Q8NCG7 · DGLB_HUMAN

  • Protein
    Diacylglycerol lipase-beta
  • Gene
    DAGLB
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Lipase that catalyzes the hydrolysis of arachidonic acid (AA)-esterified diacylglycerols (DAGs) to produce the principal endocannabinoid, 2-arachidonoylglycerol (2-AG) which can be further cleaved by downstream enzymes to release arachidonic acid (AA) for cyclooxygenase (COX)-mediated eicosanoid production (PubMed:14610053).
Preferentially hydrolyzes DAGs at the sn-1 position in a calcium-dependent manner and has negligible activity against other lipids including monoacylglycerols and phospholipids (PubMed:14610053).
Plays a key role in the regulation of 2-AG and AA pools utilized by COX1/2 to generate lipid mediators of macrophage and microglia inflammatory responses. Functions also as a polyunsaturated fatty acids-specific triacylglycerol lipase in macrophages. Plays an important role to support the metabolic and signaling demands of macrophages (By similarity).

Catalytic activity

  • a 1,2-diacyl-sn-glycerol + H2O = a 2-acylglycerol + a fatty acid + H+
    This reaction proceeds in the forward direction.
    EC:3.1.1.116 (UniProtKB | ENZYME | Rhea)
  • 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + H2O = 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H+ + octadecanoate
    This reaction proceeds in the forward direction.
  • 1,2-di-(9Z-octadecenoyl)-sn-glycerol + H2O = (9Z)-octadecenoate + 2-(9Z-octadecenoyl)-glycerol + H+
    This reaction proceeds in the forward direction.
  • 1-(9Z-octadecenoyl)-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + H2O = (9Z)-octadecenoate + 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H+
    This reaction proceeds in the forward direction.
  • 1-(9Z-octadecenoyl)-2-octadecanoyl-sn-glycerol + H2O = (9Z)-octadecenoate + 2-octadecanoylglycerol + H+
    This reaction proceeds in the forward direction.
  • 1-(9Z-octadecenoyl)-2-(9Z,12Z-octadecadienoyl)-sn-glycerol + H2O = (9Z)-octadecenoate + 2-(9Z,12Z-octadecadienoyl)-glycerol + H+
    This reaction proceeds in the forward direction.
  • 1-(9Z-octadecenoyl)-2-O-(5Z,8Z,11Z,14Z-eicosatetraenyl)-sn-glycerol + H2O = (9Z)-octadecenoate + 2-O-(5Z,8Z,11Z,14Z)-eicosatetraenylglycerol + H+
    This reaction proceeds in the forward direction.
  • a triacylglycerol + H2O = a diacylglycerol + a fatty acid + H+
    This reaction proceeds in the forward direction.
    EC:3.1.1.3 (UniProtKB | ENZYME | Rhea)
  • 1,2,3-tri-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + 1,2-di-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + H+
    This reaction proceeds in the forward direction.
  • 1,2,3-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycerol + H2O = (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + 1,2-di-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-glycerol + H+

Cofactor

Ca2+ (UniProtKB | Rhea| CHEBI:29108 )

Activity regulation

Inhibited by the 1,2,3-triazole urea covalent inhibitors KT109 and KT172 (By similarity).
Inhibited by p-hydroxy-mercuri-benzoate and HgCl2, but not by PMSF. Also inhibited by RHC80267, a drug that blocks 2-AG formation.

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
74.1 μMdiacylglycerol
Vmax pH TEMPERATURE[C] NOTES EVIDENCE
3.45 nmol/min/mg

pH Dependence

Optimum pH is 7.0.

Features

Showing features for active site.

TypeIDPosition(s)Description
Active site443Charge relay system
Active site495Charge relay system

GO annotations

AspectTerm
Cellular Componentlysosomal membrane
Cellular Componentnucleoplasm
Cellular Componentplasma membrane
Molecular Functionacylglycerol lipase activity
Molecular Functionlipase activity
Molecular Functionmetal ion binding
Molecular Functiontriglyceride lipase activity
Biological Processarachidonic acid metabolic process
Biological Processcannabinoid biosynthetic process
Biological Processdiacylglycerol catabolic process
Biological Processmonoacylglycerol biosynthetic process
Biological Processneuroblast proliferation
Biological Processneurogenesis
Biological Processpositive regulation of triglyceride catabolic process
Biological Processprostaglandin biosynthetic process
Biological Processregulation of inflammatory response

Keywords

Enzyme and pathway databases

Protein family/group databases

Chemistry

Names & Taxonomy

Protein names

  • Recommended name
    Diacylglycerol lipase-beta
  • EC number
  • Short names
    DAGL-beta
    ; DGL-beta
  • Alternative names
    • KCCR13L
    • PUFA-specific triacylglycerol lipase
      (EC:3.1.1.3
      ) . EC:3.1.1.3 (UniProtKB | ENZYME | Rhea)
    • Sn1-specific diacylglycerol lipase beta

Gene names

    • Name
      DAGLB

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q8NCG7
  • Secondary accessions
    • A4D2P3
    • B3KV90
    • B4DQU0
    • Q6PIX3
    • Q8N2N2

Proteomes

Organism-specific databases

Subcellular Location

Cell membrane
; Multi-pass membrane protein

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-17Cytoplasmic
Transmembrane18-38Helical
Topological domain39-58Extracellular
Transmembrane59-79Helical
Topological domain80-102Cytoplasmic
Transmembrane103-123Helical
Topological domain124-132Extracellular
Transmembrane133-153Helical
Topological domain154-672Cytoplasmic

Keywords

Disease & Variants

Features

Showing features for mutagenesis, natural variant.

TypeIDPosition(s)Description
Mutagenesis443Loss of activity.
Mutagenesis495Loss of activity.
Natural variantVAR_027275664in dbSNP:rs2303361

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 947 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for chain, modified residue (large scale data), modified residue.

TypeIDPosition(s)SourceDescription
ChainPRO_00002483501-672UniProtDiacylglycerol lipase-beta
Modified residue (large scale data)175PRIDEPhosphoserine
Modified residue (large scale data)178PRIDEPhosphoserine
Modified residue570UniProtPhosphoserine
Modified residue (large scale data)570PRIDEPhosphoserine
Modified residue574UniProtPhosphoserine
Modified residue (large scale data)574PRIDEPhosphoserine
Modified residue (large scale data)576PRIDEPhosphoserine
Modified residue (large scale data)577PRIDEPhosphoserine
Modified residue579UniProtPhosphoserine
Modified residue (large scale data)579PRIDEPhosphoserine
Modified residue583UniProtPhosphoserine
Modified residue (large scale data)583PRIDEPhosphoserine
Modified residue584UniProtPhosphoserine
Modified residue (large scale data)584PRIDEPhosphoserine

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Organism-specific databases

Interaction

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY Q8NCG7CLP1 Q929893EBI-721948, EBI-2559831
BINARY Q8NCG7NOTCH2NLC P0DPK43EBI-721948, EBI-22310682

Protein-protein interaction databases

Chemistry

Miscellaneous

Structure

Family & Domains

Sequence similarities

Belongs to the AB hydrolase superfamily. Lipase family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (4)
  • Sequence status
    Complete

This entry describes 4 isoforms produced by Alternative splicing.

Q8NCG7-1

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.

  • Length
    672
  • Mass (Da)
    73,732
  • Last updated
    2006-09-05 v2
  • Checksum
    AA953D737E0EFF44
MPGMVLFGRRWAIASDDLVFPGFFELVVRVLWWIGILTLYLMHRGKLDCAGGALLSSYLIVLMILLAVVICTVSAIMCVSMRGTICNPGPRKSMSKLLYIRLALFFPEMVWASLGAAWVADGVQCDRTVVNGIIATVVVSWIIIAATVVSIIIVFDPLGGKMAPYSSAGPSHLDSHDSSQLLNGLKTAATSVWETRIKLLCCCIGKDDHTRVAFSSTAELFSTYFSDTDLVPSDIAAGLALLHQQQDNIRNNQEPAQVVCHAPGSSQEADLDAELENCHHYMQFAAAAYGWPLYIYRNPLTGLCRIGGDCCRSRTTDYDLVGGDQLNCHFGSILHTTGLQYRDFIHVSFHDKVYELPFLVALDHRKESVVVAVRGTMSLQDVLTDLSAESEVLDVECEVQDRLAHKGISQAARYVYQRLINDGILSQAFSIAPEYRLVIVGHSLGGGAAALLATMLRAAYPQVRCYAFSPPRGLWSKALQEYSQSFIVSLVLGKDVIPRLSVTNLEDLKRRILRVVAHCNKPKYKILLHGLWYELFGGNPNNLPTELDGGDQEVLTQPLLGEQSLLTRWSPAYSFSSDSPLDSSPKYPPLYPPGRIIHLQEEGASGRFGCCSAAHYSAKWSHEAEFSKILIGPKMLTDHMPDILMRALDSVVSDRAACVSCPAQGVSSVDVA

Q8NCG7-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q8NCG7-3

  • Name
    3
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 249-267: IRNNQEPAQVVCHAPGSSQ → TRATGNCPRNDGLTLLSLN
    • 268-672: Missing

Q8NCG7-4

  • Name
    4
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 140-310: SWIIIAATVVSIIIVFDPLGGKMAPYSSAGPSHLDSHDSSQLLNGLKTAATSVWETRIKLLCCCIGKDDHTRVAFSSTAELFSTYFSDTDLVPSDIAAGLALLHQQQDNIRNNQEPAQVVCHAPGSSQEADLDAELENCHHYMQFAAAAYGWPLYIYRNPLTGLCRIGGDC → RTQIWCPATLRRASPCFISNRTISGTTKSLPRWSAMPQGAPS

Computationally mapped potential isoform sequences

There are 3 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
E7ET49E7ET49_HUMANDAGLB631
F8WBN0F8WBN0_HUMANDAGLB172
C9JA85C9JA85_HUMANDAGLB149

Sequence caution

The sequence BAB85017.1 differs from that shown. Reason: Erroneous initiation

Features

Showing features for alternative sequence, sequence conflict.

TypeIDPosition(s)Description
Alternative sequenceVSP_0202451-281in isoform 2
Alternative sequenceVSP_043309140-310in isoform 4
Alternative sequenceVSP_020246249-267in isoform 3
Alternative sequenceVSP_020247268-672in isoform 3
Sequence conflict270in Ref. 3; BAC11175
Sequence conflict456in Ref. 2; BAC04258
Sequence conflict545in Ref. 7; AAH27603

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF450090
EMBL· GenBank· DDBJ
AAL47020.1
EMBL· GenBank· DDBJ
mRNA
AK093958
EMBL· GenBank· DDBJ
BAC04258.1
EMBL· GenBank· DDBJ
mRNA
AK074210
EMBL· GenBank· DDBJ
BAB85017.1
EMBL· GenBank· DDBJ
mRNA Different initiation
AK122748
EMBL· GenBank· DDBJ
BAG53702.1
EMBL· GenBank· DDBJ
mRNA
AK298955
EMBL· GenBank· DDBJ
BAG61052.1
EMBL· GenBank· DDBJ
mRNA
AK074584
EMBL· GenBank· DDBJ
BAC11073.1
EMBL· GenBank· DDBJ
mRNA
AK074744
EMBL· GenBank· DDBJ
BAC11175.1
EMBL· GenBank· DDBJ
mRNA
AK075128
EMBL· GenBank· DDBJ
BAC11420.1
EMBL· GenBank· DDBJ
mRNA
AC009412
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AC072052
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH878731
EMBL· GenBank· DDBJ
EAW55033.1
EMBL· GenBank· DDBJ
Genomic DNA
CH878731
EMBL· GenBank· DDBJ
EAW55035.1
EMBL· GenBank· DDBJ
Genomic DNA
CH236963
EMBL· GenBank· DDBJ
EAL23721.1
EMBL· GenBank· DDBJ
Genomic DNA
BC027603
EMBL· GenBank· DDBJ
AAH27603.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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