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Q9Y4D2

- DGLA_HUMAN

UniProt

Q9Y4D2 - DGLA_HUMAN

Protein

Sn1-specific diacylglycerol lipase alpha

Gene

DAGLA

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 104 (01 Oct 2014)
      Sequence version 3 (05 Sep 2006)
      Previous versions | rss
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    Functioni

    Catalyzes the hydrolysis of diacylglycerol (DAG) to 2-arachidonoyl-glycerol (2-AG), the most abundant endocannabinoid in tissues. Required for axonal growth during development and for retrograde synaptic signaling at mature synapses.1 Publication

    Cofactori

    Calcium.1 Publication

    Enzyme regulationi

    Inhibited by p-hydroxy-mercuri-benzoate and HgCl2, but not to PMSF. Also inhibited by RHC80267, a drug that blocks 2-AG formation.1 Publication

    Kineticsi

    1. KM=154.7 µM for diacylglycerol1 Publication

    Vmax=33.3 nmol/min/mg enzyme1 Publication

    pH dependencei

    Optimum pH is 7.0.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei472 – 4721Charge relay systemPROSITE-ProRule annotation
    Active sitei524 – 5241Charge relay systemPROSITE-ProRule annotation

    GO - Molecular functioni

    1. metal ion binding Source: UniProtKB-KW
    2. triglyceride lipase activity Source: InterPro

    GO - Biological processi

    1. arachidonic acid metabolic process Source: UniProtKB
    2. blood coagulation Source: Reactome
    3. cell death Source: UniProtKB-KW
    4. diacylglycerol catabolic process Source: UniProtKB
    5. endocannabinoid signaling pathway Source: Ensembl
    6. neuroblast proliferation Source: Ensembl
    7. neurotransmitter biosynthetic process Source: UniProtKB
    8. platelet activation Source: Reactome

    Keywords - Molecular functioni

    Hydrolase

    Keywords - Biological processi

    Lipid degradation, Lipid metabolism

    Keywords - Ligandi

    Calcium, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_19308. Arachidonate production from DAG.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Sn1-specific diacylglycerol lipase alpha (EC:3.1.1.-)
    Short name:
    DGL-alpha
    Alternative name(s):
    Neural stem cell-derived dendrite regulator
    Gene namesi
    Name:DAGLA
    Synonyms:C11orf11, KIAA0659, NSDDR
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 11

    Organism-specific databases

    HGNCiHGNC:1165. DAGLA.

    Subcellular locationi

    GO - Cellular componenti

    1. integral component of membrane Source: UniProtKB-KW
    2. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Spinocerebellar ataxia 20 (SCA20) [MIM:608687]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA20 is an autosomal dominant, adult-onset form characterized by dysarthria due to spasmodic dysphonia followed by slowly progressive ataxia.1 Publication
    Note: The disease may be caused by mutations affecting the gene represented in this entry. A copy number variation consisting of a 260-kb duplication at chromosome 11q12.2-12.3 is responsible for SCA20. The critical gene within the duplicated segment may be DAGLA.

    Keywords - Diseasei

    Neurodegeneration, Spinocerebellar ataxia

    Organism-specific databases

    MIMi608687. phenotype.
    PharmGKBiPA162383158.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 10421042Sn1-specific diacylglycerol lipase alphaPRO_0000248347Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi133 – 1331N-linked (GlcNAc...)Sequence Analysis
    Modified residuei732 – 7321PhosphoserineBy similarity
    Modified residuei743 – 7431PhosphoserineBy similarity

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiQ9Y4D2.
    PRIDEiQ9Y4D2.

    PTM databases

    PhosphoSiteiQ9Y4D2.

    Expressioni

    Tissue specificityi

    Highly expressed in brain and pancreas.2 Publications

    Gene expression databases

    ArrayExpressiQ9Y4D2.
    BgeeiQ9Y4D2.
    CleanExiHS_DAGLA.
    GenevestigatoriQ9Y4D2.

    Organism-specific databases

    HPAiHPA062497.

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000257215.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9Y4D2.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 2222CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini44 – 6017ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini82 – 10120CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini123 – 13614ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini158 – 1042885CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei23 – 4321HelicalSequence AnalysisAdd
    BLAST
    Transmembranei61 – 8121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei102 – 12221HelicalSequence AnalysisAdd
    BLAST
    Transmembranei137 – 15721HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the AB hydrolase superfamily. Lipase family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG324741.
    HOGENOMiHOG000015738.
    HOVERGENiHBG081435.
    InParanoidiQ9Y4D2.
    KOiK13806.
    OMAiDHRNSSV.
    OrthoDBiEOG75TMB2.
    PhylomeDBiQ9Y4D2.
    TreeFamiTF312928.

    Family and domain databases

    Gene3Di3.40.50.1820. 3 hits.
    InterProiIPR029058. AB_hydrolase.
    IPR002921. Lipase_3.
    [Graphical view]
    PfamiPF01764. Lipase_3. 1 hit.
    [Graphical view]
    SUPFAMiSSF53474. SSF53474. 1 hit.
    PROSITEiPS00120. LIPASE_SER. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9Y4D2-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPGIVVFRRR WSVGSDDLVL PAIFLFLLHT TWFVILSVVL FGLVYNPHEA     50
    CSLNLVDHGR GYLGILLSCM IAEMAIIWLS MRGGILYTEP RDSMQYVLYV 100
    RLAILVIEFI YAIVGIVWLT QYYTSCNDLT AKNVTLGMVV CNWVVILSVC 150
    ITVLCVFDPT GRTFVKLRAT KRRQRNLRTY NLRHRLEEGQ ATSWSRRLKV 200
    FLCCTRTKDS QSDAYSEIAY LFAEFFRDLD IVPSDIIAGL VLLRQRQRAK 250
    RNAVLDEANN DILAFLSGMP VTRNTKYLDL KNSQEMLRYK EVCYYMLFAL 300
    AAYGWPMYLM RKPACGLCQL ARSCSCCLCP ARPRFAPGVT IEEDNCCGCN 350
    AIAIRRHFLD ENMTAVDIVY TSCHDAVYET PFYVAVDHDK KKVVISIRGT 400
    LSPKDALTDL TGDAERLPVE GHHGTWLGHK GMVLSAEYIK KKLEQEMVLS 450
    QAFGRDLGRG TKHYGLIVVG HSLGAGTAAI LSFLLRPQYP TLKCFAYSPP 500
    GGLLSEDAME YSKEFVTAVV LGKDLVPRIG LSQLEGFRRQ LLDVLQRSTK 550
    PKWRIIVGAT KCIPKSELPE EVEVTTLAST RLWTHPSDLT IALSASTPLY 600
    PPGRIIHVVH NHPAEQCCCC EQEEPTYFAI WGDNKAFNEV IISPAMLHEH 650
    LPYVVMEGLN KVLENYNKGK TALLSAAKVM VSPTEVDLTP ELIFQQQPLP 700
    TGPPMPTGLA LELPTADHRN SSVRSKSQSE MSLEGFSEGR LLSPVVAAAA 750
    RQDPVELLLL STQERLAAEL QARRAPLATM ESLSDTESLY SFDSRRSSGF 800
    RSIRGSPSLH AVLERDEGHL FYIDPAIPEE NPSLSSRTEL LAADSLSKHS 850
    QDTQPLEAAL GSGGVTPERP PSAAANDEEE EVGGGGGGPA SRGELALHNG 900
    RLGDSPSPQV LEFAEFIDSL FNLDSKSSSF QDLYCMVVPE SPTSDYAEGP 950
    KSPSQQEILL RAQFEPNLVP KPPRLFAGSA DPSSGISLSP SFPLSSSGEL 1000
    MDLTPTGLSS QECLAADKIR TSTPTGHGAS PAKQDELVIS AR 1042
    Length:1,042
    Mass (Da):114,952
    Last modified:September 5, 2006 - v3
    Checksum:iA6E675984E89CB2F
    GO

    Sequence cautioni

    The sequence BAA31634.2 differs from that shown. Reason: Erroneous initiation.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti735 – 7351G → V.
    Corresponds to variant rs35056845 [ dbSNP | Ensembl ].
    VAR_049822
    Natural varianti889 – 8891P → L.
    Corresponds to variant rs3741252 [ dbSNP | Ensembl ].
    VAR_027274
    Natural varianti945 – 9451D → E.
    Corresponds to variant rs34956386 [ dbSNP | Ensembl ].
    VAR_049823

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY275377 mRNA. Translation: AAQ17119.1.
    AB014559 mRNA. Translation: BAA31634.2. Different initiation.
    CH471076 Genomic DNA. Translation: EAW73960.1.
    BC150176 mRNA. Translation: AAI50177.1.
    BC150195 mRNA. Translation: AAI50196.1.
    BC152453 mRNA. Translation: AAI52454.1.
    CCDSiCCDS31578.1.
    PIRiT00370.
    RefSeqiNP_006124.1. NM_006133.2.
    XP_005274287.1. XM_005274230.2.
    UniGeneiHs.241564.

    Genome annotation databases

    EnsembliENST00000257215; ENSP00000257215; ENSG00000134780.
    GeneIDi747.
    KEGGihsa:747.
    UCSCiuc001nsa.3. human.

    Polymorphism databases

    DMDMi114149271.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AY275377 mRNA. Translation: AAQ17119.1 .
    AB014559 mRNA. Translation: BAA31634.2 . Different initiation.
    CH471076 Genomic DNA. Translation: EAW73960.1 .
    BC150176 mRNA. Translation: AAI50177.1 .
    BC150195 mRNA. Translation: AAI50196.1 .
    BC152453 mRNA. Translation: AAI52454.1 .
    CCDSi CCDS31578.1.
    PIRi T00370.
    RefSeqi NP_006124.1. NM_006133.2.
    XP_005274287.1. XM_005274230.2.
    UniGenei Hs.241564.

    3D structure databases

    ProteinModelPortali Q9Y4D2.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9606.ENSP00000257215.

    Chemistry

    BindingDBi Q9Y4D2.
    ChEMBLi CHEMBL5545.
    GuidetoPHARMACOLOGYi 1396.

    PTM databases

    PhosphoSitei Q9Y4D2.

    Polymorphism databases

    DMDMi 114149271.

    Proteomic databases

    PaxDbi Q9Y4D2.
    PRIDEi Q9Y4D2.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000257215 ; ENSP00000257215 ; ENSG00000134780 .
    GeneIDi 747.
    KEGGi hsa:747.
    UCSCi uc001nsa.3. human.

    Organism-specific databases

    CTDi 747.
    GeneCardsi GC11P061447.
    H-InvDB HIX0009695.
    HGNCi HGNC:1165. DAGLA.
    HPAi HPA062497.
    MIMi 608687. phenotype.
    614015. gene.
    neXtProti NX_Q9Y4D2.
    PharmGKBi PA162383158.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG324741.
    HOGENOMi HOG000015738.
    HOVERGENi HBG081435.
    InParanoidi Q9Y4D2.
    KOi K13806.
    OMAi DHRNSSV.
    OrthoDBi EOG75TMB2.
    PhylomeDBi Q9Y4D2.
    TreeFami TF312928.

    Enzyme and pathway databases

    Reactomei REACT_19308. Arachidonate production from DAG.

    Miscellaneous databases

    GenomeRNAii 747.
    NextBioi 3024.
    PROi Q9Y4D2.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9Y4D2.
    Bgeei Q9Y4D2.
    CleanExi HS_DAGLA.
    Genevestigatori Q9Y4D2.

    Family and domain databases

    Gene3Di 3.40.50.1820. 3 hits.
    InterProi IPR029058. AB_hydrolase.
    IPR002921. Lipase_3.
    [Graphical view ]
    Pfami PF01764. Lipase_3. 1 hit.
    [Graphical view ]
    SUPFAMi SSF53474. SSF53474. 1 hit.
    PROSITEi PS00120. LIPASE_SER. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "NSDDR a novel tetra-spanning transmembrane protein with a unique integration pattern to the plasma membrane regulates the extension of the dendritic trees of Purkinje cells."
      Horiguchi S., Tashiro K., Takahashi J., Hashimoto N., Nakano I., Tsuchida Y., Hirai H., Honjo T.
      Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
      Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
      DNA Res. 5:169-176(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain.
    3. "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
      Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
      DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: SEQUENCE REVISION.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    6. "Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain."
      Bisogno T., Howell F., Williams G., Minassi A., Cascio M.G., Ligresti A., Matias I., Schiano-Moriello A., Paul P., Williams E.-J., Gangadharan U., Hobbs C., Di Marzo V., Doherty P.
      J. Cell Biol. 163:463-468(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, TISSUE SPECIFICITY.
    7. "Stimulation of endocannabinoid formation in brain slice cultures through activation of group I metabotropic glutamate receptors."
      Jung K.-M., Mangieri R., Stapleton C., Kim J., Fegley D., Wallace M., Mackie K., Piomelli D.
      Mol. Pharmacol. 68:1196-1202(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    8. Cited for: POSSIBLE INVOLVEMENT IN SCA20.

    Entry informationi

    Entry nameiDGLA_HUMAN
    AccessioniPrimary (citable) accession number: Q9Y4D2
    Secondary accession number(s): A7E233, Q6WQJ0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 5, 2006
    Last sequence update: September 5, 2006
    Last modified: October 1, 2014
    This is version 104 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 11
      Human chromosome 11: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3