FA5V_OXYSU
ID FA5V_OXYSU Reviewed; 1459 AA.
AC Q58L91; Q49MF1;
DT 28-JUN-2011, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=Venom prothrombin activator oscutarin-C non-catalytic subunit;
DE Short=vPA;
DE AltName: Full=Venom coagulation factor Va-like protein;
DE Contains:
DE RecName: Full=Oscutarin-C non-catalytic subunit heavy chain;
DE Contains:
DE RecName: Full=Oscutarin-C non-catalytic subunit light chain;
DE Flags: Precursor;
OS Oxyuranus scutellatus (Coastal taipan).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Acanthophiinae; Oxyuranus.
OX NCBI_TaxID=8668;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=15930152; DOI=10.1093/molbev/msi181;
RA St Pierre L., Masci P.P., Filippovich I., Sorokina N., Marsh N.,
RA Miller D.J., Lavin M.F.;
RT "Comparative analysis of prothrombin activators from the venom of
RT Australian elapids.";
RL Mol. Biol. Evol. 22:1853-1864(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, AND SUBCELLULAR
RP LOCATION.
RC STRAIN=Oxyuranus scutellatus scutellatus; TISSUE=Venom, and Venom gland;
RX PubMed=15993914; DOI=10.1016/j.toxicon.2005.05.001;
RA Welton R.E., Burnell J.N.;
RT "Full length nucleotide sequence of a factor V-like subunit of oscutarin
RT from Oxyuranus scutellatus scutellatus (coastal Taipan).";
RL Toxicon 46:328-336(2005).
RN [3]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RC STRAIN=Oxyuranus scutellatus scutellatus; TISSUE=Venom;
RX PubMed=6986908; DOI=10.1021/bi00546a029;
RA Walker F.J., Owen W.G., Esmon C.T.;
RT "Characterization of the prothrombin activator from the venom of Oxyuranus
RT scutellatus scutellatus (taipan venom).";
RL Biochemistry 19:1020-1023(1980).
RN [4]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=3531198; DOI=10.1016/s0021-9258(18)69299-3;
RA Speijer H., Govers-Riemslag J.W.P., Zwaal R.F.A., Rosing J.;
RT "Prothrombin activation by an activator from the venom of Oxyuranus
RT scutellatus (Taipan snake).";
RL J. Biol. Chem. 261:13258-13267(1986).
RN [5]
RP NOMENCLATURE.
RX PubMed=11522026;
RA Manjunatha Kini R., Morita T., Rosing J.;
RT "Classification and nomenclature of prothrombin activators isolated from
RT snake venoms.";
RL Thromb. Haemost. 86:710-711(2001).
CC -!- FUNCTION: Snake prothrombin activator that attacks the hemostatic
CC system of prey (PubMed:6986908, PubMed:3531198). This non-catalytic
CC subunit is functionally similar to blood coagulation factor V
CC (PubMed:6986908, PubMed:3531198). It serves as a critical cofactor for
CC the prothrombinase activity of the catalytic subunit, which is similar
CC to the blood coagulation factor X (PubMed:6986908, PubMed:3531198). The
CC complex converts prothrombin to thrombin by sequential cleavage at two
CC positions, Arg-320 followed by Arg-271 (PubMed:6986908,
CC PubMed:3531198). Cleavage at Arg-320 produces an active intermediate
CC known as meizothrombin (PubMed:6986908, PubMed:3531198). Meizothrombin
CC is the 'second' substrate for prothrombinase, and it docks in an
CC altered manner to present the second cleavage site (271)
CC (PubMed:6986908, PubMed:3531198). Cleavage at Arg-271 releases active
CC thrombin from its pro-fragment (PubMed:6986908, PubMed:3531198). This
CC order of events is reversed if the protease component of prothrombinase
CC is used on its own, suggesting that the 271 site is inherently more
CC accessible to proteolysis (PubMed:6986908, PubMed:3531198).
CC {ECO:0000269|PubMed:3531198, ECO:0000269|PubMed:6986908}.
CC -!- SUBUNIT: Heterodimer of a light and a heavy chains; non-disulfide-
CC linked. The interaction between the two chains is calcium-dependent.
CC Found in its active form associated with oscutarin-C catalytic subunit
CC (AC Q58L96) (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15993914,
CC ECO:0000269|PubMed:3531198, ECO:0000269|PubMed:6986908}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:15993914}.
CC -!- PTM: In physiological conditions, blood coagulation factor V and factor
CC Va are inactivated by activated protein C (APC) through proteolytic
CC degradation of the heavy chain. However, oscutarin-C non-catalytic
CC subunit (factor V-like protein) retains its full activity even at high
CC concentration of APC. This has two explanations: this protein has only
CC one of the three cleavage sites present in factor V that are targeted
CC by the APC for inactivation, and the binding with the catalytic subunit
CC protect the cleavage site from inactivation (By similarity).
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: In contrast to blood coagulation factors that circulate
CC as inactive zymogen in plasma, venom prothrombin activators are always
CC found in the active form in the venom. Hence, catalytic and non-
CC catalytic subunits are found naturally in venom as stable complexes.
CC -!- SIMILARITY: Belongs to the multicopper oxidase family. {ECO:0000305}.
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DR EMBL; AY940209; AAX37265.1; -; mRNA.
DR EMBL; AY691656; AAY47065.1; -; mRNA.
DR AlphaFoldDB; Q58L91; -.
DR SMR; Q58L91; -.
DR BRENDA; 3.4.21.6; 4479.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; 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:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0044469; P:envenomation resulting in positive regulation of blood coagulation in another organism; IDA:UniProtKB.
DR GO; GO:0035807; P:positive regulation of blood coagulation in another organism; IDA:UniProtKB.
DR CDD; cd00057; FA58C; 2.
DR Gene3D; 2.60.40.420; -; 5.
DR InterPro; IPR011707; Cu-oxidase_N.
DR InterPro; IPR033138; Cu_oxidase_CS.
DR InterPro; IPR008972; Cupredoxin.
DR InterPro; IPR000421; FA58C.
DR InterPro; IPR024715; Factor_5/8-like.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR Pfam; PF07732; Cu-oxidase_3; 3.
DR Pfam; PF00754; F5_F8_type_C; 2.
DR PIRSF; PIRSF000354; Factors_V_VIII; 1.
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 Blood coagulation cascade activating toxin; Calcium;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hemostasis impairing toxin; Metal-binding; Prothrombin activator; Repeat;
KW Secreted; Signal; Toxin.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..771
FT /note="Oscutarin-C non-catalytic subunit heavy chain"
FT /id="PRO_0000409907"
FT PROPEP 772..817
FT /note="Activation peptide (connecting region)"
FT /evidence="ECO:0000250"
FT /id="PRO_0000409908"
FT CHAIN 818..1459
FT /note="Oscutarin-C non-catalytic subunit light chain"
FT /id="PRO_0000409909"
FT DOMAIN 32..330
FT /note="F5/8 type A 1"
FT DOMAIN 32..196
FT /note="Plastocyanin-like 1"
FT DOMAIN 206..330
FT /note="Plastocyanin-like 2"
FT DOMAIN 351..685
FT /note="F5/8 type A 2"
FT DOMAIN 351..529
FT /note="Plastocyanin-like 3"
FT DOMAIN 539..685
FT /note="Plastocyanin-like 4"
FT DOMAIN 823..1142
FT /note="F5/8 type A 3"
FT DOMAIN 823..991
FT /note="Plastocyanin-like 5"
FT DOMAIN 1000..1142
FT /note="Plastocyanin-like 6"
FT DOMAIN 1146..1297
FT /note="F5/8 type C 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DOMAIN 1302..1456
FT /note="F5/8 type C 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT REGION 693..817
FT /note="B"
FT REGION 740..759
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 740..758
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 124
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7SZN0"
FT BINDING 139
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7SZN0"
FT BINDING 142
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7SZN0"
FT BINDING 143
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q7SZN0"
FT BINDING 919
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7SZN0"
FT BINDING 934
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7SZN0"
FT BINDING 937
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7SZN0"
FT BINDING 938
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q7SZN0"
FT SITE 771..772
FT /note="Cleavage; by thrombin"
FT /evidence="ECO:0000250"
FT SITE 817..818
FT /note="Cleavage; by thrombin"
FT /evidence="ECO:0000250"
FT CARBOHYD 156
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 242
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 300
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 385
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 406
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 471
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 557
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 943
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1000
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1179
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 1396
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 170..196
FT /evidence="ECO:0000250|UniProtKB:Q7SZN0"
FT DISULFID 251..332
FT /evidence="ECO:0000250|UniProtKB:Q7SZN0"
FT DISULFID 503..529
FT /evidence="ECO:0000250|UniProtKB:Q7SZN0"
FT DISULFID 672..1031
FT /evidence="ECO:0000250|UniProtKB:Q7SZN0"
FT DISULFID 965..991
FT /evidence="ECO:0000250|UniProtKB:Q7SZN0"
FT DISULFID 1146..1297
FT /evidence="ECO:0000250|UniProtKB:Q7SZN0"
FT DISULFID 1302..1456
FT /evidence="ECO:0000250|UniProtKB:Q7SZN0"
FT CONFLICT 38
FT /note="L -> I (in Ref. 2; AAY47065)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="R -> W (in Ref. 2; AAY47065)"
FT /evidence="ECO:0000305"
FT CONFLICT 385
FT /note="Missing (in Ref. 2; AAY47065)"
FT /evidence="ECO:0000305"
FT CONFLICT 526
FT /note="P -> L (in Ref. 2; AAY47065)"
FT /evidence="ECO:0000305"
FT CONFLICT 820
FT /note="N -> Y (in Ref. 2; AAY47065)"
FT /evidence="ECO:0000305"
FT CONFLICT 1219
FT /note="Q -> H (in Ref. 2; AAY47065)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1459 AA; 166240 MW; E03B1CB20FDD5BDA CRC64;
MGRYSVSPVP KCLLLMFLGW SGLKYYQVNA AQLREYRLAA QLEDWDYNPQ PEELSRLSES
DLTFKKIVYR EYELDFKQEK PRDELSGLLG PTLRGEVGDS LIIYFKNFAT QPVSIHPQSA
VYNKWSEGSS YSDGTSDVER LDDAVPPGQS FKYVWNITAE IGPKKADPPC LTYAYYSHVN
MVRDFNSGLI GALLICKEGS LNADGAQKFF NREYVLMFSV FDESKNWYRK PSLQYTINGF
ANGTLPDVQA CAYDHISWHL IGMSSSPEIF SVHFNGQTLE QNHYKVSTIN LVGGASVTAN
MSVSRTGKWL ISSLVAKHLQ AGMYGYLNIK DCGNPDTLTR KLSFRERRRI MKWEYFIAAE
EITWDYAPEI PSSVDRRYKA QYLDNFSNFI GKKYKKAVFR QYEDSNFTKP TYAIWPKERG
ILGPVIKAKV RDTVTIVFKN LASRPYSIYV HGVSVSKDAE GAVYPSDPKE NITHGKAVEP
GQVYTYKWTV LDTDEPTVKD SECITKLYHS AVDMTRDIAS GLIGPPLVCK RKALSIRGVQ
NKADVEQHAV FAVFDENKSW YLEDNIKKYC SNPSSVKKDD PKFYKSNVMY TLNGYASDRT
EVWGFHQSEV VEWHLTSVGT VDEIVPVHLS GHTFLSKGKH QDILNLFPMS GESATVTMDN
LGTWLLSSWG SCEMSNGMRL RFLDANYDDE DEGNEEEEED DGDIFADIFN PPEVVIKKEE
VPVNFVPDPE SDALAKELGL FDDEDNPKQS RSEQTEDDEE QLMIASMLGL RSFKGSVAEE
ELKHTALALE EDAHASDPRI DSNSAHNSDD IAGRYLRTIN RRNKRRYYIA AEEVLWDYSP
IGKSQVRSLP AKTTFKKAIF RSYLDDTFQT PSTGGEYEKH LGILGPIIRA EVDDVIEVQF
RNLASRPYSL HAHGLLYEKS SEGRSYDDNS PELFKKDDAI MPNGTYTYVW QVPPRSGPTD
NTEKCKSWAY YSGVNPEKDI HSGLIGPILI CQKGMIDKYN RTIDIREFVL FFMVFDEEKS
WYFPKSDKST CEEKLIGVQS RHTFPAINGI PYQLQGLMMY KDENVHWHLL NMGGPKDVHV
VNFHGQTFTE EGREDNQLGV LPLLPGTFAS IKMKPSKIGT WLLETEVGEN QERGMQALFT
VIDKDCKLPM GLASGIIQDS QISASGHVGY WEPKLARLNN TGMFNAWSII KKEHEHPWIQ
IDLQRQVVIT GIQTQGTVQL LKHSYTVEYF VTYSKDGQNW ITFKGRHSKT QMHFEGNSDG
TTVKENHIDP PIIARYIRLH PTKFYNTPTF RIELLGCEVE GCSVPLGMES GAIKDSEITA
SSYKKTWWSS WEPFLARLNL KGRTNAWQPK VNNKDQWLQI DLQHLTKITS IITQGATSMT
TSMYVKTFSI HYTDDNSTWK PYLDVRTSME KVFTGNINSD GHVKHFFNPP ILSRFIRIIP
KTWNQYIALR IELFGCEVF
