Protein / target

Cellular tumor antigen p53

Encoded byTP53P04637Homo sapiensSwiss-Prot

UniProt: P04637 Ensembl: ENSG00000141510 HGNC: HGNC:11998 NCBI Gene: 7157

Clinical-stage

Therapeutic maturity

Clinical candidates

Small-molecule tractable

Druggability

Advanced Clinical

Research papers

Protein at a glance

Biological role

Cis-regulatory region sequence-specific DNA binding

Strongest disease association

Li-Fraumeni Syndrome

Via encoding gene TP53 · Genetic evidence · score 0.96

Therapeutic position

Clinically advancing target

Small molecules

Research activity

Emerging research

21 papers · latest 2025

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence.

View complete UniProt function annotation

Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apoptosis upon binding to its target DNA sequence (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:24652652, PubMed:35618207, PubMed:36634798, PubMed:38653238, PubMed:9840937). 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:17189187, PubMed:17317671, PubMed:17349958, PubMed:19556538, PubMed:20673990, PubMed:20959462, PubMed:22726440, PubMed:24051492, PubMed:24652652, PubMed:38653238, PubMed:9840937). Negatively regulates cell division by controlling expression of 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:24652652, PubMed:9840937). 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 (PubMed:12524540, PubMed:17189187). 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-BMAL1-mediated transcriptional activation of PER2 (PubMed:24051492)

Subcellular location

CytoplasmNucleusNucleus, PML bodyEndoplasmic reticulumMitochondrion matrixCytoplasm, cytoskeleton, microtubule organizing center, centrosome

Domains and Gene Ontology detail (115)

Gene Ontology

Ccentrosome
Cchromatin
Ccytoplasm
Ccytosol
Cendoplasmic reticulum
Cmitochondrial matrix
Cmitochondrion
Cnuclear matrix
Cnucleolus
Cnucleoplasm
Cnucleus
CPML body

393 aa · 44 kDa · 9 isoforms

Biological roles

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell proliferation & survivalGOCell-cycle regulationUniProtTumour suppressionUniProtTranscriptional regulationUniProt · GOApoptosis & cell deathGO

View supporting evidence

Cell proliferation & survival

·negative regulation of cell population proliferation

Cell-cycle regulation

·Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apopt…

Tumour suppression

·Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apopt…

Transcriptional regulation

·Multifunctional transcription factor that induces cell cycle arrest, DNA repair or apopt…
·transcription regulator complex
·DNA-binding transcription activator activity, RNA polymerase II-specific
·DNA-binding transcription factor activity

Apoptosis & cell death

·negative regulation of apoptotic process
·oligodendrocyte apoptotic process
·positive regulation of apoptotic process
·positive regulation of thymocyte apoptotic process

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene TP53

Gene-level evidence surfaced through the gene TP53 that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Li-Fraumeni Syndrome

0.98Well supported

Genetic evidence dominant · Open Targets 0.88

Carcinoma, Hepatocellular

0.98Well supported

Genetic evidence dominant · Open Targets 0.80

Squamous Cell Carcinoma of Head and Neck

0.94Well supported

Genetic evidence dominant · Open Targets 0.78

Esophageal Neoplasms

0.82Well supported

Somatic mutation evidence dominant · Open Targets 0.73

Adenocarcinoma of Lung

0.63Moderately supported

Somatic mutation evidence dominant · Open Targets 0.73

View evidence synthesis (5)

Li-Fraumeni SyndromeWell supported

0.98

agreement 0.88–1.00

Genetic62%Somatic mutation18%Animal model16%Literature4%Genetic literaturedup

Open Targets aggregate 0.88 · 4 independent evidence families · 1 not counted as duplicate

Carcinoma, HepatocellularWell supported

0.98

agreement 0.88–1.00

Genetic49%Somatic mutation30%Animal model13%Literature8%Genetic literaturedup

Open Targets aggregate 0.80 · 4 independent evidence families · 1 not counted as duplicate

Squamous Cell Carcinoma of Head and NeckWell supported

0.94

agreement 0.85–1.00

Genetic51%Somatic mutation34%Literature9%Clinical6%Genetic literaturedup

Open Targets aggregate 0.78 · 4 independent evidence families · 1 not counted as duplicate

Esophageal NeoplasmsWell supported

0.82

agreement 0.72–0.92

Somatic mutation47%Genetic literature39%Literature10%Clinical4%

Open Targets aggregate 0.73 · 4 independent evidence families

Adenocarcinoma of LungModerately supported

0.63

agreement 0.46–0.79

Somatic mutation80%Literature20%

Open Targets aggregate 0.73 · 2 independent evidence families

The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.

Show all associations

Li-Fraumeni Syndrome0.88

Carcinoma, Hepatocellular0.80

Squamous Cell Carcinoma of Head and Neck0.78

Esophageal Neoplasms0.73

Adenocarcinoma of Lung0.73

Drug development

9 compounds recorded · 9 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines.

View all recorded compounds (9)

TEPRASIRANPhase 3

SIREMADLINPhase 2

IDASANUTLINPhase 3

NAVTEMADLINPhase 3

CENERSENPhase 2

EPRENETAPOPTPhase 3

CONTUSUGENE LADENOVECPhase 3

CENERSEN SODIUMPhase 2

ALRIZOMADLINPhase 2

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small molecules — Strong

Advanced Clinical and Structure with Ligand support this modality.

Protein degraders — Emerging

Feasibility evidence (uniprot ubiquitination and database ubiquitination) — no clinical-stage drug of this modality recorded.

Other modalities — Strong

Advanced Clinical support this modality.

View underlying tractability evidence (9)

SM · Advanced ClinicalSM · Structure with LigandSM · High-Quality LigandSM · Med-Quality PocketSM · Druggable FamilyPR · UniProt UbiquitinationPR · Database UbiquitinationPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

drug toxicityClinPGxTumorigenesis, Hepatocellular carcinomaAOP-Wikiregulation of transcription factor activityToxCastneutropeniaClinPGx

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.