Cdkn2a cyclin-dependent kinase inhibitor 2A [Mus musculus] - Gene

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Summary

Official Symbol: Cdkn2aprovided by MGI
Official Full Name: cyclin-dependent kinase inhibitor 2Aprovided by MGI
Primary source: MGI:104738
Locus tag: RP23-166I8.5
See related: Ensembl:ENSMUSG00000044303; Vega:OTTMUSG00000007706
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Arf; p16; MTS1; Pctr1; p19ARF; p16INK4a; p19<ARF>; ARF-INK4a; INK4a-ARF; Ink4a/Arf; p16(INK4a)

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Genomic context

Location :: 4 C3-C6; 4 42.7 cM

Sequence :: Chromosome: 4; NC_000070.6 (89274473..89294619, complement)

See Cdkn2a in Epigenomics, MapViewer

Chromosome 4 - NC_000070.6 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?

Used a combination of somatic conditional overexpression and ligand-mediated chronic activation of EGFR in cooperation with Ink4a/Arf loss in the central nervous system of adult mice.
Title: Chronic activation of wild-type epidermal growth factor receptor and loss of Cdkn2a cause mouse glioblastoma formation.
p16 knockout mice developed the full spectrum of pancreatic intraepithelial neoplasia (mPanIN) lesions, pancreatic ductal adenocarcinoma (PDA), and metastases
Title: Disruption of p16 and activation of Kras in pancreas increase ductal adenocarcinoma formation and metastasis in vivo.
Hyperactivation of mTORC1 through Tsc1 loss resulted in a significant increase in ARF expression, activation of the p53 pathway, and a dramatic cell cycle arrest, which were completely reversed upon Arf deletion.
Title: Hypergrowth mTORC1 signals translationally activate the ARF tumor suppressor checkpoint.
Knockout of the INK4a/ARF locus results in increased tubular cell proliferation, decreased apoptosis, and decreased capillary rarefaction.
Title: INK4a deletion results in improved kidney regeneration and decreased capillary rarefaction after ischemia-reperfusion injury.
Alternative reading frame (ARF) plays an important role in regulating inflammatory processes and as a regulator of inflammatory cell signaling.
Title: The tumor suppressor ARF regulates innate immune responses in mice.
In tissues--such as adipose tissue, skeletal muscle and eye--in which p16(Ink4a) contributes to the acquisition of age-related pathologies, life-long removal of p16(Ink4a)-expressing cells delayed onset of these phenotypes.
Title: Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders.
Cdkn2a is an atherosclerosis modifier locus that regulates monocyte/macrophage proliferation.
Title: Cdkn2a is an atherosclerosis modifier locus that regulates monocyte/macrophage proliferation.
ARF limited the nucleolar localization of the RNA helicase DDX5. ARF inhibited the interaction between DDX5 and nucleophosmin preventing association of DDX5 with the rDNA promoter and nuclear pre-ribosomes.
Title: RNA helicase DDX5 is a p53-independent target of ARF that participates in ribosome biogenesis.
Data show that inactivation of Arf triggers germ cell-autonomous, p53-dependent apoptosis of primary spermatocytes in late meiotic prophase, resulting in reduced sperm production.
Title: Expression of arf tumor suppressor in spermatogonia facilitates meiotic progression in male germ cells.
p16( INK4a) is also a modulator of transcription and apoptosis through controlling the expression of two major transcription regulators, AUF1 and E2F1
Title: p16( INK4a) positively regulates cyclin D1 and E2F1 through negative control of AUF1.

Submit: New GeneRIF Correction See all (199)

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (Floxed/Frt) (4) 1 citation
Targeted (knock-out) (7) 1 citation
Targeted (Reporter) (2) 1 citation
QTL (2) 1 citation
Targeted (knock-in) (2) 1 citation

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Products	Interactant	Other Gene	Source	Pubs	Description
AF120108.1	NP_034979.2	Myc	BIND	PubMed	Myc interacts with the Cdkn2a promoter.
NC_000070.1	NP_033115.1	Polr2a	BIND	PubMed	Pol II interacts with the p16 chromatin. This interaction was modeled on a demonstrated interaction between mouse Pol II and human p16 chromatin.
NC_000070.1	NP_034861.1	Zbtb7a	BIND	PubMed	Pokemon interacts with p19Arf promoter.
NP_034007.1	NP_033961.1	Ccng1	BIND	PubMed	ARF interacts with Cyclin G1
NP_034007.1	NP_031661.2	Ccng2	BIND	PubMed	Cyclin G2 interacts with p19ARF
NP_034007.1	NP_034000.1	Cdk4	BIND	PubMed	Cdk4 interacts with p16Ink4A.
NP_034007.1	NC_000069.1	Eif4e	BIND	PubMed	ARF interacts with the eIF4E promoter.
NP_034007.1	NP_034916.1	Mdm2	BIND	PubMed	Mdm2 interacts with p14ARF. This interaction was modeled on a demonstrated interaction between human Mdm2 and mouse p19ARF.
NP_034007.1	NP_034979.2	Myc	BIND	PubMed	ARF interacts with c-Myc.
NP_034007.1	NC_000067.1	Ncl	BIND	PubMed	ARF interacts with the nucleolin promoter.
NP_034007.1	NP_035770.1	Trp53	BIND	PubMed	p53 binds to p19ARF
NP_034007.1	J01871.1		BIND	PubMed	Cdkn2a (p19ARF) interacts with 5.8S rRNA
BioGRID:198654	BioGRID:110358	MDM2	BioGRID	PubMed	Reconstituted Complex
BioGRID:198654	BioGRID:110929	NPM1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:198654	BioGRID:203414	Sp1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:198654	BioGRID:203980	Tbrg1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:198654	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-Western

Function	Evidence Code	Pubs
DNA binding	IEA Inferred from Electronic Annotation more info
MDM2 binding	ISO Inferred from Sequence Orthology more info
NF-kappaB binding	ISO Inferred from Sequence Orthology more info
cyclin-dependent protein kinase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
cyclin-dependent protein kinase inhibitor activity	ISO Inferred from Sequence Orthology more info
p53 binding	ISO Inferred from Sequence Orthology more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein kinase binding	ISO Inferred from Sequence Orthology more info
sequence-specific DNA binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
transcription factor binding	ISO Inferred from Sequence Orthology more info
ubiquitin-protein ligase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
DNA fragmentation involved in apoptotic nuclear change	ISO Inferred from Sequence Orthology more info
G1/S transition of mitotic cell cycle	ISO Inferred from Sequence Orthology more info
activation of cysteine-type endopeptidase activity involved in apoptotic process	ISO Inferred from Sequence Orthology more info
aging	IMP Inferred from Mutant Phenotype more info	PubMed
apoptotic mitochondrial changes	ISO Inferred from Sequence Orthology more info
apoptotic process	IEA Inferred from Electronic Annotation more info
cell aging	IDA Inferred from Direct Assay more info	PubMed
cell cycle	IEA Inferred from Electronic Annotation more info
cell cycle arrest	IDA Inferred from Direct Assay more info	PubMed
cell cycle arrest	ISO Inferred from Sequence Orthology more info
cell cycle checkpoint	ISO Inferred from Sequence Orthology more info
cellular senescence	ISO Inferred from Sequence Orthology more info
epidermis development	IMP Inferred from Mutant Phenotype more info	PubMed
induction of apoptosis	ISO Inferred from Sequence Orthology more info
negative regulation of B cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of NF-kappaB transcription factor activity	ISO Inferred from Sequence Orthology more info
negative regulation of cell cycle	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cell growth	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of cell growth	ISO Inferred from Sequence Orthology more info
negative regulation of cell proliferation	ISO Inferred from Sequence Orthology more info
negative regulation of cell-matrix adhesion	ISO Inferred from Sequence Orthology more info
negative regulation of cyclin-dependent protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cyclin-dependent protein kinase activity	ISO Inferred from Sequence Orthology more info
negative regulation of immature T cell proliferation in thymus	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of mammary gland epithelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of phosphorylation	ISO Inferred from Sequence Orthology more info
negative regulation of protein kinase activity	ISO Inferred from Sequence Orthology more info
negative regulation of transcription, DNA-dependent	ISO Inferred from Sequence Orthology more info
negative regulation of ubiquitin-protein ligase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of DNA damage response, signal transduction by p53 class mediator	IC Inferred by Curator more info	PubMed
positive regulation of DNA damage response, signal transduction by p53 class mediator	ISO Inferred from Sequence Orthology more info
positive regulation of apoptosis involved in mammary gland involution	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of cell cycle arrest	ISO Inferred from Sequence Orthology more info
positive regulation of cellular senescence	ISO Inferred from Sequence Orthology more info
positive regulation of macrophage apoptosis	IGI Inferred from Genetic Interaction more info
positive regulation of protein sumoylation	ISO Inferred from Sequence Orthology more info
positive regulation of sequence-specific DNA binding transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of smooth muscle cell apoptosis	IGI Inferred from Genetic Interaction more info
positive regulation of transcription from RNA polymerase II promoter	ISO Inferred from Sequence Orthology more info
positive regulation of transcription, DNA-dependent	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription, DNA-dependent	ISO Inferred from Sequence Orthology more info
protein K63-linked ubiquitination	ISO Inferred from Sequence Orthology more info
protein destabilization	ISO Inferred from Sequence Orthology more info
protein polyubiquitination	ISO Inferred from Sequence Orthology more info
protein stabilization	ISO Inferred from Sequence Orthology more info
rRNA processing	IEA Inferred from Electronic Annotation more info
rRNA transcription	IGI Inferred from Genetic Interaction more info	PubMed
regulation of G2/M transition of mitotic cell cycle	ISO Inferred from Sequence Orthology more info
regulation of cyclin-dependent protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of nucleocytoplasmic transport	IGI Inferred from Genetic Interaction more info	PubMed
regulation of protein export from nucleus	ISO Inferred from Sequence Orthology more info
regulation of protein stability	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of transcription, DNA-dependent	IDA Inferred from Direct Assay more info	PubMed
replicative senescence	ISO Inferred from Sequence Orthology more info
response to drug	ISO Inferred from Sequence Orthology more info
response to organic cyclic compound	ISO Inferred from Sequence Orthology more info
response to organic nitrogen	ISO Inferred from Sequence Orthology more info
senescence-associated heterochromatin focus assembly	ISO Inferred from Sequence Orthology more info
somatic stem cell division	IMP Inferred from Mutant Phenotype more info	PubMed
somatic stem cell maintenance	IGI Inferred from Genetic Interaction more info	PubMed
transcription, DNA-dependent	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	ISO Inferred from Sequence Orthology more info
granular component	IDA Inferred from Direct Assay more info	PubMed
nucleolus	IDA Inferred from Direct Assay more info	PubMed
nucleolus	ISO Inferred from Sequence Orthology more info
nucleoplasm	IDA Inferred from Direct Assay more info	PubMed
nucleoplasm	ISO Inferred from Sequence Orthology more info
nucleus	ISO Inferred from Sequence Orthology more info
protein complex	ISO Inferred from Sequence Orthology more info
senescence-associated heterochromatin focus	ISO Inferred from Sequence Orthology more info

General protein information

Preferred Names: cyclin-dependent kinase inhibitor 2A, isoform 3

Names: cyclin-dependent kinase inhibitor 2A, isoform 3; CDK4I; p16-INK4; p16-INK4a; mitochondrial smARF; cyclin-dependent kinase 4 inhibitor A; cyclin-dependent kinase inhibitor protein; cyclin-dependent kinase inhibitor 2A, isoforms 1/2; cyclin-dependent kinase inhibitor 2A (p16, inhibits CDK4)

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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_001040654.1 → NP_001035744.1 cyclin-dependent kinase inhibitor 2A, isoform 3 isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (2) contains an alternate open reading frame (ARF), when compared to variant 1. The ARF results from an alternative splicing between a downstream first exon, which contains the translation start codon, and the common second exon. Thus, the protein encoded by this variant lacks sequence similarity to the protein product of variant 1. This protein is also called p16INK4a.

Source sequence(s)

AL831719, L76150

Consensus CDS

CCDS38812.1

UniProtKB/Swiss-Prot

P51480

Related

ENSMUSP00000061847, OTTMUSP00000008143, ENSMUST00000060501, OTTMUST00000017644

Conserved Domains (2) summary

cd00204
Location:14 – 122
Blast Score: 202

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

pfam12796
Location:45 – 130
Blast Score: 151

Ank_2; Ankyrin repeats (3 copies)
NM_009877.2 → NP_034007.1 cyclin-dependent kinase inhibitor 2A, isoform 3 isoform 1

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1). Isoform 1 is also called p19ARF.

Source sequence(s)

AL831719, L76092

Consensus CDS

CCDS18350.1

UniProtKB/Swiss-Prot

Q64364

Related

ENSMUSP00000030237, ENSMUST00000030237

Conserved Domains (1) summary

pfam07392
Location:4 – 54
Blast Score: 137

P19Arf_N; Cyclin-dependent kinase inhibitor 2a p19Arf N-terminus

RefSeqs of Annotated Genomes: Build 38.1

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

Reference GRCm38 C57BL/6J

Genomic

NC_000070.6 Reference GRCm38 C57BL/6J

Range

89274473..89294619, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate Mm_Celera

Genomic

AC_000026.1 Alternate Mm_Celera

Range

87760902..87780610, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein	Strain
Heading	Accession and Version	Protein	Strain
genomic	AF004588.1	AAB61416.1	DBA/2 and C57BL/6
genomic	AF115545.1	AAD11438.1
genomic	AF120108.1	AAD33245.1	129/SvJE
genomic	AF332190.1	AAK83159.1	129/SvJ
genomic	AJ238890.1	CAB65598.1	129/SvJ
genomic	AL831719.6	CAM16002.1
		CAM16003.1
genomic	CH466527.2	EDL30951.1	mixed
genomic	CS066002.1	CAI84565.1
genomic	U47018.1	AAC52987.1	ICR x Swiss
genomic	U49279.1	AAC00051.1
genomic	U49280.1	AAC00052.1	A/J, A/Wy, AKR/J, SJL/J, SWR/J, ST/J, LP/J, LS/IBG, SM/J, HS/IBG, B10.A, C57BL/10SN, C57BL/6By, C57BL/10SCN, C57BR/cdJ, DBA/2J,
genomic	U49281.1	AAC00053.1
genomic	U49282.1	AAC00054.1	A/J, A/Wy, AKR/J, SJL/J, SWR/J, ST/J, LP/J, LS/IBG, SM/J, HS/IBG, B10.A, C57BL/10SN, C57BL/6By, C57BL/10SCN, C57BR/cdJ, DBA/2J,
genomic	U66086.1	AAB39600.1	C57BL/6J x DBA
genomic	U66087.1	AAB39600.1	C57BL/6J x DBA
genomic	U79625.1	AAD00223.1	C57BL/6J and RF/J
genomic	U79626.1	AAD00224.1	BALB/cJ and Mus mus poschiavinus
genomic	U79627.1	AAD00225.1	MOLF/Ei and Mus mus musculus
genomic	U79628.1	AAD00226.1	CAST/Ei
genomic	U79630.1	AAD00227.1	C57BL/6J, RF/J, and CAST/Ei
genomic	U79631.1	AAD00228.1	BALB/cJ
genomic	U79632.1	AAD00229.1	MOLF/Ei
genomic	U79633.1	AAD00230.1	Mus mus musculus
genomic	U79635.1	AAD00231.1
mRNA	AB221638.1	None
mRNA	AF044335.1	AAC08962.1	BALB/cAnPt
mRNA	AF044336.1	AAC08963.1	DBA/2N
mRNA	AK155307.1	BAE33180.1	NOD
mRNA	BC058190.1	AAH58190.3	NMRI
mRNA	EU071702.1	ABS85193.1
mRNA	L76092.1	AAC42080.1
mRNA	L76150.1	AAA85453.1
mRNA	S80650.1	AAB35770.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P51480.2	GenPept	UniProtKB/Swiss-Prot:P51480
Q64364.1	GenPept	UniProtKB/Swiss-Prot:Q64364
Q78E71	GenPept	UniProtKB/TrEMBL:Q78E71
Q9QWH4	GenPept	UniProtKB/TrEMBL:Q9QWH4
Q9QWH5	GenPept	UniProtKB/TrEMBL:Q9QWH5
Q9QWT5	GenPept	UniProtKB/TrEMBL:Q9QWT5