PA2A1_NAJAT
ID PA2A1_NAJAT Reviewed; 146 AA.
AC P00598;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=Acidic phospholipase A2 1;
DE Short=svPLA2;
DE EC=3.1.1.4;
DE AltName: Full=Muscarinic protein;
DE Short=MP;
DE AltName: Full=Phosphatidylcholine 2-acylhydrolase;
DE Flags: Precursor;
OS Naja atra (Chinese cobra).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Elapidae; Elapinae; Naja.
OX NCBI_TaxID=8656;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Venom gland;
RX PubMed=7510963; DOI=10.1006/bbrc.1994.1324;
RA Pan F.M., Yeh M.S., Chang W.C., Hung C.C., Chiou S.H.;
RT "Sequence analysis and expression of phospholipase A2 from Taiwan cobra.";
RL Biochem. Biophys. Res. Commun. 199:969-976(1994).
RN [2]
RP PROTEIN SEQUENCE OF 28-146.
RC TISSUE=Venom;
RX PubMed=7222082; DOI=10.1016/0041-0101(81)90126-4;
RA Tsai I.-H., Wu S.-H., Lo T.-B.;
RT "Complete amino acid sequence of a phospholipase A2 from the venom of Naja
RT naja atra (Taiwan cobra).";
RL Toxicon 19:141-152(1981).
RN [3]
RP PROTEIN SEQUENCE OF 28-43, FUNCTION, AND MASS SPECTROMETRY.
RC TISSUE=Venom;
RX PubMed=18281071; DOI=10.1016/j.toxicon.2008.01.006;
RA Huang L.-F., Zheng J.-B., Xu Y., Song H.-T., Yu C.-X.;
RT "A snake venom phospholipase A(2) with high affinity for muscarinic
RT acetylcholine receptors acts on guinea pig ileum.";
RL Toxicon 51:1008-1016(2008).
RN [4]
RP FUNCTION.
RX PubMed=3117784; DOI=10.1016/s0021-9258(18)47808-8;
RA Kini R.M., Evans H.J.;
RT "Structure-function relationships of phospholipases. The anticoagulant
RT region of phospholipases A2.";
RL J. Biol. Chem. 262:14402-14407(1987).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 28-145 IN COMPLEX WITH CALCIUM
RP ION, COFACTOR, AND DISULFIDE BONDS.
RX PubMed=2274787; DOI=10.1126/science.2274787;
RA White S.P., Scott D.L., Otwinowski Z., Gelb M.H., Sigler P.B.;
RT "Crystal structure of cobra-venom phospholipase A2 in a complex with a
RT transition-state analogue.";
RL Science 250:1560-1563(1990).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 28-145 IN COMPLEX WITH CALCIUM
RP ION, COFACTOR, AND DISULFIDE BONDS.
RX PubMed=2274785; DOI=10.1126/science.2274785;
RA Scott D.L., White S.P., Otwinowski Z., Yuan W., Gelb M.H., Sigler P.B.;
RT "Interfacial catalysis: the mechanism of phospholipase A2.";
RL Science 250:1541-1546(1990).
CC -!- FUNCTION: Snake venom phospholipase A2 (PLA2) that has high affinity
CC for muscarinic acetylcholine receptors mAChRs (CHRM) and has the
CC ability to activate them. In guinea-pig ileum, produces an onset and
CC dose-dependent contraction. Has also weak anticoagulant activity. PLA2
CC catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-
CC sn-phosphoglycerides. {ECO:0000269|PubMed:18281071,
CC ECO:0000269|PubMed:3117784}.
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 Evidence={ECO:0000305|PubMed:2274785, ECO:0000305|PubMed:2274787};
CC Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000305|PubMed:2274785,
CC ECO:0000305|PubMed:2274787};
CC -!- SUBUNIT: Homodimer.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- MASS SPECTROMETRY: Mass=13260; Method=Unknown;
CC Evidence={ECO:0000269|PubMed:18281071};
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. Group I subfamily.
CC D49 sub-subfamily. {ECO:0000305}.
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DR EMBL; X73225; CAA51694.1; -; mRNA.
DR PIR; JC2137; PSNJAF.
DR PDB; 1POA; X-ray; 1.50 A; A=28-145.
DR PDB; 1POB; X-ray; 2.00 A; A/B=28-145.
DR PDBsum; 1POA; -.
DR PDBsum; 1POB; -.
DR AlphaFoldDB; P00598; -.
DR SMR; P00598; -.
DR PRIDE; P00598; -.
DR BRENDA; 3.1.1.4; 3558.
DR EvolutionaryTrace; P00598; -.
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 3D-structure; Blood coagulation cascade inhibiting toxin; Calcium;
KW Direct protein sequencing; Disulfide bond;
KW G-protein coupled acetylcholine receptor impairing toxin;
KW G-protein coupled receptor impairing toxin; Hemostasis impairing toxin;
KW Hydrolase; Lipid degradation; Lipid metabolism; Metal-binding; Neurotoxin;
KW Secreted; Signal; Toxin.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..27
FT /evidence="ECO:0000269|PubMed:18281071,
FT ECO:0000269|PubMed:7222082"
FT /id="PRO_0000022916"
FT CHAIN 28..146
FT /note="Acidic phospholipase A2 1"
FT /id="PRO_0000022917"
FT ACT_SITE 74
FT /evidence="ECO:0000305|PubMed:2274785"
FT ACT_SITE 120
FT /evidence="ECO:0000305|PubMed:2274785"
FT BINDING 54
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:2274785,
FT ECO:0000269|PubMed:2274787, ECO:0007744|PDB:1POA,
FT ECO:0007744|PDB:1POB"
FT BINDING 56
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:2274785,
FT ECO:0000269|PubMed:2274787, ECO:0007744|PDB:1POA,
FT ECO:0007744|PDB:1POB"
FT BINDING 58
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:2274785,
FT ECO:0000269|PubMed:2274787, ECO:0007744|PDB:1POA,
FT ECO:0007744|PDB:1POB"
FT BINDING 75
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:2274785,
FT ECO:0000269|PubMed:2274787, ECO:0007744|PDB:1POA,
FT ECO:0007744|PDB:1POB"
FT DISULFID 38..98
FT /evidence="ECO:0000269|PubMed:2274785,
FT ECO:0000269|PubMed:2274787, ECO:0007744|PDB:1POA,
FT ECO:0007744|PDB:1POB"
FT DISULFID 53..145
FT /evidence="ECO:0000269|PubMed:2274785,
FT ECO:0000269|PubMed:2274787, ECO:0007744|PDB:1POA,
FT ECO:0007744|PDB:1POB"
FT DISULFID 55..71
FT /evidence="ECO:0000269|PubMed:2274785,
FT ECO:0000269|PubMed:2274787, ECO:0007744|PDB:1POA,
FT ECO:0007744|PDB:1POB"
FT DISULFID 70..126
FT /evidence="ECO:0000269|PubMed:2274785,
FT ECO:0000269|PubMed:2274787, ECO:0007744|PDB:1POA,
FT ECO:0007744|PDB:1POB"
FT DISULFID 77..119
FT /evidence="ECO:0000269|PubMed:2274785,
FT ECO:0000269|PubMed:2274787, ECO:0007744|PDB:1POA,
FT ECO:0007744|PDB:1POB"
FT DISULFID 87..112
FT /evidence="ECO:0000269|PubMed:2274785,
FT ECO:0000269|PubMed:2274787, ECO:0007744|PDB:1POA,
FT ECO:0007744|PDB:1POB"
FT DISULFID 105..117
FT /evidence="ECO:0000269|PubMed:2274785,
FT ECO:0000269|PubMed:2274787, ECO:0007744|PDB:1POA,
FT ECO:0007744|PDB:1POB"
FT CONFLICT 111..112
FT /note="AC -> CA (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 134..136
FT /note="NNN -> DND (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 140
FT /note="D -> N (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 146
FT /note="Q -> QE (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 29..39
FT /evidence="ECO:0007829|PDB:1POA"
FT HELIX 45..48
FT /evidence="ECO:0007829|PDB:1POA"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:1POB"
FT TURN 52..54
FT /evidence="ECO:0007829|PDB:1POA"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:1POA"
FT HELIX 66..81
FT /evidence="ECO:0007829|PDB:1POA"
FT TURN 89..91
FT /evidence="ECO:0007829|PDB:1POA"
FT STRAND 96..99
FT /evidence="ECO:0007829|PDB:1POA"
FT STRAND 102..105
FT /evidence="ECO:0007829|PDB:1POA"
FT HELIX 111..127
FT /evidence="ECO:0007829|PDB:1POA"
FT HELIX 134..136
FT /evidence="ECO:0007829|PDB:1POA"
FT HELIX 141..144
FT /evidence="ECO:0007829|PDB:1POA"
SQ SEQUENCE 146 AA; 16013 MW; 862EDF47654BFF93 CRC64;
MTPAHLLILA AVCVSPLGAS SNRPMPLNLY QFKNMIQCTV PSRSWWDFAD YGCYCGRGGS
GTPVDDLDRC CQVHDNCYNE AEKISGCWPY FKTYSYECSQ GTLTCKGGNN ACAAAVCDCD
RLAAICFAGA PYNNNNYNID LKARCQ
