SYVN1

Summary

Gene Symbol: SYVN1
Description: synoviolin 1
Alias: DER3, HRD1, E3 ubiquitin-protein ligase synoviolin, HMG-coA reductase degradation 1 homolog, RING-type E3 ubiquitin transferase synoviolin, synovial apoptosis inhibitor 1, synoviolin
Species: human
Products:     SYVN1

Top Publications

  1. Fang S, Ferrone M, Yang C, Jensen J, Tiwari S, Weissman A. The tumor autocrine motility factor receptor, gp78, is a ubiquitin protein ligase implicated in degradation from the endoplasmic reticulum. Proc Natl Acad Sci U S A. 2001;98:14422-7 pubmed
    ..gp78 has thus been found to be an example of a mammalian cellular E3 intrinsic to the ER, suggesting a potential link between ubiquitylation, ERAD, and metastasis. ..
  2. Ye Y, Shibata Y, Kikkert M, van Voorden S, Wiertz E, Rapoport T. Recruitment of the p97 ATPase and ubiquitin ligases to the site of retrotranslocation at the endoplasmic reticulum membrane. Proc Natl Acad Sci U S A. 2005;102:14132-8 pubmed
  3. Iida Y, Fujimori T, Okawa K, Nagata K, Wada I, Hosokawa N. SEL1L protein critically determines the stability of the HRD1-SEL1L endoplasmic reticulum-associated degradation (ERAD) complex to optimize the degradation kinetics of ERAD substrates. J Biol Chem. 2011;286:16929-39 pubmed publisher
    The mammalian HRD1-SEL1L complex provides a scaffold for endoplasmic reticulum (ER)-associated degradation (ERAD), thereby connecting luminal substrates for ubiquitination at the cytoplasmic surface after their retrotranslocation through ..
  4. Christianson J, Olzmann J, Shaler T, Sowa M, Bennett E, Richter C, et al. Defining human ERAD networks through an integrative mapping strategy. Nat Cell Biol. 2011;14:93-105 pubmed publisher
    ..This analysis supports an adaptive organization for the mammalian ERAD machinery and reveals a number of metazoan-specific genes not previously linked to ERAD. ..
  5. Yang H, Zhong X, Ballar P, Luo S, Shen Y, Rubinsztein D, et al. Ubiquitin ligase Hrd1 enhances the degradation and suppresses the toxicity of polyglutamine-expanded huntingtin. Exp Cell Res. 2007;313:538-50 pubmed
    ..b>Hrd1 is an endoplasmic reticulum (ER) membrane-spanning E3 with its catalytic active RING finger facing the cytosol...
  6. Shenkman M, Groisman B, Ron E, Avezov E, Hendershot L, Lederkremer G. A shared endoplasmic reticulum-associated degradation pathway involving the EDEM1 protein for glycosylated and nonglycosylated proteins. J Biol Chem. 2013;288:2167-78 pubmed publisher
    ..precursor of asialoglycoprotein receptor H2a, its nonglycosylated mutant, makes use of calnexin, EDEM1, and HRD1, but only glycosylated H2a is a substrate for the cytosolic SCF(Fbs2) E3 ubiquitin ligase with lectin activity...
  7. Kaneko M, Koike H, Saito R, Kitamura Y, Okuma Y, Nomura Y. Loss of HRD1-mediated protein degradation causes amyloid precursor protein accumulation and amyloid-beta generation. J Neurosci. 2010;30:3924-32 pubmed publisher
    ..b>HRD1 is expressed in brain neurons and acts as an ERAD ubiquitin ligase...
  8. Fernández Sáiz V, Buchberger A. Imbalances in p97 co-factor interactions in human proteinopathy. EMBO Rep. 2010;11:479-85 pubmed publisher
    ..Our results suggest that imbalanced co-factor binding to p97 is a key pathological feature of IBMPFD and potentially of other proteinopathies involving p97. ..
  9. Ballar P, Ors A, Yang H, Fang S. Differential regulation of CFTRDeltaF508 degradation by ubiquitin ligases gp78 and Hrd1. Int J Biochem Cell Biol. 2010;42:167-73 pubmed publisher
    ..We showed that endogenous gp78 co-immunoprecipitates with Hrd1. Furthermore, the results indicate that silencing the expression of another ERAD E3, Hrd1, leads to stabilization ..

More Information

Publications87

  1. Kny M, Standera S, Hartmann Petersen R, Kloetzel P, Seeger M. Herp regulates Hrd1-mediated ubiquitylation in a ubiquitin-like domain-dependent manner. J Biol Chem. 2011;286:5151-6 pubmed publisher
    ..It is involved in ER-associated protein degradation (ERAD) and interacts directly with the ubiquitin ligase Hrd1, which is found in high molecular mass complexes of the ER membrane...
  2. Groisman B, Shenkman M, Ron E, Lederkremer G. Mannose trimming is required for delivery of a glycoprotein from EDEM1 to XTP3-B and to late endoplasmic reticulum-associated degradation steps. J Biol Chem. 2011;286:1292-300 pubmed publisher
    ..In contrast, substrate association with XTP3-B and with the E3 ubiquitin ligases HRD1 and SCF(Fbs2) was inhibited...
  3. Burr M, Cano F, Svobodova S, Boyle L, Boname J, Lehner P. HRD1 and UBE2J1 target misfolded MHC class I heavy chains for endoplasmic reticulum-associated degradation. Proc Natl Acad Sci U S A. 2011;108:2034-9 pubmed publisher
    ..Using an siRNA functional screen in β2m-depleted cells, we identify an essential role for the E3 ligase HRD1 (Synoviolin) together with the E2 ubiquitin-conjugating enzyme UBE2J1 in the ubiquitination and dislocation of ..
  4. Chen X, Tukachinsky H, Huang C, Jao C, Chu Y, Tang H, et al. Processing and turnover of the Hedgehog protein in the endoplasmic reticulum. J Cell Biol. 2011;192:825-38 pubmed publisher
    ..This process requires the ubiquitin ligase Hrd1, its partner Sel1, the cytosolic adenosine triphosphatase p97, and degradation by the proteasome...
  5. Omura T, Kaneko M, Okuma Y, Orba Y, Nagashima K, Takahashi R, et al. A ubiquitin ligase HRD1 promotes the degradation of Pael receptor, a substrate of Parkin. J Neurochem. 2006;99:1456-69 pubmed
    ..We previously reported that human E3 HRD1 in the endoplasmic reticulum protects against endoplasmic reticulum stress-induced apoptosis...
  6. Blount J, Burr A, Denuc A, Marfany G, Todi S. Ubiquitin-specific protease 25 functions in Endoplasmic Reticulum-associated degradation. PLoS ONE. 2012;7:e36542 pubmed publisher
    ..Our data support a model where USP25 counteracts ubiquitination of ERAD substrates by the ubiquitin ligase HRD1, rescuing them from degradation by the proteasome.
  7. Kikkert M, Doolman R, Dai M, Avner R, Hassink G, van Voorden S, et al. Human HRD1 is an E3 ubiquitin ligase involved in degradation of proteins from the endoplasmic reticulum. J Biol Chem. 2004;279:3525-34 pubmed
    ..we characterized the structure and function of the putative human orthologue of yeast Hrd1p/Der3p, designated human HRD1. We show that human HRD1 is a non-glycosylated, stable ER protein with a cytosolic RING-H2 finger domain...
  8. Kaneko M, Ishiguro M, Niinuma Y, Uesugi M, Nomura Y. Human HRD1 protects against ER stress-induced apoptosis through ER-associated degradation. FEBS Lett. 2002;532:147-52 pubmed
    ..The predicted structures are highly conserved from yeast to humans. Indeed, human HRD1 was localized to the ER and ubiquitinated its substrates...
  9. Ballar P, Pabuccuoglu A, Kose F. Different p97/VCP complexes function in retrotranslocation step of mammalian ER-associated degradation (ERAD). Int J Biochem Cell Biol. 2011;43:613-21 pubmed publisher
    ..We investigated these pathways in mammalian cells by assessing the requirements of the mammalian ERAD E3s, gp78 and Hrd1, in degradation of four substrates each with different type of structural lesions: CD3?, Z-variant ?1-antitrypsin, ..
  10. Zhong X, Pittman R. Ataxin-3 binds VCP/p97 and regulates retrotranslocation of ERAD substrates. Hum Mol Genet. 2006;15:2409-20 pubmed
    ..These data suggest that a normal function of AT3 is to regulate flow through the ERAD pathway by modulating VCP-dependent extraction of proteins from the ER. ..
  11. Burr M, van den Boomen D, Bye H, Antrobus R, Wiertz E, Lehner P. MHC class I molecules are preferentially ubiquitinated on endoplasmic reticulum luminal residues during HRD1 ubiquitin E3 ligase-mediated dislocation. Proc Natl Acad Sci U S A. 2013;110:14290-5 pubmed publisher
    ..MHC I HCs) are targeted for endoplasmic reticulum (ER)-associated degradation (ERAD) by the ubiquitin E3 ligase HRD1, and E2 ubiquitin conjugating enzyme UBE2J1, and represent one of the few known endogenous ERAD substrates...
  12. Nadav E, Shmueli A, Barr H, Gonen H, Ciechanover A, Reiss Y. A novel mammalian endoplasmic reticulum ubiquitin ligase homologous to the yeast Hrd1. Biochem Biophys Res Commun. 2003;303:91-7 pubmed
    ..We report the identification and cloning of a human homologue of Hrd1 (hHrd1)...
  13. Bernardi K, Williams J, Kikkert M, van Voorden S, Wiertz E, Ye Y, et al. The E3 ubiquitin ligases Hrd1 and gp78 bind to and promote cholera toxin retro-translocation. Mol Biol Cell. 2010;21:140-51 pubmed publisher
    ..Two retro-translocon components are the Derlins and ER-associated multi-spanning E3 ubiquitin ligases including Hrd1 and gp78. We demonstrated previously that Derlin-1 facilitates CTA1 retro-translocation...
  14. Christianson J, Shaler T, Tyler R, Kopito R. OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD. Nat Cell Biol. 2008;10:272-82 pubmed publisher
    ..that bind to ERAD substrates and, through the SEL1L adaptor, to the ER-membrane-embedded ubiquitin ligase Hrd1. Both proteins contain conserved mannose 6-phosphate receptor homology (MRH) domains, which are required for ..
  15. Gao B, Lee S, Chen A, Zhang J, Zhang D, Kannan K, et al. Synoviolin promotes IRE1 ubiquitination and degradation in synovial fibroblasts from mice with collagen-induced arthritis. EMBO Rep. 2008;9:480-5 pubmed publisher
    The E3 ubiquitin ligase synoviolin (SYVN1) functions as an anti-apoptotic factor that is responsible for the outgrowth of synovial cells during the development of rheumatoid arthritis...
  16. Schulze A, Standera S, Buerger E, Kikkert M, van Voorden S, Wiertz E, et al. The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated degradation pathway. J Mol Biol. 2005;354:1021-7 pubmed
    ..It contains the ubiquitin domain protein (UDP) HERP, the ubiquitin protein ligase HRD1, as well as the retro-translocation factors p97, Derlin-1 and VIMP...
  17. Lilley B, Ploegh H. Multiprotein complexes that link dislocation, ubiquitination, and extraction of misfolded proteins from the endoplasmic reticulum membrane. Proc Natl Acad Sci U S A. 2005;102:14296-301 pubmed
    ..The data presented here define a set of interactions between proteins involved in dislocation of misfolded polypeptides from the ER. ..
  18. Amano T, Yamasaki S, Yagishita N, Tsuchimochi K, Shin H, Kawahara K, et al. Synoviolin/Hrd1, an E3 ubiquitin ligase, as a novel pathogenic factor for arthropathy. Genes Dev. 2003;17:2436-49 pubmed
    ..out immunoscreening by using antirheumatoid synovial cell antibody and identified and cloned "Synoviolin/Hrd1", an E3 ubiquitin ligase...
  19. Fonseca S, Ishigaki S, Oslowski C, Lu S, Lipson K, Ghosh R, et al. Wolfram syndrome 1 gene negatively regulates ER stress signaling in rodent and human cells. J Clin Invest. 2010;120:744-55 pubmed publisher
    ..Moreover, WFS1 stabilized the E3 ubiquitin ligase HRD1, brought ATF6alpha to the proteasome, and enhanced its ubiquitination and proteasome-mediated degradation, leading ..
  20. Sato T, Sako Y, Sho M, Momohara M, Suico M, Shuto T, et al. STT3B-dependent posttranslational N-glycosylation as a surveillance system for secretory protein. Mol Cell. 2012;47:99-110 pubmed publisher
    ..Hence we postulate that STT3B-dependent posttranslational N-glycosylation is part of a triage-salvage system recognizing cryptic N-glycosylation sites of secretory proteins to preserve protein homeostasis. ..
  21. Williams J, Inoue T, Banks L, Tsai B. The ERdj5-Sel1L complex facilitates cholera toxin retrotranslocation. Mol Biol Cell. 2013;24:785-95 pubmed publisher
    ..In the ER, CT is captured by the E3 ubiquitin ligase Hrd1 via an undefined mechanism to prepare for retrotranslocation...
  22. Mueller B, Klemm E, Spooner E, Claessen J, Ploegh H. SEL1L nucleates a protein complex required for dislocation of misfolded glycoproteins. Proc Natl Acad Sci U S A. 2008;105:12325-30 pubmed publisher
    ..We performed a biochemical search for proteins that interact with SEL1L, a protein that is part of the mammalian HRD1 ligase complex and involved in substrate recognition...
  23. Hosokawa N, Wada I, Nagasawa K, Moriyama T, Okawa K, Nagata K. Human XTP3-B forms an endoplasmic reticulum quality control scaffold with the HRD1-SEL1L ubiquitin ligase complex and BiP. J Biol Chem. 2008;283:20914-24 pubmed publisher
    ..using sucrose density gradient centrifugation revealed that the hXTP3-B long isoform associates with the HRD1-SEL1L membrane-anchored ubiquitin ligase complex and BiP, forming a 27 S ER quality control scaffold complex...
  24. Omura T, Kaneko M, Onoguchi M, Koizumi S, Itami M, Ueyama M, et al. Novel functions of ubiquitin ligase HRD1 with transmembrane and proline-rich domains. J Pharmacol Sci. 2008;106:512-9 pubmed
    Human ubiquitin ligase HRD1 is involved in endoplasmic reticulum-associated degradation (ERAD)...
  25. Jiao L, Zhou Q, Su Z, Xu L, Yan Y. High-level extracellular production of Rhizopus oryzae lipase in Pichia pastoris via a strategy combining optimization of gene-copy number with co-expression of ERAD-related proteins. Protein Expr Purif. 2018;147:1-12 pubmed publisher
    ..Subsequently, the endoplasmic reticulum-associated protein-degradation-related genes Ubc1 or/and Hrd1 were co-expressed with ROL to further increase ROL expression...
  26. Izumi T, Fujii R, Izumi T, Nakazawa M, Yagishita N, Tsuchimochi K, et al. Activation of synoviolin promoter in rheumatoid synovial cells by a novel transcription complex of interleukin enhancer binding factor 3 and GA binding protein alpha. Arthritis Rheum. 2009;60:63-72 pubmed publisher
    ..ILF-3 might be a target for RA treatment through its effect on IL-2 in T cells and synoviolin in rheumatoid synovial cells. ..
  27. Upadhyay A, Amanullah A, Chhangani D, Mishra R, Mishra A. Selective multifaceted E3 ubiquitin ligases barricade extreme defense: Potential therapeutic targets for neurodegeneration and ageing. Ageing Res Rev. 2015;24:138-59 pubmed publisher
    ..Here, we review recent literature on the roles of E6-AP, HRD1 and ITCH E3 ubiquitin ligases in the neuro-pathobiological mechanisms, with precise focus on the processes of ..
  28. Kumari R, Gupta P, Tiwari S. Ubc7/Ube2g2 ortholog in Entamoeba histolytica: connection with the plasma membrane and phagocytosis. Parasitol Res. 2018;117:1599-1611 pubmed publisher
    ..orthologs of ER-associated ubiquitin conjugating enzymes (E2s) Ubc6/Ube2j2 and Ubc7/Ube2g2, ubiquitin ligases (E3) Hrd1 and GP78/AMFR, and sensor of UPR, Ire1 in E...
  29. Rani J, Mittal I, Pramanik A, Singh N, Dube N, Sharma S, et al. T2DiACoD: A Gene Atlas of Type 2 Diabetes Mellitus Associated Complex Disorders. Sci Rep. 2017;7:6892 pubmed publisher
    ..A few genes ACE2, ADCYAP1, HDAC4, NCF1, NFE2L2, OSM, SMAD1, TGFB1, BDNF, SYVN1, TXNIP, CD36, CYP2J2, NLRP3 with details of protective role are catalogued...
  30. Joly P, Vignaud H, Di Martino J, Ruiz M, Garin R, Restier L, et al. ERAD defects and the HFE-H63D variant are associated with increased risk of liver damages in Alpha 1-Antitrypsin Deficiency. PLoS ONE. 2017;12:e0179369 pubmed publisher
    ..Using yeast genetic screens, we identified HRD1, an Endoplasmic Reticulum Associated Degradation (ERAD) associated protein, as an inducer of Z-mediated toxicity...
  31. Römisch K. A Case for Sec61 Channel Involvement in ERAD. Trends Biochem Sci. 2017;42:171-179 pubmed publisher
    ..Nevertheless its role as a general export channel has been dismissed, and Hrd1 and Der1 have been proposed as alternatives...
  32. Crowder J, Geigges M, Gibson R, Fults E, Buchanan B, Sachs N, et al. Rkr1/Ltn1 Ubiquitin Ligase-mediated Degradation of Translationally Stalled Endoplasmic Reticulum Proteins. J Biol Chem. 2015;290:18454-66 pubmed publisher
    ..We tested three candidate ubiquitin ligases (Rkr1 and ER-associated Doa10 and Hrd1) for roles in regulating abundance of these proteins...
  33. Chen D, Nicholas J. Promotion of Endoplasmic Reticulum-Associated Degradation of Procathepsin D by Human Herpesvirus 8-Encoded Viral Interleukin-6. J Virol. 2015;89:7979-90 pubmed publisher
    ..of particular ERAD-associated isomerases, lectins, and translocon components, including ERAD E3 ubiquitin ligase HRD1, diminished suppression of CatD by vIL-6...
  34. Huang C, Chu Y, Ye Y, Chen X. Role of HERP and a HERP-related protein in HRD1-dependent protein degradation at the endoplasmic reticulum. J Biol Chem. 2014;289:4444-54 pubmed publisher
    ..Here, we use several lumenal ERAD substrates targeted for degradation by the ubiquitin ligase HRD1 including SHH (sonic hedgehog) and NHK (null Hong Kong ?1-antitrypsin) to study the geometry, organization, and ..
  35. Madsen L, Kriegenburg F, Vala A, Best D, Prag S, Hofmann K, et al. The tissue-specific Rep8/UBXD6 tethers p97 to the endoplasmic reticulum membrane for degradation of misfolded proteins. PLoS ONE. 2011;6:e25061 pubmed publisher
    ..Thus, Rep8 tethers p97 to the ER membrane for efficient ER-associated degradation. ..
  36. Ballar P, Zhong Y, Nagahama M, Tagaya M, Shen Y, Fang S. Identification of SVIP as an endogenous inhibitor of endoplasmic reticulum-associated degradation. J Biol Chem. 2007;282:33908-14 pubmed
    ..These results suggest that SVIP is an endogenous inhibitor of ERAD that acts through regulating the assembly of the gp78-p97/VCP-Derlin1 complex. ..
  37. Sha H, Sun S, Francisco A, Ehrhardt N, Xue Z, Liu L, et al. The ER-associated degradation adaptor protein Sel1L regulates LPL secretion and lipid metabolism. Cell Metab. 2014;20:458-70 pubmed publisher
    Sel1L is an essential adaptor protein for the E3 ligase Hrd1 in the endoplasmic reticulum (ER)-associated degradation (ERAD), a universal quality-control system in the cell; but its physiological role remains unclear...
  38. Sun S, Shi G, Sha H, Ji Y, Han X, Shu X, et al. IRE1α is an endogenous substrate of endoplasmic-reticulum-associated degradation. Nat Cell Biol. 2015;17:1546-55 pubmed publisher
    ..we discover that IRE1α, the sensor of the unfolded protein response (UPR), is a bona fide substrate of the Sel1L-Hrd1 ERAD complex...
  39. van den Boomen D, Lehner P. Identifying the ERAD ubiquitin E3 ligases for viral and cellular targeting of MHC class I. Mol Immunol. 2015;68:106-11 pubmed publisher
    ..Free US11 either rebinds more MHC-I or is itself degraded by the HRD1/SEL1L E3 ligase complex...
  40. Wang W, Yan L, Liu Z, Liu L, Lin J, Liu Z, et al. HSP70-Hrd1 axis precludes the oncorepressor potential of N-terminal misfolded Blimp-1s in lymphoma cells. Nat Commun. 2017;8:363 pubmed publisher
    ..sumoylation, the degradation of lymphoma-associated mutants is accelerated by subversion of this pathway to Hrd1-mediated cytoplasmic sequestration and ubiquitination...
  41. Lee J, Kim W, Gygi S, Ye Y. Characterization of the deubiquitinating activity of USP19 and its role in endoplasmic reticulum-associated degradation. J Biol Chem. 2014;289:3510-7 pubmed publisher
    ..Moreover, our study indicates that the localization of tail-anchored membrane proteins can be subject to regulation in cells. ..
  42. Shin Y, Vavra U, Veit C, Strasser R. The glycan-dependent ERAD machinery degrades topologically diverse misfolded proteins. Plant J. 2018;94:246-259 pubmed publisher
    ..we investigated whether different misfolded glycoproteins require the same set of ERAD factors and are directed to HRD1 complex-mediated degradation in plants...
  43. Shen Y, Ballar P, Apostolou A, Doong H, Fang S. ER stress differentially regulates the stabilities of ERAD ubiquitin ligases and their substrates. Biochem Biophys Res Commun. 2007;352:919-24 pubmed
    ..effects of ER stress on ubiquitin ligase (E3) gp78-mediated ERAD and on the stabilities of gp78 and another ERAD E3 Hrd1. The results showed that ER stress-inducing agent tunicamycin significantly enhanced ERAD in cells that either ..
  44. Soundararajan R, Wang J, Melters D, Pearce D. Glucocorticoid-induced Leucine zipper 1 stimulates the epithelial sodium channel by regulating serum- and glucocorticoid-induced kinase 1 stability and subcellular localization. J Biol Chem. 2010;285:39905-13 pubmed publisher
    ..selectively decreases SGK1 localization to ER as well as its interaction with ER-associated E3 ubiquitin ligases, HRD1 and CHIP...
  45. Tan S, Jiang D, Hu R, Dai A, Gan G, Fu D, et al. Endoplasmic Reticulum Stress Induces HRD1 to Protect Alveolar Type II Epithelial Cells from Apoptosis Induced by Cigarette Smoke Extract. Cell Physiol Biochem. 2017;43:1337-1345 pubmed publisher
    ..Furthermore, CSE induced the expression of Hrd1, a key factor of ER-associated degradation, in AECII...
  46. Ge F, Li H, Yin X. Upregulation of microRNA-125b-5p is involved in the pathogenesis of osteoarthritis by downregulating SYVN1. Oncol Rep. 2017;37:2490-2496 pubmed publisher
    ..First, the levels of miR-125b-5p and synoviolin 1 (SYVN1) were detected among normal, mild OA and severe OA groups with the use of quantitative PCR...
  47. Feng L, Zhang J, Zhu N, Ding Q, Zhang X, Yu J, et al. Ubiquitin ligase SYVN1/HRD1 facilitates degradation of the SERPINA1 Z variant/?-1-antitrypsin Z variant via SQSTM1/p62-dependent selective autophagy. Autophagy. 2017;13:686-702 pubmed publisher
    ..Here, we showed that ER membrane-spanning ubiquitin ligase (E3) SYVN1/HRD1 enhances the degradation of SERPINA1E342K/ATZ through the autophagy-lysosome pathway...
  48. Hoelen H, Zaldumbide A, van Leeuwen W, Torfs E, Engelse M, Hassan C, et al. Proteasomal Degradation of Proinsulin Requires Derlin-2, HRD1 and p97. PLoS ONE. 2015;10:e0128206 pubmed publisher
    ..We demonstrate that specific silencing of Derlin-2, p97 and HRD1 by shRNAs increases steady state levels of proinsulin...
  49. Shen H, Pan X, Zhang J, Zeng Y, Zhou M, Yang L, et al. Endoplasmic Reticulum Stress Induces the Early Appearance of Pro-apoptotic and Anti-apoptotic Proteins in Neurons of Five Familial Alzheimer's Disease Mice. Chin Med J (Engl). 2016;129:2845-2852 pubmed publisher
    ..endoplasmic reticulum-associated protein degradation-associated ubiquitin ligase synovial apoptosis inhibitor 1 [SYVN1]) in the ERS-associated unfolded protein response (UPR) pathway...
  50. Sugiura K, Muro Y, Futamura K, Matsumoto K, Hashimoto N, Nishizawa Y, et al. The unfolded protein response is activated in differentiating epidermal keratinocytes. J Invest Dermatol. 2009;129:2126-35 pubmed publisher
    ..Here, we show that the expression of the UPR-induced proteins Bip/GRP78 and HRD1 was increased in cells in the supra-basal layers of normal human epidermis that contain KCs undergoing ..
  51. Ramachandran S, Osterhaus S, Parekh K, Jacobi A, Behlke M, McCray P. SYVN1, NEDD8, and FBXO2 Proteins Regulate ?F508 Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Ubiquitin-mediated Proteasomal Degradation. J Biol Chem. 2016;291:25489-25504 pubmed
    ..We found that depletion of the ubiquitin ligase SYVN1, the ubiquitin/proteasome system regulator NEDD8, or the F-box protein FBXO2 partially restored ?F508-CFTR-..
  52. Wang Q, Liu Y, Soetandyo N, Baek K, HEGDE R, Ye Y. A ubiquitin ligase-associated chaperone holdase maintains polypeptides in soluble states for proteasome degradation. Mol Cell. 2011;42:758-70 pubmed publisher
    ..Our results reveal a ubiquitin ligase-associated holdase that maintains polypeptide solubility to enhance protein quality control in mammalian cells. ..
  53. Yagishita N, Yamasaki S, Nishioka K, Nakajima T. Synoviolin, protein folding and the maintenance of joint homeostasis. Nat Clin Pract Rheumatol. 2008;4:91-7 pubmed publisher
    ..At least 30% of all newly synthesized, ER-sorted proteins are unfolded. Although degradation of unfolded proteins consumes large amounts of ATP and would seem an unconventional process, it is essential for joint homeostasis. ..
  54. Toh M, Marotte H, Blond J, Jhumka U, Eljaafari A, Mougin B, et al. Overexpression of synoviolin in peripheral blood and synoviocytes from rheumatoid arthritis patients and continued elevation in nonresponders to infliximab treatment. Arthritis Rheum. 2006;54:2109-18 pubmed
    ..Sustained up-regulation of synoviolin by IL-lbeta and TNFalpha may contribute to prolonged survival of immune cells and dysregulated FLS proliferation, leading to RA chronicity. ..
  55. Yamasaki S, Yagishita N, Nishioka K, Nakajima T. The roles of synoviolin in crosstalk between endoplasmic reticulum stress-induced apoptosis and p53 pathway. Cell Cycle. 2007;6:1319-23 pubmed
  56. van de Weijer M, Bassik M, Luteijn R, Voorburg C, Lohuis M, Kremmer E, et al. A high-coverage shRNA screen identifies TMEM129 as an E3 ligase involved in ER-associated protein degradation. Nat Commun. 2014;5:3832 pubmed publisher
  57. Yamamoto K, Suzuki N, Wada T, Okada T, Yoshida H, Kaufman R, et al. Human HRD1 promoter carries a functional unfolded protein response element to which XBP1 but not ATF6 directly binds. J Biochem. 2008;144:477-86 pubmed publisher
    ..However, the molecular basis of this finding remains unclear. Here, we analysed the promoter of human HRD1, which encodes an E3 ubiquitin ligase, an important component of ERAD...
  58. Di X, Wang Y, Han D, Fu Y, Duerfeldt A, Blagg B, et al. Grp94 Protein Delivers γ-Aminobutyric Acid Type A (GABAA) Receptors to Hrd1 Protein-mediated Endoplasmic Reticulum-associated Degradation. J Biol Chem. 2016;291:9526-39 pubmed publisher
    ..This delivers misfolded α1 subunits to the Hrd1-mediated ubiquitination and the valosin-containing protein-mediated extraction pathway...
  59. Zhang T, Xu Y, Liu Y, Ye Y. gp78 functions downstream of Hrd1 to promote degradation of misfolded proteins of the endoplasmic reticulum. Mol Biol Cell. 2015;26:4438-50 pubmed publisher
    ..b>Hrd1 and gp78 are mammalian ubiquitin ligases homologous to Hrd1p, an ubiquitin ligase essential for ERAD in ..
  60. Omura T, Kaneko M, Okuma Y, Matsubara K, Nomura Y. Endoplasmic reticulum stress and Parkinson's disease: the role of HRD1 in averting apoptosis in neurodegenerative disease. Oxid Med Cell Longev. 2013;2013:239854 pubmed publisher
    ..We previously identified the human ubiquitin ligase HRD1 that is associated with protection against ER stress and its associated apoptosis...
  61. Mao J, Xia Q, Liu C, Ying Z, Wang H, Wang G. A critical role of Hrd1 in the regulation of optineurin degradation and aggresome formation. Hum Mol Genet. 2017;26:1877-1889 pubmed publisher
    ..Moreover, we found that Hrd1, an E3 ubiquitin ligase, could play an important role in the protein quality control of OPTN...
  62. Kawada K, Mimori S. Implication of Endoplasmic Reticulum Stress in Autism Spectrum Disorder. Neurochem Res. 2018;43:147-152 pubmed publisher
    ..ER stress elevates the expression of the ubiquitin-protein ligase HRD1 for the degradation of unfolded proteins...
  63. Fukagai K, Waku T, Chowdhury A, Kubo K, Matsumoto M, Kato H, et al. USP15 stabilizes the transcription factor Nrf1 in the nucleus, promoting the proteasome gene expression. Biochem Biophys Res Commun. 2016;478:363-370 pubmed publisher
    ..into the endoplasmic reticulum (ER) and furthermore by two independent ubiquitin-proteasome pathways, comprising Hrd1 and ?-TrCP in the cytoplasm and nucleus, respectively...
  64. Harada K, Kato M, Nakamura N. USP19-Mediated Deubiquitination Facilitates the Stabilization of HRD1 Ubiquitin Ligase. Int J Mol Sci. 2016;17: pubmed
    ..In this study, HRD1, an ERAD ubiquitin ligase, is shown to be a novel substrate for USP19...
  65. Schoebel S, Mi W, Stein A, Ovchinnikov S, Pavlovicz R, DiMaio F, et al. Cryo-EM structure of the protein-conducting ERAD channel Hrd1 in complex with Hrd3. Nature. 2017;548:352-355 pubmed publisher
    ..In Saccharomyces cerevisiae, both pathways require the ubiquitin ligase Hrd1, a multi-spanning membrane protein with a cytosolic RING finger domain...
  66. Tanabe C, Maeda T, Zou K, Liu J, Liu S, Nakajima T, et al. The ubiquitin ligase synoviolin up-regulates amyloid ? production by targeting a negative regulator of ?-secretase, Rer1, for degradation. J Biol Chem. 2012;287:44203-11 pubmed publisher
    ..Thus, it is likely that Syvn regulates the assembly of the ?-secretase complex via the degradation of Rer1, which results in the generation of A?. ..
  67. Chen Q, Maltagliati A. Nrf2 at the Heart of Oxidative Stress and Cardiac Protection. Physiol Genomics. 2017;:physiolgenomics.00041.2017 pubmed publisher
    ..been revealed, including removal of Keap1 by autophagy due to p62/SQSTM1 binding, inhibition of ?TrCP or Synoviolin/Hrd1-mediated ubiquitination of Nrf2, and de novo Nrf2 protein translation...
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    ..ER degradation-enhancing mannosidase-like protein 1, ER degradation-enhancing mannosidase-like protein 2, and HRD1 were elevated in 5-day-old A?42-expressing flies as compared to controls but not in 18-day-old flies...
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    ..Here, we showed an inverse relationship between endoplasmic reticulum membrane ubiquitin ligase (E3) Hrd1 expression and p-tau accumulation in the hippocampal neurons of AD, and proposed that Hrd1 may be a negative ..
  70. Shi G, Somlo D, Kim G, Prescianotto Baschong C, Sun S, Beuret N, et al. ER-associated degradation is required for vasopressin prohormone processing and systemic water homeostasis. J Clin Invest. 2017;127:3897-3912 pubmed publisher
    ..hormone arginine-vasopressin, within the ER requires the ER-associated degradation (ERAD) activity of the Sel1L-Hrd1 protein complex...
  71. Shmueli A, Tsai Y, Yang M, Braun M, Weissman A. Targeting of gp78 for ubiquitin-mediated proteasomal degradation by Hrd1: cross-talk between E3s in the endoplasmic reticulum. Biochem Biophys Res Commun. 2009;390:758-62 pubmed publisher
    ..The two for which the greatest amount of information exists are the RING finger proteins gp78 and Hrd1, which are the structural orthologs of the yeast ERAD E3 Hrd1p...
  72. Peters S, Déry M, LeBlanc A. Familial prion protein mutants inhibit Hrd1-mediated retrotranslocation of misfolded proteins by depleting misfolded protein sensor BiP. Hum Mol Genet. 2016;25:976-88 pubmed publisher
    ..A gain- and loss-of-function approach identified human E3 ubiquitin ligase, Hrd1, as a critical regulator of PrP retrotranslocation in mammalian cells...
  73. Zhong Y, Shen H, Wang Y, Yang Y, Yang P, Fang S. Identification of ERAD components essential for dislocation of the null Hong Kong variant of α-1-antitrypsin (NHK). Biochem Biophys Res Commun. 2015;458:424-8 pubmed publisher
    ..RNAi revealed that 12 out of 21 ERAD components examined are required for efficient dislocation of NHK among which Hrd1, Sel1L, GRP94 and p97/VCP are critically required...
  74. Hwang J, Walczak C, Shaler T, Olzmann J, Zhang L, Elias J, et al. Characterization of protein complexes of the endoplasmic reticulum-associated degradation E3 ubiquitin ligase Hrd1. J Biol Chem. 2017;292:9104-9116 pubmed publisher
    b>Hrd1 is the core structural component of a large endoplasmic reticulum membrane-embedded protein complex that coordinates the destruction of folding-defective proteins in the early secretory pathway...
  75. Kaneko M, Nomura Y. [Protective effects of HRD1 and 4-phenylbutyric acid against neuronal cell death]. Nihon Yakurigaku Zasshi. 2004;124:391-8 pubmed
    ..We have identified and characterized human HRD1 as a ubiquitin ligase involved in ERAD that protects against ER stress-induced cell death...
  76. Aratani S, Fujita H, Yagishita N, Yamano Y, Okubo Y, Nishioka K, et al. Inhibitory effects of ubiquitination of synoviolin by PADI4. Mol Med Rep. 2017;16:9203-9209 pubmed publisher
    ..The group has previously cloned an E3 ubiquitin ligase, synoviolin (SYVN1), from the RA synovium, demonstrating that SYVN1 serves critical roles in synovial hyperplasia...
  77. Jiao D, Chen Y, Liu Y, Ju Y, Long J, Du J, et al. SYVN1, an ERAD E3 Ubiquitin Ligase, Is Involved in GABAA?1 Degradation Associated with Methamphetamine-Induced Conditioned Place Preference. Front Mol Neurosci. 2017;10:313 pubmed publisher
    ..CPP formation was accompanied by a significant increase in the expression of Synovial apoptosis inhibitor 1 (SYVN1), an endoplasmic reticulum (ER)-associated degradation (ERAD) E3 ubiquitin ligase, in the Dstr...
  78. Nakatsukasa K, Kamura T. Subcellular Fractionation Analysis of the Extraction of Ubiquitinated Polytopic Membrane Substrate during ER-Associated Degradation. PLoS ONE. 2016;11:e0148327 pubmed publisher
    ..By contrast, lipid droplet formation, which was suggested to be dispensable for the degradation of Hrd1-substrates in yeast, was not required for the degradation of Ste6*...