CDK2

This gene encodes a member of a family of serine/threonine protein kinases that participate in cell cycle regulation. The encoded protein is the catalytic subunit of the cyclin-dependent protein kinase complex, which regulates progression through the cell cycle. Activity of this protein is especially critical during the G1 to S phase transition. This protein associates with and regulated by other subunits of the complex including cyclin A or E, CDK inhibitor p21Cip1 (CDKN1A), and p27Kip1 (CDKN1B). Alternative splicing results in multiple transcript variants.

Cyclin Dependent Kinase 2

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. 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. Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability (By similarity).
Phosphorylates CDK2AP2 (PubMed:12944431).
Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878).

Anaphase-promoting complex-dependent catabolic process Source: Reactome
Cell division Source: UniProtKB-KW
Cellular response to nitric oxide Source: UniProtKB
Centriole replication Source: UniProtKB
Centrosome duplication Source: UniProtKB
DNA repair Source: UniProtKB-KW
DNA replication Source: UniProtKB
DNA replication initiation Source: Reactome
G1/S transition of mitotic cell cycle Source: GO_Central
G2/M transition of mitotic cell cycle Source: Reactome
Granulocyte differentiation Source: Reactome
Histone phosphorylation Source: CAFA
Meiotic cell cycle Source: UniProtKB
Mitotic G1 DNA damage checkpoint Source: UniProtKB
Peptidyl-serine phosphorylation Source: UniProtKB
Positive regulation of cell population proliferation Source: UniProtKB
Protein phosphorylation Source: UniProtKB
Ras protein signal transduction Source: BHF-UCL
Regulation of G2/M transition of mitotic cell cycle Source: GO_Central
Regulation of gene expression Source: GO_Central
Regulation of gene silencing Source: UniProtKB
Regulation of signal transduction by p53 class mediator Source: Reactome
Signal transduction Source: GO_Central
Telomere maintenance via telomerase Source: Reactome

Centrosome; Cajal body; Cytoplasm; Endosome. 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)2D3.

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.
Nitrosylated after treatment with nitric oxide (DETA-NO).