CDK5R1
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| Location (UCSC) | Chr 17: 32.49 – 32.49 Mb | Chr 11: 80.37 – 80.37 Mb | |||||||
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Cyclin-dependent kinase 5 activator 1 is an enzyme that in humans is encoded by the CDK5R1 gene.[5][6]
Function
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.[6]
In melanocytic cells CDK5R1 gene expression may be regulated by MITF.[7]
Interactions
CDK5R1 has been shown to
interact
with:
- Actinin, alpha 1[8]
- Amphiphysin,[9]
- Beta-catenin,[10]
- CAMK2A,[11]
- CDK5RAP2,[12]
- Cyclin-dependent kinase 5,[13][14]
- Protein SET,[15]
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000176749 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000048895 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- S2CID 4267944.
- ^ a b "Entrez Gene: CDK5R1 cyclin-dependent kinase 5, regulatory subunit 1 (p35)".
- S2CID 24698373.
- PMID 12084709.
- PMID 11113134.
- PMID 11168528.
- PMID 12223541.
- PMID 10915792.
- PMID 11389014.
- PMID 11583627.
- PMID 11741927.
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. 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. S2CID 30242995.
- Takahashi M, Tomizawa K, Sato K, et al. (1995). "A novel tau-tubulin kinase from bovine brain". FEBS Lett. 372 (1): 59–64. S2CID 42295269.
- 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. 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. S2CID 18685470.
- Poon RY, Lew J, Hunter T (1997). "Identification of functional domains in the neuronal Cdk5 activator protein". J. Biol. Chem. 272 (9): 5703–8. 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. 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. S2CID 4414281.
- Ching YP, Qi Z, Wang JH (2000). "Cloning of three novel neuronal Cdk5 activator binding proteins". Gene. 242 (1–2): 285–94. 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. S2CID 16438320.
- Lee MS, Kwon YT, Li M, et al. (2000). "Neurotoxicity induces cleavage of p35 to p25 by calpain". Nature. 405 (6784): 360–4. S2CID 205006589.
- 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. 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. 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. 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. 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. 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. 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. 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. PMID 11784720.
External links
- Human CDK5R1 genome location and CDK5R1 gene details page in the UCSC Genome Browser.
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