Protein: Diacylglycerol lipase-alpha (DAGL-alpha) (DGL-alpha) (EC 3.1.1.116) (Neural stem cell-derived dendrite regulator) (Sn1-specific diacylglycerol lipase alpha) (Q6WQJ1)
Organism: Mus musculus (Mouse)
Function: Serine hydrolase that hydrolyzes arachidonic acid-esterified diacylglycerols (DAGs) to produce the principal endocannabinoid (eCB), 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 central nervous system (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.
Subcellular location: Cell membrane {ECO:0000269|PubMed:17584991}; Multi-pass membrane protein {ECO:0000255}. Cell projection, dendritic spine membrane {ECO:0000269|PubMed:16723519}; Multi-pass membrane protein {ECO:0000255}. Postsynaptic density membrane {ECO:0000250|UniProtKB:Q9Y4D2}; Multi-pass membrane protein {ECO:0000255}. Early endosome membrane {ECO:0000250|UniProtKB:Q9Y4D2}; Multi-pass membrane protein {ECO:0000255}. 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. {ECO:0000250|UniProtKB:Q9Y4D2}.
Sequence: MPGIVVFRRRWSVGSDDLVLPAIFLFLLHTTWFVILSVVLFGLVYNPHEACSLNLVDHGRGYLGILLSCMIAEMAIIWLSMRGGILYTEPRDSMQYVLYVRLAILVIEFIYAIVGIVWLTQYYTSCNDLTAKNVTLGMVVCNWVVILSVCITVLCVFDPTGRTFVKLRATKRRQRNLRTYNLRHRLEEGQATSWSRRLKVFLCCTRTKDSQSDAYSEIAYLFAEFFRDLDIVPSDIIAGLVLLRQRQRAKRNAVLDEANNDILAFLSGMPVTRNTKYLDLKNSHEMLRYKEVCYYMLFALAAYGWPMYLMRKPTCGLCQLARSCSCCLCPARPRFAPGVTIEEDNCCGCNAIAIRRHFLDENMTAVDIVYTSCHDAVYETPFYVAVDHDKKKVVISIRGTLSPKDALTDLTGDAERLPVEGHRGTWLGHKGMVLSAEYIKKKLEQEMVLSQAFGRDLGRGTKHYGLIVVGHSLGAGTAAILSFLLRPQYPTLKCFAYSPPGGLLSEDAMEYSKEFVTAVVLGKDLVPRIGLSQLEGFRRQLLDVLQRSTKPKWRIIVGATKCIPKSELPEDQVEVTTLASTRLWTHPSDLTIALSASTPLYPPGRIIHVVHNHPAEQCCCCEQEEPTYFAIWGDNKAFNEVIISPAMLHEHLPYVVMEGLNKVLENYNKGKTALLSAAKVMVSPTEVDLTPELIFQQQPLPTGPPLPTGLALELPATEHRNSSVRSKSQSEMSLEGFSEGRLLSPVAAASAARQDPVELLLLSTQERLAAELQSRRAPLATMESLSDTESLYSFDSRRSSGFRSIRGSPSLHAVLERDEGHLFYIDPAIPEENPSLSSRTELLAADSLSKHSQDTQPLEAALGSGGVTPERPPSATIEEEEAAGGSEGGGVAPRGELALHNGRLGDSPSPQVLEFAEFIDSLFNLDSKSSSFQDLYCMMVPESPTSDYTEGPKSPSQQEILLRAQFEPNLVPKPPRLFAGSAEPSSGISLSPSFPLSSSGELMDLTPTGLSSQECLATDKIRTSTPTGHGASPTKQDDLVISAR
InterPro domains: - IPR029058: Alpha/Beta hydrolase fold (homologous_superfamily) [316-559]
- IPR002921: Fungal lipase-type domain (domain) [394-529]
- IPR052214: Diacylglycerol Lipase-Related (family) [1-682]
Interaction partners: - Diacylglycerol lipase-beta
- N-acyl-phosphatidylethanolamine-hydrolyzing phospholipase D
- Fatty-acid amide hydrolase 1
- Monoglyceride lipase
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016787 (hydrolase activity), GO:0016788 (hydrolase activity, acting on ester bonds), GO:0016298 (lipase activity), GO:0052689 (carboxylic ester hydrolase activity), GO:0004806 (triglyceride lipase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0023052 (signaling), GO:0032501 (multicellular organismal process), GO:0048869 (cellular developmental process), GO:0009628 (response to abiotic stimulus), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0009653 (anatomical structure morphogenesis), GO:0050794 (regulation of cellular process), GO:0051716 (cellular response to stimulus), GO:0071840 (cellular component organization or biogenesis), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0007610 (behavior), GO:0032989 (cellular component morphogenesis), GO:0000902 (cell morphogenesis), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0009314 (response to radiation), GO:0007186 (G protein-coupled receptor signaling pathway), GO:0048731 (system development), GO:0007632 (visual behavior), GO:0016043 (cellular component organization), GO:0007626 (locomotory behavior), GO:0022008 (neurogenesis), GO:0009416 (response to light stimulus), GO:0007634 (optokinetic behavior), GO:0000904 (cell morphogenesis involved in differentiation), GO:0030030 (cell projection organization), GO:0007399 (nervous system development), GO:0036269 (swimming behavior), GO:0032990 (cell part morphogenesis), GO:0048858 (cell projection morphogenesis), GO:0030182 (neuron differentiation), GO:0048666 (neuron development), GO:0048667 (cell morphogenesis involved in neuron differentiation), GO:0031175 (neuron projection development), GO:0048699 (generation of neurons), GO:0120039 (plasma membrane bounded cell projection morphogenesis), GO:0120036 (plasma membrane bounded cell projection organization), GO:0048812 (neuron projection morphogenesis), GO:0061564 (axon development), GO:0007409 (axonogenesis)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0042995 (cell projection), GO:0016020 (membrane), GO:0071944 (cell periphery), GO:0030054 (cell junction), GO:0031252 (cell leading edge), GO:0031256 (leading edge membrane), GO:0098794 (postsynapse), GO:0036477 (somatodendritic compartment), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0031090 (organelle membrane), GO:0120025 (plasma membrane bounded cell projection), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0005768 (endosome), GO:0045202 (synapse), GO:0032589 (neuron projection membrane), GO:0045211 (postsynaptic membrane), GO:0098590 (plasma membrane region), GO:0097447 (dendritic tree), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0099572 (postsynaptic specialization), GO:0097060 (synaptic membrane), GO:0099634 (postsynaptic specialization membrane), GO:0031253 (cell projection membrane), GO:0043231 (intracellular membrane-bounded organelle), GO:0098588 (bounding membrane of organelle), GO:0012506 (vesicle membrane), GO:0014069 (postsynaptic density), GO:0030425 (dendrite), GO:0043005 (neuron projection), GO:0005769 (early endosome), GO:0032590 (dendrite membrane), GO:0098984 (neuron to neuron synapse), GO:0010008 (endosome membrane), GO:0031982 (vesicle), GO:0030659 (cytoplasmic vesicle membrane), GO:0032279 (asymmetric synapse), GO:0098839 (postsynaptic density membrane), GO:0097708 (intracellular vesicle), GO:0031901 (early endosome membrane)