FAXD_HOPST
ID FAXD_HOPST Reviewed; 455 AA.
AC P83370; Q58L92;
DT 11-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 2.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Venom prothrombin activator hopsarin-D;
DE Short=vPA;
DE EC=3.4.21.6;
DE AltName: Full=Venom coagulation factor Xa-like protease;
DE Contains:
DE RecName: Full=Hopsarin-D light chain;
DE Contains:
DE RecName: Full=Hopsarin-D heavy chain;
DE Flags: Precursor;
OS Hoplocephalus stephensii (Stephens' banded snake).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Notechinae; Hoplocephalus.
OX NCBI_TaxID=196418 {ECO:0000305};
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 PROTEIN SEQUENCE OF 41-181 AND 210-455, FUNCTION, CATALYTIC ACTIVITY,
RP SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GAMMA-CARBOXYGLUTAMATION
RP AT GLU-46; GLU-47; GLU-54; GLU-56; GLU-59; GLU-60; GLU-65; GLU-66; GLU-69;
RP GLU-72 AND GLU-75, GLYCOSYLATION AT SER-92 AND ASN-254, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=12403650; DOI=10.1042/bj20020889;
RA Rao V.S., Joseph J.S., Kini R.M.;
RT "Group D prothrombin activators from snake venom are structural homologues
RT of mammalian blood coagulation factor Xa.";
RL Biochem. J. 369:635-642(2003).
RN [3]
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. This protein is functionally similar to blood
CC coagulation factor Xa. The procoagulant activity of hopsarin-D is
CC approximately 10-fold lower than that of trocarin-D and FXa.
CC {ECO:0000269|PubMed:12403650}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Selective cleavage of Arg-|-Thr and then Arg-|-Ile bonds in
CC prothrombin to form thrombin.; EC=3.4.21.6;
CC Evidence={ECO:0000269|PubMed:12403650};
CC -!- SUBUNIT: Heterodimer of a light chain and a heavy chain; disulfide-
CC linked. {ECO:0000269|PubMed:12403650}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12403650}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000269|PubMed:12403650}.
CC -!- PTM: The vitamin K-dependent, enzymatic carboxylation of some glutamate
CC residues allows the modified protein to bind calcium. {ECO:0000250}.
CC -!- MISCELLANEOUS: Is classified in the group D of snake venom prothrombin
CC activators, since it requires the mammalian factor Va for maximal
CC activity for the cleavage of prothrombin.
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.
CC -!- SIMILARITY: Belongs to the peptidase S1 family. Snake venom subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00274}.
CC -!- CAUTION: Lacks the Cys residue in position 216 that is replaced by a
CC Ser residue, resulting of a loss a disulfide bond. This may contribute
CC to the lower procoagulant activity. {ECO:0000305}.
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DR EMBL; AY940208; AAX37264.1; -; mRNA.
DR AlphaFoldDB; P83370; -.
DR SMR; P83370; -.
DR MEROPS; S01.426; -.
DR iPTMnet; P83370; -.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0016504; F:peptidase activator activity; IEA:UniProtKB-KW.
DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0007596; P:blood coagulation; IEA:InterPro.
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 GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 4.10.740.10; -; 1.
DR InterPro; IPR017857; Coagulation_fac-like_Gla_dom.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site.
DR InterPro; IPR018097; EGF_Ca-bd_CS.
DR InterPro; IPR035972; GLA-like_dom_SF.
DR InterPro; IPR000294; GLA_domain.
DR InterPro; IPR012224; Pept_S1A_FX.
DR InterPro; IPR009003; Peptidase_S1_PA.
DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin.
DR InterPro; IPR001314; Peptidase_S1A.
DR InterPro; IPR001254; Trypsin_dom.
DR InterPro; IPR018114; TRYPSIN_HIS.
DR InterPro; IPR033116; TRYPSIN_SER.
DR Pfam; PF00008; EGF; 1.
DR Pfam; PF00594; Gla; 1.
DR Pfam; PF00089; Trypsin; 1.
DR PIRSF; PIRSF001143; Factor_X; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR PRINTS; PR00001; GLABLOOD.
DR SMART; SM00181; EGF; 2.
DR SMART; SM00179; EGF_CA; 1.
DR SMART; SM00069; GLA; 1.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57630; SSF57630; 1.
DR PROSITE; PS00010; ASX_HYDROXYL; 1.
DR PROSITE; PS00022; EGF_1; 1.
DR PROSITE; PS50026; EGF_3; 1.
DR PROSITE; PS01187; EGF_CA; 1.
DR PROSITE; PS00011; GLA_1; 1.
DR PROSITE; PS50998; GLA_2; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 1: Evidence at protein level;
KW Blood coagulation cascade activating toxin; Calcium;
KW Direct protein sequencing; Disulfide bond; EGF-like domain;
KW Gamma-carboxyglutamic acid; Glycoprotein; Hemostasis impairing toxin;
KW Hydrolase; Protease; Prothrombin activator; Repeat; Secreted;
KW Serine protease; Signal; Toxin.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..40
FT /evidence="ECO:0000250"
FT /id="PRO_0000409722"
FT CHAIN 41..181
FT /note="Hopsarin-D light chain"
FT /id="PRO_0000027816"
FT PROPEP 182..209
FT /note="Activation peptide"
FT /evidence="ECO:0000269|PubMed:12403650"
FT /id="PRO_5000095361"
FT CHAIN 210..455
FT /note="Hopsarin-D heavy chain"
FT /id="PRO_0000027817"
FT DOMAIN 41..86
FT /note="Gla"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463"
FT DOMAIN 86..121
FT /note="EGF-like 1; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 129..164
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 210..453
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 251
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 308
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 405
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT SITE 103
FT /note="Not modified"
FT MOD_RES 46
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:12403650"
FT MOD_RES 47
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:12403650"
FT MOD_RES 54
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:12403650"
FT MOD_RES 56
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:12403650"
FT MOD_RES 59
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:12403650"
FT MOD_RES 60
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:12403650"
FT MOD_RES 65
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:12403650"
FT MOD_RES 66
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:12403650"
FT MOD_RES 69
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:12403650"
FT MOD_RES 72
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:12403650"
FT MOD_RES 75
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:12403650"
FT CARBOHYD 92
FT /note="O-linked (Hex...) serine"
FT /evidence="ECO:0000269|PubMed:12403650"
FT CARBOHYD 254
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12403650"
FT DISULFID 57..62
FT /evidence="ECO:0000250"
FT DISULFID 90..101
FT /evidence="ECO:0000250"
FT DISULFID 95..110
FT /evidence="ECO:0000250"
FT DISULFID 112..121
FT /evidence="ECO:0000250"
FT DISULFID 129..140
FT /evidence="ECO:0000250"
FT DISULFID 136..149
FT /evidence="ECO:0000250"
FT DISULFID 151..164
FT /evidence="ECO:0000250"
FT DISULFID 172..328
FT /note="Interchain (between light and heavy chains)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076,
FT ECO:0000255|PROSITE-ProRule:PRU00274, ECO:0000255|PROSITE-
FT ProRule:PRU00463"
FT DISULFID 236..252
FT /evidence="ECO:0000250"
FT DISULFID 376..390
FT /evidence="ECO:0000250"
FT DISULFID 401..429
FT /evidence="ECO:0000250"
FT CONFLICT 78
FT /note="E -> T (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 98
FT /note="H -> R (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 260..270
FT /note="Missing (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 402
FT /note="E -> Q (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 455 AA; 51248 MW; 39B5F4442B995E4F CRC64;
MAPQLLLCLI LTFLWSVPEA ESNVFLKSKV ANRFLQRTKR SNSLFEEIRP GNIERECIEE
KCSKEEAREV FEDNEKTETF WNVYVDGDQC SSNPCHYHGT CKDGIGSYTC TCLPNYEGKN
CEKVLFKSCR AFNGNCWHFC KRVQSETQCS CAESYRLGVD GHSCVAEGDF SCGRNIKARN
KREASLPDFV QSQKATLLKK SDNPSPDIRI VNGMDSKLGE CPWQAVLINE KGEVFCGGTI
LSPIHVLTAA HCINQTKSVS VIVGEIDISR KETRRLLSVD KIYVHTKFVP PNYYYGHQNF
DRVAYDYDIA IIRMKTPIQF SENVVPACLP TADFANEVLM KQDSGIVSGF GRIRFKEPTS
NTLKVITVPY VDRHTCMLSS DFRITQNMFC AGYDTLPQDA CEGDSGGPHI TAYGDTHFIT
GIVSWGEGCA RKGKYGVYTK VSRFIPWIKK IMSLK
