CDK5 Gene: Function, Mutations, and Associated Diseases | NCBI, UniProt

CDK5 (Cyclin Dependent Kinase 5) is a serine/threonine protein kinase that is predominantly active in post-mitotic neurons. Unlike typical cyclin-dependent kinases, CDK5 activity is regulated by its neuron-specific activators p35 (CDK5R1) and p39 (CDK5R2). CDK5 plays essential roles in neuronal migration, synaptic plasticity, and cytoskeletal dynamics. Dysregulation of CDK5 is implicated in neurodegenerative disorders such as Alzheimer disease and in various cancers.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Alzheimer disease - tau pathology (KEGG: hsa05010)

• Neurotrophin signaling pathway (KEGG: hsa04722)

• p35/CDK5 pathway (Reactome: R-HSA-8862803)

• Axon guidance (KEGG: hsa04360)

CDK5 is a 292-amino acid protein (33 kDa) belonging to the CMGC family of serine/threonine kinases. It shares high sequence homology with CDK1 and CDK2 but is unique in its requirement for non-cyclin activators p35 or p39. The protein structure includes a typical kinase domain with an N-terminal lobe and C-terminal lobe. CDK5 phosphorylates numerous substrates including tau, MAP1B, and DARPP32, regulating cytoskeletal dynamics, synaptic function, and cell survival. In the absence of its activator, CDK5 is catalytically inactive.