| IED ID | IndEnz0005000715 |
| Enzyme Type ID | lipase000715 |
| Protein Name |
Patatin-like phospholipase domain-containing protein 2 EC 3.1.1.3 Adipose triglyceride lipase |
| Gene Name | Pnpla2 Atgl |
| Organism | Rattus norvegicus (Rat) |
| 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 Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Rattus Rattus norvegicus (Rat) |
| Enzyme Sequence | MFPRETKWNISFAGCGFLGVYHIGVASCLREHAPFLVANATHIYGASAGALTATALVTGACLGEAGANIIEVSKEARKRFLGPLHPSFNLVKTIRGCLLKTLPADCHTRASGRLGISLTRVSDGENVIISHFSSKDELIQANVCSTFIPVYCGLIPPTLQGVRYVDGGISDNLPLYELKNTITVSPFSGESDICPQDSSTNIHELRITNTSIQFNLRNLYRLSKALFPPEPMVLREMCKQGYRDGLRFLRRNGLLNQPNPLLALPPVVPQEEDAEEAAVTEERTGGEDRILEHLPARLNEALLEACVEPKDLMTTLSNMLPVRLATAMMVPYTLPLESAVSFTIRLLEWLPDVPEDIRWMKEQTGSICQYLVMRAKRKLGDHLPSRLSEQVELRRAQSLPSVPLSCATYSEALPNWVRNNLSLGDALAKWEECQRQLLLGLFCTNVAFPPDALRMRAPASPTATDPATPQDPSGLPPC |
| Enzyme Length | 478 |
| Uniprot Accession Number | P0C548 |
| 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 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:0000250|UniProtKB:Q96AD5};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12045; Evidence={ECO:0000250|UniProtKB:Q96AD5}; CATALYTIC ACTIVITY: Reaction=a triacyl-sn-glycerol + H2O = a 1,2-diacylglycerol + a fatty acid + H(+); Xref=Rhea:RHEA:44864, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868, ChEBI:CHEBI:49172, ChEBI:CHEBI:64615; Evidence={ECO:0000250|UniProtKB:Q96AD5};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44865; Evidence={ECO:0000250|UniProtKB:Q96AD5}; CATALYTIC ACTIVITY: Reaction=a triacyl-sn-glycerol + H2O = 1,3-diacyl-sn-glycerol + a fatty acid + H(+); Xref=Rhea:RHEA:43732, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868, ChEBI:CHEBI:64615, ChEBI:CHEBI:77272; Evidence={ECO:0000250|UniProtKB:Q96AD5};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43733; Evidence={ECO:0000250|UniProtKB:Q96AD5}; CATALYTIC ACTIVITY: Reaction=a triacyl-sn-glycerol + H2O = a 2,3-diacyl-sn-glycerol + a fatty acid + H(+); Xref=Rhea:RHEA:38499, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:28868, ChEBI:CHEBI:64615, ChEBI:CHEBI:75524; Evidence={ECO:0000250|UniProtKB:Q8BJ56};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38500; Evidence={ECO:0000250|UniProtKB:Q8BJ56}; 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:0000250|UniProtKB:Q96AD5};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44441; Evidence={ECO:0000250|UniProtKB:Q96AD5}; 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:0000250|UniProtKB:Q96AD5};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44437; Evidence={ECO:0000250|UniProtKB:Q96AD5}; 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:0000250|UniProtKB:Q96AD5};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44433; Evidence={ECO:0000250|UniProtKB:Q96AD5}; CATALYTIC ACTIVITY: Reaction=a triacyl-sn-glycerol + all-trans-retinol = a diacylglycerol + an all-trans-retinyl ester; Xref=Rhea:RHEA:44676, ChEBI:CHEBI:17336, ChEBI:CHEBI:18035, ChEBI:CHEBI:63410, ChEBI:CHEBI:64615; Evidence={ECO:0000250|UniProtKB:Q96AD5};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44677; Evidence={ECO:0000250|UniProtKB:Q96AD5}; CATALYTIC ACTIVITY: Reaction=(9Z)-octadecenoate + 1,2-di-(9Z-octadecenoyl)-glycerol + H(+) = 1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O; Xref=Rhea:RHEA:38379, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:52323, ChEBI:CHEBI:53753; Evidence={ECO:0000250|UniProtKB:Q96AD5};PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:38381; Evidence={ECO:0000250|UniProtKB:Q96AD5}; 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:0000250|UniProtKB:Q96AD5};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38388; Evidence={ECO:0000250|UniProtKB:Q96AD5}; 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:0000250|UniProtKB:Q96AD5};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38332; Evidence={ECO:0000250|UniProtKB:Q96AD5}; 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:0000250|UniProtKB:Q96AD5};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38328; Evidence={ECO:0000250|UniProtKB:Q96AD5}; 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:0000250|UniProtKB:Q96AD5};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38324; Evidence={ECO:0000250|UniProtKB:Q96AD5}; CATALYTIC ACTIVITY: Reaction=1,2,3-tri-(9Z-octadecenoyl)-glycerol + all-trans-retinol = all-trans-retinyl 9Z-octadecenoate + di-(9Z)-octadecenoylglycerol; Xref=Rhea:RHEA:39987, ChEBI:CHEBI:17336, ChEBI:CHEBI:53753, ChEBI:CHEBI:70760, ChEBI:CHEBI:75945; Evidence={ECO:0000250|UniProtKB:Q96AD5};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39988; Evidence={ECO:0000250|UniProtKB:Q96AD5}; CATALYTIC ACTIVITY: Reaction=1,2,3-tri-(9Z)-hexadecenoylglycerol + H2O = (9Z)-hexadecenoate + 1,3-di-(9Z)-hexadecenoylglycerol + H(+); Xref=Rhea:RHEA:38395, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32372, ChEBI:CHEBI:75841, ChEBI:CHEBI:75849; Evidence={ECO:0000250|UniProtKB:Q8BJ56};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38396; Evidence={ECO:0000250|UniProtKB:Q8BJ56}; CATALYTIC ACTIVITY: Reaction=1,2,3-tri-(9Z,12Z)-octadecadienoylglycerol + H2O = (9Z,12Z)-octadecadienoate + 1,3-di-(9Z,12Z)-octadecadienoylglycerol + H(+); Xref=Rhea:RHEA:38403, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30245, ChEBI:CHEBI:75844, ChEBI:CHEBI:75850; Evidence={ECO:0000250|UniProtKB:Q8BJ56};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38404; Evidence={ECO:0000250|UniProtKB:Q8BJ56}; CATALYTIC ACTIVITY: Reaction=1,2,3-tri-(9Z,12Z,15Z)-octadecatrienoylglycerol + H2O = (9Z,12Z,15Z)-octadecatrienoate + 1,3-di-(9Z,12Z,15Z)-octadecatrienoylglycerol + H(+); Xref=Rhea:RHEA:38411, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32387, ChEBI:CHEBI:75845, ChEBI:CHEBI:75852; Evidence={ECO:0000250|UniProtKB:Q8BJ56};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38412; Evidence={ECO:0000250|UniProtKB:Q8BJ56}; CATALYTIC ACTIVITY: Reaction=1,3-di-(9Z)-octadecenoyl-2-hexadecanoylglycerol + H2O = 1,3-di-(9Z-octadecenoyl)-glycerol + H(+) + hexadecanoate; Xref=Rhea:RHEA:38419, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:75735, ChEBI:CHEBI:75846; Evidence={ECO:0000250|UniProtKB:Q8BJ56};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38420; Evidence={ECO:0000250|UniProtKB:Q8BJ56}; CATALYTIC ACTIVITY: Reaction=1,2-di-(9Z)-octadecenoyl-3-hexadecanoyl-sn-glycerol + H2O = (9Z)-octadecenoate + 1-(9Z)-octadecenoyl-3-hexadecanoyl-sn-glycerol + H(+); Xref=Rhea:RHEA:38423, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:75583, ChEBI:CHEBI:75867; Evidence={ECO:0000250|UniProtKB:Q8BJ56};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38424; Evidence={ECO:0000250|UniProtKB:Q8BJ56}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2,3-di-(9Z)-octadecenoyl-sn-glycerol + H2O = (9Z)-octadecenoate + 1-hexadecanoyl-3-(9Z)-octadecenoyl-sn-glycerol + H(+); Xref=Rhea:RHEA:38647, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:75847, ChEBI:CHEBI:75868; Evidence={ECO:0000250|UniProtKB:Q8BJ56};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38648; Evidence={ECO:0000250|UniProtKB:Q8BJ56}; CATALYTIC ACTIVITY: Reaction=1,2,3-tri-(9Z-octadecenoyl)-glycerol + H2O = (9Z)-octadecenoate + 2,3-di-(9Z)-octadecenoyl-sn-glycerol + H(+); Xref=Rhea:RHEA:38391, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:53753, ChEBI:CHEBI:75824; Evidence={ECO:0000250|UniProtKB:Q8BJ56};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38392; Evidence={ECO:0000250|UniProtKB:Q8BJ56}; CATALYTIC ACTIVITY: Reaction=1,2,3-tri-(9Z)-hexadecenoylglycerol + H2O = (9Z)-hexadecenoate + 2,3-di-(9Z)-hexadecenoyl-sn-glycerol + H(+); Xref=Rhea:RHEA:38399, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32372, ChEBI:CHEBI:75841, ChEBI:CHEBI:75853; Evidence={ECO:0000250|UniProtKB:Q8BJ56};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38400; Evidence={ECO:0000250|UniProtKB:Q8BJ56}; CATALYTIC ACTIVITY: Reaction=1,2,3-tri-(9Z,12Z)-octadecadienoylglycerol + H2O = (9Z,12Z)-octadecadienoate + 2,3-di-(9Z,12Z)-octadecadienoyl-sn-glycerol + H(+); Xref=Rhea:RHEA:38407, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30245, ChEBI:CHEBI:75844, ChEBI:CHEBI:75854; Evidence={ECO:0000250|UniProtKB:Q8BJ56};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38408; Evidence={ECO:0000250|UniProtKB:Q8BJ56}; CATALYTIC ACTIVITY: Reaction=1,2,3-tri-(9Z,12Z,15Z)-octadecatrienoylglycerol + H2O = (9Z,12Z,15Z)-octadecatrienoate + 2,3-di-(9Z,12Z,15Z)-octadecatrienoyl-sn-glycerol + H(+); Xref=Rhea:RHEA:38415, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32387, ChEBI:CHEBI:75845, ChEBI:CHEBI:75855; Evidence={ECO:0000250|UniProtKB:Q8BJ56};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38416; Evidence={ECO:0000250|UniProtKB:Q8BJ56}; CATALYTIC ACTIVITY: Reaction=1,3-di-(9Z)-octadecenoyl-2-hexadecanoylglycerol + H2O = (9Z)-octadecenoate + 2-hexadecanoyl-3-(9Z)-octadecenoyl-sn-glycerol + H(+); Xref=Rhea:RHEA:38431, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:75846, ChEBI:CHEBI:75870; Evidence={ECO:0000250|UniProtKB:Q8BJ56};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38432; Evidence={ECO:0000250|UniProtKB:Q8BJ56}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2,3-di-(9Z)-octadecenoyl-sn-glycerol + H2O = 2,3-di-(9Z)-octadecenoyl-sn-glycerol + H(+) + hexadecanoate; Xref=Rhea:RHEA:38427, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:75824, ChEBI:CHEBI:75847; Evidence={ECO:0000250|UniProtKB:Q8BJ56};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38428; Evidence={ECO:0000250|UniProtKB:Q8BJ56}; CATALYTIC ACTIVITY: Reaction=1,2-di-(9Z)-octadecenoyl-3-hexadecanoyl-sn-glycerol + H2O = (9Z)-octadecenoate + 2-(9Z-octadecenoyl)-3-hexadecanoyl-sn-glycerol + H(+); Xref=Rhea:RHEA:38643, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:75546, ChEBI:CHEBI:75583; Evidence={ECO:0000250|UniProtKB:Q8BJ56};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38644; Evidence={ECO:0000250|UniProtKB:Q8BJ56}; |
| DNA Binding | |
| EC Number | 3.1.1.3 |
| Enzyme Function | FUNCTION: Catalyzes the initial step in triglyceride hydrolysis in adipocyte and non-adipocyte lipid droplets (By similarity). Exhibits a strong preference for the hydrolysis of long-chain fatty acid esters at the sn-2 position of the glycerol backbone. Also has acylglycerol transacylase activity. Acts coordinately with LIPE/HLS and DGAT2 within the lipolytic cascade (By similarity). Transfers fatty acid from triglyceride to retinol, hydrolyzes retinylesters, and generates 1,3-diacylglycerol from triglycerides. Regulates adiposome size and may be involved in the degradation of adiposomes (By similarity). May play an important role in energy homeostasis. May play a role in the response of the organism to starvation, enhancing hydrolysis of triglycerides and providing free fatty acids to other tissues to be oxidized in situations of energy depletion (By similarity). {ECO:0000250|UniProtKB:Q8BJ56, ECO:0000250|UniProtKB:Q96AD5}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | PATHWAY: Glycerolipid metabolism; triacylglycerol degradation. |
| nucleotide Binding | |
| Features | Active site (2); Chain (1); Domain (1); Glycosylation (1); Modified residue (5); Motif (3); Region (1); Topological domain (2); Transmembrane (1) |
| Keywords | Cell membrane;Glycoprotein;Hydrolase;Lipid degradation;Lipid droplet;Lipid metabolism;Membrane;Phosphoprotein;Reference proteome;Signal-anchor;Transmembrane;Transmembrane helix |
| Interact With | |
| Induction | INDUCTION: Increased by rosiglitazone in subcutaneous and visceral white adipose tissue. {ECO:0000269|PubMed:16906479}. |
| Subcellular Location | SUBCELLULAR LOCATION: Lipid droplet {ECO:0000250}. Cell membrane {ECO:0000250}; Single-pass type II membrane protein {ECO:0000250}. |
| Modified Residue | MOD_RES 366; /note=Phosphoserine; in vitro; /evidence=ECO:0000250|UniProtKB:Q8BJ56; MOD_RES 388; /note=Phosphoserine; by PKA; /evidence=ECO:0000250|UniProtKB:Q8BJ56; MOD_RES 398; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; MOD_RES 422; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:22673903; MOD_RES 460; /note=Phosphoserine; in vitro; /evidence=ECO:0000250|UniProtKB:Q8BJ56 |
| Post Translational Modification | PTM: May be phosphorylated. {ECO:0000250}.; PTM: Phosphorylation at Ser-398 by PKA is increased during fasting and moderate intensity exercise, and moderately increases lipolytic activity. {ECO:0000250}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 19389712; 21944063; 22183409; 25436917; 25890298; 26141235; 26277390; 26511521; 27179362; 27590244; |
| 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 | 52,567 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:12044; RHEA:12045; RHEA:44864; RHEA:44865; RHEA:43732; RHEA:43733; RHEA:38499; RHEA:38500; RHEA:44440; RHEA:44441; RHEA:44436; RHEA:44437; RHEA:44432; RHEA:44433; RHEA:44676; RHEA:44677; RHEA:38379; RHEA:38381; RHEA:38387; RHEA:38388; RHEA:38331; RHEA:38332; RHEA:38327; RHEA:38328; RHEA:38323; RHEA:38324; RHEA:39987; RHEA:39988; RHEA:38395; RHEA:38396; RHEA:38403; RHEA:38404; RHEA:38411; RHEA:38412; RHEA:38419; RHEA:38420; RHEA:38423; RHEA:38424; RHEA:38647; RHEA:38648; RHEA:38391; RHEA:38392; RHEA:38399; RHEA:38400; RHEA:38407; RHEA:38408; RHEA:38415; RHEA:38416; RHEA:38431; RHEA:38432; RHEA:38427; RHEA:38428; RHEA:38643; RHEA:38644 |
| Cross Reference Brenda |