CDK5 (Cyclin-dependent p31) (FITC)

This gene encodes a proline-directed serine/threonine kinase that is a member of the cyclin-dependent kinase family of proteins. Unlike other members of the family, the protein encoded by this gene does not directly control cell cycle regulation. Instead the protein, which is predominantly expressed at high levels in mammalian postmitotic central nervous system neurons, functions in diverse processes such as synaptic plasticity and neuronal migration through phosphorylation of proteins required for cytoskeletal organization, endocytosis and exocytosis, and apoptosis. In humans, an allelic variant of the gene that results in undetectable levels of the protein has been associated with lethal autosomal recessive lissencephaly-7. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2015]

CDK5: a protein kinase of the CDK family. Unlike other members of this family, it is not activated by cyclins but by p35 (CDK5R1) and p39. An important regulator of neuronal positioning during brain development. May also play a role in synaptogenesis and neurotransmission. Substrates include TAU, MAP2, NF-H and -M, Nudel, PDE6, beta-catenin, amphyphysin, dynamin I, synapsin 1, Munc-18, and NMDA receptor 2A. Plays a role in myogenesis, haematopoietic cell differentiation, spermatogenesis, insulin secretion, and lens differentiation. Implicated in the pathology of neurofibrillary tangles and formation of senile plaques, hallmarks of Alzheimer?s disease. Induces tau phosphorylation and aggregation and neurofibrillary tangle deposition and neurodegeneration in in vitro and in vivo animal models. Brain samples from Alzeimer?s pateints show elevated CDK5 activity.

Protein type: Kinase, protein; EC 2.7.11.1; Cell cycle regulation; Protein kinase, Ser/Thr (non-receptor); Protein kinase, CMGC; CMGC group; CDK family; CDK5 subfamily; CDK/CDK5 subfamily

Chromosomal Location of Human Ortholog: 7q36

Cellular Component: cyclin-dependent protein kinase 5 activator complex; dendrite; postsynaptic density; perikaryon; cytosol; postsynaptic membrane; cytoskeleton; growth cone; membrane; cell soma; axon; lamellipodium; cytoplasm; nucleus; cell junction; neuromuscular junction; filopodium

Molecular Function: acetylcholine receptor activator activity; ephrin receptor binding; p53 binding; protein kinase activity; protein serine/threonine kinase activity; ErbB-2 class receptor binding; protein binding; ErbB-3 class receptor binding; cyclin-dependent protein kinase activity; cytoskeletal protein binding; tau-protein kinase activity; kinase activity; ATP binding

Biological Process: Schwann cell development; negative regulation of synaptic plasticity; axon extension; cerebellar cortex formation; rhythmic process; regulation of synaptic plasticity; motor axon guidance; sensory perception of pain; receptor clustering; regulation of cell migration; corpus callosum development; regulation of apoptosis; neuron differentiation; receptor catabolic process; oligodendrocyte differentiation; neurite development; central nervous system neuron development; synaptic transmission, glutamatergic; skeletal muscle development; dendrite morphogenesis; cell division; synaptic vesicle endocytosis; negative regulation of protein ubiquitination; negative regulation of transcription, DNA-dependent; axon guidance; regulated secretory pathway; synaptic transmission, dopaminergic; negative regulation of protein export from nucleus; positive regulation of protein binding; protein amino acid autophosphorylation; cell-matrix adhesion; neuron migration; nucleocytoplasmic transport; negative regulation of axon extension; negative regulation of cell cycle; synaptic transmission; intracellular protein transport; synaptogenesis; behavioral response to cocaine; positive regulation of neuron apoptosis; visual learning; cortical actin cytoskeleton organization and biogenesis; layer formation in the cerebral cortex; serine phosphorylation of STAT3 protein; negative regulation of proteolysis; hippocampus development; peptidyl-threonine phosphorylation; cell cycle; cell proliferation; positive regulation of calcium ion-dependent exocytosis; embryonic development; synaptic vesicle exocytosis; peptidyl-serine phosphorylation; neuron apoptosis; positive regulation of protein kinase activity; blood coagulation; regulation of excitatory postsynaptic membrane potential; phosphorylation

Disease: Lissencephaly 7 With Cerebellar Hypoplasia