Kinase Family G11
Kinase Classification: Group SAPPK: Family G11
This family consists of a single human gene shown to have serine/threonine kinase activity against alpha casein and histone [1]. The activity was seen in immunoprecipitates from Sf21 insect cells and primate COS cells. G11 does not autophosphorylate is not known to be a phosphoprotein (Phosphosite)
Evidence for Protein Kinase Activity
G11 was tested for ATP-binding ability. G11 immunoprecipitates reacted with FSBA, a reactive ATP analog. SDS-PAGE showed several labeled bands, of which one mapped to the G11 size (30kDa) and was competed by ATP, indicating that G11 is an ATP-binding protein. Kinase activity was blocked by increasing concentrations of FSBA. Three lysine residues (K300, K315, K317) were individually mutated to proline. K317P proteins lost all kinase activity, while K300P and K315P lost most of their activity. K317 is largely but not absolutely conserved in the family. K300 is in a predicted helix, and the other two are predicted to be in a loop between two helices, suggesting that the proline mutations may destabilize the protein fold, and could also block binding of a partner kinase.
There have been no further reports of kinase activity published as of early 2010, and no other characterization of the gene, apart from its association with several polymerases and transcription-associated proteins in human interaction studies. The kinase activity of this protein is still unclear, due to the lack of follow-on analysis. It is possible that a kinase found in both human and insects can bind human G11 (despite the lack of G11 in insects) and be immunoprecipitated. FSBA binding is not unique to kinases, as seen with H11, and many other kinases migrate at ~30kDa. The conservation pattern in the C-terminus of the protein is reasonably consistent with being an enzyme (no absolutely conserved residues, but several that are very well conserved), but does not look anything like any other known kinase.
Evolution
G11 homologs are found in most eukaryotes, including plants, and fungi, though not in nematodes or insects. No clear additional remote homologies could be found by psi-blast or HMM search. The reported weak similarity to a typical protein kinase in the original report is not supported by profile analysis using dozens of G11 homologs.
