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Database: UniProt
Entry: Q7SZN0
LinkDB: Q7SZN0
Original site: Q7SZN0 
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   29-OCT-2014, entry version 64.
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}.
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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: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
//
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