| Primary Identifier | IPR004162 | Type | Family |
| Short Name | SINA-like_animal |
| description | Proteins in this entry are E3 ubiquitin-protein ligases that mediate ubiquitination and subsequent proteasomal degradation of target proteins. Proteins in this entry include Sina and Sinah (Sina homologue) from flies and SIAH1/2 from humans.The seven in absentia (sina) gene was first identified in Drosophila. The Drosophila Sina protein is essential for the determination of the R7 pathway in photoreceptor cell development: the loss of functional Sina results in the transformation of the R7 precursor cell to a non-neuronal cell type. The Sina protein contains an N-terminal RING finger domain C3HC4-type. Through this domain, Sina binds E2 ubiquitin-conjugating enzymes (UbcD1). Sina also interacts with Tramtrack (TTK88) via PHYL. Tramtrack is a transcriptional repressor that blocks photoreceptor determination, while PHYL down-regulates the activity of TTK88. In turn, the activity of PHYL requires the activation of the Sevenless receptor tyrosine kinase, a process essential for R7 determination. It is thought that Sina targets TTK88 for degradation, therefore promoting the R7 pathway. Murine and human homologues of Sina have also been identified. The human homologue SIAH1 []also binds E2 enzymes (UbcH5) and through a series of physical interactions, targets beta-catenin for ubiquitin degradation. Siah-1 expression is enhanced by p53, itself promoted by DNA damage.Thus this pathway links DNA damage to beta-catenin degradation [, ]. |
