Kinase Family ITPK
Kinase Classification: Group PKL: Family ITPK
ITPK in an inositol lipid kinase, once thought to have protein kinase activity. ITPK is an Inositol 1, 3, 4-trisphosphate 5/6-kinase.
Kinase Domain
ITPK has an ATP-grasp domain, shared by a variety of ATP-hydrolyzing metabolic enzymes. The PIPK family of phosphatidyl inositol phosphate kinases is weakly related, in having a kinase domain that is related both to ATP-grasp and PKL kinases, so we classify this among the larger set of PKL kinases.
Claimed Protein Kinase Activity
Two reports showed protein kinase activity associated with human IPTK1 [1, 2], when moderately purified from human cell culture. The kinase activity could phosphorylate several transcription factors and copurified with the COP9 signalosome complex. However, a later study [3] separated the protein and lipid kinase activities chromatographically, indicating that the original report may have been due to a contaminating protein kinase. Several predicted kinase-dead mutations abolished lipid kinase activity but did not affect the associated protein kinase activity.
Naming
The single human member is called ITPK1, but should not be confused with the human genes ITPKA, ITPKB and ITPKC, which belong to the IP3K family.
References
- Sun Y, Wilson MP, and Majerus PW. Inositol 1,3,4-trisphosphate 5/6-kinase associates with the COP9 signalosome by binding to CSN1. J Biol Chem. 2002 Nov 29;277(48):45759-64. DOI:10.1074/jbc.M208709200 |
- Wilson MP, Sun Y, Cao L, and Majerus PW. Inositol 1,3,4-trisphosphate 5/6-kinase is a protein kinase that phosphorylates the transcription factors c-Jun and ATF-2. J Biol Chem. 2001 Nov 2;276(44):40998-1004. DOI:10.1074/jbc.M106605200 |
- Qian X, Mitchell J, Wei SJ, Williams J, Petrovich RM, and Shears SB. The Ins(1,3,4)P3 5/6-kinase/Ins(3,4,5,6)P4 1-kinase is not a protein kinase. Biochem J. 2005 Jul 15;389(Pt 2):389-95. DOI:10.1042/BJ20050297 |
