serine/threonine protein kinase Nek6; never in mitosis A-related kinase 6; NimA-related protein kinase 6; protein kinase SID6-1512 (NEK6)

Function

• protein kinase plays an important role in mitotic cell cycle progression
• required for chromosome segregation at metaphase-anaphase transition, robust mitotic spindle formation & cytokinesis
• phosphorylates ATF4, CIR1, PTN, RAD26L, RBBP6, RPS7, RPS6KB1, TRIP4, STAT3 & histones H1 & H3
• phosphorylates KIF11 to promote mitotic spindle formation
• role in G2/M phase cell cycle arrest induced by DNA damage
• inhibition of activity results in apoptosis
• may contribute to tumorigenesis by suppressing p53/TP53- induced cancer cell senescence
• binding to NEK9 stimulates its activity by releasing the autoinhibitory function of Tyr-108
• autophosphorylated
• phosphorylation at Ser-206 is required for its activation
• phosphorylated upon IR or UV-induced DNA damage
• phosphorylated by CHK1 & CHK2
• interaction with APBB1
• down-regulates phosphorylation at Thr-210
• interacts with STAT3 & RPS6KB1 (putative)
• interacts with NEK9, predominantly in mitosis
• interacts with KIF11 (via C-terminus)
• interacts with APBB1 (via WW domain)
• interacts with ANKRA2, ATF4, ARHGAP33, CDC42, CIR1, PRAM1, PTN, PRDX3, PIN1, RAD26L, RBBP6, RPS7 & TRIP4

Cofactor: Mg+2

Structure

• displays an autoinhibited conformation: Tyr-108 side chain points into the active site, interacts with the activation loop, & blocks the alphaC helix
• the autoinhibitory conformation is released upon binding with NEK9
• belongs to the protein kinase superfamily, NEK Ser/Thr protein kinase family, NIMA subfamily
• contains 1 protein kinase domain

Compartment

• cytoplasm, nucleus, nuclear speckle
• cytoskeleton, centrosome, 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 & PHF1 in the centrosome
• localizes to spindle microtubules in metaphase & anaphase & to the midbody during cytokinesis

Alternative splicing

named isoforms=4

Expression

• ubiquitous
• highest expression in heart & skeletal muscle
• up-regulated during the M phase of cell cycle progression
• down-regulated in both replicative senescence & premature senescence of cancer cells

Pathology

• up-regulated in a variety of malignant cancers, such as breast cancer, colorectal carcinoma, lung carcinoma, & gastric cancers

More general terms

• serine/threonine protein kinase NEK

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=10783
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:10783
• OMIM: https://mirror.omim.org/entry/604884
• UniProt: http://www.uniprot.org/uniprot/Q9HC98.html