CDK1_MOUSE
ID CDK1_MOUSE Reviewed; 297 AA.
AC P11440; P70337; Q3TI12;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 3.
DT 03-AUG-2022, entry version 228.
DE RecName: Full=Cyclin-dependent kinase 1;
DE Short=CDK1;
DE EC=2.7.11.22 {ECO:0000250|UniProtKB:P06493};
DE EC=2.7.11.23 {ECO:0000305|PubMed:2662013};
DE AltName: Full=Cell division control protein 2 homolog {ECO:0000303|PubMed:2208288};
DE AltName: Full=Cell division protein kinase 1;
DE AltName: Full=p34 protein kinase;
GN Name=Cdk1; Synonyms=Cdc2 {ECO:0000303|PubMed:2208288}, Cdc2a, Cdkn1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=FM3A; TISSUE=Mammary carcinoma;
RX PubMed=2208288; DOI=10.1016/0092-8674(90)90164-a;
RA Th'Ng J.P.H., Wright P.S., Hamaguchi J., Lee M.G., Norbury C.J., Nurse P.,
RA Bradbury E.M.;
RT "The FT210 cell line is a mouse G2 phase mutant with a temperature-
RT sensitive CDC2 gene product.";
RL Cell 63:313-324(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RX PubMed=2132958; DOI=10.3109/10425179009041346;
RA Spurr N.K., Gough A.C., Lee M.G.;
RT "Cloning of the mouse homologue of the yeast cell cycle control gene
RT cdc2.";
RL DNA Seq. 1:49-54(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, AND
RP CATALYTIC ACTIVITY.
RX PubMed=2662013; DOI=10.1038/339679a0;
RA Cisek L.J., Corden J.L.;
RT "Phosphorylation of RNA polymerase by the murine homologue of the cell-
RT cycle control protein cdc2.";
RL Nature 339:679-684(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=C57BL/6J;
RX PubMed=9895127;
RA Jun D., Park H.K., Nordin A.A., Nagel J.E., Kim Y.H.;
RT "Characterization of the murine cdc2 gene.";
RL Mol. Cells 8:731-740(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Muellerian duct, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [7]
RP PHOSPHORYLATION AT TYR-15.
RX PubMed=16169490; DOI=10.1016/j.cub.2005.07.056;
RA Han S.J., Chen R., Paronetto M.P., Conti M.;
RT "Wee1B is an oocyte-specific kinase involved in the control of meiotic
RT arrest in the mouse.";
RL Curr. Biol. 15:1670-1676(2005).
RN [8]
RP FUNCTION AT THE TRANSITION G1-S, INTERACTION WITH CDKN1B/P27 AND CYCLIN E1,
RP AND REGULATION BY CDKN1B/P27.
RX PubMed=16007079; DOI=10.1038/ncb1284;
RA Aleem E., Kiyokawa H., Kaldis P.;
RT "Cdc2-cyclin E complexes regulate the G1/S phase transition.";
RL Nat. Cell Biol. 7:831-836(2005).
RN [9]
RP FUNCTION IN CELL CYCLE REGULATION, AND DISRUPTION PHENOTYPE.
RX PubMed=17700700; DOI=10.1038/nature06046;
RA Santamaria D., Barriere C., Cerqueira A., Hunt S., Tardy C., Newton K.,
RA Caceres J.F., Dubus P., Malumbres M., Barbacid M.;
RT "Cdk1 is sufficient to drive the mammalian cell cycle.";
RL Nature 448:811-815(2007).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [11]
RP FUNCTION, INTERACTION WITH CDKN1A/P21, SUBCELLULAR LOCATION, AND ACTIVITY
RP REGULATION BY CDKN1A/P21.
RX PubMed=17942597; DOI=10.1091/mbc.e07-06-0525;
RA Satyanarayana A., Hilton M.B., Kaldis P.;
RT "p21 Inhibits Cdk1 in the absence of Cdk2 to maintain the G1/S phase DNA
RT damage checkpoint.";
RL Mol. Biol. Cell 19:65-77(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14 AND TYR-15, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14 AND TYR-15, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Kidney, Liver, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [14]
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 [15]
RP PHOSPHORYLATION AT TYR-15.
RX PubMed=21454751; DOI=10.1126/science.1199211;
RA Oh J.S., Susor A., Conti M.;
RT "Protein tyrosine kinase Wee1B is essential for metaphase II exit in mouse
RT oocytes.";
RL Science 332:462-465(2011).
RN [16]
RP FUNCTION IN PHOSPHORYLATION OF TEX14.
RX PubMed=22405274; DOI=10.1016/j.molcel.2012.01.013;
RA Mondal G., Ohashi A., Yang L., Rowley M., Couch F.J.;
RT "Tex14, a plk1-regulated protein, is required for kinetochore-microtubule
RT attachment and regulation of the spindle assembly checkpoint.";
RL Mol. Cell 45:680-695(2012).
RN [17]
RP FUNCTION.
RX PubMed=29518391; DOI=10.1016/j.bbrc.2018.03.016;
RA Inaba H., Yamakawa D., Tomono Y., Enomoto A., Mii S., Kasahara K., Goto H.,
RA Inagaki M.;
RT "Regulation of keratin 5/14 intermediate filaments by CDK1, Aurora-B, and
RT Rho-kinase.";
RL Biochem. Biophys. Res. Commun. 498:544-550(2018).
RN [18]
RP INTERACTION WITH PSMA8.
RX PubMed=31437213; DOI=10.1371/journal.pgen.1008316;
RA Gomez-H L., Felipe-Medina N., Condezo Y.B., Garcia-Valiente R., Ramos I.,
RA Suja J.A., Barbero J.L., Roig I., Sanchez-Martin M., de Rooij D.G.,
RA Llano E., Pendas A.M.;
RT "The PSMA8 subunit of the spermatoproteasome is essential for proper
RT meiotic exit and mouse fertility.";
RL PLoS Genet. 15:E1008316-E1008316(2019).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1; LYS-6 AND LYS-9, SUCCINYLATION
RP [LARGE SCALE ANALYSIS] AT LYS-245, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
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:16007079,
CC PubMed:17700700, PubMed:17942597, PubMed:22405274). Required in higher
CC cells for entry into S-phase and mitosis (PubMed:16007079,
CC PubMed:17700700, PubMed:17942597, PubMed:22405274). Phosphorylates
CC PARVA/actopaxin, APC, AMPH, APC, BARD1, Bcl-xL/BCL2L1, BRCA2, CALD1,
CC CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, CENPA, CSNK2 proteins/CKII,
CC FZR1/CDH1, CDK7, CEBPB, CHAMP1, DMD/dystrophin, EEF1 proteins/EF-1,
CC EZH2, KIF11/EG5, EGFR, FANCG, FOS, GFAP, GOLGA2/GM130, GRASP1,
CC UBE2A/hHR6A, HIST1H1 proteins/histone H1, HMGA1, HIVEP3/KRC, KAT5,
CC LMNA, LMNB, LMNC, LBR, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1,
CC MYB, NEFH, NFIC, NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, NCL,
CC NUCKS1, NPM1/numatrin, ORC1, PRKAR2A, EEF1E1/p18, EIF3F/p47, p53/TP53,
CC NONO/p54NRB, PAPOLA, PLEC/plectin, RB1, TPPP, UL40/R2, RAB4A, RAP1GAP,
CC RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68, ESPL1, SKI, BIRC5/survivin, STIP1,
CC TEX14, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1,
CC RUNX1/AML1, SAMHD1, SIRT2, CGAS and RUNX2 (PubMed:17942597,
CC PubMed:22405274). CDK1/CDC2-cyclin-B controls pronuclear union in
CC interphase fertilized eggs (By similarity). Essential for early stages
CC of embryonic development (By similarity). 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:16007079, PubMed:17700700). 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 (By similarity). Phosphorylates KRT5
CC during prometaphase and metaphase (PubMed:29518391). Inactivated by
CC PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop
CC cell cycle and genome replication at the G2 checkpoint thus
CC facilitating DNA repair (By similarity). Reactivated after successful
CC DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-
CC mediated dephosphorylation and restoring cell cycle progression (By
CC similarity). In proliferating cells, CDK1-mediated FOXO1
CC phosphorylation at the G2-M phase represses FOXO1 interaction with 14-
CC 3-3 proteins and thereby promotes FOXO1 nuclear accumulation and
CC transcription factor activity, leading to cell death of postmitotic
CC neurons (By similarity). The phosphorylation of beta-tubulins regulates
CC microtubule dynamics during mitosis (By similarity). 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 (By similarity). In
CC addition, CC2D1A phosphorylation regulates CC2D1A spindle pole
CC localization and association with SCC1/RAD21 and centriole cohesion
CC during mitosis (By similarity). The phosphorylation of Bcl-xL/BCL2L1
CC after prolongated G2 arrest upon DNA damage triggers apoptosis (By
CC similarity). In contrast, CASP8 phosphorylation during mitosis prevents
CC its activation by proteolysis and subsequent apoptosis (By similarity).
CC This phosphorylation occurs in cancer cell lines, as well as in primary
CC breast tissues and lymphocytes (By similarity). EZH2 phosphorylation
CC promotes H3K27me3 maintenance and epigenetic gene silencing (By
CC similarity). CALD1 phosphorylation promotes Schwann cell migration
CC during peripheral nerve regeneration (By similarity). CDK1-cyclin-B
CC complex phosphorylates NCKAP5L and mediates its dissociation from
CC centrosomes during mitosis (By similarity). Regulates the amplitude of
CC the cyclic expression of the core clock gene ARNTL/BMAL1 by
CC phosphorylating its transcriptional repressor NR1D1, and this
CC phosphorylation is necessary for SCF(FBXW7)-mediated ubiquitination and
CC proteasomal degradation of NR1D1 (By similarity). Phosphorylates EML3
CC at 'Thr-881' which is essential for its interaction with HAUS augmin-
CC like complex and TUBG1 (By similarity). Phosphorylates CGAS during
CC mitosis, leading to its inhibition, thereby preventing CGAS activation
CC by self DNA during mitosis (By similarity).
CC {ECO:0000250|UniProtKB:P06493, ECO:0000250|UniProtKB:P39951,
CC ECO:0000269|PubMed:16007079, ECO:0000269|PubMed:17700700,
CC ECO:0000269|PubMed:17942597, ECO:0000269|PubMed:22405274,
CC ECO:0000269|PubMed:29518391}.
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:0000250|UniProtKB:P06493};
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:0000250|UniProtKB:P06493};
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:0000305|PubMed:2662013};
CC -!- ACTIVITY REGULATION: Phosphorylation at Thr-14 or Tyr-15 inactivates
CC the enzyme, while phosphorylation at Thr-161 activates it.
CC {ECO:0000250|UniProtKB:P06493}.
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 (By similarity). Interacts with NR1D1
CC (By similarity). Interacts with proteasome subunit PSMA8; to
CC participate in meiosis progression during spermatogenesis
CC (PubMed:31437213). {ECO:0000250|UniProtKB:P06493,
CC ECO:0000269|PubMed:16007079, ECO:0000269|PubMed:17942597,
CC ECO:0000269|PubMed:31437213}.
CC -!- INTERACTION:
CC P11440; P51943: Ccna2; NbExp=2; IntAct=EBI-846949, EBI-846980;
CC P11440; Q61457: Ccne1; NbExp=3; IntAct=EBI-846949, EBI-643090;
CC P11440; P20263: Pou5f1; NbExp=4; IntAct=EBI-846949, EBI-1606219;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17942597}. Cytoplasm
CC {ECO:0000269|PubMed:17942597}. Mitochondrion
CC {ECO:0000269|PubMed:17942597}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:P06493}.
CC Cytoplasm, cytoskeleton, spindle {ECO:0000250|UniProtKB:P06493}.
CC Note=Colocalizes with SIRT2 on centrosome during prophase and on
CC splindle fibers during metaphase of the mitotic cell cycle (By
CC similarity). Cytoplasmic during the interphase. Reversibly translocated
CC from cytoplasm to nucleus when phosphorylated before G2-M transition
CC when associated with cyclin-B1. Accumulates in mitochondria in G2-
CC arrested cells upon DNA-damage. {ECO:0000250|UniProtKB:P06493}.
CC -!- INDUCTION: Follow 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 (Probable). {ECO:0000305}.
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 (By similarity). In response to
CC UV irradiation, phosphorylation at Tyr-15 by PRKCD activates the G2/M
CC DNA damage checkpoint. {ECO:0000250|UniProtKB:P06493,
CC ECO:0000269|PubMed:16169490, ECO:0000269|PubMed:19917613,
CC ECO:0000269|PubMed:21454751}.
CC -!- PTM: Polyubiquitinated upon genotoxic stress.
CC {ECO:0000250|UniProtKB:P06493}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality in the first cell divisions.
CC {ECO:0000269|PubMed:17700700}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
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DR EMBL; M38724; AAA37408.1; -; mRNA.
DR EMBL; X16461; CAA34481.1; -; mRNA.
DR EMBL; U58633; AAB09465.1; -; mRNA.
DR EMBL; AK030231; BAC26856.1; -; mRNA.
DR EMBL; AK135516; BAE22561.1; -; mRNA.
DR EMBL; AK168054; BAE40034.1; -; mRNA.
DR EMBL; BC024396; AAH24396.1; -; mRNA.
DR CCDS; CCDS23908.1; -.
DR PIR; A36074; A36074.
DR RefSeq; NP_031685.2; NM_007659.3.
DR AlphaFoldDB; P11440; -.
DR SMR; P11440; -.
DR BioGRID; 198624; 140.
DR ComplexPortal; CPX-2061; Cyclin A1-CDK1 complex.
DR ComplexPortal; CPX-2062; Cyclin A2-CDK1 complex.
DR ComplexPortal; CPX-2069; Cyclin B1-CDK1 complex.
DR ComplexPortal; CPX-2070; Cyclin B2-CDK1 complex.
DR CORUM; P11440; -.
DR DIP; DIP-38725N; -.
DR ELM; P11440; -.
DR IntAct; P11440; 133.
DR MINT; P11440; -.
DR STRING; 10090.ENSMUSP00000020099; -.
DR BindingDB; P11440; -.
DR ChEMBL; CHEMBL4084; -.
DR iPTMnet; P11440; -.
DR PhosphoSitePlus; P11440; -.
DR SwissPalm; P11440; -.
DR EPD; P11440; -.
DR jPOST; P11440; -.
DR MaxQB; P11440; -.
DR PaxDb; P11440; -.
DR PeptideAtlas; P11440; -.
DR PRIDE; P11440; -.
DR ProteomicsDB; 283771; -.
DR Antibodypedia; 1134; 2721 antibodies from 49 providers.
DR DNASU; 12534; -.
DR Ensembl; ENSMUST00000020099; ENSMUSP00000020099; ENSMUSG00000019942.
DR Ensembl; ENSMUST00000119827; ENSMUSP00000113184; ENSMUSG00000019942.
DR GeneID; 12534; -.
DR KEGG; mmu:12534; -.
DR UCSC; uc007fmr.1; mouse.
DR CTD; 983; -.
DR MGI; MGI:88351; Cdk1.
DR VEuPathDB; HostDB:ENSMUSG00000019942; -.
DR eggNOG; KOG0594; Eukaryota.
DR GeneTree; ENSGT00940000153335; -.
DR InParanoid; P11440; -.
DR OMA; NNDVWPE; -.
DR OrthoDB; 1010560at2759; -.
DR PhylomeDB; P11440; -.
DR TreeFam; TF101021; -.
DR BRENDA; 2.7.11.22; 3474.
DR Reactome; R-MMU-110056; MAPK3 (ERK1) activation.
DR Reactome; R-MMU-174048; APC/C:Cdc20 mediated degradation of Cyclin B.
DR Reactome; R-MMU-174184; Cdc20:Phospho-APC/C mediated degradation of Cyclin A.
DR Reactome; R-MMU-176408; Regulation of APC/C activators between G1/S and early anaphase.
DR Reactome; R-MMU-176412; Phosphorylation of the APC/C.
DR Reactome; R-MMU-176417; Phosphorylation of Emi1.
DR Reactome; R-MMU-2299718; Condensation of Prophase Chromosomes.
DR Reactome; R-MMU-2500257; Resolution of Sister Chromatid Cohesion.
DR Reactome; R-MMU-2565942; Regulation of PLK1 Activity at G2/M Transition.
DR Reactome; R-MMU-2980767; Activation of NIMA Kinases NEK9, NEK6, NEK7.
DR Reactome; R-MMU-2995383; Initiation of Nuclear Envelope (NE) Reformation.
DR Reactome; R-MMU-3301854; Nuclear Pore Complex (NPC) Disassembly.
DR Reactome; R-MMU-380259; Loss of Nlp from mitotic centrosomes.
DR Reactome; R-MMU-380270; Recruitment of mitotic centrosome proteins and complexes.
DR Reactome; R-MMU-380284; Loss of proteins required for interphase microtubule organization from the centrosome.
DR Reactome; R-MMU-380320; Recruitment of NuMA to mitotic centrosomes.
DR Reactome; R-MMU-4419969; Depolymerisation of the Nuclear Lamina.
DR Reactome; R-MMU-5620912; Anchoring of the basal body to the plasma membrane.
DR Reactome; R-MMU-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-MMU-5689896; Ovarian tumor domain proteases.
DR Reactome; R-MMU-6804114; TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest.
DR Reactome; R-MMU-6804757; Regulation of TP53 Degradation.
DR Reactome; R-MMU-68875; Mitotic Prophase.
DR Reactome; R-MMU-69273; Cyclin A/B1/B2 associated events during G2/M transition.
DR Reactome; R-MMU-69478; G2/M DNA replication checkpoint.
DR Reactome; R-MMU-75035; Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex.
DR Reactome; R-MMU-8852276; The role of GTSE1 in G2/M progression after G2 checkpoint.
DR Reactome; R-MMU-8854518; AURKA Activation by TPX2.
DR Reactome; R-MMU-8878166; Transcriptional regulation by RUNX2.
DR BioGRID-ORCS; 12534; 28 hits in 73 CRISPR screens.
DR ChiTaRS; Cdk1; mouse.
DR PRO; PR:P11440; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; P11440; protein.
DR Bgee; ENSMUSG00000019942; Expressed in maxillary prominence and 225 other tissues.
DR ExpressionAtlas; P11440; baseline and differential.
DR Genevisible; P11440; MM.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0097125; C:cyclin B1-CDK1 complex; ISO:MGI.
DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030496; C:midbody; ISO:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; ISO:MGI.
DR GO; GO:0072686; C:mitotic spindle; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005876; C:spindle microtubule; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0030332; F:cyclin binding; ISO:MGI.
DR GO; GO:0097472; F:cyclin-dependent protein kinase activity; IDA:MGI.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0035173; F:histone kinase activity; ISO:MGI.
DR GO; GO:0030544; F:Hsp70 protein binding; IPI:MGI.
DR GO; GO:0016301; F:kinase activity; IDA:MGI.
DR GO; GO:0004672; F:protein kinase activity; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0031100; P:animal organ regeneration; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:MGI.
DR GO; GO:0030261; P:chromosome condensation; ISO:MGI.
DR GO; GO:0030855; P:epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0048144; P:fibroblast proliferation; IDA:MGI.
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:0044772; P:mitotic cell cycle phase transition; IMP:MGI.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IDA:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISS:ParkinsonsUK-UCL.
DR GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; ISO:MGI.
DR GO; GO:0045740; P:positive regulation of DNA replication; ISO:MGI.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:1905448; P:positive regulation of mitochondrial ATP synthesis coupled electron transport; ISO:MGI.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISO:MGI.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISO:MGI.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISO:MGI.
DR GO; GO:0034501; P:protein localization to kinetochore; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0065003; P:protein-containing complex assembly; ISO:MGI.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS: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; ISO:MGI.
DR GO; GO:0010243; P:response to organonitrogen compound; ISO:MGI.
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 Acetylation; Apoptosis; ATP-binding; Biological rhythms; Cell cycle;
KW Cell division; Cytoplasm; Cytoskeleton; Direct protein sequencing;
KW Isopeptide bond; Kinase; Mitochondrion; Mitosis; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..297
FT /note="Cyclin-dependent kinase 1"
FT /id="PRO_0000085725"
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:23806337"
FT MOD_RES 4
FT /note="Phosphotyrosine; by PKR"
FT /evidence="ECO:0000250|UniProtKB:P06493"
FT MOD_RES 6
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 9
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 14
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19131326,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 15
FT /note="Phosphotyrosine; by PKMYT1, WEE1, WEE2 and
FT PKC/PRKCD"
FT /evidence="ECO:0000305|PubMed:16169490,
FT ECO:0000305|PubMed:19917613, ECO:0000305|PubMed:21454751,
FT ECO:0007744|PubMed:19131326, ECO:0007744|PubMed:21183079"
FT MOD_RES 15
FT /note="Phosphotyrosine; by WEE1 and WEE2"
FT /evidence="ECO:0000269|PubMed:16169490,
FT ECO:0000269|PubMed:19917613, ECO:0000269|PubMed:21454751,
FT ECO:0007744|PubMed:19131326, ECO:0007744|PubMed:21183079"
FT MOD_RES 19
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P06493"
FT MOD_RES 39
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06493"
FT MOD_RES 77
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P06493"
FT MOD_RES 141
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P06493"
FT MOD_RES 161
FT /note="Phosphothreonine; by CAK"
FT /evidence="ECO:0000250|UniProtKB:P06493"
FT MOD_RES 178
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06493"
FT MOD_RES 222
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P06493"
FT MOD_RES 245
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 248
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06493"
FT CROSSLNK 6
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P06493"
FT CROSSLNK 9
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P06493"
FT CROSSLNK 20
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P06493"
FT CROSSLNK 139
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P06493"
FT CONFLICT 112
FT /note="I -> M (in Ref. 4; AAB09465)"
FT /evidence="ECO:0000305"
FT CONFLICT 113
FT /note="L -> M (in Ref. 3; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 165
FT /note="V -> L (in Ref. 2; CAA34481)"
FT /evidence="ECO:0000305"
FT CONFLICT 245
FT /note="K -> N (in Ref. 3; AA sequence and 4; AAB09465)"
FT /evidence="ECO:0000305"
FT CONFLICT 260
FT /note="G -> C (in Ref. 3; AA sequence and 4; AAB09465)"
FT /evidence="ECO:0000305"
FT CONFLICT 263
FT /note="L -> F (in Ref. 3; AA sequence and 4; AAB09465)"
FT /evidence="ECO:0000305"
FT CONFLICT 273
FT /note="A -> T (in Ref. 2; CAA34481)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 297 AA; 34107 MW; 9C399FCC41BA7F31 CRC64;
MEDYIKIEKI GEGTYGVVYK GRHRVTGQIV AMKKIRLESE EEGVPSTAIR EISLLKELRH
PNIVSLQDVL MQDSRLYLIF EFLSMDLKKY LDSIPPGQFM DSSLVKSYLH QILQGIVFCH
SRRVLHRDLK PQNLLIDDKG TIKLADFGLA RAFGIPIRVY THEVVTLWYR SPEVLLGSAR
YSTPVDIWSI GTIFAELATK KPLFHGDSEI DQLFRIFRAL GTPNNEVWPE VESLQDYKNT
FPKWKPGSLA SHVKNLDENG LDLLSKMLVY DPAKRISGKM ALKHPYFDDL DNQIKKM
