Siah2 is a E3 Ubiquitin ligase protein 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 transfer the ubiquitin to targets. Siah2 triggers the ubiquitin-mediated degradation of many proteins, including transcription regulators (e.g. POU2AF1, PML, NCOR1), cell surface receptors (e.g. DCC), antiapoptotic proteins (e.g. BAG1), and proteins involved in synaptic vesicle function in neurons (e.g. SYP). Siah2 has some overlapping function with SIAH1 but is able to trigger the ubiquitin-mediated degradation of TRAF2, whereas SIAH1 can not.