Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

NEK2 (P51955) - Overview - Molecular Target Synopsis

Protein


NEK2, Serine/threonine-protein kinase Nek2
Enzyme Classification 2.7.11.1
UniProt P51955

Also Known as NEK2_HUMAN, NEK2, NEK2A, NLK1

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. Isoform 1, isoform 2 and isoform 4 form homo- and heterodimers. Interacts with NECAB3 and HMGA2 (By similarity). Isoform 1 interacts with CDC20, CTNB1, MAD1L1, MAPK, NEK11, NPM1, NDC80, PCNT and SGO1 (PubMed:14978040, PubMed:15358203, PubMed:15388344, PubMed:15161910, PubMed:17621308, PubMed:18086858, PubMed:18297113, PubMed:20599736, PubMed:20034488). Isoform 1 interacts with STK3/MST2 (via SARAH domain) and SAV1 (via SARAH domain) (PubMed:21076410). Isoform 1 and isoform 2 interact with MAD2L1 (PubMed:20034488). Isoform 1 and isoform 4 interact with PPP1CA and PPP1CC (PubMed:15659832, PubMed:17283141). Interacts with CEP68; the interaction leads to phosphorylation of CEP68. Interacts with CNTLN; the interaction leads to phosphorylation of CNTLN (PubMed:24554434). Isoform 1 interacts with CEP85 (PubMed:26220856).

2XNO
STRUCTURE OF NEK2 BOUND TO CCT243779
RCSB/PDB
Inspect Structure
See all 3D Structures for NEK2

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: NEK2 is active in the following subcellular-locations: centromere, centrosome, chromosome, cytoplasm, cytoskeleton, kinetochore, microtubule organizing center, nucleolus, nucleus, spindle pole.
GO terms: NEK2 is active in the following subcellular-locations: centrosome, condensed chromosome kinetochore, condensed nuclear chromosome, cytosol, kinetochore, microtubule, midbody, nucleolus, nucleoplasm, nucleus, protein-containing complex, spindle pole.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project NEK2 has gain in 3 cell-lines, loss in 1 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: T47D, COLO205, NCI_H322M

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: HCC1599, NCI-H322T, HCC1576

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HeLa-S3, A549, K562

(see details)

RNA Interference


NEK2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: HCH1, SKGT4. (see details)

3D Structures


For NEK2 there are:
25 structures (25 chains) solved
24 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


NEK2 has been screened with 1061 compounds (1848 bioactivities), 33 compounds have bioactivities that show binding affinity of <= 500nM (40 bioactivities). (see details)