P53_CRIGR
ID P53_CRIGR Reviewed; 393 AA.
AC O09185; P97258; P97788; Q64397;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Cellular tumor antigen p53;
DE AltName: Full=Tumor suppressor p53;
GN Name=TP53; Synonyms=P53;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS GLN-133 AND TRP-135.
RX PubMed=9023109; DOI=10.1093/nar/25.5.992;
RA Chaung W., Mi L.J., Boorstein R.J.;
RT "The p53 status of Chinese hamster V79 cells frequently used for studies on
RT DNA damage and DNA repair.";
RL Nucleic Acids Res. 25:992-994(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=9031625; DOI=10.1016/s0378-1119(96)00592-6;
RA Lee H., Larner J.M., Hamlin J.L.;
RT "Cloning and characterization of Chinese hamster p53 cDNA.";
RL Gene 184:177-183(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Embryonic fibroblast;
RA Shimizu T., Nikaido O., Suzuki F.;
RL Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases.
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. Induces the transcription of long intergenic non-
CC coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21
CC participates in TP53-dependent transcriptional repression leading to
CC apoptosis and seems to have an effect on cell-cycle regulation.
CC Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated
CC transcriptional activation of PER2. {ECO:0000250|UniProtKB:P02340,
CC ECO:0000250|UniProtKB:P04637}.
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: Forms homodimers and homotetramers (By similarity). Binds DNA
CC as a homotetramer. Interacts with AXIN1. Probably part of a complex
CC consisting of TP53, HIPK2 and AXIN1. Interacts with histone
CC acetyltransferases EP300 and methyltransferases HRMT1L2 and CARM1, and
CC recruits them to promoters. Interacts (via C-terminus) with TAF1; when
CC TAF1 is part of the TFIID complex. Interacts with ING4; this
CC interaction may be indirect. Found in a complex with CABLES1 and TP73.
CC Interacts with HIPK1, HIPK2, and TP53INP1. Interacts with WWOX.
CC Interacts with USP7 and SYVN1. Interacts with HSP90AB1. Interacts with
CC CHD8; leading to recruit histone H1 and prevent transactivation
CC activity. Interacts with ARMC10, BANP, CDKN2AIP, NUAK1, STK11/LKB1,
CC UHRF2 and E4F. 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-15 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 Interacts (when monomethylated at Lys-382) with L3MBTL1. Interacts with
CC GRK5. Binds to the CAK complex (CDK7, cyclin H and MAT1) in response to
CC DNA damage. Interacts with CDK5 in neurons. Interacts with AURKB,
CC SETD2, UHRF2 and NOC2L. Interacts (via N-terminus) with PTK2/FAK1; this
CC promotes ubiquitination by MDM2. Interacts with PTK2B/PYK2; this
CC promotes ubiquitination by MDM2. Interacts with PRKCG. Interacts with
CC PPIF; the association implicates preferentially tetrameric TP53, is
CC induced by oxidative stress and is impaired by cyclosporin A (CsA).
CC Interacts with SNAI1; the interaction induces SNAI1 degradation via
CC MDM2-mediated ubiquitination and inhibits SNAI1-induced cell invasion.
CC Interacts with KAT6A. Interacts with UBC9. Interacts with ZNF385B; the
CC interaction is direct. Interacts (via DNA-binding domain) with ZNF385A;
CC the interaction is direct and enhances p53/TP53 transactivation
CC functions on cell-cycle arrest target genes, resulting in growth arrest
CC (By similarity). Interacts with ANKRD2. Interacts with RFFL and RNF34;
CC involved in p53/TP53 ubiquitination. Interacts with MTA1 and COP1.
CC Interacts with CCAR2 (via N-terminus). Interacts with MORC3. Interacts
CC (via C-terminus) with POU4F2 (via C-terminus). Interacts (via
CC oligomerization region) with NOP53; the interaction is direct and may
CC prevent the MDM2-mediated proteasomal degradation of TP53. Interacts
CC with AFG1L; mediates mitochondrial translocation of TP53. Interacts
CC with UBD (By similarity). Interacts with TAF6 (By similarity).
CC Interacts with C10orf90/FATS; the interaction inhibits binding of TP53
CC and MDM2 (By similarity). Interacts with NUPR1; interaction is stress-
CC dependent. Forms a complex with EP300 and NUPR1; this complex binds
CC CDKN1A promoter leading to transcriptional induction of CDKN1A (By
CC similarity). Interacts with PRMT5 in response to DNA damage; the
CC interaction is TTC5/STRAP dependent (By similarity). Interacts with
CC PPP1R13L (via SH3 domain and ANK repeats); the interaction inhibits
CC pro-apoptotic activity of p53/TP53 (By similarity). Interacts with
CC PPP1R13B/ASPP1 and TP53BP2/ASPP2; the interactions promotes pro-
CC apoptotic activity (By similarity). When phosphorylated at Ser-15,
CC interacts with DDX3X and gamma-tubulin (By similarity). Interacts with
CC KAT7/HBO1; leading to inhibit histone acetyltransferase activity of
CC KAT7/HBO1 (By similarity). Interacts (via N-terminus) with E3
CC ubiquitin-protein ligase MUL1; the interaction results in
CC ubiquitination of cytoplasmic TP53 at Lys-24 and subsequent proteasomal
CC degradation (By similarity). Interacts with S100A4; this interaction
CC promotes TP53 degradation (By similarity). Interacts with TTC5/STRAP;
CC the interaction may result in increased mitochondrial-dependent
CC apoptosis (By similarity). Interacts with NQO1; this interaction is
CC NADH-dependent, stabilizes TP53 in response to oxidative stress and
CC protects it from ubiquitin-independent degradation by the 20S
CC proteasome. {ECO:0000250|UniProtKB:P02340,
CC ECO:0000250|UniProtKB:P04637, ECO:0000250|UniProtKB:P10361}.
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 -!- 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-9 by HIPK4 increases repression
CC activity on BIRC5 promoter (By similarity). Phosphorylated on Thr-18 by
CC VRK1, which may prevent the interaction with MDM2. Phosphorylated on
CC Ser-20 by CHEK2 in response to DNA damage, which prevents
CC ubiquitination by MDM2. Phosphorylated on Ser-20 by PLK3 in response to
CC reactive oxygen species (ROS), promoting p53/TP53-mediated apoptosis.
CC Phosphorylated on Ser-33 by CDK7 in a CAK complex in response to DNA
CC damage. Phosphorylated by HIPK1. Phosphorylated on Ser-392 following UV
CC but not gamma irradiation. Stabilized by CDK5-mediated phosphorylation
CC in response to genotoxic and oxidative stresses at Ser-15, Ser-33 and
CC Ser-47, leading to accumulation of p53/TP53, particularly in the
CC nucleus, thus inducing the transactivation of p53/TP53 target genes.
CC Phosphorylated by DYRK2 at Ser-47 in response to genotoxic stress.
CC Phosphorylated at Ser-315 and Ser-392 by CDK2 in response to DNA-damage
CC (By similarity). Phosphorylation at Ser-15 is required for interaction
CC with DDX3X and gamma-tubulin (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P04637}.
CC -!- PTM: Monomethylated at Lys-372 by SETD7, leading to stabilization and
CC increased transcriptional activation. Monomethylated at Lys-370 by
CC SMYD2, leading to decreased DNA-binding activity and subsequent
CC transcriptional regulation activity. Lys-372 monomethylation prevents
CC interaction with SMYD2 and subsequent monomethylation at Lys-370.
CC Dimethylated at Lys-373 by EHMT1 and EHMT2. Monomethylated at Lys-382
CC by KMT5A, promoting interaction with L3MBTL1 and leading to repress
CC transcriptional activity. Demethylation of dimethylated Lys-370 by
CC KDM1A prevents interaction with TP53BP1 and represses TP53-mediated
CC transcriptional activation (By similarity). Monomethylated at Arg-333
CC and dimethylated at Arg-337 by PRMT5; methylation is increased after
CC DNA damage and might possibly affect TP53 target gene specificity (By
CC similarity). {ECO:0000250|UniProtKB:P04637}.
CC -!- PTM: Sumoylated with SUMO1. Sumoylated at Lys-386 by UBC9 (By
CC similarity). {ECO:0000250}.
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, which leads to proteasomal degradation. Deubiquitinated by
CC USP10, leading to stabilize it. Ubiquitinated by TRIM24, RFFL, RNF34
CC and RNF125, which leads to proteasomal degradation. Ubiquitination by
CC TOPORS induces degradation. Deubiquitination by USP7, leading to
CC stabilize it. Ubiquitinated by COP1, which leads to proteasomal
CC degradation (By similarity). Ubiquitination and subsequent proteasomal
CC degradation is negatively regulated by CCAR2 (By similarity).
CC Polyubiquitinated by C10orf90/FATS, polyubiquitination is 'Lys-48'-
CC linkage independent and non-proteolytic, leading to TP53 stabilization
CC (By similarity). Polyubiquitinated by MUL1 at Lys-24 which leads to
CC proteasomal degradation (By similarity). {ECO:0000250|UniProtKB:P02340,
CC ECO:0000250|UniProtKB:P04637}.
CC -!- PTM: Acetylation of Lys-382 by CREBBP enhances transcriptional
CC activity. Acetylation of Lys-382 by EP300. Deacetylation of Lys-382 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 381 increases stability. Deacetylation at Lys-381 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}.
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DR EMBL; Y08900; CAA70108.1; -; mRNA.
DR EMBL; Y08901; CAA70109.1; -; mRNA.
DR EMBL; U50395; AAC53040.1; -; mRNA.
DR EMBL; D86070; BAA13004.1; -; mRNA.
DR PIR; JC6176; JC6176.
DR RefSeq; NP_001230905.1; NM_001243976.1.
DR AlphaFoldDB; O09185; -.
DR SMR; O09185; -.
DR STRING; 10029.NP_001230905.1; -.
DR GeneID; 100682525; -.
DR KEGG; cge:100682525; -.
DR CTD; 7157; -.
DR eggNOG; ENOG502QVY3; Eukaryota.
DR OrthoDB; 257530at2759; -.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0000785; C:chromatin; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0043073; C:germ cell nucleus; IEA:Ensembl.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0016363; C:nuclear matrix; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0005657; C:replication fork; IEA:Ensembl.
DR GO; GO:0035861; C:site of double-strand break; IEA:Ensembl.
DR GO; GO:0017053; C:transcription repressor complex; IEA:Ensembl.
DR GO; GO:0036310; F:ATP-dependent DNA/DNA annealing activity; ISS:UniProtKB.
DR GO; GO:0051087; F:chaperone binding; IEA:Ensembl.
DR GO; GO:0005507; F:copper ion binding; ISS:UniProtKB.
DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0097718; F:disordered domain specific binding; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0035035; F:histone acetyltransferase binding; IEA:Ensembl.
DR GO; GO:0042826; F:histone deacetylase binding; IEA:Ensembl.
DR GO; GO:0035033; F:histone deacetylase regulator activity; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0097371; F:MDM2/MDM4 family protein binding; IEA:Ensembl.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; IEA:Ensembl.
DR GO; GO:0002039; F:p53 binding; IEA:Ensembl.
DR GO; GO:1990841; F:promoter-specific chromatin binding; ISS:UniProtKB.
DR GO; GO:0002020; F:protease binding; IEA:Ensembl.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl.
DR GO; GO:0047485; F:protein N-terminus binding; IEA:Ensembl.
DR GO; GO:0051721; F:protein phosphatase 2A binding; IEA:Ensembl.
DR GO; GO:0043621; F:protein self-association; IEA:Ensembl.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IEA:Ensembl.
DR GO; GO:0001094; F:TFIID-class transcription factor complex binding; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IEA:Ensembl.
DR GO; GO:0002326; P:B cell lineage commitment; IEA:Ensembl.
DR GO; GO:0048539; P:bone marrow development; IEA:Ensembl.
DR GO; GO:0010659; P:cardiac muscle cell apoptotic process; IEA:Ensembl.
DR GO; GO:0060411; P:cardiac septum morphogenesis; IEA:Ensembl.
DR GO; GO:0072717; P:cellular response to actinomycin D; IEA:Ensembl.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0071480; P:cellular response to gamma radiation; IEA:Ensembl.
DR GO; GO:0042149; P:cellular response to glucose starvation; IEA:Ensembl.
DR GO; GO:0071494; P:cellular response to UV-C; IEA:Ensembl.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0090398; P:cellular senescence; ISS:UniProtKB.
DR GO; GO:0021549; P:cerebellum development; IEA:Ensembl.
DR GO; GO:0031497; P:chromatin assembly; IEA:Ensembl.
DR GO; GO:0048512; P:circadian behavior; ISS:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IEA:Ensembl.
DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; IEA:Ensembl.
DR GO; GO:0006978; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; IEA:Ensembl.
DR GO; GO:0006302; P:double-strand break repair; IEA:Ensembl.
DR GO; GO:0048568; P:embryonic organ development; IEA:Ensembl.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; ISS:UniProtKB.
DR GO; GO:0006983; P:ER overload response; IEA:Ensembl.
DR GO; GO:0048144; P:fibroblast proliferation; IEA:Ensembl.
DR GO; GO:0007369; P:gastrulation; IEA:Ensembl.
DR GO; GO:0014009; P:glial cell proliferation; IEA:Ensembl.
DR GO; GO:0019661; P:glucose catabolic process to lactate via pyruvate; IEA:Ensembl.
DR GO; GO:0060218; P:hematopoietic stem cell differentiation; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0060333; P:interferon-gamma-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IEA:Ensembl.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IEA:Ensembl.
DR GO; GO:1990144; P:intrinsic apoptotic signaling pathway in response to hypoxia; IEA:Ensembl.
DR GO; GO:0043504; P:mitochondrial DNA repair; IEA:Ensembl.
DR GO; GO:0000423; P:mitophagy; IEA:Ensembl.
DR GO; GO:0009299; P:mRNA transcription; IEA:Ensembl.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0070266; P:necroptotic process; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0008156; P:negative regulation of DNA replication; IEA:Ensembl.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IEA:Ensembl.
DR GO; GO:1903451; P:negative regulation of G1 to G0 transition; IEA:Ensembl.
DR GO; GO:0060253; P:negative regulation of glial cell proliferation; IEA:Ensembl.
DR GO; GO:1904024; P:negative regulation of glucose catabolic process to lactate via pyruvate; IEA:Ensembl.
DR GO; GO:1903799; P:negative regulation of miRNA maturation; IEA:Ensembl.
DR GO; GO:1901525; P:negative regulation of mitophagy; IEA:Ensembl.
DR GO; GO:0007406; P:negative regulation of neuroblast proliferation; IEA:Ensembl.
DR GO; GO:1905856; P:negative regulation of pentose-phosphate shunt; IEA:Ensembl.
DR GO; GO:0045861; P:negative regulation of proteolysis; IEA:Ensembl.
DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:2000647; P:negative regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0051974; P:negative regulation of telomerase activity; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0010666; P:positive regulation of cardiac muscle cell apoptotic process; IEA:Ensembl.
DR GO; GO:2000774; P:positive regulation of cellular senescence; IEA:Ensembl.
DR GO; GO:1900119; P:positive regulation of execution phase of apoptosis; IEA:Ensembl.
DR GO; GO:0031065; P:positive regulation of histone deacetylation; IEA:Ensembl.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:1903800; P:positive regulation of miRNA maturation; IEA:Ensembl.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IEA:Ensembl.
DR GO; GO:0035794; P:positive regulation of mitochondrial membrane permeability; IEA:Ensembl.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0062100; P:positive regulation of programmed necrotic cell death; IEA:Ensembl.
DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:0090200; P:positive regulation of release of cytochrome c from mitochondria; IEA:Ensembl.
DR GO; GO:0045899; P:positive regulation of RNA polymerase II transcription preinitiation complex assembly; IEA:Ensembl.
DR GO; GO:0070245; P:positive regulation of thymocyte apoptotic process; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:1990440; P:positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; IEA:Ensembl.
DR GO; GO:0061419; P:positive regulation of transcription from RNA polymerase II promoter in response to hypoxia; IEA:Ensembl.
DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl.
DR GO; GO:0050821; P:protein stabilization; IEA:Ensembl.
DR GO; GO:0051262; P:protein tetramerization; IEA:InterPro.
DR GO; GO:0007265; P:Ras protein signal transduction; IEA:Ensembl.
DR GO; GO:0072593; P:reactive oxygen species metabolic process; IEA:Ensembl.
DR GO; GO:1902749; P:regulation of cell cycle G2/M phase transition; IEA:Ensembl.
DR GO; GO:0043516; P:regulation of DNA damage response, signal transduction by p53 class mediator; IEA:Ensembl.
DR GO; GO:2000269; P:regulation of fibroblast apoptotic process; IEA:Ensembl.
DR GO; GO:1902253; P:regulation of intrinsic apoptotic signaling pathway by p53 class mediator; IEA:Ensembl.
DR GO; GO:1902108; P:regulation of mitochondrial membrane permeability involved in apoptotic process; IEA:Ensembl.
DR GO; GO:0034103; P:regulation of tissue remodeling; IEA:Ensembl.
DR GO; GO:1990248; P:regulation of transcription from RNA polymerase II promoter in response to DNA damage; IEA:Ensembl.
DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IEA:Ensembl.
DR GO; GO:0090399; P:replicative senescence; IEA:Ensembl.
DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
DR GO; GO:0009651; P:response to salt stress; IEA:Ensembl.
DR GO; GO:0010165; P:response to X-ray; IEA:Ensembl.
DR GO; GO:0009303; P:rRNA transcription; IEA:Ensembl.
DR GO; GO:0001756; P:somitogenesis; IEA:Ensembl.
DR GO; GO:0072089; P:stem cell proliferation; IEA:Ensembl.
DR GO; GO:0033077; P:T cell differentiation in thymus; IEA:Ensembl.
DR GO; GO:0002360; P:T cell lineage commitment; IEA:Ensembl.
DR GO; GO:0002309; P:T cell proliferation involved in immune response; IEA:Ensembl.
DR GO; GO:0070242; P:thymocyte apoptotic process; IEA:Ensembl.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0016032; P:viral process; IEA:Ensembl.
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 2: Evidence at transcript level;
KW Acetylation; Activator; Apoptosis; Biological rhythms; Cell cycle;
KW Cytoplasm; Cytoskeleton; DNA-binding; Endoplasmic reticulum;
KW Isopeptide bond; Metal-binding; Methylation; Mitochondrion; Necrosis;
KW Nucleus; Phosphoprotein; Repressor; Transcription;
KW Transcription regulation; Tumor suppressor; Ubl conjugation; Zinc.
FT CHAIN 1..393
FT /note="Cellular tumor antigen p53"
FT /id="PRO_0000185698"
FT DNA_BIND 102..292
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT REGION 1..320
FT /note="Interaction with CCAR2"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT REGION 1..45
FT /note="Transcription activation (acidic)"
FT REGION 66..110
FT /note="Interaction with WWOX"
FT /evidence="ECO:0000250"
FT REGION 100..370
FT /note="Interaction with HIPK1"
FT /evidence="ECO:0000250"
FT REGION 100..300
FT /note="Required for interaction with ZNF385A"
FT /evidence="ECO:0000250"
FT REGION 113..236
FT /note="Required for interaction with FBXO42"
FT /evidence="ECO:0000250"
FT REGION 116..292
FT /note="Interaction with AXIN1"
FT /evidence="ECO:0000250"
FT REGION 256..294
FT /note="Interaction with E4F1"
FT /evidence="ECO:0000250"
FT REGION 273..280
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT REGION 283..325
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 319..360
FT /note="Interaction with HIPK2"
FT /evidence="ECO:0000250"
FT REGION 325..356
FT /note="Oligomerization"
FT REGION 352..393
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 359..363
FT /note="Interaction with USP7"
FT /evidence="ECO:0000250"
FT REGION 368..387
FT /note="Basic (repression of DNA-binding)"
FT MOTIF 305..321
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 339..350
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT MOTIF 370..372
FT /note="[KR]-[STA]-K motif"
FT COMPBIAS 359..374
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 176
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT BINDING 179
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT BINDING 238
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT BINDING 242
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT SITE 120
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 9
FT /note="Phosphoserine; by HIPK4"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 15
FT /note="Phosphoserine; by CDK5, PRPK, AMPK, NUAK1 and ATM"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 18
FT /note="Phosphothreonine; by CK1, VRK1 and VRK2"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 20
FT /note="Phosphoserine; by CHEK2, CK1 and PLK3"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 33
FT /note="Phosphoserine; by CDK5 and CDK7"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 37
FT /note="Phosphoserine; by MAPKAPK5"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 47
FT /note="Phosphoserine; by CDK5, DYRK2, HIPK2 and PKC/PRKCG"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 120
FT /note="N6-acetyllysine; by KAT6A"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 183
FT /note="Phosphoserine; by AURKB"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 269
FT /note="Phosphoserine; by AURKB"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 284
FT /note="Phosphothreonine; by AURKB"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 305
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 315
FT /note="Phosphoserine; by AURKA, CDK1 and CDK2"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 321
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P02340"
FT MOD_RES 333
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 337
FT /note="Symmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 370
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 370
FT /note="N6-methyllysine; by SMYD2; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 372
FT /note="N6-methyllysine; by SETD7"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 373
FT /note="N6,N6-dimethyllysine; by EHMT1 and EHMT2; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 373
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 381
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 382
FT /note="N6,N6-dimethyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 382
FT /note="N6-acetyllysine; by KAT6A; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 382
FT /note="N6-methyllysine; by KMT5A; alternate"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT MOD_RES 392
FT /note="Phosphoserine; by CK2, CDK2 and NUAK1"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT CROSSLNK 24
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT CROSSLNK 291
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT CROSSLNK 292
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:P04637"
FT CROSSLNK 386
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT VARIANT 133
FT /note="L -> Q (in cell line V79-4)"
FT /evidence="ECO:0000269|PubMed:9023109"
FT VARIANT 135
FT /note="C -> W (in cell line V79-4)"
FT /evidence="ECO:0000269|PubMed:9023109"
FT CONFLICT 103
FT /note="Y -> F (in Ref. 2; AAC53040)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 393 AA; 43378 MW; 2A7830E788311689 CRC64;
MEEPQSDLSI ELPLSQETFS DLWKLLPPNN VLSTLPSSDS IEELFLSENV TGWLEDSGGA
LQGVAAAAAS TAEDPVTETP APVASAPATP WPLSSSVPSY KTYQGDYGFR LGFLHSGTAK
SVTCTYSPSL NKLFCQLAKT CPVQLWVNST PPPGTRVRAM AIYKKLQYMT EVVRRCPHHE
RSSEGDSLAP PQHLIRVEGN LHAEYLDDKQ TFRHSVVVPY EPPEVGSDCT TIHYNYMCNS
SCMGGMNRRP ILTIITLEDP SGNLLGRNSF EVRICACPGR DRRTEEKNFQ KKGEPCPELP
PKSAKRALPT NTSSSPPPKK KTLDGEYFTL KIRGHERFKM FQELNEALEL KDAQASKGSE
DNGAHSSYLK SKKGQSASRL KKLMIKREGP DSD
