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Fig. S3 The putative conopeptide precursors of (a) M superfamily, (b) con-ikot-ikot and (c) conkunitzin family. The notes are indicated in Fig. 2S (a) M superfamily *: the last 12 amino acid residues (PNSIWSKRSGAD) are repeated 7 times in tandem LtXVIA Ctr_31_T MPKLGVSLFIFLVLFPLATLQLDGDQSAGRHAQERGEDLFKMYQYLRRALERRRTGEDFLEECMGGCAFDFCCKRSLRDTTSD MSNIGIVVLIFLVLFPLATAQLDADQPADLQGEKRGGNLAKMYQQMKEVLNR-------VTRCGGSCTDDVCCKRSFLRGMAL Ctr_55_TN Ctr_103_T Im5.3 MSKVGLVLLIFLVLLTLAALHQDVDDPRRQRDEKRSPQRDILRSTLRKYRSNIQRRCSNGKTSCSTCTQQGKDCSVTRGS-RLCGTCVPRGR ---------------------------------------DILRSTLKKYSYNIQRRCTNGKTQCWKCYDDGKACSGTSGSGKRCGMCV---MLKVGVVLLIFLVLMSSAIPQ----DRGQQSDKKQIRQRDIFGSKMRRYSPNIQKRCIVG-TPCHVCRSQSKSCNGWLGKQRYCGYCG---- Conomarphin family Ctr_33_N Ctr_74_T Ctr_148_N Ctr_90_N Lt0.5 Im_conomarphin -MSKLGVVLFIFLVLFPMTTLQQDGDQSADRRADERGQGLTEQYRDLRALRLSGADPNSIWSKTLWC----MSKLGVVLFIFLVLFPMTTLQQDGDQSADRRADERGQGLTEQYRDLRALRLSGADPNSI-----------MSKLGVVLFIFLVLFPMTTLQQDGDQTADRRADERGQGLTEQYRSLRALRLSGGDPNSIWSKTLWC----MSKLGVVLFIFLVLFPMTTLQQDGDQSADRRADKRGQGLTQQHRNLRGVKRSGGDPNSIWSKRSGAD---* -MSKLGVVLFIFLVLFPMATLQLDGDQPADRRADEKDQDLTQQYLNLRRVLQRGLVCAHVRPYHNSMWS-MMSKLGVLLCIFLVLFPMATLQLDGDQTADRHADQRGQDLTEQQRNSKRVLKKRDWEYHAHPKPNSFWTLV (b) Con-ikot-ikot family Ctr_18_N Ctr_50_T MTMPMTLSLLVTIAIAATVLDSTLLRGNDPSCEDQVYHECCRHEMHSCAEECLSASDMDFCWEPCTQSAAVQCGRQTSSGCCRPFLECFSACLNDGDLLYDCWIRCRHVPC MTMPMTLSLLVTIAIAATVIDSTLLRGNDPSCEDQVYHECCRHEMHSCAEECLSASDMDFCWEPCTQSAAVQCGRQTSSGCCRPFLECFSACLNDGDVLYDCWIRCRHVPC Ctr_26_TN P03890 Ctr_39_N Ctr_67_N MTMNMSMTLSVFVMVVIAATVVGSTPLEDK-------DLNCEGLAYHECCRNEMRICIVECSSVSDADSCWDYCYYSAATNCECH-PQDGCCPDFLESYSPCLFHDGLDENECWEQARYVPCW--MAMNMSMTLCMFVMVVVAATVIDSTQLQEPDLSRMRRSGPADCCRMKECCTDRVNECLQRYSGRED--KFVSFCYQEATVTCGSFNEIVGCCYGYQMCMIRVVKPNSLSG--AHEACKTVSCGNPC --MNMWMTISMFAVVATAATVVGSTPLEER--------------QPRDCCHSIFYECAAEECSFTDDLLCAEMCWDAATDVCGGD-PDSGFCPSFFGCFKDCVFTESGPHFRCYELCKTVPCWLDK --MNMWMTISMFAVVATAATVVGSTPLEER--------------QPRDCCHSIFYECAAEECSFTDDLLCAEMCWDAATDVCGGD-PDSGFCPSFFGCFKDCVFTESGPHFRCYELCKTG-AYAN- Ctr_137_N Ctr_135_N 1 98 MAMNMWMTLSVLVVVVFTTTVVCSTSLDEDKREALQLRWDTASLCCLSIY-GC-YWECKTKGGDNCWLWCAQENYDVCNG-MYGDYCWPFANCFKECI --MNMWMTISMFAVVATAATVVGSTPLEER----------QPRDCCHSIFYECAAEECSFTDDLLCAEMCWDAATDVCGGDPDSGFCPSFFGCFKDCV Ctr_137_N Ctr_135_N 99 198 KTKSK------EHCFNG------------------CTYEAKLKCIEEGYV-------------ACCPKFMTCYNECLENTG--QYSCSNQCEGVGC---FTESGPHFRCYELCKMGQRPWDCCHSVFYECAGEACSFTDDPDCPEMCYLDAATDVCGGDPDFGCCPSFFDCFMDCVFMESGPHFGCYELCKTVPCWLDK (c) Conkunitzin family BPTI (BPTI/Kunitz domain-containing protein) from Haliotis asinine, SwissProt ID P86733.1 Btau_TFPI2 (Tissue factor pathway inhibitor 2) from Bos Taurus, SwissProt ID Q7YRQ8.1, total amino acids is 234 but until residue 151 is shown here BPTI Btau_TFPI2 Ctr_44_TN Ctr_134_N Conkunitzin_G1 Conkunitzin_B1 Ctr_29_TN Ctr_75_N Ctr_79_T Conkunitzin_Pu1 Ctr_141_T 1 82 --------------LFVG--------LTSAKYHDVCQ----------LPRDPGPCRAYIPLYYFNSRTCLCEKFVYGGCQGN MDSVRPLWLMLLSLLLVGTALGDASQAPPGNNAEICL----------LPPDDGPCRARIPSYYYDRYTQSCREFMYGGCEGN[151] MEGHRFAAVLIL-TI-CMLALGAGAFRLHGSRAEECSRSEALAKCYYLPKDPGPCKARESRYYFNRYLNTCQEFIYGGCHGN MEGHRFAAVLIL-TI-CMLALGAGAFRLHGSRAEECSRSEALAKCYYLPKDPGPCKARESRYYFNRYLNTCQEFIYGEITRMEGRRFAAVLILT-I-CMLAPGAVVSRRR-VQPSECK----------LPAAKGPCKGKYRKVYFNNFKKQCRMFTYGGCGGN MEGRRFAAVLILP-I-CMLAPGAVASKRW-TRPSVCN----------LPAESGTGTQSLKRFYYNSDKMQCRTFIYKGNGGN MDALRFSAVLLILAVACFTTVSA----------GTCD----------KAKDEGTGNLHLTRHYFDSTTRTCETFIYKGSGVD MDALRFSAVLLILAVACFTTVSA----------GTCD----------KAKDEGTGNLHLTRHYFDSTTRTCETFIYKGSGVD MKGGRFAAVLLVLTI-CRAGEVYDPRPV----VRKCE----------APRDEGTGSGSERKYFFNSNSRDCKAYTYTGHGGF MEARRFAAVLILA-I-CVLALGSGASRRQ-GAPAVCT----------MQKDPGPCKMAITRYYFNVAIFDCTTFSYGGCLGN MKATLHRCVVVLLVVLVTAVVKVSSARFVHGREADRLCEAYKKVC----PRGKVCAIQVVDLSSTTMKFPVCVHLFQVKVRS BPTI Btau_TFPI2 Ctr_44_TN Ctr_134_N Conkunitzin_G1 Conkunitzin_B1 Ctr_29_TN Ctr_75_N Ctr_79_T Conkunitzin_Pu1 Ctr_141_T 83 165 ---ANRFDTVEDCRRRCGGGD----LCSLPRDSGPCEAAIPRWWYNKRTNRCQRFTYGGCEGNANNFKTLDECRFQCRKRSTY ---ANNFETLEACNEACWKIEKVPKICRLKVNKKQCGELREQYFFNLSSMTCKKFISGGCHSNENRFPDEATCMDFCAPKRA---ANRFDTMEDCLGCCLL-----SVCRQPAEPGLCKAYVERYYFDMNSYDCKPFSYGGCNGNDNNFHTYNECYGRCGLE---------------------------------------------------------------------------------------GNKFRNAKECYHKCAYGVG---------------------------------------------------------------DNNFPRTYDCQKKCLYRPG------------------------------------------------------------DPFPNRFNTQPECENVC--------KCKLRKDPGTGESPRTRWYHNSDGSGCQQFQYLGRGGNANNFLSQSDCINECQ----DPFPNRFNTQPECENVC--------KCKLRKDPGTGESPRTRYYHNSDGSGCQQFQYLGRGGNANNFLSQSACINECE----YDQVNRFNSRLECETTC--------RCYLRLDQGSGQLHSQRYYYDRPGHSCNQFTYLGGGGNENNYYDRMACRDACMSSGGR ---GNNFENYDECYETCG----------------------------------------------------------------------------------------PVCKQAPSPGRCSAVFRRWYFNVHVAACSWFTYSGCGGND-------------------