NEK2

Serine/threonine-protein kinase Nek2 is an enzyme that in humans is encoded by the NEK2 gene.[4][5]

NEK2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2JAV, 2W5A, 2W5B, 2WQO, 2XK3, 2XK4, 2XK6, 2XK7, 2XK8, 2XKC, 2XKD, 2XKE, 2XKF, 2XNM, 2XNN, 2XNO, 2XNP, 4A4X, 4AFE
Identifiers
Aliases	NEK2, HsPK21, NEK2A, NLK1, PPP1R111, RP67, NIMA related kinase 2
External IDs	OMIM: 604043 MGI: 109359 HomoloGene: 74441 GeneCards: NEK2
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q32.3 Start 211,658,657 bp[1] End 211,675,630 bp[1]
RNA expression pattern More reference expression data
Gene ontology Molecular function • transferase activity • protein kinase activity • nucleotide binding • metal ion binding • kinase activity • protein serine/threonine kinase activity • GO:0001948 protein binding • protein phosphatase binding • ATP binding Cellular component • condensed chromosome kinetochore • cytosol • centrosome • spindle pole • chromosome • condensed nuclear chromosome • microtubule organizing center • midbody • nucleolus • microtubule • chromosome, centromeric region • cytoskeleton • kinetochore • nucleoplasm • cell nucleus • cytoplasm • macromolecular complex Biological process • positive regulation of telomere capping • regulation of mitotic centrosome separation • phosphorylation • chromosome segregation • negative regulation of DNA binding • positive regulation of telomere maintenance via telomerase • spindle assembly • cell division • protein phosphorylation • mitotic spindle assembly • G2/M transition of mitotic cell cycle • GO:0007126 meiotic cell cycle • positive regulation of telomerase activity • centrosome separation • mitotic sister chromatid segregation • autophosphorylation • cell cycle • negative regulation of centriole-centriole cohesion • regulation of attachment of spindle microtubules to kinetochore • blastocyst development • regulation of mitotic nuclear division • ciliary basal body docking • GO:0007067 mitotic cell cycle • regulation of G2/M transition of mitotic cell cycle Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4751	18005
Ensembl	ENSG00000117650	ENSMUSG00000026622
UniProt	P51955	O35942
RefSeq (mRNA)	NM_001204182 NM_001204183 NM_002497	NM_010892
RefSeq (protein)	NP_001191111 NP_001191112 NP_002488	NP_035022
Location (UCSC)	Chr 1: 211.66 – 211.68 Mb	n/a
PubMed search	[2]	[3]
Wikidata
View/Edit Human View/Edit Mouse

Interactions

NEK2 has been shown to interact with MAPK1[6] and NDC80.[7][8] 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; SGOL1; NECAB3 and NPM1. Essential for localization of MAD2L1 to kinetochore and MAPK1 and NPM1 to the centrosome. Isoform 1 phosphorylates and activates NEK11 in G1/S-arrested cells. Isoform 2, which is not present in the nucleolus, does not [Uniprot].

References

1. GRCh38: Ensembl release 89: ENSG00000117650 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. Schultz SJ, Nigg EA (Feb 1994). "Identification of 21 novel human protein kinases, including 3 members of a family related to the cell cycle regulator nimA of Aspergillus nidulans". Cell Growth Differ. 4 (10): 821–30. PMID 8274451.
5. "Entrez Gene: NEK2 NIMA (never in mitosis gene a)-related kinase 2".
6. Lou Y, Xie W, Zhang DF, Yao JH, Luo ZF, Wang YZ, Shi YY, Yao XB (Aug 2004). "Nek2A specifies the centrosomal localization of Erk2". Biochem. Biophys. Res. Commun. 321 (2): 495–501. doi:10.1016/j.bbrc.2004.06.171. PMID 15358203.
7. Chen Y, Riley DJ, Zheng L, Chen PL, Lee WH (Dec 2002). "Phosphorylation of the mitotic regulator protein Hec1 by Nek2 kinase is essential for faithful chromosome segregation". J. Biol. Chem. 277 (51): 49408–16. doi:10.1074/jbc.M207069200. PMID 12386167.
8. Chen Y, Sharp ZD, Lee WH (Sep 1997). "HEC binds to the seventh regulatory subunit of the 26 S proteasome and modulates the proteolysis of mitotic cyclins". J. Biol. Chem. 272 (38): 24081–7. doi:10.1074/jbc.272.38.24081. PMID 9295362.

Further reading

• Hayward DG, Fry AM (2006). "Nek2 kinase in chromosome instability and cancer". Cancer Lett. 237 (2): 155–66. doi:10.1016/j.canlet.2005.06.017. PMID 16084011.
• Schultz SJ, Fry AM, Sütterlin C, Ried T, Nigg EA (1994). "Cell cycle-dependent expression of Nek2, a novel human protein kinase related to the NIMA mitotic regulator of Aspergillus nidulans". Cell Growth Differ. 5 (6): 625–35. PMID 7522034.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Fry AM, Meraldi P, Nigg EA (1998). "A centrosomal function for the human Nek2 protein kinase, a member of the NIMA family of cell cycle regulators". EMBO J. 17 (2): 470–81. doi:10.1093/emboj/17.2.470. PMC 1170398. PMID 9430639.
• Fry AM, Mayor T, Meraldi P, Stierhof YD, Tanaka K, Nigg EA (1998). "C-Nap1, a novel centrosomal coiled-coil protein and candidate substrate of the cell cycle-regulated protein kinase Nek2". J. Cell Biol. 141 (7): 1563–74. doi:10.1083/jcb.141.7.1563. PMC 2133000. PMID 9647649.
• Fry AM, Arnaud L, Nigg EA (1999). "Activity of the human centrosomal kinase, Nek2, depends on an unusual leucine zipper dimerization motif". J. Biol. Chem. 274 (23): 16304–10. doi:10.1074/jbc.274.23.16304. PMID 10347187.
• Schutte BC, Bjork BC, Coppage KB, Malik MI, Gregory SG, Scott DJ, Brentzell LM, Watanabe Y, Dixon MJ, Murray JC (2000). "A preliminary gene map for the Van der Woude syndrome critical region derived from 900 kb of genomic sequence at 1q32-q41". Genome Res. 10 (1): 81–94. doi:10.1101/gr.10.1.81 (inactive 2020-03-19). PMC 310500. PMID 10645953.
• Helps NR, Luo X, Barker HM, Cohen PT (2001). "NIMA-related kinase 2 (Nek2), a cell-cycle-regulated protein kinase localized to centrosomes, is complexed to protein phosphatase 1". Biochem. J. 349 (Pt 2): 509–18. doi:10.1042/0264-6021:3490509. PMC 1221174. PMID 10880350.
• Hames RS, Fry AM (2002). "Alternative splice variants of the human centrosome kinase Nek2 exhibit distinct patterns of expression in mitosis". Biochem. J. 361 (Pt 1): 77–85. doi:10.1042/0264-6021:3610077. PMC 1222281. PMID 11742531.
• Ha Kim Y, Yeol Choi J, Jeong Y, Wolgemuth DJ, Rhee K (2002). "Nek2 localizes to multiple sites in mitotic cells, suggesting its involvement in multiple cellular functions during the cell cycle". Biochem. Biophys. Res. Commun. 290 (2): 730–6. doi:10.1006/bbrc.2001.6212. PMID 11785960.
• Eto M, Elliott E, Prickett TD, Brautigan DL (2003). "Inhibitor-2 regulates protein phosphatase-1 complexed with NimA-related kinase to induce centrosome separation". J. Biol. Chem. 277 (46): 44013–20. doi:10.1074/jbc.M208035200. PMID 12221103.
• Chen Y, Riley DJ, Zheng L, Chen PL, Lee WH (2003). "Phosphorylation of the mitotic regulator protein Hec1 by Nek2 kinase is essential for faithful chromosome segregation". J. Biol. Chem. 277 (51): 49408–16. doi:10.1074/jbc.M207069200. PMID 12386167.
• Faragher AJ, Fry AM (2004). "Nek2A kinase stimulates centrosome disjunction and is required for formation of bipolar mitotic spindles". Mol. Biol. Cell. 14 (7): 2876–89. doi:10.1091/mbc.E03-02-0108. PMC 165683. PMID 12857871.
• Lou Y, Yao J, Zereshki A, Dou Z, Ahmed K, Wang H, Hu J, Wang Y, Yao X (2004). "NEK2A interacts with MAD1 and possibly functions as a novel integrator of the spindle checkpoint signaling". J. Biol. Chem. 279 (19): 20049–57. doi:10.1074/jbc.M314205200. PMID 14978040.
• Noguchi K, Fukazawa H, Murakami Y, Uehara Y (2004). "Nucleolar Nek11 is a novel target of Nek2A in G1/S-arrested cells". J. Biol. Chem. 279 (31): 32716–27. doi:10.1074/jbc.M404104200. PMID 15161910.
• Fortna A, Kim Y, MacLaren E, Marshall K, Hahn G, Meltesen L, Brenton M, Hink R, Burgers S, Hernandez-Boussard T, Karimpour-Fard A, Glueck D, McGavran L, Berry R, Pollack J, Sikela JM (2006). "Lineage-specific gene duplication and loss in human and great ape evolution". PLOS Biol. 2 (7): E207. doi:10.1371/journal.pbio.0020207. PMC 449870. PMID 15252450.
• Lou Y, Xie W, Zhang DF, Yao JH, Luo ZF, Wang YZ, Shi YY, Yao XB (2004). "Nek2A specifies the centrosomal localization of Erk2". Biochem. Biophys. Res. Commun. 321 (2): 495–501. doi:10.1016/j.bbrc.2004.06.171. PMID 15358203.