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The Aspergillus nidulans 'never in mitosis A' (NIMA) is a serine/ threonine kinase that controls initiation of mitosis, whereas its inactivation is necessary for mitotic exit. NIMA-related kinases (NEKs) are a group of protein kinases that are homologous to NIMA. Evidence suggests that NEKs perform functions similar to those of NIMA. Human NIMA-related kinase 6 (NEK6, synonym: SID6-1512) is comprised of 338 amino acids and shows both nuclear and cytoplasmic localizations in HeLa cells. NEK6 is required for mitotic progression of human cells. NEK6 is phosphorylated and activated during M phase. Inhibition of Nek6 function by either overexpression of an inactive Nek6 mutant or elimination of endogenous Nek6 by siRNA arrests cells in M phase and triggers apoptosis. Recombinant human NEK6 protein produced in insect cells effectively phosphorylates histones H1 and H3, but not casein. Thus, these results suggest that, unlike other mammalian NIMA-related kinases, NEK6 is a mitotic histone kinase which regulates chromatin condensation in mammalian cells. NEK6 transcripts are ubiquitously expressed with the highest expression found in the heart and skeletal muscle, and the hNek6 gene is localized to human chromosome 9q33-34. NEK6 has four isoforms with MW 35-40 kDa.