ARF_HUMAN
ID ARF_HUMAN Reviewed; 132 AA.
AC Q8N726; D3DRK2; Q13195; Q13399; Q16360; Q7KZR9;
DT 11-OCT-2005, integrated into UniProtKB/Swiss-Prot.
DT 18-APR-2012, sequence version 2.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Tumor suppressor ARF {ECO:0000305};
DE AltName: Full=Alternative reading frame {ECO:0000303|PubMed:9724636};
DE Short=ARF {ECO:0000303|PubMed:9724636};
DE AltName: Full=Cyclin-dependent kinase inhibitor 2A {ECO:0000312|HGNC:HGNC:1787};
DE AltName: Full=p14ARF {ECO:0000303|PubMed:9724636};
GN Name=CDKN2A {ECO:0000312|EMBL:AAM77919.1, ECO:0000312|HGNC:HGNC:1787};
GN Synonyms=CDKN2 {ECO:0000312|EMBL:AAC60649.1}, MLM;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1] {ECO:0000312|EMBL:AAC60649.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7606716;
RA Stone S., Jiang P., Dayananth P., Tavtigian S.V., Katcher H., Parry D.,
RA Peters G., Kamb A.;
RT "Complex structure and regulation of the P16 (MTS1) locus.";
RL Cancer Res. 55:2988-2994(1995).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAB01737.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Linnenbach A.J.;
RT "mRNA isoform with alternate first exon-encoded sequences at the cyclin-
RT dependent kinase inhibitor 2 (p16INK4/MTS1) locus and mapping analysis of
RT the region by using long-PCR.";
RL Submitted (OCT-1995) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305, ECO:0000312|EMBL:AAB01737.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-17.
RG NIEHS SNPs program;
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000312|EMBL:CAH70601.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [5] {ECO:0000305, ECO:0000312|EMBL:AAB01737.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Skin;
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 [7] {ECO:0000305, ECO:0000312|EMBL:AAA82236.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Hematopoietic {ECO:0000312|EMBL:AAA82236.1};
RX PubMed=7624129;
RA Duro D., Bernard O., Della Valle V., Berger R., Larsen C.J.;
RT "A new type of p16INK4/MTS1 gene transcript expressed in B-cell
RT malignancies.";
RL Oncogene 11:21-29(1995).
RN [8] {ECO:0000305, ECO:0000312|EMBL:AAB01737.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [9] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH MDM2.
RX PubMed=9724636; DOI=10.1093/emboj/17.17.5001;
RA Stott F.J., Bates S., James M.C., McConnell B.B., Starborg M., Brookes S.,
RA Palmero I., Ryan K., Hara E., Vousden K.H., Peters G.;
RT "The alternative product from the human CDKN2A locus, p14(ARF),
RT participates in a regulatory feedback loop with p53 and MDM2.";
RL EMBO J. 17:5001-5014(1998).
RN [10] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH TOP1.
RX PubMed=11314011; DOI=10.1038/sj.onc.1204170;
RA Karayan L., Riou J.-F., Seite P., Migeon J., Cantereau A., Larsen C.-J.;
RT "Human ARF protein interacts with topoisomerase I and stimulates its
RT activity.";
RL Oncogene 20:836-848(2001).
RN [11] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH E2F1.
RX PubMed=11314038; DOI=10.1038/sj.onc.1204220;
RA Eymin B., Karayan L., Seite P., Brambilla C., Brambilla E., Larsen C.-J.,
RA Gazzeri S.;
RT "Human ARF binds E2F1 and inhibits its transcriptional activity.";
RL Oncogene 20:1033-1041(2001).
RN [12]
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 [13]
RP INTERACTION WITH CDKN2AIP.
RX PubMed=12581788; DOI=10.1016/s0531-5565(02)00180-8;
RA Wadhwa R., Sugihara T., Hasan M.K., Duncan E.L., Taira K., Kaul S.C.;
RT "A novel putative collaborator of p19ARF.";
RL Exp. Gerontol. 38:245-252(2003).
RN [14]
RP INTERACTION WITH E4F1.
RX PubMed=12446718; DOI=10.1074/jbc.m210978200;
RA Rizos H., Diefenbach E., Badhwar P., Woodruff S., Becker T.M., Rooney R.J.,
RA Kefford R.F.;
RT "Association of p14ARF with the p120E4F transcriptional repressor enhances
RT cell cycle inhibition.";
RL J. Biol. Chem. 278:4981-4989(2003).
RN [15] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH NPM1.
RX PubMed=14636574; DOI=10.1016/s1097-2765(03)00431-3;
RA Itahana K., Bhat K.P., Jin A., Itahana Y., Hawke D., Kobayashi R.,
RA Zhang Y.;
RT "Tumor suppressor ARF degrades B23, a nucleolar protein involved in
RT ribosome biogenesis and cell proliferation.";
RL Mol. Cell 12:1151-1164(2003).
RN [16] {ECO:0000305}
RP FUNCTION.
RX PubMed=12660818; DOI=10.1038/sj.onc.1206303;
RA Eymin B., Leduc C., Coll J.-L., Brambilla E., Gazzeri S.;
RT "p14ARF induces G2 arrest and apoptosis independently of p53 leading to
RT regression of tumours established in nude mice.";
RL Oncogene 22:1822-1835(2003).
RN [17] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH TOP1.
RX PubMed=15361825; DOI=10.1038/sj.onc.1207968;
RA Ayrault O., Andrique L., Larsen C.-J., Seite P.;
RT "Human Arf tumor suppressor specifically interacts with chromatin
RT containing the promoter of rRNA genes.";
RL Oncogene 23:8097-8104(2004).
RN [18] {ECO:0000305}
RP FUNCTION, 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 [19] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH HUWE1.
RX PubMed=15989956; DOI=10.1016/j.cell.2005.03.037;
RA Chen D., Kon N., Li M., Zhang W., Qin J., Gu W.;
RT "ARF-BP1/Mule is a critical mediator of the ARF tumor suppressor.";
RL Cell 121:1071-1083(2005).
RN [20] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH UBE2I.
RX PubMed=15876874; DOI=10.4161/cc.4.4.1597;
RA Rizos H., Woodruff S., Kefford R.F.;
RT "p14ARF interacts with the SUMO-conjugating enzyme Ubc9 and promotes the
RT sumoylation of its binding partners.";
RL Cell Cycle 4:597-603(2005).
RN [21]
RP INTERACTION WITH CDK5RAP3 AND MDM2, SUBCELLULAR LOCATION, AND REGION.
RX PubMed=16173922; DOI=10.1042/bj20050960;
RA Wang J., He X., Luo Y., Yarbrough W.G.;
RT "A novel ARF-binding protein (LZAP) alters ARF regulation of HDM2.";
RL Biochem. J. 393:489-501(2006).
RN [22]
RP FUNCTION (ISOFORM SMARF), ALTERNATIVE SPLICING (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 [23]
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 [24]
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 [25]
RP INTERACTION WITH COMMD1, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18305112; DOI=10.1074/jbc.m708544200;
RA Huang Y., Wu M., Li H.Y.;
RT "Tumor suppressor ARF promotes non-classic proteasome-independent
RT polyubiquitination of COMMD1.";
RL J. Biol. Chem. 283:11453-11460(2008).
RN [26]
RP UBIQUITINATION BY TRIP12.
RX PubMed=20208519; DOI=10.1038/nature08820;
RA Chen D., Shan J., Zhu W.G., Qin J., Gu W.;
RT "Transcription-independent ARF regulation in oncogenic stress-mediated p53
RT responses.";
RL Nature 464:624-627(2010).
RN [27]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22094112; DOI=10.1016/j.yexcr.2011.10.019;
RA Watari A., Li Y., Higashiyama S., Yutsudo M.;
RT "A novel proapoptotic gene PANO encodes a post-translational modulator of
RT the tumor suppressor p14ARF.";
RL Exp. Cell Res. 318:187-195(2012).
RN [28]
RP INTERACTION WITH NOP53, SUBCELLULAR LOCATION, AND UBIQUITINATION.
RX PubMed=27323397; DOI=10.18632/oncotarget.9957;
RA Lee S., Cho Y.E., Kim S.H., Kim Y.J., Park J.H.;
RT "GLTSCR2 promotes the nucleoplasmic translocation and subsequent
RT degradation of nucleolar ARF.";
RL Oncotarget 8:16293-16302(2017).
CC -!- FUNCTION: Capable of inducing cell cycle arrest in G1 and G2 phases.
CC Acts as a tumor suppressor. Binds to MDM2 and blocks its
CC nucleocytoplasmic shuttling by sequestering it in the nucleolus. This
CC inhibits the oncogenic action of MDM2 by blocking MDM2-induced
CC degradation of p53 and enhancing p53-dependent transactivation and
CC apoptosis. Also induces G2 arrest and apoptosis in a p53-independent
CC manner by preventing the activation of cyclin B1/CDC2 complexes. Binds
CC to BCL6 and down-regulates BCL6-induced transcriptional repression.
CC Binds to E2F1 and MYC and blocks their transcriptional activator
CC activity but has no effect on MYC transcriptional repression. Binds to
CC TOP1/TOPOI and stimulates its activity. This complex binds to rRNA gene
CC promoters and may play a role in rRNA transcription and/or maturation.
CC Interacts with NPM1/B23 and promotes its polyubiquitination and
CC degradation, thus inhibiting rRNA processing. Plays a role in
CC inhibiting ribosome biogenesis, perhaps by binding to the nucleolar
CC localization sequence of transcription termination factor TTF1, and
CC thereby preventing nucleolar localization of TTF1 (By similarity).
CC Interacts with COMMD1 and promotes its 'Lys63'-linked
CC polyubiquitination. Interacts with UBE2I/UBC9 and enhances sumoylation
CC of a number of its binding partners including MDM2 and E2F1. Binds to
CC HUWE1 and represses its ubiquitin ligase activity. May play a role in
CC controlling cell proliferation and apoptosis during mammary gland
CC development. {ECO:0000250|UniProtKB:Q64364,
CC ECO:0000269|PubMed:11314011, ECO:0000269|PubMed:11314038,
CC ECO:0000269|PubMed:12660818, ECO:0000269|PubMed:14636574,
CC ECO:0000269|PubMed:15361825, ECO:0000269|PubMed:15567177,
CC ECO:0000269|PubMed:15876874, ECO:0000269|PubMed:15989956,
CC ECO:0000269|PubMed:16713577, ECO:0000269|PubMed:18305112,
CC ECO:0000269|PubMed:22094112, ECO:0000269|PubMed:9724636}.
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. Binds to BCL6, E2F1, HUWE1, MDM2, MYC, NPM1/B23, TOP1/TOPOI and
CC UBE2I/UBC9. Interacts with TBRG1 and COMMD1. Interacts with CDKN2AIP
CC and E4F1. Interacts with CDK5RAP3 and MDM2; form a ternary complex
CC involved in regulation of p53/TP53 (PubMed:16173922). Interacts with
CC NOP53; the interaction is direct and promotes ARF nucleoplasmic
CC relocalization and ubiquitin-mediated proteasomal degradation
CC (PubMed:27323397). Interacts with TTF1 (via the N-terminal region (NRD)
CC and a C-terminal region); the interaction is direct and inhibits the
CC nucleolar localization of TTF1 (By similarity).
CC {ECO:0000250|UniProtKB:Q64364, ECO:0000269|PubMed:11314011,
CC ECO:0000269|PubMed:11314038, ECO:0000269|PubMed:12154087,
CC ECO:0000269|PubMed:12446718, ECO:0000269|PubMed:12581788,
CC ECO:0000269|PubMed:14636574, ECO:0000269|PubMed:15361825,
CC ECO:0000269|PubMed:15567177, ECO:0000269|PubMed:15876874,
CC ECO:0000269|PubMed:15989956, ECO:0000269|PubMed:16173922,
CC ECO:0000269|PubMed:17110379, ECO:0000269|PubMed:17486078,
CC ECO:0000269|PubMed:18305112, ECO:0000269|PubMed:27323397,
CC ECO:0000269|PubMed:9724636}.
CC -!- SUBUNIT: [Isoform smARF]: Interacts with C1QBP.
CC {ECO:0000269|PubMed:16713577}.
CC -!- INTERACTION:
CC Q8N726; Q07021: C1QBP; NbExp=3; IntAct=EBI-625922, EBI-347528;
CC Q8N726; Q9UER7: DAXX; NbExp=8; IntAct=EBI-625922, EBI-77321;
CC Q8N726; P18146: EGR1; NbExp=4; IntAct=EBI-625922, EBI-2834611;
CC Q8N726; Q7Z6Z7: HUWE1; NbExp=5; IntAct=EBI-625922, EBI-625934;
CC Q8N726; Q00987: MDM2; NbExp=5; IntAct=EBI-625922, EBI-389668;
CC Q8N726; Q13330: MTA1; NbExp=2; IntAct=EBI-625922, EBI-714236;
CC Q8N726; P04198: MYCN; NbExp=3; IntAct=EBI-625922, EBI-878369;
CC Q8N726; P06748: NPM1; NbExp=2; IntAct=EBI-625922, EBI-78579;
CC Q8N726; P08047: SP1; NbExp=4; IntAct=EBI-625922, EBI-298336;
CC Q8N726; Q14669: TRIP12; NbExp=4; IntAct=EBI-625922, EBI-308443;
CC Q8N726; Q8TAQ5: ZNF420; NbExp=8; IntAct=EBI-625922, EBI-3923307;
CC Q8N726; Q8AZK7: EBNA-LP; Xeno; NbExp=5; IntAct=EBI-625922, EBI-1185167;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:16173922,
CC ECO:0000269|PubMed:18305112, ECO:0000269|PubMed:22094112,
CC ECO:0000269|PubMed:27323397}. Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:18305112, ECO:0000269|PubMed:27323397}.
CC -!- SUBCELLULAR LOCATION: [Isoform smARF]: Mitochondrion
CC {ECO:0000269|PubMed:16713577}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
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:0000250|UniProtKB:Q64364};
CC Name=tumor suppressor ARF {ECO:0000303|PubMed:11314011};
CC Synonyms=p14ARF {ECO:0000303|PubMed:9724636}, p19ARF;
CC IsoId=Q8N726-1; Sequence=Displayed;
CC Name=1 {ECO:0000305}; Synonyms=p16INK4a {ECO:0000305};
CC IsoId=P42771-1; Sequence=External;
CC Name=2 {ECO:0000305};
CC IsoId=P42771-2; Sequence=External;
CC Name=3 {ECO:0000305}; Synonyms=p12 {ECO:0000305};
CC IsoId=P42771-3; Sequence=External;
CC Name=5; Synonyms=p16gamma;
CC IsoId=P42771-4; Sequence=External;
CC Name=smARF;
CC IsoId=Q8N726-2; Sequence=VSP_044962;
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:0000269|PubMed:20208519,
CC ECO:0000269|PubMed:27323397}.
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 P42771) which is encoded by
CC the same gene. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB01737.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAC60649.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH15960.3; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH21998.3; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAM77919.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAH70601.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=EAW58600.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=EAW58601.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cdkn2a/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CDKN2aID146.html";
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DR EMBL; S78535; AAC60649.1; ALT_INIT; mRNA.
DR EMBL; U38945; AAB01737.1; ALT_INIT; mRNA.
DR EMBL; AF527803; AAM77919.1; ALT_INIT; Genomic_DNA.
DR EMBL; AL449423; CAH70601.1; ALT_INIT; Genomic_DNA.
DR EMBL; CH471071; EAW58600.1; ALT_INIT; Genomic_DNA.
DR EMBL; CH471071; EAW58601.1; ALT_INIT; Genomic_DNA.
DR EMBL; BC015960; AAH15960.3; ALT_INIT; mRNA.
DR EMBL; BC021998; AAH21998.3; ALT_INIT; mRNA.
DR EMBL; U26727; AAA82236.1; -; mRNA.
DR EMBL; BT007020; AAP35666.1; -; mRNA.
DR CCDS; CCDS6511.2; -. [Q8N726-1]
DR PIR; I39004; I39004.
DR RefSeq; NP_478102.2; NM_058195.3. [Q8N726-1]
DR AlphaFoldDB; Q8N726; -.
DR BioGRID; 107463; 303.
DR CORUM; Q8N726; -.
DR DIP; DIP-24171N; -.
DR IntAct; Q8N726; 67.
DR MINT; Q8N726; -.
DR iPTMnet; Q8N726; -.
DR BioMuta; CDKN2A; -.
DR DMDM; 384872321; -.
DR jPOST; Q8N726; -.
DR MassIVE; Q8N726; -.
DR MaxQB; Q8N726; -.
DR PeptideAtlas; Q8N726; -.
DR PRIDE; Q8N726; -.
DR ProteomicsDB; 72258; -. [Q8N726-1]
DR Antibodypedia; 3608; 1598 antibodies from 55 providers.
DR DNASU; 1029; -.
DR Ensembl; ENST00000530628.2; ENSP00000432664.2; ENSG00000147889.18. [Q8N726-1]
DR Ensembl; ENST00000579755.2; ENSP00000462950.1; ENSG00000147889.18. [Q8N726-1]
DR GeneID; 1029; -.
DR UCSC; uc003zpl.4; human. [Q8N726-1]
DR CTD; 1029; -.
DR DisGeNET; 1029; -.
DR GeneCards; CDKN2A; -.
DR HGNC; HGNC:1787; CDKN2A.
DR HPA; ENSG00000147889; Tissue enhanced (choroid plexus, pituitary gland).
DR MalaCards; CDKN2A; -.
DR MIM; 600160; gene.
DR neXtProt; NX_Q8N726; -.
DR OpenTargets; ENSG00000147889; -.
DR PharmGKB; PA106; -.
DR VEuPathDB; HostDB:ENSG00000147889; -.
DR GeneTree; ENSGT00940000163078; -.
DR HOGENOM; CLU_134503_0_0_1; -.
DR OrthoDB; 1435166at2759; -.
DR PathwayCommons; Q8N726; -.
DR Reactome; R-HSA-111471; Apoptotic factor-mediated response.
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-HSA-2559585; Oncogene Induced Senescence.
DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-HSA-3232118; SUMOylation of transcription factors.
DR Reactome; R-HSA-6804757; Regulation of TP53 Degradation.
DR Reactome; R-HSA-69541; Stabilization of p53.
DR Reactome; R-HSA-8941858; Regulation of RUNX3 expression and activity.
DR Reactome; R-HSA-9645722; Defective Intrinsic Pathway for Apoptosis Due to p14ARF Loss of Function.
DR Reactome; R-HSA-9646303; Evasion of Oncogene Induced Senescence Due to p14ARF Defects.
DR Reactome; R-HSA-9646304; Evasion of Oxidative Stress Induced Senescence Due to p14ARF Defects.
DR Reactome; R-HSA-9759194; Nuclear events mediated by NFE2L2.
DR SignaLink; Q8N726; -.
DR SIGNOR; Q8N726; -.
DR BioGRID-ORCS; 1029; 20 hits in 1089 CRISPR screens.
DR ChiTaRS; CDKN2A; human.
DR GenomeRNAi; 1029; -.
DR Pharos; Q8N726; Tbio.
DR Proteomes; UP000005640; Chromosome 9.
DR Bgee; ENSG00000147889; Expressed in parotid gland and 173 other tissues.
DR ExpressionAtlas; Q8N726; baseline and differential.
DR Genevisible; Q8N726; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0032991; C:protein-containing complex; IDA:BHF-UCL.
DR GO; GO:0097718; F:disordered domain specific binding; IPI:CAFA.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0097371; F:MDM2/MDM4 family protein binding; IPI:UniProtKB.
DR GO; GO:0002039; F:p53 binding; IPI:BHF-UCL.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0019789; F:SUMO transferase activity; EXP:Reactome.
DR GO; GO:1990948; F:ubiquitin ligase inhibitor activity; IDA:CAFA.
DR GO; GO:0055105; F:ubiquitin-protein transferase inhibitor activity; ISS:BHF-UCL.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:BHF-UCL.
DR GO; GO:1990000; P:amyloid fibril formation; IMP:CAFA.
DR GO; GO:0008637; P:apoptotic mitochondrial changes; IMP:BHF-UCL.
DR GO; GO:0000422; P:autophagy of mitochondrion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0090398; P:cellular senescence; IMP:BHF-UCL.
DR GO; GO:0051882; P:mitochondrial depolarization; IMP:ParkinsonsUK-UCL.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; ISS:BHF-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0033088; P:negative regulation of immature T cell proliferation in thymus; ISS:BHF-UCL.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IMP:BHF-UCL.
DR GO; GO:2000435; P:negative regulation of protein neddylation; IDA:CAFA.
DR GO; GO:1903051; P:negative regulation of proteolysis involved in protein catabolic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:1904667; P:negative regulation of ubiquitin protein ligase activity; IDA:CAFA.
DR GO; GO:2000059; P:negative regulation of ubiquitin-dependent protein catabolic process; IDA:CAFA.
DR GO; GO:0051444; P:negative regulation of ubiquitin-protein transferase activity; ISS:BHF-UCL.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0043517; P:positive regulation of DNA damage response, signal transduction by p53 class mediator; IDA:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:CAFA.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IDA:UniProtKB.
DR GO; GO:0033235; P:positive regulation of protein sumoylation; IMP:BHF-UCL.
DR GO; GO:1901798; P:positive regulation of signal transduction by p53 class mediator; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; IDA:BHF-UCL.
DR GO; GO:0070534; P:protein K63-linked ubiquitination; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:BHF-UCL.
DR GO; GO:1902510; P:regulation of apoptotic DNA fragmentation; IMP:BHF-UCL.
DR GO; GO:0051726; P:regulation of cell cycle; IDA:BHF-UCL.
DR GO; GO:0010389; P:regulation of G2/M transition of mitotic cell cycle; IMP:BHF-UCL.
DR GO; GO:0046825; P:regulation of protein export from nucleus; IMP:BHF-UCL.
DR GO; GO:0031647; P:regulation of protein stability; ISS:BHF-UCL.
DR GO; GO:1903214; P:regulation of protein targeting to mitochondrion; IMP:ParkinsonsUK-UCL.
DR GO; GO:0006364; P:rRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0048103; P:somatic stem cell division; ISS:BHF-UCL.
DR DisProt; DP02167; -. [Q8N726-1]
DR InterPro; IPR010868; Tumor_suppres_ARF.
DR Pfam; PF07392; P19Arf_N; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Cell cycle; DNA-binding; Mitochondrion;
KW Nucleus; Reference proteome; rRNA processing; Transcription;
KW Transcription regulation; Tumor suppressor; Ubl conjugation;
KW Ubl conjugation pathway.
FT CHAIN 1..132
FT /note="Tumor suppressor ARF"
FT /id="PRO_0000144180"
FT REGION 1..64
FT /note="Interaction with CDK5RAP3 and MDM2"
FT /evidence="ECO:0000269|PubMed:16173922"
FT REGION 56..132
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..47
FT /note="Missing (in isoform smARF)"
FT /evidence="ECO:0000305"
FT /id="VSP_044962"
FT VARIANT 17
FT /note="P -> S (in dbSNP:rs3731190)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_029287"
FT VARIANT 106
FT /note="G -> R (in dbSNP:rs4987127)"
FT /id="VAR_053033"
FT VARIANT 113
FT /note="P -> L (in dbSNP:rs34886500)"
FT /id="VAR_053034"
FT VARIANT 116
FT /note="G -> D (in dbSNP:rs35741010)"
FT /id="VAR_053035"
FT CONFLICT 28..30
FT /note="PRL -> SWF (in Ref. 6; AAH15960/AAH21998 and 7;
FT AAP35666)"
FT /evidence="ECO:0000305"
FT CONFLICT 94
FT /note="P -> L (in Ref. 2; AAB01737)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 132 AA; 13903 MW; 7739A9050C21BC96 CRC64;
MVRRFLVTLR IRRACGPPRV RVFVVHIPRL TGEWAAPGAP AAVALVLMLL RSQRLGQQPL
PRRPGHDDGQ RPSGGAAAAP RRGAQLRRPR HSHPTRARRC PGGLPGHAGG AAPGRGAAGR
ARCLGPSARG PG
