SIAH2
entrez
6478
canonical
uniprot
O43255
canonical
ensembl
ENSG00000181788
resolver
ensp
ENSP00000322457
resolver
enst
ENST00000312960
resolver
genesymbol
SIAH2
resolver
hgnc
HGNC:10858
resolver
uniprot
O43270
resolver
uniprot_entry
SIAH2_HUMAN
resolver
uniprot_sec
O43270
resolver
activity_regulation
ACTIVITY REGULATION: Inhibited by interaction with SNCAIP (isoform 2, but not isoform 1). May be inhibited by interaction with PEG10. {ECO:0000269|PubMed:19224863}.
uniprot
proteins
amino_acid_sequence
MSRPSSTGPSANKPCSKQPPPQPQHTPSPAAPPAAATISAAGPGSSAVPAAAAVISGPGGGGGAGPVSPQHHELTSLFECPVCFDYVLPPILQCQAGHLVCNQCRQKLSCCPTCRGALTPSIRNLAMEKVASAVLFPCKYATTGCSLTLHHTEKPEHEDICEYRPYSCPCPGASCKWQGSLEAVMSHLMHAHKSITTLQGEDIVFLATDINLPGAVDWVMMQSCFGHHFMLVLEKQEKYEGHQQFFAIVLLIGTRKQAENFAYRLELNGNRRRLTWEATPRSIHDGVAAAIMNSDCLVFDTAIAHLFADNGNLGINVTISTCCP
uniprot
proteins
ec_number
2.3.2.27
uniprot
proteins
function
FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:11483518, PubMed:19224863, PubMed:9334332). 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:11483518, PubMed:19224863, PubMed:9334332). 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:11483518, PubMed:19224863, PubMed:9334332). 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:11483518, PubMed:19224863, PubMed:9334332). 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:11483518, PubMed:19224863, PubMed:22878263, PubMed:9334332). Has some overlapping function with SIAH1 (PubMed:11483518, PubMed:19224863, PubMed:9334332). 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. {ECO:0000250|UniProtKB:Q06986, ECO:0000269|PubMed:11483518, ECO:0000269|PubMed:12411493, ECO:0000269|PubMed:19224863, ECO:0000269|PubMed:22878263, ECO:0000269|PubMed:26392558, ECO:0000269|PubMed:28546513, ECO:0000269|PubMed:9334332}.
uniprot
proteins
mass_dalton
34615
uniprot
proteins
mutagenesis
MUTAGEN 16; /note="S->A: Strongly reduced phosphorylation by DYRK2; when associated with A-26; A-28; A-68 and A-119."; /evidence="ECO:0000269|PubMed:22878263"; MUTAGEN 26; /note="T->A: Strongly reduced phosphorylation by DYRK2; when associated with A-16; A-28; A-68 and A-119."; /evidence="ECO:0000269|PubMed:22878263"; MUTAGEN 28; /note="S->A: Strongly reduced phosphorylation by DYRK2; when associated with A-16; A-26; A-68 and A-119."; /evidence="ECO:0000269|PubMed:22878263"; MUTAGEN 68; /note="S->A: Strongly reduced phosphorylation by DYRK2; when associated with A-16; A-26; A-28 and A-119."; /evidence="ECO:0000269|PubMed:22878263"; MUTAGEN 119; /note="T->A: Strongly reduced phosphorylation by DYRK2; when associated with A-16; A-26; A-28 and A-68."; /evidence="ECO:0000269|PubMed:22878263
uniprot
proteins
pathway_participation
PATHWAY: Protein modification; protein ubiquitination.
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000250|UniProtKB:Q06986, ECO:0000269|PubMed:22878263}.
uniprot
proteins
protein_family
SINA (Seven in absentia) family
uniprot
proteins
pubmed
10207103
uniprot
proteins
pubmed
11389839
uniprot
proteins
pubmed
11483518
uniprot
proteins
pubmed
12411493
uniprot
proteins
pubmed
12810624
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16509823
uniprot
proteins
pubmed
19224863
uniprot
proteins
pubmed
22878263
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
26392558
uniprot
proteins
pubmed
28546513
uniprot
proteins
pubmed
9334332
uniprot
proteins
pubmed
9403064
uniprot
proteins
sequence_length
324
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19224863, ECO:0000269|PubMed:22878263}. Nucleus {ECO:0000269|PubMed:22878263}. Note=Predominantly cytoplasmic. Partially nuclear. {ECO:0000269|PubMed:22878263}.
uniprot
proteins