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 27-MAR-2024, entry version 237. DE RecName: Full=Cyclin-dependent kinase 1; DE Short=CDK1; DE EC=2.7.11.22 {ECO:0000269|PubMed:36264786}; 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). RN [20] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=36264786; DOI=10.1126/science.abq4835; RA Cheng S., Altmeppen G., So C., Welp L.M., Penir S., Ruhwedel T., RA Menelaou K., Harasimov K., Stuetzer A., Blayney M., Elder K., Moebius W., RA Urlaub H., Schuh M.; RT "Mammalian oocytes store mRNAs in a mitochondria-associated membraneless RT compartment."; RL Science 378:eabq4835-eabq4835(2022). 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 via association with multiple interphase cyclins CC (PubMed:16007079, PubMed:17700700, PubMed:17942597, PubMed:22405274). CC Phosphorylates PARVA/actopaxin, APC, AMPH, APC, BARD1, Bcl-xL/BCL2L1, CC BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, CENPA, CSNK2 CC proteins/CKII, FZR1/CDH1, CDK7, CEBPB, CHAMP1, DMD/dystrophin, EEF1 CC proteins/EF-1, EZH2, KIF11/EG5, EGFR, FANCG, FOS, GFAP, GOLGA2/GM130, CC GRASP1, UBE2A/hHR6A, HIST1H1 proteins/histone H1, HMGA1, HIVEP3/KRC, CC KAT5, LMNA, LMNB, LBR, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, CC MLST8, MYB, NEFH, NFIC, NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, CC NCL, NUCKS1, NPM1/numatrin, ORC1, PRKAR2A, EEF1E1/p18, EIF3F/p47, CC p53/TP53, NONO/p54NRB, PAPOLA, PLEC/plectin, RB1, TPPP, UL40/R2, RAB4A, CC RAP1GAP, RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68, ESPL1, SKI, BIRC5/survivin, CC STIP1, TEX14, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1, CC RUNX1/AML1, SAMHD1, SIRT2, CGAS, ZAR1 and RUNX2 (PubMed:17942597, CC PubMed:22405274, PubMed:36264786). CDK1/CDC2-cyclin-B controls CC pronuclear union in interphase fertilized eggs (By similarity). CC Essential for early stages of embryonic development (By similarity). CC During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation CC activates CDK1/cyclin complexes which phosphorylate several substrates CC that trigger at least centrosome separation, Golgi dynamics, nuclear CC envelope breakdown and chromosome condensation (PubMed:16007079, CC PubMed:17700700). Once chromosomes are condensed and aligned at the CC metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1- CC mediated phosphorylation to allow sister chromatid separation, CC chromosome decondensation, reformation of the nuclear envelope and CC cytokinesis (By similarity). Phosphorylates KRT5 during prometaphase CC and metaphase (PubMed:29518391). Inactivated by PKR/EIF2AK2- and WEE1- CC mediated phosphorylation upon DNA damage to stop cell cycle and genome CC replication at the G2 checkpoint thus facilitating DNA repair (By CC similarity). Reactivated after successful DNA repair through WIP1- CC dependent signaling leading to CDC25A/B/C-mediated dephosphorylation CC and restoring cell cycle progression (By similarity). Catalyzes lamin CC (LMNA, LMNB1 and LMNB2) phosphorylation at the onset of mitosis, CC promoting nuclear envelope breakdown (By similarity). In proliferating CC cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses CC FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 CC nuclear accumulation and transcription factor activity, leading to cell CC death of postmitotic neurons (By similarity). The phosphorylation of CC beta-tubulins regulates microtubule dynamics during mitosis (By CC similarity). NEDD1 phosphorylation promotes PLK1-mediated NEDD1 CC phosphorylation and subsequent targeting of the gamma-tubulin ring CC complex (gTuRC) to the centrosome, an important step for spindle CC formation (By similarity). In addition, CC2D1A phosphorylation CC regulates CC2D1A spindle pole localization and association with CC SCC1/RAD21 and centriole cohesion during mitosis (By similarity). The CC phosphorylation of Bcl-xL/BCL2L1 after prolongated G2 arrest upon DNA CC damage triggers apoptosis (By similarity). In contrast, CASP8 CC phosphorylation during mitosis prevents its activation by proteolysis CC and subsequent apoptosis (By similarity). This phosphorylation occurs CC in cancer cell lines, as well as in primary breast tissues and CC lymphocytes (By similarity). EZH2 phosphorylation promotes H3K27me3 CC maintenance and epigenetic gene silencing (By similarity). CALD1 CC phosphorylation promotes Schwann cell migration during peripheral nerve CC regeneration (By similarity). CDK1-cyclin-B complex phosphorylates CC NCKAP5L and mediates its dissociation from centrosomes during mitosis CC (By similarity). Regulates the amplitude of the cyclic expression of CC the core clock gene BMAL1 by phosphorylating its transcriptional CC repressor NR1D1, and this phosphorylation is necessary for SCF(FBXW7)- CC mediated ubiquitination and proteasomal degradation of NR1D1 (By CC similarity). Phosphorylates EML3 at 'Thr-881' which is essential for CC its interaction with HAUS augmin-like complex and TUBG1 (By CC similarity). Phosphorylates CGAS during mitosis, leading to its CC inhibition, thereby preventing CGAS activation by self DNA during CC mitosis (By similarity). {ECO:0000250|UniProtKB:P06493, CC ECO:0000250|UniProtKB:P39951, ECO:0000269|PubMed:16007079, CC ECO:0000269|PubMed:17700700, ECO:0000269|PubMed:17942597, CC ECO:0000269|PubMed:22405274, 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:0000269|PubMed:36264786}; 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:36264786}; 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. 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 Activity is restricted during S-phase in an ATR-dependent manner to CC prevent premature entry into G2. 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: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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 143. 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; 10090-ENSMUSP00000020099; -. DR PeptideAtlas; P11440; -. DR ProteomicsDB; 283771; -. DR Pumba; P11440; -. DR Antibodypedia; 1134; 2991 antibodies from 49 providers. DR DNASU; 12534; -. DR Ensembl; ENSMUST00000020099.13; ENSMUSP00000020099.6; ENSMUSG00000019942.14. DR Ensembl; ENSMUST00000119827.8; ENSMUSP00000113184.2; ENSMUSG00000019942.14. DR GeneID; 12534; -. DR KEGG; mmu:12534; -. DR UCSC; uc007fmr.1; mouse. DR AGR; MGI:88351; -. DR CTD; 983; -. DR MGI; MGI:88351; Cdk1. DR VEuPathDB; HostDB:ENSMUSG00000019942; -. DR eggNOG; KOG0594; Eukaryota. DR GeneTree; ENSGT00940000153335; -. DR InParanoid; P11440; -. DR OMA; YLYQITR; -. DR OrthoDB; 244018at2759; -. 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; Depolymerization 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 Reactome; R-MMU-9833482; PKR-mediated signaling. DR BioGRID-ORCS; 12534; 29 hits in 78 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 229 other cell types or tissues. DR ExpressionAtlas; P11440; baseline and differential. DR GO; GO:0005813; C:centrosome; ISS:UniProtKB. DR GO; GO:0097122; C:cyclin A2-CDK1 complex; IPI:ComplexPortal. 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; IEA:Ensembl. 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:0000082; P:G1/S transition of mitotic cell cycle; NAS:ComplexPortal. DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; ISS:UniProtKB. DR GO; GO:0090166; P:Golgi disassembly; ISS:UniProtKB. DR GO; GO:1902850; P:microtubule cytoskeleton organization involved in mitosis; ISO:MGI. 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:0062033; P:positive regulation of mitotic sister chromatid segregation; 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: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 CDD; cd07861; STKc_CDK1_euk; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR24056; CELL DIVISION PROTEIN KINASE; 1. DR PANTHER; PTHR24056:SF334; CYCLIN-DEPENDENT KINASE 1; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; P11440; MM. 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 //