ID FAXD2_NOTSC Reviewed; 453 AA.
AC Q58L94;
DT 28-JUN-2011, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 08-NOV-2023, entry version 113.
DE RecName: Full=Venom prothrombin activator notecarin-D2;
DE Short=vPA;
DE EC=3.4.21.6;
DE AltName: Full=Venom coagulation factor Xa-like protease;
DE Contains:
DE RecName: Full=Notecarin-D2 light chain;
DE Contains:
DE RecName: Full=Notecarin-D2 heavy chain;
DE Flags: Precursor;
OS Notechis scutatus scutatus (Mainland tiger snake) (Common tiger snake).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Acanthophiinae; Notechis.
OX NCBI_TaxID=70142;
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 41-76 AND 210-235, FUNCTION, SUBUNIT, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, GAMMA-CARBOXYGLUTAMATION AT GLU-46; GLU-47;
RP GLU-54; GLU-56; GLU-59; GLU-60; GLU-65; GLU-66; GLU-69; GLU-72 AND GLU-75,
RP AND IDENTIFICATION 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. {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 -!- 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: 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:12403650}.
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. The venom of this species
CC does not contain its own coagulation factor V-like.
CC -!- MISCELLANEOUS: PubMed:12403650 describes 2 isoforms of notecarin D (D1
CC and D2). We chose to name this protein D1 according to the masses
CC indicated in the paper.
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; AY940206; AAX37262.1; -; mRNA.
DR AlphaFoldDB; Q58L94; -.
DR SMR; Q58L94; -.
DR MEROPS; S01.425; -.
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:induction of blood coagulation in another organism; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00054; EGF_CA; 1.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 4.10.740.10; Coagulation Factor IX; 1.
DR Gene3D; 2.10.25.10; Laminin; 2.
DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2.
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 PANTHER; PTHR24278; COAGULATION FACTOR; 1.
DR PANTHER; PTHR24278:SF28; COAGULATION FACTOR X; 1.
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; SSF57630; GLA-domain; 1.
DR SUPFAM; SSF50494; Trypsin-like serine proteases; 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; Signal; Toxin.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..40
FT /evidence="ECO:0000250"
FT /id="PRO_0000409893"
FT CHAIN 41..181
FT /note="Notecarin-D2 light chain"
FT /id="PRO_5000095352"
FT PROPEP 182..209
FT /note="Activation peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_5000095353"
FT CHAIN 210..453
FT /note="Notecarin-D2 heavy chain"
FT /id="PRO_5000095354"
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..451
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 306
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 403
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
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:0000250"
FT CARBOHYD 254
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
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..326
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 374..388
FT /evidence="ECO:0000250"
FT DISULFID 399..427
FT /evidence="ECO:0000250"
SQ SEQUENCE 453 AA; 50872 MW; 6AEF16F233F64EED CRC64;
MAPQLLLCLI LTFLWSLPEA ESNVFLKSKV ANRFLQRTKR SNSLFEEIRP GNIERECIEE
KCSKEEAREV FEDNEKTETF WNVYVDGDQC SSNPCHYRGT CKDGIGSYTC TCLPNYEGKN
CEKVLFKSCR AFNGNCWHFC KRVQSETQCS CAESYLLGVD GHSCVAEGDF SCGRNIKARN
KREASLPDFV QSQKATVLKK SDNPSPDIRI VNGMDCKLGE CPWQAVLINE KGEVFCGGTI
LSPIHVLTAA HCINQTKSVS VIVGEIDISR KETRRLLSVD KIYVHKKFVP PNSYYQNIDR
FAYDYDIAII RMKTPIQFSE NVVPACLPTA DFAKEVLMKQ DSGIVSGFGR TQSIGYTSNI
LKVITVPYVD RHTCMLSSNF RITQNMFCAG YDTLPQDACQ GDSGGPHITA YGDTHFVTGI
ISWGEGCARK GKYGVYTKVS NFIPWIKKIM SLK
//
