| URN | urn:agi-llid:1029 |
|---|---|
| Total Entities | 0 |
| Connectivity | 1382 |
| Name | Cdkn2a |
| Description | cyclin-dependent kinase inhibitor 2A |
| Notes | 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] |
| Ariadne Ontology | CDKN |
|---|---|
| Tumor suppressors | |
| Secreted proteins | |
| Biofluids assayable substances |
| GO Molecular Function | p53 binding |
|---|---|
| MDM2-MDM4 family protein binding | |
| transcription factor binding | |
| NF-kappaB binding | |
| protein kinase binding | |
| DNA binding | |
| cyclin-dependent protein kinase inhibitor activity | |
| ubiquitin-protein ligase inhibitor activity | |
| sequence-specific DNA binding transcription factor activity |
| GO Cellular Component | nucleoplasm |
|---|---|
| nucleolus | |
| nuclear body | |
| granular component | |
| senescence-associated heterochromatin focus | |
| protein complex | |
| cytoplasm | |
| cytosol | |
| nucleus |
| GO Biological Process | cell cycle |
|---|---|
| cell aging | |
| G1-S transition of mitotic cell cycle | |
| cell cycle arrest | |
| cell cycle checkpoint | |
| positive regulation of cell cycle arrest | |
| regulation of G2-M transition of mitotic cell cycle | |
| G1 phase of mitotic cell cycle | |
| mitotic cell cycle | |
| negative regulation of cell cycle | |
| regulation of cyclin-dependent protein kinase activity | |
| negative regulation of cyclin-dependent protein kinase activity | |
| positive regulation of DNA damage response, signal transduction by p53 class mediator | |
| replicative senescence | |
| cellular senescence | |
| positive regulation of cellular senescence | |
| Ras protein signal transduction | |
| negative regulation of cell growth | |
| positive regulation of transcription, DNA-dependent | |
| positive regulation of transcription from RNA polymerase II promoter | |
| positive regulation of protein sumoylation | |
| negative regulation of transcription, DNA-dependent | |
| negative regulation of phosphorylation | |
| negative regulation of protein kinase activity | |
| negative regulation of ubiquitin-protein ligase activity | |
| regulation of transcription, DNA-dependent | |
| positive regulation of sequence-specific DNA binding transcription factor activity | |
| negative regulation of NF-kappaB transcription factor activity | |
| negative regulation of cell proliferation | |
| somatic stem cell maintenance | |
| negative regulation of B cell proliferation | |
| negative regulation of immature T cell proliferation in thymus | |
| negative regulation of cell-matrix adhesion | |
| negative regulation of mammary gland epithelial cell proliferation | |
| induction of apoptosis | |
| positive regulation of apoptotic process involved in mammary gland involution | |
| positive regulation of smooth muscle cell apoptotic process | |
| positive regulation of macrophage apoptotic process | |
| regulation of nucleocytoplasmic transport | |
| regulation of protein export from nucleus | |
| activation of cysteine-type endopeptidase activity involved in apoptotic process | |
| transcription, DNA-dependent | |
| rRNA transcription | |
| apoptotic DNA fragmentation | |
| rRNA processing | |
| protein polyubiquitination | |
| protein K63-linked ubiquitination | |
| somatic stem cell division | |
| apoptotic process | |
| senescence-associated heterochromatin focus assembly | |
| apoptotic mitochondrial changes | |
| response to organic substance | |
| response to drug | |
| response to organic nitrogen | |
| response to organic cyclic compound | |
| regulation of gene expression | |
| regulation of protein stability | |
| protein stabilization | |
| protein destabilization | |
| aging | |
| epidermis development |
| Pathway | Cell Cycle |
|---|---|
| Sialophorin -> CTNNB/MYC/TP53 signaling | |
| NGF/SMAD3/NF-kB Expression Targets | |
| TGFB1-ACVRL1 Expression Targets | |
| TGFB1-TGFBR1/AP-1 Expression Targets | |
| pancreatic cancer pathway |
| Group | CDKN |
|---|---|
| Tumor suppressors | |
| cell cycle | |
| cell aging | |
| G1-S transition of mitotic cell cycle | |
| cell cycle arrest | |
| cell cycle checkpoint | |
| positive regulation of cell cycle arrest | |
| regulation of G2-M transition of mitotic cell cycle | |
| G1 phase of mitotic cell cycle | |
| mitotic cell cycle | |
| negative regulation of cell cycle | |
| regulation of cyclin-dependent protein kinase activity | |
| negative regulation of cyclin-dependent protein kinase activity | |
| positive regulation of DNA damage response, signal transduction by p53 class mediator | |
| replicative senescence | |
| cellular senescence | |
| positive regulation of cellular senescence | |
| Ras protein signal transduction | |
| negative regulation of cell growth | |
| positive regulation of transcription, DNA-dependent | |
| positive regulation of transcription from RNA polymerase II promoter | |
| positive regulation of protein sumoylation | |
| negative regulation of transcription, DNA-dependent | |
| negative regulation of phosphorylation | |
| negative regulation of protein kinase activity | |
| negative regulation of ubiquitin-protein ligase activity | |
| regulation of transcription, DNA-dependent | |
| positive regulation of sequence-specific DNA binding transcription factor activity | |
| negative regulation of NF-kappaB transcription factor activity | |
| negative regulation of cell proliferation | |
| somatic stem cell maintenance | |
| negative regulation of B cell proliferation | |
| negative regulation of immature T cell proliferation in thymus | |
| negative regulation of cell-matrix adhesion | |
| negative regulation of mammary gland epithelial cell proliferation | |
| induction of apoptosis | |
| positive regulation of apoptotic process involved in mammary gland involution | |
| positive regulation of smooth muscle cell apoptotic process | |
| positive regulation of macrophage apoptotic process | |
| regulation of nucleocytoplasmic transport | |
| regulation of protein export from nucleus | |
| activation of cysteine-type endopeptidase activity involved in apoptotic process | |
| transcription, DNA-dependent | |
| rRNA transcription | |
| apoptotic DNA fragmentation | |
| rRNA processing | |
| protein polyubiquitination | |
| protein K63-linked ubiquitination | |
| somatic stem cell division | |
| apoptotic process | |
| senescence-associated heterochromatin focus assembly | |
| apoptotic mitochondrial changes | |
| response to organic substance | |
| response to drug | |
| response to organic nitrogen | |
| response to organic cyclic compound | |
| regulation of gene expression | |
| regulation of protein stability | |
| protein stabilization | |
| protein destabilization | |
| aging | |
| epidermis development | |
| p53 binding | |
| MDM2-MDM4 family protein binding | |
| transcription factor binding | |
| NF-kappaB binding | |
| protein kinase binding | |
| DNA binding | |
| cyclin-dependent protein kinase inhibitor activity | |
| ubiquitin-protein ligase inhibitor activity | |
| sequence-specific DNA binding transcription factor activity | |
| nucleoplasm | |
| nucleolus | |
| nuclear body | |
| granular component | |
| senescence-associated heterochromatin focus | |
| protein complex | |
| cytoplasm | |
| cytosol | |
| nucleus | |
| Secreted proteins | |
| Biofluids assayable substances |
| MedScan ID | 1029 |
|---|
| Hugo ID | 1787 |
|---|
| Human chromosome position | 9p21 |
|---|
| LocusLink ID | 1029 |
|---|---|
| 12578 | |
| 25163 |
| Alias | ARF |
|---|---|
| MLM | |
| P14 | |
| P16 | |
| P19 | |
| CMM2 | |
| INK4 | |
| MTS1 | |
| TP16 | |
| CDK4I | |
| CDKN2 | |
| INK4A | |
| MTS-1 | |
| P14ARF | |
| P19ARF | |
| P16INK4 | |
| P16INK4A | |
| P16-INK4A | |
| 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) | |
| Pctr1 | |
| p19<ARF> | |
| ARF-INK4a | |
| INK4a-ARF | |
| Ink4a/Arf | |
| p16(INK4a) | |
| RP23-166I8.5 | |
| cyclin-dependent kinase inhibitor 2A, isoform 3 | |
| p16-INK4 | |
| mitochondrial smARF | |
| cyclin-dependent kinase inhibitor protein | |
| cyclin-dependent kinase inhibitor 2A, isoforms 1/2 | |
| cyclin-dependent kinase inhibitor 2A (p16, inhibits CDK4) | |
| p16Cdkn2a | |
| cell cycle inhibitor | |
| cell cycle regulator | |
| cyclin-dependent kinase inhibitor 2a p19Arf | |
| cyclin-dependent kinase inhibitor 2a p16Ink4a | |
| cyclin-dependent kinase inhibitor 2A, isoform 1 | |
| cyclin-dependent kinase inhibitor 2A, isoform 2 | |
| Cyclin dependent kinase inhibitor 2A (p16, inhibits CDK4) | |
| multiple tumour suppressor 1 | |
| OTTHUMP00000021148 | |
| OTTHUMP00000021147 | |
| multiple tumour suppressor I | |
| OTTMUSP00000008143 | |
| multiple tumor suppressor I | |
| p19 ARF | |
| MTS I | |
| p16 INKa | |
| p16, inhibits CDK4 | |
| p16INK4a alternatively spliced form | |
| Pctr I | |
| plasmacytoma resistance 1 | |
| plasmacytoma resistance I | |
| LOC497805 | |
| CDKN2A | |
| CDN2_HUMAN | |
| cyclin dependent kinase inhibitor 2A | |
| alternative reading frame p14 | |
| cyclin-dependent kinase inhibitor 2A isoform 1 | |
| cyclin-dependent kinase inhibitor p16 | |
| CDN2 | |
| cyclin-dependent kinase inhibitor 2A isoform 2 | |
| cyclin-dependent kinase inhibitor p12, p16INK4a alternatively spliced form | |
| cyclin-dependent kinase inhibitor p12, p16alternatively spliced form | |
| cyclin-dependent kinase inhibitor p12, | |
| cyclin-dependent kinase inhibitor 2A, isoforms 1/2/3 | |
| cyclin-dependent kinase inhibitor 2A, isoform 4 | |
| cyclin-dependent kinase inhibitor 2A isoform III | |
| cyclin-dependent kinase inhibitor 2A isoform I | |
| cyclin-dependent kinase inhibitor 2A isoform 3 |
| Organism | Homo sapiens |
|---|---|
| Mus musculus | |
| Rattus norvegicus |
| OMIM ID | 600160 |
|---|---|
| 151623 | |
| 155755 | |
| 155601 | |
| 606719 |
| Unigene ID | Hs.512599 |
|---|---|
| Mm.4733 | |
| Rn.48717 |
| KEGG ID | hsa:1029 |
|---|---|
| mmu:12578 | |
| rno:25163 |
| Swiss-Prot Accession | P42771 |
|---|---|
| Q8N726 | |
| G3XAG3 | |
| P51480 | |
| Q64364 | |
| Q9R0Z3 | |
| Q8QZZ9 | |
| A5X2G7 | |
| D3DRK1 | |
| O95440 | |
| Q15191 | |
| Q5VVJ5 | |
| Q96B52 | |
| Q9NP05 | |
| D3DRK2 | |
| Q13195 | |
| Q13399 | |
| Q16360 | |
| Q7KZR9 | |
| A2ANM1 | |
| A2ANM2 | |
| O89088 | |
| P97510 | |
| P97937 | |
| Q6PEA2 | |
| Q78E39 | |
| Q78E57 | |
| Q792X7 | |
| Q9QWH6 | |
| Q9QWH7 | |
| Q9QWH8 | |
| Q4U255 | |
| Q9QXC7 | |
| Q9R051 |
| GO ID | 0003677 |
|---|---|
| 0097371 | |
| 0051059 | |
| 0004861 | |
| 0002039 | |
| 0019901 | |
| 0003700 | |
| 0008134 | |
| 0055105 | |
| 0000080 | |
| 0000082 | |
| 0007265 | |
| 0006919 | |
| 0006309 | |
| 0008637 | |
| 0007050 | |
| 0000075 | |
| 0090398 | |
| 0008544 | |
| 0006917 | |
| 0000278 | |
| 0030889 | |
| 0032088 | |
| 0030308 | |
| 0008285 | |
| 0001953 | |
| 0045736 | |
| 0033088 | |
| 0033600 | |
| 0042326 | |
| 0006469 | |
| 0045892 | |
| 0051444 | |
| 0043517 | |
| 0060058 | |
| 0071158 | |
| 2000774 | |
| 2000111 | |
| 0033235 | |
| 0034393 | |
| 0045944 | |
| 0045893 | |
| 0070534 | |
| 0031648 | |
| 0000209 | |
| 0050821 | |
| 0006364 | |
| 0009303 | |
| 0010389 | |
| 0046822 | |
| 0046825 | |
| 0031647 | |
| 0090399 | |
| 0035986 | |
| 0048103 | |
| 0035019 | |
| 0006351 | |
| 0005737 | |
| 0005829 | |
| 0016604 | |
| 0005730 | |
| 0005654 | |
| 0005634 | |
| 0043234 | |
| 0035985 | |
| 0007568 | |
| 0006915 | |
| 0007569 | |
| 0007049 | |
| 0045786 | |
| 0051091 | |
| 0000079 | |
| 0010468 | |
| 0006355 | |
| 0042493 | |
| 0014070 | |
| 0010243 | |
| 0001652 | |
| 0010033 |
| PIR ID | JE0141 |
|---|---|
| I39004 |
| Swiss-Prot ID | CD2A1_HUMAN |
|---|---|
| CD2A2_HUMAN | |
| CD2A1_MOUSE | |
| CD2A2_MOUSE | |
| CD2A1_RAT |
| Cell Localization | Cytoplasm |
|---|---|
| Nucleus | |
| nucleolus | |
| nucleoplasm |
| IPI ID | IPI00001560 |
|---|---|
| IPI00030733 | |
| IPI00942408 | |
| IPI00478390 | |
| IPI00122635 | |
| IPI00283736 | |
| IPI00133446 | |
| IPI00206876 |
| Mouse chromosome position | 4 42.7 cM |
|---|
| Rat chromosome position | 5q32 |
|---|
| Homologene ID | 55430 |
|---|
| MGI ID | 104738 |
|---|---|
| 103111 |
| RGD ID | 2323 |
|---|
| Primary Cell Localization | Cytoplasm |
|---|