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Details on Person UniProt:Q8IUQ4 SIAH1
| Class:Id | ReferenceGeneProduct:153922 |
|---|---|
| _chainChangeLog | chain:1-282 added on Fri February 6 2015 |
| _displayName | UniProt:Q8IUQ4 SIAH1 |
| _timestamp | 2026-02-20 21:34:36 |
| chain | chain:1-282 |
| checksum | FA0698D0DC1B0A15 |
| comment | 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:28546513, PubMed:32430360, PubMed:33591310, 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, PubMed:33591310). It is thereby involved in many cellular processes such as apoptosis, tumor suppression, cell cycle, axon guidance, transcription regulation, spermatogenesis and TNF 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). Also part of the Wnt signaling pathway in which it mediates the Wnt-induced ubiquitin-mediated proteasomal degradation of AXIN1 (PubMed:28546513, PubMed:32430360).CATALYTIC ACTIVITY S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.ACTIVITY REGULATION Inhibited by interaction with SNCAIP (isoform 2, but not isoform 1). May be inhibited by interaction with PEG10.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Homodimer. Interacts with group 1 glutamate receptors GRM1 and GRM5. Interacts with DAB1, which may inhibit its activity. Interacts with UBE2E2. Interacts with PEG3. Interacts with GAPDH; leading to stabilize SIAH1 (By similarity). Component of some large E3 complex composed of UBE2D1, SIAH1, CACYBP/SIP, SKP1, APC and TBL1X. Interacts with UBE2I. Interacts with alpha-tubulin. Interacts with PEG10, which may inhibit its activity. Interacts with KHDRBS3. Interacts with SNCAIP. Interacts with HIPK2; the interaction is promoted by DAZAP2 and results in SIAH1-mediated ubiquitination and subsequent proteasomal degradation of HIPK2 (PubMed:33591310). Interacts with DAZAP2; the interaction is decreased following phosphorylation of DAZAP2 by HIPK2 (PubMed:33591310). Interacts with Bassoon/BSN and Piccolo/PLCO; these interactions negatively regulate SIAH1 E3 ligase activity (By similarity). Interacts with DCC (PubMed:9334332). Interacts with AXIN1; catalyzes AXIN1 ubiquitination and subsequent proteasome-mediated ubiquitin-dependent degradation (PubMed:28546513).INTERACTION Predominantly cytoplasmic. Partially nuclear.ALTERNATIVE PRODUCTS Widely expressed at a low level. Down-regulated in advanced hepatocellular carcinomas.INDUCTION May be induced by p53/TP53, suggesting that it may be required to modulate p53/TP53 response. The relevance of such activity in vivo is however unclear and may not exist.DOMAIN The RING-type zinc finger domain is essential for ubiquitin ligase activity.DOMAIN The SBD domain (substrate-binding domain) mediates the homodimerization and the interaction with substrate proteins. It is related to the TRAF family.PTM Phosphorylated on Ser-19 by ATM and ATR. This phosphorylation disrupts SIAH1 interaction with HIPK2, and subsequent proteasomal degradation of HIPK2.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the SINA (Seven in absentia) family. |
| created | [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 |
| description | recommendedName: E3 ubiquitin-protein ligase SIAH1 ecNumber evidence="24 27"2.3.2.27 alternativeName: fullName evidence="37"RING-type E3 ubiquitin transferase SIAH1 alternativeName: Seven in absentia homolog 1 shortName: Siah-1 alternativeName: Siah-1a |
| geneName | SIAH1 HUMSIAH |
| identifier | Q8IUQ4 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Apoptosis Cell cycle Cytoplasm Developmental protein Differentiation Disease variant Intellectual disability Metal-binding Nucleus Phosphoprotein Proteomics identification Reference proteome Spermatogenesis Transferase Ubl conjugation pathway Zinc Zinc-finger |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | SIAH1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:9003235] ENSEMBL:ENSG00000196470 SIAH1 [Homo sapiens] |
| secondaryIdentifier | SIAH1_HUMAN A0FKF3 O43269 Q49A58 Q92880 |
| sequenceLength | 282 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:153923] UniProt:Q8IUQ4-2 SIAH1 [Homo sapiens] [ReferenceIsoform:248349] UniProt:Q8IUQ4-3 SIAH1 [Homo sapiens] [ReferenceIsoform:410787] UniProt:Q8IUQ4-1 SIAH1 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:374563] SIAH1 [cytosol] [Homo sapiens] |
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No pathways have been reviewed or authored by UniProt:Q8IUQ4 SIAH1 (153922)
