Structural highlights
Function
[NEK7_HUMAN] Protein kinase which plays an important role in mitotic cell cycle progression. Required for microtubule nucleation activity of the centrosome, robust mitotic spindle formation and cytokinesis. Phosphorylates RPS6KB1.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Mitosis is controlled by multiple protein kinases, many of which are abnormally expressed in human cancers. Nek2, Nek6, Nek7, and Nek9 are NIMA-related kinases essential for proper mitotic progression. We determined the atomic structure of Nek7 and discovered an autoinhibited conformation that suggests a regulatory mechanism not previously described in kinases. Additionally, Nek2 adopts the same conformation when bound to a drug-like molecule. In both structures, a tyrosine side chain points into the active site, interacts with the activation loop, and blocks the alphaC helix. Tyrosine mutants of Nek7 and the related kinase Nek6 are constitutively active. The activity of Nek6 and Nek7, but not the tyrosine mutant, is increased by interaction with the Nek9 noncatalytic C-terminal domain, suggesting a mechanism in which the tyrosine is released from its autoinhibitory position. The autoinhibitory conformation is common to three Neks and provides a potential target for selective kinase inhibitors.
An autoinhibitory tyrosine motif in the cell-cycle-regulated Nek7 kinase is released through binding of Nek9.,Richards MW, O'Regan L, Mas-Droux C, Blot JM, Cheung J, Hoelder S, Fry AM, Bayliss R Mol Cell. 2009 Nov 25;36(4):560-70. PMID:19941817[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yissachar N, Salem H, Tennenbaum T, Motro B. Nek7 kinase is enriched at the centrosome, and is required for proper spindle assembly and mitotic progression. FEBS Lett. 2006 Nov 27;580(27):6489-95. Epub 2006 Nov 7. PMID:17101132 doi:http://dx.doi.org/10.1016/j.febslet.2006.10.069
- ↑ Kim S, Lee K, Rhee K. NEK7 is a centrosomal kinase critical for microtubule nucleation. Biochem Biophys Res Commun. 2007 Aug 17;360(1):56-62. Epub 2007 Jun 8. PMID:17586473 doi:http://dx.doi.org/10.1016/j.bbrc.2007.05.206
- ↑ O'Regan L, Fry AM. The Nek6 and Nek7 protein kinases are required for robust mitotic spindle formation and cytokinesis. Mol Cell Biol. 2009 Jul;29(14):3975-90. doi: 10.1128/MCB.01867-08. Epub 2009 May , 4. PMID:19414596 doi:http://dx.doi.org/10.1128/MCB.01867-08
- ↑ Richards MW, O'Regan L, Mas-Droux C, Blot JM, Cheung J, Hoelder S, Fry AM, Bayliss R. An autoinhibitory tyrosine motif in the cell-cycle-regulated Nek7 kinase is released through binding of Nek9. Mol Cell. 2009 Nov 25;36(4):560-70. PMID:19941817 doi:10.1016/j.molcel.2009.09.038
