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CDK5R1

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CDK5R1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCDK5R1, CDK5P35, CDK5R, NCK5A, p23, p25, p35, p35nck5a, cyclin-dependent kinase 5, regulatory subunit 1 (p35), cyclin dependent kinase 5 regulatory subunit 1
External IDsOMIM: 603460; MGI: 101764; HomoloGene: 31200; GeneCards: CDK5R1; OMA:CDK5R1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003885

NM_009871

RefSeq (protein)

NP_003876

NP_034001

Location (UCSC)Chr 17: 32.49 – 32.49 MbChr 11: 80.37 – 80.37 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Cyclin-dependent kinase 5 activator 1 is an enzyme that in humans is encoded by the CDK5R1 gene.[5][6]

Function

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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

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CDK5R1 has been shown to interact with:

See also

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000176749Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000048895Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ a b "Entrez Gene: CDK5R1 cyclin-dependent kinase 5, regulatory subunit 1 (p35)".
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ 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.
  15. ^ 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

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