E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:11786535, PubMed:15951807). 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 (PubMed:11786535, PubMed:15951807). Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes (PubMed:11786535, PubMed:15951807). Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (ELL2, MYB, POU2AF1, PML and RBBP8), a cell surface receptor (DCC), cytoplasmic signal transduction molecules (KLF10/TIEG1 and NUMB), an antiapoptotic protein (BAG1), a microtubule motor protein (KIF22), a protein involved in synaptic vesicle function in neurons (SYP), a structural protein (CTNNB1) and SNCAIP (PubMed:11786535). Confers constitutive instability to HIPK2 through proteasomal degradation (By similarity). It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription, spermatogenesis and TNF-alpha signaling (By similarity). Has some overlapping function with SIAH2 (By similarity). Induces apoptosis in cooperation with PEG3 (By similarity). Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S-nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus (PubMed:15951807). GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins (PubMed:15951807). Mediates ubiquitination and degradation of EGLN2 and EGLN3 in response to the unfolded protein response (UPR), leading to their degradation and subsequent stabilization of ATF4 (By similarity). Also part of the Wnt signaling pathway in which it mediates the Wnt-induced ubiquitin-mediated proteasomal degradation of AXIN1. 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. Component of some large E3 complex composed of UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X. Interacts with UBE2I. Interacts with alpha-tubulin. Interacts with PEG10, which may inhibit its activity. Interacts with PEG3 and HIPK2 (By similarity). Interacts with group 1 glutamate receptors GRM1 and GRM5. Interacts with DAB1, which may inhibit its activity. Interacts with UBE2E2. Interacts with SNCAIP. Interacts with GAPDH; leading to stabilize SIAH1. Interacts with Bassoon/BSN and Piccolo/PLCO; these interactions negatively regulate SIAH1 E3 ligase activity. Interacts with DCC (By similarity). Interacts with AXIN1; catalyzes AXIN1 ubiquitination and subsequent proteasome-mediated ubiquitin-dependent degradation. Predominantly cytoplasmic. Partially nuclear. 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. This phosphorylation disrupts SIAH1 interaction with HIPK2, and subsequent proteasomal degradation of HIPK2 (By similarity). Belongs to the SINA (Seven in absentia) family.