Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Tumor suppressor ARF

Gene

CDKN2A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 Publications

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.Curated

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDNA-binding
Biological processApoptosis, Cell cycle, rRNA processing, Transcription, Transcription regulation, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-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
SIGNORiQ8N726

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor suppressor ARFCurated
Alternative name(s):
Alternative reading frame1 Publication
Short name:
ARF1 Publication
Cyclin-dependent kinase inhibitor 2AImported
p14ARF1 Publication
Gene namesi
Name:CDKN2AImported
Synonyms:CDKN2Imported, MLM
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000147889.16
HGNCiHGNC:1787 CDKN2A
MIMi600160 gene
neXtProtiNX_Q8N726

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion, Nucleus

Pathology & Biotechi

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi1029
MalaCardsiCDKN2A
OpenTargetsiENSG00000147889
PharmGKBiPA106

Polymorphism and mutation databases

BioMutaiUBR5
DMDMi384872321

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001441801 – 132Tumor suppressor ARFAdd BLAST132

Post-translational modificationi

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.2 Publications

Keywords - PTMi

Ubl conjugation

Proteomic databases

MaxQBiQ8N726
PeptideAtlasiQ8N726
PRIDEiQ8N726
ProteomicsDBi72258

PTM databases

iPTMnetiQ8N726

Expressioni

Gene expression databases

BgeeiENSG00000147889 Expressed in 195 organ(s), highest expression level in adenohypophysis
CleanExiHS_CDKN2A
ExpressionAtlasiQ8N726 baseline and differential
GenevisibleiQ8N726 HS

Organism-specific databases

HPAiCAB000093
CAB000445
CAB018232
HPA047838

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 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107463, 183 interactors
CORUMiQ8N726
DIPiDIP-24171N
IntActiQ8N726, 57 interactors
MINTiQ8N726

Structurei

3D structure databases

ProteinModelPortaliQ8N726
SMRiQ8N726
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 64Interaction with CDK5RAP3 and MDM21 PublicationAdd BLAST64

Phylogenomic databases

GeneTreeiENSGT00390000004527
HOGENOMiHOG000111485
HOVERGENiHBG071056

Family and domain databases

InterProiView protein in InterPro
IPR010868 Tumor_suppres_ARF
PfamiView protein in Pfam
PF07392 P19Arf_N, 1 hit

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket
Note: 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.By similarity
Isoform tumor suppressor ARF1 Publication (identifier: Q8N726-1) [UniParc]FASTAAdd to basket
Also known as: p14ARF1 Publication, p19ARF

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        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
Length:132
Mass (Da):13,903
Last modified:April 18, 2012 - v2
Checksum:i7739A9050C21BC96
GO
Isoform 1Curated (identifier: P42771-1) [UniParc]FASTAAdd to basket
Also known as: p16INK4aCurated
The sequence of this isoform can be found in the external entry P42771.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:156
Mass (Da):16,533
GO
Isoform 2Curated (identifier: P42771-2) [UniParc]FASTAAdd to basket
The sequence of this isoform can be found in the external entry P42771.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:105
Mass (Da):11,215
GO
Isoform 3Curated (identifier: P42771-3) [UniParc]FASTAAdd to basket
Also known as: p12Curated
The sequence of this isoform can be found in the external entry P42771.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:116
Mass (Da):12,083
GO
Isoform 5 (identifier: P42771-4) [UniParc]FASTAAdd to basket
Also known as: p16gamma
The sequence of this isoform can be found in the external entry P42771.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Note: Barely detectable in non-tumor cells.
Length:167
Mass (Da):17,883
GO
Isoform smARF (identifier: Q8N726-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-47: Missing.

Show »
Length:85
Mass (Da):8,731
Checksum:i4C9E739D74BEC556
GO

Sequence cautioni

The sequence AAB01737 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAC60649 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH15960 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH21998 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAM77919 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence CAH70601 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence EAW58600 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence EAW58601 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti28 – 30PRL → SWF in AAH15960 (PubMed:15489334).Curated3
Sequence conflicti28 – 30PRL → SWF in AAH21998 (PubMed:15489334).Curated3
Sequence conflicti28 – 30PRL → SWF in AAP35666 (PubMed:7624129).Curated3
Sequence conflicti94P → L in AAB01737 (Ref. 2) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02928717P → S1 PublicationCorresponds to variant dbSNP:rs3731190Ensembl.1
Natural variantiVAR_053033106G → R. Corresponds to variant dbSNP:rs4987127Ensembl.1
Natural variantiVAR_053034113P → L. Corresponds to variant dbSNP:rs34886500EnsemblClinVar.1
Natural variantiVAR_053035116G → D. Corresponds to variant dbSNP:rs35741010EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0449621 – 47Missing in isoform smARF. CuratedAdd BLAST47

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
CCDSiCCDS6511.2 [Q8N726-1]
PIRiI39004
RefSeqiNP_478102.2, NM_058195.3 [Q8N726-1]
UniGeneiHs.512599

Genome annotation databases

EnsembliENST00000530628; ENSP00000432664; ENSG00000147889 [Q8N726-1]
ENST00000579755; ENSP00000462950; ENSG00000147889 [Q8N726-1]
GeneIDi1029
UCSCiuc003zpl.4 human [Q8N726-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar 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
CCDSiCCDS6511.2 [Q8N726-1]
PIRiI39004
RefSeqiNP_478102.2, NM_058195.3 [Q8N726-1]
UniGeneiHs.512599

3D structure databases

ProteinModelPortaliQ8N726
SMRiQ8N726
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107463, 183 interactors
CORUMiQ8N726
DIPiDIP-24171N
IntActiQ8N726, 57 interactors
MINTiQ8N726

PTM databases

iPTMnetiQ8N726

Polymorphism and mutation databases

BioMutaiUBR5
DMDMi384872321

Proteomic databases

MaxQBiQ8N726
PeptideAtlasiQ8N726
PRIDEiQ8N726
ProteomicsDBi72258

Protocols and materials databases

DNASUi1029
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000530628; ENSP00000432664; ENSG00000147889 [Q8N726-1]
ENST00000579755; ENSP00000462950; ENSG00000147889 [Q8N726-1]
GeneIDi1029
UCSCiuc003zpl.4 human [Q8N726-1]

Organism-specific databases

CTDi1029
DisGeNETi1029
EuPathDBiHostDB:ENSG00000147889.16
GeneCardsiCDKN2A
HGNCiHGNC:1787 CDKN2A
HPAiCAB000093
CAB000445
CAB018232
HPA047838
MalaCardsiCDKN2A
MIMi600160 gene
neXtProtiNX_Q8N726
OpenTargetsiENSG00000147889
PharmGKBiPA106
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00390000004527
HOGENOMiHOG000111485
HOVERGENiHBG071056

Enzyme and pathway databases

ReactomeiR-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
SIGNORiQ8N726

Miscellaneous databases

ChiTaRSiCDKN2A human
GenomeRNAii1029
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000147889 Expressed in 195 organ(s), highest expression level in adenohypophysis
CleanExiHS_CDKN2A
ExpressionAtlasiQ8N726 baseline and differential
GenevisibleiQ8N726 HS

Family and domain databases

InterProiView protein in InterPro
IPR010868 Tumor_suppres_ARF
PfamiView protein in Pfam
PF07392 P19Arf_N, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiARF_HUMAN
AccessioniPrimary (citable) accession number: Q8N726
Secondary accession number(s): D3DRK2
, Q13195, Q13399, Q16360, Q7KZR9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2005
Last sequence update: April 18, 2012
Last modified: November 7, 2018
This is version 158 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

Complete proteome, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again