ID FA5V_PSETE Reviewed; 1460 AA. AC Q7SZN0; DT 31-MAY-2011, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2003, sequence version 1. DT 01-OCT-2014, entry version 63. DE RecName: Full=Venom prothrombin activator pseutarin-C non-catalytic subunit; DE Short=PCNS; DE Short=vPA; DE AltName: Full=Venom coagulation factor Va-like protein; DE Contains: DE RecName: Full=Pseutarin-C non-catalytic subunit heavy chain; DE Contains: DE RecName: Full=Pseutarin-C non-catalytic subunit light chain; DE Flags: Precursor; OS Pseudonaja textilis (Eastern brown snake). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; OC Toxicofera; Serpentes; Colubroidea; Elapidae; Acanthophiinae; OC Pseudonaja. OX NCBI_TaxID=8673; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 31-54; 58-124; RP 141-160; 309-317; 331-340; 352-372; 378-392; 430-454; 477-499; RP 507-530; 559-567; 821-840; 851-866; 868-886; 896-922; 926-949; RP 968-996; 1037-1059; 1078-1089; 1119-1134; 1149-1175; 1266-1279; RP 1327-1368; 1396-1405; 1413-1425; 1429-1435 AND 1443-1451, ABSENCE OF RP GLYCOSYLATION AT ASN-385 AND ASN-1397, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Venom, and Venom gland; RX PubMed=12730119; DOI=10.1182/blood-2002-12-3839; RA Rao V.S., Swarup S., Kini R.M.; RT "The nonenzymatic subunit of pseutarin C, a prothrombin activator from RT eastern brown snake (Pseudonaja textilis) venom, shows structural RT similarity to mammalian coagulation factor V."; RL Blood 102:1347-1354(2003). RN [2] RP PARTIAL PROTEIN SEQUENCE, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND RP TISSUE SPECIFICITY. RC TISSUE=Venom; RX PubMed=12362232; DOI=10.1267/th02100611; RA Rao V.S., Kini R.M.; RT "Pseutarin C, a prothrombin activator from Pseudonaja textilis venom: RT its structural and functional similarity to mammalian coagulation RT factor Xa-Va complex."; RL Thromb. Haemost. 88:611-619(2002). RN [3] RP NOMENCLATURE. RX PubMed=11522026; RA Manjunatha Kini R., Morita T., Rosing J.; RT "Classification and nomenclature of prothrombin activators isolated RT from snake venoms."; RL Thromb. Haemost. 86:710-711(2001). RN [4] RP TISSUE SPECIFICITY. RC TISSUE=Venom gland; RX PubMed=15735790; DOI=10.1267/THRO05030420; RA Minh Le T.N., Reza M.A., Swarup S., Kini R.M.; RT "Gene duplication of coagulation factor V and origin of venom RT prothrombin activator in Pseudonaja textilis snake."; RL Thromb. Haemost. 93:420-429(2005). RN [5] RP PHARMACEUTICAL. RX PubMed=21184772; DOI=10.1016/j.toxicon.2010.12.010; RA Earl S.T., Masci P.P., de Jersey J., Lavin M.F., Dixon J.; RT "Drug development from Australian elapid snake venoms and the Venomics RT pipeline of candidates for haemostasis: Textilinin-1 (Q8008), RT Haempatch (Q8009) and CoVase (V0801)."; RL Toxicon 59:456-463(2012). CC -!- FUNCTION: Snake prothrombin activator that attacks the hemostatic CC system of prey. This non-catalytic subunit is functionally similar CC to blood coagulation factor V. It serves as a critical cofactor CC for the prothrombinase activity of the catalytic subunit, which is CC similar to the blood coagulation factor X. CC {ECO:0000269|PubMed:12362232}. CC -!- SUBUNIT: Heterodimer of a light and a heavy chains; non-disulfide- CC linked. The interaction between the two chains is calcium- CC dependent (By similarity). Found in its active form associated CC with pseutarin-C catalytic subunit (AC Q56VR3). {ECO:0000250, CC ECO:0000269|PubMed:12362232}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12362232, CC ECO:0000269|PubMed:12730119}. CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. CC {ECO:0000269|PubMed:12362232, ECO:0000269|PubMed:12730119, CC ECO:0000269|PubMed:15735790}. CC -!- PTM: In physiological conditions, blood coagulation factor V and CC factor Va are inactivated by activated protein C (APC) through CC proteolytic degradation of the heavy chain. However, pseutarin-C CC non-catalytic subunit (factor V-like protein) retains its full CC activity even at high concentration of APC. This has two CC explanations: this protein has only one of the three cleavage CC sites present in factor V that are targeted by the APC for CC inactivation, and the binding with the catalytic subunit protect CC the cleavage site from inactivation. CC -!- PHARMACEUTICAL: Is under preclinical trial by the Australian CC biopharmaceutical company QRxPharma Ltd, its subsidiary Venomics CC Pty Ltd (VPL) and the University of Queensland (UQ) under the name CC CoVase (V0801). Tested as a procoagulant cofactor that may have CC application as a systemic anti-bleeding agent in the treatment of CC internal bleeding and non-compressible haemorrhage. CC -!- MISCELLANEOUS: In contrast to blood coagulation factors that CC circulate as inactive zymogen in plasma, venom prothrombin CC activators are always found in the active form in the venom. CC Hence, catalytic and non-catalytic subunits are found naturally in CC venom as stable complexes. CC -!- SIMILARITY: Belongs to the multicopper oxidase family. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 3 F5/8 type A domains. {ECO:0000305}. CC -!- SIMILARITY: Contains 2 F5/8 type C domains. {ECO:0000255|PROSITE- CC ProRule:PRU00081}. CC -!- SIMILARITY: Contains 6 plastocyanin-like domains. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY168281; AAO38805.1; -; mRNA. DR PDB; 4BXS; X-ray; 3.32 A; V=31-1460. DR PDBsum; 4BXS; -. DR ProteinModelPortal; Q7SZN0; -. DR SMR; Q7SZN0; 31-327, 1302-1460. DR HOVERGEN; HBG005631; -. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:0005507; F:copper ion binding; IEA:InterPro. DR GO; GO:0016504; F:peptidase activator activity; IEA:UniProtKB-KW. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR GO; GO:0007155; P:cell adhesion; IEA:InterPro. DR GO; GO:0044469; P:envenomation resulting in positive regulation of blood coagulation in other organism; IDA:UniProtKB. DR GO; GO:0035807; P:positive regulation of blood coagulation in other organism; IDA:UniProtKB. DR GO; GO:0006508; P:proteolysis; IDA:GOC. DR Gene3D; 2.60.120.260; -; 2. DR Gene3D; 2.60.40.420; -; 6. DR InterPro; IPR000421; Coagulation_fac_5/8-C_type_dom. DR InterPro; IPR011707; Cu-oxidase_3. DR InterPro; IPR002355; Cu_oxidase_Cu_BS. DR InterPro; IPR008972; Cupredoxin. DR InterPro; IPR008979; Galactose-bd-like. DR Pfam; PF07732; Cu-oxidase_3; 3. DR Pfam; PF00754; F5_F8_type_C; 2. DR SMART; SM00231; FA58C; 2. DR SUPFAM; SSF49503; SSF49503; 6. DR SUPFAM; SSF49785; SSF49785; 2. DR PROSITE; PS01285; FA58C_1; 2. DR PROSITE; PS01286; FA58C_2; 1. DR PROSITE; PS50022; FA58C_3; 2. DR PROSITE; PS00079; MULTICOPPER_OXIDASE1; 3. PE 1: Evidence at protein level; KW 3D-structure; Blood coagulation cascade activating toxin; Calcium; KW Direct protein sequencing; Disulfide bond; Glycoprotein; KW Hemostasis impairing toxin; Metal-binding; Pharmaceutical; KW Phosphoprotein; Prothrombin activator; Repeat; Secreted; Signal; KW Toxin. FT SIGNAL 1 30 {ECO:0000269|PubMed:12730119}. FT CHAIN 31 772 Pseutarin-C non-catalytic subunit heavy FT chain. {ECO:0000305}. FT /FTId=PRO_5000089286. FT PROPEP 773 818 Activation peptide (connecting region). FT /FTId=PRO_0000408521. FT CHAIN 819 1460 Pseutarin-C non-catalytic subunit light FT chain. FT /FTId=PRO_0000408522. FT DOMAIN 32 330 F5/8 type A 1. FT DOMAIN 32 196 Plastocyanin-like 1. FT DOMAIN 206 330 Plastocyanin-like 2. FT DOMAIN 351 685 F5/8 type A 2. FT DOMAIN 351 529 Plastocyanin-like 3. FT DOMAIN 539 685 Plastocyanin-like 4. FT DOMAIN 824 1143 F5/8 type A 3. FT DOMAIN 824 992 Plastocyanin-like 5. FT DOMAIN 1001 1143 Plastocyanin-like 6. FT DOMAIN 1147 1298 F5/8 type C 1. {ECO:0000255|PROSITE- FT ProRule:PRU00081}. FT DOMAIN 1303 1457 F5/8 type C 2. {ECO:0000255|PROSITE- FT ProRule:PRU00081}. FT REGION 693 818 B. FT COMPBIAS 695 699 Poly-Glu. FT METAL 142 142 Calcium. {ECO:0000250}. FT METAL 143 143 Calcium. {ECO:0000250}. FT SITE 385 385 Not glycosylated. FT SITE 537 538 Cleavage; by activated protein C. FT {ECO:0000250}. FT SITE 772 773 Cleavage; by thrombin. {ECO:0000250}. FT SITE 818 819 Cleavage; by thrombin. {ECO:0000250}. FT SITE 1397 1397 Not glycosylated. FT CARBOHYD 156 156 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 204 204 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 242 242 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 406 406 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 471 471 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 557 557 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 944 944 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 1001 1001 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 1180 1180 N-linked (GlcNAc...). {ECO:0000255}. FT DISULFID 170 196 {ECO:0000255|PROSITE-ProRule:PRU00081}. FT DISULFID 251 332 {ECO:0000255|PROSITE-ProRule:PRU00081}. FT DISULFID 503 529 {ECO:0000255|PROSITE-ProRule:PRU00081}. FT DISULFID 966 992 {ECO:0000305}. FT DISULFID 1147 1298 {ECO:0000255|PROSITE-ProRule:PRU00081}. FT DISULFID 1303 1457 {ECO:0000255|PROSITE-ProRule:PRU00081}. FT CONFLICT 80 82 EPR -> KPQ (in Ref. 1; AA sequence). FT {ECO:0000305}. FT CONFLICT 103 103 I -> Q (in Ref. 1; AA sequence). FT {ECO:0000305}. FT CONFLICT 119 124 SAVYNK -> DAVKIG (in Ref. 1; AA FT sequence). {ECO:0000305}. FT CONFLICT 146 146 P -> A (in Ref. 1; AA sequence). FT {ECO:0000305}. FT CONFLICT 156 156 N -> E (in Ref. 1; AA sequence). FT {ECO:0000305}. FT CONFLICT 350 363 IKNWEYFIAAEEIT -> AQLWEYHIAAQKED (in Ref. FT 1; AA sequence). {ECO:0000305}. FT CONFLICT 440 444 NLASR -> DLAVQ (in Ref. 1; AA sequence). FT {ECO:0000305}. FT CONFLICT 522 523 LI -> IL (in Ref. 1; AA sequence). FT {ECO:0000305}. FT CONFLICT 820 827 INRGNKRR -> QNTGNKLY (in Ref. 1; AA FT sequence). {ECO:0000305}. FT CONFLICT 840 840 S -> I (in Ref. 1; AA sequence). FT {ECO:0000305}. FT CONFLICT 876 876 G -> GK (in Ref. 1; AA sequence). FT {ECO:0000305}. FT CONFLICT 902 902 K -> R (in Ref. 1; AA sequence). FT {ECO:0000305}. FT CONFLICT 944 944 N -> F (in Ref. 1; AA sequence). FT {ECO:0000305}. FT CONFLICT 981 995 IHSGLIGPILICQKG -> VEPGLIGPLYSIAEEAV (in FT Ref. 1; AA sequence). {ECO:0000305}. FT CONFLICT 1041 1043 SLH -> NLG (in Ref. 1; AA sequence). FT {ECO:0000305}. FT CONFLICT 1055 1058 LQGL -> GK (in Ref. 1; AA sequence). FT {ECO:0000305}. FT CONFLICT 1166 1170 SGHVG -> AGHVQ (in Ref. 1; AA sequence). FT {ECO:0000305}. FT CONFLICT 1274 1274 I -> V (in Ref. 1; AA sequence). FT {ECO:0000305}. FT CONFLICT 1369 1369 I -> K (in Ref. 1; AA sequence). FT {ECO:0000305}. FT CONFLICT 1400 1404 WKPYL -> YKPYG (in Ref. 1; AA sequence). FT {ECO:0000305}. FT CONFLICT 1433 1434 LS -> SL (in Ref. 1; AA sequence). FT {ECO:0000305}. FT STRAND 33 36 FT STRAND 39 45 FT STRAND 64 69 FT HELIX 74 76 FT STRAND 84 86 FT STRAND 100 111 FT STRAND 117 120 FT TURN 124 126 FT TURN 137 139 FT TURN 141 143 FT STRAND 150 155 FT STRAND 159 162 FT TURN 164 166 FT STRAND 169 175 FT TURN 178 180 FT HELIX 181 185 FT TURN 186 188 FT STRAND 191 196 FT STRAND 205 209 FT STRAND 211 221 FT TURN 223 225 FT STRAND 226 228 FT STRAND 234 237 FT STRAND 248 251 FT STRAND 256 263 FT STRAND 272 274 FT STRAND 287 289 FT STRAND 295 300 FT STRAND 307 313 FT HELIX 316 320 FT STRAND 325 330 FT STRAND 355 366 FT HELIX 378 381 FT STRAND 392 404 FT STRAND 409 411 FT STRAND 413 415 FT STRAND 417 419 FT STRAND 426 428 FT STRAND 433 440 FT STRAND 442 444 FT STRAND 449 453 FT STRAND 475 478 FT STRAND 483 489 FT TURN 492 494 FT STRAND 498 500 FT STRAND 502 509 FT HELIX 514 519 FT STRAND 524 529 FT HELIX 556 558 FT HELIX 562 569 FT HELIX 573 575 FT HELIX 581 587 FT STRAND 595 597 FT STRAND 603 605 FT STRAND 610 612 FT STRAND 630 632 FT STRAND 634 636 FT STRAND 639 643 FT STRAND 655 657 FT STRAND 664 667 FT HELIX 674 677 FT STRAND 678 684 FT HELIX 692 698 FT STRAND 834 839 FT STRAND 855 859 FT STRAND 863 866 FT STRAND 870 872 FT HELIX 878 880 FT STRAND 889 892 FT STRAND 896 899 FT STRAND 905 907 FT STRAND 912 917 FT HELIX 933 935 FT TURN 936 938 FT STRAND 949 952 FT HELIX 955 957 FT STRAND 966 972 FT STRAND 974 976 FT HELIX 977 981 FT TURN 982 984 FT STRAND 987 992 FT STRAND 999 1002 FT STRAND 1004 1017 FT TURN 1018 1020 FT STRAND 1021 1023 FT STRAND 1044 1048 FT STRAND 1051 1053 FT STRAND 1059 1064 FT STRAND 1066 1072 FT STRAND 1080 1084 FT STRAND 1100 1104 FT STRAND 1111 1113 FT STRAND 1120 1127 FT HELIX 1129 1132 FT STRAND 1139 1143 FT STRAND 1152 1155 FT TURN 1160 1162 FT STRAND 1163 1166 FT STRAND 1169 1171 FT STRAND 1183 1185 FT STRAND 1200 1215 FT STRAND 1226 1232 FT STRAND 1235 1237 FT STRAND 1254 1256 FT STRAND 1259 1262 FT STRAND 1265 1267 FT STRAND 1273 1288 FT STRAND 1293 1298 FT TURN 1309 1311 FT TURN 1316 1318 FT STRAND 1319 1322 FT STRAND 1343 1345 FT STRAND 1359 1362 FT STRAND 1368 1374 FT STRAND 1376 1378 FT STRAND 1383 1389 FT STRAND 1392 1394 FT STRAND 1396 1398 FT STRAND 1400 1402 FT STRAND 1408 1410 FT STRAND 1418 1421 FT STRAND 1426 1432 FT STRAND 1435 1438 FT STRAND 1441 1447 FT STRAND 1452 1457 SQ SEQUENCE 1460 AA; 165932 MW; 6AFB63E2D5D275A6 CRC64; MGRYSVSPVP KCLLLMFLGW SGLKYYQVNA AQLREYHIAA QLEDWDYNPQ PEELSRLSES DLTFKKIVYR EYELDFKQEE PRDALSGLLG PTLRGEVGDS LIIYFKNFAT QPVSIHPQSA VYNKWSEGSS YSDGTSDVER LDDAVPPGQS FKYVWNITAE IGPKKADPPC LTYAYYSHVN MVRDFNSGLI GALLICKEGS LNANGSQKFF NREYVLMFSV FDESKNWYRK PSLQYTINGF ANGTLPDVQA CAYDHISWHL IGMSSSPEIF SVHFNGQTLE QNHYKVSTIN LVGGASVTAD MSVSRTGKWL ISSLVAKHLQ AGMYGYLNIK DCGNPDTLTR KLSFRELMKI KNWEYFIAAE EITWDYAPEI PSSVDRRYKA QYLDNFSNFI GKKYKKAVFR QYEDGNFTKP TYAIWPKERG ILGPVIKAKV RDTVTIVFKN LASRPYSIYV HGVSVSKDAE GAIYPSDPKE NITHGKAVEP GQVYTYKWTV LDTDEPTVKD SECITKLYHS AVDMTRDIAS GLIGPLLVCK HKALSVKGVQ NKADVEQHAV FAVFDENKSW YLEDNIKKYC SNPSAVKKDD PKFYKSNVMY TLNGYASDRT EVLRFHQSEV VQWHLTSVGT VDEIVPVHLS GHTFLSKGKH QDILNLFPMS GESATVTMDN LGTWLLSSWG SCEMSNGMRL RFLDANYDDE DEGNEEEEED DGDIFADIFI PSEVVKKKEE VPVNFVPDPE SDALAKELGL IDDEGNPIIQ PRREQTEDDE EQLMKASMLG LRSFKGSVAE EELKHTALAL EEDAHASDPR IDSNSARNPD DIAGRYLRTI NRGNKRRYYI AAEEVLWDYS PIGKSQVRSR AAKTTFKKAI FRSYLDDTFQ TPSTGGEYEK HLGILGPIIR AEVDDVIEIQ FKNLASRPYS LHAHGLLYEK SSEGRSYDDK SPELFKKDDA IMPNGTYTYV WQVPPRSGPT DNTEKCKSWA YYSGVNPEKD IHSGLIGPIL ICQKGMIDKY NRTIDIREFV LFFMVFDEEK SWYFPKSDKS TCEEKLIGVQ SLHTFPAING IPYQLQGLTM YKDENVHWHL LNMGGPKDIH VVNFHGQTFT EEGREDNQLG VLPLLPGTFA SIKMKPSKIG TWLLETEVGE NQERGMQALF TVIDKDCKLP MGLASGIIQD SQISASGHVG YWEPKLARLN NTGKYNAWSI IKKEHEHPWI QIDLQRQVVI TGIQTQGTVQ LLQHSYTVEY FVTYSEDGQN WITFKGRHSE TQMHFEGNSD GTTVKENHID PPIIARYIRL HPTKFYNRPT FRIELLGCEV EGCSVPLGME SGAIKNSEIT ASSYKKTWWS SWEPSLARLN LEGGTNAWQP EVNNKDQWLQ IDLQHLTKIT SIITQGATSM TTSMYVKTFS IHYTDDNSTW KPYLDVRTSM EKVFTGNINS DGHVKHFFKP PILSRFIRII PKTWNQYIAL RIELFGCEVF //