Alternative titles; symbols
HGNC Approved Gene Symbol: DGKG
Cytogenetic location: 3q27.2-q27.3 Genomic coordinates (GRCh38): 3:186,147,201-186,362,234 (from NCBI)
Diacylglycerol (DAG) kinases (DGKs or DAGKs; EC 2.7.1.107), such as DGKG, 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).
Kai et al. (1994) used degenerate PCR to clone a novel DGK, termed DGK-gamma, from HepG2 human hepatoma mRNA. They subsequently cloned a full-length cDNA from a HepG2 cDNA library. Sequence analysis revealed that DGK-gamma encodes a polypeptide of 791 amino acids which is 52% similar to that of DGK-alpha (DAGK1; 125855) and 62% similar to that of DGK-beta (604070). All 3 DGK isozymes contain 2 conserved EF-hand calcium-binding motifs and 2 zinc finger domains. Kai et al. (1994) also noted that some cDNAs contained a 25-amino acid truncation, which were presumed to be an alternate splicing variant. Both the full-length and truncated transcripts were present in a range of human tissues, with greatest expression observed in retina. When expressed in COS-7 cells, Kai et al. (1994) observed that full-length, but not truncated, DGK-gamma gave DGK activity. This activity was phosphatidylserine-dependent and had no apparent specificity with regard to the acyl group.
Kai et al. (1994) found that the DAGK3 gene spans over 30 kb of genomic DNA and contains 24 exons.
By FISH, Kai et al. (1994) mapped the DAGK3 gene to 3q27-q28.
Gross (2014) mapped the DGKG gene to chromosome 3q27.2-q27.3 based on an alignment of the DGKG sequence (GenBank BC089411) with the genomic sequence (GRCh37).
Exclusion Studies
Kai et al. (1994) performed mutation analysis of the entire coding region of the DAGK3 gene in 19 unrelated German patients with optic atrophy-1 (165500) and did not find any disease-causing mutations.
Gross, M. B. Personal Communication. Baltimore, Md. 4/11/2014.
Kai, M., Sakane, F., Imai, S., Wada, I., Kanoh, H. Molecular cloning of a diacylglycerol kinase isozyme predominantly expressed in human retina with a truncated and inactive enzyme expression in most other human cells. J. Biol. Chem. 269: 18492-18498, 1994. [PubMed: 8034597]
Masai, I., Okazaki, A., Hosoya, T., Hotta, Y. Drosophila retinal degeneration A gene encodes an eye-specific diacylglycerol kinase with cysteine-rich zinc-finger motifs and ankyrin repeats. Proc. Nat. Acad. Sci. 90: 11157-11161, 1993. [PubMed: 8248222] [Full Text: https://doi.org/10.1073/pnas.90.23.11157]
Stohr, H., Klein, J., Gehrig, A., Koehler, M. R., Jurklies, B., Kellner, U., Leo-Kottler, B., Schmid, M., Weber, B. H. F. Mapping and genomic characterization of the gene encoding diacylglycerol kinase gamma (DAGK3): assessment of its role in dominant optic atrophy (OPA1). Hum. Genet. 104: 99-105, 1999. [PubMed: 10071200] [Full Text: https://doi.org/10.1007/s004390050917]
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]