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Details on Person UniProt:P06493 CDK1
| Class:Id | ReferenceGeneProduct:86981 |
|---|---|
| _chainChangeLog | chain:1-297 added on Sat February 7 2015 |
| _displayName | UniProt:P06493 CDK1 |
| _timestamp | 2026-02-20 22:07:46 |
| chain | chain:1-297 |
| checksum | 942D79448EFE490A |
| comment | FUNCTION Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition via association with multiple interphase cyclins (PubMed:16407259, PubMed:16933150, PubMed:17459720, PubMed:18356527, PubMed:19509060, PubMed:19917720, PubMed:20171170, PubMed:20935635, PubMed:20937773, PubMed:21063390, PubMed:2188730, PubMed:23355470, PubMed:2344612, PubMed:23601106, PubMed:23602554, PubMed:25556658, PubMed:26829474, PubMed:27814491, PubMed:30139873, PubMed:30704899, PubMed:40440427). Phosphorylates PARVA/actopaxin, APC, AMPH, APC, ASB7, BARD1, Bcl-xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, CENPA, CSNK2 proteins/CKII, FZR1/CDH1, CDK7, CEBPB, CHAMP1, DMD/dystrophin, EEF1 proteins/EF-1, EZH2, KIF11/EG5, EGFR, FANCG, FOS, GFAP, GOLGA2/GM130, GRASP1, UBE2A/hHR6A, HIST1H1 proteins/histone H1, HMGA1, HIVEP3/KRC, UHRF1, KAT5, LMNA, LMNB, LBR, MKI67, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, MLST8, MYB, NEFH, NFIC, NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, NCL, NUCKS1, NPM1/numatrin, ORC1, PRKAR2A, EEF1E1/p18, EIF3F/p47, p53/TP53, NONO/p54NRB, PAPOLA, PLEC/plectin, RB1, TPPP, UL40/R2, RAB4A, RAP1GAP, RBBP8/CtIP, RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68, ESPL1, SKI, BIRC5/survivin, STIP1, TEX14, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1, RUNX1/AML1, SAMHD1, SIRT2, CGAS and RUNX2 (PubMed:16407259, PubMed:16933150, PubMed:17459720, PubMed:18356527, PubMed:19202191, PubMed:19509060, PubMed:19917720, PubMed:20171170, PubMed:20935635, PubMed:20937773, PubMed:21063390, PubMed:2188730, PubMed:22411829, PubMed:23355470, PubMed:2344612, PubMed:23601106, PubMed:23602554, PubMed:25012651, PubMed:25556658, PubMed:26829474, PubMed:27814491, PubMed:30704899, PubMed:32351706, PubMed:34741373, PubMed:40440427). CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs (PubMed:18480403, PubMed:20360007). Essential for early stages of embryonic development (PubMed:18480403, PubMed:20360007). During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation (PubMed:18480403, PubMed:20360007, PubMed:2188730, PubMed:2344612, PubMed:30139873). Once chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis (PubMed:18480403, PubMed:20360007). Phosphorylates KRT5 during prometaphase and metaphase (By similarity). Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair (PubMed:20360007). Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression (PubMed:20395957). Catalyzes lamin (LMNA, LMNB1 and LMNB2) phosphorylation at the onset of mitosis, promoting nuclear envelope breakdown (PubMed:2188730, PubMed:2344612, PubMed:37788673). In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons (PubMed:18356527). The phosphorylation of beta-tubulins regulates microtubule dynamics during mitosis (PubMed:16371510). NEDD1 phosphorylation promotes PLK1-mediated NEDD1 phosphorylation and subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation (PubMed:19509060). In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole localization and association with SCC1/RAD21 and centriole cohesion during mitosis (PubMed:20171170). The phosphorylation of Bcl-xL/BCL2L1 after prolongated G2 arrest upon DNA damage triggers apoptosis (PubMed:19917720). In contrast, CASP8 phosphorylation during mitosis prevents its activation by proteolysis and subsequent apoptosis (PubMed:20937773). This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes (PubMed:20937773). EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing (PubMed:20935635). CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration (By similarity). CDK1-cyclin-B complex phosphorylates NCKAP5L and mediates its dissociation from centrosomes during mitosis (PubMed:26549230). Regulates the amplitude of the cyclic expression of the core clock gene BMAL1 by phosphorylating its transcriptional repressor NR1D1, and this phosphorylation is necessary for SCF(FBXW7)-mediated ubiquitination and proteasomal degradation of NR1D1 (PubMed:27238018). Phosphorylates EML3 at 'Thr-881' which is essential for its interaction with HAUS augmin-like complex and TUBG1 (PubMed:30723163). Phosphorylates CGAS during mitosis, leading to its inhibition, thereby preventing CGAS activation by self DNA during mitosis (PubMed:32351706). Phosphorylates SKA3 on multiple sites during mitosis which promotes SKA3 binding to the NDC80 complex and anchoring of the SKA complex to kinetochores, to enable stable attachment of mitotic spindle microtubules to kinetochores (PubMed:28479321, PubMed:31804178, PubMed:32491969).FUNCTION (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry.CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)CATALYTIC ACTIVITY [DNA-directed RNA polymerase] + ATP = phospho-[DNA-directed RNA polymerase] + ADP + H(+)ACTIVITY REGULATION Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-161 activates it (PubMed:20360007, PubMed:7569953). Activated through a multistep process; binding to cyclin-B is required for relocation of cyclin-kinase complexes to the nucleus, activated by CAK/CDK7-mediated phosphorylation on Thr-161, and CDC25-mediated dephosphorylation of inhibitory phosphorylation on Thr-14 and Tyr-15 (PubMed:20360007, PubMed:7569953). Activity is restricted during S-phase in an ATR-dependent manner to prevent premature entry into G2 (PubMed:30139873). Repressed by the CDK inhibitors CDKN1A/p21 and CDKN1B/p27 during the G1 phase and by CDKN1A/p21 at the G1-S checkpoint upon DNA damage. Transient activation by rapid and transient dephosphorylation at Tyr-15 triggered by TGFB1 (PubMed:17459720). Inhibited by flavopiridol and derivatives, pyrimidine derivatives, pyridine derivatives, purine derivatives, staurosporine, paullones, oxoindoles, indazole analogs, indolin-2-ones, pyrazolo[3,4-b]pyridines, imidazo[1,2-a]pyridine (AZ703), thiazolinone analogs(RO-3306), thiazol urea, macrocyclic quinoxalin-2-one, pyrrolo[2,3-a]carbazole, pyrazolo[1,5-a]-1,3,5-triazine, pyrazolo[1,5-a]pyrimidine (Dinaciclib, SCH 727965), 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine), olomoucine, AG-024322, AT-7519, P276-00, R547/Ro-4584820 and SNS-032/BMS-387032 (PubMed:9030781).SUBUNIT Forms a stable but non-covalent complex with a regulatory subunit and with a cyclin (PubMed:20360007). The cyclin subunit imparts substrate specificity to the complex (PubMed:20360007). Interacts with cyclins-B (CCNB1, CCNB2 and CCNB3) to form a serine/threonine kinase holoenzyme complex also known as maturation promoting factor (MPF) (PubMed:20360007, PubMed:2188730, PubMed:2344612). Promotes G2-M transition when in complex with a cyclin-B (PubMed:20360007). Can also form CDK1-cylin-D and CDK1-cyclin-E complexes that phosphorylate RB1 in vitro (PubMed:17459720). Associates with cyclins-A and B1 during S-phase in regenerating hepatocytes (PubMed:20360007). Interacts with DLGAP5 (PubMed:15145941). Binds to the CDK inhibitors CDKN1A/p21 and CDKN1B/p27. Interacts with catalytically active CCNB1 and RALBP1 during mitosis to form an endocytotic complex during interphase (PubMed:12775724). Interacts with FANCC (PubMed:9242535). Interacts with CEP63; this interaction recruits CDK1 to centrosomes (PubMed:21406398). Interacts with CENPA (PubMed:25556658). Interacts with NR1D1 (PubMed:27238018). Interacts with proteasome subunit PSMA8; to participate in meiosis progression during spermatogenesis (By similarity).SUBUNIT Unable to complex with cyclin-B1 and also fails to bind to CDKN1A/p21.SUBUNIT (Microbial infection) Interacts with severe fever with thrombocytopenia syndrome virus (SFTSV) NSs; this interaction is inclusion body dependent, it inhibits the formation and nuclear import of the cyclin B1-CDK1 complex and leads to cell cycle arrest.INTERACTION Cytoplasmic during the interphase. Colocalizes with SIRT2 on centrosome during prophase and on splindle fibers during metaphase of the mitotic cell cycle. Reversibly translocated from cytoplasm to nucleus when phosphorylated before G2-M transition when associated with cyclin-B1. Accumulates in mitochondria in G2-arrested cells upon DNA-damage.ALTERNATIVE PRODUCTS Found in breast cancer tissues.INDUCTION Follows a cyclic expression; during interphase, accumulates gradually following G1, S to reach a critical threshold at the end of G2, which promotes self-activation and triggers onset of mitosis. Induced transiently by TGFB1 at an early phase of TGFB1-mediated apoptosis, but later repressed. Triggered by CKS1B during mitotic entry in breast cancer cells. Down-regulated under genotoxic stresses triggered by PKR/EIF2AK2-mediated phosphorylation.PTM Phosphorylation at Thr-161 by CAK/CDK7 activates kinase activity (PubMed:20360007). Phosphorylation at Thr-14 and Tyr-15 by PKMYT1 prevents nuclear translocation (PubMed:7569953). Phosphorylation at Tyr-15 by WEE1 and WEE2 inhibits the protein kinase activity and acts as a negative regulator of entry into mitosis (G2 to M transition) (PubMed:20360007). Phosphorylation by PKMYT1 and WEE1 takes place during mitosis to keep CDK1-cyclin-B complexes inactive until the end of G2 (PubMed:20360007, PubMed:7569953). By the end of G2, PKMYT1 and WEE1 are inactivated, but CDC25A and CDC25B are activated (PubMed:20360007). Dephosphorylation by active CDC25A and CDC25B at Thr-14 and Tyr-15, leads to CDK1 activation at the G2-M transition (PubMed:20360007). Phosphorylation at Tyr-15 by WEE2 during oogenesis is required to maintain meiotic arrest in oocytes during the germinal vesicle (GV) stage, a long period of quiescence at dictyate prophase I, leading to prevent meiotic reentry (PubMed:29606300). Phosphorylation by WEE2 is also required for metaphase II exit during egg activation to ensure exit from meiosis in oocytes and promote pronuclear formation (PubMed:29606300). Phosphorylated at Tyr-4 by PKR/EIF2AK2 upon genotoxic stress (PubMed:20395957). This phosphorylation triggers CDK1 polyubiquitination and subsequent proteolysis, thus leading to G2 arrest (PubMed:20395957). In response to UV irradiation, phosphorylation at Tyr-15 by PRKCD activates the G2/M DNA damage checkpoint (PubMed:19917613).PTM Polyubiquitinated upon genotoxic stress.MISCELLANEOUS As a key regulator of the cell cycle, CDK1 is a potent therapeutic target for inhibitors in cancer treatment.SIMILARITY Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. |
| description | recommendedName: Cyclin-dependent kinase 1 shortName: CDK1 ecNumber evidence="27 29 30 36 42"2.7.11.22 ecNumber evidence="1"2.7.11.23 alternativeName: Cell division control protein 2 homolog alternativeName: Cell division protein kinase 1 alternativeName: p34 protein kinase |
| geneName | CDK1 CDC2 CDC28A CDKN1 P34CDC2 |
| identifier | P06493 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alternative splicing Apoptosis ATP-binding Biological rhythms Cell cycle Cell division Cytoplasm Cytoskeleton Host cell receptor for virus entry Host-virus interaction Isopeptide bond Kinase Mitochondrion Mitosis Nucleotide-binding Nucleus Phosphoprotein Proteomics identification Receptor Reference proteome Serine/threonine-protein kinase Transferase Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9909836] Weiser, Joel, 2024-05-14 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | CDK1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8961925] ENSEMBL:ENSG00000170312 CDK1 [Homo sapiens] |
| secondaryIdentifier | CDK1_HUMAN A8K7C4 C9J497 O60764 |
| sequenceLength | 297 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:222512] UniProt:P06493-2 CDK1 [Homo sapiens] [ReferenceIsoform:402506] UniProt:P06493-1 CDK1 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:68889] CDK1 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:68894] p-T14,Y15-CDK1 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:157415] p-T161-CDK1 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:157468] p-T14,Y15-CDK1 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:170045] p-T14-CDK1 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:170064] p-T14-CDK1 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:170066] p-T161-CDK1 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:170071] p-T14,Y15,T161-CDK1 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:170074] p-T14,Y15,T161-CDK1 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:170075] CDK1 [cytosol] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:68893] phosphorylated residue at unknown position [ModifiedResidue:109453] O-phospho-L-threonine at 14 [ModifiedResidue:109459] O4'-phospho-L-tyrosine at 15 [ModifiedResidue:170054] O-phospho-L-threonine at 161 [ModifiedResidue:9836188] O4'-phospho-L-tyrosine at 4 |
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No pathways have been reviewed or authored by UniProt:P06493 CDK1 (86981)
