Serine/threonine-protein kinase Nek2

Details

Name
Serine/threonine-protein kinase Nek2
Synonyms
  • 2.7.11.1
  • HSPK 21
  • NEK2A
  • Never in mitosis A-related kinase 2
  • NimA-like protein kinase 1
  • NimA-related protein kinase 2
  • NLK1
Gene Name
NEK2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0007282|Serine/threonine-protein kinase Nek2
MPSRAEDYEVLYTIGTGSYGRCQKIRRKSDGKILVWKELDYGSMTEAEKQMLVSEVNLLR
ELKHPNIVRYYDRIIDRTNTTLYIVMEYCEGGDLASVITKGTKERQYLDEEFVLRVMTQL
TLALKECHRRSDGGHTVLHRDLKPANVFLDGKQNVKLGDFGLARILNHDTSFAKTFVGTP
YYMSPEQMNRMSYNEKSDIWSLGCLLYELCALMPPFTAFSQKELAGKIREGKFRRIPYRY
SDELNEIITRMLNLKDYHRPSVEEILENPLIADLVADEQRRNLERRGRQLGEPEKSQDSS
PVLSELKLKEIQLQERERALKAREERLEQKEQELCVRERLAEDKLARAENLLKNYSLLKE
RKFLSLASNPELLNLPSSVIKKKVHFSGESKENIMRSENSESQLTSKSKCKDLKKRLHAA
QLRAQALSDIEKNYQLKSRQILGMR
Number of residues
445
Molecular Weight
51762.93
Theoretical pI
9.25
GO Classification
Functions
ATP binding / metal ion binding / protein kinase activity / protein phosphatase binding / protein serine/threonine kinase activity
Processes
anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process / blastocyst development / cell division / centrosome separation / chromosome segregation / G2/M transition of mitotic cell cycle / meiotic cell cycle / mitotic cell cycle / mitotic nuclear division / mitotic sister chromatid segregation / mitotic spindle assembly / negative regulation of centriole-centriole cohesion / negative regulation of DNA binding / organelle organization / positive regulation of telomerase activity / positive regulation of telomere capping / positive regulation of telomere maintenance via telomerase / protein autophosphorylation / protein phosphorylation / regulation of attachment of spindle microtubules to kinetochore / regulation of mitotic centrosome separation / regulation of mitotic nuclear division / spindle assembly
Components
centrosome / condensed chromosome kinetochore / condensed nuclear chromosome / cytosol / kinetochore / microtubule / midbody / nucleolus / protein complex / spindle pole
General Function
Protein serine/threonine kinase activity
Specific 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; 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.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0021372|Serine/threonine-protein kinase Nek2 (NEK2)
ATGCCTTCCCGGGCTGAGGACTATGAAGTGTTGTACACCATTGGCACAGGCTCCTACGGC
CGCTGCCAGAAGATCCGGAGGAAGAGTGATGGCAAGATATTAGTTTGGAAAGAACTTGAC
TATGGCTCCATGACAGAAGCTGAGAAACAGATGCTTGTTTCTGAAGTGAATTTGCTTCGT
GAACTGAAACATCCAAACATCGTTCGTTACTATGATCGGATTATTGACCGGACCAATACA
ACACTGTACATTGTAATGGAATATTGTGAAGGAGGGGATCTGGCTAGTGTAATTACAAAG
GGAACCAAGGAAAGGCAATACTTAGATGAAGAGTTTGTTCTTCGAGTGATGACTCAGTTG
ACTCTGGCCCTGAAGGAATGCCACAGACGAAGTGATGGTGGTCATACCGTATTGCATCGG
GATCTGAAACCAGCCAATGTTTTCCTGGATGGCAAGCAAAACGTCAAGCTTGGAGACTTT
GGGCTAGCTAGAATATTAAACCATGACACGAGTTTTGCAAAAACATTTGTTGGCACACCT
TATTACATGTCTCCTGAACAAATGAATCGCATGTCCTACAATGAGAAATCAGATATCTGG
TCATTGGGCTGCTTGCTGTATGAGTTATGTGCATTAATGCCTCCATTTACAGCTTTTAGC
CAGAAAGAACTCGCTGGGAAAATCAGAGAAGGCAAATTCAGGCGAATTCCATACCGTTAC
TCTGATGAATTGAATGAAATTATTACGAGGATGTTAAACTTAAAGGATTACCATCGACCT
TCTGTTGAAGAAATTCTTGAGAACCCTTTAATAGCAGATTTGGTTGCAGACGAGCAAAGA
AGAAATCTTGAGAGAAGAGGGCGACAATTAGGAGAGCCAGAAAAATCGCAGGATTCCAGC
CCTGTATTGAGTGAGCTGAAACTGAAGGAAATTCAGTTACAGGAGCGAGAGCGAGCTCTC
AAAGCAAGAGAAGAAAGATTGGAGCAGAAAGAACAGGAGCTTTGTGTTCGTGAGAGACTA
GCAGAGGACAAACTGGCTAGAGCAGAAAATCTGTTGAAGAACTACAGCTTGCTAAAGGAA
CGGAAGTTCCTGTCTCTGGCAAGTAATCCAGAGTCTCACTTTGTTGCCCAGGCTGGAATG
CAGTGGTGTGATCACAGCTCAATGTAG
Chromosome Location
1
Locus
1q32.2-q41
External Identifiers
ResourceLink
UniProtKB IDP51955
UniProtKB Entry NameNEK2_HUMAN
GenBank Protein ID479171
GenBank Gene IDZ29066
HGNC IDHGNC:7745
General References
  1. Schultz SJ, Fry AM, Sutterlin C, Ried T, Nigg EA: Cell cycle-dependent expression of Nek2, a novel human protein kinase related to the NIMA mitotic regulator of Aspergillus nidulans. Cell Growth Differ. 1994 Jun;5(6):625-35. [Article]
  2. Hames RS, Fry AM: Alternative splice variants of the human centrosome kinase Nek2 exhibit distinct patterns of expression in mitosis. Biochem J. 2002 Jan 1;361(Pt 1):77-85. [Article]
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  5. Schultz SJ, Nigg EA: 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. 1993 Oct;4(10):821-30. [Article]
  6. Fardilha M, Wu W, Sa R, Fidalgo S, Sousa C, Mota C, da Cruz e Silva OA, da Cruz e Silva EF: Alternatively spliced protein variants as potential therapeutic targets for male infertility and contraception. Ann N Y Acad Sci. 2004 Dec;1030:468-78. [Article]
  7. Lou Y, Yao J, Zereshki A, Dou Z, Ahmed K, Wang H, Hu J, Wang Y, Yao X: NEK2A interacts with MAD1 and possibly functions as a novel integrator of the spindle checkpoint signaling. J Biol Chem. 2004 May 7;279(19):20049-57. Epub 2004 Feb 20. [Article]
  8. Faragher AJ, Fry AM: Nek2A kinase stimulates centrosome disjunction and is required for formation of bipolar mitotic spindles. Mol Biol Cell. 2003 Jul;14(7):2876-89. Epub 2003 Apr 17. [Article]
  9. Lou Y, Xie W, Zhang DF, Yao JH, Luo ZF, Wang YZ, Shi YY, Yao XB: Nek2A specifies the centrosomal localization of Erk2. Biochem Biophys Res Commun. 2004 Aug 20;321(2):495-501. [Article]
  10. Yao J, Fu C, Ding X, Guo Z, Zenreski A, Chen Y, Ahmed K, Liao J, Dou Z, Yao X: Nek2A kinase regulates the localization of numatrin to centrosome in mitosis. FEBS Lett. 2004 Sep 24;575(1-3):112-8. [Article]
  11. Noguchi K, Fukazawa H, Murakami Y, Uehara Y: Nucleolar Nek11 is a novel target of Nek2A in G1/S-arrested cells. J Biol Chem. 2004 Jul 30;279(31):32716-27. Epub 2004 May 25. [Article]
  12. Mi J, Guo C, Brautigan DL, Larner JM: Protein phosphatase-1alpha regulates centrosome splitting through Nek2. Cancer Res. 2007 Feb 1;67(3):1082-9. [Article]
  13. Fu G, Ding X, Yuan K, Aikhionbare F, Yao J, Cai X, Jiang K, Yao X: Phosphorylation of human Sgo1 by NEK2A is essential for chromosome congression in mitosis. Cell Res. 2007 Jul;17(7):608-18. [Article]
  14. Wu W, Baxter JE, Wattam SL, Hayward DG, Fardilha M, Knebel A, Ford EM, da Cruz e Silva EF, Fry AM: Alternative splicing controls nuclear translocation of the cell cycle-regulated Nek2 kinase. J Biol Chem. 2007 Sep 7;282(36):26431-40. Epub 2007 Jul 11. [Article]
  15. Bahmanyar S, Kaplan DD, Deluca JG, Giddings TH Jr, O'Toole ET, Winey M, Salmon ED, Casey PJ, Nelson WJ, Barth AI: beta-Catenin is a Nek2 substrate involved in centrosome separation. Genes Dev. 2008 Jan 1;22(1):91-105. Epub 2007 Dec 17. [Article]
  16. Zahedi RP, Lewandrowski U, Wiesner J, Wortelkamp S, Moebius J, Schutz C, Walter U, Gambaryan S, Sickmann A: Phosphoproteome of resting human platelets. J Proteome Res. 2008 Feb;7(2):526-34. Epub 2007 Dec 19. [Article]
  17. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
  18. Du J, Cai X, Yao J, Ding X, Wu Q, Pei S, Jiang K, Zhang Y, Wang W, Shi Y, Lai Y, Shen J, Teng M, Huang H, Fei Q, Reddy ES, Zhu J, Jin C, Yao X: The mitotic checkpoint kinase NEK2A regulates kinetochore microtubule attachment stability. Oncogene. 2008 Jul 3;27(29):4107-14. doi: 10.1038/onc.2008.34. Epub 2008 Feb 25. [Article]
  19. Richards MW, O'Regan L, Mas-Droux C, Blot JM, Cheung J, Hoelder S, Fry AM, Bayliss R: An autoinhibitory tyrosine motif in the cell-cycle-regulated Nek7 kinase is released through binding of Nek9. Mol Cell. 2009 Nov 25;36(4):560-70. doi: 10.1016/j.molcel.2009.09.038. [Article]
  20. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H: Large-scale proteomics analysis of the human kinome. Mol Cell Proteomics. 2009 Jul;8(7):1751-64. doi: 10.1074/mcp.M800588-MCP200. Epub 2009 Apr 15. [Article]
  21. Matsuo K, Nishimura T, Hayakawa A, Ono Y, Takahashi M: Involvement of a centrosomal protein kendrin in the maintenance of centrosome cohesion by modulating Nek2A kinase activity. Biochem Biophys Res Commun. 2010 Jul 23;398(2):217-23. doi: 10.1016/j.bbrc.2010.06.063. Epub 2010 Jun 18. [Article]
  22. Liu Q, Hirohashi Y, Du X, Greene MI, Wang Q: Nek2 targets the mitotic checkpoint proteins Mad2 and Cdc20: a mechanism for aneuploidy in cancer. Exp Mol Pathol. 2010 Apr;88(2):225-33. doi: 10.1016/j.yexmp.2009.12.004. Epub 2009 Dec 23. [Article]
  23. Mardin BR, Lange C, Baxter JE, Hardy T, Scholz SR, Fry AM, Schiebel E: Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction. Nat Cell Biol. 2010 Dec;12(12):1166-76. doi: 10.1038/ncb2120. Epub 2010 Nov 14. [Article]
  24. Croasdale R, Ivins FJ, Muskett F, Daviter T, Scott DJ, Hardy T, Smerdon SJ, Fry AM, Pfuhl M: An undecided coiled coil: the leucine zipper of Nek2 kinase exhibits atypical conformational exchange dynamics. J Biol Chem. 2011 Aug 5;286(31):27537-47. doi: 10.1074/jbc.M110.196972. Epub 2011 Jun 13. [Article]
  25. Quarmby LM, Mahjoub MR: Caught Nek-ing: cilia and centrioles. J Cell Sci. 2005 Nov 15;118(Pt 22):5161-9. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB071805-[(Z)-(5-Chloro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-N,2,4-trimethyl-1H-pyrrole-3-carboxamideexperimentalunknownDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails