CDK5R2 cyclin dependent kinase 5 regulatory subunit 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CDK5R2provided by HGNC
Official Full Name: cyclin dependent kinase 5 regulatory subunit 2provided by HGNC
Primary source: HGNC:HGNC:1776
See related: Ensembl:ENSG00000171450 MIM:603764; AllianceGenome:HGNC:1776
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: P39; NCK5AI; p39nck5ai
Summary: The protein encoded by this gene is a neuron-specific activator of CDK5 kinase. It associates with CDK5 to form an active kinase. This protein and neuron-specific CDK5 activator CDK5R1/p39NCK5A both share limited similarity to cyclins, and thus may define a distinct family of cyclin-dependent kinase activating proteins. [provided by RefSeq, Jul 2008]
Orthologs: mouse all
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Genomic context

Location:: 2q35

Exon count:: 1

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (218959666..218962155)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (219448040..219450529)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (219824388..219826877)

Chromosome 2 - NC_000002.12 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

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

S-Nitrosylation of p39 promotes its degradation and contributes to synaptic dysfunction induced by beta-amyloid peptide.
Title: S-Nitrosylation of p39 promotes its degradation and contributes to synaptic dysfunction induced by β-amyloid peptide.
a biomarker consisting of the phosphorylation of the retinoblastoma protein (Rb) on serine 249 combined with elevated p39 expression. This biomarker correlates with epithelial-to-mesenchymal transition traits in non-small cell lung carcinoma (NSCLC) cells.
Title: Hyper-phosphorylation of Rb S249 together with CDK5R2/p39 overexpression are associated with impaired cell adhesion and epithelial-to-mesenchymal transition: Implications as a potential lung cancer grading and staging biomarker.
p39 is essential for recruiting scaffolding protein muskelin to stress fibers.
Title: The Cdk5 activator P39 specifically links muskelin to myosin II and regulates stress fiber formation and actin organization in lens.
Structural basis for the different stability and activity between the Cdk5 complexes with p35 and p39 activators.
Title: Structural basis for the different stability and activity between the Cdk5 complexes with p35 and p39 activators.
Hepatocellular carcinoma patients with lower p39 expression had poorer overall survival rate than that with high expression.
Title: Decreased expression of p39 is associated with a poor prognosis in human hepatocellular carcinoma.
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.
Our data suggest that neurotoxic insults lead to calpain-mediated conversion of p39 to p29, which might contribute to deregulation of Cdk5
Title: Calpain-mediated cleavage of the cyclin-dependent kinase-5 activator p39 to p29.
role of the CDK5 molecular complex in the genetic etiology of early-onset Alzheimer disease; a yet unknown functional variant in CDK5 or in a nearby gene might lead to increased susceptibility for early-onset Alzheimer disease
Title: Association of cyclin-dependent kinase 5 and neuronal activators p35 and p39 complex in early-onset Alzheimer's disease.

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Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of cyclin-dependent kinase 5, regulatory subunit 2, p39 (CDK5R2) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables actin 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	ISS Inferred from Sequence or Structural Similarity more info
enables cyclin-dependent protein serine/threonine kinase activator activity	TAS Traceable Author Statement more info	PubMed
enables lipid binding	IEA Inferred from Electronic Annotation more info
enables protein kinase binding	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in axon guidance	IBA Inferred from Biological aspect of Ancestor more info
involved_in brain development	IBA Inferred from Biological aspect of Ancestor more info
involved_in cerebellum development	IEA Inferred from Electronic Annotation more info
involved_in hippocampus development	IEA Inferred from Electronic Annotation more info
involved_in layer formation in cerebral cortex	IEA Inferred from Electronic Annotation more info
involved_in neuron migration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of calcium ion-dependent exocytosis	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 superior olivary nucleus maturation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of cyclin-dependent protein kinase holoenzyme complex	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	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 neuron projection	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in presynapse	IEA Inferred from Electronic Annotation more info
part_of protein kinase 5 complex	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: cyclin-dependent kinase 5 activator 2

Names: CDK5 activator 2; p39I

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.

mRNA and Protein(s)

NM_003936.5 → NP_003927.1 cyclin-dependent kinase 5 activator 2

See identical proteins and their annotated locations for NP_003927.1

Status: REVIEWED

Source sequence(s)

AC097468

Consensus CDS

CCDS2427.1

UniProtKB/Swiss-Prot

Q13319, Q4ZFW6

UniProtKB/TrEMBL

Q5XKD4

Related

ENSP00000304250.4, ENST00000302625.6

Conserved Domains (1) summary

pfam03261
Location:40 → 326

CDK5_activator; Cyclin-dependent kinase 5 activator protein