HGNC Approved Gene Symbol: DGKKCytogenetic location: Xp11.22 Genomic coordinates (GRCh38): X:50,365,408-50,470,850 (from NCBI)▼ DescriptionDiacylglycerol kin...
HGNC Approved Gene Symbol: DGKK
Cytogenetic location: Xp11.22 Genomic coordinates (GRCh38): X:50,365,408-50,470,850 (from NCBI)
Diacylglycerol kinases (DGKs; EC 220.127.116.11), such as DGKK, phosphorylate diacylglycerol and thereby downregulate diacylglycerol signaling activity. In addition, phosphorylation of diacylglycerol generates another lipid signaling mediator, phosphatidic acid (summary by Imai et al., 2005).
▼ Cloning and Expression
By searching a database for sequences encoding DGKs, followed by PCR and RACE of a testis cDNA library, Imai et al. (2005) cloned human DGKK. The deduced 1,271-amino acid protein has a calculated molecular mass of 142 kD. It has an N-terminal domain containing 33 tandem repeats of glu-pro-ala-pro (EPAP), followed by a pleckstrin (PLEK; 173570) homology (PH) domain, 2 cysteine-rich zinc fingers, a catalytic domain separated into 2 subdomains, 2 putative coiled-coil structures, and a C-terminal PDZ-binding motif. In addition to the EPAP repeats, the N-terminal region also contains a proline-rich region and 5 ser-pro repeats. The split catalytic domain is characteristic of the type II DGKs, DGK-delta (DGKD; 601826) and DGK-eta (DGKH; 604071). RT-PCR analysis detected high DGKK expression in testis and weaker expression in placenta, with little to no expression in other normal tissues or in tumor-derived cells. DGKK localized to the plasma membrane of transfected HEK293 cells. DGKK expressed in COS-7 cells and endogenous pig Dgkk showed an apparent molecular mass of 170 kD by SDS-PAGE.
▼ Gene Function
Imai et al. (2005) showed that human DGKK immunoprecipitated from transfected COS-7 cells phosphorylated 1,2-dioleoyl-sn-glycerol. Unlike other type II DGKs, DGKK did not form oligomeric structures, it was phosphorylated in resting cells, and its intracellular localization at the plasma membrane was not altered by cell stimuli. However, exposure to H2O2 induced tyrosine phosphorylation of DGKK in a dose- and time-dependent manner and inhibited DGKK activity. Mutation analysis revealed that tyr78 was the main site for phosphorylation following oxidative stress. Inhibitor studies showed that tyrosine phosphorylation and inhibition of DGKK activity are regulated through different signaling pathways. Imai et al. (2005) concluded that DGKK keeps diacylglycerol concentrations low in the plasma membrane of resting cells and that its deactivation following oxidative stress changes the balance of membrane signaling lipids.
▼ Gene Structure
Imai et al. (2005) determined that the DGKK gene contains 28 exons.
By genomic sequence analysis, Imai et al. (2005) mapped the DGKK gene to chromosome Xp11.22
▼ Molecular Genetics
For discussion of a possible association between variation in the DGKK gene and susceptibility to hypospadias, see HYSP4 (300856).