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Protein

Sn1-specific diacylglycerol lipase alpha

Gene

DAGLA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Activity 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
  1. Vmax=33.3 nmol/min/mg enzyme1 Publication

pH dependencei

Optimum pH is 7.0.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei472Charge relay systemPROSITE-ProRule annotation1
Active sitei524Charge relay systemPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase
Biological processLipid degradation, Lipid metabolism
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-426048 Arachidonate production from DAG

Protein family/group databases

ESTHERihuman-DAGLA Lipase_3

Chemistry databases

SwissLipidsiSLP:000000323

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
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000134780.9
HGNCiHGNC:1165 DAGLA
MIMi614015 gene
neXtProtiNX_Q9Y4D2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 22CytoplasmicSequence analysisAdd BLAST22
Transmembranei23 – 43HelicalSequence analysisAdd BLAST21
Topological domaini44 – 60ExtracellularSequence analysisAdd BLAST17
Transmembranei61 – 81HelicalSequence analysisAdd BLAST21
Topological domaini82 – 101CytoplasmicSequence analysisAdd BLAST20
Transmembranei102 – 122HelicalSequence analysisAdd BLAST21
Topological domaini123 – 136ExtracellularSequence analysisAdd BLAST14
Transmembranei137 – 157HelicalSequence analysisAdd BLAST21
Topological domaini158 – 1042CytoplasmicSequence analysisAdd BLAST885

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Spinocerebellar ataxia 20 (SCA20)1 Publication
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.
Disease descriptionSpinocerebellar 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.
See also OMIM:608687

Keywords - Diseasei

Neurodegeneration, Spinocerebellar ataxia

Organism-specific databases

DisGeNETi747
MIMi608687 phenotype
OpenTargetsiENSG00000134780
PharmGKBiPA162383158

Chemistry databases

ChEMBLiCHEMBL5545
GuidetoPHARMACOLOGYi1396

Polymorphism and mutation databases

BioMutaiDAGLA
DMDMi114149271

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002483471 – 1042Sn1-specific diacylglycerol lipase alphaAdd BLAST1042

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi133N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei727PhosphoserineBy similarity1
Modified residuei729PhosphoserineBy similarity1
Modified residuei732PhosphoserineBy similarity1
Modified residuei743PhosphoserineBy similarity1
Modified residuei782PhosphoserineBy similarity1
Modified residuei784PhosphoserineBy similarity1
Modified residuei806PhosphoserineBy similarity1
Modified residuei833PhosphoserineBy similarity1
Modified residuei847PhosphoserineBy similarity1
Modified residuei952PhosphoserineBy similarity1
Modified residuei1023PhosphothreonineBy similarity1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ9Y4D2
PaxDbiQ9Y4D2
PeptideAtlasiQ9Y4D2
PRIDEiQ9Y4D2
ProteomicsDBi86167

PTM databases

iPTMnetiQ9Y4D2
PhosphoSitePlusiQ9Y4D2

Expressioni

Tissue specificityi

Highly expressed in brain and pancreas.2 Publications

Gene expression databases

BgeeiENSG00000134780 Expressed in 107 organ(s), highest expression level in right frontal lobe
CleanExiHS_DAGLA
ExpressionAtlasiQ9Y4D2 baseline and differential
GenevisibleiQ9Y4D2 HS

Organism-specific databases

HPAiHPA062497

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
UPK1BO758414EBI-12808806,EBI-12237619

Protein-protein interaction databases

BioGridi107205, 5 interactors
IntActiQ9Y4D2, 9 interactors
STRINGi9606.ENSP00000257215

Chemistry databases

BindingDBiQ9Y4D2

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

eggNOGiKOG2088 Eukaryota
ENOG410XRFI LUCA
GeneTreeiENSGT00530000063682
HOGENOMiHOG000015738
HOVERGENiHBG081435
InParanoidiQ9Y4D2
KOiK13806
OMAiEPRESMQ
OrthoDBiEOG091G04AM
PhylomeDBiQ9Y4D2
TreeFamiTF312928

Family and domain databases

Gene3Di3.40.50.1820, 1 hit
InterProiView protein in InterPro
IPR029058 AB_hydrolase
IPR002921 Fungal_lipase-like
PfamiView protein in Pfam
PF01764 Lipase_3, 1 hit
SUPFAMiSSF53474 SSF53474, 1 hit
PROSITEiView protein in PROSITE
PS00120 LIPASE_SER, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5GY58F5GY58_HUMAN
Sn1-specific diacylglycerol lipase ...
DAGLA
167Annotation score:

Sequence cautioni

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049822735G → V. Corresponds to variant dbSNP:rs35056845Ensembl.1
Natural variantiVAR_027274889P → L. Corresponds to variant dbSNP:rs3741252Ensembl.1
Natural variantiVAR_049823945D → E. Corresponds to variant dbSNP:rs34956386Ensembl.1

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
UniGeneiHs.241564

Genome annotation databases

EnsembliENST00000257215; ENSP00000257215; ENSG00000134780
GeneIDi747
KEGGihsa:747
UCSCiuc001nsa.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

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
CCDSiCCDS31578.1
PIRiT00370
RefSeqiNP_006124.1, NM_006133.2
UniGeneiHs.241564

3D structure databases

ProteinModelPortaliQ9Y4D2
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107205, 5 interactors
IntActiQ9Y4D2, 9 interactors
STRINGi9606.ENSP00000257215

Chemistry databases

BindingDBiQ9Y4D2
ChEMBLiCHEMBL5545
GuidetoPHARMACOLOGYi1396
SwissLipidsiSLP:000000323

Protein family/group databases

ESTHERihuman-DAGLA Lipase_3

PTM databases

iPTMnetiQ9Y4D2
PhosphoSitePlusiQ9Y4D2

Polymorphism and mutation databases

BioMutaiDAGLA
DMDMi114149271

Proteomic databases

MaxQBiQ9Y4D2
PaxDbiQ9Y4D2
PeptideAtlasiQ9Y4D2
PRIDEiQ9Y4D2
ProteomicsDBi86167

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000257215; ENSP00000257215; ENSG00000134780
GeneIDi747
KEGGihsa:747
UCSCiuc001nsa.4 human

Organism-specific databases

CTDi747
DisGeNETi747
EuPathDBiHostDB:ENSG00000134780.9
GeneCardsiDAGLA
H-InvDBiHIX0009695
HGNCiHGNC:1165 DAGLA
HPAiHPA062497
MIMi608687 phenotype
614015 gene
neXtProtiNX_Q9Y4D2
OpenTargetsiENSG00000134780
PharmGKBiPA162383158
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2088 Eukaryota
ENOG410XRFI LUCA
GeneTreeiENSGT00530000063682
HOGENOMiHOG000015738
HOVERGENiHBG081435
InParanoidiQ9Y4D2
KOiK13806
OMAiEPRESMQ
OrthoDBiEOG091G04AM
PhylomeDBiQ9Y4D2
TreeFamiTF312928

Enzyme and pathway databases

ReactomeiR-HSA-426048 Arachidonate production from DAG

Miscellaneous databases

ChiTaRSiDAGLA human
GenomeRNAii747
PROiPR:Q9Y4D2
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000134780 Expressed in 107 organ(s), highest expression level in right frontal lobe
CleanExiHS_DAGLA
ExpressionAtlasiQ9Y4D2 baseline and differential
GenevisibleiQ9Y4D2 HS

Family and domain databases

Gene3Di3.40.50.1820, 1 hit
InterProiView protein in InterPro
IPR029058 AB_hydrolase
IPR002921 Fungal_lipase-like
PfamiView protein in Pfam
PF01764 Lipase_3, 1 hit
SUPFAMiSSF53474 SSF53474, 1 hit
PROSITEiView protein in PROSITE
PS00120 LIPASE_SER, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDGLA_HUMAN
AccessioniPrimary (citable) accession number: Q9Y4D2
Secondary accession number(s): A7E233, Q6WQJ0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: September 5, 2006
Last modified: November 7, 2018
This is version 133 of the entry and version 3 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
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