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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

TP53 Gene

protein-coding GIFtS: 80
GCID: GC17M007565

tumor protein p53

Explore 594 diseases affiliated with
TP53 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

This gene clusters with an RNA gene
Subcategory (RNA class): lncRNA

Quality score for the ORGUL clustered with this gene is 3

Aliases
Tumor Protein P53¹ ²		BCC7²
LFS1¹ ² ⁵		TRP53²
P53² ³ ⁵		Cellular Tumor Antigen P53²
Antigen NY-CO-13² ³		P53 Tumor Suppressor²
Phosphoprotein P53² ³		Transformation-Related Protein 53²
P53² ³ ⁵		Tumor Suppressor P53³

External Ids:	HGNC: 11998¹	Entrez Gene: 7157²	Ensembl: ENSG00000141510⁷	OMIM: 191170⁵	UniProtKB: P04637³

ORGUL members:
	NONCODE:n335267 n337087 n343020

Export aliases for TP53 gene to outside databases

Previous GC identifers: GC17P008026 GC17M008311 GC17M007514 GC17M007772 GC17M007512 GC17M007465

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for TP53:

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 use of alternate start codons (PMIDs: 12032546, 20937277).

(provided by RefSeq, Feb 2013)

UniProtKB/Swiss-Prot: P53_HUMAN, P04637

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; te 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

summary for TP53:

p53 (aka TP53) is a transcription factor whose protein levels and post-translational modification state

alter in response to cellular stress (such as DNA damage, hypoxia, spindle damage). Activation of p53 begins

through a number of mechanisms including phosphorylation by ATM, ATR, Chk1 and MAPKs. MDM2 is a ubiquitn

ligase that binds p53 and targets p53 for proteasomal degradation. Phosphorylation, p14ARF and USP7 prevent

MDM2-p53 interactions, leading to an increase in stable p53 tetramers in the cytoplasm. Further

modifications such as methylation and acetylation lead to an increase in p53 binding to gene specific

response elements. p53 regulates a large number of genes (>100 genes) that control a number of key tumor

suppressing functions such as cell cycle arrest, DNA repair, senescence and apoptosis. Whilst the activation

of p53 often leads to apoptosis, p53 inactivation facilitates tumor progression; inactivating p53 mutations

occur in over 50% of cancers.

Gene Wiki entry for TP53 (P53)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000017.10 NC_018928.1 NT_010718.16

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the TP53 gene promoter:
CREB C/EBPbeta Sp1 ARP-1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 4): TP53 promoter sequence

Search SABiosciences Chromatin IP Primers for TP53

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat TP53

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 17p13.1 Ensembl cytogenetic band: 17p13.1 HGNC cytogenetic band: 17p13.1

TP53 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TP53 gene location

GeneLoc information about chromosome 17 GeneLoc Exon Structure

GeneLoc location for GC17M007565: view genomic region (about GC identifiers)

Start:	7,565,097 bp from pter	End:	7,590,863 bp from pter
Size:	25,767 bases	Orientation:	minus strand

ORGUL member locations:
Legend (see complete legend)

n343020
n337087
n335267

lncRNA
Full Legend

7571719 7581291 7590863 chr17

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: P53_HUMAN, P04637 (See protein sequence)

Recommended Name: Cellular tumor antigen p53

Size: 393 amino acids; 43653 Da

Cofactor: Binds 1 zinc ion per subunit

Subunit: Interacts with AXIN1. Probably part of a complex consisting of TP53, HIPK2 and AXIN1 (By similarity). Binds

DNA as a homotetramer. Interacts with histone acetyltransferases EP300 and methyltransferases HRMT1L2 and CARM1, and

recruits them to promoters. In vitro, the interaction of TP53 with cancer-associated/HPV (E6) viral proteins leads to

ubiquitination and degradation of TP53 giving a possible model for cell growth regulation. This complex formation

requires an additional factor, E6-AP, which stably associates with TP53 in the presence of E6. 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. May interact

with HCV core protein. Interacts with USP7 and SYVN1. Interacts with HSP90AB1. 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-382) with L3MBTL1. Isoform 1 interacts with isoform 2 and with

isoform 4. 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, 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 human cytomegalovirus/HHV-5 protein UL123. Interacts with

SNAI1; the interaction induces SNAI1 degradation via MDM2-mediated ubiquitination and inhibits SNAI1-induced cell

invasion

Subcellular location: 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

Subcellular location: Isoform 1: Nucleus. Cytoplasm. Note=Predominantly nuclear but localizes to the cytoplasm when

expressed with isoform 4

Subcellular location: Isoform 2: Nucleus. Cytoplasm. Note=Localized mainly in the nucleus with minor staining in the

cytoplasm

Subcellular location: Isoform 3: Nucleus. Cytoplasm. Note=Localized in the nucleus in most cells but found in the

cytoplasm in some cells

Subcellular location: Isoform 4: Nucleus. Cytoplasm. Note=Predominantly nuclear but translocates to the cytoplasm

following cell stress

Subcellular location: Isoform 7: Nucleus. Cytoplasm. Note=Localized mainly in the nucleus with minor staining in the

cytoplasm

Subcellular location: 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

Subcellular location: Isoform 9: Cytoplasm

6/102 PDB 3D structures from and Proteopedia for TP53 (see all 102):

1A1U (3D)

1AIE (3D)

1C26 (3D)

1DT7 (3D)

1GZH (3D)

1H26 (3D)

Secondary accessions: 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

Alternative promoter usage, Alternative splicing: 9 isoforms: P04637-1 P04637-2 P04637-3 P04637-4 P04637-5 P04637-6 P04637-7 P04637-8

P04637-9 (Produced by alternative promoter usage and alternative splicing)

Explore the universe of human proteins at neXtProt for TP53: NX_P04637

Post-translational modifications:

Acetylated. Acetylation of Lys-382 by CREBBP enhances transcriptional activity. Deacetylation of Lys-382 by SIRT1

impairs its ability to induce proapoptotic program and modulate cell senescence¹

Phosphorylation on Ser residues mediates transcriptional activation. Phosphorylated by HIPK1 (By similarity).

Phosphorylation at Ser-9 by HIPK4 increases repression activity on BIRC5 promoter. Phosphorylated on Thr-18 by VRK1.

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. Phosphorylated on

Thr-55 by TAF1, which promotes MDM2-mediated degradation. Phosphorylated on Ser-33 by CDK7 in a CAK complex in

response to DNA damage. Phosphorylated on Ser-46 by HIPK2 upon UV irradiation. Phosphorylation on Ser-46 is required

for acetylation by CREBBP. Phosphorylated on Ser-392 following UV but not gamma irradiation. Phosphorylated on Ser-15

upon ultraviolet irradiation; which is enhanced by interaction with BANP. Phosphorylated by NUAK1 at Ser-15 and

Ser-392; was intially thought to be mediated by STK11/LKB1 but it was later shown that it is indirect and that

STK11/LKB1-dependent phosphorylation is probably mediated by downstream NUAK1 (PubMed:21317932). It is unclear whether

AMP directly mediates phosphorylation at Ser-15. Phosphorylated on Thr-18 by isoform 1 and isoform 2 of VRK2.

Phosphorylation on Thr-18 by isoform 2 of VRK2 results in a reduction in ubiquitination by MDM2 and an increase in

acetylation by EP300. Stabilized by CDK5-mediated phosphorylation in response to genotoxic and oxidative stresses at

Ser-15, Ser-33 and Ser-46, leading to accumulation of p53/TP53, particularly in the nucleus, thus inducing the

transactivation of p53/TP53 target genes. Phosphorylated by DYRK2 at Ser-46 in response to genotoxic stress.

Phosphorylated at Ser-315 and Ser-392 by CDK2 in response to DNA-damage¹

Dephosphorylated by PP2A-PPP2R5C holoenzyme at Thr-55. SV40 small T antigen inhibits the dephosphorylation by the AC

form of PP2A¹

May be O-glycosylated in the C-terminal basic region. Studied in EB-1 cell line¹

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 at Lys-291 and Lys-292, which leads to proteasomal degradation.

Deubiquitinated by USP10, leading to its stabilization. Ubiquitinated by TRIM24, which leads to proteasomal

degradation. Ubiquitination by TOPORS induces degradation. Deubiquitination by USP7, leading to stabilization. Isoform

4 is monoubiquitinated in an MDM2-independent manner¹

Monomethylated at Lys-372 by SETD7, leading to stabilization and increased transcriptional activation. Monomethylated

at Lys-370 by SMYD2, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity.

Lys-372 monomethylation prevents interaction with SMYD2 and subsequent monomethylation at Lys-370. Dimethylated at

Lys-373 by EHMT1 and EHMT2. Monomethylated at Lys-382 by SETD8, promoting interaction with L3MBTL1 and leading to

repress transcriptional activity. Dimethylation at Lys-370 and Lys-382 diminishes p53 ubiquitination, through

stabilizing association with the methyl reader PHF20. Demethylation of dimethylated Lys-370 by KDM1A prevents

interaction with TP53BP1 and represses TP53-mediated transcriptional activation¹

Sumoylated with SUMO1¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P04637

TP53 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (8 alternative transcripts):

NP_000537.3 NP_001119584.1 NP_001119585.1 NP_001119586.1 NP_001119587.1 NP_001119588.1 NP_001119589.1 NP_001119590.1

ENSEMBL proteins:

ENSP00000410739 ENSP00000352610 ENSP00000269305 ENSP00000398846 ENSP00000391127

ENSP00000391478 ENSP00000458393 ENSP00000425104 ENSP00000423862 ENSP00000424104

ENSP00000426252

Reactome Protein details: P04637
Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant TP53 Protein
	R&D Systems Recombinant & Natural Proteins for TP53 (p53)
	Enzo Life Sciences proteins for TP53
	OriGene Purified Proteins (see all 3): TP53 OriGene Protein Over-expression Lysate (see all 4): TP53 OriGene Custom Protein Services for TP53
	GenScript Custom Purified and Recombinant Proteins Services for TP53
	Novus Biologicals TP53 Proteins Novus Biologicals TP53 Lysates
	Browse Sino Biological Recombinant Proteins
	ProSpec Recombinant Protein for TP53
	Uscn Proteins for TP53

Gene Ontology (GO): 5/18 cellular component terms (GO ID links to tree view) (see all 18): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000785	chromatin	IBA	--
GO:0000790	nuclear chromatin	IDA	--
GO:0005626	insoluble fraction	--	--
GO:0005634	nucleus	IDA	18756595
GO:0005654	nucleoplasm	TAS	--

TP53 for ontologies About GeneDecksing

TP53 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of TP53
	R&D Systems Antibodies for TP53 (p53)
	Cell Signaling Technology (CST) Antibodies for TP53 (p53)
	OriGene Antibodies (see all 21): TP53 OriGene Custom Antibody Services for TP53
	GenScript Superior Antibodies for TP53
	Novus Biologicals TP53 Antibodies
	Abcam antibodies for TP53
	Uscn Antibodies for TP53
	ThermoFisher Antibody for TP53

Assay Products for TP53:

	EMD Millipore Kits and Assays for the Analysis of TP53
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems ELISAs for TP53 (p53) (see first)
	R&D Systems Multiplex/Array Assay Kits & Reagents for TP53 (p53)
	R&D Systems Transcription Factor Binding & Immunoprecipitation Assays for TP53 (p53)
	R&D Systems Ubiquitin Proteasome Pathway (UPP) Assay Kits & Reagents for TP53 (p53)
	See all other biochemical assays at R&D Systems
	GenScript Custom Assay Services for TP53
	Cell Signaling Technology (CST) Sandwich ELISA Kits for TP53 (p53)
	Enzo Life Sciences assays for TP53
	Uscn ELISAs and CLIAs for TP53

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

TP53 for domains About GeneDecksing

5/6 InterPro domains/families (see all 6):

IPR011615 p53_DNA-bd

IPR012346 p53/RUNT-type_TF_DNA-bd

IPR002117 p53_tumour_suppressor

IPR008967 p53-like_TF_DNA-bd

IPR013872 p53_transactivation_domain

Graphical View of Domain Structure for InterPro Entry P04637

ProtoNet protein and cluster: P04637

1 Blocks protein family: IPB010991 p53

UniProtKB/Swiss-Prot: P53_HUMAN, P04637

Domain: The nuclear export signal acts as a transcriptional repression domain. The TADI and TADII motifs (residues 17

to 25 and 48 to 56) correspond both to 9aaTAD motifs which are transactivation domains present in a large number of

yeast and animal transcription factors

Similarity: Belongs to the p53 family

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: