CDC2
entrez
983
canonical
uniprot
P06493
canonical
ensembl
ENSG00000170312
resolver
ensp
ENSP00000325970
resolver
ensp
ENSP00000378699
resolver
ensp
ENSP00000526596
resolver
ensp
ENSP00000615100
resolver
ensp
ENSP00000727895
resolver
genesymbol
CDC2
resolver
genesymbol
CDK1
resolver
genesymbol_syn
CDC2
resolver
genesymbol_syn
CDC28A
resolver
genesymbol_syn
CDKN1
resolver
genesymbol_syn
P34CDC2
resolver
hgnc
HGNC:1722
resolver
uniprot
A8K7C4
resolver
uniprot
B7Z3D6
resolver
uniprot
C9J497
resolver
uniprot
I6L9I5
resolver
uniprot
O60764
resolver
uniprot_entry
B7Z3D6_HUMAN
resolver
uniprot_entry
CDK1_HUMAN
resolver
uniprot_entry
I6L9I5_HUMAN
resolver
uniprot_sec
A8K7C4
resolver
uniprot_sec
C9J497
resolver
uniprot_sec
O60764
resolver
activity_regulation
ACTIVITY REGULATION: Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-161 activates it (PubMed:20360007, PubMed:7569953). Binding to cyclin-B is required for relocation of cyclin-kinase complexes to the nucleus for activation (PubMed:20360007, PubMed:7569953). Activated by CAK/CDK7-mediated phosphorylation on Thr-161, and reciprocally phosphorylates its activating kinase CDK7 (PubMed:20360007, PubMed:41100585). CDC25-mediated dephosphorylation of inhibitory phosphorylation on Thr-14 and Tyr-15 is required for full activation (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). {ECO:0000269|PubMed:17459720, ECO:0000269|PubMed:20360007, ECO:0000269|PubMed:30139873, ECO:0000269|PubMed:41100585, ECO:0000269|PubMed:7569953, ECO:0000269|PubMed:9030781}.
uniprot
proteins
amino_acid_sequence
MEDYTKIEKIGEGTYGVVYKGRHKTTGQVVAMKKIRLESEEEGVPSTAIREISLLKELRHPNIVSLQDVLMQDSRLYLIFEFLSMDLKKYLDSIPPGQYMDSSLVKSYLYQILQGIVFCHSRRVLHRDLKPQNLLIDDKGTIKLADFGLARAFGIPIRVYTHEVVTLWYRSPEVLLGSARYSTPVDIWSIGTIFAELATKKPLFHGDSEIDQLFRIFRALGTPNNEVWPEVESLQDYKNTFPKWKPGSLASHVKNLDENGLDLLSKMLIYDPAKRISGKMALNHPYFNDLDNQIKKM
uniprot
proteins
ec_number
2.7.11.22
uniprot
proteins
ec_number
2.7.11.23
uniprot
proteins
function
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, GLI2 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:31279575, 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). Activated by the CDK-activating kinase (CAK) complex consisting of CDK7, cyclin-H/CCNH and MAT1, which is a master regulator of CDK activity (PubMed:41100585). 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). {ECO:0000250|UniProtKB:P11440, ECO:0000250|UniProtKB:P39951, ECO:0000269|PubMed:16371510, ECO:0000269|PubMed:16407259, ECO:0000269|PubMed:16933150, ECO:0000269|PubMed:17459720, ECO:0000269|PubMed:18356527, ECO:0000269|PubMed:18480403, ECO:0000269|PubMed:19202191, ECO:0000269|PubMed:19509060, ECO:0000269|PubMed:19917720, ECO:0000269|PubMed:20171170, ECO:0000269|PubMed:20360007, ECO:0000269|PubMed:20395957, ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:20937773, ECO:0000269|PubMed:21063390, ECO:0000269|PubMed:2188730, ECO:0000269|PubMed:22411829, ECO:0000269|PubMed:23355470, ECO:0000269|PubMed:2344612, ECO:0000269|PubMed:23601106, ECO:0000269|PubMed:23602554, ECO:0000269|PubMed:25012651, ECO:0000269|PubMed:25556658, ECO:0000269|PubMed:26549230, ECO:0000269|PubMed:26829474, ECO:0000269|PubMed:27238018, ECO:0000269|PubMed:27814491, ECO:0000269|PubMed:28479321, ECO:0000269|PubMed:30139873, ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:30723163, ECO:0000269|PubMed:31279575, ECO:0000269|PubMed:31804178, ECO:0000269|PubMed:32351706, ECO:0000269|PubMed:32491969, ECO:0000269|PubMed:34741373, ECO:0000269|PubMed:37788673, ECO:0000269|PubMed:41100585}.; FUNCTION: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes and facilitates its cell entry. {ECO:0000269|PubMed:21516087}.
uniprot
proteins
mass_dalton
34095
uniprot
proteins
mutagenesis
MUTAGEN 4; /note="Y->D,E: Constitutive polyubiquitination."; /evidence="ECO:0000269|PubMed:20395957"; MUTAGEN 14..15; /note="TY->AF: Abnormal cell cycle exhibiting only M-phase without completing either karyokinesis or cytokinesis."; /evidence="ECO:0000269|PubMed:18480403
uniprot
proteins
post_translational_modification
PTM: Phosphorylation at Thr-161 by CAK/CDK7 activates kinase activity (PubMed:20360007, PubMed:41100585). 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). {ECO:0000269|PubMed:19917613, ECO:0000269|PubMed:20360007, ECO:0000269|PubMed:20395957, ECO:0000269|PubMed:29606300, ECO:0000269|PubMed:41100585, ECO:0000269|PubMed:7569953}.; PTM: Polyubiquitinated upon genotoxic stress (PubMed:20395957). {ECO:0000269|PubMed:20395957}.
uniprot
proteins
protein_family
CDC2/CDKX subfamily
uniprot
proteins
protein_family
CMGC Ser/Thr protein kinase family
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
12775724
uniprot
proteins
pubmed
14654843
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15145941
uniprot
proteins
pubmed
15164054
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16236519
uniprot
proteins
pubmed
16371510
uniprot
proteins
pubmed
16407259
uniprot
proteins
pubmed
16933150
uniprot
proteins
pubmed
17459720
uniprot
proteins
pubmed
18056467
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18356527
uniprot
proteins
pubmed
18480403
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19202191
uniprot
proteins
pubmed
19238148
uniprot
proteins
pubmed
19364923
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19509060
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19917613
uniprot
proteins
pubmed
19917720
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20171170
uniprot
proteins
pubmed
20360007
uniprot
proteins
pubmed
20395957
uniprot
proteins
pubmed
20935635
uniprot
proteins
pubmed
20937773
uniprot
proteins
pubmed
21063390
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406398
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21516087
uniprot
proteins
pubmed
21517772
uniprot
proteins
pubmed
21535261
uniprot
proteins
pubmed
21655336
uniprot
proteins
pubmed
2188730
uniprot
proteins
pubmed
22411829
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23355470
uniprot
proteins
pubmed
2344612
uniprot
proteins
pubmed
23601106
uniprot
proteins
pubmed
23602554
uniprot
proteins
pubmed
25012651
uniprot
proteins
pubmed
25556658
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26549230
uniprot
proteins
pubmed
26829474
uniprot
proteins
pubmed
27238018
uniprot
proteins
pubmed
27814491
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
28479321
uniprot
proteins
pubmed
29606300
uniprot
proteins
pubmed
30139873
uniprot
proteins
pubmed
30704899
uniprot
proteins
pubmed
30723163
uniprot
proteins
pubmed
31279575
uniprot
proteins
pubmed
31804178
uniprot
proteins
pubmed
31852787
uniprot
proteins
pubmed
32351706
uniprot
proteins
pubmed
32491969
uniprot
proteins
pubmed
3289755
uniprot
proteins
pubmed
34741373
uniprot
proteins
pubmed
3553962
uniprot
proteins
pubmed
37788673
uniprot
proteins
pubmed
40440427
uniprot
proteins
pubmed
41100585
uniprot
proteins
pubmed
7569953
uniprot
proteins
pubmed
9030781
uniprot
proteins
pubmed
9242535
uniprot
proteins
pubmed
9515786
uniprot
proteins
sequence_length
297
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P11440}. Cytoplasm {ECO:0000250|UniProtKB:P11440}. Mitochondrion {ECO:0000269|PubMed:19917720}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:14654843}. Cytoplasm, cytoskeleton, spindle. Note=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.
uniprot
proteins