CDK1_PONAB
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 03-AUG-2022, entry version 110.
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, and regulates G1 progress and G1-S transition via
CC association with multiple interphase cyclins. Required in higher cells
CC for entry into S-phase and mitosis. Phosphorylates PARVA/actopaxin,
CC APC, AMPH, APC, BARD1, Bcl-xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20,
CC CDC25A, CDC25C, CC2D1A, CENPA, CSNK2 proteins/CKII, FZR1/CDH1, CDK7,
CC CEBPB, CHAMP1, DMD/dystrophin, EEF1 proteins/EF-1, EZH2, KIF11/EG5,
CC EGFR, FANCG, FOS, GFAP, GOLGA2/GM130, GRASP1, UBE2A/hHR6A, HIST1H1
CC proteins/histone H1, HMGA1, HIVEP3/KRC, KAT5, LMNA, LMNB, LMNC, LBR,
CC LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, MYB, NEFH, NFIC,
CC NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, NCL, NUCKS1,
CC 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. 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. 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. 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 ARNTL/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:P11440, 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.
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}.
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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; 1010560at2759; -.
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:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
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 InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 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
