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. 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), the cell-surface receptor-type tyrosine kinase FLT3, the 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. Confers constitutive instability to HIPK2 through proteasomal degradation. It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF-alpha signaling. Has some overlapping function with SIAH2. Induces apoptosis in cooperation with PEG3. Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S-nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus. GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins. Belongs to the SINA (Seven in absentia) family. Widely expressed at a low level. Down-regulated in advanced hepatocellular carcinomas. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Molecular Function: disordered domain specific binding; identical protein binding; metal ion binding; protein binding; protein C-terminus binding; protein homodimerization activity; transferase activity; ubiquitin conjugating enzyme binding; ubiquitin protein ligase activity; ubiquitin-protein transferase activity; zinc ion binding
Biological Process: apoptotic process; cell cycle; cell differentiation; male meiosis I; multicellular organism development; neuron apoptotic process; positive regulation of apoptotic process; positive regulation of intrinsic apoptotic signaling pathway; post-embryonic development; proteasome-mediated ubiquitin-dependent protein catabolic process; protein catabolic process; protein destabilization; regulation of multicellular organism growth; spermatogenesis; ubiquitin-dependent protein catabolic process