PA24F_MOUSE
ID PA24F_MOUSE Reviewed; 855 AA.
AC Q50L41; A2AQJ2; Q80VQ8; Q80VV9;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Cytosolic phospholipase A2 zeta;
DE Short=cPLA2-zeta;
DE EC=3.1.1.4 {ECO:0000269|PubMed:15866882, ECO:0000269|PubMed:17293613};
DE AltName: Full=Phospholipase A2 group IVF;
GN Name=Pla2g4f;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J;
RX PubMed=15866882; DOI=10.1074/jbc.m413711200;
RA Ohto T., Uozumi N., Hirabayashi T., Shimizu T.;
RT "Identification of novel cytosolic phospholipase A(2)s, murine
RT cPLA(2)delta, epsilon, and zeta, which form a gene cluster with
RT cPLA(2)beta.";
RL J. Biol. Chem. 280:24576-24583(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 19-855.
RC STRAIN=FVB/N, and NMRI; TISSUE=Mammary tumor, and Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, COFACTOR, AND
RP SUBCELLULAR LOCATION.
RX PubMed=17293613; DOI=10.1074/jbc.m608458200;
RA Ghosh M., Loper R., Ghomashchi F., Tucker D.E., Bonventre J.V., Gelb M.H.,
RA Leslie C.C.;
RT "Function, activity, and membrane targeting of cytosolic phospholipase
RT A(2)zeta in mouse lung fibroblasts.";
RL J. Biol. Chem. 282:11676-11686(2007).
CC -!- FUNCTION: Has calcium-dependent phospholipase and lysophospholipase
CC activities with a potential role in membrane lipid remodeling and
CC biosynthesis of lipid mediators (PubMed:17293613, PubMed:15866882).
CC Preferentially hydrolyzes the ester bond of the fatty acyl group
CC attached at sn-2 position of phospholipids (phospholipase A2 activity)
CC (PubMed:17293613, PubMed:15866882). Selectively hydrolyzes sn-2
CC arachidonoyl group from membrane phospholipids, providing the precursor
CC for eicosanoid biosynthesis (PubMed:15866882, PubMed:17293613). In
CC myocardial mitochondria, plays a major role in arachidonate release
CC that is metabolically channeled to the formation of cardioprotective
CC eicosanoids, epoxyeicosatrienoates (EETs) (By similarity).
CC {ECO:0000250|UniProtKB:Q68DD2, ECO:0000269|PubMed:15866882,
CC ECO:0000269|PubMed:17293613}.
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:0000269|PubMed:15866882, ECO:0000269|PubMed:17293613};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15802;
CC Evidence={ECO:0000305|PubMed:15866882, ECO:0000305|PubMed:17293613};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine
CC + H2O = 2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H(+) +
CC hexadecanoate; Xref=Rhea:RHEA:38783, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:73001,
CC ChEBI:CHEBI:76071; Evidence={ECO:0000269|PubMed:17293613};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38784;
CC Evidence={ECO:0000305|PubMed:17293613};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-
CC phosphocholine + H2O = (9Z,12Z)-octadecadienoate + 1-hexadecanoyl-sn-
CC glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:40811,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30245,
CC ChEBI:CHEBI:72998, ChEBI:CHEBI:73002;
CC Evidence={ECO:0000269|PubMed:15866882};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40812;
CC Evidence={ECO:0000305|PubMed:15866882};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-
CC hexadecanoyl-sn-glycero-3-phosphocholine + H(+);
CC Xref=Rhea:RHEA:40427, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:72998, ChEBI:CHEBI:73003;
CC Evidence={ECO:0000269|PubMed:15866882, ECO:0000269|PubMed:17293613};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40428;
CC Evidence={ECO:0000305|PubMed:17293613};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-
CC phosphoethanolamine + H2O = (9Z,12Z)-octadecadienoate + 1-
CC hexadecanoyl-sn-glycero-3-phosphoethanolamine + H(+);
CC Xref=Rhea:RHEA:40815, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30245, ChEBI:CHEBI:73004, ChEBI:CHEBI:73008;
CC Evidence={ECO:0000269|PubMed:15866882, ECO:0000269|PubMed:17293613};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40816;
CC Evidence={ECO:0000305|PubMed:15866882, ECO:0000305|PubMed:17293613};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phosphoethanolamine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-
CC hexadecanoyl-sn-glycero-3-phosphoethanolamine + H(+);
CC Xref=Rhea:RHEA:40431, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:73004, ChEBI:CHEBI:73009;
CC Evidence={ECO:0000269|PubMed:15866882, ECO:0000269|PubMed:17293613};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40432;
CC Evidence={ECO:0000305|PubMed:15866882, ECO:0000305|PubMed:17293613};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-2-O-hexadecyl-sn-glycero-3-
CC phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 2-O-
CC hexadecyl-sn-glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:41271,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32395,
CC ChEBI:CHEBI:77695, ChEBI:CHEBI:77696;
CC Evidence={ECO:0000269|PubMed:17293613};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41272;
CC Evidence={ECO:0000305|PubMed:17293613};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-hexadecyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-
CC phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-O-
CC hexadecyl-sn-glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:41067,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32395,
CC ChEBI:CHEBI:55430, ChEBI:CHEBI:64496;
CC Evidence={ECO:0000269|PubMed:17293613};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41068;
CC Evidence={ECO:0000305|PubMed:17293613};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = H(+) +
CC hexadecanoate + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40435,
CC ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16870, ChEBI:CHEBI:72998;
CC Evidence={ECO:0000269|PubMed:17293613};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40436;
CC Evidence={ECO:0000305|PubMed:17293613};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041,
CC ECO:0000269|PubMed:15866882, ECO:0000269|PubMed:17293613};
CC -!- ACTIVITY REGULATION: Stimulated by cytosolic Ca(2+).
CC {ECO:0000269|PubMed:15866882, ECO:0000269|PubMed:17293613}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:15866882,
CC ECO:0000269|PubMed:17293613}. Cell membrane
CC {ECO:0000269|PubMed:17293613}; Peripheral membrane protein
CC {ECO:0000305}. Mitochondrion {ECO:0000250|UniProtKB:Q68DD2}.
CC -!- TISSUE SPECIFICITY: Strongly expressed in thyroid, expressed at
CC intermediate level in stomach and at very low level in large intestine
CC and prostate. {ECO:0000269|PubMed:15866882}.
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 -!- SEQUENCE CAUTION:
CC Sequence=AAH39947.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB195278; BAD98154.1; -; mRNA.
DR EMBL; AL844608; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC039947; AAH39947.1; ALT_INIT; mRNA.
DR EMBL; BC046400; AAH46400.1; -; mRNA.
DR CCDS; CCDS16618.1; -.
DR RefSeq; NP_001019316.1; NM_001024145.2.
DR AlphaFoldDB; Q50L41; -.
DR SMR; Q50L41; -.
DR STRING; 10090.ENSMUSP00000062607; -.
DR SwissLipids; SLP:000001085; -.
DR PhosphoSitePlus; Q50L41; -.
DR MaxQB; Q50L41; -.
DR PaxDb; Q50L41; -.
DR PRIDE; Q50L41; -.
DR ProteomicsDB; 294373; -.
DR Antibodypedia; 42117; 69 antibodies from 25 providers.
DR DNASU; 271844; -.
DR Ensembl; ENSMUST00000054651; ENSMUSP00000062607; ENSMUSG00000046971.
DR GeneID; 271844; -.
DR KEGG; mmu:271844; -.
DR UCSC; uc008lvi.2; mouse.
DR CTD; 255189; -.
DR MGI; MGI:2685493; Pla2g4f.
DR VEuPathDB; HostDB:ENSMUSG00000046971; -.
DR eggNOG; KOG1028; Eukaryota.
DR eggNOG; KOG1325; Eukaryota.
DR GeneTree; ENSGT01030000234606; -.
DR HOGENOM; CLU_011663_0_0_1; -.
DR InParanoid; Q50L41; -.
DR OMA; WPEPRIC; -.
DR OrthoDB; 302848at2759; -.
DR PhylomeDB; Q50L41; -.
DR TreeFam; TF325228; -.
DR Reactome; R-MMU-1482788; Acyl chain remodelling of PC.
DR Reactome; R-MMU-1482801; Acyl chain remodelling of PS.
DR Reactome; R-MMU-1482839; Acyl chain remodelling of PE.
DR Reactome; R-MMU-1482922; Acyl chain remodelling of PI.
DR Reactome; R-MMU-1482925; Acyl chain remodelling of PG.
DR Reactome; R-MMU-1483115; Hydrolysis of LPC.
DR BioGRID-ORCS; 271844; 3 hits in 74 CRISPR screens.
DR PRO; PR:Q50L41; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q50L41; protein.
DR Bgee; ENSMUSG00000046971; Expressed in esophagus and 68 other tissues.
DR Genevisible; Q50L41; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0032587; C:ruffle membrane; IDA:MGI.
DR GO; GO:0031982; C:vesicle; IDA:MGI.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0047498; F:calcium-dependent phospholipase A2 activity; IDA:MGI.
DR GO; GO:0005544; F:calcium-dependent phospholipid binding; IBA:GO_Central.
DR GO; GO:0004622; F:lysophospholipase activity; IDA:MGI.
DR GO; GO:0004623; F:phospholipase A2 activity; IDA:MGI.
DR GO; GO:0050482; P:arachidonic acid secretion; IDA:MGI.
DR GO; GO:0071236; P:cellular response to antibiotic; IDA:MGI.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:MGI.
DR GO; GO:0015908; P:fatty acid transport; IDA:MGI.
DR GO; GO:0046475; P:glycerophospholipid catabolic process; IBA:GO_Central.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; IDA:MGI.
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; IPR040723; cPLA2_C2.
DR InterPro; IPR002642; LysoPLipase_cat_dom.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF18695; cPLA2_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 Calcium; Cell membrane; Cytoplasm; Hydrolase; Lipid degradation;
KW Lipid metabolism; Membrane; Metal-binding; Mitochondrion;
KW Phospholipid degradation; Phospholipid metabolism; Reference proteome.
FT CHAIN 1..855
FT /note="Cytosolic phospholipase A2 zeta"
FT /id="PRO_0000247028"
FT DOMAIN 27..145
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 304..855
FT /note="PLA2c"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00555"
FT ACT_SITE 393
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 685
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 60
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 60
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 66
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 116
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 116
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 118
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 118
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT BINDING 123
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT CONFLICT 99
FT /note="P -> H (in Ref. 3; AAH39947)"
FT /evidence="ECO:0000305"
FT CONFLICT 132
FT /note="T -> M (in Ref. 3; AAH39947)"
FT /evidence="ECO:0000305"
FT CONFLICT 234
FT /note="V -> M (in Ref. 3; AAH39947)"
FT /evidence="ECO:0000305"
FT CONFLICT 297
FT /note="S -> T (in Ref. 3; AAH39947)"
FT /evidence="ECO:0000305"
FT CONFLICT 507
FT /note="D -> Y (in Ref. 3; AAH39947/AAH46400)"
FT /evidence="ECO:0000305"
FT CONFLICT 526
FT /note="A -> V (in Ref. 3; AAH39947/AAH46400)"
FT /evidence="ECO:0000305"
FT CONFLICT 755
FT /note="A -> T (in Ref. 3; AAH39947/AAH46400)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 855 AA; 96364 MW; 4F839C857E136D6F CRC64;
MPWTLQPKWL AGKGLPLLGA ILLRKTEKSE PQWKHRRQET HPYYDLQVKV LRARNIQHTD
KLSKADCYVR LWLPTASVSP SQTRTVVNSS DPEWNETFPY QIHGAVKNVL ELALYDEDVL
DSDNVFSILF DTSTLQLGQP CTKNFTRQQD PKELEVEFTL EKSQTPASEV VTNGVLVAHP
CLRIQGTVTG DKTASLGELG SRQIQLAVPG AYEKPQPLQP TSEPGLPVNF TFHVNPVLSP
KLHIKLQEQL QVFHSGPSDE LEAQTSKMDK ASILLSSLPL NEELTKLVDL EEGQQVSLRM
KADMSSSGDL DLRLGFDLCD GEQEFLDKRK QVASKALQRV MGLSEALHCD QVPVVAVLGS
GGGTRAMTSL YGSLAGLQEL GLLDAVTYLS GVSGSSWCIS TLYRDPSWSQ KALQGPIKYA
SERVCSSKIG MLSPKQFEYY SREKRAWESR GHSMSFTDLW GLIIEYFLNQ EENPAKLSDQ
QETVSQGQNP YPIYASINVH KNISGDDFAE WCEFTPYEVG FPKYGAYVPT ELFGSEFFMG
RLLHFWPEPR ICYLQGMWGS AFAASLYEIF LKLGGLSLSF LDWHRGSVSV TDDWPKLRKQ
DPTRLPTRLF TPMSSFSQAV LDIFTSRITC AQTFNFTRGL CMYKDYTARK DFVVSEDAWH
SHNYGYPDAC PNQLTPMKDF LSLVDGGFAI NSPFPLVLQP QRAVDLIVSF DYSLEGPFEV
LQVTEKYCRD RGIPFPRIEV DPKDSEDPRE CYLFAEAEDP CSPIVLHFPL VNRTFRTHLA
PGVERQTAEE KAFGDFIING PDTAYGMMDF TYEPKEFDRL VTLSRYNVLN NKETIRHALQ
LALDRRRQAG GRVGG
