DGLA_HUMAN
ID DGLA_HUMAN Reviewed; 1042 AA.
AC Q9Y4D2; A0A024R517; A7E233; Q6WQJ0;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 3.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Diacylglycerol lipase-alpha;
DE Short=DAGL-alpha;
DE Short=DGL-alpha;
DE EC=3.1.1.116 {ECO:0000269|PubMed:14610053, ECO:0000269|PubMed:23502535, ECO:0000269|PubMed:26668358};
DE AltName: Full=Neural stem cell-derived dendrite regulator {ECO:0000303|Ref.1};
DE AltName: Full=Sn1-specific diacylglycerol lipase alpha {ECO:0000303|PubMed:14610053};
GN Name=DAGLA; Synonyms=C11orf11, KIAA0659, NSDDR {ECO:0000303|Ref.1};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
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].
RC TISSUE=Brain;
RX PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. X. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:169-176(1998).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
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 [7]
RP FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION,
RP TISSUE SPECIFICITY, AND CATALYTIC ACTIVITY.
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 [8]
RP TISSUE SPECIFICITY.
RX PubMed=16051747; DOI=10.1124/mol.105.013961;
RA Jung K.-M., Mangieri R., Stapleton C., Kim J., Fegley D., Wallace M.,
RA Mackie K., Piomelli D.;
RT "Stimulation of endocannabinoid formation in brain slice cultures through
RT activation of group I metabotropic glutamate receptors.";
RL Mol. Pharmacol. 68:1196-1202(2005).
RN [9]
RP CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES,
RP PHOSPHORYLATION AT SER-782 AND SER-808, INTERACTION WITH CAMK2A,
RP MUTAGENESIS OF SER-782 AND SER-808, AND ACTIVITY REGULATION.
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 [10]
RP SUBCELLULAR LOCATION.
RX PubMed=27595600; DOI=10.1016/j.mcn.2016.08.011;
RA Zhou Y., Howell F.V., Glebov O.O., Albrecht D., Williams G., Doherty P.;
RT "Regulated endosomal trafficking of Diacylglycerol lipase alpha (DAGLalpha)
RT generates distinct cellular pools; implications for endocannabinoid
RT signaling.";
RL Mol. Cell. Neurosci. 76:76-86(2016).
RN [11]
RP CATALYTIC ACTIVITY, FUNCTION, AND ACTIVITY REGULATION.
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).
RN [12]
RP POSSIBLE INVOLVEMENT IN SCA20.
RX PubMed=18801880; DOI=10.1093/hmg/ddn283;
RA Knight M.A., Hernandez D., Diede S.J., Dauwerse H.G., Rafferty I.,
RA van de Leemput J., Forrest S.M., Gardner R.J., Storey E., van Ommen G.J.,
RA Tapscott S.J., Fischbeck K.H., Singleton A.B.;
RT "A duplication at chromosome 11q12.2-11q12.3 is associated with
RT spinocerebellar ataxia type 20.";
RL Hum. Mol. Genet. 17:3847-3853(2008).
CC -!- FUNCTION: Serine hydrolase that hydrolyzes arachidonic acid-esterified
CC diacylglycerols (DAGs) to produce the principal endocannabinoid, 2-
CC arachidonoylglycerol (2-AG) (PubMed:14610053, PubMed:26668358,
CC PubMed:23502535). Preferentially hydrolyzes sn-1 fatty acids from
CC diacylglycerols (DAG) that contain arachidonic acid (AA) esterified at
CC the sn-2 position to biosynthesize 2-AG (PubMed:14610053,
CC PubMed:26668358, PubMed:23502535). Has negligible activity against
CC other lipids including monoacylglycerols and phospholipids
CC (PubMed:14610053). Plays a key role in regulating 2-AG signaling in the
CC central nervous system (CNS). Regulates 2-AG involved in retrograde
CC suppression at central synapses. Supports axonal growth during
CC development and adult neurogenesis. Plays a role for eCB signaling in
CC the physiological regulation of anxiety and depressive behaviors.
CC Regulates also neuroinflammatory responses in the brain, in particular,
CC LPS-induced microglial activation (By similarity).
CC {ECO:0000250|UniProtKB:Q6WQJ1, ECO:0000269|PubMed:14610053,
CC ECO:0000269|PubMed:23502535, ECO:0000269|PubMed:26668358}.
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:14610053};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33276;
CC Evidence={ECO:0000305|PubMed:14610053};
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:14610053,
CC ECO:0000269|PubMed:23502535, ECO:0000269|PubMed:26668358};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38508;
CC Evidence={ECO:0000305|PubMed:14610053, ECO:0000305|PubMed:23502535,
CC ECO:0000305|PubMed:26668358};
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:14610053};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38512;
CC Evidence={ECO:0000305|PubMed:14610053};
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:0000269|PubMed:14610053};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38516;
CC Evidence={ECO:0000305|PubMed:14610053};
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:0000269|PubMed:14610053};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38520;
CC Evidence={ECO:0000305|PubMed:14610053};
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:0000269|PubMed:14610053};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38524;
CC Evidence={ECO:0000305|PubMed:14610053};
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:0000269|PubMed:14610053};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38528;
CC Evidence={ECO:0000305|PubMed:14610053};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:14610053};
CC -!- ACTIVITY REGULATION: Inhibited by 1,2,3-triazole urea covalent
CC inhibitors KT172, DH376 and DO34 (PubMed:26668358). Inhibited by p-
CC hydroxy-mercuri-benzoate and HgCl(2), but not to PMSF. Also inhibited
CC by RHC80267 (PubMed:14610053). Diacylglycerol lipase activity is
CC inhibited by the phosphorylation of Ser-782 and Ser-808 by CAMK2A
CC (PubMed:23502535). {ECO:0000269|PubMed:14610053,
CC ECO:0000269|PubMed:23502535, ECO:0000269|PubMed:26668358}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=154.7 uM for diacylglycerol {ECO:0000269|PubMed:14610053};
CC KM=158 uM for 1-steroyl-2-arachidonoylglycerol
CC {ECO:0000269|PubMed:23502535};
CC Vmax=33.3 nmol/min/mg enzyme {ECO:0000269|PubMed:14610053};
CC Vmax=9.8 pmol/min/mg enzyme with 1-steroyl-2-arachidonoylglycerol as
CC substrat {ECO:0000269|PubMed:23502535};
CC pH dependence:
CC Optimum pH is 7.0. {ECO:0000269|PubMed:14610053};
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 (By
CC similarity). {ECO:0000250|UniProtKB:Q6WQJ1,
CC ECO:0000269|PubMed:23502535}.
CC -!- INTERACTION:
CC Q9Y4D2; Q96FZ5: CMTM7; NbExp=3; IntAct=EBI-12808806, EBI-2807956;
CC Q9Y4D2; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-12808806, EBI-2820517;
CC Q9Y4D2; P21145: MAL; NbExp=3; IntAct=EBI-12808806, EBI-3932027;
CC Q9Y4D2; Q13021: MALL; NbExp=3; IntAct=EBI-12808806, EBI-750078;
CC Q9Y4D2; Q5J8X5: MS4A13; NbExp=3; IntAct=EBI-12808806, EBI-12070086;
CC Q9Y4D2; P27105: STOM; NbExp=3; IntAct=EBI-12808806, EBI-1211440;
CC Q9Y4D2; A2RU14: TMEM218; NbExp=3; IntAct=EBI-12808806, EBI-10173151;
CC Q9Y4D2; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-12808806, EBI-11988865;
CC Q9Y4D2; O75841: UPK1B; NbExp=6; IntAct=EBI-12808806, EBI-12237619;
CC Q9Y4D2; Q3ZAQ7: VMA21; NbExp=3; IntAct=EBI-12808806, EBI-1055364;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:27595600};
CC Multi-pass membrane protein {ECO:0000255}. Postsynaptic density
CC membrane {ECO:0000269|PubMed:27595600}; Multi-pass membrane protein
CC {ECO:0000255}. Early endosome membrane {ECO:0000269|PubMed:27595600};
CC Multi-pass membrane protein {ECO:0000255}. Cell projection, dendritic
CC spine membrane {ECO:0000250|UniProtKB:Q6WQJ1}; Multi-pass membrane
CC protein {ECO:0000255}. Note=Cycles between the cell surface and an
CC intracellular endosomal compartment. Internalized by early endosomes
CC via a clathrin-independent pathway before transport back to the
CC postsynaptic membrane surface in a PKC-dependent manner.
CC {ECO:0000269|PubMed:27595600}.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain and pancreas.
CC {ECO:0000269|PubMed:14610053, ECO:0000269|PubMed:16051747}.
CC -!- PTM: Phosphorylated at Ser-782 and Ser-808 by CAMK2A; phosphorylation
CC by CAMK2A inhibits diacylglycerol lipase activity.
CC {ECO:0000269|PubMed:23502535}.
CC -!- DISEASE: Spinocerebellar ataxia 20 (SCA20) [MIM:608687]:
CC Spinocerebellar ataxia is a clinically and genetically heterogeneous
CC group of cerebellar disorders. Patients show progressive incoordination
CC of gait and often poor coordination of hands, speech and eye movements,
CC due to degeneration of the cerebellum with variable involvement of the
CC brainstem and spinal cord. SCA20 is an autosomal dominant, adult-onset
CC form characterized by dysarthria due to spasmodic dysphonia followed by
CC slowly progressive ataxia. {ECO:0000269|PubMed:18801880}. Note=The
CC disease may be caused by variants affecting the gene represented in
CC this entry. A copy number variation consisting of a 260-kb duplication
CC at chromosome 11q12.2-12.3 is responsible for SCA20. The critical gene
CC within the duplicated segment may be DAGLA.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA31634.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY275377; AAQ17119.1; -; mRNA.
DR EMBL; AB014559; BAA31634.2; ALT_INIT; mRNA.
DR EMBL; AP002380; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471076; EAW73960.1; -; Genomic_DNA.
DR EMBL; CH471076; EAW73961.1; -; Genomic_DNA.
DR EMBL; BC150176; AAI50177.1; -; mRNA.
DR EMBL; BC150195; AAI50196.1; -; mRNA.
DR EMBL; BC152453; AAI52454.1; -; mRNA.
DR CCDS; CCDS31578.1; -.
DR PIR; T00370; T00370.
DR RefSeq; NP_006124.1; NM_006133.2.
DR AlphaFoldDB; Q9Y4D2; -.
DR BioGRID; 107205; 19.
DR IntAct; Q9Y4D2; 12.
DR STRING; 9606.ENSP00000257215; -.
DR BindingDB; Q9Y4D2; -.
DR ChEMBL; CHEMBL5545; -.
DR DrugCentral; Q9Y4D2; -.
DR GuidetoPHARMACOLOGY; 1396; -.
DR SwissLipids; SLP:000000323; -.
DR ESTHER; human-DAGLA; Lipase_3.
DR GlyGen; Q9Y4D2; 1 site.
DR iPTMnet; Q9Y4D2; -.
DR PhosphoSitePlus; Q9Y4D2; -.
DR BioMuta; DAGLA; -.
DR DMDM; 114149271; -.
DR jPOST; Q9Y4D2; -.
DR MassIVE; Q9Y4D2; -.
DR MaxQB; Q9Y4D2; -.
DR PaxDb; Q9Y4D2; -.
DR PeptideAtlas; Q9Y4D2; -.
DR PRIDE; Q9Y4D2; -.
DR ProteomicsDB; 86167; -.
DR Antibodypedia; 28260; 160 antibodies from 30 providers.
DR DNASU; 747; -.
DR Ensembl; ENST00000257215.10; ENSP00000257215.5; ENSG00000134780.10.
DR GeneID; 747; -.
DR KEGG; hsa:747; -.
DR MANE-Select; ENST00000257215.10; ENSP00000257215.5; NM_006133.3; NP_006124.1.
DR UCSC; uc001nsa.4; human.
DR CTD; 747; -.
DR DisGeNET; 747; -.
DR GeneCards; DAGLA; -.
DR HGNC; HGNC:1165; DAGLA.
DR HPA; ENSG00000134780; Tissue enhanced (brain).
DR MIM; 608687; phenotype.
DR MIM; 614015; gene.
DR neXtProt; NX_Q9Y4D2; -.
DR OpenTargets; ENSG00000134780; -.
DR PharmGKB; PA162383158; -.
DR VEuPathDB; HostDB:ENSG00000134780; -.
DR eggNOG; KOG2088; Eukaryota.
DR GeneTree; ENSGT00940000161192; -.
DR HOGENOM; CLU_008300_1_0_1; -.
DR InParanoid; Q9Y4D2; -.
DR OMA; MVAPESP; -.
DR OrthoDB; 191418at2759; -.
DR PhylomeDB; Q9Y4D2; -.
DR TreeFam; TF312928; -.
DR BioCyc; MetaCyc:ENSG00000134780-MON; -.
DR BRENDA; 3.1.1.116; 2681.
DR PathwayCommons; Q9Y4D2; -.
DR Reactome; R-HSA-426048; Arachidonate production from DAG.
DR SABIO-RK; Q9Y4D2; -.
DR SignaLink; Q9Y4D2; -.
DR SIGNOR; Q9Y4D2; -.
DR BioGRID-ORCS; 747; 13 hits in 1073 CRISPR screens.
DR ChiTaRS; DAGLA; human.
DR GenomeRNAi; 747; -.
DR Pharos; Q9Y4D2; Tchem.
DR PRO; PR:Q9Y4D2; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9Y4D2; protein.
DR Bgee; ENSG00000134780; Expressed in right frontal lobe and 108 other tissues.
DR ExpressionAtlas; Q9Y4D2; baseline and differential.
DR Genevisible; Q9Y4D2; HS.
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; IDA:UniProtKB.
DR GO; GO:0032591; C:dendritic spine membrane; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IDA:UniProtKB.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0098839; C:postsynaptic density membrane; IDA:UniProtKB.
DR GO; GO:0045211; C:postsynaptic membrane; IBA:GO_Central.
DR GO; GO:0043196; C:varicosity; IEA:Ensembl.
DR GO; GO:0047372; F:acylglycerol lipase activity; TAS:Reactome.
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; IDA:UniProtKB.
DR GO; GO:0046340; P:diacylglycerol catabolic process; IDA:UniProtKB.
DR GO; GO:0071926; P:endocannabinoid signaling pathway; IBA:GO_Central.
DR GO; GO:0007216; P:G protein-coupled glutamate receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0016042; P:lipid catabolic process; IBA:GO_Central.
DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0022008; P:neurogenesis; IBA:GO_Central.
DR GO; GO:0042136; P:neurotransmitter biosynthetic process; IDA:UniProtKB.
DR GO; GO:0150077; P:regulation of neuroinflammatory response; ISS:UniProtKB.
DR GO; GO:0098921; P:retrograde trans-synaptic signaling by endocannabinoid; IMP:UniProtKB.
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 Neurodegeneration; Phosphoprotein; Postsynaptic cell membrane;
KW Reference proteome; Spinocerebellar ataxia; Synapse; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..1042
FT /note="Diacylglycerol lipase-alpha"
FT /id="PRO_0000248347"
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..1042
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 846..903
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1014..1042
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1014..1029
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 727
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5YLM1"
FT MOD_RES 729
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6WQJ1"
FT MOD_RES 732
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6WQJ1"
FT MOD_RES 743
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6WQJ1"
FT MOD_RES 782
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:23502535"
FT MOD_RES 784
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6WQJ1"
FT MOD_RES 806
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5YLM1"
FT MOD_RES 808
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:23502535"
FT MOD_RES 833
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5YLM1"
FT MOD_RES 847
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5YLM1"
FT MOD_RES 952
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6WQJ1"
FT MOD_RES 1023
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q6WQJ1"
FT CARBOHYD 133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 735
FT /note="G -> V (in dbSNP:rs35056845)"
FT /id="VAR_049822"
FT VARIANT 889
FT /note="P -> L (in dbSNP:rs3741252)"
FT /id="VAR_027274"
FT VARIANT 945
FT /note="D -> E (in dbSNP:rs34956386)"
FT /id="VAR_049823"
FT MUTAGEN 782
FT /note="S->A: Slightly reduces phosphorylation by CAMK2A.
FT Abolishes phosphorylation by CAMK2A; when associated with
FT A-808."
FT /evidence="ECO:0000269|PubMed:23502535"
FT MUTAGEN 782
FT /note="S->E: Phosphomimetic mutation; decreased the Vmax of
FT 2-AG production without affecting the KM; when associated
FT with E-808."
FT /evidence="ECO:0000269|PubMed:23502535"
FT MUTAGEN 808
FT /note="S->A: Reduces phosphorylation by CAMK2A. Abolishes
FT phosphorylation by CAMK2A; when associated with A-782."
FT /evidence="ECO:0000269|PubMed:23502535"
FT MUTAGEN 808
FT /note="S->E: Phosphomimetic mutation; decreased the Vmax of
FT 2-AG production without affecting the KM; when associated
FT with E-782."
FT /evidence="ECO:0000269|PubMed:23502535"
SQ SEQUENCE 1042 AA; 114952 MW; A6E675984E89CB2F 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 KNSQEMLRYK EVCYYMLFAL
AAYGWPMYLM RKPACGLCQL ARSCSCCLCP ARPRFAPGVT IEEDNCCGCN AIAIRRHFLD
ENMTAVDIVY TSCHDAVYET PFYVAVDHDK KKVVISIRGT LSPKDALTDL TGDAERLPVE
GHHGTWLGHK GMVLSAEYIK KKLEQEMVLS QAFGRDLGRG TKHYGLIVVG HSLGAGTAAI
LSFLLRPQYP TLKCFAYSPP GGLLSEDAME YSKEFVTAVV LGKDLVPRIG LSQLEGFRRQ
LLDVLQRSTK PKWRIIVGAT KCIPKSELPE EVEVTTLAST RLWTHPSDLT IALSASTPLY
PPGRIIHVVH NHPAEQCCCC EQEEPTYFAI WGDNKAFNEV IISPAMLHEH LPYVVMEGLN
KVLENYNKGK TALLSAAKVM VSPTEVDLTP ELIFQQQPLP TGPPMPTGLA LELPTADHRN
SSVRSKSQSE MSLEGFSEGR LLSPVVAAAA RQDPVELLLL STQERLAAEL QARRAPLATM
ESLSDTESLY SFDSRRSSGF RSIRGSPSLH AVLERDEGHL FYIDPAIPEE NPSLSSRTEL
LAADSLSKHS QDTQPLEAAL GSGGVTPERP PSAAANDEEE EVGGGGGGPA SRGELALHNG
RLGDSPSPQV LEFAEFIDSL FNLDSKSSSF QDLYCMVVPE SPTSDYAEGP KSPSQQEILL
RAQFEPNLVP KPPRLFAGSA DPSSGISLSP SFPLSSSGEL MDLTPTGLSS QECLAADKIR
TSTPTGHGAS PAKQDELVIS AR
