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

Summary

Official Symbol: CDK5R1provided by HGNC
Official Full Name: cyclin dependent kinase 5 regulatory subunit 1provided by HGNC
Primary source: HGNC:HGNC:1775
See related: Ensembl:ENSG00000176749 MIM:603460; AllianceGenome:HGNC:1775
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
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]
Expression: Biased expression in brain (RPKM 36.6), lymph node (RPKM 6.6) and 5 other tissues See more
Orthologs: all
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Genomic context

Location:: 17q11.2

Exon count:: 2

Annotation release	Status	Assembly	Chr	Location
RS_2025_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (32486993..32491253)
RS_2025_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (33432760..33437020)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (30814011..30818271)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Tumor-suppressive microRNA-152 inhibits the proliferation of Ewing's sarcoma cells by targeting CDK5R1.
Title: Tumor-suppressive microRNA-152 inhibits the proliferation of Ewing's sarcoma cells by targeting CDK5R1.
Elevated CDK5R1 predicts worse prognosis in hepatocellular carcinoma based on TCGA data.
Title: Elevated CDK5R1 predicts worse prognosis in hepatocellular carcinoma based on TCGA data.
The Cyclin-Dependent Kinase 5 Inhibitor Peptide Inhibits Herpes Simplex Virus Type 1 Replication.
Title: The Cyclin-Dependent Kinase 5 Inhibitor Peptide Inhibits Herpes Simplex Virus Type 1 Replication.
Study demonstrated that NEAT1 and HOTAIR negatively regulate CDK5R1 mRNA levels, while MALAT1 has a positive effect.
Title: Multiple Layers of CDK5R1 Regulation in Alzheimer's Disease Implicate Long Non-Coding RNAs.
the downregulation of the miR-15/107 family might have a role in the pathogenesis of AD by increasing the levels of CDK5R1/p35 and consequently enhancing CDK5 activity.
Title: The miR-15/107 Family of microRNA Genes Regulates CDK5R1/p35 with Implications for Alzheimer's Disease Pathogenesis.
It is shown that p5 binds the kinase at the same CDK5/p25 and CDK5/p35 interfaces, and is thus a non-selective competitor of both activators, in agreement with available experimental data in vitro.
Title: Computational study of the inhibitory mechanism of the kinase CDK5 hyperactivity by peptide p5 and derivation of a pharmacophore.
the minor allele of CDK5R1 3'-UTR rs735555 polymorphism was associated with increased risk for NS-ID. In conclusion, our data suggest that mutations and polymorphisms in CDK5 and CDK5R1 genes may contribute to the onset of the NS-ID phenotype
Title: Functional characterization of CDK5 and CDK5R1 mutations identified in patients with non-syndromic intellectual disability.
Under cell-free in vitro conditions, p35 is covalently modified by SUMO1. SUMO2 is conjugated to p35 in cells. The 2 major SUMO acceptor lysines in p35 are K246 and K290. Different degrees of oxidative stress resulted in differential p35 sumoylation.
Title: Sumoylation of p35 modulates p35/cyclin-dependent kinase (Cdk) 5 complex activity.
Cdk5/p35 is required for motor learning and involved in long-term synaptic plasticity.
Title: Cdk5/p35 is required for motor coordination and cerebellar plasticity.
Expression of p35 is upregulated in human pituitary adenomas.
Title: CDK5 and its activator P35 in normal pituitary and in pituitary adenomas: relationship to VEGF expression.

Submit: New GeneRIF Correction See all GeneRIFs (54)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 Tat decreases the levels of Egr-1 and p35 expression in nerve growth factor (NGF)-treated neural cells	PubMed
	tat	Neural cells expressing Tat reduces the phosphorylation level of neurofilaments by p35/Cdk5	PubMed
	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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH25988 (e-PCR)
- UniSTS:85771

D17S1369E (e-PCR)
- UniSTS:54292

RH66802 (e-PCR)
- UniSTS:19546

D17S1558 (e-PCR)
- UniSTS:1656

SHGC-63467 (e-PCR)
- UniSTS:48014

CDK5R1_1797 (e-PCR)
- UniSTS:280492

A004P02 (e-PCR)
- UniSTS:7605

D17S1458E (e-PCR)
- UniSTS:150498

SHGC-63466 (e-PCR)
- UniSTS:39907

RH70922 (e-PCR)
- UniSTS:66815

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables actin binding	IEA Inferred from Electronic Annotation more info
enables actin filament binding	IEA Inferred from Electronic Annotation more info
NOT enables alpha-tubulin binding	ISS Inferred from Sequence or Structural Similarity more info
enables alpha-tubulin binding	ISS Inferred from Sequence or Structural Similarity more info
NOT enables beta-tubulin binding	ISS Inferred from Sequence or Structural Similarity more info
enables beta-tubulin binding	ISS Inferred from Sequence or Structural Similarity more info
enables cadherin binding	ISS Inferred from Sequence or Structural Similarity more info
enables calcium ion binding	ISS Inferred from Sequence or Structural Similarity more info
enables cyclin-dependent protein serine/threonine kinase activator activity	IBA Inferred from Biological aspect of Ancestor more info
enables cyclin-dependent protein serine/threonine kinase activator activity	IEA Inferred from Electronic Annotation more info
enables cyclin-dependent protein serine/threonine kinase activator activity	IGI Inferred from Genetic Interaction more info	PubMed
enables cyclin-dependent protein serine/threonine kinase activator activity	TAS Traceable Author Statement more info	PubMed
enables ionotropic glutamate receptor binding	IEA Inferred from Electronic Annotation more info
enables kinase activity	ISS Inferred from Sequence or Structural Similarity more info
enables protease binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activator activity	TAS Traceable Author Statement more info	PubMed
enables protein kinase activity	TAS Traceable Author Statement more info	PubMed
enables protein kinase binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein kinase binding	IEA Inferred from Electronic Annotation more info
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine/threonine kinase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine kinase activator activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in G protein-coupled acetylcholine receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in axon guidance	IBA Inferred from Biological aspect of Ancestor more info
involved_in axon guidance	IEA Inferred from Electronic Annotation more info
involved_in axon guidance	ISS Inferred from Sequence or Structural Similarity more info
involved_in axonal fasciculation	IEA Inferred from Electronic Annotation more info
involved_in axonal fasciculation	ISS Inferred from Sequence or Structural Similarity more info
involved_in brain development	IBA Inferred from Biological aspect of Ancestor more info
involved_in brain development	IEA Inferred from Electronic Annotation more info
involved_in brain development	ISS Inferred from Sequence or Structural Similarity more info
involved_in brain development	NAS Non-traceable Author Statement more info	PubMed
involved_in cerebral cortex radially oriented cell migration	IEA Inferred from Electronic Annotation more info
involved_in ephrin receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in ephrin receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in ionotropic glutamate receptor signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in microtubule cytoskeleton organization	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuron cell-cell adhesion	IEA Inferred from Electronic Annotation more info
involved_in neuron cell-cell adhesion	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuron differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuron migration	IEA Inferred from Electronic Annotation more info
involved_in neuron migration	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuron projection development	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuron projection development	TAS Traceable Author Statement more info	PubMed
involved_in peptidyl-serine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in peptidyl-threonine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of MHC class II biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of microtubule polymerization	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of neuron apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of tumor necrosis factor-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of actin cytoskeleton organization	IEA Inferred from Electronic Annotation more info
involved_in regulation of cyclin-dependent protein serine/threonine kinase activity	TAS Traceable Author Statement more info	PubMed
involved_in regulation of dendritic spine morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in regulation of dendritic spine morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of macroautophagy	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of microtubule cytoskeleton organization	IEA Inferred from Electronic Annotation more info
involved_in regulation of neuron differentiation	NAS Non-traceable Author Statement more info	PubMed
involved_in rhythmic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in axon	ISS Inferred from Sequence or Structural Similarity more info
located_in contractile muscle fiber	ISS Inferred from Sequence or Structural Similarity more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in cytoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in cytosol	TAS Traceable Author Statement more info
located_in dendrite	ISS Inferred from Sequence or Structural Similarity more info
located_in dendritic spine	ISS Inferred from Sequence or Structural Similarity more info
is_active_in growth cone	IBA Inferred from Biological aspect of Ancestor more info
located_in growth cone	ISS Inferred from Sequence or Structural Similarity more info
located_in membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in neuromuscular junction	ISS Inferred from Sequence or Structural Similarity more info
located_in neuron projection	IEA Inferred from Electronic Annotation more info
located_in neuron projection	ISS Inferred from Sequence or Structural Similarity more info
located_in neuronal cell body	ISS Inferred from Sequence or Structural Similarity more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in nucleus	ISS Inferred from Sequence or Structural Similarity more info
located_in perikaryon	IEA Inferred from Electronic Annotation more info
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	TAS Traceable Author Statement more info
located_in postsynaptic density	ISS Inferred from Sequence or Structural Similarity more info
part_of protein kinase 5 complex	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: cyclin-dependent kinase 5 activator 1

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

NCBI Reference Sequences (RefSeq)

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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.