Human Gene TP73 (ENST00000378288.8) Description and Page Index
  Description: Homo sapiens tumor protein p73 (TP73), transcript variant 7, mRNA. (from RefSeq NM_001204191)
RefSeq Summary (NM_001126240): This gene encodes a member of the p53 family of transcription factors involved in cellular responses to stress and development. It maps to a region on chromosome 1p36 that is frequently deleted in neuroblastoma and other tumors, and thought to contain multiple tumor suppressor genes. The demonstration that this gene is monoallelically expressed (likely from the maternal allele), supports the notion that it is a candidate gene for neuroblastoma. Many transcript variants resulting from alternative splicing and/or use of alternate promoters have been found for this gene, but the biological validity and the full-length nature of some variants have not been determined. [provided by RefSeq, Feb 2011].
Gencode Transcript: ENST00000378288.8
Gencode Gene: ENSG00000078900.15
Transcript (Including UTRs)
   Position: hg38 chr1:3,690,672-3,736,201 Size: 45,530 Total Exon Count: 12 Strand: +
Coding Region
   Position: hg38 chr1:3,690,906-3,733,079 Size: 42,174 Coding Exon Count: 12 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:3,690,672-3,736,201)mRNA (may differ from genome)Protein (587 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGIneXtProtOMIMPubMed
ReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: P73_HUMAN
DESCRIPTION: RecName: Full=Tumor protein p73; AltName: Full=p53-like transcription factor; AltName: Full=p53-related protein;
FUNCTION: Participates in the apoptotic response to DNA damage. Isoforms containing the transactivation domain are pro-apoptotic, isoforms lacking the domain are anti-apoptotic and block the function of p53 and transactivating p73 isoforms. May be a tumor suppressor protein.
COFACTOR: Binds 1 zinc ion per subunit (By similarity).
SUBUNIT: Found in a complex with p53/TP53 and CABLES1. The C- terminal oligomerization domain binds to the ABL1 tyrosine kinase SH3 domain. Interacts with HECW2. Isoform Beta interacts homotypically and with p53/TP53, whereas isoform Alpha does not. Isoform Gamma interacts homotypically and with all p73 isoforms. Isoform Delta interacts with isoform Gamma, isoform Alpha, and homotypically. Isoforms Alpha and Beta interact with HIPK2. Isoform Alpha interacts with RANBP9. Isoform Beta interacts with WWOX. Interacts (via SAM domain) with FBXO45 (via B30.2/SPRY domain). Interacts with YAP1 (phosphorylated form). Interacts with HCK (via SH3 domain); this inhibits TP73 activity and degradation.
INTERACTION: Self; NbExp=5; IntAct=EBI-389606, EBI-389606; O14965:AURKA; NbExp=11; IntAct=EBI-389606, EBI-448680; Q9ESJ1:Cables1 (xeno); NbExp=3; IntAct=EBI-389606, EBI-604411; P03126:E6 (xeno); NbExp=2; IntAct=EBI-389619, EBI-1177242; P38646:HSPA9; NbExp=11; IntAct=EBI-389606, EBI-354932; Q96EB6:SIRT1; NbExp=4; IntAct=EBI-389606, EBI-1802965;
SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Accumulates in the nucleus in response to DNA damage.
TISSUE SPECIFICITY: Expressed in striatal neurons of patients with Huntington disease (at protein level). Brain, kidney, placenta, colon, heart, liver, spleen, skeletal muscle, prostate, thymus and pancreas. Highly expressed in fetal tissue.
INDUCTION: Not induced by DNA damage. Isoforms lacking the transactivation domain block gene induction.
DOMAIN: Possesses an acidic transactivation domain, a central DNA binding domain and a C-terminal oligomerization domain that binds to the ABL1 tyrosine kinase SH3 domain.
DOMAIN: The WW-binding motif mediates interaction with WWOX.
PTM: Isoform alpha (but not isoform beta) is sumoylated on Lys- 627, which potentiates proteasomal degradation but does not affect transcriptional activity. Phosphorylation by PLK1 and PLK3 inhibits the transcription regulator activity and pro-apoptotic function.
PTM: Higher levels of phosphorylation seen in the brain from patients with Huntington disease.
PTM: Polyubiquitinated by RCHY1/PIRH2; leading to its degradation by the proteasome.
MISCELLANEOUS: Maps to a chromosome region frequently mutated in diverse cell lines of human cancer. Appears not to be frequently mutated in human cancers, in contrast to p53/TP53. Hemizygosity is observed in neuroblastoma and oligodendroglioma.
MISCELLANEOUS: Activated and stabilized by interaction with RANBP9.
SIMILARITY: Belongs to the p53 family.
SIMILARITY: Contains 1 SAM (sterile alpha motif) domain.

-  MalaCards Disease Associations
  MalaCards Gene Search: TP73
Diseases sorted by gene-association score: small cell cancer of the lung, somatic* (202), neuroblastoma* (51), ulcerative stomatitis (10), oligodendroglioma (10), ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3 (8), childhood oligodendroglioma (7), epstein-barr virus-associated gastric carcinoma (7), ependymoma (7), neurofibrosarcoma (6), thyroid lymphoma (6), rapp-hodgkin syndrome (6), brain cancer (3), medulloblastoma (2), lung cancer (2), colorectal cancer (2), meningioma, familial (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D002945 Cisplatin
  • D015655 1-Methyl-4-phenylpyridinium
  • C504897 12-(3-adamantan-1-ylureido)dodecanoic acid
  • C451219 2,2-bis(hydroxymethyl)-1-azabicyclo(2,2,2,)octan-3-one
  • C488288 2,5,7,8-tetramethyl-2R-(4R,8R,12-trimethyltridecyl)chroman-6-yloxy acetic acid
  • C093973 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • C120227 2-(2-chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluorobenzamide
  • C529061 2-(4,5-dihydro-1,3-thiazol-2-ylthio)-1-(3,4-dihydroxyphenyl)ethanone
  • C027576 4-hydroxy-2-nonenal
  • D047310 Apigenin
          more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 7.20 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 49.19 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -81.70234-0.349 Picture PostScript Text
3' UTR -1300.803122-0.417 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR008967 - p53-like_TF_DNA-bd
IPR012346 - p53/RUNT-type_TF_DNA-bd
IPR011615 - p53_DNA-bd
IPR010991 - p53_tetrameristn
IPR002117 - p53_tumour_suppressor
IPR001660 - SAM
IPR013761 - SAM/pointed
IPR011510 - SAM_2

Pfam Domains:
PF00870 - P53 DNA-binding domain
PF07710 - P53 tetramerisation motif
PF07647 - SAM domain (Sterile alpha motif)

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1COK
- NMR MuPIT

1DXS
- X-ray MuPIT

2KBY
- NMR MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
2WQI - X-ray MuPIT 2WQJ - X-ray MuPIT 2WTT - X-ray MuPIT
2XWC - X-ray MuPIT 3VD0 - X-ray MuPIT 3VD1 - X-ray MuPIT
3VD2 - X-ray MuPIT 4A63 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on O15350
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0002039 p53 binding
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0003684 damaged DNA binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0005515 protein binding
GO:0008134 transcription factor binding
GO:0019901 protein kinase binding
GO:0042802 identical protein binding
GO:0043565 sequence-specific DNA binding
GO:0044212 transcription regulatory region DNA binding
GO:0046872 metal ion binding
GO:0097371 MDM2/MDM4 family protein binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0000187 activation of MAPK activity
GO:0001822 kidney development
GO:0006298 mismatch repair
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006366 transcription from RNA polymerase II promoter
GO:0006915 apoptotic process
GO:0006974 cellular response to DNA damage stimulus
GO:0006978 DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
GO:0007049 cell cycle
GO:0007050 cell cycle arrest
GO:0007346 regulation of mitotic cell cycle
GO:0008285 negative regulation of cell proliferation
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
GO:0010165 response to X-ray
GO:0010243 response to organonitrogen compound
GO:0010332 response to gamma radiation
GO:0010468 regulation of gene expression
GO:0016032 viral process
GO:0031571 mitotic G1 DNA damage checkpoint
GO:0034644 cellular response to UV
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:0043508 negative regulation of JUN kinase activity
GO:0043524 negative regulation of neuron apoptotic process
GO:0045665 negative regulation of neuron differentiation
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0048714 positive regulation of oligodendrocyte differentiation
GO:0051262 protein tetramerization
GO:0060044 negative regulation of cardiac muscle cell proliferation
GO:0071158 positive regulation of cell cycle arrest
GO:1900740 positive regulation of protein insertion into mitochondrial membrane involved in apoptotic signaling pathway
GO:1901796 regulation of signal transduction by p53 class mediator
GO:1902036 regulation of hematopoietic stem cell differentiation

Cellular Component:
GO:0000785 chromatin
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005667 transcription factor complex
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005794 Golgi apparatus
GO:0005829 cytosol
GO:0030054 cell junction
GO:0043231 intracellular membrane-bounded organelle


-  Descriptions from all associated GenBank mRNAs
  BC117251 - Homo sapiens tumor protein p73, mRNA (cDNA clone MGC:150860 IMAGE:40125802), complete cds.
BC117253 - Homo sapiens tumor protein p73, mRNA (cDNA clone MGC:150862 IMAGE:40125804), complete cds.
Y11416 - H.sapiens mRNA for P73.
LF385372 - JP 2014500723-A/192875: Polycomb-Associated Non-Coding RNAs.
MA620949 - JP 2018138019-A/192875: Polycomb-Associated Non-Coding RNAs.
AB590585 - Synthetic construct DNA, clone: pFN21AB7872, Homo sapiens TP73 gene for tumor protein p73, without stop codon, in Flexi system.
HQ258345 - Synthetic construct Homo sapiens clone IMAGE:100072654 tumor protein p73 (TP73) gene, encodes complete protein.
AB055065 - Homo sapiens hDNp73A mRNA for deltaN p73 alpha, complete cds.
AB055066 - Homo sapiens hDNp73B mRNA for deltaN p73 beta, complete cds.
AY040827 - Homo sapiens DN p73 alpha (TP73) mRNA, complete cds, alternatively spliced.
AY040828 - Homo sapiens DN p73 beta (TP73) mRNA, complete cds, alternatively spliced.
AY040829 - Homo sapiens DN p73 gamma (TP73) mRNA, complete cds, alternatively spliced.
AK304177 - Homo sapiens cDNA FLJ52392 complete cds, highly similar to Tumor protein p73.
AK304784 - Homo sapiens cDNA FLJ52399 complete cds, highly similar to Tumor protein p73.
AK310432 - Homo sapiens cDNA, FLJ17474.
AK302118 - Homo sapiens cDNA FLJ52358 complete cds, highly similar to Tumor protein p73.
AK295669 - Homo sapiens cDNA FLJ50534 complete cds, highly similar to Tumor protein p73.
JD320610 - Sequence 301634 from Patent EP1572962.
JD361606 - Sequence 342630 from Patent EP1572962.
JD340194 - Sequence 321218 from Patent EP1572962.
JD173207 - Sequence 154231 from Patent EP1572962.
JD323503 - Sequence 304527 from Patent EP1572962.
JD210104 - Sequence 191128 from Patent EP1572962.
JD056069 - Sequence 37093 from Patent EP1572962.
JD418214 - Sequence 399238 from Patent EP1572962.
JD192648 - Sequence 173672 from Patent EP1572962.
JD518554 - Sequence 499578 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04115 - p53 signaling pathway
hsa04722 - Neurotrophin signaling pathway

BioCarta from NCI Cancer Genome Anatomy Project
h_atmPathway - ATM Signaling Pathway

Reactome (by CSHL, EBI, and GO)

Protein O15350 (Reactome details) participates in the following event(s):

R-HSA-8956676 YAP1 binds TP73
R-HSA-8956684 ITCH polyubiquitinates TP73
R-HSA-6798082 TP53 family members bind the CASP1 gene
R-HSA-6799761 TP53 binds PPP1R13L
R-HSA-6799777 TP53 family members bind PPP1R13B or TP53BP2
R-HSA-3700981 TP53 family members bind the BAX promoter
R-HSA-4331340 TP53 binds the BBC3 (PUMA) promoter
R-HSA-6799462 TP53 family members bind the TP53I3 (PIG3) gene promoter
R-HSA-6799815 TP53 family members bind the FAS gene
R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs
R-HSA-6803207 TP53 Regulates Transcription of Caspase Activators and Caspases
R-HSA-6804759 Regulation of TP53 Activity through Association with Co-factors
R-HSA-8878171 Transcriptional regulation by RUNX1
R-HSA-6803204 TP53 Regulates Transcription of Genes Involved in Cytochrome C Release
R-HSA-139915 Activation of PUMA and translocation to mitochondria
R-HSA-6803205 TP53 regulates transcription of several additional cell death genes whose specific roles in p53-dependent apoptosis remain uncertain
R-HSA-6803211 TP53 Regulates Transcription of Death Receptors and Ligands
R-HSA-5633008 TP53 Regulates Transcription of Cell Death Genes
R-HSA-5633007 Regulation of TP53 Activity
R-HSA-212436 Generic Transcription Pathway
R-HSA-114452 Activation of BH3-only proteins
R-HSA-3700989 Transcriptional Regulation by TP53
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-109606 Intrinsic Pathway for Apoptosis
R-HSA-74160 Gene expression (Transcription)
R-HSA-109581 Apoptosis
R-HSA-5357801 Programmed Cell Death

-  Other Names for This Gene
  Alternate Gene Symbols: B7Z9C1, NM_001204191, O15350, O15351, P73, P73_HUMAN, Q17RN8, Q5TBV5, Q5TBV6, Q8NHW9, Q8TDY5, Q8TDY6, Q9NTK8, uc001akr.1, uc001akr.2, uc001akr.3
UCSC ID: uc001akr.3
RefSeq Accession: NM_001126240
Protein: O15350 (aka P73_HUMAN)
CCDS: CCDS55569.1, CCDS44049.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.