PA2B4_NAJNG
ID PA2B4_NAJNG Reviewed; 118 AA.
AC P00605;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 21-JUL-1986, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Phospholipase A2 'basic';
DE Short=svPLA2;
DE EC=3.1.1.4;
DE AltName: Full=Phosphatidylcholine 2-acylhydrolase;
DE AltName: Full=Phospholipase A2 isozyme III/IV;
DE Short=CM-III/CM-IV;
OS Naja nigricollis (Black-necked spitting cobra).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Elapinae; Naja.
OX NCBI_TaxID=8654;
RN [1]
RP PROTEIN SEQUENCE.
RC TISSUE=Venom;
RA Eaker D.;
RT "Structure and function of snake venom toxins.";
RL (In) Walter R., Meieihofer J. (eds.);
RL Peptides: chemistry, structure and function, pp.17-30, Ann Arbor Science,
RL Ann Arbor (1975).
RN [2]
RP PROTEIN SEQUENCE OF 1-25.
RC TISSUE=Venom;
RX PubMed=7364769; DOI=10.1016/s0021-9258(19)85774-5;
RA Evans H.J., Franson R., Qureshi G.D., Moo-Penn W.F.;
RT "Isolation of anticoagulant proteins from cobra venom (Naja nigricollis).
RT Identity with phospholipases A2.";
RL J. Biol. Chem. 255:3793-3797(1980).
RN [3]
RP FUNCTION.
RX PubMed=2814939; DOI=10.1016/0049-3848(89)90056-x;
RA Stefansson S., Kini R.M., Evans H.J.;
RT "The inhibition of clotting complexes of the extrinsic coagulation cascade
RT by the phospholipase A2 isoenzymes from Naja nigricollis venom.";
RL Thromb. Res. 55:481-491(1989).
RN [4]
RP FUNCTION.
RX PubMed=2271532; DOI=10.1021/bi00485a024;
RA Stefansson S., Kini R.M., Evans H.J.;
RT "The basic phospholipase A2 from Naja nigricollis venom inhibits the
RT prothrombinase complex by a novel nonenzymatic mechanism.";
RL Biochemistry 29:7742-7746(1990).
RN [5]
RP FUNCTION.
RX PubMed=8866616; DOI=10.1016/0041-0101(95)00103-4;
RA Kini R.M., Evans H.J.;
RT "The role of enzymatic activity in inhibition of the extrinsic tenase
RT complex by phospholipase A2 isoenzymes from Naja nigricollis venom.";
RL Toxicon 33:1585-1590(1995).
RN [6]
RP FUNCTION.
RX PubMed=10462445; DOI=10.1006/abbi.1999.1345;
RA Kerns R.T., Kini R.M., Stefansson S., Evans H.J.;
RT "Targeting of venom phospholipases: the strongly anticoagulant
RT phospholipase A(2) from Naja nigricollis venom binds to coagulation factor
RT Xa to inhibit the prothrombinase complex.";
RL Arch. Biochem. Biophys. 369:107-113(1999).
RN [7]
RP REVIEW, AND MOTIF.
RX PubMed=15922780; DOI=10.1016/j.toxicon.2005.02.018;
RA Kini R.M.;
RT "Structure-function relationships and mechanism of anticoagulant
RT phospholipase A2 enzymes from snake venoms.";
RL Toxicon 45:1147-1161(2005).
CC -!- FUNCTION: Snake venom phospholipase A2 (PLA2) that shows strong
CC anticoagulant activity. Binds directly with the coagulation factor FXa
CC (F10) and blocks the formation of the prothombinase complex. Acts by a
CC nonenzymatic mechanism (PubMed:10462445). Also inhibits the complex
CC composed of tissue factor (F3) and coagulation factor VIIa (F7) (TF-
CC VIIa complex) by both enzymatic and nonenzymatic mechanisms
CC (PubMed:8866616). PLA2 catalyzes the calcium-dependent hydrolysis of
CC the 2-acyl groups in 3-sn-phosphoglycerides.
CC {ECO:0000269|PubMed:10462445, ECO:0000269|PubMed:2271532,
CC ECO:0000269|PubMed:2814939, ECO:0000269|PubMed:8866616}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine + H2O = a 1-acyl-sn-
CC glycero-3-phosphocholine + a fatty acid + H(+); Xref=Rhea:RHEA:15801,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868,
CC ChEBI:CHEBI:57643, ChEBI:CHEBI:58168; EC=3.1.1.4;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10035, ECO:0000255|PROSITE-
CC ProRule:PRU10036};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Note=Binds 1 Ca(2+) ion.;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- TOXIC DOSE: LD(50) is 0.63 mg/kg by intravenous injection.
CC -!- MISCELLANEOUS: Does not bind to coagulation factor FVa (F5) or
CC prothrombin. {ECO:0000305|PubMed:10462445}.
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group I subfamily.
CC D49 sub-subfamily. {ECO:0000305}.
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 AlphaFoldDB; P00605; -.
DR SMR; P00605; -.
DR PRIDE; P00605; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0004623; F:phospholipase A2 activity; IEA:UniProtKB-EC.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0050482; P:arachidonic acid secretion; IEA:InterPro.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006644; P:phospholipid metabolic process; IEA:InterPro.
DR CDD; cd00125; PLA2c; 1.
DR Gene3D; 1.20.90.10; -; 1.
DR InterPro; IPR001211; PLipase_A2.
DR InterPro; IPR033112; PLipase_A2_Asp_AS.
DR InterPro; IPR016090; PLipase_A2_dom.
DR InterPro; IPR036444; PLipase_A2_dom_sf.
DR InterPro; IPR033113; PLipase_A2_His_AS.
DR PANTHER; PTHR11716; PTHR11716; 1.
DR Pfam; PF00068; Phospholip_A2_1; 1.
DR PRINTS; PR00389; PHPHLIPASEA2.
DR SMART; SM00085; PA2c; 1.
DR SUPFAM; SSF48619; SSF48619; 1.
DR PROSITE; PS00119; PA2_ASP; 1.
DR PROSITE; PS00118; PA2_HIS; 1.
PE 1: Evidence at protein level;
KW Blood coagulation cascade inhibiting toxin; Calcium;
KW Direct protein sequencing; Disulfide bond; Hemostasis impairing toxin;
KW Hydrolase; Lipid degradation; Lipid metabolism; Metal-binding; Secreted;
KW Toxin.
FT CHAIN 1..118
FT /note="Phospholipase A2 'basic'"
FT /id="PRO_0000161671"
FT MOTIF 52..69
FT /note="Coagulation factor Xa binding motif"
FT ACT_SITE 47
FT /evidence="ECO:0000250"
FT ACT_SITE 92
FT /evidence="ECO:0000250"
FT BINDING 27
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 29
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 31
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 48
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT DISULFID 11..70
FT /evidence="ECO:0000250"
FT DISULFID 26..117
FT /evidence="ECO:0000250"
FT DISULFID 28..44
FT /evidence="ECO:0000250"
FT DISULFID 43..98
FT /evidence="ECO:0000250"
FT DISULFID 50..91
FT /evidence="ECO:0000250"
FT DISULFID 59..84
FT /evidence="ECO:0000250"
FT DISULFID 77..89
FT /evidence="ECO:0000250"
SQ SEQUENCE 118 AA; 13268 MW; F6F2ACA8A4C11BCF CRC64;
NLYQFKNMIH CTVPSRPWWH FADYGCYCGR GGKGTPVDDL DRCCQVHDNC YEKAGKMGCW
PYLTLYKYKC SQGKLTCSGG NSKCGAAVCN CDLVAANCFA GARYIDANYN INFKKRCQ
