IED ID | IndEnz0005000797 |
Enzyme Type ID | lipase000797 |
Protein Name |
Platelet-activating factor acetylhydrolase PAF acetylhydrolase EC 3.1.1.47 1-alkyl-2-acetylglycerophosphocholine esterase 2-acetyl-1-alkylglycerophosphocholine esterase Group-VIIA phospholipase A2 gVIIA-PLA2 LDL-associated phospholipase A2 LDL-PLA 2 PAF 2-acylhydrolase |
Gene Name | PLA2G7 PAFAH |
Organism | Homo sapiens (Human) |
Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
Enzyme Sequence | MVPPKLHVLFCLCGCLAVVYPFDWQYINPVAHMKSSAWVNKIQVLMAAASFGQTKIPRGNGPYSVGCTDLMFDHTNKGTFLRLYYPSQDNDRLDTLWIPNKEYFWGLSKFLGTHWLMGNILRLLFGSMTTPANWNSPLRPGEKYPLVVFSHGLGAFRTLYSAIGIDLASHGFIVAAVEHRDRSASATYYFKDQSAAEIGDKSWLYLRTLKQEEETHIRNEQVRQRAKECSQALSLILDIDHGKPVKNALDLKFDMEQLKDSIDREKIAVIGHSFGGATVIQTLSEDQRFRCGIALDAWMFPLGDEVYSRIPQPLFFINSEYFQYPANIIKMKKCYSPDKERKMITIRGSVHQNFADFTFATGKIIGHMLKLKGDIDSNVAIDLSNKASLAFLQKHLGLHKDFDQWDCLIEGDDENLIPGTNINTTNQHIMLQNSSGIEKYN |
Enzyme Length | 441 |
Uniprot Accession Number | Q13093 |
Absorption | |
Active Site | ACT_SITE 273; /note="Nucleophile"; /evidence="ECO:0000269|PubMed:18784071"; ACT_SITE 296; /note="Charge relay system"; /evidence="ECO:0000255|PROSITE-ProRule:PRU10037, ECO:0000269|PubMed:18784071"; ACT_SITE 351; /note="Charge relay system"; /evidence="ECO:0000255|PROSITE-ProRule:PRU10037, ECO:0000269|PubMed:18784071" |
Activity Regulation | |
Binding Site | |
Calcium Binding | |
catalytic Activity | CATALYTIC ACTIVITY: Reaction=a 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-O-alkyl-sn-glycero-3-phosphocholine + acetate + H(+); Xref=Rhea:RHEA:17777, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:30909, ChEBI:CHEBI:36707; EC=3.1.1.47; Evidence={ECO:0000269|PubMed:10066756, ECO:0000269|PubMed:16371369, ECO:0000269|PubMed:18434304, ECO:0000269|PubMed:7592717, ECO:0000269|PubMed:7700381, ECO:0000269|PubMed:8624782, ECO:0000269|PubMed:8675689};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17778; Evidence={ECO:0000305|PubMed:8675689}; CATALYTIC ACTIVITY: Reaction=1-O-decyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-O-decyl-sn-glycero-3-phosphocholine + acetate + H(+); Xref=Rhea:RHEA:41376, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:78108, ChEBI:CHEBI:78109; Evidence={ECO:0000269|PubMed:10504265};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41377; Evidence={ECO:0000305|PubMed:10504265}; CATALYTIC ACTIVITY: Reaction=1-O-dodecyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-O-dodecyl-sn-glycero-3-phosphocholine + acetate + H(+); Xref=Rhea:RHEA:41372, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:78103, ChEBI:CHEBI:78104; Evidence={ECO:0000269|PubMed:10504265};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41373; Evidence={ECO:0000305|PubMed:10504265}; CATALYTIC ACTIVITY: Reaction=1-O-tetradecyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-O-tetradecyl-sn-glycero-3-phosphocholine + acetate + H(+); Xref=Rhea:RHEA:41368, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:78101, ChEBI:CHEBI:78102; Evidence={ECO:0000269|PubMed:10504265};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41369; Evidence={ECO:0000305|PubMed:10504265}; CATALYTIC ACTIVITY: Reaction=1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-O-hexadecyl-sn-glycero-3-phosphocholine + acetate + H(+); Xref=Rhea:RHEA:40479, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:44811, ChEBI:CHEBI:64496; Evidence={ECO:0000269|PubMed:10504265, ECO:0000269|PubMed:11590221};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40480; Evidence={ECO:0000305|PubMed:10504265}; CATALYTIC ACTIVITY: Reaction=1-O-octadecyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-O-octadecyl-sn-glycero-3-phosphocholine + acetate + H(+); Xref=Rhea:RHEA:41183, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:52450, ChEBI:CHEBI:75216; Evidence={ECO:0000269|PubMed:10504265};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41184; Evidence={ECO:0000305|PubMed:10504265}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + acetate + H(+); Xref=Rhea:RHEA:41203, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:72998, ChEBI:CHEBI:75219; Evidence={ECO:0000269|PubMed:2040620};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41204; Evidence={ECO:0000305|PubMed:2040620}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-propionyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+) + propanoate; Xref=Rhea:RHEA:41191, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17272, ChEBI:CHEBI:72998, ChEBI:CHEBI:77831; Evidence={ECO:0000269|PubMed:2040620};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41192; Evidence={ECO:0000305|PubMed:2040620}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-butanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + butanoate + H(+); Xref=Rhea:RHEA:41195, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17968, ChEBI:CHEBI:72998, ChEBI:CHEBI:77832; Evidence={ECO:0000269|PubMed:2040620};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41196; Evidence={ECO:0000305|PubMed:2040620}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-pentanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + H(+) + pentanoate; Xref=Rhea:RHEA:41199, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:31011, ChEBI:CHEBI:72998, ChEBI:CHEBI:77833; Evidence={ECO:0000269|PubMed:2040620};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41200; Evidence={ECO:0000305|PubMed:2040620}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-glutaroyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + glutarate + H(+); Xref=Rhea:RHEA:41159, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30921, ChEBI:CHEBI:72998, ChEBI:CHEBI:77756; Evidence={ECO:0000269|PubMed:2040620, ECO:0000269|PubMed:7700381};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41160; Evidence={ECO:0000305|PubMed:2040620, ECO:0000305|PubMed:7700381}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(5-oxopentanoyl)-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + 5-oxopentanoate + H(+); Xref=Rhea:RHEA:40483, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16120, ChEBI:CHEBI:72998, ChEBI:CHEBI:77890; Evidence={ECO:0000269|PubMed:16371369, ECO:0000269|PubMed:2040620};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40484; Evidence={ECO:0000305|PubMed:16371369, ECO:0000305|PubMed:2040620}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(9-oxononanoyl)-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + 9-oxononanoate + H(+); Xref=Rhea:RHEA:41179, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:61042, ChEBI:CHEBI:72998, ChEBI:CHEBI:77812; Evidence={ECO:0000269|PubMed:2040620};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41180; Evidence={ECO:0000305|PubMed:2040620}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-[9-hydroperoxy-(10E-octadecenoyl)]-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + 9-hydroperoxy-10E-octadecenoate + H(+); Xref=Rhea:RHEA:41151, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:72998, ChEBI:CHEBI:77753, ChEBI:CHEBI:77754; Evidence={ECO:0000269|PubMed:16371369, ECO:0000269|PubMed:17090529};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41152; Evidence={ECO:0000305|PubMed:16371369, ECO:0000305|PubMed:17090529}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(10-hydroperoxy-8E-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphocholine + 10-hydroperoxy-8E-octadecenoate + H(+); Xref=Rhea:RHEA:41155, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:72998, ChEBI:CHEBI:77749, ChEBI:CHEBI:77755; Evidence={ECO:0000269|PubMed:17090529};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41156; Evidence={ECO:0000305|PubMed:17090529}; |
DNA Binding | |
EC Number | 3.1.1.47 |
Enzyme Function | FUNCTION: Lipoprotein-associated calcium-independent phospholipase A2 involved in phospholipid catabolism during inflammatory and oxidative stress response (PubMed:7700381, PubMed:8624782, PubMed:2040620, PubMed:16371369, PubMed:17090529, PubMed:10066756). At the lipid-aqueous interface, hydrolyzes the ester bond of fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) (PubMed:2040620, PubMed:10504265). Specifically targets phospholipids with a short-chain fatty acyl group at sn-2 position (PubMed:2040620). Can hydrolyze phospholipids with long fatty acyl chains, only if they carry oxidized functional groups (PubMed:2040620, PubMed:8624782). Hydrolyzes and inactivates platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), a potent proinflammatory signaling lipid that acts through PTAFR on various innate immune cells (PubMed:10504265, PubMed:10066756, PubMed:7592717, PubMed:11590221, PubMed:7700381, PubMed:18434304, PubMed:16371369, PubMed:8675689, PubMed:8624782). Hydrolyzes oxidatively truncated phospholipids carrying an aldehyde group at omega position, preventing their accumulation in low-density lipoprotein (LDL) particles and uncontrolled proinflammatory effects (PubMed:2040620, PubMed:7700381). As part of high-density lipoprotein (HDL) particles, can hydrolyze phospholipids having long-chain fatty acyl hydroperoxides at sn-2 position and protect against potential accumulation of these oxylipins in the vascular wall (PubMed:17090529). Catalyzes the release from membrane phospholipids of F2-isoprostanes, lipid biomarkers of cellular oxidative damage (PubMed:16371369). {ECO:0000269|PubMed:10066756, ECO:0000269|PubMed:10504265, ECO:0000269|PubMed:11590221, ECO:0000269|PubMed:16371369, ECO:0000269|PubMed:17090529, ECO:0000269|PubMed:18434304, ECO:0000269|PubMed:2040620, ECO:0000269|PubMed:7592717, ECO:0000269|PubMed:7700381, ECO:0000269|PubMed:8624782, ECO:0000269|PubMed:8675689}. |
Temperature Dependency | |
PH Dependency | |
Pathway | |
nucleotide Binding | |
Features | Active site (3); Beta strand (15); Chain (1); Glycosylation (2); Helix (16); Mutagenesis (18); Natural variant (7); Signal peptide (1); Turn (2) |
Keywords | 3D-structure;Asthma;Direct protein sequencing;Disease variant;Glycoprotein;HDL;Hydrolase;LDL;Lipid degradation;Lipid metabolism;Phospholipid degradation;Phospholipid metabolism;Reference proteome;Secreted;Signal |
Interact With | |
Induction | INDUCTION: Up-regulated upon monocyte differentiation toward macrophage lineage. {ECO:0000269|PubMed:11590221}. |
Subcellular Location | SUBCELLULAR LOCATION: Secreted, extracellular space {ECO:0000269|PubMed:10066756, ECO:0000269|PubMed:11590221, ECO:0000269|PubMed:12821559, ECO:0000269|PubMed:18434304}. Note=Associates with both LDL and HDL particles in plasma (PubMed:11590221, PubMed:12821559, PubMed:18434304, PubMed:10066756). Mainly associates with proinflammatory electronegative LDL particles (PubMed:12821559). {ECO:0000269|PubMed:10066756, ECO:0000269|PubMed:11590221, ECO:0000269|PubMed:12821559, ECO:0000269|PubMed:18434304}. |
Modified Residue | |
Post Translational Modification | PTM: N-glycosylated. Macrophage-derived PLA2G7 carries sialylated complex-type N-glycans that hinder its binding to HDL particles. {ECO:0000269|PubMed:11590221}. |
Signal Peptide | SIGNAL 1..21 |
Structure 3D | X-ray crystallography (33) |
Cross Reference PDB | 3D59; 3D5E; 3F96; 3F97; 3F98; 3F9C; 5I8P; 5I9I; 5JAD; 5JAH; 5JAL; 5JAN; 5JAO; 5JAP; 5JAR; 5JAS; 5JAT; 5JAU; 5LP1; 5LYY; 5LZ2; 5LZ4; 5LZ5; 5LZ7; 5LZ8; 5LZ9; 5YE7; 5YE8; 5YE9; 5YEA; 6M06; 6M07; 6M08; |
Mapped Pubmed ID | 11248283; 11369691; 11501940; 11807372; 11810302; 11850055; 11861667; 12068200; 12428682; 12466264; 12548211; 12590019; 12649088; 12801611; 14563588; 14671207; 14709372; 15081260; 15115767; 15148590; 15215249; 15318030; 15364890; 15956136; 16086290; 16308493; 16438975; 16530769; 16787988; 17092424; 17160904; 17174223; 17251670; 17289852; 17502572; 17509958; 17587752; 17908960; 17981297; 18001304; 18061193; 18094516; 18165686; 18201705; 18204052; 18259035; 18356547; 18396350; 18408575; 18431085; 18587071; 18660489; 18779277; 18789441; 18832472; 18930040; 18983494; 19034521; 19069165; 19135199; 19247692; 19272461; 19280057; 19336475; 19359705; 19373214; 19500354; 19578796; 19583678; 19596311; 19644070; 19763134; 19850020; 19886071; 19892409; 19910444; 19913121; 19948975; 20067121; 20080080; 20185515; 20185811; 20200624; 20331434; 20367923; 20442857; 20444451; 20479152; 20507838; 20625038; 20628086; 20634581; 20711500; 20926117; 21107710; 21176638; 21182203; 21247435; 21281786; 21316774; 21432021; 21476960; 21490708; 21553808; 21606947; 21616491; 21620406; 21708876; 21714927; 21834908; 21880383; 21882811; 21933589; 21942556; 22024276; 22028154; 22139405; 22153151; 22178747; 22197603; 22202492; 22246459; 22300679; 22338104; 22340269; 22359537; 22447189; 22499993; 22632920; 22665167; 22755553; 22784637; 22797139; 22859728; 22898284; 23083783; 23089713; 23089916; 23103135; 23118945; 23140470; 23361301; 23413990; 23439604; 23546765; 23623642; 23746626; 23747086; 24008317; 24089018; 24092915; 24161325; 24358251; 24393260; 24397392; 24416164; 24463064; 24492522; 24513482; 24555913; 24580749; 24682749; 24732951; 24742198; 24818163; 24904022; 24930071; 25056687; 25078067; 25186013; 25291938; 25458708; 25463126; 25501698; 25581763; 25587968; 25647459; 25690150; 25874928; 25893499; 25934512; 26004387; 26117401; 26311748; 26460076; 26499399; 26504820; 26595893; 26642708; 26775119; 26791069; 26828804; 26848158; 27078579; 27097870; 27167608; 27206945; 27301456; 27392709; 27450918; 27461004; 27487154; 27614353; 27641736; 27710915; 27776715; 27905470; 27928450; 27933945; 27941334; 27956130; 27992874; 28005267; 28105273; 28110894; 28142077; 28222638; 28332853; 28334001; 28475940; 28502488; 28514697; 28608449; 28704853; 28784006; 28934604; 28951620; 28960681; 29027597; 29050675; 29101839; 29121808; 29138849; 29169030; 29193967; 29424477; 29427237; 29525223; 29623345; 29636060; 29728838; 29737567; 30094934; 30168082; 30289950; 30850840; 30904742; 31103624; 31115024; 31236414; 31489677; 31630457; 31713292; 31875617; 32109154; 32145524; 32152936; 32459096; 32460702; 32546193; 32636298; 32679127; 32710501; 33029257; 33073951; 33089697; 33107310; 33188662; 33299319; 33458873; 33583415; 33676381; 33760156; 33762651; 33978383; 34093570; 34220834; 34315293; 34388201; 34404374; 34427055; 34740601; |
Motif | |
Gene Encoded By | |
Mass | 50,077 |
Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=12.5 uM for 1-hexadecanoyl-2-acetyl-sn-glycero-3-phosphocholine {ECO:0000269|PubMed:2040620}; KM=3.1 uM for 1-hexadecanoyl-2-propionyl-sn-glycero-3-phosphocholine {ECO:0000269|PubMed:2040620}; KM=7.9 uM for 1-hexadecanoyl-2-butanoyl-sn-glycero-3-phosphocholine {ECO:0000269|PubMed:2040620}; KM=6.2 uM for 1-hexadecanoyl-2-pentanoyl-sn-glycero-3-phosphocholine {ECO:0000269|PubMed:2040620}; KM=11.3 uM for 1-hexadecanoyl-2-(5-oxopentanoyl)-sn-glycero-3-phosphocholine {ECO:0000269|PubMed:2040620}; KM=15.5 uM for 1-hexadecanoyl-2-(9-oxononanoyl)-sn-glycero-3-phosphocholine {ECO:0000269|PubMed:2040620}; KM=43.1 uM for 1-hexadecanoyl-2-(5-oxopentanoyl)-sn-glycero-3-phosphocholine {ECO:0000269|PubMed:16371369}; Vmax=167 umol/h/mg enzyme toward 1-hexadecanoyl-2-acetyl-sn-glycero-3-phosphocholine {ECO:0000269|PubMed:2040620}; Vmax=36.1 umol/h/mg enzyme toward 1-hexadecanoyl-2-propionyl-sn-glycero-3-phosphocholine {ECO:0000269|PubMed:2040620}; Vmax=43.4 umol/h/mg enzyme toward 1-hexadecanoyl-2-butanoyl-sn-glycero-3-phosphocholine {ECO:0000269|PubMed:2040620}; Vmax=42.2 umol/h/mg enzyme toward 1-hexadecanoyl-2-pentanoyl-sn-glycero-3-phosphocholine {ECO:0000269|PubMed:2040620}; Vmax=100 umol/h/mg enzyme toward 1-hexadecanoyl-2-(5-oxopentanoyl)-sn-glycero-3-phosphocholine {ECO:0000269|PubMed:2040620}; Vmax=98.4 umol/h/mg enzyme toward 1-hexadecanoyl-2-(9-oxononanoyl)-sn-glycero-3-phosphocholine {ECO:0000269|PubMed:2040620}; Vmax=5.0 umol/min/mg enzyme toward 1-hexadecanoyl-2-(5-oxopentanoyl)-sn-glycero-3-phosphocholine {ECO:0000269|PubMed:16371369}; |
Metal Binding | |
Rhea ID | RHEA:17777; RHEA:17778; RHEA:41376; RHEA:41377; RHEA:41372; RHEA:41373; RHEA:41368; RHEA:41369; RHEA:40479; RHEA:40480; RHEA:41183; RHEA:41184; RHEA:41203; RHEA:41204; RHEA:41191; RHEA:41192; RHEA:41195; RHEA:41196; RHEA:41199; RHEA:41200; RHEA:41159; RHEA:41160; RHEA:40483; RHEA:40484; RHEA:41179; RHEA:41180; RHEA:41151; RHEA:41152; RHEA:41155; RHEA:41156 |
Cross Reference Brenda | 3.1.1.4;3.1.1.47; |