DGKA gene

The DGKA gene (DGKA stands for: Diacylglycerol Kinase Alpha) is a protein-coding gene located on chromosome 12q13.2. Several transcript variants encoding different isoforms have been identified for this gene.

The protein encoded by this gene, diacylglycerol kinase alpha, belongs to the family of eukaryotic diacylglycerol kinases. The kinase acts as a modulator that competes with protein kinase C for the second messenger diacylglycerol in intracellular signaling pathways. It also plays an important role in the resynthesis of phosphatidylinositols and the phosphorylation of diacylglycerol to phosphatidic acid.

Diacylglycerol kinase converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (Schaap D et al. 1990; Epand RM et al. 2004). Thus, it acts as a central switch between the signaling pathways activated by these messengers with different cellular targets and opposing effects in numerous biological processes (Schaap D et al. 1990; Epand RM et al. 2004). The kinase also plays an important role in the biosynthesis of complex lipids. Can also phosphorylate 1-alkyl-2-acylglycerol in vitro just as efficiently as diacylglycerol, provided it contains an arachidonoyl group (Epand RM et al. 2004). Is also involved in the production of alkyl-lysophosphatidic acid, another bioactive lipid, by phosphorylation of 1-alkyl-2-acetylglycerol (Gellett AM et al. 2012).

Diseases associated with DGKA include lymphoproliferative syndrome, X-linked, 1 and Bardet-Biedl syndrome 1.

Diacylglycerol kinases (DGKs) are a group of ten enzymes that convert 1,2,diacylglycerol (DAG) to phosphatidic acid (PA). They all contain a conserved C'-terminal catalytic domain and two cysteine-rich Zn2+ finger motifs with different regulatory domains.

1. Epand RM et al. (2004) The alpha isoform of diacylglycerol kinase exhibits arachidonoyl specificity with alkylacylglycerol. Biochemistry 43:14778-14783.
2. Gellett AM et al. (2012) Biosynthesis of alkyl lysophosphatidic acid by diacylglycerol kinases. Biochem Biophys Res Commun 422:758-763.
3. Schaap D et al. (1990) Purification, cDNA-cloning and expression of human diacylglycerol kinase. FEBS Lett 275:151-158.