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Database: UniProt
Entry: Q56VR3
LinkDB: Q56VR3
Original site: Q56VR3 
ID   FAXC_PSETE              Reviewed;         467 AA.
AC   Q56VR3; A5X463; Q6IT09;
DT   31-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT   28-JUN-2011, sequence version 2.
DT   16-JAN-2019, entry version 100.
DE   RecName: Full=Venom prothrombin activator pseutarin-C catalytic subunit;
DE            Short=PCCS;
DE            Short=vPA;
DE            EC=3.4.21.6;
DE   AltName: Full=Venom coagulation factor Xa-like protease;
DE   Contains:
DE     RecName: Full=Pseutarin-C catalytic subunit light chain;
DE   Contains:
DE     RecName: Full=Pseutarin-C catalytic subunit heavy chain;
DE   Flags: Precursor;
OS   Pseudonaja textilis (Eastern brown snake).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata;
OC   Toxicofera; Serpentes; Colubroidea; Elapidae; Acanthophiinae;
OC   Pseudonaja.
OX   NCBI_TaxID=8673;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], PROTEIN SEQUENCE OF 41-70;
RP   77-119; 142-177; 210-242 AND 271-281, TOXIC DOSE, GLYCOSYLATION AT
RP   SER-92 AND ASN-254, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=Venom gland;
RX   PubMed=15351847; DOI=10.1267/THRO04090509;
RA   Rao V.S., Swarup S., Kini R.M.;
RT   "The catalytic subunit of pseutarin C, a group C prothrombin activator
RT   from the venom of Pseudonaja textilis, is structurally similar to
RT   mammalian blood coagulation factor Xa.";
RL   Thromb. Haemost. 92:509-521(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom gland;
RX   PubMed=16197456; DOI=10.1111/j.1365-2141.2005.05744.x;
RA   Filippovich I., Sorokina N., St Pierre L., Flight S., de Jersey J.,
RA   Perry N., Masci P.P., Lavin M.F.;
RT   "Cloning and functional expression of venom prothrombin activator
RT   protease from Pseudonaja textilis with whole blood procoagulant
RT   activity.";
RL   Br. J. Haematol. 131:237-246(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-17.
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
RT   factor X gene to the venom gland.";
RL   J. Thromb. Haemost. 5:117-126(2007).
RN   [4]
RP   PROTEIN SEQUENCE OF 41-70 AND 210-246, FUNCTION, CATALYTIC ACTIVITY,
RP   ACTIVITY REGULATION, SUBUNIT, SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, AND GAMMA-CARBOXYGLUTAMATION AT GLU-46; GLU-47; GLU-54;
RP   GLU-56; GLU-59; GLU-60; GLU-65 AND GLU-66.
RC   TISSUE=Venom;
RX   PubMed=12362232; DOI=10.1267/th02100611;
RA   Rao V.S., Kini R.M.;
RT   "Pseutarin C, a prothrombin activator from Pseudonaja textilis venom:
RT   its structural and functional similarity to mammalian coagulation
RT   factor Xa-Va complex.";
RL   Thromb. Haemost. 88:611-619(2002).
RN   [5]
RP   TOXIC DOSE, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC   STRAIN=Pseudonaja textilis textilis; TISSUE=Venom;
RX   PubMed=3075905;
RA   Masci P.P., Whitaker A.N., de Jersey J.;
RT   "Purification and characterization of a prothrombin activator from the
RT   venom of the Australian brown snake, Pseudonaja textilis textilis.";
RL   Biochem. Int. 17:825-835(1988).
RN   [6]
RP   NOMENCLATURE.
RX   PubMed=11522026;
RA   Manjunatha Kini R., Morita T., Rosing J.;
RT   "Classification and nomenclature of prothrombin activators isolated
RT   from snake venoms.";
RL   Thromb. Haemost. 86:710-711(2001).
RN   [7]
RP   PHARMACEUTICAL.
RX   PubMed=21184772; DOI=10.1016/j.toxicon.2010.12.010;
RA   Earl S.T., Masci P.P., de Jersey J., Lavin M.F., Dixon J.;
RT   "Drug development from Australian elapid snake venoms and the Venomics
RT   pipeline of candidates for haemostasis: Textilinin-1 (Q8008),
RT   Haempatch (Q8009) and CoVase (V0801).";
RL   Toxicon 59:456-463(2012).
CC   -!- FUNCTION: Snake prothrombin activator that attacks the hemostatic
CC       system of prey. This catalytic subunit is functionally similar to
CC       blood coagulation factor Xa. It requires a non-catalytic subunit
CC       present in the venom, which is similar to coagulation factor Va,
CC       to be fully active. {ECO:0000269|PubMed:12362232}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Selective cleavage of Arg-|-Thr and then Arg-|-Ile bonds
CC         in prothrombin to form thrombin.; EC=3.4.21.6;
CC         Evidence={ECO:0000269|PubMed:12362232};
CC   -!- ACTIVITY REGULATION: Activated by calcium and negatively charged
CC       phospholipids. {ECO:0000269|PubMed:12362232}.
CC   -!- SUBUNIT: Heterodimer of a light and a heavy chains; disulfide-
CC       linked. Is associated with pseutarin-C non-catalytic subunit (AC
CC       Q7SZN0) in a non-covalent manner. {ECO:0000269|PubMed:12362232,
CC       ECO:0000269|PubMed:3075905}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12362232,
CC       ECO:0000269|PubMed:3075905}.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC       {ECO:0000269|PubMed:12362232, ECO:0000269|PubMed:3075905}.
CC   -!- PTM: Gamma-carboxyglutamate residues are formed by vitamin K
CC       dependent carboxylation. These residues are essential for the
CC       binding of calcium. {ECO:0000255|PROSITE-ProRule:PRU00463,
CC       ECO:0000269|PubMed:12362232}.
CC   -!- TOXIC DOSE: Intravenous injection (23 ug/kg bodyweight) of the
CC       group C prothrombin activator causes death in rats through
CC       disseminated intravascular coagulopathy (PubMed:3075905), whereas
CC       pseutarin-C is not lethal even at 10 mg/kg in mice when injected
CC       intraperitoneally (PubMed:15351847). {ECO:0000269|PubMed:15351847,
CC       ECO:0000269|PubMed:3075905}.
CC   -!- PHARMACEUTICAL: Is under preclinical trial by the Australian
CC       biopharmaceutical company QRxPharma Ltd, its subsidiary Venomics
CC       Pty Ltd (VPL) and the University of Queensland (UQ) under the name
CC       Haempatch (Q8009). Tested as a topical hemostatic agent to reduce
CC       blood loss resulting from surgery or trauma.
CC   -!- MISCELLANEOUS: Is classified in the group C of snake venom
CC       prothrombin activators, since it does not require the mammalian
CC       factor Va for the cleavage of prothrombin as the venom contains
CC       its own non-catalytic factor Va-like molecule.
CC   -!- MISCELLANEOUS: In contrast to blood coagulation factors that
CC       circulate as inactive zymogen in plasma, venom prothrombin
CC       activators are always found in the active form in the venom.
CC       Hence, catalytic and non-catalytic subunits are found naturally in
CC       venom as stable complexes.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family. Snake venom
CC       subfamily. {ECO:0000255|PROSITE-ProRule:PRU00274}.
DR   EMBL; AY260939; AAP86642.1; -; mRNA.
DR   EMBL; AY631239; AAT42491.1; -; mRNA.
DR   EMBL; DQ533835; ABG02407.1; -; Genomic_DNA.
DR   ProteinModelPortal; Q56VR3; -.
DR   SMR; Q56VR3; -.
DR   iPTMnet; Q56VR3; -.
DR   HOVERGEN; HBG013304; -.
DR   BRENDA; 3.4.21.60; 6821.
DR   GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR   GO; GO:0032991; C:protein-containing complex; 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 other organism; IDA:UniProtKB.
DR   GO; GO:0035807; P:positive regulation of blood coagulation in other organism; IDA:UniProtKB.
DR   CDD; cd00190; Tryp_SPc; 1.
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; IPR013032; EGF-like_CS.
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; IPR009030; Growth_fac_rcpt_cys_sf.
DR   InterPro; IPR012224; Pept_S1A_FX.
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   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; SSF57184; SSF57184; 1.
DR   SUPFAM; SSF57630; SSF57630; 1.
DR   PROSITE; PS00010; ASX_HYDROXYL; 1.
DR   PROSITE; PS00022; EGF_1; 1.
DR   PROSITE; PS01186; EGF_2; 2.
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;
KW   Glycoprotein; Hemostasis impairing toxin; Hydrolase; Pharmaceutical;
KW   Protease; Prothrombin activator; Repeat; Secreted; Serine protease;
KW   Signal; Toxin.
FT   SIGNAL        1     20       {ECO:0000255}.
FT   PROPEP       21     40       {ECO:0000269|PubMed:12362232,
FT                                ECO:0000269|PubMed:15351847}.
FT                                /FTId=PRO_0000408523.
FT   CHAIN        41    181       Pseutarin-C catalytic subunit light
FT                                chain.
FT                                /FTId=PRO_5000090539.
FT   PROPEP      182    209       Activation peptide. {ECO:0000250}.
FT                                /FTId=PRO_0000408525.
FT   CHAIN       210    467       Pseutarin-C catalytic subunit heavy
FT                                chain.
FT                                /FTId=PRO_0000408526.
FT   DOMAIN       41     86       Gla. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463}.
FT   DOMAIN       86    122       EGF-like 1; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN      129    164       EGF-like 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      210    454       Peptidase S1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00274}.
FT   ACT_SITE    251    251       Charge relay system. {ECO:0000250}.
FT   ACT_SITE    309    309       Charge relay system. {ECO:0000250}.
FT   ACT_SITE    406    406       Charge relay system. {ECO:0000250}.
FT   SITE         75     75       Not modified. {ECO:0000305}.
FT   SITE        103    103       Not modified.
FT   SITE        209    210       Cleavage.
FT   MOD_RES      46     46       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:12362232}.
FT   MOD_RES      47     47       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:12362232}.
FT   MOD_RES      54     54       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:12362232}.
FT   MOD_RES      56     56       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:12362232}.
FT   MOD_RES      59     59       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:12362232}.
FT   MOD_RES      60     60       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:12362232}.
FT   MOD_RES      65     65       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:12362232}.
FT   MOD_RES      66     66       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:12362232}.
FT   MOD_RES      69     69       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463}.
FT   MOD_RES      72     72       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463}.
FT   CARBOHYD     92     92       O-linked (Hex...) serine.
FT                                {ECO:0000269|PubMed:15351847}.
FT   CARBOHYD    254    254       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:15351847}.
FT   DISULFID     57     62       {ECO:0000250}.
FT   DISULFID     90    101       {ECO:0000250}.
FT   DISULFID     95    110       {ECO:0000250}.
FT   DISULFID    112    121       {ECO:0000250}.
FT   DISULFID    129    140       {ECO:0000250}.
FT   DISULFID    136    149       {ECO:0000250}.
FT   DISULFID    151    164       {ECO:0000250}.
FT   DISULFID    172    329       Interchain (between light and heavy
FT                                chains). {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076, ECO:0000255|PROSITE-
FT                                ProRule:PRU00274, ECO:0000255|PROSITE-
FT                                ProRule:PRU00463}.
FT   DISULFID    216    221       {ECO:0000250}.
FT   DISULFID    236    252       {ECO:0000250}.
FT   DISULFID    377    391       {ECO:0000250}.
FT   DISULFID    402    430       {ECO:0000250}.
FT   CONFLICT     70     70       V -> A (in Ref. 1; AAP86642).
FT                                {ECO:0000305}.
FT   CONFLICT    193    193       H -> Q (in Ref. 1; AAP86642).
FT                                {ECO:0000305}.
FT   CONFLICT    196    196       T -> P (in Ref. 1; AAP86642).
FT                                {ECO:0000305}.
FT   CONFLICT    200    200       K -> I (in Ref. 1; AAP86642).
FT                                {ECO:0000305}.
FT   CONFLICT    450    467       Missing (in Ref. 1; AAP86642).
FT                                {ECO:0000305}.
SQ   SEQUENCE   467 AA;  52215 MW;  C773D41DB08F9844 CRC64;
     MAPQLLLCLI LTFLWSLPEA ESNVFLKSKV ANRFLQRTKR ANSLVEEFKS GNIERECIEE
     RCSKEEAREV FEDDEKTETF WNVYVDGDQC SSNPCHYRGI CKDGIGSYTC TCLSGYEGKN
     CERVLYKSCR VDNGNCWHFC KSVQNDIQCS CAEGYLLGED GHSCVAGGNF SCGRNIKTRN
     KREASLPDFV QSHNATLLKK SDNPSPDIRI VNGMDCKLGE CPWQAALVDD KKGVFCGGTI
     LSPIYVLTAA HCINETETIS VVVGEIDRSR AETGPLLSVD KVYVHKKFVP PKKSQEFYEK
     FDLVSYDYDI AIIQMKTPIQ FSENVVPACL PTADFANQVL MKQDFGIVSG FGGIFERGPN
     SKTLKVLKVP YVDRHTCMLS SNFPITPTMF CAGYDTLPQD ACQGDSGGPH ITAYRDTHFI
     TGIVSWGEGC ARKGRYGIYT KLSKFIPWIK RIMRQKLPST ESSTGRL
//
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