SIAH2

This gene encodes a protein that is a member of the seven in absentia homolog (SIAH) family. The protein is an E3 ligase and is involved in ubiquitination and proteasome-mediated degradation of specific proteins. The activity of this ubiquitin ligase has been implicated in regulating cellular response to hypoxia. [provided by RefSeq]

seven in absentia homolog 2 (Drosophila)

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).
Also part of the Wnt signaling pathway in which it mediates the Wnt-induced ubiquitin-mediated proteasomal degradation of AXIN1.

Biological Process amyloid fibril formationTAS:Reactome
Biological Process apoptotic processIEA:UniProtKB-KW
Biological Process canonical Wnt signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process cell cycleIEA:UniProtKB-KW
Biological Process negative regulation of apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of canonical Wnt signaling pathwayManual Assertion Based On ExperimentIGI:MGI
Biological Process negative regulation of cysteine-type endopeptidase activity involved in apoptotic processManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of extrinsic apoptotic signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process proteasome-mediated ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIBA:GO_Central
Biological Process regulation of circadian rhythmManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process regulation of protein ubiquitinationIEA:Ensembl
Biological Process rhythmic processIEA:UniProtKB-KW
Biological Process small GTPase mediated signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Biological Process ubiquitin-dependent protein catabolic processManual Assertion Based On ExperimentIMP:UniProtKB

Cytoplasm
Nucleus
Predominantly cytoplasmic. Partially nuclear.

Phosphorylated at Ser-28 by MAPK14, which mediates the degradation by the proteasome of EGLN3 (By similarity).
Phosphorylated at Ser-28 by DYRK2; this increases the ubiquitin ligase activity and promotes degradation of EGLN3.