NEK2

Domain

The leucine-zipper domain is required for its dimerization and activation.

Function

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). Phosphorylates CCDC102B either directly or indirectly which causes CCDC102B to dissociate from the centrosome and allows for centrosome separation (PubMed:30404835).

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.

Involvement in disease

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

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.

Sequence similarities

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

Tissue specificity

Isoform 1 and isoform 2 are expressed in peripheral blood T-cells and a wide variety of transformed cell types. Isoform 1 and isoform 4 are expressed in the testis. Up-regulated in various cancer cell lines, as well as primary breast tumors.

Cellular localization

• Isoform 1
• Nucleus
• Nucleus
• Nucleolus
• Cytoplasm
• Cytoplasm
• Cytoskeleton
• Microtubule organizing center
• Centrosome
• Cytoplasm
• Cytoskeleton
• Spindle pole
• Chromosome
• Centromere
• Kinetochore
• Chromosome
• Centromere
• 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
• Predominantly cytoplasmic.
• Isoform 4
• Nucleus
• Cytoplasm
• Cytoskeleton
• Microtubule organizing center
• Centrosome
• Predominantly nuclear.

Alternative names

• NEK2A
• NLK1
• NLK1
• NEK2A
• NEK2
• Serine/threonine-protein kinase Nek2
• HSPK 21
• Never in mitosis A-related kinase 2
• NimA-like protein kinase 1
• NimA-related protein kinase 2

Database links

• entrezGene:4751
• omim:604043
• swissprot:P51955

Target type

Proteins

Primary research area

Oncology

Molecular weight

51763Da