{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSYVN1—also known as HRD1 or synoviolin—is an evolutionarily conserved, ER‐resident E3 ubiquitin ligase that plays a central role in endoplasmic reticulum–associated degradation (ERAD) and protein quality control. It recognizes misfolded, unassembled, or aberrant proteins in the early secretory pathway and earmarks them for ubiquitination and subsequent degradation by the proteasome (thereby sometimes also engaging autophagic mechanisms). SYVN1 acts in conjunction with a cohort of adaptor proteins and ER‐resident chaperones—including SEL1L, OS-9, XTP3-B, and others—to form dynamic, multiprotein “quality control” complexes that mediate substrate selection, retro‐translocation across the ER membrane, and efficient degradation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its housekeeping function in proteostasis, SYVN1 modulates the degradation of several physiologically and pathologically important substrates. For example, it promotes the clearance of proteins implicated in neurodegenerative (e.g. mutant amyloid precursor protein and polyglutamine-expanded huntingtin), metabolic, immunological, and proliferative disorders (e.g. defective T-cell receptor components, unassembled Ig chains, mutant CFTR, misfolded PMP22, and even tumor suppressors such as p53). Defects or dysregulation in SYVN1 activity have been linked to the pathogenesis of conditions such as Alzheimer’s disease, rheumatoid arthritis, liver cirrhosis, type 1 diabetes, and various cancers, underscoring its dual role in cellular protection and disease progression when ER homeostasis is compromised."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "34"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nSYVN1 activity and expression are tightly regulated by its assembly into higher‐order complexes and through interactions with other regulatory factors such as deubiquitinating enzymes (e.g. USP19), stress‐inducible cofactors (e.g. Herp and FAM8A1), and components of the retro‐translocation apparatus (e.g. Derlin family proteins). These interactions modulate its substrate specificity, stability, and post‐translational modification status, thereby ensuring an appropriate balance between protein folding and degradation under both basal and stress conditions. The manipulation of SYVN1 function—by either restoring its activity to alleviate proteotoxic stress or inhibiting it to prevent unwanted degradation of partially functional proteins—offers promising therapeutic avenues for a wide range of human pathologies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "35", "end_ref": "39"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Masayuki Kaneko, Masataro Ishiguro, Yoshifumi Niinuma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human HRD1 protects against ER stress-induced apoptosis through ER-associated degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0014-5793(02)03660-8"}], "href": "https://doi.org/10.1016/s0014-5793(02"}, {"type": "t", "text": "03660-8) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12459480"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12459480"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Eran Nadav, Ayelet Shmueli, Haim Barr, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel mammalian endoplasmic reticulum ubiquitin ligase homologous to the yeast Hrd1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0006-291x(03)00279-1"}], "href": "https://doi.org/10.1016/s0006-291x(03"}, {"type": "t", "text": "00279-1) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12646171"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12646171"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Marjolein Kikkert, Ram Doolman, Min Dai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human HRD1 is an E3 ubiquitin ligase involved in degradation of proteins from the endoplasmic reticulum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M307453200"}], "href": "https://doi.org/10.1074/jbc.M307453200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14593114"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14593114"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Satoshi Yamasaki, Naoko Yagishita, Takeshi Sasaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase 'Synoviolin'."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7601490"}], "href": "https://doi.org/10.1038/sj.emboj.7601490"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17170702"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17170702"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Masayuki Kaneko, Saori Yasui, Yoshifumi Niinuma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A different pathway in the endoplasmic reticulum stress-induced expression of human HRD1 and SEL1 genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2007.10.033"}], "href": "https://doi.org/10.1016/j.febslet.2007.10.033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17967421"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17967421"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "John C Christianson, Thomas A Shaler, Ryan E Tyler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1689"}], "href": "https://doi.org/10.1038/ncb1689"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18264092"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18264092"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Monica Cattaneo, Mieko Otsu, Claudio Fagioli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SEL1L and HRD1 are involved in the degradation of unassembled secretory Ig-mu chains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.21364"}], "href": "https://doi.org/10.1002/jcp.21364"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18314878"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18314878"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Nobuko Hosokawa, Ikuo Wada, Koji Nagasawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human XTP3-B forms an endoplasmic reticulum quality control scaffold with the HRD1-SEL1L ubiquitin ligase complex and BiP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M709336200"}], "href": "https://doi.org/10.1074/jbc.M709336200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18502753"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18502753"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Keisuke Yamamoto, Natsumi Suzuki, Tadashi Wada, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human HRD1 promoter carries a functional unfolded protein response element to which XBP1 but not ATF6 directly binds."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biochem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jb/mvn091"}], "href": "https://doi.org/10.1093/jb/mvn091"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18664523"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18664523"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Marian L Burr, Florencia Cano, Stanislava Svobodova, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HRD1 and UBE2J1 target misfolded MHC class I heavy chains for endoplasmic reticulum-associated degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1016229108"}], "href": "https://doi.org/10.1073/pnas.1016229108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21245296"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21245296"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Hui Yang, Xiaoyan Zhong, Petek Ballar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitin ligase Hrd1 enhances the degradation and suppresses the toxicity of polyglutamine-expanded huntingtin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2006.10.031"}], "href": "https://doi.org/10.1016/j.yexcr.2006.10.031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17141218"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17141218"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Satoshi Yamasaki, Naoko Yagishita, Kusuki Nishioka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The roles of synoviolin in crosstalk between endoplasmic reticulum stress-induced apoptosis and p53 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cc.6.11.4277"}], "href": "https://doi.org/10.4161/cc.6.11.4277"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17582219"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17582219"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Naoko Yagishita, Satoshi Yamasaki, Kusuki Nishioka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Synoviolin, protein folding and the maintenance of joint homeostasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Clin Pract Rheumatol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncprheum0699"}], "href": "https://doi.org/10.1038/ncprheum0699"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18235538"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18235538"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Petek Ballar, Ahmet Uygar Ors, Hui Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential regulation of CFTRDeltaF508 degradation by ubiquitin ligases gp78 and Hrd1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biochem Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.biocel.2009.10.005"}], "href": "https://doi.org/10.1016/j.biocel.2009.10.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19828134"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19828134"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Ayelet Shmueli, Yien Che Tsai, Mei Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeting of gp78 for ubiquitin-mediated proteasomal degradation by Hrd1: cross-talk between E3s in the endoplasmic reticulum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2009.10.045"}], "href": "https://doi.org/10.1016/j.bbrc.2009.10.045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19835843"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19835843"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Kaleena M Bernardi, Jeffrey M Williams, Marjolein Kikkert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The E3 ubiquitin ligases Hrd1 and gp78 bind to and promote cholera toxin retro-translocation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e09-07-0586"}], "href": "https://doi.org/10.1091/mbc.e09-07-0586"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19864457"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19864457"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Shuhei Ishikura, Allan M Weissman, Juan S Bonifacino "}, {"type": "b", "children": [{"type": "t", "text": "Serine residues in the cytosolic tail of the T-cell antigen receptor alpha-chain mediate ubiquitination and endoplasmic reticulum-associated degradation of the unassembled protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.127936"}], "href": "https://doi.org/10.1074/jbc.M110.127936"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20519503"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20519503"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Ryo Saito, Masayuki Kaneko, Yasunobu Okuma, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Correlation between decrease in protein levels of ubiquitin ligase HRD1 and amyloid-beta production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pharmacol Sci (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1254/jphs.10118sc"}], "href": "https://doi.org/10.1254/jphs.10118sc"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20606367"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20606367"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Melanie Kny, Sybille Standera, Rasmus Hartmann-Petersen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Herp regulates Hrd1-mediated ubiquitylation in a ubiquitin-like domain-dependent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.134551"}], "href": "https://doi.org/10.1074/jbc.M110.134551"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21149444"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21149444"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Jeffrey M Williams, Takamasa Inoue, Lindsey Banks, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ERdj5-Sel1L complex facilitates cholera toxin retrotranslocation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E12-07-0522"}], "href": "https://doi.org/10.1091/mbc.E12-07-0522"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23363602"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23363602"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Elisa Bianchini, Marina Fanin, Kamel Mamchaoui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Unveiling the degradative route of the V247M α-sarcoglycan mutant responsible for LGMD-2D."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddu088"}], "href": "https://doi.org/10.1093/hmg/ddu088"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24565866"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24565866"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Hanneke Hoelen, Arnaud Zaldumbide, Wouter F van Leeuwen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proteasomal Degradation of Proinsulin Requires Derlin-2, HRD1 and p97."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0128206"}], "href": "https://doi.org/10.1371/journal.pone.0128206"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26107514"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26107514"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Yue-Mei Xu, Hong-Jiang Wang, Fang Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HRD1 suppresses the growth and metastasis of breast cancer cells by promoting IGF-1R degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.5733"}], "href": "https://doi.org/10.18632/oncotarget.5733"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26536657"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26536657"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Kumi Harada, Masako Kato, Nobuhiro Nakamura "}, {"type": "b", "children": [{"type": "t", "text": "USP19-Mediated Deubiquitination Facilitates the Stabilization of HRD1 Ubiquitin Ligase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms17111829"}], "href": "https://doi.org/10.3390/ijms17111829"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27827840"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27827840"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Lijie Feng, Jin Zhang, Na Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitin ligase SYVN1/HRD1 facilitates degradation of the SERPINA1 Z variant/α-1-antitrypsin Z variant via SQSTM1/p62-dependent selective autophagy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autophagy (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15548627.2017.1280207"}], "href": "https://doi.org/10.1080/15548627.2017.1280207"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28121484"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28121484"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Jiahui Mao, Qin Xia, Chunfeng Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A critical role of Hrd1 in the regulation of optineurin degradation and aggresome formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddx096"}], "href": "https://doi.org/10.1093/hmg/ddx096"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28334804"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28334804"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Jasmin Schulz, Dönem Avci, Markus A Queisser, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Conserved cytoplasmic domains promote Hrd1 ubiquitin ligase complex formation for ER-associated degradation (ERAD)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.206847"}], "href": "https://doi.org/10.1242/jcs.206847"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28827405"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28827405"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Yujie Huang, Yifei Sun, Yizhi Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HRD1 prevents apoptosis in renal tubular epithelial cells by mediating eIF2α ubiquitylation and degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-017-0002-y"}], "href": "https://doi.org/10.1038/s41419-017-0002-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29233968"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29233968"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Hisae Kadowaki, Pasjan Satrimafitrah, Yasunari Takami, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular mechanism of ER stress-induced pre-emptive quality control involving association of the translocon, Derlin-1, and HRD1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-25724-x"}], "href": "https://doi.org/10.1038/s41598-018-25724-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29743537"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29743537"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Zejun Gao, Hai Wang, Hangyu Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Long non-coding RNA CASC2 inhibits breast cancer cell growth and metastasis through the regulation of the miR-96-5p/SYVN1 pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2018.4522"}], "href": "https://doi.org/10.3892/ijo.2018.4522"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30106139"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30106139"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Liu Liu, Le Yu, Cheng Zeng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "E3 Ubiquitin Ligase HRD1 Promotes Lung Tumorigenesis by Promoting Sirtuin 2 Ubiquitination and Degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00257-19"}], "href": "https://doi.org/10.1128/MCB.00257-19"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31932479"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31932479"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Neha Shrestha, Tongyu Liu, Yewei Ji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sel1L-Hrd1 ER-associated degradation maintains β cell identity via TGF-β signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI134874"}], "href": "https://doi.org/10.1172/JCI134874"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32182217"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32182217"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Xin Guo, Aman Wang, Wen Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HRD1 inhibits fatty acid oxidation and tumorigenesis by ubiquitinating CPT2 in triple-negative breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Oncol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1878-0261.12856"}], "href": "https://doi.org/10.1002/1878-0261.12856"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33207079"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33207079"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Ya Fan, Jia Wang, Wen Jin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CircNR3C2 promotes HRD1-mediated tumor-suppressive effect via sponging miR-513a-3p in triple-negative breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12943-021-01321-x"}], "href": "https://doi.org/10.1186/s12943-021-01321-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33530981"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33530981"}]}, {"type": "r", "ref": 35, "children": [{"type": "t", "text": "Myew-Ling Toh, Hubert Marotte, Jean-Luc Blond, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of synoviolin in peripheral blood and synoviocytes from rheumatoid arthritis patients and continued elevation in nonresponders to infliximab treatment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arthritis Rheum (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/art.21926"}], "href": "https://doi.org/10.1002/art.21926"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16802346"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16802346"}]}, {"type": "r", "ref": 36, "children": [{"type": "t", "text": "Tomohiro Omura, Masayuki Kaneko, Masayuki Onoguchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel functions of ubiquitin ligase HRD1 with transmembrane and proline-rich domains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pharmacol Sci (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1254/jphs.08005fp"}], "href": "https://doi.org/10.1254/jphs.08005fp"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18344614"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18344614"}]}, {"type": "r", "ref": 37, "children": [{"type": "t", "text": "Marian L Burr, Dick J H van den Boomen, Helen Bye, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MHC class I molecules are preferentially ubiquitinated on endoplasmic reticulum luminal residues during HRD1 ubiquitin E3 ligase-mediated dislocation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1303380110"}], "href": "https://doi.org/10.1073/pnas.1303380110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23929775"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23929775"}]}, {"type": "r", "ref": 38, "children": [{"type": "t", "text": "Julia Leitman, Marina Shenkman, Yana Gofman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Herp coordinates compartmentalization and recruitment of HRD1 and misfolded proteins for ERAD."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E13-06-0350"}], "href": "https://doi.org/10.1091/mbc.E13-06-0350"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24478453"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24478453"}]}, {"type": "r", "ref": 39, "children": [{"type": "t", "text": "Juncheng Wei, Bryan T Harada, Dan Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HRD1-mediated METTL14 degradation regulates m"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "6"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "A mRNA modification to suppress ER proteotoxic liver disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2021.10.028"}], "href": "https://doi.org/10.1016/j.molcel.2021.10.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34847358"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34847358"}]}]}]}