InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TP53

Summary

InnateDB Protein

IDBP-26366.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TP53

Protein Name

tumor protein p53

Synonyms

BCC7; LFS1; P53; TRP53;

Species

Homo sapiens

Ensembl Protein

ENSP00000269305

InnateDB Gene

IDBG-26364 (TP53)

Protein Structure

UniProt Annotation

Function

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. 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 seem to have to 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. {ECO:0000269PubMed:11025664, ECO:0000269PubMed:12810724, ECO:0000269PubMed:15186775, ECO:0000269PubMed:15340061, ECO:0000269PubMed:17317671, ECO:0000269PubMed:17349958, ECO:0000269PubMed:19556538, ECO:0000269PubMed:20673990, ECO:0000269PubMed:20959462, ECO:0000269PubMed:22726440, ECO:0000269PubMed:9840937}.

Subcellular Localization

Cytoplasm. Nucleus. Nucleus, PML body. Endoplasmic reticulum. Mitochondrion matrix. Note=Interaction with BANP promotes nuclear localization. Recruited into PML bodies together with CHEK2. Translocates to mitochondria upon oxidative stress.Isoform 1: Nucleus. Cytoplasm. Note=Predominantly nuclear but localizes to the cytoplasm when expressed with isoform 4.Isoform 2: Nucleus. Cytoplasm. Note=Localized mainly in the nucleus with minor staining in the cytoplasm.Isoform 3: Nucleus. Cytoplasm. Note=Localized in the nucleus in most cells but found in the cytoplasm in some cells.Isoform 4: Nucleus. Cytoplasm. Note=Predominantly nuclear but translocates to the cytoplasm following cell stress.Isoform 7: Nucleus. Cytoplasm. Note=Localized mainly in the nucleus with minor staining in the cytoplasm.Isoform 8: Nucleus. Cytoplasm. Note=Localized in both nucleus and cytoplasm in most cells. In some cells, forms foci in the nucleus that are different from nucleoli.Isoform 9: Cytoplasm.

Disease Associations

Note=TP53 is found in increased amounts in a wide variety of transformed cells. TP53 is frequently mutated or inactivated in about 60% of cancers. TP53 defects are found in Barrett metaplasia a condition in which the normally stratified squamous epithelium of the lower esophagus is replaced by a metaplastic columnar epithelium. The condition develops as a complication in approximately 10% of patients with chronic gastroesophageal reflux disease and predisposes to the development of esophageal adenocarcinoma.Esophageal cancer (ESCR) [MIM:133239]: A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage. Note=The disease is caused by mutations affecting the gene represented in this entry.Li-Fraumeni syndrome (LFS) [MIM:151623]: Autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers. {ECO:0000269PubMed:10484981, ECO:0000269PubMed:1565144, ECO:0000269PubMed:1737852, ECO:0000269PubMed:1933902, ECO:0000269PubMed:1978757, ECO:0000269PubMed:2259385, ECO:0000269PubMed:7887414, ECO:0000269PubMed:8825920, ECO:0000269PubMed:9452042}. Note=The disease is caused by mutations affecting the gene represented in this entry.Squamous cell carcinoma of the head and neck (HNSCC) [MIM:275355]: A non-melanoma skin cancer affecting the head and neck. The hallmark of cutaneous SCC is malignant transformation of normal epidermal keratinocytes. Note=The gene represented in this entry is involved in disease pathogenesis.Lung cancer (LNCR) [MIM:211980]: A common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Note=The disease is caused by mutations affecting the gene represented in this entry.Papilloma of choroid plexus (CPP) [MIM:260500]: A benign tumor of neuroectodermal origin that generally occurs in childhood, but has also been reported in adults. Although generally found within the ventricular system, choroid plexus papillomas can arise ectopically in the brain parenchyma or disseminate throughout the neuraxis. Patients present with signs and symptoms of increased intracranial pressure including headache, hydrocephalus, papilledema, nausea, vomiting, cranial nerve deficits, gait impairment, and seizures. {ECO:0000269PubMed:12085209}. Note=The disease is caused by mutations affecting the gene represented in this entry.Adrenocortical carcinoma (ADCC) [MIM:202300]: A malignant neoplasm of the adrenal cortex and a rare childhood tumor. It occurs with increased frequency in patients with Beckwith- Wiedemann syndrome and Li-Fraumeni syndrome. {ECO:0000269PubMed:11481490}. Note=The disease is caused by mutations affecting the gene represented in this entry.Basal cell carcinoma 7 (BCC7) [MIM:614740]: A common malignant skin neoplasm that typically appears on hair-bearing skin, most commonly on sun-exposed areas. It is slow growing and rarely metastasizes, but has potentialities for local invasion and destruction. It usually develops as a flat, firm, pale area that is small, raised, pink or red, translucent, shiny, and waxy, and the area may bleed following minor injury. Tumor size can vary from a few millimeters to several centimeters in diameter. {ECO:0000269PubMed:21946351}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Tissue Specificity

Ubiquitous. Isoforms are expressed in a wide range of normal tissues but in a tissue-dependent manner. Isoform 2 is expressed in most normal tissues but is not detected in brain, lung, prostate, muscle, fetal brain, spinal cord and fetal liver. Isoform 3 is expressed in most normal tissues but is not detected in lung, spleen, testis, fetal brain, spinal cord and fetal liver. Isoform 7 is expressed in most normal tissues but is not detected in prostate, uterus, skeletal muscle and breast. Isoform 8 is detected only in colon, bone marrow, testis, fetal brain and intestine. Isoform 9 is expressed in most normal tissues but is not detected in brain, heart, lung, fetal liver, salivary gland, breast or intestine. {ECO:0000269PubMed:16131611}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 1328 experimentally validated interaction(s) in this database.
They are also associated with 85 interaction(s) predicted by orthology.

Experimentally validated
Total	1328 [view]
Protein-Protein	1244 [view]
Protein-DNA	66 [view]
Protein-RNA	0
DNA-DNA	18 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	85 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000979	RNA polymerase II core promoter sequence-specific DNA binding
GO:0001077	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
GO:0001085	RNA polymerase II transcription factor binding
GO:0001228	RNA polymerase II transcription regulatory region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription
GO:0002020	protease binding
GO:0002039	p53 binding
GO:0003677	DNA binding
GO:0003682	chromatin binding
GO:0003684	damaged DNA binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0005507	copper ion binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008134	transcription factor binding
GO:0008270	zinc ion binding
GO:0019899	enzyme binding
GO:0019901	protein kinase binding
GO:0019903	protein phosphatase binding
GO:0030971	receptor tyrosine kinase binding
GO:0031625	ubiquitin protein ligase binding
GO:0035033	histone deacetylase regulator activity
GO:0035035	histone acetyltransferase binding
GO:0042802	identical protein binding
GO:0044212	transcription regulatory region DNA binding
GO:0046872	metal ion binding
GO:0046982	protein heterodimerization activity
GO:0047485	protein N-terminus binding
GO:0051087	chaperone binding
GO:0051721	protein phosphatase 2A binding
GO:0097371	MDM2/MDM4 family protein binding

Biological Process

GO:0000060	protein import into nucleus, translocation
GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0000733	DNA strand renaturation
GO:0001701	in utero embryonic development
GO:0001756	somitogenesis
GO:0001836	release of cytochrome c from mitochondria
GO:0002309	T cell proliferation involved in immune response
GO:0002326	B cell lineage commitment
GO:0002360	T cell lineage commitment
GO:0002931	response to ischemia
GO:0006284	base-excision repair
GO:0006289	nucleotide-excision repair
GO:0006302	double-strand break repair
GO:0006355	regulation of transcription, DNA-templated
GO:0006357	regulation of transcription from RNA polymerase II promoter
GO:0006461	protein complex assembly
GO:0006915	apoptotic process
GO:0006974	cellular response to DNA damage stimulus
GO:0006977	DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
GO:0006978	DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
GO:0006979	response to oxidative stress
GO:0006983	ER overload response
GO:0007050	cell cycle arrest
GO:0007179	transforming growth factor beta receptor signaling pathway
GO:0007219	Notch signaling pathway
GO:0007265	Ras protein signal transduction
GO:0007275	multicellular organismal development
GO:0007369	gastrulation
GO:0007406	negative regulation of neuroblast proliferation
GO:0007417	central nervous system development
GO:0007569	cell aging
GO:0007596	blood coagulation
GO:0008104	protein localization
GO:0008156	negative regulation of DNA replication
GO:0008283	cell proliferation
GO:0008285	negative regulation of cell proliferation
GO:0008340	determination of adult lifespan
GO:0009303	rRNA transcription
GO:0009411	response to UV
GO:0009651	response to salt stress
GO:0009792	embryo development ending in birth or egg hatching
GO:0010165	response to X-ray
GO:0010332	response to gamma radiation
GO:0010666	positive regulation of cardiac muscle cell apoptotic process
GO:0016032	viral process
GO:0021549	cerebellum development
GO:0030154	cell differentiation
GO:0030308	negative regulation of cell growth
GO:0030330	DNA damage response, signal transduction by p53 class mediator
GO:0030512	negative regulation of transforming growth factor beta receptor signaling pathway
GO:0031065	positive regulation of histone deacetylation
GO:0031497	chromatin assembly
GO:0031571	mitotic G1 DNA damage checkpoint
GO:0032461	positive regulation of protein oligomerization
GO:0033077	T cell differentiation in thymus
GO:0034103	regulation of tissue remodeling
GO:0034613	cellular protein localization
GO:0034644	cellular response to UV
GO:0035264	multicellular organism growth
GO:0035690	cellular response to drug
GO:0035794	positive regulation of mitochondrial membrane permeability
GO:0042127	regulation of cell proliferation
GO:0042149	cellular response to glucose starvation
GO:0042493	response to drug
GO:0042771	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0042981	regulation of apoptotic process
GO:0043065	positive regulation of apoptotic process
GO:0043066	negative regulation of apoptotic process
GO:0043523	regulation of neuron apoptotic process
GO:0043525	positive regulation of neuron apoptotic process
GO:0045087	innate immune response (InnateDB)
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046677	response to antibiotic
GO:0046902	regulation of mitochondrial membrane permeability
GO:0048147	negative regulation of fibroblast proliferation
GO:0048568	embryonic organ development
GO:0050731	positive regulation of peptidyl-tyrosine phosphorylation
GO:0051097	negative regulation of helicase activity
GO:0051262	protein tetramerization
GO:0051276	chromosome organization
GO:0051402	neuron apoptotic process
GO:0051726	regulation of cell cycle
GO:0070243	regulation of thymocyte apoptotic process
GO:0070245	positive regulation of thymocyte apoptotic process
GO:0070266	necroptotic process
GO:0071158	positive regulation of cell cycle arrest
GO:0071456	cellular response to hypoxia
GO:0071479	cellular response to ionizing radiation
GO:0071850	mitotic cell cycle arrest
GO:0072332	intrinsic apoptotic signaling pathway by p53 class mediator
GO:0090200	positive regulation of release of cytochrome c from mitochondria
GO:0090343	positive regulation of cell aging
GO:0090399	replicative senescence
GO:0090403	oxidative stress-induced premature senescence
GO:0097193	intrinsic apoptotic signaling pathway
GO:0097252	oligodendrocyte apoptotic process
GO:1900740	positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
GO:1901525	negative regulation of macromitophagy
GO:1902108	regulation of mitochondrial membrane permeability involved in apoptotic process
GO:2000378	negative regulation of reactive oxygen species metabolic process
GO:2000379	positive regulation of reactive oxygen species metabolic process
GO:2001244	positive regulation of intrinsic apoptotic signaling pathway

Cellular Component

GO:0000785	chromatin
GO:0000790	nuclear chromatin
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005657	replication fork
GO:0005669	transcription factor TFIID complex
GO:0005730	nucleolus
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005759	mitochondrial matrix
GO:0005783	endoplasmic reticulum
GO:0005829	cytosol
GO:0016363	nuclear matrix
GO:0016604	nuclear body
GO:0016605	PML body
GO:0043234	protein complex

Protein Structure and Domains

PDB ID

InterPro

IPR002117 p53 tumour suppressor family
IPR008967 p53-like transcription factor, DNA-binding
IPR010991 p53, tetramerisation domain
IPR011615 p53, DNA-binding domain
IPR013872 p53 transactivation domain

PFAM

PF07710
PF00870
PF08563

PRINTS

PR00386

PIRSF

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

P04637