IED Industry Enzyme Database

Detail Information for IndEnz0010000021
IED ID IndEnz0010000021
Enzyme Type ID esterase000021
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 pro-inflammatory 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 pro-inflammatory 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 pro-inflammatory 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; 35143297;
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;