Kinase Family IPPK
Kinase Classification: Group PKL: Family IPPK
IPPK is a non-protein kinase that phosphorylates the 2 position of an inositol already phosphorylated on all other positions, to make InsP6 - inositol hexakisphosphate, a signaling molecule involved in several pathways including functions, including endocytosis, DNA repair, and mRNA export.
Kinase Domain
The IPPK kinase domain is related both to the PKL kinases as well as to the ATP-Grasp fold of ATP-driven enzymes. This was first predicted by deep sequence comparison [1] and confirmed by a crystal structure [2, 3]. Like PIPK kinases, the N-lobe is closer to PKL while the C-lobe has similarities to the ATP-Grasp fold. The K72, D166 and D184 catalytic residues of PKLs are well conserved in IPPK [1].
Evolution
IPPK is a single-copy gene in most eukaryotes, including human.
Naming
As with most inositol kinases, IPPK have several names, including Ipk1 (after the yeast homolog), InsP5 2-kinase (IP5 2-K)
References
- Cheek S, Ginalski K, Zhang H, and Grishin NV. A comprehensive update of the sequence and structure classification of kinases. BMC Struct Biol. 2005 Mar 16;5:6. DOI:10.1186/1472-6807-5-6 |
- González B, Baños-Sanz JI, Villate M, Brearley CA, and Sanz-Aparicio J. Inositol 1,3,4,5,6-pentakisphosphate 2-kinase is a distant IPK member with a singular inositide binding site for axial 2-OH recognition. Proc Natl Acad Sci U S A. 2010 May 25;107(21):9608-13. DOI:10.1073/pnas.0912979107 |
- Gosein V, Leung TF, Krajden O, and Miller GJ. Inositol phosphate-induced stabilization of inositol 1,3,4,5,6-pentakisphosphate 2-kinase and its role in substrate specificity. Protein Sci. 2012 May;21(5):737-42. DOI:10.1002/pro.2049 |
