UniProtKB - P10361 (P53_RAT)
Protein
Cellular tumor antigen p53
Gene
Tp53
Organism
Rattus norvegicus (Rat)
Status
Functioni
Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 (By similarity). However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP (By similarity). In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seems to have an effect on cell-cycle regulation. Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER2.By similarity
Cofactori
Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Metal bindingi | 174 | ZincBy similarity | 1 | |
| Metal bindingi | 177 | ZincBy similarity | 1 | |
| Metal bindingi | 236 | ZincBy similarity | 1 | |
| Metal bindingi | 240 | ZincBy similarity | 1 |
Regions
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| DNA bindingi | 100 – 290 | By similarityAdd BLAST | 191 |
GO - Molecular functioni
- ATP binding Source: UniProtKB
- chaperone binding Source: RGD
- chromatin binding Source: RGD
- cis-regulatory region sequence-specific DNA binding Source: RGD
- copper ion binding Source: UniProtKB
- core promoter sequence-specific DNA binding Source: RGD
- disordered domain specific binding Source: RGD
- DNA binding Source: UniProtKB
- DNA-binding transcription activator activity Source: RGD
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: RGD
- DNA-binding transcription factor activity Source: RGD
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: UniProtKB
- enzyme binding Source: RGD
- histone acetyltransferase binding Source: RGD
- histone deacetylase binding Source: RGD
- histone deacetylase regulator activity Source: RGD
- identical protein binding Source: RGD
- MDM2/MDM4 family protein binding Source: RGD
- mRNA 3'-UTR binding Source: RGD
- p53 binding Source: RGD
- promoter-specific chromatin binding Source: UniProtKB
- protease binding Source: RGD
- protein C-terminus binding Source: RGD
- protein heterodimerization activity Source: RGD
- protein kinase binding Source: RGD
- protein N-terminus binding Source: RGD
- protein phosphatase 2A binding Source: RGD
- protein phosphatase binding Source: RGD
- protein self-association Source: RGD
- receptor tyrosine kinase binding Source: RGD
- RNA polymerase II activating transcription factor binding Source: ARUK-UCL
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: UniProtKB
- RNA polymerase II transcription factor binding Source: RGD
- RNA polymerase II transcription regulatory region sequence-specific DNA binding Source: RGD
- sequence-specific DNA binding Source: RGD
- TFIID-class transcription factor complex binding Source: RGD
- transcription coregulator binding Source: RGD
- transcription factor binding Source: RGD
- transcription regulatory region sequence-specific DNA binding Source: RGD
- ubiquitin protein ligase binding Source: RGD
GO - Biological processi
- aging Source: RGD
- apoptotic process Source: RGD
- autophagy Source: RGD
- B cell lineage commitment Source: RGD
- bone marrow development Source: RGD
- cardiac septum morphogenesis Source: RGD
- cell aging Source: UniProtKB
- cell cycle arrest Source: RGD
- cellular response to actinomycin D Source: RGD
- cellular response to DNA damage stimulus Source: UniProtKB
- cellular response to drug Source: RGD
- cellular response to gamma radiation Source: RGD
- cellular response to glucose starvation Source: RGD
- cellular response to heat Source: RGD
- cellular response to hypoxia Source: RGD
- cellular response to ionizing radiation Source: RGD
- cellular response to organonitrogen compound Source: RGD
- cellular response to reactive oxygen species Source: RGD
- cellular response to UV Source: RGD
- cellular response to UV-C Source: RGD
- central nervous system development Source: RGD
- cerebellum development Source: RGD
- chromatin assembly Source: RGD
- chromosome organization Source: RGD
- circadian behavior Source: UniProtKB
- circadian rhythm Source: RGD
- determination of adult lifespan Source: RGD
- DNA damage response, signal transduction by p53 class mediator Source: RGD
- DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Source: RGD
- DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator Source: RGD
- DNA strand renaturation Source: UniProtKB
- double-strand break repair Source: RGD
- embryo development ending in birth or egg hatching Source: RGD
- embryonic organ development Source: RGD
- entrainment of circadian clock by photoperiod Source: UniProtKB
- ER overload response Source: RGD
- gastrulation Source: RGD
- heart development Source: RGD
- hematopoietic progenitor cell differentiation Source: RGD
- hematopoietic stem cell differentiation Source: RGD
- interferon-gamma-mediated signaling pathway Source: RGD
- intrinsic apoptotic signaling pathway by p53 class mediator Source: RGD
- intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: RGD
- intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: RGD
- intrinsic apoptotic signaling pathway in response to hypoxia Source: RGD
- in utero embryonic development Source: RGD
- mitochondrial DNA repair Source: RGD
- mitotic cell cycle arrest Source: RGD
- mitotic G1 DNA damage checkpoint Source: RGD
- mRNA transcription Source: RGD
- multicellular organism growth Source: RGD
- necroptotic process Source: RGD
- negative regulation of apoptotic process Source: RGD
- negative regulation of cell growth Source: UniProtKB
- negative regulation of cell population proliferation Source: ARUK-UCL
- negative regulation of DNA biosynthetic process Source: RGD
- negative regulation of DNA replication Source: RGD
- negative regulation of fibroblast proliferation Source: RGD
- negative regulation of gene expression Source: RGD
- negative regulation of glucose catabolic process to lactate via pyruvate Source: RGD
- negative regulation of mitophagy Source: RGD
- negative regulation of mitotic cell cycle Source: RGD
- negative regulation of neuroblast proliferation Source: RGD
- negative regulation of pentose-phosphate shunt Source: RGD
- negative regulation of production of miRNAs involved in gene silencing by miRNA Source: RGD
- negative regulation of proteolysis Source: RGD
- negative regulation of reactive oxygen species metabolic process Source: RGD
- negative regulation of smooth muscle cell proliferation Source: RGD
- negative regulation of telomerase activity Source: RGD
- negative regulation of transcription, DNA-templated Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: RGD
- negative regulation of transforming growth factor beta receptor signaling pathway Source: RGD
- neuron apoptotic process Source: RGD
- nucleotide-excision repair Source: UniProtKB
- oligodendrocyte apoptotic process Source: UniProtKB
- oxidative stress-induced premature senescence Source: RGD
- positive regulation of apoptotic process Source: RGD
- positive regulation of cardiac muscle cell apoptotic process Source: RGD
- positive regulation of cell aging Source: RGD
- positive regulation of cell cycle Source: RGD
- positive regulation of cell cycle arrest Source: ARUK-UCL
- positive regulation of execution phase of apoptosis Source: RGD
- positive regulation of gene expression Source: ARUK-UCL
- positive regulation of histone deacetylation Source: RGD
- positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
- positive regulation of leukocyte migration Source: RGD
- positive regulation of mitochondrial membrane permeability Source: RGD
- positive regulation of neuron apoptotic process Source: RGD
- positive regulation of peptidyl-tyrosine phosphorylation Source: RGD
- positive regulation of pri-miRNA transcription by RNA polymerase II Source: RGD
- positive regulation of production of miRNAs involved in gene silencing by miRNA Source: RGD
- positive regulation of programmed necrotic cell death Source: RGD
- positive regulation of reactive oxygen species metabolic process Source: RGD
- positive regulation of release of cytochrome c from mitochondria Source: RGD
- positive regulation of RNA polymerase II transcription preinitiation complex assembly Source: RGD
- positive regulation of thymocyte apoptotic process Source: RGD
- positive regulation of transcription, DNA-templated Source: RGD
- positive regulation of transcription by RNA polymerase II Source: BHF-UCL
- positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress Source: RGD
- positive regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: RGD
- positive regulation of transcription from RNA polymerase II promoter in response to stress Source: RGD
- protein-containing complex assembly Source: RGD
- protein import into nucleus Source: RGD
- protein localization Source: RGD
- protein stabilization Source: RGD
- protein tetramerization Source: InterPro
- Ras protein signal transduction Source: RGD
- regulation of apoptotic process Source: RGD
- regulation of cell cycle Source: RGD
- regulation of cell population proliferation Source: RGD
- regulation of cellular senescence Source: RGD
- regulation of DNA damage response, signal transduction by p53 class mediator Source: RGD
- regulation of fibroblast apoptotic process Source: RGD
- regulation of hydrogen peroxide-induced cell death Source: UniProtKB
- regulation of intracellular pH Source: RGD
- regulation of intrinsic apoptotic signaling pathway by p53 class mediator Source: RGD
- regulation of mitochondrial membrane permeability involved in apoptotic process Source: RGD
- regulation of neuron apoptotic process Source: RGD
- regulation of thymocyte apoptotic process Source: RGD
- regulation of tissue remodeling Source: RGD
- regulation of transcription, DNA-templated Source: RGD
- regulation of transcription by RNA polymerase II Source: RGD
- regulation of transcription from RNA polymerase II promoter in response to DNA damage Source: RGD
- release of cytochrome c from mitochondria Source: RGD
- replicative senescence Source: RGD
- response to amino acid Source: RGD
- response to antibiotic Source: RGD
- response to caffeine Source: RGD
- response to cytokine Source: RGD
- response to drug Source: RGD
- response to ethanol Source: RGD
- response to gamma radiation Source: RGD
- response to hyperoxia Source: RGD
- response to inorganic substance Source: RGD
- response to ischemia Source: RGD
- response to metal ion Source: RGD
- response to organic cyclic compound Source: RGD
- response to organonitrogen compound Source: RGD
- response to oxidative stress Source: RGD
- response to retinoic acid Source: RGD
- response to salt stress Source: RGD
- response to UV Source: RGD
- response to UV-B Source: RGD
- response to vitamin B3 Source: RGD
- response to X-ray Source: RGD
- rRNA transcription Source: RGD
- signal transduction by p53 class mediator Source: RGD
- somitogenesis Source: RGD
- T cell differentiation in thymus Source: RGD
- T cell lineage commitment Source: RGD
- T cell proliferation involved in immune response Source: RGD
- transforming growth factor beta receptor signaling pathway Source: RGD
- tumor necrosis factor-mediated signaling pathway Source: RGD
- viral process Source: RGD
- wound healing Source: RGD
Keywordsi
| Molecular function | Activator, DNA-binding, Repressor |
| Biological process | Apoptosis, Biological rhythms, Cell cycle, Necrosis, Transcription, Transcription regulation |
| Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
| Reactomei | R-RNO-2559580, Oxidative Stress Induced Senescence R-RNO-2559584, Formation of Senescence-Associated Heterochromatin Foci (SAHF) R-RNO-2559585, Oncogene Induced Senescence R-RNO-2559586, DNA Damage/Telomere Stress Induced Senescence R-RNO-349425, Autodegradation of the E3 ubiquitin ligase COP1 R-RNO-5689880, Ub-specific processing proteases R-RNO-5689896, Ovarian tumor domain proteases R-RNO-5693565, Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks R-RNO-6804754, Regulation of TP53 Expression R-RNO-6804756, Regulation of TP53 Activity through Phosphorylation R-RNO-6804757, Regulation of TP53 Degradation R-RNO-6804758, Regulation of TP53 Activity through Acetylation R-RNO-6804759, Regulation of TP53 Activity through Association with Co-factors R-RNO-6804760, Regulation of TP53 Activity through Methylation R-RNO-69473, G2/M DNA damage checkpoint R-RNO-69481, G2/M Checkpoints R-RNO-69541, Stabilization of p53 R-RNO-69895, Transcriptional activation of cell cycle inhibitor p21 R-RNO-8852276, The role of GTSE1 in G2/M progression after G2 checkpoint R-RNO-8941855, RUNX3 regulates CDKN1A transcription |
Names & Taxonomyi
| Protein namesi | Recommended name: Cellular tumor antigen p53Alternative name(s): Tumor suppressor p53 |
| Gene namesi | Name:Tp53 Synonyms:P53 |
| Organismi | Rattus norvegicus (Rat) |
| Taxonomic identifieri | 10116 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
| Proteomesi |
|
Organism-specific databases
| RGDi | 3889, Tp53 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm By similarity
Cytoskeleton
- centrosome By similarity
Nucleus
Endoplasmic reticulum
- Endoplasmic reticulum By similarity
Mitochondrion
- Mitochondrion matrix By similarity
Note: Interaction with BANP promotes nuclear localization. Recruited into PML bodies together with CHEK2. Translocates to mitochondria upon oxidative stress. Translocates to mitochondria in response to mitomycin C treatment (By similarity).By similarity
Cytoskeleton
- centrosome Source: UniProtKB
Cytosol
- cytosol Source: RGD
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB-SubCell
Mitochondrion
- mitochondrial matrix Source: RGD
- mitochondrion Source: RGD
Nucleus
- nuclear matrix Source: RGD
- nucleolus Source: UniProtKB
- nucleoplasm Source: RGD
- nucleus Source: RGD
- PML body Source: RGD
- RNA polymerase II transcription regulator complex Source: ARUK-UCL
Other locations
- chromatin Source: RGD
- cytoplasm Source: RGD
- protein-containing complex Source: RGD
- replication fork Source: RGD
- site of double-strand break Source: RGD
- transcription regulator complex Source: RGD
Keywords - Cellular componenti
Cytoplasm, Cytoskeleton, Endoplasmic reticulum, Mitochondrion, NucleusPathology & Biotechi
Involvement in diseasei
p53 is found in increased amounts in a wide variety of transformed cells. p53 is frequently mutated or inactivated in many types of cancer.
Keywords - Diseasei
Tumor suppressorPTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000185712 | 1 – 391 | Cellular tumor antigen p53Add BLAST | 391 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 9 | Phosphoserine; by HIPK4By similarity | 1 | |
| Modified residuei | 15 | Phosphoserine; by CDK5, PRPK, AMPK, NUAK1 and ATMBy similarity | 1 | |
| Modified residuei | 18 | Phosphothreonine; by CK1, VRK1 and VRK2By similarity | 1 | |
| Modified residuei | 20 | Phosphoserine; by CHEK2, CK1 and PLK3By similarity | 1 | |
| Cross-linki | 24 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
| Modified residuei | 39 | Phosphoserine; by MAPKAPK5By similarity | 1 | |
| Modified residuei | 118 | N6-acetyllysine; by KAT6ABy similarity | 1 | |
| Modified residuei | 181 | Phosphoserine; by AURKBBy similarity | 1 | |
| Modified residuei | 267 | Phosphoserine; by AURKBBy similarity | 1 | |
| Modified residuei | 282 | Phosphothreonine; by AURKBBy similarity | 1 | |
| Cross-linki | 289 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
| Cross-linki | 290 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
| Modified residuei | 303 | N6-acetyllysineBy similarity | 1 | |
| Modified residuei | 313 | Phosphoserine; by AURKA, CDK1 and CDK2By similarity | 1 | |
| Modified residuei | 319 | N6-acetyllysineBy similarity | 1 | |
| Modified residuei | 331 | Omega-N-methylarginineBy similarity | 1 | |
| Modified residuei | 333 | Symmetric dimethylarginineBy similarity | 1 | |
| Modified residuei | 335 | Symmetric dimethylarginineBy similarity | 1 | |
| Modified residuei | 368 | N6,N6-dimethyllysine; alternateBy similarity | 1 | |
| Modified residuei | 368 | N6-methyllysine; by SMYD2; alternateBy similarity | 1 | |
| Modified residuei | 370 | N6-methyllysine; by SETD7By similarity | 1 | |
| Modified residuei | 371 | N6,N6-dimethyllysine; by EHMT1 and EHMT2; alternateBy similarity | 1 | |
| Modified residuei | 371 | N6-acetyllysine; alternateBy similarity | 1 | |
| Modified residuei | 379 | N6-acetyllysineBy similarity | 1 | |
| Modified residuei | 380 | N6,N6-dimethyllysine; alternateBy similarity | 1 | |
| Modified residuei | 380 | N6-acetyllysine; by KAT6A; alternateBy similarity | 1 | |
| Modified residuei | 380 | N6-methyllysine; by KMT5A; alternateBy similarity | 1 | |
| Cross-linki | 384 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity | ||
| Modified residuei | 390 | Phosphoserine; by CK2, CDK2 and NUAK1By similarity | 1 |
Post-translational modificationi
Phosphorylation on Ser residues mediates transcriptional activation. Phosphorylation at Ser-9 by HIPK4 increases repression activity on BIRC5 promoter (By similarity). Phosphorylated on Thr-18 by VRK1, which may prevent the interaction with MDM2. Phosphorylated on Ser-20 by CHEK2 in response to DNA damage, which prevents ubiquitination by MDM2. Phosphorylated on Ser-20 by PLK3 in response to reactive oxygen species (ROS), promoting p53/TP53-mediated apoptosis. Probably phosphorylated on by CDK7 in a CAK complex in response to DNA damage. Phosphorylated by HIPK1. Phosphorylated on Ser-390 following UV but not gamma irradiation. Phosphorylated on Ser-15 upon ultraviolet irradiation; which is enhanced by interaction with BANP. Stabilized by CDK5-mediated phosphorylation in response to genotoxic and oxidative stresses at Ser-15, leading to accumulation of p53/TP53, particularly in the nucleus, thus inducing the transactivation of p53/TP53 target genes. Phosphorylated at Ser-313 and Ser-390 by CDK2 in response to DNA-damage (By similarity). Phosphorylation at Ser-15 is required for interaction with DDX3X and gamma-tubulin (By similarity).By similarity
Acetylated. Its deacetylation by SIRT1 impairs its ability to induce proapoptotic program and modulate cell senescence. Deacetylation by SIRT2 impairs its ability to induce transcription activation in a AKT-dependent manner (By similarity).By similarity
Monomethylated at Lys-370 by SETD7, leading to stabilization and increased transcriptional activation. Monomethylated at Lys-368 by SMYD2, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity. Lys-370 monomethylation prevents interaction with SMYD2 and subsequent monomethylation at Lys-368. Dimethylated at Lys-371 by EHMT1 and EHMT2. Monomethylated at Lys-380 by KMT5A, promoting interaction with L3MBTL1 and leading to repress transcriptional activity. Demethylation of dimethylated Lys-368 by KDM1A prevents interaction with TP53BP1 and represses TP53-mediated transcriptional activation (By similarity). Monomethylated at Arg-331 and dimethylated at Arg-333 and Arg-335 by PRMT5; methylation is increased after DNA damage and might possibly affect TP53 target gene specificity (By similarity).By similarity
Sumoylated with SUMO1. Sumoylated at Lys-384 by UBC9 (By similarity).By similarity
Ubiquitinated by MDM2 and SYVN1, which leads to proteasomal degradation. Ubiquitinated by RFWD3, which works in cooperation with MDM2 and may catalyze the formation of short polyubiquitin chains on p53/TP53 that are not targeted to the proteasome. Ubiquitinated by MKRN1, which leads to proteasomal degradation. Deubiquitinated by USP10, leading to stabilize it. Ubiquitinated by TRIM24, RFFL, RNF34 and RNF125, which leads to proteasomal degradation. Ubiquitination by TOPORS induces degradation. Deubiquitination by USP7, leading to stabilize it. Ubiquitinated by COP1, which leads to proteasomal degradation (By similarity). Ubiquitination and subsequent proteasomal degradation is negatively regulated by CCAR2 (By similarity). Polyubiquitinated by C10orf90/FATS, polyubiquitination is 'Lys-48'-linkage independent and non-proteolytic, leading to TP53 stabilization (By similarity). Polyubiquitinated by MUL1 at Lys-24 which leads to proteasomal degradation (By similarity).By similarity
Keywords - PTMi
Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugationProteomic databases
| PaxDbi | P10361 |
| PRIDEi | P10361 |
PTM databases
| iPTMneti | P10361 |
| PhosphoSitePlusi | P10361 |
Expressioni
Gene expression databases
| Bgeei | ENSRNOG00000010756, Expressed in thymus and 22 other tissues |
| ExpressionAtlasi | P10361, baseline and differential |
| Genevisiblei | P10361, RN |
Interactioni
Subunit structurei
Forms homodimers and homotetramers (By similarity). Binds DNA as a homotetramer.
Interacts with AXIN1. Probably part of a complex consisting of TP53, HIPK2 and AXIN1 (By similarity).
Interacts with histone acetyltransferases EP300 and methyltransferases HRMT1L2 and CARM1, and recruits them to promoters.
Interacts (via C-terminus) with TAF1; when TAF1 is part of the TFIID complex.
Interacts with ING4; this interaction may be indirect.
Found in a complex with CABLES1 and TP73.
Interacts with HIPK1, HIPK2, and TP53INP1.
Interacts with WWOX.
Interacts with USP7 and SYVN1.
Interacts with HSP90AB1 (PubMed:8663025).
Interacts with CHD8; leading to recruit histone H1 and prevent transactivation activity (By similarity).
Interacts with ARMC10, BANP, CDKN2AIP, NUAK1, STK11/LKB1, UHRF2 and E4F1.
Interacts with YWHAZ; the interaction enhances TP53 transcriptional activity. Phosphorylation of YWHAZ on 'Ser-58' inhibits this interaction.
Interacts (via DNA-binding domain) with MAML1 (via N-terminus).
Interacts with MKRN1.
Interacts with PML (via C-terminus).
Interacts with MDM2; leading to ubiquitination and proteasomal degradation of TP53. Directly interacts with FBXO42; leading to ubiquitination and degradation of TP53.
Interacts (phosphorylated at Ser-15 by ATM) with the phosphatase PP2A-PPP2R5C holoenzyme; regulates stress-induced TP53-dependent inhibition of cell proliferation.
Interacts with PPP2R2A.
Interacts with AURKA, DAXX, BRD7 and TRIM24.
Interacts (when monomethylated at Lys-380) with L3MBTL1.
Interacts with GRK5. Binds to the CAK complex (CDK7, cyclin H and MAT1) in response to DNA damage.
Interacts with CDK5 in neurons.
Interacts with AURKB, SETD2, UHRF2 and NOC2L.
Interacts (via N-terminus) with PTK2/FAK1; this promotes ubiquitination by MDM2.
Interacts with PTK2B/PYK2; this promotes ubiquitination by MDM2.
Interacts with PRKCG.
Interacts with PPIF; the association implicates preferentially tetrameric TP53, is induced by oxidative stress and is impaired by cyclosporin A (CsA).
Interacts with SNAI1; the interaction induces SNAI1 degradation via MDM2-mediated ubiquitination and inhibits SNAI1-induced cell invasion.
Interacts with KAT6A.
Interacts with UBC9.
Interacts with ZNF385B; the interaction is direct.
Interacts (via DNA-binding domain) with ZNF385A; the interaction is direct and enhances p53/TP53 transactivation functions on cell-cycle arrest target genes, resulting in growth arrest.
Interacts with ANKRD2.
Interacts with RFFL and RNF34; involved in p53/TP53 ubiquitination.
Interacts with MTA1 and COP1.
Interacts with CCAR2 (via N-terminus).
Interacts with MORC3.
Interacts (via C-terminus) with POU4F2 (via C-terminus).
Interacts (via oligomerization region) with NOP53; the interaction is direct and may prevent the MDM2-mediated proteasomal degradation of TP53.
Interacts with AFG1L; mediates mitochondrial translocation of TP53.
Interacts with UBD (By similarity).
Interacts with TAF6 (By similarity). Binds DNA as a homotetramer.
Interacts with AXIN1. Probably part of a complex consisting of TP53, HIPK2 and AXIN1.
Interacts with histone acetyltransferases EP300 and methyltransferases HRMT1L2 and CARM1, and recruits them to promoters.
Interacts (via C-terminus) with TAF1; when TAF1 is part of the TFIID complex.
Interacts with ING4; this interaction may be indirect.
Found in a complex with CABLES1 and TP73.
Interacts with HIPK1, HIPK2, and TP53INP1.
Interacts with WWOX.
Interacts with USP7 and SYVN1.
Interacts with HSP90AB1.
Interacts with CHD8; leading to recruit histone H1 and prevent transactivation activity.
Interacts with ARMC10, BANP, CDKN2AIP, NUAK1, STK11/LKB1, UHRF2 and E4F.
Interacts with YWHAZ; the interaction enhances TP53 transcriptional activity. Phosphorylation of YWHAZ on 'Ser-58' inhibits this interaction.
Interacts (via DNA-binding domain) with MAML1 (via N-terminus).
Interacts with MKRN1.
Interacts with PML (via C-terminus).
Interacts with MDM2; leading to ubiquitination and proteasomal degradation of TP53. Directly interacts with FBXO42; leading to ubiquitination and degradation of TP53.
Interacts (phosphorylated at Ser-18 by ATM) with the phosphatase PP2A-PPP2R5C holoenzyme; regulates stress-induced TP53-dependent inhibition of cell proliferation.
Interacts with PPP2R2A.
Interacts with AURKA, DAXX, BRD7 and TRIM24.
Interacts (when monomethylated at Lys-379) with L3MBTL1.
Interacts with GRK5. Binds to the CAK complex (CDK7, cyclin H and MAT1) in response to DNA damage.
Interacts with CDK5 in neurons.
Interacts with AURKB, SETD2, UHRF2 and NOC2L.
Interacts (via N-terminus) with PTK2/FAK1; this promotes ubiquitination by MDM2.
Interacts with PTK2B/PYK2; this promotes ubiquitination by MDM2.
Interacts with PRKCG.
Interacts with PPIF; the association implicates preferentially tetrameric TP53, is induced by oxidative stress and is impaired by cyclosporin A (CsA).
Interacts with SNAI1; the interaction induces SNAI1 degradation via MDM2-mediated ubiquitination and inhibits SNAI1-induced cell invasion.
Interacts with KAT6A.
Interacts with UBC9.
Interacts with ZNF385B; the interaction is direct.
Interacts (via DNA-binding domain) with ZNF385A; the interaction is direct and enhances p53/TP53 transactivation functions on cell-cycle arrest target genes, resulting in growth arrest (By similarity).
Interacts with ANKRD2.
Interacts with RFFL and RNF34; involved in p53/TP53 ubiquitination.
Interacts with MTA1 and COP1.
Interacts with CCAR2 (via N-terminus).
Interacts with MORC3.
Interacts (via C-terminus) with POU4F2 (via C-terminus).
Interacts (via oligomerization region) with NOP53; the interaction is direct and may prevent the MDM2-mediated proteasomal degradation of TP53.
Interacts with AFG1L; mediates mitochondrial translocation of TP53.
Interacts with UBD (By similarity).
Interacts with TAF6 (By similarity).
Interacts with C10orf90/FATS; the interaction inhibits binding of TP53 and MDM2 (By similarity).
Interacts with NUPR1; interaction is stress-dependent.
Forms a complex with EP300 and NUPR1; this complex binds CDKN1A promoter leading to transcriptional induction of CDKN1A (By similarity).
Interacts with PRMT5 in response to DNA damage; the interaction is STRAP dependent (By similarity).
Interacts with PPP1R13L (via SH3 domain and ANK repeats); the interaction inhibits pro-apoptotic activity of p53/TP53 (By similarity).
Interacts with PPP1R13B/ASPP1 and TP53BP2/ASPP2; the interactions promotes pro-apoptotic activity (By similarity). When phosphorylated at Ser-15, interacts with DDX3X and gamma-tubulin (By similarity).
Interacts with KAT7/HBO1; leading to inhibit histone acetyltransferase activity of KAT7/HBO1 (By similarity).
Interacts (via N-terminus) with E3 ubiquitin-protein ligase MUL1; the interaction results in ubiquitination of cytoplasmic TP53 at Lys-24 and subsequent proteasomal degradation (By similarity).
Interacts with S100A4; this interaction promotes TP53 degradation (By similarity).
By similarity1 PublicationSites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sitei | 118 | Interaction with DNABy similarity | 1 |
GO - Molecular functioni
- chaperone binding Source: RGD
- disordered domain specific binding Source: RGD
- enzyme binding Source: RGD
- histone acetyltransferase binding Source: RGD
- histone deacetylase binding Source: RGD
- identical protein binding Source: RGD
- MDM2/MDM4 family protein binding Source: RGD
- p53 binding Source: RGD
- protease binding Source: RGD
- protein C-terminus binding Source: RGD
- protein heterodimerization activity Source: RGD
- protein kinase binding Source: RGD
- protein N-terminus binding Source: RGD
- protein phosphatase 2A binding Source: RGD
- protein phosphatase binding Source: RGD
- protein self-association Source: RGD
- receptor tyrosine kinase binding Source: RGD
- RNA polymerase II activating transcription factor binding Source: ARUK-UCL
- RNA polymerase II transcription factor binding Source: RGD
- TFIID-class transcription factor complex binding Source: RGD
- transcription coregulator binding Source: RGD
- transcription factor binding Source: RGD
- ubiquitin protein ligase binding Source: RGD
Protein-protein interaction databases
| BioGRIDi | 246960, 11 interactors |
| DIPi | DIP-46016N |
| IntActi | P10361, 5 interactors |
| MINTi | P10361 |
| STRINGi | 10116.ENSRNOP00000047840 |
Family & Domainsi
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Regioni | 1 – 318 | Interaction with CCAR2By similarityAdd BLAST | 318 | |
| Regioni | 1 – 47 | Transcription activation (acidic)Add BLAST | 47 | |
| Regioni | 64 – 108 | Interaction with WWOXBy similarityAdd BLAST | 45 | |
| Regioni | 98 – 368 | Interaction with HIPK1By similarityAdd BLAST | 271 | |
| Regioni | 98 – 298 | Required for interaction with ZNF385ABy similarityAdd BLAST | 201 | |
| Regioni | 111 – 234 | Required for interaction with FBXO42By similarityAdd BLAST | 124 | |
| Regioni | 114 – 290 | Interaction with AXIN1By similarityAdd BLAST | 177 | |
| Regioni | 254 – 292 | Interaction with E4F1By similarityAdd BLAST | 39 | |
| Regioni | 271 – 278 | Interaction with DNABy similarity | 8 | |
| Regioni | 317 – 358 | Interaction with HIPK2By similarityAdd BLAST | 42 | |
| Regioni | 323 – 354 | OligomerizationAdd BLAST | 32 | |
| Regioni | 357 – 361 | Interaction with USP7By similarity | 5 | |
| Regioni | 366 – 385 | Basic (repression of DNA-binding)Add BLAST | 20 |
Motif
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Motifi | 303 – 319 | Bipartite nuclear localization signalBy similarityAdd BLAST | 17 | |
| Motifi | 337 – 348 | Nuclear export signalBy similarityAdd BLAST | 12 | |
| Motifi | 368 – 370 | [KR]-[STA]-K motif | 3 |
Domaini
The [KR]-[STA]-K motif is specifically recognized by the SETD7 methyltransferase.By similarity
Sequence similaritiesi
Belongs to the p53 family.Curated
Phylogenomic databases
| eggNOGi | ENOG502QVY3, Eukaryota |
| GeneTreei | ENSGT00950000183153 |
| HOGENOMi | CLU_019621_0_0_1 |
| InParanoidi | P10361 |
| OMAi | FHKKGEP |
| OrthoDBi | 257530at2759 |
| PhylomeDBi | P10361 |
| TreeFami | TF106101 |
Family and domain databases
| CDDi | cd08367, P53, 1 hit |
| Gene3Di | 2.60.40.720, 1 hit 4.10.170.10, 1 hit |
| InterProi | View protein in InterPro IPR008967, p53-like_TF_DNA-bd IPR012346, p53/RUNT-type_TF_DNA-bd_sf IPR011615, p53_DNA-bd IPR036674, p53_tetramer_sf IPR010991, p53_tetrameristn IPR013872, p53_transactivation_domain IPR002117, p53_tumour_suppressor |
| PANTHERi | PTHR11447, PTHR11447, 1 hit |
| Pfami | View protein in Pfam PF00870, P53, 1 hit PF08563, P53_TAD, 1 hit PF07710, P53_tetramer, 1 hit |
| PRINTSi | PR00386, P53SUPPRESSR |
| SUPFAMi | SSF47719, SSF47719, 1 hit SSF49417, SSF49417, 1 hit |
| PROSITEi | View protein in PROSITE PS00348, P53, 1 hit |
Sequence (1+)i
Sequence statusi: Complete.
This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All
P10361-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MEDSQSDMSI ELPLSQETFS CLWKLLPPDD ILPTTATGSP NSMEDLFLPQ
60 70 80 90 100
DVAELLEGPE EALQVSAPAA QEPGTEAPAP VAPASATPWP LSSSVPSQKT
110 120 130 140 150
YQGNYGFHLG FLQSGTAKSV MCTYSISLNK LFCQLAKTCP VQLWVTSTPP
160 170 180 190 200
PGTRVRAMAI YKKSQHMTEV VRRCPHHERC SDGDGLAPPQ HLIRVEGNPY
210 220 230 240 250
AEYLDDRQTF RHSVVVPYEP PEVGSDYTTI HYKYMCNSSC MGGMNRRPIL
260 270 280 290 300
TIITLEDSSG NLLGRDSFEV RVCACPGRDR RTEEENFRKK EEHCPELPPG
310 320 330 340 350
SAKRALPTST SSSPQQKKKP LDGEYFTLKI RGRERFEMFR ELNEALELKD
360 370 380 390
ARAAEESGDS RAHSSYPKTK KGQSTSRHKK PMIKKVGPDS D
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket| Q9EQL0 | Q9EQL0_RAT | Cellular tumor antigen p53 | Tp53 rCG_34931 | 271 | Annotation score: | ||
| A0A0G2KB75 | A0A0G2KB75_RAT | Cellular tumor antigen p53 | Tp53 | 170 | Annotation score: | ||
| A0A0G2KBB2 | A0A0G2KBB2_RAT | Cellular tumor antigen p53 | Tp53 | 170 | Annotation score: |
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sequence conflicti | 174 | C → W in AAA41788 (PubMed:8441680).Curated | 1 |
Natural variant
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural varianti | 103 | G → S. | 1 | |
| Natural varianti | 256 | E → G. | 1 |
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X13058 mRNA Translation: CAA31457.1 L07910 , L07904, L07905, L07906, L07907, L07908, L07909 Genomic DNA Translation: AAA41788.1 U90328 mRNA Translation: AAB80959.1 BC081788 mRNA Translation: AAH81788.2 BC098663 mRNA Translation: AAH98663.1 |
| PIRi | S02192 |
| RefSeqi | NP_112251.2, NM_030989.3 XP_006246656.1, XM_006246594.3 XP_006246657.1, XM_006246595.3 |
Genome annotation databases
| Ensembli | ENSRNOT00000046490; ENSRNOP00000047840; ENSRNOG00000010756 ENSRNOT00000085115; ENSRNOP00000074031; ENSRNOG00000010756 |
| GeneIDi | 24842 |
| KEGGi | rno:24842 |
| UCSCi | RGD:3889, rat |
Similar proteinsi
Cross-referencesi
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X13058 mRNA Translation: CAA31457.1 L07910 , L07904, L07905, L07906, L07907, L07908, L07909 Genomic DNA Translation: AAA41788.1 U90328 mRNA Translation: AAB80959.1 BC081788 mRNA Translation: AAH81788.2 BC098663 mRNA Translation: AAH98663.1 |
| PIRi | S02192 |
| RefSeqi | NP_112251.2, NM_030989.3 XP_006246656.1, XM_006246594.3 XP_006246657.1, XM_006246595.3 |
3D structure databases
| SMRi | P10361 |
| ModBasei | Search... |
Protein-protein interaction databases
| BioGRIDi | 246960, 11 interactors |
| DIPi | DIP-46016N |
| IntActi | P10361, 5 interactors |
| MINTi | P10361 |
| STRINGi | 10116.ENSRNOP00000047840 |
PTM databases
| iPTMneti | P10361 |
| PhosphoSitePlusi | P10361 |
Proteomic databases
| PaxDbi | P10361 |
| PRIDEi | P10361 |
Genome annotation databases
| Ensembli | ENSRNOT00000046490; ENSRNOP00000047840; ENSRNOG00000010756 ENSRNOT00000085115; ENSRNOP00000074031; ENSRNOG00000010756 |
| GeneIDi | 24842 |
| KEGGi | rno:24842 |
| UCSCi | RGD:3889, rat |
Organism-specific databases
| CTDi | 7157 |
| RGDi | 3889, Tp53 |
Phylogenomic databases
| eggNOGi | ENOG502QVY3, Eukaryota |
| GeneTreei | ENSGT00950000183153 |
| HOGENOMi | CLU_019621_0_0_1 |
| InParanoidi | P10361 |
| OMAi | FHKKGEP |
| OrthoDBi | 257530at2759 |
| PhylomeDBi | P10361 |
| TreeFami | TF106101 |
Enzyme and pathway databases
| Reactomei | R-RNO-2559580, Oxidative Stress Induced Senescence R-RNO-2559584, Formation of Senescence-Associated Heterochromatin Foci (SAHF) R-RNO-2559585, Oncogene Induced Senescence R-RNO-2559586, DNA Damage/Telomere Stress Induced Senescence R-RNO-349425, Autodegradation of the E3 ubiquitin ligase COP1 R-RNO-5689880, Ub-specific processing proteases R-RNO-5689896, Ovarian tumor domain proteases R-RNO-5693565, Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks R-RNO-6804754, Regulation of TP53 Expression R-RNO-6804756, Regulation of TP53 Activity through Phosphorylation R-RNO-6804757, Regulation of TP53 Degradation R-RNO-6804758, Regulation of TP53 Activity through Acetylation R-RNO-6804759, Regulation of TP53 Activity through Association with Co-factors R-RNO-6804760, Regulation of TP53 Activity through Methylation R-RNO-69473, G2/M DNA damage checkpoint R-RNO-69481, G2/M Checkpoints R-RNO-69541, Stabilization of p53 R-RNO-69895, Transcriptional activation of cell cycle inhibitor p21 R-RNO-8852276, The role of GTSE1 in G2/M progression after G2 checkpoint R-RNO-8941855, RUNX3 regulates CDKN1A transcription |
Miscellaneous databases
| PROi | PR:P10361 |
Gene expression databases
| Bgeei | ENSRNOG00000010756, Expressed in thymus and 22 other tissues |
| ExpressionAtlasi | P10361, baseline and differential |
| Genevisiblei | P10361, RN |
Family and domain databases
| CDDi | cd08367, P53, 1 hit |
| Gene3Di | 2.60.40.720, 1 hit 4.10.170.10, 1 hit |
| InterProi | View protein in InterPro IPR008967, p53-like_TF_DNA-bd IPR012346, p53/RUNT-type_TF_DNA-bd_sf IPR011615, p53_DNA-bd IPR036674, p53_tetramer_sf IPR010991, p53_tetrameristn IPR013872, p53_transactivation_domain IPR002117, p53_tumour_suppressor |
| PANTHERi | PTHR11447, PTHR11447, 1 hit |
| Pfami | View protein in Pfam PF00870, P53, 1 hit PF08563, P53_TAD, 1 hit PF07710, P53_tetramer, 1 hit |
| PRINTSi | PR00386, P53SUPPRESSR |
| SUPFAMi | SSF47719, SSF47719, 1 hit SSF49417, SSF49417, 1 hit |
| PROSITEi | View protein in PROSITE PS00348, P53, 1 hit |
| ProtoNeti | Search... |
| MobiDBi | Search... |
Entry informationi
| Entry namei | P53_RAT | |
| Accessioni | P10361Primary (citable) accession number: P10361 Secondary accession number(s): O09168, Q4KMA9, Q66HM0 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 1, 1989 |
| Last sequence update: | July 1, 1989 | |
| Last modified: | April 7, 2021 | |
| This is version 225 of the entry and version 1 of the sequence. See complete history. | ||
| Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Chordata Protein Annotation Program | |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families
