Property Summary

NCBI Gene PubMed Count 68
PubMed Score 34.50
PubTator Score 79.89

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (7)

Disease log2 FC p
ependymoma 1.100 2.1e-02
oligodendroglioma 1.100 1.1e-02
pancreatic ductal adenocarcinoma liver m... -1.177 1.5e-03
breast carcinoma 1.100 1.8e-02
non primary Sjogren syndrome sicca 1.200 1.9e-02
lung adenocarcinoma 1.100 1.5e-09
ovarian cancer 1.200 1.5e-04

Protein-protein Interaction (4)

Gene RIF (42)

PMID Text
26945068 OS-9, an ER-resident lectin, acts downstream of Grp94 to further recognize misfolded alpha1 subunits in a glycan-dependent manner. This delivers misfolded alpha1 subunits to the Hrd1-mediated ubiquitination and the valosin-containing protein-mediated extraction pathway.
26536657 These findings uncover a novel role for HRD1 in breast cancer.
26471130 The inherently unstable nature of the human SEL1L protein lies in its transmembrane domain, and that association of HRD1 with the SEL1L transmembrane domain restored its stability.
26107514 specific silencing of Derlin-2, p97 and HRD1 by shRNAs increases steady state levels of proinsulin. these ERAD constituents are critically involved in proinsulin degradation and may therefore also play a role in subsequent antigen generation.
25385046 Charcot-Marie-Tooth disease-related PMP22 is trapped in the endoplasmic reticulum by calnexin-dependent retention and Rer1-mediated early Golgi retrieval systems and partly degraded by the Hrd1-mediated endoplasmic reticulum-associated degradation system.
24636985 identified Hrd1 as a novel E3 ubiquitin ligase responsible for compromised Nrf2 response during liver cirrhosis
24584735 HRD1 and RMA1 may therefore be negative regulators of disease-associated transporter ABCG5/ABCG8.
24565866 Results show that HRD1 and RFP2 contributes are required for the disposal of V247M alpha-sarcoglycan mutant.
24478453 Herp localizes to the endoplasmic reticulum-derived quality control compartment (ERQC) and recruits HRD1, which targets to endoplasmic reticulum associated degradation the substrate presented by the OS-9 lectin at the ERQC.
24366871 a new HRD1-associated membrane protein named HERP2, which is homologous to the previously identified HRD1 partner HERP1. Despite sequence homology, HERP2 is constitutively expressed in cells, whereas HERP1 is highly induced by ER stress.
24100225 the interactions between P97 and these motifs, including VCP-binding motif (VBM) and VCP-interacting motif (VIM). The solution structures of the VBM motif from HRD1 and the VIM motif from SVIP are both comprised mainly of a single alpha-helix.
23929775 subset of integral membrane proteins, therefore, requires an early dislocation event to expose part of their luminal domain to the cytosol, before HRD1-mediated polyubiquitination and dislocation
23867461 derlin2 functions with HRD1 in ERAD of certain substrates independent of their glycosylation status.
23363602 ERdj5, by binding to Sel1L, triggers BiP-Cholera toxin interaction proximal to the Hrd1 complex; postulate this scenario enables the Hrd1-associated retrotranslocation machinery to capture the toxin efficiently once the toxin is released from BiP
23129766 Synoviolin up-regulates amyloid beta production by targeting a negative regulator of gamma-secretase, Rer1, for degradation.
22280354 Hrd1 functions as an E3 targeting tau or abnormal p-tau for proteasome degradation.
21454652 regulation of the stability and assembly of the HRD1-SEL1L complex is critical to optimize the degradation kinetics of ERAD substrates
21245296 data support a physiological role for HRD1 and UBE2J1 in the homeostatic regulation of MHC class I assembly and expression
21149444 binding of Herp to Hrd1-containing ERAD complexes positively regulates the ubiquitylation activity of these complexes, thus permitting survival of the cell during ER stress.
20606367 Using brain tissue from Alzheimer's disease and normal subjects, a negative correlation was found between the expressed levels of HRD1 and of amyloid-beta; this suggests the possible involvement of HRD1 in amyloid-beta generation.
20519503 serine-dependent, HRD1-mediated ubiquitination targets TCRalpha to the ERAD pathway
20237263 HRD1 promotes ubiquitination and degradation of amyloid precursor protein (APP) that leads to decreased amyloid beta production, whereas HRD1 loss in Alzheimer's disease leads to accumulation of APP and increased levels of amyloid beta.
19864457 These data demonstrate a role of the E3 ubiquitin ligases in CTA1 retro-translocation.
19835843 Hrd1 targets gp78 for proteasomal degradation independent of the ubiquitin ligase activity of gp78, without evidence of a reciprocal effect.
19828134 The results support that gp78 is an E3 targeting CFTRDeltaF508 for degradation and Hrd1 inhibits CFTRDeltaF508 degradation by acting as an E3 for gp78.
19443960 involved in endoplasmic reticulum-associated degradation that protects against ER stress-induced cell death.(review)
19116932 ILF-3, which has been known to regulate IL-2 expression in T cells, up-regulates synoviolin expression with GABPalpha in rheumatoid synovial cells
18664523 analysed the promoter of human HRD1, which encodes an E3 ubiquitin ligase, an important component of ERAD
18502753 XTP3-B forms an endoplasmic reticulum quality control scaffold with the HRD1-SEL1L ubiquitin ligase complex and BiP
18344614 proline-rich domain of HRD1 is necessary to promote the degradation of Pael-R and that the protein's transmembrane domain is necessary to transfer Pael-R from the endoplasmic reticulum (ER) to the cytosol.
18314878 These findings reveal a role for SEL1L and HRD1 in IgM quality control.
18264092 OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD
18235538 overexpressed in the synovial cells of patients with rheumatoid arthritis, resulting in a state in which the cell deals with accumulated unfolded proteins excessively
17967421 endoplasmic reticulum stress-induced HRD1 and SEL1 expressions are mediated by IRE1-XBP1- and ATF6-dependent pathways, respectively
17582219 Review. In addition to its canonical role in endoplasmic-reticulum-associated degradation, synoviolin targets tumor suppressor gene p53 for proteasomal degradation, suggesting crosstalk between ERAD and p53 mediated apoptotic pathway under ER stress.
17170702 the endoplasmic reticulum-resident ubiquitin ligase 'Synoviolin' destroys p53
17141218 These results suggest that Hrd1 is a novel htt-interacting protein that can target pathogenic httN for degradation and is able to protect cells against httN-induced cell death.
16802346 Elevated peripheral blood (PB) levels of synoviolin were associated with nonresponse to infliximab treatment. Upregulation of synoviolin by IL-lbeta and TNFalpha may contribute to prolonged survival of immune cells and rheumatoid arthritis chronicity.
16786162 Results showed that Synoviolin, a novel causative factor for rheumatoid arthritis, is up-regulated in proliferating synovial cells in the disease.
14593114 Human HRD1 is an E3 ubiquitin ligase involved in degradation of proteins from the endoplasmic reticulum
12646171 endogenous hHrd1 resides in the ER and has a ubiquitin-ligase activity
12459480 HRD1 protects against endoplasmic reticulum stress-induced apoptosis through endoplasmic reticulum-associated degradation.

AA Sequence

MFRTAVMMAASLALTGAVVAHAYYLKHQFYPTVVYLTKSSPSMAVLYIQAFVLVFLLGKVMGKVFFGQLR      1 - 70
AAEMEHLLERSWYAVTETCLAFTVFRDDFSPRFVALFTLLLFLKCFHWLAEDRVDFMERSPNISWLFHCR     71 - 140
IVSLMFLLGILDFLFVSHAYHSILTRGASVQLVFGFEYAILMTMVLTIFIKYVLHSVDLQSENPWDNKAV    141 - 210
YMLYTELFTGFIKVLLYMAFMTIMIKVHTFPLFAIRPMYLAMRQFKKAVTDAIMSRRAIRNMNTLYPDAT    211 - 280
PEELQAMDNVCIICREEMVTGAKRLPCNHIFHTSCLRSWFQRQQTCPTCRMDVLRASLPAQSPPPPEPAD    281 - 350
QGPPPAPHPPPLLPQPPNFPQGLLPPFPPGMFPLWPPMGPFPPVPPPPSSGEAVAPPSTSAAALSRPSGA    351 - 420
ATTTAAGTSATAASATASGPGSGSAPEAGPAPGFPFPPPWMGMPLPPPFAFPPMPVPPAGFAGLTPEELR    421 - 490
ALEGHERQHLEARLQSLRNIHTLLDAAMLQINQYLTVLASLGPPRPATSVNSTEETATTVVAAASSTSIP    491 - 560
SSEATTPTPGASPPAPEMERPPAPESVGTEEMPEDGEPDAAELRRRRLQKLESPVAH                 561 - 617
//

Text Mined References (76)

PMID Year Title
26945068 2016 Grp94 Protein Delivers ?-Aminobutyric Acid Type A (GABAA) Receptors to Hrd1 Protein-mediated Endoplasmic Reticulum-associated Degradation.
26536657 2015 HRD1 suppresses the growth and metastasis of breast cancer cells by promoting IGF-1R degradation.
26471130 2016 Association of the SEL1L protein transmembrane domain with HRD1 ubiquitin ligase regulates ERAD-L.
26107514 2015 Proteasomal Degradation of Proinsulin Requires Derlin-2, HRD1 and p97.
25660456 2015 Identification of ERAD components essential for dislocation of the null Hong Kong variant of ?-1-antitrypsin (NHK).
25385046 2014 Rer1 and calnexin regulate endoplasmic reticulum retention of a peripheral myelin protein 22 mutant that causes type 1A Charcot-Marie-Tooth disease.
24636985 2014 Hrd1 suppresses Nrf2-mediated cellular protection during liver cirrhosis.
24584735 2014 Inhibition of post-translational N-glycosylation by HRD1 that controls the fate of ABCG5/8 transporter.
24565866 2014 Unveiling the degradative route of the V247M ?-sarcoglycan mutant responsible for LGMD-2D.
24478453 2014 Herp coordinates compartmentalization and recruitment of HRD1 and misfolded proteins for ERAD.
24366871 2014 Role of HERP and a HERP-related protein in HRD1-dependent protein degradation at the endoplasmic reticulum.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24100225 2013 Structural and mechanistic insights into the arginine/lysine-rich peptide motifs that interact with P97/VCP.
24068323 2013 A deubiquitinase negatively regulates retro-translocation of nonubiquitinated substrates.
23929775 2013 MHC class I molecules are preferentially ubiquitinated on endoplasmic reticulum luminal residues during HRD1 ubiquitin E3 ligase-mediated dislocation.
23867461 2013 Derlin2 protein facilitates HRD1-mediated retro-translocation of sonic hedgehog at the endoplasmic reticulum.
23710284 2013 Endoplasmic reticulum stress and Parkinson's disease: the role of HRD1 in averting apoptosis in neurodegenerative disease.
23363602 2013 The ERdj5-Sel1L complex facilitates cholera toxin retrotranslocation.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23129766 2012 The ubiquitin ligase synoviolin up-regulates amyloid ? production by targeting a negative regulator of ?-secretase, Rer1, for degradation.
22607976 2012 STT3B-dependent posttranslational N-glycosylation as a surveillance system for secretory protein.
22590560 2012 Ubiquitin-specific protease 25 functions in Endoplasmic Reticulum-associated degradation.
22280354 2012 Hrd1 facilitates tau degradation and promotes neuron survival.
22013210 2011 The unfolded protein response: integrating stress signals through the stress sensor IRE1?.
21949850 2011 The tissue-specific Rep8/UBXD6 tethers p97 to the endoplasmic reticulum membrane for degradation of misfolded proteins.
21636303 2011 A ubiquitin ligase-associated chaperone holdase maintains polypeptides in soluble states for proteasome degradation.
21454652 2011 SEL1L protein critically determines the stability of the HRD1-SEL1L endoplasmic reticulum-associated degradation (ERAD) complex to optimize the degradation kinetics of ERAD substrates.
21269460 2011 Initial characterization of the human central proteome.
21245296 2011 HRD1 and UBE2J1 target misfolded MHC class I heavy chains for endoplasmic reticulum-associated degradation.
21149444 2011 Herp regulates Hrd1-mediated ubiquitylation in a ubiquitin-like domain-dependent manner.
21062743 2011 Mannose trimming is required for delivery of a glycoprotein from EDEM1 to XTP3-B and to late endoplasmic reticulum-associated degradation steps.
20606367 2010 Correlation between decrease in protein levels of ubiquitin ligase HRD1 and amyloid-beta production.
20519503 2010 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.
20237263 2010 Loss of HRD1-mediated protein degradation causes amyloid precursor protein accumulation and amyloid-beta generation.
20068231 2010 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
19946888 2010 Defining the membrane proteome of NK cells.
19864457 2010 The E3 ubiquitin ligases Hrd1 and gp78 bind to and promote cholera toxin retro-translocation.
19835843 2009 Targeting of gp78 for ubiquitin-mediated proteasomal degradation by Hrd1: cross-talk between E3s in the endoplasmic reticulum.
19828134 2010 Differential regulation of CFTRDeltaF508 degradation by ubiquitin ligases gp78 and Hrd1.
19443960 2009 [Possible involvement of HRD1 (ubiquitin E3 ligase) in neurodegenerative diseases].
19135427 2009 USP14 inhibits ER-associated degradation via interaction with IRE1alpha.
19116932 2009 Activation of synoviolin promoter in rheumatoid synovial cells by a novel transcription complex of interleukin enhancer binding factor 3 and GA binding protein alpha.
19103148 2009 CYP3A4 ubiquitination by gp78 (the tumor autocrine motility factor receptor, AMFR) and CHIP E3 ligases.
18691976 2008 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18664523 2008 Human HRD1 promoter carries a functional unfolded protein response element to which XBP1 but not ATF6 directly binds.
18656546 2008 Ubxd1 is a novel co-factor of the human p97 ATPase.
18502753 2008 Human XTP3-B forms an endoplasmic reticulum quality control scaffold with the HRD1-SEL1L ubiquitin ligase complex and BiP.
18369366 2008 Synoviolin promotes IRE1 ubiquitination and degradation in synovial fibroblasts from mice with collagen-induced arthritis.
18344614 2008 Novel functions of ubiquitin ligase HRD1 with transmembrane and proline-rich domains.
18314878 2008 SEL1L and HRD1 are involved in the degradation of unassembled secretory Ig-mu chains.
18264092 2008 OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD.
18235538 2008 Synoviolin, protein folding and the maintenance of joint homeostasis.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17974005 2007 The full-ORF clone resource of the German cDNA Consortium.
17967421 2007 A different pathway in the endoplasmic reticulum stress-induced expression of human HRD1 and SEL1 genes.
17582219 2007 The roles of synoviolin in crosstalk between endoplasmic reticulum stress-induced apoptosis and p53 pathway.
17170702 2007 Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase 'Synoviolin'.
17141218 2007 Ubiquitin ligase Hrd1 enhances the degradation and suppresses the toxicity of polyglutamine-expanded huntingtin.
17059562 2006 A ubiquitin ligase HRD1 promotes the degradation of Pael receptor, a substrate of Parkin.
16847254 2006 An amphipathic helix targets serum and glucocorticoid-induced kinase 1 to the endoplasmic reticulum-associated ubiquitin-conjugation machinery.
16802346 2006 Overexpression of synoviolin in peripheral blood and synoviocytes from rheumatoid arthritis patients and continued elevation in nonresponders to infliximab treatment.
16786162 2006 Resistance to endoplasmic reticulum stress is an acquired cellular characteristic of rheumatoid synovial cells.
16751776 2006 A germline-specific class of small RNAs binds mammalian Piwi proteins.
16713569 2006 A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration.
16289116 2005 The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated degradation pathway.
16186510 2005 Recruitment of the p97 ATPase and ubiquitin ligases to the site of retrotranslocation at the endoplasmic reticulum membrane.
16186509 2005 Multiprotein complexes that link dislocation, ubiquitination, and extraction of misfolded proteins from the endoplasmic reticulum membrane.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
14593114 2004 Human HRD1 is an E3 ubiquitin ligase involved in degradation of proteins from the endoplasmic reticulum.
12975321 2003 Synoviolin/Hrd1, an E3 ubiquitin ligase, as a novel pathogenic factor for arthropathy.
12646171 2003 A novel mammalian endoplasmic reticulum ubiquitin ligase homologous to the yeast Hrd1.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12459480 2002 Human HRD1 protects against ER stress-induced apoptosis through ER-associated degradation.
11347906 2001 Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro.
11256614 2000 Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing.