My NCBISign In

Display Settings:

Format

Send to:

Choose Destination

    CDKN2A cyclin-dependent kinase inhibitor 2A [ Homo sapiens ]

    Gene ID: 1029, updated on 20-May-2012
    Help top of page

    Summary

    Official Symbol
    CDKN2Aprovided by HGNC
    Official Full Name
    cyclin-dependent kinase inhibitor 2Aprovided by HGNC
    Primary source
    HGNC:1787
    See related
    Ensembl:ENSG00000147889; HPRD:02542; MIM:600160; Vega:OTTHUMG00000019686
    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
    ARF; MLM; P14; P16; P19; CMM2; INK4; MTS1; TP16; CDK4I; CDKN2; INK4A; MTS-1; P14ARF; P19ARF; P16INK4; P16INK4A; P16-INK4A
    Summary
    This gene generates several transcript variants which differ in their first exons. At least three alternatively spliced variants encoding distinct proteins have been reported, two of which encode structurally related isoforms known to function as inhibitors of CDK4 kinase. The remaining transcript includes an alternate first exon located 20 Kb upstream of the remainder of the gene; this transcript contains an alternate open reading frame (ARF) that specifies a protein which is structurally unrelated to the products of the other variants. This ARF product functions as a stabilizer of the tumor suppressor protein p53 as it can interact with, and sequester, MDM1, a protein responsible for the degradation of p53. In spite of the structural and functional differences, the CDK inhibitor isoforms and the ARF product encoded by this gene, through the regulatory roles of CDK4 and p53 in cell cycle G1 progression, share a common functionality in cell cycle G1 control. This gene is frequently mutated or deleted in a wide variety of tumors, and is known to be an important tumor suppressor gene. [provided by RefSeq, Jul 2008]
    Help top of page

    Genomic context

    Location :
    9p21
    Sequence :
    Chromosome: 9; NC_000009.11 (21967751..21994490, complement)
    See CDKN2A in Epigenomics, MapViewer

    Chromosome 9 - NC_000009.11Genomic Context describing neighboring genes Neighboring gene tubulin, beta 8 class VIII pseudogene Neighboring gene methylthioadenosine phosphorylase Neighboring gene HERV-FRD provirus ancestral Env polyprotein pseudogene Neighboring gene chromosome 9 open reading frame 53 Neighboring gene CDKN2B antisense RNA 1 (non-protein coding) Neighboring gene cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) Neighboring gene ubiquitin A-52 residue ribosomal protein fusion product 1 pseudogene 6

    Help top of page

    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
    Helptop of page

    Bibliography

    Related articles in PubMed

    1. Diagnostic utility of p16, CDK4, and MDM2 as an immunohistochemical panel in distinguishing well-differentiated and dedifferentiated liposarcomas from other adipocytic tumors. Thway K, et al. Am J Surg Pathol, 2012 Mar. PMID 22301498.
    2. Implications of continued upregulation of p16(INK4a) through the evolution from high-grade squamous intraepithelial lesion to invasive squamous carcinoma of the cervix. Cheah PL, et al. Malays J Pathol, 2011 Dec. PMID 22299207.
    3. RUVBL2 is a novel repressor of ARF transcription. Xie C, et al. FEBS Lett, 2012 Feb 17. PMID 22285491.
    4. Mechanisms of MEOX1 and MEOX2 regulation of the cyclin dependent kinase inhibitors p21 and p16 in vascular endothelial cells. Douville JM, et al. PLoS One, 2011. PMID 22206000.
    5. Immunohistochemical assessment of p16, COX-2 and EGFR in HPV-positive cervical squamous intraepithelial lesions. Balan R, et al. Rom J Morphol Embryol, 2011. PMID 22203921.

    See all (1327) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. Our finding suggests that polymorphisms in DNA repair genes, POLN and PRKDC, were associated with increased melanoma risk in melanoma families with and without CDKN2A mutations.
      Title: Genetic variants in DNA repair genes and the risk of cutaneous malignant melanoma in melanoma-prone families with/without CDKN2A mutations.
    2. Loss of p16 expression is associated with the stem cell characteristics of surface markers and therapeutic resistance in estrogen receptor-negative breast cancer.
      Title: Loss of p16 expression is associated with the stem cell characteristics of surface markers and therapeutic resistance in estrogen receptor-negative breast cancer.
    3. Data indicate that MYCN is a central modulator of the p53/MDM2/p14ARF negative feedback loop.
      Title: MYCN sensitizes neuroblastoma to the MDM2-p53 antagonists Nutlin-3 and MI-63.
    4. rs10811661 of CDKN2A/B confers risk for type 2 diabetes.
      Title: Association between type 2 diabetes and CDKN2A/B: a meta-analysis study.
    5. findings indicate that the inactivation of the CDKN2A/B locus is a frequent event in Ph+ acute lymphoblastic leukemia; deletions are frequently acquired at leukemia progression and are a poor prognostic marker
      Title: CDKN2A/B alterations impair prognosis in adult BCR-ABL1-positive acute lymphoblastic leukemia patients.
    6. Cigarette smoking is positively correlated to p16(INK4alpha) gene hypermethylation in non-small cell lung carcinoma patients.
      Title: Cigarette smoking and p16INK4α gene promoter hypermethylation in non-small cell lung carcinoma patients: a meta-analysis.
    7. MEOX1 and MEOX2 activate p16(INK4a) in a DNA binding dependent manner, whereas they induce p21(CIP1/WAF1) in a DNA binding independent manner.
      Title: Mechanisms of MEOX1 and MEOX2 regulation of the cyclin dependent kinase inhibitors p21 and p16 in vascular endothelial cells.
    8. The assessment of p16, EGFR, and COX-2 allows to an integrative approach for the progression of squamous intraepithelial lesion, associated or not with the human papilloma virus infection.
      Title: Immunohistochemical assessment of p16, COX-2 and EGFR in HPV-positive cervical squamous intraepithelial lesions.
    9. We found a pattern of global hypomethylation and promoter region hypomethylation of TP53 and p16 in cases of gastric cancer versus controls for a population of Omani Arabs.
      Title: Global DNA methylation and tumor suppressor gene promoter methylation and gastric cancer risk in an Omani Arab population.
    10. Six SNP(rs7754840 in CDKAL1, rs391300 in SRR, rs2383208 in CDKN2A/2B, rs4402960 in IGF2BP2, rs10830963 in MTNR1B, rs4607517 in GCK)risk alleles of type 2 diabetes were associated with GDM in pregnant Chinese women.
      Title: Association of six single nucleotide polymorphisms with gestational diabetes mellitus in a Chinese population.
    Submit: New GeneRIF Correction See all (1063)
    Help top of page

    Phenotypes

    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    A common variant on chromosome 9p21 affects the risk of myocardial infarction.

    A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants.

    Chromosome 7p11.2 (EGFR) variation influences glioma risk.

    Confirmation of multiple risk Loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population.

    Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.

    Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants.

    Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm.

    Genome-wide association study identifies five new breast cancer susceptibility loci.

    Genome-wide association study identifies five susceptibility loci for glioma.

    Genome-wide association study identifies three loci associated with melanoma risk.

    Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.

    Genome-wide association study of intracranial aneurysm identifies three new risk loci.

    Genome-wide association study of type 2 diabetes in a sample from Mexico City and a meta-analysis of a Mexican-American sample from Starr County, Texas.

    Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.

    Li Fraumeni syndrome

    Melanoma and neural system tumor syndrome

    Melanoma, cutaneous malignant, 2

    Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.

    Orolaryngeal cancer, multiple

    Pancreatic cancer/melanoma syndrome

    Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes.

    Susceptibility loci for intracranial aneurysm in European and Japanese populations.

    Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.

    Help top of page

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    AAP35666.1 NP_113584.3 HUWE1    BIND  PubMed ARF interacts with ARF-BP1. 
    AAR05391.1 NP_000066.1 CDK4    BIND  PubMed p16 interacts with cdk4. 
    AAR05391.1 NP_001250.1 CDK6    BIND  PubMed p16 interacts with cdk6. 
    NC_000009.9 NP_006302.2 NCOR1    BIND  PubMed NCOR1 (N-CoR) interacts with p-p14(ARF) (p14(ARF) promoter). 
    NC_000009.9 NP_006303.2 NCOR2    BIND  PubMed NCOR2 (SMRT) interacts with p-p14(ARF) (p14(ARF) promoter). 
    NP_000068.1 NP_000066.1 CDK4    BIND  PubMed p16 interacts with cdk4. This interaction was modeled on a demonstrated interaction between human p16 and cdk4 from an unspecified species. 
    NP_000068.1 NP_000066.1 CDK4    BIND  PubMed p16 interacts with CDK4. This interaction was modeled on a demonstrated interaction between human p16 and CDK4 from an unspecified species. 
    NP_000068.1 NP_000066.1 CDK4    BIND  PubMed CDKN2A interacts with CDK4 
    NP_000068.1 NP_001250.1 CDK6    BIND  PubMed p16 interacts with cdk6. This interaction was modeled on a demonstrated interaction between human p16 and cdk6 from an unspecified species. 
    NP_000068.1 NP_001250.1 CDK6    BIND  PubMed p16 interacts with CDK6. This interaction was modeled on a demonstrated interaction between human p16 and CDK6 from an unspecified species. 
    NP_000068.1 NP_001250.1 CDK6    BIND  PubMed CDKN2A interacts with CDK6 
    NP_000068.1 NP_620448.1 MAPK10    BIND  PubMed CDKN2A (p16INK4a) interacts with MAPK10 (JNK3) 
    NP_000068.1 NP_620637.1 MAPK8    BIND  PubMed CDKN2A (p16INK4a) interacts with MAPK8 (JNK1) 
    NP_478102.1 NP_001521.1 HIF1A    BIND  PubMed p14ARF interacts with HIF-1alpha. 
    NP_478102.1 NP_002383.1 MDM2    BIND  PubMed Mdm2 interacts with p14ARF. 
    NP_478102.1 NP_002383.1 MDM2    BIND  PubMed p14 interacts with MDM2. 
    NP_478102.1 NP_002383.1 MDM2    BIND  PubMed MDM2 interacts with p14ARF 
    NP_478102.1 MDM2    BIND  PubMed p14ARF interacts with an unspecified isoform of Mdm2. 
    NP_478102.1 NP_002458.1 MYC    BIND  PubMed p14ARF interacts with c-Myc. 
    NP_478102.1 NP_115984.1 PPP1R9B    BIND  PubMed SPINO interacts with p14ARF. 
    NP_478102.1 NP_002795.2 PSMC3    BIND  PubMed p14ARF interacts with TBP-1. 
    NP_478102.1 NP_000544.1 WRN    BIND  PubMed p14 interacts with WRN. 
    NP_478102.1 NP_003394.1 YY1    BIND  PubMed YY1 interacts with p14ARF. 
    Q8N726 Q09666 AHNAK    HPRD  PubMed  
    Q8N726 Q8N187 ALS2CR8    HPRD  PubMed  
    Q8N726 Q6UB98 ANKRD12    HPRD  PubMed  
    Q8N726 P51959 CCNG1    HPRD  PubMed  
    Q8N726 O75419 CDC45    HPRD  PubMed  
    Q8N726 Q99459 CDC5L    HPRD  PubMed  
    Q8N726 Q99741 CDC6    HPRD  PubMed  
    Q8N726 O00311 CDC7    HPRD  PubMed  
    Q8N726 P11802 CDK4    HPRD  PubMed  
    Q8N726 Q00534 CDK6    HPRD  PubMed  
    Q8N726 Q8N726 CDKN2A    HPRD  PubMed  
    Q8N726 Collaborates/cooperates with ARF protein CDKN2AIP    HPRD  PubMed  
    Q8N726 P42773 CDKN2C    HPRD  PubMed  
    Q8N726 Q01094 E2F1    HPRD  PubMed  
    Q8N726 E4F transcription factor 1 E4F1    HPRD  PubMed  
    Q8N726 P18146 EGR1    HPRD  PubMed  
    Q8N726 O75496 GMNN    HPRD  PubMed  
    Q8N726 P15170 GSPT1    HPRD  PubMed  
    Q8N726 Q16665 HIF1A    HPRD  PubMed  
    Q8N726 P08238 HSP90AB1    HPRD  PubMed  
    Q8N726 Q7Z6Z7 HUWE1    HPRD  PubMed  
    Q8N726 KIAA1984 KIAA1984    HPRD  PubMed  
    Q8N726 Q7L590 MCM10    HPRD  PubMed  
    Q8N726 P49736 MCM2    HPRD  PubMed  
    Q8N726 P33992 MCM5    HPRD  PubMed  
    Q8N726 Q00987 MDM2    HPRD  PubMed  
    Q8N726 P01106 MYC    HPRD  PubMed  
    Q8N726 P19338 NCL    HPRD  PubMed  
    Q8N726 O43929 ORC4    HPRD  PubMed  
    Q8N726 P40855 PEX19    HPRD  PubMed  
    Q8N726 Q96SB3 PPP1R9B    HPRD  PubMed  
    Q8N726 P17980 PSMC3    HPRD  PubMed  
    Q8N726 P62081 RPS7    HPRD  PubMed  
    Q8N726 Q9UHV2 SERTAD1    HPRD  PubMed  
    Q8N726 P02730 SLC4A1    HPRD  PubMed  
    Q8N726 Q3YBR2 TBRG1    HPRD  PubMed  
    Q8N726 P60174 TPI1    HPRD  PubMed  
    Q8N726 P49459 UBE2A    HPRD  PubMed  
    Q8N726 Q14191 WRN    HPRD  PubMed  
    Q8N726 Q96JP5 ZFP91    HPRD  PubMed  
    Q8N726 Q86WZ6 ZNF227    HPRD  PubMed  
    Q8N726 Q86VK4 ZNF410    HPRD  PubMed  
    BioGRID:107463 BioGRID:106563 ACLY    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:106575 ACTB    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:106586 ACTG1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:106596 ACTN4    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:112666 AURKA    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:107067 CCND1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:107463 BioGRID:107334 CCND2    BioGRID  PubMed Reconstituted Complex 
    BioGRID:107463 BioGRID:107340 CCNG1    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:107463 BioGRID:107454 CDK4    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Protein-peptide; Reconstituted Complex; Two-hybrid 
    BioGRID:107463 BioGRID:107456 CDK6    BioGRID  PubMed Affinity Capture-MS; Co-crystal Structure; Protein-peptide; Reconstituted Complex 
    BioGRID:107463 BioGRID:107985 DAXX    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    NP_005216.1 E2F1    BIND  PubMed p14ARF interacts with E2F-1. 
    BioGRID:107463 BioGRID:108209 E4F1    BioGRID  PubMed Affinity Capture-Western; Two-hybrid 
    BioGRID:107463 BioGRID:108258 EEF2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:108356 EPHA3    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:108576 FKBP2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107463 BioGRID:108868 GAPDH    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:109422 HNRNPA2B1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:109424 HNRNPC    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:109552 HSP90AA1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:109558 HSP90AB1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:109540 HSPA4    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:109544 HSPA8    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:109545 HSPA9    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:115385 HUWE1    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex 
    BioGRID:107463 BioGRID:109833 ING1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107463 BioGRID:119331 ING4    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107463 BioGRID:115779 KAT5    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:107463 BioGRID:114201 LAMTOR3    BioGRID  PubMed Co-crystal Structure 
    BioGRID:107463 BioGRID:110343 MCM6    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:107463 BioGRID:110358 MDM2    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Protein-peptide; Reconstituted Complex; Two-hybrid 
    BioGRID:107463 BioGRID:110359 MDM4    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107463 BioGRID:116577 MMRN1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:110642 MTR    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:115871 MYL12A    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:110929 NPM1    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex 
    BioGRID:107463 BioGRID:111142 PCNA    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:107463 BioGRID:115333 PDCD6    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:114523 PIAS2    BioGRID  PubMed Affinity Capture-Western; Two-hybrid 
    BioGRID:107463 BioGRID:124225 PLEKHA8    BioGRID  PubMed Reconstituted Complex 
    BioGRID:107463 BioGRID:124202 PPP1R9B    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex; Two-hybrid 
    BioGRID:107463 BioGRID:111675 PSMC3    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107463 BioGRID:115492 PSME3    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107463 BioGRID:119960 RIN2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:112055 RPL11    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107463 BioGRID:116067 RUVBL2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:941018 SAP25    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:118987 SERTAD1    BioGRID  PubMed Reconstituted Complex; Two-hybrid 
    BioGRID:107463 BioGRID:112481 SMARCA4    BioGRID  PubMed Affinity Capture-Western; Two-hybrid 
    BioGRID:107463 BioGRID:112510 SNRPA    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:112512 SNRPB    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:112550 SP1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107463 BioGRID:113003 TOP1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107463 BioGRID:113010 TP53    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107463 BioGRID:114731 TRIP12    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:107463 BioGRID:113603 TUBA1A    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:124259 TUBA1C    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:128444 TUBB    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:115656 TUBB4B    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:204381 Tubb5    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:107463 BioGRID:113167 UBE2A    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107463 BioGRID:115566 UBE4B    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:113192 UCHL1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107463 BioGRID:123764 USP26    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107463 BioGRID:113269 VHL    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:107463 BioGRID:113360 YY1    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    Help top of page

    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Apoptosis, organism-specific biosystem (from WikiPathways)
      Apoptosis, organism-specific biosystemApoptosis is a distinct form of cell death that is functionally and morphologically different from necrosis. Nuclear chromatin condensation, cytoplasmic shrinking, dilated endoplasmic reticulum, and ...
    • Bladder cancer, organism-specific biosystem (from KEGG)
      Bladder cancer, organism-specific biosystemThe urothelium covers the luminal surface of almost the entire urinary tract, extending from the renal pelvis, through the ureter and bladder, to the proximal urethra. The majority of urothelial carc...
    • Bladder cancer, conserved biosystem (from KEGG)
      Bladder cancer, conserved biosystemThe urothelium covers the luminal surface of almost the entire urinary tract, extending from the renal pelvis, through the ureter and bladder, to the proximal urethra. The majority of urothelial carc...
    • Cell Cycle, organism-specific biosystem (from REACTOME)
      Cell Cycle, organism-specific biosystem
      Cell Cycle
    • Cell Cycle, Mitotic, organism-specific biosystem (from REACTOME)
      Cell Cycle, Mitotic, organism-specific biosystemThe replication of the genome and the subsequent segregation of chromosomes into daughter cells are controlled by a series of events collectively known as the cell cycle. DNA replication is carried o...
    • Cell cycle, organism-specific biosystem (from WikiPathways)
      Cell cycle, organism-specific biosystem(From http://en.wikipedia.org/wiki/Cell_cycle) The cell cycle is the series of events that takes place in a cell leading to its division and duplication (replication). Regulation of the cell cycle in...
    • Cell cycle, organism-specific biosystem (from KEGG)
      Cell cycle, organism-specific biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
    • Cell cycle, conserved biosystem (from KEGG)
      Cell cycle, conserved biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
    • Chronic myeloid leukemia, organism-specific biosystem (from KEGG)
      Chronic myeloid leukemia, organism-specific biosystemChronic myelogenous leukemia (CML) originates in a pluripotent hematopoetic stem cell of the bone marrow and is characterized by greatly increased numbers of granulocytes in the blood. Myeloid and ot...
    • Chronic myeloid leukemia, conserved biosystem (from KEGG)
      Chronic myeloid leukemia, conserved biosystemChronic myelogenous leukemia (CML) originates in a pluripotent hematopoetic stem cell of the bone marrow and is characterized by greatly increased numbers of granulocytes in the blood. Myeloid and ot...
    • Cyclin D associated events in G1, organism-specific biosystem (from REACTOME)
      Cyclin D associated events in G1, organism-specific biosystemThree D-type cyclins are essential for progression from G1 to S-phase. These D cyclins bind to and activate both CDK4 and CDK6. The formation of all possible complexes between the D-type cyclins and...
    • G1 Phase, organism-specific biosystem (from REACTOME)
      G1 Phase, organism-specific biosystemEarly cell cycle progression in G1 is under the control of the D-type cyclins together with Cdk4 and Cdk6. An important target for these CDKs is the Retinoblastoma (Rb) protein, which when phosphoryl...
    • G1 to S cell cycle control, organism-specific biosystem (from WikiPathways)
      G1 to S cell cycle control, organism-specific biosystemIn the G1 phase there are two types of DNA damage responses, the p53-dependent and the p53-independent pathways. The p53-dependent responses inhibit CDKs through the up-regulation of genes encoding C...
    • Glioma, organism-specific biosystem (from KEGG)
      Glioma, organism-specific biosystemGliomas are the most common of the primary brain tumors and account for more than 40% of all central nervous system neoplasms. Gliomas include tumours that are composed predominantly of astrocytes (a...
    • Glioma, conserved biosystem (from KEGG)
      Glioma, conserved biosystemGliomas are the most common of the primary brain tumors and account for more than 40% of all central nervous system neoplasms. Gliomas include tumours that are composed predominantly of astrocytes (a...
    • HTLV-I infection, organism-specific biosystem (from KEGG)
      HTLV-I infection, organism-specific biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
    • HTLV-I infection, conserved biosystem (from KEGG)
      HTLV-I infection, conserved biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
    • Melanoma, organism-specific biosystem (from KEGG)
      Melanoma, organism-specific biosystemMelanoma is a form of skin cancer that has a poor prognosis and which is on the rise in Western populations. Melanoma arises from the malignant transformation of pigment-producing cells, melanocytes...
    • Melanoma, conserved biosystem (from KEGG)
      Melanoma, conserved biosystemMelanoma is a form of skin cancer that has a poor prognosis and which is on the rise in Western populations. Melanoma arises from the malignant transformation of pigment-producing cells, melanocytes...
    • Mitotic G1-G1/S phases, organism-specific biosystem (from REACTOME)
      Mitotic G1-G1/S phases, organism-specific biosystem
      Mitotic G1-G1/S phases
    • Non-small cell lung cancer, organism-specific biosystem (from KEGG)
      Non-small cell lung cancer, organism-specific biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer and represents a heter...
    • Non-small cell lung cancer, conserved biosystem (from KEGG)
      Non-small cell lung cancer, conserved biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer and represents a heter...
    • Pancreatic cancer, organism-specific biosystem (from KEGG)
      Pancreatic cancer, organism-specific biosystemInfiltrating ductal adenocarcinoma is the most common malignancy of the pancreas. When most investigators use the term 'pancreatic cancer' they are referring to pancreatic ductal adenocarcinoma (PDA)...
    • Pancreatic cancer, conserved biosystem (from KEGG)
      Pancreatic cancer, conserved biosystemInfiltrating ductal adenocarcinoma is the most common malignancy of the pancreas. When most investigators use the term 'pancreatic cancer' they are referring to pancreatic ductal adenocarcinoma (PDA)...
    • Pathways in cancer, organism-specific biosystem (from KEGG)
      Pathways in cancer, organism-specific biosystem
      Pathways in cancer
    • Senescence and Autophagy, organism-specific biosystem (from WikiPathways)
      Senescence and Autophagy, organism-specific biosystemSenescense and Autophagy Pathways in Cancer
    • TP53 network, organism-specific biosystem (from WikiPathways)
      TP53 network, organism-specific biosystemP53 is not a lonely genome guardian, it operates with the assistance of p73 and p63 within a complex network including distinct but complementary pathways. This protein family presents a high le...
    • p53 signaling pathway, organism-specific biosystem (from KEGG)
      p53 signaling pathway, organism-specific biosystemp53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated ge...
    • p53 signaling pathway, conserved biosystem (from KEGG)
      p53 signaling pathway, conserved biosystemp53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated ge...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    DNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    MDM2 binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    NF-kappaB binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cyclin-dependent protein kinase inhibitor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    p53 binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    protein kinase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    transcription factor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    ubiquitin-protein ligase inhibitor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    DNA fragmentation involved in apoptotic nuclear change IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    G1 phase of mitotic cell cycle TAS
    Traceable Author Statement
    more info
    		  
    G1/S transition of mitotic cell cycle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Ras protein signal transduction IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    activation of cysteine-type endopeptidase activity involved in apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    apoptotic mitochondrial changes IMP
    Inferred from Mutant Phenotype
    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 IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    cell cycle checkpoint IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    cellular senescence IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    induction of apoptosis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    induction of apoptosis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    mitotic cell cycle TAS
    Traceable Author Statement
    more info
    		  
    negative regulation of B cell proliferation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    negative regulation of NF-kappaB transcription factor activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    negative regulation of cell growth IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    negative regulation of cell proliferation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    negative regulation of cell proliferation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    negative regulation of cell-matrix adhesion IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    negative regulation of cyclin-dependent protein kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    negative regulation of immature T cell proliferation in thymus ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    negative regulation of phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    negative regulation of protein kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    negative regulation of transcription, DNA-dependent IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    negative regulation of ubiquitin-protein ligase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    positive regulation of DNA damage response, signal transduction by p53 class mediator IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    positive regulation of cell cycle arrest IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    positive regulation of cellular senescence IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    positive regulation of macrophage apoptosis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    positive regulation of protein sumoylation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    positive regulation of smooth muscle cell apoptosis ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    positive regulation of transcription from RNA polymerase II promoter IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    positive regulation of transcription, DNA-dependent IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    protein K63-linked ubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    protein destabilization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    protein polyubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    protein stabilization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    rRNA processing IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of G2/M transition of mitotic cell cycle IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    regulation of protein export from nucleus IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    regulation of protein stability ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    replicative senescence IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    senescence-associated heterochromatin focus assembly IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    somatic stem cell division ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cytosol TAS
    Traceable Author Statement
    more info
    		  
    colocalizes_with nuclear body IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleolus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    protein complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    senescence-associated heterochromatin focus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Help top of page

    General protein information

    Preferred Names
    cyclin-dependent kinase inhibitor 2A
    Names
    cyclin-dependent kinase inhibitor 2A
    CDK4 inhibitor p16-INK4
    multiple tumor suppressor 1
    cell cycle negative regulator beta
    cyclin-dependent kinase 4 inhibitor A
    cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)
    Help top of page

    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.

    Genomic

    1. NG_007485.1 RefSeqGene

      Range
      5001..31740
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_11

    mRNA and Protein(s)

    1. NM_000077.4 → NP_000068.1  cyclin-dependent kinase inhibitor 2A isoform p16INK4a

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) is also known as alpha. Transcripts 1 and 4, encoding p16INK4a and p14ARF, 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 (1) lacks sequence similarity to the protein product of variant 4 (p14ARF).
      Source sequence(s)
      AL449423, BI258230, BQ012762, BX099567, L27211
      Consensus CDS
      CCDS6510.1
      UniProtKB/Swiss-Prot
      P42771
      Related
      ENSP00000307101, OTTHUMP00000021147, ENST00000304494, OTTHUMT00000051915
      Conserved Domains (2) summary
      cd00204
      Location:31 – 130
      Blast Score: 167
      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 ...
      pfam13857
      Location:63 – 118
      Blast Score: 91
      Ank_5; Ankyrin repeats (many copies)

    2. NM_001195132.1 → NP_001182061.1  cyclin-dependent kinase inhibitor 2A isoform p16gamma

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) includes an additional exon that causes a frameshift in the 3' coding region, compared to variant 1 (encoding p16INK4a). The resulting isoform (p16gamma) has a distinct C-terminus and is longer than p16INK4a. This variant has been described in PMID:17486064. It is a candidate for nonsense-mediated mRNA decay (NMD), but it is not known if the endogenous protein is expressed in vivo.
      Source sequence(s)
      AL449423, BX099567, DQ318021
      Consensus CDS
      CCDS56565.1
      Related
      ENSP00000418915, OTTHUMP00000215051, ENST00000498124, OTTHUMT00000354927
      Conserved Domains (2) summary
      cd00204
      Location:31 – 130
      Blast Score: 164
      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 ...
      pfam13857
      Location:63 – 118
      Blast Score: 90
      Ank_5; Ankyrin repeats (many copies)

    3. NM_058195.3 → NP_478102.2  cyclin-dependent kinase inhibitor 2A isoform p14ARF

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4), also known as beta, encodes isoform p14ARF. Transcripts 1 and 4, encoding p16INK4a and p14ARF 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 (1) lacks sequence similarity to the protein product of variant 4 (p14ARF). Note that this variant may use an alternative upstream start codon, which would produce an isoform that is 41 aa longer at the N-terminus, or an alternative downstream start codon, which would produce an isoform (smARF, described in PMID:16713577) that is 47 aa shorter at the N-terminus; it is unclear if the isoforms derived from the alternative start codons are present in vivo. The p14ARF isoform is known to be nucleoplasmic but may also be recruited to mitochondria, as described in PMID:20107316.
      Source sequence(s)
      BQ012762, BX099567, S78535, U38945
      Consensus CDS
      CCDS6511.2
      UniProtKB/Swiss-Prot
      Q8N726
      Related
      ENSP00000432664, OTTHUMP00000215053, ENST00000530628, OTTHUMT00000051918
      Conserved Domains (1) summary
      pfam07392
      Location:4 – 34
      Blast Score: 93
      P19Arf_N; Cyclin-dependent kinase inhibitor 2a p19Arf N-terminus

    4. NM_058197.4 → NP_478104.2  cyclin-dependent kinase inhibitor 2A isoform p12

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) contains an alternate open reading frame (ARF), when compared to variants 1 or 4. The ARF results from an alternative splicing between a distinct first exon, which contains the translation start codon, and the common second exon. Thus, the protein encoded by this variant (p12) lacks sequence similarity to the protein product of variant 4. This variant is specifically expressed in pancreas, and has been described in PMID:10445844. It is a candidate for nonsense-mediated mRNA decay (NMD), but it is not known if the endogenous protein is expressed in vivo.
      Source sequence(s)
      AF115544, AL449423, BQ012762, BX099567
      UniProtKB/TrEMBL
      G3XAG3
      UniProtKB/Swiss-Prot
      P42771
      Related
      ENSP00000369496, OTTHUMP00000215052, ENST00000380151, OTTHUMT00000051917

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000009.11 Reference GRCh37.p5 Primary Assembly

      Range
      21967751..21994490, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000141.1 Alternate HuRef

      Range
      21930969..21957759, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_058196.1: Suppressed sequence

      Description
      NM_058196.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    Help top of page

    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AB060808.1 BAB91133.1
    genomic AF044170.1 AAD02319.1
    genomic AF527803.1 AAM77919.1
      AAR05391.1
    genomic AF527803.1 AAM77919.1
      AAR05391.1
    genomic AL449423.14 CAH70600.1
      CAH70601.1
    genomic CH471071.2 EAW58598.1
      EAW58599.1
      EAW58600.1
      EAW58601.1
      EAW58602.1
      EAW58603.1
    genomic DQ325544.1 ABC50001.1
    genomic DQ406745.1 ABD72255.1
    genomic S69804.1 AAD14048.1
    genomic U12818.1 AAB60645.1
    genomic U12819.1 AAB60645.1
    genomic U12820.1 AAB60645.1
    genomic X94154.1 CAA63870.1
    mRNA AF115544.1 AAD11437.1
    mRNA AI859822.1 None
    mRNA AL582909.3 None
    mRNA BC015960.2 AAH15960.3
    mRNA BC021998.2 AAH21998.3
    mRNA BI258230.1 None
    mRNA BQ012762.1 None
    mRNA BT007020.1 AAP35666.1
    mRNA BX099567.1 None
    mRNA DQ318021.1 ABC47036.1
    mRNA L27211.1 AAA92554.1
    mRNA S78535.1 AAC60649.1
    mRNA U26727.1 AAA82236.1
    mRNA U38945.1 AAB01737.1
    mRNA AJ844636.1 CAH59950.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P42771.2 GenPept UniProtKB/Swiss-Prot:P42771
    Q208B5 GenPept UniProtKB/TrEMBL:Q208B5
    Q2MJK0 GenPept UniProtKB/TrEMBL:Q2MJK0
    Q5ZEY9 GenPept UniProtKB/TrEMBL:Q5ZEY9
    Q8N726.2 GenPept UniProtKB/Swiss-Prot:Q8N726
    Q9UPB7 GenPept UniProtKB/TrEMBL:Q9UPB7
    Help top of page

    Additional Links

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

      Supplemental Content

      Table of contents

      Links

      Links to other resources

      General information

      Related sites

      Feedback

      Subscription

      Recent activity

      Clear Turn Off Turn On

      Your browsing activity is empty.

      Activity recording is turned off.

      Turn recording back on

      See more...