CDK5R1

Cyclin-dependent kinase 5, regulatory subunit 1 (p35)
PDB rendering based on 1h4l.
Available structures PDB 1H4L, 1UNG, 1UNH, 1UNL
Identifiers
Symbols	CDK5R1; CDK5P35; CDK5R; MGC33831; NCK5A; p23; p25; p35; p35nck5a
External IDs	OMIM: 603460 MGI: 101764 HomoloGene: 31200 GeneCards: CDK5R1 Gene
Gene Ontology Molecular function • protein kinase activity • calcium ion binding • protein binding • kinase activity • cyclin-dependent protein kinase 5 activator activity • protein kinase binding • protein serine/threonine kinase activator activity • protein serine/threonine kinase activator activity • cadherin binding Cellular component • nucleus • cytoplasm • cytosol • plasma membrane • membrane • cyclin-dependent protein kinase 5 holoenzyme complex • axon • dendrite • growth cone • neuromuscular junction • neuronal cell body • dendritic spine • contractile fiber • perinuclear region of cytoplasm Biological process • regulation of cyclin-dependent protein kinase activity • neuron migration • protein phosphorylation • neuron cell-cell adhesion • muscarinic acetylcholine receptor signaling pathway • axon guidance • axon guidance • axonal fasciculation • brain development • brain development • cell proliferation • embryo development • phosphorylation • peptidyl-serine phosphorylation • peptidyl-threonine phosphorylation • neuron differentiation • neuron projection development • ionotropic glutamate receptor signaling pathway • positive regulation of neuron apoptosis • regulation of neuron differentiation • negative regulation of transcription, DNA-dependent • positive regulation of protein serine/threonine kinase activity • positive regulation of protein serine/threonine kinase activity Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	8851	12569
Ensembl	ENSG00000176749	ENSMUSG00000048895
UniProt	Q15078	Q3V3I8
RefSeq (mRNA)	NM_003885	NM_009871.2
RefSeq (protein)	NP_003876	NP_034001.1
Location (UCSC)	Chr 17: 30.81 – 30.82 Mb	Chr 11: 80.29 – 80.29 Mb
PubMed search	[1]	[2]

Cyclin-dependent kinase 5 activator 1 is an enzyme that in humans is encoded by the CDK5R1 gene.

The protein encoded by this gene (p35) is a neuron-specific activator of cyclin-dependent kinase 5 (CDK5); the activation of CDK5 is required for proper development of the central nervous system. The p35 form of this protein is proteolytically cleaved by calpain, generating a p25 form. The cleavage of p35 into p25 results in relocalization of the protein from the cell periphery to nuclear and perinuclear regions. P25 deregulates CDK5 activity by prolonging its activation and changing its cellular location. The p25 form accumulates in the brain neurons of patients with Alzheimer's disease. This accumulation correlates with an increase in CDK5 kinase activity, and may lead to aberrantly phosphorylated forms of the microtubule-associated protein tau, which contributes to Alzheimer's disease.

In melanocytic cells CDK5R1 gene expression may be regulated by MITF.

Interactions

CDK5R1 has been shown to interact with CDK5RAP2, Beta-catenin, Cyclin-dependent kinase 5, Amphiphysin, Protein SET, CAMK2A, Actinin, alpha 1 and PCTK1.

Further reading

• Peruzzi F, Gordon J, Darbinian N, Amini S (2003). "Tat-induced deregulation of neuronal differentiation and survival by nerve growth factor pathway". J. Neurovirol. 8 Suppl 2 (2): 91–6. doi:10.1080/13550280290167885. PMID 12491158. 
• Studzinski GP, Harrison JS (2003). "The neuronal cyclin-dependent kinase 5 activator p35Nck5a and Cdk5 activity in monocytic cells". Leuk. Lymphoma 44 (2): 235–40. doi:10.1080/1042819021000030009. PMID 12688339. 
• Takahashi M, Tomizawa K, Sato K, et al. (1995). "A novel tau-tubulin kinase from bovine brain". FEBS Lett. 372 (1): 59–64. doi:10.1016/0014-5793(95)00955-9. PMID 7556643. 
• Tang D, Yeung J, Lee KY, et al. (1995). "An isoform of the neuronal cyclin-dependent kinase 5 (Cdk5) activator". J. Biol. Chem. 270 (45): 26897–903. doi:10.1074/jbc.270.45.26897. PMID 7592934. 
• Chae T, Kwon YT, Bronson R, et al. (1997). "Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality". Neuron 18 (1): 29–42. doi:10.1016/S0896-6273(01)80044-1. PMID 9010203. 
• Poon RY, Lew J, Hunter T (1997). "Identification of functional domains in the neuronal Cdk5 activator protein". J. Biol. Chem. 272 (9): 5703–8. doi:10.1074/jbc.272.9.5703. PMID 9038181. 
• Fletcher AI, Shuang R, Giovannucci DR, et al. (1999). "Regulation of exocytosis by cyclin-dependent kinase 5 via phosphorylation of Munc18". J. Biol. Chem. 274 (7): 4027–35. doi:10.1074/jbc.274.7.4027. PMID 9933594. 
• Patrick GN, Zukerberg L, Nikolic M, et al. (2000). "Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration". Nature 402 (6762): 615–22. doi:10.1038/45159. PMID 10604467. 
• Ching YP, Qi Z, Wang JH (2000). "Cloning of three novel neuronal Cdk5 activator binding proteins". Gene 242 (1–2): 285–94. doi:10.1016/S0378-1119(99)00499-0. PMID 10721722. 
• Kwon YT, Gupta A, Zhou Y, et al. (2000). "Regulation of N-cadherin-mediated adhesion by the p35-Cdk5 kinase". Curr. Biol. 10 (7): 363–72. doi:10.1016/S0960-9822(00)00411-5. PMID 10753743. 
• Lee MS, Kwon YT, Li M, et al. (2000). "Neurotoxicity induces cleavage of p35 to p25 by calpain". Nature 405 (6784): 360–4. doi:10.1038/35012636. PMID 10830966. 
• Wang X, Ching YP, Lam WH, et al. (2000). "Identification of a common protein association region in the neuronal Cdk5 activator". J. Biol. Chem. 275 (41): 31763–9. doi:10.1074/jbc.M004358200. PMID 10915792. 
• Floyd SR, Porro EB, Slepnev VI, et al. (2001). "Amphiphysin 1 binds the cyclin-dependent kinase (cdk) 5 regulatory subunit p35 and is phosphorylated by cdk5 and cdc2". J. Biol. Chem. 276 (11): 8104–10. doi:10.1074/jbc.M008932200. PMID 11113134. 
• Kesavapany S, Lau KF, McLoughlin DM, et al. (2001). "p35/cdk5 binds and phosphorylates beta-catenin and regulates beta-catenin/presenilin-1 interaction". Eur. J. Neurosci. 13 (2): 241–7. doi:10.1046/j.1460-9568.2001.01376.x. PMID 11168528. 
• Chen F, Studzinski GP (2001). "Expression of the neuronal cyclin-dependent kinase 5 activator p35Nck5a in human monocytic cells is associated with differentiation". Blood 97 (12): 3763–7. doi:10.1182/blood.V97.12.3763. PMID 11389014. 
• Tarricone C, Dhavan R, Peng J, et al. (2001). "Structure and regulation of the CDK5-p25(nck5a) complex". Mol. Cell 8 (3): 657–69. doi:10.1016/S1097-2765(01)00343-4. PMID 11583627. 
• Rashid T, Banerjee M, Nikolic M (2002). "Phosphorylation of Pak1 by the p35/Cdk5 kinase affects neuronal morphology". J. Biol. Chem. 276 (52): 49043–52. doi:10.1074/jbc.M105599200. PMID 11604394. 
• Qu D, Li Q, Lim HY, et al. (2002). "The protein SET binds the neuronal Cdk5 activator p35nck5a and modulates Cdk5/p35nck5a activity". J. Biol. Chem. 277 (9): 7324–32. doi:10.1074/jbc.M107270200. PMID 11741927. 
• Patzke H, Tsai LH (2002). "Calpain-mediated cleavage of the cyclin-dependent kinase-5 activator p39 to p29". J. Biol. Chem. 277 (10): 8054–60. doi:10.1074/jbc.M109645200. PMID 11784720.