Siah-1 is a member of the seven in absentia homolog (SIAH) family. It is a E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins, including many proteins involved in transcription regulation, a cell surface receptor (DCC), cytoplasmic signal transduction molecules, an antiapoptotic protein (BAG1), a microtubule motor protein (KIF22), a protein involved in synaptic vesicle function in neurons (SYP) and a structural protein. Consequently Siah-1 is involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis, and TNF-alpha signaling. It is predominantly a cytoplasmic protein but is also partially a nuclear protein. It is widely expressed at low levels and is down-regulated in advanced hepatocellular carcinomas.