CDK5R1

CDK5R1 (Cyclin Dependent Kinase 5 Regulatory Subunit 1) is a Protein Coding gene. Diseases associated with CDK5R1 include Alzheimer Disease and Non-Syndromic Intellectual Disability. Among its related pathways are Semaphorin interactions and Gene Expression. Gene Ontology (GO) annotations related to this gene include calcium ion binding and protein kinase binding. An important paralog of this gene is CDK5R2.

Full Name

Cyclin Dependent Kinase 5 Regulatory Subunit 1

Function

p35 is a neuron specific activator of CDK5. The complex p35/CDK5 is required for neurite outgrowth and cortical lamination. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. Activator of TPKII. The complex p35/CDK5 participates in the regulation of the circadian clock by modulating the function of CLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer in association with altered stability and subcellular distribution.

Biological Process

Axonal fasciculation Source: UniProtKB
Axon guidance Source: UniProtKB
Brain development Source: UniProtKB
Cerebellum development Source: Ensembl
Embryo development ending in birth or egg hatching Source: Ensembl
Ephrin receptor signaling pathway Source: UniProtKB
G protein-coupled acetylcholine receptor signaling pathway Source: UniProtKB
Hippocampus development Source: Ensembl
Ionotropic glutamate receptor signaling pathway Source: UniProtKB
Layer formation in cerebral cortex Source: Ensembl
Microtubule cytoskeleton organization Source: ARUK-UCL
Negative regulation of axon extension Source: Ensembl
Negative regulation of transcription, DNA-templated Source: DFLAT
Neuron cell-cell adhesion Source: UniProtKB
Neuron differentiation Source: UniProtKB
Neuron migration Source: UniProtKB
Neuron projection development Source: UniProtKB
Peptidyl-serine phosphorylation Source: UniProtKB
Peptidyl-threonine phosphorylation Source: UniProtKB
Positive regulation of cell cycle arrest Source: Ensembl
Positive regulation of MHC class II biosynthetic process Source: ARUK-UCL
Positive regulation of microtubule polymerization Source: ARUK-UCL
Positive regulation of neuron apoptotic process Source: UniProtKB
Positive regulation of protein targeting to membrane Source: Ensembl
Positive regulation of signaling receptor activity Source: ARUK-UCL
Regulation of actin cytoskeleton organization Source: Ensembl
Regulation of cyclin-dependent protein serine/threonine kinase activity Source: ProtInc
Regulation of dendritic spine morphogenesis Source: UniProtKB
Regulation of macroautophagy Source: ParkinsonsUK-UCL
Regulation of neuron differentiation Source: UniProtKB
Regulation of signal transduction by p53 class mediator Source: Reactome
Regulation of synaptic vesicle cycle Source: Ensembl
Rhythmic process Source: UniProtKB-KW
Serine phosphorylation of STAT protein Source: Ensembl
Superior olivary nucleus maturation Source: Ensembl

Cellular Location

Cyclin-dependent kinase 5 activator 1, p35: Cell membrane; Neuron projection. In the primary cortical neurons, p35 is present in the peripheries and nerve terminals.
Cyclin-dependent kinase 5 activator 1, p25: Nucleus; Perinuclear region; Perikaryon. The conversion of p35 to p25 relocalizes the protein from the cell periphery to the cytoplasm, in nuclear and perinuclear regions. In the primary cortical neurons, p25 is primarily concentrated in the cell soma and is largely absent from neurites.

PTM

The p35 form is proteolytically cleaved by calpain, giving rise to the p25 form. P35 has a 5 to 10 fold shorter half-life compared to p25. The conversion results in deregulation of the CDK5 kinase: p25/CDK5 kinase displays an increased and altered tau phosphorylation in comparison to the p35/CDK5 kinase in vivo (By similarity).
Myristoylated. A proper myristoylation signal is essential for the proper distribution of p35.
Ubiquitinated. Degradation of p35 by proteasome results in down-regulation of CDK5 activity. During this process, CDK5 phosphorylates p35 and induces its ubiquitination and subsequent degradation.
Phosphorylation at Ser-8 and Thr-138 by CDK5 prevents calpain-mediated proteolysis.