Diacylglycerol lipase-beta (DAGLB)

The protein contains 672 amino acids for an estimated molecular weight of 73732 Da.

 

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). (updated: June 17, 2020)

Protein identification was indicated in the following studies:

  1. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  2. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 0%
Model score: 0
No model available.

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VariantDescription
dbSNP:rs2303361

No binding partner found

The reference OMIM entry for this protein is 614016

Diacylglycerol lipase, beta; daglb
Dagl-beta
Dgl-beta
Dglb

DESCRIPTION

DAGLB is a diacylglycerol (DAG) lipase (EC 3.1.1.34) that catalyzes the hydrolysis of DAG to 2-arachidonoyl-glycerol, the most abundant endocannabinoid in tissues. In brain, DAGL activity is required for axonal growth during development and for retrograde synaptic signaling at mature synapses (summary by Bisogno et al., 2003).

CLONING

By searching the human genome for sequences similar to Penicilium Dagl, Bisogno et al. (2003) identified DAGLA (614015) and DAGLB. The deduced full-length 672-amino acid DAGLB protein contains 4 transmembrane domains near its N terminus, followed by a serine lipase motif, a lipase-3 motif, and a C-terminal tail. The N terminus and catalytic domain were predicted to reside inside the cell. Mouse and human DAGLB share 79% amino acid identity. Dagla and Daglb were coexpressed in axonal tracts of embryonic mouse at embryonic day 10, but were absent from axonal tracts in adult mouse brain. In adult cerebellum, Dagla and Daglb expression was restricted to deep cerebellar nuclei and synaptic fields, including Purkinje cell dendrites.

GENE FUNCTION

Using sn-1-steroyl-2-arachidonoyl-glycerol as substrate, Bisogno et al. (2003) showed that the membrane fraction of COS cells transfected with mouse Daglb showed optimal activity at pH 7. Daglb showed a 3- to 8-fold selectivity for the sn-1 over the sn-2 position of DAGs, and it appeared to prefer sn-1-oleoyl-2 acyl-glycerols with linoleic acid more than oleic, arachidonic, or stearic acids in the 2 position. Daglb was sensitive to ser/cys-hydrolase inhibitors and to a drug that blocked 2-arachidonoyl-glycerol synthesis. Glutathione and calcium stimulated Daglb activity.

MAPPING

Hartz (2011) mapped the DAGLB gene to chromosome 7p22.1 based on an alignment of the DAGLB sequence (GenBank GENBANK AF450090) with the genomic sequence (GRCh37).

ANIMAL MODEL

Tanimura et al. (2010) found that Dglb -/- mice were viable and appeared normal. Histologic examination revealed no brain abnormalities, and synaptic transmission, kinetics, and currents were no different from wildtype. Endocannabinoid-mediated retrograde synaptic suppression was intact in Dglb -/- brain. ... More on the omim web site

Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 614016 was added.

June 29, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).