Affinage

HSP90B1

Endoplasmin · UniProt P14625

Round 2 corrected
Length
803 aa
Mass
92.5 kDa
Annotated
2026-04-28
130 papers in source corpus 47 papers cited in narrative 47 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HSP90B1 (GRP94/gp96/endoplasmin) is the ER-resident paralog of the Hsp90 chaperone family, functioning as an ATP-dependent homodimeric chaperone that folds and stabilizes a selective repertoire of secretory and membrane protein clients—including integrins, Toll-like receptors, GARP, the platelet GPIb-IX-V complex, EGFR, and immunoglobulins—thereby governing processes from innate and adaptive immunity to platelet biogenesis, pancreatic β-cell development, and muscle maintenance (PMID:3612810, PMID:21576699, PMID:25607841, PMID:29272356). Its chaperone cycle is regulated by a pre-N domain that suppresses basal ATPase activity; BiP (via its nucleotide-binding domain) acts as a closure-accelerating cochaperone whose interaction with the Grp94 middle domain is promoted by the J-domain cochaperone DnaJB11, together driving Grp94 into the active closed conformation required for client folding (PMID:35078937, PMID:38483986). GRP94 also binds antigenic peptides—including those translocated by TAP—and upon release from necrotic cells is internalized by antigen-presenting cells to facilitate MHC class I cross-presentation and dendritic cell maturation via TLR2/TLR4 signaling (PMID:8650232, PMID:9130645, PMID:11086034, PMID:11912201). In addition, GRP94 participates in ER quality control by associating with OS-9 and the Hrd1/SEL1L complex to direct misfolded substrates such as mutant α1-antitrypsin to ERAD (PMID:18264092).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1987 High

    Establishing GRP94 as the ER-resident Hsp90 paralog resolved the question of whether the Hsp90 chaperone family operated in the secretory pathway, grounding all subsequent client-specific studies.

    Evidence cDNA cloning and sequence analysis of hamster GRP94 showing ~50% homology to Hsp90 and a C-terminal KDEL ER-retention signal

    PMID:3612810

    Open questions at the time
    • No client proteins identified at this stage
    • Chaperone activity inferred from homology, not demonstrated biochemically
  2. 1995 High

    Demonstration that GRP94 possesses intrinsic ATPase/autophosphorylation activity utilizing both ATP and GTP, with calcium activation, established it as an enzymatically active chaperone rather than a passive scaffold.

    Evidence In vitro autophosphorylation assay with purified GRP94, nucleotide competition, and limited proteolysis mapping catalytic activity to the C-terminal region

    PMID:7890776

    Open questions at the time
    • Relationship between autophosphorylation and chaperone function not resolved
    • No structural model of nucleotide-binding site
  3. 1996 High

    Identification of GRP94 as a peptide-binding chaperone that associates with viral antigenic peptides independently of MHC haplotype provided the biochemical basis for gp96-mediated tumor/pathogen immunity.

    Evidence Purification of gp96 from VSV-infected cells, peptide elution and sequencing, T cell activation assay; parallel identification of HER2 as a GRP94-associated client via co-IP

    PMID:8617772 PMID:8650232

    Open questions at the time
    • Peptide-binding site not yet mapped
    • Whether GRP94-HER2 interaction is direct or via cytoplasmic Hsp90 not resolved
  4. 1997 High

    Showing that GRP94 binds TAP-translocated peptides in the ER lumen linked the ER chaperone machinery to the antigen processing pathway, explaining how ER peptides reach GRP94.

    Evidence Photo-cross-linking of photoreactive peptides to gp96 after TAP-mediated translocation into ER membranes

    PMID:9130645

    Open questions at the time
    • Mechanism of peptide transfer from TAP to GRP94 unknown
    • Whether other ER chaperones compete for TAP-translocated peptides unclear
  5. 2000 High

    Discovery that extracellular GRP94 activates dendritic cell maturation in vivo and binds the receptor CD91 established GRP94 as a danger signal linking cell death to innate immune activation, though CD91 dependence was subsequently disputed.

    Evidence In vivo mouse immunization showing DC maturation and lymph node enlargement; direct CD91 binding assay with antibody/ligand competition

    PMID:11086034 PMID:11248808

    Open questions at the time
    • CD91 was later shown to be dispensable for GRP94 uptake and re-presentation (PMID:11970968)
    • Identity of the non-CD91 receptor for GRP94 on APCs remains unknown
  6. 2002 High

    Multiple studies clarified GRP94's immune signaling: it activates DCs via TLR2/TLR4, though rigorous depyrogenation later revealed that NF-κB activation was partly attributable to endotoxin contamination, while ERK phosphorylation was a genuine GRP94 effect; concurrently, the HER2-GRP94 interaction was reassigned to cytoplasmic Hsp90 rather than ER-luminal GRP94.

    Evidence TLR2/TLR4 KO mouse DCs unresponsive to gp96; novel depyrogenation protocol separating endotoxin effects from GRP94 effects; domain deletion of ErbB2 kinase domain with Hsp90/Grp94-selective geldanamycin derivatives

    PMID:11892991 PMID:11912201 PMID:12805368

    Open questions at the time
    • Whether any TLR activation by GRP94 is endotoxin-independent at physiological concentrations remains debated
    • ERK phosphorylation mechanism downstream of GRP94 not fully elucidated
  7. 2002 High

    Identification of a large ER multiprotein complex containing GRP94, BiP, PDI, ERdj3, and other chaperones associated with unassembled immunoglobulin heavy chains revealed that GRP94 operates within a cooperative ER quality control network rather than in isolation.

    Evidence Co-immunoprecipitation and chemical cross-linking from multiple cell types

    PMID:12475965

    Open questions at the time
    • Stoichiometry and assembly order of the complex unknown
    • Whether this complex is constitutive or stress-responsive not determined
  8. 2004 High

    Demonstrating that ATP/ADP suppress GRP94 conformational changes and oligomerization while client dissociation depends on client structural maturation (not ATP hydrolysis) distinguished the GRP94 chaperone cycle from cytoplasmic Hsp90.

    Evidence In vitro conformational assays, native gel oligomerization, co-IP of GRP94-Ig heavy chain complexes from myeloma cells with nucleotide treatment

    PMID:15236592

    Open questions at the time
    • No structural model of GRP94 conformational states
    • Cochaperone regulation not yet addressed
  9. 2008 High

    Linking GRP94 to ERAD through its interaction with OS-9 and the Hrd1/SEL1L ubiquitin ligase complex expanded GRP94's role from folding to disposal of terminally misfolded ER clients, though this collaboration was later refined.

    Evidence Co-IP of GRP94-OS-9-Hrd1/SEL1L, siRNA knockdown, pulse-chase degradation of mutant α1-antitrypsin

    PMID:18264092

    Open questions at the time
    • Subsequent study showed OS-9 preferentially targets hyperglycosylated, nonfunctional GRP94 itself for lysosomal degradation rather than cooperating in ERAD (PMID:24899641)
    • Whether GRP94 directly hands off clients to the Hrd1 complex or simply retains them is unclear
  10. 2011 High

    Conditional knockouts revealed non-redundant in vivo roles: GRP94 is the obligate chaperone for the platelet GPIb-IX-V complex (binding the GPIX subunit), and maternal GRP94 is required for the first mitotic division, establishing client-specific physiological essentiality.

    Evidence Hematopoietic and oocyte-specific Cre knockouts; co-IP of GRP94 with GPIX; spindle analysis and cell-cycle arrest in GRP94-null zygotes

    PMID:21358806 PMID:21576699

    Open questions at the time
    • Mechanism of GRP94 in spindle assembly unclear—may be indirect through ER-dependent signaling
    • Whether GPIbα/β require additional ER chaperones not tested
  11. 2013 High

    Discovery that GRP94 is the essential chaperone for GARP—a docking receptor for latent TGF-β on regulatory T cells—explained how GRP94 deletion destabilizes Foxp3 expression and Treg suppressive function, connecting ER proteostasis to immune tolerance.

    Evidence T cell-specific conditional KO, co-IP of GARP-GRP94, flow cytometry for GARP/integrin surface expression, TGF-β activity assay

    PMID:25607841

    Open questions at the time
    • Whether GRP94 chaperones GARP directly or via integrin co-clients not fully separated
    • Therapeutic window of GRP94 inhibition on Treg function not defined
  12. 2013 High

    GRP94 was shown to be required in tumor-associated macrophages for inflammatory colon tumorigenesis, linking macrophage-intrinsic GRP94 to TLR-dependent genotoxic signaling and cytokine production in the tumor microenvironment.

    Evidence Macrophage-specific conditional KO mice in AOM/DSS model; cytokine profiling and β-catenin mutation analysis

    PMID:24322981

    Open questions at the time
    • Which specific TLR clients in macrophages are GRP94-dependent not identified
    • Whether the effect is solely through TLR chaperoning or also involves integrin clients
  13. 2018 High

    Pancreas-specific GRP94 deletion demonstrated its requirement for β-cell development and glucose homeostasis, broadening the tissue-specific essential roles beyond immunity and platelets.

    Evidence Pdx1-Cre conditional KO; histomorphometry, proliferation/apoptosis assays, glucose tolerance tests

    PMID:29272356

    Open questions at the time
    • Specific β-cell client proteins chaperoned by GRP94 not identified
    • Whether adult β-cell maintenance also requires GRP94 not tested
  14. 2022 High

    Single-molecule FRET demonstrated that BiP acts as a closure-accelerating cochaperone for GRP94: BiP's nucleotide-binding domain contacts the Grp94 middle domain and stabilizes a high-energy conformational intermediate, providing the first mechanistic model of how Hsp70 and Hsp90 cooperate in the ER lumen.

    Evidence Reconstituted BiP/Grp94 system with single-molecule FRET, domain-specific interaction mapping, nucleotide-binding domain mutants

    PMID:35078937

    Open questions at the time
    • Whether client is present during BiP-Grp94 handoff not resolved at single-molecule level
    • Structural basis of the BiP-Grp94 interface not determined at atomic resolution
  15. 2024 High

    Identification of the pre-N domain as an autoinhibitory element of GRP94 ATPase activity, relieved by the cochaperone DnaJB11 acting through BiP, completed a three-component regulatory model (pre-N domain/BiP/DnaJB11) governing the GRP94 chaperone cycle.

    Evidence Pre-N domain deletion constructs, DnaJB11 reconstitution, ATPase assay, single-molecule FRET, client folding assay

    PMID:38483986

    Open questions at the time
    • How client identity influences the cochaperone-regulated cycle is unknown
    • Whether other J-domain proteins substitute for DnaJB11 in specific tissues not tested
    • Structural model of the full Grp94-BiP-DnaJB11-client complex lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the identity of the GRP94 receptor on APCs responsible for cross-presentation; the structural basis of client selectivity among the limited set of GRP94 clients; and whether tissue-specific phenotypes (β-cell, platelet, Treg, muscle) reflect distinct client repertoires or shared downstream pathways.
  • No atomic-resolution structure of GRP94 bound to a full-length client protein
  • APC receptor mediating GRP94 internalization and cross-presentation not identified
  • Client selectivity determinants not systematically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0044183 protein folding chaperone 8 GO:0140657 ATP-dependent activity 4 GO:0016740 transferase activity 1
Localization
GO:0005886 plasma membrane 5 GO:0005783 endoplasmic reticulum 4 GO:0005576 extracellular region 1
Pathway
R-HSA-168256 Immune System 10 R-HSA-392499 Metabolism of proteins 5 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4
Partners
DNAJB11EGFRGARPGPIXHSPA5MYH9OS9SEL1L
Complex memberships
ER multiprotein chaperone complex (BiP/GRP94/PDI/ERdj3/CaBP1/cyclophilin B/ERp72/GRP170/UGGT/SDF2-L1)GRP94 homodimer

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 GRP94 (HSP90B1) was identified as an ER-resident protein with ~50% amino acid sequence homology to Drosophila Hsp83 and yeast Hsp90, establishing it as the ER paralog of the Hsp90 family. Its C-terminal tetrapeptide (KDEL) was identified as part of an ER retention signal shared with GRP78 and PDI. cDNA cloning and sequence analysis of hamster GRP94 Journal of molecular biology High 3612810
1993 The human HSP90B1 gene (TRA1) was mapped to chromosome 12q24.2→q24.3; two additional related sequences (TRA1P1, TRAP2) were identified as processed pseudogenes on chromosomes 1 and 15, establishing that only the chromosome 12 locus is a coding gene. Southern blot hybridization and in situ hybridization with gene-specific probes Somatic cell and molecular genetics High 8460400
1994 GRP94 resides within cardiac sarcoplasmic reticulum vesicles as a luminal protein and is phosphorylated at two or more sites near both ends of the molecule by casein kinase II, identifying it as a high-capacity Ca2+-binding protein in the SR lumen. Protein purification, cDNA cloning, co-sedimentation with SR markers, casein kinase II phosphorylation assay, alkali/detergent extraction The Journal of biological chemistry High 8119936
1995 GRP94 (endoplasmin) possesses intrinsic autophosphorylation activity on serine and threonine residues, utilizes both ATP and GTP as substrates (Km ~243 µM and ~116 µM respectively), and this activity is activated by micromolar calcium concentrations. The N-terminal 85-kDa fragment can bind ATP-agarose but lacks autophosphorylation activity, suggesting the catalytic site resides in the C-terminal region. In vitro autophosphorylation assay with purified GRP94, concanavalin A affinity chromatography, immunoprecipitation, SDS-PAGE renaturation, limited proteolysis, ATP/GTP competition The Journal of biological chemistry High 7890776
1996 Membrane-associated p185erbB2 (HER2) exists in a stable complex with GRP94 in cells. Binding of geldanamycin (benzoquinone ansamycin) to GRP94 disrupts this complex, leading to degradation of pre-existing p185erbB2 and altered subcellular distribution of newly synthesized p185erbB2. Co-immunoprecipitation from SKBr3 cells, photoaffinity labeling, Western blot, geldanamycin treatment The Journal of biological chemistry High 8617772
1996 GRP94 endogenously binds antigenic peptides (specifically the immunodominant VSV nucleoprotein peptide) in virus-infected cells, regardless of the MHC haplotype, providing a biochemical basis for the vaccine function of gp96. Biochemical purification of gp96 from VSV-infected cells, peptide elution, sequencing, and T cell activation assay Proceedings of the National Academy of Sciences of the United States of America High 8650232
1996 Purified GRP94 exists as a noncovalent homodimer in solution as a soluble luminal protein, and displays heterogeneity in native and denaturing PAGE attributable to variable N-linked glycosylation state. Purification from porcine pancreas rough microsomes, native PAGE, 2D non-reducing/reducing gels, alkali/detergent extraction Protein expression and purification High 9172775
1997 GRP94 binds peptides translocated into the ER by TAP (transporter associated with antigen processing), as demonstrated by specific photo-cross-linking of photoreactive peptides to gp96 after TAP-mediated translocation. TAP-dependent peptide translocation assay, photoreactive peptide cross-linking to gp96 in ER membranes European journal of immunology High 9130645
1999 GRP94 undergoes receptor-mediated endocytosis by macrophages via a cell-surface receptor distinct from the mannose/fucose receptor; internalized GRP94 co-localizes predominantly with transferrin-positive early endosomes and not lysosomes within 20 minutes, suggesting a trafficking pathway compatible with MHC class I peptide loading. Fluorescence microscopy, transferrin co-localization, mannan/dimethylamiloride inhibition, LAMP-2 co-staining in elicited macrophages Journal of cell science High 10362546
1999 GRP94 functions as a putative HDL-binding protein at the plasma membrane of hepatocytes; deletion of its C-terminal KDEL ER-retention sequence results in plasma membrane localization when expressed in COS-1 cells, demonstrating that the KDEL motif is required for ER retention. HDL-binding assay with stably transfected cells, immunoelectron microscopy, KDEL deletion construct expression in COS-1 cells Biochimica et biophysica acta Medium 10101271
2000 CD91 (alpha-2-macroglobulin receptor/LRP) is a cell surface receptor for GRP94 on antigen-presenting cells. CD91 binds gp96 directly (not through another ligand), and alpha-2-macroglobulin inhibits re-presentation of gp96-chaperoned antigenic peptides by macrophages, as do anti-CD91 antibodies. Direct binding assay, competition with alpha-2-macroglobulin, antibody inhibition of antigen re-presentation, macrophage assay Nature immunology High 11248808
2000 Immunization with gp96 but not control proteins induces maturation and migration of CD11c+ dendritic cells in vivo, causing 5-7-fold enlargement of draining lymph nodes specifically at the injection site, peaking at 12-24 hours post-injection, demonstrating a direct role for GRP94 in innate immune activation. In vivo mouse immunization, flow cytometry, histology of draining lymph nodes Journal of immunology High 11086034
2001 Virally induced lytic cell death (but not apoptosis) causes release of immunogenic GRP94 into the extracellular space; this released GRP94 retains antigenicity and elicits dose-dependent, ovalbumin-specific T-cell hybridoma activation when pulsed onto APCs, linking necrotic cell death to GRP94-mediated immune activation. Cell death induction, tissue culture supernatant fractionation, APC pulsing, T cell hybridoma activation assay The Journal of biological chemistry High 11279246
2001 Binding of antigenic peptides to GRP94 involves aromatic amino acid residues in the peptide-binding pocket: substitution of Tyr-667 or Tyr-678 to Ala reduced peptide affinity, Trp-621 to Phe/Leu/Ala/Ile decreased binding while Trp-621 to Tyr or Val increased it, and Trp-654 to Tyr increased binding. Peptide binding occurs in stable multimeric GRP94 complexes. Site-directed mutagenesis of GRP94, peptide-binding assays, scanning transmission electron microscopy of gp96-peptide complexes The Journal of biological chemistry High 11148208
2002 GRP94 internalization by APCs and peptide re-presentation occurs via a CD91-independent pathway; excess CD91 ligands (activated alpha-2-macroglobulin) or receptor-associated protein (RAP, antagonist of all CD91 ligands) do not affect GRP94 cell-surface binding, receptor-mediated endocytosis, or peptide re-presentation. Cell surface binding assay, endocytosis assay with RAP and alpha-2-macroglobulin competition, antigen re-presentation assay in APCs Journal of immunology High 11970968
2002 GRP94 internalized by receptor-mediated endocytosis traffics to a Rab5a/CD1/transferrin-negative, Fc-receptor and MHC class I-positive endocytic compartment (not back to the ER). GRP94-associated peptides are transferred onto MHC class I molecules at a post-ER compartment accessed by mature MHC class I molecules. Immunofluorescence co-localization with endosomal markers, kinetic analysis of peptide re-presentation with MHC class I synthesis inhibition, antibody 25-D1.16 assay Traffic (Copenhagen, Denmark) High 11967129
2002 Hsp90 (cytoplasmic), not Grp94 (ER luminal), regulates the intracellular trafficking and stability of nascent ErbB2. The drug sensitivity of nascent ErbB2 to geldanamycin is mediated by its cytoplasmic kinase domain interacting with cytoplasmic Hsp90, not by the luminal domain interacting with Grp94. ErbB2 deletion constructs (ErbB2/DK lacking kinase domain), geldanamycin derivatives with Hsp90/Grp94 selectivity, pulse-chase analysis of ErbB2 maturation Cell stress & chaperones High 11892991
2002 GRP94 activates dendritic cells via Toll-like receptor 2 and TLR4 signaling, resulting in NF-κB activation, IκBα degradation, and MAP kinase activation. Bone marrow-derived DCs from C3H/HeJ (TLR4-mutant) and TLR2/TLR4 double-deficient mice fail to respond to Gp96, and DC activation requires endocytosis of Gp96. NF-κB reporter assay, IκBα Western blot, MAP kinase assays, TLR2/TLR4 knockout mouse DCs, endocytosis inhibition The Journal of biological chemistry High 11912201
2003 Low-endotoxin GRP94 does not activate macrophage NF-κB signaling, nitric oxide production, or iNOS expression, indicating that previously reported macrophage NF-κB activation by GRP94 was due to contaminating endotoxin. However, endotoxin-free GRP94 retains native conformation, ligand-binding activity, in vitro chaperone function, and does elicit ERK phosphorylation in macrophages at ≥2 µg/ml. Novel depyrogenation purification, NF-κB assay, NO assay, ERK phosphorylation assay, chaperone activity assay, endotoxin quantification The Journal of biological chemistry High 12805368
2004 ATP and ADP (but not GTP) suppress a time/temperature-dependent tertiary conformational change in apo-GRP94 that exposes protein-protein interaction sites, and both nucleotides inhibit GRP94 homooligomerization. Unlike BiP, GRP94 remains in stable association with immunoglobulin heavy chain folding intermediates in the presence of ATP or ADP, suggesting that structural maturation of the client protein (rather than ATP hydrolysis) is the primary signal for GRP94-client dissociation. In vitro conformational assay, native gel oligomerization analysis, immunoprecipitation of GRP94-Ig heavy chain complexes from myeloma cells with ATP/ADP treatment Biochemistry High 15236592
2005 Cell-surface GRP94 (gp96) acts as a receptor for the Listeria monocytogenes virulence factor Vip, a surface LPXTG protein; the Vip-Gp96 interaction is critical for bacterial entry into mammalian cells, and Vip contributes to Listeria virulence in vivo. Ligand overlay approach, co-immunoprecipitation, siRNA knockdown of Gp96, in vivo infection of transgenic mice The EMBO journal High 16015374
2008 GRP94 associates with OS-9 and together with Hrd1/SEL1L ubiquitin ligase complex promotes ERAD of mutant alpha-1-antitrypsin. OS-9 contains a mannose 6-phosphate receptor homology (MRH) domain required for SEL1L interaction, and both GRP94 and Hrd1/SEL1L are required for degradation of the misfolded substrate. Co-immunoprecipitation, siRNA knockdown, pulse-chase degradation assay, domain mutagenesis of OS-9 MRH domain Nature cell biology High 18264092
2009 GRP94 associates with pro-ADAMTS9 and furin at the cell surface, and geldanamycin treatment or gp96 siRNA knockdown decreases furin-mediated processing of pro-ADAMTS9 and reduces cell-surface levels of pro-ADAMTS9, identifying GRP94 as a chaperone regulating ADAMTS9 secretion and cell-surface processing. Cross-linking and mass spectrometry identification of GRP94 as pro-ADAMTS9 binding partner, co-immunoprecipitation, siRNA knockdown, geldanamycin treatment The Journal of biological chemistry High 19875450
2011 GRP94 (gp96/grp94/HSP90B1) is an essential chaperone for the platelet glycoprotein Ib-IX-V complex: GRP94 binds selectively to the GPIX subunit (but not GPIbα or GPIbβ), and its deletion in the murine hematopoietic system causes thrombocytopenia, prolonged bleeding time, and giant platelets phenotypically identical to Bernard-Soulier Syndrome due to ER-associated degradation of the GPIb-IX complex. Conditional knockout mice, co-immunoprecipitation of GRP94 with GPIX, flow cytometry, bleeding time assay, pulse-chase degradation assay Blood High 21576699
2011 Oocyte-specific conditional deletion of Hsp90b1 (GRP94) causes arrest of mouse zygotes at the first mitosis: mutant zygotes exhibit G2/M block or abnormal mitotic spindles, and GRP94 does not fully co-localize with BiP/HSPA5 in zygotes; BiP overexpression does not rescue GRP94 deficiency, indicating non-redundant maternal functions. ZP3-Cre conditional knockout, immunofluorescence spindle analysis, cell cycle flow cytometry, HSPA5 immunostaining and co-localization PloS one High 21358806
2002 A large ER multiprotein chaperone complex was identified comprising BiP, GRP94, CaBP1, PDI, ERdj3, cyclophilin B, ERp72, GRP170, UDP-glucosyltransferase, and SDF2-L1; this complex associates with unassembled immunoglobulin heavy chains and forms independently of nascent protein synthesis in multiple cell types. Co-immunoprecipitation, chemical cross-linking, immunoblotting from multiple cell types Molecular biology of the cell High 12475965
2012 GRP94 developed as a druggable target distinct from cytoplasmic Hsp90 isoforms: a structure-based inhibitor (compound 2) selectively inhibits Grp94 over Hsp90α/β, prevents intracellular trafficking of the Toll receptor, inhibits IGF-II secretion, and suppresses Drosophila larval growth (all Grp94-dependent processes) without affecting cytosolic Hsp90 clients or cell viability. Structure-based inhibitor design, Toll receptor trafficking assay, IGF-II secretion assay, Drosophila larval growth assay, client protein Western blot Journal of the American Chemical Society High 22642269
2013 GRP94 is required for Treg maintenance and function: genetic deletion of GP96 in T cells results in loss of FOXP3 expression stability, accumulation of pathogenic IFN-γ- and IL-17-producing T cells, and impaired suppressive function. Mechanistically, GP96 is an essential chaperone for GARP (glycoprotein A repetitions predominant), a docking receptor for latent membrane-associated TGF-β, and loss of both GARP and integrins on GP96-deficient Tregs prevents mLTGF-β expression and active TGF-β production. Murine conditional knockout, FOXP3 expression analysis, flow cytometry, co-immunoprecipitation of GARP and GP96, TGF-β activity assay The Journal of clinical investigation High 25607841
2013 Grp94 recognizes on-pathway aggregates of myocilin olfactomedin domain (myoc-OLF) rather than unfolded monomers, accelerates myoc-OLF aggregation rates, and co-precipitates with myoc-OLF aggregates. A selective Grp94 inhibitor reduces mutant myocilin levels in primary human trabecular meshwork cells and rescues toxicity. In vitro aggregation kinetics assay, co-precipitation, selective Grp94 inhibitor treatment in primary cells, cell viability assay Human molecular genetics High 25027323
2013 GRP94 is essential in tumor-associated macrophages for licensing their role in inflammatory colon tumorigenesis; macrophage-specific gp96 deletion reduces colitis, colon tumorigenesis, β-catenin mutation rates, DNA repair gene expression, and pro-inflammatory cytokines (IL-17, IL-23) in the tumor microenvironment, placing GRP94 upstream of TLR-mediated TAM genotoxic activity. Macrophage-specific conditional knockout mice, AOM/DSS colon cancer model, cytokine profiling, DNA repair gene expression, β-catenin mutation analysis Cancer research High 24322981
2013 Grp94 counteracts muscle disuse atrophy by stabilizing subsarcolemmal neuronal nitric oxide synthase (nNOS): Grp94 immunoprecipitates with 160 kDa nNOS, and recombinant Grp94 (but not N-terminal deleted forms) expression in unloaded rat soleus myofibers maintains nNOS localization at the sarcolemma, reduces carbonylation, and attenuates atrophy. In vivo transfection of rat soleus, immunoprecipitation, confocal microscopy, NADPH-diaphorase histochemistry, N-terminal deletion constructs Antioxidants & redox signaling High 24093939
2014 Liver-specific GRP94 knockout disrupts cell adhesion proteins and activates ERK selectively (not AKT) in gp96/PTEN double-knockout livers; loss of GRP94 promotes hyperproliferation of liver progenitor cells and accelerates hepatocellular carcinoma and cholangiocarcinoma development, suggesting GRP94 normally suppresses ERK-mediated oncogenic signaling in the liver. Albumin-Cre conditional KO mice, double KO with PTEN, ERK/AKT Western blot, histopathology, progenitor cell analysis Hepatology High 24027047
2014 OS-9 binds preferentially to a hyperglycosylated subpopulation of GRP94 that has nonnative conformation and reduced chaperone activity; this hyperglycosylated GRP94 is degraded faster than the major monoglycosylated form via an OS-9-mediated, ERAD-independent, lysosomal-like mechanism. GRP94 does not collaborate with OS-9 in ERAD of misfolded client substrates. Pulse-chase degradation assay, glycosylation mutants, lysosomal inhibitors, OS-9 knockdown, chaperone activity assay Molecular biology of the cell High 24899641
2015 Cell membrane GRP94 interacts with HER2, facilitates HER2 dimerization, and promotes cell proliferation in breast cancer; mgp96 levels correlate with HER2 phosphorylation in primary breast tumors, and targeting mgp96 with a monoclonal antibody decreases cell growth and increases apoptosis in vitro and suppresses tumor growth in vivo. Co-immunoprecipitation, HER2 dimerization assay, monoclonal antibody blockade, cell proliferation assay, mouse xenograft model International journal of cancer Medium 25546612
2015 Cell membrane GRP94 (mgp96) interacts with uPAR (urokinase-type plasminogen activator receptor), stabilizes uPAR protein, and promotes invasion and metastasis of liver cancer. Reduced KDELR1 levels in hepatoma cells contribute to plasma membrane translocation of normally ER-resident gp96; blocking mgp96-uPAR interaction with siRNA or mAb inhibits growth and metastasis in vitro and in vivo. Co-immunoprecipitation identifying uPAR as mgp96 client, KDELR1 siRNA for mechanism of translocation, siRNA/mAb functional assay, mouse xenograft Molecular oncology Medium 25841765
2015 GRP94 decreases p53 protein stability by interacting with both p53 and Mdm2, enhancing Mdm2-mediated p53 ubiquitination and degradation in liver cancer cells; gp96 knockdown by siRNA increases p53 levels, induces apoptosis, and suppresses tumor growth in vivo. Co-immunoprecipitation of gp96-p53-Mdm2 complex, ubiquitination assay, siRNA knockdown, apoptosis assay, mouse xenograft Cancer letters Medium 25637791
2015 Cell membrane gp96 directly interacts with ER-α36 (a variant of estrogen receptor α) via the C-terminal domain of mgp96, stabilizes ER-α36 protein, and increases its signaling, thereby promoting tumor cell growth and invasion; blocking this interaction with siRNA or monoclonal antibody inhibits breast cancer growth in vitro and in vivo. Co-immunoprecipitation with domain mapping, siRNA and mAb functional assay, protein stability assay, mouse xenograft Oncotarget Medium 26396174
2016 Gp96 interacts with non-muscle myosin heavy chain IIA (NMHCIIA), controls NMHCIIA activity and remodeling, and is required for appropriate bleb formation and retraction in response to pore-forming toxins (listeriolysin O). Gp96 and NMHCIIA are recruited to plasma membrane blebs, protecting cells from LLO during Listeria infection. Gp96 also promotes NMHCIIA-dependent uropod retraction in migrating cells. Co-immunoprecipitation of Gp96-NMHCIIA, siRNA knockdown, live-cell imaging of blebbing, in vivo validation in zebrafish/mouse infection models EMBO reports High 28039206
2018 GRP94 is an essential regulator of pancreatic β-cell development: conditional deletion of Hsp90b1 in Pdx1-expressing cells causes pancreatic hypoplasia at E16.5-E18.5, significantly reduced β-cell mass at 4 weeks, reduced β-cell proliferation with increased apoptosis in both progenitor and differentiated β cells, and impaired glucose tolerance. Pdx1-Cre conditional knockout, histomorphometry, BrdU proliferation assay, TUNEL apoptosis assay, glucose tolerance test Endocrinology High 29272356
2019 GRP94 promotes muscle differentiation through interaction with PI3K-interacting protein 1 (Pik3ip1): co-immunoprecipitation and proximity ligation assays demonstrate GRP94-Pik3ip1 interaction in myoblasts, GRP94 regulates Pik3ip1 expression, and GRP94-induced inhibition of PI3K/AKT/mTOR signaling (reducing proliferation and increasing differentiation) is abolished when Pik3ip1 is knocked down. Co-immunoprecipitation, proximity ligation assay, PI3K/AKT/mTOR pathway Western blot, Pik3ip1 siRNA knockdown, in vitro and in vivo myoblast differentiation assays Journal of cellular physiology Medium 31025379
2020 GRP94 regulates M1 macrophage polarization: macrophage-specific GRP94 KO mice on high-fat diet show improved glucose tolerance, increased insulin sensitivity, and reduced M1 macrophage numbers in adipose tissue. GRP94-deficient BMDMs show lower M1 marker gene expression after LPS/IFN-γ stimulation and partially increased M2 markers after IL-4 stimulation. Macrophage-specific conditional KO mice, high-fat diet challenge, glucose/insulin tolerance tests, flow cytometry, BMDM polarization assay American journal of physiology. Endocrinology and metabolism High 32208002
2021 GRP94 interacts with intracellular complement C3 in M2 macrophages; ER stress (thapsigargin) increases GRP94-C3 interaction and promotes co-secretion of GRP94 with C3 and C3b, where cathepsin L cleaves C3. The iC3b inactivated fragment, present only on non-stressed M2 macrophages, depends on functional GRP94, making GRP94 and iC3b potential markers of M2 polarization. Co-immunoprecipitation of GRP94-C3/C3b, flow cytometry of membrane GRP94, thapsigargin/tunicamycin ER stress induction, functional GRP94 inhibition Cell death & disease Medium 33483465
2021 FBXL2 targets EGFR for proteasome-mediated degradation; Grp94 protects EGFR from FBXL2-mediated degradation by blocking FBXL2 binding to EGFR, establishing a FBXL2-Grp94-EGFR axis. Grp94 inhibition combined with FBXL2 upregulation (nebivolol) or osimertinib exhibits synergistic inhibition of TKI-resistant NSCLC. Co-immunoprecipitation of Grp94-EGFR and FBXL2-EGFR, ubiquitination assay, Grp94 inhibitor treatment, nebivolol + osimertinib combination assay Nature communications High 34635651
2022 BiP (ER Hsp70) acts as a closure-accelerating cochaperone of Grp94: BiP's nucleotide binding domain interacts with the Grp94 middle domain, client binding to BiP causes a conformational change that enables BiP to bind Grp94 and accelerate ATP-dependent Grp94 closure by stabilizing a high-energy conformational intermediate. Single-molecule FRET measurements demonstrate that BiP accelerates Grp94 closure. Single-molecule FRET, reconstituted BiP/Grp94 system, domain-specific interaction mapping, nucleotide binding domain mutants, in vitro ATPase assay Proceedings of the National Academy of Sciences of the United States of America High 35078937
2023 HSP90B1 interacts with c-Myc in bladder cancer cells; HSP90B1 knockdown reverses p21 overexpression caused by c-Myc overexpression, and reducing HSP90B1 alleviates rapid growth, accelerates cellular senescence, and improves cisplatin sensitivity, placing HSP90B1 in the c-Myc/p21 signaling axis regulating cellular senescence. Immunoprecipitation confirming HSP90B1-c-Myc interaction, Western blot for p21, siRNA knockdown, SA-β-galactosidase senescence assay, cisplatin sensitivity assay Aging Medium 37433010
2023 METTL5/TRMT112-mediated m6A modification at 18S rRNA position 1832 promotes translation of HSF4b mRNA, which transcriptionally activates HSP90B1; HSP90B1 then binds mutant p53 (mutp53) and prevents its ubiquitination-dependent degradation, thereby facilitating NPC tumorigenesis and chemoresistance. m6A modification analysis, polysome profiling, HSF4b ChIP at HSP90B1 promoter, co-immunoprecipitation of HSP90B1-mutp53, ubiquitination assay, in vitro and in vivo tumor models Cell chemical biology Medium 36800991
2024 Grp94's pre-N domain suppresses ATP hydrolysis and conformational transitions to the active chaperone conformation but is not necessary for client interactions. The BiP co-chaperone DnaJB11 promotes BiP-Grp94 interaction and relieves pre-N domain suppression of Grp94 ATPase activity. ATP binding reduces Grp94 affinity for clients, and BiP binding stabilizes a partially closed Grp94 intermediate; together BiP and ATP push Grp94 into the active closed conformation for client folding. In vitro ATPase assay, structural studies, single-molecule FRET, client folding assay, in vivo and in vitro functional assays, pre-N domain deletion constructs Proceedings of the National Academy of Sciences of the United States of America High 38483986

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2010 Network organization of the human autophagy system. Nature 1286 20562859
2009 Defining the human deubiquitinating enzyme interaction landscape. Cell 1282 19615732
2003 Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nature biotechnology 1176 12754519
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2011 Global landscape of HIV-human protein complexes. Nature 593 22190034
2017 Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15. Science (New York, N.Y.) 533 28302793
2000 CD91: a receptor for heat shock protein gp96. Nature immunology 516 11248808
2011 Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell 507 21565611
2011 Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation. Nature cell biology 490 21423176
2011 The unfolded protein response: integrating stress signals through the stress sensor IRE1α. Physiological reviews 487 22013210
2003 Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nature biotechnology 485 12665801
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2015 A Dynamic Protein Interaction Landscape of the Human Centrosome-Cilium Interface. Cell 433 26638075
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2011 Defining human ERAD networks through an integrative mapping strategy. Nature cell biology 427 22119785
2002 A subset of chaperones and folding enzymes form multiprotein complexes in endoplasmic reticulum to bind nascent proteins. Molecular biology of the cell 422 12475965
2008 OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD. Nature cell biology 419 18264092
2004 Dissection of the mammalian midbody proteome reveals conserved cytokinesis mechanisms. Science (New York, N.Y.) 417 15166316
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2004 14-3-3-affinity purification of over 200 human phosphoproteins reveals new links to regulation of cellular metabolism, proliferation and trafficking. The Biochemical journal 372 14744259
2015 Proteome-wide profiling of protein assemblies by cross-linking mass spectrometry. Nature methods 370 26414014
2002 The endoplasmic reticulum-resident heat shock protein Gp96 activates dendritic cells via the Toll-like receptor 2/4 pathway. The Journal of biological chemistry 368 11912201
2015 Aerobic glycolysis tunes YAP/TAZ transcriptional activity. The EMBO journal 362 25796446
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2001 Recruitment of HAT complexes by direct activator interactions with the ATM-related Tra1 subunit. Science (New York, N.Y.) 296 11423663
2015 Role of the unfolded protein response, GRP78 and GRP94 in organ homeostasis. Journal of cellular physiology 252 25546813
1996 p185erbB2 binds to GRP94 in vivo. Dissociation of the p185erbB2/GRP94 heterocomplex by benzoquinone ansamycins precedes depletion of p185erbB2. The Journal of biological chemistry 242 8617772
2010 GRP94 in ER quality control and stress responses. Seminars in cell & developmental biology 187 20223290
1996 Isolation of an immunodominant viral peptide that is endogenously bound to the stress protein GP96/GRP94. Proceedings of the National Academy of Sciences of the United States of America 169 8650232
1998 The ATM-related cofactor Tra1 is a component of the purified SAGA complex. Molecular cell 165 9885573
2000 Cutting edge: heat shock protein gp96 induces maturation and migration of CD11c+ cells in vivo. Journal of immunology (Baltimore, Md. : 1950) 154 11086034
1999 GRP94, an ER chaperone with protein and peptide binding properties. Seminars in cell & developmental biology 150 10597632
2005 Gp96 is a receptor for a novel Listeria monocytogenes virulence factor, Vip, a surface protein. The EMBO journal 138 16015374
1987 The glucose-regulated protein grp94 is related to heat shock protein hsp90. Journal of molecular biology 129 3612810
2005 Roles of heat shock protein gp96 in the ER quality control: redundant or unique function? Molecules and cells 124 16267390
2012 Development of a Grp94 inhibitor. Journal of the American Chemical Society 98 22642269
1997 The endoplasmic reticulum-resident stress protein gp96 binds peptides translocated by TAP. European journal of immunology 89 9130645
2007 Differentially expressed genes in radioresistant nasopharyngeal cancer cells: gp96 and GDF15. Molecular cancer therapeutics 81 17671084
2016 Clients and Oncogenic Roles of Molecular Chaperone gp96/grp94. Current topics in medicinal chemistry 80 27072698
2015 GP96 is a GARP chaperone and controls regulatory T cell functions. The Journal of clinical investigation 80 25607841
2003 GRP94/gp96 elicits ERK activation in murine macrophages. A role for endotoxin contamination in NF-kappa B activation and nitric oxide production. The Journal of biological chemistry 79 12805368
1999 Receptor mediated and fluid phase pathways for internalization of the ER Hsp90 chaperone GRP94 in murine macrophages. Journal of cell science 73 10362546
1995 Autophosphorylation of grp94 (endoplasmin). The Journal of biological chemistry 72 7890776
2002 Cutting edge: CD91-independent cross-presentation of GRP94(gp96)-associated peptides. Journal of immunology (Baltimore, Md. : 1950) 71 11970968
2001 Virally induced lytic cell death elicits the release of immunogenic GRP94/gp96. The Journal of biological chemistry 68 11279246
2010 Domains of Tra1 important for activator recruitment and transcription coactivator functions of SAGA and NuA4 complexes. Molecular and cellular biology 67 21149579
2002 Hsp90, not Grp94, regulates the intracellular trafficking and stability of nascent ErbB2. Cell stress & chaperones 67 11892991
1994 GRP94 resides within cardiac sarcoplasmic reticulum vesicles and is phosphorylated by casein kinase II. The Journal of biological chemistry 67 8119936
2013 Molecular chaperone gp96 is a novel therapeutic target of multiple myeloma. Clinical cancer research : an official journal of the American Association for Cancer Research 65 24077352
2002 Overexpression of glucose-regulated protein 94 (Grp94) in esophageal adenocarcinomas of a rat surgical model and humans. Carcinogenesis 64 11756233
2015 GRP94/gp96 in Cancer: Biology, Structure, Immunology, and Drug Development. Advances in cancer research 62 26916005
2011 Heat-shock protein gp96/grp94 is an essential chaperone for the platelet glycoprotein Ib-IX-V complex. Blood 58 21576699
2014 Liver-specific knockout of GRP94 in mice disrupts cell adhesion, activates liver progenitor cells, and accelerates liver tumorigenesis. Hepatology (Baltimore, Md.) 54 24027047
2014 Endoplasmic reticulum heat shock protein gp96 maintains liver homeostasis and promotes hepatocellular carcinogenesis. Journal of hepatology 53 25463537
1996 Purification and partial molecular characterization of GRP94, an ER resident chaperone. Protein expression and purification 53 9172775
2021 Molecular Chaperone GRP94/GP96 in Cancers: Oncogenesis and Therapeutic Target. Frontiers in oncology 52 33898309
2021 FBXL2 counteracts Grp94 to destabilize EGFR and inhibit EGFR-driven NSCLC growth. Nature communications 52 34635651
2013 Immune chaperone gp96 drives the contributions of macrophages to inflammatory colon tumorigenesis. Cancer research 51 24322981
2010 The anti-myeloma activity of a novel purine scaffold HSP90 inhibitor PU-H71 is via inhibition of both HSP90A and HSP90B1. Journal of hematology & oncology 50 20977755
2002 Functional and mutational analysis of conjugative transfer region 1 (Tra1) from the IncHI1 plasmid R27. Journal of bacteriology 50 11914349
2002 Transfer of GRP94(Gp96)-associated peptides onto endosomal MHC class I molecules. Traffic (Copenhagen, Denmark) 46 11967129
2015 Cell membrane gp96 facilitates HER2 dimerization and serves as a novel target in breast cancer. International journal of cancer 45 25546612
2017 Second Generation Grp94-Selective Inhibitors Provide Opportunities for the Inhibition of Metastatic Cancer. Chemistry (Weinheim an der Bergstrasse, Germany) 43 28857290
2001 Enhanced expression of mRNAs of antisecretory factor-1, gp96, DAD1 and CDC34 in human hepatocellular carcinomas. Biochimica et biophysica acta 43 11335099
2014 Exploiting the interaction between Grp94 and aggregated myocilin to treat glaucoma. Human molecular genetics 42 25027323
2016 Transformation of the Non-Selective Aminocyclohexanol-Based Hsp90 Inhibitor into a Grp94-Seletive Scaffold. ACS chemical biology 41 27959508
2019 Small molecule grp94 inhibitors block dengue and Zika virus replication. Antiviral research 39 31421166
2012 Active-specific immunotherapy of human cancers with the heat shock protein Gp96-revisited. International journal of cancer 39 22052568
2011 Overexpression of GRP78 and GRP94 is involved in colorectal carcinogenesis. Histology and histopathology 39 21472681
2004 Adenosine nucleotides and the regulation of GRP94-client protein interactions. Biochemistry 39 15236592
2010 Identification of gp96 as a novel target for treatment of autoimmune disease in mice. PloS one 38 20352117
2023 Senescence-related gene c-Myc affects bladder cancer cell senescence by interacting with HSP90B1 to regulate cisplatin sensitivity. Aging 37 37433010
2021 The HSP GRP94 interacts with macrophage intracellular complement C3 and impacts M2 profile during ER stress. Cell death & disease 37 33483465
2009 Cell-surface processing of the metalloprotease pro-ADAMTS9 is influenced by the chaperone GRP94/gp96. The Journal of biological chemistry 37 19875450
2017 Cryo-EM structure of the SAGA and NuA4 coactivator subunit Tra1 at 3.7 angstrom resolution. eLife 35 28767037
2004 The messenger and the message: gp96 (GRP94)-peptide interactions in cellular immunity. Cell stress & chaperones 35 15633290
2021 The loss-of-function PCSK9Q152H variant increases ER chaperones GRP78 and GRP94 and protects against liver injury. The Journal of clinical investigation 34 33211673
2017 Structure of the transcription activator target Tra1 within the chromatin modifying complex SAGA. Nature communications 34 29146944
2002 Three-step purification of gp96 from human liver tumor tissues suitable for isolation of gp96-bound peptides. Journal of immunological methods 34 12191506
2017 Resorcinol-Based Grp94-Selective Inhibitors. ACS medicinal chemistry letters 31 29057043
2009 Silencing of GRP94 expression promotes apoptosis in pancreatic cancer cells. International journal of oncology 31 19724918
2004 DNA vaccination with gp96-peptide fusion proteins induces protection against an intracellular bacterial pathogen. International immunology 31 15039390
2023 N6-methyladenosine modification in 18S rRNA promotes tumorigenesis and chemoresistance via HSF4b/HSP90B1/mutant p53 axis. Cell chemical biology 30 36800991
2014 OS-9 facilitates turnover of nonnative GRP94 marked by hyperglycosylation. Molecular biology of the cell 29 24899641
2020 Overexpression of molecule GRP94 favors tumor progression in lung adenocarcinoma by interaction with regulatory T cells. Thoracic cancer 28 31970893
2019 New insights into the evolutionary conservation of the sole PIKK pseudokinase Tra1/TRRAP. Biochemical Society transactions 28 31769470
2007 Structure/function analysis of the phosphatidylinositol-3-kinase domain of yeast tra1. Genetics 27 17660562
2019 GRP94 promotes muscle differentiation by inhibiting the PI3K/AKT/mTOR signaling pathway. Journal of cellular physiology 26 31025379
2022 The biology and inhibition of glucose-regulated protein 94/gp96. Medicinal research reviews 25 35861260
2016 Endoplasmic reticulum chaperone Gp96 controls actomyosin dynamics and protects against pore-forming toxins. EMBO reports 25 28039206
2014 Development of radamide analogs as Grp94 inhibitors. Bioorganic & medicinal chemistry 25 25027801
2012 Analysis of Gal4-directed transcription activation using Tra1 mutants selectively defective for interaction with Gal4. Proceedings of the National Academy of Sciences of the United States of America 25 22308403
2011 Oocyte-targeted deletion reveals that hsp90b1 is needed for the completion of first mitosis in mouse zygotes. PloS one 25 21358806
2002 Expression of endoplasmic reticulum molecular chaperon GRP94 in human lung cancer tissues and its clinical significance. Chinese medical journal 25 12609072
2015 Heat shock protein gp96 decreases p53 stability by regulating Mdm2 E3 ligase activity in liver cancer. Cancer letters 24 25637791
2015 Plasma membrane gp96 enhances invasion and metastatic potential of liver cancer via regulation of uPAR. Molecular oncology 24 25841765
2010 Mutational analysis of the C-terminal FATC domain of Saccharomyces cerevisiae Tra1. Current genetics 24 20635087
2007 Association analysis of HSP90B1 with bipolar disorder. Journal of human genetics 24 17805476
2002 Adenovirus E1A requires the yeast SAGA histone acetyltransferase complex and associates with SAGA components Gcn5 and Tra1. Oncogene 24 11857084
2018 Cell entry of a host-targeting protein of oomycetes requires gp96. Nature communications 23 29904064
2018 Toll-like receptor chaperone HSP90B1 and the immune response to Mycobacteria. PloS one 23 30550567
2000 Expression of stress protein gp96, a tumor rejection antigen, in human colorectal cancer. International journal of cancer 23 10797260
1993 Mapping of the genes for human endoplasmic reticular heat shock protein gp96/grp94. Somatic cell and molecular genetics 23 8460400
2022 A Pan-Cancer Analysis of Heat-Shock Protein 90 Beta1(HSP90B1) in Human Tumours. Biomolecules 22 36291587
2018 GRP94 Is an Essential Regulator of Pancreatic β-Cell Development, Mass, and Function in Male Mice. Endocrinology 22 29272356
2013 The stress protein/chaperone Grp94 counteracts muscle disuse atrophy by stabilizing subsarcolemmal neuronal nitric oxide synthase. Antioxidants & redox signaling 22 24093939
2022 The endoplasmic reticulum chaperone BiP is a closure-accelerating cochaperone of Grp94. Proceedings of the National Academy of Sciences of the United States of America 21 35078937
2013 Placenta-derived gp96 as a multivalent prophylactic cancer vaccine. Scientific reports 21 23739295
2024 Identification of HSP90B1 in pan-cancer hallmarks to aid development of a potential therapeutic target. Molecular cancer 20 38243263
2001 Binding of antigenic peptide to the endoplasmic reticulum-resident protein gp96/GRP94 heat shock chaperone occurs in higher order complexes. Essential role of some aromatic amino acid residues in the peptide-binding site. The Journal of biological chemistry 20 11148208
1999 Gp96/GRP94 is a putative high density lipoprotein-binding protein in liver. Biochimica et biophysica acta 20 10101271
2015 MicroRNA-223 is a novel negative regulator of HSP90B1 in CLL. BMC cancer 19 25880332
2014 Targeted deletion of ER chaperone GRP94 in the liver results in injury, repopulation of GRP94-positive hepatocytes, and spontaneous hepatocellular carcinoma development in aged mice. Neoplasia (New York, N.Y.) 19 25220589
2021 Biological Evaluation of 5'-(N-Ethylcarboxamido)adenosine Analogues as Grp94-Selective Inhibitors. ACS medicinal chemistry letters 18 33738064
2020 GRP94 regulates M1 macrophage polarization and insulin resistance. American journal of physiology. Endocrinology and metabolism 18 32208002
2002 Antigenic properties of the Leishmania infantum GRP94 and mapping of linear B-cell epitopes. Immunology letters 18 11803053
2012 Genetic evidence links the ASTRA protein chaperone component Tti2 to the SAGA transcription factor Tra1. Genetics 17 22505622
1989 Mutagenesis of the Tra1 core region of RK2 by using Tn5: identification of plasmid-specific transfer genes. Journal of bacteriology 17 2544570
1980 Cloning the Tra1 region of RP1. Plasmid 17 6100930
2024 Structural transitions modulate the chaperone activities of Grp94. Proceedings of the National Academy of Sciences of the United States of America 16 38483986
2015 Chaperone gp96 mediates ER-α36 cell membrane expression. Oncotarget 16 26396174
2008 Secreted heat shock protein gp96-Ig: an innovative vaccine approach. American journal of reproductive immunology (New York, N.Y. : 1989) 16 18405311