P53_MOUSE
ID P53_MOUSE Reviewed; 390 AA.
AC P02340; Q9QUP3;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2018, sequence version 4.
DT 03-AUG-2022, entry version 257.
DE RecName: Full=Cellular tumor antigen p53;
DE AltName: Full=Tumor suppressor p53;
GN Name=Tp53; Synonyms=P53, Trp53;
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]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6092064; DOI=10.1002/j.1460-2075.1984.tb02110.x;
RA Bienz B., Zakut-Houri R., Givol D., Oren M.;
RT "Analysis of the gene coding for the murine cellular tumour antigen p53.";
RL EMBO J. 3:2179-2183(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6646235; DOI=10.1038/306594a0;
RA Zakut-Houri R., Oren M., Bienz B., Lavie V., Hazum S., Givol D.;
RT "A single gene and a pseudogene for the cellular tumour antigen p53.";
RL Nature 306:594-597(1983).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=6379601; DOI=10.1093/nar/12.14.5609;
RA Jenkins J.R., Rudge K., Redmond S., Wade-Evans A.;
RT "Cloning and expression analysis of full length mouse cDNA sequences
RT encoding the transformation associated protein p53.";
RL Nucleic Acids Res. 12:5609-5626(1984).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (CLONES PCD53; P53-M11 AND P53-M8).
RX PubMed=3023970; DOI=10.1128/mcb.6.9.3232-3239.1986;
RA Arai N., Nomura D., Yokota K., Wolf D., Brill E., Shohat O., Rotter V.;
RT "Immunologically distinct p53 molecules generated by alternative
RT splicing.";
RL Mol. Cell. Biol. 6:3232-3239(1986).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT VAL-135.
RX PubMed=3329909;
RA Chumakov P.M.;
RT "Primary structure of DNA complementary to mRNA of murine oncoprotein
RT p53.";
RL Bioorg. Khim. 13:1691-1694(1987).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=SCID;
RA Araki R., Fukumura R., Fujimori A., Tatsumi K., Abe M.;
RT "Cell cycle in DNA-PKcs knock-out mice.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10403253; DOI=10.1038/21913;
RA Jimenez G.S., Bryntesson F., Torres-Arzayus M.I., Priestley A., Beeche M.,
RA Saito S., Sakaguchi K., Appella E., Jeggo P.A., Taccioli G.E., Wahl G.M.,
RA Hubank M.;
RT "DNA-dependent protein kinase is not required for the p53-dependent
RT response to DNA damage.";
RL Nature 400:81-83(1999).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Mammary carcinoma;
RA Araki R., Fukumura R., Fujimori A., Tatsumi K., Abe M.;
RT "Characterization of DNA-PKcs null mutant SX9.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=129/SvJ; TISSUE=Lung fibroblast;
RA Fujimori A., Abe M.;
RT "p53 in 129-SVJ mice.";
RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 222-258.
RX PubMed=1766680;
RA Burns P.A., Kemp C.J., Gannon J.V., Lane D.P., Bremner R., Balmain A.;
RT "Loss of heterozygosity and mutational alterations of the p53 gene in skin
RT tumours of interspecific hybrid mice.";
RL Oncogene 6:2363-2369(1991).
RN [12]
RP DISCOVERY OF P53.
RX PubMed=221923; DOI=10.1073/pnas.76.5.2420;
RA DeLeo A.B., Jay G., Appella E., Dubois G.C., Law L.W., Old L.J.;
RT "Detection of a transformation-related antigen in chemically induced
RT sarcomas and other transformed cells of the mouse.";
RL Proc. Natl. Acad. Sci. U.S.A. 76:2420-2424(1979).
RN [13]
RP INTERACTION WITH E4F1.
RX PubMed=10644996; DOI=10.1038/sj.onc.1203250;
RA Sandy P., Gostissa M., Fogal V., Cecco L.D., Szalay K., Rooney R.J.,
RA Schneider C., Del Sal G.;
RT "p53 is involved in the p120E4F-mediated growth arrest.";
RL Oncogene 19:188-199(2000).
RN [14]
RP INTERACTION WITH HIPK1, AND PHOSPHORYLATION.
RX PubMed=12702766; DOI=10.1073/pnas.0530308100;
RA Kondo S., Lu Y., Debbas M., Lin A.W., Sarosi I., Itie A., Wakeham A.,
RA Tuan J., Saris C., Elliott G., Ma W., Benchimol S., Lowe S.W., Mak T.W.,
RA Thukral S.K.;
RT "Characterization of cells and gene-targeted mice deficient for the p53-
RT binding kinase homeodomain-interacting protein kinase 1 (HIPK1).";
RL Proc. Natl. Acad. Sci. U.S.A. 100:5431-5436(2003).
RN [15]
RP INTERACTION WITH AXIN1, AND IDENTIFICATION IN A COMPLEX WITH HIPK2 AND
RP AXIN1.
RX PubMed=15526030; DOI=10.1038/sj.emboj.7600475;
RA Rui Y., Xu Z., Lin S., Li Q., Rui H., Luo W., Zhou H.-M., Cheung P.-Y.,
RA Wu Z., Ye Z., Li P., Han J., Lin S.-C.;
RT "Axin stimulates p53 functions by activation of HIPK2 kinase through
RT multimeric complex formation.";
RL EMBO J. 23:4583-4594(2004).
RN [16]
RP PHOSPHORYLATION AT SER-312 AND SER-389, AND RNA-BINDING.
RX PubMed=3006031; DOI=10.1073/pnas.83.4.897;
RA Samad A., Anderson C.W., Carroll R.B.;
RT "Mapping of phosphomonoester and apparent phosphodiester bonds of the
RT oncogene product p53 from simian virus 40-transformed 3T3 cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:897-901(1986).
RN [17]
RP PHOSPHORYLATION AT SER-389.
RX PubMed=2145148; DOI=10.1002/j.1460-2075.1990.tb07524.x;
RA Meek D.W., Simon S., Kikkawa U., Eckhart W.;
RT "The p53 tumour suppressor protein is phosphorylated at serine 389 by
RT casein kinase II.";
RL EMBO J. 9:3253-3260(1990).
RN [18]
RP PUTATIVE RNA-BINDING.
RX PubMed=1406686; DOI=10.1128/mcb.12.11.5145-5151.1992;
RA Fontoura B.M., Sorokina E.A., David E., Carroll R.B.;
RT "p53 is covalently linked to 5.8S rRNA.";
RL Mol. Cell. Biol. 12:5145-5151(1992).
RN [19]
RP DEACETYLATION BY SIRT1.
RX PubMed=11672522; DOI=10.1016/s0092-8674(01)00524-4;
RA Luo J., Nikolaev A.Y., Imai S., Chen D., Su F., Shiloh A., Guarente L.,
RA Gu W.;
RT "Negative control of p53 by Sir2alpha promotes cell survival under
RT stress.";
RL Cell 107:137-148(2001).
RN [20]
RP INTERACTION WITH USP7.
RX PubMed=14719112;
RA Lim S.-K., Shin J.-M., Kim Y.-S., Baek K.-H.;
RT "Identification and characterization of murine mHAUSP encoding a
RT deubiquitinating enzyme that regulates the status of p53 ubiquitination.";
RL Int. J. Oncol. 24:357-364(2004).
RN [21]
RP IDENTIFICATION IN A COMPLEX WITH CABLES1 AND TP73.
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 [22]
RP INTERACTION WITH BANP.
RX PubMed=12494467; DOI=10.1002/ijc.10881;
RA Kaul R., Mukherjee S., Ahmed F., Bhat M.K., Chhipa R., Galande S.,
RA Chattopadhyay S.;
RT "Direct interaction with and activation of p53 by SMAR1 retards cell-cycle
RT progression at G2/M phase and delays tumor growth in mice.";
RL Int. J. Cancer 103:606-615(2003).
RN [23]
RP PHOSPHORYLATION AT SER-18, LYSINE ACETYLATION, UBIQUITINATION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=15195100; DOI=10.1038/ncb1147;
RA Bernardi R., Scaglioni P.P., Bergmann S., Horn H.F., Vousden K.H.,
RA Pandolfi P.P.;
RT "PML regulates p53 stability by sequestering Mdm2 to the nucleolus.";
RL Nat. Cell Biol. 6:665-672(2004).
RN [24]
RP PHOSPHORYLATION AT SER-37.
RX PubMed=17254968; DOI=10.1016/j.cell.2006.11.050;
RA Sun P., Yoshizuka N., New L., Moser B.A., Li Y., Liao R., Xie C., Chen J.,
RA Deng Q., Yamout M., Dong M.Q., Frangou C.G., Yates J.R. III, Wright P.E.,
RA Han J.;
RT "PRAK is essential for ras-induced senescence and tumor suppression.";
RL Cell 128:295-308(2007).
RN [25]
RP INTERACTION WITH ZNF385A.
RX PubMed=17719541; DOI=10.1016/j.cell.2007.06.013;
RA Das S., Raj L., Zhao B., Kimura Y., Bernstein A., Aaronson S.A., Lee S.W.;
RT "Hzf Determines cell survival upon genotoxic stress by modulating p53
RT transactivation.";
RL Cell 130:624-637(2007).
RN [26]
RP PHOSPHORYLATION AT SER-12.
RX PubMed=18022393; DOI=10.1016/j.febslet.2007.11.022;
RA Arai S., Matsushita A., Du K., Yagi K., Okazaki Y., Kurokawa R.;
RT "Novel homeodomain-interacting protein kinase family member, HIPK4,
RT phosphorylates human p53 at serine 9.";
RL FEBS Lett. 581:5649-5657(2007).
RN [27]
RP INTERACTION WITH CHD8.
RX PubMed=19151705; DOI=10.1038/ncb1831;
RA Nishiyama M., Oshikawa K., Tsukada Y.I., Nakagawa T., Iemura S.,
RA Natsume T., Fan Y., Kikuchi A., Skoultchi A.I., Nakayama K.I.;
RT "CHD8 suppresses p53-mediated apoptosis through histone H1 recruitment
RT during early embryogenesis.";
RL Nat. Cell Biol. 11:172-182(2009).
RN [28]
RP FUNCTION, UBIQUITINATION, AND INTERACTION WITH TRIM24.
RX PubMed=19556538; DOI=10.1073/pnas.0813177106;
RA Allton K., Jain A.K., Herz H.M., Tsai W.W., Jung S.Y., Qin J., Bergmann A.,
RA Johnson R.L., Barton M.C.;
RT "Trim24 targets endogenous p53 for degradation.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:11612-11616(2009).
RN [29]
RP FUNCTION.
RX PubMed=20673990; DOI=10.1016/j.cell.2010.06.040;
RA Huarte M., Guttman M., Feldser D., Garber M., Koziol M.J.,
RA Kenzelmann-Broz D., Khalil A.M., Zuk O., Amit I., Rabani M., Attardi L.D.,
RA Regev A., Lander E.S., Jacks T., Rinn J.L.;
RT "A large intergenic noncoding RNA induced by p53 mediates global gene
RT repression in the p53 response.";
RL Cell 142:409-419(2010).
RN [30]
RP FUNCTION.
RX PubMed=22726440; DOI=10.1016/j.cell.2012.05.014;
RA Vaseva A.V., Marchenko N.D., Ji K., Tsirka S.E., Holzmann S., Moll U.M.;
RT "p53 opens the mitochondrial permeability transition pore to trigger
RT necrosis.";
RL Cell 149:1536-1548(2012).
RN [31]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-318, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [32]
RP FUNCTION, AND INDUCTION.
RX PubMed=24051492; DOI=10.1038/ncomms3444;
RA Miki T., Matsumoto T., Zhao Z., Lee C.C.;
RT "p53 regulates Period2 expression and the circadian clock.";
RL Nat. Commun. 4:2444-2444(2013).
RN [33]
RP INTERACTION WITH C10ORF90, AND UBIQUITINATION BY C10ORF90.
RX PubMed=24240685; DOI=10.1038/onc.2013.494;
RA Yan S., Qiu L., Ma K., Zhang X., Zhao Y., Zhang J., Li X., Hao X., Li Z.;
RT "FATS is an E2-independent ubiquitin ligase that stabilizes p53 and
RT promotes its activation in response to DNA damage.";
RL Oncogene 33:5424-5433(2014).
RN [34]
RP UBIQUITINATION, AND PROTEASOMAL DEGRADATION.
RX PubMed=25732823; DOI=10.1016/j.celrep.2015.01.066;
RA Qin B., Minter-Dykhouse K., Yu J., Zhang J., Liu T., Zhang H., Lee S.,
RA Kim J., Wang L., Lou Z.;
RT "DBC1 functions as a tumor suppressor by regulating p53 stability.";
RL Cell Rep. 10:1324-1334(2015).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 99-284.
RX PubMed=11152481; DOI=10.1074/jbc.m011644200;
RA Zhao K., Chai X., Johnston K., Clements A., Marmorstein R.;
RT "Crystal structure of the mouse p53 core DNA-binding domain at 2.7 A
RT resolution.";
RL J. Biol. Chem. 276:12120-12127(2001).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 95-292.
RX PubMed=17139084; DOI=10.1107/s090744490603890x;
RA Ho W.C., Luo C., Zhao K., Chai X., Fitzgerald M.X., Marmorstein R.;
RT "High-resolution structure of the p53 core domain: implications for binding
RT small-molecule stabilizing compounds.";
RL Acta Crystallogr. D 62:1484-1493(2006).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 95-292 IN COMPLEX WITH DNA AND
RP ZINC IONS, AND SUBUNIT.
RX PubMed=16717092; DOI=10.1074/jbc.m603634200;
RA Ho W.C., Fitzgerald M.X., Marmorstein R.;
RT "Structure of the p53 core domain dimer bound to DNA.";
RL J. Biol. Chem. 281:20494-20502(2006).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 95-287.
RX PubMed=17876829; DOI=10.1002/prot.21608;
RA Kwon E., Kim D.Y., Suh S.W., Kim K.K.;
RT "Crystal structure of the mouse p53 core domain in zinc-free state.";
RL Proteins 70:280-283(2008).
RN [39]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 96-292 IN COMPLEX WITH DNA, AND
RP SUBUNIT.
RX PubMed=18978813; DOI=10.1038/onc.2008.400;
RA Malecka K.A., Ho W.C., Marmorstein R.;
RT "Crystal structure of a p53 core tetramer bound to DNA.";
RL Oncogene 28:325-333(2009).
CC -!- FUNCTION: Acts as a tumor suppressor in many tumor types; induces
CC growth arrest or apoptosis depending on the physiological circumstances
CC and cell type. Involved in cell cycle regulation as a trans-activator
CC that acts to negatively regulate cell division by controlling a set of
CC genes required for this process. One of the activated genes is an
CC inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be
CC mediated either by stimulation of BAX and FAS antigen expression, or by
CC repression of Bcl-2 expression. Its pro-apoptotic activity is activated
CC via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 (By
CC similarity). However, this activity is inhibited when the interaction
CC with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP (By
CC similarity). In cooperation with mitochondrial PPIF is involved in
CC activating oxidative stress-induced necrosis; the function is largely
CC independent of transcription. Prevents CDK7 kinase activity when
CC associated to CAK complex in response to DNA damage, thus stopping cell
CC cycle progression (By similarity). Induces the transcription of long
CC intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-
CC p21 participates in TP53-dependent transcriptional repression leading
CC to apoptosis, but seems to have to effect on cell-cycle regulation.
CC Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated
CC transcriptional activation of PER2 (PubMed:24051492).
CC {ECO:0000250|UniProtKB:P04637, ECO:0000269|PubMed:19556538,
CC ECO:0000269|PubMed:20673990, ECO:0000269|PubMed:22726440,
CC ECO:0000269|PubMed:24051492}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:16717092};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:16717092};
CC -!- SUBUNIT: Forms homodimers and homotetramers (By similarity). Binds DNA
CC as a homotetramer. Interacts with AXIN1 (PubMed:15526030). Probably
CC part of a complex consisting of TP53, HIPK2 and AXIN1
CC (PubMed:15526030). Interacts with histone acetyltransferases EP300 and
CC methyltransferases HRMT1L2 and CARM1, and recruits them to promoters.
CC Interacts (via C-terminus) with TAF1; when TAF1 is part of the TFIID
CC complex. Interacts with ING4; this interaction may be indirect
CC (PubMed:12702766). Found in a complex with CABLES1 and TP73
CC (PubMed:11706030). Interacts with HIPK1, HIPK2, and TP53INP1. Interacts
CC with WWOX. Interacts with USP7 and SYVN1 (PubMed:14719112). Interacts
CC with HSP90AB1. Interacts with CHD8; leading to recruit histone H1 and
CC prevent transactivation activity (PubMed:19151705). Interacts with
CC ARMC10, BANP, CDKN2AIP, NUAK1, STK11/LKB1, UHRF2 and E4F
CC (PubMed:10644996). Interacts with YWHAZ; the interaction enhances TP53
CC transcriptional activity. Phosphorylation of YWHAZ on 'Ser-58' inhibits
CC this interaction. Interacts (via DNA-binding domain) with MAML1 (via N-
CC terminus). Interacts with MKRN1. Interacts with PML (via C-terminus).
CC Interacts with MDM2; leading to ubiquitination and proteasomal
CC degradation of TP53. Directly interacts with FBXO42; leading to
CC ubiquitination and degradation of TP53. Interacts (phosphorylated at
CC Ser-18 by ATM) with the phosphatase PP2A-PPP2R5C holoenzyme; regulates
CC stress-induced TP53-dependent inhibition of cell proliferation.
CC Interacts with PPP2R2A. Interacts with AURKA, DAXX, BRD7 and TRIM24
CC (PubMed:19556538). Interacts (when monomethylated at Lys-379) with
CC L3MBTL1. Interacts with GRK5. Binds to the CAK complex (CDK7, cyclin H
CC and MAT1) in response to DNA damage. Interacts with CDK5 in neurons.
CC Interacts with AURKB, SETD2, UHRF2 and NOC2L. Interacts (via N-
CC terminus) with PTK2/FAK1; this promotes ubiquitination by MDM2.
CC Interacts with PTK2B/PYK2; this promotes ubiquitination by MDM2.
CC Interacts with PRKCG. Interacts with PPIF; the association implicates
CC preferentially tetrameric TP53, is induced by oxidative stress and is
CC impaired by cyclosporin A (CsA). Interacts with SNAI1; the interaction
CC induces SNAI1 degradation via MDM2-mediated ubiquitination and inhibits
CC SNAI1-induced cell invasion. Interacts with KAT6A. Interacts with UBC9.
CC Interacts with ZNF385B; the interaction is direct. Interacts (via DNA-
CC binding domain) with ZNF385A; the interaction is direct and enhances
CC p53/TP53 transactivation functions on cell-cycle arrest target genes,
CC resulting in growth arrest (PubMed:17719541). Interacts with ANKRD2.
CC Interacts with RFFL and RNF34; involved in p53/TP53 ubiquitination.
CC Interacts with MTA1 and COP1. Interacts with CCAR2 (via N-terminus).
CC Interacts with MORC3. Interacts (via C-terminus) with POU4F2 (via C-
CC terminus). Interacts (via oligomerization region) with NOP53; the
CC interaction is direct and may prevent the MDM2-mediated proteasomal
CC degradation of TP53. Interacts with AFG1L; mediates mitochondrial
CC translocation of TP53. Interacts with UBD (By similarity). Interacts
CC with TAF6 (By similarity). Interacts with C10orf90/FATS; the
CC interaction inhibits binding of TP53 and MDM2 (PubMed:24240685).
CC Interacts with NUPR1; interaction is stress-dependent. Forms a complex
CC with EP300 and NUPR1; this complex binds CDKN1A promoter leading to
CC transcriptional induction of CDKN1A (By similarity). Interacts with
CC PRMT5 in response to DNA damage; the interaction is TTC5/STRAP
CC dependent (By similarity). Interacts with PPP1R13L (via SH3 domain and
CC ANK repeats); the interaction inhibits pro-apoptotic activity of
CC p53/TP53 (By similarity). Interacts with PPP1R13B/ASPP1 and
CC TP53BP2/ASPP2; the interactions promotes pro-apoptotic activity (By
CC similarity). When phosphorylated at Ser-18, interacts with DDX3X and
CC gamma-tubulin (By similarity). Interacts with KAT7/HBO1; leading to
CC inhibit histone acetyltransferase activity of KAT7/HBO1 (By
CC similarity). Interacts (via N-terminus) with E3 ubiquitin-protein
CC ligase MUL1; the interaction results in ubiquitination of cytoplasmic
CC TP53 at Lys-27 and subsequent proteasomal degradation (By similarity).
CC Interacts with S100A4; this interaction promotes TP53 degradation (By
CC similarity). Interacts with TTC5/STRAP; the interaction may result in
CC increased mitochondrial-dependent apoptosis (By similarity). Interacts
CC with NQO1; this interaction is NADH-dependent, stabilizes TP53 in
CC response to oxidative stress and protects it from ubiquitin-independent
CC degradation by the 20S proteasome. {ECO:0000250|UniProtKB:P04637,
CC ECO:0000250|UniProtKB:P10361, ECO:0000269|PubMed:10644996,
CC ECO:0000269|PubMed:11706030, ECO:0000269|PubMed:12494467,
CC ECO:0000269|PubMed:12702766, ECO:0000269|PubMed:14719112,
CC ECO:0000269|PubMed:15526030, ECO:0000269|PubMed:17719541,
CC ECO:0000269|PubMed:19151705, ECO:0000269|PubMed:19556538,
CC ECO:0000269|PubMed:24240685}.
CC -!- INTERACTION:
CC P02340; P97302: Bach1; NbExp=4; IntAct=EBI-474016, EBI-2552417;
CC P02340; B2RWS6: Ep300; NbExp=3; IntAct=EBI-474016, EBI-3953360;
CC P02340; P23804: Mdm2; NbExp=9; IntAct=EBI-474016, EBI-641788;
CC P02340; P23804-1: Mdm2; NbExp=2; IntAct=EBI-474016, EBI-3386476;
CC P02340; Q9QUR7: Pin1; NbExp=3; IntAct=EBI-474016, EBI-2432975;
CC P02340; P54099: Polg; NbExp=2; IntAct=EBI-474016, EBI-863636;
CC P02340; Q99KR7: Ppif; NbExp=2; IntAct=EBI-474016, EBI-6455001;
CC P02340; O08586: Pten; NbExp=4; IntAct=EBI-474016, EBI-1186266;
CC P02340; Q61466: Smarcd1; NbExp=4; IntAct=EBI-474016, EBI-371529;
CC P02340; P09671: Sod2; NbExp=2; IntAct=EBI-474016, EBI-1635071;
CC P02340; Q64127: Trim24; NbExp=2; IntAct=EBI-474016, EBI-307947;
CC P02340; P62991: Ubc; NbExp=4; IntAct=EBI-474016, EBI-413074;
CC P02340; Q07817-1: BCL2L1; Xeno; NbExp=3; IntAct=EBI-474016, EBI-287195;
CC P02340; P03070; Xeno; NbExp=19; IntAct=EBI-474016, EBI-617698;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P04637}. Nucleus
CC {ECO:0000250|UniProtKB:P04637}. Nucleus, PML body
CC {ECO:0000250|UniProtKB:P04637}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:P04637}. Mitochondrion matrix
CC {ECO:0000250|UniProtKB:P04637}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:P04637}.
CC Note=Interaction with BANP promotes nuclear localization. Recruited
CC into PML bodies together with CHEK2. Translocates to mitochondria upon
CC oxidative stress. Translocates to mitochondria in response to mitomycin
CC C treatment (By similarity). {ECO:0000250|UniProtKB:P04637}.
CC -!- INDUCTION: Expressed in a circadian manner in the suprachiasmatic
CC nucleus (SCN) of the brain with a peak seen at ZT8.
CC {ECO:0000269|PubMed:24051492}.
CC -!- DOMAIN: The [KR]-[STA]-K motif is specifically recognized by the SETD7
CC methyltransferase. {ECO:0000250}.
CC -!- PTM: Phosphorylation on Ser residues mediates transcriptional
CC activation. Phosphorylation at Ser-12 by HIPK4 increases repression
CC activity on BIRC5 promoter. Phosphorylated on Thr-21 by VRK1.
CC Phosphorylated on Ser-23 by CHEK2 in response to DNA damage, which
CC prevents ubiquitination by MDM2. Phosphorylated on Ser-23 by PLK3 in
CC response to reactive oxygen species (ROS), promoting p53/TP53-mediated
CC apoptosis. Probably phosphorylated on by CDK7 in a CAK complex in
CC response to DNA damage. Stabilized by CDK5-mediated phosphorylation in
CC response to genotoxic and oxidative stresses at Ser-18 leading to
CC accumulation of p53/TP53, particularly in the nucleus, thus inducing
CC the transactivation of p53/TP53 target genes (By similarity).
CC Phosphorylated on Ser-389 following UV but not gamma irradiation.
CC Phosphorylated by HIPK1. Phosphorylation at Ser-18 is required for
CC interaction with DDX3X and gamma-tubulin (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P04637, ECO:0000269|PubMed:12702766,
CC ECO:0000269|PubMed:15195100, ECO:0000269|PubMed:17254968,
CC ECO:0000269|PubMed:18022393, ECO:0000269|PubMed:19556538,
CC ECO:0000269|PubMed:2145148, ECO:0000269|PubMed:3006031}.
CC -!- PTM: Ubiquitinated by MDM2 and SYVN1, which leads to proteasomal
CC degradation. Ubiquitinated by RFWD3, which works in cooperation with
CC MDM2 and may catalyze the formation of short polyubiquitin chains on
CC p53/TP53 that are not targeted to the proteasome. Ubiquitinated by
CC MKRN1 at Lys-288 and Lys-289, which leads to proteasomal degradation.
CC Deubiquitinated by USP10, leading to stabilize it. Ubiquitinated by
CC TRIM24, RFFL, RNF34 and RNF125, which leads to proteasomal degradation.
CC Ubiquitination by TOPORS induces degradation. Deubiquitination by USP7,
CC leading to stabilize it. Ubiquitinated by COP1, which leads to
CC proteasomal degradation (By similarity). Ubiquitination and subsequent
CC proteasomal degradation is negatively regulated by CCAR2
CC (PubMed:25732823). Polyubiquitinated by C10orf90/FATS,
CC polyubiquitination is 'Lys-48'-linkage independent and non-proteolytic,
CC leading to TP53 stabilization (PubMed:24240685).
CC {ECO:0000250|UniProtKB:P04637, ECO:0000269|PubMed:24240685,
CC ECO:0000269|PubMed:25732823}.
CC -!- PTM: Monomethylated at Lys-369 by SETD7, leading to stabilization and
CC increased transcriptional activation. Monomethylated at Lys-367 by
CC SMYD2, leading to decreased DNA-binding activity and subsequent
CC transcriptional regulation activity. Lys-369 monomethylation prevents
CC interaction with SMYD2 and subsequent monomethylation at Lys-367.
CC Dimethylated at Lys-370 by EHMT1 and EHMT2. Monomethylated at Lys-379
CC by KMT5A, promoting interaction with L3MBTL1 and leading to repress
CC transcriptional activity. Demethylation of dimethylated Lys-367 by
CC KDM1A prevents interaction with TP53BP1 and represses TP53-mediated
CC transcriptional activation (By similarity). Monomethylated at Arg-330
CC and dimethylated at Arg-332 and Arg-334 by PRMT5; methylation is
CC increased after DNA damage and might possibly affect TP53 target gene
CC specificity (By similarity). Polyubiquitinated by MUL1 at Lys-27 which
CC leads to proteasomal degradation (By similarity).
CC {ECO:0000250|UniProtKB:P04637}.
CC -!- PTM: Sumoylated with SUMO1. Sumoylated at Lys-383 by UBC9 (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Acetylation of Lys-379 by CREBBP enhances transcriptional
CC activity. Acetylation of Lys-379 by EP300. Deacetylation of Lys-379 by
CC SIRT1 impairs its ability to induce proapoptotic program and modulate
CC cell senescence. Deacetylation by SIRT2 impairs its ability to induce
CC transcription activation in a AKT-dependent manner. Acetylation at Lys-
CC 378 increases stability. Deacetylation at Lys-378 by SIRT6 decreases
CC its stability, thereby regulating cell senescence.
CC {ECO:0000250|UniProtKB:P04637}.
CC -!- DISEASE: Note=p53 is found in increased amounts in a wide variety of
CC transformed cells. p53 is frequently mutated or inactivated in many
CC types of cancer.
CC -!- SIMILARITY: Belongs to the p53 family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-4 is the initiator.
CC {ECO:0000305}.
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DR EMBL; X00876; CAA25420.1; -; Genomic_DNA.
DR EMBL; X00877; CAA25420.1; JOINED; Genomic_DNA.
DR EMBL; X00878; CAA25420.1; JOINED; Genomic_DNA.
DR EMBL; X00879; CAA25420.1; JOINED; Genomic_DNA.
DR EMBL; X00880; CAA25420.1; JOINED; Genomic_DNA.
DR EMBL; X00881; CAA25420.1; JOINED; Genomic_DNA.
DR EMBL; X00882; CAA25420.1; JOINED; Genomic_DNA.
DR EMBL; X00883; CAA25420.1; JOINED; Genomic_DNA.
DR EMBL; X00884; CAA25420.1; JOINED; Genomic_DNA.
DR EMBL; X00885; CAA25420.1; JOINED; Genomic_DNA.
DR EMBL; X01237; CAA25625.1; -; mRNA.
DR EMBL; X00741; CAA25323.1; -; mRNA.
DR EMBL; M13872; AAA39881.1; -; mRNA.
DR EMBL; M13873; AAA39882.1; -; mRNA.
DR EMBL; M13874; AAA39883.1; ALT_SEQ; mRNA.
DR EMBL; AB021961; BAA82344.1; -; mRNA.
DR EMBL; AF151353; AAD39535.1; -; mRNA.
DR EMBL; AB017815; BAA82339.1; -; mRNA.
DR EMBL; AB017816; BAA82340.1; -; mRNA.
DR EMBL; AB020317; BAA82343.1; -; mRNA.
DR EMBL; BC005448; AAH05448.1; -; mRNA.
DR EMBL; S77930; AAB21108.2; -; Genomic_DNA.
DR CCDS; CCDS36193.1; -.
DR PIR; A22739; DNMS53.
DR PIR; S38824; S38824.
DR RefSeq; NP_001120705.1; NM_001127233.1.
DR RefSeq; NP_035770.2; NM_011640.3.
DR RefSeq; XP_006533220.1; XM_006533157.3.
DR PDB; 1HU8; X-ray; 2.70 A; A/B/C=99-284.
DR PDB; 2GEQ; X-ray; 2.30 A; A/B=92-292.
DR PDB; 2IOI; X-ray; 1.55 A; A=92-292.
DR PDB; 2IOM; X-ray; 2.00 A; A=92-292.
DR PDB; 2IOO; X-ray; 2.02 A; A=92-292.
DR PDB; 2P52; X-ray; 1.50 A; A=92-287.
DR PDB; 3EXJ; X-ray; 2.00 A; A/B=96-292.
DR PDB; 3EXL; X-ray; 2.20 A; A=96-292.
DR PDBsum; 1HU8; -.
DR PDBsum; 2GEQ; -.
DR PDBsum; 2IOI; -.
DR PDBsum; 2IOM; -.
DR PDBsum; 2IOO; -.
DR PDBsum; 2P52; -.
DR PDBsum; 3EXJ; -.
DR PDBsum; 3EXL; -.
DR AlphaFoldDB; P02340; -.
DR SMR; P02340; -.
DR BioGRID; 204323; 136.
DR CORUM; P02340; -.
DR DIP; DIP-369N; -.
DR IntAct; P02340; 50.
DR MINT; P02340; -.
DR STRING; 10090.ENSMUSP00000104298; -.
DR ChEMBL; CHEMBL4164; -.
DR iPTMnet; P02340; -.
DR PhosphoSitePlus; P02340; -.
DR SwissPalm; P02340; -.
DR EPD; P02340; -.
DR PaxDb; P02340; -.
DR PRIDE; P02340; -.
DR ABCD; P02340; 20 sequenced antibodies.
DR Antibodypedia; 3525; 9422 antibodies from 64 providers.
DR DNASU; 22059; -.
DR Ensembl; ENSMUST00000108658; ENSMUSP00000104298; ENSMUSG00000059552.
DR GeneID; 22059; -.
DR KEGG; mmu:22059; -.
DR UCSC; uc007jql.2; mouse.
DR CTD; 22059; -.
DR MGI; MGI:98834; Trp53.
DR VEuPathDB; HostDB:ENSMUSG00000059552; -.
DR eggNOG; ENOG502QVY3; Eukaryota.
DR GeneTree; ENSGT00950000183153; -.
DR HOGENOM; CLU_019621_0_0_1; -.
DR InParanoid; P02340; -.
DR OMA; FHKKGEP; -.
DR OrthoDB; 257530at2759; -.
DR Reactome; R-MMU-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-MMU-2559584; Formation of Senescence-Associated Heterochromatin Foci (SAHF).
DR Reactome; R-MMU-2559585; Oncogene Induced Senescence.
DR Reactome; R-MMU-2559586; DNA Damage/Telomere Stress Induced Senescence.
DR Reactome; R-MMU-349425; Autodegradation of the E3 ubiquitin ligase COP1.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-5689896; Ovarian tumor domain proteases.
DR Reactome; R-MMU-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR Reactome; R-MMU-6804754; Regulation of TP53 Expression.
DR Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-MMU-6804757; Regulation of TP53 Degradation.
DR Reactome; R-MMU-6804758; Regulation of TP53 Activity through Acetylation.
DR Reactome; R-MMU-6804759; Regulation of TP53 Activity through Association with Co-factors.
DR Reactome; R-MMU-6804760; Regulation of TP53 Activity through Methylation.
DR Reactome; R-MMU-6811555; PI5P Regulates TP53 Acetylation.
DR Reactome; R-MMU-69473; G2/M DNA damage checkpoint.
DR Reactome; R-MMU-69481; G2/M Checkpoints.
DR Reactome; R-MMU-69541; Stabilization of p53.
DR Reactome; R-MMU-69895; Transcriptional activation of cell cycle inhibitor p21.
DR Reactome; R-MMU-8852276; The role of GTSE1 in G2/M progression after G2 checkpoint.
DR Reactome; R-MMU-8941855; RUNX3 regulates CDKN1A transcription.
DR BioGRID-ORCS; 22059; 15 hits in 115 CRISPR screens.
DR ChiTaRS; Trp53; mouse.
DR EvolutionaryTrace; P02340; -.
DR PRO; PR:P02340; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P02340; protein.
DR Bgee; ENSMUSG00000059552; Expressed in embryonic post-anal tail and 232 other tissues.
DR ExpressionAtlas; P02340; baseline and differential.
DR Genevisible; P02340; MM.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0000785; C:chromatin; ISS:ARUK-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0043073; C:germ cell nucleus; IDA:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0016363; C:nuclear matrix; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:ARUK-UCL.
DR GO; GO:0016605; C:PML body; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0005657; C:replication fork; IDA:MGI.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:MGI.
DR GO; GO:0035861; C:site of double-strand break; IDA:MGI.
DR GO; GO:0005667; C:transcription regulator complex; ISO:MGI.
DR GO; GO:0017053; C:transcription repressor complex; ISO:MGI.
DR GO; GO:0036310; F:ATP-dependent DNA/DNA annealing activity; ISS:UniProtKB.
DR GO; GO:0051087; F:chaperone binding; ISO:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0005507; F:copper ion binding; ISS:UniProtKB.
DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0097718; F:disordered domain specific binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:MGI.
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; ISO:MGI.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0140296; F:general transcription initiation factor binding; ISO:MGI.
DR GO; GO:0035035; F:histone acetyltransferase binding; ISO:MGI.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI.
DR GO; GO:0035033; F:histone deacetylase regulator activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0097371; F:MDM2/MDM4 family protein binding; IPI:BHF-UCL.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; ISO:MGI.
DR GO; GO:0002039; F:p53 binding; ISO:MGI.
DR GO; GO:1990841; F:promoter-specific chromatin binding; ISS:UniProtKB.
DR GO; GO:0002020; F:protease binding; ISO:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:MGI.
DR GO; GO:0051721; F:protein phosphatase 2A binding; ISO:MGI.
DR GO; GO:0019903; F:protein phosphatase binding; ISO:MGI.
DR GO; GO:0043621; F:protein self-association; ISO:MGI.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0001094; F:TFIID-class transcription factor complex binding; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0001221; F:transcription coregulator binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IDA:MGI.
DR GO; GO:0006914; P:autophagy; ISO:MGI.
DR GO; GO:0002326; P:B cell lineage commitment; IMP:MGI.
DR GO; GO:0048539; P:bone marrow development; ISO:MGI.
DR GO; GO:0010659; P:cardiac muscle cell apoptotic process; IMP:MGI.
DR GO; GO:0060411; P:cardiac septum morphogenesis; IGI:MGI.
DR GO; GO:0008283; P:cell population proliferation; IGI:MGI.
DR GO; GO:0072717; P:cellular response to actinomycin D; ISO:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:MGI.
DR GO; GO:0071480; P:cellular response to gamma radiation; IDA:MGI.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISO:MGI.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IDA:CAFA.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; ISO:MGI.
DR GO; GO:0034644; P:cellular response to UV; IDA:CAFA.
DR GO; GO:0071494; P:cellular response to UV-C; IGI:MGI.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0090398; P:cellular senescence; ISS:UniProtKB.
DR GO; GO:0007417; P:central nervous system development; IGI:MGI.
DR GO; GO:0021549; P:cerebellum development; IDA:MGI.
DR GO; GO:0031497; P:chromatin assembly; ISO:MGI.
DR GO; GO:0051276; P:chromosome organization; IGI:MGI.
DR GO; GO:0048512; P:circadian behavior; IMP:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:BHF-UCL.
DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; IDA:MGI.
DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; IGI:MGI.
DR GO; GO:0006978; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; IDA:MGI.
DR GO; GO:0006302; P:double-strand break repair; IMP:MGI.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IGI:MGI.
DR GO; GO:0048568; P:embryonic organ development; IGI:MGI.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; IMP:UniProtKB.
DR GO; GO:0006983; P:ER overload response; ISO:MGI.
DR GO; GO:0048144; P:fibroblast proliferation; IMP:MGI.
DR GO; GO:0007369; P:gastrulation; IGI:MGI.
DR GO; GO:0014009; P:glial cell proliferation; IGI:MGI.
DR GO; GO:0019661; P:glucose catabolic process to lactate via pyruvate; IMP:MGI.
DR GO; GO:0007507; P:heart development; IGI:MGI.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; ISO:MGI.
DR GO; GO:0060218; P:hematopoietic stem cell differentiation; ISO:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IGI:MGI.
DR GO; GO:0060333; P:interferon-gamma-mediated signaling pathway; IMP:CAFA.
DR GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; IDA:CAFA.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IDA:CAFA.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IMP:ParkinsonsUK-UCL.
DR GO; GO:1990144; P:intrinsic apoptotic signaling pathway in response to hypoxia; IMP:MGI.
DR GO; GO:0043504; P:mitochondrial DNA repair; IMP:MGI.
DR GO; GO:0000423; P:mitophagy; IMP:MGI.
DR GO; GO:0031571; P:mitotic G1 DNA damage checkpoint signaling; IMP:MGI.
DR GO; GO:0009299; P:mRNA transcription; ISO:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IGI:MGI.
DR GO; GO:0070266; P:necroptotic process; IGI:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:MGI.
DR GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:BHF-UCL.
DR GO; GO:2000279; P:negative regulation of DNA biosynthetic process; ISO:MGI.
DR GO; GO:0008156; P:negative regulation of DNA replication; IDA:MGI.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IMP:MGI.
DR GO; GO:1903451; P:negative regulation of G1 to G0 transition; ISO:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; IGI:MGI.
DR GO; GO:0060253; P:negative regulation of glial cell proliferation; IGI:MGI.
DR GO; GO:1904024; P:negative regulation of glucose catabolic process to lactate via pyruvate; IMP:MGI.
DR GO; GO:1903799; P:negative regulation of miRNA maturation; IGI:MGI.
DR GO; GO:1901525; P:negative regulation of mitophagy; IMP:MGI.
DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IGI:MGI.
DR GO; GO:0007406; P:negative regulation of neuroblast proliferation; IGI:MGI.
DR GO; GO:1905856; P:negative regulation of pentose-phosphate shunt; ISO:MGI.
DR GO; GO:0045861; P:negative regulation of proteolysis; IMP:MGI.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IMP:MGI.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:2000647; P:negative regulation of stem cell proliferation; IGI:MGI.
DR GO; GO:0051974; P:negative regulation of telomerase activity; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IMP:MGI.
DR GO; GO:0007405; P:neuroblast proliferation; IGI:MGI.
DR GO; GO:0051402; P:neuron apoptotic process; IMP:MGI.
DR GO; GO:0006289; P:nucleotide-excision repair; ISS:UniProtKB.
DR GO; GO:0097252; P:oligodendrocyte apoptotic process; ISS:UniProtKB.
DR GO; GO:0090403; P:oxidative stress-induced premature senescence; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:MGI.
DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; IMP:MGI.
DR GO; GO:0045787; P:positive regulation of cell cycle; ISO:MGI.
DR GO; GO:2000774; P:positive regulation of cellular senescence; IMP:BHF-UCL.
DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0031065; P:positive regulation of histone deacetylation; IDA:MGI.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0002687; P:positive regulation of leukocyte migration; ISO:MGI.
DR GO; GO:1903800; P:positive regulation of miRNA maturation; ISO:MGI.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; ISO:MGI.
DR GO; GO:0035794; P:positive regulation of mitochondrial membrane permeability; IGI:MGI.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IDA:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IMP:BHF-UCL.
DR GO; GO:0062100; P:positive regulation of programmed necrotic cell death; IMP:ARUK-UCL.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; ISO:MGI.
DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; ISO:MGI.
DR GO; GO:0045899; P:positive regulation of RNA polymerase II transcription preinitiation complex assembly; ISO:MGI.
DR GO; GO:0070245; P:positive regulation of thymocyte apoptotic process; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:1990440; P:positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; IMP:ParkinsonsUK-UCL.
DR GO; GO:0061419; P:positive regulation of transcription from RNA polymerase II promoter in response to hypoxia; IMP:MGI.
DR GO; GO:0036003; P:positive regulation of transcription from RNA polymerase II promoter in response to stress; IDA:CAFA.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0006606; P:protein import into nucleus; IDA:MGI.
DR GO; GO:0008104; P:protein localization; ISO:MGI.
DR GO; GO:0050821; P:protein stabilization; IGI:MGI.
DR GO; GO:0051262; P:protein tetramerization; IEA:InterPro.
DR GO; GO:0065003; P:protein-containing complex assembly; ISO:MGI.
DR GO; GO:0007265; P:Ras protein signal transduction; IEA:Ensembl.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IMP:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; ISO:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:MGI.
DR GO; GO:1902749; P:regulation of cell cycle G2/M phase transition; ISO:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:MGI.
DR GO; GO:2000772; P:regulation of cellular senescence; IGI:MGI.
DR GO; GO:0043516; P:regulation of DNA damage response, signal transduction by p53 class mediator; IGI:MGI.
DR GO; GO:2000269; P:regulation of fibroblast apoptotic process; IGI:MGI.
DR GO; GO:1903205; P:regulation of hydrogen peroxide-induced cell death; ISO:MGI.
DR GO; GO:0051453; P:regulation of intracellular pH; ISO:MGI.
DR GO; GO:1902253; P:regulation of intrinsic apoptotic signaling pathway by p53 class mediator; IMP:MGI.
DR GO; GO:1902108; P:regulation of mitochondrial membrane permeability involved in apoptotic process; IGI:MGI.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IDA:MGI.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; IGI:MGI.
DR GO; GO:0070243; P:regulation of thymocyte apoptotic process; IGI:MGI.
DR GO; GO:0034103; P:regulation of tissue remodeling; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:1990248; P:regulation of transcription from RNA polymerase II promoter in response to DNA damage; ISS:ARUK-UCL.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IDA:MGI.
DR GO; GO:0090399; P:replicative senescence; ISO:MGI.
DR GO; GO:0010332; P:response to gamma radiation; IDA:MGI.
DR GO; GO:0002931; P:response to ischemia; IMP:MGI.
DR GO; GO:0006979; P:response to oxidative stress; IMP:MGI.
DR GO; GO:0009651; P:response to salt stress; IGI:MGI.
DR GO; GO:0009411; P:response to UV; IDA:MGI.
DR GO; GO:0010165; P:response to X-ray; IDA:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:MGI.
DR GO; GO:0009303; P:rRNA transcription; IGI:MGI.
DR GO; GO:0072331; P:signal transduction by p53 class mediator; ISO:MGI.
DR GO; GO:0001756; P:somitogenesis; IGI:MGI.
DR GO; GO:0007283; P:spermatogenesis; ISO:MGI.
DR GO; GO:0072089; P:stem cell proliferation; IGI:MGI.
DR GO; GO:0033077; P:T cell differentiation in thymus; IGI:MGI.
DR GO; GO:0002360; P:T cell lineage commitment; IMP:MGI.
DR GO; GO:0002309; P:T cell proliferation involved in immune response; IGI:MGI.
DR GO; GO:0070242; P:thymocyte apoptotic process; IMP:MGI.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IGI:MGI.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; ISO:MGI.
DR GO; GO:0016032; P:viral process; ISO:MGI.
DR CDD; cd08367; P53; 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; IPR013872; p53_transactivation_domain.
DR InterPro; IPR002117; p53_tumour_suppressor.
DR PANTHER; PTHR11447; PTHR11447; 1.
DR Pfam; PF00870; P53; 1.
DR Pfam; PF08563; P53_TAD; 1.
DR Pfam; PF07710; P53_tetramer; 1.
DR PRINTS; PR00386; P53SUPPRESSR.
DR SUPFAM; SSF47719; SSF47719; 1.
DR SUPFAM; SSF49417; SSF49417; 1.
DR PROSITE; PS00348; P53; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Apoptosis; Biological rhythms;
KW Cell cycle; Cytoplasm; Cytoskeleton; Disease variant; DNA-binding;
KW Endoplasmic reticulum; Isopeptide bond; Metal-binding; Methylation;
KW Mitochondrion; Necrosis; Nucleus; Phosphoprotein; Reference proteome;
KW Repressor; Transcription; Transcription regulation; Tumor suppressor;
KW Ubl conjugation; Zinc.
FT CHAIN 1..390
FT /note="Cellular tumor antigen p53"
FT /id="PRO_0000185709"
FT DNA_BIND 99..289
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT REGION 4..317
FT /note="Interaction with CCAR2"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT REGION 4..45
FT /note="Transcription activation (acidic)"
FT REGION 63..107
FT /note="Interaction with WWOX"
FT /evidence="ECO:0000250"
FT REGION 97..367
FT /note="Interaction with HIPK1"
FT /evidence="ECO:0000269|PubMed:12702766"
FT REGION 97..297
FT /note="Required for interaction with ZNF385A"
FT /evidence="ECO:0000250"
FT REGION 110..233
FT /note="Required for interaction with FBXO42"
FT /evidence="ECO:0000250"
FT REGION 113..289
FT /note="Interaction with AXIN1"
FT /evidence="ECO:0000269|PubMed:15526030"
FT REGION 256..294
FT /note="Interaction with E4F1"
FT /evidence="ECO:0000250"
FT REGION 270..277
FT /note="Interaction with DNA"
FT REGION 316..357
FT /note="Interaction with HIPK2"
FT /evidence="ECO:0000250"
FT REGION 322..353
FT /note="Oligomerization"
FT REGION 348..390
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 356..360
FT /note="Interaction with USP7"
FT /evidence="ECO:0000250"
FT REGION 365..384
FT /note="Basic (repression of DNA-binding)"
FT MOTIF 302..318
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 336..347
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT MOTIF 367..369
FT /note="[KR]-[STA]-K motif"
FT COMPBIAS 348..365
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 173
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:16717092"
FT BINDING 176
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:16717092"
FT BINDING 235
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:16717092"
FT BINDING 239
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:16717092"
FT SITE 117
FT /note="Interaction with DNA"
FT /evidence="ECO:0000269|PubMed:16717092"
FT MOD_RES 12
FT /note="Phosphoserine; by HIPK4"
FT /evidence="ECO:0000269|PubMed:18022393"
FT MOD_RES 18
FT /note="Phosphoserine; by CDK5, PRPK, AMPK, NUAK1 and ATM"
FT /evidence="ECO:0000269|PubMed:15195100"
FT MOD_RES 21
FT /note="Phosphothreonine; by CK1, VRK1 and VRK2"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 23
FT /note="Phosphoserine; by CHEK2, CK1 and PLK3"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 37
FT /note="Phosphoserine; by MAPKAPK5"
FT /evidence="ECO:0000269|PubMed:17254968"
FT MOD_RES 117
FT /note="N6-acetyllysine; by KAT6A"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 180
FT /note="Phosphoserine; by AURKB"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 266
FT /note="Phosphoserine; by AURKB"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 281
FT /note="Phosphothreonine; by AURKB"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 302
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 312
FT /note="Phosphoserine; by AURKA, CDK1 and CDK2"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 318
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 330
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 332
FT /note="Symmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 334
FT /note="Symmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 367
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 367
FT /note="N6-methyllysine; by SMYD2; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 369
FT /note="N6-methyllysine; by SETD7"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 370
FT /note="N6,N6-dimethyllysine; by EHMT1 and EHMT2; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 370
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 378
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 379
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 379
FT /note="N6-acetyllysine; by KAT6A; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 379
FT /note="N6-methyllysine; by KMT5A; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 389
FT /note="Phosphoserine; by CK2, CDK2 and NUAK1"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT CROSSLNK 27
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT CROSSLNK 288
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT CROSSLNK 289
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT CROSSLNK 383
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT VARIANT 135
FT /note="A -> V (can cooperate with an activated Ras to
FT transform fibroblasts)"
FT /evidence="ECO:0000269|PubMed:3329909"
FT VARIANT 168
FT /note="E -> G (in clone P53-M11)"
FT VARIANT 191
FT /note="L -> R"
FT CONFLICT 48
FT /note="Q -> R (in Ref. 3; CAA25323)"
FT /evidence="ECO:0000305"
FT CONFLICT 79..81
FT /note="PVA -> QW (in Ref. 3; CAA25323)"
FT /evidence="ECO:0000305"
FT HELIX 102..104
FT /evidence="ECO:0007829|PDB:2P52"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:2P52"
FT HELIX 116..119
FT /evidence="ECO:0007829|PDB:3EXJ"
FT STRAND 120..124
FT /evidence="ECO:0007829|PDB:2P52"
FT TURN 125..128
FT /evidence="ECO:0007829|PDB:2P52"
FT STRAND 129..132
FT /evidence="ECO:0007829|PDB:2P52"
FT STRAND 137..143
FT /evidence="ECO:0007829|PDB:2P52"
FT STRAND 153..162
FT /evidence="ECO:0007829|PDB:2P52"
FT TURN 163..167
FT /evidence="ECO:0007829|PDB:2P52"
FT HELIX 174..178
FT /evidence="ECO:0007829|PDB:2P52"
FT STRAND 184..186
FT /evidence="ECO:0007829|PDB:2P52"
FT STRAND 191..196
FT /evidence="ECO:0007829|PDB:2P52"
FT STRAND 201..204
FT /evidence="ECO:0007829|PDB:2P52"
FT TURN 206..208
FT /evidence="ECO:0007829|PDB:2P52"
FT STRAND 211..216
FT /evidence="ECO:0007829|PDB:2P52"
FT STRAND 225..233
FT /evidence="ECO:0007829|PDB:2P52"
FT HELIX 238..240
FT /evidence="ECO:0007829|PDB:2P52"
FT HELIX 242..245
FT /evidence="ECO:0007829|PDB:2P52"
FT STRAND 248..255
FT /evidence="ECO:0007829|PDB:2P52"
FT STRAND 261..271
FT /evidence="ECO:0007829|PDB:2P52"
FT HELIX 275..286
FT /evidence="ECO:0007829|PDB:2P52"
FT TURN 288..290
FT /evidence="ECO:0007829|PDB:3EXJ"
SQ SEQUENCE 390 AA; 43458 MW; ED5A607378D921D7 CRC64;
MTAMEESQSD ISLELPLSQE TFSGLWKLLP PEDILPSPHC MDDLLLPQDV EEFFEGPSEA
LRVSGAPAAQ DPVTETPGPV APAPATPWPL SSFVPSQKTY QGNYGFHLGF LQSGTAKSVM
CTYSPPLNKL FCQLAKTCPV QLWVSATPPA GSRVRAMAIY KKSQHMTEVV RRCPHHERCS
DGDGLAPPQH LIRVEGNLYP EYLEDRQTFR HSVVVPYEPP EAGSEYTTIH YKYMCNSSCM
GGMNRRPILT IITLEDSSGN LLGRDSFEVR VCACPGRDRR TEEENFRKKE VLCPELPPGS
AKRALPTCTS ASPPQKKKPL DGEYFTLKIR GRKRFEMFRE LNEALELKDA HATEESGDSR
AHSSYLKTKK GQSTSRHKKT MVKKVGPDSD
