FAXD_TROCA
ID FAXD_TROCA Reviewed; 455 AA.
AC P81428; Q1L657; Q5UAE9;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 06-DEC-2005, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Venom prothrombin activator trocarin-D;
DE Short=vPA;
DE EC=3.4.21.6;
DE AltName: Full=Venom coagulation factor Xa-like protease;
DE Contains:
DE RecName: Full=Trocarin-D light chain;
DE Contains:
DE RecName: Full=Trocarin-D heavy chain;
DE Flags: Precursor;
OS Tropidechis carinatus (Australian rough-scaled snake).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Notechinae; Tropidechis.
OX NCBI_TaxID=100989;
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 [GENOMIC DNA / MRNA].
RC TISSUE=Venom gland;
RX PubMed=17239167; DOI=10.1111/j.1538-7836.2006.02266.x;
RA Reza M.A., Swarup S., Kini R.M.;
RT "Structure of two genes encoding parallel prothrombin activators in
RT Tropidechis carinatus snake: gene duplication and recruitment of factor X
RT gene to the venom gland.";
RL J. Thromb. Haemost. 5:117-126(2007).
RN [3]
RP PROTEIN SEQUENCE OF 41-181 AND 210-455, FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, GAMMA-CARBOXYGLUTAMATION AT GLU-46; GLU-47; GLU-54;
RP GLU-56; GLU-59; GLU-60; GLU-65; GLU-66; GLU-69; GLU-72 AND GLU-75, AND
RP GLYCOSYLATION AT SER-92 AND ASN-254.
RC TISSUE=Venom;
RX PubMed=10397729;
RA Joseph J.S., Chung M.C.M., Jeyaseelan K., Kini R.M.;
RT "Amino acid sequence of trocarin, a prothrombin activator from Tropidechis
RT carinatus venom: its structural similarity to coagulation factor Xa.";
RL Blood 94:621-631(1999).
RN [4]
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).
RN [5]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION AT SER-92 AND
RP ASN-254, SIALIC ACID CONTENT, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=12871464; DOI=10.1046/j.1538-7836.2003.00090.x;
RA Joseph J.S., Valiyaveettil M., Gowda D.C., Kini R.M.;
RT "Occurrence of O-linked Xyl-GlcNAc and Xyl-Glc disaccharides in trocarin, a
RT factor Xa homolog from snake venom.";
RL J. Thromb. Haemost. 1:545-550(2003).
CC -!- FUNCTION: Snake prothrombin activator that attacks the hemostatic
CC system of prey. This protein is functionally similar to blood
CC coagulation factor Xa. Induces cyanosis and death in mice at 1 mg/kg
CC body weight during blood clotting. {ECO:0000269|PubMed:10397729}.
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 -!- ACTIVITY REGULATION: Activated by calcium and phospholipids.
CC -!- SUBUNIT: Heterodimer of a light chain and a heavy chain; disulfide-
CC linked.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10397729,
CC ECO:0000269|PubMed:12871464}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000269|PubMed:10397729, ECO:0000269|PubMed:12871464}.
CC -!- PTM: Gamma-carboxyglutamate residues are formed by vitamin K dependent
CC carboxylation. These residues are essential for the binding of calcium.
CC {ECO:0000255|PROSITE-ProRule:PRU00463, ECO:0000269|PubMed:10397729}.
CC -!- PTM: The O-linked saccharides at Ser-92 are a mixture of Xyl-Glc, and
CC Glc along with smaller amounts of Xyl-GlcNAc, GlcNAc, Gal, GalNAc, Xyl-
CC Gal, and Xyl-GalNAc, suggesting that the glycosyl transferases
CC responsible for this modification are non-specific. The N-linked
CC carbohydrate at Asn-254 (Asn-45 of the heavy chain) is a sialylated and
CC diantennary oligosaccharide. {ECO:0000269|PubMed:10397729,
CC ECO:0000269|PubMed:12871464}.
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}.
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DR EMBL; AY769963; AAV34695.1; -; mRNA.
DR EMBL; DQ017707; AAY85309.1; -; mRNA.
DR EMBL; DQ533832; ABG02404.1; -; Genomic_DNA.
DR AlphaFoldDB; P81428; -.
DR SMR; P81428; -.
DR MEROPS; S01.425; -.
DR GlyConnect; 103; 1 N-Linked glycan, 6 O-Linked glycans.
DR iPTMnet; P81428; -.
DR PRIDE; P81428; -.
DR BRENDA; 3.4.21.6; 14115.
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 Cleavage on pair of basic residues; Direct protein sequencing;
KW Disulfide bond; EGF-like domain; Gamma-carboxyglutamic acid; Glycoprotein;
KW Hemostasis impairing toxin; Hydrolase; Protease; Prothrombin activator;
KW Repeat; Secreted; Serine protease; Sialic acid; Signal; Toxin.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..40
FT /evidence="ECO:0000269|PubMed:10397729"
FT /id="PRO_0000043207"
FT CHAIN 41..181
FT /note="Trocarin-D light chain"
FT /id="PRO_0000027822"
FT PROPEP 182..209
FT /note="Activation peptide"
FT /evidence="ECO:0000269|PubMed:10397729"
FT /id="PRO_0000043208"
FT CHAIN 210..455
FT /note="Trocarin-D heavy chain"
FT /id="PRO_0000027823"
FT DOMAIN 41..86
FT /note="Gla"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463"
FT DOMAIN 86..122
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:10397729"
FT MOD_RES 47
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10397729"
FT MOD_RES 54
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10397729"
FT MOD_RES 56
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10397729"
FT MOD_RES 59
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10397729"
FT MOD_RES 60
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10397729"
FT MOD_RES 65
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10397729"
FT MOD_RES 66
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10397729"
FT MOD_RES 69
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10397729"
FT MOD_RES 72
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10397729"
FT MOD_RES 75
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10397729"
FT CARBOHYD 92
FT /note="O-linked (Hex...) serine"
FT /evidence="ECO:0000269|PubMed:10397729,
FT ECO:0000269|PubMed:12871464"
FT CARBOHYD 254
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:10397729,
FT ECO:0000269|PubMed:12871464"
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 216..221
FT /evidence="ECO:0000250"
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 260..270
FT /note="Missing (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 455 AA; 51407 MW; 65C8571B662782DC CRC64;
MAPQLLLCLI LTFLWSLPEA ESNVFLKSKV ANRFLQRTKR SNSLFEEIRP GNIERECIEE
KCSKEEAREV FEDNEKTETF WNVYVDGDQC SSNPCHYRGT CKDGIGSYTC TCLPNYEGKN
CEKVLYQSCR VDNGNCWHFC KRVQSETQCS CAESYRLGVD GHSCVAEGDF SCGRNIKARN
KREASLPDFV QSQKATLLKK SDNPSPDIRI VNGMDCKLGE CPWQAVLINE KGEVFCGGTI
LSPIHVLTAA HCINQTKSVS VIVGEIDISR KETRRLLSVD KIYVHTKFVP PNYYYVHQNF
DRVAYDYDIA IIRMKTPIQF SENVVPACLP TADFANEVLM KQDSGIVSGF GRIQFKQPTS
NTLKVITVPY VDRHTCMLSS DFRITQNMFC AGYDTLPQDA CQGDSGGPHI TAYRDTHFIT
GIISWGEGCA RKGKYGVYTK VSKFIPWIKK IMSLK
