CDK5R1: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''Cyclin-dependent kinase 5 activator 1''' is an [[enzyme]] that in humans is encoded by the ''CDK5R1'' [[gene]].<ref name="pmid8090221">{{cite journal | vauthors = Tsai LH, Delalle I, ((Caviness VS Jr)), Chae T, Harlow E | title = p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5 | journal = Nature | volume = 371 | issue = 6496 | pages = 419–23 |date=October 1994 | pmid = 8090221 | pmc =  | doi = 10.1038/371419a0 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: CDK5R1 cyclin-dependent kinase 5, regulatory subunit 1 (p35)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8851| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image = PBB_Protein_CDK5R1_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1h4l.
| PDB = {{PDB2|1h4l}}, {{PDB2|1ung}}, {{PDB2|1unh}}, {{PDB2|1unl}}
| Name = Cyclin-dependent kinase 5, regulatory subunit 1 (p35)
| HGNCid = 1775
| Symbol = CDK5R1
| AltSymbols =; CDK5P35; CDK5R; MGC33831; NCK5A; p23; p25; p35; p35nck5a
| OMIM = 603460
| ECnumber = 
| Homologene = 31200
| MGIid = 101764
| GeneAtlas_image1 = PBB_GE_CDK5R1_204995_at_tn.png
| GeneAtlas_image2 = PBB_GE_CDK5R1_204996_s_at_tn.png
| Function = {{GNF_GO|id=GO:0004672 |text = protein kinase activity}} {{GNF_GO|id=GO:0005509 |text = calcium ion binding}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0016534 |text = cyclin-dependent protein kinase 5 activator activity}} {{GNF_GO|id=GO:0043539 |text = protein serine/threonine kinase activator activity}} {{GNF_GO|id=GO:0045296 |text = cadherin binding}}
| Component = {{GNF_GO|id=GO:0005624 |text = membrane fraction}} {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0016020 |text = membrane}} {{GNF_GO|id=GO:0016533 |text = cyclin-dependent protein kinase 5 activator complex}} {{GNF_GO|id=GO:0030424 |text = axon}} {{GNF_GO|id=GO:0030426 |text = growth cone}} {{GNF_GO|id=GO:0031594 |text = neuromuscular junction}} {{GNF_GO|id=GO:0043025 |text = cell soma}} {{GNF_GO|id=GO:0043197 |text = dendritic spine}} {{GNF_GO|id=GO:0043292 |text = contractile fiber}}
| Process = {{GNF_GO|id=GO:0000079 |text = regulation of cyclin-dependent protein kinase activity}} {{GNF_GO|id=GO:0001764 |text = neuron migration}} {{GNF_GO|id=GO:0007158 |text = neuron adhesion}} {{GNF_GO|id=GO:0007213 |text = acetylcholine receptor signaling, muscarinic pathway}} {{GNF_GO|id=GO:0007411 |text = axon guidance}} {{GNF_GO|id=GO:0007413 |text = axonal fasciculation}} {{GNF_GO|id=GO:0007420 |text = brain development}} {{GNF_GO|id=GO:0008283 |text = cell proliferation}} {{GNF_GO|id=GO:0009790 |text = embryonic development}} {{GNF_GO|id=GO:0031175 |text = neurite development}} {{GNF_GO|id=GO:0035235 |text = ionotropic glutamate receptor signaling pathway}} {{GNF_GO|id=GO:0043525 |text = positive regulation of neuron apoptosis}} {{GNF_GO|id=GO:0045664 |text = regulation of neuron differentiation}} {{GNF_GO|id=GO:0048675 |text = axon extension}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 8851
    | Hs_Ensembl = ENSG00000176749
    | Hs_RefseqProtein = NP_003876
    | Hs_RefseqmRNA = NM_003885
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 17
    | Hs_GenLoc_start = 27838214
    | Hs_GenLoc_end = 27842383
    | Hs_Uniprot = Q15078
    | Mm_EntrezGene = 12569
    | Mm_Ensembl = ENSMUSG00000048895
    | Mm_RefseqmRNA = XM_001001743
    | Mm_RefseqProtein = XP_001001743
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 11
    | Mm_GenLoc_start = 80293218
    | Mm_GenLoc_end = 80297379
    | Mm_Uniprot = Q3V3I8
  }}
}}
'''Cyclin-dependent kinase 5, regulatory subunit 1 (p35)''', also known as '''CDK5R1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: CDK5R1 cyclin-dependent kinase 5, regulatory subunit 1 (p35)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8851| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
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]].<ref name="entrez"/>
{{PBB_Summary
 
| section_title =
In melanocytic cells CDK5R1 gene expression may be regulated by [[Microphthalmia-associated transcription factor|MITF]].<ref name="pmid19067971">{{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 |display-authors=etal}}</ref>
| summary_text = 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.<ref name="entrez">{{cite web | title = Entrez Gene: CDK5R1 cyclin-dependent kinase 5, regulatory subunit 1 (p35)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8851| accessdate = }}</ref>
 
}}
== Interactions ==
CDK5R1 has been shown to [[Protein-protein interaction|interact]] with:
* [[Actinin, alpha 1]]<ref name="pmid12084709">{{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 }}</ref>
* [[Amphiphysin]],<ref name="pmid11113134">{{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 }}</ref>
* [[Beta-catenin]],<ref name="pmid11168528">{{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 }}</ref>
* [[CAMK2A]],<ref name="pmid12223541">{{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 =  }}</ref>
* [[CDK5RAP2]],<ref name="pmid10915792">{{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 }}</ref>
* [[Cyclin-dependent kinase 5]],<ref name="pmid11389014">{{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 }}</ref><ref name="pmid11583627">{{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 }}</ref>
* [[Protein SET]],<ref name="pmid11741927">{{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 }}</ref>
 
==See also==
* [[CDK5RAP1]]
* [[CDK5RAP2]]
* [[CDK5RAP3]]


==References==
==References==
{{reflist|2}}
{{reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
*{{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 }}
| citations =
*{{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 }}
*{{cite journal  | author=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=  |pages= 91-6 |year= 2003 |pmid= 12491158 |doi= 10.1080/13550280290167885 }}
*{{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  |display-authors=etal}}
*{{cite journal  | author=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=  }}
*{{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}}
*{{cite journal  | author=Takahashi M, Tomizawa K, Sato K, ''et al.'' |title=A novel tau-tubulin kinase from bovine brain. |journal=FEBS Lett. |volume=372 |issue= 1 |pages= 59-64 |year= 1995 |pmid= 7556643 |doi= }}
*{{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  |display-authors=etal}}
*{{cite journal  | author=Tang D, Yeung J, Lee KY, ''et al.'' |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= }}
*{{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 }}
*{{cite journal  | author=Tsai LH, Delalle I, Caviness VS, ''et al.'' |title=p35 is a neural-specific regulatory subunit of cyclin-dependent kinase 5. |journal=Nature |volume=371 |issue= 6496 |pages= 419-23 |year= 1994 |pmid= 8090221 |doi= 10.1038/371419a0 }}
*{{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}}
*{{cite journal  | author=Chae T, Kwon YT, Bronson R, ''et al.'' |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=  }}
*{{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 |display-authors=etal}}
*{{cite journal  | author=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=  }}
*{{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  | author=Fletcher AI, Shuang R, Giovannucci DR, ''et al.'' |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= }}
*{{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 |display-authors=etal}}
*{{cite journal  | author=Patrick GN, Zukerberg L, Nikolic M, ''et al.'' |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 }}
*{{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 |display-authors=etal}}
*{{cite journal  | author=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=  }}
*{{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}}
*{{cite journal  | author=Kwon YT, Gupta A, Zhou Y, ''et al.'' |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= }}
*{{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}}
*{{cite journal  | author=Lee MS, Kwon YT, Li M, ''et al.'' |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 }}
*{{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  | author=Wang X, Ching YP, Lam WH, ''et al.'' |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 }}
*{{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  }}
*{{cite journal  | author=Floyd SR, Porro EB, Slepnev VI, ''et al.'' |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 }}
*{{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}}
*{{cite journal  | author=Kesavapany S, Lau KF, McLoughlin DM, ''et al.'' |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= }}
*{{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 }}
*{{cite journal  | author=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=  }}
*{{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}}
*{{cite journal  | author=Tarricone C, Dhavan R, Peng J, ''et al.'' |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= }}
*{{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 }}
*{{cite journal  | author=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 }}
*{{cite journal  | author=Qu D, Li Q, Lim HY, ''et al.'' |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 }}
*{{cite journal  | author=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 }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
==External links==
{{WikiDoc Sources}}
* {{UCSC gene info|CDK5R1}}
{{PDB Gallery|geneid=8851}}

Latest revision as of 01:43, 27 October 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Cyclin-dependent kinase 5 activator 1 is an enzyme that in humans is encoded by the CDK5R1 gene.[1][2]

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.[2]

In melanocytic cells CDK5R1 gene expression may be regulated by MITF.[3]

Interactions

CDK5R1 has been shown to interact with:

See also

References

  1. ↑ 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. doi:10.1038/371419a0. PMID 8090221.
  2. ↑ 2.0 2.1 "Entrez Gene: CDK5R1 cyclin-dependent kinase 5, regulatory subunit 1 (p35)".
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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. PMID 12223541.
  8. ↑ 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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. 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. 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.

External links

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