P73_HUMAN
ID P73_HUMAN Reviewed; 636 AA.
AC O15350; B7Z7J4; B7Z8Z1; B7Z9C1; C9J521; O15351; Q17RN8; Q5TBV5; Q5TBV6;
AC Q8NHW9; Q8TDY5; Q8TDY6; Q9NTK8;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 236.
DE RecName: Full=Tumor protein p73;
DE AltName: Full=p53-like transcription factor;
DE AltName: Full=p53-related protein;
GN Name=TP73; Synonyms=P73;
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]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA).
RC TISSUE=Colon;
RX PubMed=9288759; DOI=10.1016/s0092-8674(00)80540-1;
RA Kaghad M., Bonnet H., Yang A., Creancier L., Biscan J.-C., Valent A.,
RA Minty A., Chalon P., Lelias J.-M., Dumont X., Ferrara P., McKeon F.,
RA Caput D.;
RT "Monoallelically expressed gene related to p53 at 1p36, a region frequently
RT deleted in neuroblastoma and other human cancers.";
RL Cell 90:809-819(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM ALPHA).
RX PubMed=9721206; DOI=10.1006/geno.1998.5387;
RA Mai M., Huang H., Reed C., Qian C., Smith J.S., Alderete B., Jenkins R.,
RA Smith D.I., Liu W.;
RT "Genomic organization and mutation analysis of p73 in oligodendrogliomas
RT with chromosome 1 p-arm deletions.";
RL Genomics 51:359-363(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS GAMMA AND DELTA).
RC TISSUE=Neuroblastoma;
RX PubMed=9802988; DOI=10.1084/jem.188.9.1763;
RA De Laurenzi V., Costanzo A., Barcaroli D., Terrinoni A., Falco M.,
RA Annicchiarico-Petruzzelli M., Levrero M., Melino G.;
RT "Two new p73 splice variants, gamma and delta, with different
RT transcriptional activity.";
RL J. Exp. Med. 188:1763-1768(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS EPSILON AND ZETA).
RC TISSUE=Hepatoma, Lymphocyte, Mammary cancer, and Skin;
RX PubMed=10381648; DOI=10.1038/sj.cdd.4400521;
RA De Laurenzi V., Catani M.V., Terrinoni A., Corazzari M., Melino G.,
RA Costanzo A., Levrero M., Knight R.A.;
RT "Additional complexity in p73: induction by mitogens in lymphoid cells and
RT identification of two new splicing variants epsilon and zeta.";
RL Cell Death Differ. 6:389-390(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM ALPHA).
RX PubMed=10362363; DOI=10.1038/sj.onc.1202677;
RA Yoshikawa H., Nagashima M., Khan M.A., McMenamin M.G., Hagiwara K.,
RA Harris C.C.;
RT "Mutational analysis of p73 and p53 in human cancer cell lines.";
RL Oncogene 18:3415-3421(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS DN-ALPHA; DN-BETA AND DN-GAMMA),
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=11753569; DOI=10.1038/sj.cdd.4400962;
RA Grob T.J., Novak U., Maisse C., Barcaroli D., Luthi A.U., Pirnia F.,
RA Hugli B., Graber H.U., De Laurenzi V., Fey M.F., Melino G., Tobler A.;
RT "Human DeltaNp73 regulates a dominant negative feedback loop for TAp73 and
RT p53.";
RL Cell Death Differ. 8:1213-1223(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS DN-ALPHA AND DN-BETA).
RA Nakagawa T., Takahashi M., Ozaki T., Watanabe K., Nakagawara A.;
RT "Identification of the p73-specific target sequence present in the
RT deltaNp73 proper promoter.";
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS DN-ALPHA; 10 AND 11).
RC TISSUE=Testis, and Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [10]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
RC TISSUE=Colon;
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 [12]
RP INTERACTION WITH ABL1, PHOSPHORYLATION AT TYR-99 BY ABL1, AND MUTAGENESIS
RP OF TYR-99.
RX PubMed=10391251; DOI=10.1038/21704;
RA Yuan Z.-M., Shioya H., Ishiko T., Sun X., Gu J., Huang Y., Lu H.,
RA Kharbanda S., Weichselbaum R., Kufe D.;
RT "p73 is regulated by tyrosine kinase c-Abl in the apoptotic response to DNA
RT damage.";
RL Nature 399:814-817(1999).
RN [13]
RP ERRATUM OF PUBMED:10391251.
RA Yuan Z.-M., Shioya H., Ishiko T., Sun X., Gu J., Huang Y., Lu H.,
RA Kharbanda S., Weichselbaum R., Kufe D.;
RL Nature 400:792-792(1999).
RN [14]
RP FUNCTION.
RX PubMed=10203277; DOI=10.1093/jnci/91.7.594;
RA Kaelin W.G. Jr.;
RT "The emerging p53 gene family.";
RL J. Natl. Cancer Inst. 91:594-598(1999).
RN [15]
RP SUMOYLATION AT LYS-627, AND MUTAGENESIS OF LYS-627.
RX PubMed=10961991; DOI=10.1074/jbc.m004293200;
RA Minty A., Dumont X., Kaghad M., Caput D.;
RT "Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73
RT identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction
RT motif.";
RL J. Biol. Chem. 275:36316-36323(2000).
RN [16]
RP IDENTIFICATION IN A COMPLEX WITH CABLES1 AND TP53.
RX PubMed=11706030; DOI=10.1074/jbc.m108535200;
RA Tsuji K., Mizumoto K., Yamochi T., Nishimoto I., Matsuoka M.;
RT "Differential effect of ik3-1/cables on p53- and p73-induced cell death.";
RL J. Biol. Chem. 277:2951-2957(2002).
RN [17]
RP INTERACTION WITH HIPK2.
RX PubMed=11925430; DOI=10.1074/jbc.m200153200;
RA Kim E.-J., Park J.-S., Um S.-J.;
RT "Identification and characterization of HIPK2 interacting with p73 and
RT modulating functions of the p53 family in vivo.";
RL J. Biol. Chem. 277:32020-32028(2002).
RN [18]
RP INTERACTION WITH HECW2.
RX PubMed=12890487; DOI=10.1016/s0006-291x(03)01347-0;
RA Miyazaki K., Ozaki T., Kato C., Hanamoto T., Fujita T., Irino S.,
RA Watanabe K., Nakagawa T., Nakagawara A.;
RT "A novel HECT-type E3 ubiquitin ligase, NEDL2, stabilizes p73 and enhances
RT its transcriptional activity.";
RL Biochem. Biophys. Res. Commun. 308:106-113(2003).
RN [19]
RP INTERACTION WITH WWOX, DOMAIN, AND MUTAGENESIS OF TYR-487.
RX PubMed=15070730; DOI=10.1073/pnas.0400805101;
RA Aqeilan R.I., Pekarsky Y., Herrero J.J., Palamarchuk A., Letofsky J.,
RA Druck T., Trapasso F., Han S.-Y., Melino G., Huebner K., Croce C.M.;
RT "Functional association between Wwox tumor suppressor protein and p73, a
RT p53 homolog.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:4401-4406(2004).
RN [20]
RP INTERACTION WITH RANBP9, AND SUBCELLULAR LOCATION.
RX PubMed=15558019; DOI=10.1038/sj.onc.1208257;
RA Kramer S., Ozaki T., Miyazaki K., Kato C., Hanamoto T., Nakagawara A.;
RT "Protein stability and function of p73 are modulated by a physical
RT interaction with RanBPM in mammalian cultured cells.";
RL Oncogene 24:938-944(2005).
RN [21]
RP PHOSPHORYLATION, AND TISSUE SPECIFICITY.
RX PubMed=16461361; DOI=10.1083/jcb.200509132;
RA Hoshino M., Qi M.-L., Yoshimura N., Tagawa K., Wada Y.-I., Enokido Y.,
RA Marubuchi S., Harjes P., Arai N., Oyanagi K., Blandino G., Sudol M.,
RA Rich T., Kanazawa I., Wanker E.E., Saitoe M., Okazawa H.;
RT "Transcriptional repression induces a slowly progressive atypical neuronal
RT death associated with changes of YAP isoforms and p73.";
RL J. Cell Biol. 172:589-604(2006).
RN [22]
RP PHOSPHORYLATION AT THR-27.
RX PubMed=18418051; DOI=10.4161/cc.7.9.5777;
RA Soond S.M., Barry S.P., Melino G., Knight R.A., Latchman D.S.,
RA Stephanou A.;
RT "p73-mediated transcriptional activity is negatively regulated by polo-like
RT kinase 1.";
RL Cell Cycle 7:1214-1223(2008).
RN [23]
RP FUNCTION, PHOSPHORYLATION AT THR-27, AND MUTAGENESIS OF THR-27.
RX PubMed=18174154; DOI=10.1074/jbc.m710608200;
RA Koida N., Ozaki T., Yamamoto H., Ono S., Koda T., Ando K., Okoshi R.,
RA Kamijo T., Omura K., Nakagawara A.;
RT "Inhibitory role of Plk1 in the regulation of p73-dependent apoptosis
RT through physical interaction and phosphorylation.";
RL J. Biol. Chem. 283:8555-8563(2008).
RN [24]
RP PHOSPHORYLATION AT TYR-28, SUBCELLULAR LOCATION, AND INTERACTION WITH HCK.
RX PubMed=17535448; DOI=10.1186/1471-2199-8-45;
RA Paliwal P., Radha V., Swarup G.;
RT "Regulation of p73 by Hck through kinase-dependent and independent
RT mechanisms.";
RL BMC Mol. Biol. 8:45-45(2007).
RN [25]
RP INTERACTION WITH YAP1.
RX PubMed=18280240; DOI=10.1016/j.molcel.2007.12.022;
RA Levy D., Adamovich Y., Reuven N., Shaul Y.;
RT "Yap1 phosphorylation by c-Abl is a critical step in selective activation
RT of proapoptotic genes in response to DNA damage.";
RL Mol. Cell 29:350-361(2008).
RN [26]
RP PHOSPHORYLATION BY PLK3.
RX PubMed=19490146; DOI=10.1111/j.1365-2443.2009.01309.x;
RA Sang M., Ando K., Okoshi R., Koida N., Li Y., Zhu Y., Shimozato O.,
RA Geng C., Shan B., Nakagawara A., Ozaki T.;
RT "Plk3 inhibits pro-apoptotic activity of p73 through physical interaction
RT and phosphorylation.";
RL Genes Cells 14:775-788(2009).
RN [27]
RP INTERACTION WITH FBXO45, AND UBIQUITINATION.
RX PubMed=19581926; DOI=10.1038/onc.2009.177;
RA Peschiaroli A., Scialpi F., Bernassola F., Pagano M., Melino G.;
RT "The F-box protein FBXO45 promotes the proteasome-dependent degradation of
RT p73.";
RL Oncogene 28:3157-3166(2009).
RN [28]
RP UBIQUITINATION BY RCHY1/PIRH2.
RX PubMed=21994467; DOI=10.1158/1541-7786.mcr-11-0157;
RA Wu H., Zeinab R.A., Flores E.R., Leng R.P.;
RT "Pirh2, a ubiquitin E3 ligase, inhibits p73 transcriptional activity by
RT promoting its ubiquitination.";
RL Mol. Cancer Res. 9:1780-1790(2011).
RN [29]
RP INTERACTION WITH EPSTEIN-BARR VIRUS PROTEIN EBNA6 (MICROBIAL INFECTION),
RP AND SUBCELLULAR LOCATION.
RX PubMed=24314664; DOI=10.1016/j.virol.2013.10.023;
RA Sahu S.K., Mohanty S., Kumar A., Kundu C.N., Verma S.C., Choudhuri T.;
RT "Epstein-Barr virus nuclear antigen 3C interact with p73: Interplay between
RT a viral oncoprotein and cellular tumor suppressor.";
RL Virology 448:333-343(2014).
RN [30]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-627, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [31]
RP INTERACTION WITH NQO1.
RX PubMed=28291250; DOI=10.1038/srep44532;
RA Medina-Carmona E., Neira J.L., Salido E., Fuchs J.E., Palomino-Morales R.,
RA Timson D.J., Pey A.L.;
RT "Site-to-site interdomain communication may mediate different loss-of-
RT function mechanisms in a cancer-associated NQO1 polymorphism.";
RL Sci. Rep. 7:44532-44532(2017).
RN [32]
RP STRUCTURE BY NMR OF 487-554.
RX PubMed=10449409; DOI=10.1093/emboj/18.16.4438;
RA Chi S.W., Ayed A., Arrowsmith C.H.;
RT "Solution structure of a conserved C-terminal domain of p73 with structural
RT homology to the SAM domain.";
RL EMBO J. 18:4438-4445(1999).
RN [33]
RP VARIANTS CILD47 205-GLU--HIS-636 DEL AND 332-GLN--HIS-636 DEL, INVOLVEMENT
RP IN CILD47, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=34077761; DOI=10.1016/j.ajhg.2021.05.002;
RA Wallmeier J., Bracht D., Alsaif H.S., Dougherty G.W., Olbrich H.,
RA Cindric S., Dzietko M., Heyer C., Teig N., Thiels C., Faqeih E.,
RA Al-Hashim A., Khan S., Mogarri I., Almannai M., Al Otaibi W.,
RA Alkuraya F.S., Koerner-Rettberg C., Omran H.;
RT "Mutations in TP73 cause impaired mucociliary clearance and
RT lissencephaly.";
RL Am. J. Hum. Genet. 108:1318-1329(2021).
CC -!- FUNCTION: Participates in the apoptotic response to DNA damage.
CC Isoforms containing the transactivation domain are pro-apoptotic,
CC isoforms lacking the domain are anti-apoptotic and block the function
CC of p53 and transactivating p73 isoforms. May be a tumor suppressor
CC protein. Is an activator of FOXJ1 expression (By similarity). It is an
CC essential factor for the positive regulation of lung ciliated cell
CC differentiation (PubMed:34077761). {ECO:0000250|UniProtKB:Q9JJP2,
CC ECO:0000269|PubMed:10203277, ECO:0000269|PubMed:11753569,
CC ECO:0000269|PubMed:18174154, ECO:0000269|PubMed:34077761}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- SUBUNIT: Found in a complex with p53/TP53 and CABLES1. The C-terminal
CC oligomerization domain binds to the ABL1 tyrosine kinase SH3 domain.
CC Interacts with HECW2. Isoform Beta interacts homotypically and with
CC p53/TP53, whereas isoform Alpha does not. Isoform Gamma interacts
CC homotypically and with all p73 isoforms. Isoform Delta interacts with
CC isoform Gamma, isoform Alpha, and homotypically. Isoforms Alpha and
CC Beta interact with HIPK2. Isoform Alpha interacts with RANBP9. Isoform
CC Beta interacts with WWOX. Interacts (via SAM domain) with FBXO45 (via
CC B30.2/SPRY domain). Interacts with YAP1 (phosphorylated form).
CC Interacts with HCK (via SH3 domain); this inhibits TP73 activity and
CC degradation. Interacts (via SAM domain) with NQO1; this interaction is
CC NADH-dependent, stabilizes TP73 in response to oxidative stress and
CC protects it from ubiquitin-independent degradation by the 20S
CC proteasome. {ECO:0000269|PubMed:10391251, ECO:0000269|PubMed:11706030,
CC ECO:0000269|PubMed:11925430, ECO:0000269|PubMed:12890487,
CC ECO:0000269|PubMed:15070730, ECO:0000269|PubMed:15558019,
CC ECO:0000269|PubMed:17535448, ECO:0000269|PubMed:18280240,
CC ECO:0000269|PubMed:19581926, ECO:0000269|PubMed:28291250}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus
CC protein EBNA6; this interaction inhibits TP73-mediated apoptotic
CC pathway. {ECO:0000269|PubMed:24314664}.
CC -!- INTERACTION:
CC O15350; O14965: AURKA; NbExp=11; IntAct=EBI-389606, EBI-448680;
CC O15350; Q09472: EP300; NbExp=2; IntAct=EBI-389606, EBI-447295;
CC O15350; P38646: HSPA9; NbExp=11; IntAct=EBI-389606, EBI-354932;
CC O15350; Q96J02: ITCH; NbExp=3; IntAct=EBI-389606, EBI-1564678;
CC O15350; Q00987: MDM2; NbExp=4; IntAct=EBI-389606, EBI-389668;
CC O15350; P54278-1: PMS2; NbExp=3; IntAct=EBI-389606, EBI-15726984;
CC O15350; Q7Z419: RNF144B; NbExp=2; IntAct=EBI-389606, EBI-2129982;
CC O15350; Q13950: RUNX2; NbExp=3; IntAct=EBI-389606, EBI-976402;
CC O15350; Q96EB6: SIRT1; NbExp=4; IntAct=EBI-389606, EBI-1802965;
CC O15350; Q13625: TP53BP2; NbExp=2; IntAct=EBI-389606, EBI-77642;
CC O15350; Q9H3D4: TP63; NbExp=2; IntAct=EBI-389606, EBI-2337775;
CC O15350; O15350: TP73; NbExp=10; IntAct=EBI-389606, EBI-389606;
CC O15350; P46937: YAP1; NbExp=4; IntAct=EBI-389606, EBI-1044059;
CC O15350; Q9ESJ1: Cables1; Xeno; NbExp=3; IntAct=EBI-389606, EBI-604411;
CC O15350-1; Q9UKL3: CASP8AP2; NbExp=2; IntAct=EBI-389619, EBI-2339650;
CC O15350-1; Q96J02: ITCH; NbExp=5; IntAct=EBI-389619, EBI-1564678;
CC O15350-1; P46937: YAP1; NbExp=7; IntAct=EBI-389619, EBI-1044059;
CC O15350-1; P03126: E6; Xeno; NbExp=2; IntAct=EBI-389619, EBI-1177242;
CC O15350-8; Q96J02: ITCH; NbExp=2; IntAct=EBI-5651259, EBI-1564678;
CC O15350-8; Q7Z419: RNF144B; NbExp=2; IntAct=EBI-5651259, EBI-2129982;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24314664}. Cytoplasm.
CC Note=Accumulates in the nucleus in response to DNA damage.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=12;
CC Name=Alpha;
CC IsoId=O15350-1; Sequence=Displayed;
CC Name=Beta;
CC IsoId=O15350-2; Sequence=VSP_006539;
CC Name=Gamma;
CC IsoId=O15350-3; Sequence=VSP_006540, VSP_006541;
CC Name=Delta;
CC IsoId=O15350-4; Sequence=VSP_006542, VSP_006543;
CC Name=Epsilon;
CC IsoId=O15350-5; Sequence=VSP_006544, VSP_006545;
CC Name=Zeta;
CC IsoId=O15350-6; Sequence=VSP_006546;
CC Name=dN-Alpha;
CC IsoId=O15350-8; Sequence=VSP_014368;
CC Name=dN-Beta;
CC IsoId=O15350-9; Sequence=VSP_014368, VSP_006539;
CC Name=dN-Gamma;
CC IsoId=O15350-10; Sequence=VSP_014368, VSP_006540, VSP_006541;
CC Name=10;
CC IsoId=O15350-11; Sequence=VSP_045082;
CC Name=11;
CC IsoId=O15350-12; Sequence=VSP_014368, VSP_053809;
CC Name=12;
CC IsoId=O15350-13; Sequence=VSP_053810;
CC -!- TISSUE SPECIFICITY: Expressed in striatal neurons of patients with
CC Huntington disease (at protein level). Brain, kidney, placenta, colon,
CC heart, liver, spleen, skeletal muscle, prostate, thymus and pancreas.
CC Highly expressed in fetal tissue. Expressed in the respiratory
CC epithelium (PubMed:34077761). {ECO:0000269|PubMed:11753569,
CC ECO:0000269|PubMed:16461361, ECO:0000269|PubMed:34077761}.
CC -!- INDUCTION: Not induced by DNA damage. Isoforms lacking the
CC transactivation domain block gene induction.
CC {ECO:0000269|PubMed:11753569}.
CC -!- DOMAIN: Possesses an acidic transactivation domain, a central DNA
CC binding domain and a C-terminal oligomerization domain that binds to
CC the ABL1 tyrosine kinase SH3 domain. {ECO:0000269|PubMed:15070730}.
CC -!- DOMAIN: The PPxY motif mediates interaction with WWOX.
CC {ECO:0000269|PubMed:15070730}.
CC -!- PTM: Isoform alpha (but not isoform beta) is sumoylated on Lys-627,
CC which potentiates proteasomal degradation but does not affect
CC transcriptional activity. Phosphorylation by PLK1 and PLK3 inhibits the
CC transcription regulator activity and pro-apoptotic function.
CC {ECO:0000269|PubMed:10961991}.
CC -!- PTM: Higher levels of phosphorylation seen in the brain from patients
CC with Huntington disease.
CC -!- PTM: Polyubiquitinated by RCHY1/PIRH2; leading to its degradation by
CC the proteasome. {ECO:0000269|PubMed:19581926,
CC ECO:0000269|PubMed:21994467}.
CC -!- DISEASE: Ciliary dyskinesia, primary, 47, and lissencephaly (CILD47)
CC [MIM:619466]: A form of primary ciliary dyskinesia, a disorder
CC characterized by abnormalities of motile cilia. Respiratory infections
CC leading to chronic inflammation and bronchiectasis are recurrent, due
CC to defects in the respiratory cilia. CILD47 is an autosomal recessive
CC form characterized by onset soon after birth or in early childhood.
CC Affected individuals also have neurologic features, such as impaired
CC intellectual development and central hypotonia, associated with
CC structural brain abnormalities, most notably lissencephaly and thin or
CC absent corpus callosum. No situs abnormalities have been observed.
CC {ECO:0000269|PubMed:34077761}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Maps to a chromosome region frequently mutated in
CC diverse cell lines of human cancer. Appears not to be frequently
CC mutated in human cancers, in contrast to p53/TP53. Hemizygosity is
CC observed in neuroblastoma and oligodendroglioma.
CC -!- MISCELLANEOUS: Activated and stabilized by interaction with RANBP9.
CC -!- MISCELLANEOUS: [Isoform Beta]: Produced by alternative splicing of
CC isoform Alpha. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform Gamma]: Produced by alternative splicing of
CC isoform Alpha. The splicing of exon 11 results in a frameshift from the
CC original reading frame. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform Delta]: Produced by alternative splicing of
CC isoform Alpha. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform Epsilon]: Produced by alternative splicing of
CC isoform Alpha. The splicing of exon 11 results in a frameshift from the
CC original reading frame. The splicing of exon 13 reverts the reading
CC frame to the sequence of isoform Alpha. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform Zeta]: Produced by alternative splicing of
CC isoform Alpha. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform dN-Alpha]: Produced by alternative promoter
CC usage. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform dN-Beta]: Produced by alternative splicing of
CC isoform dN-Alpha. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform dN-Gamma]: Produced by alternative splicing of
CC isoform dN-Alpha. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the p53 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; Y11416; CAA72220.1; -; mRNA.
DR EMBL; Y11416; CAA72221.1; -; mRNA.
DR EMBL; Y11416; CAA72219.1; -; mRNA.
DR EMBL; AF079094; AAD39696.1; -; Genomic_DNA.
DR EMBL; AF079082; AAD39696.1; JOINED; Genomic_DNA.
DR EMBL; AF079083; AAD39696.1; JOINED; Genomic_DNA.
DR EMBL; AF079084; AAD39696.1; JOINED; Genomic_DNA.
DR EMBL; AF079085; AAD39696.1; JOINED; Genomic_DNA.
DR EMBL; AF079086; AAD39696.1; JOINED; Genomic_DNA.
DR EMBL; AF079087; AAD39696.1; JOINED; Genomic_DNA.
DR EMBL; AF079088; AAD39696.1; JOINED; Genomic_DNA.
DR EMBL; AF079089; AAD39696.1; JOINED; Genomic_DNA.
DR EMBL; AF079090; AAD39696.1; JOINED; Genomic_DNA.
DR EMBL; AF079091; AAD39696.1; JOINED; Genomic_DNA.
DR EMBL; AF079092; AAD39696.1; JOINED; Genomic_DNA.
DR EMBL; AF079093; AAD39696.1; JOINED; Genomic_DNA.
DR EMBL; AF077628; AAC61887.1; -; Genomic_DNA.
DR EMBL; AF077616; AAC61887.1; JOINED; Genomic_DNA.
DR EMBL; AF077617; AAC61887.1; JOINED; Genomic_DNA.
DR EMBL; AF077618; AAC61887.1; JOINED; Genomic_DNA.
DR EMBL; AF077619; AAC61887.1; JOINED; Genomic_DNA.
DR EMBL; AF077620; AAC61887.1; JOINED; Genomic_DNA.
DR EMBL; AF077621; AAC61887.1; JOINED; Genomic_DNA.
DR EMBL; AF077624; AAC61887.1; JOINED; Genomic_DNA.
DR EMBL; AF077625; AAC61887.1; JOINED; Genomic_DNA.
DR EMBL; AF077626; AAC61887.1; JOINED; Genomic_DNA.
DR EMBL; AF077627; AAC61887.1; JOINED; Genomic_DNA.
DR EMBL; AY040827; AAK81884.1; -; mRNA.
DR EMBL; AY040828; AAK81885.1; -; mRNA.
DR EMBL; AY040829; AAK81886.1; -; mRNA.
DR EMBL; AB055065; BAB87244.1; -; mRNA.
DR EMBL; AB055066; BAB87245.1; -; mRNA.
DR EMBL; AK302118; BAH13630.1; -; mRNA.
DR EMBL; AK304177; BAH14127.1; -; mRNA.
DR EMBL; AK304784; BAH14257.1; -; mRNA.
DR EMBL; AL136528; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471130; EAW71464.1; -; Genomic_DNA.
DR EMBL; BC117251; AAI17252.1; -; mRNA.
DR EMBL; BC117253; AAI17254.1; -; mRNA.
DR CCDS; CCDS44049.1; -. [O15350-8]
DR CCDS; CCDS44050.1; -. [O15350-9]
DR CCDS; CCDS49.1; -. [O15350-1]
DR CCDS; CCDS55566.1; -. [O15350-2]
DR CCDS; CCDS55567.1; -. [O15350-13]
DR CCDS; CCDS55568.1; -. [O15350-6]
DR CCDS; CCDS55569.1; -. [O15350-11]
DR CCDS; CCDS59965.1; -. [O15350-4]
DR RefSeq; NP_001119712.1; NM_001126240.2. [O15350-8]
DR RefSeq; NP_001119713.1; NM_001126241.2. [O15350-9]
DR RefSeq; NP_001119714.1; NM_001126242.2.
DR RefSeq; NP_001191113.1; NM_001204184.1. [O15350-2]
DR RefSeq; NP_001191114.1; NM_001204185.1.
DR RefSeq; NP_001191115.1; NM_001204186.1. [O15350-4]
DR RefSeq; NP_001191116.1; NM_001204187.1. [O15350-13]
DR RefSeq; NP_001191117.1; NM_001204188.1. [O15350-6]
DR RefSeq; NP_001191118.1; NM_001204189.1.
DR RefSeq; NP_001191119.1; NM_001204190.1.
DR RefSeq; NP_001191120.1; NM_001204191.1.
DR RefSeq; NP_001191121.1; NM_001204192.1. [O15350-11]
DR RefSeq; NP_005418.1; NM_005427.3. [O15350-1]
DR PDB; 1COK; NMR; -; A=487-554.
DR PDB; 1DXS; X-ray; 2.54 A; A=487-564.
DR PDB; 2KBY; NMR; -; A/B/C/D=351-398.
DR PDB; 2MPS; NMR; -; B=10-25.
DR PDB; 2NB1; NMR; -; B/D=351-398.
DR PDB; 2WQI; X-ray; 1.70 A; A/B/C/D=351-399.
DR PDB; 2WQJ; X-ray; 2.00 A; 1/2/A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y/Z=351-383.
DR PDB; 2WTT; X-ray; 2.30 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=351-399.
DR PDB; 2XWC; X-ray; 1.82 A; A=112-311.
DR PDB; 3VD0; X-ray; 2.95 A; A/B/C/D/I/J/K/L=115-312.
DR PDB; 3VD1; X-ray; 2.95 A; A/B/C/D/I/J/K/L=115-312.
DR PDB; 3VD2; X-ray; 4.00 A; A/B/C/D/I/J=115-312.
DR PDB; 4A63; X-ray; 2.27 A; A/C/E/G/I/K=112-311.
DR PDB; 4G82; X-ray; 3.10 A; A/B=115-312.
DR PDB; 4G83; X-ray; 4.00 A; A/B=115-312.
DR PDB; 4GUO; X-ray; 3.19 A; A/B/C/D/I/J/K/L=115-312.
DR PDB; 4GUQ; X-ray; 3.70 A; A/B=115-312.
DR PDB; 5HOB; X-ray; 1.22 A; A/B/C/D/E/F/G/H=351-398.
DR PDB; 5HOC; X-ray; 1.36 A; A/B=351-398.
DR PDB; 5KBD; X-ray; 2.80 A; A/B=115-312.
DR PDB; 6FGS; NMR; -; A=10-31.
DR PDB; 6IJQ; NMR; -; A=10-25.
DR PDB; 7EZJ; X-ray; 2.90 A; A/B/C/D/I/J/K/L/a/b/c/d/i/j/k/l=115-312.
DR PDBsum; 1COK; -.
DR PDBsum; 1DXS; -.
DR PDBsum; 2KBY; -.
DR PDBsum; 2MPS; -.
DR PDBsum; 2NB1; -.
DR PDBsum; 2WQI; -.
DR PDBsum; 2WQJ; -.
DR PDBsum; 2WTT; -.
DR PDBsum; 2XWC; -.
DR PDBsum; 3VD0; -.
DR PDBsum; 3VD1; -.
DR PDBsum; 3VD2; -.
DR PDBsum; 4A63; -.
DR PDBsum; 4G82; -.
DR PDBsum; 4G83; -.
DR PDBsum; 4GUO; -.
DR PDBsum; 4GUQ; -.
DR PDBsum; 5HOB; -.
DR PDBsum; 5HOC; -.
DR PDBsum; 5KBD; -.
DR PDBsum; 6FGS; -.
DR PDBsum; 6IJQ; -.
DR PDBsum; 7EZJ; -.
DR AlphaFoldDB; O15350; -.
DR SMR; O15350; -.
DR BioGRID; 113014; 153.
DR DIP; DIP-24202N; -.
DR ELM; O15350; -.
DR IntAct; O15350; 40.
DR MINT; O15350; -.
DR STRING; 9606.ENSP00000367545; -.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR iPTMnet; O15350; -.
DR PhosphoSitePlus; O15350; -.
DR BioMuta; TP73; -.
DR EPD; O15350; -.
DR jPOST; O15350; -.
DR MassIVE; O15350; -.
DR MaxQB; O15350; -.
DR PaxDb; O15350; -.
DR PeptideAtlas; O15350; -.
DR PRIDE; O15350; -.
DR ProteomicsDB; 48597; -. [O15350-1]
DR ProteomicsDB; 48598; -. [O15350-10]
DR ProteomicsDB; 48599; -. [O15350-2]
DR ProteomicsDB; 48600; -. [O15350-3]
DR ProteomicsDB; 48601; -. [O15350-4]
DR ProteomicsDB; 48602; -. [O15350-5]
DR ProteomicsDB; 48603; -. [O15350-6]
DR ProteomicsDB; 48604; -. [O15350-8]
DR ProteomicsDB; 48605; -. [O15350-9]
DR ProteomicsDB; 6877; -.
DR ProteomicsDB; 8551; -.
DR Antibodypedia; 3467; 1168 antibodies from 43 providers.
DR DNASU; 7161; -.
DR Ensembl; ENST00000346387.8; ENSP00000340740.4; ENSG00000078900.15. [O15350-6]
DR Ensembl; ENST00000354437.8; ENSP00000346423.4; ENSG00000078900.15. [O15350-2]
DR Ensembl; ENST00000357733.7; ENSP00000350366.3; ENSG00000078900.15. [O15350-13]
DR Ensembl; ENST00000378285.5; ENSP00000367534.1; ENSG00000078900.15. [O15350-9]
DR Ensembl; ENST00000378288.8; ENSP00000367537.4; ENSG00000078900.15. [O15350-8]
DR Ensembl; ENST00000378290.4; ENSP00000367539.4; ENSG00000078900.15. [O15350-11]
DR Ensembl; ENST00000378295.9; ENSP00000367545.4; ENSG00000078900.15. [O15350-1]
DR Ensembl; ENST00000603362.5; ENSP00000474626.1; ENSG00000078900.15. [O15350-13]
DR Ensembl; ENST00000604074.5; ENSP00000475143.1; ENSG00000078900.15. [O15350-4]
DR Ensembl; ENST00000604479.5; ENSP00000474322.1; ENSG00000078900.15. [O15350-6]
DR GeneID; 7161; -.
DR KEGG; hsa:7161; -.
DR MANE-Select; ENST00000378295.9; ENSP00000367545.4; NM_005427.4; NP_005418.1.
DR UCSC; uc001akp.4; human. [O15350-1]
DR CTD; 7161; -.
DR DisGeNET; 7161; -.
DR GeneCards; TP73; -.
DR HGNC; HGNC:12003; TP73.
DR HPA; ENSG00000078900; Tissue enhanced (choroid plexus, fallopian tube, skin).
DR MalaCards; TP73; -.
DR MIM; 601990; gene.
DR MIM; 619466; phenotype.
DR neXtProt; NX_O15350; -.
DR OpenTargets; ENSG00000078900; -.
DR Orphanet; 70573; Small cell lung cancer.
DR PharmGKB; PA36684; -.
DR VEuPathDB; HostDB:ENSG00000078900; -.
DR eggNOG; ENOG502QQ48; Eukaryota.
DR GeneTree; ENSGT00950000183153; -.
DR HOGENOM; CLU_019621_1_0_1; -.
DR InParanoid; O15350; -.
DR OMA; MKDWRWI; -.
DR PhylomeDB; O15350; -.
DR TreeFam; TF106101; -.
DR PathwayCommons; O15350; -.
DR Reactome; R-HSA-139915; Activation of PUMA and translocation to mitochondria.
DR Reactome; R-HSA-6803204; TP53 Regulates Transcription of Genes Involved in Cytochrome C Release.
DR Reactome; R-HSA-6803205; TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain.
DR Reactome; R-HSA-6803207; TP53 Regulates Transcription of Caspase Activators and Caspases.
DR Reactome; R-HSA-6803211; TP53 Regulates Transcription of Death Receptors and Ligands.
DR Reactome; R-HSA-6804759; Regulation of TP53 Activity through Association with Co-factors.
DR Reactome; R-HSA-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs.
DR SignaLink; O15350; -.
DR SIGNOR; O15350; -.
DR BioGRID-ORCS; 7161; 19 hits in 1106 CRISPR screens.
DR ChiTaRS; TP73; human.
DR EvolutionaryTrace; O15350; -.
DR GeneWiki; P73; -.
DR GenomeRNAi; 7161; -.
DR Pharos; O15350; Tbio.
DR PRO; PR:O15350; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O15350; protein.
DR Bgee; ENSG00000078900; Expressed in right uterine tube and 101 other tissues.
DR ExpressionAtlas; O15350; baseline and differential.
DR Genevisible; O15350; HS.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:AgBase.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:ARUK-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB.
DR GO; GO:0097371; F:MDM2/MDM4 family protein binding; IPI:CAFA.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0002039; F:p53 binding; IPI:CAFA.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:ARUK-UCL.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
DR GO; GO:0001222; F:transcription corepressor binding; IPI:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; TAS:ProtInc.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IDA:UniProtKB.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0006298; P:mismatch repair; TAS:ProtInc.
DR GO; GO:0060044; P:negative regulation of cardiac muscle cell proliferation; IMP:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:AgBase.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:1901248; P:positive regulation of lung ciliated cell differentiation; IMP:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IEA:Ensembl.
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:0051262; P:protein tetramerization; IEA:InterPro.
DR GO; GO:0051726; P:regulation of cell cycle; IDA:ParkinsonsUK-UCL.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0010243; P:response to organonitrogen compound; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR CDD; cd08367; P53; 1.
DR CDD; cd09571; SAM_tumor-p73; 1.
DR DisProt; DP00319; -.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 2.60.40.720; -; 1.
DR Gene3D; 4.10.170.10; -; 1.
DR InterPro; IPR008967; p53-like_TF_DNA-bd.
DR InterPro; IPR012346; p53/RUNT-type_TF_DNA-bd_sf.
DR InterPro; IPR011615; p53_DNA-bd.
DR InterPro; IPR036674; p53_tetramer_sf.
DR InterPro; IPR010991; p53_tetrameristn.
DR InterPro; IPR002117; p53_tumour_suppressor.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR032646; Tp73.
DR InterPro; IPR037612; Tumour-p73_SAM.
DR PANTHER; PTHR11447; PTHR11447; 1.
DR PANTHER; PTHR11447:SF21; PTHR11447:SF21; 1.
DR Pfam; PF00870; P53; 1.
DR Pfam; PF07710; P53_tetramer; 1.
DR Pfam; PF07647; SAM_2; 1.
DR PRINTS; PR00386; P53SUPPRESSR.
DR SMART; SM00454; SAM; 1.
DR SUPFAM; SSF47719; SSF47719; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF49417; SSF49417; 1.
DR PROSITE; PS00348; P53; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative promoter usage; Alternative splicing;
KW Apoptosis; Cell cycle; Ciliopathy; Cytoplasm; Disease variant; DNA-binding;
KW Host-virus interaction; Isopeptide bond; Lissencephaly; Metal-binding;
KW Nucleus; Phosphoprotein; Primary ciliary dyskinesia; Reference proteome;
KW Transcription; Transcription regulation; Tumor suppressor; Ubl conjugation;
KW Zinc.
FT CHAIN 1..636
FT /note="Tumor protein p73"
FT /id="PRO_0000185728"
FT DOMAIN 485..551
FT /note="SAM"
FT REGION 1..46
FT /note="Transactivation"
FT /evidence="ECO:0000250"
FT REGION 78..104
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 131..310
FT /note="DNA-binding"
FT /evidence="ECO:0000255"
FT REGION 314..345
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 345..386
FT /note="Oligomerization"
FT /evidence="ECO:0000255"
FT REGION 345..380
FT /note="Interaction with HIPK2"
FT /evidence="ECO:0000269|PubMed:11925430"
FT MOTIF 483..487
FT /note="PPxY motif"
FT BINDING 194
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 197
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 258
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 262
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MOD_RES 27
FT /note="Phosphothreonine; by PLK1"
FT /evidence="ECO:0000269|PubMed:18174154,
FT ECO:0000269|PubMed:18418051"
FT MOD_RES 28
FT /note="Phosphotyrosine; by SRC and HCK"
FT /evidence="ECO:0000269|PubMed:17535448"
FT MOD_RES 99
FT /note="Phosphotyrosine; by ABL1"
FT /evidence="ECO:0000269|PubMed:10391251"
FT CROSSLNK 627
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); in isoform Alpha"
FT /evidence="ECO:0000269|PubMed:10961991"
FT CROSSLNK 627
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..71
FT /note="Missing (in isoform 10)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045082"
FT VAR_SEQ 1..62
FT /note="MAQSTATSPDGGTTFEHLWSSLEPDSTYFDLPQSSRGNNEVVGGTDSSMDVF
FT HLEGMTTSVM -> MLYVGDPARHLAT (in isoform dN-Alpha, isoform
FT dN-Beta, isoform dN-Gamma and isoform 11)"
FT /evidence="ECO:0000303|PubMed:11753569,
FT ECO:0000303|PubMed:14702039, ECO:0000303|Ref.7"
FT /id="VSP_014368"
FT VAR_SEQ 400..636
FT /note="Missing (in isoform 11)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_053809"
FT VAR_SEQ 400..526
FT /note="SHLQPPSYGPVLSPMNKVHGGMNKLPSVNQLVGQPPPHSSAATPNLGPVGPG
FT MLNNHGHAVPANGEMSSSHSAQSMVSGSHCTPPPPYHADPSLVSFLTGLGCPNCIEYFT
FT SQGLQSIYHLQNLTIE -> PRDAQQPWPRSASQRRDEQQPQRPVHGLGVPLHSATPLP
FT RRPQPRQ (in isoform 12)"
FT /evidence="ECO:0000305"
FT /id="VSP_053810"
FT VAR_SEQ 400..495
FT /note="Missing (in isoform Zeta)"
FT /evidence="ECO:0000303|PubMed:10381648"
FT /id="VSP_006546"
FT VAR_SEQ 400..476
FT /note="SHLQPPSYGPVLSPMNKVHGGMNKLPSVNQLVGQPPPHSSAATPNLGPVGPG
FT MLNNHGHAVPANGEMSSSHSAQSMV -> PRDAQQPWPRSASQQRRDEQQPQRPVHGLG
FT VPLHSATPLPRRPQPRQFFNRIGVSKLHRVFHLPRVTEHLPPAEPDH (in isoform
FT Gamma and isoform dN-Gamma)"
FT /evidence="ECO:0000303|PubMed:11753569,
FT ECO:0000303|PubMed:9802988"
FT /id="VSP_006540"
FT VAR_SEQ 400..445
FT /note="SHLQPPSYGPVLSPMNKVHGGMNKLPSVNQLVGQPPPHSSAATPNL -> PR
FT DAQQPWPRSASQQRRDEQQPQRPVHGLGVPLHSATPLPRRPQPR (in isoform
FT Epsilon)"
FT /evidence="ECO:0000303|PubMed:10381648"
FT /id="VSP_006544"
FT VAR_SEQ 400..403
FT /note="SHLQ -> TWGP (in isoform Delta)"
FT /evidence="ECO:0000303|PubMed:9802988"
FT /id="VSP_006542"
FT VAR_SEQ 404..636
FT /note="Missing (in isoform Delta)"
FT /evidence="ECO:0000303|PubMed:9802988"
FT /id="VSP_006543"
FT VAR_SEQ 446..526
FT /note="Missing (in isoform Epsilon)"
FT /evidence="ECO:0000303|PubMed:10381648"
FT /id="VSP_006545"
FT VAR_SEQ 477..636
FT /note="Missing (in isoform Gamma and isoform dN-Gamma)"
FT /evidence="ECO:0000303|PubMed:11753569,
FT ECO:0000303|PubMed:9802988"
FT /id="VSP_006541"
FT VAR_SEQ 495..636
FT /note="SFLTGLGCPNCIEYFTSQGLQSIYHLQNLTIEDLGALKIPEQYRMTIWRGLQ
FT DLKQGHDYSTAQQLLRSSNAATISIGGSGELQRQRVMEAVHFRVRHTITIPNRGGPGGG
FT PDEWADFGFDLPDCKARKQPIKEEFTEAEIH -> RTWGP (in isoform Beta
FT and isoform dN-Beta)"
FT /evidence="ECO:0000303|PubMed:11753569,
FT ECO:0000303|PubMed:9288759, ECO:0000303|Ref.7"
FT /id="VSP_006539"
FT VARIANT 205..636
FT /note="Missing (in CILD47)"
FT /evidence="ECO:0000269|PubMed:34077761"
FT /id="VAR_086144"
FT VARIANT 332..636
FT /note="Missing (in CILD47)"
FT /evidence="ECO:0000269|PubMed:34077761"
FT /id="VAR_086145"
FT MUTAGEN 27
FT /note="T->A: Impaired phosphorylation."
FT /evidence="ECO:0000269|PubMed:18174154"
FT MUTAGEN 99
FT /note="Y->F: Impaired phosphorylation of isoform beta by
FT ABL1."
FT /evidence="ECO:0000269|PubMed:10391251"
FT MUTAGEN 487
FT /note="Y->A: Loss of interaction with WWOX."
FT /evidence="ECO:0000269|PubMed:15070730"
FT MUTAGEN 627
FT /note="K->R: Strongly diminishes sumoylation but does not
FT affect transcriptional activity."
FT /evidence="ECO:0000269|PubMed:10961991"
FT HELIX 15..20
FT /evidence="ECO:0007829|PDB:2MPS"
FT TURN 123..126
FT /evidence="ECO:0007829|PDB:2XWC"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:2XWC"
FT STRAND 136..138
FT /evidence="ECO:0007829|PDB:4G82"
FT STRAND 141..145
FT /evidence="ECO:0007829|PDB:2XWC"
FT TURN 146..149
FT /evidence="ECO:0007829|PDB:2XWC"
FT STRAND 150..153
FT /evidence="ECO:0007829|PDB:2XWC"
FT STRAND 157..164
FT /evidence="ECO:0007829|PDB:2XWC"
FT STRAND 174..181
FT /evidence="ECO:0007829|PDB:2XWC"
FT TURN 184..188
FT /evidence="ECO:0007829|PDB:2XWC"
FT HELIX 195..199
FT /evidence="ECO:0007829|PDB:2XWC"
FT TURN 202..206
FT /evidence="ECO:0007829|PDB:2XWC"
FT STRAND 214..219
FT /evidence="ECO:0007829|PDB:2XWC"
FT STRAND 224..227
FT /evidence="ECO:0007829|PDB:2XWC"
FT TURN 229..231
FT /evidence="ECO:0007829|PDB:2XWC"
FT STRAND 234..239
FT /evidence="ECO:0007829|PDB:2XWC"
FT STRAND 250..256
FT /evidence="ECO:0007829|PDB:2XWC"
FT HELIX 260..262
FT /evidence="ECO:0007829|PDB:2XWC"
FT TURN 263..268
FT /evidence="ECO:0007829|PDB:4A63"
FT STRAND 271..278
FT /evidence="ECO:0007829|PDB:2XWC"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:3VD1"
FT STRAND 284..294
FT /evidence="ECO:0007829|PDB:2XWC"
FT HELIX 298..311
FT /evidence="ECO:0007829|PDB:2XWC"
FT STRAND 354..361
FT /evidence="ECO:0007829|PDB:5HOB"
FT HELIX 362..377
FT /evidence="ECO:0007829|PDB:5HOB"
FT HELIX 378..380
FT /evidence="ECO:0007829|PDB:5HOB"
FT HELIX 383..394
FT /evidence="ECO:0007829|PDB:5HOB"
FT HELIX 493..499
FT /evidence="ECO:0007829|PDB:1DXS"
FT TURN 503..505
FT /evidence="ECO:0007829|PDB:1COK"
FT HELIX 506..510
FT /evidence="ECO:0007829|PDB:1DXS"
FT TURN 511..513
FT /evidence="ECO:0007829|PDB:1DXS"
FT HELIX 517..521
FT /evidence="ECO:0007829|PDB:1DXS"
FT HELIX 525..530
FT /evidence="ECO:0007829|PDB:1DXS"
FT TURN 535..537
FT /evidence="ECO:0007829|PDB:1DXS"
FT HELIX 538..547
FT /evidence="ECO:0007829|PDB:1DXS"
SQ SEQUENCE 636 AA; 69623 MW; A467493C5D93EEE0 CRC64;
MAQSTATSPD GGTTFEHLWS SLEPDSTYFD LPQSSRGNNE VVGGTDSSMD VFHLEGMTTS
VMAQFNLLSS TMDQMSSRAA SASPYTPEHA ASVPTHSPYA QPSSTFDTMS PAPVIPSNTD
YPGPHHFEVT FQQSSTAKSA TWTYSPLLKK LYCQIAKTCP IQIKVSTPPP PGTAIRAMPV
YKKAEHVTDV VKRCPNHELG RDFNEGQSAP ASHLIRVEGN NLSQYVDDPV TGRQSVVVPY
EPPQVGTEFT TILYNFMCNS SCVGGMNRRP ILIIITLEMR DGQVLGRRSF EGRICACPGR
DRKADEDHYR EQQALNESSA KNGAASKRAF KQSPPAVPAL GAGVKKRRHG DEDTYYLQVR
GRENFEILMK LKESLELMEL VPQPLVDSYR QQQQLLQRPS HLQPPSYGPV LSPMNKVHGG
MNKLPSVNQL VGQPPPHSSA ATPNLGPVGP GMLNNHGHAV PANGEMSSSH SAQSMVSGSH
CTPPPPYHAD PSLVSFLTGL GCPNCIEYFT SQGLQSIYHL QNLTIEDLGA LKIPEQYRMT
IWRGLQDLKQ GHDYSTAQQL LRSSNAATIS IGGSGELQRQ RVMEAVHFRV RHTITIPNRG
GPGGGPDEWA DFGFDLPDCK ARKQPIKEEF TEAEIH
