NEK2

This gene encodes a serine/threonine-protein kinase that is involved in mitotic regulation. This protein is localized to the centrosome, and undetectable during G1 phase, but accumulates progressively throughout the S phase, reaching maximal levels in late G2 phase. Alternatively spliced transcript variants encoding different isoforms with distinct C-termini have been noted for this gene.

NIMA (never in mitosis gene a)-related kinase 2

Protein kinase which is involved in the control of centrosome separation and bipolar spindle formation in mitotic cells and chromatin condensation in meiotic cells. Regulates centrosome separation (essential for the formation of bipolar spindles and high-fidelity chromosome separation) by phosphorylating centrosomal proteins such as CROCC, CEP250 and NINL, resulting in their displacement from the centrosomes. Regulates kinetochore microtubule attachment stability in mitosis via phosphorylation of NDC80. Involved in regulation of mitotic checkpoint protein complex via phosphorylation of CDC20 and MAD2L1. Plays an active role in chromatin condensation during the first meiotic division through phosphorylation of HMGA2. Phosphorylates: PPP1CC; SGO1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates CEP68 and CNTLN directly or indirectly (PubMed:24554434).

NEK2-mediated phosphorylation of CEP68 promotes CEP68 dissociation from the centrosome and its degradation at the onset of mitosis (PubMed:25704143).

Involved in the regulation of centrosome disjunction (PubMed:26220856).

Isoform 1:
Phosphorylates and activates NEK11 in G1/S-arrested cells.

Isoform 2:
Not present in the nucleolus and, in contrast to isoform 1, does not phosphorylate and activate NEK11 in G1/S-arrested cells.

Blastocyst development Source: Ensembl
Cell division Source: UniProtKB-KW
Centrosome separation Source: UniProtKB
Chromosome segregation Source: UniProtKB
Meiotic cell cycle Source: UniProtKB-KW
Mitotic cell cycle Source: ProtInc
Mitotic sister chromatid segregation Source: Ensembl
Mitotic spindle assembly Source: Ensembl
Negative regulation of centriole-centriole cohesion Source: UniProtKB
Negative regulation of DNA binding Source: Ensembl
Positive regulation of telomerase activity Source: BHF-UCL
Positive regulation of telomere capping Source: BHF-UCL
Positive regulation of telomere maintenance via telomerase Source: BHF-UCL
Protein autophosphorylation Source: UniProtKB
Protein phosphorylation Source: UniProtKB
Regulation of attachment of spindle microtubules to kinetochore Source: UniProtKB
Regulation of mitotic centrosome separation Source: UniProtKB
Regulation of mitotic nuclear division Source: ProtInc
Spindle assembly Source: UniProtKB

Isoform 1:
Nucleus
nucleolus
Cytoplasm
Cytoskeleton
centrosome
spindle pole
Other locations
kinetochore
centromere
Note: STK3/MST2 and SAV1 are required for its targeting to the centrosome. Colocalizes with SGO1 and MAD1L1 at the kinetochore. Not associated with kinetochore in the interphase but becomes associated with it upon the breakdown of the nuclear envelope. Has a nucleolar targeting/ retention activity via a coiled-coil domain at the C-terminal end.
Isoform 2:
Cytoplasm
Note: Predominantly cytoplasmic.
Isoform 4:
Nucleus
Cytoskeleton
centrosome
Note: Predominantly nuclear.

Retinitis pigmentosa 67 (RP67):
A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.

Activated by autophosphorylation. Protein phosphatase 1 represses autophosphorylation and activation of isoform 1 by dephosphorylation. Phosphorylation by STK3/MST2 is necessary for its localization to the centrosome.