Human Gene SYVN1 (ENST00000294256.12) from GENCODE V44
Description: Homo sapiens synoviolin 1 (SYVN1), transcript variant 1, mRNA. (from RefSeq NM_032431) RefSeq Summary (NM_032431): This gene encodes a protein involved in endoplasmic reticulum (ER)-associated degradation. The encoded protein removes unfolded proteins, accumulated during ER stress, by retrograde transport to the cytosol from the ER. This protein also uses the ubiquitin-proteasome system for additional degradation of unfolded proteins. Sequence analysis identified two transcript variants that encode different isoforms. [provided by RefSeq, May 2011]. Gencode Transcript: ENST00000294256.12 Gencode Gene: ENSG00000162298.19 Transcript (Including UTRs) Position: hg38 chr11:65,127,279-65,134,532 Size: 7,254 Total Exon Count: 16 Strand: - Coding Region Position: hg38 chr11:65,128,382-65,133,601 Size: 5,220 Coding Exon Count: 15
ID:SYVN1_HUMAN DESCRIPTION: RecName: Full=E3 ubiquitin-protein ligase synoviolin; EC=6.3.2.-; AltName: Full=Synovial apoptosis inhibitor 1; Flags: Precursor; FUNCTION: Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated UBC7 E2 ligase and transfers it to substrates, promoting their degradation. Component of the endoplasmic reticulum quality control (ERQC) system also called ER-associated degradation (ERAD) involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins. Also promotes the degradation of normal but naturally short-lived proteins such as SGK. Protects cells from ER stress-induced apoptosis. Protects neurons from apoptosis induced by polyglutamine-expanded huntingtin (HTT) or unfolded GPR37 by promoting their degradation. Sequesters p53/TP53 in the cytoplasm and promotes its degradation, thereby negatively regulating its biological function in transcription, cell cycle regulation and apoptosis. PATHWAY: Protein modification; protein ubiquitination. SUBUNIT: Homodimer. Interacts with p53/TP53 and HTT. Interacts with VCP, HERPUD1 and DERL1. Part of a complex containing SYVN1, HERPUD1, VIMP and DERL1; which probably transfer misfolded proteins from the ER to VCP. Part of a complex containing SYVN1, SEL1L and DERL2. Interacts with UBXN6. Interacts with SEL1L; recruits ERLEC1 and OS9. May form a complex with ERLEC1; HSPA5; OS9 AND SEL1L. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass membrane protein. TISSUE SPECIFICITY: Ubiquitously expressed, with highest levels in liver and kidney (at protein level). Up-regulated in synovial tissues from patients with rheumatoid arthritis (at protein level). INDUCTION: By endoplasmic reticulum stress-inducing agents such as thapsigargin, tunicamycin or brefeldin A, but not by heat shock. DOMAIN: The RING-type zinc finger is required for E3 ligase activity. PTM: Not N-glycosylated. PTM: Auto-ubiquitinated. SIMILARITY: Belongs to the HRD1 family. SIMILARITY: Contains 1 RING-type zinc finger. SEQUENCE CAUTION: Sequence=BAB47439.1; Type=Erroneous initiation;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q86TM6
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006511 ubiquitin-dependent protein catabolic process GO:0016567 protein ubiquitination GO:0018279 protein N-linked glycosylation via asparagine GO:0030433 ER-associated ubiquitin-dependent protein catabolic process GO:0030968 endoplasmic reticulum unfolded protein response GO:0030970 retrograde protein transport, ER to cytosol GO:0036498 IRE1-mediated unfolded protein response GO:0036503 ERAD pathway GO:0050821 protein stabilization GO:0070936 protein K48-linked ubiquitination GO:1902236 negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway GO:1904380 endoplasmic reticulum mannose trimming
Cellular Component: GO:0000836 Hrd1p ubiquitin ligase complex GO:0000839 Hrd1p ubiquitin ligase ERAD-L complex GO:0005654 nucleoplasm GO:0005783 endoplasmic reticulum GO:0005789 endoplasmic reticulum membrane GO:0005790 smooth endoplasmic reticulum GO:0016020 membrane GO:0016021 integral component of membrane GO:0030176 integral component of endoplasmic reticulum membrane GO:0036513 Derlin-1 retrotranslocation complex GO:0044322 endoplasmic reticulum quality control compartment
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04120 - Ubiquitin mediated proteolysis
Reactome (by CSHL, EBI, and GO)
Protein Q86TM6 (Reactome details) participates in the following event(s):
R-HSA-5362441 C-terminal Hh fragments are recruited to SEL1:SYVN1 at the ER membrane R-HSA-5387386 Hh processing variants are recruited to SEL1:SYVN at the ER membrane R-HSA-5362459 VCP-catalyzed ATP hydrolysis promotes the translocation of Hh-C into the cytosol R-HSA-5387389 Hh processing variants are translocated to the cytosol in a VCP-dependent manner R-HSA-5362412 SYVN1 ubiquitinates Hh C-terminal fragments R-HSA-5483238 Hh processing variants are ubiquitinated R-HSA-8867288 OS9:SEL1:ERAD E3 ligase:DERL2 ubiquitinates unfolded protein:(GlcNAc)2 (Man)9-5 R-HSA-1022127 OS9:SEL1:ERAD E3 ligase:DERL2 transports Ub-unfolded protein:(GlcNAc)2 (Man)9-5 from ERQC to cytosol R-HSA-381038 XBP1(S) activates chaperone genes R-HSA-381070 IRE1alpha activates chaperones R-HSA-5358346 Hedgehog ligand biogenesis R-HSA-5362768 Hh mutants that don't undergo autocatalytic processing are degraded by ERAD R-HSA-381119 Unfolded Protein Response (UPR) R-HSA-5358351 Signaling by Hedgehog R-HSA-5387390 Hh mutants abrogate ligand secretion R-HSA-901032 ER Quality Control Compartment (ERQC) R-HSA-392499 Metabolism of proteins R-HSA-162582 Signal Transduction R-HSA-5663202 Diseases of signal transduction R-HSA-901042 Calnexin/calreticulin cycle R-HSA-1643685 Disease R-HSA-532668 N-glycan trimming in the ER and Calnexin/Calreticulin cycle R-HSA-446203 Asparagine N-linked glycosylation R-HSA-597592 Post-translational protein modification
US Server
