UniProtKB - P04637 (P53_HUMAN)
Cellular tumor antigen p53
TP53
Functioni
Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:9840937, PubMed:24652652).
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 (PubMed:11025664, PubMed:12524540, PubMed:12810724, PubMed:15186775, PubMed:15340061, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:9840937, PubMed:24652652).
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 (PubMed:12524540).
However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP (PubMed:12524540).
In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. 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. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis. Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER2 (PubMed:24051492).
14 PublicationsCaution
Cofactori
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 176 | Zinc7 Publications | 1 | |
Metal bindingi | 179 | Zinc7 Publications | 1 | |
Metal bindingi | 238 | Zinc7 Publications | 1 | |
Metal bindingi | 242 | Zinc7 Publications | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 102 – 292 | 3 PublicationsAdd BLAST | 191 |
GO - Molecular functioni
- ATP-dependent DNA/DNA annealing activity Source: UniProtKB
- chaperone binding Source: UniProtKB
- chromatin binding Source: UniProtKB
- cis-regulatory region sequence-specific DNA binding Source: ARUK-UCL
- copper ion binding Source: UniProtKB
- core promoter sequence-specific DNA binding Source: CAFA
- disordered domain specific binding Source: CAFA
- DNA binding Source: UniProtKB
- DNA-binding transcription activator activity, RNA polymerase II-specific Source: GO_Central
- DNA-binding transcription factor activity Source: UniProtKB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: UniProtKB
- DNA-binding transcription repressor activity, RNA polymerase II-specific Source: ARUK-UCL
- enzyme binding Source: UniProtKB
- general transcription initiation factor binding Source: BHF-UCL
- histone acetyltransferase binding Source: UniProtKB
- histone deacetylase binding Source: CAFA
- histone deacetylase regulator activity Source: Ensembl
- identical protein binding Source: UniProtKB
- MDM2/MDM4 family protein binding Source: Ensembl
- mRNA 3'-UTR binding Source: CAFA
- p53 binding Source: CAFA
- promoter-specific chromatin binding Source: UniProtKB
- protease binding Source: UniProtKB
- protein heterodimerization activity Source: UniProtKB
- protein kinase binding Source: UniProtKB
- protein N-terminus binding Source: UniProtKB
- protein phosphatase 2A binding Source: UniProtKB
- protein phosphatase binding Source: UniProtKB
- protein self-association Source: AgBase
- receptor tyrosine kinase binding Source: BHF-UCL
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: ARUK-UCL
- RNA polymerase II-specific DNA-binding transcription factor binding Source: UniProtKB
- TFIID-class transcription factor complex binding Source: ParkinsonsUK-UCL
- transcription cis-regulatory region binding Source: BHF-UCL
- ubiquitin protein ligase binding Source: UniProtKB
- zinc ion binding Source: UniProtKB
GO - Biological processi
- autophagy Source: CAFA
- B cell lineage commitment Source: Ensembl
- bone marrow development Source: UniProtKB
- cardiac septum morphogenesis Source: Ensembl
- cell aging Source: UniProtKB
- cellular protein localization Source: UniProtKB
- cellular response to actinomycin D Source: CAFA
- cellular response to DNA damage stimulus Source: UniProtKB
- cellular response to gamma radiation Source: CAFA
- cellular response to glucose starvation Source: UniProtKB
- cellular response to hypoxia Source: UniProtKB
- cellular response to ionizing radiation Source: BHF-UCL
- cellular response to UV Source: CAFA
- cellular response to UV-C Source: Ensembl
- cellular response to xenobiotic stimulus Source: UniProtKB
- cerebellum development Source: Ensembl
- chromatin assembly Source: UniProtKB
- circadian behavior Source: UniProtKB
- determination of adult lifespan Source: BHF-UCL
- DNA damage response, signal transduction by p53 class mediator Source: BHF-UCL
- DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Source: CAFA
- DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator Source: CAFA
- double-strand break repair Source: Ensembl
- embryonic organ development Source: Ensembl
- entrainment of circadian clock by photoperiod Source: UniProtKB
- ER overload response Source: MGI
- gastrulation Source: Ensembl
- hematopoietic progenitor cell differentiation Source: UniProtKB
- hematopoietic stem cell differentiation Source: UniProtKB
- interferon-gamma-mediated signaling pathway Source: Ensembl
- intrinsic apoptotic signaling pathway Source: HGNC-UCL
- intrinsic apoptotic signaling pathway by p53 class mediator Source: UniProtKB
- intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: UniProtKB
- intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Source: Ensembl
- intrinsic apoptotic signaling pathway in response to hypoxia Source: Ensembl
- in utero embryonic development Source: Ensembl
- mitochondrial DNA repair Source: Ensembl
- mitotic G1 DNA damage checkpoint signaling Source: BHF-UCL
- mRNA transcription Source: UniProtKB
- multicellular organism growth Source: Ensembl
- necroptotic process Source: Ensembl
- negative regulation of apoptotic process Source: UniProtKB
- negative regulation of cell growth Source: UniProtKB
- negative regulation of cell population proliferation Source: CACAO
- negative regulation of DNA replication Source: Ensembl
- negative regulation of fibroblast proliferation Source: UniProtKB
- negative regulation of G1 to G0 transition Source: CAFA
- negative regulation of glucose catabolic process to lactate via pyruvate Source: Ensembl
- negative regulation of helicase activity Source: UniProtKB
- negative regulation of mitophagy Source: Ensembl
- negative regulation of neuroblast proliferation Source: Ensembl
- negative regulation of pentose-phosphate shunt Source: CACAO
- negative regulation of production of miRNAs involved in gene silencing by miRNA Source: Ensembl
- negative regulation of proteolysis Source: Ensembl
- negative regulation of reactive oxygen species metabolic process Source: Ensembl
- negative regulation of telomerase activity Source: BHF-UCL
- negative regulation of transcription, DNA-templated Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: ARUK-UCL
- negative regulation of transforming growth factor beta receptor signaling pathway Source: Ensembl
- neuron apoptotic process Source: Ensembl
- nucleotide-excision repair Source: UniProtKB
- oligodendrocyte apoptotic process Source: UniProtKB
- oxidative stress-induced premature senescence Source: BHF-UCL
- positive regulation of apoptotic process Source: UniProtKB
- positive regulation of cardiac muscle cell apoptotic process Source: Ensembl
- positive regulation of cell aging Source: Ensembl
- positive regulation of execution phase of apoptosis Source: AgBase
- positive regulation of gene expression Source: CAFA
- positive regulation of histone deacetylation Source: Ensembl
- positive regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
- positive regulation of miRNA transcription Source: BHF-UCL
- positive regulation of mitochondrial membrane permeability Source: Ensembl
- positive regulation of neuron apoptotic process Source: Ensembl
- positive regulation of peptidyl-tyrosine phosphorylation Source: BHF-UCL
- positive regulation of production of miRNAs involved in gene silencing by miRNA Source: BHF-UCL
- positive regulation of programmed necrotic cell death Source: Ensembl
- positive regulation of reactive oxygen species metabolic process Source: BHF-UCL
- positive regulation of release of cytochrome c from mitochondria Source: UniProtKB
- positive regulation of RNA polymerase II transcription preinitiation complex assembly Source: BHF-UCL
- positive regulation of thymocyte apoptotic process Source: BHF-UCL
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress Source: ParkinsonsUK-UCL
- positive regulation of transcription from RNA polymerase II promoter in response to hypoxia Source: Ensembl
- positive regulation of transcription from RNA polymerase II promoter in response to stress Source: ARUK-UCL
- protein-containing complex assembly Source: UniProtKB
- protein import into nucleus Source: Ensembl
- protein localization Source: UniProtKB
- protein stabilization Source: Ensembl
- protein tetramerization Source: InterPro
- Ras protein signal transduction Source: BHF-UCL
- regulation of apoptotic process Source: MGI
- regulation of cell cycle Source: BHF-UCL
- regulation of cell cycle G2/M phase transition Source: UniProtKB
- regulation of cellular senescence Source: Ensembl
- regulation of DNA damage response, signal transduction by p53 class mediator Source: Ensembl
- regulation of fibroblast apoptotic process Source: Ensembl
- regulation of intrinsic apoptotic signaling pathway by p53 class mediator Source: Ensembl
- regulation of mitochondrial membrane permeability involved in apoptotic process Source: Ensembl
- regulation of tissue remodeling Source: Ensembl
- regulation of transcription, DNA-templated Source: UniProtKB
- regulation of transcription by RNA polymerase II Source: GO_Central
- regulation of transcription from RNA polymerase II promoter in response to DNA damage Source: ARUK-UCL
- release of cytochrome c from mitochondria Source: Ensembl
- replicative senescence Source: BHF-UCL
- response to antibiotic Source: UniProtKB
- response to gamma radiation Source: BHF-UCL
- response to ischemia Source: Ensembl
- response to salt stress Source: Ensembl
- response to X-ray Source: Ensembl
- rRNA transcription Source: Ensembl
- signal transduction by p53 class mediator Source: CAFA
- somitogenesis Source: Ensembl
- T cell differentiation in thymus Source: Ensembl
- T cell lineage commitment Source: Ensembl
- T cell proliferation involved in immune response Source: Ensembl
- transforming growth factor beta receptor signaling pathway Source: Ensembl
- tumor necrosis factor-mediated signaling pathway Source: BHF-UCL
- viral process Source: CACAO
Keywordsi
Molecular function | Activator, DNA-binding, Repressor |
Biological process | Apoptosis, Biological rhythms, Cell cycle, Host-virus interaction, Necrosis, Transcription, Transcription regulation |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | P04637 |
Reactomei | R-HSA-111448, Activation of NOXA and translocation to mitochondria R-HSA-139915, Activation of PUMA and translocation to mitochondria R-HSA-1912408, Pre-NOTCH Transcription and Translation R-HSA-2559580, Oxidative Stress Induced Senescence R-HSA-2559584, Formation of Senescence-Associated Heterochromatin Foci (SAHF) R-HSA-2559585, Oncogene Induced Senescence R-HSA-2559586, DNA Damage/Telomere Stress Induced Senescence R-HSA-3232118, SUMOylation of transcription factors R-HSA-349425, Autodegradation of the E3 ubiquitin ligase COP1 R-HSA-390471, Association of TriC/CCT with target proteins during biosynthesis R-HSA-5620971, Pyroptosis R-HSA-5628897, TP53 Regulates Metabolic Genes R-HSA-5689880, Ub-specific processing proteases R-HSA-5689896, Ovarian tumor domain proteases R-HSA-5693565, Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks R-HSA-6785807, Interleukin-4 and Interleukin-13 signaling R-HSA-6796648, TP53 Regulates Transcription of DNA Repair Genes R-HSA-6803204, TP53 Regulates Transcription of Genes Involved in Cytochrome C Release R-HSA-6803205, TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain R-HSA-6803207, TP53 Regulates Transcription of Caspase Activators and Caspases R-HSA-6803211, TP53 Regulates Transcription of Death Receptors and Ligands R-HSA-6804114, TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest R-HSA-6804115, TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain R-HSA-6804116, TP53 Regulates Transcription of Genes Involved in G1 Cell Cycle Arrest R-HSA-6804754, Regulation of TP53 Expression R-HSA-6804756, Regulation of TP53 Activity through Phosphorylation R-HSA-6804757, Regulation of TP53 Degradation R-HSA-6804758, Regulation of TP53 Activity through Acetylation R-HSA-6804759, Regulation of TP53 Activity through Association with Co-factors R-HSA-6804760, Regulation of TP53 Activity through Methylation R-HSA-6811555, PI5P Regulates TP53 Acetylation R-HSA-69473, G2/M DNA damage checkpoint R-HSA-69481, G2/M Checkpoints R-HSA-69541, Stabilization of p53 R-HSA-69895, Transcriptional activation of cell cycle inhibitor p21 R-HSA-8852276, The role of GTSE1 in G2/M progression after G2 checkpoint R-HSA-8853884, Transcriptional Regulation by VENTX R-HSA-8941855, RUNX3 regulates CDKN1A transcription R-HSA-8943724, Regulation of PTEN gene transcription R-HSA-9723905, Loss of function of TP53 in cancer due to loss of tetramerization ability R-HSA-983231, Factors involved in megakaryocyte development and platelet production |
SABIO-RKi | P04637 |
SignaLinki | P04637 |
SIGNORi | P04637 |
Protein family/group databases
MoonDBi | P04637, Predicted |
TCDBi | 1.C.110.1.1, the pore-forming pnc-27 peptide of 32 aas from the p53 tumor suppressor protein (pnc-27) family |
Names & Taxonomyi
Protein namesi | Recommended name: Cellular tumor antigen p53Alternative name(s): Antigen NY-CO-13 Phosphoprotein p53 Tumor suppressor p53 |
Gene namesi | Name:TP53 Synonyms:P53 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:11998, TP53 |
MIMi | 191170, gene+phenotype |
neXtProti | NX_P04637 |
VEuPathDBi | HostDB:ENSG00000141510 |
Subcellular locationi
Cytoplasm and Cytosol
- Cytoplasm 5 Publications
Mitochondrion
- Mitochondrion matrix 3 Publications
Cytoskeleton
- centrosome 1 Publication
Nucleus
Endoplasmic reticulum
- Endoplasmic reticulum 1 Publication
Note: Recruited into PML bodies together with CHEK2 (PubMed:12810724). Translocates to mitochondria upon oxidative stress (PubMed:22726440). Translocates to mitochondria in response to mitomycin C treatment (PubMed:27323408).3 Publications
Cytoplasm and Cytosol
Cytoskeleton
- centrosome Source: UniProtKB
Cytosol
- cytosol Source: UniProtKB
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB-SubCell
Mitochondrion
- mitochondrial matrix Source: UniProtKB-SubCell
- mitochondrion Source: UniProtKB
Nucleus
- nuclear matrix Source: UniProtKB
- nucleolus Source: UniProtKB
- nucleoplasm Source: UniProtKB
- nucleus Source: UniProtKB
- PML body Source: UniProtKB
Other locations
- chromatin Source: BHF-UCL
- cytoplasm Source: UniProtKB
- protein-containing complex Source: CAFA
- replication fork Source: Ensembl
- site of double-strand break Source: Ensembl
- transcription regulator complex Source: ARUK-UCL
- transcription repressor complex Source: ComplexPortal
Keywords - Cellular componenti
Cytoplasm, Cytoskeleton, Endoplasmic reticulum, Mitochondrion, NucleusPathology & Biotechi
Involvement in diseasei
Esophageal cancer (ESCR)
Li-Fraumeni syndrome (LFS)9 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_044621 | 82 | P → L in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs534447939EnsemblClinVar. | 1 | |
Natural variantiVAR_044661 | 105 | G → C in LFS; germline mutation and in sporadic cancers; somatic mutation. | 1 | |
Natural variantiVAR_044740 | 132 | K → E in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs747342068EnsemblClinVar. | 1 | |
Natural variantiVAR_044747 | 133 | M → R in LFS; germline mutation and in sporadic cancers; somatic mutation. | 1 | |
Natural variantiVAR_005875 | 133 | M → T in LFS; germline mutation and in sporadic cancers; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs28934873EnsemblClinVar. | 1 | |
Natural variantiVAR_005881 | 138 | A → P in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs28934875EnsemblClinVar. | 1 | |
Natural variantiVAR_044764 | 138 | A → S in LFS; germline mutation. | 1 | |
Natural variantiVAR_005886 | 141 | C → Y in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs587781288EnsemblClinVar. | 1 | |
Natural variantiVAR_044790 | 144 | Q → L in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs786203071EnsemblClinVar. | 1 | |
Natural variantiVAR_005895 | 151 | P → S in LFS; germline mutation and in sporadic cancers; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs28934874EnsemblClinVar. | 1 | |
Natural variantiVAR_005896 | 151 | P → T in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs28934874EnsemblClinVar. | 1 | |
Natural variantiVAR_005897 | 152 | P → L in LFS; germline mutation and in sporadic cancers; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs587782705EnsemblClinVar. | 1 | |
Natural variantiVAR_044836 | 155 | T → N in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs786202752EnsemblClinVar. | 1 | |
Natural variantiVAR_044841 | 156 | R → H in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs371524413EnsemblClinVar. | 1 | |
Natural variantiVAR_005906 | 158 | R → G in LFS; germline mutation and in sporadic cancers; somatic mutation. | 1 | |
Natural variantiVAR_005907 | 158 | R → H in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs587782144EnsemblClinVar. | 1 | |
Natural variantiVAR_033035 | 163 | Y → C in LFS; germline mutation and in sporadic cancers; somatic mutation. 2 PublicationsCorresponds to variant dbSNP:rs148924904EnsemblClinVar. | 1 | |
Natural variantiVAR_044885 | 167 | Q → K in LFS; germline mutation and in a sporadic cancer; somatic mutation. | 1 | |
Natural variantiVAR_044906 | 172 | V → F in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs1131691043EnsemblClinVar. | 1 | |
Natural variantiVAR_005926 | 173 | V → M in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs876660754EnsemblClinVar. | 1 | |
Natural variantiVAR_044911 | 174 | R → G in LFS; germline mutation and in a sporadic cancer; somatic mutation. Corresponds to variant dbSNP:rs864622115EnsemblClinVar. | 1 | |
Natural variantiVAR_005929 | 175 | R → G in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs138729528EnsemblClinVar. | 1 | |
Natural variantiVAR_005932 | 175 | R → H in LFS; germline mutation and in sporadic cancers; somatic mutation; does not induce SNAI1 degradation; reduces interaction with ZNF385A; loss of susceptibility to calpain. 7 PublicationsCorresponds to variant dbSNP:rs28934578EnsemblClinVar. | 1 | |
Natural variantiVAR_005930 | 175 | R → L in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs28934578EnsemblClinVar. | 1 | |
Natural variantiVAR_044939 | 179 | H → Y in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs587780070EnsemblClinVar. | 1 | |
Natural variantiVAR_044943 | 180 | E → K in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs879253911EnsemblClinVar. | 1 | |
Natural variantiVAR_044946 | 181 | R → C in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs587782596EnsemblClinVar. | 1 | |
Natural variantiVAR_044948 | 181 | R → H in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs397514495EnsemblClinVar. | 1 | |
Natural variantiVAR_005948 | 193 | H → R in LFS; germline mutation and in sporadic cancers; somatic mutation. 2 PublicationsCorresponds to variant dbSNP:rs786201838EnsemblClinVar. | 1 | |
Natural variantiVAR_045007 | 196 | R → P in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs483352697EnsemblClinVar. | 1 | |
Natural variantiVAR_045013 | 197 | V → M in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs786204041EnsemblClinVar. | 1 | |
Natural variantiVAR_036506 | 213 | R → P in LFS; germline mutation and in sporadic cancers; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs587778720EnsemblClinVar. | 1 | |
Natural variantiVAR_005955 | 213 | R → Q in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs587778720EnsemblClinVar. | 1 | |
Natural variantiVAR_005957 | 220 | Y → C in LFS; germline mutation and in sporadic cancers; somatic mutation. 2 PublicationsCorresponds to variant dbSNP:rs121912666EnsemblClinVar. | 1 | |
Natural variantiVAR_045151 | 227 | S → T in LFS; germline mutation and in a sporadic cancer; somatic mutation. | 1 | |
Natural variantiVAR_045175 | 233 | H → D in LFS; germline mutation and in a sporadic cancer; somatic mutation. | 1 | |
Natural variantiVAR_005963 | 234 | Y → C in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs587780073EnsemblClinVar. | 1 | |
Natural variantiVAR_045186 | 235 | N → S in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs144340710EnsemblClinVar. | 1 | |
Natural variantiVAR_045189 | 236 | Y → C in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs730882026EnsemblClinVar. | 1 | |
Natural variantiVAR_005965 | 237 | M → I in LFS; germline mutation and in sporadic cancers; somatic mutation; no effect on susceptibility to calpain. 1 PublicationCorresponds to variant dbSNP:rs587782664EnsemblClinVar. | 1 | |
Natural variantiVAR_045200 | 238 | C → G in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs1057519981EnsemblClinVar. | 1 | |
Natural variantiVAR_045202 | 238 | C → S in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs730882005EnsemblClinVar. | 1 | |
Natural variantiVAR_005969 | 241 | S → F in LFS; germline mutation and in sporadic cancers; somatic mutation. 2 PublicationsCorresponds to variant dbSNP:rs28934573EnsemblClinVar. | 1 | |
Natural variantiVAR_047183 | 241 | S → T in LFS; germline mutation and in sporadic cancers; somatic mutation. | 1 | |
Natural variantiVAR_045232 | 244 | G → D in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs1057517983Ensembl. | 1 | |
Natural variantiVAR_045236 | 244 | G → V in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs985033810EnsemblClinVar. | 1 | |
Natural variantiVAR_005972 | 245 | G → C in LFS; germline mutation and in sporadic cancers; somatic mutation. 2 PublicationsCorresponds to variant dbSNP:rs28934575EnsemblClinVar. | 1 | |
Natural variantiVAR_005973 | 245 | G → D in LFS; germline mutation and in sporadic cancers; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs121912656EnsemblClinVar. | 1 | |
Natural variantiVAR_005974 | 245 | G → S in LFS; germline mutation and in sporadic cancers; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs28934575EnsemblClinVar. | 1 | |
Natural variantiVAR_005975 | 245 | G → V in LFS; germline mutation and in sporadic cancers; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs121912656EnsemblClinVar. | 1 | |
Natural variantiVAR_005978 | 246 | M → V in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs483352695EnsemblClinVar. | 1 | |
Natural variantiVAR_005983 | 248 | R → Q in LFS; germline mutation and in sporadic cancers; somatic mutation. 4 PublicationsCorresponds to variant dbSNP:rs11540652EnsemblClinVar. | 1 | |
Natural variantiVAR_005984 | 248 | R → W in LFS; germline mutation and in sporadic cancers; somatic mutation; no effect on susceptibility to calpain. 4 PublicationsCorresponds to variant dbSNP:rs121912651EnsemblClinVar. | 1 | |
Natural variantiVAR_045258 | 251 | I → M in LFS; germline mutation. Corresponds to variant dbSNP:rs878854074EnsemblClinVar. | 1 | |
Natural variantiVAR_005988 | 252 | L → P in LFS; germline mutation and in sporadic cancers; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs121912653EnsemblClinVar. | 1 | |
Natural variantiVAR_045284 | 257 | L → Q in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs28934577EnsemblClinVar. | 1 | |
Natural variantiVAR_005991 | 258 | E → K in LFS; germline mutation and in sporadic cancers; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs121912652EnsemblClinVar. | 1 | |
Natural variantiVAR_045321 | 265 | L → P in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs879253942EnsemblClinVar. | 1 | |
Natural variantiVAR_045330 | 267 | R → Q in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs587780075EnsemblClinVar. | 1 | |
Natural variantiVAR_005992 | 272 | V → L in LFS; germline mutation and in sporadic cancers; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs121912657EnsemblClinVar. | 1 | |
Natural variantiVAR_005993 | 273 | R → C in LFS; germline mutation and in sporadic cancers; somatic mutation. 4 PublicationsCorresponds to variant dbSNP:rs121913343EnsemblClinVar. | 1 | |
Natural variantiVAR_005994 | 273 | R → G in LFS; germline mutation and in sporadic cancers; somatic mutation. | 1 | |
Natural variantiVAR_005995 | 273 | R → H in LFS; germline mutation and in sporadic cancers; somatic mutation; abolishes sequence-specific DNA binding; does not induce SNAI1 degradation. 9 PublicationsCorresponds to variant dbSNP:rs28934576EnsemblClinVar. | 1 | |
Natural variantiVAR_036509 | 273 | R → L in LFS; germline mutation and in sporadic cancers; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs28934576EnsemblClinVar. | 1 | |
Natural variantiVAR_005998 | 275 | C → Y in LFS; germline mutation and in sporadic cancers; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs863224451EnsemblClinVar. | 1 | |
Natural variantiVAR_006003 | 278 | P → L in LFS; germline mutation and in sporadic cancers; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs876659802EnsemblClinVar. | 1 | |
Natural variantiVAR_006004 | 278 | P → S in LFS; germline mutation and in sporadic cancers; somatic mutation. 3 PublicationsCorresponds to variant dbSNP:rs17849781EnsemblClinVar. | 1 | |
Natural variantiVAR_006005 | 278 | P → T in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs17849781EnsemblClinVar. | 1 | |
Natural variantiVAR_047202 | 281 | D → N in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs764146326EnsemblClinVar. | 1 | |
Natural variantiVAR_045384 | 282 | R → G in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs28934574EnsemblClinVar. | 1 | |
Natural variantiVAR_006016 | 282 | R → W in LFS; germline mutation and in sporadic cancers; somatic mutation; does not induce SNAI1 degradation. 2 PublicationsCorresponds to variant dbSNP:rs28934574EnsemblClinVar. | 1 | |
Natural variantiVAR_006017 | 283 | R → C in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs149633775EnsemblClinVar. | 1 | |
Natural variantiVAR_006024 | 285 | E → Q in LFS; germline mutation and in sporadic cancers; somatic mutation. | 1 | |
Natural variantiVAR_006026 | 286 | E → A in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs1057519985EnsemblClinVar. | 1 | |
Natural variantiVAR_045411 | 290 | R → H in LFS; germline mutation and in sporadic cancers; somatic mutation. Corresponds to variant dbSNP:rs55819519EnsemblClinVar. | 1 | |
Natural variantiVAR_045412 | 290 | R → L in LFS; germline mutation and in sporadic cancers; somatic mutation. | 1 | |
Natural variantiVAR_015819 | 292 | K → I in LFS; germline mutation and in a sporadic cancer; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs121912663EnsemblClinVar. | 1 | |
Natural variantiVAR_045475 | 306 | R → P in LFS; germline mutation and in a sporadic cancer; somatic mutation. | 1 | |
Natural variantiVAR_006038 | 309 | P → S in LFS; germline mutation and in sporadic cancers; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1555525012EnsemblClinVar. | 1 | |
Natural variantiVAR_006039 | 325 | G → V in LFS; germline mutation. 1 PublicationCorresponds to variant dbSNP:rs121912659EnsemblClinVar. | 1 | |
Natural variantiVAR_006041 | 337 | R → C in LFS; germline mutation and in sporadic cancers; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs587782529EnsemblClinVar. | 1 | |
Natural variantiVAR_035016 | 337 | R → H in LFS; germline mutation and in sporadic cancers; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs121912664EnsemblClinVar. | 1 | |
Natural variantiVAR_045546 | 344 | L → P in LFS; germline mutation and in a sporadic cancer; somatic mutation. Corresponds to variant dbSNP:rs121912662EnsemblClinVar. | 1 |
Squamous cell carcinoma of the head and neck (HNSCC)
Lung cancer (LNCR)
Papilloma of choroid plexus (CPP)1 Publication
Adrenocortical carcinoma (ADCC)1 Publication
Basal cell carcinoma 7 (BCC7)1 Publication
Bone marrow failure syndrome 5 (BMFS5)1 Publication
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 15 | S → A: Loss of interaction with PPP2R5C, PPP2CA AND PPP2R1A. 1 Publication | 1 | |
Mutagenesisi | 18 | T → A: No effect on interaction with MDM2 and increase in protein levels after DNA damage. 1 Publication | 1 | |
Mutagenesisi | 20 | S → A: Abolishes phosphorylation site. Abolishes increase in protein levels after DNA damage. 1 Publication | 1 | |
Mutagenesisi | 20 | S → D: Constitutively increased TP53 protein levels. 1 Publication | 1 | |
Mutagenesisi | 22 – 23 | LW → QS: Loss of interaction with MDM2, leading to constitutively increased TP53 protein levels. 1 Publication | 2 | |
Mutagenesisi | 24 | K → R: Abolishes ubiquitination by MUL1. 1 Publication | 1 | |
Mutagenesisi | 37 | S → D: Abolishes phosphorylation by MAPKAPK5. 1 Publication | 1 | |
Mutagenesisi | 46 | S → A: Abolishes phosphorylation by DYRK2 and HIPK2 and acetylation of K-382 by CREBBP. 3 Publications | 1 | |
Mutagenesisi | 46 | Missing : Alters interaction with WWOX. 3 Publications | 1 | |
Mutagenesisi | 55 | T → A: Blocks phosphorylation by TAF1. 1 Publication | 1 | |
Mutagenesisi | 183 | S → A: Abolishes strongly phosphorylation. 1 Publication | 1 | |
Mutagenesisi | 183 | S → E: Inhibits slightly its transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 248 | R → S: Does not induce SNAI1 degradation. 1 Publication | 1 | |
Mutagenesisi | 269 | S → A: Abolishes phosphorylation. 1 Publication | 1 | |
Mutagenesisi | 269 | S → E: Inhibits strongly its transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 284 | T → E: Inhibits strongly its transcriptional activity. 1 Publication | 1 | |
Mutagenesisi | 291 – 292 | KK → RR: Abolishes polyubiquitination by MKRN1. 1 Publication | 2 | |
Mutagenesisi | 319 | K → A: Loss of nuclear localization; when associated with A-320 and A-321. 1 Publication | 1 | |
Mutagenesisi | 320 | K → A: Loss of nuclear localization; when associated with A-319 and A-321. 1 Publication | 1 | |
Mutagenesisi | 321 | K → A: Loss of nuclear localization; when associated with A-319 and A-320. 1 Publication | 1 | |
Mutagenesisi | 333 – 337 | RGRER → KGKEK: Reduced methylation by PRMT5. Reduced nuclear localization. Decreased binding to promoters of target genes. Reduced transcriptional activity. Decrease in cell cycle arrest. 1 Publication | 5 | |
Mutagenesisi | 359 | P → D: Abolishes binding to USP7. 1 Publication | 1 | |
Mutagenesisi | 361 | G → E: Abolishes binding to USP7. 1 Publication | 1 | |
Mutagenesisi | 362 | S → A: Abolishes binding to USP7. 1 Publication | 1 | |
Mutagenesisi | 370 | K → R: Induces a decrease in methylation by SMYD2. 1 Publication | 1 | |
Mutagenesisi | 372 | K → R: Induces a decrease in protein stabilization. 1 Publication | 1 | |
Mutagenesisi | 373 | K → R: Abolishes dimethylation by EHMT1 and EHMT2. 1 Publication | 1 | |
Mutagenesisi | 381 | K → Q: Mimics acetylation, leading to increased stability. 1 Publication | 1 | |
Mutagenesisi | 381 | K → R: Decreased acetylation. 1 Publication | 1 | |
Mutagenesisi | 382 | K → A: Abolishes acetylation by CREBBP. 4 Publications | 1 | |
Mutagenesisi | 382 | K → R: Abolishes monomethylation by KMT5A. 4 Publications | 1 | |
Mutagenesisi | 383 | L → A: Abolishes S-315 phosphorylation by CDK2/cyclin A. 1 Publication | 1 | |
Mutagenesisi | 385 | F → A: Reduced SUMO1 conjugation. 2 Publications | 1 | |
Mutagenesisi | 386 | K → A: Abolishes SUMO1 conjugation, in vitro and in vivo. 2 Publications | 1 | |
Mutagenesisi | 387 | T → A: No effect SUMO1 conjugation. 1 Publication | 1 | |
Mutagenesisi | 388 | E → A: Abolishes SUMO1 conjugation. 1 Publication | 1 |
Keywords - Diseasei
Disease variant, Li-Fraumeni syndrome, Tumor suppressorOrganism-specific databases
DisGeNETi | 7157 |
GeneReviewsi | TP53 |
MalaCardsi | TP53 |
MIMi | 133239, phenotype 151623, phenotype 191170, gene+phenotype 202300, phenotype 211980, phenotype 260500, phenotype 275355, phenotype 614740, phenotype 618165, phenotype |
OpenTargetsi | ENSG00000141510 |
Orphaneti | 1501, Adrenocortical carcinoma 210159, Adult hepatocellular carcinoma 67038, B-cell chronic lymphocytic leukemia 585877, B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormality 251899, Choroid plexus carcinoma 3318, Essential thrombocythemia 1333, Familial pancreatic carcinoma 251579, Giant cell glioblastoma 251576, Gliosarcoma 145, Hereditary breast and ovarian cancer syndrome 524, Li-Fraumeni syndrome 668, Osteosarcoma 2807, Papilloma of choroid plexus 70573, Small cell lung cancer |
PharmGKBi | PA36679 |
Miscellaneous databases
Pharosi | P04637, Tchem |
Chemistry databases
ChEMBLi | CHEMBL4096 |
DrugBanki | DB08363, 1-(9-ethyl-9H-carbazol-3-yl)-N-methylmethanamine DB00945, Acetylsalicylic acid DB05404, AZD 3355 DB03347, Triethyl phosphate DB01593, Zinc DB14487, Zinc acetate DB14533, Zinc chloride DB14548, Zinc sulfate, unspecified form |
Genetic variation databases
BioMutai | TP53 |
DMDMi | 269849759 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000185703 | 1 – 393 | Cellular tumor antigen p53Add BLAST | 393 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 9 | Phosphoserine; by HIPK41 Publication | 1 | |
Modified residuei | 15 | Phosphoserine; by CDK5, PRPK, AMPK, NUAK1 and ATM8 Publications | 1 | |
Modified residuei | 18 | Phosphothreonine; by CK1, VRK1 and VRK23 Publications | 1 | |
Modified residuei | 20 | Phosphoserine; by CHEK2, CK1 and PLK35 Publications | 1 | |
Cross-linki | 24 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Modified residuei | 33 | Phosphoserine; by CDK5 and CDK72 Publications | 1 | |
Modified residuei | 37 | Phosphoserine; by MAPKAPK51 Publication | 1 | |
Modified residuei | 46 | Phosphoserine; by CDK5, DYRK2, HIPK2 and PKC/PRKCG5 Publications | 1 | |
Modified residuei | 55 | Phosphothreonine; by TAF1 and GRK52 Publications | 1 | |
Modified residuei | 120 | N6-acetyllysine; by KAT6A1 Publication | 1 | |
Modified residuei | 183 | Phosphoserine; by AURKB1 Publication | 1 | |
Modified residuei | 269 | Phosphoserine; by AURKB1 Publication | 1 | |
Modified residuei | 284 | Phosphothreonine; by AURKB1 Publication | 1 | |
Cross-linki | 291 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Cross-linki | 292 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Modified residuei | 305 | N6-acetyllysine1 Publication | 1 | |
Modified residuei | 315 | Phosphoserine; by AURKA, CDK1 and CDK22 Publications | 1 | |
Modified residuei | 321 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 333 | Omega-N-methylarginine; by PRMT51 Publication | 1 | |
Modified residuei | 335 | Symmetric dimethylarginine; by PRMT51 Publication | 1 | |
Modified residuei | 337 | Symmetric dimethylarginine; by PRMT51 Publication | 1 | |
Modified residuei | 370 | N6,N6-dimethyllysine; alternate2 Publications | 1 | |
Modified residuei | 370 | N6-methyllysine; by SMYD2; alternate2 Publications |