Serine/threonine-protein kinase Nek6

Domain

Displays an autoinhibited conformation: Tyr-108 side chain points into the active site, interacts with the activation loop, and blocks the alphaC helix. The autoinhibitory conformation is released upon binding with NEK9.

Function

Protein kinase which plays an important role in mitotic cell cycle progression (PubMed:11516946, PubMed:14563848). Required for chromosome segregation at metaphase-anaphase transition, robust mitotic spindle formation and cytokinesis (PubMed:19414596). Phosphorylates ATF4, CIR1, PTN, RAD26L, RBBP6, RPS7, RPS6KB1, TRIP4, STAT3 and histones H1 and H3 (PubMed:12054534, PubMed:20873783). Phosphorylates KIF11 to promote mitotic spindle formation (PubMed:19001501). Involved in G2/M phase cell cycle arrest induced by DNA damage (PubMed:18728393). Inhibition of activity results in apoptosis. May contribute to tumorigenesis by suppressing p53/TP53-induced cancer cell senescence (PubMed:21099361). Phosphorylates EML4 at 'Ser-144', promoting its dissociation from microtubules during mitosis which is required for efficient chromosome congression (PubMed:31409757).

Post-translational modifications

Autophosphorylated. Phosphorylation at Ser-206 is required for its activation. Phosphorylated upon IR or UV-induced DNA damage. Phosphorylated by CHEK1 and CHEK2. Interaction with APBB1 down-regulates phosphorylation at Thr-210.

Sequence Similarities

Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.

Tissue Specificity

Ubiquitous, with highest expression in heart and skeletal muscle.

Cellular localization

• Cytoplasm
• Nucleus
• Nucleus speckle
• Cytoplasm
• Cytoskeleton
• Microtubule organizing center
• Centrosome
• Cytoplasm
• Cytoskeleton
• Spindle pole
• Colocalizes with APBB1 at the nuclear speckles. Colocalizes with PIN1 in the nucleus. Colocalizes with ATF4, CIR1, ARHGAP33, ANKRA2, CDC42, NEK9, RAD26L, RBBP6, RPS7, TRIP4, RELB and PHF1 in the centrosome. Localizes to spindle microtubules in metaphase and anaphase and to the midbody during cytokinesis.

Alternative names

Serine/threonine-protein kinase Nek6, Never in mitosis A-related kinase 6, Protein kinase SID6-1512, NimA-related protein kinase 6, NEK6

Database links

swissprot:Q9HC98 omim:604884 cloneId:BC004174 entrezGene:10783