CDK2 Gene - Cyclin-Dependent Kinase 2: Function, Mutations, and Disease

CDK2 (cyclin-dependent kinase 2) is a serine/threonine protein kinase that plays a critical role in the regulation of the cell cycle, particularly during the G1/S phase transition. It forms active complexes with cyclin E (G1 phase) and cyclin A (S phase), phosphorylating key substrates such as RB1 to promote DNA replication. CDK2 activity is tightly controlled by cyclin binding, phosphorylation, and interaction with CDK inhibitors (e.g., p21, p27). Dysregulation of CDK2 is implicated in various cancers and developmental disorders.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Cell Cycle (KEGG: hsa04110)

• p53 signaling pathway (KEGG: hsa04115)

• Cellular Senescence (KEGG: hsa04218)

• FoxO signaling pathway (KEGG: hsa04068)

CDK2 is a 298-amino acid serine/threonine kinase (33 kDa) with a typical kinase domain. It is activated by binding to cyclin E or cyclin A and by phosphorylation at Thr160 by CAK (CDK-activating kinase). The active CDK2-cyclin complex phosphorylates substrates including RB1, p107, p130, and CDC25A to drive G1/S transition and S phase progression. CDK2 is negatively regulated by CDK inhibitors p21 (CDKN1A) and p27 (CDKN1B). Structural studies reveal a bilobal kinase fold with an N-terminal lobe (β-sheet) and a C-terminal lobe (α-helical), with the active site cleft between them.