ID PA24A_CHICK Reviewed; 748 AA. AC P49147; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1996, sequence version 1. DT 27-MAR-2024, entry version 151. DE RecName: Full=Cytosolic phospholipase A2; DE Short=cPLA2; DE AltName: Full=Phospholipase A2 group IVA; DE Includes: DE RecName: Full=Phospholipase A2; DE EC=3.1.1.4; DE AltName: Full=Phosphatidylcholine 2-acylhydrolase; DE Includes: DE RecName: Full=Lysophospholipase; DE EC=3.1.1.5; GN Name=PLA2G4A; Synonyms=CPLA2, PLA2G4; OS Gallus gallus (Chicken). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda; OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae; OC Phasianinae; Gallus. OX NCBI_TaxID=9031; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION. RX PubMed=8027085; DOI=10.1016/s0021-9258(17)32440-7; RA Nalefski E.A., Sultzman L.A., Martin D.M., Kriz R.W., Towler P.S., RA Knopf J.L., Clark J.D.; RT "Delineation of two functionally distinct domains of cytosolic RT phospholipase A2, a regulatory Ca(2+)-dependent lipid-binding domain and a RT Ca(2+)-independent catalytic domain."; RL J. Biol. Chem. 269:18239-18249(1994). CC -!- FUNCTION: Selectively hydrolyzes arachidonyl phospholipids in the sn-2 CC position releasing arachidonic acid. Together with its lysophospholipid CC activity, it is implicated in the initiation of the inflammatory CC response. 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 -!- CATALYTIC ACTIVITY: CC Reaction=a 1-acyl-sn-glycero-3-phosphocholine + H2O = a fatty acid + CC H(+) + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:15177, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16870, CC ChEBI:CHEBI:28868, ChEBI:CHEBI:58168; EC=3.1.1.5; CC -!- ACTIVITY REGULATION: Stimulated by agonists such as ATP, EGF, thrombin CC and bradykinin as well as by cytosolic Ca(2+). CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cytoplasmic vesicle CC {ECO:0000250}. Note=Translocates to membrane vesicles in a calcium- CC dependent fashion. {ECO:0000250}. CC -!- DOMAIN: The N-terminal C2 domain associates with lipid membranes upon CC calcium binding. It modulates enzyme activity by presenting the active CC site to its substrate in response to elevations of cytosolic Ca(2+) (By CC similarity). {ECO:0000250}. CC -!- PTM: Activated by phosphorylation on a serine residue. {ECO:0000250}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U10329; AAA53228.1; -; mRNA. DR PIR; I50699; I50699. DR RefSeq; NP_990754.1; NM_205423.1. DR RefSeq; XP_015146058.1; XM_015290572.1. DR PDB; 6IEJ; X-ray; 2.21 A; A/B/C=16-140. DR PDBsum; 6IEJ; -. DR AlphaFoldDB; P49147; -. DR SMR; P49147; -. DR STRING; 9031.ENSGALP00000008107; -. DR PaxDb; 9031-ENSGALP00000008107; -. DR Ensembl; ENSGALT00000048470; ENSGALP00000048642; ENSGALG00000005065. DR Ensembl; ENSGALT00010050885.1; ENSGALP00010030076.1; ENSGALG00010021027.1. DR Ensembl; ENSGALT00015051323; ENSGALP00015029632; ENSGALG00015021056. DR GeneID; 396394; -. DR KEGG; gga:396394; -. DR CTD; 5321; -. DR VEuPathDB; HostDB:geneid_396394; -. DR eggNOG; KOG1012; Eukaryota. DR eggNOG; KOG1325; Eukaryota. DR GeneTree; ENSGT01030000234606; -. DR HOGENOM; CLU_011663_1_1_1; -. DR InParanoid; P49147; -. DR OMA; NFMRGLS; -. DR OrthoDB; 4250045at2759; -. DR PhylomeDB; P49147; -. DR Reactome; R-GGA-111995; phospho-PLA2 pathway. DR Reactome; R-GGA-1482788; Acyl chain remodelling of PC. DR Reactome; R-GGA-1482798; Acyl chain remodeling of CL. DR Reactome; R-GGA-1482801; Acyl chain remodelling of PS. DR Reactome; R-GGA-1482839; Acyl chain remodelling of PE. DR Reactome; R-GGA-1482922; Acyl chain remodelling of PI. DR Reactome; R-GGA-1482925; Acyl chain remodelling of PG. DR Reactome; R-GGA-1483115; Hydrolysis of LPC. DR Reactome; R-GGA-1483166; Synthesis of PA. DR Reactome; R-GGA-2142753; Arachidonic acid metabolism. DR Reactome; R-GGA-418592; ADP signalling through P2Y purinoceptor 1. DR Reactome; R-GGA-432142; Platelet sensitization by LDL. DR Reactome; R-GGA-6811436; COPI-independent Golgi-to-ER retrograde traffic. DR PRO; PR:P49147; -. DR Proteomes; UP000000539; Chromosome 8. DR Bgee; ENSGALG00000005065; Expressed in cerebellum and 12 other cell types or tissues. DR ExpressionAtlas; P49147; baseline and differential. DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central. DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central. DR GO; GO:0000139; C:Golgi membrane; IEA:Ensembl. DR GO; GO:0005635; C:nuclear envelope; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central. DR GO; GO:0047498; F:calcium-dependent phospholipase A2 activity; IBA:GO_Central. DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IBA:GO_Central. DR GO; GO:0047499; F:calcium-independent phospholipase A2 activity; IEA:Ensembl. DR GO; GO:1902387; F:ceramide 1-phosphate binding; IEA:Ensembl. DR GO; GO:0004622; F:lysophospholipase activity; IEA:UniProtKB-EC. DR GO; GO:0008374; F:O-acyltransferase activity; IEA:Ensembl. DR GO; GO:0102545; F:phosphatidyl phospholipase B activity; IEA:UniProtKB-EC. DR GO; GO:0032266; F:phosphatidylinositol-3-phosphate binding; IEA:Ensembl. DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IEA:Ensembl. DR GO; GO:0010314; F:phosphatidylinositol-5-phosphate binding; IEA:Ensembl. DR GO; GO:0019369; P:arachidonic acid metabolic process; IEA:Ensembl. DR GO; GO:0050482; P:arachidonic acid secretion; IEA:Ensembl. DR GO; GO:0071236; P:cellular response to antibiotic; IEA:Ensembl. DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl. DR GO; GO:0046475; P:glycerophospholipid catabolic process; IBA:GO_Central. DR GO; GO:0019370; P:leukotriene biosynthetic process; IEA:Ensembl. DR GO; GO:0006640; P:monoacylglycerol biosynthetic process; IEA:Ensembl. DR GO; GO:0036151; P:phosphatidylcholine acyl-chain remodeling; IEA:Ensembl. DR GO; GO:0034638; P:phosphatidylcholine catabolic process; IEA:Ensembl. DR GO; GO:0034478; P:phosphatidylglycerol catabolic process; IEA:Ensembl. DR GO; GO:0006663; P:platelet activating factor biosynthetic process; IEA:Ensembl. DR GO; GO:0043032; P:positive regulation of macrophage activation; IEA:Ensembl. DR GO; GO:0010572; P:positive regulation of platelet activation; IEA:Ensembl. DR GO; GO:0032308; P:positive regulation of prostaglandin secretion; IEA:Ensembl. DR GO; GO:0002827; P:positive regulation of T-helper 1 type immune response; IEA:Ensembl. DR GO; GO:0001516; P:prostaglandin biosynthetic process; IEA:Ensembl. DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl. DR CDD; cd04036; C2_cPLA2; 1. DR CDD; cd07200; cPLA2_Grp-IVA; 1. DR Gene3D; 2.60.40.150; C2 domain; 1. DR Gene3D; 3.40.1090.10; Cytosolic phospholipase A2 catalytic domain; 1. DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase. DR InterPro; IPR041847; C2_cPLA2. DR InterPro; IPR000008; C2_dom. DR InterPro; IPR035892; C2_domain_sf. DR InterPro; IPR002642; LysoPLipase_cat_dom. DR PANTHER; PTHR10728; CYTOSOLIC PHOSPHOLIPASE A2; 1. DR PANTHER; PTHR10728:SF13; CYTOSOLIC PHOSPHOLIPASE A2; 1. DR Pfam; PF00168; C2; 1. DR Pfam; PF01735; PLA2_B; 1. DR SMART; SM00239; C2; 1. DR SMART; SM00022; PLAc; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF52151; FabD/lysophospholipase-like; 1. DR PROSITE; PS50004; C2; 1. DR PROSITE; PS51210; PLA2C; 1. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Cytoplasm; Cytoplasmic vesicle; Hydrolase; KW Lipid degradation; Lipid metabolism; Metal-binding; Phosphoprotein; KW Reference proteome. FT CHAIN 1..748 FT /note="Cytosolic phospholipase A2" FT /id="PRO_0000187266" FT DOMAIN 6..124 FT /note="C2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041" FT DOMAIN 138..740 FT /note="PLA2c" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00555" FT REGION 1..178 FT /note="Phospholipid binding" FT REGION 431..459 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 431..450 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 228 FT /note="Nucleophile" FT /evidence="ECO:0000250" FT ACT_SITE 549 FT /note="Proton acceptor" FT /evidence="ECO:0000250" FT BINDING 40 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 40 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 41 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 43 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 43 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 65 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 93 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 94 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 95 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250" FT MOD_RES 505 FT /note="Phosphoserine; by MAPK" FT /evidence="ECO:0000250" FT STRAND 18..29 FT /evidence="ECO:0007829|PDB:6IEJ" FT HELIX 34..39 FT /evidence="ECO:0007829|PDB:6IEJ" FT STRAND 44..49 FT /evidence="ECO:0007829|PDB:6IEJ" FT STRAND 53..55 FT /evidence="ECO:0007829|PDB:6IEJ" FT STRAND 57..59 FT /evidence="ECO:0007829|PDB:6IEJ" FT STRAND 66..68 FT /evidence="ECO:0007829|PDB:6IEJ" FT STRAND 70..79 FT /evidence="ECO:0007829|PDB:6IEJ" FT STRAND 86..93 FT /evidence="ECO:0007829|PDB:6IEJ" FT STRAND 96..98 FT /evidence="ECO:0007829|PDB:6IEJ" FT STRAND 100..108 FT /evidence="ECO:0007829|PDB:6IEJ" FT HELIX 109..111 FT /evidence="ECO:0007829|PDB:6IEJ" FT STRAND 117..124 FT /evidence="ECO:0007829|PDB:6IEJ" FT TURN 125..127 FT /evidence="ECO:0007829|PDB:6IEJ" FT STRAND 128..138 FT /evidence="ECO:0007829|PDB:6IEJ" SQ SEQUENCE 748 AA; 84979 MW; 996A5256CA032F75 CRC64; MSFIDPYQHI VVEHQYSHVF TVTVRKATNV TKGAIGDMLD TPDPYVELFI PSAPDCRKRT KHFNNDVNPV WNETFEFILD PNQDNVLEVT LMDANYVMDE TLGMATFPIS SLKLGEKKEV QLTFNNVTEM TLELSLEVCS STDLRFSMAL CDEEKKFRQQ RKDNIMQSMK SFLGEENSKN LTTSRDVPVI AVLGSGGGFR AMVGFAGVMK ALYESGVLDC ATYIAGLSGS TWYMSTLYSH PDFPEKGPKE INQELMNSVS HNPLLLLTPQ KVKRYIEALW NKKSSGQPVT FTDIFGMLIG ETLIHNRMDT TLSDMKEKVS EAQCALPLFT CLHVKPDVSE LMFADWVEFS PYEIGMAKYG TFMSPDLFGS KFFMGTVVKK YSENPLHFLM GVWGSAFSIL FNRVLGVSNS QNKGPTMEEE LENIRLKHLV SNDSSDSEDE SQHPKGTENS EANEEYQNSS QESWVQRMLM ALVGDSALFN TREGRAGKVH NFMLGLNLNS CYPLSPLADL LTQESVEEDE LDAAVADPDE FERIYEPLDV KSKKIHIVDS GLTFNLPYPL ILRPQRGVDL IISFDFSARP SDSSPPFKEI LLAEKWAKMN KLPFPKIDPN VFDREGLKEC YVFKPKDTSS EKDCPTIIHF VLANINFRKY KAPGLPRESK EEKDFADFDI FDDPNTPFST FNFQYPNEAF KRLHDLMEFN TLNNLDVIKQ AMMESIEYRK ENPSRCSVSL SSVEARRFFN KNNLNNHT //