Recombinant Human Diacylglycerol kinase epsilon (DGKE) Protein

Function

Membrane-bound diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:15544348, PubMed:19744926, PubMed:21477596, PubMed:22108654, PubMed:23949095). Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (PubMed:15544348, PubMed:8626589). Also plays an important role in the biosynthesis of complex lipids (PubMed:8626589). Displays specificity for diacylglycerol substrates with an arachidonoyl acyl chain at the sn-2 position, with the highest activity toward 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol the main diacylglycerol intermediate within the phosphatidylinositol turnover cycle (PubMed:19744926, PubMed:22108654, PubMed:23274426). Can also phosphorylate diacylglycerol substrates with a linoleoyl acyl chain at the sn-2 position but much less efficiently (PubMed:22108654)

Subcellular Location

Membrane (Single-pass membrane protein); Cytoplasm

Disease Association

Nephrotic syndrome 7 (NPHS7) : A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. NPHS7 is an autosomal recessive form characterized by onset of proteinuria usually in the first decade of life. The disorder is progressive, and some patients develop end-stage renal disease within several years. Renal biopsy typically shows membranoproliferative glomerulonephritis. [The disease is caused by variants affecting the gene represented in this entry] | Hemolytic uremic syndrome, atypical, 7 (AHUS7) : An atypical form of hemolytic uremic syndrome characterized by acute onset in the first year of life of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. After the acute episode, most patients develop chronic renal insufficiency. Unlike other genetic forms of aHUS, AHUS7 is not related to abnormal activation of the complement system. [Disease susceptibility is associated with variants affecting the gene represented in this entry]

Tissue Specificity

Expressed predominantly in testis. Expressed in endothelium, platelets and podocytes (at protein level)

Pathway

Lipid metabolism; glycerolipid metabolism

• Tang W. et al. Molecular cloning of a novel human diacylglycerol kinase highly selective for arachidonate-containing substrates. — J. Biol. Chem. (1996)
• Zody M.C. et al. DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. — Nature (2006)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Tang W. et al. Characterization of the human diacylglycerol kinase epsilon gene and its assessment as a candidate for inherited retinitis pigmentosa. — Gene (1999)
• Epand R.M. et al. The alpha isoform of diacylglycerol kinase exhibits arachidonoyl specificity with alkylacylglycerol. — Biochemistry (2004)
• Epand R.M. et al. Substrate chirality and specificity of diacylglycerol kinases and the multisubstrate lipid kinase. — Biochemistry (2007)
• Lung M. et al. Diacylglycerol kinase epsilon is selective for both acyl chains of phosphatidic acid or diacylglycerol. — J. Biol. Chem. (2009)
• Shulga Y.V. et al. Substrate specificity of diacylglycerol kinase-epsilon and the phosphatidylinositol cycle. — FEBS Lett. (2011)