UniProtKB - Q8N726 (ARF_HUMAN)
Tumor suppressor ARF
CDKN2A
Functioni
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. 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. Isoform smARF may be involved in regulation of autophagy and caspase-independent cell death; the short-lived mitochondrial isoform is stabilized by C1QBP.
12 PublicationsCaution
GO - Molecular functioni
- disordered domain specific binding Source: CAFA
- DNA binding Source: UniProtKB-KW
- MDM2/MDM4 family protein binding Source: UniProtKB
- p53 binding Source: BHF-UCL
- RNA polymerase II-specific DNA-binding transcription factor binding Source: BHF-UCL
- SUMO transferase activity Source: Reactome
- ubiquitin ligase inhibitor activity Source: CAFA
- ubiquitin-protein transferase inhibitor activity Source: BHF-UCL
GO - Biological processi
- activation of cysteine-type endopeptidase activity involved in apoptotic process Source: BHF-UCL
- amyloid fibril formation Source: CAFA
- apoptotic mitochondrial changes Source: BHF-UCL
- autophagy of mitochondrion Source: ParkinsonsUK-UCL
- cell cycle Source: UniProtKB-KW
- cellular senescence Source: BHF-UCL
- mitochondrial depolarization Source: ParkinsonsUK-UCL
- negative regulation of B cell proliferation Source: BHF-UCL
- negative regulation of cell population proliferation Source: UniProtKB
- negative regulation of immature T cell proliferation in thymus Source: BHF-UCL
- negative regulation of protein kinase activity Source: BHF-UCL
- negative regulation of protein neddylation Source: CAFA
- negative regulation of proteolysis involved in cellular protein catabolic process Source: ParkinsonsUK-UCL
- negative regulation of ubiquitin-dependent protein catabolic process Source: CAFA
- negative regulation of ubiquitin protein ligase activity Source: CAFA
- negative regulation of ubiquitin-protein transferase activity Source: BHF-UCL
- positive regulation of apoptotic process Source: UniProtKB
- positive regulation of DNA damage response, signal transduction by p53 class mediator Source: BHF-UCL
- positive regulation of gene expression Source: CAFA
- positive regulation of protein localization to nucleus Source: UniProtKB
- positive regulation of protein sumoylation Source: BHF-UCL
- positive regulation of signal transduction by p53 class mediator Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- protein destabilization Source: BHF-UCL
- protein K63-linked ubiquitination Source: UniProtKB
- protein polyubiquitination Source: UniProtKB
- protein stabilization Source: BHF-UCL
- regulation of apoptotic DNA fragmentation Source: BHF-UCL
- regulation of cell cycle Source: BHF-UCL
- regulation of G2/M transition of mitotic cell cycle Source: BHF-UCL
- regulation of protein export from nucleus Source: BHF-UCL
- regulation of protein stability Source: BHF-UCL
- regulation of protein targeting to mitochondrion Source: ParkinsonsUK-UCL
- rRNA processing Source: UniProtKB-KW
- somatic stem cell division Source: BHF-UCL
Keywordsi
Molecular function | DNA-binding |
Biological process | Apoptosis, Cell cycle, rRNA processing, Transcription, Transcription regulation, Ubl conjugation pathway |
Enzyme and pathway databases
PathwayCommonsi | Q8N726 |
Reactomei | R-HSA-111471, Apoptotic factor-mediated response R-HSA-2559580, Oxidative Stress Induced Senescence R-HSA-2559585, Oncogene Induced Senescence R-HSA-3108214, SUMOylation of DNA damage response and repair proteins R-HSA-3232118, SUMOylation of transcription factors R-HSA-6804757, Regulation of TP53 Degradation R-HSA-69541, Stabilization of p53 R-HSA-8941858, Regulation of RUNX3 expression and activity R-HSA-9645722, Defective Intrinsic Pathway for Apoptosis Due to p14ARF Loss of Function R-HSA-9646303, Evasion of Oncogene Induced Senescence Due to p14ARF Defects R-HSA-9646304, Evasion of Oxidative Stress Induced Senescence Due to p14ARF Defects |
SignaLinki | Q8N726 |
SIGNORi | Q8N726 |
Names & Taxonomyi
Protein namesi | Recommended name: Tumor suppressor ARFCuratedAlternative name(s): Alternative reading frame1 Publication Short name: ARF1 Publication Cyclin-dependent kinase inhibitor 2AImported p14ARF1 Publication |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:1787, CDKN2A |
MIMi | 600160, gene |
neXtProti | NX_Q8N726 |
VEuPathDBi | HostDB:ENSG00000147889 |
Subcellular locationi
Nucleus
- nucleolus 4 Publications
- nucleoplasm 2 Publications
Mitochondrion
- Mitochondrion 1 Publication
Cytosol
- cytosol Source: Reactome
Mitochondrion
- mitochondrial matrix Source: Reactome
- mitochondrion Source: ParkinsonsUK-UCL
Nucleus
- nucleolus Source: UniProtKB
- nucleoplasm Source: BHF-UCL
- nucleus Source: BHF-UCL
Other locations
- protein-containing complex Source: BHF-UCL
Keywords - Cellular componenti
Mitochondrion, NucleusPathology & Biotechi
Keywords - Diseasei
Tumor suppressorOrganism-specific databases
DisGeNETi | 1029 |
MalaCardsi | CDKN2A |
OpenTargetsi | ENSG00000147889 |
PharmGKBi | PA106 |
Miscellaneous databases
Pharosi | Q8N726, Tbio |
Genetic variation databases
BioMutai | CDKN2A |
DMDMi | 384872321 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000144180 | 1 – 132 | Tumor suppressor ARFAdd BLAST | 132 |
Post-translational modificationi
Keywords - PTMi
Ubl conjugationProteomic databases
jPOSTi | Q8N726 |
MassIVEi | Q8N726 |
MaxQBi | Q8N726 |
PeptideAtlasi | Q8N726 |
PRIDEi | Q8N726 |
ProteomicsDBi | 72258 [Q8N726-1] |
PTM databases
iPTMneti | Q8N726 |
Expressioni
Gene expression databases
Bgeei | ENSG00000147889, Expressed in adenohypophysis and 209 other tissues |
ExpressionAtlasi | Q8N726, baseline and differential |
Genevisiblei | Q8N726, HS |
Organism-specific databases
HPAi | ENSG00000147889, Tissue enhanced (choroid plexus, pituitary gland) |
Interactioni
Subunit structurei
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). Isoform smARF interacts with C1QBP.
Interacts with NOP53; the interaction is direct and promotes ARF nucleoplasmic relocalization and ubiquitin-mediated proteasomal degradation (PubMed:27323397).
16 PublicationsBinary interactionsi
Q8N726
GO - Molecular functioni
- disordered domain specific binding Source: CAFA
- MDM2/MDM4 family protein binding Source: UniProtKB
- p53 binding Source: BHF-UCL
- RNA polymerase II-specific DNA-binding transcription factor binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 107463, 281 interactors |
CORUMi | Q8N726 |
DIPi | DIP-24171N |
IntActi | Q8N726, 67 interactors |
MINTi | Q8N726 |
Structurei
3D structure databases
AlphaFoldDBi | Q8N726 |
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 64 | Interaction with CDK5RAP3 and MDM21 PublicationAdd BLAST | 64 | |
Regioni | 56 – 132 | DisorderedSequence analysisAdd BLAST | 77 |
Phylogenomic databases
GeneTreei | ENSGT00940000163078 |
HOGENOMi | CLU_134503_0_0_1 |
OrthoDBi | 1435166at2759 |
Family and domain databases
DisProti | DP02167 [Q8N726-1] |
InterProi | View protein in InterPro IPR010868, Tumor_suppres_ARF |
Pfami | View protein in Pfam PF07392, P19Arf_N, 1 hit |
s (6+)i Sequence
Sequence statusi: Complete.
This entry describes 6 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 6 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MVRRFLVTLR IRRACGPPRV RVFVVHIPRL TGEWAAPGAP AAVALVLMLL
60 70 80 90 100
RSQRLGQQPL PRRPGHDDGQ RPSGGAAAAP RRGAQLRRPR HSHPTRARRC
110 120 130
PGGLPGHAGG AAPGRGAAGR ARCLGPSARG PG
The sequence of this isoform differs from the canonical sequence as follows:
1-47: Missing.
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketK7ENC6 | K7ENC6_HUMAN | Cyclin-dependent kinase inhibitor 2... | CDKN2A | 121 | Annotation score: | ||
K7ES20 | K7ES20_HUMAN | Cyclin-dependent kinase inhibitor 2... | CDKN2A | 104 | Annotation score: | ||
J3QRG6 | J3QRG6_HUMAN | Cyclin-dependent kinase inhibitor 2... | CDKN2A | 138 | Annotation score: |
Sequence cautioni
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 28 – 30 | PRL → SWF in AAH15960 (PubMed:15489334).Curated | 3 | |
Sequence conflicti | 28 – 30 | PRL → SWF in AAH21998 (PubMed:15489334).Curated | 3 | |
Sequence conflicti | 28 – 30 | PRL → SWF in AAP35666 (PubMed:7624129).Curated | 3 | |
Sequence conflicti | 94 | P → L in AAB01737 (Ref. 2) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_029287 | 17 | P → S1 PublicationCorresponds to variant dbSNP:rs3731190EnsemblClinVar. | 1 | |
Natural variantiVAR_053033 | 106 | G → R. Corresponds to variant dbSNP:rs4987127Ensembl. | 1 | |
Natural variantiVAR_053034 | 113 | P → L. Corresponds to variant dbSNP:rs34886500EnsemblClinVar. | 1 | |
Natural variantiVAR_053035 | 116 | G → D. Corresponds to variant dbSNP:rs35741010EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_044962 | 1 – 47 | Missing in isoform smARF. CuratedAdd BLAST | 47 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | S78535 mRNA Translation: AAC60649.1 Different initiation. U38945 mRNA Translation: AAB01737.1 Different initiation. AF527803 Genomic DNA Translation: AAM77919.1 Different initiation. AL449423 Genomic DNA Translation: CAH70601.1 Different initiation. CH471071 Genomic DNA Translation: EAW58600.1 Different initiation. CH471071 Genomic DNA Translation: EAW58601.1 Different initiation. BC015960 mRNA Translation: AAH15960.3 Different initiation. BC021998 mRNA Translation: AAH21998.3 Different initiation. U26727 mRNA Translation: AAA82236.1 BT007020 mRNA Translation: AAP35666.1 |
CCDSi | CCDS6511.2 [Q8N726-1] |
PIRi | I39004 |
RefSeqi | NP_478102.2, NM_058195.3 [Q8N726-1] |
Genome annotation databases
Ensembli | ENST00000530628.2; ENSP00000432664.2; ENSG00000147889.18 ENST00000579755.2; ENSP00000462950.1; ENSG00000147889.18 |
GeneIDi | 1029 |
UCSCi | uc003zpl.4, human [Q8N726-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
NIEHS-SNPs |
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | S78535 mRNA Translation: AAC60649.1 Different initiation. U38945 mRNA Translation: AAB01737.1 Different initiation. AF527803 Genomic DNA Translation: AAM77919.1 Different initiation. AL449423 Genomic DNA Translation: CAH70601.1 Different initiation. CH471071 Genomic DNA Translation: EAW58600.1 Different initiation. CH471071 Genomic DNA Translation: EAW58601.1 Different initiation. BC015960 mRNA Translation: AAH15960.3 Different initiation. BC021998 mRNA Translation: AAH21998.3 Different initiation. U26727 mRNA Translation: AAA82236.1 BT007020 mRNA Translation: AAP35666.1 |
CCDSi | CCDS6511.2 [Q8N726-1] |
PIRi | I39004 |
RefSeqi | NP_478102.2, NM_058195.3 [Q8N726-1] |
3D structure databases
AlphaFoldDBi | Q8N726 |
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 107463, 281 interactors |
CORUMi | Q8N726 |
DIPi | DIP-24171N |
IntActi | Q8N726, 67 interactors |
MINTi | Q8N726 |
PTM databases
iPTMneti | Q8N726 |
Genetic variation databases
BioMutai | CDKN2A |
DMDMi | 384872321 |
Proteomic databases
jPOSTi | Q8N726 |
MassIVEi | Q8N726 |
MaxQBi | Q8N726 |
PeptideAtlasi | Q8N726 |
PRIDEi | Q8N726 |
ProteomicsDBi | 72258 [Q8N726-1] |
Protocols and materials databases
Antibodypediai | 3608, 1485 antibodies from 55 providers |
DNASUi | 1029 |
Genome annotation databases
Ensembli | ENST00000530628.2; ENSP00000432664.2; ENSG00000147889.18 ENST00000579755.2; ENSP00000462950.1; ENSG00000147889.18 |
GeneIDi | 1029 |
UCSCi | uc003zpl.4, human [Q8N726-1] |
Organism-specific databases
CTDi | 1029 |
DisGeNETi | 1029 |
GeneCardsi | CDKN2A |
HGNCi | HGNC:1787, CDKN2A |
HPAi | ENSG00000147889, Tissue enhanced (choroid plexus, pituitary gland) |
MalaCardsi | CDKN2A |
MIMi | 600160, gene |
neXtProti | NX_Q8N726 |
OpenTargetsi | ENSG00000147889 |
PharmGKBi | PA106 |
VEuPathDBi | HostDB:ENSG00000147889 |
GenAtlasi | Search... |
Phylogenomic databases
GeneTreei | ENSGT00940000163078 |
HOGENOMi | CLU_134503_0_0_1 |
OrthoDBi | 1435166at2759 |
Enzyme and pathway databases
PathwayCommonsi | Q8N726 |
Reactomei | R-HSA-111471, Apoptotic factor-mediated response R-HSA-2559580, Oxidative Stress Induced Senescence R-HSA-2559585, Oncogene Induced Senescence R-HSA-3108214, SUMOylation of DNA damage response and repair proteins R-HSA-3232118, SUMOylation of transcription factors R-HSA-6804757, Regulation of TP53 Degradation R-HSA-69541, Stabilization of p53 R-HSA-8941858, Regulation of RUNX3 expression and activity R-HSA-9645722, Defective Intrinsic Pathway for Apoptosis Due to p14ARF Loss of Function R-HSA-9646303, Evasion of Oncogene Induced Senescence Due to p14ARF Defects R-HSA-9646304, Evasion of Oxidative Stress Induced Senescence Due to p14ARF Defects |
SignaLinki | Q8N726 |
SIGNORi | Q8N726 |
Miscellaneous databases
BioGRID-ORCSi | 1029, 20 hits in 1089 CRISPR screens |
ChiTaRSi | CDKN2A, human |
GenomeRNAii | 1029 |
Pharosi | Q8N726, Tbio |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000147889, Expressed in adenohypophysis and 209 other tissues |
ExpressionAtlasi | Q8N726, baseline and differential |
Genevisiblei | Q8N726, HS |
Family and domain databases
DisProti | DP02167 [Q8N726-1] |
InterProi | View protein in InterPro IPR010868, Tumor_suppres_ARF |
Pfami | View protein in Pfam PF07392, P19Arf_N, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | ARF_HUMAN | |
Accessioni | Q8N726Primary (citable) accession number: Q8N726 Secondary accession number(s): D3DRK2 Q7KZR9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 11, 2005 |
Last sequence update: | April 18, 2012 | |
Last modified: | May 25, 2022 | |
This is version 181 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 9
Human chromosome 9: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot