Tchem TP53 Cellular tumor antigen p53

Protein Summary

Description

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 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). This gene encodes a tumor suppressor protein containing transcriptional activation, DNA binding, and oligomerization domains. The encoded protein responds to diverse cellular stresses to regulate expression of target genes, thereby inducing cell cycle arrest, apoptosis, senescence, DNA repair, or changes in metabolism. Mutations in this gene are associated with a variety of human cancers, including hereditary cancers such as Li-Fraumeni syndrome. Alternative splicing of this gene and the use of alternate promoters result in multiple transcript variants and isoforms. Additional isoforms have also been shown to result from the use of alternate translation initiation codons from identical transcript variants (PMIDs: 12032546, 20937277). [provided by RefSeq, Dec 2016]

Uniprot Accession IDs

• P04637
• Q15086
• Q15087
• Q15088
• Q16535
• Q16807
• Q16808
• Q16809
• Q16810
• Q16811
• Q16848
• Q2XN98
• Q3LRW1
• Q3LRW2
• Q3LRW3
• Q3LRW4
• Q3LRW5
• Q86UG1
• Q8J016
• Q99659
• Q9BTM4
• Q9HAQ8
• Q9NP68
• Q9NPJ2
• Q9NZD0
• Q9UBI2
• Q9UQ61

Gene Name

• TP53

Ensembl ID

• ENST00000269305
• ENSP00000269305
• ENSG00000141510
• ENST00000420246
• ENSP00000391127
• ENST00000445888
• ENSP00000391478
• ENST00000455263
• ENSP00000398846
• ENST00000504290
• ENSP00000484409
• ENST00000504937
• ENSP00000481179
• ENST00000510385
• ENSP00000478499
• ENST00000610292
• ENSP00000478219
• ENST00000610538
• ENSP00000480868
• ENST00000617185
• ENSP00000482258
• ENST00000619485
• ENSP00000482537
• ENST00000620739
• ENSP00000481638
• ENST00000622645
• ENSP00000482222

Symbol

• P53
• P53
• BCC7
• LFS1
• BMFS5
• TRP53

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
biological term	1
chemical	1
hub protein	1
interacting protein	1

Protein Classes

PANTHER Classes

Protein / Transcription Factor / Cellular Tumor Antigen P53

Protein / ... / P53-like Transcription Factor / Cellular Tumor Antigen P53

DTO Classes

Protein / Transcription Factor / Immunoglobulin Fold Transcription Factor / P53-like Transcription Factor / Cellular Tumor Antigen P53

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 59503.16   (req: < 5)

Gene RIFs: 7632   (req: <= 3)

Antibodies: 8417   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 59503.16   (req: >= 5)

Gene RIFs: 7632   (req: > 3)

Antibodies: 8417   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 110

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 14

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (14)

Explore Active Ligands

1 – 10 of 14

CHEMBL2059435

TP53Tchem TF

pKd : 9.4

CHEMBL2059300

TP53Tchem TF

pKd : 9

Nutlin 3A

TP53Tchem TF

pKd : 6.16

CHEMBL4248974

TP53Tchem TF

pEC50 : 8.7

CHEMBL4246320

TP53Tchem TF

pEC50 : 8.4

CHEMBL4238053

TP53Tchem TF

pEC50 : 8.4

CHEMBL4243509

TP53Tchem TF

pEC50 : 8.05

CHEMBL4240212

TP53Tchem TF

pEC50 : 7.92

CHEMBL4244338

TP53Tchem TF

pEC50 : 7.19

CHEMBL4240141

TP53Tchem TF

pEC50 : 7.13

Protein-Protein Interactions (1985)

Explore Interacting Targets

1 – 10 of 1985

• See Interactions on String-DB

MDM4

Tchem

Novelty:  0.00321558

p_int:  1

Score:  0.999

Data Source:  BioPlex,Reactome,STRINGDB

CUL9

Tbio

Novelty:  0.1104365

p_int:  0.999999972

p_ni:  1.7e-8

p_wrong:  1.1e-8

Score:  0.681

Data Source:  BioPlex,STRINGDB

CUL7

Tbio

Novelty:  0.02183958

p_int:  0.999991499

p_ni:  0.000008501

Score:  0.661

Data Source:  BioPlex,STRINGDB

FBXW7

Tbio

Novelty:  0.00180856

p_int:  0.999684998

p_ni:  0.000315002

Score:  0.856

Data Source:  BioPlex,STRINGDB

CELA2B

Tdark

Family:  Enzyme

Novelty:  0.43122129

p_int:  0.995715315

p_ni:  0.004284685

Score:  0.542

Data Source:  BioPlex,STRINGDB

MDM2

Tchem

Family:  Enzyme

Novelty:  0.00028385

p_int:  0.988675145

p_ni:  0.011324855

Score:  0.999

Data Source:  BioPlex,Reactome,STRINGDB

FAM111A

Tbio

Novelty:  0.06507063

p_int:  0.952013352

p_ni:  0.047986648

Score:  0.403

Data Source:  BioPlex,STRINGDB

MZF1

Tbio

Family:  TF

Novelty:  0.01193919

p_int:  0.938674001

p_ni:  0.061325997

p_wrong:  2e-9

Score:  0.259

Data Source:  BioPlex,STRINGDB

HNF4A

Tchem

Family:  NR

Novelty:  0.00041409

p_int:  0.907107395

p_ni:  0.092892605

Score:  0.737

Data Source:  BioPlex,STRINGDB

AURKA

Tchem

Family:  Kinase

Novelty:  0.0010868

p_int:  0.895481844

p_ni:  0.104518156

Score:  0.995

Data Source:  BioPlex,Reactome,STRINGDB

Nearest Tclin Targets (2)

Explore Nearest Tclin Targets

Upstream (1)

Downstream (1)

1 – 1 of 1

BCL2

Tclin

Family:  Other

KEGG Distance:  1

Common Pathways:  19

1: PI3K-Akt signaling pathway

2: Platinum drug resistance

3: Endocrine resistance

4: Gastric cancer

more:  15 more common pathways

Pathways (210)

Reactome (83)

KEGG (48)

PathwayCommons (22)

WikiPathways (57)

Activation of BH3-only proteins (R-HSA-114452)

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5

1 – 5 of 83

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activation of BH3-only proteins	31 targets	R-HSA-114452
Reactome	Activation of NOXA and translocation to mitochondria	5 targets	R-HSA-111448
Reactome	Activation of PUMA and translocation to mitochondria	10 targets	R-HSA-139915
Reactome	Apoptosis	177 targets	R-HSA-109581
Reactome	Association of TriC/CCT with target proteins during biosynthesis	39 targets	R-HSA-390471

Name	Explore in Pharos	Explore in Source
Activation of BH3-only proteins	31 targets	R-HSA-114452
Activation of NOXA and translocation to mitochondria	5 targets	R-HSA-111448
Activation of PUMA and translocation to mitochondria	10 targets	R-HSA-139915
Apoptosis	177 targets	R-HSA-109581
Association of TriC/CCT with target proteins during biosynthesis	39 targets	R-HSA-390471

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (124)

Functions (34)

Components (14)

Processes (76)

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10

1 – 10 of 34

GO Term	Evidence	Assigned by
ATP binding	Inferred from Direct Assay (IDA)	UniProtKB
chromatin binding	Inferred from Direct Assay (IDA)	UniProtKB
copper ion binding	Inferred from Direct Assay (IDA)	UniProtKB
core promoter sequence-specific DNA binding	Inferred from Direct Assay (IDA)	CAFA
DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
DNA-binding transcription activator activity, RNA polymerase II-specific	Inferred from Direct Assay (IDA)	ARUK-UCL
DNA-binding transcription factor activity	Inferred from Direct Assay (IDA)	UniProtKB
DNA-binding transcription factor activity, RNA polymerase II-specific	Inferred from Direct Assay (IDA)	UniProtKB
mRNA 3'-UTR binding	Inferred from Direct Assay (IDA)	CAFA
promoter-specific chromatin binding	Inferred from Direct Assay (IDA)	UniProtKB

Disease Associations (null)

No disease associations found

GWAS Traits (58)

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1 – 5 of 58

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
testosterone measurement	EFO_0004908	13	29	36	1.6	99.9
sex hormone-binding globulin measurement	EFO_0004696	10	8	24		99.7
hormone measurement	EFO_0004730	2	3	1	57	98.7
central nervous system cancer	EFO_0000326	4	2	0	2.6	97.2
glioblastoma multiforme	EFO_0000519	3	2	0	2.8	96.6

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
testosterone measurement	EFO_0004908	36	1.6	99.9
sex hormone-binding globulin measurement	EFO_0004696	24		99.7
hormone measurement	EFO_0004730	1	57	98.7
central nervous system cancer	EFO_0000326	0	2.6	97.2
glioblastoma multiforme	EFO_0000519	0	2.8	96.6

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Activator
Alternative promoter usage
Alternative splicing
Apoptosis
Biological rhythms
Cell cycle
Complete proteome
Cytoplasm

GWAS Trait Find Similar Targets

No Header	No Header
age at onset
alcohol consumption measurement
apolipoprotein B measurement
appendicular lean mass
basal cell carcinoma
birth weight
blood protein measurement
BMI-adjusted waist circumference
BMI-adjusted waist-hip ratio
body weight

MGI Phenotype Find Similar Targets

No Header	No Header
adipose tissue phenotype
behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
craniofacial phenotype
digestive/alimentary phenotype
embryo phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hearing/vestibular/ear phenotype

IDG Resources

No IDG generated resources found

Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	tumor protein p53	VGNC:9734	455214
Macaque	tumor protein p53		716170
Mouse	transformation related protein 53	MGI:98834	22059
Rat	tumor protein p53	RGD:3889	24842
Dog	tumor protein p53	VGNC:47719	403869

Species	Name	OMA	EggNOG	Inparanoid
Chimp	tumor protein p53
Macaque	tumor protein p53
Mouse	transformation related protein 53
Rat	tumor protein p53
Dog	tumor protein p53

Publication Statistics

PubMed Score 59503.16

PubMed score by year

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PubTator Score 38146.37

PubTator score by year

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Related Publications

Text Mined References (8560)

GeneRif Annotations (7632)

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PMID	Year	Title