Cdkn2a cyclin dependent kinase inhibitor 2A [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Cdkn2aprovided by MGI
Official Full Name: cyclin dependent kinase inhibitor 2Aprovided by MGI
Primary source: MGI:MGI:104738
See related: Ensembl:ENSMUSG00000044303 AllianceGenome:MGI:104738
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Arf; p16; MTS1; Pctr1; p19ARF; p16INK4a; p19<ARF>; ARF-INK4a; INK4a-ARF; Ink4a/Arf; p16(INK4a)
Summary: Enables MDM2/MDM4 family protein binding activity; enzyme inhibitor activity; and protein N-terminus binding activity. Involved in several processes, including negative regulation of lymphocyte proliferation; positive regulation of apoptotic process; and regulation of transcription, DNA-templated. Acts upstream of or within several processes, including negative regulation of cellular protein metabolic process; negative regulation of mammary gland epithelial cell proliferation; and positive regulation of apoptotic process involved in mammary gland involution. Located in cytoplasm and granular component. Part of protein-containing complex. Is expressed in several structures, including bone marrow; central nervous system; dorsal root ganglion; eye; and testis. Human ortholog(s) of this gene implicated in several diseases, including breast cancer (multiple); carcinoma (multiple); hematologic cancer (multiple); melanoma (multiple); and nervous system cancer (multiple). Orthologous to human CDKN2A (cyclin dependent kinase inhibitor 2A). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in placenta adult (RPKM 11.1), testis adult (RPKM 4.1) and 7 other tissues See more
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Genomic context

Location:: 4 C4; 4 42.15 cM

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	4	NC_000070.7 (89192710..89212856, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	4	NC_000070.6 (89274473..89294619, complement)

Chromosome 4 - NC_000070.7 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: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Rejuvenating aged microglia by p16[ink4a]-siRNA-loaded nanoparticles increases amyloid-beta clearance in animal models of Alzheimer's disease.
Title: Rejuvenating aged microglia by p16(ink4a)-siRNA-loaded nanoparticles increases amyloid-β clearance in animal models of Alzheimer's disease.
NRF2 Activation in Trp53;p16-deficient Mice Drives Oral Squamous Cell Carcinoma.
Title: NRF2 Activation in Trp53;p16-deficient Mice Drives Oral Squamous Cell Carcinoma.
Dietary Folate and Cofactors Accelerate Age-dependent p16 Epimutation to Promote Intestinal Tumorigenesis.
Title: Dietary Folate and Cofactors Accelerate Age-dependent p16 Epimutation to Promote Intestinal Tumorigenesis.
LncRNA NEAT1 suppresses cellular senescence in hepatocellular carcinoma via KIF11-dependent repression of CDKN2A.
Title: LncRNA NEAT1 suppresses cellular senescence in hepatocellular carcinoma via KIF11-dependent repression of CDKN2A.
Loss of CDKN2A Cooperates with WWTR1(TAZ)-CAMTA1 Gene Fusion to Promote Tumor Progression in Epithelioid Hemangioendothelioma.
Title: Loss of CDKN2A Cooperates with WWTR1(TAZ)-CAMTA1 Gene Fusion to Promote Tumor Progression in Epithelioid Hemangioendothelioma.
Developmental Expression of the Cell Cycle Regulator p16[INK4a] in Retinal Glial Cells: A Novel Marker for Immature Ocular Astrocytes?
Title: Developmental Expression of the Cell Cycle Regulator p16(INK4a) in Retinal Glial Cells: A Novel Marker for Immature Ocular Astrocytes?
p16 INK4A drives nonalcoholic fatty liver disease phenotypes in high fat diet fed mice through biliary E2F1/FOXO1/IGF-1 signaling.
Title: p16 INK4A drives nonalcoholic fatty liver disease phenotypes in high fat diet fed mice through biliary E2F1/FOXO1/IGF-1 signaling.
TYMS promotes genomic instability and tumor progression in Ink4a/Arf null background.
Title: TYMS promotes genomic instability and tumor progression in Ink4a/Arf null background.
Genetically prolonged beige fat in male mice confers long-lasting metabolic health.
Title: Genetically prolonged beige fat in male mice confers long-lasting metabolic health.
Cdkn2a inactivation promotes malignant transformation of mouse immature thymocytes before the beta-selection checkpoint.
Title: Cdkn2a inactivation promotes malignant transformation of mouse immature thymocytes before the β-selection checkpoint.

Submit: New GeneRIF Correction See all GeneRIFs (375)

Phenotypes

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Associated conditions

Description	Tests
plasmacytoma resistance 1 GeneReviews: Not available

Variation

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Alleles

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

Targeted (24) 1 citation
QTL (2) 1 citation
Endonuclease-mediated (20) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Cdkn2a (e-PCR), detects polymorphism
- UniSTS:141312

Cdkn2a (e-PCR), detects polymorphism
- UniSTS:141313

Cdkn2a (e-PCR), detects polymorphism
- UniSTS:141314

PMC19364P1 (e-PCR)
- UniSTS:141315

PMC280656P2 (e-PCR)
- UniSTS:272395

Cdkn2a (e-PCR), detects polymorphism
- UniSTS:516653

Cdkn2a (e-PCR), detects polymorphism
- UniSTS:225857

Cdkn2a (e-PCR), detects polymorphism
- UniSTS:225858

PMC122612P2 (e-PCR)
- UniSTS:270403

PMC152255P1 (e-PCR)
- UniSTS:271207

PMC152255P2 (e-PCR)
- UniSTS:271208

PMC316663P1 (e-PCR)
- UniSTS:273029

PMC316663P2 (e-PCR)
- UniSTS:273030

PMC112377P1 (e-PCR)
- UniSTS:270230

PMC112377P2 (e-PCR)
- UniSTS:270231

PMC112377P3 (e-PCR)
- UniSTS:270232

PMC55531P3 (e-PCR)
- UniSTS:273347

PMC55531P4 (e-PCR)
- UniSTS:273348

Cdkn2a (e-PCR), detects polymorphism
- UniSTS:547813

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables DNA binding	IEA Inferred from Electronic Annotation more info
enables DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables MDM2/MDM4 family protein binding	IPI Inferred from Physical Interaction more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed
enables cyclin-dependent protein serine/threonine kinase inhibitor activity	ISO Inferred from Sequence Orthology more info	PubMed
enables disordered domain specific binding	ISO Inferred from Sequence Orthology more info
enables p53 binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in activation of cysteine-type endopeptidase activity involved in apoptotic process	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
acts_upstream_of_or_within apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of apoptotic process involved in mammary gland involution	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in autophagy of mitochondrion	ISO Inferred from Sequence Orthology more info
acts_upstream_of cell cycle	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within cellular response to hydrogen peroxide	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within cellular senescence	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within cellular senescence	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within cellular senescence	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular senescence	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within epidermis development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within epidermis development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within glucose homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within keratinocyte differentiation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within keratinocyte proliferation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of mammary gland epithelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mitochondrial depolarization	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of B cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of NF-kappaB transcription factor activity	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of cell cycle	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell growth	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell growth	ISO Inferred from Sequence Orthology 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
acts_upstream_of_or_within negative regulation of cyclin-dependent protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of cyclin-dependent protein serine/threonine kinase activity	ISO Inferred from Sequence Orthology more info	PubMed
involved_in negative regulation of cyclin-dependent protein serine/threonine kinase activity	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of hepatocyte proliferation	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of immature T cell proliferation in thymus	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of mammary gland epithelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of phosphorylation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of protein binding	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of protein kinase activity	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of protein localization to nucleolus	IDA Inferred from Direct Assay more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of ubiquitin protein ligase activity	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of ubiquitin-dependent protein catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of ubiquitin-dependent protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of ubiquitin-protein transferase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in nuclear body organization	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within oncogene-induced cell senescence	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within oncogene-induced cell senescence	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of DNA damage response, signal transduction by p53 class mediator	IC Inferred by Curator more info	PubMed
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-binding transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of apoptotic process involved in mammary gland involution	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of gene expression	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of macrophage apoptotic process	IGI Inferred from Genetic Interaction more info	PubMed
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	IGI Inferred from Genetic Interaction more info	PubMed
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 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 stabilization	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within rRNA processing	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within rRNA transcription	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within regulation of DNA-binding transcription factor activity	IGI Inferred from Genetic Interaction more info	PubMed
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
acts_upstream_of_or_within regulation of cell cycle	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cell cycle	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of cyclin-dependent protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of nucleocytoplasmic transport	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of protein export from nucleus	ISO Inferred from Sequence Orthology more info
involved_in regulation of protein stability	IMP Inferred from Mutant Phenotype more info	PubMed
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 organic cyclic compound	ISO Inferred from Sequence Orthology more info
involved_in response to organonitrogen compound	ISO Inferred from Sequence Orthology more info
involved_in response to xenobiotic stimulus	ISO Inferred from Sequence Orthology more info
involved_in somatic stem cell division	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within somatic stem cell population maintenance	IGI Inferred from Genetic Interaction more info	PubMed

Component	Evidence Code	Pubs
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in granular component	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	ISO Inferred from Sequence Orthology more info
colocalizes_with nuclear body	ISO Inferred from Sequence Orthology more info
located_in nucleolus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleolus	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
located_in nucleus	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	IMP Inferred from Mutant Phenotype more info	PubMed
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; alternative reading frame; cyclin-dependent kinase 4 inhibitor A; cyclin-dependent kinase inhibitor 2A (p16, inhibits CDK4); cyclin-dependent kinase inhibitor protein; mitochondrial smARF; 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_001040654.1 → NP_001035744.1 cyclin-dependent kinase inhibitor 2A isoform p16INK4a

See identical proteins and their annotated locations for NP_001035744.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) contains an alternate open reading frame, when compared to variant 1. Transcripts 1 and 2, encoding p19ARF and p16INK4a, have distinct first exons which contain the translation start codon, and share a common second exon, which is translated in different reading frames. Thus, the p16INK4a protein encoded by this variant (2) lacks sequence similarity to the protein product of variant 1 (p19ARF).

Source sequence(s)

AL831719, L76150

Consensus CDS

CCDS38812.1

UniProtKB/Swiss-Prot

A2ANM1, A2ANM2, O89088, P51480, P97510, P97937, Q6PEA2, Q78E39, Q78E57, Q792X7, Q9QWH6, Q9QWH7, Q9QWH8

Related

ENSMUSP00000061847.4, ENSMUST00000060501.5

Conserved Domains (3) summary

cd00204
Location:15 → 122

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:14 → 100

Ank_2; Ankyrin repeats (3 copies)

sd00045
Location:36 → 66

ANK; ANK repeat [structural motif]
NM_009877.2 → NP_034007.1 cyclin-dependent kinase inhibitor 2A isoform p19ARF

See identical proteins and their annotated locations for NP_034007.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1, also known as p19ARF) and contains an alternate open reading frame (ARF), when compared to variant 2. Transcripts 1 and 2, encoding p19ARF and p16INK4a, have distinct first exons which contain the translation start codon, and share a common second exon, which is translated in different reading frames. Thus, the p19ARF protein encoded by this variant (1) lacks sequence similarity to the protein product of variant 2 (p16INK4a).

Source sequence(s)

AL831719, L76092

Consensus CDS

CCDS18350.1

UniProtKB/Swiss-Prot

Q4U255, Q64364, Q9QXC7, Q9R051

Related

ENSMUSP00000102748.3, ENSMUST00000107131.2

Conserved Domains (1) summary

pfam07392
Location:4 → 45

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