Cdk4 cyclin-dependent kinase 4 [Rattus norvegicus (Norway rat)] - Gene

Summary

Symbol: Cdk4provided by RGD
Full Name: cyclin-dependent kinase 4provided by RGD
Primary source: RGD:621120
See related: AllianceGenome:RGD:621120
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Summary: Enables cyclin binding activity and cyclin-dependent protein serine/threonine kinase activity. Involved in several processes, including cellular response to polyamine macromolecule; positive regulation of cell size; and response to testosterone. Located in nucleus and perinuclear region of cytoplasm. Biomarker of hepatocellular carcinoma; pancreatic cancer; prostatic hypertrophy; and urinary bladder cancer. Human ortholog(s) of this gene implicated in several diseases, including carcinoma (multiple); familial melanoma; glioblastoma; obesity; and type 2 diabetes mellitus. Orthologous to human CDK4 (cyclin dependent kinase 4). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Biased expression in Thymus (RPKM 573.2), Adrenal (RPKM 371.5) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 7q22

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	7	NC_086025.1 (64771453..64774891)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	7	NC_051342.1 (62886124..62889562)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	7	NC_005106.4 (70345971..70352689)

Chromosome 7 - NC_086025.1 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: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Cyclin D1-Cdk4 regulates neuronal activity through phosphorylation of GABAA receptors.
Title: Cyclin D1-Cdk4 regulates neuronal activity through phosphorylation of GABAA receptors.
LncRNA SNHG1 attenuates neuropathic pain following spinal cord injury by regulating CDK4 level.
Title: LncRNA SNHG1 attenuates neuropathic pain following spinal cord injury by regulating CDK4 level.
CDK4 and CDK5 Inhibition Have Comparable Mild Hypothermia Effects in Preventing Drp1-Dependent Mitochondrial Fission and Neuron Death Induced by MPP().
Title: CDK4 and CDK5 Inhibition Have Comparable Mild Hypothermia Effects in Preventing Drp1-Dependent Mitochondrial Fission and Neuron Death Induced by MPP().
A small molecule dual inhibitor of the c-MYC activated kinases ARK5 and CDK4/6, is being developed.
Title: Effect of Gender on the Pharmacokinetics of ON 123300, A Dual Inhibitor of ARK5 and CDK4/6 for the Treatment of Cancer, in Rats.
that status epilepticus may lead to nucleocytoplasmic p27(Kip1) export that initiates CDK4, not CDK5, induction, which an abortive and fatal cell cycle re-entry progress in CA1 neurons
Title: Suppression of nucleocytoplasmic p27(Kip1) export attenuates CDK4-mediated neuronal death induced by status epilepticus.
the experimental results show that changes in the expression of cyclin D1 and CDK4 may accelerate apoptosis of amygdala neurons in PTSD-like rats.
Title: Alterations in cyclin D1 and cyclin‑dependent kinase 4 expression in the amygdalae of post‑traumatic stress disorder rats.
This study highlights the importance of differentially expressed proteins Txn1, Ctsd and Cdk4 against liver fibrosis, which may provide a more precise and comprehensive perspective for clarifying the roles of combination therapy as a potential agent for treatment of liver fibrosis.
Title: Txn1, Ctsd and Cdk4 are key proteins of combination therapy with taurine, epigallocatechin gallate and genistein against liver fibrosis in rats.
The robust increase in the expression of cyclin D1 and CDK4 at day 2 suggests that Muller glia may be in G1 phase of the cell cycle at this stage.
Title: DNA Damage Response in Proliferating Müller Glia in the Mammalian Retina.
These results establish CDK4 as a GATA4 partner in cardiogenesis
Title: Carboxy terminus of GATA4 transcription factor is required for its cardiogenic activity and interaction with CDK4.
CDK4 is a critical downstream target of MEN1-dependent tumor suppression and is required for tumorigenic proliferation in the pituitary and pancreatic islet, whereas CDK2 is dispensable for tumorigenesis in these neuroendocrine cell types.
Title: MEN1 tumorigenesis in the pituitary and pancreatic islet requires Cdk4 but not Cdk2.

Submit: New GeneRIF Correction See all GeneRIFs (31)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC212738P3 (e-PCR)
- UniSTS:272029

Cdk4 (e-PCR), detects polymorphism
- UniSTS:527078

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables cyclin binding	IBA Inferred from Biological aspect of Ancestor more info
enables cyclin binding	IEA Inferred from Electronic Annotation more info
enables cyclin binding	IPI Inferred from Physical Interaction more info	PubMed
enables cyclin binding	ISO Inferred from Sequence Orthology more info
enables cyclin-dependent protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables cyclin-dependent protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables cyclin-dependent protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables cyclin-dependent protein serine/threonine kinase activity	ISO Inferred from Sequence Orthology more info
enables kinase activity	ISO Inferred from Sequence Orthology more info
enables protein kinase activity	ISO Inferred from Sequence Orthology more info
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein-containing complex binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in G1/S transition of mitotic cell cycle	IBA Inferred from Biological aspect of Ancestor more info
involved_in G1/S transition of mitotic cell cycle	IEA Inferred from Electronic Annotation more info
involved_in G1/S transition of mitotic cell cycle	ISO Inferred from Sequence Orthology more info
involved_in G1/S transition of mitotic cell cycle	NAS Non-traceable Author Statement more info	PubMed
involved_in animal organ regeneration	IEP Inferred from Expression Pattern more info	PubMed
involved_in cell division	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cellular response to interleukin-4	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cellular response to ionomycin	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cellular response to lipopolysaccharide	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cellular response to phorbol 13-acetate 12-myristate	ISO Inferred from Sequence Orthology more info
involved_in cellular response to polyamine macromolecule	IEP Inferred from Expression Pattern more info	PubMed
involved_in circadian rhythm	IEP Inferred from Expression Pattern more info	PubMed
involved_in lens development in camera-type eye	IEP Inferred from Expression Pattern more info	PubMed
involved_in positive regulation of G2/M transition of mitotic cell cycle	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of G2/M transition of mitotic cell cycle	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of G2/M transition of mitotic cell cycle	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell population proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell size	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of epithelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of fibroblast proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of fibroblast proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of translation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein phosphorylation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within protein phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in protein phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in regulation of G2/M transition of mitotic cell cycle	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within regulation of cell cycle	ISO Inferred from Sequence Orthology more info
involved_in regulation of cell cycle	ISO Inferred from Sequence Orthology more info
involved_in regulation of gene expression	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in regulation of gene expression	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of type B pancreatic cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in response to hyperoxia	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to testosterone	IDA Inferred from Direct Assay more info	PubMed
involved_in response to toxic substance	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in response to xenobiotic stimulus	ISO Inferred from Sequence Orthology more info
involved_in signal transduction	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within signal transduction	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in bicellular tight junction	ISO Inferred from Sequence Orthology more info
located_in chromatin	IEA Inferred from Electronic Annotation more info
located_in chromatin	ISO Inferred from Sequence Orthology more info
part_of cyclin D1-CDK4 complex	IEA Inferred from Electronic Annotation more info
part_of cyclin D1-CDK4 complex	ISO Inferred from Sequence Orthology more info
part_of cyclin D2-CDK4 complex	IEA Inferred from Electronic Annotation more info
part_of cyclin D2-CDK4 complex	ISO Inferred from Sequence Orthology more info
part_of cyclin D3-CDK4 complex	IEA Inferred from Electronic Annotation more info
part_of cyclin D3-CDK4 complex	ISO Inferred from Sequence Orthology more info
part_of cyclin-dependent protein kinase holoenzyme complex	IBA Inferred from Biological aspect of Ancestor more info
part_of cyclin-dependent protein kinase holoenzyme complex	ISO Inferred from Sequence Orthology more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in nuclear membrane	IEA Inferred from Electronic Annotation more info
located_in nuclear membrane	ISO Inferred from Sequence Orthology more info
located_in nucleolus	IEA Inferred from Electronic Annotation more info
located_in nucleolus	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	ISO Inferred from Sequence Orthology more info
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
part_of transcription regulator complex	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: cyclin-dependent kinase 4

Names: PSK-J3; cell division protein kinase 4

NP_001389324.1

EC 2.7.11.22

NP_446045.1

EC 2.7.11.22

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_001402395.1 → NP_001389324.1 cyclin-dependent kinase 4 isoform 2

Status: VALIDATED

Source sequence(s)

JAXUCZ010000007
NM_053593.3 → NP_446045.1 cyclin-dependent kinase 4 isoform 1

See identical proteins and their annotated locations for NP_446045.1

Status: VALIDATED

Source sequence(s)

JAXUCZ010000007

UniProtKB/Swiss-Prot

P35426

UniProtKB/TrEMBL

A0A8L2QI74, A6HQS0

Conserved Domains (1) summary

cl21453
Location:5 → 295

PKc_like; Protein Kinases, catalytic domain