleuaspargglugluleu859095tgtgggacactgccctcttgcactgtaactctggagttggtagtggag453cysglythrleuprosercysthrvalthrleugluleuvalvalglu100105110aacccgctggagctgttcagcgtggaagtggtgatccaggacatcaac501asnproleugluleupheservalgluvalvalileglnaspileasn115120125gacaacaatcctgctttccctacccaggaaatgaaattggagattagc549aspasnasnproalapheprothrglnglumetlysleugluileser130135140145gaggccgtggctccggggacgcgctttccgctcgagagcgcgcacgat597glualavalalaproglythrargpheproleugluseralahisasp150155160cccgatctgggaagcaactctttacaaacctatgagctgagccgaaat645proaspleuglyserasnserleuglnthrtyrgluleuserargasn165170175gaatactttgcgcttcgcgtgcagacgcgggaggacagcaccaagtac693glutyrphealaleuargvalglnthrarggluaspserthrlystyr180185190gcggagctggtgttggagcgcgccctggaccgagaacgggagcctagt741alagluleuvalleugluargalaleuasparggluarggluproser195200205ctccagttagtgctgacggcgttggacggagggaccccagctctctcc789leuglnleuvalleuthralaleuaspglyglythrproalaleuser210215220225gccagcctgcctattcacatcaaggtgctggacgcgaatgacaatgcg837alaserleuproilehisilelysvalleuaspalaasnaspasnala230235240cctgtcttcaaccagtccttgtaccgggcgcgcgttcctggaggatgc885provalpheasnglnserleutyrargalaargvalproglyglycys245250255acctccggcacgcgcgtggtacaagtccttgcaacggatctggatgaa933thrserglythrargvalvalglnvalleualathraspleuaspglu260265270ggccccaacggtgaaattatttactccttcggcagccacaaccgcgcc981glyproasnglygluileiletyrserpheglyserhisasnargala275280285ggcgtgcggcaactattcgccttagaccttgtaaccgggatgctgaca1029glyvalargglnleuphealaleuaspleuvalthrglymetleuthr290295300305atcaagggtcggctggacttcgaggacaccaaactccatgagatttac1077ilelysglyargleuaspphegluaspthrlysleuhisgluiletyr310315320atccaggccaaagacaagggcgccaatcccgaaggagcacattgcaaa1125ileglnalalysasplysglyalaasnprogluglyalahiscyslys325330335gtgttggtggaggttgtggatgtgaatgacaacgccccggagatcaca1173valleuvalgluvalvalaspvalasnaspasnalaprogluilethr340345350gtcacctccgtgtacagcccagtacccgaggatgcctctgggactgtc1221valthrservaltyrserprovalprogluaspalaserglythrval355360365atcgctttgctcagtgtgactgacctggatgctggcgagaacgggctg1269ilealaleuleuservalthraspleuaspalaglygluasnglyleu370375380385gtgacctgcgaagttccaccgggtctccctttcagccttacttcttcc1317valthrcysgluvalproproglyleupropheserleuthrserser390395400ctcaagaattacttcactttgaaaaccagtgcagacctggatcgggag1365leulysasntyrphethrleulysthrseralaaspleuaspargglu405410415actgtgccagaatacaacctcagcatcaccgcccgagacgccggaacc1413thrvalproglutyrasnleuserilethralaargaspalaglythr420425430ccttccctctcagcccttacaatagtgcgtgttcaagtgtccgacatc1461proserleuseralaleuthrilevalargvalglnvalseraspile435440445aatgacaaccctccacaatcttctcaatcttcctacgacgtttacatt1509asnaspasnproproglnserserglnsersertyraspvaltyrile450455460465gaagaaaacaacctccccggggctccaatactaaacctaagtgtctgg1557glugluasnasnleuproglyalaproileleuasnleuservaltrp470475480gaccccgacgccccgcagaatgctcggctttctttctttctcttggag1605aspproaspalaproglnasnalaargleuserphepheleuleuglu485490495caaggagctgaaaccgggctagtgggtcgctatttcacaataaatcgt1653glnglyalagluthrglyleuvalglyargtyrphethrileasnarg500505510gacaatggcatagtgtcatccttagtgcccctagactatgaggatcgg1701aspasnglyilevalserserleuvalproleuasptyrgluasparg515520525cgggaatttgaattaacagctcatatcagcgatgggggcaccccggtc1749arggluphegluleuthralahisileseraspglyglythrproval530535540545ctagccaccaacatcagcgtgaacatatttgtcactgatcgcaatgac1797leualathrasnileservalasnilephevalthraspargasnasp550555560aatgccccccaggtcctatatcctcggccaggtgggagctcggtggag1845asnalaproglnvalleutyrproargproglyglyserservalglu565570575atgctgcctcgaggtacctcagctggccacctagtgtcacgggtggta1893metleuproargglythrseralaglyhisleuvalserargvalval580585590ggctgggacgcggatgcagggcacaatgcctggctctcctacagtctc1941glytrpaspalaaspalaglyhisasnalatrpleusertyrserleu595600605tttggatcccctaaccagagcctttttgccatagggctgcacactggt1989pheglyserproasnglnserleuphealaileglyleuhisthrgly610615620625caaatcagtactgcccgtccagtccaagacacagattcacccaggcag2037glnileserthralaargprovalglnaspthraspserproarggln630635640actctcactgtcttgatcaaagacaatggggagccttcgctctccacc2085thrleuthrvalleuilelysaspasnglygluproserleuserthr645650655actgctaccctcactgtgtcagtaaccgaggactctcctgaagcccga2133thralathrleuthrvalservalthrgluaspserproglualaarg660665670gccgagttcccctctggctctgccccccgggagcagaaaaaaaatctc2181alaglupheproserglyseralaproarggluglnlyslysasnleu675680685accttttatctacttctttctctaatcctggtttctgtgggcttcgtg2229thrphetyrleuleuleuserleuileleuvalservalglypheval690695700705gtcacagtgttcggagtaatcatattcaaagtttacaagtggaagcag2277valthrvalpheglyvalileilephelysvaltyrl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( 2 ) information for seq id no : 105 :( i ) sequence characteristics :( a ) length : 836 amino acids ( b ) type : amino acid ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 105 : metvalproglualatrpargserglyleuvalserthrglyargval151015valglyvalleuleuleuleuglyalaleuasnlysalaserthrval202530ilehistyrgluileproglugluargglulysglyphealavalgly354045asnvalvalalaasnleuglyleuaspleuglyserleuseralaarg505560argpheprovalvalserglyalaserargargphephegluvalasn65707580arggluthrglyglumetphevalasnaspargleuasparggluglu859095leucysglythrleuprosercysthrvalthrleugluleuvalval100105110gluasnproleugluleupheservalgluvalvalileglnaspile115120125asnaspasnasnproalapheprothrglnglumetlysleugluile130135140serglualavalalaproglythrargpheproleugluseralahis145150155160aspproaspleuglyserasnserleuglnthrtyrgluleuserarg165170175asnglutyrphealaleuargvalglnthrarggluaspserthrlys180185190tyralagluleuvalleugluargalaleuasparggluargglupro195200205serleuglnleuvalleuthralaleuaspglyglythrproalaleu210215220seralaserleuproilehisilelysvalleuaspalaasnaspasn225230235240alaprovalpheasnglnserleutyrargalaargvalproglygly245250255cysthrserglythrargvalvalglnvalleualathraspleuasp260265270gluglyproasnglygluileiletyrserpheglyserhisasnarg275280285alaglyvalargglnleuphealaleuaspleuvalthrglymetleu290295300thrilelysglyargleuaspphegluaspthrlysleuhisgluile305310315320tyrileglnalalysasplysglyalaasnprogluglyalahiscys325330335lysvalleuvalgluvalvalaspvalasnaspasnalaprogluile340345350thrvalthrservaltyrserprovalprogluaspalaserglythr355360365valilealaleuleuservalthraspleuaspalaglygluasngly370375380leuvalthrcysgluvalproproglyleupropheserleuthrser385390395400serleulysasntyrphethrleulysthrseralaaspleuasparg405410415gluthrvalproglutyrasnleuserilethralaargaspalagly420425430thrproserleuseralaleuthrilevalargvalglnvalserasp435440445ileasnaspasnproproglnserserglnsersertyraspvaltyr450455460ileglugluasnasnleuproglyalaproileleuasnleuserval465470475480trpaspproaspalaproglnasnalaargleuserphepheleuleu485490495gluglnglyalagluthrglyleuvalglyargtyrphethrileasn500505510argaspasnglyilevalserserleuvalproleuasptyrgluasp515520525argarggluphegluleuthralahisileseraspglyglythrpro530535540valleualathrasnileservalasnilephevalthraspargasn545550555560aspasnalaproglnvalleutyrproargproglyglyserserval565570575glumetleuproargglythrseralaglyhisleuvalserargval580585590valglytrpaspalaaspalaglyhisasnalatrpleusertyrser595600605leupheglyserproasnglnserleuphealaileglyleuhisthr610615620glyglnileserthralaargprovalglnaspthraspserproarg625630635640glnthrleuthrvalleuilelysaspasnglygluproserleuser645650655thrthralathrleuthrvalservalthrgluaspserprogluala660665670argalaglupheproserglyseralaproarggluglnlyslysasn675680685leuthrphetyrleuleuleuserleuileleuvalservalglyphe690695700valvalthrvalpheglyvalileilephelysvaltyrlystrplys705710715720glnserargaspleutyrargalaprovalserserleutyrargthr725730735proglyproserleuhisalaaspalavalargglyglyleumetser740745750prohisleutyrhisglnvaltyrleuthrthraspserargargser755760765aspproleuleulyslysproglyalaalaserproleualaserarg770775780glnasnthrleuargsercysaspprovalphetyrargglnvalleu785790795800glyalagluseralaproproglyglnvalargpheserlyssercys805810815leuthrleuleuvalprophetyrsertyrileileleuargargleu820825830gluleuphephe835 ( 2 ) information for seq id no : 106 :( i ) sequence characteristics :( a ) length : 2751 base pairs ( b ) type : nucleic acid ( c ) strandedness : single ( d ) topology : linear ( ii ) molecule type : cdna ( ix ) feature :( a ) name / key : cds ( b ) location : 115 .. 2160 ( xi ) sequence description : seq id no : 106 : cgaaagccatgtcggactcgtcgcccagcgcccaagcgctaacccgctgaaagtttctca60gcgaaatctcagggacgatctggaccccgctgagaggaactgcttttgagtgagatg117met1gtcccagaggcctggaggagcggactggtaagcaccgggagggtagtg165valproglualatrpargserglyleuvalserthrglyargvalval51015ggagttttgcttctgcttggtgccttgaacaaggcttccacggtcatt213glyvalleuleuleuleuglyalaleuasnlysalaserthrvalile202530cactatgagatcccggaggaaagagagaagggtttcgctgtgggcaac261histyrgluileproglugluargglulysglyphealavalglyasn354045gtggtcgcgaaccttggtttggatctcggtagcctctcagcccgcagg309valvalalaasnleuglyleuaspleuglyserleuseralaargarg50556065ttcccggtggtgtctggagctagccgaagattctttgaggtgaaccgg357pheprovalvalserglyalaserargargphephegluvalasnarg707580gagaccggagagatgtttgtgaacgaccgtctggatcgagaggagctg405gluthrglyglumetphevalasnaspargleuaspargglugluleu859095tgtgggacactgccctcttgcactgtaactctggagttggtagtggag453cysglythrleuprosercysthrvalthrleugluleuvalvalglu100105110aacccgctggagctgttcagcgtggaagtggtgatccaggacatcaac501asnproleugluleupheservalgluvalvalileglnaspileasn115120125gacaacaatcctgctttccctacccaggaaatgaaattggagattagc549aspasnasnproalapheprothrglnglumetlysleugluileser130135140145gaggccgtggctccggggacgcgctttccgctcgagagcgcgcacgat597glualavalalaproglythrargpheproleugluseralahisasp150155160cccgatctgggaagcaactctttacaaacctatgagctgagccgaaat645proaspleuglyserasnserleuglnthrtyrgluleuserargasn165170175gaatactttgcgcttcgcgtgcagacgcgggaggacagcaccaagtac693glutyrphealaleuargvalglnthrarggluaspserthrlystyr180185190gcggagctggtgttggagcgcgccctggaccgagaacgggagcctagt741alagluleuvalleugluargalaleuasparggluarggluproser195200205ctccagttagtgctgacggcgttggacggagggaccccagctctctcc789leuglnleuvalleuthralaleuaspglyglythrproalaleuser210215220225gccagcctgcctattcacatcaaggtgctggacgcgaatgacaatgcg837alaserleuproilehisilelysvalleuaspalaasnaspasnala230235240cctgtcttcaaccagtccttgtaccgggcgcgcgttcctggaggatgc885provalpheasnglnserleutyrargalaargvalproglyglycys245250255acctccggcacgcgcgtggtacaagtccttgcaacggatctggatgaa933thrserglythrargvalvalglnvalleualathraspleuaspglu260265270ggccccaacggtgaaattatttactccttcggcagccacaaccgcgcc981glyproasnglygluileiletyrserpheglyserhisasnargala275280285ggcgtgcggcaactattcgccttagaccttgtaaccgggatgctgaca1029glyvalargglnleuphealaleuaspleuvalthrglymetleuthr290295300305atcaagggtcggctggacttcgaggacaccaaactccatgagatttac1077ilelysglyargleuaspphegluaspthrlysleuhisgluiletyr310315320atccaggccaaagacaagggcgccaatcccgaaggagcacattgcaaa1125ileglnalalysasplysglyalaasnprogluglyalahiscyslys325330335gtgttggtggaggttgtggatgtgaatgacaacgccccggagatcaca1173valleuvalgluvalvalaspvalasnaspasnalaprogluilethr340345350gtcacctccgtgtacagcccagtacccgaggatgcctctgggactgtc1221valthrservaltyrserprovalprogluaspalaserglythrval355360365atcgctttgctcagtgtgactgacctggatgctggcgagaacgggctg1269ilealaleuleuservalthraspleuaspalaglygluasnglyleu370375380385gtgacctgcgaagttccaccgggtctccctttcagccttacttcttcc1317valthrcysgluvalproproglyleupropheserleuthrserser390395400ctcaagaattacttcactttgaaaaccagtgcagacctggatcgggag1365leulysasntyrphethrleulysthrseralaaspleuaspargglu405410415actgtgccagaatacaacctcagcatcaccgcccgagacgccggaacc1413thrvalproglutyrasnleuserilethralaargaspalaglythr420425430ccttccctctcagcccttacaatagtgcgtgttcaagtgtccgacatc1461proserleuseralaleuthrilevalargvalglnvalseraspile435440445aatgacaaccctccacaatcttctcaatcttcctacgacgtttacatt1509asnaspasnproproglnserserglnsersertyraspvaltyrile450455460465gaagaaaacaacctccccggggctccaatactaaacctaagtgtctgg1557glugluasnasnleuproglyalaproileleuasnleuservaltrp470475480gaccccgacgccccgcagaatgctcggctttctttctttctcttggag1605aspproaspalaproglnasnalaargleuserphepheleuleuglu485490495caaggagctgaaaccgggctagtgggtcgctatttcacaataaatcgt1653glnglyalagluthrglyleuvalglyargtyrphethrileasnarg500505510gacaatggcatagtgtcatccttagtgcccctagactatgaggatcgg1701aspasnglyilevalserserleuvalproleuasptyrgluasparg515520525cgggaatttgaattaacagctcatatcagcgatgggggcaccccggtc1749arggluphegluleuthralahisileseraspglyglythrproval530535540545ctagccaccaacatcagcgtgaacatatttgtcactgatcgcaatgac1797leualathrasnileservalasnilephevalthraspargasnasp550555560aatgccccccaggtcctatatcctcggccaggtgggagctcggtggag1845asnalaproglnvalleutyrproargproglyglyserservalglu565570575atgctgcctcgaggtacctcagctggccacctagtgtcacgggtggta1893metleuproargglythrseralaglyhisleuvalserargvalval580585590ggctgggacgcggatgcagggcacaatgcctggctctcctacagtctc1941glytrpaspalaaspalaglyhisasnalatrpleusertyrserleu595600605tttggatcccctaaccagagcctttttgccatagggctgcacactggt1989pheglyserproasnglnserleuphealaileglyleuhisthrgly610615620625caaatcagtactgcccgtccagtccaagacacagattcacccaggcag2037glnileserthralaargprovalglnaspthraspserproarggln630635640actctcactgtcttgatcaaagacaatggggagccttcgctctccacc2085thrleuthrvalleuilelysaspasnglygluproserleuserthr645650655actgctaccctcactgtgtcagtaaccgaggactctcctgaagcccga2133thralathrleuthrvalservalthrgluaspserproglualaarg660665670gccgagttcccctctggctctgccagttaaaccttctttaattatgg2180alaglupheproserglyseralaser675680attagccattaacatttttgaaacgtggaccatttaacctcggcctaccccctccaactg2240tcctggtgatgagttcattagctaagttaaattaattgaactttgatctaaaccaaaaca2300aatcaggaaaataaagctgtaaaggaacttatcaagcattccaaaaccaactagaaatta2360cttgaagtttcgagtgagcattgcctgtgccagtattcttcattataggattataaactc2420gtttttttcccaaagcgcatgtctacgccaggcagaggagtaattattcagccaatttca2480tggatgtaacgatggatataaataattgatagcacctagaggcttccagtttgggtggaa2540ggctaaaagtagaggggaactcactcacttgagaaatgatatttaagtgaataaatagtt2600ctcttctatgaaactattactatttagttctctggaaaacttaagtgtattaatgattag2660aacatcaaatcctaagtaaagaaatgacattttaaatataaaaagccaaactttaaataa2720atcatagagacctcagacataatataggaaa2751 ( 2 ) information for seq id no : 107 :( i ) sequence characteristics :( a ) length : 682 amino acids ( b ) type : amino acid ( d ) topology : linear ( ii ) molecule type : protein ( xi ) sequence description : seq id no : 107 : metvalproglualatrpargserglyleuvalserthrglyargval151015valglyvalleuleuleuleuglyalaleuasnlysalaserthrval202530ilehistyrgluileproglugluargglulysglyphealavalgly354045asnvalvalalaasnleuglyleuaspleuglyserleuseralaarg505560argpheprovalvalserglyalaserargargphephegluvalasn65707580arggluthrglyglumetphevalasnaspargleuasparggluglu859095leucysglythrleuprosercysthrvalthrleugluleuvalval100105110gluasnproleugluleupheservalgluvalvalileglnaspile115120125asnaspasnasnproalapheprothrglnglumetlysleugluile130135140serglualavalalaproglythrargpheproleugluseralahis145150155160aspproaspleuglyserasnserleuglnthrtyrgluleuserarg165170175asnglutyrphealaleuargvalglnthrarggluaspserthrlys180185190tyralagluleuvalleugluargalaleuasparggluargglupro195200205serleuglnleuvalleuthralaleuaspglyglythrproalaleu210215220seralaserleuproilehisilelysvalleuaspalaasnaspasn225230235240alaprovalpheasnglnserleutyrargalaargvalproglygly245250255cysthrserglythrargvalvalglnvalleualathraspleuasp260265270gluglyproasnglygluileiletyrserpheglyserhisasnarg275280285alaglyvalargglnleuphealaleuaspleuvalthrglymetleu290295300thrilelysglyargleuaspphegluaspthrlysleuhisgluile305310315320tyrileglnalalysasplysglyalaasnprogluglyalahiscys325330335lysvalleuvalgluvalvalaspvalasnaspasnalaprogluile340345350thrvalthrservaltyrserprovalprogluaspalaserglythr355360365valilealaleuleuservalthraspleuaspalaglygluasngly370375380leuvalthrcysgluvalproproglyleupropheserleuthrser385390395400serleulysasntyrphethrleulysthrseralaaspleuasparg405410415gluthrvalproglutyrasnleuserilethralaargaspalagly420425430thrproserleuseralaleuthrilevalargvalglnvalserasp435440445ileasnaspasnproproglnserserglnsersertyraspvaltyr450455460ileglugluasnasnleuproglyalaproileleuasnleuserval465470475480trpaspproaspalaproglnasnalaargleuserphepheleuleu485490495gluglnglyalagluthrglyleuvalglyargtyrphethrileasn500505510argaspasnglyilevalserserleuvalproleuasptyrgluasp515520525argarggluphegluleuthralahisileseraspglyglythrpro530535540valleualathrasnileservalasnilephevalthraspargasn545550555560aspasnalaproglnvalleutyrproargproglyglyserserval565570575glumetleuproargglythrseralaglyhisleuvalserargval580585590valglytrpaspalaaspalaglyhisasnalatrpleusertyrser595600605leupheglyserproasnglnserleuphealaileglyleuhisthr610615620glyglnileserthralaargprovalglnaspthraspserproarg625630635640glnthrleuthrvalleuilelysaspasnglygluproserleuser645650655thrthralathrleuthrvalservalthrgluaspserprogluala660665670argalaglupheproserglyseralaser675680__________________________________________________________________________