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
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.
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.
ModBase Predicted Comparative 3D Structure on O15350
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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.
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