SIAH2 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 (GPS2, POU2AF1, PML, NCOR1), a cell surface receptor (DCC), an antiapoptotic protein (BAG1), and a protein involved in synaptic vesicle function in neurons (SYP). Mediates ubiquitination and proteasomal degradation of DYRK2 in response to hypoxia. It is thereby involved in apoptosis, tumor suppression, cell cycle, transcription and signaling processes. Has some overlapping function with SIAH1. Triggers the ubiquitin-mediated degradation of TRAF2, whereas SIAH1 does not. Promotes monoubiquitination of SNCA. Regulates cellular clock function via ubiquitination of the circadian transcriptional repressors NR1D1 and NR1D2 leading to their proteasomal degradation. Plays an important role in mediating the rhythmic degradation/clearance of NR1D1 and NR1D2 contributing to their circadian profile of protein abundance. Belongs to the SINA (Seven in absentia) family. Widely expressed at low level. Note: This description may include information from UniProtKB.
Protein type: EC 6.3.2.-; EC; Ligase; Transcription, coactivator/corepressor; Ubiquitin conjugating system; Ubiquitin ligase
Chromosomal Location of human Ortholog: 3q25.1
Cellular Component:  cytoplasm; cytosol; early endosome; intracellular membrane-bounded organelle; neuron projection; neuronal cell body; nucleoplasm
Molecular Function:  protein binding; transcription corepressor activity; ubiquitin conjugating enzyme binding; ubiquitin protein ligase activity; ubiquitin-protein transferase activity; zinc ion binding
Biological Process:  amyloid fibril formation; apoptotic process; canonical Wnt signaling pathway; cell cycle; negative regulation of apoptotic process; negative regulation of canonical Wnt signaling pathway; negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; negative regulation of DNA-templated transcription; negative regulation of extrinsic apoptotic signaling pathway; proteasome-mediated ubiquitin-dependent protein catabolic process; protein ubiquitination; regulation of circadian rhythm; regulation of protein ubiquitination; rhythmic process; small GTPase mediated signal transduction; ubiquitin-dependent protein catabolic process
Reference #:  O43255 (UniProtKB)
Alt. Names/Synonyms: E3 ubiquitin-protein ligase SIAH2; hSiah2; RING-type E3 ubiquitin transferase SIAH2; Seven in absentia homolog 2; seven in absentia homolog 2 (Drosophila); siah E3 ubiquitin protein ligase 2; Siah-2; SIAH2
Gene Symbols: SIAH2
Molecular weight: 34,615 Da
Basal Isoelectric point: 6.71  Predict pI for various phosphorylation states
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Protein Structure Not Found.

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