PA24A_DANRE
ID PA24A_DANRE Reviewed; 741 AA.
AC P50392;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 141.
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 Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Embryo;
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; U10330; AAA53229.1; -; mRNA.
DR PIR; B54908; B54908.
DR RefSeq; NP_571370.1; NM_131295.2.
DR AlphaFoldDB; P50392; -.
DR SMR; P50392; -.
DR STRING; 7955.ENSDARP00000090686; -.
DR PaxDb; P50392; -.
DR GeneID; 30554; -.
DR KEGG; dre:30554; -.
DR CTD; 30554; -.
DR ZFIN; ZDB-GENE-990415-45; pla2g4aa.
DR eggNOG; KOG1012; Eukaryota.
DR eggNOG; KOG1325; Eukaryota.
DR InParanoid; P50392; -.
DR OrthoDB; 302848at2759; -.
DR PhylomeDB; P50392; -.
DR BRENDA; 3.1.1.4; 928.
DR Reactome; R-DRE-111995; phospho-PLA2 pathway.
DR Reactome; R-DRE-1482788; Acyl chain remodelling of PC.
DR Reactome; R-DRE-1482798; Acyl chain remodeling of CL.
DR Reactome; R-DRE-1482801; Acyl chain remodelling of PS.
DR Reactome; R-DRE-1482839; Acyl chain remodelling of PE.
DR Reactome; R-DRE-1482922; Acyl chain remodelling of PI.
DR Reactome; R-DRE-1482925; Acyl chain remodelling of PG.
DR Reactome; R-DRE-1483115; Hydrolysis of LPC.
DR Reactome; R-DRE-1483166; Synthesis of PA.
DR Reactome; R-DRE-2142753; Arachidonic acid metabolism.
DR Reactome; R-DRE-418592; ADP signalling through P2Y purinoceptor 1.
DR Reactome; R-DRE-432142; Platelet sensitization by LDL.
DR Reactome; R-DRE-6811436; COPI-independent Golgi-to-ER retrograde traffic.
DR PRO; PR:P50392; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
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: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:0004622; F:lysophospholipase activity; IEA:UniProtKB-EC.
DR GO; GO:0102545; F:phosphatidyl phospholipase B activity; IEA:UniProtKB-EC.
DR GO; GO:0004623; F:phospholipase A2 activity; IBA:GO_Central.
DR GO; GO:0004620; F:phospholipase activity; IDA:ZFIN.
DR GO; GO:0046475; P:glycerophospholipid catabolic process; IBA:GO_Central.
DR GO; GO:0090594; P:inflammatory response to wounding; IMP:ZFIN.
DR GO; GO:0001541; P:ovarian follicle development; IEP:ZFIN.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IGI:ZFIN.
DR GO; GO:0009611; P:response to wounding; IMP:ZFIN.
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 2: Evidence at transcript level;
KW Calcium; Cytoplasm; Cytoplasmic vesicle; Hydrolase; Lipid degradation;
KW Lipid metabolism; Metal-binding; Phosphoprotein; Reference proteome.
FT CHAIN 1..741
FT /note="Cytosolic phospholipase A2"
FT /id="PRO_0000187265"
FT DOMAIN 1..116
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 132..729
FT /note="PLA2c"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00555"
FT REGION 1..172
FT /note="Phospholipid binding"
FT /evidence="ECO:0000305"
FT REGION 406..453
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 414..453
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 223
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 540
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 34
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 34
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 35
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 37
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 37
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 59
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 87
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 88
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 89
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MOD_RES 498
FT /note="Phosphoserine; by MAPK"
FT /evidence="ECO:0000250"
SQ SEQUENCE 741 AA; 83809 MW; 34896B1A8364A9D4 CRC64;
MSNIIVEHQY SHRLKLTVVR AENVTKGAFG DLLDTPDPYV ELSVPTTPES RKRTRHINND
INPKWNETFE FILDPNQSNV LEVTLMDANY VMDETLGTAK YSLSKLKVAQ MEHVTLSIGK
TTKVFLDLLL EVCASTDLRF SMTLCDQEKL FMQTRRDRVM LSIKKLLKME NPRFLPSSPR
EVPTIAILGS GGGFRAMVGF SGVMKALYES GVFDCATYVA GLSGSTWYMS MLYSHPEFPA
KGPGDINKEL MNRVSNNPLK LLLPQNINRY VKALWKKKSA GQPVTFTDIF GMLIGETLIP
GRMNIKLSSL KGKINEGQSP LPLFTCLHVK PDVSELMFAD WVEFSPYEIG MAKYGTFMSP
GLFGSKFFMG SVVKQYEENP LHFLMGVWGS AFSILFNRVL GVKETTSSST MEEELEQIKP
EHIVGDDSAD NEEETQRGGT ESADAEDERQ RHAQASWVQR MLTSIMGDTT LFTTREGRAG
KVHNFMLGLN LNSTLPFSPF SGITHQTSLE EEVDAVTDPD EFERIYEPLD VKSKKIHVVD
SGLTFNLPYP LILRCQRGVD LIISFDFSAR PSDSSPPFKE LLLAEKWARM NKLPFPKIDS
KVFDREGLKE CYVFKPAKGD KNCPTIIHFV LANINFRNFK APGVPRDSDK DIEFGDFDIF
DEPASPYSTF NFKYNNQAFK RLHDLMEFNT LNNIEVIKEA IKDSILLRRE NPARCSVSLS
LSEIENKKFL KRDNSIAKRP T
