E3 ubiquitin-protein ligase SIAH2 (EC 2.3.2.27) (RING-type E3 ubiquitin transferase SIAH2) (Seven in absentia homolog 2) (Siah-2) (hSiah2)
1_MSRPS 6_ STGPS 11_ ANKPC 16_ SKQPP 21_ PQPQH 26_ TPSPA 31_ APPAA 36_ ATISA 41_ AGPGS 46_ SAVPA 51_ AAAVI 56_ SGPGG 61_ GGGAG 66_ PVSPQ 71_ HHELT 76_ SLFEC 81_ PVCFD 86_ YVLPP 91_ ILQCQ 96_ AGHLV 101_ CNQCR 106_ QKLSC 111_ CPTCR 116_ GALTP 121_ SIRNL 126_ AMEKV 131_ ASAVL 136_ FPCKY 141_ ATTGC 146_ SLTLH 151_ HTEKP 156_ EHEDI 161_ CEYRP 166_ YSCPC 171_ PGASC 176_ KWQGS 181_ LEAVM 186_ SHLMH 191_ AHKSI 196_ TTLQG 201_ EDIVF 206_ LATDI 211_ NLPGA 216_ VDWVM 221_ MQSCF 226_ GHHFM 231_ LVLEK 236_ QEKYE 241_ GHQQF 246_ FAIVL 251_ LIGTR 256_ KQAEN 261_ FAYRL 266_ ELNGN 271_ RRRLT 276_ WEATP 281_ RSIHD 286_ GVAAA 291_ IMNSD 296_ CLVFD 301_ TAIAH 306_ LFADN 311_ GNLGI 316_NVTIS
1: 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