| Description |
E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins (PMID:14506261, PMID:14645235, PMID:14654780, PMID:15064394, PMID:16085652, PMID:19224863, PMID:20508617, PMID:22483617, PMID:9334332, PMID:9858595). 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 (PMID:14506261, PMID:14645235, PMID:14654780, PMID:15064394, PMID:16085652, PMID:19224863, PMID:20508617, PMID:22483617, PMID:9334332, PMID:9858595). Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes (PMID:14506261, PMID:14645235, PMID:14654780, PMID:15064394, PMID:16085652, PMID:19224863, PMID:20508617, PMID:22483617, PMID:9334332, PMID:9858595). 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 (PMID:10747903, PMID:11146551, PMID:11389839, PMID:11389840, PMID:11483517, PMID:11483518, PMID:11752454, PMID:12072443). Confers constitutive instability to HIPK2 through proteasomal degradation (PMID:18536714). It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF-alpha signaling (PMID:14506261, PMID:14645235, PMID:14654780, PMID:15064394, PMID:16085652, PMID:19224863, PMID:20508617, PMID:22483617, PMID:9334332, PMID:9858595). Has some overlapping function with SIAH2 (PMID:14506261, PMID:14645235, PMID:14654780, PMID:15064394, PMID:16085652, PMID:19224863, PMID:20508617, PMID:22483617, PMID:9334332, PMID:9858595). 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 . 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 . |
