Alternative titles; symbols
HGNC Approved Gene Symbol: DGKH
Cytogenetic location: 13q14.11 Genomic coordinates (GRCh38): 13:42,040,070-42,256,584 (from NCBI)
Diacylglycerol (DAG) kinases (DGKs or DAGKs; EC 2.7.1.107), such as DGKH, phosphorylate DAG to phosphatidic acid, thus removing DAG. Phosphatidic acid functions both in signaling and phospholipid synthesis. In intracellular signaling pathways, DAGK can be viewed as a modulator that competes with protein kinase C (PKC; see 600448) for the second messenger DAG (review by Topham and Prescott, 1999).
Klauck et al. (1996) isolated hamster glucocorticoid-inducible cDNAs encoding a novel 130-kD DGK that they designated DGK-eta. Sequence analysis revealed that the predicted protein is closely related to DGK-delta (DGKD; 601826). Both enzymes contain an N-terminal pleckstrin homology domain and a putative catalytic domain that is separated into 2 subdomains. Northern blot and immunoblot analyses indicated that DGK-eta was expressed in most hamster tissues. When expressed in insect cells, DGK-eta exhibited DGK activity.
By searching genomic databases for sequences similar to that encoding the SAM domain of DGKD, Murakami et al. (2003) identified a splice variant of DGKH, which they called DGKH2. DGKH2 utilizes all 30 DGKH exons and encodes a deduced 1,220-amino acid protein with a calculated molecular mass of 135 kD. DGKH1, which lacks exon 29, encodes a deduced 1,164-amino acid protein has a calculated molecular mass of 128 kD. The 2 proteins differ at their C-terminal ends, and DGKH2 contains a SAM domain and a C-terminal PDZ-binding domain not found in DGKH1. RT-PCR detected DGKH1 in most normal and tumor tissues examined, with lowest expression in lung and skeletal muscle. DGKH2 was detected in testis, kidney, and colon with lower expression in tumor cells compared to DGKH1. Western blot analysis of transfected COS-7 cells detected DGKH1 and DGKH2 at apparent molecular masses of 128 and 135 kD, respectively.
Murakami et al. (2003) reported that both the DGKH1 and DGKH2 isoforms of DGKH showed diacylglycerol kinase activity; however, the 2 isoforms differed in several other characteristics. Expression of DGKH2 in transfected cells was suppressed by glucocorticoid in contrast to the marked induction of DGKH1. In response to stress stimuli, DGKH1 and DGKH2 were both rapidly translocated from the cytoplasm to endosomes, but only DGKH1 relocated back to the cytoplasm upon removal of stress stimuli. Mutation analysis indicated that oligomerization of DGKH2, mediated by its SAM domain, was largely responsible for its sustained endosomal localization. Oligomerization of DGKH2 appeared to negatively regulate its catalytic activity. Coimmunoprecipitation analysis indicated that DGKH2 was able to form higher-order oligomers with DGKD isoforms 1 and 2 through its SAM domain.
Murakami et al. (2003) determined that the DGKH gene contains 30 exons.
Gross (2014) mapped the DGKH gene to chromosome 13q14.11 based on an alignment of the DGKH sequence (GenBank AB078967) with the genomic sequence (GRCh37).
Gross, M. B. Personal Communication. Baltimore, Md. 4/11/2014.
Klauck, T. M., Xu, X., Mousseau, B., Jaken, S. Cloning and characterization of a glucocorticoid-induced diacylglycerol kinase. J. Biol. Chem. 271: 19781-19788, 1996. [PubMed: 8702685] [Full Text: https://doi.org/10.1074/jbc.271.33.19781]
Murakami, T., Sakane, F., Imai, S., Houkin, K., Kanoh, H. Identification and characterization of two splice variants of human diacylglycerol kinase eta. J. Biol. Chem. 278: 34364-34372, 2003. [PubMed: 12810723] [Full Text: https://doi.org/10.1074/jbc.M301542200]
Topham, M. K., Prescott, S. M. Mammalian diacylglycerol kinases, a family of lipid kinases with signaling functions. J. Biol. Chem. 274: 11447-11450, 1999. [PubMed: 10206945] [Full Text: https://doi.org/10.1074/jbc.274.17.11447]