p73 beta Recombinant Protein

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]

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. Ref.6 Ref.14 Ref.23

Cofactor: Binds 1 zinc ion per subunit

By similarity.

Subunit structure: 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. Ref.12 Ref.16 Ref.17 Ref.18 Ref.19 Ref.20 Ref.24 Ref.25 Ref.27

Subcellular location: Nucleus. Cytoplasm. Note: Accumulates in the nucleus in response to DNA damage. Ref.20 Ref.24

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. Ref.6 Ref.21

Induction: Not induced by DNA damage. Isoforms lacking the transactivation domain block gene induction. Ref.6

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. Ref.19The WW-binding motif mediates interaction with WWOX. Ref.19

Post-translational modification: 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. Ref.15Higher levels of phosphorylation seen in the brain from patients with Huntington disease.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.Activated and stabilized by interaction with RANBP9.

Sequence similarities: Belongs to the p53 family.Contains 1 SAM (sterile alpha motif) domain.