ID CDK1_PONAB Reviewed; 297 AA. AC Q5RCH1; DT 16-AUG-2005, integrated into UniProtKB/Swiss-Prot. DT 21-DEC-2004, sequence version 1. DT 27-MAR-2024, entry version 114. 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: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, CDKN1; OS Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Pongo. OX NCBI_TaxID=9601; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Heart; RG The German cDNA consortium; RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases. 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 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 and RUNX2. CDK1/CDC2-cyclin-B controls CC pronuclear union in interphase fertilized eggs. Essential for early CC stages of embryonic development. 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. 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. Phosphorylates KRT5 during prometaphase and metaphase (By CC similarity). Inactivated by PKR/EIF2AK2- and WEE1-mediated CC phosphorylation upon DNA damage to stop cell cycle and genome CC replication at the G2 checkpoint thus facilitating DNA repair. CC Reactivated after successful DNA repair through WIP1-dependent CC signaling leading to CDC25A/B/C-mediated dephosphorylation and CC restoring cell cycle progression. Catalyzes lamin (LMNA, LMNB1 and CC LMNB2) phosphorylation at the onset of mitosis, promoting nuclear CC envelope breakdown. 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. The phosphorylation of beta-tubulins regulates microtubule CC dynamics during mitosis. NEDD1 phosphorylation promotes PLK1-mediated CC NEDD1 phosphorylation and subsequent targeting of the gamma-tubulin CC ring complex (gTuRC) to the centrosome, an important step for spindle CC formation. In addition, CC2D1A phosphorylation regulates CC2D1A spindle CC pole localization and association with SCC1/RAD21 and centriole CC cohesion during mitosis. The phosphorylation of Bcl-xL/BCL2L1 after CC prolongated G2 arrest upon DNA damage triggers apoptosis. In contrast, CC CASP8 phosphorylation during mitosis prevents its activation by CC proteolysis and subsequent apoptosis. This phosphorylation occurs in CC cancer cell lines, as well as in primary breast tissues and CC lymphocytes. EZH2 phosphorylation promotes H3K27me3 maintenance and CC epigenetic gene silencing. CALD1 phosphorylation promotes Schwann cell CC migration during peripheral nerve regeneration. CDK1-cyclin-B complex CC phosphorylates NCKAP5L and mediates its dissociation from centrosomes CC during mitosis. Regulates the amplitude of the cyclic expression of the CC core clock gene BMAL1 by phosphorylating its transcriptional repressor CC NR1D1, and this phosphorylation is necessary for SCF(FBXW7)-mediated CC ubiquitination and proteasomal degradation of NR1D1 (By similarity). CC Phosphorylates EML3 at 'Thr-881' which is essential for its interaction CC with HAUS augmin-like complex and TUBG1 (By similarity). Phosphorylates CC CGAS during mitosis, leading to its inhibition, thereby preventing CGAS CC activation by self DNA during mitosis (By similarity). CC {ECO:0000250|UniProtKB:P06493, ECO:0000250|UniProtKB:P11440, CC ECO:0000250|UniProtKB:P39951}. 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: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 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. Interacts with NR1D1 (By CC similarity). Interacts with proteasome subunit PSMA8; to participate in CC meiosis progression during spermatogenesis (By similarity). CC {ECO:0000250|UniProtKB:P06493, ECO:0000250|UniProtKB:P11440}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P11440}. Cytoplasm CC {ECO:0000250|UniProtKB:P11440}. Mitochondrion CC {ECO:0000250|UniProtKB:P11440}. 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). CC {ECO:0000250|UniProtKB:P06493}. CC -!- PTM: Polyubiquitinated upon genotoxic stress. CC {ECO:0000250|UniProtKB:P06493}. 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; CR858299; CAH90536.1; -; mRNA. DR RefSeq; NP_001125286.1; NM_001131814.1. DR AlphaFoldDB; Q5RCH1; -. DR SMR; Q5RCH1; -. DR STRING; 9601.ENSPPYP00000002808; -. DR GeneID; 100172184; -. DR KEGG; pon:100172184; -. DR CTD; 983; -. DR eggNOG; KOG0594; Eukaryota. DR InParanoid; Q5RCH1; -. DR OrthoDB; 244018at2759; -. DR Proteomes; UP000001595; Unplaced. DR GO; GO:0005813; C:centrosome; ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0072686; C:mitotic spindle; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; ISS:UniProtKB. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB. DR GO; GO:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; IEA:UniProtKB-EC. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. 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:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB. DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISS:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB. DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB. DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW. 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; 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; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. PE 2: Evidence at transcript level; KW Acetylation; Apoptosis; ATP-binding; Biological rhythms; Cell cycle; KW Cell division; Cytoplasm; Cytoskeleton; Isopeptide bond; Kinase; KW Mitochondrion; Mitosis; Nucleotide-binding; Nucleus; Phosphoprotein; KW Reference proteome; Serine/threonine-protein kinase; Transferase; KW Ubl conjugation. FT CHAIN 1..297 FT /note="Cyclin-dependent kinase 1" FT /id="PRO_0000085726" 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:0000250|UniProtKB:P06493" 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:0000250|UniProtKB:P06493" 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:0000250|UniProtKB:P06493" FT MOD_RES 15 FT /note="Phosphotyrosine; by PKMYT1, WEE1 and WEE2" FT /evidence="ECO:0000250|UniProtKB:P06493" FT MOD_RES 15 FT /note="Phosphotyrosine; by WEE1 and WEE2" FT /evidence="ECO:0000250|UniProtKB:P06493" 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:0000250|UniProtKB:P11440" 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" SQ SEQUENCE 297 AA; 34125 MW; 612D7D14CBFE420A CRC64; MEDYTKIEKI GEGTYGVVYK GRHKTTGQVV TMKKIRLESE 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 //