PA2A1_CERCE
ID PA2A1_CERCE Reviewed; 137 AA.
AC P0CAR9; C3UWC9;
DT 16-JUN-2009, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 36.
DE RecName: Full=Acidic phospholipase A2 CC-PLA2-1;
DE Short=svPLA2;
DE EC=3.1.1.4;
DE AltName: Full=Phosphatidylcholine 2-acylhydrolase;
DE Flags: Precursor;
OS Cerastes cerastes (Horned desert viper).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Viperinae; Cerastes.
OX NCBI_TaxID=8697;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND 3D-STRUCTURE MODELING.
RC TISSUE=Venom, and Venom gland;
RX PubMed=20142800; DOI=10.1038/labinvest.2009.137;
RA Kessentini-Zouari R., Jebali J., Taboubi S., Srairi-Abid N., Morjen M.,
RA Kallech-Ziri O., Bezzine S., Marvaldi J., El Ayeb M., Marrakchi N.,
RA Luis J.;
RT "CC-PLA2-1 and CC-PLA2-2, two Cerastes cerastes venom-derived
RT phospholipases A2, inhibit angiogenesis both in vitro and in vivo.";
RL Lab. Invest. 90:510-519(2010).
RN [2]
RP PROTEIN SEQUENCE OF 17-66, FUNCTION, COFACTOR, MASS SPECTROMETRY, AND
RP SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RA Zouari-Kessentini R., Luis J., Karray A., Kallech-Ziri O., Srairi-Abid N.,
RA Bazaa A., Loret E., Bezzine S., El Ayeb M., Marrakchi N.;
RT "Two purified and characterized phospholipases A2 from Cerastes cerastes
RT venom, that inhibit cancerous cell adhesion and migration.";
RL Toxicon 53:444-453(2009).
CC -!- FUNCTION: Snake venom phospholipase A2 (PLA2) that inhibits blood
CC coagulation and platelet aggregation induced by ADP and arachidonic
CC acid. Inhibits tumor cell adhesion and migration in a dose-dependent
CC manner. Abolishes the attachment of human brain microvascular
CC endothelial cells (HBMEC) to fibrinogen (IC(50)=0.12 uM) and
CC dramatically reduces it adhesion to fibronectin (IC(50)=0.12 uM),
CC whereas no effect is observed on type I collagen, vitronectin or
CC laminin 1. Also blocks the cell migration toward fibronectin and
CC fibrinogen. These effects are not dependent of the catalytic activity,
CC but are mediated by alpha-5/beta-1 (ITGA5/ITGB1) and alpha-v-containing
CC (ITGAV) integrins. Also shows anti-angiogenic activity in chicken
CC chorioallantoix membrane assay. Has a relatively high enzymatic
CC activity. PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl
CC groups in 3-sn-phosphoglycerides. {ECO:0000269|PubMed:20142800,
CC ECO:0000269|Ref.2}.
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; Evidence={ECO:0000269|Ref.2};
CC Note=Binds 1 Ca(2+) ion. {ECO:0000269|Ref.2};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|Ref.2}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland. {ECO:0000305|Ref.2}.
CC -!- PTM: Glycosylated (2.5%).
CC -!- MASS SPECTROMETRY: Mass=13737.52; Method=MALDI;
CC Evidence={ECO:0000269|Ref.2};
CC -!- MISCELLANEOUS: Does not show cytotoxic activity on human fibrosarcoma
CC and melanoma cell lines. {ECO:0000305|PubMed:20142800}.
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group II subfamily.
CC D49 sub-subfamily. {ECO:0000305}.
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DR EMBL; FJ754186; ACO92622.1; -; mRNA.
DR AlphaFoldDB; P0CAR9; -.
DR SMR; P0CAR9; -.
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:0001525; P:angiogenesis; 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 Angiogenesis; Blood coagulation cascade inhibiting toxin; Calcium;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hemostasis impairing toxin; Hydrolase; Lipid degradation; Lipid metabolism;
KW Metal-binding; Platelet aggregation inhibiting toxin; Secreted; Signal;
KW Toxin.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|Ref.2"
FT CHAIN 17..137
FT /note="Acidic phospholipase A2 CC-PLA2-1"
FT /id="PRO_0000377503"
FT ACT_SITE 63
FT /evidence="ECO:0000250"
FT ACT_SITE 104
FT /evidence="ECO:0000250"
FT BINDING 43
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 45
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 47
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 64
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT DISULFID 42..130
FT /evidence="ECO:0000250"
FT DISULFID 44..60
FT /evidence="ECO:0000250"
FT DISULFID 59..110
FT /evidence="ECO:0000250"
FT DISULFID 65..137
FT /evidence="ECO:0000250"
FT DISULFID 66..103
FT /evidence="ECO:0000250"
FT DISULFID 73..96
FT /evidence="ECO:0000250"
FT DISULFID 90..101
FT /evidence="ECO:0000250"
SQ SEQUENCE 137 AA; 15365 MW; 7CE05CB1852DA8E8 CRC64;
MRTLWIVAVW LMGVEGNLYQ FGKMIKHKTG KSALLSYSAY GCYCGWGGQG KPQDATDHCC
FVHDCCYGEV SGCYPKTAFT LKFENQDIIC GDEDPCNRAV CECDRVAAIC FGENVNTSDK
KYLFYSSSYC EEESEQC
