Protein-coding gene in the species Homo sapiens
CDK5R1 Identifiers Aliases CDK5R1 External IDs OMIM : 603460 MGI : 101764 HomoloGene : 31200 GeneCards : CDK5R1 Wikidata
Cyclin-dependent kinase 5 activator 1 is an enzyme that in humans is encoded by the CDK5R1 gene .[5] [6]
Function [ edit ] 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 [ edit ] CDK5R1 has been shown to interact with:
See also [ edit ] References [ edit ]
^ 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 .^ Tsai LH, Delalle I, Caviness VS Jr, Chae T, Harlow E (October 1994). "p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5". Nature . 371 (6496): 419–23. Bibcode :1994Natur.371..419T . doi :10.1038/371419a0 . PMID 8090221 . S2CID 4267944 . ^ a b "Entrez Gene: CDK5R1 cyclin-dependent kinase 5, regulatory subunit 1 (p35)" .^ Hoek KS, Schlegel NC, Eichhoff OM, et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy" . Pigment Cell Melanoma Res . 21 (6): 665–76. doi :10.1111/j.1755-148X.2008.00505.x PMID 19067971 . S2CID 24698373 . ^ Cheng K, Li Z, Fu WY, Wang JH, Fu AK, Ip NY (August 2002). "Pctaire1 interacts with p35 and is a novel substrate for Cdk5/p35" . J. Biol. Chem . 277 (35): 31988–93. doi :10.1074/jbc.M201161200 PMID 12084709 . ^ Floyd SR, Porro EB, Slepnev VI, Ochoa GC, Tsai LH, De Camilli P (March 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, Brownlees J, Ackerley S, Leigh PN, Shaw CE, Miller CC (January 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 . ^ Dhavan R, Greer PL, Morabito MA, Orlando LR, Tsai LH (September 2002). "The cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II and alpha-actinin-1 in a calcium-dependent manner" . J. Neurosci . 22 (18): 7879–91. doi :10.1523/JNEUROSCI.22-18-07879.2002 . PMC 6758084 PMID 12223541 . ^ Wang X, Ching YP, Lam WH, Qi Z, Zhang M, Wang JH (October 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 . ^ Chen F, Studzinski GP (June 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, Areces LB, Tsai LH, Musacchio A (September 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 . ^ Qu D, Li Q, Lim HY, Cheung NS, Li R, Wang JH, Qi RZ (March 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 hdl :10536/DRO/DU:30101408 PMID 11741927 .
Further reading [ edit ]
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 . 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. doi :10.1016/0014-5793(95)00955-9 PMID 7556643 . 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. 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 . 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. 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 . S2CID 4414281 . 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. Bibcode :2000CBio...10..363K . doi :10.1016/S0960-9822(00)00411-5 PMID 10753743 . 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. Bibcode :2000Natur.405..360L . doi :10.1038/35012636 . PMID 10830966 . 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. 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 hdl :10536/DRO/DU:30101408 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 .
External links [ edit ]
PDB gallery
1h4l : STRUCTURE AND REGULATION OF THE CDK5-P25(NCK5A) COMPLEX
1ung : STRUCTURAL MECHANISM FOR THE INHIBITION OF CDK5-P25 BY ROSCOVITINE, ALOISINE AND INDIRUBIN.
1unh : STRUCTURAL MECHANISM FOR THE INHIBITION OF CDK5-P25 BY ROSCOVITINE, ALOISINE AND INDIRUBIN.
1unl : STRUCTURAL MECHANISM FOR THE INHIBITION OF CD5-P25 FROM THE ROSCOVITINE, ALOISINE AND INDIRUBIN.
