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866

Supplemental Fig. 1

a

423

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LN :S...........R....R..S......G..........R.......LM.DN...GS.E-T.GG.LNF......M..M..P.L.PASRRVPKLM....GS..V....R..------------------------------TTTLTH................VF.L..S.NM.I.EAG.Q.V..V......TLNDTN..P..........K.......................KE..A...I.......S..G........................A...FRI.N..FE............H..G...L.R......S...................G..GDTD.LLDR..S.P.KGE..C..PAK...T.P.ES...M-------I..P.D...V.------------------------------------....S.SP..V.V.....

SHH :S...........R....R..S......G..........R.......LM.DN...GS.E-T.GG.LNF...S..M..M..P.L.PASRRVPKLM....GS..V....R..------------------------------TTTLTH.................F.L..S.NM.I.EAG.Q.V..V......ILNDTN..P..........K.......................KE..A...I.......S..G........................A...FRI.N..FE.F..........P..G...L.R......S...........P.......G..GDTD.LLDR..S.P.KGE..CG.PAK...M.P.ES...M-------T..P.D...V.------------------------------------......S...L.V.....

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JXwn06 :S...........R....R..S......G..........R.......LM.DN...GS.E-T.GG.LNF...S..M..M..P.L.PASRRVPKLM....GS..V....R..------------------------------TTTLTH.................F.L..S.NM.I.EAG.Q.V..V......ILNDTN..P..........K.......................KE..A...I.......S..G........................A...FRI.N..FE............H..G...L.R......S...................G..GDTD.LLDR..S.P.KGE..C..PAK...M.P.ES...M-------I..P.D...V.------------------------------------......S...V.V.....

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HEB1 :S....A......R....R..S....L.D..........R...C...LM.DN...GS.E-T.GG.LNF...S..M..M..P.L.PASRRVPKLM....GS..V....R..------------------------------TTTLTH...........R.....F.L..S.NM.I.EAG.Q.V..V......ILNDTN..P..........K.......................KE..A...I.......S..S........................A...FRI.N..FE............H..G...L........S...................G..GDTD.LLDR..S.P.TGE..C..PAK...M.P.ES...I-------I..P.DI..V.------------------------------------......S...V.V.....

HeN-LY :S...........R....R..S......D..........R.......LM.DN...GS.E-T.GG.LNF...S..M..M..P.L.PASRRVPKLM....GS..V....R..------------------------------TTTLTH.................F.L..S.NM.I.EAG.Q....V......ILNDTN..P..........K.....H......N..........KE..A...I.......S..N........................A...FRI.N..FE............H..G...L........S...................G..GDTD.LLDR..S.P.KGE..C..PAK...M.P.ES...I-------I..P.D...V.------------------------------------......S...V.V.....

HeN-KF :S...........R....R..S......D..........R.......LM.DN...GS.E-T.GG.LNF...S..M..M..P.L.PA.RRVPKLM....GS..V....R..------------------------------TTTLTH.................F.L..S.NM.I.EAG.Q....V......ILNDTN..P..........K.......................KE..A...I.......S..S........................A...FRI.N..FE............H..G...L........S...................G..GDTD.LLDR..S.P.KGE..C..PAK...M.P.ES...I-------I..P.D...V.------------------------------------......S...V.V.....

HeN-LH :S...........R....R..S......D..........R.......LM.DN...GS.E-T.GG.LNF...S..M..M..P.L.PASRRVPKLM....GS..V....R..------------------------------TTTLTH.................F.L..S.NM.I.EAG.Q....V......ILNDTN..P..........K.......................KE..A...I.......SR.S........................A...FRI.N..FE............H..G...L........S...................G..GDTD.LLDR..S.P.KGE..C..PAK...M.P.ESN..I-------I..P.D...V.------------------------------------......S...V.V.....

SY0608 :S...........R....R..S......D..........RFN....GLM.DN...GS.E-T.GG.LNF...S..M..M..P.L.PASRRVPKLM...GGS..V....R..------------------------------TTTLTH.................F.L..S.NM.I.EAG.Q....V......ILNDTN..P..........K.......................KE..A...I.......S..S....R...................A...FRI.N..FE............H..G...L........S...................G..GDTD.LLDR..S.P.KGE..C..PAK...M.P.ES...I-------I..P.D...V.------------------------------------......S...V.V.....

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LS-4 :S...........R....R..S......D..........R.......LM.DN...GS.E-I.GGLLNF...S..M..M..P.L.PASRRVPKLM....GS..V....R..------------------------------TTTLTH.................F.L..S.NM.I.EAG.Q....V......ILNDTN..P..........K.......................KE..A...I.......S..S........................A...FRI.N...E............H..G...L........S...................G.MGDTD.LLDR..SVP.KGE..C..PAK...M.P.ES...I-------I..P.D...V.------------------------------------......S.....V.....

HUB1 :S...........R....R..S......D..........R.......LM.DN...GS.E-T.GG.LNF...S..M..M..P.L.PASRRVPKLM....GS..V....R..------------------------------TTTLTH.................F.L..S.NM.I.EAG.Q....V......ILNDTN..P..........K.......................KE..A...I.......S..S........................A...FRI.N..FE............H..G...L........S...................G.MGDTD.LLDR..S.P.KGE..C..PAK...M.P.ES...I-------I..P.D...V.------------------------------------......S...V.V.....

HUB2 :S...........R....R..S......D..........R.......LM.DN...GS.E-T.GG.LNF...S..M..M..P.L.PASRRVPKLM....GS..V....R..------------------------------TTTLTH.................F.L..S.NM.I.EAG.Q....V......ILNDTN..P..........K.......................KE..A...I.......S..S........................A...FRI.N..FE............H..G...L........S...................G.MGDTD.LLDR..S.P.KGE..C..PAK...M.P.ES...I-------I..P.D...V.------------------------------------......S...V.V.....

HuN :S...........R....R..S......D..........R.......LM.DN...GS.E-T.GG.LNF...S..M..M..P.L.PASRRVPKLM....GS..V....R..------------------------------TTTLTH.................F.L..S.NM.I.EAG.Q....V......ILNDTN..P..........K.......................KG..A...I.......S..S.......................CA...FRI.N..FE........K...H..G...L........S....P..............G..GHTD.LIDR..S.P.KGE..G..PAK...MCLPES...I-------I..P.N...V.------------------------------------......S...V.V.....

HuNh1 :S...........R....R..S......D..........R.......LM.DN...GS.E-T.GG.LNF...S..M..M..P.L.PASRRVPKLM....GS..V....R..------------------------------TTTLTH.................F.L..S.NM.I.EAG.Q....V......ILNDTN..P..........K.......................KG..A...I.......S..S.......................CA...FRI.N..FE........K...H..G...L........S....P..............G..GHTD.LIDR..S.P.KGE..G..PAK...MCLPES...I-------I..P.N...V.------------------------------------......S...V.V.....

JX0612 :S...........R....R..S......D..........R.......LM.DN...GS.E-T.GG.LNF...S..M..M..P.L.PASRRVPKLM....GS..V....R..------------------------------TTTLTH.................F.L..S.NM.I.EAG.Q....V......ILNDTN..P.........FK...........T...........KE..A...I.......S..S..V.....................A...FRI.N..FE............H..G...L........S.............V.....G..GDTD.LLDR..S.P.KGE..C..PAK...M.P.ES...I-------I..P.D...V.------------------------------------......S...V.V.....

JX1 :S...........R....R..S......D..........R.......LM.DN...GS.E-T.GG.LNF...S..M..M..P.L.PASRRVPKLM....GS..V....R..------------------------------TTTLTH.................F.L..S.NM.I.EAG.Q....V......ILNDTN..P.........FK...........T...........KE..A...I.......S..S..V.....................A...FRI.N..FE............H..G...L........S.............V.....G..GDTD.LLDR..S.P.KGE..C..PAK...M.P.ES...I-------I..P.D...V.------------------------------------......S...V.V.....

HNXT1 :S...........R....R..S......G..........R.......LM.DN...GS.E-T.GG.LNF...S..M..M..P.L.PASRRVPKLM....GS..V....R..------------------------------TTTLTH.................F.L..S.NM.I.EAG.Q....V......ILNDTN..P..........K...........T...........KE..A...I.......S..S..V.....................A...FRI.N..FE............H..G...L........S...................G..GDTD.LLDR..S.P.KGE..C..PAK...M.P.ES...I-------I..P.N...V.------------------------------------......S...V.V.....

GD :S...........R....R..S......D..........R.......LM.DN...GS.E-T.GG.LNF...S..M..M..P.L.PASRRVPKLM....GS..V....R..------------------------------TTTLTH................VF.L..S.NM.I.EAG.Q....V.......LNDTN..P..........K.......................KE..A...I.......S..S........................A...FRI.N..FE............H..G...L........S...................G..GDTD.LLDR..S.P..GE..C..PAK...M.P.ES...I-------I..P.D...V.------------------------------------......S...V.V.....

MN184A :-----------..F....AES......SR.L....K.IR.R....I....NL.D.Q...-AGGS..F..L..-------------------LVVSS..SV.V....RV...L.SSPIVST.......GLR..-EGMNL..VTLAC...................L.L.L.ED..A..RR.V..V..G..G..DD.RL.P.........IE............N.....C........KY.N....................................IF..PF..ADKF.S..............G.....R.............V............G.VQG...TTD.....LFA.ELA...PARE..TQTPPASAGG-------AGLVLDS..SP------------------------------------EL....LPX.T..G....

MN184B :-----------..F....AES......SR.L....K.I..R....I....NL.D.R...-AGGS..F..L..-------------------LVASS...V.V....RV...L.SSPIVST.......GLR..-EGMNL..VTLAC...................L.L.L.ED..A..RR.V..V..G..G.PDD.RL.P.........IE............N.....C........KY.N....................................IF..PF..ADKF.T..............G.....R.............V............GNVQG...TTD.....PFA.ELA....ARE..TQTPPASTGG-------AGLVSDS.RSP------------------------------------EL....L.N.T..G....

SP :............I.......L......S..........R...DC.TLS.NNL.D.......GC.S....S...V..L..PAS..A.RRS...VK.....V.V....K.....A...................-EKVNP...TLGC...FP......H.......LVL..N.D..E..ER....I..G...ILDA.....A.........A.................Y.............I.S....V.............................H..SR...D.F................G.....R.........................FG.VND.CK.ID.R..VLF.NELA...PAR...T..Q.F.G..-------P..P...D.T.LASGPGVREVDSCEASSTEKIEQPFVLNGGASTQAST..N...PG.I..G.S..

Jyt2 :K.......L...G.....SRL......N.........IR.G.DGSTPS.NSSSD...N..A.G.S...I....V..LC.SAP.FAL.RSS..V......T.V..L.KI.......................T-EKMNAV.VTLACR.G..............PF.TL..N.DI.EM.ERG...V..GT..ILDDV..V.A.........E............N.................NI......V.............C..............A...FR...N.F................G.....S.......T........I.........GETNG.CKLTD.R..VLF.NEL.....AR.LQT..QK..GI.-------P..P.D.S.T.LASGPGVGEVGLCEASSTEKSEQPSVSDGGVSTQASTPIN..S.G.T..G....

EDRD-1 :............S.R...A.S......S..........R.A....TPS.D..LDR......GG.SG...L.A---------------------------------------.A......V...........A-...NL...TLT............H....V..IV...NE.......Q....V...L..ILDDT.L..A...............C.....................M...I............S..........................S...AD.FE...............G.....R..........................GRTKD..KTT.....VLL.N..A..RPAKN.QTLLQGS.G..-------P..P.S...T.LVSGLGVEGVGSCGVSLAEKNEHPFLLNDGVNAPTPTP..P..L..V.......

Gu922M :.........S..S.R...S.S.....GS..........R.A....TPS.D..LD..G.P.AGG.SG.T.L.A---------------------------------------.A......V.......R...A-EK.NL...TLT............H....V..T....NED......Q....V...L..ILDDT.L..A...............C.V.........Y....KD...M.F.I.................................S..H..FR..AD.FE...............G.....R......S...................GRMKD..KTT.....VPFGNE....RTAE..QAL.QG..G..-------P....S...T.LVSGLGVEEVGLCEVSLAEKNDHPFALNGCVNAPASTS..P..L..V.......

Kagoshima-N14 :......S..S..SA...RA.S......S..........R.A....TPS.D.ILD......AGG.SG...LST---------------------------------------.A...GK.V...........A-.K.NLM..TLT............H....V..T....NE.......Q....V...L..ILDDT.LT.A.........K.....C.....................M...I........R...............................R..A..FE...............G...T.R..........................GRVKG..KTT.....VSFKNEST..RPTKN.Q.LLQGS.G..-------P.S..S..ST.LVAGLGVEEVGLCEVSLAEKNVHPFVLDGSVNAPAPTS..P..L..VE......

Aomori :.......S.T..S.....A.S......N..........R.A....TPSSDNALD......AGG.SG...L.T---------------------------------------LA.....TV...........A-.Q.NL...TLTC..K........Y....V..TV...NE.A.....L....V...L...LDDA.L..A...............C.....................M...I...................................A...FR..A..FE...............G.....R...........................R.KD...TT.....VPF..E.A.GRPAK..QTL.QGS.G..-------P...TS...T.L-LGLGVGEVGLCEVSLTEKNEHPFALNGSVDAPAPTP..P..LN.V.......

Jtg1 :.....IS.T...IA....A.S.....GSV...V.....R.A....TPS.DG.L..R.G.VAG.SSG.S...T---------------------------------------.A...CWSV......H....KREKSNL..VTLM............H.GH.V..TV...NE..P.AG..D...V...L..ILDDTRL..................C..................I..............................................PL..AN.FE...............G.....R.....................I....GGTKDA.KTT....P.SF.NE.A.--------------------------------------LGLGVEEVGLCEVGLAEKDEHPLVLNGCVNASAPTT..S..L..V......S

Ibaraki3 :......S.T...IA....A.S.T....S..........R.AR...TPS.D..LD..G.F.AGG.SG...L.T---------------------------------------.A......V......H....N-.KMGL...TLT............H....V..TV...NE...SAGEQ.V..V...L...LDDT.L..A...........I...C.........................I....................C............A.....SR..AN.FE...............G.....R..........................GR.KD..KTT.L..S.SF.NE.AN.RPAR..QTL.QGS.G.A-------P.L..S.S.T.LVSGLGVEEVGLCKVSLAEKNEHPFVLNGSVNASAPTP..P..L..E......S

Jyt1 :.........S..S.....A.S......S.......K..R.A....TPSC..ALD..V.S.AGGSSG...LLT---------------------------------------.A.L....V......H....A-EKPNLV..TLTC...........H....V..TV.LLDKS.....EQ....V...F...LDGT.Q..A.........K.....C..................A..M...I.......................................SR..A...E...Q...........G.....R.......................C..GMKKI..KTT..R...PF.GE.AG.R.AK.LQTL.QGS.G.I-------P...TSA..T.LVSGLGVEGVGLCEVSLAEKSDYPFVSDGSVNAPAPTPA.P..L..V.......

Jyn1 :.......QSS..S.....A.S......S........R.R.A....TPS.N.ALD...NF.AGG.SG....LT---------------------------------------T...................A-.EMDQ...TLMH...........C.......TV.L.NE.......Q....I...L..VL.DT.L..A...............C..................E......I....................C..................LR..AN.SE...R...........G.....R.......................Y..GGVK.A.KTTS.....PF.NE.AGGRPA.G.QTLPQK..G..-------P..P.S...I.LVSGLEAEEVGLRKVSLAVEDEHPAALNSSVNAPAPTP..P..L..V......L

Jsa1 :......S.TL..TAR...A.S.V.FS.S..........R.T.D..TP..DGAFD..G...AGG.SGP..SST---------------------------------------.T....K.V........L.RK-EK.NQ...TLAH...........H....VPTTV....E.I....RQ....V...L...LDDA.L..................C.....................M...I.......................................SR..AN.SE...R........H..G.....R......ST..................G..KD..VTT.....EPF------S.PAENSQALL.G.GG..-------P.L..S.S.T.LISGLGVEEVGLCEVSSAEKSEHPFVLNSCVNASAPTP..SLSL...NT.....

Jib1 :D...........S.....A.S....LGSR........AR.A....T.S.D..LDG..N.TA.G.SG..ALTV---------------------------------------.A..S...V..........L.-.G.NL...TLTC...........C....F..TV...EE.....DVR....V...L..TL.DT.L.PA...............C..................I..M...I.................................K..F..FR..AN..E...R...........G.....R......S.................L.GRMKD.SKTT...LS.PF.NE.A..R.AK..QTQ.PGSKGA.-------P.SP.SA..I.LVSGLGVEKVGLCEVNLAEKDEHPFASNDGVNAPAPTP..S..LN.IN......

Chiba14 :............S.....A.S......S.........AR.T.D..TPS.D..LD......AGG.SG...LTA---------------------------------------.A.....SV............-.G.NL...TLT.....P......C....V..TV...DE.A...DVQ....I...L..TL.DT.L..A...............C.....................M...I.......................................FR..AN.FE...............G.....R..........................GR.KD..KTT...H.VPF.NE.A.GRPAKN.QTL.QGS.G..-------P....S...T.LVSGLEVKEMGLCEASLAEKNEHPVVLNGGVNASAPTL..P..L..V.......

EDRD-8 :S...........S.....A.S......S..........R.I....TLS.D.ALG..G.S.AGG.SG...L.T---------------------------------------LA.S.G..V...........A-.Q.DL..VTLT............H....V..TV...NE.A.....Q....V...L..ILDDT.L.PA.........K...........................M...I...................F...............T...LR..AN.FD...............G.....R...........................R.KD..STT..E...PL.NE.A.GRPAE..QTL.QGS.G..-------P....S...T.LVSGLGVGEVGLCEVSPTEKNEHPFASNDSVNAPAPTP..P..L..V.......

Jst1 :S......S.S..S.....ARS......SR.........R.V....TPS.NGAL.......TGG.SG...SST---------------------------------------.A...G..V...........A-.K.NLL..TLTS...........R....F..AV....K...S...Q....V...L...LDDT..T.A...D.....K....R........A.........G..KA...I...................................A...FR..A..VE...............G.....R..........................GDVKG..N.ID....IPLKPE..N.RPAK..QTLLQGS.G..-------P.S..S...T.LVSGLGVEEVDLRKVSTAEKNEHPFVLDGSVDAPTPTPA.P..L..........

Jeh1 :........A...SA....AES...S.VG..........R.A...LTPS.D..LDC.G...NGG..GF..LTT---------------------------------------.A.....SF......L....A-.K.NLE..ALAC...........H.......TV...NK.......L....A...L...ADDT.LV.T.........K.....C.....................A...I......V.R.N........L...................SR..AN..E...............G...L.R..V.....................V.GRVKDI.KTV......PL.N..A.GRPTE..QT..QGSNG..-------PTLF.RV...SLAPGPGVEEAGLCEVGLAEKDEYSFVLNGSVNAPAPTP..P..L.SV...RV.T

Jfs1 :......A..S..ST....A.S......SR.........R.A....TPS.D.ALD..G...GRN.SS..AL.T---------------------------------------.A......V.........R.G-.EMNLM..TLMSHG.........H.......T.L..NE.......Q....V...L..VLDDA.LTPA...C....L......W......E..............V...I........R..........................A...VR..A..FE...............G.....R......D.G.......I.........GGVRDD..TT....VVS.KKR..N..PSKS.QT.LQGT....-------PV...SA..T.LASGLGAEKMGLCEVGLAEENEHPFASNDIVNAPAPTP.NP..L....T....S

Jiw1 :......S.FL..SA....A.S.....GS..........R.T....IPS.E..LD...E.VACHTSGP.ILTI---------------------------------------.A......V........L.R.-.EMNL...TQT............H....V..T....NE...DMG.K....V...F.YT..D..H.FA.........M....NC..........S..........V...I......................................TVH..A..FE...............G.....R.............V.........L..GR.KG..PAT.....IP..H..A.GRSAK..Q.LLQ.S.GRA-------P....SA.DT.PASSLRIEGAGLCEVSLVEKIEHPFGLDSHANAPAQTP..PS....V...R..L

Jiw2 :...........SSM.LQ.A.S.EN...S..........R.A....TKS.DG.LD......AGR.PGP.D..T---------------------------------------.T......V...........A-..MNL...TLTH........T..H..C.V..AV....E.......Q....V..DF..I.DDT.L----.......AK........................A..M.....C....V...N.....................H..A..TVR..A...E...............G.....R...........I.........I.H..W.TQ...KTT..KL..SL.NESA..L.AKNTQTLPQG..G..-------P.....I..TCPVSGLGVEEVGLCEVSLAEKNEHPFALSSSANAPARTP..P..L...N......

Jnt1 :-------.....S....TA.S......SR...T.....R.A.A..TLS.DG.LG..GNP.A.G..G.LPL.T---------------------------------------.A....G.V..........RA-EQSDL.V.ALTF..A........H.......AV....EDA...D.Q....V...L..ILD.T.L..A...............W.V..............R.E..A.FCI..........G........................P...FRI.ADKCQ...............G.....R.......................H.F.EVKDA.KTP....F.LF.NE.AE..PTK.SQT.PQGSGGGA-------PT...S..NT.LVSGLGVGKVSSREVSLAEESEHPFTLHGNVNAPAPMP..P.SP.DV.VG...A

Jsz2 :S.....L.....I.....A.S.....DS..........K.A....TPS....LG....S..GGL.GQ..L.T---------------------------------------.....CK.V.........R.G-.E.DL...TLTC..G........R.......TV...DES.S..G.Q..DDV...L...L.DT.L..A..........V....H.V..............R.A..M...I...................................AW..VR..AD.SE...............G.....R........................V.GMMKD..KTTI...S.HCGNE.AG.RSAK..QTL..EA.L..-------P.R..SA..V.LASGLGVEGVGVCEVGLADENEHSFALNGSANTPVPEPA.P..L.NV.VG...L

Jsz3 :............VAR...A.S......G..........M......TP..NNALGN......GG.TG...L.T---------------------------------------RA......V.........KKE--K.NLV..TLTCL...V.P..P.R..H.V.ST....DE.......Q....VS.GF...LDDT.L.PA.......................L.................I......T............................A...LH..AN.FE...............G.....R.......................L..GRMKG..KTT...Q..PF.NESAN.LPAK.LQT...G.....-------PV...S.S.T.LASGLGAEEVGLCEVSLVKKIEHPLAPNDSVNAPVSVH..SL.L..V.S..V..

Jyt3 :S......L.S..S.....AR..Q....S..........R.A....TP.N.G.LD..K....DG.SR..PL.T---------------------------------------.A......V...V.......A--K......TLI............H.....F.A.L.LNE....A..Q....V...F..ILDDT.L..A...G..A........H.................DE......I...................................AF...G..A.KFE...............G.....R.......................H.F.ATKD..KTT..W.S.PF.NE.AGNW..KE.QTLLQGS.G..EQNQSRGL....D.S.T.LVSGPGAKEVSSCEVNLVEKIEHTFASNSSVNTPVPTPA.T..L..V.......

b

297

444

VR-2332 :AATQTIKLPQVNQCRALVPVVTQKSLDNNSVPLTAFSLANYYYRAQGDEVRHRERLTAVLSKLEKVVREEYGLMPTEPGPRPTLPRGLDELKDQMEEDLLKLANAQTTSDMMAWAVEQVDLKTWVKNYPRWTPPPPPPKVQPRKTKPV

BJ-4 :.............................................................N......................................................................................

NVSL7895 :.S...T.QLH.............EP..KD.........S.C..P............NS......G........T........A..N..V.............V...A..E.....A......A...............R.......S.

MN184A :X.A.AA...LT..RH..AT..X.R..---------------------------------------------------------------------------------------------------------------..F....AES.

MN184B :..A.AA...LT..RH..AT....R..---------------------------------------------------------------------------------------------------------------..F....AES.

SP :.....TE.........................................................G...........G...................V.........M...............................I.......L.

EDRD-1 :.....T...LA...H..............P........S.H..H.........D..NI......EA..K..D....G..........................D..A..E.....A.....EA...............S.R...A.S.

Jnt1 :V.N..TE------------------------------------------------------------------------------------------------------------------------------.....S....TA.S.


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