CDK2
entrez
1017
canonical
uniprot
P24941
canonical
ensembl
ENSG00000123374
resolver
ensp
ENSP00000243067
resolver
ensp
ENSP00000266970
resolver
ensp
ENSP00000393605
resolver
ensp
ENSP00000452514
resolver
enst
ENST00000440311
resolver
enst
ENST00000553376
resolver
genesymbol
CDK2
resolver
genesymbol_syn
CDKN2
resolver
hgnc
HGNC:1771
resolver
uniprot
A8K7C6
resolver
uniprot
B4DDL9
resolver
uniprot
E7ESI2
resolver
uniprot
G3V5T9
resolver
uniprot
O75100
resolver
uniprot_entry
B4DDL9_HUMAN
resolver
uniprot_entry
CDK2_HUMAN
resolver
uniprot_entry
E7ESI2_HUMAN
resolver
uniprot_entry
G3V5T9_HUMAN
resolver
uniprot_sec
A8K7C6
resolver
uniprot_sec
O75100
resolver
activity_regulation
ACTIVITY REGULATION: Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-160 activates it (PubMed:1396589, PubMed:41100585). Phosphorylated and activated by CDK7 in the CDK-activating kinase (CAK) complex, and reciprocally phosphorylating its activating kinase CDK7 (PubMed:41100585). Inhibited by 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)), AG-024322, N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), R547 (Ro-4584820), purine, pyrimidine and pyridine derivatives, 2-aminopyrimidines, paullones, thiazo derivatives, macrocyclic quinoxalin-2-one, pyrazolo[1,5-a]-1,3,5-triazine, pyrazolo[1,5-a]pyrimidine, 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine, seliciclib and CYC202), SNS-032 (BMS-387032), triazolo[1,5-a]pyrimidines, staurosporine and olomoucine. Stimulated by MYC. Inactivated by CDKN1A (p21). {ECO:0000269|PubMed:1396589, ECO:0000269|PubMed:20147522, ECO:0000269|PubMed:28666995, ECO:0000269|PubMed:41100585, ECO:0000269|PubMed:9030781, ECO:0000269|PubMed:9334743}.
uniprot
proteins
amino_acid_sequence
MENFQKVEKIGEGTYGVVYKARNKLTGEVVALKKIRLDTETEGVPSTAIREISLLKELNHPNIVKLLDVIHTENKLYLVFEFLHQDLKKFMDASALTGIPLPLIKSYLFQLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGLARAFGVPVRTYTHEVVTLWYRAPEILLGCKYYSTAVDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDYKPSFPKWARQDFSKVVPPLDEDGRSLLSQMLHYDPNKRISAKAALAHPFFQDVTKPVPHLRL
uniprot
proteins
ec_number
2.7.11.22
uniprot
proteins
function
FUNCTION: Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis (PubMed:10499802, PubMed:10884347, PubMed:10995386, PubMed:10995387, PubMed:11051553, PubMed:11113184, PubMed:12944431, PubMed:15800615, PubMed:17495531, PubMed:19966300, PubMed:20935635, PubMed:21262353, PubMed:21596315, PubMed:28216226, PubMed:28666995). Phosphorylates CABLES1, CTNNB1, CDK2AP2, ERCC6, NBN, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, SUV39H1, EZH2 (PubMed:10499802, PubMed:10995386, PubMed:10995387, PubMed:11051553, PubMed:11113184, PubMed:12944431, PubMed:15800615, PubMed:19966300, PubMed:20935635, PubMed:21262353, PubMed:21596315, PubMed:24728993, PubMed:28216226). Triggers duplication of centrosomes and DNA (PubMed:11051553). Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus (PubMed:18372919, PubMed:19238148, PubMed:19561645). Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in embryonic stem cells (ESCs) (PubMed:18372919, PubMed:19238148, PubMed:19561645). 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). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase (PubMed:18372919, PubMed:19238148, PubMed:19561645). EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing (PubMed:20935635). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC (PubMed:19966300). Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis (PubMed:15800615, PubMed:20195506, PubMed:21319273). In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation (PubMed:15800615). Involved in regulation of telomere repair by mediating phosphorylation of NBN (PubMed:28216226). Phosphorylation of RB1 disturbs its interaction with E2F1 (PubMed:10499802). NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication (PubMed:11051553). Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase (PubMed:10995386, PubMed:10995387). Required for vitamin D-mediated growth inhibition by being itself inactivated (PubMed:20147522). Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner (PubMed:20079829). USP37 is activated by phosphorylation and thus triggers G1-S transition (PubMed:21596315). CTNNB1 phosphorylation regulates insulin internalization (PubMed:21262353). Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability (By similarity). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878). Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of the C-terminus of protein kinase B (PKB/AKT1 and PKB/AKT2), promoting its activation (PubMed:24670654). {ECO:0000250|UniProtKB:P97377, ECO:0000269|PubMed:10499802, ECO:0000269|PubMed:10884347, ECO:0000269|PubMed:10995386, ECO:0000269|PubMed:10995387, ECO:0000269|PubMed:11051553, ECO:0000269|PubMed:11113184, ECO:0000269|PubMed:12944431, ECO:0000269|PubMed:15800615, ECO:0000269|PubMed:17495531, ECO:0000269|PubMed:18372919, ECO:0000269|PubMed:19966300, ECO:0000269|PubMed:20079829, ECO:0000269|PubMed:20147522, ECO:0000269|PubMed:20195506, ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:21262353, ECO:0000269|PubMed:21319273, ECO:0000269|PubMed:21596315, ECO:0000269|PubMed:24670654, ECO:0000269|PubMed:24728993, ECO:0000269|PubMed:28216226, ECO:0000269|PubMed:28666995, ECO:0000269|PubMed:29203878, ECO:0000269|PubMed:41100585, ECO:0000303|PubMed:19238148, ECO:0000303|PubMed:19561645}.
uniprot
proteins
mass_dalton
33930
uniprot
proteins
mutagenesis
MUTAGEN 9; /note="K->F: Reduced phosphorylation by CAK."; /evidence="ECO:0000269|PubMed:17373709"; MUTAGEN 14; /note="T->A: 2-fold increase in activity."; /evidence="ECO:0000269|PubMed:1396589"; MUTAGEN 15; /note="Y->F: 2-fold increase in activity."; /evidence="ECO:0000269|PubMed:1396589"; MUTAGEN 88..89; /note="KK->EV: Reduced phosphorylation by CAK."; /evidence="ECO:0000269|PubMed:17373709"; MUTAGEN 145; /note="D->N: Dominant negative kinase dead mutant."; /evidence="ECO:0000269|PubMed:24728993"; MUTAGEN 160; /note="T->A: Abolishes activity."; /evidence="ECO:0000269|PubMed:1396589"; MUTAGEN 166; /note="L->R: Reduced phosphorylation by CAK and reduced kinase activity."; /evidence="ECO:0000269|PubMed:17373709"; MUTAGEN 209; /note="I->R: Impairs phosphorylation by CAK."; /evidence="ECO:0000269|PubMed:41100585
uniprot
proteins
post_translational_modification
PTM: Phosphorylated at Thr-160 by CDK7 in a CAK complex (PubMed:28666995). Phosphorylation at Thr-160 promotes kinase activity, whereas phosphorylation at Tyr-15 by WEE1 reduces slightly kinase activity. Phosphorylated on Thr-14 and Tyr-15 during S and G2 phases before being dephosphorylated by CDC25A. {ECO:0000269|PubMed:11113184, ECO:0000269|PubMed:1396589, ECO:0000269|PubMed:14597612, ECO:0000269|PubMed:16325401, ECO:0000269|PubMed:17095507, ECO:0000269|PubMed:17373709, ECO:0000269|PubMed:17570665, ECO:0000269|PubMed:20147522, ECO:0000269|PubMed:20360007, ECO:0000269|PubMed:21565702, ECO:0000269|PubMed:23781148, ECO:0000305|PubMed:28666995}.; PTM: Nitrosylated after treatment with nitric oxide (DETA-NO). {ECO:0000269|PubMed:20079829}.
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
10499802
uniprot
proteins
pubmed
10884347
uniprot
proteins
pubmed
10995386
uniprot
proteins
pubmed
10995387
uniprot
proteins
pubmed
11051553
uniprot
proteins
pubmed
11113184
uniprot
proteins
pubmed
11980914
uniprot
proteins
pubmed
12185076
uniprot
proteins
pubmed
12839962
uniprot
proteins
pubmed
12944431
uniprot
proteins
pubmed
12972555
uniprot
proteins
pubmed
1396589
uniprot
proteins
pubmed
14597612
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15107404
uniprot
proteins
pubmed
15178429
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15611625
uniprot
proteins
pubmed
15800615
uniprot
proteins
pubmed
16325401
uniprot
proteins
pubmed
1653904
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
17095507
uniprot
proteins
pubmed
1714386
uniprot
proteins
pubmed
1717994
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17373709
uniprot
proteins
pubmed
17495531
uniprot
proteins
pubmed
17570665
uniprot
proteins
pubmed
17937404
uniprot
proteins
pubmed
18372919
uniprot
proteins
pubmed
18656911
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19238148
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19445729
uniprot
proteins
pubmed
19561645
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19829063
uniprot
proteins
pubmed
19966300
uniprot
proteins
pubmed
20079829
uniprot
proteins
pubmed
20147522
uniprot
proteins
pubmed
20195506
uniprot
proteins
pubmed
20360007
uniprot
proteins
pubmed
20713526
uniprot
proteins
pubmed
20935635
uniprot
proteins
pubmed
21262353
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21319273
uniprot
proteins
pubmed
21406398
uniprot
proteins
pubmed
21517772
uniprot
proteins
pubmed
21565702
uniprot
proteins
pubmed
21596315
uniprot
proteins
pubmed
21684737
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23711367
uniprot
proteins
pubmed
23781148
uniprot
proteins
pubmed
24670654
uniprot
proteins
pubmed
24728993
uniprot
proteins
pubmed
28216226
uniprot
proteins
pubmed
28666995
uniprot
proteins
pubmed
29203878
uniprot
proteins
pubmed
41100585
uniprot
proteins
pubmed
7630397
uniprot
proteins
pubmed
8510751
uniprot
proteins
pubmed
8601310
uniprot
proteins
pubmed
8610110
uniprot
proteins
pubmed
8684460
uniprot
proteins
pubmed
8756328
uniprot
proteins
pubmed
8917641
uniprot
proteins
pubmed
9030781
uniprot
proteins
pubmed
9334743
uniprot
proteins
pubmed
9677190
uniprot
proteins
sequence_length
298
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Nucleus, Cajal body. Cytoplasm. Endosome. Note=Localized at the centrosomes in late G2 phase after separation of the centrosomes but before the start of prophase. Nuclear-cytoplasmic trafficking is mediated during the inhibition by 1,25-(OH)(2)D(3).
uniprot
proteins