Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q9Y4D2 (DGLA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sn1-specific diacylglycerol lipase alpha

Short name=DGL-alpha
EC=3.1.1.-
Alternative name(s):
Neural stem cell-derived dendrite regulator
Gene names
Name:DAGLA
Synonyms:C11orf11, KIAA0659, NSDDR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1042 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6

Cofactor

Calcium. Ref.6

Enzyme regulation

Inhibited by p-hydroxy-mercuri-benzoate and HgCl2, but not to PMSF. Also inhibited by RHC80267, a drug that blocks 2-AG formation. Ref.6

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Highly expressed in brain and pancreas. Ref.6 Ref.7

Involvement in disease

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.
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. Ref.8

Sequence similarities

Belongs to the AB hydrolase superfamily. Lipase family.

Biophysicochemical properties

Kinetic parameters:

KM=154.7 µM for diacylglycerol Ref.6

Vmax=33.3 nmol/min/mg enzyme

pH dependence:

Optimum pH is 7.0.

Sequence caution

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10421042Sn1-specific diacylglycerol lipase alpha
PRO_0000248347

Regions

Topological domain1 – 2222Cytoplasmic Potential
Transmembrane23 – 4321Helical; Potential
Topological domain44 – 6017Extracellular Potential
Transmembrane61 – 8121Helical; Potential
Topological domain82 – 10120Cytoplasmic Potential
Transmembrane102 – 12221Helical; Potential
Topological domain123 – 13614Extracellular Potential
Transmembrane137 – 15721Helical; Potential
Topological domain158 – 1042885Cytoplasmic Potential

Sites

Active site4721Charge relay system By similarity
Active site5241Charge relay system By similarity

Amino acid modifications

Modified residue7321Phosphoserine By similarity
Modified residue7431Phosphoserine By similarity
Glycosylation1331N-linked (GlcNAc...) Potential

Natural variations

Natural variant7351G → V.
Corresponds to variant rs35056845 [ dbSNP | Ensembl ].
VAR_049822
Natural variant8891P → L.
Corresponds to variant rs3741252 [ dbSNP | Ensembl ].
VAR_027274
Natural variant9451D → E.
Corresponds to variant rs34956386 [ dbSNP | Ensembl ].
VAR_049823

Sequences

Sequence LengthMass (Da)Tools
Q9Y4D2 [UniParc].

Last modified September 5, 2006. Version 3.
Checksum: A6E675984E89CB2F

FASTA1,042114,952
        10         20         30         40         50         60 
MPGIVVFRRR WSVGSDDLVL PAIFLFLLHT TWFVILSVVL FGLVYNPHEA CSLNLVDHGR 

        70         80         90        100        110        120 
GYLGILLSCM IAEMAIIWLS MRGGILYTEP RDSMQYVLYV RLAILVIEFI YAIVGIVWLT 

       130        140        150        160        170        180 
QYYTSCNDLT AKNVTLGMVV CNWVVILSVC ITVLCVFDPT GRTFVKLRAT KRRQRNLRTY 

       190        200        210        220        230        240 
NLRHRLEEGQ ATSWSRRLKV FLCCTRTKDS QSDAYSEIAY LFAEFFRDLD IVPSDIIAGL 

       250        260        270        280        290        300 
VLLRQRQRAK RNAVLDEANN DILAFLSGMP VTRNTKYLDL KNSQEMLRYK EVCYYMLFAL 

       310        320        330        340        350        360 
AAYGWPMYLM RKPACGLCQL ARSCSCCLCP ARPRFAPGVT IEEDNCCGCN AIAIRRHFLD 

       370        380        390        400        410        420 
ENMTAVDIVY TSCHDAVYET PFYVAVDHDK KKVVISIRGT LSPKDALTDL TGDAERLPVE 

       430        440        450        460        470        480 
GHHGTWLGHK GMVLSAEYIK KKLEQEMVLS QAFGRDLGRG TKHYGLIVVG HSLGAGTAAI 

       490        500        510        520        530        540 
LSFLLRPQYP TLKCFAYSPP GGLLSEDAME YSKEFVTAVV LGKDLVPRIG LSQLEGFRRQ 

       550        560        570        580        590        600 
LLDVLQRSTK PKWRIIVGAT KCIPKSELPE EVEVTTLAST RLWTHPSDLT IALSASTPLY 

       610        620        630        640        650        660 
PPGRIIHVVH NHPAEQCCCC EQEEPTYFAI WGDNKAFNEV IISPAMLHEH LPYVVMEGLN 

       670        680        690        700        710        720 
KVLENYNKGK TALLSAAKVM VSPTEVDLTP ELIFQQQPLP TGPPMPTGLA LELPTADHRN 

       730        740        750        760        770        780 
SSVRSKSQSE MSLEGFSEGR LLSPVVAAAA RQDPVELLLL STQERLAAEL QARRAPLATM 

       790        800        810        820        830        840 
ESLSDTESLY SFDSRRSSGF RSIRGSPSLH AVLERDEGHL FYIDPAIPEE NPSLSSRTEL 

       850        860        870        880        890        900 
LAADSLSKHS QDTQPLEAAL GSGGVTPERP PSAAANDEEE EVGGGGGGPA SRGELALHNG 

       910        920        930        940        950        960 
RLGDSPSPQV LEFAEFIDSL FNLDSKSSSF QDLYCMVVPE SPTSDYAEGP KSPSQQEILL 

       970        980        990       1000       1010       1020 
RAQFEPNLVP KPPRLFAGSA DPSSGISLSP SFPLSSSGEL MDLTPTGLSS QECLAADKIR 

      1030       1040 
TSTPTGHGAS PAKQDELVIS AR 

« Hide

References

« Hide 'large scale' references
[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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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]"A duplication at chromosome 11q12.2-11q12.3 is associated with spinocerebellar ataxia type 20."
Knight M.A., Hernandez D., Diede S.J., Dauwerse H.G., Rafferty I., van de Leemput J., Forrest S.M., Gardner R.J., Storey E., van Ommen G.J., Tapscott S.J., Fischbeck K.H., Singleton A.B.
Hum. Mol. Genet. 17:3847-3853(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: POSSIBLE INVOLVEMENT IN SCA20.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRT00370.
RefSeqNP_006124.1. NM_006133.2.
XP_005274287.1. XM_005274230.1.
UniGeneHs.241564.

3D structure databases

ProteinModelPortalQ9Y4D2.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000257215.

Chemistry

BindingDBQ9Y4D2.
ChEMBLCHEMBL5545.
GuidetoPHARMACOLOGY1396.

PTM databases

PhosphoSiteQ9Y4D2.

Polymorphism databases

DMDM114149271.

Proteomic databases

PaxDbQ9Y4D2.
PRIDEQ9Y4D2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000257215; ENSP00000257215; ENSG00000134780.
GeneID747.
KEGGhsa:747.
UCSCuc001nsa.3. human.

Organism-specific databases

CTD747.
GeneCardsGC11P061447.
H-InvDBHIX0009695.
HGNCHGNC:1165. DAGLA.
HPAHPA062497.
MIM608687. phenotype.
614015. gene.
neXtProtNX_Q9Y4D2.
PharmGKBPA162383158.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG324741.
HOGENOMHOG000015738.
HOVERGENHBG081435.
InParanoidQ9Y4D2.
KOK13806.
OMADHRNSSV.
OrthoDBEOG75TMB2.
TreeFamTF312928.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpressQ9Y4D2.
BgeeQ9Y4D2.
CleanExHS_DAGLA.
GenevestigatorQ9Y4D2.

Family and domain databases

InterProIPR002921. Lipase_3.
[Graphical view]
PfamPF01764. Lipase_3. 1 hit.
[Graphical view]
PROSITEPS00120. LIPASE_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi747.
NextBio3024.
PROQ9Y4D2.
SOURCESearch...

Entry information

Entry nameDGLA_HUMAN
AccessionPrimary (citable) accession number: Q9Y4D2
Secondary accession number(s): A7E233, Q6WQJ0
Entry history
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: September 5, 2006
Last modified: February 19, 2014
This is version 99 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM