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Protein

Sn1-specific diacylglycerol lipase beta

Gene

DAGLB

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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=74.1 µM for diacylglycerol1 Publication
  1. Vmax=3.45 nmol/min/mg enzyme1 Publication

pH dependencei

Optimum pH is 7.0.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei443Charge relay system1
Active sitei495Charge relay system1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Lipid degradation, Lipid metabolism

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-426048. Arachidonate production from DAG.

Protein family/group databases

ESTHERihuman-DAGLB. Lipase_3.

Chemistry databases

SwissLipidsiSLP:000000322.

Names & Taxonomyi

Protein namesi
Recommended name:
Sn1-specific diacylglycerol lipase beta (EC:3.1.1.-)
Short name:
DGL-beta
Alternative name(s):
KCCR13L
Gene namesi
Name:DAGLB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:28923. DAGLB.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 17CytoplasmicSequence analysisAdd BLAST17
Transmembranei18 – 38HelicalSequence analysisAdd BLAST21
Topological domaini39 – 58ExtracellularSequence analysisAdd BLAST20
Transmembranei59 – 79HelicalSequence analysisAdd BLAST21
Topological domaini80 – 102CytoplasmicSequence analysisAdd BLAST23
Transmembranei103 – 123HelicalSequence analysisAdd BLAST21
Topological domaini124 – 132ExtracellularSequence analysis9
Transmembranei133 – 153HelicalSequence analysisAdd BLAST21
Topological domaini154 – 672CytoplasmicSequence analysisAdd BLAST519

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB-KW
  • lysosomal membrane Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi443S → A: Loss of activity. 1 Publication1
Mutagenesisi495D → A: Loss of activity. 1 Publication1

Organism-specific databases

OpenTargetsiENSG00000164535.
PharmGKBiPA162383203.

Chemistry databases

ChEMBLiCHEMBL5521.
GuidetoPHARMACOLOGYi1397.

Polymorphism and mutation databases

BioMutaiDAGLB.
DMDMi114149272.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002483501 – 672Sn1-specific diacylglycerol lipase betaAdd BLAST672

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei570PhosphoserineCombined sources1
Modified residuei574PhosphoserineCombined sources1
Modified residuei579PhosphoserineCombined sources1
Modified residuei583PhosphoserineBy similarity1
Modified residuei584PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8NCG7.
MaxQBiQ8NCG7.
PaxDbiQ8NCG7.
PeptideAtlasiQ8NCG7.
PRIDEiQ8NCG7.

PTM databases

iPTMnetiQ8NCG7.
PhosphoSitePlusiQ8NCG7.
SwissPalmiQ8NCG7.

Expressioni

Gene expression databases

BgeeiENSG00000164535.
CleanExiHS_DAGLB.
ExpressionAtlasiQ8NCG7. baseline and differential.
GenevisibleiQ8NCG7. HS.

Interactioni

Protein-protein interaction databases

BioGridi128772. 26 interactors.
IntActiQ8NCG7. 3 interactors.
MINTiMINT-1386028.
STRINGi9606.ENSP00000297056.

Chemistry databases

BindingDBiQ8NCG7.

Structurei

3D structure databases

ProteinModelPortaliQ8NCG7.
SMRiQ8NCG7.
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.
HOGENOMiHOG000246993.
HOVERGENiHBG055573.
InParanoidiQ8NCG7.
KOiK13806.
OMAiCRIGGDC.
OrthoDBiEOG091G04AM.
PhylomeDBiQ8NCG7.
TreeFamiTF312928.

Family and domain databases

Gene3Di3.40.50.1820. 2 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]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8NCG7-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPGMVLFGRR WAIASDDLVF PGFFELVVRV LWWIGILTLY LMHRGKLDCA
60 70 80 90 100
GGALLSSYLI VLMILLAVVI CTVSAIMCVS MRGTICNPGP RKSMSKLLYI
110 120 130 140 150
RLALFFPEMV WASLGAAWVA DGVQCDRTVV NGIIATVVVS WIIIAATVVS
160 170 180 190 200
IIIVFDPLGG KMAPYSSAGP SHLDSHDSSQ LLNGLKTAAT SVWETRIKLL
210 220 230 240 250
CCCIGKDDHT RVAFSSTAEL FSTYFSDTDL VPSDIAAGLA LLHQQQDNIR
260 270 280 290 300
NNQEPAQVVC HAPGSSQEAD LDAELENCHH YMQFAAAAYG WPLYIYRNPL
310 320 330 340 350
TGLCRIGGDC CRSRTTDYDL VGGDQLNCHF GSILHTTGLQ YRDFIHVSFH
360 370 380 390 400
DKVYELPFLV ALDHRKESVV VAVRGTMSLQ DVLTDLSAES EVLDVECEVQ
410 420 430 440 450
DRLAHKGISQ AARYVYQRLI NDGILSQAFS IAPEYRLVIV GHSLGGGAAA
460 470 480 490 500
LLATMLRAAY PQVRCYAFSP PRGLWSKALQ EYSQSFIVSL VLGKDVIPRL
510 520 530 540 550
SVTNLEDLKR RILRVVAHCN KPKYKILLHG LWYELFGGNP NNLPTELDGG
560 570 580 590 600
DQEVLTQPLL GEQSLLTRWS PAYSFSSDSP LDSSPKYPPL YPPGRIIHLQ
610 620 630 640 650
EEGASGRFGC CSAAHYSAKW SHEAEFSKIL IGPKMLTDHM PDILMRALDS
660 670
VVSDRAACVS CPAQGVSSVD VA
Length:672
Mass (Da):73,732
Last modified:September 5, 2006 - v2
Checksum:iAA953D737E0EFF44
GO
Isoform 2 (identifier: Q8NCG7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-281: Missing.

Note: No experimental confirmation available.
Show »
Length:391
Mass (Da):43,191
Checksum:i4DAEA2A26417EA69
GO
Isoform 3 (identifier: Q8NCG7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     249-267: IRNNQEPAQVVCHAPGSSQ → TRATGNCPRNDGLTLLSLN
     268-672: Missing.

Note: No experimental confirmation available.
Show »
Length:267
Mass (Da):28,899
Checksum:i661A57D0B8F4CB6A
GO
Isoform 4 (identifier: Q8NCG7-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     140-310: SWIIIAATVV...TGLCRIGGDC → RTQIWCPATL...WSAMPQGAPS

Note: No experimental confirmation available.
Show »
Length:543
Mass (Da):59,837
Checksum:iBD549DBC7456917F
GO

Sequence cautioni

The sequence BAB85017 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti270D → Y in BAC11175 (PubMed:16303743).Curated1
Sequence conflicti456L → V in BAC04258 (PubMed:14702039).Curated1
Sequence conflicti545T → K in AAH27603 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_027275664Q → R.2 PublicationsCorresponds to variant rs2303361dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0202451 – 281Missing in isoform 2. 1 PublicationAdd BLAST281
Alternative sequenceiVSP_043309140 – 310SWIII…IGGDC → RTQIWCPATLRRASPCFISN RTISGTTKSLPRWSAMPQGA PS in isoform 4. 1 PublicationAdd BLAST171
Alternative sequenceiVSP_020246249 – 267IRNNQ…PGSSQ → TRATGNCPRNDGLTLLSLN in isoform 3. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_020247268 – 672Missing in isoform 3. 1 PublicationAdd BLAST405

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF450090 mRNA. Translation: AAL47020.1.
AK093958 mRNA. Translation: BAC04258.1.
AK074210 mRNA. Translation: BAB85017.1. Different initiation.
AK122748 mRNA. Translation: BAG53702.1.
AK298955 mRNA. Translation: BAG61052.1.
AK074584 mRNA. Translation: BAC11073.1.
AK074744 mRNA. Translation: BAC11175.1.
AK075128 mRNA. Translation: BAC11420.1.
AC009412 Genomic DNA. No translation available.
AC072052 Genomic DNA. No translation available.
CH878731 Genomic DNA. Translation: EAW55033.1.
CH878731 Genomic DNA. Translation: EAW55035.1.
CH236963 Genomic DNA. Translation: EAL23721.1.
BC027603 mRNA. Translation: AAH27603.1.
CCDSiCCDS47536.1. [Q8NCG7-4]
CCDS5350.1. [Q8NCG7-1]
RefSeqiNP_001136408.1. NM_001142936.1. [Q8NCG7-4]
NP_631918.3. NM_139179.3. [Q8NCG7-1]
UniGeneiHs.487498.

Genome annotation databases

EnsembliENST00000297056; ENSP00000297056; ENSG00000164535. [Q8NCG7-1]
ENST00000425398; ENSP00000391171; ENSG00000164535. [Q8NCG7-4]
GeneIDi221955.
KEGGihsa:221955.
UCSCiuc003sqa.4. human. [Q8NCG7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF450090 mRNA. Translation: AAL47020.1.
AK093958 mRNA. Translation: BAC04258.1.
AK074210 mRNA. Translation: BAB85017.1. Different initiation.
AK122748 mRNA. Translation: BAG53702.1.
AK298955 mRNA. Translation: BAG61052.1.
AK074584 mRNA. Translation: BAC11073.1.
AK074744 mRNA. Translation: BAC11175.1.
AK075128 mRNA. Translation: BAC11420.1.
AC009412 Genomic DNA. No translation available.
AC072052 Genomic DNA. No translation available.
CH878731 Genomic DNA. Translation: EAW55033.1.
CH878731 Genomic DNA. Translation: EAW55035.1.
CH236963 Genomic DNA. Translation: EAL23721.1.
BC027603 mRNA. Translation: AAH27603.1.
CCDSiCCDS47536.1. [Q8NCG7-4]
CCDS5350.1. [Q8NCG7-1]
RefSeqiNP_001136408.1. NM_001142936.1. [Q8NCG7-4]
NP_631918.3. NM_139179.3. [Q8NCG7-1]
UniGeneiHs.487498.

3D structure databases

ProteinModelPortaliQ8NCG7.
SMRiQ8NCG7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi128772. 26 interactors.
IntActiQ8NCG7. 3 interactors.
MINTiMINT-1386028.
STRINGi9606.ENSP00000297056.

Chemistry databases

BindingDBiQ8NCG7.
ChEMBLiCHEMBL5521.
GuidetoPHARMACOLOGYi1397.
SwissLipidsiSLP:000000322.

Protein family/group databases

ESTHERihuman-DAGLB. Lipase_3.

PTM databases

iPTMnetiQ8NCG7.
PhosphoSitePlusiQ8NCG7.
SwissPalmiQ8NCG7.

Polymorphism and mutation databases

BioMutaiDAGLB.
DMDMi114149272.

Proteomic databases

EPDiQ8NCG7.
MaxQBiQ8NCG7.
PaxDbiQ8NCG7.
PeptideAtlasiQ8NCG7.
PRIDEiQ8NCG7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000297056; ENSP00000297056; ENSG00000164535. [Q8NCG7-1]
ENST00000425398; ENSP00000391171; ENSG00000164535. [Q8NCG7-4]
GeneIDi221955.
KEGGihsa:221955.
UCSCiuc003sqa.4. human. [Q8NCG7-1]

Organism-specific databases

CTDi221955.
GeneCardsiDAGLB.
H-InvDBHIX0006466.
HGNCiHGNC:28923. DAGLB.
MIMi614016. gene.
neXtProtiNX_Q8NCG7.
OpenTargetsiENSG00000164535.
PharmGKBiPA162383203.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2088. Eukaryota.
ENOG410XRFI. LUCA.
GeneTreeiENSGT00530000063682.
HOGENOMiHOG000246993.
HOVERGENiHBG055573.
InParanoidiQ8NCG7.
KOiK13806.
OMAiCRIGGDC.
OrthoDBiEOG091G04AM.
PhylomeDBiQ8NCG7.
TreeFamiTF312928.

Enzyme and pathway databases

ReactomeiR-HSA-426048. Arachidonate production from DAG.

Miscellaneous databases

ChiTaRSiDAGLB. human.
GenomeRNAii221955.
PROiQ8NCG7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164535.
CleanExiHS_DAGLB.
ExpressionAtlasiQ8NCG7. baseline and differential.
GenevisibleiQ8NCG7. HS.

Family and domain databases

Gene3Di3.40.50.1820. 2 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]
ProtoNetiSearch...

Entry informationi

Entry nameiDGLB_HUMAN
AccessioniPrimary (citable) accession number: Q8NCG7
Secondary accession number(s): A4D2P3
, B3KV90, B4DQU0, Q6PIX3, Q8N2N2, Q8N9S1, Q8TED3, Q8WXE6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: September 5, 2006
Last modified: November 30, 2016
This is version 116 of the entry and version 2 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 7
    Human chromosome 7: 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.