CDK5R1

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.{{cite journal | vauthors = Hoek KS, Schlegel NC, Eichhoff OM | title = Novel MITF targets identified using a two-step DNA microarray strategy | journal = Pigment Cell Melanoma Res. | volume = 21 | issue = 6 | pages = 665–76 | year = 2008 | pmid = 19067971 | doi = 10.1111/j.1755-148X.2008.00505.x | s2cid = 24698373 |display-authors=etal| doi-access = free }}

CDK5R1 has been shown to interact with:

• Actinin, alpha 1{{cite journal | vauthors = Cheng K, Li Z, Fu WY, Wang JH, Fu AK, Ip NY | title = Pctaire1 interacts with p35 and is a novel substrate for Cdk5/p35 | journal = J. Biol. Chem. | volume = 277 | issue = 35 | pages = 31988–93 |date=August 2002 | pmid = 12084709 | doi = 10.1074/jbc.M201161200 | doi-access = free }}
• Amphiphysin,{{cite journal | vauthors = Floyd SR, Porro EB, Slepnev VI, Ochoa GC, Tsai LH, De Camilli P | title = Amphiphysin 1 binds the cyclin-dependent kinase (cdk) 5 regulatory subunit p35 and is phosphorylated by cdk5 and cdc2 | journal = J. Biol. Chem. | volume = 276 | issue = 11 | pages = 8104–10 |date=March 2001 | pmid = 11113134 | doi = 10.1074/jbc.M008932200 | doi-access = free }}
• Beta-catenin,{{cite journal | vauthors = Kesavapany S, Lau KF, McLoughlin DM, Brownlees J, Ackerley S, Leigh PN, Shaw CE, Miller CC | title = p35/cdk5 binds and phosphorylates beta-catenin and regulates beta-catenin/presenilin-1 interaction | journal = Eur. J. Neurosci. | volume = 13 | issue = 2 | pages = 241–7 |date=January 2001 | pmid = 11168528 | doi = 10.1046/j.1460-9568.2001.01376.x }}
• CAMK2A,{{cite journal | vauthors = Dhavan R, Greer PL, Morabito MA, Orlando LR, Tsai LH | title = 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 | journal = J. Neurosci. | volume = 22 | issue = 18 | pages = 7879–91 |date=September 2002 | pmid = 12223541 | doi = 10.1523/JNEUROSCI.22-18-07879.2002| pmc = 6758084 }}
• CDK5RAP2,{{cite journal | vauthors = Wang X, Ching YP, Lam WH, Qi Z, Zhang M, Wang JH | title = Identification of a common protein association region in the neuronal Cdk5 activator | journal = J. Biol. Chem. | volume = 275 | issue = 41 | pages = 31763–9 |date=October 2000 | pmid = 10915792 | doi = 10.1074/jbc.M004358200 | doi-access = free }}
• Cyclin-dependent kinase 5,{{cite journal | vauthors = Chen F, Studzinski GP | title = Expression of the neuronal cyclin-dependent kinase 5 activator p35Nck5a in human monocytic cells is associated with differentiation | journal = Blood | volume = 97 | issue = 12 | pages = 3763–7 |date=June 2001 | pmid = 11389014 | doi = 10.1182/blood.V97.12.3763 | doi-access = free }}{{cite journal | vauthors = Tarricone C, Dhavan R, Peng J, Areces LB, Tsai LH, Musacchio A | title = Structure and regulation of the CDK5-p25(nck5a) complex | journal = Mol. Cell | volume = 8 | issue = 3 | pages = 657–69 |date=September 2001 | pmid = 11583627 | doi = 10.1016/S1097-2765(01)00343-4 | doi-access = free }}
• Protein SET,{{cite journal | vauthors = Qu D, Li Q, Lim HY, Cheung NS, Li R, Wang JH, Qi RZ | title = The protein SET binds the neuronal Cdk5 activator p35nck5a and modulates Cdk5/p35nck5a activity | journal = J. Biol. Chem. | volume = 277 | issue = 9 | pages = 7324–32 |date=March 2002 | pmid = 11741927 | doi = 10.1074/jbc.M107270200 | doi-access = free | hdl = 10536/DRO/DU:30101408 | hdl-access = free }}

• CDK5RAP1
• CDK5RAP2
• CDK5RAP3

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• {{cite journal | vauthors=Peruzzi F, Gordon J, Darbinian N, Amini S |title=Tat-induced deregulation of neuronal differentiation and survival by nerve growth factor pathway |journal=J. Neurovirol. |volume=8 Suppl 2 |issue= 2|pages= 91–6 |year= 2003 |pmid= 12491158 |doi= 10.1080/13550280290167885 }}
• {{cite journal | vauthors=Studzinski GP, Harrison JS |title=The neuronal cyclin-dependent kinase 5 activator p35Nck5a and Cdk5 activity in monocytic cells |journal=Leuk. Lymphoma |volume=44 |issue= 2 |pages= 235–40 |year= 2003 |pmid= 12688339 |doi=10.1080/1042819021000030009 |s2cid=30242995 }}
• {{cite journal | vauthors=Takahashi M, Tomizawa K, Sato K |title=A novel tau-tubulin kinase from bovine brain |journal=FEBS Lett. |volume=372 |issue= 1 |pages= 59–64 |year= 1995 |pmid= 7556643 |doi=10.1016/0014-5793(95)00955-9 |s2cid=42295269 |display-authors=etal|doi-access=free }}
• {{cite journal | vauthors=Tang D, Yeung J, Lee KY |title=An isoform of the neuronal cyclin-dependent kinase 5 (Cdk5) activator |journal=J. Biol. Chem. |volume=270 |issue= 45 |pages= 26897–903 |year= 1995 |pmid= 7592934 |doi=10.1074/jbc.270.45.26897 |display-authors=etal|doi-access=free }}
• {{cite journal | vauthors=Chae T, Kwon YT, Bronson R |title=Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality |journal=Neuron |volume=18 |issue= 1 |pages= 29–42 |year= 1997 |pmid= 9010203 |doi=10.1016/S0896-6273(01)80044-1 |s2cid=18685470 |display-authors=etal|doi-access=free }}
• {{cite journal | vauthors=Poon RY, Lew J, Hunter T |title=Identification of functional domains in the neuronal Cdk5 activator protein |journal=J. Biol. Chem. |volume=272 |issue= 9 |pages= 5703–8 |year= 1997 |pmid= 9038181 |doi=10.1074/jbc.272.9.5703 |doi-access=free }}
• {{cite journal | vauthors=Fletcher AI, Shuang R, Giovannucci DR |title=Regulation of exocytosis by cyclin-dependent kinase 5 via phosphorylation of Munc18 |journal=J. Biol. Chem. |volume=274 |issue= 7 |pages= 4027–35 |year= 1999 |pmid= 9933594 |doi=10.1074/jbc.274.7.4027 |display-authors=etal|doi-access=free }}
• {{cite journal | vauthors=Patrick GN, Zukerberg L, Nikolic M |title=Conversion of p35 to p25 deregulates Cdk5 activity and promotes neurodegeneration |journal=Nature |volume=402 |issue= 6762 |pages= 615–22 |year= 2000 |pmid= 10604467 |doi= 10.1038/45159 |s2cid=4414281 |display-authors=etal}}
• {{cite journal | vauthors=Ching YP, Qi Z, Wang JH |title=Cloning of three novel neuronal Cdk5 activator binding proteins |journal=Gene |volume=242 |issue= 1–2 |pages= 285–94 |year= 2000 |pmid= 10721722 |doi=10.1016/S0378-1119(99)00499-0 }}
• {{cite journal | vauthors=Kwon YT, Gupta A, Zhou Y |title=Regulation of N-cadherin-mediated adhesion by the p35-Cdk5 kinase |journal=Curr. Biol. |volume=10 |issue= 7 |pages= 363–72 |year= 2000 |pmid= 10753743 |doi=10.1016/S0960-9822(00)00411-5 |s2cid=16438320 |display-authors=etal|doi-access=free |bibcode=2000CBio...10..363K }}
• {{cite journal | vauthors=Lee MS, Kwon YT, Li M |title=Neurotoxicity induces cleavage of p35 to p25 by calpain |journal=Nature |volume=405 |issue= 6784 |pages= 360–4 |year= 2000 |pmid= 10830966 |doi= 10.1038/35012636 |bibcode=2000Natur.405..360L |s2cid=205006589 |display-authors=etal}}
• {{cite journal | vauthors=Wang X, Ching YP, Lam WH |title=Identification of a common protein association region in the neuronal Cdk5 activator |journal=J. Biol. Chem. |volume=275 |issue= 41 |pages= 31763–9 |year= 2000 |pmid= 10915792 |doi= 10.1074/jbc.M004358200 |display-authors=etal|doi-access=free }}
• {{cite journal | vauthors=Floyd SR, Porro EB, Slepnev VI |title=Amphiphysin 1 binds the cyclin-dependent kinase (cdk) 5 regulatory subunit p35 and is phosphorylated by cdk5 and cdc2 |journal=J. Biol. Chem. |volume=276 |issue= 11 |pages= 8104–10 |year= 2001 |pmid= 11113134 |doi= 10.1074/jbc.M008932200 |display-authors=etal|doi-access=free }}
• {{cite journal | vauthors=Kesavapany S, Lau KF, McLoughlin DM |title=p35/cdk5 binds and phosphorylates beta-catenin and regulates beta-catenin/presenilin-1 interaction |journal=Eur. J. Neurosci. |volume=13 |issue= 2 |pages= 241–7 |year= 2001 |pmid= 11168528 |doi=10.1046/j.1460-9568.2001.01376.x |display-authors=etal}}
• {{cite journal | vauthors=Chen F, Studzinski GP |title=Expression of the neuronal cyclin-dependent kinase 5 activator p35Nck5a in human monocytic cells is associated with differentiation |journal=Blood |volume=97 |issue= 12 |pages= 3763–7 |year= 2001 |pmid= 11389014 |doi=10.1182/blood.V97.12.3763 |doi-access=free }}
• {{cite journal | vauthors=Tarricone C, Dhavan R, Peng J |title=Structure and regulation of the CDK5-p25(nck5a) complex |journal=Mol. Cell |volume=8 |issue= 3 |pages= 657–69 |year= 2001 |pmid= 11583627 |doi=10.1016/S1097-2765(01)00343-4 |display-authors=etal|doi-access=free }}
• {{cite journal | vauthors=Rashid T, Banerjee M, Nikolic M |title=Phosphorylation of Pak1 by the p35/Cdk5 kinase affects neuronal morphology |journal=J. Biol. Chem. |volume=276 |issue= 52 |pages= 49043–52 |year= 2002 |pmid= 11604394 |doi= 10.1074/jbc.M105599200 |doi-access= free }}
• {{cite journal | vauthors=Qu D, Li Q, Lim HY |title=The protein SET binds the neuronal Cdk5 activator p35nck5a and modulates Cdk5/p35nck5a activity |journal=J. Biol. Chem. |volume=277 |issue= 9 |pages= 7324–32 |year= 2002 |pmid= 11741927 |doi= 10.1074/jbc.M107270200 |display-authors=etal|doi-access=free |hdl=10536/DRO/DU:30101408 |hdl-access=free }}
• {{cite journal | vauthors=Patzke H, Tsai LH |title=Calpain-mediated cleavage of the cyclin-dependent kinase-5 activator p39 to p29 |journal=J. Biol. Chem. |volume=277 |issue= 10 |pages= 8054–60 |year= 2002 |pmid= 11784720 |doi= 10.1074/jbc.M109645200 |doi-access= free }}

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• {{UCSC gene info|CDK5R1}}

{{PDB Gallery|geneid=8851}}