DGLA_RAT
ID DGLA_RAT Reviewed; 1044 AA.
AC Q5YLM1;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Diacylglycerol lipase-alpha;
DE EC=3.1.1.116 {ECO:0000250|UniProtKB:Q9Y4D2};
DE AltName: Full=Neural stem cell-derived dendrite regulator {ECO:0000303|Ref.1};
DE AltName: Full=Sn1-specific diacylglycerol lipase alpha;
DE Short=DGL-alpha;
GN Name=Dagla; Synonyms=Nsddr;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-728; SER-733; SER-744;
RP SER-784; SER-786; SER-808; SER-835 AND SER-849, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Serine hydrolase that hydrolyzes arachidonic acid-esterified
CC diacylglycerols (DAGs) to produce the principal endocannabinoid, 2-
CC arachidonoylglycerol (2-AG). Preferentially hydrolyzes sn-1 fatty acids
CC from diacylglycerols (DAG) that contain arachidonic acid (AA)
CC esterified at the sn-2 position to biosynthesize 2-AG. Has negligible
CC activity against other lipids including monoacylglycerols and
CC phospholipids. Plays a key role in regulating 2-AG signaling in the
CC CNS. Controls the activity of 2-AG as a retrograde messenger at
CC neuronal synapses. Supports axonal growth during development and adult
CC neurogenesis. Plays a role for eCB signaling in the physiological
CC regulation of anxiety and depressive behaviors. Regulates also
CC neuroinflammatory responses in the brain, in particular, LPS-induced
CC microglial activation. {ECO:0000250|UniProtKB:Q6WQJ1}.
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:0000250|UniProtKB:Q6WQJ1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33276;
CC Evidence={ECO:0000250|UniProtKB:Q6WQJ1};
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:0000250|UniProtKB:Q9Y4D2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38508;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4D2};
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:0000250|UniProtKB:Q9Y4D2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38512;
CC Evidence={ECO:0000250|UniProtKB:Q9Y4D2};
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 inhibitors KT172, DH376 and DO34 (By similarity). Inhibited by p-
CC hydroxy-mercuri-benzoate and HgCl(2), but not to PMSF. Also inhibited
CC by RHC80267. Diacylglycerol lipase activity is inhibited by the
CC phosphorylation of Ser-784 and Ser-810 by CAMK2A (By similarity).
CC {ECO:0000250|UniProtKB:Q6WQJ1, ECO:0000250|UniProtKB:Q9Y4D2}.
CC -!- SUBUNIT: Interacts (via C-terminal) with CAMK2A; leading to the
CC phosphorylation and inhibition of DAGLA enzymatic activity. Interacts
CC (via PPXXF motif) with HOMER1 and HOMER2; this interaction is required
CC for DAGLA membrane localization. {ECO:0000250|UniProtKB:Q6WQJ1}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9Y4D2};
CC Multi-pass membrane protein {ECO:0000255}. Cell projection, dendritic
CC spine membrane {ECO:0000250|UniProtKB:Q6WQJ1}; Multi-pass membrane
CC protein {ECO:0000255}. Postsynaptic density membrane
CC {ECO:0000250|UniProtKB:Q9Y4D2}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9Y4D2}. Early endosome membrane
CC {ECO:0000250|UniProtKB:Q9Y4D2}; Multi-pass membrane protein
CC {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:0000250|UniProtKB:Q9Y4D2}.
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 -!- SIMILARITY: Belongs to the AB hydrolase superfamily. Lipase family.
CC {ECO:0000305}.
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DR EMBL; AY275375; AAQ17117.1; -; mRNA.
DR RefSeq; NP_001005886.1; NM_001005886.1.
DR RefSeq; XP_017444750.1; XM_017589261.1.
DR AlphaFoldDB; Q5YLM1; -.
DR STRING; 10116.ENSRNOP00000033416; -.
DR ChEMBL; CHEMBL4523331; -.
DR ESTHER; ratno-q5ylm1; Lipase_3.
DR GlyGen; Q5YLM1; 1 site.
DR iPTMnet; Q5YLM1; -.
DR PhosphoSitePlus; Q5YLM1; -.
DR SwissPalm; Q5YLM1; -.
DR PaxDb; Q5YLM1; -.
DR PRIDE; Q5YLM1; -.
DR Ensembl; ENSRNOT00000037624; ENSRNOP00000033416; ENSRNOG00000027264.
DR GeneID; 309207; -.
DR KEGG; rno:309207; -.
DR CTD; 747; -.
DR RGD; 1359461; Dagla.
DR eggNOG; KOG2088; Eukaryota.
DR GeneTree; ENSGT00940000161192; -.
DR HOGENOM; CLU_008300_1_0_1; -.
DR InParanoid; Q5YLM1; -.
DR OMA; MVAPESP; -.
DR OrthoDB; 191418at2759; -.
DR PhylomeDB; Q5YLM1; -.
DR TreeFam; TF312928; -.
DR Reactome; R-RNO-426048; Arachidonate production from DAG.
DR PRO; PR:Q5YLM1; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000027264; Expressed in frontal cortex and 16 other tissues.
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; ISS:UniProtKB.
DR GO; GO:0032591; C:dendritic spine membrane; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0098839; C:postsynaptic density membrane; ISS:UniProtKB.
DR GO; GO:0045211; C:postsynaptic membrane; ISO:RGD.
DR GO; GO:0043196; C:varicosity; ISO:RGD.
DR GO; GO:0016787; F:hydrolase activity; ISO:RGD.
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; ISS:UniProtKB.
DR GO; GO:0046340; P:diacylglycerol catabolic process; ISS:UniProtKB.
DR GO; GO:0071926; P:endocannabinoid signaling pathway; ISS:UniProtKB.
DR GO; GO:0007216; P:G protein-coupled glutamate receptor signaling pathway; ISO:RGD.
DR GO; GO:0016042; P:lipid catabolic process; IBA:GO_Central.
DR GO; GO:0007405; P:neuroblast proliferation; ISS:UniProtKB.
DR GO; GO:0022008; P:neurogenesis; ISS:UniProtKB.
DR GO; GO:0042136; P:neurotransmitter biosynthetic process; ISS:UniProtKB.
DR GO; GO:0150077; P:regulation of neuroinflammatory response; ISS:UniProtKB.
DR GO; GO:0098921; P:retrograde trans-synaptic signaling by endocannabinoid; ISS: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 Phosphoprotein; Postsynaptic cell membrane; Reference proteome; Synapse;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..1044
FT /note="Diacylglycerol lipase-alpha"
FT /id="PRO_0000248349"
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..905
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:0007744|PubMed:22673903"
FT MOD_RES 730
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6WQJ1"
FT MOD_RES 733
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 744
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 784
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4D2,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 786
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 808
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 810
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4D2"
FT MOD_RES 835
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 849
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 954
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6WQJ1"
FT MOD_RES 1025
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q6WQJ1"
FT CARBOHYD 133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1044 AA; 115301 MW; 513F144EFF7E995A 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 DQVEVTALAS 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 RPPSAANDEE EAAGGSEGGG VAPRGELALH
NGRLGDSPSP QVLEFAEFID SLFNLDSKSS SFQDLYCMMV PESPTSDYTE GPKSPSQQEI
LLRAQFEPNL VPKPPRLFAG SAEPSSGISL SPSFPLSSSG ELMDLTPTGL SSQECLATDK
IRTSTPTGHG ASPTKQDDLV ISAR
