PA2GA_RABIT
ID PA2GA_RABIT Reviewed; 68 AA.
AC P14422;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 2.
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: Fragments;
GN Name=PLA2G2A;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP PROTEIN SEQUENCE OF 1-34 AND 40-68, FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, AND SUBCELLULAR LOCATION.
RC TISSUE=Platelet;
RX PubMed=2668261; DOI=10.1093/oxfordjournals.jbchem.a122699;
RA Mizushima H., Kudo I., Horigome K., Murakami M., Hayakawa M., Kim D.K.,
RA Kondo E., Tomita M., Inoue K.;
RT "Purification of rabbit platelet secretory phospholipase A2 and its
RT characteristics.";
RL J. Biochem. 105:520-525(1989).
RN [2]
RP PROTEIN SEQUENCE OF 1-39.
RX PubMed=3548813; DOI=10.1021/bi00374a008;
RA Forst S., Weiss J., Elsbach P., Maraganore J.M., Reardon I.,
RA Heinrikson R.L.;
RT "Structural and functional properties of a phospholipase A2 purified from
RT an inflammatory exudate.";
RL Biochemistry 25:8381-8385(1986).
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 (PubMed:2668261). 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, ECO:0000269|PubMed:2668261}.
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:0000269|PubMed:2668261};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44605;
CC Evidence={ECO:0000305|PubMed:2668261};
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-acyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-
CC phosphoethanolamine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + a 1-
CC acyl-sn-glycero-3-phosphoethanolamine + H(+); Xref=Rhea:RHEA:40647,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32395,
CC ChEBI:CHEBI:64381, ChEBI:CHEBI:75067;
CC Evidence={ECO:0000269|PubMed:2668261};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40648;
CC Evidence={ECO:0000305|PubMed:2668261};
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:0000269|PubMed:2668261};
CC Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000250|UniProtKB:P14555};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 8.5. {ECO:0000269|PubMed:2668261};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2668261}. 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 -!- SIMILARITY: Belongs to the phospholipase A2 family. {ECO:0000305}.
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DR PIR; PX0019; PX0019.
DR STRING; 9986.ENSOCUP00000026675; -.
DR BindingDB; P14422; -.
DR ChEMBL; CHEMBL5481; -.
DR InParanoid; P14422; -.
DR SABIO-RK; P14422; -.
DR Proteomes; UP000001811; Unplaced.
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; IEA:InterPro.
DR GO; GO:0047498; F:calcium-dependent phospholipase A2 activity; ISS:UniProtKB.
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:1902563; P:regulation of neutrophil activation; ISS:UniProtKB.
DR Gene3D; 1.20.90.10; -; 1.
DR InterPro; IPR001211; PLipase_A2.
DR InterPro; IPR016090; PLipase_A2_dom.
DR InterPro; IPR036444; PLipase_A2_dom_sf.
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.
PE 1: Evidence at protein level;
KW Antimicrobial; Bacteriolytic enzyme; Calcium; Cell membrane;
KW Direct protein sequencing; Disulfide bond; Hydrolase;
KW Inflammatory response; Lipid degradation; Lipid metabolism; Membrane;
KW Metal-binding; Mitochondrion; Mitochondrion outer membrane;
KW Phospholipid metabolism; Reference proteome; Secreted.
FT CHAIN 1..>68
FT /note="Phospholipase A2, membrane associated"
FT /id="PRO_0000161589"
FT BINDING 27
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P14555"
FT BINDING 29
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P14555"
FT BINDING 31
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P14555"
FT DISULFID 26..66
FT /evidence="ECO:0000250|UniProtKB:P14555"
FT CONFLICT 27
FT /note="H -> S (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT NON_CONS 39..40
FT /evidence="ECO:0000305"
FT NON_CONS 49..50
FT /evidence="ECO:0000305"
FT NON_CONS 56..57
FT /evidence="ECO:0000305"
FT NON_TER 68
SQ SEQUENCE 68 AA; 7592 MW; 422BAE45B79773A3 CRC64;
HLLDFRKMIR YTTGKEATTS YGAYGCHCGV GGRGAPKXAK FLSYKFSMKK AAAACFKYQF
YPNNRCXG
