Summary

Name SIAH1
Full Name E3 ubiquitin-protein ligase SIAH1
Synonyms Seven in absentia homolog 1, Siah-1, Siah-1a | HUMSIAH
Primary ID Q8IUQ4
Links - -
Type protein
Relations 16
Function E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). 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:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). 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:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Triggers the ubiquitin-mediated degradation of many substrates, including proteins involved in transcription regulation (ELL2, MYB, POU2AF1, PML and RBBP8), a cell surface receptor (DCC), the cell-surface receptor-type tyrosine kinase FLT3, the cytoplasmic signal transduction molecules (KLF10/TIEG1 and NUMB), an antiapoptotic protein (BAG1), a microtubule motor protein (KIF22), a protein involved in synaptic vesicle function in neurons (SYP), a structural protein (CTNNB1) and SNCAIP (PubMed:10747903, PubMed:11146551, PubMed:11389839, PubMed:11389840, PubMed:11483517, PubMed:11483518, PubMed:11752454, PubMed:12072443). Confers constitutive instability to HIPK2 through proteasomal degradation (PubMed:18536714). It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF-alpha signaling (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Has some overlapping function with SIAH2 (PubMed:14506261, PubMed:14645235, PubMed:14654780, PubMed:15064394, PubMed:16085652, PubMed:19224863, PubMed:20508617, PubMed:22483617, PubMed:9334332, PubMed:9858595). Induces apoptosis in cooperation with PEG3 (By similarity). Upon nitric oxid (NO) generation that follows apoptotic stimulation, interacts with S-nitrosylated GAPDH, mediating the translocation of GAPDH to the nucleus (By similarity). GAPDH acts as a stabilizer of SIAH1, facilitating the degradation of nuclear proteins (By similarity). 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
+ SIAH1down-regulates quantity by destabilization img/direct_inhibition.png ubiquitination YBX1 0.244
Publications: 1 Organism: Homo Sapiens
+ ATRdown-regulates activity img/direct_inhibition.png phosphorylation SIAH1 0.2
Publications: 1 Organism: Homo Sapiens
+ ATMdown-regulates img/direct_inhibition.png phosphorylation SIAH1 0.31
Publications: 1 Organism: Homo Sapiens
+ SIAH1down-regulates quantity img/direct_inhibition.png ubiquitination HIPK2 0.518
Publications: 1 Organism: Homo Sapiens
+ TP53up-regulates quantity by expression img/direct-activation.png transcriptional regulation SIAH1 0.376
Publications: 2 Organism: Homo Sapiens
+ Ub:E2up-regulates activity img/direct-activation.png ubiquitination SIAH1 0.2
Publications: 1 Organism: Homo Sapiens
+ SIAH1down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination JADE1 0.293
Publications: 1 Organism: Homo Sapiens
+ SIAH1up-regulates img/direct-activation.png relocalization NOTCH1 0.261
Publications: 1 Organism: Homo Sapiens
+ SIAH1form complex img/form-complex.png binding SCF(TBL1) 0.485
Publications: 1 Organism: Homo Sapiens
+ SIAH1down-regulates img/direct_inhibition.png ubiquitination NUMB 0.401
Publications: 1 Organism: Homo Sapiens
+ SIAH1down-regulates img/direct_inhibition.png ubiquitination SNCAIP 0.674
Publications: 1 Organism: Homo Sapiens
+ SIAH1down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination KHDRBS3 0.476
Publications: 1 Organism: Mus Musculus
+ SIAH1down-regulates quantity by destabilization img/direct_inhibition.png polyubiquitination HIPK2 0.518
Publications: 1 Organism: Homo Sapiens
+ PKD1up-regulates activity img/direct-activation.png binding SIAH1 0.333
Publications: 1 Organism: Homo Sapiens
+ SIAH1up-regulates img/direct-activation.png relocalization NOTCH 0.261
Publications: 1 Organism: Homo Sapiens