Cdkn2a cyclin-dependent kinase inhibitor 2A [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Cdkn2aprovided by RGD
Official Full Name: cyclin-dependent kinase inhibitor 2Aprovided by RGD
Primary source: RGD:2323
See related: Ensembl:ENSRNOG00000059837 AllianceGenome:RGD:2323
Gene type: protein coding
RefSeq status: PROVISIONAL
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: Arf; p16; MTS1; INK4A; p19ARF; p16Cdkn2a
Summary: Predicted to enable several functions, including MDM2/MDM4 family protein binding activity; NF-kappaB binding activity; and enzyme inhibitor activity. Involved in several processes, including cellular response to glucose stimulus; negative regulation of hepatocyte proliferation; and nervous system development. Located in cytoplasm and nucleus. Used to study carcinoma (multiple); endometrial cancer; pre-malignant neoplasm; rhabdomyosarcoma; and sarcomatoid mesothelioma. Biomarker of hepatocellular carcinoma; hypertension; obesity; and osteoarthritis. Human ortholog(s) of this gene implicated in several diseases, including breast cancer (multiple); hematologic cancer (multiple); melanoma (multiple); nervous system cancer (multiple); and pancreatic cancer (multiple). Orthologous to human CDKN2A (cyclin dependent kinase inhibitor 2A). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in Adrenal (RPKM 6.0), Thymus (RPKM 4.6) and 7 other tissues See more
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Genomic context

Location:: 5q32

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	5	NC_086023.1 (109100763..109114448, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	5	NC_051340.1 (103984949..103992143, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	5	NC_005104.4 (107823323..107832405, complement)

Chromosome 5 - NC_086023.1 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
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?

Expression of p16(Ink4a) protein in pleomorphic adenoma and carcinoma ex pleomorphic adenoma proves diversity of tumour biology and predicts clinical course.
Title: Expression of p16(Ink4a) protein in pleomorphic adenoma and carcinoma ex pleomorphic adenoma proves diversity of tumour biology and predicts clinical course.
Loss of p16/Ink4a drives high frequency of rhabdomyosarcoma in a rat model of Duchenne muscular dystrophy.
Title: Loss of p16/Ink4a drives high frequency of rhabdomyosarcoma in a rat model of Duchenne muscular dystrophy.
Angiotensin inhibition and cellular senescence in the developing rat kidney.
Title: Angiotensin inhibition and cellular senescence in the developing rat kidney.
the loss of Cdkn2a/2b, which are the most frequently lost foci in human MM, were observed in 8 cases of rat MM (homozygous deletion [5/8] and loss of heterozygosity [3/8]) by array-based comparative genomic hybridization techniques.
Title: Frequent homozygous deletion of Cdkn2a/2b in tremolite-induced malignant mesothelioma in rats.
streptozotocin-induced experimental diabetes mellitus induced p16 expression but did not show any difference in p53, Bcl-2, and Ki67 levels.
Title: The Impact of Type II Diabetes on Tongue Dysplasia and p16-Related Aging Process: An Experimental Study.
5-aza-CdR attenuated lung fibrosis in neonatal rats exposed to hyperoxia by lowering hydroxyproline and TGF-beta1 expression and via re-expression of P16 in neonatal rats
Title: 5-aza-2'-deoxycytidine, a DNA methylation inhibitor, attenuates hyperoxia-induced lung fibrosis via re-expression of P16 in neonatal rats.
Our findings indicated that p16 alteration is a common event in the carcinogenesis of this model and that the mutation pattern is analogous to that of human lesions.
Title: Mutations in the p16 gene in DMBA-induced pancreatic intraepithelial neoplasia and pancreatic cancer in rats.
These findings indicate that p16(INK4a) plays a significant role in the inhibition of DNA synthesis.
Title: Role of p16(INK4a) in the inhibition of DNA synthesis stimulated by HGF or EGF in primary cultured rat hepatocytes.
Ezh2 knockdown induced changes in DNA methylation of the p16INK4a gene and premature senescence in mesenchymal stem cells.
Title: H3K9me-enhanced DNA hypermethylation of the p16INK4a gene: an epigenetic signature for spontaneous transformation of rat mesenchymal stem cells.
Data show that an accumulation of p16(INK4a)-positive senescent astrocytes may link increased age and increased risk for sporadic Alzheimer's disease (AD).
Title: Astrocyte senescence as a component of Alzheimer's disease.

Submit: New GeneRIF Correction See all GeneRIFs (35)

General gene information

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Markers

D5Lev17 (e-PCR)
- UniSTS:239711

PMC152255P1 (e-PCR)
- UniSTS:271207

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables DNA binding	IEA Inferred from Electronic Annotation more info
enables DNA-binding transcription factor binding	ISO Inferred from Sequence Orthology more info
enables MDM2/MDM4 family protein binding	ISO Inferred from Sequence Orthology more info
enables NF-kappaB binding	ISO Inferred from Sequence Orthology more info
enables RNA polymerase II-specific DNA-binding transcription factor binding	ISO Inferred from Sequence Orthology more info
enables SUMO transferase activity	ISO Inferred from Sequence Orthology more info
enables cyclin-dependent protein serine/threonine kinase inhibitor activity	ISO Inferred from Sequence Orthology more info
enables disordered domain specific binding	ISO Inferred from Sequence Orthology more info
enables p53 binding	ISO Inferred from Sequence Orthology more info
enables protein kinase binding	ISO Inferred from Sequence Orthology more info
enables ubiquitin ligase inhibitor activity	ISO Inferred from Sequence Orthology more info
enables ubiquitin-protein transferase inhibitor activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in Ras protein signal transduction	ISO Inferred from Sequence Orthology more info
involved_in amyloid fibril formation	ISO Inferred from Sequence Orthology more info
involved_in apoptotic mitochondrial changes	ISO Inferred from Sequence Orthology more info
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of apoptotic process involved in mammary gland involution	ISO Inferred from Sequence Orthology more info
involved_in cellular response to glucose stimulus	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within cellular response to hydrogen peroxide	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cellular senescence	ISO Inferred from Sequence Orthology more info
involved_in cellular senescence	ISO Inferred from Sequence Orthology more info
involved_in cerebellum development	IEP Inferred from Expression Pattern more info	PubMed
acts_upstream_of_or_within epidermis development	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within glucose homeostasis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within keratinocyte differentiation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within keratinocyte proliferation	ISO Inferred from Sequence Orthology more info
acts_upstream_of mammary gland epithelial cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in mitochondrial depolarization	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of B cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of cell cycle	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell growth	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of cell-matrix adhesion	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of hepatocyte proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of immature T cell proliferation in thymus	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of mammary gland epithelial cell proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of protein localization to nucleolus	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of protein neddylation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of proteolysis involved in protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of proteolysis involved in protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of ribosome biogenesis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of ubiquitin-dependent protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of ubiquitin-dependent protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in neurogenesis	IEP Inferred from Expression Pattern more info	PubMed
involved_in nuclear body organization	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within oncogene-induced cell senescence	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of DNA damage response, signal transduction by p53 class mediator	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of apoptotic process involved in mammary gland involution	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of macrophage apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein localization to nucleus	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein sumoylation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of signal transduction by p53 class mediator	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of smooth muscle cell apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in protein K63-linked ubiquitination	ISO Inferred from Sequence Orthology more info
involved_in protein K63-linked ubiquitination	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein destabilization	ISO Inferred from Sequence Orthology more info
involved_in protein localization to nucleolus	ISO Inferred from Sequence Orthology more info
involved_in protein localization to nucleus	ISO Inferred from Sequence Orthology more info
involved_in protein polyubiquitination	ISO Inferred from Sequence Orthology more info
involved_in protein polyubiquitination	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein stabilization	ISO Inferred from Sequence Orthology more info
involved_in rRNA processing	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within rRNA transcription	ISO Inferred from Sequence Orthology more info
involved_in regulation of G1/S transition of mitotic cell cycle	ISO Inferred from Sequence Orthology more info
involved_in regulation of G2/M transition of mitotic cell cycle	ISO Inferred from Sequence Orthology more info
involved_in regulation of apoptotic DNA fragmentation	ISO Inferred from Sequence Orthology more info
involved_in regulation of cell cycle	IEA Inferred from Electronic Annotation 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
acts_upstream_of_or_within regulation of gene expression	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of nucleocytoplasmic transport	ISO Inferred from Sequence Orthology more info
involved_in regulation of protein export from nucleus	ISO Inferred from Sequence Orthology more info
involved_in regulation of protein stability	ISO Inferred from Sequence Orthology more info
involved_in regulation of protein targeting to mitochondrion	ISO Inferred from Sequence Orthology more info
involved_in replicative senescence	ISO Inferred from Sequence Orthology more info
involved_in response to caloric restriction	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to fatty acid	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to organic cyclic compound	IDA Inferred from Direct Assay more info	PubMed
involved_in response to organic substance	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to organonitrogen compound	IDA Inferred from Direct Assay more info	PubMed
involved_in response to salt stress	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to xenobiotic stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in response to xenobiotic stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in somatic stem cell division	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within somatic stem cell population maintenance	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in granular component	ISO Inferred from Sequence Orthology more info
located_in mitochondrion	ISO Inferred from Sequence Orthology more info
located_in nuclear body	ISO Inferred from Sequence Orthology more info
located_in nucleolus	ISO Inferred from Sequence Orthology more info
located_in nucleolus	ISS Inferred from Sequence or Structural Similarity more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISS Inferred from Sequence or Structural Similarity more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info
part_of senescence-associated heterochromatin focus	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: cyclin-dependent kinase inhibitor 2A

Names: CDK4I; Cyclin dependent kinase inhibitor 2A (p16, inhibits CDK4); alternative reading frame; cell cycle inhibitor; cell cycle regulator; cyclin-dependent kinase 4 inhibitor A; cyclin-dependent kinase inhibitor 2a p16Ink4a; cyclin-dependent kinase inhibitor 2a p19Arf; p16-INK4; p16-INK4a

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_031550.2 → NP_113738.1 cyclin-dependent kinase inhibitor 2A

See identical proteins and their annotated locations for NP_113738.1

Status: PROVISIONAL

Source sequence(s)

JAXUCZ010000005

UniProtKB/Swiss-Prot

Q9R0Z3

UniProtKB/TrEMBL

A0A0G2K4G8, A6JRF2

Related

ENSRNOP00000087870.1, ENSRNOT00000103638.1

Conserved Domains (2) summary

COG0666
Location:15 → 123

ANKYR; Ankyrin repeat [Signal transduction mechanisms]

sd00045
Location:36 → 66

ANK; ANK repeat [structural motif]