PA24A_CHICK
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 03-AUG-2022, entry version 144.
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}.
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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; P49147; -.
DR PRIDE; P49147; -.
DR Ensembl; ENSGALT00000048470; ENSGALP00000048642; ENSGALG00000005065.
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; KFFMGKV; -.
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 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:0004623; F:phospholipase A2 activity; IBA:GO_Central.
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 Gene3D; 2.60.40.150; -; 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 Pfam; PF00168; C2; 1.
DR Pfam; PF01735; PLA2_B; 1.
DR SMART; SM00239; C2; 1.
DR SMART; SM00022; PLAc; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF52151; SSF52151; 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
