ID:NEK6_HUMAN DESCRIPTION: RecName: Full=Serine/threonine-protein kinase Nek6; EC=2.7.11.1; AltName: Full=Never in mitosis A-related kinase 6; Short=NimA-related protein kinase 6; AltName: Full=Protein kinase SID6-1512; FUNCTION: Protein kinase which plays an important role in mitotic cell cycle progression. Required for chromosome segregation at metaphase-anaphase transition, robust mitotic spindle formation and cytokinesis. Phosphorylates ATF4, CIR1, PTN, RAD26L, RBBP6, RPS7, RPS6KB1, TRIP4, STAT3 and histones H1 and H3. Phosphorylates KIF11 to promote mitotic spindle formation. Involved 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium. ENZYME REGULATION: Binding to NEK9 stimulates its activity by releasing the autoinhibitory function of Tyr-108. SUBUNIT: Interacts with STAT3 and RPS6KB1 (By similarity). 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 and TRIP4. INTERACTION: Q13526:PIN1; NbExp=3; IntAct=EBI-740364, EBI-714158; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Nucleus speckle. Cytoplasm, cytoskeleton, centrosome. Cytoplasm, cytoskeleton, spindle pole. Note=Co-localizes with APBB1 at the nuclear speckles. Co-localizes with PIN1 in the nucleus. Co-localizes 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. TISSUE SPECIFICITY: Ubiquitous, with highest expression in heart and skeletal muscle. Up-regulated in a variety of malignant cancers, such as breast, colon, lung, and gastric cancers. INDUCTION: Up-regulated during the M phase of cell cycle progression. Down-regulated in both replicative and premature senescence of cancer cells. 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. PTM: 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. SIMILARITY: Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily. SIMILARITY: Contains 1 protein kinase domain. SEQUENCE CAUTION: Sequence=AAG13417.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part; Sequence=AAH00101.2; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAH04174.2; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=AAH04209.2; Type=Erroneous initiation; Note=Translation N-terminally extended; Sequence=BAA85045.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00069 - Protein kinase domain PF07714 - Protein tyrosine and serine/threonine kinase
SCOP Domains: 56112 - Protein kinase-like (PK-like)
ModBase Predicted Comparative 3D Structure on Q9HC98
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.