Homo sapiens Protein: CDK2
InnateDB Protein IDBP-39549.7
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol CDK2
Protein Name cyclin-dependent kinase 2
Synonyms CDKN2; p33(CDK2);
Species Homo sapiens
Ensembl Protein ENSP00000243067
InnateDB Gene IDBG-39545 (CDK2)
Protein Structure
UniProt Annotation
Function Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis. Phosphorylates CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, EZH2. Interacts with cyclins A, B1, B3, D, or E. Triggers duplication of centrosomes and DNA. 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. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). 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. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. Phosphorylates CABLES1 (By similarity). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC. 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. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. Phosphorylation of RB1 disturbs its interaction with E2F1. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication. 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. Required for vitamin D-mediated growth inhibition by being itself inactivated. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner. USP37 is activated by phosphorylation and thus triggers G1-S transition. CTNNB1 phosphorylation regulates insulin internalization. {ECO:0000250, ECO:0000269PubMed:10499802, ECO:0000269PubMed:10884347, ECO:0000269PubMed:10995386, ECO:0000269PubMed:10995387, ECO:0000269PubMed:11051553, ECO:0000269PubMed:11113184, ECO:0000269PubMed:15800615, ECO:0000269PubMed:17495531, ECO:0000269PubMed:18372919, ECO:0000269PubMed:19966300, ECO:0000269PubMed:20079829, ECO:0000269PubMed:20147522, ECO:0000269PubMed:20195506, ECO:0000269PubMed:20935635, ECO:0000269PubMed:21262353, ECO:0000269PubMed:21319273, ECO:0000269PubMed:21596315}.
Subcellular Localization 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).
Disease Associations
Tissue Specificity
Number of Interactions This gene and/or its encoded proteins are associated with 655 experimentally validated interaction(s) in this database.
They are also associated with 19 interaction(s) predicted by orthology.
Experimentally validated
Total 655 [view]
Protein-Protein 646 [view]
Protein-DNA 6 [view]
Protein-RNA 0
DNA-DNA 3 [view]
Predicted by orthology
Total 19 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0004672 protein kinase activity
GO:0004693 cyclin-dependent protein serine/threonine kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016772 transferase activity, transferring phosphorus-containing groups
GO:0030332 cyclin binding
GO:0035173 histone kinase activity
GO:0046872 metal ion binding
Biological Process
GO:0000082 G1/S transition of mitotic cell cycle
GO:0000085 mitotic G2 phase
GO:0000086 G2/M transition of mitotic cell cycle
GO:0000278 mitotic cell cycle
GO:0006260 DNA replication
GO:0006281 DNA repair
GO:0006468 protein phosphorylation
GO:0006977 DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
GO:0007067 mitotic nuclear division
GO:0007126 meiotic nuclear division
GO:0007265 Ras protein signal transduction
GO:0007596 blood coagulation
GO:0008284 positive regulation of cell proliferation
GO:0016572 histone phosphorylation
GO:0031145 anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process
GO:0031571 mitotic G1 DNA damage checkpoint
GO:0051298 centrosome duplication
GO:0051439 regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
GO:0060968 regulation of gene silencing
GO:0071732 cellular response to nitric oxide
Cellular Component
GO:0000307 cyclin-dependent protein kinase holoenzyme complex
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005768 endosome
GO:0005813 centrosome
GO:0005829 cytosol
GO:0015030 Cajal body
Protein Structure and Domains
InterPro IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain
PFAM PF00069
Post-translational Modifications
SwissProt P24941
PhosphoSite PhosphoSite-P24941
UniProt Splice Variant
Entrez Gene 1017
UniGene Hs.717547
RefSeq NP_439892
OMIM 116953
HPRD 00310
EMBL AB012305 AC025162 AC034102 AF512553 AK291941 BC003065 BT006821 CH471054 M68520 X61622 X62071
GenPept AAA35667 AAH03065 AAM34794 AAP35467 BAA32794 BAF84630 CAA43807 CAA43985 EAW96856 EAW96857 EAW96858