ID   PA2_APIME               Reviewed;         167 AA.
AC   P00630; A5JGM7; Q8WPH5;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   25-OCT-2002, sequence version 3.
DT   02-SEP-2026, entry version 185.
DE   RecName: Full=Phospholipase A2;
DE            Short=bvPLA2;
DE            EC=3.1.1.4;
DE   AltName: Full=Allergen Api m I;
DE   AltName: Full=Phosphatidylcholine 2-acylhydrolase;
DE   AltName: Allergen=Api m 1;
DE   Flags: Precursor;
OS   Apis mellifera (Honeybee).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Altocrustacea; Allotriocarida;
OC   Hexapoda; Insecta; Pterygota; Neoptera; Eumetabola; Endopterygota;
OC   Hymenoptera; Apocrita; Aculeata; Apoidea; Anthophila; Apidae; Apis.
OX   NCBI_TaxID=7460;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Venom gland;
RX   PubMed=12167627; DOI=10.1074/jbc.m206647200;
RA   Moreira L.A., Ito J., Ghosh A., Devenport M., Zieler H., Abraham E.G.,
RA   Crisanti A., Nolan T., Catteruccia F., Jacobs-Lorena M.;
RT   "Bee venom phospholipase inhibits malaria parasite development in
RT   transgenic mosquitoes.";
RL   J. Biol. Chem. 277:40839-40843(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Venom gland;
RX   PubMed=17466468; DOI=10.1016/j.gene.2007.03.007;
RA   Valdez-Cruz N.A., Segovia L., Corona M., Possani L.D.;
RT   "Sequence analysis and phylogenetic relationship of genes encoding
RT   heterodimeric phospholipases A2 from the venom of the scorpion Anuroctonus
RT   phaiodactylus.";
RL   Gene 396:149-158(2007).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 6-167.
RC   TISSUE=Venom gland;
RX   PubMed=2776767; DOI=10.1111/j.1432-1033.1989.tb15014.x;
RA   Kuchler K., Gmachl M., Sippl M.J., Kreil G.;
RT   "Analysis of the cDNA for phospholipase A2 from honeybee venom glands. The
RT   deduced amino acid sequence reveals homology to the corresponding
RT   vertebrate enzymes.";
RL   Eur. J. Biochem. 184:249-254(1989).
RN   [4]
RP   PROTEIN SEQUENCE OF 34-167.
RC   TISSUE=Venom;
RX   PubMed=4448181; DOI=10.1111/j.1432-1033.1974.tb03787.x;
RA   Shipolini R.A., Callewaert G.L., Cottrell R.C., Vernon C.A.;
RT   "The amino-acid sequence and carbohydrate content of phospholipase A2 from
RT   bee venom.";
RL   Eur. J. Biochem. 48:465-476(1974).
RN   [5]
RP   PROTEIN SEQUENCE OF 34-60, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP   SEASONAL VARIATION.
RX   PubMed=20403370; DOI=10.1016/j.toxicon.2010.03.023;
RA   Ferreira Junior R.S., Sciani J.M., Marques-Porto R., Junior A.L.,
RA   Orsi R.D., Barraviera B., Pimenta D.C.;
RT   "Africanized honey bee (Apis mellifera) venom profiling: Seasonal variation
RT   of melittin and phospholipase A(2) levels.";
RL   Toxicon 56:355-362(2010).
RN   [6]
RP   DISULFIDE BONDS.
RX   PubMed=4614976; DOI=10.1111/j.1432-1033.1974.tb03788.x;
RA   Shipolini R.A., Doonan S., Vernon C.A.;
RT   "The disulphide bridges of phospholipase A2 from bee venom.";
RL   Eur. J. Biochem. 48:477-483(1974).
RN   [7]
RP   GLYCOSYLATION AT ASN-46.
RX   PubMed=8504812; DOI=10.1111/j.1432-1033.1993.tb17870.x;
RA   Kubelka V., Altmann F., Staudacher E., Tretter V., Marz L., Hard K.,
RA   Kamerling J.P., Vliegenthart J.F.;
RT   "Primary structures of the N-linked carbohydrate chains from honeybee venom
RT   phospholipase A2.";
RL   Eur. J. Biochem. 213:1193-1204(1993).
RN   [8]
RP   FUNCTION, AND BIOASSAY.
RC   TISSUE=Venom;
RX   PubMed=36550366; DOI=10.1038/s41598-022-26867-8;
RA   Shi N., Szanto T.G., He J., Schroeder C.I., Walker A.A., Deuis J.R.,
RA   Vetter I., Panyi G., King G.F., Robinson S.D.;
RT   "Venom composition and pain-causing toxins of the Australian great
RT   carpenter bee Xylocopa aruana.";
RL   Sci. Rep. 12:22168-22168(2022).
RN   [9]
RP   X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 34-167 IN COMPLEX WITH CALCIUM
RP   ION, COFACTOR, AND DISULFIDE BONDS.
RX   PubMed=2274788; DOI=10.1126/science.2274788;
RA   Scott D.L., Otwinowski Z., Gelb M.H., Sigler P.B.;
RT   "Crystal structure of bee-venom phospholipase A2 in a complex with a
RT   transition-state analogue.";
RL   Science 250:1563-1566(1990).
CC   -!- FUNCTION: In vivo, intraplantar injection in mice cause spontaneous
CC       pain behaviors and paw swelling (PubMed:36550366). PLA2 catalyzes the
CC       calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-
CC       phosphoglycerides. {ECO:0000269|PubMed:36550366}.
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};
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC         Evidence={ECO:0000305|PubMed:2274788};
CC       Note=Binds 1 Ca(2+) ion. {ECO:0000305|PubMed:2274788};
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC   -!- PTM: N-glycosylated; contains mannose, N-acetylglucosamine and fucose
CC       alphal-6 and/or alphal-3 linked to the innermost N-acetylglucosamine.
CC       {ECO:0000269|PubMed:8504812}.
CC   -!- ALLERGEN: Causes an allergic reaction in human.
CC   -!- MISCELLANEOUS: The secretion of this protein into venom follows a
CC       seasonal pattern. This variation is synchronized with melittin
CC       variation, i.e. their production increase in the same months.
CC   -!- SIMILARITY: Belongs to the phospholipase A2 family. Group III
CC       subfamily. {ECO:0000305}.
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DR   EMBL; AF438408; AAL30844.1; -; mRNA.
DR   EMBL; EF373554; ABQ28728.1; -; Genomic_DNA.
DR   EMBL; X16709; CAA34681.1; -; mRNA.
DR   PIR; S05650; PSHBA.
DR   RefSeq; NP_001011614.1; NM_001011614.1.
DR   PDB; 1POC; X-ray; 2.00 A; A=34-167.
DR   PDB; 8PIH; X-ray; 1.76 A; A=35-167.
DR   PDB; 8PKC; X-ray; 4.10 A; A/B=34-167.
DR   AlphaFoldDB; P00630; -.
DR   SMR; P00630; -.
DR   FunCoup; P00630; 57.
DR   STRING; 7460.P00630; -.
DR   BindingDB; P00630; -.
DR   ChEMBL; CHEMBL4807; -.
DR   Allergome; 2493; Api m A1-A2.
DR   Allergome; 2778; Api m A1-A2-A3.
DR   Allergome; 3088; Api m 1.0101.
DR   Allergome; 45; Api m 1.
DR   GlyConnect; P00630; 16 N-Linked glycans (1 site).
DR   PaxDb; 7460-P00630; -.
DR   ABCD; P00630; 2 sequenced antibodies.
DR   EnsemblMetazoa; NM_001011614; NP_001011614; GeneID_406141.
DR   GeneID; 406141; -.
DR   KEGG; ame:406141; -.
DR   CTD; 124432273; -.
DR   eggNOG; ENOG502S1MS; Eukaryota.
DR   HOGENOM; CLU_118255_0_0_1; -.
DR   InParanoid; P00630; -.
DR   OMA; TTGCKEY; -.
DR   OrthoDB; 10059604at2759; -.
DR   PhylomeDB; P00630; -.
DR   BRENDA; 3.1.1.4; 387.
DR   EvolutionaryTrace; P00630; -.
DR   PRO; PR:P00630; -.
DR   Proteomes; UP000005203; Linkage group LG13.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0004623; F:A2-type glycerophospholipase activity; IEA:UniProtKB-EC.
DR   GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR   GO; GO:0050482; P:arachidonate secretion; IEA:InterPro.
DR   GO; GO:0006644; P:phospholipid metabolic process; IEA:InterPro.
DR   CDD; cd04704; PLA2_bee_venom_like; 1.
DR   FunFam; 1.20.90.10:FF:000002; Phospholipase A2 group III; 1.
DR   Gene3D; 1.20.90.10; Phospholipase A2 domain; 1.
DR   InterPro; IPR016090; PLA2-like_dom.
DR   InterPro; IPR033113; PLA2_histidine.
DR   InterPro; IPR036444; PLipase_A2_dom_sf.
DR   PANTHER; PTHR12253; RH14732P; 1.
DR   Pfam; PF05826; Phospholip_A2_2; 1.
DR   SMART; SM00085; PA2c; 1.
DR   SUPFAM; SSF48619; Phospholipase A2, PLA2; 1.
DR   PROSITE; PS00118; PA2_HIS; 1.
DR   PDBsum; 1POC; -.
DR   PDBsum; 8PIH; -.
DR   PDBsum; 8PKC; -.
PE   1: Evidence at protein level;
KW   3D-structure; Allergen; Calcium; Direct protein sequencing; Disulfide bond;
KW   Glycoprotein; Hydrolase; Lipid degradation; Lipid metabolism;
KW   Metal-binding; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..18
FT                   /evidence="ECO:0000255"
FT   PROPEP          19..33
FT                   /evidence="ECO:0000269|PubMed:20403370,
FT                   ECO:0000269|PubMed:4448181"
FT                   /id="PRO_0000022982"
FT   CHAIN           34..167
FT                   /note="Phospholipase A2"
FT                   /evidence="ECO:0000269|PubMed:2274788"
FT                   /id="PRO_0000022983"
FT   ACT_SITE        67
FT                   /evidence="ECO:0000305|PubMed:2274788"
FT   ACT_SITE        97
FT                   /evidence="ECO:0000305|PubMed:2274788"
FT   BINDING         41
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000269|PubMed:2274788,
FT                   ECO:0007744|PDB:1POC"
FT   BINDING         43
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000269|PubMed:2274788,
FT                   ECO:0007744|PDB:1POC"
FT   BINDING         45
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000269|PubMed:2274788,
FT                   ECO:0007744|PDB:1POC"
FT   BINDING         68
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000269|PubMed:2274788,
FT                   ECO:0007744|PDB:1POC"
FT   CARBOHYD        46
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:8504812"
FT                   /id="CAR_000001"
FT   DISULFID        42..64
FT                   /evidence="ECO:0000269|PubMed:2274788,
FT                   ECO:0000269|PubMed:4614976"
FT   DISULFID        63..103
FT                   /evidence="ECO:0000269|PubMed:2274788,
FT                   ECO:0000269|PubMed:4614976"
FT   DISULFID        70..96
FT                   /evidence="ECO:0000269|PubMed:2274788,
FT                   ECO:0000269|PubMed:4614976"
FT   DISULFID        94..128
FT                   /evidence="ECO:0000269|PubMed:2274788,
FT                   ECO:0000269|PubMed:4614976"
FT   DISULFID        138..146
FT                   /evidence="ECO:0000269|PubMed:2274788,
FT                   ECO:0000269|PubMed:4614976"
FT   CONFLICT        72
FT                   /note="D -> N (in Ref. 4; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        85
FT                   /note="N -> D (in Ref. 4; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        89..90
FT                   /note="Missing (in Ref. 4; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        95..99
FT                   /note="DCDDK -> NNND (in Ref. 4; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        102..104
FT                   /note="Missing (in Ref. 4; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        125
FT                   /note="D -> N (in Ref. 4; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   TURN            40..42
FT                   /evidence="ECO:0007829|PDB:8PIH"
FT   HELIX           59..68
FT                   /evidence="ECO:0007829|PDB:8PIH"
FT   STRAND          71..74
FT                   /evidence="ECO:0007829|PDB:1POC"
FT   STRAND          87..89
FT                   /evidence="ECO:0007829|PDB:8PIH"
FT   STRAND          91..93
FT                   /evidence="ECO:0007829|PDB:8PIH"
FT   HELIX           94..106
FT                   /evidence="ECO:0007829|PDB:8PIH"
FT   HELIX           110..121
FT                   /evidence="ECO:0007829|PDB:8PIH"
FT   STRAND          127..133
FT                   /evidence="ECO:0007829|PDB:8PIH"
FT   STRAND          135..142
FT                   /evidence="ECO:0007829|PDB:8PIH"
FT   STRAND          145..151
FT                   /evidence="ECO:0007829|PDB:8PIH"
FT   STRAND          158..164
FT                   /evidence="ECO:0007829|PDB:8PIH"
SQ   SEQUENCE   167 AA;  19058 MW;  88D5086A0E47DCC1 CRC64;
     MQVVLGSLFL LLLSTSHGWQ IRDRIGDNEL EERIIYPGTL WCGHGNKSSG PNELGRFKHT
     DACCRTHDMC PDVMSAGESK HGLTNTASHT RLSCDCDDKF YDCLKNSADT ISSYFVGKMY
     FNLIDTKCYK LEHPVTGCGE RTEGRCLHYT VDKSKPKVYQ WFDLRKY
//