Structural highlights
Function
[DGKD_HUMAN] May function as signaling molecule.[1] Isoform 2 may be involved in cell growth and tumorigenesis. Involved in clathrin-dependent endocytosis.[2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The diacylglycerol kinase (DGK) enzymes function as regulators of intracellular signaling by altering the levels of the second messengers, diacylglycerol and phosphatidic acid. The DGK delta and eta isozymes possess a common protein-protein interaction module known as a sterile alpha-motif (SAM) domain. In DGK delta, SAM domain self-association inhibits the translocation of DGK delta to the plasma membrane. Here we show that DGK delta SAM forms a polymer and map the polymeric interface by a genetic selection for soluble mutants. A crystal structure reveals that DGKSAM forms helical polymers through a head-to-tail interaction similar to other SAM domain polymers. Disrupting polymerization by polymer interface mutations constitutively localizes DGK delta to the plasma membrane. Thus, polymerization of DGK delta regulates the activity of the enzyme by sequestering DGK delta in an inactive cellular location. Regulation by dynamic polymerization is an emerging theme in signal transduction.
Regulation of enzyme localization by polymerization: polymer formation by the SAM domain of diacylglycerol kinase delta1.,Harada BT, Knight MJ, Imai S, Qiao F, Ramachander R, Sawaya MR, Gingery M, Sakane F, Bowie JU Structure. 2008 Mar;16(3):380-7. PMID:18334213[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kawasaki T, Kobayashi T, Ueyama T, Shirai Y, Saito N. Regulation of clathrin-dependent endocytosis by diacylglycerol kinase delta: importance of kinase activity and binding to AP2alpha. Biochem J. 2008 Jan 15;409(2):471-9. PMID:17880279 doi:http://dx.doi.org/10.1042/BJ20070755
- ↑ Kawasaki T, Kobayashi T, Ueyama T, Shirai Y, Saito N. Regulation of clathrin-dependent endocytosis by diacylglycerol kinase delta: importance of kinase activity and binding to AP2alpha. Biochem J. 2008 Jan 15;409(2):471-9. PMID:17880279 doi:http://dx.doi.org/10.1042/BJ20070755
- ↑ Harada BT, Knight MJ, Imai S, Qiao F, Ramachander R, Sawaya MR, Gingery M, Sakane F, Bowie JU. Regulation of enzyme localization by polymerization: polymer formation by the SAM domain of diacylglycerol kinase delta1. Structure. 2008 Mar;16(3):380-7. PMID:18334213 doi:10.1016/j.str.2007.12.017