3.0
Summary
| Name |  SIAH2View Modifications |
| Full Name | E3 ubiquitin-protein ligase SIAH2 |
| Synonyms | Seven in absentia homolog 2, Siah-2, hSiah2 |
| Primary ID | O43255 |
| Links |  -  -  |
| Type | protein |
| Relations | 11 |
| Function | E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:9334332, PubMed:11483518, PubMed:19224863). 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:9334332, PubMed:11483518, PubMed:19224863). 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:9334332, PubMed:11483518, PubMed:19224863). 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) (PubMed:9334332, PubMed:11483518, PubMed:19224863). Mediates ubiquitination and proteasomal degradation of DYRK2 in response to hypoxia (PubMed:22878263). It is thereby involved in apoptosis, tumor suppression, cell cycle, transcription and signaling processes (PubMed:9334332, PubMed:11483518, PubMed:19224863, PubMed:22878263). Has some overlapping function with SIAH1 (PubMed:9334332, PubMed:11483518, PubMed:19224863). Triggers the ubiquitin-mediated degradation of TRAF2, whereas SIAH1 does not (PubMed:12411493). Promotes monoubiquitination of SNCA (PubMed:19224863). Regulates cellular clock function via ubiquitination of the circadian transcriptional repressors NR1D1 and NR1D2 leading to their proteasomal degradation (PubMed:26392558). Plays an important role in mediating the rhythmic degradation/clearance of NR1D1 and NR1D2 contributing to their circadian profile of protein abundance (PubMed:26392558). 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). |
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Modifications Tables
Relations
| Regulator | Mechanism | target | score ℹ | |
|---|---|---|---|---|
| + | DYRK2 | up-regulates 
phosphorylation
|
SIAH2 | 0.42 |
| Publications: | 5 | Organism: | Homo Sapiens | |
| + | MAPK14 | up-regulates
phosphorylation
|
SIAH2 | 0.2 |
| Publications: | 1 | Organism: | Homo Sapiens | |
| + | SIAH2 | down-regulates quantity by destabilization 
polyubiquitination
|
AKAP1 | 0.522 |
| Publications: | 1 | Organism: | Homo Sapiens | |
| + | SIAH2 | down-regulates
ubiquitination
|
SNCAIP | 0.604 |
| Publications: | 1 | Organism: | Homo Sapiens | |
| + | Ub:E2 | up-regulates activity
ubiquitination
|
SIAH2 | 0.2 |
| Publications: | 1 | Organism: | Homo Sapiens | |
| + | SIAH2 | up-regulates 
|
HIF1A | 0.37 |
| Publications: | 1 | Organism: | Homo Sapiens | |
| + | SIAH2 | down-regulates quantity by destabilization
polyubiquitination
|
PSMD4 | 0.443 |
| Publications: | 1 | Organism: | In Vitro | |