Kinase Subfamily NEK10
Kinase Classification: Group Other: Family NEK: Subfamily NEK10
NEK10 is involved in UV radiation response and cilium biology.
Evolution
NEK10 is animal-specific, and is single copy in all genomes. It is lost from insects and arachnids, including Drosophila.
Domain Structure
Unlike other NEKs, NEK10 has the kinase domain in the middle. Armadillo repeats are present upstream of the kinase domain, which is followed by a long poorly conserved region and then by a conserved region that is not a known domain.
Functions
Like other NEKs, NEK10 is associated with cilium biology in multiple species. Mutations in human NEK10 are associated with cilium function in lung [1] and with Primary Ciliary Dyskinesia [2]. The worm homolog, nekl-4 localizes to the base of cilia and implicated in microtubule glutamylation and ciliary integrity [3]. Protein Interaction mapping shows few associated proteins, but one, KIAA0586, is a conserved centrosomal protein that functions in ciliogenesis and responds to hedgehog signaling. Both KIAA0586 and NEK10 are expressed particularly highly in testis.
Human NEK10 is also implicated in the DNA damage response, similar to other NEK subfamilies: UV radiation induces NEK10 to bind Raf-1 and induce MEK1 autophosphorylation, to activate the G2/M cell cycle checkpoint [4]. NEK10 also phosphorylates p53 on Y327F and this enhances its transcriptional activity [5]
References
- Chivukula RR, Montoro DT, Leung HM, Yang J, Shamseldin HE, Taylor MS, Dougherty GW, Zariwala MA, Carson J, Daniels MLA, Sears PR, Black KE, Hariri LP, Almogarri I, Frenkel EM, Vinarsky V, Omran H, Knowles MR, Tearney GJ, Alkuraya FS, and Sabatini DM. A human ciliopathy reveals essential functions for NEK10 in airway mucociliary clearance. Nat Med. 2020 Feb;26(2):244-251. DOI:10.1038/s41591-019-0730-x |
- Al Mutairi F, Alkhalaf R, Alkhorayyef A, Alroqi F, Yusra A, Umair M, Nouf F, Khan A, Meshael A, Hamad A, Monira A, Asiri A, Alhamoudi KM, and Alfadhel M. Homozygous truncating NEK10 mutation, associated with primary ciliary dyskinesia: a case report. BMC Pulm Med. 2020 May 15;20(1):141. DOI:10.1186/s12890-020-1175-1 |
- Power KM, Akella JS, Gu A, Walsh JD, Bellotti S, Morash M, Zhang W, Ramadan YH, Ross N, Golden A, Smith HE, Barr MM, and O'Hagan R. Mutation of NEKL-4/NEK10 and TTLL genes suppress neuronal ciliary degeneration caused by loss of CCPP-1 deglutamylase function. PLoS Genet. 2020 Oct;16(10):e1009052. DOI:10.1371/journal.pgen.1009052 |
- Moniz LS and Stambolic V. Nek10 mediates G2/M cell cycle arrest and MEK autoactivation in response to UV irradiation. Mol Cell Biol. 2011 Jan;31(1):30-42. DOI:10.1128/MCB.00648-10 |
- Haider N, Dutt P, van de Kooij B, Ho J, Palomero L, Pujana MA, Yaffe M, and Stambolic V. NEK10 tyrosine phosphorylates p53 and controls its transcriptional activity. Oncogene. 2020 Jul;39(30):5252-5266. DOI:10.1038/s41388-020-1361-x |
