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Q9Y4D2

- DGLA_HUMAN

UniProt

Q9Y4D2 - DGLA_HUMAN

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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

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

Ca2+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. hydrolase activity Source: UniProtKB-KW
  2. metal ion binding Source: UniProtKB-KW

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
Complete GO annotation...

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2222CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei23 – 4321HelicalSequence AnalysisAdd
BLAST
Topological domaini44 – 6017ExtracellularSequence AnalysisAdd
BLAST
Transmembranei61 – 8121HelicalSequence AnalysisAdd
BLAST
Topological domaini82 – 10120CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei102 – 12221HelicalSequence AnalysisAdd
BLAST
Topological domaini123 – 13614ExtracellularSequence AnalysisAdd
BLAST
Transmembranei137 – 15721HelicalSequence AnalysisAdd
BLAST
Topological domaini158 – 1042885CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

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

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

MaxQBiQ9Y4D2.
PaxDbiQ9Y4D2.
PRIDEiQ9Y4D2.

PTM databases

PhosphoSiteiQ9Y4D2.

Expressioni

Tissue specificityi

Highly expressed in brain and pancreas.2 Publications

Gene expression databases

BgeeiQ9Y4D2.
CleanExiHS_DAGLA.
ExpressionAtlasiQ9Y4D2. baseline and differential.
GenevestigatoriQ9Y4D2.

Organism-specific databases

HPAiHPA062497.

Interactioni

Protein-protein interaction databases

BioGridi107205. 1 interaction.
STRINGi9606.ENSP00000257215.

Structurei

3D structure databases

ProteinModelPortaliQ9Y4D2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the AB hydrolase superfamily. Lipase family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG324741.
GeneTreeiENSGT00530000063682.
HOGENOMiHOG000015738.
HOVERGENiHBG081435.
InParanoidiQ9Y4D2.
KOiK13806.
OMAiDHRNSSV.
OrthoDBiEOG75TMB2.
PhylomeDBiQ9Y4D2.
TreeFamiTF312928.

Family and domain databases

Gene3Di3.40.50.1820. 3 hits.
InterProiIPR029058. AB_hydrolase.
IPR002921. Fungal_lipase-like.
[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

        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 KNSQEMLRYK EVCYYMLFAL
310 320 330 340 350
AAYGWPMYLM RKPACGLCQL ARSCSCCLCP ARPRFAPGVT IEEDNCCGCN
360 370 380 390 400
AIAIRRHFLD ENMTAVDIVY TSCHDAVYET PFYVAVDHDK KKVVISIRGT
410 420 430 440 450
LSPKDALTDL TGDAERLPVE GHHGTWLGHK 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 EVEVTTLAST RLWTHPSDLT IALSASTPLY
610 620 630 640 650
PPGRIIHVVH NHPAEQCCCC EQEEPTYFAI WGDNKAFNEV IISPAMLHEH
660 670 680 690 700
LPYVVMEGLN KVLENYNKGK TALLSAAKVM VSPTEVDLTP ELIFQQQPLP
710 720 730 740 750
TGPPMPTGLA LELPTADHRN SSVRSKSQSE MSLEGFSEGR LLSPVVAAAA
760 770 780 790 800
RQDPVELLLL STQERLAAEL QARRAPLATM ESLSDTESLY SFDSRRSSGF
810 820 830 840 850
RSIRGSPSLH AVLERDEGHL FYIDPAIPEE NPSLSSRTEL LAADSLSKHS
860 870 880 890 900
QDTQPLEAAL GSGGVTPERP PSAAANDEEE EVGGGGGGPA SRGELALHNG
910 920 930 940 950
RLGDSPSPQV LEFAEFIDSL FNLDSKSSSF QDLYCMVVPE SPTSDYAEGP
960 970 980 990 1000
KSPSQQEILL RAQFEPNLVP KPPRLFAGSA DPSSGISLSP SFPLSSSGEL
1010 1020 1030 1040
MDLTPTGLSS QECLAADKIR TSTPTGHGAS PAKQDELVIS AR
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. Curated

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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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

BioGridi 107205. 1 interaction.
STRINGi 9606.ENSP00000257215.

Chemistry

BindingDBi Q9Y4D2.
ChEMBLi CHEMBL5545.
GuidetoPHARMACOLOGYi 1396.

PTM databases

PhosphoSitei Q9Y4D2.

Polymorphism databases

DMDMi 114149271.

Proteomic databases

MaxQBi Q9Y4D2.
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.
GeneTreei ENSGT00530000063682.
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

ChiTaRSi DAGLA. human.
GenomeRNAii 747.
NextBioi 3024.
PROi Q9Y4D2.
SOURCEi Search...

Gene expression databases

Bgeei Q9Y4D2.
CleanExi HS_DAGLA.
ExpressionAtlasi Q9Y4D2. baseline and differential.
Genevestigatori Q9Y4D2.

Family and domain databases

Gene3Di 3.40.50.1820. 3 hits.
InterProi IPR029058. AB_hydrolase.
IPR002921. Fungal_lipase-like.
[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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 106 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