UniProtKB - Q5YLM1 (DGLA_RAT)
Protein
Diacylglycerol lipase-alpha
Gene
Dagla
Organism
Rattus norvegicus (Rat)
Status
Functioni
Serine hydrolase that hydrolyzes arachidonic acid-esterified diacylglycerols (DAGs) to produce the principal endocannabinoid, 2-arachidonoylglycerol (2-AG). Preferentially hydrolyzes sn-1 fatty acids from diacylglycerols (DAG) that contain arachidonic acid (AA) esterified at the sn-2 position to biosynthesize 2-AG. Has negligible activity against other lipids including monoacylglycerols and phospholipids. Plays a key role in regulating 2-AG signaling in the CNS. Controls the activity of 2-AG as a retrograde messenger at neuronal synapses. Supports axonal growth during development and adult neurogenesis. Plays a role for eCB signaling in the physiological regulation of anxiety and depressive behaviors. Regulates also neuroinflammatory responses in the brain, in particular, LPS-induced microglial activation.By similarity
Catalytic activityi
- 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + H2O = 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H+ + octadecanoateBy similarityThis reaction proceeds in the forwardBy similarity direction.
- 1,2-di-(9Z-octadecenoyl)-sn-glycerol + H2O = (9Z)-octadecenoate + 2-(9Z-octadecenoyl)-glycerol + H+By similarityThis reaction proceeds in the forwardBy similarity direction.
- 1-(9Z-octadecenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + H2O = (9Z)-octadecenoate + 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H+By similarityThis reaction proceeds in the forwardBy similarity direction.
- 1-(9Z-octadecenoyl)-2-octadecanoyl-sn-glycerol + H2O = (9Z)-octadecenoate + 2-octadecanoylglycerol + H+By similarityThis reaction proceeds in the forwardBy similarity direction.
- 1-(9Z-octadecenoyl)-2-(9Z,12Z-octadecadienoyl)-sn-glycerol + H2O = (9Z)-octadecenoate + 2-(9Z,12Z-octadecadienoyl)-glycerol + H+By similarityThis reaction proceeds in the forwardBy similarity direction.
- 1-(9Z-octadecenoyl)-2-O-(5Z,8Z,11Z,14Z-eicosatetraenyl)-sn-glycerol + H2O = (9Z)-octadecenoate + 2-O-(5Z,8Z,11Z,14Z)-eicosatetraenylglycerol + H+By similarityThis reaction proceeds in the forwardBy similarity direction.
Cofactori
Ca2+By similarity
Activity regulationi
Inhibited by 1,2,3-triazole urea covalent inhibitors KT172, DH376 and DO34 (By similarity). Inhibited by p-hydroxy-mercuri-benzoate and HgCl2, but not to PMSF. Also inhibited by RHC80267. Diacylglycerol lipase activity is inhibited by the phosphorylation of Ser-784 and Ser-810 by CAMK2A (By similarity).By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 472 | Charge relay systemPROSITE-ProRule annotation | 1 | |
Active sitei | 524 | Charge relay systemPROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- hydrolase activity Source: RGD
- metal ion binding Source: UniProtKB-KW
GO - Biological processi
- arachidonic acid metabolic process Source: UniProtKB
- diacylglycerol catabolic process Source: UniProtKB
- endocannabinoid signaling pathway Source: UniProtKB
- G protein-coupled glutamate receptor signaling pathway Source: RGD
- neuroblast proliferation Source: UniProtKB
- neurogenesis Source: UniProtKB
- neurotransmitter biosynthetic process Source: UniProtKB
- regulation of neuroinflammatory response Source: UniProtKB
- retrograde trans-synaptic signaling by endocannabinoid Source: UniProtKB
Keywordsi
Molecular function | Hydrolase |
Biological process | Lipid degradation, Lipid metabolism |
Ligand | Calcium, Metal-binding |
Enzyme and pathway databases
Reactomei | R-RNO-426048, Arachidonate production from DAG |
Protein family/group databases
ESTHERi | ratno-q5ylm1, Lipase_3 |
Names & Taxonomyi
Protein namesi | Recommended name: Diacylglycerol lipase-alpha (EC:3.1.1.-By similarity)Alternative name(s): Neural stem cell-derived dendrite regulator1 Publication Sn1-specific diacylglycerol lipase alpha Short name: DGL-alpha |
Gene namesi | Name:Dagla Synonyms:Nsddr |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 1359461, Dagla |
Subcellular locationi
Endosome
- Early endosome membrane By similarity; Multi-pass membrane protein Sequence analysis
Plasma membrane
- Cell membrane By similarity; Multi-pass membrane protein Sequence analysis
- dendritic spine membrane By similarity; Multi-pass membrane protein Sequence analysis
- postsynaptic density membrane By similarity; Multi-pass membrane protein By similarity
Note: Cycles between the cell surface and an intracellular endosomal compartment. Internalized by early endosomes via a clathrin-independent pathway before transport back to the postsynaptic membrane surface in a PKC-dependent manner.By similarity
Endosome
- early endosome membrane Source: UniProtKB
Plasma Membrane
- dendrite membrane Source: UniProtKB
- dendritic spine membrane Source: UniProtKB
- integral component of postsynaptic membrane Source: RGD
- plasma membrane Source: RGD
- postsynaptic density membrane Source: UniProtKB
- postsynaptic membrane Source: RGD
Other locations
- varicosity Source: RGD
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 22 | CytoplasmicSequence analysisAdd BLAST | 22 | |
Transmembranei | 23 – 43 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 44 – 60 | ExtracellularSequence analysisAdd BLAST | 17 | |
Transmembranei | 61 – 81 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 82 – 101 | CytoplasmicSequence analysisAdd BLAST | 20 | |
Transmembranei | 102 – 122 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 123 – 136 | ExtracellularSequence analysisAdd BLAST | 14 | |
Transmembranei | 137 – 157 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 158 – 1044 | CytoplasmicSequence analysisAdd BLAST | 887 |
Keywords - Cellular componenti
Cell junction, Cell membrane, Cell projection, Endosome, Membrane, Postsynaptic cell membrane, SynapsePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000248349 | 1 – 1044 | Diacylglycerol lipase-alphaAdd BLAST | 1044 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 133 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Modified residuei | 728 | PhosphoserineCombined sources | 1 | |
Modified residuei | 730 | PhosphoserineBy similarity | 1 | |
Modified residuei | 733 | PhosphoserineCombined sources | 1 | |
Modified residuei | 744 | PhosphoserineCombined sources | 1 | |
Modified residuei | 784 | PhosphoserineCombined sourcesBy similarity | 1 | |
Modified residuei | 786 | PhosphoserineCombined sources | 1 | |
Modified residuei | 808 | PhosphoserineCombined sources | 1 | |
Modified residuei | 810 | PhosphoserineBy similarity | 1 | |
Modified residuei | 835 | PhosphoserineCombined sources | 1 | |
Modified residuei | 849 | PhosphoserineCombined sources | 1 | |
Modified residuei | 954 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1025 | PhosphothreonineBy similarity | 1 |
Post-translational modificationi
Phosphorylated at Ser-784 and Ser-810 by CAMK2A; phosphorylation by CAMK2A inhibits diacylglycerol lipase activity.By similarity
Keywords - PTMi
Glycoprotein, PhosphoproteinProteomic databases
PaxDbi | Q5YLM1 |
PRIDEi | Q5YLM1 |
PTM databases
GlyGeni | Q5YLM1, 1 site |
iPTMneti | Q5YLM1 |
PhosphoSitePlusi | Q5YLM1 |
SwissPalmi | Q5YLM1 |
Expressioni
Gene expression databases
Bgeei | ENSRNOG00000027264, Expressed in frontal cortex and 20 other tissues |
Interactioni
Subunit structurei
Interacts (via C-terminal) with CAMK2A; leading to the phosphorylation and inhibition of DAGLA enzymatic activity.
Interacts (via PPXXF motif) with HOMER1 and HOMER2; this interaction is required for DAGLA membrane localization.
By similarityProtein-protein interaction databases
STRINGi | 10116.ENSRNOP00000033416 |
Family & Domainsi
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 315 – 349 | Cys-richAdd BLAST | 35 |
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG2088, Eukaryota |
GeneTreei | ENSGT00940000161192 |
HOGENOMi | CLU_008300_1_0_1 |
InParanoidi | Q5YLM1 |
OMAi | GIVVCNW |
OrthoDBi | 191418at2759 |
PhylomeDBi | Q5YLM1 |
TreeFami | TF312928 |
Family and domain databases
Gene3Di | 3.40.50.1820, 1 hit |
InterProi | View protein in InterPro IPR029058, AB_hydrolase IPR002921, Fungal_lipase-like |
Pfami | View protein in Pfam PF01764, Lipase_3, 1 hit |
SUPFAMi | SSF53474, SSF53474, 1 hit |
PROSITEi | View protein in PROSITE PS00120, LIPASE_SER, 1 hit |
i Sequence
Sequence statusi: Complete.
Q5YLM1-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MPGIVVFRRR WSVGSDDLVL PAIFLFLLHT TWFVILSVVL FGLVYNPHEA
60 70 80 90 100
CSLNLVDHGR GYLGILLSCM IAEMAIIWLS MRGGILYTEP RDSMQYVLYV
110 120 130 140 150
RLAILVIEFI YAIVGIVWLT QYYTSCNDLT AKNVTLGMVV CNWVVILSVC
160 170 180 190 200
ITVLCVFDPT GRTFVKLRAT KRRQRNLRTY NLRHRLEEGQ ATSWSRRLKV
210 220 230 240 250
FLCCTRTKDS QSDAYSEIAY LFAEFFRDLD IVPSDIIAGL VLLRQRQRAK
260 270 280 290 300
RNAVLDEANN DILAFLSGMP VTRNTKYLDL KNSHEMLRYK EVCYYMLFAL
310 320 330 340 350
AAYGWPMYLM RKPTCGLCQL ARSCSCCLCP ARPRFAPGVT IEEDNCCGCN
360 370 380 390 400
AIAIRRHFLD ENMTAVDIVY TSCHDAVYET PFYVAVDHDK KKVVISIRGT
410 420 430 440 450
LSPKDALTDL TGDAERLPVE GHRGTWLGHK GMVLSAEYIK KKLEQEMVLS
460 470 480 490 500
QAFGRDLGRG TKHYGLIVVG HSLGAGTAAI LSFLLRPQYP TLKCFAYSPP
510 520 530 540 550
GGLLSEDAME YSKEFVTAVV LGKDLVPRIG LSQLEGFRRQ LLDVLQRSTK
560 570 580 590 600
PKWRIIVGAT KCIPKSELPE DQVEVTALAS TRLWTHPSDL TIALSASTPL
610 620 630 640 650
YPPGRIIHVV HNHPAEQCCC CEQEEPTYFA IWGDNKAFNE VIISPAMLHE
660 670 680 690 700
HLPYVVMEGL NKVLENYNKG KTALLSAAKV MVSPTEVDLT PELIFQQQPL
710 720 730 740 750
PTGPPLPTGL ALELPATEHR NSSVRSKSQS EMSLEGFSEG RLLSPVAAAS
760 770 780 790 800
AARQDPVELL LLSTQERLAA ELQSRRAPLA TMESLSDTES LYSFDSRRSS
810 820 830 840 850
GFRSIRGSPS LHAVLERDEG HLFYIDPAIP EENPSLSSRT ELLAADSLSK
860 870 880 890 900
HSQDTQPLEA ALGSGGVTPE RPPSAANDEE EAAGGSEGGG VAPRGELALH
910 920 930 940 950
NGRLGDSPSP QVLEFAEFID SLFNLDSKSS SFQDLYCMMV PESPTSDYTE
960 970 980 990 1000
GPKSPSQQEI LLRAQFEPNL VPKPPRLFAG SAEPSSGISL SPSFPLSSSG
1010 1020 1030 1040
ELMDLTPTGL SSQECLATDK IRTSTPTGHG ASPTKQDDLV ISAR
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY275375 mRNA Translation: AAQ17117.1 |
RefSeqi | NP_001005886.1, NM_001005886.1 XP_017444750.1, XM_017589261.1 |
Genome annotation databases
Ensembli | ENSRNOT00000037624; ENSRNOP00000033416; ENSRNOG00000027264 |
GeneIDi | 309207 |
KEGGi | rno:309207 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY275375 mRNA Translation: AAQ17117.1 |
RefSeqi | NP_001005886.1, NM_001005886.1 XP_017444750.1, XM_017589261.1 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
STRINGi | 10116.ENSRNOP00000033416 |
Protein family/group databases
ESTHERi | ratno-q5ylm1, Lipase_3 |
PTM databases
GlyGeni | Q5YLM1, 1 site |
iPTMneti | Q5YLM1 |
PhosphoSitePlusi | Q5YLM1 |
SwissPalmi | Q5YLM1 |
Proteomic databases
PaxDbi | Q5YLM1 |
PRIDEi | Q5YLM1 |
Genome annotation databases
Ensembli | ENSRNOT00000037624; ENSRNOP00000033416; ENSRNOG00000027264 |
GeneIDi | 309207 |
KEGGi | rno:309207 |
Organism-specific databases
CTDi | 747 |
RGDi | 1359461, Dagla |
Phylogenomic databases
eggNOGi | KOG2088, Eukaryota |
GeneTreei | ENSGT00940000161192 |
HOGENOMi | CLU_008300_1_0_1 |
InParanoidi | Q5YLM1 |
OMAi | GIVVCNW |
OrthoDBi | 191418at2759 |
PhylomeDBi | Q5YLM1 |
TreeFami | TF312928 |
Enzyme and pathway databases
Reactomei | R-RNO-426048, Arachidonate production from DAG |
Miscellaneous databases
PROi | PR:Q5YLM1 |
Gene expression databases
Bgeei | ENSRNOG00000027264, Expressed in frontal cortex and 20 other tissues |
Family and domain databases
Gene3Di | 3.40.50.1820, 1 hit |
InterProi | View protein in InterPro IPR029058, AB_hydrolase IPR002921, Fungal_lipase-like |
Pfami | View protein in Pfam PF01764, Lipase_3, 1 hit |
SUPFAMi | SSF53474, SSF53474, 1 hit |
PROSITEi | View protein in PROSITE PS00120, LIPASE_SER, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | DGLA_RAT | |
Accessioni | Q5YLM1Primary (citable) accession number: Q5YLM1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 5, 2006 |
Last sequence update: | November 23, 2004 | |
Last modified: | December 2, 2020 | |
This is version 100 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families