cyclin-dependent kinase inhibitor 2A


CDKN2A (may also be known as: None)




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, the E3 ubiquitin-protein ligase MDM2, 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, Sep 2012]

Links to external resources

Changes associated with this gene

GO Terms

GO IDGO TermGO Category
GO:0000075 cell cycle checkpoint biological_process
GO:0000080 G1 phase of mitotic cell cycle biological_process
GO:0000082 G1/S transition of mitotic cell cycle biological_process
GO:0000209 protein polyubiquitination biological_process
GO:0000278 mitotic cell cycle biological_process
GO:0001953 negative regulation of cell-matrix adhesion biological_process
GO:0006309 DNA fragmentation involved in apoptotic nuclear change biological_process
GO:0006364 rRNA processing biological_process
GO:0006469 negative regulation of protein kinase activity biological_process
GO:0006917 induction of apoptosis biological_process
GO:0006919 activation of caspase activity biological_process
GO:0007049 cell cycle biological_process
GO:0007050 cell cycle arrest biological_process
GO:0007265 Ras protein signal transduction biological_process
GO:0007569 cell aging biological_process
GO:0008285 negative regulation of cell proliferation biological_process
GO:0008544 epidermis development biological_process
GO:0008637 apoptotic mitochondrial changes biological_process
GO:0009303 rRNA transcription biological_process
GO:0010389 regulation of G2/M transition of mitotic cell cycle biological_process
GO:0030308 negative regulation of cell growth biological_process
GO:0030889 negative regulation of B cell proliferation biological_process
GO:0031647 regulation of protein stability biological_process
GO:0031648 protein destabilization biological_process
GO:0032088 negative regulation of NF-kappaB transcription factor activity biological_process
GO:0033088 negative regulation of immature T cell proliferation in thymus biological_process
GO:0033235 positive regulation of protein sumoylation biological_process
GO:0033600 negative regulation of mammary gland epithelial cell proliferation biological_process
GO:0034393 positive regulation of smooth muscle cell apoptosis biological_process
GO:0035019 somatic stem cell maintenance biological_process
GO:0035986 senescence-associated heterochromatin focus assembly biological_process
GO:0042326 negative regulation of phosphorylation biological_process
GO:0043517 positive regulation of DNA damage response, signal transduction by p53 class mediator biological_process
GO:0045736 negative regulation of cyclin-dependent protein kinase activity biological_process
GO:0045892 negative regulation of transcription, DNA-dependent biological_process
GO:0045893 positive regulation of transcription, DNA-dependent biological_process
GO:0045944 positive regulation of transcription from RNA polymerase II promoter biological_process
GO:0046822 regulation of nucleocytoplasmic transport biological_process
GO:0046825 regulation of protein export from nucleus biological_process
GO:0048103 somatic stem cell division biological_process
GO:0050821 protein stabilization biological_process
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity biological_process
GO:0051444 negative regulation of ubiquitin-protein ligase activity biological_process
GO:0060058 positive regulation of apoptosis involved in mammary gland involution biological_process
GO:0070534 protein K63-linked ubiquitination biological_process
GO:0071158 positive regulation of cell cycle arrest biological_process
GO:0090398 cellular senescence biological_process
GO:0090399 replicative senescence biological_process
GO:2000111 positive regulation of macrophage apoptosis biological_process
GO:2000774 positive regulation of cellular senescence biological_process
GO:0001652 granular component cellular_component
GO:0005634 nucleus cellular_component
GO:0005654 nucleoplasm cellular_component
GO:0005730 nucleolus cellular_component
GO:0005737 cytoplasm cellular_component
GO:0005829 cytosol cellular_component
GO:0016604 nuclear body cellular_component
GO:0035985 senescence-associated heterochromatin focus cellular_component
GO:0043234 protein complex cellular_component
GO:0002039 p53 binding molecular_function
GO:0003677 DNA binding molecular_function
GO:0004861 cyclin-dependent protein kinase inhibitor activity molecular_function
GO:0005515 protein binding molecular_function
GO:0008134 transcription factor binding molecular_function
GO:0016301 kinase activity molecular_function
GO:0019901 protein kinase binding molecular_function
GO:0051059 NF-kappaB binding molecular_function
GO:0055105 ubiquitin-protein ligase inhibitor activity molecular_function
GO:0070215 MDM2 binding molecular_function