NEK2_HUMAN
ID NEK2_HUMAN Reviewed; 445 AA.
AC P51955; Q53FD6; Q5I1Z9; Q5VXZ1; Q6NZX8; Q7Z634; Q86XH2; Q96QN9;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 224.
DE RecName: Full=Serine/threonine-protein kinase Nek2;
DE EC=2.7.11.1;
DE AltName: Full=HSPK 21;
DE AltName: Full=Never in mitosis A-related kinase 2;
DE Short=NimA-related protein kinase 2;
DE AltName: Full=NimA-like protein kinase 1;
GN Name=NEK2; Synonyms=NEK2A, NLK1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Nasopharynx, Placenta, and T-cell;
RX PubMed=7522034;
RA Schultz S.J., Fry A.M., Suetterlin C., Ried T., Nigg E.A.;
RT "Cell cycle-dependent expression of Nek2, a novel human protein kinase
RT related to the NIMA mitotic regulator of Aspergillus nidulans.";
RL Cell Growth Differ. 5:625-635(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE
RP SPECIFICITY, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DIMERIZATION, AND
RP INDUCTION.
RX PubMed=11742531; DOI=10.1042/0264-6021:3610077;
RA Hames R.S., Fry A.M.;
RT "Alternative splice variants of the human centrosome kinase Nek2 exhibit
RT distinct patterns of expression in mitosis.";
RL Biochem. J. 361:77-85(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Lu K.P., Hunter T.;
RT "Molecular cloning and expression of NLK1, a human NIMA-like kinase.";
RL Submitted (JUL-1994) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT SER-354.
RC TISSUE=Testis;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Mammary gland, Skin, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 83-203.
RX PubMed=8274451;
RA Schultz S.J., Nigg E.A.;
RT "Identification of 21 novel human protein kinases, including 3 members of a
RT family related to the cell cycle regulator nimA of Aspergillus nidulans.";
RL Cell Growth Differ. 4:821-830(1993).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 216-445 (ISOFORM 4), INTERACTION WITH PPP1CC,
RP AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=15659832; DOI=10.1196/annals.1329.059;
RA Fardilha M., Wu W., Sa R., Fidalgo S., Sousa C., Mota C.,
RA da Cruz e Silva O.A., da Cruz e Silva E.F.;
RT "Alternatively spliced protein variants as potential therapeutic targets
RT for male infertility and contraception.";
RL Ann. N. Y. Acad. Sci. 1030:468-478(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 305-445, FUNCTION, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH MAD1L1.
RX PubMed=14978040; DOI=10.1074/jbc.m314205200;
RA Lou Y., Yao J., Zereshki A., Dou Z., Ahmed K., Wang H., Hu J., Wang Y.,
RA Yao X.;
RT "NEK2A interacts with MAD1 and possibly functions as a novel integrator of
RT the spindle checkpoint signaling.";
RL J. Biol. Chem. 279:20049-20057(2004).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12857871; DOI=10.1091/mbc.e03-02-0108;
RA Faragher A.J., Fry A.M.;
RT "Nek2A kinase stimulates centrosome disjunction and is required for
RT formation of bipolar mitotic spindles.";
RL Mol. Biol. Cell 14:2876-2889(2003).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Lymphoblast;
RX PubMed=14654843; DOI=10.1038/nature02166;
RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.;
RT "Proteomic characterization of the human centrosome by protein correlation
RT profiling.";
RL Nature 426:570-574(2003).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MAPK1.
RX PubMed=15358203; DOI=10.1016/j.bbrc.2004.06.171;
RA Lou Y., Xie W., Zhang D.F., Yao J.H., Luo Z.F., Wang Y.Z., Shi Y.Y.,
RA Yao X.B.;
RT "Nek2A specifies the centrosomal localization of Erk2.";
RL Biochem. Biophys. Res. Commun. 321:495-501(2004).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH NPM1.
RX PubMed=15388344; DOI=10.1016/j.febslet.2004.08.047;
RA Yao J., Fu C., Ding X., Guo Z., Zenreski A., Chen Y., Ahmed K., Liao J.,
RA Dou Z., Yao X.;
RT "Nek2A kinase regulates the localization of numatrin to centrosome in
RT mitosis.";
RL FEBS Lett. 575:112-118(2004).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, ACTIVITY REGULATION, INTERACTION WITH
RP NEK11, AND MUTAGENESIS OF LYS-37.
RX PubMed=15161910; DOI=10.1074/jbc.m404104200;
RA Noguchi K., Fukazawa H., Murakami Y., Uehara Y.;
RT "Nucleolar Nek11 is a novel target of Nek2A in G1/S-arrested cells.";
RL J. Biol. Chem. 279:32716-32727(2004).
RN [16]
RP FUNCTION, ACTIVITY REGULATION, AND INTERACTION WITH PPP1CA AND PPP1CC.
RX PubMed=17283141; DOI=10.1158/0008-5472.can-06-3071;
RA Mi J., Guo C., Brautigan D.L., Larner J.M.;
RT "Protein phosphatase-1alpha regulates centrosome splitting through Nek2.";
RL Cancer Res. 67:1082-1089(2007).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SGO1.
RX PubMed=17621308; DOI=10.1038/cr.2007.55;
RA Fu G., Ding X., Yuan K., Aikhionbare F., Yao J., Cai X., Jiang K., Yao X.;
RT "Phosphorylation of human Sgo1 by NEK2A is essential for chromosome
RT congression in mitosis.";
RL Cell Res. 17:608-618(2007).
RN [18]
RP ALTERNATIVE SPLICING, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION,
RP AUTOPHOSPHORYLATION, AND INTERACTION WITH PPP1A.
RX PubMed=17626005; DOI=10.1074/jbc.m704969200;
RA Wu W., Baxter J.E., Wattam S.L., Hayward D.G., Fardilha M., Knebel A.,
RA Ford E.M., da Cruz e Silva E.F., Fry A.M.;
RT "Alternative splicing controls nuclear translocation of the cell cycle-
RT regulated Nek2 kinase.";
RL J. Biol. Chem. 282:26431-26440(2007).
RN [19]
RP FUNCTION, AND INTERACTION WITH CTNB1.
RX PubMed=18086858; DOI=10.1101/gad.1596308;
RA Bahmanyar S., Kaplan D.D., Deluca J.G., Giddings T.H. Jr., O'Toole E.T.,
RA Winey M., Salmon E.D., Casey P.J., Nelson W.J., Barth A.I.;
RT "beta-Catenin is a Nek2 substrate involved in centrosome separation.";
RL Genes Dev. 22:91-105(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-397, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-296, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [22]
RP FUNCTION, AND INTERACTION WITH NDC80.
RX PubMed=18297113; DOI=10.1038/onc.2008.34;
RA Du J., Cai X., Yao J., Ding X., Wu Q., Pei S., Jiang K., Zhang Y., Wang W.,
RA Shi Y., Lai Y., Shen J., Teng M., Huang H., Fei Q., Reddy E.S., Zhu J.,
RA Jin C., Yao X.;
RT "The mitotic checkpoint kinase NEK2A regulates kinetochore microtubule
RT attachment stability.";
RL Oncogene 27:4107-4114(2008).
RN [23]
RP ACTIVITY REGULATION.
RX PubMed=19941817; DOI=10.1016/j.molcel.2009.09.038;
RA Richards M.W., O'Regan L., Mas-Droux C., Blot J.M., Cheung J., Hoelder S.,
RA Fry A.M., Bayliss R.;
RT "An autoinhibitory tyrosine motif in the cell-cycle-regulated Nek7 kinase
RT is released through binding of Nek9.";
RL Mol. Cell 36:560-570(2009).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-296, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [25]
RP INTERACTION WITH PCNT.
RX PubMed=20599736; DOI=10.1016/j.bbrc.2010.06.063;
RA Matsuo K., Nishimura T., Hayakawa A., Ono Y., Takahashi M.;
RT "Involvement of a centrosomal protein kendrin in the maintenance of
RT centrosome cohesion by modulating Nek2A kinase activity.";
RL Biochem. Biophys. Res. Commun. 398:217-223(2010).
RN [26]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MAD2L1 AND CDC20.
RX PubMed=20034488; DOI=10.1016/j.yexmp.2009.12.004;
RA Liu Q., Hirohashi Y., Du X., Greene M.I., Wang Q.;
RT "Nek2 targets the mitotic checkpoint proteins Mad2 and Cdc20: a mechanism
RT for aneuploidy in cancer.";
RL Exp. Mol. Pathol. 88:225-233(2010).
RN [27]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH STK3/MST2 AND SAV1, AND
RP PHOSPHORYLATION AT SER-356; SER-365; SER-406 AND SER-438.
RX PubMed=21076410; DOI=10.1038/ncb2120;
RA Mardin B.R., Lange C., Baxter J.E., Hardy T., Scholz S.R., Fry A.M.,
RA Schiebel E.;
RT "Components of the Hippo pathway cooperate with Nek2 kinase to regulate
RT centrosome disjunction.";
RL Nat. Cell Biol. 12:1166-1176(2010).
RN [28]
RP DOMAIN LEUCINE-ZIPPER.
RX PubMed=21669869; DOI=10.1074/jbc.m110.196972;
RA Croasdale R., Ivins F.J., Muskett F., Daviter T., Scott D.J., Hardy T.,
RA Smerdon S.J., Fry A.M., Pfuhl M.;
RT "An undecided coiled-coil: the leucine zipper of NEK2 kinase exhibits
RT atypical conformational exchange dynamics.";
RL J. Biol. Chem. 286:27537-27547(2011).
RN [29]
RP REVIEW.
RX PubMed=16280549; DOI=10.1242/jcs.02681;
RA Quarmby L.M., Mahjoub M.R.;
RT "Caught Nek-ing: cilia and centrioles.";
RL J. Cell Sci. 118:5161-5169(2005).
RN [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-171; SER-184 AND SER-300, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [31]
RP INVOLVEMENT IN RP67.
RX PubMed=24043777; DOI=10.1073/pnas.1308243110;
RA Nishiguchi K.M., Tearle R.G., Liu Y.P., Oh E.C., Miyake N., Benaglio P.,
RA Harper S., Koskiniemi-Kuendig H., Venturini G., Sharon D., Koenekoop R.K.,
RA Nakamura M., Kondo M., Ueno S., Yasuma T.R., Beckmann J.S., Ikegawa S.,
RA Matsumoto N., Terasaki H., Berson E.L., Katsanis N., Rivolta C.;
RT "Whole genome sequencing in patients with retinitis pigmentosa reveals
RT pathogenic DNA structural changes and NEK2 as a new disease gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:16139-16144(2013).
RN [32]
RP FUNCTION, AND INTERACTION WITH CNTLN AND CEP68.
RX PubMed=24554434; DOI=10.1242/jcs.139451;
RA Fang G., Zhang D., Yin H., Zheng L., Bi X., Yuan L.;
RT "Centlein mediates an interaction between C-Nap1 and Cep68 to maintain
RT centrosome cohesion.";
RL J. Cell Sci. 127:1631-1639(2014).
RN [33]
RP FUNCTION.
RX PubMed=25704143; DOI=10.1016/j.ejcb.2015.01.004;
RA Man X., Megraw T.L., Lim Y.P.;
RT "Cep68 can be regulated by Nek2 and SCF complex.";
RL Eur. J. Cell Biol. 94:162-172(2015).
RN [34]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CEP85.
RX PubMed=26220856; DOI=10.1242/jcs.171637;
RA Chen C., Tian F., Lu L., Wang Y., Xiao Z., Yu C., Yu X.;
RT "Characterization of Cep85 - a new antagonist of Nek2A that is involved in
RT the regulation of centrosome disjunction.";
RL J. Cell Sci. 128:3290-3303(2015).
RN [35]
RP ERRATUM OF PUBMED:26220856.
RX PubMed=26471995; DOI=10.1242/jcs.180463;
RA Chen C., Tian F., Lu L., Wang Y., Xiao Z., Yu C., Yu X.;
RL J. Cell Sci. 128:3837-3837(2015).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-271 IN COMPLEX WITH INHIBITOR
RP SU11652, PHOSPHORYLATION AT THR-170; SER-171; THR-175; THR-179; SER-241;
RP SER-356; SER-387; SER-390; SER-397; SER-402 AND SER-428, MUTAGENESIS OF
RP LYS-37; ASP-141; THR-170; SER-171; THR-175; THR-179 AND SER-241, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=17197699; DOI=10.1074/jbc.m609721200;
RA Rellos P., Ivins F.J., Baxter J.E., Pike A., Nott T.J., Parkinson D.M.,
RA Das S., Howell S., Fedorov O., Shen Q.Y., Fry A.M., Knapp S., Smerdon S.J.;
RT "Structure and regulation of the human Nek2 centrosomal kinase.";
RL J. Biol. Chem. 282:6833-6842(2007).
RN [37]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-354 AND TYR-410.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Protein kinase which is involved in the control of centrosome
CC separation and bipolar spindle formation in mitotic cells and chromatin
CC condensation in meiotic cells. Regulates centrosome separation
CC (essential for the formation of bipolar spindles and high-fidelity
CC chromosome separation) by phosphorylating centrosomal proteins such as
CC CROCC, CEP250 and NINL, resulting in their displacement from the
CC centrosomes. Regulates kinetochore microtubule attachment stability in
CC mitosis via phosphorylation of NDC80. Involved in regulation of mitotic
CC checkpoint protein complex via phosphorylation of CDC20 and MAD2L1.
CC Plays an active role in chromatin condensation during the first meiotic
CC division through phosphorylation of HMGA2. Phosphorylates: PPP1CC;
CC SGO1; NECAB3 and NPM1. Essential for localization of MAD2L1 to
CC kinetochore and MAPK1 and NPM1 to the centrosome. Phosphorylates CEP68
CC and CNTLN directly or indirectly (PubMed:24554434). NEK2-mediated
CC phosphorylation of CEP68 promotes CEP68 dissociation from the
CC centrosome and its degradation at the onset of mitosis
CC (PubMed:25704143). Involved in the regulation of centrosome disjunction
CC (PubMed:26220856). {ECO:0000269|PubMed:11742531,
CC ECO:0000269|PubMed:12857871, ECO:0000269|PubMed:14978040,
CC ECO:0000269|PubMed:15358203, ECO:0000269|PubMed:15388344,
CC ECO:0000269|PubMed:17283141, ECO:0000269|PubMed:17621308,
CC ECO:0000269|PubMed:17626005, ECO:0000269|PubMed:18086858,
CC ECO:0000269|PubMed:18297113, ECO:0000269|PubMed:20034488,
CC ECO:0000269|PubMed:21076410, ECO:0000269|PubMed:24554434,
CC ECO:0000269|PubMed:25704143, ECO:0000269|PubMed:26220856}.
CC -!- FUNCTION: [Isoform 1]: Phosphorylates and activates NEK11 in G1/S-
CC arrested cells. {ECO:0000269|PubMed:15161910}.
CC -!- FUNCTION: [Isoform 2]: Not present in the nucleolus and, in contrast to
CC isoform 1, does not phosphorylate and activate NEK11 in G1/S-arrested
CC cells. {ECO:0000269|PubMed:15161910}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: Isoform 1 is inhibited by ionizing radiation in
CC the presence of PPP1CA. Its catalytic activity is inhibited by the
CC inhibitor CCT241950. In the presence of this inhibitor, displays an
CC autoinhibited conformation: Tyr-70 side chain points into the active
CC site, interacts with the activation loop, and blocks the alphaC helix.
CC {ECO:0000269|PubMed:15161910, ECO:0000269|PubMed:17283141,
CC ECO:0000269|PubMed:19941817}.
CC -!- SUBUNIT: Isoform 1, isoform 2 and isoform 4 form homo- and
CC heterodimers. Interacts with NECAB3 and HMGA2 (By similarity). Isoform
CC 1 interacts with CDC20, CTNB1, MAD1L1, MAPK, NEK11, NPM1, NDC80, PCNT
CC and SGO1 (PubMed:14978040, PubMed:15358203, PubMed:15388344,
CC PubMed:15161910, PubMed:17621308, PubMed:18086858, PubMed:18297113,
CC PubMed:20599736, PubMed:20034488). Isoform 1 interacts with STK3/MST2
CC (via SARAH domain) and SAV1 (via SARAH domain) (PubMed:21076410).
CC Isoform 1 and isoform 2 interact with MAD2L1 (PubMed:20034488). Isoform
CC 1 and isoform 4 interact with PPP1CA and PPP1CC (PubMed:15659832,
CC PubMed:17283141). Interacts with CEP68; the interaction leads to
CC phosphorylation of CEP68. Interacts with CNTLN; the interaction leads
CC to phosphorylation of CNTLN (PubMed:24554434). Isoform 1 interacts with
CC CEP85 (PubMed:26220856). {ECO:0000250|UniProtKB:O35942,
CC ECO:0000269|PubMed:14978040, ECO:0000269|PubMed:15161910,
CC ECO:0000269|PubMed:15358203, ECO:0000269|PubMed:15388344,
CC ECO:0000269|PubMed:15659832, ECO:0000269|PubMed:17197699,
CC ECO:0000269|PubMed:17283141, ECO:0000269|PubMed:17621308,
CC ECO:0000269|PubMed:17626005, ECO:0000269|PubMed:18086858,
CC ECO:0000269|PubMed:18297113, ECO:0000269|PubMed:20034488,
CC ECO:0000269|PubMed:20599736, ECO:0000269|PubMed:21076410,
CC ECO:0000269|PubMed:24554434, ECO:0000269|PubMed:26220856}.
CC -!- INTERACTION:
CC P51955; Q9UJX5: ANAPC4; NbExp=6; IntAct=EBI-633182, EBI-2554854;
CC P51955; P30260: CDC27; NbExp=2; IntAct=EBI-633182, EBI-994813;
CC P51955; Q5T7B8: KIF24; NbExp=7; IntAct=EBI-633182, EBI-2556811;
CC P51955; Q8NG66: NEK11; NbExp=5; IntAct=EBI-633182, EBI-633195;
CC P51955; P36873-1: PPP1CC; NbExp=2; IntAct=EBI-633182, EBI-356289;
CC P51955; Q6GQ04: cdc27.S; Xeno; NbExp=2; IntAct=EBI-633182, EBI-995003;
CC P51955-1; Q8NG66: NEK11; NbExp=2; IntAct=EBI-687792, EBI-633195;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus. Nucleus, nucleolus
CC {ECO:0000269|PubMed:15161910}. Cytoplasm. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome {ECO:0000269|PubMed:14654843,
CC ECO:0000269|PubMed:26220856}. Cytoplasm, cytoskeleton, spindle pole.
CC Chromosome, centromere, kinetochore. Chromosome, centromere
CC {ECO:0000250}. Note=STK3/MST2 and SAV1 are required for its targeting
CC to the centrosome. Colocalizes with SGO1 and MAD1L1 at the kinetochore.
CC Not associated with kinetochore in the interphase but becomes
CC associated with it upon the breakdown of the nuclear envelope. Has a
CC nucleolar targeting/ retention activity via a coiled-coil domain at the
CC C-terminal end.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm. Note=Predominantly
CC cytoplasmic.
CC -!- SUBCELLULAR LOCATION: [Isoform 4]: Nucleus. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome. Note=Predominantly nuclear.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Nek2A;
CC IsoId=P51955-1; Sequence=Displayed;
CC Name=2; Synonyms=Nek2B;
CC IsoId=P51955-2; Sequence=VSP_015578, VSP_015579;
CC Name=3;
CC IsoId=P51955-3; Sequence=VSP_015576, VSP_015577;
CC Name=4; Synonyms=Nek2C, Nek2A-T;
CC IsoId=P51955-4; Sequence=VSP_041758;
CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 2 are expressed in peripheral
CC blood T-cells and a wide variety of transformed cell types. Isoform 1
CC and isoform 4 are expressed in the testis. Up-regulated in various
CC cancer cell lines, as well as primary breast tumors.
CC {ECO:0000269|PubMed:11742531, ECO:0000269|PubMed:15659832}.
CC -!- INDUCTION: Expression and activity peak in the G2 phase of the mitotic
CC cycle and decrease once the cells have entered mitosis due to
CC degradation by the anaphase promoting complex APC/C-CDC20. In G1 phase,
CC both isoform 1 and isoform 2 are almost undetectable. However, at the
CC G1/S transition, there is an increase in expression of both isoforms
CC which then remain at this increased level throughout S and G2. At the
CC onset of mitosis, isoform 1 undergoes a rapid disappearance whereas
CC isoform 2 continues to be present at about the same level as in G2.
CC During the rest of mitosis, isoform 1 remains absent, while isoform 2
CC only begins to decline upon re-entry into the next G1 phase.
CC {ECO:0000269|PubMed:11742531, ECO:0000269|PubMed:26220856}.
CC -!- DOMAIN: The leucine-zipper domain is required for its dimerization and
CC activation. {ECO:0000269|PubMed:21669869}.
CC -!- PTM: Activated by autophosphorylation. Protein phosphatase 1 represses
CC autophosphorylation and activation of isoform 1 by dephosphorylation.
CC Phosphorylation by STK3/MST2 is necessary for its localization to the
CC centrosome. {ECO:0000269|PubMed:17197699, ECO:0000269|PubMed:21076410}.
CC -!- DISEASE: Retinitis pigmentosa 67 (RP67) [MIM:615565]: A retinal
CC dystrophy belonging to the group of pigmentary retinopathies. Retinitis
CC pigmentosa is characterized by retinal pigment deposits visible on
CC fundus examination and primary loss of rod photoreceptor cells followed
CC by secondary loss of cone photoreceptors. Patients typically have night
CC vision blindness and loss of midperipheral visual field. As their
CC condition progresses, they lose their far peripheral visual field and
CC eventually central vision as well. {ECO:0000269|PubMed:24043777}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. NEK Ser/Thr
CC protein kinase family. NIMA subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH65932.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; Z29066; CAA82309.1; -; mRNA.
DR EMBL; AY045701; AAK92212.1; -; mRNA.
DR EMBL; U11050; AAA19558.1; -; mRNA.
DR EMBL; BT019729; AAV38534.1; -; mRNA.
DR EMBL; AK223353; BAD97073.1; -; mRNA.
DR EMBL; AC096637; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356310; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC043502; AAH43502.2; -; mRNA.
DR EMBL; BC052807; AAH52807.1; -; mRNA.
DR EMBL; BC065932; AAH65932.1; ALT_FRAME; mRNA.
DR EMBL; Z25425; CAA80912.1; -; mRNA.
DR EMBL; AY863109; AAW56418.1; -; mRNA.
DR CCDS; CCDS1500.1; -. [P51955-1]
DR CCDS; CCDS55682.1; -. [P51955-2]
DR PIR; G01452; G01452.
DR PIR; I38215; I38215.
DR RefSeq; NP_001191111.1; NM_001204182.1.
DR RefSeq; NP_001191112.1; NM_001204183.1. [P51955-2]
DR RefSeq; NP_002488.1; NM_002497.3. [P51955-1]
DR RefSeq; XP_005273204.1; XM_005273147.1. [P51955-4]
DR PDB; 2JAV; X-ray; 2.20 A; A=1-271.
DR PDB; 2W5A; X-ray; 1.55 A; A=1-271.
DR PDB; 2W5B; X-ray; 2.40 A; A=1-271.
DR PDB; 2W5H; X-ray; 2.33 A; A=1-271.
DR PDB; 2WQO; X-ray; 2.17 A; A=1-271.
DR PDB; 2XK3; X-ray; 2.20 A; A=1-271.
DR PDB; 2XK4; X-ray; 2.10 A; A=1-271.
DR PDB; 2XK6; X-ray; 2.20 A; A=1-271.
DR PDB; 2XK7; X-ray; 1.99 A; A=1-271.
DR PDB; 2XK8; X-ray; 2.00 A; A=1-271.
DR PDB; 2XKC; X-ray; 2.50 A; A=1-271.
DR PDB; 2XKD; X-ray; 1.96 A; A=1-271.
DR PDB; 2XKE; X-ray; 2.20 A; A=1-271.
DR PDB; 2XKF; X-ray; 2.35 A; A=1-271.
DR PDB; 2XNM; X-ray; 1.85 A; A=1-271.
DR PDB; 2XNN; X-ray; 2.50 A; A=1-271.
DR PDB; 2XNO; X-ray; 1.98 A; A=1-271.
DR PDB; 2XNP; X-ray; 1.98 A; A=1-271.
DR PDB; 4A4X; X-ray; 2.40 A; A=1-271.
DR PDB; 4AFE; X-ray; 2.60 A; A=1-271.
DR PDB; 5M51; X-ray; 1.90 A; A=1-271.
DR PDB; 5M53; X-ray; 1.90 A; A=1-271.
DR PDB; 5M55; X-ray; 2.40 A; A=1-271.
DR PDB; 5M57; X-ray; 2.30 A; A=1-271.
DR PDB; 6SGD; X-ray; 2.00 A; A=1-271.
DR PDB; 6SGH; X-ray; 3.00 A; A=1-271.
DR PDB; 6SGI; X-ray; 2.30 A; A=1-271.
DR PDB; 6SGK; X-ray; 2.00 A; A=1-271.
DR PDB; 6SK9; X-ray; 2.00 A; A=1-271.
DR PDB; 6TM5; EM; 3.90 A; Q/S=1-445.
DR PDBsum; 2JAV; -.
DR PDBsum; 2W5A; -.
DR PDBsum; 2W5B; -.
DR PDBsum; 2W5H; -.
DR PDBsum; 2WQO; -.
DR PDBsum; 2XK3; -.
DR PDBsum; 2XK4; -.
DR PDBsum; 2XK6; -.
DR PDBsum; 2XK7; -.
DR PDBsum; 2XK8; -.
DR PDBsum; 2XKC; -.
DR PDBsum; 2XKD; -.
DR PDBsum; 2XKE; -.
DR PDBsum; 2XKF; -.
DR PDBsum; 2XNM; -.
DR PDBsum; 2XNN; -.
DR PDBsum; 2XNO; -.
DR PDBsum; 2XNP; -.
DR PDBsum; 4A4X; -.
DR PDBsum; 4AFE; -.
DR PDBsum; 5M51; -.
DR PDBsum; 5M53; -.
DR PDBsum; 5M55; -.
DR PDBsum; 5M57; -.
DR PDBsum; 6SGD; -.
DR PDBsum; 6SGH; -.
DR PDBsum; 6SGI; -.
DR PDBsum; 6SGK; -.
DR PDBsum; 6SK9; -.
DR PDBsum; 6TM5; -.
DR AlphaFoldDB; P51955; -.
DR SMR; P51955; -.
DR BioGRID; 110826; 125.
DR CORUM; P51955; -.
DR IntAct; P51955; 47.
DR MINT; P51955; -.
DR STRING; 9606.ENSP00000355966; -.
DR BindingDB; P51955; -.
DR ChEMBL; CHEMBL3835; -.
DR DrugBank; DB07180; 5-[(Z)-(5-Chloro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-N,2,4-trimethyl-1H-pyrrole-3-carboxamide.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; P51955; -.
DR GuidetoPHARMACOLOGY; 2117; -.
DR iPTMnet; P51955; -.
DR PhosphoSitePlus; P51955; -.
DR BioMuta; NEK2; -.
DR DMDM; 1709252; -.
DR CPTAC; CPTAC-1258; -.
DR CPTAC; CPTAC-1259; -.
DR EPD; P51955; -.
DR jPOST; P51955; -.
DR MassIVE; P51955; -.
DR MaxQB; P51955; -.
DR PaxDb; P51955; -.
DR PeptideAtlas; P51955; -.
DR PRIDE; P51955; -.
DR ProteomicsDB; 56453; -. [P51955-1]
DR ProteomicsDB; 56454; -. [P51955-2]
DR ProteomicsDB; 56455; -. [P51955-3]
DR ProteomicsDB; 56456; -. [P51955-4]
DR Antibodypedia; 4308; 464 antibodies from 38 providers.
DR DNASU; 4751; -.
DR Ensembl; ENST00000366998.4; ENSP00000355965.3; ENSG00000117650.13. [P51955-2]
DR Ensembl; ENST00000366999.9; ENSP00000355966.4; ENSG00000117650.13. [P51955-1]
DR GeneID; 4751; -.
DR KEGG; hsa:4751; -.
DR MANE-Select; ENST00000366999.9; ENSP00000355966.4; NM_002497.4; NP_002488.1.
DR UCSC; uc001hir.3; human. [P51955-1]
DR CTD; 4751; -.
DR DisGeNET; 4751; -.
DR GeneCards; NEK2; -.
DR HGNC; HGNC:7745; NEK2.
DR HPA; ENSG00000117650; Group enriched (bone marrow, lymphoid tissue, testis).
DR MalaCards; NEK2; -.
DR MIM; 604043; gene.
DR MIM; 615565; phenotype.
DR neXtProt; NX_P51955; -.
DR OpenTargets; ENSG00000117650; -.
DR Orphanet; 791; Retinitis pigmentosa.
DR PharmGKB; PA31546; -.
DR VEuPathDB; HostDB:ENSG00000117650; -.
DR eggNOG; KOG1826; Eukaryota.
DR GeneTree; ENSGT00940000156989; -.
DR HOGENOM; CLU_000288_63_23_1; -.
DR InParanoid; P51955; -.
DR OMA; PSRPEDY; -.
DR OrthoDB; 1290401at2759; -.
DR PhylomeDB; P51955; -.
DR TreeFam; TF101184; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; P51955; -.
DR Reactome; R-HSA-179409; APC-Cdc20 mediated degradation of Nek2A.
DR Reactome; R-HSA-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-HSA-380259; Loss of Nlp from mitotic centrosomes.
DR Reactome; R-HSA-380270; Recruitment of mitotic centrosome proteins and complexes.
DR Reactome; R-HSA-380284; Loss of proteins required for interphase microtubule organization from the centrosome.
DR Reactome; R-HSA-380320; Recruitment of NuMA to mitotic centrosomes.
DR Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane.
DR Reactome; R-HSA-8854518; AURKA Activation by TPX2.
DR SignaLink; P51955; -.
DR SIGNOR; P51955; -.
DR BioGRID-ORCS; 4751; 56 hits in 1103 CRISPR screens.
DR ChiTaRS; NEK2; human.
DR EvolutionaryTrace; P51955; -.
DR GeneWiki; NEK2; -.
DR GenomeRNAi; 4751; -.
DR Pharos; P51955; Tchem.
DR PRO; PR:P51955; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P51955; protein.
DR Bgee; ENSG00000117650; Expressed in sperm and 144 other tissues.
DR ExpressionAtlas; P51955; baseline and differential.
DR Genevisible; P51955; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0000794; C:condensed nuclear chromosome; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0030496; C:midbody; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IMP:UniProtKB.
DR GO; GO:0000922; C:spindle pole; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0019903; F:protein phosphatase binding; IPI:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0001824; P:blastocyst development; IEA:Ensembl.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0051299; P:centrosome separation; IDA:UniProtKB.
DR GO; GO:0007059; P:chromosome segregation; IDA:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0000278; P:mitotic cell cycle; TAS:ProtInc.
DR GO; GO:0000070; P:mitotic sister chromatid segregation; IEA:Ensembl.
DR GO; GO:0090307; P:mitotic spindle assembly; IEA:Ensembl.
DR GO; GO:1903126; P:negative regulation of centriole-centriole cohesion; IMP:UniProtKB.
DR GO; GO:0043392; P:negative regulation of DNA binding; IEA:Ensembl.
DR GO; GO:0051973; P:positive regulation of telomerase activity; IMP:BHF-UCL.
DR GO; GO:1904355; P:positive regulation of telomere capping; IMP:BHF-UCL.
DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; IMP:BHF-UCL.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0051988; P:regulation of attachment of spindle microtubules to kinetochore; IMP:UniProtKB.
DR GO; GO:0046602; P:regulation of mitotic centrosome separation; IMP:UniProtKB.
DR GO; GO:0007088; P:regulation of mitotic nuclear division; TAS:ProtInc.
DR GO; GO:0051225; P:spindle assembly; TAS:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell cycle; Cell division;
KW Centromere; Chromosome; Chromosome partition; Coiled coil; Cytoplasm;
KW Cytoskeleton; Kinase; Kinetochore; Magnesium; Meiosis; Metal-binding;
KW Microtubule; Mitosis; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Retinitis pigmentosa; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..445
FT /note="Serine/threonine-protein kinase Nek2"
FT /id="PRO_0000086421"
FT DOMAIN 8..271
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 264..445
FT /note="Interaction with PCNT"
FT /evidence="ECO:0000269|PubMed:20599736"
FT REGION 301..445
FT /note="Interaction with CEP85"
FT /evidence="ECO:0000269|PubMed:26220856"
FT REGION 306..334
FT /note="Leucine-zipper"
FT REGION 329..445
FT /note="Necessary for interaction with MAD1L1"
FT /evidence="ECO:0000269|PubMed:14978040"
FT REGION 333..370
FT /note="Required for microtubule binding and for
FT localization to the centrosomes"
FT REGION 403..439
FT /note="Interaction with SAV1 and STK3/MST2"
FT /evidence="ECO:0000269|PubMed:21076410"
FT COILED 303..362
FT /evidence="ECO:0000255"
FT COILED 406..430
FT /evidence="ECO:0000255"
FT ACT_SITE 141
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 14..22
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 37
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 170
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:17197699"
FT MOD_RES 171
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:17197699,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 175
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:17197699"
FT MOD_RES 179
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:17197699"
FT MOD_RES 184
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 241
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:17197699"
FT MOD_RES 296
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 300
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 356
FT /note="Phosphoserine; by STK3/MST2"
FT /evidence="ECO:0000269|PubMed:17197699,
FT ECO:0000269|PubMed:21076410"
FT MOD_RES 365
FT /note="Phosphoserine; by STK3/MST2"
FT /evidence="ECO:0000269|PubMed:21076410"
FT MOD_RES 387
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17197699"
FT MOD_RES 390
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17197699"
FT MOD_RES 397
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17197699,
FT ECO:0007744|PubMed:18088087"
FT MOD_RES 402
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17197699"
FT MOD_RES 406
FT /note="Phosphoserine; by STK3/MST2"
FT /evidence="ECO:0000269|PubMed:21076410"
FT MOD_RES 428
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:17197699"
FT MOD_RES 438
FT /note="Phosphoserine; by STK3/MST2"
FT /evidence="ECO:0000269|PubMed:21076410"
FT VAR_SEQ 323..326
FT /note="REER -> KKKK (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015576"
FT VAR_SEQ 327..445
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015577"
FT VAR_SEQ 371..384
FT /note="ELLNLPSSVIKKKV -> GMRINLVNRSWCYK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11742531"
FT /id="VSP_015578"
FT VAR_SEQ 371..378
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15659832"
FT /id="VSP_041758"
FT VAR_SEQ 385..445
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11742531"
FT /id="VSP_015579"
FT VARIANT 354
FT /note="N -> S (in dbSNP:rs2230489)"
FT /evidence="ECO:0000269|PubMed:17344846, ECO:0000269|Ref.5"
FT /id="VAR_019990"
FT VARIANT 410
FT /note="C -> Y (in dbSNP:rs56102977)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040907"
FT MUTAGEN 37
FT /note="K->R: Loss of kinase activity and of ability to
FT activate NEK11."
FT /evidence="ECO:0000269|PubMed:15161910,
FT ECO:0000269|PubMed:17197699"
FT MUTAGEN 141
FT /note="D->A: Loss of autophosphorylation."
FT /evidence="ECO:0000269|PubMed:17197699"
FT MUTAGEN 170
FT /note="T->A: No effect on kinase activity."
FT /evidence="ECO:0000269|PubMed:17197699"
FT MUTAGEN 170
FT /note="T->E: Kinase activity increased by two fold."
FT /evidence="ECO:0000269|PubMed:17197699"
FT MUTAGEN 171
FT /note="S->A: No effect on kinase activity."
FT /evidence="ECO:0000269|PubMed:17197699"
FT MUTAGEN 171
FT /note="S->D: Kinase activity increased by two fold."
FT /evidence="ECO:0000269|PubMed:17197699"
FT MUTAGEN 175
FT /note="T->A: Kinase activity decreased by two fold."
FT /evidence="ECO:0000269|PubMed:17197699"
FT MUTAGEN 175
FT /note="T->E: Kinase activity increased by two fold."
FT /evidence="ECO:0000269|PubMed:17197699"
FT MUTAGEN 179
FT /note="T->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:17197699"
FT MUTAGEN 179
FT /note="T->E: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:17197699"
FT MUTAGEN 241
FT /note="S->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:17197699"
FT MUTAGEN 241
FT /note="S->D: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:17197699"
FT CONFLICT 84..85
FT /note="IV -> LY (in Ref. 8; CAA80912)"
FT /evidence="ECO:0000305"
FT CONFLICT 325
FT /note="E -> K (in Ref. 5; BAD97073)"
FT /evidence="ECO:0000305"
FT HELIX 5..7
FT /evidence="ECO:0007829|PDB:2W5A"
FT STRAND 8..16
FT /evidence="ECO:0007829|PDB:2W5A"
FT STRAND 18..27
FT /evidence="ECO:0007829|PDB:2W5A"
FT TURN 28..30
FT /evidence="ECO:0007829|PDB:2W5A"
FT STRAND 33..40
FT /evidence="ECO:0007829|PDB:2W5A"
FT HELIX 41..43
FT /evidence="ECO:0007829|PDB:6SGK"
FT HELIX 46..61
FT /evidence="ECO:0007829|PDB:2W5A"
FT STRAND 70..76
FT /evidence="ECO:0007829|PDB:2W5A"
FT HELIX 77..79
FT /evidence="ECO:0007829|PDB:2W5A"
FT STRAND 81..87
FT /evidence="ECO:0007829|PDB:2W5A"
FT HELIX 94..103
FT /evidence="ECO:0007829|PDB:2W5A"
FT HELIX 110..130
FT /evidence="ECO:0007829|PDB:2W5A"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:2W5A"
FT STRAND 147..149
FT /evidence="ECO:0007829|PDB:2W5A"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:2W5A"
FT STRAND 155..157
FT /evidence="ECO:0007829|PDB:2W5A"
FT HELIX 162..165
FT /evidence="ECO:0007829|PDB:2W5A"
FT HELIX 171..177
FT /evidence="ECO:0007829|PDB:2W5A"
FT HELIX 180..182
FT /evidence="ECO:0007829|PDB:5M53"
FT HELIX 185..189
FT /evidence="ECO:0007829|PDB:2W5A"
FT HELIX 195..211
FT /evidence="ECO:0007829|PDB:2W5A"
FT HELIX 221..230
FT /evidence="ECO:0007829|PDB:2W5A"
FT HELIX 242..251
FT /evidence="ECO:0007829|PDB:2W5A"
FT HELIX 256..258
FT /evidence="ECO:0007829|PDB:2W5A"
FT HELIX 262..266
FT /evidence="ECO:0007829|PDB:2W5A"
SQ SEQUENCE 445 AA; 51763 MW; D33A37778ABB6D9E CRC64;
MPSRAEDYEV LYTIGTGSYG RCQKIRRKSD GKILVWKELD YGSMTEAEKQ MLVSEVNLLR
ELKHPNIVRY YDRIIDRTNT TLYIVMEYCE GGDLASVITK GTKERQYLDE EFVLRVMTQL
TLALKECHRR SDGGHTVLHR DLKPANVFLD GKQNVKLGDF GLARILNHDT SFAKTFVGTP
YYMSPEQMNR MSYNEKSDIW SLGCLLYELC ALMPPFTAFS QKELAGKIRE GKFRRIPYRY
SDELNEIITR MLNLKDYHRP SVEEILENPL IADLVADEQR RNLERRGRQL GEPEKSQDSS
PVLSELKLKE IQLQERERAL KAREERLEQK EQELCVRERL AEDKLARAEN LLKNYSLLKE
RKFLSLASNP ELLNLPSSVI KKKVHFSGES KENIMRSENS ESQLTSKSKC KDLKKRLHAA
QLRAQALSDI EKNYQLKSRQ ILGMR
