PA2A2_VIPRE
ID PA2A2_VIPRE Reviewed; 137 AA.
AC F8QN53;
DT 03-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 21-SEP-2011, sequence version 1.
DT 03-AUG-2022, entry version 34.
DE RecName: Full=Acidic phospholipase A2 Vur-PL2B;
DE Short=Vur-PL2 {ECO:0000303|PubMed:21185324};
DE Short=svPLA2;
DE EC=3.1.1.4;
DE AltName: Full=Phosphatidylcholine 2-acylhydrolase;
DE Flags: Precursor;
OS Vipera renardi (Steppe viper) (Vipera ursinii renardi).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Viperinae; Vipera.
OX NCBI_TaxID=927686;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 17-43, FUNCTION, CATALYTIC
RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MASS SPECTROMETRY, TOXIC DOSE,
RP CIRCULAR DICHROISM, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom, and Venom gland;
RX PubMed=21185324; DOI=10.1016/j.toxicon.2010.12.012;
RA Tsai I.-H., Wang Y.M., Cheng A.C., Starkov V., Osipov A., Nikitin I.,
RA Makarova Y., Ziganshin R., Utkin Y.;
RT "cDNA cloning, structural, and functional analyses of venom phospholipases
RT A and a Kunitz-type protease inhibitor from steppe viper Vipera ursinii
RT renardi.";
RL Toxicon 57:332-341(2011).
RN [2]
RP FUNCTION.
RC TISSUE=Venom;
RX PubMed=25522251; DOI=10.1371/journal.pone.0115428;
RA Vulfius C.A., Kasheverov I.E., Starkov V.G., Osipov A.V., Andreeva T.V.,
RA Filkin S.Y., Gorbacheva E.V., Astashev M.E., Tsetlin V.I., Utkin Y.N.;
RT "Inhibition of nicotinic acetylcholine receptors, a novel facet in the
RT pleiotropic activities of snake venom phospholipases A2.";
RL PLoS ONE 9:e115428-e115428(2014).
CC -!- FUNCTION: Snake venom phospholipase A2 that causes internal bleeding,
CC shows very strong anticoagulant activities and inhibits ADP-induced
CC platelet aggregation (PubMed:21185324). Shows very low cytotoxicity
CC (PubMed:21185324). Is not able (or very weakly) to suppress the
CC acetylcholine (ACh)-evoked current mediated by alpha-7-similar nAChRs
CC in L.stagnalis neurons (IC(50)>30 uM) and to compete with alpha-
CC bungarotoxin for binding to muscle- and alpha-7 neuronal nAChR types,
CC as well as to AChBPs (PubMed:25522251). In inhibition of alpha-
CC bungarotoxin binding, this toxin is similarly active against
CC T.californica nAChR (IC(50)>100 uM), human alpha-7 nAChR (IC(50)=29
CC uM), and L.stagnalis AChBP (IC(50)>30 uM) (PubMed:25522251).
CC {ECO:0000269|PubMed:21185324, ECO:0000269|PubMed:25522251}.
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, ECO:0000269|PubMed:21185324};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC Note=Binds 1 Ca(2+) ion. {ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Vmax=3592 umol/min/mg enzyme (Vur-PL2B)
CC {ECO:0000269|PubMed:21185324};
CC Note=Vmax=1736 umol/min/mg enzyme (Vur-PL2A).
CC {ECO:0000269|PubMed:21185324};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:21185324}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:21185324}.
CC -!- MASS SPECTROMETRY: Mass=13547.9; Method=MALDI;
CC Evidence={ECO:0000269|PubMed:21185324};
CC -!- TOXIC DOSE: LD(50) is 10.7 mg/kg by intraperitoneal injection into
CC mice. {ECO:0000269|PubMed:21185324}.
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group II subfamily.
CC D49 sub-subfamily. {ECO:0000305}.
CC -!- CAUTION: Two proteins (Vur-PL2A and Vur-PL2B) with different masses and
CC detected in two different fractions have been isolated from the venom.
CC They both seem to have the same sequence. Vur-PL2B is possibly a more
CC stable conformer than Vur-PL2A. Since data on both proteins are very
CC similar, information reported here mainly concerns Vur-PL2B.
CC {ECO:0000305}.
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DR EMBL; GQ304907; ADG86231.1; -; mRNA.
DR AlphaFoldDB; F8QN53; -.
DR SMR; F8QN53; -.
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; Direct protein sequencing;
KW Disulfide bond; Hemorrhagic toxin; Hemostasis impairing toxin; Hydrolase;
KW Lipid degradation; Lipid metabolism; Metal-binding;
KW Platelet aggregation inhibiting toxin; Secreted; Signal; Toxin.
FT SIGNAL 1..16
FT /evidence="ECO:0000269|PubMed:21185324"
FT CHAIN 17..137
FT /note="Acidic phospholipase A2 Vur-PL2B"
FT /id="PRO_0000419639"
FT ACT_SITE 63
FT /evidence="ECO:0000250"
FT ACT_SITE 105
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..131
FT /evidence="ECO:0000250"
FT DISULFID 44..60
FT /evidence="ECO:0000250"
FT DISULFID 59..111
FT /evidence="ECO:0000250"
FT DISULFID 65..137
FT /evidence="ECO:0000250"
FT DISULFID 66..104
FT /evidence="ECO:0000250"
FT DISULFID 73..97
FT /evidence="ECO:0000250"
FT DISULFID 91..102
FT /evidence="ECO:0000250"
SQ SEQUENCE 137 AA; 15316 MW; 282C6D9F894F708D CRC64;
MRILWIVAVC LIGVEGNLYQ FGKMIRYKTG KSALLSYSDY GCYCGWGGQG KPKDATDRCC
FVHDCCYGRV NGCDPKLTIY SYSFENGDIV CGGDDSCKRA VCECDRVAAI CFGENLNTYD
KKYKNYPSSQ CTETEQC
