CDK2 Protein, Human

CDK2, a serine/threonine-protein kinase, intricately regulates the cell cycle, playing an indispensable role in meiosis while being dispensable for mitosis. Operating at the nexus of cellular processes, CDK2 phosphorylates a diverse array of substrates, including CTNNB1, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, and EZH2. It orchestrates critical events such as centrosome duplication and DNA synthesis initiation at the G1-S transition, modulating G2 progression and finely tuning the balance between cellular proliferation, death, and DNA repair in human embryonic stem cells. Activated sequentially by cyclin E and cyclin A2, CDK2 regulates the transition from S phase to mitosis. Notably, its phosphorylation of EZH2 is implicated in maintaining H3K27me3 and epigenetic gene silencing. CDK2's involvement extends to DNA damage responses, where it regulates the G1-S phase checkpoint, phosphorylates BRCA2, and modulates homologous recombination-dependent repair. Furthermore, CDK2 participates in diverse signaling pathways, including vitamin D-mediated growth inhibition, NO-mediated signaling, and the phosphorylation of substrates such as FOXP3 and ERCC6, highlighting its multifaceted role in cellular physiology.