NIMA-related kinase 1 (protein kinase) (NEK1)

NIMA-related kinase 1 is a serine/threonine protein kinase of the NEK family that participates in centrosome dynamics, mitotic spindle assembly, primary cilium function, and is essential for early DNA damage response signaling, including priming of ATR and phosphorylation of Rad54. The human NEK1 kinase domain structure has been solved in apo and ATP-mimetic inhibitor-bound forms, supporting efforts to design selective inhibitors and suggesting possible use as chemo- or radiosensitizers. NEK1 is highly expressed in germ cells, has functional similarity to fungal NIMA in chromatin condensation, and its deficiency leads to defective checkpoint activation, chromosome breaks, aneuploidy, and tumor predisposition in mice. Mutations in NEK1 are associated with ciliopathies (including polycystic kidney disease), short-rib thoracic dysplasia, Mohr syndrome, and have been implicated in amyotrophic lateral sclerosis and cancers.

Other names

NEK1Kidney, anemia and testis (kat) mutant locus (mouse; historical/alias context)NIMA (never in mitosis gene A)-related kinase 1

ATP-competitive kinase inhibition of NEK1 (based on kinase domain structures with ATP-mimetic inhibitors; anticipated mechanism for experimental/tool inhibitors). Chemo- or radio-sensitization via NEK1 inhibition to impair DNA damage repair signaling (proposed based on structural/functional data).