PA2A1_NAJKA
ID PA2A1_NAJKA Reviewed; 146 AA.
AC P00596; Q9PWS2;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-2002, sequence version 2.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Acidic phospholipase A2 CM-II {ECO:0000303|PubMed:10669032, ECO:0000303|PubMed:7460933};
DE Short=CM 2 {ECO:0000303|PubMed:19622365};
DE Short=svPLA2;
DE EC=3.1.1.4;
DE AltName: Full=Acidic phospholipase A2 1;
DE AltName: Full=NnkPLA-I {ECO:0000303|PubMed:10669032};
DE AltName: Full=Phosphatidylcholine 2-acylhydrolase;
DE Flags: Precursor;
OS Naja kaouthia (Monocled cobra) (Naja siamensis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Elapinae; Naja.
OX NCBI_TaxID=8649;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=10669032; DOI=10.1016/s0041-0101(99)00165-8;
RA Chuman Y., Nobuhisa I., Ogawa T., Deshimaru M., Chijiwa T., Tan N.-T.,
RA Fukumaki Y., Shimohigashi Y., Ducancel F., Boulain J.-C., Menez A.,
RA Ohno M.;
RT "Regional and accelerated molecular evolution in group I snake venom gland
RT phospholipase A2 isozymes.";
RL Toxicon 38:449-462(2000).
RN [2]
RP PROTEIN SEQUENCE OF 28-146, AND SUBCELLULAR LOCATION.
RC TISSUE=Venom;
RX PubMed=7460933; DOI=10.1111/j.1432-1033.1980.tb06112.x;
RA Joubert F.J., Taljaard N.;
RT "Purification, some properties and amino-acid sequences of two
RT phospholipases A (CM-II and CM-III) from Naja naja kaouthia venom.";
RL Eur. J. Biochem. 112:493-499(1980).
RN [3]
RP CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=19622365; DOI=10.1016/j.toxicon.2009.07.011;
RA Osipov A.V., Filkin S.Y., Makarova Y.V., Tsetlin V.I., Utkin Y.N.;
RT "A new type of thrombin inhibitor, noncytotoxic phospholipase A2, from the
RT Naja haje cobra venom.";
RL Toxicon 55:186-194(2010).
RN [4]
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: PLA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl
CC groups in 3-sn-phosphoglycerides (Probable). Is able to suppress the
CC acetylcholine (ACh)-evoked current mediated by alpha-7-similar nAChRs
CC in L.stagnalis neurons (IC(50)=37 nM) 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)=1.2 uM), human alpha-7 nAChR (IC(50)=3.2
CC uM), and L.stagnalis AChBP (IC(50)=1.0 uM), whereas it is not active
CC against A.californica AChBP (IC(50)>100 uM) (PubMed:25522251).
CC {ECO:0000269|PubMed:25522251, ECO:0000305}.
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:0000250};
CC Note=Binds 1 Ca(2+) ion. {ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC Vmax=165 umol/min/mg enzyme {ECO:0000269|PubMed:19622365};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7460933}.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC {ECO:0000305|PubMed:7460933}.
CC -!- TOXIC DOSE: LD(50) is 10 mg/kg by intravenous injection.
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group I subfamily.
CC D49 sub-subfamily. {ECO:0000305}.
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DR EMBL; AB011388; BAA36403.1; -; mRNA.
DR AlphaFoldDB; P00596; -.
DR SMR; P00596; -.
DR PRIDE; P00596; -.
DR BRENDA; 3.1.1.4; 6939.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030550; F:acetylcholine receptor inhibitor activity; IEA:UniProtKB-KW.
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 Acetylcholine receptor inhibiting toxin; Calcium;
KW Direct protein sequencing; Disulfide bond; Hydrolase; Lipid degradation;
KW Lipid metabolism; Metal-binding; Neurotoxin; Postsynaptic neurotoxin;
KW Secreted; Signal; Toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..27
FT /evidence="ECO:0000269|PubMed:7460933"
FT /id="PRO_0000022920"
FT CHAIN 28..146
FT /note="Acidic phospholipase A2 CM-II"
FT /id="PRO_0000022921"
FT ACT_SITE 74
FT /evidence="ECO:0000250"
FT ACT_SITE 120
FT /evidence="ECO:0000250"
FT BINDING 54
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 56
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 58
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 75
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT DISULFID 38..98
FT /evidence="ECO:0000250"
FT DISULFID 53..145
FT /evidence="ECO:0000250"
FT DISULFID 55..71
FT /evidence="ECO:0000250"
FT DISULFID 70..126
FT /evidence="ECO:0000250"
FT DISULFID 77..119
FT /evidence="ECO:0000250"
FT DISULFID 87..112
FT /evidence="ECO:0000250"
FT DISULFID 105..117
FT /evidence="ECO:0000250"
FT CONFLICT 79
FT /note="N -> D (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305|PubMed:10669032"
FT CONFLICT 107..110
FT /note="GDND -> NGNN (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305|PubMed:10669032"
SQ SEQUENCE 146 AA; 16271 MW; F3FBB7172A829588 CRC64;
MNPAHLLILA AVCVSPLGAF SNRPMPLNLY QFKNMIQCTV PNRSWWDFAD YGCYCGRGGS
GTPVDDLDRC CQVHDNCYNE AEKISRCWPY FKTYSYECSQ GTLTCKGDND ACAAAVCDCD
RLAAICFAGA PYNNNNYNID LKARCQ
