Subdomain I Subdomain II Subdomain III Subdomain IV Akt1 ... - PLOS

Akt1 DDB0220670 DDB0216386 DDB0220701 DDB0220700 DDB0185113 DDB0229452 NdrA NdrB NdrC NdrD DDB0231558 DDB0216387 Pdk1A Pdk1B PKA pk4 DDB0185224 pk2 DDB0220702 pk3 Aurora MLCK-A DDB0216385 DDB0216309 pXi DDB0216308 DDB0229351 DDB0216307 DDB0216312 Snf1 DDB0229364 Lkb1 MARK-A MARK-B MARK-C DDB0231454 DDB0219986 FHAK-A FHAK-B FHAK-C FHAK-D FHAK-E DDB0220010 Apg1 tsunami Cdk1 Cdk5 Cdk7 Cdk8 Cdk9 Cdk10 Cdk11 DDB0229294 DDB0229424 DDB0230050 CK2 DDB0219953 ClkA DDB0229841 DDB0229333 DDB0229296 Dyrk1 Dyrk2

120 173 86 1527 64 810 232 112 130 718 1555 756 40 69 271 336 679 334 153 128 498 110 8 13 38 18 20 566 56 6 31 9 40 109 65 46 542 1158 180 625 199 218 145 201 7 5 10 4 4 44 209 7 52 64 4 4 47 312 590 74 46 102 304 605

Subdomain I Subdomain II Subdomain III Subdomain IV FELLNLVGKGSFGKV.IQVRKKDTGE........VYAMKVLSKK.........................HIVEHNEVEHTLSERNILQKIN.........HPFLVNLNYSFQ FIFLRMIGRGAFGQV.NLVKKIDTGR........LYAMKVIKKD.........................KCLNMNAVGHTFTERKLLKKYY.........HPFIVGLKYSFQ YYFIKPISKGGYGQV.FLAITKSN.K........FFAIKSINKR.........................DTIGKHMVKELMVERNILVQYQ.........NQSIVKLFECFQ FEIIKPISRGAFGRV.YLAQKKKTGD........LYAIKVLKKL.........................DTIRKNMVNHVIVERNILAMVQ.........NEFVVKLFYAFQ FNFLKVISKGGFGKV.YLAENKITKK........TVAIKVIKKS.........................DTIKKMMVDQVNIEKTILSNYK.........CNFIVELFSSFQ FEFIKPITKGGYGKV.FLAKKIRTGD........IYAIKRLKKS.........................DMIKKNQLDHVKVERNILAYTS.........NPFVVKMYYSFQ YKHVECIGKGGYGVV.CKFINKKTNE........IRAIKTIRKD.................................YSALKEINTLKELG.........GQFTVNIFHTFL FEVIRIIGRGAFGEV.SLVRHRESND........LYAMKRLKKS.........................EMLKKEQAAHVRAERDVLASAN.........TNWVVKLYYSFQ FESIRIIGRGAFGEV.RLVKMKKNNK........FFAMKKLDKS.........................KMIEKHQTIHVRSERDILADSNNI....HGSNPWIVSLYYSFQ FKILTQIGKGGFGQV.FLAQKKDTGD........IVTLKRLKKQ.........................TVEWANQRNQVSQEKSVML.VD.........NKWITKLLYSFQ FQKLTAIGKGGFGKV.YLARKKDSNE........IVTLKVIRKS.........................TYHRANQMTSVTKEKEVMMIPHSSK....DQSQWITRLLYSFH FTLIEKIGEGGFGQV.FLAKKKDTGE........IVAIKRMSKE.........................LIWSKNKVSHIKNERDILAQGKN........HRWIVSLVYSFQ YDIISTIGSGSYGEV.CIVREKSTKQ........VYAMKKIYYT........................EVSDTELVKKRALRERDAMVICNNKN.....NKRAPKLYCSFID FIIGKVLGEGSYGAV.VLGTEKETQQ........QYAIKILEKK.........................QIIKENKIKYVQIEKEIFCKSN.........HPNIVKLFFTFR FDFIRTIGKGAYGKV.KLVIEKETQL........IFASKILNKK.........................LIIKEKKAKYVNTEKTILDSLD.........NPNIVKLFYTFQ FKQIRVIGTGTFGKV.YLIQNTKDGC........YYAMKCLNKA.........................YVVQLKQVEHLNSEKSILSSIH.........HPFIVNLYQAFQ FKLFDLLGSGSFAKV.RLCQHIPSER........LFCMKILNQN.........................KIIRLRQEVHVCNEKQVLMLTD.........NPFIVKLYSTFK FNFYGSLGSGSFGTA.KLCRHRGSGL........FFCSKTLRRE.........................TIVHEKHKEHVNNEINIMLNIS.........HPYIVKTYSTFN FELLNVIGKGSFGKV.MQVKKKGEDK........IFAMKVLRKD.........................AIIARKQVNHTKSEKTILQCIS.........HPFIVNLHYAFQ FIIKHLVGKGGFGKV.FQVVHVDTQK........VYALKVIKKN.........................HIIAKKSVVNTLAEKDILKKIS.........HPFIVNLHYAFQ FELLKVLGVGSFGRV.YLVRRKDTGK........FYAMKVLNKK.........................DMLKKKQIAHTNTEKMVLSTMD.........HPFIVRLHFAFQ FDIGKLLGMGRFGHV.YLAREKKSQF........IVALKVLFKN.........................QLQTHNIEHQLRREIEIQSHLR.........HPNILRLFGYFY YEFKEELGRGAFSIV.YLGENKQTKQ........RYAIKVINKS..........................ELGKDYEKNLKMEVDILKKVN.........HPNIIALKELFD YNITDIIGEGTFSTV.TLANHIEKIE.......DKYAIKIISKE..........................VLDNERRTYVDWEISILSKCQ.........HPNIIKFYEHYE YILGNEIGRGAFSIV.REATSRATGT........KVAIKSINTR.............................FIKNKLLMREIEIMKKVGD........HPNILKLYEVYE YEIGSQIGNGKFAQV.HSGTNKSTGK........KSAIKIMKKS.............................IVEESAIIKEIEMMTEIN.........HQNIIKLQEVYE YEFGPEIGRGAFSIV.RQGTHKDTGD........QVAIKAISKQ..........................HVSEADMKRFTREIEIMKKLK.........HKNIIQLIEVFD YQIFDRLGSGTFSDV.YLCINKENGK........QYAMKIIDKS.......................LVTMIAQHTDMKVETEVNILKQSF.........HPHVIQIIDHFE YVVGKELGRGAFSVV.REGTRKTTSD........KVALKYIEKK..........................FVKKKHIEQLRREIDIMKKVK.........HENVLSLKEIFE YELHKEIGKGAFSVV.FLVTEKKTKK........QWAMKIIDKK.............................SSSKAALETEIEIMKKVD.........HPNIVKMHEYFE YRLDKTLGIGSFGKV.KLAEHIRTGV........KVAIKILNRT.........................KIKNLKMDEKIRREIQNMKLFR.........HPHIIKLYEVIE FIIGKTLGQGTTGKV.KLGFHKDTGF........KVGIKIINKE........................LLINKPSMRRKIEREIVLMKLID.........HPNAMKMYEVYE YILGEVLGEGAYGKV.KDGMDSFTQK........RVAVKILKRA........................RLKKIPGGEASVLKEINITKKLH.........NKHIIKLIDHFI YLVIKTIGRGQFGKV.KLGYHKKIPN.......EKVAIKIINKG..........................KLDPETLKMVQREVRIMKLLH.........HPNIIRLYEVIE YLLGKTIGSGTSSKV.KIGTNILTGK........QYAIKITKPK............................RIKERKEIEREISILKRLK.........HDNIIQLHDAIY YEVGKTLGNGTFGKV.KLGTNICTKE........NVAIKFIKNN..........................KLSGKQKETCFREIDIMKLLD.........HPNIVKLLDVVD YTLGKTLGRGNYGVV.KLGTHINTKE........EIAIKILYKE..........................QMTESEFTRCKREIEILKQLY.........HPFINKLLNVLE YDIIKTLSTHPHN.V.YLANFNDQ..........LVVLKEFGIG............................DAFGKQIFERQVSLLKQMN.........HKCIMPIQAVFY YDFIKELGSGNFSVV.YEGVNKNTGK........RVAIKHLNLS.......................KINTHTPKFKSQLNREIEILKFIN.........HENVVEIYDIFY YYFVKEIGSGGYGIV.YEGLYKLNGK........RVAIKHIDLL........................KNGSTSKSMELVSKEYNALKNIK.........HRNVIEFFDIVF YSIQGILGTGNFSVV.KRCIRRDTGE........VFAVKIIDKK........................KFWSQTKTRRQMESEVEILQKIK.........HPNIISIIDIVQ YDLREVLGTGNFASV.RLGVEKETGN........KYAIKIIDKK........................KMSMTSKRKDSLMDEVNVLTKVK.........HQNIISIKEVFE YFIGEMLGQGNFATV.KLAVERTTGV........KYAVKIVDKK.......................KYFMNSSARKDSLMDEVNILRGLS.........HPNIIQIIEVFE YVFVRKLGKGTFGKV.KLAYHHDTHH........LYAIKIFNKI..................RLKKQTMGIGRPNAFDDVLKEIAIMKKMN.........HINVVKLYEVIN YILDKRIGWGAFAQV.YKGFSIKTNE........PFAIKVVDVC.......................RLADKNSKLTENLNYEIRILKELS.........HTNIVRLYDVLN YKLIGQIGEGSFGKV.YKYRKKFTGQ........LVACKVISKK..........................GKNEEDILSLRQEIDILKNLS.........HPNIIQFISCFE YQKLEKLGEGTYGKV.YKAKEKATGR........MVALKKIRLE............................DDGVPSTALREISLLKEVP.........HPNVVSLFDVLH YSKIEKLGEGTYGIV.YKAKNRETGE........IVALKRIRLD..........................SEDEGVPCTAIREISLLKELK.........HPNIVRLHDVIH YNIEALIGEGTYGVV.SRATVKATGQ........IVAIKKIRKI......................LIQNQTDDGINFSAIREIKILQELK.........HDNVVNLLDIFA YTFSYEIGSGTYGMV.YKADDKKRPN.......NKVAVKKFRST..........................KEGEGLSLTAYREIGLLKELS.........NENIVKLLDVCL HEKIEQIGEGTFGQV.YKAKNKSNGD........IVALKKVIMD..........................NEVEGFPITAIREIKILKELN.........HANVVNLKEVVT FEKLDSIGEGTYGIV.SKGRDKETGR........IVALKKVKIG.........................QQDKDGIPLTSLREIQILKEIK.........HPNIVSLLEVVI FKKLYTINEGAFGVV.YCAQDKETEE........IVALKKIKME..........................REREGIPITSVREIKVLMELK.........HDNIVQIKEIVL YEIISKIGEGISGSV.FKAIKKGTEE........MVALKNFKGW.............................TEGDRASKEECSLLQQLR.........HIPYITPVIDIY FQIIELIGSGSYGKV.YKAIHNLSKC........TVALKIISVM..............................NIENGLPVEVKYLMKLRD........CKNIVHLIEYFY YIILSKCGQGTYGSV.FKGIHKITHS........LVALKRVTDI..............................AQEDGEPVEVKYLNQLKN........LSNIVNLRDHFY YEIIRKIGRGKYSEV.FEGANIKNNE........KCVIKVLKPV...............................KKKKIKREIKILQNLCG........GPNIITLYDVVR YEVIQKIGRGKYSEV.FSGIDIETSD........EVVIKVLKPV...............................QKLKIQREIKILESLNG........GPNIIPLLDSVK YKVLCTVGSGTFSTV.VECWDTNSSG........QVAIKIVRSA.............................KKYTEDALVEIDILRNLEKTGNSNGKYLSHCIRLLDSFL IDPNTIVDCGTNGIM.FIAFNFETQK........RVILKKLSKR.........................MFDNELNGHRIIRNLIFQNLFQG........GKHISTYQSIFK ITKKTIYACDINGTM.FQTYNMDTNR........LLIIKKISLL.........................QFKNHLQGRMMLRNCHYQRFFNH........HPFVSGFKVSKR INLKSITDCGPDGVM.FRAKNEDSKE........EVIVKKISVF.........................LMKDDKMARKLLRNLLFQRHFQQ........HPLVSTFQSVFK FEIISSLGKGSFGQV.VKAFDSVLKE........YVAIKIIKNK.............................VPFYNQALIEIRLLELMNNKD...PEDQYKIIKLKHHFK FEIVSILGQGSFCQV.VKGYDYKTGE........MVALKILRNQ.............................KRFHNQALTEIKILEYLKTND...PNSTASIVHLNNYFY p. 1

YakA Prpf4B GSK-3 GlkA Erk1 Erk2 DDB0229430 Sky1 DDB0230051 DDB0230126 Cdc7 DDB0229971 DDB0229896 DDB0229877 DDB0231212 DDB0229915 FNIPK-A FNIPK-B FNIPK-C FNIPK-D FNIPK-Ea FNIPK-Eb DPYK4-a ZakA-a DDB0230002 DDB0229378 Mek1 MEKKalpha DDB0229911 DDB0230012 MkcA MkcB MkcC MkcD MkcE MkcF PakA PakB PakC PakD PakE PakF PakG PakH Krs1 DDB0216375 SvkA DDB0216374 DDB0216379 DDB0216377 DDB0216378 DDB0230010 DDB0229972 DDB0229973 IfkA-a SAMK-A SAMK-B SAMK-C SAMK-D DDB0230038 DDB0230124 DDB0229871b DDB0229850 ARCK-1

205 490 56 91 149 14 4 135 414 654 622 77 18 13 22 36 11 11 33 33 368 860 9 9 16 31 292 495 71 97 585 438 616 369 429 401 911 570 205 1376 650 394 139 42 20 23 12 21 23 29 20 935 173 848 449 191 186 181 136 521 961 695 51 1112

Subdomain I Subdomain II Subdomain III Subdomain IV YKVLDSLGQGTFGQV.VKCKNCDTDE........LVAIKILKNK.............................QAYFQQGRLEIQTLKSLNDQHD..PEDKNHILRLLDSFI YQIFSPIGSGVFSTV.VSAKETKTNE........DVVIKIIRNR.............................PSMHRSGLKEIEILQKISNTPTS.SNQKSHCIQMKDHFN YITEGVIGNGSFGVV.TQAIVADTKE........VVAIKKVLQD................................QRYKNRELQIMKMLN.........HINIVSLKNSFY YEIIKQVGQGTFGKV.YEAKNQDNKR.........VAIKKVEKS................................NHFISREYDILKIVA.........HPNCLRILDMFY YSIVKCIGHGAYGVV.CSAKDNLTGE........KVAIKKISKA..........................FDNLKDTKRTLREIHLLRHFK.........HENLISIKDILK YEVLQKIGKGAYGIV.WKAIDKKTKQ........TVALKKIFDA..........................FQNATDAQRTFREIMFLQELHG........HENIIKLLNVIK YQFIKQVGDGAYGDV.IKAIDVKTGE........IVAIKRMKKK...........................FSDWKECIQLREIKALKKLK.........HPNIVKLLEIIL YQVVDKLGWGHFSTV.WLCNDKDTPITTSS(29)QVALKIVRSA.............................RTYSETAEDEIKILNAISKY....NAQDKCVARLLDHFT QIHKVSIGNGCGHFV.IKLIPTVSGTNVG.....NSYSKFIYNS.......................IYSSTLAESEILLFREAMLLYKLN.........HNNILKLESITK YHLGPLISE.NSTTV.FRAFDCKSLI........PVAVKVLPPV................................ALNIPV..................HENLTKVYQVCQ YRILEKIGQGTFSGV.YKSVCIDGPNI.....GLIVALKRVAPT..............................SSPARILNEIHSLLRVGG........HYNVSALFGALR VISDIAIGKGAFATV.FKGLNTLSGD........FVAIKRFEKS..........................KISNEQHSSVSTEFDILQRLN.........HENIVRILGREE YNLGVVIGKGGFGTV.YQGLDIEDGD........FVAIKQINLT..........................KIPKDQLQGIMNEIDLLKNLN.........HANIVKYIKYVK YQIGEAVGKGAFGKV.FKALNAETGD........FCAIKQIEKT..........................IISEKQLPSIIQEIKLLQTLQ.........HPNIVKFIESYE YLLIDIIGKGGFGVV.YKGLHKTKGY........FSAIKKIKIM.......................KKKKLQSESQISLMAEINLLKVLS.........HHNIVRYYEHIP YTLGEKIGRGAFGQV.FKGLNGKTGE........FVAIKQIDSN..........................KIDESSLQSVKGEVEILHKLR.........HNNIVKVLGVVE WEILSQLGTGAFGRV.VKAKKINCDGTGI..IIDICAIKIIKKS.................................VFTKNEIEILKQLD.........HPLIVKYYGYGV WEIVETL....KSNV.FKVNNKNNIVLNG.NSFKTCILKIIINK................................DKNVWKEGQVLEKLKN........IDSIVKCYGWCC FEIIRILKKDEFSTT.CKAKKLSGQFNEK..RVNFCIIKIIKKR...................VKKFDSKKNEIIIEIDPRKEREILEKIK.........HICVLEYYGYSE WEIITQLESNEQFTV.YMSKKLKGPNFTN.NRFGLCTVKKIKSQ...................................YFNENEILNHIKLRD......NKYVLKYYGCGK WEIIKP............QKNISEN..............KVYYT..................................TKHKNAKIIDVLN........ICKCSLKLYGYVK WEIISTLGSGNFGKV.FKARKINGIINGS..KVSLCAIKKIEKK.............................DKLKIKLSTEVEILNKLKD........NEHSMKYYGYGY WEEISSIGSCNSKSRVLKCRKKNGLIENE..KVDIVAVKIINKK.................................FFKRNETDILEKIR.........LFNIPRYYSHAE WEEISFIGEGQYGRV.IKCRKKNGFILNE..QVDYVAIKIISKD.................................KFKRNETDILEKIR.........LFNIPRYYSHAE IEKNYR..KGGFSKI.SKAKKKNGIINGTIVNKKMIAIKKIKFD.............................DKIQFNEVNNLELIKNKNK........EMQISSIIDYFG WVIERQLSKGSFGQV.YKAHKKLDPN.......FVCAIKVIQYC.................................KFTMKEVDYLKKLN.........DPKFVKYYSLEF LKIIRVLGRGAGGVV.KLAYHETSGT........YIALKVITLD...........................IQENIRKQIILELKTLHKTS.........YPYIVSFYDAFY WQKGQILGRGGYGSV.YLGLNKDTGE........LFAVKQLEIV.....................DINSDPKLKNMILSFSKEIEVMRSLR.........HDNIVRYLGTSL YELKETIGKGGSGLV.QRAICLPFQE........NVAIKIIDLE..........................HCKNVSLEEIRKEIQAMSLCH.........HPNVVAYHTSFV YNLIEPIGEGTEGRV.FKAYCIPLKE........NVAIKVVELD..........................KMDPQFVKDVIKEVKVMNGNN.........HPNLIHYHTSFL YTFREKVGKGGFGTV.YLVRNNMDKSK......SRIAIKKLPHV............................RKKEKKFNVKEIRVLEFTN.........HPNIITYYNSHM YKDSDQVGKGGFGTV.YFAKSTKEKR........LVAIKKMPHV............................TKRQQQQNFREAAILAKCD.........HPNIVKLHTCHI YKNLKQIGSGGFGSV.FLAKSTVDKC........EIAIKKIAHV............................SAKAQRTNLNEIGFLNFCK.........HPNIVSYLRSHL FKNLDFEARGGFGSV.FCAKNKNPHSAYD...KQMVALKKMPIK............................TLRHKRMNLSEIGFLKYFN.........HPNIVKFLCAYQ GENAEV..KGAFGTV.YQVFYVNGQYN.....NVDVALKKMDHK............................SEKKRRNNLNEISILRYLK.........HPNIVTYINSYE IKFTHMVGRGQYGKV.YDALYDKKR..........VCVKVVNYS............................TPKEQHNVLQEIGFLTQCD.........HPNILKYNCSVL YYNINKIGEGGAGEV.FEAINSRTNQ........TIAIKKMKLK.............................AQNLKTVINEIGMMKNSN.........HENIVQYIDSYI GEGSTKIGEGAAGEV.FVVTQLKTNN........KVAIKKMPLN.............................QQNMKLIVTEIGIMKSCR.........HQNIIDYIDSYL YKNMTKIGEGAAGEV.FVATSSKNNK........RVAIKKIEIN.............................NDNAKLLVTEIAIMKTSH.........HDNIVNYIDSYI YKVREVVGGGSTGKV.YVGENSITGE........KVAIKKMKVD.............................NNNIKNIINEISTMKNSK.........HKNVIKYVSSHL FEFKEKLGQGGYGAV.FKVLHRETNF........PLAIKVLSIT.............................PTRIKDIEKEIDLLKKCR.........CPNVLSYYGSIS FILDEKLGDGAYGSV.YKGTHKDLGF........TLAIKVIEMK.............................ESESVSLQNEINILKNCK.........SPNIVSYFGSLQ FLIDCILGTGSYGTV.YKAIHKDTNF........VLAIKSIPIK...............................ESEEIEKEISILKKCK.........SQNIVSYFGSGQ FEIQEKLGEGSFGSV.YRAIHKSSNT........SIAIKEFEIF............................EANDVEPISKEIQILKKCN.........NPYVVSYFGSIM FTIVEKLGEGSYGSV.YKAINISTGI........VVAIKKVSVD..............................NDLEDMEKEISFMKQCK.........SPYIVTYYASFR FDLIECLGRGSFGSV.YKATYKKTGN........IVAVKLVPIN..............................EDFQEILKEINIMKQCK.........SKYVVQYYGNYF YVRQEKIGKGSFGEV.FKGINKKTNE........TIAIKTIDLE...........................DAEDEIEDIQQEINVLSQCE.........SPFVTKYFGSFL FRVLEVIGQGSFGVV.CTCINTVNNE........VVAIKFLEME.............................GEENSSLKKEITILKNTVR........CPYIVKYHGCYI FQIVEVVGSGSFGTV.CACRWMKKKDRES.NGNRLIACKFVEVN..........................ADDVETNLNLVKEIDILKESMD........CPYIVEYKGCYL YHIQERLGKGSFGQV.FKAVHFANGK........VVAIKIISLD............................DQEAIKDVRKEISILAECN.........YPNIVQYFGSYF FELIEEIAEGSFGTV.YKGKHLPTGN........IMAVKIIALD............................EDETFEDLVVEIDILNRCN.........HNNIVKYYGSWV FRDKIKLGTGAFGNV.FYAIRKSDSS........PVAIKVLMER.............................TKKDSPIIPELYIHSACN.........HSNIVTYIESYL YESPPTLGK..YDKV.ILVILSQQYLQN...QVNIFPIKLIDRE..........................RINLIHQNILSNEFQLLKSLK.........HSGIVNYIGMIN IKLCEQIGSGGSGCTVHRCTVDGFT..........CAVKVLKLK..........................NTSPFLVEQFISEITIMVKLS.........HQNIAKYLGHRL WKKGSCIERKSNYSV.YRGVDEDTDRKLIC(55)VVELKKRLIE...............................KVKMIQKEIESMKYLG.........NPYIIKYLGTNF YEYVESISLGVFSVV.GKYKRKGQENE.......FIAIKKIDIL.............................SLNEEKIIKEINKLYSIN.........HPNIIKIIGYCK YKLIEEIGRGAFSIV.EKYENKLKPN.......EFISIKRINVL.............................ASEKEMIVKEINMLYSIN.........HPNIIKIIGYYK YVFIKQMKGSVNCSL.EKYINKKTKE........RILIKRIGKS.............................NINEETIINEISILCSID.........HPNIIKTYGYYK YIETISKNKFCEIEKY.KKSQTKVNEY........IIIKKIIKN............................STLNEEKLINEIDTIYLLD.........HPNLIKIIGYCK AQPSDIIGSGNNGTTQRAGIHKDKR..........IVMKQWNFI............................TSQATPMLFNEIEQLVAIK.........HPNILALAGASF IQVGSRLGLGSFGDC.YTGNAFSIP..........TILKKLRTQ..........................RFTDQFLGQFKNEVMQIRELQ.........HENLVPVSGCCL IKTIIVKDSYSILEGQYKGKL..............VSIKQINGS...............................INDFEMKQLGVLASIK.........SPLAVRFIGVVF IEYVCRLGSGSLCRV.YKGRLNGKP..........VAIKVFSPI...............................RFEEFKTEFLMMQSLRS........SPFLISFYGVSI LEYTEKIGSGASGKV.FKGIYRGRV..........VAIKVLKSA...........................DDEMTREDFLKEFGVLASLE.........SHTIVGLYGVVL p. 2

SAPKalpha DDB0229849 DDB0229848 Phg2 DDB0229847 SplA DPYK4-b DDB0229872 DDB0229844 ZakA-b 7TMK1 rk1 rk2 rk3 DDB0214883 Shk1 Shk2 Shk3 Shk4 Shk5 DDB0229963 DDB0231199 DDB0229940 DDB0218878e Rck1 DDB0231197 DPYK2 DPYK3-b Gdt1 Gdt2 Gdt4 Gdt6 Gdt8 Gdt9 KinX KinY DDB0229853 DDB0229863 DDB0229866 DDB0229851 DDB0229865 GefX DDB0229867 HH498 GbpC Pats1 QkgA Roco4 Roco5 Roco6 Roco7 Roco8 Roco9 Roco10 Roco11 DPYK3-a DDB0229956 DDB0229957 DDB0220138 DDB0220436 DDB0230133 DDB0229871a DDB0229955 Bud32 DDB0231196

351 529 601 807 1949 2058 299 177 1476 379 363 374 391 491 851 45 174 24 277 237 1073 1377 386 702 842 599 853 1057 1372 1290 1349 1194 1038 1290 22 32 33 336 35 23 15 21 18 530 878 2247 1242 1026 2175 1356 1775 1456 3008 2069 1185 726 758 986 946 345 192 360 662 35 459

Subdomain I Subdomain II Subdomain III Subdomain IV LEYTEKLGAGSSGKV.YKGLYRGKE..........VAIKVLKSM...........................TESKEIEEFKKEFQIMSAIR.........SKHVVHFYGAVL LEYTLKLGSGSSGKV.YKGLYKGKE..........VAVKVLKSI...........................TTQSQLEEFKKEFQIMGSIR.........SQFMVTFYGACI LTYNVLLGTGASGKV.YKGTFNGQE..........VAIKVLKSF...........................TDKKDIAEFKKEFQIVSALR.........APGVVYFHGAGI LEYIKRIGSGTYSKV.YKGKYRDKF..........VAIKTMRGS..........................NMTTEQIESFKKECDILSTIQ.........SPLLISFYGSCI IVFLNKLGEGTSAKV.YRATWRNQE..........VAVKVLRSE...........................PESQKLLDFLKELEIMSSLR.........SPHVVYFYGMVL LEFGQTIGKGFFGEV.KRGYWRETD..........VAIKIIYRD.........................QFKTKSSLVMFQNEVGILSKLR.........HPNVVQFLGACT NKDDTVGGDGFFSVV.KKGYYNETE..........VAIKLIKKA.........................HGENVTVCDTFYHEVLIISNLR.........HPNIVQFIAACI LTVEKEIGQGFFGKV.YKARWRGKS..........VALKKITLI.........................KFRDLTETEIFDKEVSIMSKLC.........HPTCVMFIGACS LFLIKKIGAGSFSKV.YKAKYMGE..........IVAIKVLKGE...........................ATSEQIELFKKEYDILSLVS.........SQNLIKFYGACK DKDDSEGGAGNFGDV.KKGLLNETE..........VAIKFVKKA.........................HCEAITVCDTFYHEVLILSNLR.........HPNIVQFMAACI FKFGQVIGEGYFGEV.RKAVWKGAV..........VAVKILHRN......................SFRNTDGNKEENVFLKEVAILSILR.........HPNVLQFLGVCS IKIGVRIGKGNYGEV.YLGTWRGSQ..........VAVKKLPAH..........................NINENILKEFHREINLMKNLR.........HPNVIQFLGSCL IKIGVRIGKGNFGEV.YLGTWRGSQ..........VAVKKLPAH..........................NINENILKEFHREINLMKNLR.........HPNVIQFLGSCL IVVQNRIGRGSCAEV.FTGTWRGI..........IVAIKKAKLL.........................NEDDEDFLNELAQEATIMSQLR.........HPNICQFLGTCN IAIGARIGRGGYGQV.FRGSWRGTE..........VAVKMLFND..........................NVNLKLISDLRKEVDLLCKLR.........HPNIVLFMGACT ITTESILGDGSFGTV.YKGRCRLKD..........VAVKVMLKQ...........................VDQKTLTDFRKEVAIMSKIF.........HPNIVLFLGACT YNREAKLGSGAFGSV.YKGIVRGKE..........VAIKKLTQT..........................VFEENTMNEFKKEVSLMAKLR.........NPHLLLFMGACT INFEELIGTGSFGKV.YKGRCRQKA..........VAVKLLHKQ..........................NFDAATLSAFRKEVHLMSKIY.........HPNICLFMGACT IDRTDFLGQGSFGSV.YKGKCRGQE..........VAVKIPRKQ..........................KLSLYELTSFRHEVKIMSKIF.........HPNVVLFLGACT DVKTDLLGGGAYGKV.YKATCRGKK..........VAVKVPKKQ..........................TLSESELKSFKNEVEIMKQIF.........HPNVVLCLGACT IKIDKEIGKGHFSKV.LKGNWKGKD..........VAVKKLNSN........................KDKAREEMIQEFKAEVELLGSLQ.........HPNLVTCYGYSL LQILQFLGEGALAEV.HKGIWKGKE..........VAVKIFNEG...........................SFSFRLEDFLKEVAILGLIS.........HPNLLKLKGACI VAFGDVIASGASGKV.YKGIYKGRD..........VAIKVYSSE...........................NFCFNIEEFDREVTIMSLIDS.......DHPNFTRFYGANK VIFGDVIAAGASGKV.YKGIYKGRD..........VAIKVYSSE...........................NFCFNIDEFDREVTIMSLIDS.......DHPNFTRFYGANK VSIHKWIASGSSGRV.YNGQYKGKD..........VAIKVLGPE..........................VCVHFDLNEFKREVALMSIFK.........HDNLARCLGAGQ VKINVEIYDSPLCTV.YSGVYNGMD..........VAIKEFSQD...........................GMGFDWVSFYKEITIVSASQ.........HPKVIKCYGAHT IQFIQKVGEGAFSEV.WEGWWKGIH..........VAIKKLKII..........................GDEEQFKERFIREVQNLKKGN.........HQNIVMFIGACY VAIVEKVGAGSFANV.FLGIWNGYK..........VAIKILKNE............................SISNDEKFIKEVSSLIKSH.........HPNVVTFMGACI IHFQELIEKYSWEIL.YRGTVGDKN..........ALLKLIKLK.............................TKNCEEAYRELNIISRLK.........HQNILPLIGCVI IIIKNYISEGTFGIV.YRGIWRSSP..........VAVKLLKNE.............................YVDHDEIEKEISLLERLR.........HPNILLYVGRFI IVLEKYLSEGSFGVV.YSAIWRSSS..........VAVKLFKHH..............................YSKDEIDKETSILSKIK.........HPNIVSFIGSL. IEVKELISQNNLSTV.NIANYRGLQ..........VVLRKIKTH.....................SANYTKTYSQAIKKFYTEMDILSKLK.........NKNIVSFIGCTH TEQLIASYLPSKVYV.FKGYYRDLA..........VAVKKFAIS...........................DNSKSFEKIKNEVQILSKVN.........NINVVRYIGSAQ LDFDEICGQGTYGMV.YKGKWRSQV..........VAIKMMRVG.............................TVNCDEVYREMDIMGKIR.........HQNVISFIGCVV LDFISEIGSGGFGKV.FKGEYLGAP..........VAIKKIHIL.......................PDDPNRVDLEKFLNREIETIKLFT.........HPNVIQFVGISE LKVGESIGSGAYGIV.YRGTLFNSD..........VAIKKIQNE.........................KSEKNEFIKYLKREVAVLKNIQ.........HPNIVQFIGVYY LFMDVEIGRGSFGQV.QKASYFGTD..........VAVKQLSTL.........................VSIDPDYFKFMLREIKILKGMR.........HPNIVQYIGACC ..VGNEIGSGKYGSV.SLGYWLGTP..........VAIKKLHEN............................NEETEILVQRELQILKEIR.........HPQIVQFLGVSR LEFGQEIGKGAYGKI.FKGEYFGTP..........VAIKEISLQ.......................PNDVKYKDLTKFIQREVAMLRFS..........HPNLVQFIGVSE FDPLSIIGSGGFGKV.YQGVLNGKE..........IGIKKITIS.......................DNDPNRDILLKFLEREIYTLKMLS.........HPNVIKFYGIAE IEENEF.SKGSFAKV.YKGSYYGNP..........VCVKVIKKD.........................TLIDKESWVFLKREIGILKNLLNQ......GHKNIIRFIGIGE LEFNEKIGKGSFGSV.FRGCYLGLD..........VAIKKIEKA...........................DDPEYLKYIDREVSMLQSLR.........HPFIVNFSGICV LVFKDIIGKGNFGCV.YRGNYLGVE..........VAIKQIPSF...........................DDPDYCKYTEREVKALRYIR.........HPFVVHFFGACK FKTARKIGAGAFGDV.YLVEWRNKN..........VAVKRVKIE....................KILESGKSYQWIRDKFILEAVLMVKLSN........FSSFVKLYATCI VKINKEVGRGAFGIV.YEAEWMSEW..........IALKKLLLP..SSTDTTNLNGNGEVMVYDDPDQLIEDRLRVFREFRHEVYYMSGLN.........HPNVMKISGFCI LMIEELIGEGGAALV.YRARWQGQT..........VAVKKLKTI...............ENLDSPIEINDISLSKAFNEFRRECWVMSELE.........HPNIVQLKGLCL ILYERQIGEGGFGLI.HKGKLISNKS........DIAIKSLILCNSNNNNNSNNNNNSNNSNNFKNNNNEDEFIEKFQEFQHEVFIMSNLN.........HPNIVKLYGLMH IEYEKQIGKGGFGLV.HKGRLVKDKS........VVAIKSLILG.....................DSEGETEMIEKFQEFQREVFIMSNLN.........HPNIVKLYGLMH LEIIEKVGEGGFGIV.YKGKLRGQ..........LVAIKQITID......................SGQAEAASEIYREFRREVWLSNTLT.........HPSIVSLKGYCL FESPKLIGRGASGKI.YRANLNDTM..........VAVKQLEVV.........................GEDAPRIFSEFRREIHVMSDLK.........HSNVVNLLGFTL LKFGPQLGSGSYANV.YRGIWNGSE..........VAIKVLNFD.......................DGHANTTEKYREFRNEAHITGELR.........HANTVSLMGVSL LIYQEEIGVGGFSRV.YKGIYKNNT..........VAIKQFNFE(120)LSTSSLSSNSSQGEDSMNQISSGKLNAINEFRREVWLMSGLS.........HSNIVLMKGFC. ELDPNPIGEGGTATV.YKGKWRQSD..........VAIKLLKTD.......................VVGSDFSKVFAEYRREIFCLSSFI.........HDNILDLKGFCL HSNQNENGTSTQSMMGMYGKQF.............VNIKVFNAP...................LLGADFQNNCARILSSFRHEALSLYNFR.........HSNVLSIIGISM VVCEEQIGVGGFGLV.HKGKLILQDKS......LVVAIKSYIVG......................NSSASDIIRKFQEFHHEMYIMSSLN.........HLNIVKLFGSMQ IKLLEKLESNSKSSNIWQIEYKSTQ..........LVLKQPKDQ(11)LFNGSNVSGSNNSGSSGGNNHNHHHCNNSNGSNSEVIPSKYTMIQ.......HKNLGLLVGWCG LELTKEIGRGVSGVV.KRGKWKGYE..........IAVKQFNEE...........................ELGFSEREFHSEATIMSVLR.........HDNIVHCVGGSA VVLHERLGTGATGDI.YRGLISQDNLNRHI(42)IVAVKKLHPL.........................ADPSPEMIQDFYNEVRVLSMFN.........HPNVVKYVGGCT IQFFNLIGQGGFSKV.YHGVWRSKD..........VAIKQIELQ............................NNKSLDDFRREVGILSKLKP........HENLLAYYGACK FNDSNKIGEG..GQC.SIYKYMG............TAMKRFKPS..........................LSSSLISKEFENEVLILERLN.........HPNIVKIITYST LEIGNVIGGGGYGAI.YKAKWRGLS..........VAVKVISEL..............................SDGSEFEKELEMHKELLH........HPNIVHFVGFCV LLFIKKIGSGACGEV.CQYEWKGTP..........VAVKTIFKS..........................LLRKDKKEEFEKEVSILKCLR.........HPNVVLFMGTCL LKISSKLGEGTFGVV.YKGLWRGSS..........VAIKQIKIN.........................EDVNNQVLEEFRKELTILSRLR.........HPNIVLLMAACT DEIGILISQGAEAKT.Y.....ETD.........LYGLKCIVKE................RFSKAYRHPILDQKISSKRILQEVRSLNKCK.........KKGIQVPSLYLV IDFHTQIGSAGNASV.FEGTYKGIP..........IACKEMPVS...........................GTYEQSVDSIKEIAAVGQIKK......LGCATVVETIGVLK p. 3

DDB0229339 DDB0231195 DDB0229335 DDB0216331 DDB0229344 DDB0231281a DDB0230037a DDB0219988a DDB0231281b DDB0230037b DDB0219988b DDB0231182 IksA IreA IrlA IrlB IrlC IrlD IrlE IrlF DDB0216373 DDB0229347 DDB0229350 Nek2 Nek3 Nek4 DDB0229345 IfkA-b IfkB DDB0216407 DDB0229432 DDB0220611e DDB0220652 PLK Vps15 TBCK TtkA DDB0220004 DDB0229384 DDB0216398 Scy1 Scy2 SLOB1 SLOB2 DDB0229334 DDB0231326 DDB0231559 DhkG-a DDB0231198 DDB0231179 DDB0231335 7TMK2 DDB0229381 Bub1 DDB0230007 DDB0229337 DDB0229346 LvsG DDB0230125 DDB0204911e CK1 DDB0216336

482 777 312 4 8 25 27 24 1328 1187 1108 186 261 575 987 1027 981 1054 903 950 22 54 16 4 4 4 12 1024 1 494 379 83 236 163 21 77 714 508 177 77 22 30 129 90 1 1730 508 366 865 136 355 317 13 1003 8 57 72 403 364 420 9 16

Subdomain I Subdomain II Subdomain III Subdomain IV IDFHTQIGSAGNASV.FEGTYKGMP..........IACKEMPVS...........................GTYEQRVDSIKEIAAVGQIEDL......GGCTVVKTVGVLK LSDFSIIGEGGFSTV.HKATYINLQNT....IT.PVAIKSFKNY............................DDDSFERIYKEVSVHQSLQ.........GENILKLIGVSK IERRNELGRGGNGTV.YSGVLKEIDSQGN.EISIPVAIKIPTQF............................YKSKLVEVYKELAIHQKIN.........GICGPKLFGCVK YEVVKLIGVGGEAKA.LLVKRINSDK........LYVMKQRMFF............................LLEEANEGLCEAMSLAKIQ.........SPYIVRFEEVFL YKLIKDLRSGGEGKA.ILYEKDGVK..........YVGKKR............................LFDNLKDANQGLKEAMSLARIV.........HPNTVRFEDAIM EERLISIAKDKSGKL.CVLKEIKY...........LNNK...............KKLEE.FKKEEKNEEGIQKRIYQRNFNLEFNHLKNFSQ......MNHTSIIKYIEHIE ..............V.YIVLNKSNEK.........FICKEIIYT..........................QNSNIDNEKRKSEYINLKKFSDTI...KYPHLNISKYIEHFI ..............V.QLVKNKKDGK........LYVCKTIDFN........................NNNETKDSKVKREREYLFLKQYSSP....SFSHLNIAKYIKHFE GKNYGGIDLSNPRSLGTYNLIGDSVFR....NISFFENKKLFEK.......FDTNVNFQKEIEFVKNYSKFLNFDISNRIPREYSILKSIK........GMNGVVQIDSWYL EVGSISKIREWKK.FGIISSHPDAV..........VFLKYGKKD..........LKSAMLDNGKVNDENYYGIAVEDYMKSNELNILYYLLSK.....QEEPDFTNIERYYL ..............V.WLIRDKNNNNYIR...KLSGYIKSKFKE(16)PYLKIAVENGWPISFLSSHFKRDNSNLFDYLFNKELIILELLKE......KGVDGISQLESYFV INNNMQKTGGRNGSV.FFVNNNNNSNNNNN(52)TFAIKQQLVS...........................TPKNKLSQTYREKVILEHLNILI..ESNKACNFPKLINWYK FKEDIKIGSGGFGSV.YLCRHLINGVD.....LGEFAVKKVPVG...........................ENLPWLFRVLREVKALETLTK........HRNIINYKHSWL IITNKILGTGSCGTI.VYEGKMEGRK.........VAVKRMLSQ...............................FVKFADREVSILIHSDE........HTNVVRYYAKEE RDENNIIGRGSNGTL.VFRGIWNDRI........PVAVKQMQKA...............................FNPHISKEIEVLIRLTSN......NCSNMIRYIDQEE RNESNILGRGSNGTL.VFKGLWSDKI........PVAIKQMQKA...............................FNPLINKEVEALISLTSK......NCSNMIRYIDKEE RKEENVLGRGSNGTL.VFKGIWNNRI........PVAIKQMQKM...............................FNPLISKEIEVLITLTNK......NCYNIVRYIDQEE RKDEFIIGRGSNGTL.VFKGIWNDRI........PVAIKQMHKA...............................FNPLISKEIEVLITLTNK......NCNNIVRYIDQEE KKESNILGRGSNGTL.VFKGIWNNRI........PVAIKQMQKM...............................FNPLISKEIEILIGLTN.......KNLNLVGYIDQEE RNESNILGRGSNGTL.VFKGIWSDKI........PVAIKQMQKA...............................FNPLINKEVEALITLTNK......NCSNMIRYIDKEE YTVNRILGEGGFSFV.YLVKDNSNSK........KYALKVMICQ............................TQESINTAKREINAFQTFN.........HENIMKLIDHSI VTEVKLVAEGGFGFV.YLVRDDYNNM.........YALKRMFIQ............................ERERLEAMKNEIDVMQKLRN........NPNIVKLEGFKI LNFVKQIAEGGFSYV.FLVKDSNTSK........HYALKRILIR............................DEDELKGVKHEISIMKRLTK........HKNIVKILDYHK YEILGALGKGSFGVV.SKIKRKEDGR........VLVWKEICYE..........................NMQEKEKQLLVNEVNILQKLK.........HQNIVRYYDRII YEEIKTIGKGSFGRA.ILVKRKSDGL........LLVLKEINVM..........................EMQPKERSDAMNEVNLLSMLD.........HENIIGYYDSFI YDIIKQIGNGSHGDV.YLVRSTIDKK........KYVMKKIFLK............................EREKTKDTLHEVNVLSQLK.........HPNIVEYFESFQ YLIKSQIGSGSYGNT.FKVTHKESGQ........VFCKKSIQVN............................NQENIEKVLEEGKILTVMD.........HVNVVKLNDSFF FEEIEMIGKGGFGVV.VKSRNKLDCR........YYAIKKIKTK......................GYTDSNQEPLTNKLLREVTTLSRLH.........HQFVVRYYQAWI .....MIGKGGFGVV.VKSRNKLDCR........YYAIKKIKTK......................GYTDSNQEPLTNKLLREVTTLSRLH.........HQFVVRYYQAWI FEEIQLLGRGGFGQV.VKVRNKLDGR........YYAIKKIKL..........................DSNQS.LNRRILREVITLSRLH.........HQHVVRYYQAWI FKEISKLGSGGFGSV.YLSEYVLDGH........KYAIKKVNFS...................ISNNQSPTNASSKIEKVVREVVALAKLD.........HINILRYHNAWL FCEIEKVGKGGYGSV.FKVKNKLDGE........YYALKKIPFK..........................NTTKTFLEKVLREVKTLASLN.........HRNIVRYHSAWL FNDVRVLGKGGFGIV.FQCCNIFDQM........EYAVKRIKVN............................QKIPTKELM.EVRAMARLN.........HPNIVRYYGSWI YRQGEFLGKGGFAKC.YLMTEVETNR........IYAAKIIPKS.........................TLQKTRARSKLKSEIKIHSSLS.........HENIVKFEHCFE IVFKKSLGNARFLKT.VKAYHSEEGY.........VVVKIYKKR........................NTKESLEKYKIMLKEIKDNFNITP........SFNIMPYQHFIE NQNNGSIG.GSSSSS.STSNSVSTPKPQSFYVDDAGIAKQLNQS................................VFDILSRSRYLSSLS.........HENLAEFIAAEP YLRIEFIGKGGSGKV.YK.VLSGDLK........IYALKYVCLS............................DPNEIEAQLNEIEMLKRLRK........QVNIIQLIDYEV FQELDLIGEGSFGHV.YKVRHRIDGC........LYAIKKTKKP..........................LKGQKDRDIVLREVYGLSAIKD........HTNIVRYFNAWE FDVVCKLGSGSFSDV.FKVKSKFDGN........SYAIKQARHQ..........................FRGFQERERAVREVKAAVSLPP........HTNVLQYYSSWE FEYINQIGEGSFAKV.YKARSFVDGR........LYAVKKSKKP..........................IWETSERNQHIQEIENGMKLGH........HNNIAQVMCAWE GPIVTGYVGKSIWTL.HSGTKKEDG..........SAVSIFSFD..............................IKKNPSKLEVAKNGFKRAKTTR....HPNVLKYLDGLE HDLKEVVGQDKFWKI.YQSTKKTTNTEC...SLFVFEKKLYEKV.................................SKSNLENVITFLKKEATTLQRLRHPSILQVVSVME ...KNSMGGGEECVV.SIITPTPSSC.........PWS..MSNE................................KKKRKFEKTLL.SLK.........HPYILTPINVEV KVYFGVLGN.......SLNKLENDRI.....MAMVPVSKHWPIP.............................LNSEAGRTTFRTIIKSLE........IHPFISVPLLVDF ...................MDIE............CDIRKINKL................................NYNNENEIYKLKKLN.........HPSIIKHYDIDE FKDLKRVAKGAYGTV.YKGTLGNDEG.......LEIAVKLMPVP........................KTIHDRCVLYDIFTEILIMDTFRS........DSRGCHMFDYGV SELGKLIGKGANGKV.YELHYNFGGVEK......HCAVKEIKVD.............................KYRVGAVLKEIESTALSQ.........SPFTVGIYGYFE YNVLSLL.NGVGGCA.SFTNYNLNYN..............INNS(42)SASAFKPFQLNSSTNSTGSPLIITSQPMPFQLNSNSNTTASSSSP.....ITHSNLNTAITSTT ETEIEPFASGGQANI.YMVKHIDWPMLSN.CPEGSYVFKQFIET(19)YQTYKTGESVDNFKYNFSNVEQTDKKSLETLFYEEVDKLKRLQ........FSDYIIKMPAISD QQNRVLIGEGHYGKV.YRSMYVSSDG.......RSLVNKMLKG.................................KRECTKEVEALIDVFD.......ASKMVTTQYFT.T IQFDALQSNGMNGIV.KSGT.I.............GSMKVVVKF(93)NNNNNNSNNNNNSDGSSGDDNRNSDNLIKSDLIDECFLNETVS.........H.LLINEFQIN. IAIHELLGMGGSGAMVHKCTVKKGPLR.....GGTFAVKVMKDC............................TNEDIESLENEIRVYEKLK.........SPYIVSYQGSSK YNNIKELGRGVSGVV.YKASHKKTGQ........IVAIKLVDMK...........................QSKISTEQIQGEIRALLTLNPEN...ERTHINIIKLIQCFI ..................................WLSCKVQDPPSIW......................EFYIGNQIHQRLQERSLTISNSK........FPTIHSLYYYTD ......................................KRIKSD.........................HQNQNQDQINYVDE.NVKENLS.........TYYLVKRISFE. ................................................................................................................ .......................................................................KVQKKSNKAMKELTVMQKIG.......YYSNHVVNVYGYFN ................................................................................................................ ..................................EFVYKWFNYP.................................YFFQTEVKYLTFID.........GIEGTPSI.... ..................................EFVYKWFNHP.................................NFFKTEVKYLTFID.........GIEGTPTIKQQ. YRISRKIGGGSFGEI.YLGTNISTNE........EVAIKLEPAK..............................AIHPQLLFESKLYKIFQ.........GGIGIPAVKWFG WTVVKKIGQGAFGEI.FSGKNIINNE........QIAIKVEKVD..............................TKKQVLRLEVAVLKKLQ........LCPYVCRFITCGR

p. 4

Akt1 DDB0220670 DDB0216386 DDB0220701 DDB0220700 DDB0185113 DDB0229452 NdrA NdrB NdrC NdrD DDB0231558 DDB0216387 Pdk1A Pdk1B PKA pk4 DDB0185224 pk2 DDB0220702 pk3 Aurora MLCK-A DDB0216385 DDB0216309 pXi DDB0216308 DDB0229351 DDB0216307 DDB0216312 Snf1 DDB0229364 Lkb1 MARK-A MARK-B MARK-C DDB0231454 DDB0219986 FHAK-A FHAK-B FHAK-C FHAK-D FHAK-E DDB0220010 Apg1 tsunami Cdk1 Cdk5 Cdk7 Cdk8 CDK9 Cdk10 Cdk11 DDB0229294 DDB0229424 DDB0230050 CK2 DDB0219953 ClkA DDB0229841 DDB0229333 DDB0229296 Dyrk1 Dyrk2

Subdomain V Subdomain VIA T...................................EDKLYFILDYV.NGG...ELFYHLQ...................................KDKKFTEDRVRYYGAEIVLALE T...................................QDSLCMVLDYI.GGG...ELFYHIS...................................ERETFSEETARFYIGQIMLAIG T...................................KKKLYMVMEFL.HGG...DCASLLH...................................SLNTLEEREAKNIIAQIVNGLE S...................................TDKLYLVMEYL.IGG...DCASLLR...................................ALGCFEEHMAKHYIAETVLCLE T...................................DKKLFFVMEFL.NGG...DCASLLR..................................SFNNNMPEDLTKNIIAQIIICLE T...................................KEYYYLVMEYL.QGG...DCFSLLQ...................................MLGSMDENMAKMIIAETVLALE SP.................................CKEKVLIEMEYL.SGG...DCAFHLN..................................DVGVGFPEELAKQYTAETVLCLD D...................................DNYLYLIMEYL.PGG...DMMSLLI...................................KYDIFTENQARFYIAETILAIE D...................................ANFLYLIMEYV.PGG...DMMTQLI...................................KYDTFTEDATRFYIAETVLALH D...................................ANYLYLAMEYH.CGG...DFRALLN...................................NLGTLSEDEARFYMIEMIEAIS D...................................SQYLYLAMEYH.CGG...DFKTLLN...................................NLQRLEDDIAPFYMAEMILAVE D...................................DQYLYLAMEYV.PGG...DLRSLLS...................................ALNSLDEDSARFYMAEMVEAVD D..................................NEGVFYYVMEFI.AGG...DFNSYCYKRLV...............................DGKKFTEEEIKFYIAELVLCLE S...................................EQCLYYVLELC.SQG...DLLHQIK...................................KVGSFDYRSCQYYVAEIISGLE D...................................ENNLYFILEYC.PNG...DLLGALK...................................KAGCFSIDVVRFYAAEILIALE D...................................EKKLYLLFEYV.AGG...EVFTHLR...................................KSMKFSNSTAKFYAAEIVLALE D...................................DRYLYFLQEFI.PGG...ELFDYIR...................................ANGSLSLYVTQIYAAEIVLALE T...................................PTKIHFIMEYA.GKK...DLFHHLR...................................ANKCFTEQTTKLIVAEIVLAIE T...................................KDKLYMVLDFV.NGG...ELFFHLK...................................REGRFSEPRVKIYAAEIVSALD N...................................EKKLYLVMDFV.NGG...QLFYHLQ...................................KEAIFSEDQVRFYMAELILALE N...................................EDFLFMCMDYV.PGG...ELFHHLQ...................................KAGKFPEELAKFYIAEVICSLH D...................................DKRVFLIIEFA.KGG...ECFKELQ...................................KVGSFNEQTAATYTLQIADALR T...................................PEKLYLVMELV.TGG...ELFDKIV...................................EKGSYSEADAANLVKKIVSAVG S...................................DEDICLVLEWI.PNG...DLFDRIV...................................KKGVFNEEEARLTMKSLLSAVE T...................................TKHLHLVLELV.TGG...ELFDKIV...................................QRGEYSEQDASKIVRQIVSAVG T...................................DNEVLLVLELV.TGG...ELFDKIV...................................EREFYTEQDASTLIGTVTKVIQ S...................................NDYLYLVLELI.RGG...ELFDKIV...................................EKGNYSEKDACNLVRQIVSAVE S...................................ELYYYIVTELL.QGG...ELLYQLEK...........................NHPSTNENVSNYTEEHARKIIKQVIQAVG S...................................DSHLTLVMELV.TGG...ELFYKIV...................................ERGSFTEKGARNVVRQVCAGVE S...................................TDKIYLVVELV.TGG...PLFDRIV...................................DKKSFTEKEAKLITQQLLQSLV T...................................TTDIFMVMEYV.TGG...ELFEYIV...................................KNGKLLEDESRRLFQQMISGVD T...................................SKYLFLILEYV.EGG...ELFDYLV...................................EKGGLESGEALFFFQQIIIGLE IE.................................EKGKLYIVYEYV.GGG...TSQNILE.................................NAPNGRLPPHQSQFIFRQLIEACE T...................................SRALYLIMEYA.GEG...EVMDFMI...................................AHGVLTESQARTFFTQIVSAIN ED.................................DVGRICLILELV.SGG...ELFDYIV...................................ARGRLSEKEGRKFFRQMLCGLI KR................................EEEGTTYLIVEYV.SGG...ELFDYIV...................................AREYIKEKEARKFFRQMISAIE K...................................DDAMFILMDYC.QGG...DLFHYVNKFGLKGVK...............MVNSPDIGDQVLMGVPLPEDDTKRIFTQICLGIA ....................................DRNAFMQMEYI.SGG...NLLDWCRN............................NNNDNENNKRRQPWEIQKIFQQIIQAIA T..................................KDQQLFFILELA.NGG...ELYNKIG..................................FNEPLLNENQSKFIFKQILNAVS S...................................STDCFFIVELA.TN....DLSNLLR....................................KRCVDEDDIKRICKQLLLGFN S...................................DRYFYIVLELA.TGG...ELFEKIK...................................QKGRFSEPEAKDTFKQILEAVS T...................................QKNLYLVLELV.TGG...ELFDKIV...................................SERKFQEDTCRYILKQLCDSVR N...................................EKVLSLILELV.ECG...ELLNDIVS...................................NLFYTEDKAKTLFRQIVDGVL DP.................................QEEYIYIVMEYI.EGG...SIM.......................................SANETSEDLARKYFRDIVFGLE EE................................TDPTFIYMIMECC.EGG...DFSKYIR...................................THKKLTEEKALYFMKQLANGLK N...................................KNEFTLVTEYA.DG....DLSQIIS...................................EEKTLSVDLIQSICYQLVIALN C...................................QNRLYLVFEYL.DQ....DLKKYMD...................................SVPALCPQLIKSYLYQLLKGLA T...................................ERKLTLVFEYL.DQ....DLKKYLD..................................ECGGEISKPTIKSFMYQLLKGVA H...................................KSNVYLVFELM.QW....DLQEVIE..................................DKSIILKPADIKSYMKMLLQGIE NP.................................KDKLLYLIFDYA.EF....DLFGIIK...............................YHRENGSHFSDATIKSLIWQVLNGIH SKASA...........................SNNHKGSVYMVFEYM.DH....DLNGLMDSP.................................AFKYFAPGQIKCYLKQLLEGLD GS.................................TGDKIYLVFEYL.EH....DVASLIDNI..................................NKPFKLSEIKCFLLQLLRAVE .................................GKNINSIFMAMEFI.DH....DLRGLMEVI..................................KKPFLPSEIKTLIQQLLNGVS TNF................................ETSEYIIVFPYF.EH....DLSGLLS....................................EHRLSIPQVKCYFKQLLEGIN S..................................NDDKLVMVFEYL.EY....DLWKFIS..................................PKNKYMTLSCTKFFIHQLLEGLD ID.................................KNSVLVLIMEFI.EG....DLWKIMS..................................NPQCTLSLGQIKNFTKQLLEGVK DP.................................QSKTPSLIFEYI.NNT...DFK......................................HLSPTLTDFDVRYYIRELLHALD DQ.................................SSKVCSLVFPFV.NKT...DIRELVY......................................TLDDYDIRYYIFELLKAID F...................................KDHICLVFKRY.GL....SLYEFLK.................................KNRYRPLPLSQIQNISKQLLTAIY RKCSDSYQPPLTSILNSIISSNDNPQQHSTLIQQKDDEDFYFESIQP.QY....SLLNLIS....................................NNMLDQDDICQLFYEILMGLK KSLNIKTKN...................LIESPVDDGTDLYFEFDQS.DF....TLYQMIR...................................SDKAASRKQCPYVLYQLLTTIK RKSSENYLISNKNN.........RNNVRLPLLQQKGDDDIYFEYLLP.EF....TLLQMIH....................................NKLLTEYNIMIFLYQLLTVVK F...................................RNHLCIVTELL.SY....NLYDLLR.................................NTHFHGVSLNLIKKFAHQILTALF F...................................RNHLILTFELL.SM....NLYDFLK.................................VNHFQGYNLNLVRRFGAQILTSLR p. 5


Subdomain V Subdomain VIA H...................................KMHLCIVFELL.SV....NLFELIK.................................QNNFRGLSTNLIKVFLIQILDALI Y...................................RNHLCIVFEPM.SM....SLHQLIK................................KYGKDIGLSLNAVRVYAKQLFLALK TS...............................DNDEVYLNLVLEYV.PD....TVYRVSRHY...............................SMSKQPVPNIFVKLYIYQLCRSIN TA...............................EDNKKMQNLVFDFI.PY....TLASLLK....................................KRQLSINFIKVLFYQLCQAIK PNS..............................KEQFEDVYIVSELM.DT....DLHQIIT...................................SPQPLSDDHCQYFVYQMLRGLK AD.................................NDRDIYLVFEHM.ET....DLHAVIR....................................AKILEEIHKQYTIYQLLKALK E...................................RDELFFVFEYL.EN....NLYESIK..................................DRTKLLPETTIRNIIYQILQALH HRG...............................PNGRHYCMVFELL.GN....NLLDLIK.................................HHRYRGMPITLVKTLMKQTLIALD DE................................SSGKYYSVLSPFV.PK....DLEFILA.......................ENSQNFGGLGKISPTTLTFSDIKYIVYQLISVVH T...................................PQSIYVIMEPS.TT....SLKPLVE.................................SMDQHQLPISMVISIMKQLLQCLL Y...................................KDQVTLILPFF.EHD...SFKDYFF......................................QMSNENIKHYLYALFDSLR N...................................ENYIYIFLEYM.ENG...SLSTILN...................................NFGTFPESLICNYVENVLKGLV T...................................KDNLYIVLEYV.ENG...SLSGIIK...................................KFGKFPETLVCVYIRQVLEGLV T...................................SRYLYFALEFI.EGG...SLAKIAK...................................RYGCFQEPLLSRYFSQVLKGLA S...................................SSHSYIVMEFI.ENG...SLEKIIK...................................RHGLLPESLVTVYIAQVLNGLE V...................................QAQLNFILEYV.ENG...SLRDVIE...................................KFGPLSEELCIIYLYQMLQGLA GE.................................IDDNIYIYMEYI.DGY...PVSSILR.................................KQPKNQFPEDIISKIVIDLALILS N...................................KHTTYIFIEYI.NGY...TLEEYVL...................................KNHPIPEKELSEIIEDLIKSLA D...................................EDNGYIYTEYI.QGGI..DIVETVTN............................KLLKEHSHSFQSEDIIRRCAFQLVLLLN D..................................NNQDVYIYLEFI.EYSI..PISKVKLI...........................PNDSSIDNFNNVSNTIIELVTCKLVESLN D..................................RNNEFNIYFEYI.DKAI..PLSRLLE......................................KLNKKEQFIVATEIIKSIK D..................................EDDNLFIYTEYI.EGST..SISDLIK.................................KKPNNRFEEEEIKSLMIKIVKALS D...................................DNYIYIYMEYI.EDK...KQL..........................................RFKESEIISMIADLTETLS D...................................DNFIYIYMEYI.EGE...NLANILK.................................TKKQGRFKESRIISMIADLVETLS YGI...............................KGKNKLYIYLEFI.EGK...TIY...................................ELKKKKFPLNEKQISIILKKCLETMK NN.................................SKTYAYIIMEFI.EGE...SMKSIIE....................................NKKFSDIEIKEIIKELLKALV T...................................EGSIFIALEFM.ELG...SLSDIMK...................................KTSTIPEPVLGKIAFQVLQGLV D...................................QSFLSVFLEYI.PGG...SISSLLG...................................KFGAFSENVIKVYTKQILQGLS Y...................................NESLWVIMDFL.SAG...SCSDIMR.................................FSFPQGFEEHVIATILKEALKAIC E...................................NNQLWLVMDYL.GGG...SLADIMK.................................FKYPDGIPEVLAVTVLKSLLKGLE L...................................HDEVWIAMEFM.EGG...TLA....................................EASNQYPFQESNIAYVAREVLQGLA D..................................KDSNLWIVMEFM.EGG...TFE....................................EAAKAWKFNENNLAYVAKELLKGLQ V...................................DDTIWIAMEYM.QGG...TLT....................................EASQGHTFNESCIAYVAKGMLEGLM K..................................SNDELWMIMEFL.SGG...TLK....................................NAASNFKFCERKIAYVCREILQGLD K..................................NDEEIWMVMEYM.DGG...TIRDAIS....................................NFTFTEKYVAYITKEILHSLE Y...................................GSDLFIVSEFI.QGG...TLE...................................QASASSHVFKETQVGFIGLELLKAIS V...................................ADELWVAMEFM.SGG...CLTEVLDQY.................................RDIQLNESQIAFVCQEVLRGLE V...................................GDSLWVAMEFM.GGG...CLTEILE.................................QFNSVKLVEAQIAYVCAETLKGLA V..................................NDRELWVAMEFM.GGG...CLTDILE.................................AFDNIKMSEIQIAYVVKETLKALQ V...................................INHIWLIMEYM.SYG...SLTDLISNCINIQCN...............GNNQQQQQQQQQQQTYFIESHIAYICQQVLQGMD S..................................KLTELWILMDHC.AVG...SINDMMK..................................ICCDTLDEEQIAVVTLNVLNGLG T...................................ESHIWILLDFC.ALG...SIRDIIE..................................STEKTLNEAQISFVVKNTLKGLI Q...................................GDNLWILMEYC.SAN...SIRDMLE..................................LTEKSLTEKQISVILQQALKGLH L...................................KNKYWILMDYC.SLS...SFNDIMQ..................................SIGKTFKEKEISLILQQSLLGLV K...................................ENEVWIVMEHC.GAG...SVCDAMK..................................ITDKTLSEDQIAVVSRDVLQGLA K...................................DETCWIIMEYC.AFG...SVSDMMN..................................ITNRVLNEEQIALVCYSTLKGLY K...................................GSKLWIIMEYL.AGG...SVLDLMK....................................PGPFDEGYIAIILRELLKGLE K...................................ENNLMIVMEYC.DGG...SILDIMQ..................................MCSITLTEAQIAAILYQIVEGLV K...................................SSMLLIVMEYC.KGG...SLLDIIE..................................LCGKRLIEEEIAAVCAGVVKGLV K...................................DHQLWIVMEYC.GGG...SVSDLLQ...................................VIDTISEDEIALICREALKGLN K...................................GDELFIAMECC.GGG...SITEIYQ..................................ELNIPLNESQIAYVCRETLKGLE C...................................KGHVWIILEYC.DGG...TVRDLLQ..........................ATCTPGNPNNLQLFEETLIAYIITELLEGLV D...................................NTGFGIVQEFY.ENG...SLSDIYN...................................RSGAFQESLVAKYTLQILEALG S...................................GNQLWLFMEFY.PH....SLKDVIT..................................KRTSPFPATEVIWMALEIAKGLE QE.................................GQNTLYIFQEYN.STL...TLQQKILS..................................NGIGFEESQVKKFTYQLLLGLL D...................................QKNYYIASKYY.PKG...SIK....................................KNTKQSPYSEMNAKRISVKILSGID D...................................EHYYYIATPYY.KKG...SIAKIVK..............................SIKSKNNSGFSESNVRNISKKILNAID D...................................ENYYYVASKFY.PKG...SIK....................................TKSKSTPYNEINAKKVFGKVLKAID D...................................KNYFYIGMKYY.ETF...KFK.................................QSNISKFGKNF.EQVIRKISFKILSAID D...................................NQTFTTFTEYI.TGS...NLDIVIK..................................NLDEKNELQLILRLSEEIASAMS ....................................DNNIYIVHPYY.DAS...NLQTLLFEQSHN.......NNNNNNNNNNNNNNNNNNNNNNNNHTIISNEFIHRVSLGISKAMT N...................................TDEYAIISEHVGNNG...SLLTLMQ..................................NHSNQLNWSNTIDLAIQITQSIQ VEE...............................PQKQCYCIITEFC.SRD...SLYHIMT..................................DRLIEIGWNRFFQFSMQIILGLQ ....................................EPKICLVMEYC.SNG...SIYHSIR....................................KNPPSWERFFSFVQQMLAGIN p. 6


Subdomain V Subdomain VIA ....................................EPKLCMVMENC.SRG...SLYHVMD..................................NNSLDIGWERTFRFAIETVRGIE ....................................EPKLCMVMEYC.SRD...SLYHVMN..................................TKKYDIGWDRFFQFTMQMTLGVQ ....................................KDKLCIVMEYC.SRG...SLYHILK..................................DDTTQFTWDNFFNLGTQAINSLD E...................................ESQLSMVVEYC.SKG...TLHKVLN..................................NPLLDFDWDKWFKWMTEVVEGVR ....................................DPKICMIMEYC.SNQ...TLYHLMH...................................LQMNFTWDWVFKFAIEMVRGVN AG.................................GEDHHCIVTEWM.GGG...SLRQFLT................................DHFNLLEQNPHIRLKLALDIAKGMN KFD...............................NKEVNHCIVSEWM.SGG...NLSQFIS................................NERKILEINPHLRVKILLDIAKGML LD................................GPSNDRSIIMEYM.EGG...SLRRLLD.................................EKSSYHLPPSLQLSIARDIAEGMN ....................................EKKLRMVTEYC.QHG...SLYHIMS..................................KRKMDISWPLVFKWMHQAVDGIN KYG...............................EKETNHCIVSEWM.SGG...NLTQFLM................................NNHKVLENNPHLRVKLLTDIAKGIL ...................................ETNLNGIVTEYM.GGG...SLDRLLT................................DRYFLIKQNPILAWNMAISIARGMF I...................................PPDICICTEYM.PRG...SLYSILH..................................DQALQLQWSLLIKMMIDAAKGVI I...................................SPDICICTEYM.PRG...SLYSILH..................................NEKIKISWSLVKRMMIDAAKGII N...................................PPEILIVMEYM.PLG...SLYRILH..................................DPSISLDWPRMKSMALDIAKGMN E...................................PSSPCIVTEYL.SRG...SLANILL..................................DESIEMDWGLRLQLGFDCARGMT S..................................TPGKLMICTELM.KG....NLESLLL..................................DPMVKLPLITRMRMAKDAALGVL A...................................PEDLSIVTELM.PKG...SVHSLLRA...............................KEDTSDFITFKRAILIARDTVLGMT I...................................PGRCVIVTELV.PKG...NLETLLH..................................DQKIQLPLYLRMRMARDAALGIN Q...................................SGKMQIVTELC.QTD....LEKLLHND................................RTKKEFSLFRRMQMAKDAALGMN K...................................PGKVMIVSELM.QTD....LEKLIHSS.................................EVEPPPLYERMKMCLDAALGIN .....................................NPMCIVMEFL.PSG...NLFELIHSKPSE............................QQQSIKLDSTLILAIAFDIARGMQ APR...............................SHKSTFMIVTELM.HKG...TLLEVIN...................................KNKPLSLEDIIKYALSVAQGLA Q..................................NKKYLFHVSELV.KSG...SLRDLLL..................................DKEKPLAYFTQLSIASDIANAMK Q..................................NKKYLFHVSELV.KSG...SLRDLLL..................................DKEKPLLYFTQLSIASDIANAMK Y...................................DDKYFHLTEYC.HNG...SLFSYLR..................................DQRNNISFGQRLHFALGIARGMR K..................................NTNKPFIVTELC.SRG...TISNALNQIR..............................KTTGQPPAIPLIVHMAIDAAQSLE .....................................KPACIITEYM.AGG...SLYNILHNPN.............................SSTPKVKYSFPLVLKMATDMALGLL .....................................DPPCIFTEYL.QGG...SLYDVLH..................................IQKIKLNPLMMYKMIHDLSLGME ...................................SKDYLCLAFEYP.PLG...SLDYIIS..................................KKKLKMSITQKIRILIDVAKGCK ...................................FSGIHGIVTDYC.SKG...CLSKYIH..................................ENKYKITIIQKIRILIDISKACA N..................................FLNTYGIVIDYH.PRG...SLNYYTR..................................NQNIKLSMVQNIRISLDISRACS ...................................DSSHLWIVTEYA.PLG...SLSSLIH..................................QKKEKLSLIQKVKLMLDTAKGCE N...................................ISHVCIVTEYA.KEG...SLGSLIH..................................DSKIKLSFIQKVKFMLDAAKGFT S...................................LEHLCIVTEFS.PIG...SLGDLIHGDNNQKKSNTNT......ITNTITNTNTNTNTSTSTSTKLTVKQKLRIAIDIARGCQ N...................................NGILFIVTELI.EGG...DLQYYLK..................................NQSIDLPWFLRANIALDVSLAMS EPLASPS......................LVNRLLNSSSTWIVTEYI.GGG...NLHERIK..................................DTKKDFPIELRIKLSLDIALAMA H...................................EGRYMIVTEYI.KGG...DLHQFIK.................................ARGVSNISWTLRMKLALDIASAFS N..................................EKDEIHIITEFM.DGG...DLFDALI..................................FGDIPLTWKEKLRISLDIAQSCR R...................................GSSLYIVTEFV.QGG...DLAYYLFRNKFDDTPEQYIHRKVNVGSSSTPDLSDPTVHNGEKLVQLAWPLRIKIAYDVACAMA K...................................ERSLFLLTELV.SGG...DLHWYIK..................................NKSIDITWKLKVKIARDIAASMA K...................................DSLLFLVTELI.NGG...DLGNILL..................................DHKFHIPWSLRVKIAKDIAEGME H...................................SSGLYIVTEFV.SGG...DVRQLLK...................................KTPPIGWDKRVSIAVDLAKAMV H...................................ESGFYLITEFI.EGL...DLRRYLK..................................SVPKPPKWLSRVNIALGVAKTFL E...................................EKELLLVLEFC.DNG...SLYTILNTIPIGGAG.................ANNNNNNNNNNDIIQSLPSINTLSLNIANGMN .....................................QPLCMALEYV.RYG...SLYSLLS..................................NSSIEISWGLRLQIASEIAKGMQ .....................................DPLCIVTEYL.PHG...NLYSFLH..................................KPEMEFSWLFRLKVALDISSGMA N.....................................PPRMVMEYV.EHG...DLYHLCQ................................DKERYASLGWTLKLRLMIDIAKGIG N.....................................PPRMVMEFV.PCG...DLYHRLL..................................DKAHPIKWSVKLRLMLDIALGIE .....................................DPCCIVMEYI.PNG...TLYSHLR..................................KSFSSITWQLKLKIAINIADAIK .....................................SPFTMVMEYI.DCG...DLHKFLH...............................SPIGDQLNGNWALILKLALDIAKGME .....................................SPFCLVTELL.QYG...DLAKFIR..................................NTAETFSWGTVLKLAIDVAKGMN ....................................FEPYAIVMEYM.DIG...SLSSFLKK...............................KKEDGQVLDWQMLLKIVTDIASGMA E.....................................PLAIITEFQ.SGG...NLYDYIH..................................DLKNPLDWQLRIKIAKGIAASLQ .....................................NPIAIITENP.TFG...SKGSTTLSEYIQD...........................RQKHPEIPWNIKLKIALDIARAMD N.....................................PPRMVMEFA.PHG...DLYHFLE...................................KKKNIKWSFKVRLMLDIAKGIE D...................................S....IIFESF.KGMN..SLHDLIH..................................RDGLKIDMALFIKISKDIASVMG Q...................................PGKMYLVCDYY.SRG...SLYSVIT..................................ANICPLSNARIVHLALQVAKGMN K...................................IANWSIVMEYV.PGG...NLMDVLA..................................NPVLVIPYKLVLRMALDIAKGLH H...................................ANYCYIITEYL.PRG...SLHDLLH.................................REQLMKLDFKQKVSFAICVALGCY .....................................IERIILLEFI.DGN...SLDKYPSQSLPL............................SPSSSLPNPLKVIQDFQQIVDAMI S.....................................PKCLVLEYI.EGG...SLDKYLH..................................NPNYTFSPQLRLKMANDIAKGMC L...................................NGNLAIITEYL.NRG...SLRDVLT.................................TMNKSELSLSVKVKMLIDVAQGMN A...................................PPNLCFITEYL.PGG...SLYDALH..................................SKKIKMNMQLYKKLAIQIAQGMN DI...................................GNNRIYMEFI.KGE...TVKHYLY.................................KNQESTQHQNQIESIMKELGNQIG Y...................................NQKLFLVMVKE.KCN...LLSFLCNKSEILK............................MQREGI.WTSIFKISKDILKGLV p. 7


Subdomain V Subdomain VIA Y...................................NEKLFLVMVKE.KCN...LLSFLSNKSEILK............................MQRGGI.WTSIFKISKEILKGLI L...................................KFGLSIIIEKC.DM....DLKNFIS....................................CNQINLDLFFILSTQMVNSVS L...................................NVGFGIIIERF.DC....SLHDYIQ....................................NNNIDFDLFFELALKMVITIR D...............................NNSNMFSLCIVMEYC.EGG...DLMDNLFKRISDSFLKNSG(328)NIESSLNINGNNNNNNCSTLLKLPRKLFYTWIYQICLGVQ TQI...............................GDQIEITIMMEFC.EMG...DLLDFLIELSEPQHHHTVT(189)LNIEEHVIHSNEIKKGVDSIYLIEQTQLIEWLLDLSYGVQ SKDE.............................FGLVDRCIFVTEYY.EDG...DLS.......................................SIKEIEFKDIINLFLKMLINLK ILENQ..........................QEKEKIKKQYIITEFY.DGG...DLSSLKIT................................NKKCFSIKNGDIIYLFLKMLIIFK TRDN.............................HGYLQKLTIIIEYY.EGG...DLT.......................................NLKNLNEVLPKDIIYLFFTMLV ...................................ENDIIYILMDYF.DGQ...NLL.....................................EVSQDLINDFTLFSILNQLSKILF E...................................NDKIYAMFPYV.NG....SCN..LS...................................EIDNLNEMDLLNILYQLCFQLH E...................................NNIIYILTKYH.GDY...SNL......................................EEINELNQEDLFEILVQMSDKLK AAPTSNLSNVNNNNSNNN(45)TKTITTTTASIKPNIQYMHLILEYA.NMG...TLKEYGK..................................DNNFEFTISQMKSLLFQVIYSLA EYDQP.........................ADFGPKVPCLYILMEYA.NNG...NLQDYMA..................................EKRDLIPENEIWSFFIDLCHGIG D...................................DEFIYLAISFC.QK....SLDMYVQQTLSLQISP....TDSPSIQSSNNNGNGNNGNNNNNNQIIIDNKTKQMILELFKGLE D...................................QLFVYLGLTLC.EE....SLQDLMESK...........RYKEFIEKTTTTNITTTFNNNIIDENLYEQRILSLFKDVINGIN D...................................KLHVYLGLTLC.DG....SLQNLVE..............................SGKLNDFVISSNKSIIELAKDILFGIQ D...................................ESCVYLGLTLC.DG....SLQNLVEKGDNNLT...................LTQFLGYDINSSSKNNSRLLELIKDIVYGIQ D...................................DMFVYLGLTLC.NG....SLQNLVEKDLEIN..............LISTSNNENNNNNKLKNFIGSELRLLELIKDIVYGIQ D...................................ENCVYLGLTLC.DG....SLQSLYDQS......................KLNEFINQNNNQNNNNNNNRVLDLIIGMINGVI D...................................KHFVYLGLTLC.DV....SLQ.YLV.............................ENGKLNEFINSSGKSLNELAKDIINGVQ SNH..............................SQDTKEYRLLLPYY.KDG...TLQDLIDN.........................QRTIYGKDTKKPLFKEKKCLQFFLKVCEAIQ NENR.............................NTRETEVLMLMEYC.SGG...SVLDIMN................................ARGEFTRLEEREILAIFSDVCNGVL VSD...............................KNNTEMFILMEYC.SGG...HLVEIMQ...............................KRLSSGSKFTDQEILKIFQDICESVA DK.................................PSSRLYIIMEHC.SGG...DLSQLIK...............................KCRNERTYMDEEVIWRTLLQILSALQ L...................................NGCLYIIMEYA.NAG...DIN...............................LEIKKRTLQNKTFSEFEILSWFSQICKALQ IE.................................NNQFLCIIMAYC.ESG...DLFTTLQ.................................KKKNEFISEYQILDWFIQIALGLL E...................................NGNYVIIMEFA.ENG...DLFQKIE...............................NQKRSGKPFSDFEIMHYFCQLVIALN EKSCDSFQSLEEGNEDLS(263)LSTSSSRKKPPKETHTLYIQMEYC.SKK...TLKTLID...................................NVGGIAEEEAFRLLRQIVEGLN EKSCDSFQSLEEGNEDLS(261)LSTSSSRKKPPKETHTLYIQMEYC.SKK...TLKTLID...................................NVGGIAEEEAFRLLRQIVEGLN ESAESLSLTNDNSDDDDD(178)SSSKLKNIKKSTSIPYLYIQMEYC.QK....ILR...................................NLTETGMNLEDDDIWKLFRQIVEGMA ELDPKNNKPRSSSFSSVE(256)NNDKNSNSNNLRLKYTVYIQTQYC.EGK...TLRDLLE.................................NPDFKNNSKTTILSLFKQIITGVN ETEELLPPSSSMASTSLS(305)NNKNNIVSPKINRITTLFIVMQLY.SQ....TLSQWLENR.................................PPDQVNEEENLNIFKQICIGLR E.EEIITNNSIDHYGEND(70)TNDDNNNYNQLKQKKFSLYIQMELC.KYS...TLRNLINEINNIKSI...........TSIQSTSSIANPIGTNILISLDIKQCREITRQILVALK N...................................EENVYILLELC.NQK...TVMDIH...................................KKRKYLMEYETKYYVYQVIMAVQ T...................................DRSGYLIRQYF.HN....NLYDRLS...................................TRPFLSMIEKKFIAFQLLKALE SQ................................KHHDQMLIVSEDY.KN....SLEKQIEIQ...............................AKRQTPIPSNTIGRYAYQILKALS NM.................................AKNYILLVLEFG.EI....DLSKLLQ................................RLQTPNGTNVNFIRIYWQQMLQAVH E...................................DSHIFIQMEHC.NGG...NIYKWVT...................................EHIKQSESNLLLLAKQILTGIV Q...................................NNTLFIQTELC.ENG...SLQDFLD................................SLSPDQILSEELIWNFLLDVCLGIQ E...................................GGHIFIQMELC.ERG...NLKDALN............................LAVQEEGGLGKLPEYMIWQYLCDIANGLS T...................................ETNIYIVTEPI.Q.....LLDELL....................................EDIRNFENAISWGLYQ..EGLS E..................................TKTHIHFATEPI.LA....TLEDLLGYY.............RQRKKSTVDQSSQSEEGYKKKDFTFEELELKAGIFQILDGLL SG.................................ANDKILVIRTFF.KQG...SLRDQVYKSKPLSPYD...TKYIYKQPKSSSSSSSSSSSSSQSQSVLPIKSIQKYCKQILESLL IPEKH.................................VAVSVRPFYADRG...SLRDFIHKSKP......................KMPYADKYDTHLQLNEKIVSKFGRQILEALI KK.................................SEKNVIIYQESI.NGGI..SID....................................KFDNNNFFSQEVIREICEQILLALR D...................................GENYWIVMKSY.KC....SLK................................EWRLKQTLPFLELLPLLLNIFTNVLQSVQ DE.................................KNNFLYIFLEYC.PNG...NLFDIIN...................................KEKMKSFDEFFSYAFGVVHCTH TSNSNSNNNSNNNNSGG..GGGGGGGGGGGGGTKINNKRRASLTPTS...T...PLS..............................ASPLLFNTKKYADIDINTFLSIAIQLTTILE D..................................NPNKRGMLLECA.TAG...SLKTNLLE.....................................YRSWKLVIRFMMDICLGMI ....................................LGFSSIIMENM.VDIGYVTLKQLLS........................MDDKQFSALASPFTCRSQMIKPIINAMVIALYS .............................NTPSIVGIGINMIVMEKV.DGT...ELE.......................................KYDK.TKLTKKIFMDLVIYLME VV.............................GSSGQIFEIRLFMEYI.PH....TLDKYLLARSVCGDSNGGG(29)NNNNNNSPLIQPQQQQQYVYPYYFRYSQVVWYLYQISIGLD H...................................KTTAIFILEYV.DGG...TLEDFMY..................................SFERGMPLSLISHCLYQSVNAIE K......................................SIMLMDHTIDQG...TLDDVVS.................................STNGVPMEEPLAMFHCIELLKMIE ........................................YSFKEFL.NSDQ..YL.............................................SIDTSIIFSKNIMNALY .....................................................................................................SGSLPSKLIQSIFKIIL LKGCDRM......................LKPRLLSDNDELIFMECE.DMGQYQTLEMIIER..................................RKCKGSLVMTRFIMRGILASAY .......................................................LQYLQRNQKIT........................................TFMIYQLIQLFS ................................KQQNQTENW..IQIS.PRG...QLIKNL.....................................EGKPIDISFYTKVFCRNTQ.K N...................................QTENW..IQIS.PRG...QLIKNL.....................................EGKLIDISFYTKSVEILKN.I F..................................DGDYNIMVMDLL.GPSLE.DLFNYC.....................................GRKFSLKTVLMLGDQMLRRIE H...................................NDYNYMVMELL.GE....NLSELRR.................................KQLDGKFSLGSTLKLGVQMIQSLQ

p. 8


Subdomain VIB Subdomain VII HLHLS......GVIYRDLKPENLLLT.NEGHI.............................................CMTDFGLCKEG.............................. FLHEH......GVIYRDLKLENLLMD.LDGNI.............................................CLVDLGLCKEG.............................. FIHSC......GIIHRDLKVENLIFD.KNGII.............................................KIVDFGFSEVGFTG........................... YLHKS......AIVHRDLKPDNMLID.GLGHI.............................................KLTDFGLSKIGIIDDKKMEDSGNTNTNTHFNFSTSPTNTSM YLHNH......GIIHRDLKPDNILID.SNGHI.............................................KLADFGLSKFDFVDESCNIKI.................... YLHSH......GIVHRDVKPDNLLID.KKGHI.............................................KLTDFGLSKVGLLDRQTVVPPSYFSPTLSGKNNQSSSSSSV FIHEK......SIIHCDIKPNNMVID.SDGHI.............................................KLLDFGNAKKF.............................. SVHTL......GYIHRDIKPDNLLLD.SKGHV.............................................KLCDLGLCTGFHRLHSSEFYQMLVGDAMTIK.......... SIHKL......SYIHRDIKPDNLLID.QKGHI.............................................KVSDFGLCTGLQTNRVPTLAEIYKKYEGDNN.......... SLHEM......GIVHRDCKPSNFVLD.KLGHI.............................................KLIDFGLSKEGIEKRNGWNKATMNELRKSCLSA........ SLHRL......GYIHRDLKPSNFVVD.KLGHL.............................................KLIDFGLSKEGFISRNSKYHTTWKNLREDNTPSNNNNNP.. SCHRL......GYCHRDLKPENFLIS.RDGHV.............................................KLADFGLSKNVVTRYHLRSASADNTINTTTSTPTTSSNINQ AFHSY......GLLHRDVKPENLMIN.KDGHL.............................................VLGDFGSSKLANNSGGGGGNFGNTLTVPMSTSYSTSPSSSI HLHSL......GIVHRDLKPENILMS.SDLHV.............................................KITDFGTGKILPPPQSSQQQQQQQQQQQQLPTNSSGNLSSL YLHGK......GIAHRDLKPENILLG.KNQHL.............................................KLSDFGSAKQLSI............................ FLHKQ......NIVYRDLKPENLLID.NQGHI.............................................KITDFGFAKR............................... YLHNQ......DIIYRDLKPENLLID.QYGHI.............................................KLTDFGFAKR............................... YLHAE......NIIYRDLKPENILID.EKGHI.............................................KLTDFGFSKK............................... HLHKQ......DIVYRDLKPENILLD.SEGHI.............................................CITDFGLSKK............................... HLHDS......NIVHRDLKPENILLD.SQGHC.............................................ILTDFGLAKLE.............................. YLHSN......NIIYRDIKPENILLD.EEGHI.............................................KLTDFGLSKSGITSVV......................... YCHSK......HVIHRDIKPENLLIG.VGGEI.............................................KIADFGWSV................................ YLHGL......NIVHRDLKPENLLLKSKENHL...........................................EVAIADFGLSKI............................... YLHDK......SVVHRDIKPENILFSDSYGGI.............................................KLGDFGLAKF............................... HLHAN......GIAHRDLKPQNLLCAGEEGDD............................................IRVADFGLSKI............................... YLHSK......DIVHCDLKPENLLYS.DNSDQA..........................................IIKLCDFGLSQR............................... YMHQH......GVCHRDLKPENLLCSGDDEKEE..........................................IVRIADFGLSKI............................... FLHSN......KIVHRDLKPENILFR.DKSLGS..........................................ILKIIDFGLASYVDHDCNCNNNNDNNNNN.............. YLHSQ......GIAHRDLKPENLLCNGEGEDM...........................................TIKIADFGLSKI............................... YLHSI......GIVHRDLKPENLLLK.TPTDL...........................................TVALSDFGLSKI............................... YCHHH......MVVHRDLKPENLLLD.PINKC............................................IKIADFGLSNM............................... YCHSR......NICHRDLKPENLLLS.GDKRI.............................................KIADFGMGSI............................... YIHSQ......KILHRDIKPDNILFT.HANVL.............................................KLSDFGVAEDSS............................. YCHSK......RAVHRDLKPENLLLD.CNRQI.............................................KIIDFGLSNV............................... YCHSN......MVCHRDLKLENLLVD.EDGNL.............................................KISDFGYSNI............................... YCHAN......LIVHRDLKPENLLLD.SNGDI.............................................KISDFGLSNN............................... HCHKL......NIAHRDIKHKNILFD.NQMNV.............................................KIIDFGLS................................. YMHSN......CIIHRDLKLENVLIR.QDGTP.............................................VISDFDLSKDIS............................. YLHSK......GIAHRDLKPENILFDSYGDDYL..........................................KIKITDFGLARF............................... YLHNL......GIVHRDLKPENILYNEFKQGFS...........................................IKITDFGLSSF............................... YLHDL......NISHRDLKPENILISAVSHGKS.........................................SVIKVTDFGLAKI............................... YLHSN......GIAHRDLKPENILLATPNSFL............................................LKISDFGLSRA............................... YLHNK......GIAHRDLKPENILLKHKNFNQND.........................................AIKLTDFGLSRT............................... YLHEQ......KVIHKDLKPENLLVN.SEGVV.............................................KITDFGVSHI............................... FLRQK......QIVHRDLKPQNLLLSDDSEHP...........................................ILKIGDFGFAKF............................... YLHYK......KVIHRDIKPQNILIT.SGGQI.............................................KVCDFGFAKTI.............................. YSHGH......RILHRDLKPQNLLID.RQGAL.............................................KLADFGLARAV.............................. FCHDH......RVLHRDLKPQNLLIN.RKGEL.............................................KLADFGLARAF.............................. ACHRN......WVLHRDLKPNNLLMS.INGDL.............................................KLADFGLARQY.............................. YLHSN......WVIHRDLKPSNILVM.GEGKECG.........................................TVKIGDFGLARIFQ............................. YCHRN......NVLHRDIKGSNLLLD.NNGIL.............................................KLADFGLARPFN............................. YLHSH......WIIHRDLKCSNLLYG.NNGNL.............................................KLADFGLARKF.............................. YMHDN......WVIHRDLKTANLLYT.NKGVL.............................................KIADFGLAREY.............................. EIHNA......GVMHRDIKAANLLVN.NKGSL.............................................FIGDLGTATS............................... ELHSQ......KIMHLDIKPSNLLIN.PRFDL.............................................KIADFGFTT................................ QCHVN......GIMHRDIKPANLLIT.TNGVL.............................................KLTDFGLSTSY.............................. FCHSN......GIMHRDVKPSNVMID.HQKRK............................................LYLIDWGLAEF............................... YTHSK......GIIHRDIKPLNIAID.HSKRK............................................LSLIDWGLAEY............................... SMHKL......SLVHTDLKPENILLE.SSRFTYFDNSIPLQFKNSIDT............TSNNSVDHYCHLVDTDIVVIDFGGA................................. FMHSA......GVIHRDLDPENSIFVDENFNI.............................................KFTEFNNCFLLDTD........................... YINSA......GVIHRSLDPKTIAVN.KEYKT.............................................KLFDFSFS..IST............................ FMHSA......GVIHRDIDPSAITID..QNQC............................................LKLTEFYFC..FPSNC.......................... FMSTP....EVDVIHCDLKPENILLRNPKRSA............................................IKIIDFGSSC................................ FLSKR......NIIHADLKPENILLKSPTKSGI............................................KLIDFGSSCF............................... p. 9


Subdomain VIB Subdomain VII VLANA......NIIHCDLKPENILLQ.NVNSP...........................................AIKIIDFGSAC................................ HIKNS......KILHADIKPDNIVVN.EAKNT............................................IKIVDFGSAG................................ YIHSL......GICHRDIKPQNLLLDTSTSTL.............................................KLCDFGSAKI............................... HIHSK......AICHRDITPNNILLS.SKGEL.............................................TLADFGSAKI............................... HIHSA......NVLHRDLKPSNLLIN.EDCLL.............................................KICDLGLARV.E............................. YMHSA......NVLHRDIKPSNLLLN.SECLV.............................................KVADFGLARSITSL........................... FMHTN......GFFHRDLKPENIMLV.GER..............................................LKIADFGLARE............................... YIHTKC.....KIIHTDLKPENVLLE.KSFDFFTSNDYIWSEKYGYFKNRTSSS(135)YKFKKNNELFNENHYPRAQLVDLGNAC................................ YLHTQ......DLVHRDLKPTSILLF.DDYQI.............................................KLCSFGNAISVFTN........................... FLHSS......SLVYRDLNPSRVLLT.TTTTTANDDVDCEL..........................QQQQQQQVKVKLTHFGIMRSLQ............................. HIHQN......NICHRDVKPTNFLYSIKNNSF.............................................LLIDFGLAQEMPNSNSNSNSNSNSNSNSNSNSNSNSNSNNN YLHQE......GVIHRDIKAANILIN.KAGEA.............................................KLSDFGTAGEI.............................. YLHEQ......GVVHRDIKGANILTT.KEGKI.............................................KLADFGVAT................................ YLHEK......GVIHRDIKSDNILIT.KEGVI.............................................KLADFGSCT................................ YLHRQ......GVIHRDIKAANLLIS.TDGSI.............................................KLADFGVATKVS............................. YLHSN......KVIHRDIKASNILIT.KEGVI.............................................KLADFGVASQI.............................. YIHDNE....RKIIHRDLKCDNIMLV.NDNTHSCDVNGNCSRNGGGSAKSANQS(60)GQSSTCRLINCIYSVSKKIKLIDFGLSKG............................... SIHEI......GVIHRDLKLENVMFD.KESNK............................................WKLIDFGLSFSFS............................. HLHNN.....LHIIHGNINTDNVLIADQEFSL.............................................KLFDFSLSKDISYYSKDNNNNNNNNNNNNNNNNNNNNNNNN CIHKDN.....KIVHGNIKGENILLV.NDESE.................................................YGFSVKF.............................. SIHEM......GIIHFDIKCQNILIL.YDENEKMLP.....................................TDFIKIIGFDHST................................ KIHES......GVIHRDIKSDHIILA.QDKNNET.........................................IVKFIDFGLSKQ............................... FLHKH......QILHRDIKPSNIILD.KNGVL.............................................KLIDFGSS.IIDQQQ.......................... FLHKH......HVIHRDIKTANLVLD.KNKNL.............................................KLIDFGASTIQNKKQFEQYLNETTNNNNNPNNNNNNNNNNN FLHNNC.....NLIHMDLKCDNIILKPNNYDNNNNNNNNNNNNNNNNNNNSN.....INDDNNNSNSNINDDNNFDIKIIDYGLSQKI.............................. YLNDK......GIMHRDLKPENIMFQ.NQNQNQNQN....................................NKINLKLIDFGLSKAINE............................ YLHRKL.....HLIHRDIKPSNILVN.NKGEA.............................................KIADFGVSGQL.............................. FLHAN......SIIHRDIKGANILID.TKGIV.............................................KLSDFGCSKSF.............................. YFHKT......GRIHRDIKSGNILID.SNGNI.............................................QLSDFGVSATL.............................. YLHSH......QRIHRDLKSDNILIG.EDGAI.............................................ELADFGVSAMF.............................. YLHGI......QLVHRDLKSQNIMMT.TSGEI.............................................KLIDFGLCA................................ YLHEN......HMVHRDLKSANIMMS.VEGKV.............................................KLIDFGLCE................................ YLHAH......NIVHRDIKSGNIMMT.IDGKI.............................................KIVDFGLCV................................ YLHKQ......NIAHRDLKSANVMVN.DKGEI.............................................KLIDFGLCIDF.............................. YLASL......NIAHRDLKSSNIMIN.SKAEV.............................................KLIDFGFSID............................... YLHEK......KLIHRDIKAANVMVS.TDGEV.............................................KLIDFGLCA................................ YIHKF......NRIHRDIKSDNILIG.ANGEI.............................................KLADFGYAAQL.............................. YIHSQ......HRIHRDIKSDNILLG.SDGSV.............................................KLADFGYAAQL.............................. YIHSL......HRIHRDIKSDNILLG.SEGSV.............................................KIADFGYAAQL.............................. YIHKG......HRTHRDIKSDNILLG.KDGSV.............................................KIADFGFVANL.............................. YLHSK......GIVHLDVKAANILLT.EDKQI.............................................KIADFGVSQQL.............................. YLHSQ......NIIHRDVKAANVLLS.EGCDV.............................................KIADFGVSEKL.............................. YLHQS......NIIHRDIKAANILIN.EDAIV.............................................KLADFGVSSQLE............................. YLHSK......QIIHRDIKSANILLD.ETGQV.............................................KIADFGVSQQ............................... YLHSV......RKIHRDIKAGNILMN.HKGES.............................................KLADFGVSGQL.............................. YLHRN......SKIHRDIKPGNILVS.EEGEC.............................................KLADFGVSGQL.............................. YLHSE......GKIHRDIKAANVLLS.ASGDV.............................................KLADFGVSGQL.............................. YLHSN......KILHRDIKAGNVLVN.KLGQA.............................................KLADFGVSAIL.............................. YLHSK......RTTHRDIKAGNVLLD.EEGLP.............................................KLADFGVSTI............................... YLHEF......KKIHRDIKGGNILLN.DRGEV.............................................KLADFGVSAQL.............................. YLHHT......NVIHRDLKGANILLT.ESGDV.............................................KLADFGVSGL............................... YLRSK......GIIHRDLKSRNILLT.RKGKV.............................................KIADFGLATT............................... YIHSQ......GIVHRNLKSNNVLLA.KGGKV.............................................KISDFAIGIRS.............................. FLHTQK....NPIIHRDLKPGNIMCS.LDDKG........................................RVCSIRVCDFDTSKE............................... YLHSQ......HIPHRDFKSHNIFFN.QSTSK............................................MLLSNYG................................... YLHSLN....PPIIHRDIKCDNILLD.ENDDP.............................................ILIDFGLSYKT.............................. YLHSSN....PPIVHRDIKGDNILLN.DSDEP.............................................ILADFGLSYLA.............................. YLHSLD....PPIIHRDINSDNILFD.ENDEP.............................................ILIDFGLSYKELKDDNNNDDDNYDNH............... YLHSLE....PPIIHGNINAKNILLDNENNEP.............................................ILIDFGLSYKS.............................. FLHSF......NIVHRSLHPKNILLN.SDLKI.............................................YIKDYGFTSLKDETLKK........................ YLHSH......DVVHRALKLNNILID.RVSGN............................................VLVRDYGF.N................................ YLHKHQ....PPILHRNITSDCFLLS.SLNNNSNQNNNNNNNNNNNNNNNNNNN(25)TTTTATNITNELNINEIKIKVHDFGLSR.FN............................. SLHNRK...PKPIVHRDVTSLNILVN.EDWEC.............................................KISNFSASR.FNC............................ ALHQST....PQVLHRDIKTLNFLVN.HNNKV.............................................KVADFGLSR.FN............................. p. 10


Subdomain VIB Subdomain VII CLHKWD....PPIVHRDLKSLNLLVN.DKWEI.............................................KVCDFGLSR.FN............................. CLHNWT....PQIVHRDFKSLNLLVN.EDWEC.............................................KVSDFGLSR.FN............................. SLHNWT....PQVLHRDLKSLNLLVT.ENWTV.............................................KICDFGLSR.FD............................. YLHSMN....PPMVHRDLKTLNILIS.SDWTA.............................................KLCDFGLTRTMT............................. CLHSWK....PVIVHRDLKSLNLLVS.DNWTI.............................................KVADFGLSR.FA............................. YLHGWT....PPILHRDLSSRNILLD.HNIDPKNPVVS................................SRQDIKCKISDFGLSRLK.............................. YSHRQ......GIIHRDLTSNNVLLN.FRKKKLLNNNSSNNDE........................QFYDSDEIIAKVCDFGLS................................. YLHTNFK..EGPIVHRDLTSSNILLN.SSYTVA............................................KINDFGLSKEM.............................. SLHTMR....PALVHRDIKSQNLLIN.SQFDL.............................................KVADFGLAKP............................... YLHKQ......HIIHRDLTSNNVLLD.FKREILPNQLYG................................SNEFTAKVCDFGLS................................. YLHDWK...PNPILHRDLSTKNILLD.ESLTIA............................................KVADFGLSK................................ YLHNST....PVILHRDLKSHNLLVD.ENWKV.............................................KVADFGLST................................ YLHGST....PVILHRDLKSHNLLVD.ENWKV.............................................KVADFGLST................................ YLHCCD....PIVIHRDLKSHNLLVD.EHYRV.............................................KISDFGLSTRFK............................. YLHSRN....PIIIHRDLKTDNLLVD.DSWQV.............................................KVADFGLAT................................ WLHSSN....PVFIHRDLKTSNLLVD.ANLTV.............................................KVCDFGLSQIKQR............................ WLHAS......NILHLDLKPANLLVD.QNWVV.............................................KVADFGLSKYMK............................. WLHESN....PVFVHRDIKSSNLLVD.ENMRV.............................................KICDFGLSALKQ............................. WLHGI.....TRIVHNDLKTANLLVD.INLRV.............................................KVTDFGFSQ................................ WLHGIC.....NIIHRDLKLANLMIS.KDKTV.............................................KIGDFGFSQVIK............................. HLHTR......NIIHRDLKSSNLLMD.KHFNI.............................................KIADLGIAR................................ YLHSV......DFIHRDIKAANILVD.KNNNA.............................................KVGDFGLSRV............................... HLHSI......GVIHRDLKSLNVLIT.EDFTA.............................................KVIDFGTSRN............................... HLHSI......GVIHRDLKSLNVLIT.EDFTA.............................................KVIDFGTSRN............................... YLHSM......SIIHRDLKSMNILLT.KRLKI.............................................KIVDFGTSR................................ FIHSK......NIIHRDVKGNNFLVN.ENWEV.............................................KLIDFGVSR................................ HLHSI......TIVHRDLTSQNILLD.ELGNI.............................................KISDFGLSREKS............................. HLHSI......QMLHRDLTSKNILLD.EFKNI.............................................KIADFGLAT................................ FLQQS......SIIQKTLRARNIFLYDTNENAEV.........................................CAKVLDLTSSKT............................... YLHRN......GITHRDLKPENILIT.SLNPKSL........................................VCAKVSDFGTSKE............................... FLHKN......GIIHRDLKPDNVLIV.SFDPDSS........................................ICAKISDFGTCRE............................... FLHSN......DITNCNIKSNNLLLFSTMEKDDV.........................................CVKISDFGIKKF............................... FLHAS......EIVHGDIKPDNLLVF.SKE.ISG........................................VCVKICDFGNSEE............................... FLHQC......GIIHRDLKPDNVLVF.DINHNAP........................................VCAKISDFGTSKET.............................. YLHSK......SIVHRDLKSTNLLVD.KNWKI.............................................KVCDFGFARIV.............................. YLHSR......DIIFRDLKSKNILID.DSSSP..........................................IRGKVCDFGFARILN............................. YLHSK......KVIFRDLKAKNILVD.EIGDG.........................................LYRAKVIDFGFARIF.............................. FLHAR......GILHRDLKSQNILLS.TNRRA.............................................KLCDLGLARMF.............................. YLHSR......NVIHRDLKSTNLLVG.DNWRI.............................................KVCDMGFARTAQV............................ YLHEN......GVIHRDLKSTNLLVA.ENWVI.............................................KVCDMGLARKM.............................. YLHSK......QIMHRDLKSNNLLLG.RNWTI.............................................KICDFGFAKEI.............................. FLHAK......KIIHRDLKSKNILLD.EFQRI.............................................RLCDFGFAR.MS............................. FLHSK......NLLHRDLKSKNILLDISRNQI.............................................KLCDFGFARVGSQYSNGSDSSSSEDESDSEC.......... YLHSLK....PQIIHRDLTSQNILID.RNGIA.............................................KIADFGISRFK.............................. HLHSHN....PPVIHRDLKSPNILLNGITEGQNS.........................................VATIIDFGTST................................ FLHSST....PPIIHRDLKSPNILLA.SINENAQ........................................TIAKVVDFGLS................................. YMQNQN....PPIVHRDLRSPNIFLK.SLDENSP........................................VCAKIADFGLS................................. YMQNQN....PPIVHRDLRSPNIFLQ.SLDENAP........................................VCAKVADFGLS................................. HMHGFT....PKICHRDLKSPNILML.SDMNAAV.........................................VCKVSDFGETRA............................... FLHSVT....PPLLHRDLKSPNVLL..SMKDGVY.........................................TAKVGDFGLSSRMFI............................ FLHSCK....PMIVHRDLKSANILLGGSSMDNLVA..........................................KVGDFGLSI................................ FLHNIT....PPLVHRDLKSPNILLA.SHPTNPNE.......................................ISAKVSDFGLSR................................ TLHDSR....PSVVHRDLKSPNILLS.SKDSLTM.........................................ECHLCDFSLS................................. KLNSHS....PPFLLTNLTSSGIILE.KSNDHQSSGNGLE..............................IEPFVNAKIIDFSQS................................. YLQNQN....PPIVHRDLRSPNIFLF.SLDENAP........................................VCAKVADFGLS................................. LLHSK......DVAHGNLTSRSIYLD.RFQI.............................................VKVSF..................................... YLHSL......GIIHRDLKPGNLLID.QDWNI.............................................RISDFGLSR................................ YLHSL......GILHLDMKSPNLLVS.SLSTSAK........................................VNIKVADFNTCINRSRITAGFF...................... HLSTYEP....PIYHTDLKTKNLLVT.NALKI.............................................KIADFGLASFAKKSLTTIINNNNNTNNTAT........... YLHNEI.....GIIHFDLKPSNILKN.SKNNK............................................LKLIDFGISKFLNN............................ FLHRN......EILHLDLKPQNFLVV.SISPEAP........................................VSIKLADFGLA................................. YLHTYS....PPIIHRDLKSLNLLVD.NNFNV.............................................KVSDFGLSRFIS............................. YLHLS......GVIHRDIKSLNLLLD.EHMNV.............................................KICDFGLSKL............................... IIHEM......NVIHGDLTTSNMLLR.ESTNE............................................LVFIDFGLSYT............................... SLREA......GMYHRDFKTANFLVS.NTGKI.............................................LISDFGTSR................................ p. 11


Subdomain VIB Subdomain VII SLREV......GMYHRDFKTANFLVS.NTGKI.............................................LISDFGTSR................................ QVHNHYPEAEINVYHRDIKLENWLIK.TIDGNHT..........................................VFISDFGLSR..SN............................ NLHKCH...LNEIFHRDIKPHNWLVKKTKDELV...........................................VVLSDFGLSRENS............................. SIHKN......HLVHLDLKSENIFLS.ESQKI.............................................KIGDFGLAK................................ ALHRA......SMIHRDLKSENIFIS.GSNKL.............................................KIGDFGLAIQ.S............................. EFQN.......VIIHRDIKPENIFLR.KFKNNDGK.....................................VELDCYLGDYGSAQ................................ EFQT.......VIIHRDIKPDGSIVN..DYYL...............................................CDLGSST................................ ILKEFKN....SIIHRDIKPENIFFVKNGPDL...........................................EFYLGDMGSSS................................ ELETV.....YSIHHRDLKPDNILIK.NDLTI.............................................CLADFGIS.HFSK............................ QLENL......GIFHRDVKPENIISL.RYGNGGIV.........................................VFIVDFGISQYK.............................. ILESL......QIYHRDIKPENILFK.REIVNGNI......................................QSKVCLIDFSIS................................. ISQKE.....FEFVHNDLHFGNVLLT.SFPVDKKYIVYQDKLDNG...................EFNNWIVGGDFIVKISDFGLSRIK.............................. YLHHS......GIIHRDIKPPNILIHQSYDSITDR.....................................EVTHLMISDFGTCDTIGPLES......................... HLHSL......NIVHRDIKPHNVLID.PNNRV.............................................KISDMGLGKL............................... FLHCQ......DIVHNDLNPRNILVH.KGNF..............................................VISDLGLSKMQ.............................. FLHSH......DIVHNDLNPRNILTL.IGKTSNNNNSS...................................NNSFIISDLGLSKME.............................. FLHQQ......GIVHNDLNPRNILIK.DDRFI..............................................ISDLGLSKME.............................. FLHQQ......GIVHNDLNPRNILIK.DDRFI..............................................ISDLGLSKME.............................. FLHDQ......NIVHNDLNPRNILVK.DNRLI..............................................ISDLGLSKMN.............................. FLHSH......DIVHNDLNPRNILTL.STNKNNNNNNKSNNKIKSN................NNSNNNSNNNSNNSFIISDLGLSKME.............................. VFHNHS....PPLAHRDIKPGNIVLQ.NLRRPSNNNNNNNNNNNNNNNNNNNNN(17)NNNNNNNNNSEDSDIEAIPILMDFGSVREARIKIE......................... AMHQQQ....PPIAHRDLKIENVLYC.EHSNR............................................YKLCDFGSSTIKTFNT.......................... YMHSQQ....PLIIHRDLKVENVLLD.EESGI............................................YKLCDFGSATEEITRM.......................... EIHNRK...DGVILHRDIKPGNLFLD.ENKNI.............................................KLGDFGLAKI............................... YISSR......NILHRDLKTQNIFLS.IVNGD..........................................YFIKLGDFGIAKIL.............................. YMHKK......KVIHRDLKTQNIFLT.KKNII.............................................KIGDFGISRV............................... YIHSQ......NIIHRDIKPKNIVLS.SSDSGSGSGSGSGS............................SNDSIPLLKIADFGVSKLM.............................. HIHSQ......QIIHRDLKPANIFID.NEQNV.............................................KIGDFGLATSGAPVSKSDDLNSSTSNTANN........... HIHSQ......QIIHRDLKPANIFID.NEQNV.............................................KIGDFGLATSGAPVSKSDDLNSSTSNAANN........... YVHGQ......GIIHRDLKPSNIFFD.SCGDI.............................................KIGDFGLAINNKTTSTLSPTTNINSSTSSAGSLTTSSNSVQ YIHSM......GMIHRDLKPANLFLS.S.GVI.............................................KIGDFGLVKDITATTPSTTPLTNNTPSTTPIDTTPTSSANT YIHSK......GIIHRDLKPGNVFLV.REEDHHQQSSFSNISSS.....................FEENSDGGGLLVSLGDFGLAVQHTIVSSTPSPTPTSTPSLTPVNSHISPIDQI YIHSQ......GFVHRDITPDNVFVCQSPFGI.............................................KIGDFGLATTIESLTVDSNN..................... YLHNN......NIIHRDLKLGNLFID..NMRI.............................................KLGDFGLSTK............................... QSSFK......GVFHGDIKSENVLVT.TSNWV.............................................YLSDFACYKPT.............................. YLHSQ......DLTHRSLSLDNIKLD.DNNQI.............................................KLTNYGLYY................................ TIHEE......KIIHGDLKPANFVSV..QGSL.............................................KLIDFGIAKAIQS............................ YIHSL......GLVHLDIKPENIYII.YKCNQNQIITNNNNTCSINNSSNGSDS(43)QNNYLIIDGNKINFNSITFKIGDLGL.................................. HIHSY......NMLHLDIKPENLFIS.SQGNI.............................................KIGDFGMAVKLETTNNNNNGNGGCQS............... HVHEK......GIMHLDIKPENLLFS.NDGVL.............................................KIGDFGVCS................................ FLNNKC.....NLTHGNIQSSSIFVN.KGGDW.............................................QIGGLDFVSDVKD............................ FLNQTA.....KLLHRNISPESIFIT.KDLKW.............................................KLGGLGFTCSIETKEPPISNLSLQDL............... YLKSK......GIQFSHLHLSNILINQSNDTC.............................................QLVDIENCL................................ FLKNH......NFPYFHLNSANVLVD..DQIC.............................................LISDYENSF................................ FMDNH......QIVHRDLNCSNVIIFPETLTI.............................................KIIDFGVTKT............................... FLGDH......KINHFDIKCDNFLVHPLKKGTIEEDFWNQP............................TNDPNFAVCLADWGEAKVY.............................. DIHSNP...KGALIHRDIKASNFLVD.KNNLV.............................................KIGDFGTARFD.............................. SIHGK......GCIHRDIRPNNIYIN.SECKV.............................................KLANFQFSIFKKTSSFLKKSKFQQQHQQSENNNNNTLDSDI DIHKC......QIIHRDLKPDNILVF.ENFNSSEASDENDE..........................RQREFGGLICKITDLGASIQKE............................. VNIEK......NYTHFDLNHGNIFVNIHTLDTCQSISGSGSGS......................GSGSGSNTRNPVVLGDFGCARKM.............................. MNIF.......EIQHRDLHAANILIK.EDGSL.............................................SIIDYGY.................................. NLHAN......KIAHRDLKSNNIFVTLSESEVK..........................................ICKIGDFDISRSFNNPKVLNVLS.................... YMNSK......KCSHRDIKPANILML.RNRKPKLKQQSEQQQQEDGGYIRYSGQFQLEPSSQENNNYQFDPDELPILKVTDYGYAS.IS............................. DLHLV......GIIHGNICANNLHFL.FGQTSDWPDWTAG..........................ECKGAWKSKGFTLTDFSRSIDTT............................. YLHSN......NIIYADLKPSNILID.SKGIFKLNSINNSILIENNNNNNNNNN...NNNNNNNNNNNNNQQIMITSRQQIFNLYNNNIDNDNNNNINE................... SNYDY......NAIGKHFKTESILIG.ESLF.........................................KWPSPRIQQFD................................... YFESH......QVIHQTLHPGNIYIL.EDSLG...................................................................................... FLHQR......EIVHGDLQPSNIHLN.NQMW....................................................................................... H.TSR......EVIHRDIRLSNLLMD.SGGDP.............................................LLVDFGFANF............................... H..QR......EVIHRDIRLSNLLMD.SGGDP.............................................LLVDFGFANF............................... FIHSN......NFIHRDIKPDNFLMGIGKRGHV...........................................VNLIDFGLAKRYRDPK.......................... AVHDL......GYLHRDVKPSNFAIGLNPSKRN..........................................ITYLIDFGLARRFVLA...........................

p. 12


Subdomain VIII Subdomain IX ..............................................LLTPTDKTGTFCGTPEYLAPEVLQ............GNGYGKQVDWWSFGSLLYEMLTGL............ ...............................................IQEGHVTYTMCGSPEYVAPEIIN............GTGYSKSVDWWALGTLFYEMIAGL............ ............................................NSIKNGNKKNNKCLGTPYYMSPEVIN............KRGYGKTIDWWALGIIIFELLSGE............ MDDS..........STTGNPNGNGNTSLNSSQTNILSPYPQRKNTLKTPLKKPVKKVVGTPDYLSPEILL............GTGHGQTVDWWALGIILYEFLTGS............ ....................................LKNSFTLYNTNNNNTTENQKILGTPYYIPPEVIL............GKGYGKTIDWWSLGIILYEFLIGY............ SNIGGSNTI(98)SNIPTTTTTTTTTTTGQQSQQQSQQQQQTTPPLPPHNIHRKLSCVGTPDYLAPEILL............GIGHGASADWFSLGVILYEFLCGV............ ..............................................NQKKPTSNDGILGSPRYISPEVLL............FEPQSPAVDYWSLGIVMFELITGT............ ............................MKLIEATPLTQTERIASWKKARRALAYSAVGTPDYTAPEVFL............QIGYNKEVDWWSLGVILYEMVVGH............ ............................IREEDQTPQSRSARFDSWKRQRRVLAYSNVGTPDYTAPEVLM............KDGYSAECDWWSVGVIMFEMLVGY............ ..........................SFTSNTMKAASAYLSGGTNVMAYRRPIAHSAVGSPEYMSPEIVN............DQGYDMTCDYWSLGCVFVEMLCGF............ .................NNNSLKSSTSLKNSSDCVGNIHGNNFKQ.PLNKKV.TFSKVGSPEYMAPEMLA............GKGYDISYDYWSLGVVFFEMLIGD............ LSS..........SMIEHTPMKFGAAANGNGPLNSSVTDFGSFKD.LSVAARLAYSVVGSPFYMAPEVLQ...........ATRGYGDEVDWWSLGCMFYEFIFGV............ SSSLLGGSGGFTPSHWNGMAGSAGSSFGSSSLGRSFDNTPPNFNSFLRNPHSSYTSYIGTPQYMAVEVVQ............GVNYSKLCDFWSLGAILFELVTGQ............ LNNVNNLSV(48)NNNNTAAGSNTNTNTNTNINTNINANINNIKTTEIPKLTRNNSFVGTAEYVSPELIS............NKETSTDSDLWALGCIIYQMASGR............ .............................................GSHHKGSRSGSFCGTAEYVCPELLT............EKSAGVEADIWSYGCLLYQLVSGK............ .................................................VEDRTFTLCGTPEYLAPEIIQ............SKGHGKAVDWWALGILIFEMLAGY............ .................................................ITENTKSMCGTPEYIAPEILS............GHGHGKSADWWSLGILIYEMLVGV............ ...............................................TVGGKNTSSVCGTFDYMAPEILN...........SSNGHGKPVDWWALGVVVYELVTGK............ ...............................................IETTDGTFTFCGTPEYLAPEVLN............GHGHGCAVDWWSLGTLLYEMLTGL............ ...............................................VKTNNETFSFAGTLEYMAPEMIQ............HATCGKAVDWWSIGILMYDMMIGK............ ...........................................GSKNGGEGGFATTFCGTPEYLAPEIIT............GAGHGKAADWWSVGILLFEMLTGR............ ...............................................HAPNTKRSTFCGTLEYLPPEVIE............KKGYDQTADVWSLGILIFEFLVGR............ ...............................................IGQTLVMQTACGTPSYVAPEVLN............ATGYDKEVDMWSIGVITYILLCGF............ ...............................................YEESIGLELACGTLAYSAPEITN............NQVYRKSVDMWSCGCILYFILFGR............ ...............................................FGDGDYLETCCGSPEYVAPEVLE............CKPYDKACDLWSVGVITYVLLTGC............ ...............................................CGSGSPLRSLVGTLTYMAPEISS............CTGYGKPVDLWSIGVISYILLCGF............ ...............................................FEGGEELKTACGTPDYVAPEILE............CKPYDTSVDMWSIGVITYILLCGF............ ...............................NNNNNNNTNGEVIQPSSPPPTKLIDVCGTPEFQAPEMVK............RLGYSYPVDIWSTGIILYILLCGH............ ...............................................FGTGEALETSCGTPDYVAPEVLT............GGSYDNAVDMWSIGVITYILLCGF............ ...............................................VGDDVFMKTTCGTPSYVAPEVLNNI.......SNSPTAYSDAVDMWGVGVITYILLCGF............ ...............................................MQDGDFLKTSCGSPNYAAPEVIS...........GKLYAGPEVDVWSCGVILYAFLCAK............ ...............................................VRKDMLLHTSCGSPHYASPEVVS...........GIDYDGQKADVWSCGVILYALLTGK............ ..............................................QLEDFECLSRSYGSPAFQPPELTQ..........FQTTFSPFKIDIWAMGVTLYLMTIGK............ ...............................................FTPGSYLKTFCGSPTYASPELIL...........RKEYNGPSVDVWSMGVVLFVLVTGY............ ...............................................IKPGNLLSTFCGSPVYAPPEILL...........EKRYNGNEVDIWSMGVILYAMVTGQ............ ...............................................IQPGKLLESFCGSPLYAAPEILK...........AEKYLGPPVDIWSLGVIMYAVLCGN............ ...............................................NWSYQEKMSFCGTPAYAAPEMLL...........GINYNGPEVDIWSLGVILYSLVTGK............ ..............................................ANVNVTVFNINGGTELYKAPEMKE...........QNVKGSYSTDIWAFGVMLYKCIFQFVNNNNNGNNGKN ...............................................IHEGELAKTLCGSPLYVAPEVILSLHHK(16)DINSVGYGKSCDAWSLGAILYIVLCGT............ ...............................................VEESQYLQTFCGTPLFFAPEVIAN........NFFSNGYGKSCDLWSIGVTLYLSLCKY............ ...............................................IGEKEMATTLCGTPLYVAPEIIRNCLHG.DGGAQVNTGYGKEVDVWSLGCILYILLSGR............ ...............................................MDEGTYMKTMCGTPQYVAPEILTK.........GEREGYGKSVDLWSIGVITYILLCGF............ ...............................................VSDGSFMKTMCGTPQYLAPEILTS........SGGHNGYGLEVDCWSMGAILYIMLCGY............ ...............................................FDDDDVVRCSRGSPAFLAPELCRN.........ESQPISGKGVDVWALGVSLYCLIFAR............ ...............................................IDPFSLSDTFCGSPLYMAPEILH............RKNYTVKADLWSVGIILYEMLVGE............ ...............................................SSNSILLTSLKGTPLYLAPEIIQ............EQPYDYKADLWSLGIILYQILVGS............ ...............................................SIPVRVYTHEIVTLWYRAPEVLL...........GSKSYSVPVDMWSVGCIFGEMLNKK............ ...............................................GIPVRTYSHEVVTLWYRAPDVLM...........GSRKYSTPIDIWSAGCIFAEMASGR............ ...............................................GSPNKVFSPQAVTIFYRAPELLF...........GAKSYGPSVDIWSIGCIFAELMLRT............ ..............................................SPLKPLNENGVVVTIWYRSPELLL...........GSKHYTRAVDIWAIGCIFAELITTK............ ..............................................SSEKKQILTNRVITLWYRPPELLL...........GTFHYGPEIDMWSVGCIMAELLSKK............ ...............................................GYPIESITPCMVTLWYRSPELLL...........GCQKYSTAVDLWSIGSIFGELLIGR............ ...............................................GSPLKPLSKGVVTLWYRAPELLL...........DTEIYTPAIDIWSVGCIFAEIISKE............ ...............................................YTKRSVFSSKVVTLWYRAPELLL...........GSTQYGPEIDMWSIGCVLIELVTSR............ ...............................................YIGNPHLAHQVISLFYRPPELLM...........GSRNYGPEVDIWSVGCIIVEMLTGF............ ..............................................SKRSEKFLSSNVVSLYYRPPELLL...........GSCIYGPEIDMWSVGCILMEMINNS............ ...............................................YHPNQDYNVRVASRPYKGPELLV...........DMEDYDYSLDMWSLGCMFAGMLFQK............ ...............................................YHPGKNYNVRVASRHYKPPELLV...........NMFDYDYSLDMWSLGCLFAGLILDR............ ...............................................TFENTHHTAIVCSRPYRPPEIIL............GMGWSYPCDIWGVGCILVELYLGY............ ..............................................PT.FLFNKEYITNTYSYRAPETIW...........GDSLYTEATDVWGAGVLFAELLLGK............ ............................................DYPTDIFF.KDYEETPWPYRSPETII...........MLKEFSFECDVWSIGVIFAELILGE............ ..............................................PVDLFF.NDYDTSSFIYRAPETIW...........RNTTYTTAIDVWNIGVIFGEMILGK............ ................................................HSNERMYKYIQSRFYRSPEILL............ELEYSFSIDMWSLGCILVEMHVGE............ .................................................ENEQIFTYIQSRFYRSPEVIL............GTKYDKSIDIWSLGCILVEIFTGV............ p. 13


Subdomain VIII Subdomain IX ................................................YEKSTLYTYIQSRHYRSPEVLV............GTVYCASIDMWSLGCISAELFLGL............ ...............................................EIHESEITPYLVSRFYRAPEIIL............GHKYDYSIDVWSVGCCLAEFFTGK............ ...............................................LIKGETNVSYICSRHYRAPELIF...........GSTNYTTTIDVWSLGCVLAELLLGQ............ ...............................................LESNHTSMSYICSRYYRAPELLV...........GCSNYTTKIDIWSIGCILAEMLIGK............ ..............................................DATHQGFMTEYVATRWYRAPEVIL...........SWNKYTKAIDIWSVGCIFAELLGRK............ ............................................ESIAEANPVLTEYVATRWYRAPEILL...........GSTKYTKGVDMWSIGCILGELLGEK............ ...............................................IESKPPFTDYISTRWYRAPEVLL...........RCTYYNAPIDIWAVGAIMAELYSLK............ ...............................................WTDKHFTDDIQ.TRQYRAPEAIV............KAKWGTPVDIWSAACMAFELATGD............ .............................................FGNSITQPTYSNPSSYSYLSPEYICSVLDKENHSKLSNEIDWKAFDMWSIGCIFLELIYKK............ ................................................GNVDSEPAEDG.MIYGSPEI.............FGRVINTESDIWSLGVIFIYLLQTKQE.......RTK NNNNNNNTN(64)PSTNENGTTTSNASSTSNTTSSSSSSSNKSKNLRNDPKPQPAPRAGTRGFRAPEVLL...........KYNKQTTAIDIWSVGVILLCMISGR............ ...............................................IKESDKRYSVVGTPYWMAPEVIE............ISGHCQVSDIWSLGCTIIELFTSY............ ...............................................KFDDTSAAAVVGTPYWMAPEIIE............LNGATTKSDIWSVGCTVIELLTGS............ ...............................................YSAIDRKLTVVGTPFWMAPEVIQ..........MDMNARSTACDIWSLGCTLLEMLTGN............ ..............................................DLSSDNPDDTFAGTPYWMAPEVIQ............MQGISTACDVWSLGCTIIELLTGT............ ...............................................DSESQLRFSVVGTPYWMAPESIE............ISGCSSASDIWSLGSTMIELLTGN............ ...............................................CDGDSKYYSLVGTSTHMPPEVALR...........NNTACRKSDIWSLGCTIIEMAGGN............ ..............................................PSNDGSKCYTQCGSIGYIPPEIKL............GGQCGRKSDIWIFGCLVIKMLGGE............ NNNNNNANN(28)GGGGGGEASITSTISTILSGSSSSQLSTPSTSLESSFSLEINLNDSSCYLIAPEIRN.......QQKITSKGLSKKSDIWGLGCLLLLMVGG............. ...............................................INFS................LNI............GYEDSIHLDMFNLGCVLIQMLG.............. ...............................................LDSEVNSNIIGVTETHMAPEIKLK...........NGKLGYKSDIWSLGCTLIEIVGGN............ ...............................................IEKNSKYYSFVGTDSHMAPEVKLQ...........NGKAGSKSDIFCIGCTMIEMAG.L............ ...........................................DDGDNICKESSFAITGTHTYMAPEVKK............LHRSTKKSDVWSLGCTVLEIVGG............. NNN..........NNNNNNNNNNNNINNINNNNDLNGSGSGISTYLNEQYKQSSFAIIGTFNYMAPEVKR............NYRATRKSDVWSLGCTIIEMAGG............. ...............................................GDLKRDHYG.....TYLPDECIL..........NNVSIVNYTFDVYSLGFISFELFYPTQF.......... ...........................................NIINKTVKLQTISSVGTTLYMAPEILL...........NNKGSNSSLDIWSLGCIIVEMKWG............. ...............................................QHTLSKAVTWVGTVTYMSPERIS............GRSYSFDSEIWSLGLTILECAIGK............ ...............................................SGIVSQFKSMQGTPYWMAPEVIK............QTGHGRSSDIWSLGCVIVEMATAQ............ ..............................................IDTGETSRNTFVGTPCWMAPEIME............QVNYDYAVDIWSFGITALELARGK............ ..............................................EKNTCCSRKTIVGTPCWMAPEIIS............ERGYNQGVDIWSFGITAIELIRGK............ ...............................................NLSKGERIRMCGSPIWMPPEMIQ............QKQHGYTCDIWSTAICLLELANRN............ ...............................................DVATSTPMHMVGSPFWMAPEMIQ............QKYHSTPVDIWSFAISLLEMANQR............ ...............................................DANERKLVHMAGSPFWMSPEMIR............GESYGCPTDIWSFAICLLELANGE............ ................................................SIEKEEINMLGSPSYISPEMIN............GNPHSLSTDIWSFGICALEMLLGK............ ...............................................LTHLKQDINMCGSPFYMSPEQIQ............DKAHGLAVDIWSLGIVVAEMVRGR............ ...............................................SVEKGGSQHMVGSPYYMSPEMIR............GEECSYPSDIWSFGICILELLFKK............ ...............................................TQIRQERNSVVGTPYWMAPELIR............GNNYDFKVDVWSLGIMTREMAEGE............ ...............................................TKSKQKRVTIVGTPYWMAPELIR............GQNYDRKVDIWSLGIMAMEMAESE............ ...............................................TQKQQKRNTVVGTPYWMAPELIR............GHDYGVKVDIWSLGIMMMEMAEGE............ ...............................................TRKKLQRNSVVGTPYFMAPELIR............GNQYNHKVDIWSLGILARELSEGE............ ...............................................QTEYGQANVYIGSPLYMAPEVIL............KAPYNSKADIWSLGITLIELAEGR............ ...............................................NGALDQSKEMIGTPLWMAPEVIL............KKNYDYKADIWSLGITIIEMADGL............ ...............................................DSLRGEASQLVGTPLWMAPEIIK............RQNYNNKCDIWSLGITAIEMAESF............ ...............................................IQSTFSKGSIAGTPYWMAPEILN............QTDYNNKIDVWSLGIVAIELADGE............ ...............................................SDTMAKRQTVIGTPFWMAPEVIQ............EIGYDYKADIWSYGITCIEMAESK............ ...............................................SERTRKRNTVIGTPFFLAPEVIQ............EVGYDNKADIWALGISAIEMAEFH............ ...............................................TDQMTKRNTFVGTPFWMAPEVIK............QTGYDSKADIWSMGITALEMAKGE............ ...............................................VNTGFKQKTVVGSPYWMSPEVISP........PKGSNGYDSKADIWSLGITAIEMAESK............ ...............................................AEQGQKMNTVIGSPYWMAPEIIM............GQGYDQKADIWSLGITAIEIAELV............ ...............................................FNTFSKRNTFVGTPYWMAPEVIQ............ENKYDGKADVWSLGITAIEMAEGL............ ...............................................LDKSSKRNTFIGTPYWMAPEVIEN........RSNPVPYDTKADIWSLGITLIELAEAE............ ...............................................CSLGRGRTRMCGTMGRIAPEVIR............REPYDTQSDIYSLGCLIIEMAEGT............ ..............................................SAIEPSIRFSLNGYPFWTSPEVLS............MKPFNHKVDSWSIGCLIMELIVGH............ ...............................................LGNGVTLKTCIGTPCYMAAEVLNVA.......DGGNSGYSLKADIWSFAMLCFEIISLL............ ..................................................GRNIKIFDHFEKLNSLKNLNSWISS(28)NQINNEIDRREDIINLGIVVLEMLCGSDLAN(22)FIQP ...............................................IDDSTNLKTLCKKPFWASPDVNN..........QEIQIFSEKTDIYSFGCTIFEMIVGW............ ...............................................IENNTNFKTACCSPFWAAPEILN..........KSTSDFSRKCDIYSFGCTILEMIVGS............ ..............................NHNHNHNHNHNHDNDNDNDTNVKIKTQCMEPRWPSPEIHR...........EPPHFSKESDIFSFGCTLFEILG.............. ...............................................IDLLTNQKTQFISPCFITPEYFYK.........KTKNKISKEADIFSFGSTISNMIKGG............ ..........................................KFMSFQLKNQLLHTQ.....YLAPELFNVL.......SGSKGGYDTKVDVFSFGVLLWEMFA.............. ...............................................FVKDGIFRTGQQSSPYLAPELFNSN..........CNQYDTNSDQFGFAMILLQLFTRS............ ..............................................TQENEESLKEIKGNFLYSPPELLS............LNTYSNKSDIYSLSIVLYELFETCLTK......TYK ..............................................LNTEYINSNNQNKSFAFCSPESSDFQDID.DDYTSLSSSITSKSDIYSFGIIMFELISRIING......EYS ..............................................TESNQETLNKTRGTSVYCAPEVFE............GKEYNERSDMYSMGIVMWEIVYCVVYG......CYM p. 14


Subdomain VIII Subdomain IX ..............................................TGSNLETLVKMRGTFAYCAPEVYY............GEQFSGKSDVYSIAVILWELVTRCING......RYE ..............................................TADNLETLSKIRGTFAYCSPEVAVG..........NGSLYTTKSDIYSIGIVFWELVTRVING......EYS ..............................................TGSNLETLGKLRGTYAYVAPEVYF............GKKYTTKSDVYSMGIILWEMTYRCIKG......THL ...............................................MTNVSTLGMLRGTMAYTAPEIYD............GLLFNTKSDVYSLGVIMWEAIQRCISG......VYL ...............................................TAKSASNRTTRGTFAYCAPEVF.............YGIHTTKGDIFSIGIILWELAVRCIKS......KYE ...............................................MEQASQMTQSVGCIPYMAPEVFK............GDSNSEKSDVYSYGMVLFELLTSD............ ...............................................SNQSESKKLRGGSIHYMAPENLN............GSPINEKSDIYSFGLLVWQMFS.............. ...............................................KPGPTEMTAAMGSLAWMAPECFK............AENYTEKVDVYSFAIILWEIVTCR............ ..............................................TELQTGSNSTIKGTMAYCAPELYN............GISYSEKADVYSLGIVLWEITTRVITG......KYQ ...............................................SNQSESKKLRGGSIHYMAPENLN............GSPINEKSDIYSFGLLVWQMFS.Y............ ...............................................EQGFE.MTSTVGHLCYQAPEVFI............GELYTPKADVYSFGLLVWCIITGE............ ...............................................IEQQGATMTACGTPCWTSPEVLR............SQRYTEKADVYSFGIILWECATRQ............ ...............................................IEQQGATMTACGTPCWTSPEVLR............SQRYTEKADVYSFGIILWECATRQ............ ..............................................KHLDKKTAMTPVGTPCWTAPEVLR............NDPYTEKADVFSFAIVLWEIVTRE............ ...............................................VKSHTFAKTMCGTTGWVAPEVLA............EEGYTEKADVYSYAIVLWELLTRL............ ..............................................GENLKDGQDGAKGTPLWMAPEVLQ............GRLFNEKADVYSFGLVLWQIFTRQ............ ...............................................PDSKDKLLGQAGSPLYMAPEMLV............NQPYDGKVDVFSFSILLWELLTKQ............ ..............................................KHKMLKDQSSAKGTPLYMAPEVMM............FKEFNESSDVYSFGIVLWEILTRK............ .............................................IKEGEEFQDKAAKGTPLWMAPEVMM............GNPYNEKADVYSFGIILWEILTKE............ ..............................................TGTTLSDQKGPKGTALYMAPEVMM............KHEFNEKADVYSFGLILYEMATCE............ ...............................................ETSFTQTMTTIGTVAWTAPEILR............HESYNQKADVYSYAIVLYELLTGE............ ...............................................IDNNFNMTAVAGTPKWESPECLM............GEAYTSASDVYSYGMMLFELATGD............ ...............................................VDLAKQMTLNLGTSCYMSPELFK............GNGYDETCDVYAFGIVLWEIIARK............ ...............................................VDLAKHMTMNLGTSCYMSPELFK............GNGYDETCDVYAFGIVLWEIIARK............ ...............................................VANKYNMTTHVGTQAWMAPEIFT............SRTYTNKVDVYSYAIILFEIFTRK............ ...............................................FVEARLGYTIVGTPNYMACELFN............GQPYHQPADVFSFGVVLWEMFTQD............ ..............................................REGSMTMTNGGICNPRWRPPELTK...........NLGHYSEKVDVYCFSLVVWEILTGE............ ...............................................TLSDDMTLSGITNPRWRSPELTK............GLVYNEKVDVYSFGLVVYEIYTGK............ .............................................IKGLACNNYIERVDTPINLTREISIIRDPK(29)NNSNNSSSLKYNIHSFAVLSYELLIDE............ ...............................................TNERYNLQTRRGTVAYMSNEILS............QGSYTKSTDIYSFGMLCYELFSER............ ...............................................INGKHELNSKAGTTRYMSPEILE............GLPYTYSTDVYSFAILFFELLSGR............ ..........................................................EVQNQNEKEIFK............DEKDQKLIDVYEFGITFYETMLEE............ ...............................................LGEKESKSKPDSTMNYLPNEVFD............GEGYQKSADVYAFGVSLYEVMVEK............ ...............................................NEFSNKNTNCVGTPIYMSNEILE............KKTYDNSTDVYSFAVLFYEMMIEE............ ...............................................EEDNNKSMTICGTDNWMSPEMIT............GLDYDERSDIFSFGIVLLEIISRVK..........P ..............................................KKQQGNRHLSICGTDSIMAPELIL............GMEYDESVDIFSFGVVLLEMILRKKV........SK ...............................................DGKDTNNLTICGSENTMSPEVIV............GSSYNDSCDVYSYGVLLLELICGS............ ...............................................EERINKRYTCVGTEIWMAPEVCL............DQSYSTAVDVFSFGIVLVEIITEKI.........PD .............................................GGGSRAKRTMTICGTTNCMAPEVVL............GQDYNEACDVFSYGIVLSEIITRMDTTNNL...RPS ...............................................DKSEKSKMTICGTDDWMAPEVLI............GEEYDASCDVFSFGMVLIELITRE............ ...............................................TIQNPLSMTICGTDEFMSPEVIL............GIQYSYSADIYSFGMVLLELIT.R............ ..............................................EQTKKSRHMTMCGTEGWVAPEILL............GMSYDTSCDVFSYGVVLAELITG............. ..........................VNGAAGGGGDDVYKNNGNGKPANYRLRRMSICGTPSFMPPEILL............QQKYDWSVDVFSFGILCTELIT.............. ...............................................NDIGDKTMTSIGNPRFRSPEVTK............GQKYSEKVDVFGFGMILYEMFTRR............ ..............................................ALYGGAALIRCVDQPLWLGPEVLA............GTAYSEPSDVYSFGIILWELYTRA............ ...............................................GLQHTITNRGVENPLWLAPEILN...........KTKEASTQTDVYAFGVILWELVTRK............ ...............................................QQSVYSVSGLLGNFQWMAPETIG..........VEDESYTEKVDTYSFAMILFTILTGE............ ...............................................QQSVHSVSGLLGNFQWMAPETIG..........AEEESYTEKADTYSFAMILYTILTGE............ ...............................................VVTSALGRDKLSNPIWLSPEIMR............GDEYTEKADVYSFGIVLWEILTGL............ ..............................................QALKHKLRNFPVGNITWVAPEILR............EEEYTVKSDVYAFGLILHELLTRK............ ..............................................KPIGKEVKGRKVWNWRWLAPECMG............DGQYTEKIDIYSYAIVLWEIITRD............ ...............................................SIVQNFSSKVVDNPTWQSPEVLK............GMEYNEKSDIYSFGMILWECYHLE............ ...............................................GFSTTVANRSVQNPVWLAPEVIN............NELCSDKSDVYAYGVILFELLSRT............ ...............................................SFLPSLFPTSTTPKSYHSPEVLQ............KLNYHENSDVYSFGIILYELLTRS............ ...............................................QQSLYSVSGLLGNFQWMAPETIG...........AEESYTEKIDTYSFSMILFTILTGE............ ..............................................PKLNATDLNNPAIEPRYMAPEMTR..........MEEDQISCSIDVYAYAFVLWEALTSH............ ...............................................VVDNR.MTKTVGTPCYMAVEVLK...........GLTDYSQQADVYSFAFVLWECISRQ............ ........................................NRHTGSGDNNKVEKDSKKGTTLWMAPEVIR............GAMYSEKCDVYSFAIIMWEMVTRK............ ............................SSTTTSSANGANSISNNNNNGTTSVDQSRLAYAFYAAPEILN............SKHFSEKSDVFSFGTILWELVTNK............ ..............................................NNQNNNNNSLNMGSYRYSPPELLCNN.......NQNNNLINKSVDVFSFGIMLWECLNWT............ .............................................TSSSRSFYGPTVEGSFLYMSPEVFT............QKKFSRAADVWSYGACLIEILTNK............ ...............................................GGIGSSAKTFCGTLSWIAPEVFN............GSGYTTKVDVYSFGIVLWEILTHK............ ...............................................KSKSTEMTKSIGSPIWMSPELLM............GEDYTEKVDVYAFGIILWELGTGE............ .................................................................................SNSVEDKAVDLY........VLERA............ ............................................DENEKRLNTFAKTIGTMWYRCPRLGDCSED.....EKTLTHYNEKSEIYSLGIILWELVCVAMTGTYI...SPK p. 15


Subdomain VIII Subdomain IX ............................................DENEKRFNTFAKTIGTLWYRCPRLGDCSGD.....EKTLNHYNEKSEIYSLGIILWELICIAMTGTYV...SPK ..............................................TESNGCTLQQIRGTNLHIAPECYK............GFLFSSQSDIFSVGISLYQLAYKLVYG......KFV ..............................................ETNENT.LQKYRGTSVFIPPELND............NILYNEKSDIYSLGVSFMMLLYKVVYG......KME ...............................................KYENS.MSGVAGTYYYLSPEILL............NKNYSRPADIFSLGCIFYEMYTLNL........... ..............................................AHHTGSIHSETVGTYCYSSPEILN.............STYDKTTDIFSLGCIFYELITLK............ ...............................................TLYTQNKSTLIGTNQYIAPEVIE............KKGHTNLIDIYSLGKTLLSLSKRN............ ...............................................QVKTINSSTLIGTNQYIAPDVIK............RGGYTGTIDIYGLGKTLLLLLN.............. ...............................................MVITDQKNTLIGTNQYMAPEIDLG.............GYTCKVDIYSLGKTMLSLIT.............. .............................................ELKNDQDLYYSKDGTLGYQSPEIYSSEL....RGNGDIKNQPYKMDVFGLRCVMKYLMSK............. ...............................................GKHLENYYSRDGTFGYQAPEIYREEL....RGDGDIKTQKYKMDVFSLGCTMAFLIKK............. ...............................................DFGFILKTNESGSKMYQAPEIYQEEYRS...KENDITNQHYKLDIYSLGFTLSHLMKK............. ...............................................LPSNEIIYNQRNDR...SKEFC..................FYSDLYSFSSLLNKIKIKE............ ..........................................LAPPLYKNNIKRTGNTGTIEYLAPELLQKGV.....NGEYNSDYDEKCDIWSLGILLYQMAYGT............ .............................................LDNDDQ.SLTFTSDSHGWQPAEYLN...........GTNRNTKKVDIFSLGCVVYYLLTGA............ ............................................VETSYSF.TNNAPTGQEGYHPIEVLQ............EKRKTKSVDIFSLGCILFYLLTNGQ........... ............................................VESSYSF.TSNIPTGQGGYHPFEVLQ............SKRMTKSVDIFSLGCILFYLLTNGQ........... ............................................VTSSYSF.TMHAPTGQEGFHPAEVLL............EKRKTKSVDIFSMGCILFYLMTGGQ........... ............................................VTSSYSF.TMHAPTGQEGFHPAEVLL............EKRKTKSVDIFSMGCILFYLMTGGQ........... ............................................VSSTYNFSTNAIPTGQDGYHPVEVLL............EKRKTKSVDVFSLGCLIYFIMTNGA........... ............................................VESSYSF.TTNVPTGQGGYHPVEVLQ............SKRMTKSVDIFSLGCILFYLFTNGQ........... ...........................................NRKDALSLQDEVEQNTTPFYRAPELFDIPS.........DCQIDERIDVWALGCLLYTMAYNN............ ............................................ATERGKAEDDINMFTTLFYRAPEMVDLYR.........GQIIDEKVDVWALGCLLFKMAFYV............ ..........................................KNKTEMQNAEDDISRHTTLQYRAPEIVDFYR.........SPVINEKIDIWALGCLLYKLLFYV............ ...............................................LNESLYAHTFVGTPYYMSPEQIH............GLKYNERSDVWSVGCLIYEMATLS............ ...............................................NSETSLASTVLGTPYYLSPELIQ...........NEKGYDHKSDIWSLGCVLYELTTLK............ ...............................................LNSSEFAKTMIGTPYYMSPECFG............SRAYDFKSDIWSLGCCLYEMITLK............ ...............................................SETDLYANTTAGTPQYVSYEICN............KKPYTNKTDIWSLGVVLYELMTLS............ ............................INLSSSTNSTAQQTPMWDLNDENLSMTGGVGTPFYCCPEILE..........KNTKHYGTKVDMYSLGIIFFEMCFQ............. ............................INLSSSTNSTAQQTPMWDLNDENLSMTGGVGTPFYCCPEILE..........KNTKHYGTKVDMYSLGIIFFEMCFQ............. SVIN.....TKQQQQQQQPQNYWEDEVEGQQQQQQQQQQQQQQQQQQQQQQQQHTARVGTLFYTSPEQEA........GTNGDSAYDDKVDMYSLGIVFFEMWY.............. IPISTPPTS(21)AATTHLNSSLGCTISSSSSTTTATATTSTTPFMFYNSISVNTVGVGTLTYASPEQLSNKGVF.GGGGYTNTWYTNKTDIYSCGIILFEMIVG............. ININQQLQQ(>63)PTGQSQQSIPSTPSSLSSSSTTPSVSTGTSLSRSLEHCKHTSAVGTLTYSSPEQ.............KKGLYNEKTDIYSLGIILFELYF.............. .......................................NNNNNINNNNNNNKKVGGLGTYLYSSNEQEQ............GDNYNQKTDLYSVGVIFFEMLSQFK........... ...............................................VEHGERKKTICGTPNYIAPEILD...........NSNGHSYEVDVWSIGIILYTLLIGK............ ........................................FIPEDNPADFSFYFDTSGRRTCYIAPERFYETNRG....APSNNELTPKMDIFSLGCVIAELFLDG............ ..............................................LSDHGENVSFPIGNLLYLSPESIL.........RGAKGSSNTKADVWALGCILLHICLGY............ ..............................................DDTTNIVRESQIGTINYISPEALIDTSQ...GGPKQCMKLGRASDIWSLGCILYEMAFGY............ ..............................................LNEATNTKIYSEGDSRYLSRELLH...........DDMSALKKSDIFSLGCTLYELARCK............ .................................NNTSMDSDCNNLSLDEDDIFFDFLEGDSRYLAYEFLL...........DKKQISKPSDIFSIGVTFFEMVTGNEMP......TNG .................................................TTTGGDDSEGDQIYMAPELLN.............DIHTPSADIFSLGITLYEMATNY............ .............................................INNSILRNHNDLIPN.KYKSPEIMKSQ......WQQIQQSPSYSIDSWMLGCLMYECYNGT............ ....................................REYQYISGGGGGESSNNSNYILPQLDYLAPEFIS............QRKFETNSDLFSIGRLIFELSINLEQKALDSHLISQ ..........................................................LGMKPLFNDYIYG.......................IG.LPQSFKDNLE........... ..........................................................LGLEPRFSDFIRQ..........HNEKIDP..DVLSFGLVLFEMACG............. ........................................................NFLNQDYQSPEVLK............SNNFTHKSDIWSFGFILLKMIDK............. ..............................................TQDVEGYTTRNRGTEFIKSPEMLTIAYAS(7)DRRKKVGSNTASDVWSLGCLFYELLTGD............ ..............................................CTLNLSSLKNGAGTVCFQAPEASR.............GKATIQSDIYSLGVVLFELCGAIPYKNY....NYF TMID.......NIDLTNSYNNNNNSSTNNIFFNFNNDYDEESINELFKSYPDLSRFSTSTYYYISPEDTGRTIH..........PVDEKSDLYSLGVTFFELLTGR............ ................................................LVHDNNFTSTFHTDDYVPEEYG...........RFQYDGEKVDIYSFGCTFFEMVTKHR........... ................................................DVPIRLCDTNGHENYKSLERYWDYNQC...RIKTTSFIRDNEDIFSLGVLIFEMLLTF...........V ................................................................................SNIGDDRKGYDISNLKSIYYDFFNNY............ .....................................NPTALQQQKLNNFFQSATTTTTTEQTTEPIEVAA......TTTPQTIHSAFQHDILSFGFIVLDFLTLSN........... ..............................................GNDSAEIHSTLAGSPLYMAPEIIHIILSP(11)DSSEGYNPLLVDVWAIGAVAFRLITGDDL........IS .............................................IYSQDARYQSPIELLPIGTPLEWLKI.....NQSSTTNVGWSYNLDYLGICKVMFHILTCGK........... ...........................................................SIYYLSPEVLK............GYTYSFSSDIWSFGVLLFKCITGY............ ......................................................QFFFQDYLYSSPENYK..........GSLVGVNEYSMVWTLGIILYQCLTGE............ ...................................................................................................................... ...................................................................................................................... ...............................................TENEEFYQGTMNTASNRIYNILIN......NRTNHAFSVVESDDLESL.VKVYIMENEQ............ ...............................................TENEEFYQGTMNTASNRIYNILIK......NETNHAFSVDESDDLESL.VKVYIMENEQ............ ............................................THQHIPYREHKNLTGTARYASLNTHQ............GIEQSRRDDLESLGYVLMYFNRGS............ ............................................SGEVRPARESTGFRGTARYASINSHL............SKDLGRRDDLWSIFYVLIEFAEGQ............

p. 16


Subdomain X PPFYNQ...............DVQEMYRKIMM...................................................................................... PPFYSE...............DPHEMTKLILS...................................................................................... TPFVGD...............NQNMIFEKITNYT.................................................................................... PPFNDD...............TPELIFQHILHRD.................................................................................... PPFQEDEPNESINPKSDNDEKNVRIIFNKITNHK.................................................................................... SPFNGS...............SVQETFQNILQ...................................................................................... TPFIGE...............TPEEIFESILS...................................................................................... PPFLSD...............NTTETCLKILNCKETL................................................................................. PPFCSE...............SIRETYHKIMNWKQTL...............................................................................PK NPFCAD...............TPNDVFINILRWKETL................................................................................. TPFNGD...............TPEEVFMNILDWKNIL................................................................................. PPFDGD...............SPEEVMETVLKWK.................................................................................... ALFVES............PDTTEQKIRENIGNWRGLL................................................................................. VPFRGK...............TEFLTFQKVSN...................................................................................... LPFKGF...............NEYQTFLLITK...................................................................................... PPFYDD...............DTFAIYNKILA...................................................................................... PPFVSE...............GSQNDIFRLIR...................................................................................... LPFSNSK................ESLLNRKAD...................................................................................... PPFYSQ...............NVSTMYQKILN...................................................................................... PPFEHK...............NRALMQEKIIS...................................................................................... SPFLAS...............NRNDMYKSMIQ...................................................................................... SPFTSD...................EEKNIFH....................................................................................NI PPFYGD...............TVPEIFEQIME....................................................................................AN PPFYSD...............DESEMFELITK....................................................................................GQ FPFWDK...............NNAVLYEKIRN...................................................................................... PPFDET........................TG....................................................................................YV APFYAD...............THHELFQKILD....................................................................................LE PPFQGK...............NNMIVMSLIIK...................................................................................GEL PPFYAS...............SQNLLFEKILT....................................................................................AD PPFYSE...............DIRKLFESILS....................................................................................AS LPFDDE...............SIPMLFKKIRE....................................................................................GV LPFDDE...............NIRRLLNKVKN....................................................................................GA FPFSGA...............NMFVLFENISK....................................................................................CK LPFDGD...............NYVELFQKILA....................................................................................GN LPWTLT.............DGVQVEGMDRLLR....................................................................................GE LPWEGD...............SQAEISFNSVH....................................................................................GN LPFINV...............TDMIVGKFILP...................................................................................... NNSDGNENDNN......NNNNFLIIREPFLLP....................................................................................EE PPFDDD..........DDEEMSTPQLFEKIVS....................................................................................GN KPFIVDC................RDLYHSFIN....................................................................................GN PPFDFDH..............TNNFNLKLINQ....................................................................................GL PPFGDP...............QTKDFFEKIKN....................................................................................GG PPFDDS...............REVSIFEQIRN....................................................................................AK TPFISK.................TNSLLDIYD....................................................................................QI PAYNSG...................SVPDLLN....................................................................................QL PPFSAN...................SLADLVHMTLES...............................................................................NI PLFSGD............CEIDQIFRIFRVLGTPDDSIWPGVTKLPEYVSTFPNWP.............................................................. PLFPGS............GTSDQLFRIFKILGTPNEESWPSITELPEYKTDFPVHP.............................................................. PYLPGT............GEIDQLRKICSALGTPNESNWPGVTCLPNYIK.FTDHP.............................................................. PLFPGKEKDPKI...PSLFQDDQVEKIIRVLGKPTLDMWPDIKHLPEWKRLSSMEAF............................................................P TLFPGR............NSIDQLDKIYQVCGSPNANNWPEAMDLPFWDALKPKRE.......................................................YNSLSLK PLITGN............NEVDQIMRIFNLLGEPNEQIWPGFSSLPNFKRLNNIPHQ............................................................P VLLQGS............SEIDQMDKIFKLFGTPTEKSWPAFFKLPLAKYFNLTDQ.............................................................P NFLPGS............SEQQQLEAICKLCGTPTDEIWPNVSQLQNFNQISHLPV.............................................................Y YMFAGS............NDSLQLELIFKTFGTPTEKNWPGISKLSGYSPYLGSKSKKY........................................................PSK YLFAGA............DETAQLDLIFKLFGCPTEKSWPGVSSLPGYNDLFNKQQQQQQNE(38)YNNISTSCLQSPSSSPPIGGYASSLSSDFNSNEYNGYNQTFSNEDCLAISQK DPFFHGH...........DNIDQLVKIVKILGTEEFYAYLDKYGIVVDHTILSIIGKHPK......................................................KPWS DPFFNGD...........NNNDQLLKIVKVLGTDDLFNFLDKFGLSLTDEQSSLIKP......................................................RQKSNWE TLFDTH............NNVQHLAMMEKVMG.PFPNSMSNVSKKYFNDYGTLNRPQNSDE................................................IKSMERVEG RLFRSF............NSKEHLKSIYKLIGAPKASEGAYVVKGELLFFLMEYNRKN..........................................................SF QLFRGE............SKQSLLIEISELIGTPTYDECKESTNGFARNFILNIPLK...........................................................SR RLFKTQ............DFEDHLISISKLIGNPTAEDLSIVLSKSIFQYMEKIPKST.........................................................LTP PLFSGQ............NEQDQLTKIIEVLDLPPSHMIDSSPKAKKFFTKDPINSTYQLKKNEKLKTNVEFC........................KKKLSEIIGVETGGPQSRRKN PLFPGS............DEPEQLACIMEVLGAPPKSVIDNSTRKDIFFEDDGTPKPVKNSTT................................................GELYTIG p. 17


Subdomain X PLFPGN............SEYNQISRIVEMRGIFPSDLLDKGKSSTRYFHRHLGSNSDDNNNNNNNNNGKPYYYTLKSEEDYQRD.SKTTLLPSKKYFNYKTLPEIIQNYGFKKSMSP FLFPGK............TNNDMIRLFMEYRGAFSKKMLKKSEFVSNHFNENLVFMKQEIDNIEKTVRKVPH..............................DITKPTKDILQFLLPK PLFPGE............NGIDQLVEIIKVLGTPTKEQIHAM...NPYYTSFKFPEIKA..........................................................N PLFPGT............NSNDQLGRIIEVLGSPTKDDMEAMKPSKPYH.L.QLPNI............................................................N PLFQGK............DYIHQITLIIETIGSPSEEDICNIANEQARQFIRNMGNQ............................................................P AMFPGN............STMNQLDLIIEVTGRPSAEDIEAIKSPFAGTMLESLPP............................................................SN PMFPGS............SEIDQLFKICTIMGSPTSATWIDGIKLANSMGFTFPNVQP..........................................................PS HLFKPKSG......KGFEKSDDHLALMIELLGKPPRFIFAGGDESRVYFTHKGDLRKIPDLSD................................................QWPLFSV KLFNNLNLDNNNNN(52)QLYSVLNNISTYKESAPKNGNLYFKENHNIIIKSKVERDFNGANLPT..................................................... PLFHGH............NNKSVIESIVKIVGRPFQKDIDRMIANGNMTSDAIQLLQYAASL.................................................PVPFEDS YPFFIS...........PDDMTSLAEIVSIIG..TKKIVDIAHLLEKKISISHSIPPTPW...................................................RDLSRRL PPYFDL..................NPLGAMYRIC.................................................................................... PPYYDL..................GQMPALFRIV.................................................................................... PPYWDL..................GTMPAMFAMV.................................................................................... PPYFGL..................APAAALYKIV.................................................................................... PPYYTL..................QPMAAMFRIV.................................................................................... .............................LFEKD.................................................................................... LEETEI..................QIDGASFNNNNNKP................................................................................ ...DPK..........................IT.................................................................................... ..CDCT.......................KDENI.................................................................................... LKLLDI................................................................................................................ NLCHSE..........................RD.................................................................................... .............................NPKKI.................................................................................... .............................DLSQK.................................................................................... EIKPIK..........................LT.................................................................................... ..........................LNQLCLQR.................................................................................... FPYGSNLPHQQQQP(83)SVPEGMGFWVLLDCIV.................................................................................... PPWSNI...............TELAAVMYHIA.S.................................................................................... APFAEY..................PPMKVLLLTLQN................................................................................PP PPGYDL..............PPSKVFMNLLFGNSPS.................................................................................. NKLR.K..................NPIKTMFMVGSEG................................................................................. PPMMES...................AVKAMFTVATD.................................................................................. PPHR.K..................SSLTAMFTTATE.................................................................................. LPYHDS...................RLKAMVFVATNNL................................................................................ VPHH.K..................SKIKAMFLAGTVGVK............................................................................... PPHRDS...................RMKAMFYNAIN.................................................................................. PPYLEF..................PPLRALFLLTTQ.................................................................................. PPYMSF..................PPLRALFLITTK.................................................................................. PPYMDF..................PPLRALFLITTK.................................................................................. PPYAKY..................PPVRALFLLTLE.................................................................................. PPNRGL..................RSMNQLVEIPNM.................................................................................. PPHIDL..................PPMRAMKMVPNW.................................................................................. PPLYTM..................PPTRAMLMIPNK.................................................................................. PPLSEV..................NPMRAMYMIGRR.................................................................................. PPLFNV..................HPMRVIFMIPNPSR................................................................................ PPYHDL..................HPMRVLFMIPTS.................................................................................. PPRADL..................HPMRALFLIPKD.................................................................................. PPLFNL..................NPVKVIFVIPFR.................................................................................. PPRFDV..................PPSRVIFTIPHQ.................................................................................. PPNSNV..................HPMRVIFMIPRE.................................................................................. PPLSEI..................HPMKVLFQIPYR.................................................................................. VPYGKD..................SSLKALFYTAIH.................................................................................. PPFSHL..................GPMEALIEIINPSTTI............................................................................LP PPYHQF..................QHLQSIEMIINGTC..............................................................................PP PPLQYQL................QQQYDLIKEIEQ................................................................................... ESYSKK...............ENNQPNLQKLP...................................................................................... DPWGGK..............RNHQSHSPPIPT...................................................................................... ...YII..............TTPIIILPSIPS...................................................................................... TDFKEDE..........EGFEELKRTFAGVLT...................................................................................... ....RD...........IKLSDLKSNTVNGYT.................................................................................HYLRP PLFQDI................HVSRITDTIL.................................................................................NGVRP KPYHEV............TLDFDFQIIHKTSK.................................................................................LNLRP HPFSEF...........KDIKNDFQLLL.SSK.................................................................................NGLRP IPYQEY..............NKMFNAFQVALL............................................................................VNSSKRVLRP p. 18


Subdomain X RPFSEY...........KNLQHDFQIIIQTAK.................................................................................KNLRP RPYSEY...............SHIKMDFQIML..............................................................................NSKEGLRP LPYAEY...............PHLKFDYQILI.............................................................................SSAKKDVRP RPFHEH............PISMDIQIIILTSK.................................................................................NKVRP KPFSEF...........KHIQYDFQILVQTSK.................................................................................FNLRP EPQQDM...............KPMKMAHLAAY.................................................................................ESYRP .YASPN............TIYSPKEMASMVSD...............................................................................EKLNYRP DPYNGM...............EPLRLAFLASV.................................................................................EDYRL RPYEDN...........TEISFDFQIVIMSSK.................................................................................QGIRP APPNTI..............YSPKEMASMVSD...............................................................................PKQNYRP QPNQNL...............QPLKMAHLAAY.................................................................................ENYRP DPYFGI...............PPFQVIFAVGR.................................................................................EGMRP DPYFGI...............PPFQVIFAVGR.................................................................................EGMRP DPYQGM...............PTFQIVISVGQ.................................................................................HKLRP IPYAGK...............NTMQVVRSIDR..................................................................................GERL ELFPEF.............DNFFKFVAAICEK..................................................................................QLRP EPYNKL............YSSYPQLVEGVVNK..................................................................................KNRP EPFSHH.............RELEKFREAVCVK..................................................................................HERP APYSHH.............KDYDIFFNAICNE..................................................................................KERP ELFPEY.............SEIDPFYDAICNK..................................................................................KLRP EPYQGI..............PPMNAGILVASK..................................................................................GLRP EPFLEI.............QSIVELARSVCDK..................................................................................KLKP EPYENI...............NSWSIPVLVAK..................................................................................GERP EPYENI...............NSWSIPVMVAK..................................................................................GDRP SAYDEN...............ANINIPNMVMK..................................................................................GERP TPYKNL...............TRIEQALFVQS..................................................................................GGRP IPFSDL..............DGSQASAQVAYA..................................................................................GLRP IPFEGL..............DGTASAAKAAFE..................................................................................NYRP ILVGDT........................RK................................................................................FGQEKP IPYYSE...............PHWRIRELVLK..................................................................................NERP VPFREI...............PKREIPRFVRL..................................................................................GTRP TPENLS.....................NLILE..................................................................................GERP IPFHEI...............CYNDIPNRVQD..................................................................................GFRP VPFSEI.............D.EKWEIPSKVIS..................................................................................GWRP APYMRD...............ASFGLAEDIVR....................................................................................NQ VLERGP...............QSAFEIDQDSA....................................................................................RQ RVVKTQ..........LKRTPMNAFDMNLEKA....................................................................................EH ERFPQH.................RFQFDAPAF....................................................................................LK SLKYGL.....................DVDVL....................................................................................LP NLTPRI..............RNEDLGVDQKFF....................................................................................LS SKLDER................LPQNNFDIDY.................................................................................EELQN .RKPGV...........DLWVRSPETCFDINP.................................................................................EELKQ LKRPGKD.......YWVRSQNNGFDINIEELN...................................................................................VNI VPFHDY...............EQIAASFKIAN..................................................................................AERP HPFDEF...........QFGQWMSKLEDEIIR..................................................................................GLRP DYFGEI..............GFMTLIEEKVIN..................................................................................GERP IPFDEY..............SFGKMQFINLIR................................................................................EENLRP GPFDEY..............SYGKIKFINMIR................................................................................EEGLRP LPFDEY.........PVAHSSFMYQLEDEI.T.................................................................................NGLRP HPYREF............NYS.MVSLQEDAIK.................................................................................NGLRP LPFEEY..........VDQLKWNSIIEDKIMK..................................................................................GLRP LPFDEF............DFKFMSTLEDNILS..................................................................................GLRP RFFSNI...............TFMSEVEGLIT.................................................................................EGVRP IAFQDH..................DRFSNIVI.................................................................................SGQRP CPFDEF............TSFGKMEFIRKIRE.................................................................................EDLRP LPFRKF...............NDISVAAKVAY.................................................................................ENLRP IPYKDF...............AQIQWISMVLE.................................................................................DSFRP LPYSHI...............AFNCEVEDQVL.................................................................................KGLRP IPFDGM................DPYEVKELLK.................................................................................SGKRL LPYESL................SREQVKQIKT................................................................................DMERES RPYQEY.............DQLGYLELARVRE.................................................................................EGLPP QPSGNI....................SATSLG....................................................................................HP LPYSGL................DSVQLALAVT................................................................................TKSLRP FISTHP...............NSEQLFQTILS....NYELTS............................................................................ IPLFQNE.................VDFLIWIHKDYRFSFPVGTP.......................................................................... p. 19


Subdomain X IALFQNE.................VDFSIWIHKDYRFSFPIGTP.......................................................................... HPYHEYQI............ADEPENLNIIQNTGLIPTIPPNLP.......................................................................... NPFYEF...........KISKMEYFKTVVALENFLVPIVPTFLP.......................................................................... LPLTKRS..............FGQELIEGKFDRKAFKQEFDDSD.......................................................................... LLSHNR............IYLGEDMLNDRFDSMQFLSTFPEKY........................................................................... TGFVYN...............RIYLKLFEIMTNPFETR................................................................................ .........................RVQQNQY...................................................................................... .LVHSP..............MNSIFESLFQLCTLENFKIR.............................................................................. ..FNSS................................................................................................................ ...........................FNITS...................................................................................... ..FNCNP............................................................................................................... SPSSSS...............TTSTSTSQVLIKSDSDSSSSASSSSSSSSSSSSSSSSSLP....................................................KSKNK LPYRYSGDPF........IDEDPNRNLPSLIDEIAGFSNNRLIFPQIPQRS................................................................... HPFGHRY.................NREKNVLKGKFDIDQIKHL........................................................................... HPFGNN................KLLRVANIVYDKPDLEPLKFN........................................................................... HPFGND................KLFRIVNIISNKMNLTPLNSN........................................................................... HPFG.D................KFYRIVNILTDKPILEPLKHN........................................................................... HPFG.D................KFFRMANILTDKPILEPLKHN........................................................................... HPFG.D................KFSRLRYITKSKYNLSQLSNLN.......................................................................... HPFGND................KLFRIYNIMLNKVNLELLGHN........................................................................... SPFEVC...........DNEPNGSVALKVLSG.....................................................................................L DPFDGG...................SLQIINN...................................................................................... TPFEDS..................GSLGILNS...................................................................................... PPFEAT...............NQAQLTSKIQV...................................................................................... HAFNAA...............NLPALVLKILK...................................................................................... HAFDAK...............EMPSLIFQILQ...................................................................................... LPFDGR.................KETVMRNIQTESTIFKPVNHPN......................................................................... ..FQTQ...............MERSNILRDLRDNLKFPPGFESTK......................................................................... ..FQTQ...............MERSNILRDLRDNLKFPPGFESTK......................................................................... .VFSTG...............HERVIVLRNLREKFEFPSDFERNH......................................................................... .GFETQ...............FERTTHIKNLKNGIL.PSWFTSKH......................................................................... .PISTR...............MEKARVLTDLRNGVL.PKSFLQKY......................................................................... TTMERS............TTLSKLKKSLSVLKTN....PNLKQKY......................................................................... PPFETS................DVKHTYQRIKQNQYSFPDEPIIS......................................................................... FPIFDF...............SQLLSYRKGEYSPEPIIRQRIQD.......................................................................... CIWQDN...............NPSIVTNRILHLSGYSTTQSFNSISKSFEQCELKKTIINEKQHEEYEEYDDDEDISEEEKEKRIKDIKLNNRDNMNNFINSLKREEKENSDSNSGSS PPFK.....................SFSNIISKYQAIINPHHKIEFPVHPN................................................................... PLPKSGM........EWDSIRNGILSFEKEDS...IYDDNKNDFS......................................................................... PLWEQL...............RSDKAIDFLEPGK.........YS......................................................................... NLPQKGQ..................WWRNLREGKIPFPENDDSIS......................................................................... MTKAED.................IKNLDQIPKQLHQAYQKS............................................................................. LPKLGVISYYNT.............MIEQVRRQSTMNTQRSDSA.......................................................................... VICF..................GHCLFEMIIGIPLGDHSNINSFIPLFP..................................................................... ..........................YEMENPHSVDISIPAHCY.......................................................................... ..SLNN....................IPDDLP...................................................................................... FLFYDDD........WVKFFIRVTQPGQELITPERKSKVANI............................................................................ FPFGDL............KYLRVASAVSNYLRPILHPVIP.............................................................................. LPFQSS...................DLSELIHSHLAKKPPLVIDLNQNVP.................................................................... YQYKHP.................TPLHRDFLTTDFQYIP............................................................................... HPGTTLFEQN........VLFLLKFHGIEIVPTGGPNNNYTTLKVAFSNDIRNFT.............................................................SN DTINHDKKEKIKNV(66)NLNSNQKILIDLLNILIEDEEILIPI.......................................................................... YSCFDSKFDTSN....YYDDDKFNNKSNTKIKKPDLPDYIKKDEKLW....................................................................... VIFPNL...............NQTTVLAALVNLAKMIDNGDFQKGLDSIPNE.IR............................................................... ....E....................ELKLSLSQQ.................................................................................... YPFYSN...............DATKLIESIIYDNYLDPIIRLPSDNNDLIQQ.................................................................. LPFPTY..................PKIVNFITSSSQNVEIPP............................................................................ ...................................................................................................................... ...................................................................................................................... AVKRTI...........KSIPNSEIGLFRTMWEFFNTECFPQYSTL........................................................................ TVKRNI...........LSIPNSEFGLFRTMWEILKTEFYPQYSTL........................................................................ LPWQGL............KAYTKRDKYEKICDKKAQTKIDTLCQ.......................................................................... LPWRKL............KDKDQIGEMKQKYNTPD.....LVKDLP........................................................................

p. 20


Subdomain XI ..EKLSFPHFISPDARSLLEQLLERDPEKRLA......DPNLIKRHPFF ..SPLKFPPQISKNAASLVSLLLNRDPSKRLGSG..ESDVEEIKAHPFF ..NEINFPSYFSEVAIDLIQKLLQVDPLKRLGA....NGADEVKRHPFF ..REMEWPEEISSEAKDLILKLLNPDPYKRLGA....NGAYEVKTHPFF ..KKLYFPKKLYPVAIDLIEKLLDPNPSVRLGA....NGVDEVKCHPFF ..RNISWPEDMSPEARDLIDKLLALDPRQRLGF....NGAEEIKSHPFF ..RN.TECIEIQKDAKDLIIKLLDPNPSTRIG.......SKDIKNHPYF ...QIPTDMGLSKEVIDLIKRLVCEKDRYK.S.......ADEIKLHPFF IMEEAKAEVNLSPEAQDLIERFLT.DPMTRIGF....NGVEEIQSHPFF ..DWPLFTQELSVEAADLLKNMLM.EQPHRLGG....KGKQDFKNHPFF ..DWDLYSDYISEYAVDLLQKLIC.EPDKRIG.......IDEMKVHPYF ..TMLQRPDGVSDELWDLISGLIN.DGSTRLGSG..EKGVENIKNHIFF .NTAVQKNQPMSKQAESLIRECIAPE.RKRPD.......ASTIKKHPFF ..RELVYPINMNPVIKDLVEKLLVIKPTDRLGSSSTPGGFDNLKAHPFF ..REFSYPDNFDKCCMNLIDQLLDLDPYKRPT.......ISEIKNHEFF ..GRITFPLGFDVDAKDLIKRLLTADRTRRLGAL..KDGALDVKNHRWF .EARIQVPPEVDQVARDLIEKLVVTDVEKRLGSL..EGGIEDIKNHPFF .FQLIFQNSYLSDEIKDFIFQLLSVDPSKRLGT....FDSCSIRNHKWF ..GELKIPTYISPEAKSLLEGLLTREVDKRLGT....KGGGEVKQHPWF ..EKAKFPKFVSSSARSLINGLLTKDPTKRLGA....NGAIEIKRHPFF ..GNLRMPMFLSSDAQDLLEKLLVPDPNKRLGST...QGFEEISSHPFF QENDVYYPSSISPEAKDLISRLLVSDPHQRIT.......LKDVINHPWI YEFPEEYWGGISKEAKDFIGKLLVVDVSKRLN.......ATNALNHPWL WEFPSKTQHKYSDQVKDLIKLLLENDPNKRLT.......VKQSLAHKWI VDYGWPEGLEVSNEAKDLVSHLIEKNPEKRFT.......FEQCLIHPWV LEFPSPEWDNISDSAKSLIKGLLNNDPSKRFT.......IDQTLKHPWI YDFPEPEWNGITDLAKDFISQLLIINPEERWT.......ASQCIKHPWL NFDSSVGWDNVSESAKDLIRKMLNPDPEKRLT.......AQQVLLHEWI YDFPEPEWTHVSEHAKAFIRNLIVKDPDQRHT.......AKQCLDDLWL YDFPNDYWGNVSKEAKHFINCLLTVEPTKRYS.......AKQALEHPWI FSIP.DF...VSPSCADLIKKMLVVDPVKRIT.......IHEIRNHPWF FSMP.PY...IHKDAQDLLTKMLTVDPSKRIS.......IKEIKEHPWF IEFP.ND...LDKDLVNLIKGILQVDHIQRFS.......LGQIKNHPWC YTIP.SY...LTHECKSLISRMLVVDPDKRAT.......MEEIINHPWL FKYP.SHV.ILSDDVKDLINRMIVAEPVERAT.......LDEIKTHVWV YEDP.TH...LSAEAVHILRRMIVPNPKDRAT.......IQELKNHPWT PSIP........LDLQDLIKKMLTVDREHRLN.......IMNVLNHPWL NNLPLPANH.SDQRLISLLSSIFQRNPKLRPT.......AHQIAVHPYF YRVEKLEKSLISSSAADLVKGLLTVDPDKRLT.......VEQALNHPWI LGFTSKKWAKISNYAKDLVRRLLVIDPEHRIT.......IKEALNHPWF YNFSLPVWDVVTENAKDLIKKLLNVDPTKRIS.......TKGALSHDWF FSFPSPYWDEISDEAKSLIKNLIKVDVEKRFT.......IDQALNHPWF FEFDPEDWSSVSEEAKDLIKRLLCVDPHKRYT.......CNNIIQHPWF VNHEPTYPREISNDLMDLFKRLLDKNPLTRIQ.......IAEIKSHKWT QNKKIKLPSHISSDCQNLIYSLLQIDVEKRIS.......WEDFFNHKWL EIPKELNKY...PDLVSLFRQLLCKNPDKRIG.......WPDLLYHPFV GQPYNKIFPRCEPLALDLIAKMLQYEPSKRIS.......AKEALLHPYF AHQLSSIVHGLDEKGLNLLSKMLQYDPNQRIT.......AAAALKHPYF ATPFKQLFTAASDEAIDLISKMLLFNPSNRIS.......AADALNHPYF NSLAKCVGIDENSQAYDLLSKMILYDPSKRIT.......ASEALDHPYF DFYQHENPSFFTKEAFDLLDKLLCMDPKKRIT.......ASEALDHQYF YNNLRELVPTISDTAFDLLNQLLTYDPTKRIT.......ASDAIKHPFF YNNLKSKFPHITDNAFDLLNKLLELNPEARIS.......ASDALKHPYF PSRLRTVFKNFSNDFIELLEGLLTLNPKKRLT.......AEQALQSPFF SLKDISKFKSFSNSTLDIILRMLTLCPKNRIS.......TKEALNHPWF KLIDKFPHLVLLPSVLDLASKMLTLDPKKRIN.......SLEALEHPWF RFITKENQHLAVPEAIDFLEKLLRYDPAERLT.......TREAMEHPYF RFIPYENDDIAQPDAIDFLDKLLRYDPTERLT.......AKEAMKHPYF LKQLKEYFHPCHDSFFDLASRLLEYQPSKRIS.......ASDALSHPFL QPTFNNTFIGCNQIQIDLLKNMLCWDPRDRYS.......VNEILESPYF HGGIKKRIPNATEEEIEILEGMLCWNPKKRWP.......IERIIQHPYF SVGIKRRFKGASKDQIELLQGMLCWDPRKRMT.......IDQLLAHKYF EPGHALVDY...LKFLDLIEKMLIYDPQKRIT.......PLEALQHSFF TKSFKDSIRSGDEDFDNFILDCLKWEPSQRIT.......AEQGLKHDWI p. 21


Subdomain XI QDIEKEKQHR..IVFTDFINGLLQLDPNERWS.......PMQAKEHPFI NVSIPDQDMKKLIQLKDLIEKCTILDPEKRIT.......PFEALNHEFL PWPRVFKAKDVPAESIDLISKILLYDPSSRLK.......PVEICAHPFF PKFFESLHNVEDKTVVDLLSKIFIFDPVKRAS.......IDEIIAHPFL KVNFANMFPKANPDAIDLLERMLYFDPSKRLT.......VEEALAHPYF PRSLSDMYPSASVDALDLLKKLLQFNPDKRIT.......AEEALAHPFV INPLSTLLPNANQDAIELITDLLQYDPLKRPT.......PLQALQHRYF LTEKYKFSIQEAKDFEAFLLPMLNYLPEKRAT.......AKDCLNHTWL .............DAYNLLCALLSFNPTTRIK.......ANQAAFHKFF IDNLRSHCSLASDSALDLLTQMLQFVPHKRIS.......IEQALSHPFI RSESSCDKQDVPVELYDLLERCLDPNPLTRIT.......ASEALLHPFL QDDRPPLPDDISSELANFLERCFCKSTEERAT.......AKELLSHPWI QDDCPPLPEGISPPLKDWLMQCFQKDPNLRIS.......AQKLLKHKWI NNPHPPIPNNISADLKHFLLACFVRDINKRPT.......ASQLLEHPWI QEDHPPIPPGISAALKDFLLNCFKKDENIRSS.......AKQLLHHPWV SDQHPPFPTDISKEFLDYFQQSFKKDPTQRPT.......AQELLQHPIF IHGKPKIPDHLSASCKNFIQRCLTIDPNHRDD.......IINLISHNFI NIWIPKIPPHASKFLQNFIQKCFFEEEVLRFD.......SITLIDHPFL TNFEPTIPYHLSNNCKNFIQKCLIQDPYHRWD.......TNLLLTHKFI DFLFSKIPNHLVEKFKKVISQLLSKNINNQIL.......TDIISNKITT .NGIPLIPDHLSNLFKNTIQHCLQINPNARFN.......ANELYNYVIK DKGIPSIPTHLSNSFKNIIQNCLKFDTNARHS.......VESLIITLSN FDGIPIIPNHVSEIMVDFIKRCLIIDPNKRSH.......MEELLTHRLI LNGIPIIPDHLSDTLKDFLNHCLVIDPKKRSY.......MEELLSHKLI HIYEYVEKSQISPLFLNFIKKCI....GRYLD.......IDVLEIHPFL PNNIPVFPVN.S.LFTEILNLCFQTEPSKRIK.......SHQLIKHPFF KEEVPILPSTFSKEFRSFISECLQKEPTERPT.......ASNLLNHEFV SNSIPNIPSHMSQEAFDFLNLCFKRDPKERPD.......ANQLLKHPFI PSLEGDGESKWSHSFKDLVEKCLQKDPSKRPL.......PSKLLEHRFF .LQEEEDKGVCSHLYKDLVDKCLQKEPSKRPN.......ASKLLEHKVF IKDPFEDPHKWSDEFHDIINKCLQMDPHKRPS.......AQELLKHPFI GATGFDDPALWSDCFKDFLSLCLKQDPAERAT.......AEELLKHPFI GCAGLDKPERWTEHFTHFLNLCLEMDPSKRST.......AEQLLKHPWI NLPLLLSTTTSSLEFRDFLTNCLQFDPSKRLT.......SSQLLQHPFL FSKEKKYSCHWSPELFDFLNVCLQMDPTKRPT.......PTQLLQHPFI GI..DFPKIRCSIDLKDMLWQCFESNPEKRST.......VDKLMRHPFF GLPPIRDAHKWSKEFNDFLALCLEKDTEKRAS.......SSSLLHHPFL GIPDLKDQNKWSDDFKDFVKKCLDKDVENRPE.......AKVLLNHPFL GIPPLKETTKWSKTFQDFFSKCLDINVANRPD.......ATDLLKHPFM GVPDFKEPNKWSSDFIEFVNLCLNLDDKRRPD.......AHYLLRHPFL PPPKLSNPKDWSPCFNNFLATCLVKDPVQRPS.......VIDLLSHDFI PPPTFAEPKKWSPLLNDFLARCLVKDPEKRAS.......PIDLLCHPFL PPPTLSKPHHFSKELNDFIGQCCQKDPEKRPS.......AIELLTHPFL PPPTFKDPKKWSPEFVSFVDKCLTKDINERWS.......PSQLLDHPFI PPPKLTEPEKWSPEFNDFLAKCLTRKPELRPS.......AEELLKHPFI TSPTLKEPHKWSPEFSDFIALCLAKEQSQRPS.......AKDLLKHSFF PPPTLE..GNFSKGFKEFCALCLNKDPNQRPT.......AKDLLKHKFI QAPTLEVPGNWSPEFNDFISVCLNKEADKRPS.......AVDLLNHPFI PPPSLKIPSDWSPEFNDFVKQCLSMNPALRPS.......AQQLLSHPFI ESPALTDKSIWSDKFQDFISKCLTKDPAERPT.......AKELLNHEFI DPPKLKNQENYSKDFINFIQSCLQKDPNQRKT.......ATELLKHPFV .QYKLPNPKKYTKEFVDFLYLCLNPDPFKRPT.......PEMLLHHTFL NCLDENEQSLFSLELNQFLELCFKKEPSDRAS.......VHDLLRHPWL LPTDLIQPKLL.QPLIELLVTCIDLNPNHRPN.......ASQLVQKLTK ...KTHPSSPISNNAKDFLSLCFTINGNGSTNDS...LEAGILLKHPFL ........DNLTISCRLALGDIIGLEQNFKPD.......SKDLQKLSWF .........YLTLECKEVLNETLKYNQNFRAD.......SKQLLEAQWF .........GMSLECQILFNETTKIDSCFRPT.......SKQLLNFSWF ......SRDKVSFDYRSLFTEINKDEPCFRPS.......SKELLKSFWF PLP.NCP.....FTIEKLIKLCLSTDPSVRPT.......FTTILKILRQ EIPDNVP.....SVFSRLIKACWSADSSARPS.......FLTISKILSQ TISNNMP.....NEISKILQQGWFSDSVLRPS.......LDTIIKELLI SLPNICP.....EPLEKLYKQCVDQSPLNRPS.......CEEVIISLNQ TIPIGVP.....QVLKDLIYCLWDHDVSSRPT.......ATEAMTALAV p. 22


Subdomain XI TIPNACP.....ESLVSLIQDCWDPNLENRPT.......CTDILSRLVT TLPQNTP.....PGLEALYKQCVNQEQTLRPS.......CEEIIETLNR TTPENAP.....ESLKNLIARTLVKDSTLRPT.......TLEFYEELLK KISENCP.....EQLKTLITRCWDENPDKRPN.......CDEILEILLT TIPQNCP.....EAFSNLISNCWESSPDNRPS.......CPEILDSLLD PIPLTTS.....SKWKEILTQCWDSNPDSRPT.......FKQIIVHLKE QIPFNVP.....LKFKELITQCWDRNPLNRPK......DFSEIIDKLKD PL.NGFP.....PYWVELISKCWNITPSLRPS.......FKEILQILNQ TMPPNVP.....PKLSYLIQKCWNQDPNERPS.......CQQILLAITS QIPFNVP.....LKFKELITQCWDRNPLNRPK......DFSIIIEKLKE PMPQPMDPMW..ENLGKLIEMCWKKSPEERPS.......FSFILDFLEA PVPQNGP.....PKYIQLLIDCLNENPSHRPT.......MEQCLERLES PTPKYGP.....PKYIQLLKDCLNENPSQRPT.......MEQCLEILES IVPPQVS.....APFTRLITECWSEDPQQRPS.......FQEIVKRLEA PMPAWCP.....PKYAALMNRCWETDPTHRPS.......FPEILPIMEG SIPDDCP.....KSLKELIQKCWDPNPEVRPS.......FEGIVSELEE IIPDYFP.....TRLKDLLARCWDHYPSRRPS.......FAEISKQRIL PIPNDCL.....DSLRRLIEKCWDKEPISRPS.......FKEIISALDH PIPADTL.....PSLRHLIQTCWDHNPQNRPS.......FSEILFRLNE PIPDSFP.....KSLKTLIQKCWDHDPNKRPS.......FNEVTQRMNE ELPDNCD.....PNWKKLVVWCWSEDPNKRPS.......FEEITNYLTK KISSSVP.....NFISSLIKDCLHNSPKKRPT.......MNQIIQKLCN TIPADCP.....SEYSKLIKACWTDKPKKRPS.......FKEICDTLKK TIPADCP.....SEYSKLIKACWTDKPKKRPS.......FKEICDTLKK ELPKDMQ.....TSISNIIKKCWQQKPSNRPS.......FIKIVAYLES TIPPTVP.....TTIANLIESCWVQTPHLRPT.......FTEILKVFYS PIPEYCD.....PELKLLLTQCWEADPNDRPP.......FTYIVNKLKE AIPPDCP.....VSLRKLITKCWASDPSQRPS.......FTEILTELET SIGLDKI.D...PNIKNFIHKCW..NPIDGFT.......FNEILKTLKD SLDQEIFKD...TDISDIVTRCWSKNPSQRPT.......FDYLSKYLKH RLDQDVFAD...NDISLILLACWNPNPRGRPT.......FDTLIDLLEK TLDLEKL.D...ADIRNIIERCWNQN..KRST.......FSEISISLKE TADLDTI.D...DDIRKIIECCWIKEKSKRPS.......FSEISLHLEI TKGLNSL.D...RDIKNLINICWA..PHSLPS.......FDEIVFSLVK LIPTDCP.....ESLIDLTFNCCSVDPNNRPS.......FKEISQTLKQ LIPDDIP.....VLYSDLALDCIKYQPEERPN.......FSHIIHVLKQ LAPESCP.....RAFMDLAKWCCSYNPKDRPT.......FKIVVEGLKV KVPKECP.....PDFSKLCVDCTKYNPKERPS.......FIKVLDTIQN LVPKDCP.....PPFLKLVLDCTEYDPDNRPT.......FKEITERLKS KVPADCP.....KELLRLVSECCKVAPSGRPS.......ASNILGLLEY KIPSECP.....REFLELSMKCCNYDPNDRPS.......FTDIVQTLDQ KSIPGCP.....SELISVCVECCLYEPLTRPK.......FDEILSQLKV PSPNDCP.....IQFYDLALKCCSYKHTNRPM.......FSTIVTILES PLPQTID.....HRWSNLIQICWDQNPNNRPS.......FDQILTIIQN TIPPTCP.....PEYVELIQSCWTHEPNSRPT.......FTSIVEILGQ KIPEDCP.....EMYSKLIVECWQTDASQRPK.......FSEIEDRLIK TLPFDCD.....PRLSNLIQLCWSTNPKKRPS.......FTFIIKELLE TIPEDCP.....PRLRNVIELCWSGDPKKRPH.......FSYIVKELSE TIPQNSVCGH..PDFITLITDCWQNDPLKRPT.......FIDIHSRLLI TISPSYTQTVTGHEYCGLIQDCWDSDIDRRPT.......FNKIVKRIKQ TIPNECP.....PDMKQLITDCWSGDPKKRPS.......FNSILERLST SINQNCN.....RMYSSLITKCWNADPNLRPS.......FNSILKTLNE SLPSHNL.....PEYDSLLNICWAQDPTCRPS.......FIEITKKLEE SIPLDCL.....PSFADLIKDCWSGEPLNRPS.......PSKIISQLYT TIPSDCP.....PTISNLIELCWSGDPKKRPH.......FSYIVKELTN KIPTSCP.....LIIRKLINRCWAPLPSDRPT.......FNDILKLFDH PIPDSCL.....PEFRDLITMCWTSNPDDRPS.......FQQIITYLEN PIPMHCN.....KNYTDLMEQCWDDDPENRPY.......FDTIIHSISK EIPENCN.....EVLKNIIQDCWNQQSEDRPT.......FLSIYHRLEN HLPLDHLP....KGIQDLIRLCWKHDPSIRPS.......FIEIRSRLSE MIPPEIE.....GDLRKIIEACFHRDHTKRPN.......FENIEQFLDA ELPSNCP.....QSFSDLIKECCNRNPDQRPN.......FSQILLKLKL PIPNAWP.....YQLSHLIQACWHQDPLKRPS.......FTEILNLLNE ............SNSKIVIQKLNQVRLRGRKK.......TCFG...... ............QSFVKLITRMCLPFRDRRPT.......VRQVLDNVKA p. 23


Subdomain XI ............QSLVKLITSMCLPCRDRRPT.......VHQILDEVGI ............SRLKRLLFLMMSKMPERRPS.......IKECIEEIQK ............DSFKEFLFSTMNRIYTCRPN.......SEECVERLIT ............EPIADLILDMLNLDQNLRPT.......IDLILQNKLF ............EKLAPLVLSMISKNPTFRPS.......IESIIETLQK ............PNVNQLIEFMCRHHENLKYT.........LLVSDFQH ...........NKINKILFEMMCSNESTERPT.......VDQLIEFMVC ............PSIDQLIEFVCRQYDQSRYT.......ISLSSYTHPN ...........SSKLKELVEKMGFFNYDDRIS.......LKELIECLNK ............TYLNDFIDNM.........T.......QPHVCKSFKK ............PSLVQIVKKMIKHKAF..............LLKQPTL SNRSKDNQSKLDPE.KRLLTK.LKKSMKDLP........PYKLLDHPFF ............RDLKDMITILLRAKPHERPT.......ISQILSTHFI ............PDIHQLVHSMIQFEPEKRPD.......IGECINHPFF ............APALDLVRLMISQDEKKRPT.......IDTILNHPLF ............QLACTLIKSMISKDESIRPT.......IQNVLNHPLF ............LVACDLISQMISKNESDRPT.......IEKILLHPFF ............LVACDLISQMISKNESDRPT.......TENILLHPFF ............LVATHLIELMISYDESKRPT.......LSSVLKHPLF ............LLACDLIKSMISNDESKRPT.......IENVLNHPLF PKPFPPSQTNYSNQFNQLIIDMVNLDKDERLH.......LNQVIERINQ .NYKIPDNSKYSNNFHKLIQFILVADPTQRPS.......INDLLNYLNE .NYTIPPNHTHSNDLISLIKIMLNPDPINRPN.......IFEITNQLNL .GRYNPIPSQYSEHLSKVISLMINVDPKSRPN.......VNELLGYSFI .GTYPPIPSHYSNDLRNLISSMLQIDPKNRPS.......VNDILELPFI .GQPLPISPNYSQDLQNLVYQLLEKQPTKRPS.......IFDIFQMPYI ............EELSSLLFKLLNKNPESRFS.......TQQILEQVFI ............PDQTQIIRSLLSRDPTQRPS.......TKQLLESGLL ............PDQTQIIRSLLSRDPTQRPS.......TKQLLESGLL ............SRQATLIRMLIDKDPAKRPS.......AQQLLQSELM ............PEESNLILRMIDINPDNRPT.......SDQILSELLP ............PKVSELILLMMKTNPDERPS.......ASDILKSDLF ............PNDTDFIDH.LIQSFATRPF.......SNQISTDYDN ............HYGKSLIISILNPVPEQRPN.......LTQILEHDFF ............PNIQTLILHMIQKDPDQRYT.......PEKYISKWNT NSNIGIGLNGLGKELIEIIEQCLIPNPMDRPD.......SETLLDHPYF ............ENLLKVLKLCLIRNPHERPT.......IPTLLNHDFL ............TEFWQLIKSMIHPDPSVRPS.......AEQLLEHPLI ............DSLYQVILDMMKSNITERIS.......LDQILLNENI ............QDLKDLIILMMNPDHTKRIT.......IQSLLKYDKL ......................FAVKTESRLN.......PQKFLESPYF ............KVCTILLG.....DPMLRGD.......LENFIRSSFF ............DKVFLLLQQIFS...EKTPT.......LEELVKNPWF ............PEVRKVLEAIFKPFYGTPIT.......LEELSKMDFF ............TEQFDFLHSCLATNLSDRLD.......AQTLLHHPFI ............PAILDYLDYVFIRDPFYRPT.......LRDLLTKFIA ............QPLSDLIYSMLNHNEYDRPT.......SFEVFQKLKK ............LILSNIVNKLLQKSPDDRYQ.......SAYGLKKDLE ............IRIKTLIASLLAEQSQRKQS.......FNEVYNDLQD TQFTTITFDSKFNPIISQIINYIQ.YYRNRPN.......SSQVLESLIN ........HSKSYNDERQIEYIFAKRDNDKF...........LLNDKTF ............EPVIQLYKSCTSDDPNKRPS.......SLGVKFHLAN ...KYGLVDPDIELGISFITSLLQLDPKKRLP.......LKETLNHPFL ............TGKLEIINQSIIQK..DSFS.......ELDTLWLPFL ............QHFNDLISKILEKNPQKRIT.......WPKLFIHPFF .....QFYKPENSLLIQLITCCLFKNPAQRIS.......WNEIVNHSFF ................................................. ................................................. ......................FQQAQNINYE.........EL.KNEFI ......................FQQAQDKNYE.........EL.KNEFI .........GFPSEFATFLNYTRFLKFEDKPD.......FLYLRKLLRE ............PQFSQFMKHLKSLNYEDRPN.......YVFLQTLLND

p. 24