UniProtKB - Q64364 (ARF_MOUSE)
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 (By similarity).
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.
By similarity8 PublicationsCaution
GO - Molecular functioni
- cyclin-dependent protein serine/threonine kinase inhibitor activity Source: MGI
- disordered domain specific binding Source: MGI
- DNA binding Source: UniProtKB-KW
- MDM2/MDM4 family protein binding Source: CAFA
- NF-kappaB binding Source: MGI
- p53 binding Source: MGI
- protein kinase binding Source: MGI
- protein N-terminus binding Source: MGI
- RNA polymerase II-specific DNA-binding transcription factor binding Source: MGI
- SUMO transferase activity Source: MGI
- ubiquitin ligase inhibitor activity Source: MGI
- ubiquitin-protein transferase inhibitor activity Source: BHF-UCL
GO - Biological processi
- activation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
- aging Source: MGI
- amyloid fibril formation Source: MGI
- apoptotic mitochondrial changes Source: MGI
- autophagy of mitochondrion Source: MGI
- cell aging Source: MGI
- cell cycle Source: UniProtKB-KW
- cellular response to hydrogen peroxide Source: MGI
- cellular senescence Source: MGI
- epidermis development Source: MGI
- glucose homeostasis Source: MGI
- mitochondrial depolarization Source: MGI
- negative regulation of B cell proliferation Source: HGNC-UCL
- negative regulation of cell cycle Source: MGI
- negative regulation of cell growth Source: BHF-UCL
- negative regulation of cell-matrix adhesion Source: MGI
- negative regulation of cell population proliferation Source: MGI
- negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: MGI
- negative regulation of hepatocyte proliferation Source: MGI
- negative regulation of immature T cell proliferation in thymus Source: HGNC-UCL
- negative regulation of mammary gland epithelial cell proliferation Source: MGI
- negative regulation of NF-kappaB transcription factor activity Source: MGI
- negative regulation of phosphorylation Source: MGI
- negative regulation of protein binding Source: MGI
- negative regulation of protein kinase activity Source: MGI
- negative regulation of protein neddylation Source: MGI
- negative regulation of proteolysis involved in cellular protein catabolic process Source: MGI
- negative regulation of transcription, DNA-templated Source: MGI
- negative regulation of ubiquitin-dependent protein catabolic process Source: MGI
- negative regulation of ubiquitin protein ligase activity Source: MGI
- negative regulation of ubiquitin-protein transferase activity Source: BHF-UCL
- positive regulation of apoptotic process Source: UniProtKB
- positive regulation of apoptotic process involved in mammary gland involution Source: MGI
- positive regulation of DNA-binding transcription factor activity Source: BHF-UCL
- positive regulation of DNA damage response, signal transduction by p53 class mediator Source: MGI
- positive regulation of gene expression Source: MGI
- positive regulation of protein localization to nucleus Source: MGI
- positive regulation of protein sumoylation Source: MGI
- positive regulation of signal transduction by p53 class mediator Source: MGI
- positive regulation of transcription, DNA-templated Source: BHF-UCL
- positive regulation of transcription by RNA polymerase II Source: MGI
- protein destabilization Source: MGI
- protein K63-linked ubiquitination Source: UniProtKB
- protein polyubiquitination Source: UniProtKB
- protein stabilization Source: MGI
- regulation of apoptotic DNA fragmentation Source: MGI
- regulation of cell cycle Source: MGI
- regulation of cyclin-dependent protein serine/threonine kinase activity Source: MGI
- regulation of DNA-binding transcription factor activity Source: MGI
- regulation of G1/S transition of mitotic cell cycle Source: MGI
- regulation of G2/M transition of mitotic cell cycle Source: MGI
- regulation of gene expression Source: MGI
- regulation of nucleocytoplasmic transport Source: MGI
- regulation of protein export from nucleus Source: MGI
- regulation of protein stability Source: BHF-UCL
- regulation of protein targeting to mitochondrion Source: MGI
- replicative senescence Source: MGI
- response to organic cyclic compound Source: MGI
- response to organonitrogen compound Source: MGI
- response to xenobiotic stimulus Source: MGI
- rRNA processing Source: UniProtKB-KW
- rRNA transcription Source: MGI
- somatic stem cell division Source: HGNC-UCL
- somatic stem cell population maintenance Source: MGI
Keywordsi
Molecular function | DNA-binding |
Biological process | Apoptosis, Cell cycle, rRNA processing, Transcription, Transcription regulation, Ubl conjugation pathway |
Names & Taxonomyi
Protein namesi | Recommended name: Tumor suppressor ARFCuratedAlternative name(s): Alternative reading frame Short name: ARF Cyclin-dependent kinase inhibitor 2A p19ARF |
Gene namesi | Name:Cdkn2aImported |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:104738, Cdkn2a |
VEuPathDBi | HostDB:ENSMUSG00000044303 |
Subcellular locationi
Nucleus
- nucleolus By similarity4 Publications
- nucleoplasm By similarity
Mitochondrion
- Mitochondrion 1 Publication
Mitochondrion
- mitochondrion Source: MGI
Nucleus
- granular component Source: BHF-UCL
- nucleolus Source: MGI
- nucleoplasm Source: MGI
- nucleus Source: MGI
Other locations
- cytoplasm Source: MGI
- protein-containing complex Source: CAFA
- senescence-associated heterochromatin focus Source: MGI
Keywords - Cellular componenti
Mitochondrion, NucleusPathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 85 | L → P or R: No effect on activity. 1 Publication | 1 | |
Mutagenesisi | 93 | P → S: No effect on activity. 1 Publication | 1 | |
Mutagenesisi | 97 | R → Q: No effect on activity. 1 Publication | 1 | |
Mutagenesisi | 105 – 106 | Missing : No effect on activity. 1 Publication | 2 | |
Mutagenesisi | 120 | A → T: No effect on activity. 1 Publication | 1 |
Keywords - Diseasei
Tumor suppressorPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000144182 | 1 – 169 | Tumor suppressor ARFAdd BLAST | 169 |
Post-translational modificationi
Keywords - PTMi
Ubl conjugationProteomic databases
EPDi | Q64364 |
MaxQBi | Q64364 |
PaxDbi | Q64364 |
PeptideAtlasi | Q64364 |
PRIDEi | Q64364 |
ProteomicsDBi | 282012 [Q64364-1] 282013 [Q64364-2] |
PTM databases
iPTMneti | Q64364 |
Expressioni
Developmental stagei
Inductioni
Gene expression databases
Bgeei | ENSMUSG00000044303, Expressed in spinal cord and 80 other tissues |
ExpressionAtlasi | Q64364, baseline and differential |
Genevisiblei | Q64364, MM |
Interactioni
Subunit structurei
Does not interact with cyclins, CDK1, CDK2, CDK4, CDK5 or CDK6.
Interacts with COMMD1 (By similarity). Binds to BCL6, E2F1, HUWE1, MDM2, MYC, NPM1/B23, TOP1/TOPOI and UBE2I/UBC9.
Interacts with TBRG1.
Interacts with CDKN2AIP and E4F1. Isoform smARF interacts with C1QBP.
Interacts with CDK5RAP3 and MDM2; form a ternary complex involved in regulation of p53/TP53.
Interacts with NOP53; the interaction is direct and promotes ARF nucleoplasmic relocalization and ubiquitin-mediated proteasomal degradation (By similarity).
By similarity6 PublicationsBinary interactionsi
Q64364
With | #Exp. | IntAct |
---|---|---|
Mta1 [Q8K4B0] | 2 | EBI-1202287,EBI-1216353 |
C1QBP [Q07021] from Homo sapiens. | 4 | EBI-1202287,EBI-347528 |
NPM1 [P06748] from Homo sapiens. | 2 | EBI-1202287,EBI-78579 |
Isoform tumor suppressor ARF [Q64364-1]
With | #Exp. | IntAct |
---|---|---|
Pex19 [Q8VCI5] | 4 | EBI-1202306,EBI-1810767 |
GO - Molecular functioni
- disordered domain specific binding Source: MGI
- MDM2/MDM4 family protein binding Source: CAFA
- NF-kappaB binding Source: MGI
- p53 binding Source: MGI
- protein kinase binding Source: MGI
- protein N-terminus binding Source: MGI
- RNA polymerase II-specific DNA-binding transcription factor binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 198654, 40 interactors |
CORUMi | Q64364 |
DIPi | DIP-24169N |
IntActi | Q64364, 11 interactors |
STRINGi | 10090.ENSMUSP00000102748 |
Miscellaneous databases
RNActi | Q64364, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q64364 |
SMRi | Q64364 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q64364 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 63 | Interaction with CDK5RAP3 and MDM2By similarityAdd BLAST | 63 | |
Regioni | 54 – 73 | DisorderedSequence analysisAdd BLAST | 20 |
Phylogenomic databases
eggNOGi | ENOG502T9HM, Eukaryota |
GeneTreei | ENSGT00940000168083 |
HOGENOMi | CLU_134503_0_0_1 |
InParanoidi | Q64364 |
PhylomeDBi | Q64364 |
Family and domain databases
DisProti | DP00335 |
IDEALi | IID50036 |
InterProi | View protein in InterPro IPR010868, Tumor_suppres_ARF |
Pfami | View protein in Pfam PF07392, P19Arf_N, 1 hit |
s (4)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis 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
MGRRFLVTVR IQRAGRPLQE RVFLVKFVRS RRPRTASCAL AFVNMLLRLE
60 70 80 90 100
RILRRGPHRN PGPGDDDGQR SRSSSSAQLR CRFELRGPHY LLPPGARRSA
110 120 130 140 150
GRLPGHAGGA ARVRGSAGCA RCLGSPAARL GPRAGTSRHR AIFAFRWVLF
160
VFRWVVFVYR WERRPDRRA
The sequence of this isoform differs from the canonical sequence as follows:
1-44: Missing.
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_044963 | 1 – 44 | Missing in isoform smARF. CuratedAdd BLAST | 44 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L76092 mRNA Translation: AAC42080.1 BC058190 mRNA Translation: AAH58190.3 S80650 mRNA Translation: AAB35770.1 AJ238890 Genomic DNA Translation: CAB65598.1 U49281 Genomic DNA Translation: AAC00053.1 U49282 Genomic DNA Translation: AAC00054.1 AF120108 Genomic DNA Translation: AAD33245.1 |
CCDSi | CCDS18350.1 [Q64364-1] |
RefSeqi | NP_034007.1, NM_009877.2 [Q64364-1] |
Genome annotation databases
Ensembli | ENSMUST00000107131; ENSMUSP00000102748; ENSMUSG00000044303 [Q64364-1] |
GeneIDi | 12578 |
UCSCi | uc008toi.1, mouse [Q64364-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L76092 mRNA Translation: AAC42080.1 BC058190 mRNA Translation: AAH58190.3 S80650 mRNA Translation: AAB35770.1 AJ238890 Genomic DNA Translation: CAB65598.1 U49281 Genomic DNA Translation: AAC00053.1 U49282 Genomic DNA Translation: AAC00054.1 AF120108 Genomic DNA Translation: AAD33245.1 |
CCDSi | CCDS18350.1 [Q64364-1] |
RefSeqi | NP_034007.1, NM_009877.2 [Q64364-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1HN3 | NMR | - | A | 1-37 | [»] | |
AlphaFoldDBi | Q64364 | |||||
SMRi | Q64364 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 198654, 40 interactors |
CORUMi | Q64364 |
DIPi | DIP-24169N |
IntActi | Q64364, 11 interactors |
STRINGi | 10090.ENSMUSP00000102748 |
PTM databases
iPTMneti | Q64364 |
Proteomic databases
EPDi | Q64364 |
MaxQBi | Q64364 |
PaxDbi | Q64364 |
PeptideAtlasi | Q64364 |
PRIDEi | Q64364 |
ProteomicsDBi | 282012 [Q64364-1] 282013 [Q64364-2] |
Protocols and materials databases
DNASUi | 12578 |
Genome annotation databases
Ensembli | ENSMUST00000107131; ENSMUSP00000102748; ENSMUSG00000044303 [Q64364-1] |
GeneIDi | 12578 |
UCSCi | uc008toi.1, mouse [Q64364-1] |
Organism-specific databases
CTDi | 1029 |
MGIi | MGI:104738, Cdkn2a |
VEuPathDBi | HostDB:ENSMUSG00000044303 |
Phylogenomic databases
eggNOGi | ENOG502T9HM, Eukaryota |
GeneTreei | ENSGT00940000168083 |
HOGENOMi | CLU_134503_0_0_1 |
InParanoidi | Q64364 |
PhylomeDBi | Q64364 |
Miscellaneous databases
BioGRID-ORCSi | 12578, 5 hits in 72 CRISPR screens |
ChiTaRSi | Cdkn2a, mouse |
EvolutionaryTracei | Q64364 |
RNActi | Q64364, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000044303, Expressed in spinal cord and 80 other tissues |
ExpressionAtlasi | Q64364, baseline and differential |
Genevisiblei | Q64364, MM |
Family and domain databases
DisProti | DP00335 |
IDEALi | IID50036 |
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_MOUSE | |
Accessioni | Q64364Primary (citable) accession number: Q64364 Secondary accession number(s): Q4U255, Q9QXC7, Q9R051 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 11, 2005 |
Last sequence update: | November 1, 1996 | |
Last modified: | May 25, 2022 | |
This is version 171 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references