Reactome: A Curated Pathway Database
THIS SITE IS USED FOR CURATION AND TESTING
IT IS NOT STABLE, IS LINKED TO AN INCOMPLETE DATA SET, AND IS NOT MONITORED FOR PERFORMANCE. WE STRONGLY RECOMMEND THE USE OF OUR PUBLIC SITE

Query author contributions in Reactome

Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.

If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.

Name Email address

Details on Person UniProt:Q8N726-2 CDKN2A

Class:IdReferenceIsoform:8965065
_chainChangeLogchain:1-132 added on Fri February 17 2017
_displayNameUniProt:Q8N726-2 CDKN2A
_timestamp2026-05-15 21:12:48
chainchain:1-132
checksum7739A9050C21BC96
commentFUNCTION 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
descriptionrecommendedName: 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
geneNameCDKN2A
CDKN2
MLM
identifierQ8N726
isoformParent
isSequenceChangedFALSE
keywordAlternative 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
nameCDKN2A
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:3200016] ENSEMBL:ENSG00000147889 CDKN2A [Homo sapiens]
secondaryIdentifierARF_HUMAN
D3DRK2
Q13195
Q13399
Q16360
Q7KZR9
sequenceLength132
species[Species:48887] Homo sapiens
variantIdentifierQ8N726-2
[Change default viewing format]
No pathways have been reviewed or authored by UniProt:Q8N726-2 CDKN2A (8965065)