Kinase Family IPK

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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.

The IPK family has the following subfamilies:

IP3K

Inositol-trisphosphate 3-kinase

IP6K

Inositol hexaphosphate kinase

IPMK

Inositol polyphosphate multikinase

Kinase Domain

The IPK kinase domain is related to the PIPK family. SCOP classifies both families in the SAICAR synthase-like superfamily with similarity to both the PKL and the ATP-Grasp folds. In both families, the N-lobe is closer to PKL while the C-lobe is more related to ATP-Grasp. This similarity was first predicted by deep sequence comparison [1] and confirmed by a crystal structures [2, 3, 4, 5]. The K72, D166 and D184 catalytic residues of PKLs are well conserved in most IPK [1].

Evolution

The family is found in most eukaryotes.

References

  1. 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 | PubMed ID:15771780 | HubMed [Cheek]
  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 | PubMed ID:15350215 | HubMed [Miller]
  3. 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 | PubMed ID:1847047 | HubMed [Takazawa]
  4. González B, Schell MJ, Letcher AJ, Veprintsev DB, Irvine RF, and Williams RL. Structure of a human inositol 1,4,5-trisphosphate 3-kinase: substrate binding reveals why it is not a phosphoinositide 3-kinase. Mol Cell. 2004 Sep 10;15(5):689-701. DOI:10.1016/j.molcel.2004.08.004 | PubMed ID:15350214 | HubMed [Gonzalez]
  5. Holmes W and Jogl G. Crystal structure of inositol phosphate multikinase 2 and implications for substrate specificity. J Biol Chem. 2006 Dec 8;281(49):38109-16. DOI:10.1074/jbc.M606883200 | PubMed ID:17050532 | HubMed [Holmes]
All Medline abstracts: PubMed | HubMed