CDK2 in complex with FragLite37

Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis ^[1–15]. Phosphorylates CABLES1, CTNNB1, CDK2AP2, ERCC6, NBN, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, SUV39H1, EZH2 ^{[1, 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 16, 14]}. Triggers duplication of centrosomes and DNA ^[5].

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 ^{[17, 18, 19]}. Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in embryonic stem cells (ESCs) ^{[17, 18, 19]}. Activated by the CDK-activating kinase (CAK) complex consisting of CDK7, cyclin-H/CCNH and MAT1, which is a master regulator of CDK activity ^[20].

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 ^{[17, 18, 19]}. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing ^[11]. Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC ^[10].

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 ^{[8, 21, 22]}. In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation ^[8]. Involved in regulation of telomere repair by mediating phosphorylation of NBN ^[14].

Phosphorylation of RB1 disturbs its interaction with E2F1 ^[1]. NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication ^[5]. 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 ^{[3, 4]}.

Required for vitamin D-mediated growth inhibition by being itself inactivated ^[23]. Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner ^[24]. USP37 is activated by phosphorylation and thus triggers G1-S transition ^[13].

CTNNB1 phosphorylation regulates insulin internalization ^[12]. 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 ^[25].

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 ^[26]