Kinase Family IPK

Kinase Classification: Group PKL: Family IPK

A set of 3 subfamilies that further phosphorylate inositol phosphates, and have structures intermediate between PKL and ATP-Grasp folds. These have primary sequence similarity to each other.

Subfamilies

IP3K

IP6K

IPMK

Kinase Domain

The IPPK kinase domain is most similar to that of PIPK, which is itself a remote member of the PKL fold, and related to other inositol phosphate kinase families [1, 2]. SCOP classifies both IP3K (called IPK) and PIPK in the SAICAR synthase-like superfamamily with similarity to both the PKL and the ATP-Grasp folds. This was first predicted by deep sequence comparison [3] and confirmed by a crystal structures [1, 2, 4]. 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 IP3K [3].

Evolution

The family is found in most eukaryotes, and has three copies in human (ITPKA, ITPKB, ITPKC).

Naming

As with most inositol kinases, IP3K have several names, I3P3K, IP3-3K, ITPK (inositol-trisphosphate 3-kinase) and 1D-myo-inositol 1,4,5-trisphosphate 3-kinase. While human names are named with the root ITPK, this is also the name of a different family of lipid kinases.

References

2. Miller GJ and Hurley JH. Crystal structure of the catalytic core of inositol 1,4,5-trisphosphate 3-kinase. Mol Cell. 2004 Sep 10;15(5):703-11. DOI:10.1016/j.molcel.2004.08.005 |
3. 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 |
4. Takazawa K, Perret J, Dumont JE, and Erneux C. Molecular cloning and expression of a human brain inositol 1,4,5-trisphosphate 3-kinase. Biochem Biophys Res Commun. 1991 Jan 31;174(2):529-35. DOI:10.1016/0006-291x(91)91449-m |

Unlinked References

1. Gonzalez pmid= 15350214