IED Industry Enzyme Database

Detail Information for IndEnz0005000828
IED ID IndEnz0005000828
Enzyme Type ID lipase000828
Protein Name 1-acylglycerol-3-phosphate O-acyltransferase PNPLA3
EC 2.3.1.51
Acylglycerol transacylase
Adiponutrin
ADPN
Calcium-independent phospholipase A2-epsilon
iPLA2-epsilon
Lysophosphatidic acid acyltransferase
Patatin-like phospholipase domain-containing protein 3
EC 3.1.1.3
Gene Name PNPLA3 ADPN C22orf20
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 MYDAERGWSLSFAGCGFLGFYHVGATRCLSEHAPHLLRDARMLFGASAGALHCVGVLSGIPLEQTLQVLSDLVRKARSRNIGIFHPSFNLSKFLRQGLCKCLPANVHQLISGKIGISLTRVSDGENVLVSDFRSKDEVVDALVCSCFIPFYSGLIPPSFRGVRYVDGGVSDNVPFIDAKTTITVSPFYGEYDICPKVKSTNFLHVDITKLSLRLCTGNLYLLSRAFVPPDLKVLGEICLRGYLDAFRFLEEKGICNRPQPGLKSSSEGMDPEVAMPSWANMSLDSSPESAALAVRLEGDELLDHLRLSILPWDESILDTLSPRLATALSEEMKDKGGYMSKICNLLPIRIMSYVMLPCTLPVESAIAIVQRLVTWLPDMPDDVLWLQWVTSQVFTRVLMCLLPASRSQMPVSSQQASPCTPEQDWPCWTPCSPKGCPAETKAEATPRSILRSSLNFFLGNKVPAGAEGLSTFPSFSLEKSL
Enzyme Length 481
Uniprot Accession Number Q9NST1
Absorption
Active Site ACT_SITE 47; /note=Nucleophile; /evidence=ECO:0000255|PROSITE-ProRule:PRU01161; ACT_SITE 166; /note=Proton acceptor; /evidence=ECO:0000255|PROSITE-ProRule:PRU01161
Activity Regulation
Binding Site
Calcium Binding
catalytic Activity CATALYTIC ACTIVITY: Reaction=a 1-acyl-sn-glycero-3-phosphate + an acyl-CoA = a 1,2-diacyl-sn-glycero-3-phosphate + CoA; Xref=Rhea:RHEA:19709, ChEBI:CHEBI:57287, ChEBI:CHEBI:57970, ChEBI:CHEBI:58342, ChEBI:CHEBI:58608; EC=2.3.1.51; Evidence={ECO:0000269|PubMed:21878620, ECO:0000269|PubMed:22560221}; CATALYTIC ACTIVITY: Reaction=a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H(+); Xref=Rhea:RHEA:12044, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17855, ChEBI:CHEBI:18035, ChEBI:CHEBI:28868; EC=3.1.1.3; Evidence={ECO:0000269|PubMed:15364929, ECO:0000269|PubMed:20034933, ECO:0000269|PubMed:21878620, ECO:0000269|PubMed:22560221}; CATALYTIC ACTIVITY: Reaction=a 1,3-diacylglycerol + a 1-acylglycerol = a triacylglycerol + glycerol; Xref=Rhea:RHEA:44440, ChEBI:CHEBI:17754, ChEBI:CHEBI:17855, ChEBI:CHEBI:35759, ChEBI:CHEBI:47777; Evidence={ECO:0000269|PubMed:15364929}; CATALYTIC ACTIVITY: Reaction=a 1,2-diacylglycerol + a 1-acylglycerol = a triacylglycerol + glycerol; Xref=Rhea:RHEA:44436, ChEBI:CHEBI:17754, ChEBI:CHEBI:17855, ChEBI:CHEBI:35759, ChEBI:CHEBI:49172; Evidence={ECO:0000269|PubMed:15364929}; CATALYTIC ACTIVITY: Reaction=2 a 1-acylglycerol = a 1,2-diacylglycerol + glycerol; Xref=Rhea:RHEA:44432, ChEBI:CHEBI:17754, ChEBI:CHEBI:35759, ChEBI:CHEBI:49172; Evidence={ECO:0000269|PubMed:15364929}; CATALYTIC ACTIVITY: Reaction=(9Z)-octadecenoyl-CoA + 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + CoA; Xref=Rhea:RHEA:37131, ChEBI:CHEBI:57287, ChEBI:CHEBI:57387, ChEBI:CHEBI:74544, ChEBI:CHEBI:74546; Evidence={ECO:0000269|PubMed:22560221};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37132; Evidence={ECO:0000305|PubMed:22560221}; CATALYTIC ACTIVITY: Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + hexadecanoyl-CoA = 1-(9Z)-octadecenoyl-2-hexadecanoyl-sn-glycero-3-phosphate + CoA; Xref=Rhea:RHEA:37143, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:74544, ChEBI:CHEBI:74551; Evidence={ECO:0000269|PubMed:22560221};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37144; Evidence={ECO:0000305|PubMed:22560221}; CATALYTIC ACTIVITY: Reaction=(9Z,12Z)-octadecadienoyl-CoA + 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate = 1-(9Z)-octadecenoyl-2-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phosphate + CoA; Xref=Rhea:RHEA:37159, ChEBI:CHEBI:57287, ChEBI:CHEBI:57383, ChEBI:CHEBI:74544, ChEBI:CHEBI:74563; Evidence={ECO:0000269|PubMed:22560221};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37160; Evidence={ECO:0000305|PubMed:22560221}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate = 1-(9Z)-octadecenoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphate + CoA; Xref=Rhea:RHEA:37443, ChEBI:CHEBI:57287, ChEBI:CHEBI:57368, ChEBI:CHEBI:74544, ChEBI:CHEBI:74928; Evidence={ECO:0000269|PubMed:22560221};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37444; Evidence={ECO:0000305|PubMed:22560221}; CATALYTIC ACTIVITY: Reaction=2 1-(9Z-octadecenoyl)-glycerol = 1,2-di-(9Z-octadecenoyl)-glycerol + glycerol; Xref=Rhea:RHEA:38323, ChEBI:CHEBI:17754, ChEBI:CHEBI:52323, ChEBI:CHEBI:75342; Evidence={ECO:0000269|PubMed:15364929};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38324; Evidence={ECO:0000305|PubMed:15364929}; CATALYTIC ACTIVITY: Reaction=1,2-di-(9Z-octadecenoyl)-glycerol + 1-(9Z-octadecenoyl)-glycerol = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + glycerol; Xref=Rhea:RHEA:38327, ChEBI:CHEBI:17754, ChEBI:CHEBI:52323, ChEBI:CHEBI:53753, ChEBI:CHEBI:75342; Evidence={ECO:0000269|PubMed:15364929};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38328; Evidence={ECO:0000305|PubMed:15364929}; CATALYTIC ACTIVITY: Reaction=1,3-di-(9Z-octadecenoyl)-glycerol + 1-(9Z-octadecenoyl)-glycerol = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + glycerol; Xref=Rhea:RHEA:38331, ChEBI:CHEBI:17754, ChEBI:CHEBI:53753, ChEBI:CHEBI:75342, ChEBI:CHEBI:75735; Evidence={ECO:0000269|PubMed:15364929};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38332; Evidence={ECO:0000305|PubMed:15364929}; CATALYTIC ACTIVITY: Reaction=1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + 1,3-di-(9Z-octadecenoyl)-glycerol + H(+); Xref=Rhea:RHEA:38387, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:53753, ChEBI:CHEBI:75735; Evidence={ECO:0000269|PubMed:21878620};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38388; Evidence={ECO:0000269|PubMed:21878620};
DNA Binding
EC Number 2.3.1.51; 3.1.1.3
Enzyme Function FUNCTION: Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and precursor for both triglycerides and glycerophospholipids. Does not esterify other lysophospholipids. Acyl donors are long chain (at least C16) fatty acyl-CoAs: arachidonoyl-CoA, linoleoyl-CoA, oleoyl-CoA and at a lesser extent palmitoyl-CoA (PubMed:22560221). Additionally possesses low triacylglycerol lipase and CoA-independent acylglycerol transacylase activities and thus may play a role in acyl-chain remodeling of triglycerides (PubMed:15364929, PubMed:20034933, PubMed:22560221). Has hydrolytic activity against glycerolipids triacylglycerol, diacylglycerol and monoacylglycerol, with a strong preference for oleic acid as the acyl moiety (PubMed:21878620). {ECO:0000269|PubMed:15364929, ECO:0000269|PubMed:20034933, ECO:0000269|PubMed:21878620, ECO:0000269|PubMed:22560221}.
Temperature Dependency
PH Dependency
Pathway PATHWAY: Phospholipid metabolism. {ECO:0000269|PubMed:22560221}.; PATHWAY: Glycerolipid metabolism. {ECO:0000269|PubMed:15364929, ECO:0000269|PubMed:20034933, ECO:0000269|PubMed:22560221}.
nucleotide Binding
Features Active site (2); Alternative sequence (1); Chain (1); Domain (1); Glycosylation (2); Motif (3); Mutagenesis (4); Natural variant (9); Topological domain (2); Transmembrane (1)
Keywords Acyltransferase;Alternative splicing;Disease variant;Glycoprotein;Hydrolase;Lipid biosynthesis;Lipid droplet;Lipid metabolism;Membrane;Obesity;Phospholipid biosynthesis;Phospholipid metabolism;Reference proteome;Signal-anchor;Transferase;Transmembrane;Transmembrane helix
Interact With
Induction INDUCTION: By changes in energy balance: down-regulated following very low-calorie diet, whereas refeeding elevates the mRNA level. {ECO:0000269|PubMed:15181042}.
Subcellular Location SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:15364929, ECO:0000269|PubMed:22560221}; Single-pass type II membrane protein {ECO:0000269|PubMed:15364929}. Lipid droplet {ECO:0000269|PubMed:20034933, ECO:0000269|PubMed:22560221}.
Modified Residue
Post Translational Modification
Signal Peptide
Structure 3D
Cross Reference PDB -
Mapped Pubmed ID 16150821; 16505250; 18940312; 19239840; 19390624; 19524579; 19542081; 19596471; 19619606; 19651814; 19729411; 19844213; 19946271; 20373368; 20546964; 20585554; 20648472; 20648474; 20684021; 20803499; 20826584; 20852027; 20962157; 21036152; 21068004; 21145868; 21168155; 21168459; 21176169; 21236304; 21254164; 21319195; 21334404; 21381068; 21488075; 21525193; 21665509; 21745282; 21745286; 21745307; 21777557; 21893698; 21898508; 21988832; 22087248; 22105854; 22140488; 22141340; 22162034; 22189977; 22258181; 22276112; 22338072; 22530607; 22543885; 22546774; 22629460; 22704398; 22719190; 22719876; 22724004; 22792295; 22841784; 22863562; 22869157; 22878467; 22884299; 22898488; 22978414; 23032985; 23042597; 23069476; 23155331; 23176674; 23278404; 23333103; 23334462; 23398201; 23416328; 23418085; 23505555; 23510779; 23512881; 23535911; 23564580; 23734760; 23776098; 23800943; 23804528; 23808989; 23859071; 23872669; 23913731; 24005099; 24009255; 24069270; 24123231; 24152445; 24155878; 24222094; 24222941; 24269995; 24349054; 24369119; 24417250; 24461483; 24477042; 24511104; 24553484; 24607626; 24621583; 24670599; 24680680; 24689094; 24763554; 24785259; 24828988; 24831885; 24905495; 24916969; 24927606; 24947770; 24947803; 24972532; 25040896; 25060292; 25069572; 25171251; 25240529; 25250621; 25273282; 25284145; 25290313; 25297933; 25378656; 25457210; 25522307; 25536644; 25543233; 25581573; 25624712; 25646328; 25676803; 25678388; 25776890; 25791171; 25801076; 25939720; 25964223; 25986529; 26136587; 26139292; 26148225; 26200108; 26229402; 26259026; 26264356; 26272871; 26305067; 26337813; 26352693; 26355465; 26379412; 26419236; 26439088; 26485523; 26493626; 26519102; 26599080; 26605757; 26610348; 26632699; 26707313; 26745088; 26745555; 26760234; 26806136; 26847197; 27015186; 27059980; 27128907; 27150500; 27411039; 27514759; 27537584; 27575312; 27576208; 27596100; 27615511; 27742777; 27744419; 27752939; 27836992; 27888630; 27889599; 27905898; 27908400; 27973562; 28073161; 28253210; 28338112; 28362682; 28436986; 28520213; 28544258; 28617615; 28626169; 28695131; 28744823; 28776448; 28797039; 28928439; 28950858; 28975533; 29055919; 29089161; 29122391; 29150621; 29160303; 29218813; 29258449; 29271184; 29307798; 29364097; 29396131; 29469042; 29474507; 29493856; 29535416; 29577560; 29578593; 29648650; 29674183; 29956823; 30032630; 30132178; 30139224; 30161167; 30171718; 30189691; 30227635; 30246767; 30289982; 30362098; 30403964; 30506232; 30572387; 30649436; 30672430; 30673802; 30701779; 30710115; 30762732; 30763699; 30772256; 30912854; 31054977; 31054980; 31184438; 31219225; 31250467; 31255630; 31305457; 31356578; 31377187; 31419571; 31454802; 31484215; 31497752; 31519069; 31527889; 31642820; 31669075; 31677195; 31793207; 31826069; 31851849; 31945251; 32020770; 32035968; 32043752; 32068025; 32093693; 32103509; 32145261; 32173542; 32190914; 32220085; 32323349; 32333362; 32360822; 32443539; 32525256; 32557704; 32561908; 32592869; 32636123; 32680469; 32690320; 32811452; 32862405; 32877766; 32898995; 32910776; 33057914; 33064150; 33071176; 33131062; 33218077; 33228237; 33306506; 33544416; 33565643; 33616244; 33622266; 33652012; 33685085; 33896117; 34065978; 34076851; 34106646; 34147109; 34198853; 34280991; 34288010; 34749354; 34833371; 34833467; 34879108;
Motif MOTIF 14..19; /note=GXGXXG; /evidence=ECO:0000255|PROSITE-ProRule:PRU01161; MOTIF 45..49; /note=GXSXG; /evidence=ECO:0000255|PROSITE-ProRule:PRU01161; MOTIF 166..168; /note=DGA/G; /evidence=ECO:0000255|PROSITE-ProRule:PRU01161
Gene Encoded By
Mass 52,865
Kinetics BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=32.2 uM for triacylglycerol {ECO:0000269|PubMed:21878620}; KM=29.1 uM for diacylglycerol {ECO:0000269|PubMed:21878620}; KM=32.9 uM for monoacylglycerol {ECO:0000269|PubMed:21878620}; KM=6.2 uM for oleoyl-CoA {ECO:0000269|PubMed:21878620}; Vmax=10.5 nmol/min/mg enzyme toward triacylglycerol {ECO:0000269|PubMed:21878620}; Vmax=21.8 nmol/min/mg enzyme toward diacylglycerol {ECO:0000269|PubMed:21878620}; Vmax=27.4 nmol/min/mg enzyme toward monoacylglycerol {ECO:0000269|PubMed:21878620}; Vmax=2.8 nmol/min/mg enzyme toward oleoyl-CoA {ECO:0000269|PubMed:21878620};
Metal Binding
Rhea ID RHEA:19709; RHEA:12044; RHEA:44440; RHEA:44436; RHEA:44432; RHEA:37131; RHEA:37132; RHEA:37143; RHEA:37144; RHEA:37159; RHEA:37160; RHEA:37443; RHEA:37444; RHEA:38323; RHEA:38324; RHEA:38327; RHEA:38328; RHEA:38331; RHEA:38332; RHEA:38387; RHEA:38388
Cross Reference Brenda