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E3 ubiquitin-protein ligase SIAH2

E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins^1,2,3. 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^4,5,6. Mediates E3 ubiquitin ligase activity either through direct binding to substrates or by functioning as the essential RING domain subunit of larger E3 complexes^7,8,9. Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (GPS2, POU2AF1, PML, NCOR1), a cell surface receptor (DCC), an antiapoptotic protein (BAG1), and a protein involved in synaptic vesicle function in neurons (SYP)^10,11,12. Mediates ubiquitination and proteasomal degradation of DYRK2 in response to hypoxia¹³. It is thereby involved in apoptosis, tumor suppression, cell cycle, transcription and signaling processes^14,15,16,17. Has some overlapping function with SIAH1^18,19,20. Triggers the ubiquitin-mediated degradation of TRAF2, whereas SIAH1 does not²¹. Promotes monoubiquitination of SNCA²². Regulates cellular clock function via ubiquitination of the circadian transcriptional repressors NR1D1 and NR1D2 leading to their proteasomal degradation²³. Plays an important role in mediating the rhythmic degradation/clearance of NR1D1 and NR1D2 contributing to their circadian profile of protein abundance²⁴. 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.

AlphaFold DB , UniProt , Accession O43255, Species HUMAN (Homo sapiens, Human), Gene SIAH2, Length 324 aa.