DGLA_MOUSE
ID DGLA_MOUSE Reviewed; 1044 AA.
AC Q6WQJ1; A8WFL4; Q6ZQ76;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Diacylglycerol lipase-alpha {ECO:0000303|PubMed:26779719};
DE Short=DAGL-alpha {ECO:0000303|PubMed:26779719};
DE Short=DGL-alpha {ECO:0000303|PubMed:21183079};
DE EC=3.1.1.116 {ECO:0000269|PubMed:17584991, ECO:0000269|PubMed:23103940};
DE AltName: Full=Neural stem cell-derived dendrite regulator;
DE AltName: Full=Sn1-specific diacylglycerol lipase alpha;
GN Name=Dagla; Synonyms=Kiaa0659, Nsddr;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RA Horiguchi S., Tashiro K., Takahashi J., Hashimoto N., Nakano I.,
RA Tsuchida Y., Hirai H., Honjo T.;
RT "NSDDR a novel tetra-spanning transmembrane protein with a unique
RT integration pattern to the plasma membrane regulates the extension of the
RT dendritic trees of Purkinje cells.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 894-1044.
RC TISSUE=Brain;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=14610053; DOI=10.1083/jcb.200305129;
RA Bisogno T., Howell F., Williams G., Minassi A., Cascio M.G., Ligresti A.,
RA Matias I., Schiano-Moriello A., Paul P., Williams E.-J., Gangadharan U.,
RA Hobbs C., Di Marzo V., Doherty P.;
RT "Cloning of the first sn1-DAG lipases points to the spatial and temporal
RT regulation of endocannabinoid signaling in the brain.";
RL J. Cell Biol. 163:463-468(2003).
RN [5]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=16723519; DOI=10.1523/jneurosci.0309-06.2006;
RA Katona I., Urban G.M., Wallace M., Ledent C., Jung K.M., Piomelli D.,
RA Mackie K., Freund T.F.;
RT "Molecular composition of the endocannabinoid system at glutamatergic
RT synapses.";
RL J. Neurosci. 26:5628-5637(2006).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-733 AND SER-744, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [7]
RP CATALYTIC ACTIVITY, FUNCTION, INTERACTION WITH HOMER1 AND HOMER2,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF PRO-975 AND PHE-978.
RX PubMed=17584991; DOI=10.1124/mol.107.037796;
RA Jung K.M., Astarita G., Zhu C., Wallace M., Mackie K., Piomelli D.;
RT "A key role for diacylglycerol lipase-alpha in metabotropic glutamate
RT receptor-dependent endocannabinoid mobilization.";
RL Mol. Pharmacol. 72:612-621(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-730; SER-744; SER-786;
RP SER-954 AND THR-1025, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Brain, and Brown adipose tissue;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=20159446; DOI=10.1016/j.neuron.2010.01.021;
RA Tanimura A., Yamazaki M., Hashimotodani Y., Uchigashima M., Kawata S.,
RA Abe M., Kita Y., Hashimoto K., Shimizu T., Watanabe M., Sakimura K.,
RA Kano M.;
RT "The endocannabinoid 2-arachidonoylglycerol produced by diacylglycerol
RT lipase alpha mediates retrograde suppression of synaptic transmission.";
RL Neuron 65:320-327(2010).
RN [10]
RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=20147530; DOI=10.1523/jneurosci.5693-09.2010;
RA Gao Y., Vasilyev D.V., Goncalves M.B., Howell F.V., Hobbs C.,
RA Reisenberg M., Shen R., Zhang M.Y., Strassle B.W., Lu P., Mark L.,
RA Piesla M.J., Deng K., Kouranova E.V., Ring R.H., Whiteside G.T., Bates B.,
RA Walsh F.S., Williams G., Pangalos M.N., Samad T.A., Doherty P.;
RT "Loss of retrograde endocannabinoid signaling and reduced adult
RT neurogenesis in diacylglycerol lipase knock-out mice.";
RL J. Neurosci. 30:2017-2024(2010).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=23103940; DOI=10.1038/nchembio.1105;
RA Hsu K.L., Tsuboi K., Adibekian A., Pugh H., Masuda K., Cravatt B.F.;
RT "DAGLbeta inhibition perturbs a lipid network involved in macrophage
RT inflammatory responses.";
RL Nat. Chem. Biol. 8:999-1007(2012).
RN [12]
RP INTERACTION WITH CAMK2A.
RX PubMed=23502535; DOI=10.1038/nn.3353;
RA Shonesy B.C., Wang X., Rose K.L., Ramikie T.S., Cavener V.S., Rentz T.,
RA Baucum A.J. II, Jalan-Sakrikar N., Mackie K., Winder D.G., Patel S.,
RA Colbran R.J.;
RT "CaMKII regulates diacylglycerol lipase-alpha and striatal endocannabinoid
RT signaling.";
RL Nat. Neurosci. 16:456-463(2013).
RN [13]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=25466252; DOI=10.1016/j.celrep.2014.11.001;
RA Shonesy B.C., Bluett R.J., Ramikie T.S., Baldi R., Hermanson D.J.,
RA Kingsley P.J., Marnett L.J., Winder D.G., Colbran R.J., Patel S.;
RT "Genetic disruption of 2-arachidonoylglycerol synthesis reveals a key role
RT for endocannabinoid signaling in anxiety modulation.";
RL Cell Rep. 9:1644-1653(2014).
RN [14]
RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=26779719; DOI=10.7554/elife.12345;
RA Viader A., Ogasawara D., Joslyn C.M., Sanchez-Alavez M., Mori S.,
RA Nguyen W., Conti B., Cravatt B.F.;
RT "A chemical proteomic atlas of brain serine hydrolases identifies cell
RT type-specific pathways regulating neuroinflammation.";
RL Elife 5:e12345-e12345(2016).
RN [15]
RP ACTIVITY REGULATION, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=26668358; DOI=10.1073/pnas.1522364112;
RA Ogasawara D., Deng H., Viader A., Baggelaar M.P., Breman A., den Dulk H.,
RA van den Nieuwendijk A.M., van den Nieuwendijk A.M., Soethoudt M.,
RA van der Wel T., Zhou J., Overkleeft H.S., Sanchez-Alavez M., Mori S.,
RA Mo S., Nguyen W., Conti B., Liu X., Chen Y., Liu Q.S., Cravatt B.F.,
RA van der Stelt M.;
RT "Rapid and profound rewiring of brain lipid signaling networks by acute
RT diacylglycerol lipase inhibition.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:26-33(2016).
CC -!- FUNCTION: Serine hydrolase that hydrolyzes arachidonic acid-esterified
CC diacylglycerols (DAGs) to produce the principal endocannabinoid (eCB),
CC 2-arachidonoylglycerol (2-AG) (PubMed:17584991, PubMed:23103940).
CC Preferentially hydrolyzes sn-1 fatty acids from diacylglycerols (DAG)
CC that contain arachidonic acid (AA) esterified at the sn-2 position to
CC biosynthesize 2-AG. Has negligible activity against other lipids
CC including monoacylglycerols and phospholipids (PubMed:17584991). Plays
CC a key role in regulating 2-AG signaling in the central nervous system
CC (CNS) (PubMed:20159446, PubMed:20147530, PubMed:25466252,
CC PubMed:26668358, PubMed:26779719). Controls the activity of 2-AG as a
CC retrograde messenger at neuronal synapses (PubMed:20159446,
CC PubMed:20147530, PubMed:26668358). Supports axonal growth during
CC development and adult neurogenesis (PubMed:20147530). Plays a role for
CC eCB signaling in the physiological regulation of anxiety and depressive
CC behaviors (PubMed:25466252). Regulates also neuroinflammatory responses
CC in the brain, in particular, LPS-induced microglial activation
CC (PubMed:26779719). {ECO:0000269|PubMed:17584991,
CC ECO:0000269|PubMed:20147530, ECO:0000269|PubMed:20159446,
CC ECO:0000269|PubMed:23103940, ECO:0000269|PubMed:25466252,
CC ECO:0000269|PubMed:26668358, ECO:0000269|PubMed:26779719}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycerol + H2O = a 2-acylglycerol + a fatty
CC acid + H(+); Xref=Rhea:RHEA:33275, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17389, ChEBI:CHEBI:17815,
CC ChEBI:CHEBI:28868; EC=3.1.1.116;
CC Evidence={ECO:0000269|PubMed:17584991};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33276;
CC Evidence={ECO:0000305|PubMed:17584991};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol
CC + H2O = 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H(+) +
CC octadecanoate; Xref=Rhea:RHEA:38507, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:25629, ChEBI:CHEBI:52392,
CC ChEBI:CHEBI:75728; Evidence={ECO:0000269|PubMed:17584991,
CC ECO:0000269|PubMed:23103940};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38508;
CC Evidence={ECO:0000305|PubMed:17584991};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycerol + H2O = (9Z)-
CC octadecenoate + 2-(9Z-octadecenoyl)-glycerol + H(+);
CC Xref=Rhea:RHEA:38511, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:52333, ChEBI:CHEBI:73990;
CC Evidence={ECO:0000269|PubMed:17584991};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38512;
CC Evidence={ECO:0000305|PubMed:17584991};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-
CC glycerol + H2O = (9Z)-octadecenoate + 2-(5Z,8Z,11Z,14Z-
CC eicosatetraenoyl)-glycerol + H(+); Xref=Rhea:RHEA:38515,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:52392, ChEBI:CHEBI:75449;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4D2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38516;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4D2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-2-octadecanoyl-sn-glycerol + H2O = (9Z)-
CC octadecenoate + 2-octadecanoylglycerol + H(+); Xref=Rhea:RHEA:38519,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:75448, ChEBI:CHEBI:75456;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4D2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38520;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4D2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-2-(9Z,12Z-octadecadienoyl)-sn-glycerol +
CC H2O = (9Z)-octadecenoate + 2-(9Z,12Z-octadecadienoyl)-glycerol +
CC H(+); Xref=Rhea:RHEA:38523, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30823, ChEBI:CHEBI:75450, ChEBI:CHEBI:75457;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4D2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38524;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4D2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(9Z-octadecenoyl)-2-O-(5Z,8Z,11Z,14Z-eicosatetraenyl)-sn-
CC glycerol + H2O = (9Z)-octadecenoate + 2-O-(5Z,8Z,11Z,14Z)-
CC eicosatetraenylglycerol + H(+); Xref=Rhea:RHEA:38527,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823,
CC ChEBI:CHEBI:75913, ChEBI:CHEBI:75914;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4D2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38528;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4D2};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4D2};
CC -!- ACTIVITY REGULATION: Inhibited by 1,2,3-triazole urea covalent
CC inhibitor KT172, DH376 and DO34 (PubMed:23103940, PubMed:26668358).
CC Inhibited by p-hydroxy-mercuri-benzoate and HgCl(2), but not to PMSF.
CC Also inhibited by RHC80267. Diacylglycerol lipase activity is inhibited
CC by the phosphorylation of Ser-784 and Ser-810 by CAMK2A (By
CC similarity). {ECO:0000250|UniProtKB:Q9Y4D2,
CC ECO:0000269|PubMed:23103940, ECO:0000269|PubMed:26668358}.
CC -!- SUBUNIT: Interacts (via C-terminal) with CAMK2A; leading to the
CC phosphorylation and inhibition of DAGLA enzymatic activity
CC (PubMed:23502535). Interacts (via PPXXF motif) with HOMER1 and HOMER2;
CC this interaction is required for DAGLA membrane localization
CC (PubMed:17584991). {ECO:0000269|PubMed:17584991,
CC ECO:0000269|PubMed:23502535}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17584991};
CC Multi-pass membrane protein {ECO:0000255}. Cell projection, dendritic
CC spine membrane {ECO:0000269|PubMed:16723519}; Multi-pass membrane
CC protein {ECO:0000255}. Postsynaptic density membrane
CC {ECO:0000250|UniProtKB:Q9Y4D2}; Multi-pass membrane protein
CC {ECO:0000255}. Early endosome membrane {ECO:0000250|UniProtKB:Q9Y4D2};
CC Multi-pass membrane protein {ECO:0000255}. Note=Cycles between the cell
CC surface and an intracellular endosomal compartment. Internalized by
CC early endosomes via a clathrin-independent pathway before transport
CC back to the postsynaptic membrane surface in a PKC-dependent manner.
CC {ECO:0000250|UniProtKB:Q9Y4D2}.
CC -!- TISSUE SPECIFICITY: Highly expressed by principal cells in the
CC hippocampus. In embryonic brains, it is present in axonal tracts, while
CC in adults it localizes to dendritic fields, correlating with the
CC developmental change in requirement for 2-AG synthesis from the pre- to
CC the postsynaptic compartment. Concentrated in heads of dendritic spines
CC throughout the hippocampal formation. Highly compartmentalized into a
CC wide perisynaptic annulus around the postsynaptic density of axospinous
CC contacts but not intrasynaptically (at protein level).
CC {ECO:0000269|PubMed:14610053, ECO:0000269|PubMed:16723519}.
CC -!- PTM: Phosphorylated at Ser-784 and Ser-810 by CAMK2A; phosphorylation
CC by CAMK2A inhibits diacylglycerol lipase activity.
CC {ECO:0000250|UniProtKB:Q9Y4D2}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice are viable, fertile and display
CC normal physiological behaviors (PubMed:20159446, PubMed:20147530).
CC Deficient mice show 80-90% reductions in brain 2-AG as well as the
CC downstream product arachidonic acid (AA), in particular in neurons and
CC astrocytes (PubMed:20159446, PubMed:20147530, PubMed:26779719,
CC PubMed:25466252). The endocannabinoid-mediated retrograde synaptic
CC suppression of neurotransmitter release is absent in the cerebellum,
CC hippocampus, and striatum of knockout mice (PubMed:20159446,
CC PubMed:20147530). In addition, reduction in adult neurogenesis is
CC observed in deficient mice in both the hippocampus and the
CC subventricular zone (PubMed:20147530). DAGLA deletion increases
CC anxiety-like and depressive behaviors (PubMed:25466252). Reduction in
CC LPS-stimulated neuroinflammation is also observed in knockout mice
CC (PubMed:26779719). {ECO:0000269|PubMed:20147530,
CC ECO:0000269|PubMed:20159446, ECO:0000269|PubMed:25466252,
CC ECO:0000269|PubMed:26779719}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family.
CC {ECO:0000305}.
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DR EMBL; AY275376; AAQ17118.1; -; mRNA.
DR EMBL; BC148308; AAI48309.1; -; mRNA.
DR EMBL; AK129183; BAC97993.1; -; mRNA.
DR CCDS; CCDS29574.1; -.
DR RefSeq; NP_932782.2; NM_198114.2.
DR RefSeq; XP_006527177.1; XM_006527114.3.
DR RefSeq; XP_017173702.1; XM_017318213.1.
DR AlphaFoldDB; Q6WQJ1; -.
DR BioGRID; 234600; 1.
DR IntAct; Q6WQJ1; 1.
DR MINT; Q6WQJ1; -.
DR STRING; 10090.ENSMUSP00000046358; -.
DR BindingDB; Q6WQJ1; -.
DR ChEMBL; CHEMBL5180; -.
DR ESTHER; mouse-q6wqj1; Lipase_3.
DR GlyGen; Q6WQJ1; 1 site.
DR iPTMnet; Q6WQJ1; -.
DR PhosphoSitePlus; Q6WQJ1; -.
DR SwissPalm; Q6WQJ1; -.
DR MaxQB; Q6WQJ1; -.
DR PaxDb; Q6WQJ1; -.
DR PRIDE; Q6WQJ1; -.
DR ProteomicsDB; 279860; -.
DR Antibodypedia; 28260; 160 antibodies from 30 providers.
DR DNASU; 269060; -.
DR Ensembl; ENSMUST00000039327; ENSMUSP00000046358; ENSMUSG00000035735.
DR GeneID; 269060; -.
DR KEGG; mmu:269060; -.
DR UCSC; uc008gpm.1; mouse.
DR CTD; 747; -.
DR MGI; MGI:2677061; Dagla.
DR VEuPathDB; HostDB:ENSMUSG00000035735; -.
DR eggNOG; KOG2088; Eukaryota.
DR GeneTree; ENSGT00940000161192; -.
DR HOGENOM; CLU_008300_1_0_1; -.
DR InParanoid; Q6WQJ1; -.
DR OMA; MVAPESP; -.
DR OrthoDB; 191418at2759; -.
DR PhylomeDB; Q6WQJ1; -.
DR TreeFam; TF312928; -.
DR BRENDA; 3.1.1.116; 3474.
DR Reactome; R-MMU-426048; Arachidonate production from DAG.
DR BioGRID-ORCS; 269060; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Dagla; mouse.
DR PRO; PR:Q6WQJ1; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q6WQJ1; protein.
DR Bgee; ENSMUSG00000035735; Expressed in medial dorsal nucleus of thalamus and 172 other tissues.
DR ExpressionAtlas; Q6WQJ1; baseline and differential.
DR Genevisible; Q6WQJ1; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0032590; C:dendrite membrane; ISO:MGI.
DR GO; GO:0032591; C:dendritic spine membrane; IDA:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IDA:SynGO.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0098839; C:postsynaptic density membrane; ISS:UniProtKB.
DR GO; GO:0045211; C:postsynaptic membrane; IDA:SynGO.
DR GO; GO:0043196; C:varicosity; IDA:MGI.
DR GO; GO:0016787; F:hydrolase activity; IMP:UniProtKB.
DR GO; GO:0016298; F:lipase activity; IBA:GO_Central.
DR GO; GO:0004465; F:lipoprotein lipase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004806; F:triglyceride lipase activity; IBA:GO_Central.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IMP:UniProtKB.
DR GO; GO:0046340; P:diacylglycerol catabolic process; ISS:UniProtKB.
DR GO; GO:0071926; P:endocannabinoid signaling pathway; IMP:MGI.
DR GO; GO:0007216; P:G protein-coupled glutamate receptor signaling pathway; IMP:SynGO.
DR GO; GO:0016042; P:lipid catabolic process; IBA:GO_Central.
DR GO; GO:0007405; P:neuroblast proliferation; IMP:MGI.
DR GO; GO:0022008; P:neurogenesis; IMP:MGI.
DR GO; GO:0042136; P:neurotransmitter biosynthetic process; IMP:MGI.
DR GO; GO:0150077; P:regulation of neuroinflammatory response; IMP:UniProtKB.
DR GO; GO:0098921; P:retrograde trans-synaptic signaling by endocannabinoid; IDA:SynGO.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR002921; Fungal_lipase-like.
DR Pfam; PF01764; Lipase_3; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR PROSITE; PS00120; LIPASE_SER; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Cell projection; Endosome; Glycoprotein; Hydrolase;
KW Lipid degradation; Lipid metabolism; Membrane; Metal-binding;
KW Phosphoprotein; Postsynaptic cell membrane; Reference proteome; Synapse;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..1044
FT /note="Diacylglycerol lipase-alpha"
FT /id="PRO_0000248348"
FT TOPO_DOM 1..22
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 23..43
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 44..60
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 61..81
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 82..101
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 102..122
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 123..136
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 137..157
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 158..1044
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 848..897
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1013..1044
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1013..1032
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 472
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT ACT_SITE 524
FT /note="Charge relay system"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037"
FT MOD_RES 728
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5YLM1"
FT MOD_RES 730
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 733
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16452087"
FT MOD_RES 744
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16452087,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 784
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5YLM1"
FT MOD_RES 786
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 808
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5YLM1"
FT MOD_RES 810
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4D2"
FT MOD_RES 835
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5YLM1"
FT MOD_RES 849
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5YLM1"
FT MOD_RES 954
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1025
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 975
FT /note="P->C: Abolishes interaction with HOMER1. Does not
FT affect enzymatic activity. Fails to associate with the
FT plasma membrane."
FT /evidence="ECO:0000269|PubMed:17584991"
FT MUTAGEN 978
FT /note="F->R: Abolishes interaction with HOMER1."
FT /evidence="ECO:0000269|PubMed:17584991"
FT CONFLICT 191
FT /note="A -> P (in Ref. 1; AAQ17118)"
FT /evidence="ECO:0000305"
FT CONFLICT 830
FT /note="P -> S (in Ref. 1; AAQ17118)"
FT /evidence="ECO:0000305"
FT CONFLICT 945
FT /note="T -> S (in Ref. 1; AAQ17118)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1044 AA; 115375 MW; 77E301AE127014F1 CRC64;
MPGIVVFRRR WSVGSDDLVL PAIFLFLLHT TWFVILSVVL FGLVYNPHEA CSLNLVDHGR
GYLGILLSCM IAEMAIIWLS MRGGILYTEP RDSMQYVLYV RLAILVIEFI YAIVGIVWLT
QYYTSCNDLT AKNVTLGMVV CNWVVILSVC ITVLCVFDPT GRTFVKLRAT KRRQRNLRTY
NLRHRLEEGQ ATSWSRRLKV FLCCTRTKDS QSDAYSEIAY LFAEFFRDLD IVPSDIIAGL
VLLRQRQRAK RNAVLDEANN DILAFLSGMP VTRNTKYLDL KNSHEMLRYK EVCYYMLFAL
AAYGWPMYLM RKPTCGLCQL ARSCSCCLCP ARPRFAPGVT IEEDNCCGCN AIAIRRHFLD
ENMTAVDIVY TSCHDAVYET PFYVAVDHDK KKVVISIRGT LSPKDALTDL TGDAERLPVE
GHRGTWLGHK GMVLSAEYIK KKLEQEMVLS QAFGRDLGRG TKHYGLIVVG HSLGAGTAAI
LSFLLRPQYP TLKCFAYSPP GGLLSEDAME YSKEFVTAVV LGKDLVPRIG LSQLEGFRRQ
LLDVLQRSTK PKWRIIVGAT KCIPKSELPE DQVEVTTLAS TRLWTHPSDL TIALSASTPL
YPPGRIIHVV HNHPAEQCCC CEQEEPTYFA IWGDNKAFNE VIISPAMLHE HLPYVVMEGL
NKVLENYNKG KTALLSAAKV MVSPTEVDLT PELIFQQQPL PTGPPLPTGL ALELPATEHR
NSSVRSKSQS EMSLEGFSEG RLLSPVAAAS AARQDPVELL LLSTQERLAA ELQSRRAPLA
TMESLSDTES LYSFDSRRSS GFRSIRGSPS LHAVLERDEG HLFYIDPAIP EENPSLSSRT
ELLAADSLSK HSQDTQPLEA ALGSGGVTPE RPPSATIEEE EAAGGSEGGG VAPRGELALH
NGRLGDSPSP QVLEFAEFID SLFNLDSKSS SFQDLYCMMV PESPTSDYTE GPKSPSQQEI
LLRAQFEPNL VPKPPRLFAG SAEPSSGISL SPSFPLSSSG ELMDLTPTGL SSQECLATDK
IRTSTPTGHG ASPTKQDDLV ISAR
