PA2GX_RAT
ID PA2GX_RAT Reviewed; 151 AA.
AC Q9QZT3;
DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Group 10 secretory phospholipase A2;
DE EC=3.1.1.4 {ECO:0000250|UniProtKB:O15496};
DE AltName: Full=Group X secretory phospholipase A2;
DE Short=GX sPLA2;
DE Short=sPLA2-X;
DE AltName: Full=Phosphatidylcholine 2-acylhydrolase 10;
DE Flags: Precursor;
GN Name=Pla2g10;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10531313; DOI=10.1074/jbc.274.44.31195;
RA Valentin E., Ghomashchi F., Gelb M.H., Lazdunski M., Lambeau G.;
RT "On the diversity of secreted phospholipases A2. Cloning, tissue
RT distribution, and functional expression of two novel mouse group II
RT enzymes.";
RL J. Biol. Chem. 274:31195-31202(1999).
CC -!- FUNCTION: Secretory calcium-dependent phospholipase A2 that primarily
CC targets extracellular phospholipids. Hydrolyzes the ester bond of the
CC fatty acyl group attached at sn-2 position of phospholipids with
CC preference for phosphatidylcholines and phosphatidylglycerols over
CC phosphatidylethanolamines. Preferentially releases sn-2 omega-6 and
CC omega-3 polyunsaturated fatty acyl (PUFA) chains over saturated fatty
CC acyls. Contributes to phospholipid remodeling of very low-density
CC lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density
CC lipoprotein (HDL) particles. Hydrolyzes LDL phospholipids releasing
CC unsaturated fatty acids that regulate macrophage differentiation toward
CC foam cells. Efficiently hydrolyzes and inactivates platelet activating
CC factor (PAF), a potent lipid mediator present in oxidized LDL (By
CC similarity). May act in an autocrine and paracrine manner. Secreted by
CC lung epithelium, targets membrane phospholipids of infiltrating
CC eosinophils, releasing arachidonate and boosting eicosanoid and
CC cysteinyl leukotriene synthesis involved in airway inflammatory
CC response. Secreted by gut epithelium, hydrolyzes dietary and biliary
CC phosphatidylcholines in the gastrointestinal lumen. Plays a stem cell
CC regulator role in colon epithelium. Within intracellular compartment,
CC mediates Paneth-like cell differentiation and its stem cell supporting
CC functions by inhibiting the Wnt signaling pathway in intestinal stem
CC cell (ISC). Secreted in the intestinal lumen upon inflammation, acts in
CC an autocrine way and promotes prostaglandin E2 synthesis that
CC stimulates Wnt signaling pathway in ISCs and tissue regeneration. May
CC participate in hair follicle morphogenesis by regulating
CC phosphatidylethanolamines metabolism at the outermost epithelial layer
CC and facilitating melanin synthesis. By releasing
CC lysophosphatidylcholines (LPCs) at sperm acrosome, controls sperm cell
CC capacitation, acrosome reaction and overall fertility. May promote
CC neurite outgrowth in neuron fibers involved in nociception (By
CC similarity). Contributes to lipid remodeling of cellular membranes and
CC generation of lipid mediators involved in pathogen clearance. Cleaves
CC sn-2 fatty acyl chains of phosphatidylglycerols and
CC phosphatidylethanolamines, which are major components of membrane
CC phospholipids in bacteria. Displays bactericidal activity against Gram-
CC positive bacteria by directly hydrolyzing phospholipids of the
CC bacterial membrane. In pulmonary epithelium, may contribute to host
CC defense response against adenoviral infection. Prevents adenovirus
CC entry into host cells by hydrolyzing host cell plasma membrane,
CC releasing C16:0 LPCs that inhibit virus-mediated membrane fusion and
CC viral infection. Likely prevents adenoviral entry into the endosomes of
CC host cells (By similarity). May play a role in maturation and
CC activation of innate immune cells including macrophages, group 2 innate
CC lymphoid cells and mast cells (By similarity).
CC {ECO:0000250|UniProtKB:O15496, ECO:0000250|UniProtKB:Q9QXX3}.
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:0000250|UniProtKB:O15496, ECO:0000255|PROSITE-
CC ProRule:PRU10035, ECO:0000255|PROSITE-ProRule:PRU10036};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15802;
CC Evidence={ECO:0000250|UniProtKB:O15496};
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:O15496};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38780;
CC Evidence={ECO:0000250|UniProtKB:O15496};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1-
CC octadecanoyl-sn-glycero-3-phosphocholine + H(+);
CC Xref=Rhea:RHEA:40519, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:73858, ChEBI:CHEBI:74965;
CC Evidence={ECO:0000250|UniProtKB:O15496};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40520;
CC Evidence={ECO:0000250|UniProtKB:O15496};
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:O15496};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41224;
CC Evidence={ECO:0000250|UniProtKB:O15496};
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:O15496};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44525;
CC Evidence={ECO:0000250|UniProtKB:O15496};
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:Q9QXX3};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45473;
CC Evidence={ECO:0000250|UniProtKB:Q9QXX3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-
CC serine + H2O = (9Z)-octadecenoate + 1-hexadecanoyl-sn-glycero-3-
CC phospho-L-serine + H(+); Xref=Rhea:RHEA:41752, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:75020,
CC ChEBI:CHEBI:75029; Evidence={ECO:0000250|UniProtKB:O15496};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41753;
CC Evidence={ECO:0000250|UniProtKB:O15496};
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:O15496};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40816;
CC Evidence={ECO:0000250|UniProtKB:O15496};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate +
CC H2O = (9Z)-octadecenoate + 1-hexadecanoyl-sn-glycero-3-phosphate +
CC H(+); Xref=Rhea:RHEA:63996, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:57518, ChEBI:CHEBI:64839;
CC Evidence={ECO:0000250|UniProtKB:O15496};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63997;
CC Evidence={ECO:0000250|UniProtKB:O15496};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-
CC O-hexadecyl-sn-glycero-3-phosphocholine + acetate + H(+);
CC Xref=Rhea:RHEA:40479, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30089, ChEBI:CHEBI:44811, ChEBI:CHEBI:64496;
CC Evidence={ECO:0000250|UniProtKB:O15496};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40480;
CC Evidence={ECO:0000250|UniProtKB:O15496};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:O15496};
CC Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000250|UniProtKB:O15496};
CC -!- SUBUNIT: Interacts with PLA2R1; this interaction mediates PLA2G10
CC clearance and inactivation. {ECO:0000250|UniProtKB:Q9QXX3}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9QXX3}. Lysosome
CC {ECO:0000250|UniProtKB:Q9QXX3}. Cytoplasmic vesicle, secretory vesicle,
CC acrosome {ECO:0000250|UniProtKB:Q9QXX3}.
CC -!- SIMILARITY: Belongs to the phospholipase A2 family. {ECO:0000305}.
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DR EMBL; AF166100; AAF04501.1; -; mRNA.
DR RefSeq; NP_058872.1; NM_017176.2.
DR AlphaFoldDB; Q9QZT3; -.
DR SMR; Q9QZT3; -.
DR STRING; 10116.ENSRNOP00000004237; -.
DR PaxDb; Q9QZT3; -.
DR GeneID; 29359; -.
DR KEGG; rno:29359; -.
DR UCSC; RGD:61935; rat.
DR CTD; 8399; -.
DR RGD; 61935; Pla2g10.
DR eggNOG; KOG4087; Eukaryota.
DR InParanoid; Q9QZT3; -.
DR OrthoDB; 1422829at2759; -.
DR PhylomeDB; Q9QZT3; -.
DR Reactome; R-RNO-1482788; Acyl chain remodelling of PC.
DR Reactome; R-RNO-1482801; Acyl chain remodelling of PS.
DR Reactome; R-RNO-1482839; Acyl chain remodelling of PE.
DR Reactome; R-RNO-1482922; Acyl chain remodelling of PI.
DR Reactome; R-RNO-1482925; Acyl chain remodelling of PG.
DR Reactome; R-RNO-1483166; Synthesis of PA.
DR PRO; PR:Q9QZT3; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0001669; C:acrosomal vesicle; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:RGD.
DR GO; GO:0005615; C:extracellular space; ISO:RGD.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0003847; F:1-alkyl-2-acetylglycerophosphocholine esterase activity; ISS:UniProtKB.
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:0004623; F:phospholipase A2 activity; IDA:RGD.
DR GO; GO:0004620; F:phospholipase activity; ISO:RGD.
DR GO; GO:0005543; F:phospholipid binding; IBA:GO_Central.
DR GO; GO:0050482; P:arachidonic acid secretion; IEA:InterPro.
DR GO; GO:0007411; P:axon guidance; ISO:RGD.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; ISO:RGD.
DR GO; GO:0042632; P:cholesterol homeostasis; ISO:RGD.
DR GO; GO:0051607; P:defense response to virus; ISO:RGD.
DR GO; GO:0043249; P:erythrocyte maturation; ISO:RGD.
DR GO; GO:0009566; P:fertilization; ISO:RGD.
DR GO; GO:0031069; P:hair follicle morphogenesis; ISO:RGD.
DR GO; GO:0036335; P:intestinal stem cell homeostasis; ISO:RGD.
DR GO; GO:0034374; P:low-density lipoprotein particle remodeling; ISO:RGD.
DR GO; GO:0051977; P:lysophospholipid transport; ISO:RGD.
DR GO; GO:0042116; P:macrophage activation; ISO:RGD.
DR GO; GO:0090370; P:negative regulation of cholesterol efflux; ISO:RGD.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; ISO:RGD.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISO:RGD.
DR GO; GO:0046473; P:phosphatidic acid metabolic process; ISS:UniProtKB.
DR GO; GO:0034638; P:phosphatidylcholine catabolic process; ISO:RGD.
DR GO; GO:0046470; P:phosphatidylcholine metabolic process; ISS:UniProtKB.
DR GO; GO:0046337; P:phosphatidylethanolamine metabolic process; ISS:UniProtKB.
DR GO; GO:0046471; P:phosphatidylglycerol metabolic process; ISS:UniProtKB.
DR GO; GO:0006658; P:phosphatidylserine metabolic process; ISS:UniProtKB.
DR GO; GO:0006644; P:phospholipid metabolic process; ISO:RGD.
DR GO; GO:0062234; P:platelet activating factor catabolic process; ISS:UniProtKB.
DR GO; GO:2000344; P:positive regulation of acrosome reaction; ISS:UniProtKB.
DR GO; GO:0090238; P:positive regulation of arachidonic acid secretion; ISO:RGD.
DR GO; GO:0010884; P:positive regulation of lipid storage; ISO:RGD.
DR GO; GO:0032308; P:positive regulation of prostaglandin secretion; ISO:RGD.
DR GO; GO:0002532; P:production of molecular mediator involved in inflammatory response; ISO:RGD.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; ISO:RGD.
DR GO; GO:0043030; P:regulation of macrophage activation; ISO:RGD.
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 Calcium; Cleavage on pair of basic residues; Cytoplasmic vesicle;
KW Disulfide bond; Hydrolase; Lipid metabolism; Lysosome; Metal-binding;
KW Phospholipid metabolism; Reference proteome; Secreted; Signal.
FT SIGNAL 1..17
FT /evidence="ECO:0000250"
FT PROPEP 18..28
FT /evidence="ECO:0000250"
FT /id="PRO_0000022768"
FT CHAIN 29..151
FT /note="Group 10 secretory phospholipase A2"
FT /id="PRO_0000022769"
FT ACT_SITE 74
FT /evidence="ECO:0000250|UniProtKB:O15496"
FT ACT_SITE 119
FT /evidence="ECO:0000250|UniProtKB:O15496"
FT BINDING 54
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250"
FT BINDING 56
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O15496"
FT BINDING 58
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O15496"
FT BINDING 75
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:O15496"
FT DISULFID 39..97
FT /evidence="ECO:0000250|UniProtKB:O15496"
FT DISULFID 53..143
FT /evidence="ECO:0000250|UniProtKB:O15496"
FT DISULFID 55..71
FT /evidence="ECO:0000250|UniProtKB:O15496"
FT DISULFID 70..125
FT /evidence="ECO:0000250|UniProtKB:O15496"
FT DISULFID 76..150
FT /evidence="ECO:0000250|UniProtKB:O15496"
FT DISULFID 77..118
FT /evidence="ECO:0000250|UniProtKB:O15496"
FT DISULFID 86..111
FT /evidence="ECO:0000250|UniProtKB:O15496"
FT DISULFID 104..116
FT /evidence="ECO:0000250|UniProtKB:O15496"
SQ SEQUENCE 151 AA; 17088 MW; 2581E1520A455089 CRC64;
MLLLLLLLLL GPGSCLSEAT RRSHVYKRGL LELAGTLDCV GPRSPMAYMN YGCYCGLGGH
GEPRDAIDWC CYYHDCCYSQ AQDAGCSPKL YRYPWKCMDH RILCGPAENK CQELLCRCDE
TLAYCLADTE YHLKYLFFPS VLCEKDSPKC N
