H. sapiens ME----------DPSGAREPRARPRERDPGRRPHPDQGRTHDRPRDRPGDPRRKRSSDGNRRRDGDRDPERDQERDGNRDRNRDRERERERERDPDRGPRRDTHRDAGPRAGEHGVWEKP 110M. musculus MK----------NTSGHREPRTRPRERDPDRRPHPDRDHHVERSRDRGGDRHRER--NGDVRGNGDR-------RAG-------------REQRTDRDQRQDRHRDAGHRASEQRALEKS 88C. lupus MSGRGTGERTWGDTRGAREPRARQKERDRERQPRPDRDRHPERQRDRPGDRRRRR--IGAERGDGHR------------------------GRGRDRDARQD--GDGDRRAG-----EKA 87G. gallus VB -----------------------MAERSCPRAPRGGGDGRGSARHGGSGGGREERGGMAGGRG--------------------------------------------------------- 40 **. * *: . . . :. *. :..* . * H. sapiens RQSRTRDGARGLTWDAAAPPGPAPWEAPEPPQPQRKGDPGRRRPESEPPSERYLPSTPRPGREEVEYYQSEAEGLLECHKCKYLCTGRGVVQIVEVVLNGMVLICIVASYFVLAGFSASF 230M. musculus RQSRARPEPWGPSWDAAPTPGPAPWGPPE--LSQKHG-LGRRGLESERASERYVPTYSVPALQEEEYYQSEAEGLLDCHKCRYLCTGRGVVQIMEVILNAMVLICIVASYFVLAGFSASF 205C. lupus RRGRAREAPRRPAGPAAPPPWPAPRETPEP-PPQRRERLGPRGPASEPTSGRYLPSNPRSGLEEVEYYQSEAEGLLECHKCRYLCTGR-VVQIVEVILNGMVLMCVVASYFVLAGFSASF 205G. gallus VB -VARLPPLPLTPLSPGSAVPGAGP----------------PRG-------------------------RADTPGLLECRRCRYLRTGRACCQLVGALLAALILVCSSVSYGSAGGYTGVP 118 .* . .:. * ..* * :::: ***:*::*:** *** *:: .:* .::*:* .** .*::. .* . .:. * ..* * :::: ***:*::*:** *** *:: .:* .::*:* .** .*::.

H. sapiens SSGGGFGNNY---YSPFEGTELEQVRQLDQQYTILRSPLIYGGVAVSLGLGVLTMGVLLQGAKSRTMLSGKWLLTEAAFSLLAAVGYCTGIGVYLHVALQINSTDTCKTRERLYARKGLT 347M. musculus ASGSGFGNNY---YSPFEGTELEQVRQLDQQYTILRSPLIYGGVAVSLGLGVLTMGVLLQGAKSLRKLPRRWLLLEAAFSLLAAVGYCVAIGFYLYAALRINSTDTCKTRERVYARKGLT 322C. lupus TSGGGFGNNY---YSPFEGTELEQVRQLDQQYTVLRAPLIYGGVAVSLGLGVLTMGVLLQGAKSLTKLWGKWLLLEAAFSLLAALSYGAGIGIYLHVALQINST-TCRARARLYARKGLT 321G. gallus VB DQGSIYYYMYGGAYSGLSGAEGEKAQQLDRRFTQLKVPIARAAMAVGGALMVFSSALIVVGVVRLPWRFPALLIVECILDAVVAVGLLFALYYFFHHLLGVYDSSVCKERAQLYQSKGYR 238G. gallus VB DQGSIYYYMYGGAYSGLSGAEGEKAQQLDRRFTQLKVPIARAAMAVGGALMVFSSALIVVGVVRLPWRFPALLIVECILDAVVAVGLLFALYYFFHHLLGVYDSSVCKERAQLYQSKGYR 238 .*. : * ** :.*:* *:.:***:::* *: *: ..:**. .* *:: .::: *. *: *. :. :.*:. .: ::: * : .: .*: * ::* ** H. sapiens WMDCQLAGTDGAAATFACLLVIMYGASVVLALRSYREQKRYKGSREQPGSYSDAPEYLWSGTL 410M. musculus WMNCQLAGTDGAAATFACLLVILYAASVVMALRAYREQKHYKDSQEQHRNYRDVPEYLWSGTL 385C. lupus WMNCELAGTDGAAATFACLLVIMYGASVVLALRSHREQQRRKEGQAQPREYHDGPEYLWSGTL 384G. gallus VB GFSCSMHGAEIAAGLLGCAAVVAFLLGAGLAIRGYRIVHKLKQKPEHAYEP------------ 289 :.*.: *:: **. :.* *: : .. :*:*.:* :: * : . :.*.: *:: **. :.* *: : .. :*:*.:* :: * : .

H. sapiens ME----------DPSGAREPRARPRERD----PGRRPH----PDQGRTHDRPRDRPGDPRRKRSSDGNRRRDGDRDPERDQERDGNRDRNRDRERERERERDPDRGPRRDTHRDAGPRAG 102M. musculus MK----------NTSGHREPRTRPRERD----PDRRPH----PDRDHHVERSRDRGGDRHRER--NGDVRGNGDR-------RAG-------------REQRTDRDQRQDRHRDAGHRAS 80C. lupus MSGRGTGERTWGDTRGAREPRARQKERD----RERQPR----PDRDRHPERQRDRPGDRRRRR--IGAERGDGHR------------------------GRGRDRDARQD--GDGDRRAG 84X. laevis VA MR----------DSVTDGENRAPRKHRDHLENDTHKPHNRNLPESDQYSKQYHDERTQSRIKQEKNRNHYTERDQ---------------------THEERTSSRNQGEKNKNWSEQREK 89D. rerio VA ------------MAGSNRHHHTRDRDRR---------------DDHRHDRRYREDRGTPDGED---------------------------------------RSRNHR------------ 42D. rerio VA ------------MAGSNRHHHTRDRDRR---------------DDHRHDRRYREDRGTPDGED---------------------------------------RSRNHR------------ 42G. gallus VA -----------MAQVLPRARGPPPRGGR---------------SGGGGGRIWPGREPELRAALR----------------------------------KLFLKERVHVRDKMAHAGRRYQ 60 . : . .* H. sapiens EHGVWEKPRQSRTRDGARGLTWDAAAPPGPAPWEAPEPP-QPQRKGDPGRRRPESEPPSERYLP---------------STPRPGREEVEYYQS-----------------EAEG-LLEC 188M. musculus EQRALEKSRQSRARPEPWGPSWDAAPTPGPAPWGPPE---LSQKHG-LGRRGLESERASERYVP---------------TYSVPALQEEEYYQS-----------------EAEG-LLDC 163M. musculus EQRALEKSRQSRARPEPWGPSWDAAPTPGPAPWGPPE---LSQKHG-LGRRGLESERASERYVP---------------TYSVPALQEEEYYQS-----------------EAEG-LLDC 163C. lupus -----EKARRGRAREAPRRPAGPAAPPPWPAPRETPEP--PPQRRERLGPRGPASEPTSGRYLP---------------SNPRSGLEEVEYYQS-----------------EAEG-LLEC 164X. laevis VA YYRERETSRNQQERSQGRYDDKDGYYKERVQDRNKKQYLEKENYQKEPEKVRKNTERSRNEFMERDEYRENASYSKDRHQYPMENKEQERYYADQRSFSVHGSNMEYVEDHETDGGILEC 209D. rerio VA -----DKQRYTDPQRDPR-VYEDTRYHRQAAP-------------------SSYAENSSSYYGD----------------SQTYHREEALYNLG-------------------------- 95G. gallus VA DKQGRYHENHGSDGYEEDRKTRKPSPYNGRSAKDTRGGQHSRASIVCSEPYSKASAASQEYFEP----------------PPQYYPTKETLSMK-------------------------- 138G. gallus VA DKQGRYHENHGSDGYEEDRKTRKPSPYNGRSAKDTRGGQHSRASIVCSEPYSKASAASQEYFEP----------------PPQYYPTKETLSMK-------------------------- 138 . : . : : H. sapiens HKCKYLCTGRACCQMLEVLLNLLILACSSVSYSSTGGYTGITSLGGIYYYQFGGAYSGFDGADGEKAQQLDVQFYQLKLPMVTVAMACSGALTALCCLFVAMGVLRVPWHCPLLLVTEGL 308M. musculus HKCRYLCTGRACCQMLEALLNLLILACSSVSYNSTGGYTGITSLGGIYYYQYGGAYSGFDGADGERAQQLDVQFYQLKLPTVTAAMAYSGALMTFSCLTLLAGALRVPWHCPLWLVIEGL 283C. lupus HKCRYLCTGRACCQMLEALLNLLVLACSSVSYGSTGGYTGLPSLGGIYYYQFGGAYSGFDGAAGERAQQLDVQFYQLKLPTVTTAMACGGALMAFCCLLVLLGVLRVPWHCPPWLVAEGL 284X. laevis VA HKCKYLCTGRALCQLVEVLLNMLILICCSVSYNSTGGFTGITNLGGIYYYQFGGAYSGFSGADGEKAQKLDVQFYQLKLPTVTASMAFGGALMAFCCLLVLLGVLRIPWRFPIWLLVECV 329X. laevis VA HKCKYLCTGRALCQLVEVLLNMLILICCSVSYNSTGGFTGITNLGGIYYYQFGGAYSGFSGADGEKAQKLDVQFYQLKLPTVTASMAFGGALMAFCCLLVLLGVLRIPWRFPIWLLVECV 329D. rerio VA ----YLTTSRGVCQGLEFTLSLLIIICAGVNYSNSGRYRDIASLGGLYQYYYGGAN-AFTGAEAQKVQQLDDQFYQLKLPPYIFSMACGGALMFYAGVLLALGVFRMPYRFPPLLLGEAL 210G. gallus VA --CSKVCTTRGILKFVEITVNLLVLICVGAAQASVAGFTSVGGLG-IGSFNLNSAYSPFEGTELQEVRELDMQITQMRAPCVYGGVAFSLAAAALTLVFLVVGAKPIHRLKMGLLGGECT 255 : * *. : :* :.:*:: * .. . . : .: .** : : ..* * *: :..::** *: *:: * .:* . * : : *. : * *

H. sapiens LDMLIAGGYIPALYFYFHYLSAAYGSPVCKERQALYQSKGYSGFGCSFHGADIGAGIFAALGIVVFALGAVLAIKGYRKVRKLKEKPAEMFEF-------------------------------- 401H. sapiens LDMLIAGGYIPALYFYFHYLSAAYGSPVCKERQALYQSKGYSGFGCSFHGADIGAGIFAALGIVVFALGAVLAIKGYRKVRKLKEKPAEMFEF-------------------------------- 401M. musculus MDALIAGAYVPGLYFFFQHLSAAYSSDVCKERETLYQSKGYSGFNCGVHGGDIGAGVFAAMAIGVFAVGAVLAFRGYRKVKKLKEKPTEMLEF-------------------------------- 376C. lupus LDVLIAAAHVPALYFYFQRLSAAYASPVCKEREALYQSKGYSGFSCSLHGGDIGAGIFAALSAGVFAVGAVLAIRGYRKVRKLKEKPAEMLEF-------------------------------- 377X. laevis VA LDILIAVGYIPALYFYFRRLQDAYDSQVCKDRESLYSSKGYKGFSCALHGADIAAALFACMAVIAFFLSAVLAIKGYKRVRQLKKKPNNYV---------------------------------- 420D. rerio VA LDVLIGLGFLPAVAFYFIKLQEIYNNSICKEREAMYSSKALRGFECNFNGADIAGGLFGVLGVIIFPVSAVFAIRAFRRVRKMKQRPAEDNNL-------------------------------- 303D. rerio VA LDVLIGLGFLPAVAFYFIKLQEIYNNSICKEREAMYSSKALRGFECNFNGADIAGGLFGVLGVIIFPVSAVFAIRAFRRVRKMKQRPAEDNNL-------------------------------- 303G. gallus VA FNLLAGVGYIVAVGLYLHFVTQVNATEACKRRERLYARRGYTSMNCVVQGGDAAVGLFGVAAACLYFASFVVCILAIRTVRAFQSRMAKAQHSPKSSVRDRSVRNDRPVHRPSESSHNIQALATL 380 :: * . ..: .: ::: : . ** *: :* :. .: * .:*.* . .:*. . : . *..: . : *: ::.: :

Isoform1 MEDPSGAREPRARPRERDPGRRPHPDQGRTHDRPRDRPGDPRRKRSSDGNRRRDGDRDPERDQERDGNRDRNRDRERERERERDPDRGPRRDTHRDAGPRAGEHGVWEKPRQSRTRDGAR 120Isoform2 MEDPSGAREPRARPRERDPGRRPHPDQGRTHDRPRDRPGDPRRKRSSDGNRRRDGDRDPERDQERDGNRDRNRDRERERERERDPDRGPRRDTHRDAGPRAGEHGVWEKPRQSRTRDGAR 120 ************************************************************************************************************************

Isoform1 GLTWDAAAPPGPAPWEAPEPPQPQRKGDPGRRRPESEPPSERYLPSTPRPGREEVEYYQSEAEGLLECHKCKYLCTGRGVVQIVEVVLNGMVLICIVASYFVLAGFSASFSSGGGFGNNY 240Isoform2 GLTWDAAAPPGPAPWEAPEPPQPQRKGDPGRRRPESEPPSERYLPSTPRPGREEVEYYQSEAEGLLECHKCKYLCTGRACCQMLEVLLNLLILACSSVSYSSTGGYTGITSLGGIYYYQF 240Isoform2 GLTWDAAAPPGPAPWEAPEPPQPQRKGDPGRRRPESEPPSERYLPSTPRPGREEVEYYQSEAEGLLECHKCKYLCTGRACCQMLEVLLNLLILACSSVSYSSTGGYTGITSLGGIYYYQF 240 ******************************************************************************. *::**:** ::* * .** .*::. * ** : ::

Isoform1 ---YSPFEGTELEQVRQLDQQYTILRSPLIYGGVAVSLGLGVLTMGVLLQGAKSRTMLSGKWLLTEAAFSLLAAVGYCTGIGVYLHVALQINSTDTCKTRERLYARKGLTWMDCQLAGTD 357Isoform2 GGAYSGFDGADGEKAQQLDVQFYQLKLPMVTVAMACSGALTALCCLFVAMGVLRVPWHCPLLLVTEGLLDMLIAGGYIPALYFYFHYLSAAYGSPVCKERQALYQSKGYSGFGCSFHGAD 360 ** *:*:: *:.:*** *: *: *:: .:* * .* .* .: *. . . *:**. :.:* * ** ..: .*:* .: .** *: ** ** : :.*.: *:*

Isoform1 GAAATFACLLVIMYGASVVLALRSYREQKRYKGSREQPGSYSDAPEYLWSGTL 410Isoform1 GAAATFACLLVIMYGASVVLALRSYREQKRYKGSREQPGSYSDAPEYLWSGTL 410Isoform2 IGAGIFAALGIVVFALGAVLAIKGYRKVRKLK---EKP---AEMFEF------ 401 .*. **.* ::::. ..***::.**: :: * *:* :: *:

A

B

C