ARF_MOUSE
ID ARF_MOUSE Reviewed; 169 AA.
AC Q64364; Q4U255; Q9QXC7; Q9R051;
DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Tumor suppressor ARF {ECO:0000305};
DE AltName: Full=Alternative reading frame;
DE Short=ARF;
DE AltName: Full=Cyclin-dependent kinase inhibitor 2A;
DE AltName: Full=p19ARF;
GN Name=Cdkn2a {ECO:0000312|EMBL:AAB35770.1, ECO:0000312|MGI:MGI:104738};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAB35770.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=8521522; DOI=10.1016/0092-8674(95)90214-7;
RA Quelle D.E., Zindy F., Ashmun R.A., Sherr C.J.;
RT "Alternative reading frames of the INK4a tumor suppressor gene encode two
RT unrelated proteins capable of inducing cell cycle arrest.";
RL Cell 83:993-1000(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NMRI; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3] {ECO:0000305, ECO:0000312|EMBL:CAB65598.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-64.
RC STRAIN=129/SvJ {ECO:0000312|EMBL:CAB65598.1};
RX PubMed=10753221; DOI=10.1093/carcin/21.4.817;
RA Melendez B., Malumbres M., de Castro I.P., Santos J., Pellicer A.,
RA Fernandez-Piqueras J.;
RT "Characterization of the murine p19ARF promoter CpG island and its
RT methylation pattern in primary lymphomas.";
RL Carcinogenesis 21:817-821(2000).
RN [4] {ECO:0000305, ECO:0000312|EMBL:AAC00053.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-63.
RC STRAIN=020 {ECO:0000269|PubMed:9021155},
RC 129/J {ECO:0000312|EMBL:AAC00054.1}, A/J {ECO:0000312|EMBL:AAC00054.1},
RC A/Wy {ECO:0000312|EMBL:AAC00054.1}, AKR/J {ECO:0000312|EMBL:AAC00054.1},
RC B10.A {ECO:0000312|EMBL:AAC00054.1},
RC B10.D2(58N) {ECO:0000312|EMBL:AAC00054.1},
RC BALB/cJ {ECO:0000269|PubMed:9021155},
RC C3H/21BG {ECO:0000269|PubMed:9021155},
RC C3H/HeJ {ECO:0000269|PubMed:9021155},
RC C57BL/10ScNJ {ECO:0000312|EMBL:AAC00054.1},
RC C57BL/10SN {ECO:0000312|EMBL:AAC00054.1},
RC C57BL/6By {ECO:0000312|EMBL:AAC00054.1},
RC C57BL/6J {ECO:0000269|PubMed:9021155},
RC C57BR/cdJ {ECO:0000312|EMBL:AAC00054.1},
RC CBA/J {ECO:0000269|PubMed:9021155}, DBA/2J {ECO:0000312|EMBL:AAC00054.1},
RC HS/IBG {ECO:0000312|EMBL:AAC00054.1}, LP/J {ECO:0000312|EMBL:AAC00054.1},
RC LS/IBG {ECO:0000312|EMBL:AAC00054.1}, MA/M4J {ECO:0000312|EMBL:AAC00053.1},
RC PL/J {ECO:0000269|PubMed:9021155}, RF/J {ECO:0000312|EMBL:AAC00054.1},
RC Sencar {ECO:0000269|PubMed:9021155}, SJL/J {ECO:0000312|EMBL:AAC00054.1},
RC SM/J {ECO:0000312|EMBL:AAC00054.1}, ST/J {ECO:0000312|EMBL:AAC00054.1}, and
RC SWR/J {ECO:0000312|EMBL:AAC00054.1};
RC TISSUE=Lung {ECO:0000269|PubMed:9021155};
RX PubMed=9021155; DOI=10.1007/s003359900352;
RA Herzog C.R., You M.;
RT "Sequence variation and chromosomal mapping of the murine Cdkn2a tumor
RT suppressor gene.";
RL Mamm. Genome 8:65-66(1997).
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAD33245.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-63.
RC STRAIN=129/SvjE {ECO:0000312|EMBL:AAD33245.1};
RX PubMed=10097151; DOI=10.1073/pnas.96.7.3993;
RA Inoue K., Roussel M.F., Sherr C.J.;
RT "Induction of ARF tumor suppressor gene expression and cell cycle arrest by
RT transcription factor DMP1.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:3993-3998(1999).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=9393858; DOI=10.1016/s0092-8674(00)80452-3;
RA Kamijo T., Zindy F., Roussel M.F., Quelle D.E., Downing J.R., Ashmun R.A.,
RA Grosveld G., Sherr C.J.;
RT "Tumor suppression at the mouse INK4a locus mediated by the alternative
RT reading frame product p19ARF.";
RL Cell 91:649-659(1997).
RN [7] {ECO:0000305}
RP MUTAGENESIS OF LEU-85; PRO-93; ARG-97; 105-GLY-HIS-106 AND ALA-120.
RX PubMed=9012842; DOI=10.1073/pnas.94.2.669;
RA Quelle D.E., Cheng M., Ashmun R.A., Sherr C.J.;
RT "Cancer-associated mutations at the INK4a locus cancel cell cycle arrest by
RT p16INK4a but not by the alternative reading frame protein p19ARF.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:669-673(1997).
RN [8] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH MDM2.
RX PubMed=9529248; DOI=10.1016/s0092-8674(00)81400-2;
RA Pomerantz J., Schreiber-Agus N., Liegeois N.J., Silverman A., Alland L.,
RA Chin L., Potes J., Chen K., Orlow I., Lee H.-W., Cordon-Cardo C.,
RA DePinho R.A.;
RT "The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and
RT neutralizes MDM2's inhibition of p53.";
RL Cell 92:713-723(1998).
RN [9] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10359817; DOI=10.1073/pnas.96.12.6937;
RA Tao W., Levine A.J.;
RT "P19(ARF) stabilizes p53 by blocking nucleo-cytoplasmic shuttling of
RT Mdm2.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:6937-6941(1999).
RN [10]
RP INDUCTION.
RX PubMed=10898794;
RA Inoue K., Wen R., Rehg J.E., Adachi M., Cleveland J.L., Roussel M.F.,
RA Sherr C.J.;
RT "Disruption of the ARF transcriptional activator DMP1 facilitates cell
RT immortalization, Ras transformation, and tumorigenesis.";
RL Genes Dev. 14:1797-1809(2000).
RN [11]
RP INTERACTION WITH CDKN2AIP.
RX PubMed=12154087; DOI=10.1074/jbc.m204177200;
RA Hasan M.K., Yaguchi T., Sugihara T., Kumar P.K.R., Taira K., Reddel R.R.,
RA Kaul S.C., Wadhwa R.;
RT "CARF is a novel protein that cooperates with mouse p19ARF (human p14ARF)
RT in activating p53.";
RL J. Biol. Chem. 277:37765-37770(2002).
RN [12] {ECO:0000305}
RP DEVELOPMENTAL STAGE, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15105443; DOI=10.1091/mbc.e03-11-0785;
RA Yi Y., Shepard A., Kittrell F., Mulac-Jericevic B., Medina D., Said T.K.;
RT "p19ARF determines the balance between normal cell proliferation rate and
RT apoptosis during mammary gland development.";
RL Mol. Biol. Cell 15:2302-2311(2004).
RN [13] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH MYC.
RX PubMed=15361884; DOI=10.1038/nature02958;
RA Qi Y., Gregory M.A., Li Z., Brousal J.P., West K., Hann S.R.;
RT "p19ARF directly and differentially controls the functions of c-Myc
RT independently of p53.";
RL Nature 431:712-717(2004).
RN [14] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BCL6.
RX PubMed=15567177; DOI=10.1016/j.bbrc.2004.11.016;
RA Suzuki H., Kurita M., Mizumoto K., Moriyama M., Aiso S., Nishimoto I.,
RA Matsuoka M.;
RT "The ARF tumor suppressor inhibits BCL6-mediated transcriptional
RT repression.";
RL Biochem. Biophys. Res. Commun. 326:242-248(2005).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=15601844; DOI=10.1128/mcb.25.1.220-232.2005;
RA Sreeramaneni R., Chaudhry A., McMahon M., Sherr C.J., Inoue K.;
RT "Ras-Raf-Arf signaling critically depends on the Dmp1 transcription
RT factor.";
RL Mol. Cell. Biol. 25:220-232(2005).
RN [16]
RP ALTERNATIVE SPLICING (ISOFORM SMARF), FUNCTION (ISOFORM SMARF), AND
RP SUBCELLULAR LOCATION (ISOFORM SMARF).
RX PubMed=16713577; DOI=10.1016/j.molcel.2006.04.014;
RA Reef S., Zalckvar E., Shifman O., Bialik S., Sabanay H., Oren M.,
RA Kimchi A.;
RT "A short mitochondrial form of p19ARF induces autophagy and caspase-
RT independent cell death.";
RL Mol. Cell 22:463-475(2006).
RN [17]
RP FUNCTION.
RX PubMed=17936562; DOI=10.1016/j.ccr.2007.08.034;
RA Mallakin A., Sugiyama T., Taneja P., Matise L.A., Frazier D.P.,
RA Choudhary M., Hawkins G.A., D'Agostino R.B. Jr., Willingham M.C., Inoue K.;
RT "Mutually exclusive inactivation of DMP1 and ARF/p53 in lung cancer.";
RL Cancer Cell 12:381-394(2007).
RN [18]
RP INTERACTION WITH TBRG1.
RX PubMed=17110379; DOI=10.1074/jbc.m609612200;
RA Tompkins V.S., Hagen J., Frazier A.A., Lushnikova T., Fitzgerald M.P.,
RA di Tommaso A.D., Ladeveze V., Domann F.E., Eischen C.M., Quelle D.E.;
RT "A novel nuclear interactor of ARF and MDM2 (NIAM) that maintains
RT chromosomal stability.";
RL J. Biol. Chem. 282:1322-1333(2007).
RN [19]
RP INTERACTION WITH C1QBP.
RX PubMed=17486078; DOI=10.1038/sj.onc.1210485;
RA Reef S., Shifman O., Oren M., Kimchi A.;
RT "The autophagic inducer smARF interacts with and is stabilized by the
RT mitochondrial p32 protein.";
RL Oncogene 26:6677-6683(2007).
RN [20]
RP INDUCTION.
RX PubMed=17546045; DOI=10.1038/sj.onc.1210568;
RA Taneja P., Mallakin A., Matise L.A., Frazier D.P., Choudhary M., Inoue K.;
RT "Repression of Dmp1 and Arf transcription by anthracyclins: critical roles
RT of the NF-kappaB subunit p65.";
RL Oncogene 26:7457-7466(2007).
RN [21]
RP FUNCTION, INTERACTION WITH TTF1, AND SUBCELLULAR LOCATION.
RX PubMed=20513429; DOI=10.1016/j.molcel.2010.03.015;
RA Lessard F., Morin F., Ivanchuk S., Langlois F., Stefanovsky V., Rutka J.,
RA Moss T.;
RT "The ARF tumor suppressor controls ribosome biogenesis by regulating the
RT RNA polymerase I transcription factor TTF-I.";
RL Mol. Cell 38:539-550(2010).
RN [22] {ECO:0000305}
RP STRUCTURE BY NMR OF 1-37.
RX PubMed=11327858; DOI=10.1021/bi0024005;
RA DiGiammarino E.L., Filippov I., Weber J.D., Bothner B., Kriwacki R.W.;
RT "Solution structure of the p53 regulatory domain of the p19Arf tumor
RT suppressor protein.";
RL Biochemistry 40:2379-2386(2001).
CC -!- FUNCTION: Capable of inducing cell cycle arrest in G1 and G2 phases
CC (PubMed:8521522, PubMed:9393858). Acts as a tumor suppressor
CC (PubMed:8521522, PubMed:9393858, PubMed:15601844, PubMed:17936562).
CC Binds to MDM2 and blocks its nucleocytoplasmic shuttling by
CC sequestering it in the nucleolus (PubMed:9529248, PubMed:10359817).
CC This inhibits the oncogenic action of MDM2 by blocking MDM2-induced
CC degradation of p53 and enhancing p53-dependent transactivation and
CC apoptosis (PubMed:10359817). Also induces G2 arrest and apoptosis in a
CC p53-independent manner by preventing the activation of cyclin B1/CDC2
CC complexes (PubMed:15361884). Binds to BCL6 and down-regulates BCL6-
CC induced transcriptional repression (PubMed:15567177). Binds to E2F1 and
CC MYC and blocks their transcriptional activator activity but has no
CC effect on MYC transcriptional repression (By similarity). Binds to
CC TOP1/TOPOI and stimulates its activity (By similarity). This complex
CC binds to rRNA gene promoters and may play a role in rRNA transcription
CC and/or maturation (By similarity). Interacts with NPM1/B23 and promotes
CC its polyubiquitination and degradation, thus inhibiting rRNA processing
CC (By similarity). Plays a role in inhibiting ribosome biogenesis,
CC perhaps by binding to the nucleolar localization sequence of
CC transcription termination factor TTF1, and thereby preventing nucleolar
CC localization of TTF1 (PubMed:20513429). Interacts with COMMD1 and
CC promotes its 'Lys63'-linked polyubiquitination (By similarity).
CC Interacts with UBE2I/UBC9 and enhances sumoylation of a number of its
CC binding partners including MDM2 and E2F1 (By similarity). Binds to
CC HUWE1 and represses its ubiquitin ligase activity (By similarity). May
CC play a role in controlling cell proliferation and apoptosis during
CC mammary gland development (By similarity).
CC {ECO:0000250|UniProtKB:Q8N726, ECO:0000269|PubMed:10359817,
CC ECO:0000269|PubMed:15361884, ECO:0000269|PubMed:15567177,
CC ECO:0000269|PubMed:15601844, ECO:0000269|PubMed:17936562,
CC ECO:0000269|PubMed:20513429, ECO:0000269|PubMed:8521522,
CC ECO:0000269|PubMed:9393858, ECO:0000269|PubMed:9529248}.
CC -!- FUNCTION: [Isoform smARF]: May be involved in regulation of autophagy
CC and caspase-independent cell death; the short-lived mitochondrial
CC isoform is stabilized by C1QBP. {ECO:0000269|PubMed:16713577}.
CC -!- SUBUNIT: Does not interact with cyclins, CDK1, CDK2, CDK4, CDK5 or
CC CDK6. Interacts with COMMD1 (By similarity). Binds to BCL6, E2F1,
CC HUWE1, MDM2, MYC, NPM1/B23, TOP1/TOPOI and UBE2I/UBC9. Interacts with
CC TBRG1. Interacts with CDKN2AIP and E4F1. Interacts with CDK5RAP3 and
CC MDM2; form a ternary complex involved in regulation of p53/TP53.
CC Interacts with NOP53; the interaction is direct and promotes ARF
CC nucleoplasmic relocalization and ubiquitin-mediated proteasomal
CC degradation (By similarity). Interacts with TTF1 (via the N-terminal
CC region (NRD) and a C-terminal region); the interaction is direct and
CC inhibits the nucleolar localization of TTF1 (PubMed:20513429).
CC {ECO:0000250|UniProtKB:Q8N726, ECO:0000269|PubMed:12154087,
CC ECO:0000269|PubMed:15361884, ECO:0000269|PubMed:15567177,
CC ECO:0000269|PubMed:17110379, ECO:0000269|PubMed:17486078,
CC ECO:0000269|PubMed:9529248}.
CC -!- SUBUNIT: [Isoform smARF]: Interacts with C1QBP.
CC {ECO:0000269|PubMed:16713577}.
CC -!- INTERACTION:
CC Q64364; Q8K4B0: Mta1; NbExp=2; IntAct=EBI-1202287, EBI-1216353;
CC Q64364; Q07021: C1QBP; Xeno; NbExp=4; IntAct=EBI-1202287, EBI-347528;
CC Q64364; P06748: NPM1; Xeno; NbExp=2; IntAct=EBI-1202287, EBI-78579;
CC Q64364-1; Q8VCI5: Pex19; NbExp=4; IntAct=EBI-1202306, EBI-1810767;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000250|UniProtKB:Q8N726,
CC ECO:0000269|PubMed:10359817, ECO:0000269|PubMed:15567177,
CC ECO:0000269|PubMed:15601844, ECO:0000269|PubMed:8521522,
CC ECO:0000305|PubMed:20513429}. Nucleus, nucleoplasm
CC {ECO:0000250|UniProtKB:Q8N726, ECO:0000305|PubMed:20513429}.
CC -!- SUBCELLULAR LOCATION: [Isoform smARF]: Mitochondrion
CC {ECO:0000269|PubMed:16713577}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Isoform 1 and isoform tumor suppressor ARF arise due to the
CC use of two alternative first exons joined to a common exon 2 at the
CC same acceptor site but in different reading frames, resulting in two
CC completely different isoforms. {ECO:0000269|PubMed:8521522};
CC Name=tumor suppressor ARF {ECO:0000303|PubMed:10097151};
CC Synonyms=p19ARF {ECO:0000303|PubMed:8521522};
CC IsoId=Q64364-1; Sequence=Displayed;
CC Name=1 {ECO:0000305}; Synonyms=p16INK4a {ECO:0000305};
CC IsoId=P51480-1; Sequence=External;
CC Name=2 {ECO:0000305};
CC IsoId=P51480-2; Sequence=External;
CC Name=smARF;
CC IsoId=Q64364-2; Sequence=VSP_044963;
CC -!- DEVELOPMENTAL STAGE: Not detected in 12-week virgin mammary glands.
CC Expression increases (at protein level) six-fold during pregnancy and
CC remains at this level during lactation. During involution, a slight
CC increase is observed at days 2 and 8 followed by a sharp decline at day
CC 15. {ECO:0000269|PubMed:15105443}.
CC -!- INDUCTION: By progesterone. Induced by activated Ras, and this requires
CC DMTF1. Repressed by non-classical inhibitors of NF-kappa-B signaling
CC such as doxorubicin, daunorubicin and UVC, and by the NF-kappa-B p65
CC subunit (RELA). {ECO:0000269|PubMed:10898794,
CC ECO:0000269|PubMed:15105443, ECO:0000269|PubMed:15601844,
CC ECO:0000269|PubMed:17546045}.
CC -!- PTM: Ubiquitinated in normal cells by TRIP12 via the ubiquitin fusion
CC degradation (UFD) pathway, a process that mediates ubiquitination at
CC the N-terminus, regardless of the absence of lysine residues.
CC Ubiquitination leads to its proteasomal degradation. In cancer cells,
CC however, TRIP12 is located in a different cell compartment, preventing
CC ubiquitination and degradation. {ECO:0000250|UniProtKB:Q8N726}.
CC -!- DISRUPTION PHENOTYPE: Mice lacking isoform tumor suppressor ARF of
CC Cdkn2a display delayed mammary gland involution.
CC {ECO:0000269|PubMed:15105443}.
CC -!- CAUTION: The proteins described here are encoded by the gene CDKN2A,
CC but are completely unrelated in terms of sequence and function to
CC cyclin-dependent kinase inhibitor 2A (AC P51480) which is encoded by
CC the same gene. {ECO:0000305}.
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DR EMBL; L76092; AAC42080.1; -; mRNA.
DR EMBL; BC058190; AAH58190.3; -; mRNA.
DR EMBL; S80650; AAB35770.1; -; mRNA.
DR EMBL; AJ238890; CAB65598.1; -; Genomic_DNA.
DR EMBL; U49281; AAC00053.1; -; Genomic_DNA.
DR EMBL; U49282; AAC00054.1; -; Genomic_DNA.
DR EMBL; AF120108; AAD33245.1; -; Genomic_DNA.
DR CCDS; CCDS18350.1; -. [Q64364-1]
DR RefSeq; NP_034007.1; NM_009877.2. [Q64364-1]
DR PDB; 1HN3; NMR; -; A=1-37.
DR PDBsum; 1HN3; -.
DR AlphaFoldDB; Q64364; -.
DR SMR; Q64364; -.
DR BioGRID; 198654; 40.
DR CORUM; Q64364; -.
DR DIP; DIP-24169N; -.
DR IntAct; Q64364; 11.
DR STRING; 10090.ENSMUSP00000102748; -.
DR iPTMnet; Q64364; -.
DR EPD; Q64364; -.
DR MaxQB; Q64364; -.
DR PaxDb; Q64364; -.
DR PeptideAtlas; Q64364; -.
DR PRIDE; Q64364; -.
DR ProteomicsDB; 282012; -. [Q64364-1]
DR ProteomicsDB; 282013; -. [Q64364-2]
DR DNASU; 12578; -.
DR Ensembl; ENSMUST00000107131; ENSMUSP00000102748; ENSMUSG00000044303. [Q64364-1]
DR GeneID; 12578; -.
DR UCSC; uc008toi.1; mouse. [Q64364-1]
DR CTD; 1029; -.
DR MGI; MGI:104738; Cdkn2a.
DR VEuPathDB; HostDB:ENSMUSG00000044303; -.
DR eggNOG; ENOG502T9HM; Eukaryota.
DR GeneTree; ENSGT00940000168083; -.
DR HOGENOM; CLU_134503_0_0_1; -.
DR InParanoid; Q64364; -.
DR PhylomeDB; Q64364; -.
DR BioGRID-ORCS; 12578; 5 hits in 72 CRISPR screens.
DR ChiTaRS; Cdkn2a; mouse.
DR EvolutionaryTrace; Q64364; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q64364; protein.
DR Bgee; ENSMUSG00000044303; Expressed in yolk sac and 53 other tissues.
DR ExpressionAtlas; Q64364; baseline and differential.
DR Genevisible; Q64364; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0001652; C:granular component; IDA:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; IMP:CAFA.
DR GO; GO:0035985; C:senescence-associated heterochromatin focus; ISO:MGI.
DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; IDA:MGI.
DR GO; GO:0097718; F:disordered domain specific binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0097371; F:MDM2/MDM4 family protein binding; IPI:CAFA.
DR GO; GO:0051059; F:NF-kappaB binding; ISO:MGI.
DR GO; GO:0002039; F:p53 binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:MGI.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0019789; F:SUMO transferase activity; ISO:MGI.
DR GO; GO:1990948; F:ubiquitin ligase inhibitor activity; ISO:MGI.
DR GO; GO:0055105; F:ubiquitin-protein transferase inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0007568; P:aging; IMP:MGI.
DR GO; GO:1990000; P:amyloid fibril formation; ISO:MGI.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; ISO:MGI.
DR GO; GO:0060057; P:apoptotic process involved in mammary gland involution; IMP:MGI.
DR GO; GO:0000422; P:autophagy of mitochondrion; ISO:MGI.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IDA:MGI.
DR GO; GO:0090398; P:cellular senescence; IDA:MGI.
DR GO; GO:0008544; P:epidermis development; IMP:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IMP:MGI.
DR GO; GO:0033598; P:mammary gland epithelial cell proliferation; IMP:MGI.
DR GO; GO:0051882; P:mitochondrial depolarization; ISO:MGI.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; IMP:HGNC-UCL.
DR GO; GO:0045786; P:negative regulation of cell cycle; IDA:MGI.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:BHF-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0001953; P:negative regulation of cell-matrix adhesion; ISO:MGI.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:MGI.
DR GO; GO:2000346; P:negative regulation of hepatocyte proliferation; ISO:MGI.
DR GO; GO:0033088; P:negative regulation of immature T cell proliferation in thymus; IMP:HGNC-UCL.
DR GO; GO:0033600; P:negative regulation of mammary gland epithelial cell proliferation; IMP:MGI.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0042326; P:negative regulation of phosphorylation; ISO:MGI.
DR GO; GO:0032091; P:negative regulation of protein binding; IDA:MGI.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISO:MGI.
DR GO; GO:2000435; P:negative regulation of protein neddylation; ISO:MGI.
DR GO; GO:1903051; P:negative regulation of proteolysis involved in protein catabolic process; IDA:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:1904667; P:negative regulation of ubiquitin protein ligase activity; ISO:MGI.
DR GO; GO:2000059; P:negative regulation of ubiquitin-dependent protein catabolic process; IDA:MGI.
DR GO; GO:0051444; P:negative regulation of ubiquitin-protein transferase activity; IDA:BHF-UCL.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0060058; P:positive regulation of apoptotic process involved in mammary gland involution; IMP:MGI.
DR GO; GO:0043517; P:positive regulation of DNA damage response, signal transduction by p53 class mediator; ISO:MGI.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISO:MGI.
DR GO; GO:0033235; P:positive regulation of protein sumoylation; ISO:MGI.
DR GO; GO:1901798; P:positive regulation of signal transduction by p53 class mediator; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:BHF-UCL.
DR GO; GO:0031648; P:protein destabilization; ISO:MGI.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISO:MGI.
DR GO; GO:1902510; P:regulation of apoptotic DNA fragmentation; ISO:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; IDA:MGI.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:MGI.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; IGI:MGI.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:0010389; P:regulation of G2/M transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0046822; P:regulation of nucleocytoplasmic transport; IGI:MGI.
DR GO; GO:0046825; P:regulation of protein export from nucleus; ISO:MGI.
DR GO; GO:0031647; P:regulation of protein stability; IMP:BHF-UCL.
DR GO; GO:1903214; P:regulation of protein targeting to mitochondrion; ISO:MGI.
DR GO; GO:0090399; P:replicative senescence; ISO:MGI.
DR GO; GO:0014070; P:response to organic cyclic compound; ISO:MGI.
DR GO; GO:0010243; P:response to organonitrogen compound; ISO:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0006364; P:rRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0009303; P:rRNA transcription; IGI:MGI.
DR GO; GO:0048103; P:somatic stem cell division; IMP:HGNC-UCL.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IGI:MGI.
DR DisProt; DP00335; -.
DR IDEAL; IID50036; -.
DR InterPro; IPR010868; Tumor_suppres_ARF.
DR Pfam; PF07392; P19Arf_N; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; Cell cycle; DNA-binding;
KW Mitochondrion; Nucleus; Reference proteome; rRNA processing; Transcription;
KW Transcription regulation; Tumor suppressor; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..169
FT /note="Tumor suppressor ARF"
FT /id="PRO_0000144182"
FT REGION 1..63
FT /note="Interaction with CDK5RAP3 and MDM2"
FT /evidence="ECO:0000250|UniProtKB:Q8N726"
FT REGION 54..73
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..44
FT /note="Missing (in isoform smARF)"
FT /evidence="ECO:0000305"
FT /id="VSP_044963"
FT MUTAGEN 85
FT /note="L->P,R: No effect on activity."
FT /evidence="ECO:0000269|PubMed:9012842"
FT MUTAGEN 93
FT /note="P->S: No effect on activity."
FT /evidence="ECO:0000269|PubMed:9012842"
FT MUTAGEN 97
FT /note="R->Q: No effect on activity."
FT /evidence="ECO:0000269|PubMed:9012842"
FT MUTAGEN 105..106
FT /note="Missing: No effect on activity."
FT /evidence="ECO:0000269|PubMed:9012842"
FT MUTAGEN 120
FT /note="A->T: No effect on activity."
FT /evidence="ECO:0000269|PubMed:9012842"
FT HELIX 4..14
FT /evidence="ECO:0007829|PDB:1HN3"
FT HELIX 20..29
FT /evidence="ECO:0007829|PDB:1HN3"
SQ SEQUENCE 169 AA; 19238 MW; 644505EFE1CBF478 CRC64;
MGRRFLVTVR IQRAGRPLQE RVFLVKFVRS RRPRTASCAL AFVNMLLRLE RILRRGPHRN
PGPGDDDGQR SRSSSSAQLR CRFELRGPHY LLPPGARRSA GRLPGHAGGA ARVRGSAGCA
RCLGSPAARL GPRAGTSRHR AIFAFRWVLF VFRWVVFVYR WERRPDRRA
