CDK1_HUMAN
ID CDK1_HUMAN Reviewed; 297 AA.
AC P06493; A8K7C4; C9J497; O60764;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 31-MAY-2011, sequence version 3.
DT 03-AUG-2022, entry version 262.
DE RecName: Full=Cyclin-dependent kinase 1;
DE Short=CDK1;
DE EC=2.7.11.22 {ECO:0000269|PubMed:23355470, ECO:0000269|PubMed:26829474, ECO:0000269|PubMed:30704899};
DE EC=2.7.11.23 {ECO:0000250|UniProtKB:P11440};
DE AltName: Full=Cell division control protein 2 homolog;
DE AltName: Full=Cell division protein kinase 1;
DE AltName: Full=p34 protein kinase;
GN Name=CDK1; Synonyms=CDC2, CDC28A, CDKN1, P34CDC2;
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).
RX PubMed=3553962; DOI=10.1038/327031a0;
RA Lee M.G., Nurse P.;
RT "Complementation used to clone a human homologue of the fission yeast cell
RT cycle control gene cdc2.";
RL Nature 327:31-35(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Mammary cancer;
RX PubMed=9515786;
RA Ohta T., Okamoto K., Isohashi F., Shibata K., Fukuda M., Yamaguchi S.,
RA Xiong Y.;
RT "T-loop deletion of CDC2 from breast cancer tissues eliminates binding to
RT cyclin B1 and cyclin-dependent kinase inhibitor p21.";
RL Cancer Res. 58:1095-1098(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
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 (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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 [9]
RP PHOSPHORYLATION, AND ASSOCIATION WITH P13.
RX PubMed=3289755; DOI=10.1016/0092-8674(88)90175-4;
RA Draetta G., Beach D.;
RT "Activation of cdc2 protein kinase during mitosis in human cells: cell
RT cycle-dependent phosphorylation and subunit rearrangement.";
RL Cell 54:17-26(1988).
RN [10]
RP PHOSPHORYLATION AT THR-14 AND TYR-15 BY PKMYT1.
RX PubMed=7569953; DOI=10.1126/science.270.5233.86;
RA Mueller P.R., Coleman T.R., Kumagai A., Dunphy W.G.;
RT "Myt1: a membrane-associated inhibitory kinase that phosphorylates Cdc2 on
RT both threonine-14 and tyrosine-15.";
RL Science 270:86-90(1995).
RN [11]
RP INTERACTION WITH FANCC.
RX PubMed=9242535;
RA Kupfer G.M., Yamashita T., Naf D., Suliman A., Asano S., D'Andrea A.D.;
RT "The Fanconi anemia polypeptide, FAC, binds to the cyclin-dependent kinase,
RT cdc2.";
RL Blood 90:1047-1054(1997).
RN [12]
RP ACTIVITY REGULATION BY ROSCOVITINE AND OLOMOUCINE.
RX PubMed=9030781; DOI=10.1111/j.1432-1033.1997.t01-2-00527.x;
RA Meijer L., Borgne A., Mulner O., Chong J.P.J., Blow J.J., Inagaki N.,
RA Inagaki M., Delcros J.-G., Moulinoux J.-P.;
RT "Biochemical and cellular effects of roscovitine, a potent and selective
RT inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5.";
RL Eur. J. Biochem. 243:527-536(1997).
RN [13]
RP INTERACTION WITH RALBP1.
RX PubMed=12775724; DOI=10.1074/jbc.m302191200;
RA Rosse C., L'Hoste S., Offner N., Picard A., Camonis J.;
RT "RLIP, an effector of the Ral GTPases, is a platform for Cdk1 to
RT phosphorylate epsin during the switch off of endocytosis in mitosis.";
RL J. Biol. Chem. 278:30597-30604(2003).
RN [14]
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 [15]
RP INTERACTION WITH DLGAP5.
RX PubMed=15145941; DOI=10.1074/jbc.m404950200;
RA Hsu J.-M., Lee Y.-C.G., Yu C.-T.R., Huang C.-Y.F.;
RT "Fbx7 functions in the SCF complex regulating Cdk1-cyclin B-phosphorylated
RT hepatoma up-regulated protein (HURP) proteolysis by a proline-rich
RT region.";
RL J. Biol. Chem. 279:32592-32602(2004).
RN [16]
RP FUNCTION AS RUNX2 KINASE.
RX PubMed=16407259; DOI=10.1074/jbc.m508162200;
RA Qiao M., Shapiro P., Fosbrink M., Rus H., Kumar R., Passaniti A.;
RT "Cell cycle-dependent phosphorylation of the RUNX2 transcription factor by
RT cdc2 regulates endothelial cell proliferation.";
RL J. Biol. Chem. 281:7118-7128(2006).
RN [17]
RP FUNCTION AS BETA-TUBULINS KINASE.
RX PubMed=16371510; DOI=10.1091/mbc.e05-07-0621;
RA Fourest-Lieuvin A., Peris L., Gache V., Garcia-Saez I., Juillan-Binard C.,
RA Lantez V., Job D.;
RT "Microtubule regulation in mitosis: tubulin phosphorylation by the cyclin-
RT dependent kinase Cdk1.";
RL Mol. Biol. Cell 17:1041-1050(2006).
RN [18]
RP INDUCTION BY CKS1B.
RX PubMed=18056467; DOI=10.1158/0008-5472.can-06-4173;
RA Westbrook L., Manuvakhova M., Kern F.G., Estes N.R. II, Ramanathan H.N.,
RA Thottassery J.V.;
RT "Cks1 regulates cdk1 expression: a novel role during mitotic entry in
RT breast cancer cells.";
RL Cancer Res. 67:11393-11401(2007).
RN [19]
RP FUNCTION AS RB1 KINASE, ACTIVITY REGULATION BY TGFB1, AND REPRESSION BY
RP TGFB1.
RX PubMed=17459720; DOI=10.1016/j.cyto.2007.03.009;
RA Hu X., Cui D., Moscinski L.C., Zhang X., Maccachero V., Zuckerman K.S.;
RT "TGFbeta regulates the expression and activities of G2 checkpoint kinases
RT in human myeloid leukemia cells.";
RL Cytokine 37:155-162(2007).
RN [20]
RP FUNCTION AS SIRT2 KINASE, AND SUBCELLULAR LOCATION.
RX PubMed=16933150; DOI=10.1007/s11064-006-9127-6;
RA Southwood C.M., Peppi M., Dryden S., Tainsky M.A., Gow A.;
RT "Microtubule deacetylases, SirT2 and HDAC6, in the nervous system.";
RL Neurochem. Res. 32:187-195(2007).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [22]
RP FUNCTION DURING THE M PHASE, AND MUTAGENESIS OF 14-THR-TYR-15.
RX PubMed=18480403; DOI=10.1091/mbc.e08-02-0172;
RA Pomerening J.R., Ubersax J.A., Ferrell J.E. Jr.;
RT "Rapid cycling and precocious termination of G1 phase in cells expressing
RT CDK1AF.";
RL Mol. Biol. Cell 19:3426-3441(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-19; SER-39; TYR-77 AND
RP THR-222, AND IDENTIFICATION BY 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 [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14 AND TYR-15, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [25]
RP FUNCTION AS FOXO1 KINASE, AND INTERACTION WITH FOXO1.
RX PubMed=18356527; DOI=10.1126/science.1152337;
RA Yuan Z., Becker E.B.E., Merlo P., Yamada T., DiBacco S., Konishi Y.,
RA Schaefer E.M., Bonni A.;
RT "Activation of FOXO1 by Cdk1 in cycling cells and postmitotic neurons.";
RL Science 319:1665-1668(2008).
RN [26]
RP FUNCTION AS NEDD1 KINASE.
RX PubMed=19509060; DOI=10.1242/jcs.042747;
RA Zhang X., Chen Q., Feng J., Hou J., Yang F., Liu J., Jiang Q., Zhang C.;
RT "Sequential phosphorylation of Nedd1 by Cdk1 and Plk1 is required for
RT targeting of the gammaTuRC to the centrosome.";
RL J. Cell Sci. 122:2240-2251(2009).
RN [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT TYR-19; SER-39; SER-178; THR-222 AND SER-248, AND
RP IDENTIFICATION BY 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 [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14; TYR-15 AND THR-161, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [29]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-6, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [30]
RP FUNCTION AS CC2D1A KINASE.
RX PubMed=20171170; DOI=10.1016/j.bbrc.2010.02.103;
RA Nakamura A., Naito M., Arai H., Fujita N.;
RT "Mitotic phosphorylation of Aki1 at Ser208 by cyclin B1-Cdk1 complex.";
RL Biochem. Biophys. Res. Commun. 393:872-876(2010).
RN [31]
RP FUNCTION IN G2 ARREST UPON DNA DAMAGE, PHOSPHORYLATION AT TYR-4 BY
RP PKR/EIF2AK2, POLYUBIQUITINATION, AND MUTAGENESIS OF TYR-4.
RX PubMed=20395957; DOI=10.1038/embor.2010.45;
RA Yoon C.-H., Miah M.A., Kim K.P., Bae Y.-S.;
RT "New Cdc2 Tyr 4 phosphorylation by dsRNA-activated protein kinase triggers
RT Cdc2 polyubiquitination and G2 arrest under genotoxic stresses.";
RL EMBO Rep. 11:393-399(2010).
RN [32]
RP PHOSPHORYLATION AT TYR-15.
RX PubMed=19917613; DOI=10.1074/jbc.m109.055392;
RA LaGory E.L., Sitailo L.A., Denning M.F.;
RT "The protein kinase Cdelta catalytic fragment is critical for maintenance
RT of the G2/M DNA damage checkpoint.";
RL J. Biol. Chem. 285:1879-1887(2010).
RN [33]
RP FUNCTION IN G2-M TRANSITION, DEPHOSPHORYLATION AT THR-14 AND TYR-15 BY
RP CDC25, PHOSPHORYLATION AT THR-161 BY CDK7/CAK, AND INTERACTION WITH
RP B-CYCLIN.
RX PubMed=20360007; DOI=10.1074/jbc.m109.096552;
RA Timofeev O., Cizmecioglu O., Settele F., Kempf T., Hoffmann I.;
RT "Cdc25 phosphatases are required for timely assembly of CDK1-cyclin B at
RT the G2/M transition.";
RL J. Biol. Chem. 285:16978-16990(2010).
RN [34]
RP FUNCTION AS BCL-XL/BCL2L1 KINASE, AND SUBCELLULAR LOCATION.
RX PubMed=19917720; DOI=10.1128/mcb.00882-09;
RA Terrano D.T., Upreti M., Chambers T.C.;
RT "Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a
RT functional link coupling mitotic arrest and apoptosis.";
RL Mol. Cell. Biol. 30:640-656(2010).
RN [35]
RP FUNCTION AS CASP8 KINASE.
RX PubMed=20937773; DOI=10.1128/mcb.00731-10;
RA Matthess Y., Raab M., Sanhaji M., Lavrik I.N., Strebhardt K.;
RT "Cdk1/cyclin B1 controls Fas-mediated apoptosis by regulating caspase-8
RT activity.";
RL Mol. Cell. Biol. 30:5726-5740(2010).
RN [36]
RP FUNCTION AS EZH2 KINASE.
RX PubMed=20935635; DOI=10.1038/ncb2116;
RA Chen S., Bohrer L.R., Rai A.N., Pan Y., Gan L., Zhou X., Bagchi A.,
RA Simon J.A., Huang H.;
RT "Cyclin-dependent kinases regulate epigenetic gene silencing through
RT phosphorylation of EZH2.";
RL Nat. Cell Biol. 12:1108-1114(2010).
RN [37]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-161, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [38]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [39]
RP INTERACTION WITH CEP63, AND SUBCELLULAR LOCATION.
RX PubMed=21406398; DOI=10.1158/0008-5472.can-10-2684;
RA Loffler H., Fechter A., Matuszewska M., Saffrich R., Mistrik M.,
RA Marhold J., Hornung C., Westermann F., Bartek J., Kramer A.;
RT "Cep63 recruits Cdk1 to the centrosome: implications for regulation of
RT mitotic entry, centrosome amplification, and genome maintenance.";
RL Cancer Res. 71:2129-2139(2011).
RN [40]
RP FUNCTION AS CHAMP1 KINASE.
RX PubMed=21063390; DOI=10.1038/emboj.2010.276;
RA Itoh G., Kanno S., Uchida K.S., Chiba S., Sugino S., Watanabe K.,
RA Mizuno K., Yasui A., Hirota T., Tanaka K.;
RT "CAMP (C13orf8, ZNF828) is a novel regulator of kinetochore-microtubule
RT attachment.";
RL EMBO J. 30:130-144(2011).
RN [41]
RP REVIEW ON SUBSTRATES, AND GENE FAMILY.
RX PubMed=16236519; DOI=10.1016/j.tibs.2005.09.005;
RA Malumbres M., Barbacid M.;
RT "Mammalian cyclin-dependent kinases.";
RL Trends Biochem. Sci. 30:630-641(2005).
RN [42]
RP REVIEW ON SUBCELLULAR TRANSLOCATION.
RX PubMed=19364923; DOI=10.1083/jcb.200812045;
RA Lindqvist A., Rodriguez-Bravo V., Medema R.H.;
RT "The decision to enter mitosis: feedback and redundancy in the mitotic
RT entry network.";
RL J. Cell Biol. 185:193-202(2009).
RN [43]
RP REVIEW ON CELL CYCLE CONTROL AND INHIBITORS, AND GENE FAMILY.
RX PubMed=19238148; DOI=10.1038/nrc2602;
RA Malumbres M., Barbacid M.;
RT "Cell cycle, CDKs and cancer: a changing paradigm.";
RL Nat. Rev. Cancer 9:153-166(2009).
RN [44]
RP REVIEW ON CELL CYCLE CONTROL.
RX PubMed=21535261; DOI=10.1111/j.1365-2184.2011.00753.x;
RA Hu X., Moscinski L.C.;
RT "Cdc2: a monopotent or pluripotent CDK?";
RL Cell Prolif. 44:205-211(2011).
RN [45]
RP REVIEW ON CELL CYCLE CONTROL AND INHIBITORS.
RX PubMed=21517772; DOI=10.2174/092986711795590110;
RA Wang Q., Su L., Liu N., Zhang L., Xu W., Fang H.;
RT "Cyclin dependent kinase 1 inhibitors: a review of recent progress.";
RL Curr. Med. Chem. 18:2025-2043(2011).
RN [46]
RP REVIEW ON CELL CYCLE CONTROL.
RX PubMed=21655336; DOI=10.3410/b3-10;
RA Medema R.H., Macurek L.;
RT "Checkpoint recovery in cells: how a molecular understanding can help in
RT the fight against cancer.";
RL F1000 Biol. Rep. 3:10-10(2011).
RN [47]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=21516087; DOI=10.1038/nm.2341;
RA Lupberger J., Zeisel M.B., Xiao F., Thumann C., Fofana I., Zona L.,
RA Davis C., Mee C.J., Turek M., Gorke S., Royer C., Fischer B., Zahid M.N.,
RA Lavillette D., Fresquet J., Cosset F.L., Rothenberg S.M., Pietschmann T.,
RA Patel A.H., Pessaux P., Doffoel M., Raffelsberger W., Poch O.,
RA McKeating J.A., Brino L., Baumert T.F.;
RT "EGFR and EphA2 are host factors for hepatitis C virus entry and possible
RT targets for antiviral therapy.";
RL Nat. Med. 17:589-595(2011).
RN [48]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-161, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [49]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [50]
RP FUNCTION.
RX PubMed=23602554; DOI=10.1016/j.celrep.2013.03.017;
RA Cribier A., Descours B., Valadao A.L., Laguette N., Benkirane M.;
RT "Phosphorylation of SAMHD1 by cyclin A2/CDK1 regulates its restriction
RT activity toward HIV-1.";
RL Cell Rep. 3:1036-1043(2013).
RN [51]
RP FUNCTION.
RX PubMed=23601106; DOI=10.1016/j.chom.2013.03.005;
RA White T.E., Brandariz-Nunez A., Valle-Casuso J.C., Amie S., Nguyen L.A.,
RA Kim B., Tuzova M., Diaz-Griffero F.;
RT "The retroviral restriction ability of SAMHD1, but not its deoxynucleotide
RT triphosphohydrolase activity, is regulated by phosphorylation.";
RL Cell Host Microbe 13:441-451(2013).
RN [52]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=23355470; DOI=10.1074/jbc.m112.441048;
RA Schofield A.V., Gamell C., Suryadinata R., Sarcevic B., Bernard O.;
RT "Tubulin polymerization promoting protein 1 (Tppp1) phosphorylation by Rho-
RT associated coiled-coil kinase (rock) and cyclin-dependent kinase 1 (Cdk1)
RT inhibits microtubule dynamics to increase cell proliferation.";
RL J. Biol. Chem. 288:7907-7917(2013).
RN [53]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-39; THR-141 AND THR-161, 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 [54]
RP FUNCTION.
RX PubMed=26549230; DOI=10.1016/j.bbrc.2015.11.004;
RA Mori Y., Inoue Y., Taniyama Y., Tanaka S., Terada Y.;
RT "Phosphorylation of the centrosomal protein, Cep169, by Cdk1 promotes its
RT dissociation from centrosomes in mitosis.";
RL Biochem. Biophys. Res. Commun. 468:642-646(2015).
RN [55]
RP FUNCTION, AND INTERACTION WITH CENPA.
RX PubMed=25556658; DOI=10.1016/j.devcel.2014.11.030;
RA Yu Z., Zhou X., Wang W., Deng W., Fang J., Hu H., Wang Z., Li S., Cui L.,
RA Shen J., Zhai L., Peng S., Wong J., Dong S., Yuan Z., Ou G., Zhang X.,
RA Xu P., Lou J., Yang N., Chen P., Xu R.M., Li G.;
RT "Dynamic phosphorylation of CENP-A at Ser68 orchestrates its cell-cycle-
RT dependent deposition at centromeres.";
RL Dev. Cell 32:68-81(2015).
RN [56]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [57]
RP FUNCTION, AND INTERACTION WITH NR1D1.
RX PubMed=27238018; DOI=10.1016/j.cell.2016.05.012;
RA Zhao X., Hirota T., Han X., Cho H., Chong L.W., Lamia K., Liu S.,
RA Atkins A.R., Banayo E., Liddle C., Yu R.T., Yates J.R. III, Kay S.A.,
RA Downes M., Evans R.M.;
RT "Circadian amplitude regulation via FBXW7-targeted REV-ERBalpha
RT degradation.";
RL Cell 165:1644-1657(2016).
RN [58]
RP FUNCTION.
RX PubMed=26829474; DOI=10.1038/nchembio.2017;
RA Mo F., Zhuang X., Liu X., Yao P.Y., Qin B., Su Z., Zang J., Wang Z.,
RA Zhang J., Dou Z., Tian C., Teng M., Niu L., Hill D.L., Fang G., Ding X.,
RA Fu C., Yao X.;
RT "Acetylation of Aurora B by TIP60 ensures accurate chromosomal
RT segregation.";
RL Nat. Chem. Biol. 12:226-232(2016).
RN [59]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-6; LYS-9; LYS-20 AND LYS-139, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [60]
RP FUNCTION AS EML3 KINASE.
RX PubMed=30723163; DOI=10.1074/jbc.ra118.007164;
RA Luo J., Yang B., Xin G., Sun M., Zhang B., Guo X., Jiang Q., Zhang C.;
RT "The microtubule-associated protein EML3 regulates mitotic spindle assembly
RT by recruiting the Augmin complex to spindle microtubules.";
RL J. Biol. Chem. 294:5643-5656(2019).
RN [61]
RP FUNCTION.
RX PubMed=30704899; DOI=10.1016/j.molcel.2018.12.017;
RA Cheng X., Ma X., Zhu Q., Song D., Ding X., Li L., Jiang X., Wang X.,
RA Tian R., Su H., Shen Z., Chen S., Liu T., Gong W., Liu W., Sun Q.;
RT "Pacer is a mediator of mTORC1 and GSK3-TIP60 signaling in regulation of
RT autophagosome maturation and lipid metabolism.";
RL Mol. Cell 73:1-15(2019).
RN [62]
RP FUNCTION AS CGAS KINASE.
RX PubMed=32351706; DOI=10.1038/s41421-020-0162-2;
RA Zhong L., Hu M.M., Bian L.J., Liu Y., Chen Q., Shu H.B.;
RT "Phosphorylation of cGAS by CDK1 impairs self-DNA sensing in mitosis.";
RL Cell Discov. 6:26-26(2020).
RN [63]
RP INTERACTION WITH SFTSV VIRUS NSS (MICROBIAL INFECTION).
RX PubMed=31852787; DOI=10.1128/jvi.01575-19;
RA Liu S., Liu H., Kang J., Xu L., Zhang K., Li X., Hou W., Wang Z., Wang T.;
RT "The Severe Fever with Thrombocytopenia Syndrome Virus NSs Protein
RT Interacts with CDK1 To Induce G2 Cell Cycle Arrest and Positively Regulate
RT Viral Replication.";
RL J. Virol. 94:0-0(2020).
CC -!- FUNCTION: Plays a key role in the control of the eukaryotic cell cycle
CC by modulating the centrosome cycle as well as mitotic onset; promotes
CC G2-M transition, and regulates G1 progress and G1-S transition via
CC association with multiple interphase cyclins (PubMed:16407259,
CC PubMed:17459720, PubMed:16933150, PubMed:18356527, PubMed:19509060,
CC PubMed:20171170, PubMed:19917720, PubMed:20937773, PubMed:20935635,
CC PubMed:21063390, PubMed:23355470, PubMed:23601106, PubMed:23602554,
CC PubMed:25556658, PubMed:26829474, PubMed:30704899). Required in higher
CC cells for entry into S-phase and mitosis (PubMed:16407259,
CC PubMed:17459720, PubMed:16933150, PubMed:18356527, PubMed:19509060,
CC PubMed:20171170, PubMed:19917720, PubMed:20937773, PubMed:20935635,
CC PubMed:21063390, PubMed:23355470, PubMed:23601106, PubMed:23602554,
CC PubMed:25556658). Phosphorylates PARVA/actopaxin, APC, AMPH, APC,
CC BARD1, Bcl-xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C,
CC CC2D1A, CENPA, CSNK2 proteins/CKII, FZR1/CDH1, CDK7, CEBPB, CHAMP1,
CC DMD/dystrophin, EEF1 proteins/EF-1, EZH2, KIF11/EG5, EGFR, FANCG, FOS,
CC GFAP, GOLGA2/GM130, GRASP1, UBE2A/hHR6A, HIST1H1 proteins/histone H1,
CC HMGA1, HIVEP3/KRC, KAT5, LMNA, LMNB, LMNC, LBR, LATS1, MAP1B, MAP4,
CC MARCKS, MCM2, MCM4, MKLP1, MYB, NEFH, NFIC, NPC/nuclear pore complex,
CC PITPNM1/NIR2, NPM1, NCL, NUCKS1, NPM1/numatrin, ORC1, PRKAR2A,
CC EEF1E1/p18, EIF3F/p47, p53/TP53, NONO/p54NRB, PAPOLA, PLEC/plectin,
CC RB1, TPPP, UL40/R2, RAB4A, RAP1GAP, RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68,
CC ESPL1, SKI, BIRC5/survivin, STIP1, TEX14, beta-tubulins, MAPT/TAU,
CC NEDD1, VIM/vimentin, TK1, FOXO1, RUNX1/AML1, SAMHD1, SIRT2, CGAS and
CC RUNX2 (PubMed:16407259, PubMed:17459720, PubMed:16933150,
CC PubMed:18356527, PubMed:19509060, PubMed:20171170, PubMed:19917720,
CC PubMed:20937773, PubMed:20935635, PubMed:21063390, PubMed:23355470,
CC PubMed:23601106, PubMed:23602554, PubMed:25556658, PubMed:32351706,
CC PubMed:26829474, PubMed:30704899). CDK1/CDC2-cyclin-B controls
CC pronuclear union in interphase fertilized eggs (PubMed:18480403,
CC PubMed:20360007). Essential for early stages of embryonic development
CC (PubMed:18480403, PubMed:20360007). During G2 and early mitosis,
CC CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes
CC which phosphorylate several substrates that trigger at least centrosome
CC separation, Golgi dynamics, nuclear envelope breakdown and chromosome
CC condensation (PubMed:18480403, PubMed:20360007). Once chromosomes are
CC condensed and aligned at the metaphase plate, CDK1 activity is switched
CC off by WEE1- and PKMYT1-mediated phosphorylation to allow sister
CC chromatid separation, chromosome decondensation, reformation of the
CC nuclear envelope and cytokinesis (PubMed:18480403, PubMed:20360007).
CC Phosphorylates KRT5 during prometaphase and metaphase (By similarity).
CC Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA
CC damage to stop cell cycle and genome replication at the G2 checkpoint
CC thus facilitating DNA repair (PubMed:20360007). Reactivated after
CC successful DNA repair through WIP1-dependent signaling leading to
CC CDC25A/B/C-mediated dephosphorylation and restoring cell cycle
CC progression (PubMed:20395957). In proliferating cells, CDK1-mediated
CC FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction
CC with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation
CC and transcription factor activity, leading to cell death of postmitotic
CC neurons (PubMed:18356527). The phosphorylation of beta-tubulins
CC regulates microtubule dynamics during mitosis (PubMed:16371510). NEDD1
CC phosphorylation promotes PLK1-mediated NEDD1 phosphorylation and
CC subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the
CC centrosome, an important step for spindle formation (PubMed:19509060).
CC In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole
CC localization and association with SCC1/RAD21 and centriole cohesion
CC during mitosis (PubMed:20171170). The phosphorylation of Bcl-xL/BCL2L1
CC after prolongated G2 arrest upon DNA damage triggers apoptosis
CC (PubMed:19917720). In contrast, CASP8 phosphorylation during mitosis
CC prevents its activation by proteolysis and subsequent apoptosis
CC (PubMed:20937773). This phosphorylation occurs in cancer cell lines, as
CC well as in primary breast tissues and lymphocytes (PubMed:20937773).
CC EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene
CC silencing (PubMed:20935635). CALD1 phosphorylation promotes Schwann
CC cell migration during peripheral nerve regeneration (By similarity).
CC CDK1-cyclin-B complex phosphorylates NCKAP5L and mediates its
CC dissociation from centrosomes during mitosis (PubMed:26549230).
CC Regulates the amplitude of the cyclic expression of the core clock gene
CC ARNTL/BMAL1 by phosphorylating its transcriptional repressor NR1D1, and
CC this phosphorylation is necessary for SCF(FBXW7)-mediated
CC ubiquitination and proteasomal degradation of NR1D1 (PubMed:27238018).
CC Phosphorylates EML3 at 'Thr-881' which is essential for its interaction
CC with HAUS augmin-like complex and TUBG1 (PubMed:30723163).
CC Phosphorylates CGAS during mitosis, leading to its inhibition, thereby
CC preventing CGAS activation by self DNA during mitosis
CC (PubMed:32351706). {ECO:0000250|UniProtKB:P11440,
CC ECO:0000250|UniProtKB:P39951, ECO:0000269|PubMed:16371510,
CC ECO:0000269|PubMed:16407259, ECO:0000269|PubMed:16933150,
CC ECO:0000269|PubMed:17459720, ECO:0000269|PubMed:18356527,
CC ECO:0000269|PubMed:18480403, ECO:0000269|PubMed:19509060,
CC ECO:0000269|PubMed:19917720, ECO:0000269|PubMed:20171170,
CC ECO:0000269|PubMed:20360007, ECO:0000269|PubMed:20395957,
CC ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:20937773,
CC ECO:0000269|PubMed:21063390, ECO:0000269|PubMed:23355470,
CC ECO:0000269|PubMed:23601106, ECO:0000269|PubMed:23602554,
CC ECO:0000269|PubMed:25556658, ECO:0000269|PubMed:26549230,
CC ECO:0000269|PubMed:26829474, ECO:0000269|PubMed:27238018,
CC ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:30723163,
CC ECO:0000269|PubMed:32351706}.
CC -!- FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C
CC virus (HCV) in hepatocytes and facilitates its cell entry.
CC {ECO:0000269|PubMed:21516087}.
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=2.7.11.22;
CC Evidence={ECO:0000269|PubMed:23355470, ECO:0000269|PubMed:26829474,
CC ECO:0000269|PubMed:30704899};
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=2.7.11.22; Evidence={ECO:0000269|PubMed:23355470,
CC ECO:0000269|PubMed:26829474, ECO:0000269|PubMed:30704899};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[DNA-directed RNA polymerase] + ATP = ADP + H(+) + phospho-
CC [DNA-directed RNA polymerase]; Xref=Rhea:RHEA:10216, Rhea:RHEA-
CC COMP:11321, Rhea:RHEA-COMP:11322, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43176, ChEBI:CHEBI:68546,
CC ChEBI:CHEBI:456216; EC=2.7.11.23;
CC Evidence={ECO:0000250|UniProtKB:P11440};
CC -!- ACTIVITY REGULATION: Phosphorylation at Thr-14 or Tyr-15 inactivates
CC the enzyme, while phosphorylation at Thr-161 activates it. Activated
CC through a multistep process; binding to cyclin-B is required for
CC relocation of cyclin-kinase complexes to the nucleus, activated by
CC CAK/CDK7-mediated phosphorylation on Thr-161, and CDC25-mediated
CC dephosphorylation of inhibitory phosphorylation on Thr-14 and Tyr-15.
CC Inhibited by flavopiridol and derivatives, pyrimidine derivatives,
CC pyridine derivatives, purine derivatives, staurosporine, paullones,
CC oxoindoles, indazole analogs, indolin-2-ones, pyrazolo[3,4-b]pyridines,
CC imidazo[1,2-a]pyridine (AZ703), thiazolinone analogs(RO-3306), thiazol
CC urea, macrocyclic quinoxalin-2-one, pyrrolo[2,3-a]carbazole,
CC pyrazolo[1,5-a]-1,3,5-triazine, pyrazolo[1,5-a]pyrimidine (Dinaciclib,
CC SCH 727965), 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-
CC isopropylpurine (roscovitine), olomoucine, AG-024322, AT-7519, P276-00,
CC R547/Ro-4584820 and SNS-032/BMS-387032. Repressed by the CDK inhibitors
CC CDKN1A/p21 and CDKN1B/p27 during the G1 phase and by CDKN1A/p21 at the
CC G1-S checkpoint upon DNA damage. Transient activation by rapid and
CC transient dephosphorylation at Tyr-15 triggered by TGFB1.
CC {ECO:0000269|PubMed:17459720, ECO:0000269|PubMed:9030781}.
CC -!- SUBUNIT: Forms a stable but non-covalent complex with a regulatory
CC subunit and with a cyclin. Interacts with cyclins-B (CCNB1, CCNB2 and
CC CCNB3) to form a serine/threonine kinase holoenzyme complex also known
CC as maturation promoting factor (MPF). The cyclin subunit imparts
CC substrate specificity to the complex. Can also form CDK1-cylin-D and
CC CDK1-cyclin-E complexes that phosphorylate RB1 in vitro. Binds to RB1
CC and other transcription factors such as FOXO1 and RUNX2. Promotes G2-M
CC transition when in complex with a cyclin-B. Interacts with DLGAP5.
CC Binds to the CDK inhibitors CDKN1A/p21 and CDKN1B/p27. Isoform 2 is
CC unable to complex with cyclin-B1 and also fails to bind to CDKN1A/p21.
CC Interacts with catalytically active CCNB1 and RALBP1 during mitosis to
CC form an endocytotic complex during interphase. Associates with cyclins-
CC A and B1 during S-phase in regenerating hepatocytes. Interacts with
CC FANCC. Interacts with CEP63; this interaction recruits CDK1 to
CC centrosomes. Interacts with CENPA (PubMed:25556658). Interacts with
CC NR1D1 (PubMed:27238018). Interacts with proteasome subunit PSMA8; to
CC participate in meiosis progression during spermatogenesis (By
CC similarity). {ECO:0000250|UniProtKB:P11440,
CC ECO:0000269|PubMed:12775724, ECO:0000269|PubMed:15145941,
CC ECO:0000269|PubMed:18356527, ECO:0000269|PubMed:20360007,
CC ECO:0000269|PubMed:21406398, ECO:0000269|PubMed:25556658,
CC ECO:0000269|PubMed:27238018, ECO:0000269|PubMed:9242535}.
CC -!- SUBUNIT: (Microbial infection) Interacts with severe fever with
CC thrombocytopenia syndrome virus (SFTSV) NSs; this interaction is
CC inclusion body dependent, it inhibits the formation and nuclear import
CC of the cyclin B1-CDK1 complex and leads to cell cycle arrest.
CC {ECO:0000269|PubMed:31852787}.
CC -!- INTERACTION:
CC P06493; Q86V81: ALYREF; NbExp=4; IntAct=EBI-444308, EBI-347640;
CC P06493; P05067: APP; NbExp=3; IntAct=EBI-444308, EBI-77613;
CC P06493; O15392: BIRC5; NbExp=6; IntAct=EBI-444308, EBI-518823;
CC P06493; P14635: CCNB1; NbExp=24; IntAct=EBI-444308, EBI-495332;
CC P06493; P30307: CDC25C; NbExp=3; IntAct=EBI-444308, EBI-974439;
CC P06493; Q99741: CDC6; NbExp=2; IntAct=EBI-444308, EBI-374862;
CC P06493; P38936: CDKN1A; NbExp=7; IntAct=EBI-444308, EBI-375077;
CC P06493; P46527: CDKN1B; NbExp=5; IntAct=EBI-444308, EBI-519280;
CC P06493; P61024: CKS1B; NbExp=10; IntAct=EBI-444308, EBI-456371;
CC P06493; O75618-1: DEDD; NbExp=2; IntAct=EBI-444308, EBI-15621191;
CC P06493; P36957: DLST; NbExp=3; IntAct=EBI-444308, EBI-351007;
CC P06493; P00533: EGFR; NbExp=3; IntAct=EBI-444308, EBI-297353;
CC P06493; P19525: EIF2AK2; NbExp=4; IntAct=EBI-444308, EBI-640775;
CC P06493; Q12778: FOXO1; NbExp=5; IntAct=EBI-444308, EBI-1108782;
CC P06493; O95835: LATS1; NbExp=3; IntAct=EBI-444308, EBI-444209;
CC P06493; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-444308, EBI-9090282;
CC P06493; Q99640: PKMYT1; NbExp=7; IntAct=EBI-444308, EBI-495308;
CC P06493; O43508: TNFSF12; NbExp=3; IntAct=EBI-444308, EBI-6932080;
CC P06493; P0CG48: UBC; NbExp=6; IntAct=EBI-444308, EBI-3390054;
CC P06493; P21796: VDAC1; NbExp=3; IntAct=EBI-444308, EBI-354158;
CC P06493; P03070; Xeno; NbExp=2; IntAct=EBI-444308, EBI-617698;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P11440}. Cytoplasm
CC {ECO:0000250|UniProtKB:P11440}. Mitochondrion
CC {ECO:0000269|PubMed:19917720}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000269|PubMed:14654843}. Cytoplasm,
CC cytoskeleton, spindle. Note=Cytoplasmic during the interphase.
CC Colocalizes with SIRT2 on centrosome during prophase and on splindle
CC fibers during metaphase of the mitotic cell cycle. Reversibly
CC translocated from cytoplasm to nucleus when phosphorylated before G2-M
CC transition when associated with cyclin-B1. Accumulates in mitochondria
CC in G2-arrested cells upon DNA-damage.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P06493-1; Sequence=Displayed;
CC Name=2; Synonyms=CDC2deltaT;
CC IsoId=P06493-2; Sequence=VSP_021375;
CC -!- TISSUE SPECIFICITY: Isoform 2 is found in breast cancer tissues.
CC -!- INDUCTION: Follows a cyclic expression; during interphase, accumulates
CC gradually following G1, S to reach a critical threshold at the end of
CC G2, which promotes self-activation and triggers onset of mitosis.
CC Induced transiently by TGFB1 at an early phase of TGFB1-mediated
CC apoptosis, but later repressed. Triggered by CKS1B during mitotic entry
CC in breast cancer cells. Down-regulated under genotoxic stresses
CC triggered by PKR/EIF2AK2-mediated phosphorylation.
CC {ECO:0000269|PubMed:17459720, ECO:0000269|PubMed:18056467}.
CC -!- PTM: Phosphorylation at Thr-161 by CAK/CDK7 activates kinase activity.
CC Phosphorylation at Thr-14 and Tyr-15 by PKMYT1 prevents nuclear
CC translocation. Phosphorylation at Tyr-15 by WEE1 and WEE2 inhibits the
CC protein kinase activity and acts as a negative regulator of entry into
CC mitosis (G2 to M transition). Phosphorylation by PKMYT1 and WEE1 takes
CC place during mitosis to keep CDK1-cyclin-B complexes inactive until the
CC end of G2. By the end of G2, PKMYT1 and WEE1 are inactivated, but
CC CDC25A and CDC25B are activated. Dephosphorylation by active CDC25A and
CC CDC25B at Thr-14 and Tyr-15, leads to CDK1 activation at the G2-M
CC transition. Phosphorylation at Tyr-15 by WEE2 during oogenesis is
CC required to maintain meiotic arrest in oocytes during the germinal
CC vesicle (GV) stage, a long period of quiescence at dictyate prophase I,
CC leading to prevent meiotic reentry. Phosphorylation by WEE2 is also
CC required for metaphase II exit during egg activation to ensure exit
CC from meiosis in oocytes and promote pronuclear formation.
CC Phosphorylated at Tyr-4 by PKR/EIF2AK2 upon genotoxic stress. This
CC phosphorylation triggers CDK1 polyubiquitination and subsequent
CC proteolysis, thus leading to G2 arrest. In response to UV irradiation,
CC phosphorylation at Tyr-15 by PRKCD activates the G2/M DNA damage
CC checkpoint. {ECO:0000269|PubMed:19917613, ECO:0000269|PubMed:20360007,
CC ECO:0000269|PubMed:20395957, ECO:0000269|PubMed:3289755,
CC ECO:0000269|PubMed:7569953}.
CC -!- PTM: Polyubiquitinated upon genotoxic stress.
CC {ECO:0000269|PubMed:20395957}.
CC -!- MISCELLANEOUS: As a key regulator of the cell cycle, CDK1 is a potent
CC therapeutic target for inhibitors in cancer treatment.
CC {ECO:0000305|PubMed:21517772}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAW54204.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cdc2/";
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DR EMBL; X05360; CAA28963.1; -; mRNA.
DR EMBL; Y00272; CAA68376.1; -; mRNA.
DR EMBL; D88357; BAA26001.1; -; mRNA.
DR EMBL; AK291939; BAF84628.1; -; mRNA.
DR EMBL; BT007004; AAP35650.1; -; mRNA.
DR EMBL; AF512554; AAM34793.1; -; Genomic_DNA.
DR EMBL; AC022390; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471083; EAW54204.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC014563; AAH14563.1; -; mRNA.
DR CCDS; CCDS44408.1; -. [P06493-1]
DR CCDS; CCDS7260.1; -. [P06493-2]
DR PIR; A29539; A29539.
DR RefSeq; NP_001307847.1; NM_001320918.1. [P06493-1]
DR RefSeq; NP_001777.1; NM_001786.4. [P06493-1]
DR RefSeq; NP_203698.1; NM_033379.4. [P06493-2]
DR RefSeq; XP_005270360.1; XM_005270303.3. [P06493-1]
DR PDB; 4Y72; X-ray; 2.30 A; A=1-297.
DR PDB; 4YC3; X-ray; 2.70 A; A=1-297.
DR PDB; 4YC6; X-ray; 2.60 A; A/C/E/G=1-297.
DR PDB; 5HQ0; X-ray; 2.30 A; A=1-297.
DR PDB; 5LQF; X-ray; 2.06 A; A/D=1-297.
DR PDB; 6GU2; X-ray; 2.00 A; A=1-297.
DR PDB; 6GU3; X-ray; 2.65 A; A=1-297.
DR PDB; 6GU4; X-ray; 2.73 A; A=1-297.
DR PDB; 6GU6; X-ray; 2.33 A; A=1-297.
DR PDB; 6GU7; X-ray; 2.75 A; A/C/E/G=1-297.
DR PDB; 6TWN; X-ray; 2.28 A; C/D=207-223.
DR PDB; 7NJ0; EM; 3.60 A; B=1-297.
DR PDBsum; 4Y72; -.
DR PDBsum; 4YC3; -.
DR PDBsum; 4YC6; -.
DR PDBsum; 5HQ0; -.
DR PDBsum; 5LQF; -.
DR PDBsum; 6GU2; -.
DR PDBsum; 6GU3; -.
DR PDBsum; 6GU4; -.
DR PDBsum; 6GU6; -.
DR PDBsum; 6GU7; -.
DR PDBsum; 6TWN; -.
DR PDBsum; 7NJ0; -.
DR AlphaFoldDB; P06493; -.
DR SMR; P06493; -.
DR BioGRID; 107420; 407.
DR ComplexPortal; CPX-2003; Cyclin A1-CDK1 complex.
DR ComplexPortal; CPX-2004; Cyclin A2-CDK1 complex.
DR ComplexPortal; CPX-2007; Cyclin B1-CDK1 complex.
DR ComplexPortal; CPX-2008; Cyclin B2-CDK1 complex.
DR CORUM; P06493; -.
DR DIP; DIP-35N; -.
DR ELM; P06493; -.
DR IntAct; P06493; 192.
DR MINT; P06493; -.
DR STRING; 9606.ENSP00000378699; -.
DR BindingDB; P06493; -.
DR ChEMBL; CHEMBL308; -.
DR DrugBank; DB04014; Alsterpaullone.
DR DrugBank; DB03496; Alvocidib.
DR DrugBank; DB08142; AT-7519.
DR DrugBank; DB16652; Avotaciclib.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB02950; Hymenialdisine.
DR DrugBank; DB02052; Indirubin-3'-monoxime.
DR DrugBank; DB02116; Olomoucine.
DR DrugBank; DB06195; Seliciclib.
DR DrugBank; DB03428; SU9516.
DR DrugCentral; P06493; -.
DR GuidetoPHARMACOLOGY; 1961; -.
DR TCDB; 1.I.1.1.3; the nuclear pore complex (npc) family.
DR GlyGen; P06493; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P06493; -.
DR MetOSite; P06493; -.
DR PhosphoSitePlus; P06493; -.
DR SwissPalm; P06493; -.
DR BioMuta; CDK1; -.
DR DMDM; 334302921; -.
DR SWISS-2DPAGE; P06493; -.
DR CPTAC; CPTAC-1040; -.
DR CPTAC; CPTAC-1041; -.
DR CPTAC; CPTAC-1042; -.
DR CPTAC; CPTAC-1200; -.
DR CPTAC; CPTAC-797; -.
DR CPTAC; CPTAC-798; -.
DR CPTAC; CPTAC-801; -.
DR EPD; P06493; -.
DR jPOST; P06493; -.
DR MassIVE; P06493; -.
DR MaxQB; P06493; -.
DR PaxDb; P06493; -.
DR PeptideAtlas; P06493; -.
DR PRIDE; P06493; -.
DR ProteomicsDB; 51905; -. [P06493-1]
DR ProteomicsDB; 51906; -. [P06493-2]
DR Antibodypedia; 1134; 2721 antibodies from 49 providers.
DR CPTC; P06493; 1 antibody.
DR DNASU; 983; -.
DR Ensembl; ENST00000316629.8; ENSP00000325970.4; ENSG00000170312.17. [P06493-2]
DR Ensembl; ENST00000373809.2; ENSP00000362915.2; ENSG00000170312.17. [P06493-2]
DR Ensembl; ENST00000395284.8; ENSP00000378699.3; ENSG00000170312.17. [P06493-1]
DR GeneID; 983; -.
DR KEGG; hsa:983; -.
DR MANE-Select; ENST00000395284.8; ENSP00000378699.3; NM_001786.5; NP_001777.1.
DR UCSC; uc001jld.3; human. [P06493-1]
DR CTD; 983; -.
DR DisGeNET; 983; -.
DR GeneCards; CDK1; -.
DR HGNC; HGNC:1722; CDK1.
DR HPA; ENSG00000170312; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 116940; gene.
DR neXtProt; NX_P06493; -.
DR OpenTargets; ENSG00000170312; -.
DR PharmGKB; PA99; -.
DR VEuPathDB; HostDB:ENSG00000170312; -.
DR eggNOG; KOG0594; Eukaryota.
DR GeneTree; ENSGT00940000153335; -.
DR HOGENOM; CLU_000288_181_6_1; -.
DR InParanoid; P06493; -.
DR OMA; NNDVWPE; -.
DR OrthoDB; 286319at2759; -.
DR PhylomeDB; P06493; -.
DR TreeFam; TF101021; -.
DR BRENDA; 2.7.11.22; 2681.
DR PathwayCommons; P06493; -.
DR Reactome; R-HSA-110056; MAPK3 (ERK1) activation.
DR Reactome; R-HSA-113507; E2F-enabled inhibition of pre-replication complex formation.
DR Reactome; R-HSA-1362300; Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1.
DR Reactome; R-HSA-162658; Golgi Cisternae Pericentriolar Stack Reorganization.
DR Reactome; R-HSA-170145; Phosphorylation of proteins involved in the G2/M transition by Cyclin A:Cdc2 complexes.
DR Reactome; R-HSA-174048; APC/C:Cdc20 mediated degradation of Cyclin B.
DR Reactome; R-HSA-174184; Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
DR Reactome; R-HSA-176408; Regulation of APC/C activators between G1/S and early anaphase.
DR Reactome; R-HSA-176412; Phosphorylation of the APC/C.
DR Reactome; R-HSA-176417; Phosphorylation of Emi1.
DR Reactome; R-HSA-2299718; Condensation of Prophase Chromosomes.
DR Reactome; R-HSA-2465910; MASTL Facilitates Mitotic Progression.
DR Reactome; R-HSA-2500257; Resolution of Sister Chromatid Cohesion.
DR Reactome; R-HSA-2514853; Condensation of Prometaphase Chromosomes.
DR Reactome; R-HSA-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-HSA-2980767; Activation of NIMA Kinases NEK9, NEK6, NEK7.
DR Reactome; R-HSA-2995383; Initiation of Nuclear Envelope (NE) Reformation.
DR Reactome; R-HSA-3301854; Nuclear Pore Complex (NPC) Disassembly.
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-4419969; Depolymerisation of the Nuclear Lamina.
DR Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane.
DR Reactome; R-HSA-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-HSA-5689896; Ovarian tumor domain proteases.
DR Reactome; R-HSA-6804114; TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest.
DR Reactome; R-HSA-6804757; Regulation of TP53 Degradation.
DR Reactome; R-HSA-68875; Mitotic Prophase.
DR Reactome; R-HSA-69205; G1/S-Specific Transcription.
DR Reactome; R-HSA-69273; Cyclin A/B1/B2 associated events during G2/M transition.
DR Reactome; R-HSA-69478; G2/M DNA replication checkpoint.
DR Reactome; R-HSA-75035; Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex.
DR Reactome; R-HSA-8852276; The role of GTSE1 in G2/M progression after G2 checkpoint.
DR Reactome; R-HSA-8854518; AURKA Activation by TPX2.
DR Reactome; R-HSA-8878166; Transcriptional regulation by RUNX2.
DR SignaLink; P06493; -.
DR SIGNOR; P06493; -.
DR BioGRID-ORCS; 983; 826 hits in 1071 CRISPR screens.
DR ChiTaRS; CDK1; human.
DR GeneWiki; Cdk1; -.
DR GeneWiki; Cyclin-dependent_kinase_1; -.
DR GenomeRNAi; 983; -.
DR Pharos; P06493; Tchem.
DR PRO; PR:P06493; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P06493; protein.
DR Bgee; ENSG00000170312; Expressed in ventricular zone and 150 other tissues.
DR ExpressionAtlas; P06493; baseline and differential.
DR Genevisible; P06493; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0000781; C:chromosome, telomeric region; HDA:BHF-UCL.
DR GO; GO:0097125; C:cyclin B1-CDK1 complex; IMP:CAFA.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:CACAO.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; TAS:UniProtKB.
DR GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:CACAO.
DR GO; GO:0005876; C:spindle microtubule; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0030332; F:cyclin binding; IDA:MGI.
DR GO; GO:0097472; F:cyclin-dependent protein kinase activity; IDA:UniProtKB.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0035173; F:histone kinase activity; IDA:UniProtKB.
DR GO; GO:0030544; F:Hsp70 protein binding; IEA:Ensembl.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; IDA:UniProtKB.
DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0016477; P:cell migration; TAS:UniProtKB.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
DR GO; GO:0007098; P:centrosome cycle; TAS:UniProtKB.
DR GO; GO:0030261; P:chromosome condensation; IEA:Ensembl.
DR GO; GO:0006281; P:DNA repair; TAS:UniProtKB.
DR GO; GO:0006260; P:DNA replication; TAS:UniProtKB.
DR GO; GO:0030855; P:epithelial cell differentiation; IEP:UniProtKB.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; TAS:Reactome.
DR GO; GO:0048144; P:fibroblast proliferation; IEA:Ensembl.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0090166; P:Golgi disassembly; ISS:UniProtKB.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; TAS:UniProtKB.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0045740; P:positive regulation of DNA replication; IEA:Ensembl.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IMP:CAFA.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:1905448; P:positive regulation of mitochondrial ATP synthesis coupled electron transport; IMP:CAFA.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IEA:Ensembl.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IMP:UniProtKB.
DR GO; GO:0007344; P:pronuclear fusion; TAS:UniProtKB.
DR GO; GO:0016579; P:protein deubiquitination; TAS:Reactome.
DR GO; GO:0034501; P:protein localization to kinetochore; IDA:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; IEA:Ensembl.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:0045995; P:regulation of embryonic development; TAS:UniProtKB.
DR GO; GO:0014038; P:regulation of Schwann cell differentiation; TAS:UniProtKB.
DR GO; GO:0014823; P:response to activity; IEA:Ensembl.
DR GO; GO:0014075; P:response to amine; IEA:Ensembl.
DR GO; GO:0048678; P:response to axon injury; IEA:Ensembl.
DR GO; GO:0046686; P:response to cadmium ion; IEA:Ensembl.
DR GO; GO:0046688; P:response to copper ion; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0055015; P:ventricular cardiac muscle cell development; IEA:Ensembl.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
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; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding;
KW Biological rhythms; Cell cycle; Cell division; Cytoplasm; Cytoskeleton;
KW Host cell receptor for virus entry; Host-virus interaction;
KW Isopeptide bond; Kinase; Mitochondrion; Mitosis; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Receptor; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..297
FT /note="Cyclin-dependent kinase 1"
FT /id="PRO_0000085724"
FT DOMAIN 4..287
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 128
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 10..18
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 33
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 4
FT /note="Phosphotyrosine; by PKR"
FT /evidence="ECO:0000269|PubMed:20395957"
FT MOD_RES 6
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 9
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P11440"
FT MOD_RES 14
FT /note="Phosphothreonine; by PKMYT1"
FT /evidence="ECO:0000269|PubMed:7569953,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332"
FT MOD_RES 15
FT /note="Phosphotyrosine; by PKMYT1, WEE1, WEE2 and
FT PKC/PRKCD"
FT /evidence="ECO:0000269|PubMed:19917613,
FT ECO:0000269|PubMed:7569953, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 19
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 39
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT MOD_RES 77
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 141
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 161
FT /note="Phosphothreonine; by CAK"
FT /evidence="ECO:0000269|PubMed:20360007,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 178
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 222
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 245
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P11440"
FT MOD_RES 248
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT CROSSLNK 6
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 9
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 20
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 139
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 107..163
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9515786"
FT /id="VSP_021375"
FT MUTAGEN 4
FT /note="Y->D,E: Constitutive polyubiquitination."
FT /evidence="ECO:0000269|PubMed:20395957"
FT MUTAGEN 14..15
FT /note="TY->AF: Abnormal cell cycle exhibiting only M-phase
FT without completing either karyokinesis or cytokinesis."
FT /evidence="ECO:0000269|PubMed:18480403"
FT HELIX 1..3
FT /evidence="ECO:0007829|PDB:6GU2"
FT STRAND 4..13
FT /evidence="ECO:0007829|PDB:6GU2"
FT STRAND 16..23
FT /evidence="ECO:0007829|PDB:6GU2"
FT TURN 24..26
FT /evidence="ECO:0007829|PDB:6GU2"
FT STRAND 29..35
FT /evidence="ECO:0007829|PDB:6GU2"
FT HELIX 40..42
FT /evidence="ECO:0007829|PDB:6GU2"
FT HELIX 46..57
FT /evidence="ECO:0007829|PDB:6GU2"
FT STRAND 66..72
FT /evidence="ECO:0007829|PDB:6GU2"
FT STRAND 75..81
FT /evidence="ECO:0007829|PDB:6GU2"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:5LQF"
FT HELIX 87..93
FT /evidence="ECO:0007829|PDB:6GU2"
FT HELIX 102..120
FT /evidence="ECO:0007829|PDB:6GU2"
FT TURN 121..123
FT /evidence="ECO:0007829|PDB:6GU2"
FT HELIX 131..133
FT /evidence="ECO:0007829|PDB:6GU2"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:6GU2"
FT STRAND 142..144
FT /evidence="ECO:0007829|PDB:6GU2"
FT HELIX 149..152
FT /evidence="ECO:0007829|PDB:6GU6"
FT STRAND 155..158
FT /evidence="ECO:0007829|PDB:6GU2"
FT TURN 161..163
FT /evidence="ECO:0007829|PDB:4YC6"
FT HELIX 164..167
FT /evidence="ECO:0007829|PDB:6GU6"
FT HELIX 172..175
FT /evidence="ECO:0007829|PDB:6GU2"
FT STRAND 179..181
FT /evidence="ECO:0007829|PDB:4YC6"
FT HELIX 184..199
FT /evidence="ECO:0007829|PDB:6GU2"
FT HELIX 209..220
FT /evidence="ECO:0007829|PDB:6GU2"
FT TURN 225..227
FT /evidence="ECO:0007829|PDB:6GU2"
FT HELIX 231..233
FT /evidence="ECO:0007829|PDB:6GU2"
FT HELIX 249..251
FT /evidence="ECO:0007829|PDB:6GU2"
FT HELIX 258..267
FT /evidence="ECO:0007829|PDB:6GU2"
FT TURN 272..274
FT /evidence="ECO:0007829|PDB:6GU2"
FT HELIX 278..282
FT /evidence="ECO:0007829|PDB:6GU2"
FT HELIX 285..287
FT /evidence="ECO:0007829|PDB:6GU2"
FT HELIX 292..295
FT /evidence="ECO:0007829|PDB:4YC3"
SQ SEQUENCE 297 AA; 34095 MW; 942D79448EFE490A CRC64;
MEDYTKIEKI GEGTYGVVYK GRHKTTGQVV AMKKIRLESE EEGVPSTAIR EISLLKELRH
PNIVSLQDVL MQDSRLYLIF EFLSMDLKKY LDSIPPGQYM DSSLVKSYLY QILQGIVFCH
SRRVLHRDLK PQNLLIDDKG TIKLADFGLA RAFGIPIRVY THEVVTLWYR SPEVLLGSAR
YSTPVDIWSI GTIFAELATK KPLFHGDSEI DQLFRIFRAL GTPNNEVWPE VESLQDYKNT
FPKWKPGSLA SHVKNLDENG LDLLSKMLIY DPAKRISGKM ALNHPYFNDL DNQIKKM
