| IED ID | IndEnz0005000018 |
| Enzyme Type ID | lipase000018 |
| Protein Name |
Diacylglycerol lipase-beta DAGL-beta DAGLbeta DGL-beta EC 3.1.1.116 PUFA-specific triacylglycerol lipase EC 3.1.1.3 Sn1-specific diacylglycerol lipase beta |
| Gene Name | Daglb |
| Organism | Mus musculus (Mouse) |
| 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 Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MPGMVLFGRRWSLASDDLVFPGSFELFLRVLWWIVSLTLYLTHRRRLDCPGGVLLSTYLIVLLVLLAVIICTVLAIVCVSMRGTICNPGPRKSMSKLLYIRLALFLPEMVWASLGAAWVAKGIQCDRTVVIGIIATVIVSWIVIAATMVTIIFVFDPLGGKMAPYPPCIPEHLDSNSSNRLLTGLKTAAKSVWETRVQFCCCCVGQDDNTRVAFSSTADLFSTYFSDTDLVPSDIAAGFTLLHQQQDNISHSREPPEVVTHTPGQPQETELDAEVENCHHYMPFAAAAYGWPLYIYRNPFTGLCRIGGDCCRARDIEYDAVEGDQHNCHFASILKTTGLQYRDFIHISFHDKVYELPFIVVLDHRKESVVVAVRGTMSLQDVLTDLSAESETLELGIELQDCVAHKGIAQAARYIHRRLVNDGILSQAFSVAPEYQLVLVGHSLGAGAAALLAIMLRGAYPQVRAYAFSPPRGLLSKSLYEYSKDFVVSLILGMDVIPRLSVTNMEDLKRRILRVIANCNKPKYKILLHGCWYGLFGGSPDNFPTELDEGTQGALTQPLLGEQTLLTRYSPGYCSSDSPLDSPTKYPTLYPPGRIIHLEEEGGSGRFGCCSAAQYRARWAHEAEFSKILIGPKMLIDHMPDVMIRALDRVLADRTACVSCPGQGGSSVP |
| Enzyme Length | 669 |
| Uniprot Accession Number | Q91WC9 |
| Absorption | |
| Active Site | ACT_SITE 443; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:Q8NCG7; ACT_SITE 495; /note=Charge relay system; /evidence=ECO:0000250|UniProtKB:Q8NCG7 |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by the 1,2,3-triazole urea covalent inhibitors KT109 and KT172 (PubMed:23103940, PubMed:31991095). Inhibited by p-hydroxy-mercuri-benzoate and HgCl(2), but not by PMSF. Also inhibited by RHC80267, a drug that blocks 2-AG formation (By similarity). {ECO:0000250|UniProtKB:Q8NCG7, ECO:0000269|PubMed:23103940, ECO:0000269|PubMed:31991095}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycerol + H2O = a 2-acylglycerol + a fatty acid + H(+); Xref=Rhea:RHEA:33275, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17389, ChEBI:CHEBI:17815, ChEBI:CHEBI:28868; EC=3.1.1.116; Evidence={ECO:0000269|PubMed:23103940};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33276; Evidence={ECO:0000305|PubMed:23103940}; CATALYTIC ACTIVITY: Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + H2O = 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H(+) + octadecanoate; Xref=Rhea:RHEA:38507, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:25629, ChEBI:CHEBI:52392, ChEBI:CHEBI:75728; Evidence={ECO:0000269|PubMed:23103940}; CATALYTIC ACTIVITY: Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycerol + H2O = (9Z)-octadecenoate + 2-(9Z-octadecenoyl)-glycerol + H(+); Xref=Rhea:RHEA:38511, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:52333, ChEBI:CHEBI:73990; Evidence={ECO:0000250|UniProtKB:Q8NCG7}; CATALYTIC ACTIVITY: Reaction=1-(9Z-octadecenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + H2O = (9Z)-octadecenoate + 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H(+); Xref=Rhea:RHEA:38515, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:52392, ChEBI:CHEBI:75449; Evidence={ECO:0000250|UniProtKB:Q8NCG7}; CATALYTIC ACTIVITY: Reaction=1-(9Z-octadecenoyl)-2-octadecanoyl-sn-glycerol + H2O = (9Z)-octadecenoate + 2-octadecanoylglycerol + H(+); Xref=Rhea:RHEA:38519, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:75448, ChEBI:CHEBI:75456; Evidence={ECO:0000250|UniProtKB:Q8NCG7}; CATALYTIC ACTIVITY: Reaction=1-(9Z-octadecenoyl)-2-(9Z,12Z-octadecadienoyl)-sn-glycerol + H2O = (9Z)-octadecenoate + 2-(9Z,12Z-octadecadienoyl)-glycerol + H(+); Xref=Rhea:RHEA:38523, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:75450, ChEBI:CHEBI:75457; Evidence={ECO:0000250|UniProtKB:Q8NCG7}; CATALYTIC ACTIVITY: Reaction=1-(9Z-octadecenoyl)-2-O-(5Z,8Z,11Z,14Z-eicosatetraenyl)-sn-glycerol + H2O = (9Z)-octadecenoate + 2-O-(5Z,8Z,11Z,14Z)-eicosatetraenylglycerol + H(+); Xref=Rhea:RHEA:38527, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:75913, ChEBI:CHEBI:75914; Evidence={ECO:0000250|UniProtKB:Q8NCG7}; 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:31991095};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12045; Evidence={ECO:0000305|PubMed:31991095}; CATALYTIC ACTIVITY: Reaction=1,2,3-tri-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + a di-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H(+); Xref=Rhea:RHEA:63432, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:32395, ChEBI:CHEBI:147308, ChEBI:CHEBI:147309; Evidence={ECO:0000269|PubMed:31991095};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63433; Evidence={ECO:0000305|PubMed:31991095}; CATALYTIC ACTIVITY: Reaction=1,2,3-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycerol + H2O = (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + a di-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycerol + H(+); Xref=Rhea:RHEA:63436, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:77016, ChEBI:CHEBI:147310, ChEBI:CHEBI:147311; Evidence={ECO:0000269|PubMed:31991095}; |
| DNA Binding | |
| EC Number | 3.1.1.116; 3.1.1.3 |
| Enzyme Function | FUNCTION: Lipase that catalyzes the hydrolysis of arachidonic acid (AA)-esterified diacylglycerols (DAGs) to produce the principal endocannabinoid, 2-arachidonoylglycerol (2-AG) which can be further cleaved by downstream enzymes to release arachidonic acid (AA) for cyclooxygenase (COX)-mediated eicosanoid production (PubMed:20159446, PubMed:20147530, PubMed:23103940). Preferentially hydrolyzes DAGs at the sn-1 position in a calcium-dependent manner and has negligible activity against other lipids including monoacylglycerols and phospholipids (By similarity). Plays a key role in the regulation of 2-AG and AA pools utilized by COX1/2 to generate lipid mediators of macrophage and microglia inflammatory responses (PubMed:23103940, PubMed:26779719). Functions also as a polyunsaturated fatty acids-specific triacylglycerol lipase in macrophages (PubMed:31991095). Plays an important role to support the metabolic and signaling demands of macrophages (PubMed:31991095, PubMed:23103940). {ECO:0000250|UniProtKB:Q8NCG7, ECO:0000269|PubMed:20147530, ECO:0000269|PubMed:20159446, ECO:0000269|PubMed:23103940, ECO:0000269|PubMed:26779719, ECO:0000269|PubMed:31991095}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (2); Chain (1); Frameshift (1); Modified residue (3); Sequence conflict (1); Topological domain (5); Transmembrane (4) |
| Keywords | Calcium;Cell membrane;Hydrolase;Lipid degradation;Lipid metabolism;Membrane;Metal-binding;Phosphoprotein;Reference proteome;Transmembrane;Transmembrane helix |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:31991095}; Multi-pass membrane protein {ECO:0000255}. |
| Modified Residue | MOD_RES 570; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q8NCG7; MOD_RES 578; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q8NCG7; MOD_RES 582; /note=Phosphoserine; /evidence=ECO:0007744|PubMed:21183079 |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 12466851; 16964442; 18562289; 20962221; 21267068; 21677750; 21807615; 23806960; 26082754; 26668358; 31105063; |
| Motif | |
| Gene Encoded By | |
| Mass | 73,905 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:33275; RHEA:33276; RHEA:38507; RHEA:38511; RHEA:38515; RHEA:38519; RHEA:38523; RHEA:38527; RHEA:12044; RHEA:12045; RHEA:63432; RHEA:63433; RHEA:63436 |
| Cross Reference Brenda |