E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes. S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. Protein modification; protein ubiquitination. Homodimer. Predominantly cytoplasmic. Partially nuclear. Widely expressed at low level in embryos and adults. Due to the high similarity between SIAH1A and SIAH1B, it is difficult to distinguish its own tissue specificity. Overexpressed in endothelial cells of adult lung. Induced by p53/TP53, suggesting that it may be required to modulate p53/TP53 response. The RING-type zinc finger domain is essential for ubiquitin ligase activity. The SBD domain (substrate-binding domain) mediates the homodimerization and the interaction with substrate proteins. It is related to the TRAF family. Phosphorylated on Ser-19 by ATM and ATR. Belongs to the SINA (Seven in absentia) family.