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   02-SEP-2026, entry version 128.
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 (Eastern tiger snake) (Naja scutata scutata).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Serpentes; Colubroidea; Elapidae; Hydrophiinae; 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; DOI=10.1055/s-0037-1616108;
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 contain 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}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
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:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0007596; P:blood coagulation; IEA:InterPro.
DR   GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR   GO; GO:0044469; P:venom-mediated blood coagulation; IDA:UniProtKB.
DR   CDD; cd00054; EGF_CA; 1.
DR   CDD; cd00190; Tryp_SPc; 1.
DR   FunFam; 2.10.25.10:FF:000513; Coagulation factor VII; 1.
DR   FunFam; 2.40.10.10:FF:000013; Coagulation factor X; 1.
DR   FunFam; 2.10.25.10:FF:000162; Coagulation factor X (Predicted); 1.
DR   FunFam; 4.10.740.10:FF:000001; vitamin K-dependent protein S; 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; IPR000742; EGF.
DR   InterPro; IPR001881; EGF-like_Ca-bd_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; IPR050442; Peptidase_S1_coag_factors.
DR   InterPro; IPR009003; Peptidase_S1_PA.
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; PF14670; FXa_inhibition; 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; SSF57196; EGF/Laminin; 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; 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
//