serine/threonine protein kinase Nek9; nercc1 kinase; never in mitosis A-related kinase 9; NimA-related protein kinase 9 (NEK9, KIAA1995, NERCC)
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Function
- pleiotropic regulator of mitotic progression, participating in the control of spindle dynamics & chromosome separation
- phosphorylates different histones, myelin basic protein, beta-casein, & BICD2
- phosphorylates histone H3 on Ser & Thr & beta-casein on Ser
- important for G1/S transition & S phase progression
- phosphorylates NEK6 & NEK7 & stimulates their activity by releasing the autoinhibitory functions of Tyr-108 & Tyr-97 respectively
- activated during mitosis by intramolecular autophosphorylation
- activity & autophosphorylation is activated by Mn+2 >> Mg+2
- sensitive to increasing concentration of detergents
- not cell-cycle regulated but activity is higher in G0-arrested cells
- autophosphorylated on Ser & Thr
- when complexed with FACT, exhibits markedly elevated phosphorylation on Thr-210
- during mitosis, not phosphorylated on Thr-210
- phosphorylated by CDK1 in vitro
- binds to Ran GTPase
- has a greater affinity for Ran-GDP over Ran-GTP
- interacts with NEK6, NEK7 & BICD2
- interacts with SSRP1 & SUPT16H, the 2 subunits of the FACT complex
Structure
- homodimer
- dimerizes through its coiled-coil domain
- belongs to the protein kinase superfamily, NEK Ser/Thr protein kinase family, NIMA subfamily
- contains 1 protein kinase domain
- contains 6 RCC1 repeats
Compartment
Expression
- highest expression in heart, liver, kidney & testis
- also expressed in smooth muscle cells & fibroblasts
- expression varied mildly across the cell cycle
- highest expression in G1 & stationary-phase cells