PA2GA_BOVIN
ID PA2GA_BOVIN Reviewed; 144 AA.
AC Q56JZ2; Q3T193;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Phospholipase A2, membrane associated;
DE EC=3.1.1.4 {ECO:0000250|UniProtKB:P14555};
DE AltName: Full=GIIC sPLA2;
DE AltName: Full=Group IIA phospholipase A2;
DE AltName: Full=Phosphatidylcholine 2-acylhydrolase 2A;
DE Flags: Precursor;
GN Name=PLA2G2A;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymphoid epithelium;
RA Yu J., Meng Y., Wang Z., Hansen C., Li C., Moore S.S.;
RT "Analysis of sequences obtained from constructed full-length bovine cDNA
RT libraries.";
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Ileum;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Secretory calcium-dependent phospholipase A2 that primarily
CC targets extracellular phospholipids with implications in host
CC antimicrobial defense, inflammatory response and tissue regeneration
CC (By similarity). Hydrolyzes the ester bond of the fatty acyl group
CC attached at sn-2 position of phospholipids (phospholipase A2 activity)
CC with preference for phosphatidylethanolamines and phosphatidylglycerols
CC over phosphatidylcholines (By similarity). Contributes to lipid
CC remodeling of cellular membranes and generation of lipid mediators
CC involved in pathogen clearance. Displays bactericidal activity against
CC Gram-positive bacteria by directly hydrolyzing phospholipids of the
CC bacterial membrane. Upon sterile inflammation, targets membrane
CC phospholipids of extracellular mitochondria released from activated
CC platelets, generating free unsaturated fatty acids such as arachidonate
CC that is used by neighboring leukocytes to synthesize inflammatory
CC eicosanoids such as leukotrienes. Simultaneously, by compromising
CC mitochondrial membrane integrity, promotes the release in circulation
CC of potent damage-associated molecular pattern molecules that activate
CC the innate immune response (By similarity). Plays a stem cell regulator
CC role in the intestinal crypt. Within intracellular compartment mediates
CC Paneth cell differentiation and its stem cell supporting functions by
CC inhibiting Wnt signaling pathway in intestinal stem cell (ICS).
CC Secreted in the intestinal lumen upon inflammation, acts in an
CC autocrine way and promotes prostaglandin E2 synthesis that stimulates
CC Wnt signaling pathway in ICS cells and tissue regeneration (By
CC similarity). May play a role in the biosynthesis of N-acyl
CC ethanolamines that regulate energy metabolism and inflammation.
CC Hydrolyzes N-acyl phosphatidylethanolamines to N-acyl
CC lysophosphatidylethanolamines, which are further cleaved by a
CC lysophospholipase D to release N-acyl ethanolamines. Independent of its
CC catalytic activity, acts as a ligand for integrins. Binds to and
CC activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1. Binds to
CC a site (site 2) which is distinct from the classical ligand-binding
CC site (site 1) and induces integrin conformational changes and enhanced
CC ligand binding to site 1. Induces cell proliferation in an integrin-
CC dependent manner (By similarity). {ECO:0000250|UniProtKB:P14555,
CC ECO:0000250|UniProtKB:P31482}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + H2O = a 1-
CC acyl-sn-glycero-3-phosphoethanolamine + a fatty acid + H(+);
CC Xref=Rhea:RHEA:44604, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:28868, ChEBI:CHEBI:64381, ChEBI:CHEBI:64612;
CC Evidence={ECO:0000250|UniProtKB:P14555};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44605;
CC Evidence={ECO:0000250|UniProtKB:P14555};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphoethanolamine + H2O = (9Z)-octadecenoate + 1-hexadecanoyl-sn-
CC glycero-3-phosphoethanolamine + H(+); Xref=Rhea:RHEA:40911,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:73004, ChEBI:CHEBI:73007;
CC Evidence={ECO:0000250|UniProtKB:P14555};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40912;
CC Evidence={ECO:0000250|UniProtKB:P14555};
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:0000250|UniProtKB:P14555};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40816;
CC Evidence={ECO:0000250|UniProtKB:P14555};
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:0000250|UniProtKB:P14555};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40432;
CC Evidence={ECO:0000250|UniProtKB:P14555};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-hexadecanoyl-1,2-di-(9Z-octadecenoyl)-sn-glycero-3-
CC phosphoethanolamine = (9Z)-octadecenoate + H(+) + N-hexadecanoyl-1-
CC (9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine;
CC Xref=Rhea:RHEA:45424, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:78097, ChEBI:CHEBI:85217;
CC Evidence={ECO:0000250|UniProtKB:P14555};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45425;
CC Evidence={ECO:0000250|UniProtKB:P14555};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phospho-(1'-sn-glycerol) + H2O
CC = 1-hexadecanoyl-sn-glycero-3-phospho-(1'-sn-glycerol) + H(+) +
CC hexadecanoate; Xref=Rhea:RHEA:45472, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:72829,
CC ChEBI:CHEBI:75158; Evidence={ECO:0000250|UniProtKB:P14555};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45473;
CC Evidence={ECO:0000250|UniProtKB:P14555};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-
CC glycerol + H2O = (9Z)-octadecenoate + 1-hexadecanoyl-sn-glycero-3-
CC phospho-glycerol + H(+); Xref=Rhea:RHEA:44524, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:84472,
CC ChEBI:CHEBI:84475; Evidence={ECO:0000250|UniProtKB:P14555};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44525;
CC Evidence={ECO:0000250|UniProtKB:P14555};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-(1'-
CC sn-glycerol) + H2O = (9Z)-octadecenoate + 1-hexadecanoyl-sn-glycero-
CC 3-phospho-(1'-sn-glycerol) + H(+); Xref=Rhea:RHEA:40919,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:72841, ChEBI:CHEBI:75158;
CC Evidence={ECO:0000250|UniProtKB:P14555};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40920;
CC Evidence={ECO:0000250|UniProtKB:P14555};
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, ECO:0000255|PROSITE-
CC ProRule:PRU10036};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15802;
CC Evidence={ECO:0000250|UniProtKB:P14555};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-
CC hexadecanoyl-sn-glycero-3-phosphocholine + H(+) + hexadecanoate;
CC Xref=Rhea:RHEA:41223, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:72998, ChEBI:CHEBI:72999;
CC Evidence={ECO:0000250|UniProtKB:P14555};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41224;
CC Evidence={ECO:0000250|UniProtKB:P14555};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine
CC + H2O = (9Z)-octadecenoate + 1-hexadecanoyl-sn-glycero-3-
CC phosphocholine + H(+); Xref=Rhea:RHEA:38779, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:72998,
CC ChEBI:CHEBI:73001; Evidence={ECO:0000250|UniProtKB:P14555};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38780;
CC Evidence={ECO:0000250|UniProtKB:P14555};
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:0000250|UniProtKB:P14555};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40812;
CC Evidence={ECO:0000250|UniProtKB:P14555};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-
CC glycero-3-phosphocholine + H2O = (4Z,7Z,10Z,13Z,16Z,19Z)-
CC docosahexaenoate + 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+);
CC Xref=Rhea:RHEA:41231, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:72998, ChEBI:CHEBI:74963, ChEBI:CHEBI:77016;
CC Evidence={ECO:0000250|UniProtKB:P14555};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41232;
CC Evidence={ECO:0000250|UniProtKB:P14555};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:P14555};
CC Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000250|UniProtKB:P14555};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P14555}. Cell
CC membrane {ECO:0000250|UniProtKB:P14555}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P14555}. Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:P14555}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P14555}.
CC -!- MISCELLANEOUS: Group II phospholipase A2 is found in many cells and
CC also extracellularly. The membrane-bound and secreted forms are
CC identical and are encoded by a single gene.
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. {ECO:0000305}.
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DR EMBL; AY911335; AAW82103.1; -; mRNA.
DR EMBL; BC102063; AAI02064.1; -; mRNA.
DR RefSeq; NP_001020495.1; NM_001025324.2.
DR AlphaFoldDB; Q56JZ2; -.
DR SMR; Q56JZ2; -.
DR STRING; 9913.ENSBTAP00000007570; -.
DR PaxDb; Q56JZ2; -.
DR Ensembl; ENSBTAT00000007570; ENSBTAP00000007570; ENSBTAG00000005759.
DR GeneID; 507201; -.
DR KEGG; bta:507201; -.
DR CTD; 5320; -.
DR VEuPathDB; HostDB:ENSBTAG00000005759; -.
DR eggNOG; KOG4087; Eukaryota.
DR GeneTree; ENSGT00940000155096; -.
DR HOGENOM; CLU_090683_3_0_1; -.
DR InParanoid; Q56JZ2; -.
DR OMA; NTITCED; -.
DR OrthoDB; 1422829at2759; -.
DR TreeFam; TF319283; -.
DR Reactome; R-BTA-1482788; Acyl chain remodelling of PC.
DR Reactome; R-BTA-1482801; Acyl chain remodelling of PS.
DR Reactome; R-BTA-1482839; Acyl chain remodelling of PE.
DR Reactome; R-BTA-1482922; Acyl chain remodelling of PI.
DR Reactome; R-BTA-1482925; Acyl chain remodelling of PG.
DR Reactome; R-BTA-1483166; Synthesis of PA.
DR Reactome; R-BTA-6803157; Antimicrobial peptides.
DR Proteomes; UP000009136; Chromosome 2.
DR Bgee; ENSBTAG00000005759; Expressed in nasopharynx and 70 other tissues.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0047498; F:calcium-dependent phospholipase A2 activity; ISS:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; IBA:GO_Central.
DR GO; GO:0050482; P:arachidonic acid secretion; IEA:InterPro.
DR GO; GO:0019835; P:cytolysis; IEA:UniProtKB-KW.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0036335; P:intestinal stem cell homeostasis; ISS:UniProtKB.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0046470; P:phosphatidylcholine metabolic process; ISS:UniProtKB.
DR GO; GO:0046337; P:phosphatidylethanolamine metabolic process; ISS:UniProtKB.
DR GO; GO:0006644; P:phospholipid metabolic process; IBA:GO_Central.
DR GO; GO:1902563; P:regulation of neutrophil activation; ISS:UniProtKB.
DR CDD; cd00125; PLA2c; 1.
DR Gene3D; 1.20.90.10; -; 1.
DR InterPro; IPR001211; PLipase_A2.
DR InterPro; IPR033112; PLipase_A2_Asp_AS.
DR InterPro; IPR016090; PLipase_A2_dom.
DR InterPro; IPR036444; PLipase_A2_dom_sf.
DR InterPro; IPR033113; PLipase_A2_His_AS.
DR PANTHER; PTHR11716; PTHR11716; 1.
DR Pfam; PF00068; Phospholip_A2_1; 1.
DR PRINTS; PR00389; PHPHLIPASEA2.
DR SMART; SM00085; PA2c; 1.
DR SUPFAM; SSF48619; SSF48619; 1.
DR PROSITE; PS00119; PA2_ASP; 1.
DR PROSITE; PS00118; PA2_HIS; 1.
PE 2: Evidence at transcript level;
KW Antimicrobial; Bacteriolytic enzyme; Calcium; Cell membrane;
KW Disulfide bond; Hydrolase; Inflammatory response; Lipid degradation;
KW Lipid metabolism; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion outer membrane; Phospholipid metabolism; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000250"
FT CHAIN 21..144
FT /note="Phospholipase A2, membrane associated"
FT /id="PRO_0000239271"
FT ACT_SITE 67
FT /evidence="ECO:0000250"
FT ACT_SITE 111
FT /evidence="ECO:0000250"
FT BINDING 47
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 49
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P14555"
FT BINDING 51
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 68
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P14555"
FT DISULFID 46..137
FT /evidence="ECO:0000250|UniProtKB:P14555"
FT DISULFID 48..64
FT /evidence="ECO:0000250|UniProtKB:P14555"
FT DISULFID 63..117
FT /evidence="ECO:0000250|UniProtKB:P14555"
FT DISULFID 69..144
FT /evidence="ECO:0000250|UniProtKB:P14555"
FT DISULFID 70..110
FT /evidence="ECO:0000250|UniProtKB:P14555"
FT DISULFID 79..103
FT /evidence="ECO:0000250|UniProtKB:P14555"
FT DISULFID 97..108
FT /evidence="ECO:0000250|UniProtKB:P14555"
FT CONFLICT 75
FT /note="E -> K (in Ref. 2; AAI02064)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 144 AA; 16347 MW; 7D5CA6254CBDAC55 CRC64;
MKTLLLLAVI MAIGLLQVHG DLLNFRKMIK LTTGKEPATR YSFYGCYCGM SGRGTPKDAT
DWCCRAHDCC YKNLESRGCR TKFLKYNVTY QEDQIVCEDA DDCKSQVCQC DKIAANCFAA
NLKTYNKKLR FYNKFRCRGA APAC
