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Details on Person UniProt:Q8N726-2 CDKN2A
| Class:Id | ReferenceIsoform:8965065 |
|---|---|
| _chainChangeLog | chain:1-132 added on Fri February 17 2017 |
| _displayName | UniProt:Q8N726-2 CDKN2A |
| _timestamp | 2026-05-15 21:12:48 |
| chain | chain:1-132 |
| checksum | 7739A9050C21BC96 |
| comment | FUNCTION Capable of inducing cell cycle arrest in G1 and G2 phases. Acts as a tumor suppressor. Binds to MDM2 and blocks its nucleocytoplasmic shuttling by sequestering it in the nucleolus. This inhibits the oncogenic action of MDM2 by blocking MDM2-induced degradation of p53 and enhancing p53-dependent transactivation and apoptosis. Also induces G2 arrest and apoptosis in a p53-independent manner by preventing the activation of cyclin B1/CDC2 complexes. Binds to BCL6 and down-regulates BCL6-induced transcriptional repression. Binds to E2F1 and MYC and blocks their transcriptional activator activity but has no effect on MYC transcriptional repression. Binds to TOP1/TOPOI and stimulates its activity. This complex binds to rRNA gene promoters and may play a role in rRNA transcription and/or maturation. Interacts with NPM1/B23 and promotes its polyubiquitination and degradation, thus inhibiting rRNA processing. Plays a role in inhibiting ribosome biogenesis, perhaps by binding to the nucleolar localization sequence of transcription termination factor TTF1, and thereby preventing nucleolar localization of TTF1 (By similarity). Interacts with COMMD1 and promotes its 'Lys63'-linked polyubiquitination. Interacts with UBE2I/UBC9 and enhances sumoylation of a number of its binding partners including MDM2 and E2F1. Binds to HUWE1 and represses its ubiquitin ligase activity. May play a role in controlling cell proliferation and apoptosis during mammary gland development.FUNCTION May be involved in regulation of autophagy and caspase-independent cell death; the short-lived mitochondrial isoform is stabilized by C1QBP.SUBUNIT Does not interact with cyclins, CDK1, CDK2, CDK4, CDK5 or CDK6. Binds to BCL6, E2F1, HUWE1, MDM2, MYC, NPM1/B23, TOP1/TOPOI and UBE2I/UBC9. Interacts with TBRG1 and COMMD1. Interacts with CDKN2AIP and E4F1. Interacts with CDK5RAP3 and MDM2; form a ternary complex involved in regulation of p53/TP53 (PubMed:16173922). Interacts with NOP53; the interaction is direct and promotes ARF nucleoplasmic relocalization and ubiquitin-mediated proteasomal degradation (PubMed:27323397). Interacts with TTF1 (via the N-terminal region (NRD) and a C-terminal region); the interaction is direct and inhibits the nucleolar localization of TTF1 (By similarity).SUBUNIT Interacts with C1QBP.INTERACTION Isoform 1 and isoform tumor suppressor ARF arise due to the use of two alternative first exons joined to a common exon 2 at the same acceptor site but in different reading frames, resulting in two completely different isoforms.PTM Ubiquitinated in normal cells by TRIP12 via the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination at the N-terminus, regardless of the absence of lysine residues. Ubiquitination leads to its proteasomal degradation. In cancer cells, however, TRIP12 is located in a different cell compartment, preventing ubiquitination and degradation.CAUTION The proteins described here are encoded by the gene CDKN2A, but are completely unrelated in terms of sequence and function to cyclin-dependent kinase inhibitor 2A (AC P42771) which is encoded by the same gene.SEQUENCE CAUTION Extended N-terminus.SEQUENCE CAUTION Extended N-terminus.SEQUENCE CAUTION Extended N-terminus.SEQUENCE CAUTION Extended N-terminus.SEQUENCE CAUTION Extended N-terminus.SEQUENCE CAUTION Extended N-terminus.SEQUENCE CAUTION Extended N-terminus.SEQUENCE CAUTION Extended N-terminus. |
| created | [InstanceEdit:8964659] Weiser, JD |
| description | recommendedName: fullName evidence="26"Tumor suppressor ARF alternativeName: fullName evidence="25"Alternative reading frame shortName evidence="25"ARF alternativeName: fullName evidence="32"Cyclin-dependent kinase inhibitor 2A alternativeName: fullName evidence="25"p14ARF |
| geneName | CDKN2A CDKN2 MLM |
| identifier | Q8N726 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | Alternative splicing Apoptosis Cell cycle DNA-binding Mitochondrion Nucleus Proteomics identification Reference proteome rRNA processing Transcription Transcription regulation Tumor suppressor Ubl conjugation Ubl conjugation pathway |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9909836] Weiser, Joel, 2024-05-14 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9948485] Weiser, Joel, 2025-05-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9970787] Weiser, Joel, 2025-10-31 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 [InstanceEdit:9989145] Weiser, Joel, 2026-05-15 |
| name | CDKN2A |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:3200016] ENSEMBL:ENSG00000147889 CDKN2A [Homo sapiens] |
| secondaryIdentifier | ARF_HUMAN D3DRK2 Q13195 Q13399 Q16360 Q7KZR9 |
| sequenceLength | 132 |
| species | [Species:48887] Homo sapiens |
| variantIdentifier | Q8N726-2 |
| [Change default viewing format] | |
No pathways have been reviewed or authored by UniProt:Q8N726-2 CDKN2A (8965065)
