Q9Y4D2 (DGLA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1042 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Defects in DAGLA may be a cause of spinocerebellar ataxia type 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=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.

Ontologies

Keywords
Biological process	Lipid degradation
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Neurodegeneration Spinocerebellar ataxia
Domain	Transmembrane Transmembrane helix
Ligand	Calcium Metal-binding
Molecular function	Hydrolase
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cell death Inferred from electronic annotation. Source: UniProtKB-KW lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW platelet activation Traceable author statement. Source: Reactome
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW triglyceride lipase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1042	1042	Sn1-specific diacylglycerol lipase alpha		PRO_0000248347
Regions
	Topological domain	1 – 22	22	Cytoplasmic Potential
	Transmembrane	23 – 43	21	Helical; Potential
	Topological domain	44 – 60	17	Extracellular Potential
	Transmembrane	61 – 81	21	Helical; Potential
	Topological domain	82 – 101	20	Cytoplasmic Potential
	Transmembrane	102 – 122	21	Helical; Potential
	Topological domain	123 – 136	14	Extracellular Potential
	Transmembrane	137 – 157	21	Helical; Potential
	Topological domain	158 – 1042	885	Cytoplasmic Potential
Sites
	Active site	472	1	Charge relay system By similarity
	Active site	524	1	Charge relay system By similarity
Amino acid modifications
	Modified residue	727	1	Phosphoserine By similarity
	Modified residue	732	1	Phosphoserine By similarity
	Glycosylation	133	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	735	1	G → V. Corresponds to variant rs35056845 [ dbSNP | Ensembl ].		VAR_049822
	Natural variant	889	1	P → L. Corresponds to variant rs3741252 [ dbSNP | Ensembl ].		VAR_027274
	Natural variant	945	1	D → E. Corresponds to variant rs34956386 [ dbSNP | Ensembl ].		VAR_049823

Sequences

	Sequence		Length	Mass (Da)
	Q9Y4D2 [UniParc]. Last modified September 5, 2006. Version 3. Checksum: A6E675984E89CB2F	FASTA	1,042	114,952
	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

References

	« Hide 'large scale' referencesShow '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: 9734811] [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: 12168954] [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. , 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: 15489334] [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: 14610053] [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: 16051747] [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: 18801880] [Abstract] Cited for: POSSIBLE INVOLVEMENT IN SCA20.

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.
IPI	IPI00000706.
PIR	T00370.
RefSeq	NP_006124.1. NM_006133.2.
UniGene	Hs.241564.
3D structure databases
ProteinModelPortal	Q9Y4D2.
SMR	Q9Y4D2. Positions 369-531.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9Y4D2.
PTM databases
PhosphoSite	Q9Y4D2.
Polymorphism databases
DMDM	114149271.
Proteomic databases
PRIDE	Q9Y4D2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000257215; ENSP00000257215; ENSG00000134780.
GeneID	747.
KEGG	hsa:747.
UCSC	uc001nsa.1. human.
Organism-specific databases
CTD	747.
GeneCards	GC11P061447.
H-InvDB	HIX0009695.
HGNC	HGNC:1165. DAGLA.
MIM	608687. phenotype. 614015. gene.
neXtProt	NX_Q9Y4D2.
PharmGKB	PA162383158.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG15854.
GeneTree	ENSGT00530000063682.
HOGENOM	HBG446718.
HOVERGEN	HBG081435.
InParanoid	Q9Y4D2.
OMA	EGQASSW.
OrthoDB	EOG4RR6GK.
PhylomeDB	Q9Y4D2.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction. REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	Q9Y4D2.
Bgee	Q9Y4D2.
CleanEx	HS_DAGLA.
Genevestigator	Q9Y4D2.
GermOnline	ENSG00000134780. Homo sapiens.
Family and domain databases
InterPro	IPR002921. Lipase_3. [Graphical view]
KO	K13806.
Pfam	PF01764. Lipase_3. 1 hit. [Graphical view]
PROSITE	PS00120. LIPASE_SER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	3024.
SOURCE	Search...

Entry information

Entry name

DGLA_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 81 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.