CDK5R1 cyclin-dependent kinase 5, regulatory subunit 1 (p35) [Homo sapiens] - Gene

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Summary

Official Symbol: CDK5R1provided by HGNC
Official Full Name: cyclin-dependent kinase 5, regulatory subunit 1 (p35)provided by HGNC
Primary source: HGNC:1775
See related: Ensembl:ENSG00000176749; HPRD:04586; MIM:603460; Vega:OTTHUMG00000132814
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: p23; p25; p35; CDK5R; NCK5A; CDK5P35; p35nck5a; MGC33831
Summary: 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. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 17q11.2

Sequence :: Chromosome: 17; NC_000017.10 (30814105..30818271)

See CDK5R1 in Epigenomics, MapViewer

Chromosome 17 - NC_000017.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

The decrease in membrane-associated p35 in socially isolated transgenic mice reduces associated levels of p35, alpha-CaMKII, and GluR1 and leads to endocytosis of AMPA receptors.
Title: The involvement of Cdk5 activator p35 in social isolation-triggered onset of early Alzheimer's disease-related cognitive deficit in the transgenic mice.
CDK5/p35 may represent a biomarker for prognosis in patients with non-small cell lung cancer
Title: Expression of CDK5/p35 in resected patients with non-small cell lung cancer: relation to prognosis.
findings indicate that miR-103 and miR-107 regulate CDK5R1 expression, allowing us to hypothesize that a miRNA-mediated mechanism may influence CDK5 activity and the associated molecular pathways
Title: The role of miR-103 and miR-107 in regulation of CDK5R1 expression and in cellular migration.
This study suggested that reduced p35 expression in schizophrenia has an impact on synaptic protein expression and cognition and that these deficits can be rescued, at least in part, by the inhibition of histone deacetylase 1.
Title: Schizophrenia is associated with dysregulation of a Cdk5 activator that regulates synaptic protein expression and cognition.
Study reveals a unique role of Cdk5/p35 in activation of the major noncanonical function of EPRS, namely translational control of macrophage inflammatory gene expression.
Title: Phosphorylation of glutamyl-prolyl tRNA synthetase by cyclin-dependent kinase 5 dictates transcript-selective translational control.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
These are the first quantitative and site-specific measurements of phosphorylation of p35
Title: Quantitative measurement of in vivo phosphorylation states of Cdk5 activator p35 by Phos-tag SDS-PAGE.
both proteasomal degradation and calpain cleavage of p35 and p39 are stimulated by membrane association, which is in turn mediated via myristoylation of their p10 regions.
Title: Membrane association facilitates degradation and cleavage of the cyclin-dependent kinase 5 activators p35 and p39.
p25 and cyclin-dependent kinase 5 play important roles as mediators of dopamine and glutamate in the neurotoxicity associated with Huntington's disease.
Title: Dopaminergic and glutamatergic signaling crosstalk in Huntington's disease neurodegeneration: the role of p25/cyclin-dependent kinase 5.
a role for Cdk5-p35 as a survival factor in countering MPP+-induced neuronal cell death.
Title: Commitment of 1-methyl-4-phenylpyrinidinium ion-induced neuronal cell death by proteasome-mediated degradation of p35 cyclin-dependent kinase 5 activator.

Submit: New GeneRIF Correction See all (39)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 Tat downregulates the expression of p35, a neuron-specific activator of cdk5, and also binds to Puralpha, which associates with cdk5, leading to deregulation of neuronal differentiation and survival	PubMed

Go to the HIV-1, Human Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_003876.1	NP_001626.1	AMPH	BIND	PubMed	Amphiphysin 1 interacts with p35. This interaction was modeled on a demonstrated interaction between human amphiphysin 1 and rat p35.
NP_003876.1	NP_004926.1	CDK5	BIND	PubMed	p35 interacts with Cdk5. This interaction was modeled on a demonstrated interaction between bovine p35 and human Cdk5.
NP_003876.1	NP_004926.1	CDK5	BIND	PubMed	Cdk5 interacts with p35.
Q15078	P12814	ACTN1	HPRD	PubMed
Q15078	P49418	AMPH	HPRD	PubMed
Q15078	Q9UQM7	CAMK2A	HPRD	PubMed
Q15078	P07384	CAPN1	HPRD	PubMed
Q15078	P17655	CAPN2	HPRD	PubMed
Q15078	Q00536	CDK16	HPRD	PubMed
Q15078	Q00535	CDK5	HPRD	PubMed
Q15078	Q15078	CDK5R1	HPRD	PubMed
Q15078	Q96SZ6	CDK5RAP1	HPRD	PubMed
Q15078	Q96SN8	CDK5RAP2	HPRD	PubMed
Q15078	Q96JB5	CDK5RAP3	HPRD	PubMed
Q15078	P50750	CDK9	HPRD	PubMed
Q15078	P15882	CHN1	HPRD	PubMed
Q15078	P35222	CTNNB1	HPRD	PubMed
Q15078	Q8IWU2	LMTK2	HPRD	PubMed
Q15078	P48681	NES	HPRD	PubMed
Q15078	Q13153	PAK1	HPRD	PubMed
Q15078	Q01105	SET	HPRD	PubMed
Q15078	P61764	STXBP1	HPRD	PubMed
Q15078	Q9Y3Q8	TSC22D4	HPRD	PubMed
Q15078	Q5TCY1	TTBK1	HPRD	PubMed
BioGRID:114376	BioGRID:106602	ACTN1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:114376	BioGRID:106770	AMPH	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:114376	BioGRID:107265	CAMK2A	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:114376	BioGRID:111154	CDK16	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:114376	BioGRID:107455	CDK5	BioGRID	PubMed	Affinity Capture-Western; Co-crystal Structure
BioGRID:114376	BioGRID:119661	CDK5RAP1	BioGRID	PubMed	Reconstituted Complex
BioGRID:114376	BioGRID:120873	CDK5RAP2	BioGRID	PubMed	Reconstituted Complex
BioGRID:114376	BioGRID:123213	CDK5RAP3	BioGRID	PubMed	Reconstituted Complex
BioGRID:114376	BioGRID:107880	CTNNB1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:114376	BioGRID:109315	HDAC1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:114376	BioGRID:109552	HSP90AA1	BioGRID	PubMed	Reconstituted Complex
BioGRID:114376	BioGRID:110811	NEDD4	BioGRID	PubMed	Reconstituted Complex
BioGRID:114376	BioGRID:115983	NES	BioGRID	PubMed	Affinity Capture-Western
BioGRID:114376	BioGRID:112316	SET	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:114376	BioGRID:215053	Suds3	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex; Two-hybrid
BioGRID:114376	BioGRID:123563	TSC22D4	BioGRID	PubMed	Two-hybrid
BioGRID:114376	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-Western

Function	Evidence Code	Pubs
cadherin binding	ISS Inferred from Sequence or Structural Similarity more info
calcium ion binding	ISS Inferred from Sequence or Structural Similarity more info
cyclin-dependent protein kinase 5 activator activity	IEA Inferred from Electronic Annotation more info
kinase activity	ISS Inferred from Sequence or Structural Similarity more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase activity	TAS Traceable Author Statement more info	PubMed
protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
protein serine/threonine kinase activator activity	IDA Inferred from Direct Assay more info	PubMed
protein serine/threonine kinase activator activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
G-protein coupled acetylcholine receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
axon guidance	ISS Inferred from Sequence or Structural Similarity more info
axon guidance	TAS Traceable Author Statement more info
axonal fasciculation	ISS Inferred from Sequence or Structural Similarity more info
brain development	ISS Inferred from Sequence or Structural Similarity more info
brain development	NAS Non-traceable Author Statement more info	PubMed
cell proliferation	TAS Traceable Author Statement more info	PubMed
cerebral cortex radially oriented cell migration	IEA Inferred from Electronic Annotation more info
embryo development	ISS Inferred from Sequence or Structural Similarity more info
ephrin receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
ionotropic glutamate receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of transcription, DNA-dependent	IMP Inferred from Mutant Phenotype more info
neuron cell-cell adhesion	ISS Inferred from Sequence or Structural Similarity more info
neuron differentiation	ISS Inferred from Sequence or Structural Similarity more info
neuron migration	ISS Inferred from Sequence or Structural Similarity more info
neuron projection development	ISS Inferred from Sequence or Structural Similarity more info
peptidyl-serine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
peptidyl-threonine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of neuron apoptosis	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of protein serine/threonine kinase activity	ISS Inferred from Sequence or Structural Similarity more info
protein phosphorylation	TAS Traceable Author Statement more info	PubMed
regulation of actin cytoskeleton organization	IEA Inferred from Electronic Annotation more info
regulation of cyclin-dependent protein kinase activity	TAS Traceable Author Statement more info	PubMed
regulation of dendritic spine morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
regulation of microtubule cytoskeleton organization	IEA Inferred from Electronic Annotation more info
regulation of neuron differentiation	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
axon	ISS Inferred from Sequence or Structural Similarity more info
contractile fiber	ISS Inferred from Sequence or Structural Similarity more info
cyclin-dependent protein kinase 5 holoenzyme complex	IEA Inferred from Electronic Annotation more info
cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
cytosol	TAS Traceable Author Statement more info
dendrite	ISS Inferred from Sequence or Structural Similarity more info
dendritic spine	ISS Inferred from Sequence or Structural Similarity more info
growth cone	ISS Inferred from Sequence or Structural Similarity more info
membrane	ISS Inferred from Sequence or Structural Similarity more info
neuromuscular junction	ISS Inferred from Sequence or Structural Similarity more info
neuronal cell body	ISS Inferred from Sequence or Structural Similarity more info
nucleus	ISS Inferred from Sequence or Structural Similarity more info
perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	IEA Inferred from Electronic Annotation more info
postsynaptic density	ISS Inferred from Sequence or Structural Similarity more info

General protein information

Preferred Names: cyclin-dependent kinase 5 activator 1

Names: cyclin-dependent kinase 5 activator 1; CDK5 activator 1; neuronal CDK5 activator; TPKII regulatory subunit; regulatory partner for CDK5 kinase; tau protein kinase II 23kDa subunit; cyclin-dependent kinase 5 regulatory subunit 1

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_003885.2 → NP_003876.1 cyclin-dependent kinase 5 activator 1

Status: REVIEWED

Source sequence(s)

BC030792

Consensus CDS

CCDS11273.1

UniProtKB/Swiss-Prot

Q15078

UniProtKB/TrEMBL

Q8N619

Related

ENSP00000318486, OTTHUMP00000163708, ENST00000313401, OTTHUMT00000256264

Conserved Domains (1) summary

pfam03261
Location:1 – 296
Blast Score: 1106

CDK5_activator; Cyclin-dependent kinase 5 activator protein

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000017.10 Reference GRCh37.p5 Primary Assembly

Range

30814105..30818271

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000149.1 Alternate HuRef

Range

27000601..27004486

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC079336.5 (65110..69276)	None
genomic	AY376350.1	AAQ74776.1
genomic	CH471147.2	EAW80227.1
		EAW80228.1
mRNA	AK095754.1	None
mRNA	BC020580.2	AAH20580.1
mRNA	BC026347.1	AAH26347.1
mRNA	BC030792.1	AAH30792.1
mRNA	BC032081.1	None
mRNA	BC035448.1	None
mRNA	BT019573.1	AAV38380.1
mRNA	X80343.1	CAA56587.1
other-genetic	HQ448723.1	ADQ33201.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
Q15078.1	GenPept	UniProtKB/Swiss-Prot:Q15078
Q8N619	GenPept	UniProtKB/TrEMBL:Q8N619
Q8TAM4	GenPept	UniProtKB/TrEMBL:Q8TAM4