FAXD1_NOTSC
ID FAXD1_NOTSC Reviewed; 455 AA.
AC P82807; Q4F879;
DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 28-JUN-2011, sequence version 2.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Venom prothrombin activator notecarin-D1;
DE Short=vPA;
DE EC=3.4.21.6;
DE AltName: Full=Venom coagulation factor Xa-like protease;
DE Contains:
DE RecName: Full=Notecarin-D1 light chain;
DE Contains:
DE RecName: Full=Notecarin-D1 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;
RA Panizzi P.R., Panizzi J.R., Bock P.E.;
RT "Notecarin D, a prothrombin activator and factor Xa-like protease.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP PROTEIN SEQUENCE OF 41-80; 210-247 AND 296-315, FUNCTION, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND GAMMA-CARBOXYGLUTAMATION AT GLU-46;
RP GLU-47; GLU-54; GLU-56; GLU-59; GLU-60; GLU-65; GLU-66; GLU-69; GLU-72 AND
RP GLU-75.
RC TISSUE=Venom;
RX PubMed=10779512; DOI=10.1074/jbc.m002298200;
RA Brown M.A., Stenberg L.M., Persson U., Stenflo J.;
RT "Identification and purification of vitamin K-dependent proteins and
RT peptides with monoclonal antibodies specific for gamma-carboxyglutamyl
RT (Gla) residues.";
RL J. Biol. Chem. 275:19795-19802(2000).
RN [3]
RP PROTEIN SEQUENCE OF 41-76 AND 210-235, 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 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 [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).
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:10779512,
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 -!- SUBUNIT: Heterodimer of a light chain and a heavy chain; disulfide-
CC linked. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10779512,
CC ECO:0000269|PubMed:12403650}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000269|PubMed:10779512, 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:10779512,
CC 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 contains its own coagulation factor V-like.
CC -!- MISCELLANEOUS: 2 isoforms of notecarin D (D1 and D2) are described in
CC PubMed:12403650. We chose to name this protein D1 according to the
CC masses 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; DQ104218; AAZ14091.1; -; mRNA.
DR AlphaFoldDB; P82807; -.
DR SMR; P82807; -.
DR MEROPS; S01.426; -.
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; Signal; Toxin.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..40
FT /evidence="ECO:0000250"
FT /id="PRO_0000409723"
FT CHAIN 41..181
FT /note="Notecarin-D1 light chain"
FT /id="PRO_0000027819"
FT PROPEP 182..209
FT /note="Activation peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000409724"
FT CHAIN 210..455
FT /note="Notecarin-D1 heavy chain"
FT /id="PRO_0000027821"
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 MOD_RES 46
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10779512, ECO:0000269|PubMed:12403650"
FT MOD_RES 47
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10779512, ECO:0000269|PubMed:12403650"
FT MOD_RES 54
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10779512, ECO:0000269|PubMed:12403650"
FT MOD_RES 56
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10779512, ECO:0000269|PubMed:12403650"
FT MOD_RES 59
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10779512, ECO:0000269|PubMed:12403650"
FT MOD_RES 60
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10779512, ECO:0000269|PubMed:12403650"
FT MOD_RES 65
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10779512, ECO:0000269|PubMed:12403650"
FT MOD_RES 66
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10779512, ECO:0000269|PubMed:12403650"
FT MOD_RES 69
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10779512, ECO:0000269|PubMed:12403650"
FT MOD_RES 72
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10779512, ECO:0000269|PubMed:12403650"
FT MOD_RES 75
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:10779512, 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..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"
SQ SEQUENCE 455 AA; 51464 MW; F70377EA9A05BCD2 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 GRIRFKEPTS
NTLKVITVPY VDRHTCMLSS DFRITQNMFC AGYDTLPQDA CQGDSGGPHI TAYRDTHFIT
GIISWGEGCA RKGKYGVYTK VSRFIPWIKK IMSLK
