CLUSTAL W (1.83) multiple sequence alignment IRR_Hsap MAVPS------------------------------------------------------- INSR_Hsap MATGGR------------------------------------------------------ IGF1R_Hsap MKSGSG------------------------------------------------------ InR_Dmel MFNMPR---------------GVTKSKSKRGKIKMENDMAAAATTTACTLGHICVLCRQE IRR_Mmus MAVPA------------------------------------------------------- INSR_Mmus MGFGRG------------------------------------------------------ IGF1R_Mmus MKSGSG------------------------------------------------------ daf-2_Cele MNIVRCRRRHKILENLEEENLG-----PS------------CSSTTST---------T-- ILGFR_Spur MVGVAW------------------------------------------------------ InsRL_Spur MSD--------------------------------------------------------- * IRR_Hsap ------------------------------------------------------------ INSR_Hsap ------------------------------------------------------------ IGF1R_Hsap ------------------------------------------------------------ InR_Dmel MLLDTCCCRQAVEAVDSPA--------SSEEAYSSSNSSSCQASSEISAEEVWFLSHDDI IRR_Mmus ------------------------------------------------------------ INSR_Mmus ------------------------------------------------------------ IGF1R_Mmus ------------------------------------------------------------ daf-2_Cele ---------AATE-----ALGTTTEDMRLKQQ-----RSS-------------------- ILGFR_Spur ------------------------------------------------------------ InsRL_Spur ------------------------------------------------------------ IRR_Hsap ------------------------------------------------------------ INSR_Hsap ------------------------------------------------------------ IGF1R_Hsap ------------------------------------------------------------ InR_Dmel VLCRRPKFDEVETTGKKRDVKCSGHQCSNECDDGSTKNNRQQRENFNIFSNCHNILRTLQ IRR_Mmus ------------------------------------------------------------ INSR_Mmus ------------------------------------------------------------ IGF1R_Mmus ------------------------------------------------------------ daf-2_Cele ---------S--RATEHDIVD--------------------------------------- ILGFR_Spur ------------------------------------------------------------ InsRL_Spur ------------------------------------------------------------ IRR_Hsap ------------------------------------------------------------ INSR_Hsap ------------------------------------------------------------ IGF1R_Hsap ------------------------------------------------------------ InR_Dmel SLLLLMFNCGIFNKRRRRQHQQQHHHHYQHHHQQHHQQHHQRQQANVSYTKFLLLLQTLA IRR_Mmus ------------------------------------------------------------ INSR_Mmus ------------------------------------------------------------ IGF1R_Mmus ------------------------------------------------------------ daf-2_Cele ----------------------------GNHHDDEHITMRR--------LRL-------- ILGFR_Spur ------------------------------------------------------------ InsRL_Spur ------------------------------------------------------------ IRR_Hsap -----------------------------------------------------------L INSR_Hsap -------------------------------------------------------RGAAA IGF1R_Hsap -------------------------------------------------------GGSPT InR_Dmel AATTRLSLSPKNYKQQQQLQHNQQLPRATPQQ----KQQEKDRH-KCFHYKHNYSYSPGI IRR_Mmus -----------------------------------------------------------L INSR_Mmus -------------------------------------------------------CETTA IGF1R_Mmus -------------------------------------------------------GGSPT daf-2_Cele ------------------VKNSRTRRRTTPDSSMDCYEENPPSQKTSINYSWISKKSSMT ILGFR_Spur ------------------------------------------------------------ InsRL_Spur ------------------------------------------------------------ IRR_Hsap WPWGACLPVIFLSLGFGL------------------------------------------ INSR_Hsap APLLVAVAALLLGAAGHL------------------------------------------ IGF1R_Hsap SLW----GLLFLSAALSLW----------------------------------------- InR_Dmel SLL----LFILLANTLAIQAVVLPAHQQHLLHNDIADGLDKTALSVSGTQSRWTRSESNP IRR_Mmus WPWGVHLLMSLLSLGSGL------------------------------------------ INSR_Mmus VPLLVAVAALLVGTAGHL------------------------------------------ IGF1R_Mmus SLW----GLVFLSAALSLW----------------------------------------- daf-2_Cele SLM----LLLLFAFVQPCA----------------------------------------- ILGFR_Spur ------------------------------------------------------------ InsRL_Spur ------------------------------------------------------------ IRR_Hsap -----DTVEVC-PSLDIRSEVAEL-----------------RQLENCSVVEGHLQILLMF INSR_Hsap -----YPGEVC-PGMDIRNNLTRL-----------------HELENCSVIEGHLQILLMF IGF1R_Hsap ----PTSGEICGPGIDIRNDYQQL-----------------KRLENCTVIEGYLHILLIS InR_Dmel TMRLSQNVKPC-KSMDIRNMVSHF-----------------NQLENCTVIEGFLLIDLIN IRR_Mmus -----DTLEVC-PSLDIRSEVTEL-----------------RRLENCSVVEGHLQILLMF INSR_Mmus -----YPGEVC-PGMDIRNNLTRL-----------------HELENCSVIEGHLQILLMF IGF1R_Mmus ----PTSGEICGPGIDIRNDYQQL-----------------KRLENCTVIEGFLHILLIS daf-2_Cele ----SIVEKRC-GPIDIRNRPWDIKPQWSKLGDPNEKDLAGQRMVNCTVVEGSLTISFVL ILGFR_Spur ------------IGPNLKSTVQQR-----------------QEKNQPT---------LFF InsRL_Spur ------------------------------------------------------------ IRR_Hsap TATGE----D----------FRGLSFPRLTQVTDYLLLFRVYGLESLRDLFPNLAVIRGT INSR_Hsap KTRPE----D----------FRDLSFPKLIMITDYLLLFRVYGLESLKDLFPNLTVIRGS IGF1R_Hsap K--AE----D----------YRSYRFPKLTVITEYLLLFRVAGLESLGDLFPNLTVIRGW InR_Dmel DASP-----------------LNRSFPKLTEVTDYIIIYRVTGLHSLSKIFPNLSVIRGN IRR_Mmus AATGE----D----------FRGLSFPRLTQVTDYLLLFRVYGLESLRDLFPNLTVIRGT INSR_Mmus KTRPE----D----------FRDLSFPKLIMITDYLLLFRVYGLESLKDLFPNLTVIRGS IGF1R_Mmus K--AE----D----------YRSYRFPKLTVITEYLLLFRVAGLESLGDLFPNLTVIRGW daf-2_Cele KHKTKAQEEMHRSLQPRYSQDEFITFPHLREITGTLLVFETEGLVDLRKIFPNLRVIGGR ILGFR_Spur GWTPD----DLTSS----GAFSRVAFPS-------------------------------- InsRL_Spur --------------------FQAMDFHAMDLL---------------------------- * IRR_Hsap RLFLGYALVIFEMPHLRDVALPALGAVLRGAVRVEKNQELCHLSTIDWGLLQPAPGANHI INSR_Hsap RLFFNYALVIFEMVHLKELGLYNLMNITRGSVRIEKNNELCYLATIDWSRILDSVEDNYI IGF1R_Hsap KLFYNYALVIFEMTNLKDIGLYNLRNITRGAIRIEKNADLCYLSTVDWSLILDAVSNNYI InR_Dmel KLFDGYALVVYSNFDLMDLGLHKLRSITRGGVRIEKNHKLCYDRTIDWLEILAENETQLV IRR_Mmus RLFLGYALIIFEMPHLRDVGLPSLGAVLRGAVRVEKNQELCHLSTIDWGLLQPAPGTNHI INSR_Mmus RLFFNYALVIFEMVHLKELGLYNLMNITRGSVRIEKNNELCYLATIDWSRILDSVEDNYI IGF1R_Mmus KLFYNYALVIFEMTNLKDIGLYNLRNITRGAIRIEKNADLCYLSTIDWSLILDAVSNNYI daf-2_Cele SLIQHYALIIYRNPDL-EIGLDKLSVIRNGGVRIIDNRKLCYTKTIDWKHLITSSINDVV ILGFR_Spur ------------------------------------------------------CQENAA InsRL_Spur ----------------------QLLYRNRPDTRRRKKRDV-------------------- IRR_Hsap VGNKL---GEECA-DVCPGVLGAA---GEPCAKTTF-----SGHTD---------YRCWT INSR_Hsap VLNKDD--NEECG-DICPGTAKG----KTNCPATVI-----NGQFV---------ERCWT IGF1R_Hsap VGNKP---PKECG-DLCPGTMEE----KPMCEKTTI-----NNEYN---------YRCWT InR_Dmel VLTENGK-EKECRLSKCPGEIRI----EEGHDTTAI-----EGELNASCQLHNNRRLCWN IRR_Mmus VGNKL---GEECA-DVCPGVLGAA---GEPCSRTTF-----SGRTD---------YRCWT INSR_Mmus VLNKDD--NEECG-DVCPGTAKG----KTNCPATVI-----NGQFV---------ERCWT IGF1R_Mmus VGNKP---PKECG-DLCPGTLEE----KPMCEKTTI-----NNEYN---------YRCWT daf-2_Cele VDNAAEYAVTETG-LMCPRGACEEDKGESKCHYLEEKNQEQGVERV---------QSCWS ILGFR_Spur EDNPA---SLNCL-HVVPDVDGA------------------------------------- InsRL_Spur -----------------PGSAI-------------------------------------- * IRR_Hsap SSHCQRVC------PCPH-GMACTARGECCHTECLGGCSQPE-DPRACVACRHLYFQGAC INSR_Hsap HSHCQKVC------PTICKSHGCTAEGLCCHSECLGNCSQPD-DPTKCVACRNFYLDGRC IGF1R_Hsap TNRCQKMC------PSTCGKRACTENNECCHPECLGSCSAPD-NDTACVACRHYYYAGVC InR_Dmel SKLCQTKC------PEKCR-NNCIDEHTCCSQDCLGGCVIDKNGNESCISCRNVSFNNIC IRR_Mmus SSHCQKVC------PCPR-GMACTAGGDCCHSECLGGCSQPE-DPRACVACRHLYFQGVC INSR_Mmus HSHCQKVC------PTICKSHGCTAEGLCCHKECLGNCSEPD-DPTKCVACRNFYLDGQC IGF1R_Mmus TNRCQKMC------PSVCGKRACTENNECCHPECLGSCHTPD-DNTTCVACRHYYYKGVC daf-2_Cele NTTCQKSCAYDRLLPTKEIGPGCDANGDRCHDQCVGGCERVN-DATACHACKNVYHKGKC ILGFR_Spur ----------------------------------TGGCDFPW-QNVNKVAWRPLVVGA-- InsRL_Spur ------------------------------------------------------------ IRR_Hsap LWACPPGTYQYESWRCVTAERCA------SLHSVPGRA-----STFGIHQGSCLAQCPSG INSR_Hsap VETCPPPYYHFQDWRCVNFSFCQ------DLHHKCKNSRRQGCHQYVIHNNKCIPECPSG IGF1R_Hsap VPACPPNTYRFEGWRCVDRDFCA------NILSAESSD----SEGFVIHDGECMQECPSG InR_Dmel MDSCPKGYYQFDS-RCVTANECI------TLTKFETNS----VYSGIPYNGQCITHCPTG IRR_Mmus LRACPPGTYQYESWRCVTAELCA------HLREVPGLA-----TTFGIYEGSCLAQCPPG INSR_Mmus VETCPPPYYHFQDWRCVNFSFCQ------DLHFKCRNSRKPGCHQYVIHNNKCIPECPSG IGF1R_Mmus VPACPPGTYRFEGWRCVDRDFCA------NIPNAESSD----SDGFVIHDDECMQECPSG daf-2_Cele IEKCDAHLYLLLQRRCVTREQCL------QLNPVLSNK----TVPIKATAGLCSDKCPDG ILGFR_Spur -------PYIYDLLKDVTFASSKMDGIMYSYYFSRLNMAEFACEWVQRNSGTWEPWIPSG InsRL_Spur ------------------------------------------------------------ IRR_Hsap FTRNSS-SIFCHKCEG-LCPKECKV---GTKTIDSIQAAQDLVGCTHVEGS--LILNLRQ INSR_Hsap YTMNSS-NLLCTPCLG-PCPKVCHL-LEGEKTIDSVTSAQELRGCTVINGS--LIINIRG IGF1R_Hsap FIRNGSQSMYCIPCEG-PCPKVCEE-EKKTKTIDSVTSAQMLQGCTIFKGN--LLINIRR InR_Dmel YQKSEN-KRMCEPCPGGKCDKECS-----SGLIDSLERAREFHGCTIITGTEPLTISIKR IRR_Mmus FTRNGS-SIFCHKCEG-LCPKECKV---GTKTIDSVQATQDLVGCTHVEGN--LILNLRQ INSR_Mmus YTMNSS-NLMCTPCLG-PCPKVCQI-LEGEKTIDSVTSAQELRGCTVINGS--LIINIRG IGF1R_Mmus FIRNSTQSMYCIPCEG-PCPKVCGDEEKKTKTIDSVTSAQMLQGCTILKGN--LLINIRR daf-2_Cele YQINPDDHRECRKCVG-KCEIVCEI----NHVIDTFPKAQAIRLCNIIDGN--LTIEIRG ILGFR_Spur SAG---------------------------------------IKRTILLG--GLFETLID InsRL_Spur ------------------------------------------------------------ IRR_Hsap --GYNLEPQLQHSLG-LVETITGFLKIKHSFALVSLGFFKNLKLIRGDAMVD-GNYTLYV INSR_Hsap --GNNLAAELEANLG-LIEEISGYLKIRRSYALVSLSFFRKLRLIRGETLEI-GNYSFYA IGF1R_Hsap --GNNIASELENFMG-LIEVVTGYVKIRHSHALVSLSFLKNLRLILGEEQLE-GNYSFYV InR_Dmel ESGAHVMDELKYGLA-AVHKIQSSLMVHLTYGLKSLKFFQSLTEISGDPPMDADKYALYV IRR_Mmus --GYNLEPELQRNLG-LVETITGFLKIKHSFALVTLGFFKNLKLIRGDSMVD-GNYTLYV INSR_Mmus --GNNLAAELEANLG-LIEEISGFLKIRRSYALVSLSFFRKLHLIRGETLEI-GNYSFYA IGF1R_Mmus --GNNIASELENFMG-LIEVVTGYVKIRHSHALVSLSFLKNLRLILGEEQLE-GNYSFYV daf-2_Cele KQDSGMASELKDIFA-NIHTITGYLLVRQSSPFISLNMFRNLRRIEAKSLFR-NLYAITV ILGFR_Spur PT--SPNSGIEPGARMAIDAVNADLNILPNYKLTLASMETG---CSPETSL-LSYFKFYE InsRL_Spur ------------------------------------------------------------ IRR_Hsap LDNQNLQQLGSWVAAGLTIPVGKIYFAFNPRLCLEHIYRLEEVTGTRGR-QNKAEINPRT INSR_Hsap LDNQNLRQLWDWSKHNLTITQGKLFFHYNPKLCLSEIHKMEEVSGTKGR-QERNDIALKT IGF1R_Hsap LDNQNLQQLWDWDHRNLTIKAGKMYFAFNPKLCVSEIYRMEEVTGTKGR-QSKGDINTRN InR_Dmel LDNRDLDELWGP-NQTVFIRKGGVFFHFNPKLCVSTINQLLPMLASKPKFFEKSDVGADS IRR_Mmus LDNQNLQQLGSWVTAGLTIPVGKIYFAFNPRLCLEHIYQLEEVTGTRGR-QSKAEINPRT INSR_Mmus LDNQNLRQLWDWSKHNLTITQGKLFFHYNPKLCLSEIHKMEEVSGTKGR-QERNDIALKT IGF1R_Mmus LDNQNLQQLWDWNHRNLTVRSGKMYFAFNPKLCVSEIYRMEEVTGTKGR-QSKGDINTRN daf-2_Cele FENPNLKKLFDS-TTDLTLDRGTVSIANNKMLCFKYIKQLMSKLNI--P-LDPIDQSEGT ILGFR_Spur DRGQSLAGLVG-------------------PMCSSE------------------------ InsRL_Spur ------------------------------------------------------------ IRR_Hsap NGDRAACQTRTLRFVSNVTEADRILLRWE-------RYEP-------LEARDLLSFIVYY INSR_Hsap NGDQASCENELLKFSYIRTSFDKILLRWE-------PYWP-------PDFRDLLGFMLFY IGF1R_Hsap NGERASCESDVLHFTSTTTSKNRIIITWH-------RYRP-------PDYRDLISFTVYY InR_Dmel NGNRGSCGTAVLNVTLQSVGANSAMLNVTTKVEIGEPQKPSNATIVFKDPRAFIGFVFYH IRR_Mmus NGDRAACQTRTLRFVFNLTEEDRILLRWE-------RYEP-------LEARDLLSFIVYY INSR_Mmus NGDQASCENELLKFSFIRTSFDKILLRWE-------PYWP-------PDFRDLLGFMLFY IGF1R_Mmus NGERASCESDVLRFTSTTTWKNRIIITWH-------RYRP-------PDYRDLISFTVYY daf-2_Cele NGEKAICEDMAINVSITAVNADSVFFSWP-------SFNI-----TDIDQRKFLGYELFF ILGFR_Spur ----------AEVVGSVSRFLNTVVVSY----QSDS-----------PSLSNKDQYPYYF InsRL_Spur ------------------------------------------------------------ IRR_Hsap KESPF--QNATEHVGPDACGTQSWNLLDVELPLSR-------TQEPG--VT-----LASL INSR_Hsap KEAPY--QNVTEFDGQDACGSNSWTVVDIDPPLRSNDPK--SQNHPG--WL-----MRGL IGF1R_Hsap KEAPF--KNVTEYDGQDACGSNSWNMVDVDLPPNK-------DVEPG--IL-----LHGL InR_Dmel MIDPY--GNSTKS-SDDPCD-DRWKVS-------S-------PEKSG-VMV-----LSNL IRR_Mmus KESPF--QNATEHVGPDACGTQSWNLLDVELPLSR-------TQEPG--VT-----LAPL INSR_Mmus KEAPY--QNVTEFDGQDACGSNSWTVVDIDPPQRSNDPKSQTPSHPG--WL-----MRGL IGF1R_Mmus KEAPF--KNVTEYDGQDACGSNSWNMVDVDLPPNK-------EGEPG--IL-----LHGL daf-2_Cele KEVPRIDENMTIEEDRSAC-VDSWQSVFKQYYETS-------NGEPTPDIFMDIGPRERI ILGFR_Spur RTFP--DTTEQCYAL---------------------------------------IELFQN InsRL_Spur -------------------------------------------QDAG--TT--------- IRR_Hsap KPWTQYAVFVRAITLTT-----EEDSPHQGAQSPI--VYLRTLPAAPT-VPQDVISTSNS INSR_Hsap KPWTQYAIFVKTLV-TF-----SDERRTYGAKSDI--IYVQTDATNPS-VPLDPISVSNS IGF1R_Hsap KPWTQYAVYVKAVTLTM-----VENDHIRGAKSEI--LYIRTNASVPS-IPLDVLSASNS InR_Dmel IPYTNYSYYVRTMAI---------SSELTNAESDV--KNFRTN---PG-RPSKVVATAIS IRR_Mmus KPWTQYAVFVRAITLTT-----AEDSPHQGAQSPI--VYLRTLPAAPT-VPQDVISTSNS INSR_Mmus KPWTQYAIFVKTLV-TF-----SDERRTYGAKSDI--IYVQTDATNPS-VPLDPISVSNS IGF1R_Mmus KPWTQYAVYVKAVTLTM-----VENDHIRGAKSEI--LYIRTNASVPS-IPLDVLSASNS daf-2_Cele RPNTLYAYYVATQM-VL-------HAGAKNGVSKI--GFVRTSYYTPD-PPTLALAQVDS ILGFR_Spur FGWGRYALLSDSEDITYKVMKNMEEVMIEGGIEMVVDIYMATNEVNQAAVTSYLEEIVSK InsRL_Spur -PTTT--------------------------------SFITPIPTTPT-------SG--- . . IRR_Hsap SSHLLVRWKPPTQRNGNL--------------TYYLVLWQRLAE-DGDLYLNDY------ INSR_Hsap SSQIILKWKPPSDPNGNI--------------THYLVFWERQAE-DSELFELDY------ IGF1R_Hsap SSQLIVKWNPPSLPNGNL--------------SYYIVRWQRQPQ-DGYLYRHNY------ InR_Dmel DSKINVTWSYLDKPYGVL--------------TRYFIKAKLINR-PTRNNNRDY------ IRR_Mmus SSHLLVRWKPPVQRNGNI--------------TYYLVLWQRLAE-DGDLYINDY------ INSR_Mmus SSQIILKWKPPSDPNGNI--------------THYLVYWERQAE-DSELFELDY------ IGF1R_Mmus SSQLIVKWNPPTLPNGNL--------------SYYIVRWQRQPQ-DGYLYRHNY------ daf-2_Cele -DAIHITWEAPLQPNGDL--------------THYTIMWRENEV-SPYEEAEKF------ ILGFR_Spur KAHIIVGYFPENVARLVLCEAHKQGLTGEKGYQWFLPEWYQDAWWDT-----DYHNKNSP InsRL_Spur ------------------------------------------------------------ IRR_Hsap -----CHRGLRLPTSN-N----------------------------DPRFDGEDGDPEA- INSR_Hsap -----CLKGLKLPSRT-W----------------------------SPPFESEDSQKHNQ IGF1R_Hsap -----CSKD-KIPIRK-Y---------------------------ADGTIDIEEVTENPK InR_Dmel -----CTEPLVKAME--ND-----------LPATTPT----------------------- IRR_Mmus -----CHRGLRLPTSS-H----------------------------DTRFDREDPALEA- INSR_Mmus -----CLKGLKLPSRT-W----------------------------SPPFESDDSQKHNQ IGF1R_Mmus -----CSKD-KIPIRK-Y---------------------------ADGTIDVEEVTENPK daf-2_Cele -----CTDA-STPANR-QHTKDPKETIVADKPVDIPSSR-----TVAPTLLTMMGHED-Q ILGFR_Spur SYSIFSTSPSSFNISCTTT-----EMMQAIKGYISL-SRAYIANWD-KPVPGHETVEGWI InsRL_Spur ------------------------------------------------------------ IRR_Hsap ----E-MESDCCPCQHPPPGQV---LPPLEAQEASFQKKFENFLHNAITIPISPWKVTSI INSR_Hsap SEY-EDSAGECCSCP---KTDS---QILKELEESSFRKTFEDYLHNVVFVPRKTS---SG IGF1R_Hsap TEVCGGEKGPCCACP---KTEA---EKQAEKEEAEYRKVFENFLHNSIFVPRP------- InR_Dmel KKISDP-LAGDCKCVEGSKKT--S-SQEYDDRKVQAGMEFENALQNFIFVPNIRK---SK IRR_Mmus ----E-PEQGCCPCQHSPPGQA---LPALEAQEVTFQKKFENFLHHAITIPKAPWKVTSI INSR_Mmus SEY-DDSASECCSCP---KTDS---QILKELEESSFRKTFEDYLHNVVFVPRKTS---SG IGF1R_Mmus TEVCGGDKGPCCACP---KTEA---EKQAEKEEAEYRKVFENFLHNSIFVPRP------- daf-2_Cele QKTCAA-TPGCCSCSAIEESSEQNKKKRPDPMSAIESSAFENKLLDEVLMPRDTMRVRRS ILGFR_Spur NE---------------------------------------------------------- InsRL_Spur ------------------------------------------FNLNGSLYPSSPA--TGV IRR_Hsap NKSPQ--------------------RDSGRHRRAA----GPL------------------ INSR_Hsap TGAED--------------------PRPSRKRRSL----GDV---GN---------VT-- IGF1R_Hsap ----------------------------ERKRRDV----MQV---AN---------TT-- InR_Dmel NGSSDKSDGAEGAALDSNAIPNGGATNPSRRRRDV----ALEPELDD---------VEGS IRR_Mmus NKNPQ--------------------RDSERHRREA----GLL------------------ INSR_Mmus NGAED--------------------SRPSRKRRSL----EEV---GN---------VT-- IGF1R_Mmus ----------------------------ERRRRDV----MQV---AN---------TT-- daf-2_Cele IEDAN--------------------RVSEELEKAENLGKAPK-TLGGKKPLIHISKKKPS ILGFR_Spur -----------------------------------------------YNSLIE------- InsRL_Spur N-AST--------------------TSPSRV----------------------------- IRR_Hsap ------------------------------RLG-GNSSD----FEIQE----------D- INSR_Hsap --------VAVPTVAA--FPNTSST-----SVP-TSPEE----HRPFE----------K- IGF1R_Hsap --------MSSRSRNT-TAADTYNI-----TDP-EELET---EYPFFE----------SR InR_Dmel VLLRHVRSITDDTDAFFEKDDENTY-----KDE-EDLSSNKQFYEVFA----------KE IRR_Mmus ------------------------------RLG-KNNSD----FEIQE----------D- INSR_Mmus --------ATTLTLPD--FPNVSST-----IVP-TSQEE----HRPFE----------K- IGF1R_Mmus --------MSSRSRNT-TVADTYNI-----TDP-EEFET---EYPFFE----------SR daf-2_Cele S--S----STTSTPAP-TIASMYALTRKPTTVPGTRIR----LYEIYEPLPGSWAINVSA ILGFR_Spur ----------------------------------------------KE----------GK InsRL_Spur ----------------------------------------------EE----------RV IRR_Hsap K-VPRERAVLSGLRHFT-EYRIDIHACNH-AAHTV----------GCSAATFV--FARTM INSR_Hsap V-VNKESLVISGLRHFT-GYRIELQACNQ-DTPEE----------RCSVAAYV--SARTM IGF1R_Hsap V-DNKERTVISNLRPFT-LYRIDIHSCNH-EAEKL----------GCSASNFV--FARTM InR_Dmel LPPNQTHFVFEKLRHFT-RYAIFVVACRE-EIPSEKLRDTSFKKSLCSDYDTV--FQTTK IRR_Mmus K-VPRERAILSGLRHFT-EYRIDIHACNH-AAHTV----------GCSAATFV--FARTM INSR_Mmus V-VNKESLVISGLRHFT-GYRIELQACNQ-DSPDE----------RCSVAAYV--SARTM IGF1R_Mmus V-DNKERTVISNLRPFT-LYRIDIHSCNH-EAEKL----------GCSASNFV--FARTM daf-2_Cele L-ALDNSYVIRNLKHYT-LYAISLSACQNMTVPGA----------SCSISHRAGALKRTK ILGFR_Spur MP--STYAAYAYDTVWTYAYALDKLLFNDV-AA--------LDTLSSQQTI--RTYLRHL InsRL_Spur I-GLVESFHVTGLEHFT-EYFITLQACNS-K--------------DCSRAAAM--YGRSL :* * : . .. IRR_Hsap PH----------READGIPGK-VAW--EASS-KNSVLLRWLEPPDPNGLILKYEIKYRRL INSR_Hsap PE----------AKADDIVGP-VTH--EIFE-NNVVHLMWQEPKEPNGLIVLYEVSYRRY IGF1R_Hsap PA----------EGADDIPGP-VTW--EPRP-ENSIFLKWPEPENPNGLILMYEIKYGSQ InR_Dmel RK----------KFADIVMDLKVDLEHANNT-ESPVRVRWTPPVDPNGEIVTYEVAYKLQ IRR_Mmus PH----------READGIPGK-VAW--KAAG-KSSVTLHWLEPPDPNGLILKYEIKYRRL INSR_Mmus PE----------AKADDIVGP-VTH--EIFE-NNVVHLMWQEPKEPNGLIVLYEVSYRRY IGF1R_Mmus PA----------EGADDIPGP-VTW--EPRP-ENSIFLKWPEPENPNGLILMYEIKYGSQ daf-2_Cele HI----------TDIDKVLNETIEW--RFMNNSQQVNVTWDPPTEVNGGIFGYVVKLKSK ILGFR_Spur SN----------TSFSGVTGE-V--KFMDQDRRGPISIHQHHPPTT-TIIGSYIPDMDTK InsRL_Spur PKGWSHLRYDGRESADQIESA-VMI--NHTS-TDRVHLTWAEPSNPNGIIVIHEIRFEMM . : . : : : * * : IRR_Hsap GE---------------------------EATVLCVSRLR-Y-AKFGGVHLALLPPGNYS INSR_Hsap GD---------------------------EELHLCVSRKH-F-ALERGCRLRGLSPGNYS IGF1R_Hsap VE---------------------------D-QRECVSRQE-Y-RKYGGAKLNRLNPGNYT InR_Dmel KPD-------------------------QVEEKKCIPAAD-F-NQTAGY-LIKLNEGLYS IRR_Mmus GE---------------------------EATVLCVSRLR-Y-AKVGGVHLALLPPGNYS INSR_Mmus GD---------------------------EELHLCVSRKH-F-ALERGCRLRGLSPGNYS IGF1R_Mmus VE---------------------------D-QRECVSRQE-Y-RKYGGAKLNRLNPGNYT daf-2_Cele VDG-------------------------SIVMTRCVGAKRGYSTRNQGVLFQNLADGRYF ILGFR_Spur DQG-------------------------S--LS------------------LN-TSGIMW InsRL_Spur DVEVDDVGDERDAYTVVESHSTPKPVTQSTENTECVSAEG-Y-KRVLGAELLGLKVGNYT * IRR_Hsap ARVRATSLAGNGSWTDSVAFYILGPEEEDAGG--------LHVLLTATPVGLTLLIV-LA INSR_Hsap VRIRATSLAGNGSWTEPTYFYVTDYLDVPSNI--------AKIIIG--PLIFVFLFSVVI IGF1R_Hsap ARIQATSLSGNGSWTDPVFFYVQAKTGYENFI---------HLII-ALPVAVLLIVGGLV InR_Dmel FRVRANSIAGYGDFTEVEHIKVEPPPSYAK---------VFFWLL-GIGLAF-LIVSLFG IRR_Mmus AKVRATSLAGNGSWTDGVTFYITDLEEEDTGG--------MRIFLTVTPVGFMLLVT-LA INSR_Mmus VRVRATSLAGNGSWTEPTYFYVTDYLDVPSNI--------AKIIIG--PLIFVFLFSVVI IGF1R_Mmus ARIQATSLSGNGSWTDPVFFYVPAKTTYENFM---------HLII-ALPVAILLIVGGLV daf-2_Cele VSVTATSVHGAGPEAESSDPIVVMTPGF--FT--------VEIILG-MLLVFLILMSIAG ILGFR_Spur ASGSQPTDGANGPTCMVEGLR----QALGSDC-RTAI------ALMNTILLLVILVSTII InsRL_Spur AMVRAVSLAGEGPWTKPVMFSVPDITNNPTYEPDKALPPMMGVTI-AVSIAAVIIIIVFI : . * : : ::. IRR_Hsap ALGFFYGKKRN-R-----T-LYASVNPEYFSASD------MYVPDEWEVPREQISIIREL INSR_Hsap GSIYLFLRKRQPDG-PLGP-LYASSNPEYLSASDV-FPCSVYVPDEWEVSREKITLLREL IGF1R_Hsap IMLYVFHRKRNNSRLGNGV-LYASVNPEYFSAAD------VYVPDEWEVAREKITMSREL InR_Dmel YVCYLH--KRKVPS-NDLH-MNTEVNPFY--ASM------QYIPDDWEVLRENIIQLAPL IRR_Mmus ALGFFYSRKRN-S-----T-LYTSVNPEYFSASH------MYVPDEWEVPREQIAIIREL INSR_Mmus GSIYLFLRKRQPDG-PMGP-LYASSNPEYLSASDVVFPSSVYVPDEWEVPREKITLLREL IGF1R_Mmus IMLYVFHRKRNNSRLGNGV-LYASVNPEYFSAAD------VYVPDEWEVAREKITMNREL daf-2_Cele CIIYYYIQVRYGKKVKALS-DFMQLNPEYC-VDN------KYNADDWELRQDDVVLGQQC ILGFR_Spur --LAVFIKRRYDRKVKRTEQHIKQLTLMGLGEGA------LITLDEWEMPRENVVLNRKL InsRL_Spur I-IFLRWHYRKDQM-PDGV-LYASVNPEYMSTSD------MYVADEWEFPRDKLEIIREL * . . *:**. ::.: IRR_Hsap GQGSFGMVYEGLARGLEA--GEE-STPVALKTVNELASPRECIEFLKEASVMKAFKCHHV INSR_Hsap GQGSFGMVYEGNARDIIK--GEA-ETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHV IGF1R_Hsap GQGSFGMVYEGVAKGVVK--DEP-ETRVAIKTVNEAASMRERIEFLNEASVMKEFNCHHV InR_Dmel GQGSFGMVYEGILKSFPP--NGV-DRECAIKTVNENATDRERTNFLSEASVMKEFDTYHV IRR_Mmus GQGSFGMVYEGLARGLEA--GEE-STPVALKTVNELASARERVEFLKEASVMKAFKCHHV INSR_Mmus GQGSFGMVYEGNAKDIIK--GEA-ETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHV IGF1R_Mmus GQGSFGMVYEGVAKGVVK--DEP-ETRVAIKTVNEAASMRERIEFLNEASVMKEFNCHHV daf-2_Cele GEGSFGKVYLGTGNNVVSLMGDR-FGPCAIKINVDDPASTENLNYLMEANIMKNFKTNFI ILGFR_Spur GEGAFGTVYGGEA--LLD--DNK-WAAVAVKTLKLGASVEEKLDFLSEAEVMKRFNHKNI InsRL_Spur GKGSFGMVYEGLAKGILP--EEEEISRVAIKSVQANASMRDRIEFLNEASVMKLIDAHNV *:*:** ** * . *:* .: : ::* **.:** : : IRR_Hsap VRLLGVVSQGQPTLVIMELMTRGDLKSHLRSLRPEAE-NNPGL------------PQPAL INSR_Hsap VRLLGVVSKGQPTLVVMELMAHGDLKSYLRSLRPEAE-NNPGR------------PPPTL IGF1R_Hsap VRLLGVVSQGQPTLVIMELMTRGDLKSYLRSLRPEME-NNPVL------------APPSL InR_Dmel VRLLGVCSRGQPALVVMELMKKGDLKSYLRAHRPEER-DEAMMTYLNRIGVTGNVQPPTY IRR_Mmus VRLLGVVSQGQPTLVIMELMTRGDLKSHLRSLRPEAE-NNPGL------------PQPAL INSR_Mmus VRLLGVVSKGQPTLVVMELMAHGDLKSHLRSLRPDAE-NNPGR------------PPPTL IGF1R_Mmus VRLLGVVSQGQPTLVIMELMTRGDLKSYLRSLRPEVEQNNLVL------------IPPSL daf-2_Cele VKLYGVISTVQPAMVVMEMMDLGNLRDYLRSKREDEVF-NETDC--------NFFDIIPR ILGFR_Spur VNLLGVCTRGEPMYAVMEFMLYGDLKTFLLGRRHLVGE-GVYER--------N-QHVMCP InsRL_Spur VRLLGVVSKGQPTYVIMEFMAQGDLKNWLRARRPENQ-QDLPLI--------DRKSVPTL *.* ** : :* .:**:* *:*: * . * IRR_Hsap GEMIQMAGEIADGMAYLAANKFVHRDLAARNCMVSQDFTVKIGDFGMTRDVYETDYYRKG INSR_Hsap QEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKG IGF1R_Hsap SKMIQMAGEIADGMAYLNANKFVHRDLAARNCMVAEDFTVKIGDFGMTRDIYETDYYRKG InR_Dmel GRIYQMAIEIADGMAYLAAKKFVHRDLAARNCMVADDLTVKIGDFGMTRDIYETDYYRKG IRR_Mmus SDMIQMAGEIADGMAYLAAKKFVHRDLAARNCMVSQDFTVKIGDFGMTRDVYETDYYRKG INSR_Mmus QEMIQMTAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDYYRKG IGF1R_Mmus SKMIQMAGEIADGMAYLNANKFVHRDLAARNCMVAEDFTVKIGDFGMTRDIYETDYYRKG daf-2_Cele DKFHEWAAQICDGMAYLESLKFCHRDLAARNCMINRDETVKIGDFGMARDLFYHDYYKPS ILGFR_Spur DQLTSMVSDIASGLSYLASINYVHRDLACRNCLVDASYTVKIGDFGMTRALYDSDYYRLG InsRL_Spur EQLLNMAAEIADGMSFLAARKYVHRDLSARNCLVSGEGTCKVADFGLARDIYQSDYYRKE : . . :*..*:::* : :: ****:.***:: . * *:.***::* :: ***: IRR_Hsap GKGLLPVRWMAPESLKDGIFTTHSDVWSFGVVLWEIVTLAEQPYQGLSNEQVLKFV-MDG INSR_Hsap GKGLLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFV-MDG IGF1R_Hsap GKGLLPVRWMSPESLKDGVFTTYSDVWSFGVVLWEIATLAEQPYQGLSNEQVLRFV-MEG InR_Dmel TKGLLPVRWMPPESLRDGVYSSASDVFSFGVVLWEMATLAAQPYQGLSNEQVLRYV-IDG IRR_Mmus GKGLLPVRWMAPESLKDGIFTTHSDVWSFGVVLWEIVTLAEQPYQGLSNEQVLKFV-MDG INSR_Mmus GKGLLPVRWMSPESLKDGVFTASSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFV-MDG IGF1R_Mmus GKGLLPVRWMSPESLKDGVFTTHSDVWSFGVVLWEIATLAEQPYQGLSNEQVLRFV-MEG daf-2_Cele GKRMMPVRWMSPESLKDGKFDSKSDVWSFGVVLYEMVTLGAQPYIGLSNDEVLNYIGMAR ILGFR_Spur KRSKLPVRWMAPESLTEGIFTTMSDVWSLGVVIYEVVTFGSFPYQELSNAEVLDYI-RNR InsRL_Spur RGGMLPIRWMAPESVKDGVFQASSDVWSFGILLWEMATLGELPYQGLSNEEAGEYI-KGG :*:***.***: :* : : **::*:*::::*:.::. ** *** :. :: IRR_Hsap GVLEELEGCPLQLQELMSRCWQPNPRLRPSFTHILDSIQEE------------------- INSR_Hsap GYLDQPDNCPERVTDLMRMCWQFNPKMRPTFLEIVNLLKDD------------------- IGF1R_Hsap GLLDKPDNCPDMLFELMRMCWQYNPKMRPSFLEIISSIKEE------------------- InR_Dmel GVMERPENCPDFLHKLMQRCWHHRSSARPSFLDIIAYLEPQ------------------- IRR_Mmus GVLEELENCPIQLQELMRLCWQHSPRLRPTFVHILDRIQDE------------------- INSR_Mmus GYLDPPDNCPERLTDLMRMCWQFNPKMRPTFLEIVNLLKDD------------------- IGF1R_Mmus GLLDKPDNCPDMLFELMRMCWQYNPKMRPSFLEIIGSIKDE------------------- daf-2_Cele KVIKKPECCENYWYKVMKMCWRYSPRDRPTFLQLVHLLAAE------------------- ILGFR_Spur NSLRPPEGCSPALGALMMQCWAIQPQHRPTAKDVNDILCQRPHLITPCLGVPLGSIPPEE InsRL_Spur NVLRPPENCPEKMQEIMMACWQYQEKLRPLFGEIILNLQDYG------------------ : : * :* ** ** .: : IRR_Hsap ------------------------------------------------------------ INSR_Hsap ------------------------------------------------------------ IGF1R_Hsap ------------------------------------------------------------ InR_Dmel ------------------------------------------------------------ IRR_Mmus ------------------------------------------------------------ INSR_Mmus ------------------------------------------------------------ IGF1R_Mmus ------------------------------------------------------------ daf-2_Cele ------------------------------------------------------------ ILGFR_Spur IHSTGLPLSPVRPKHPAPKHSTRSNSSTEMHMGREFNRIHDDEFLTGHLASVGHIFRASK InsRL_Spur ------------------------------------------------------------ IRR_Hsap ----LRPSFRLLSFYYSPECRG-------------------------------------- INSR_Hsap ----LHPSFPEVSFFHSEENKA-------------------------------------- IGF1R_Hsap ----MEPGFREVSFYYSEENKL-------------------------------------- InR_Dmel ---CPNSQFKEVSFYHSEAGLQ-------------------------------------- IRR_Mmus ----LRPSFRLCSFYYSPECQR-------------------------------------- INSR_Mmus ----LHPSFPEVSFFYSEENKA-------------------------------------- IGF1R_Mmus ----MEPSFQEVSFYYSEENKP-------------------------------------- daf-2_Cele ----ASPEFRDLSFVLTDNQMI-------------------------------------- ILGFR_Spur RRSKNKKSFSRCSFELAPSGSRRLRRDSETERNCISIISSTASAPSTSMSNTSTPSTSQD InsRL_Spur ---LLRDSFAQNCFFLNEQLNA-------------------------------------- * .* IRR_Hsap ----------------------------------------------------ARGSLPTT INSR_Hsap ----------------------------------------------------PESEELEM IGF1R_Hsap ----------------------------------------------------PEPEELDL InR_Dmel ---------------------------------------------------HREKERKER IRR_Mmus ----------------------------------------------------GQASLLPT INSR_Mmus ----------------------------------------------------PESEELEM IGF1R_Mmus ----------------------------------------------------PEPEELEM daf-2_Cele ---------------------------------------------------LDDSEALDL ILGFR_Spur SCVVAVEDLPPVIHRGRSRTSATLEHNFLHRLPSGGTFTKLLKKAATEDNIYSESESRQH InsRL_Spur ----------------------------------------------------SAA-PADM IRR_Hsap D-----------------------------AEP-DSSPT---------PRD---C----- INSR_Hsap E-----------------------------FEDMENVPL---------DRSSHCQ----- IGF1R_Hsap E-----------------------------PENMESVPL---------DPSASSS----- InR_Dmel NQ----------------------------LDAFAAVPL---------DQDLQDREQQED IRR_Mmus E-----------------------------AEP-DSPPT---------LNGASDY----- INSR_Mmus E-----------------------------FEDMENVPL---------DRSSHCQ----- IGF1R_Mmus E-----------------------------PENMESVPL---------DPSASSA----- daf-2_Cele DD-IDDTDMNDQVVEVAPDVENVEVQSDSERRNTDSIPLKQFKTIPPINATTSHS----- ILGFR_Spur SWSL-----------------FSCI----DSERFEGLPL---------LQHQSSR----- InsRL_Spur S-----------------------------SKELETVSIL--------DQNAKN------ . . IRR_Hsap ------------------------------------------------------------ INSR_Hsap ------------------------------------------------------------ IGF1R_Hsap ------------------------------------------------------------ InR_Dmel ATTPLRMGDYQQNSSLDQPPESPIAMVDDQGSHLPFSLPSGFIASSTPDGQTVMATAFQN IRR_Mmus ------------------------------------------------------------ INSR_Mmus ------------------------------------------------------------ IGF1R_Mmus ------------------------------------------------------------ daf-2_Cele ----------------------------------TISIDETPMKAKQREGSLDEEYALMN ILGFR_Spur ------------------------------------------------------------ InsRL_Spur ------------------------------------------------------------ IRR_Hsap ------------------------------------------------------------ INSR_Hsap ------------------------------------------------------------ IGF1R_Hsap ------------------------------------SLPLP------------------- InR_Dmel IPAAQGDISATYVVPDADALDGDRGYEIYDPSPKCAELPTSRSGSTGGGKLSGEQHLLPR IRR_Mmus ------------------------------------------------------------ INSR_Mmus ------------------------------------------------------------ IGF1R_Mmus ------------------------------------SLPLP------------------- daf-2_Cele HSGGPSDAEVRTYAGDGDYVERDV---------RENDVPTR------------------- ILGFR_Spur ------------------------------------RG---------------------- InsRL_Spur ------------------------------------NENLY------------------- IRR_Hsap ------------------------------------------------------------ INSR_Hsap ------------------------------------------------------------ IGF1R_Hsap ----------------------------------DRHSGH-------------------- InR_Dmel KGRQPTIMSSSMPDDVIGGSSLQPSTASAGSSNASSHTGRPSLKKTVADSVRNKANFINR IRR_Mmus ------------------------------------------------------------ INSR_Mmus ------------------------------------------------------------ IGF1R_Mmus ----------------------------------ERHSGH-------------------- daf-2_Cele -----------------------------------RNTGAS------------------- ILGFR_Spur --------------------------------------SK-------------------- InsRL_Spur ----------------------------------TSMSNN-------------------- IRR_Hsap --------------S---------P----------------------------------- INSR_Hsap --------------R---------E------------------E--AGGRDGGSSLGFK- IGF1R_Hsap --------------K---------A------------------E--NGP--GPGVLVLR- InR_Dmel HLFNHKRTGSNASHKSNASNAPSTSSNTNLTSHPVAMGNLGTIES-GGSGSAGSYTGTPR IRR_Mmus --------------S---------A----------------------------------- INSR_Mmus --------------R---------E------------------E--AGGREGGSSLSIK- IGF1R_Mmus --------------K---------A------------------E--NGP--GPGVLVLR- daf-2_Cele -------------TSSYTGGGPYCL------------------TNRGGSNERGAGFGEAV ILGFR_Spur --------------R------PRSK------------------S--LGSKSSGSK----- InsRL_Spur --------------K------PEGA------------------SN-GGNRAGGSVEVPI- IRR_Hsap ------------------------------------------------------------ INSR_Hsap ---------------------------------------------RSYEEH--------- IGF1R_Hsap ---------------------------------------------ASFDER--------- InR_Dmel FYTPSATPGGGSGMAISD------------NPNYRLLDESIASEQATILTTSSPNPNYEM IRR_Mmus ------------------------------------------------------------ INSR_Mmus ---------------------------------------------RTYDEH--------- IGF1R_Mmus ---------------------------------------------ASFDER--------- daf-2_Cele R----------------LTDGVGSGHLNDDD--------YVEKEISSMDTRRSTGASSS- ILGFR_Spur ---------------------------------------------SPSSKH--------- InsRL_Spur ---------------------------------------------VTGPSS--------- IRR_Hsap ------------------------------------------------------------ INSR_Hsap ----IPY----------------------------------------------------- IGF1R_Hsap ----QPY----------------------------------------------------- InR_Dmel MHPP--TSLVSTNPNYMPMNETPVQMAGVTISHNPNYQPMQAPLNARQSQSSSDEDNEQE IRR_Mmus ------------------------------------------------------------ INSR_Mmus ----IPY----------------------------------------------------- IGF1R_Mmus ----QPY----------------------------------------------------- daf-2_Cele -SYGVPQ--TNWSGN-----------RGA-------------TYYTSKAQQAATAAAAAA ILGFR_Spur ----SLY----------------------------------------------------- InsRL_Spur ----SPK--DR------------------------------------------------- IRR_Hsap ----------------------QNGG---------------------------------- INSR_Hsap --------------------THMNGGKKNGRILTLP------------------------ IGF1R_Hsap --------------------AHMNGGRKNERALPLP------------------------ InR_Dmel EDDEDEDDDVDDEHVEHIKMERMPLSRPRQRALPSKTQ-----------------PPRS- IRR_Mmus ----------------------PNGG---------------------------------- INSR_Mmus --------------------THMNGGKKNGRVLTLP------------------------ IGF1R_Mmus --------------------AHMNGGRANERALPLP------------------------ daf-2_Cele A----------------ALQQQQNGGRG-DRLTQLPGTGHLQSTRGGQDGDYIETEPKNY ILGFR_Spur -----------------VT-LSRNGFDDSKEEETMI------------------------ InsRL_Spur -------------------NGSLTGNGSIPHGVGVG------------------------ IRR_Hsap --------------------------------------------------PGH INSR_Hsap ------------------------------------------------RSNPS IGF1R_Hsap ------------------------------------------------QSSTC InR_Dmel RSVSQTRKSPTNPNSGIGATGAGNRSNLLKENWLRPASTPRPPPPNGFIGREA IRR_Mmus --------------------------------------------------PGH INSR_Mmus ------------------------------------------------RSNPS IGF1R_Mmus ------------------------------------------------QSSTC daf-2_Cele RNNGSPSRNGNSRDIFNGRSAFGENEHLIED-------NE--------HHPLV ILGFR_Spur ------------------------------------------------SFVSN InsRL_Spur ------------------------------------------------KCTEC