The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Hsp90b1  -  heat shock protein 90, beta (Grp94), member 1

Mus musculus

Synonyms: 90 kDa, 94 kDa glucose-regulated protein, ERp99, Endoplasmic reticulum resident protein 99, Endoplasmin, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Hsp90b1


High impact information on Hsp90b1

  • Perforin is required for innate and adaptive immunity induced by heat shock protein gp96 [6].
  • Postuptake processing of gp96-chaperoned peptides requires proteasomes and the transporters associated with antigen processing, utilizing the classical endogenous antigen presentation pathway [7].
  • In addition, vaccination with irradiated cells secreting the GRP94 NH(2)-terminal geldanamycin-binding domain (NTD), a region lacking canonical peptide-binding motifs, yielded a similar suppression of tumor growth and metastatic progression [1].
  • Moreover, we show that in both humans and mice, only professional APCs like dendritic cells (DCs), macrophages, and B cells, but not T cells, are able to bind gp96 [8].
  • Thus, we provide evidence on the mechanisms by which gp96 is participating in the cross-presentation of antigens from cellular origin [8].

Chemical compound and disease context of Hsp90b1

  • GRP78 increased in a dose- and time-dependent fashion in embryonic hearts exposed to either 40 mg/dl or 80 mg/dl glucose, whereas GRP94 levels increased in hearts only after 24 h of hypoglycemia [9].
  • A lower percentage of propidium-iodide positive/GFP-fluorescent myocytes co-expressing exogenous Grp94, with respect to myocytes expressing GFP alone, was observed after exposure to either A23187 (6.6% vs. 14.0%, respectively) or simulated ischemia (8.5% vs. 17.7%, respectively) [10].
  • The number of necrotic cells, evaluated by propidium iodide uptake, was reduced when cells from the Grp94-overexpressing H9c2 clone were exposed to conditions simulating ischemia [10].
  • Rabbit antiserum to murine gp96 detects an antigenically related Mr 96,000 cell surface glycoprotein on two cultured human melanoma cell lines, SK-MEL-13 and SK-MEL-177 [11].

Biological context of Hsp90b1


Anatomical context of Hsp90b1


Associations of Hsp90b1 with chemical compounds

  • In addition, we have shown that the interaction of the chaperoned peptides with hsc70 and gp96 is not compromised during heparin chromatography [18].
  • We have isolated an expressible full-length cDNA clone encoding murine ERp99, an abundant, conserved transmembrane glycoprotein of the endoplasmic reticulum membrane [19].
  • When GRP94 was present in the medium, and thus accessible to both receptor-mediated and fluid phase internalization pathways, internalization was modestly inhibited in the presence of yeast mannan, a competitive inhibitor of mannose/fucose receptor activity, and substantially inhibited by dimethylamiloride, an inhibitor of macropinocytosis [20].
  • All EtRGs, including GRP94 and GRP78, showed similar ethanol concentration-dependent increases in mRNA abundance [21].
  • Expression of the glucose regulated proteins (GRP78 and GRP94) is greatly increased after cells are exposed to stress agents (including A23187 and tunicamycin) which inhibit ER function [22].

Physical interactions of Hsp90b1


Co-localisations of Hsp90b1


Regulatory relationships of Hsp90b1

  • The GRP78 protein is constitutively expressed in the undifferentiated F9 cells whereas the level of GRP94 is below detection limit [4].

Other interactions of Hsp90b1

  • The three main immunogenic HSPs, gp96, hsp86/84, and hsc70 can be further isolated to homogeneity using additional purification methods [18].
  • Low endotoxin GRP94/gp96 retained its native conformation, ligand binding activity, and in vitro chaperone function, yet did not activate macrophage NF-kappa B signaling, nitric oxide production or inducible nitric-oxide synthase production [12].
  • The data demonstrate an essential role for perforin-mediated functions in the activation of innate and adaptive immunity by heat shock protein gp96-peptide complexes [6].
  • The heat shock proteins (HSP) gp96, Hsp70 and Hsp60 activate professional antigen-presenting cells (APC) to secrete proinflammatory cytokines and to express costimulatory molecules [24].
  • Furthermore, the novel role of gp96 in Th cell proliferation skewing its differentiation toward Th2 phenotype has also been established [17].

Analytical, diagnostic and therapeutic context of Hsp90b1


  1. GRP94 (gp96) and GRP94 N-terminal geldanamycin binding domain elicit tissue nonrestricted tumor suppression. Baker-LePain, J.C., Sarzotti, M., Fields, T.A., Li, C.Y., Nicchitta, C.V. J. Exp. Med. (2002) [Pubmed]
  2. Cell surface expression of an endoplasmic reticulum resident heat shock protein gp96 triggers MyD88-dependent systemic autoimmune diseases. Liu, B., Dai, J., Zheng, H., Stoilova, D., Sun, S., Li, Z. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  3. Down-regulation of gp96 by Orientia tsutsugamushi. Cho, N.H., Choi, C.Y., Seong, S.Y. Microbiol. Immunol. (2004) [Pubmed]
  4. Expression of the glucose-regulated proteins (GRP94 and GRP78) in differentiated and undifferentiated mouse embryonic cells and the use of the GRP78 promoter as an expression system in embryonic cells. Kim, S.K., Kim, Y.K., Lee, A.S. Differentiation (1990) [Pubmed]
  5. Mouse lymphoma cells destined to undergo apoptosis in response to thapsigargin treatment fail to generate a calcium-mediated grp78/grp94 stress response. McCormick, T.S., McColl, K.S., Distelhorst, C.W. J. Biol. Chem. (1997) [Pubmed]
  6. Perforin is required for innate and adaptive immunity induced by heat shock protein gp96. Strbo, N., Oizumi, S., Sotosek-Tokmadzic, V., Podack, E.R. Immunity (2003) [Pubmed]
  7. CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Basu, S., Binder, R.J., Ramalingam, T., Srivastava, P.K. Immunity (2001) [Pubmed]
  8. Cross-presentation of glycoprotein 96-associated antigens on major histocompatibility complex class I molecules requires receptor-mediated endocytosis. Singh-Jasuja, H., Toes, R.E., Spee, P., Münz, C., Hilf, N., Schoenberger, S.P., Ricciardi-Castagnoli, P., Neefjes, J., Rammensee, H.G., Arnold-Schild, D., Schild, H. J. Exp. Med. (2000) [Pubmed]
  9. Expression of glucose-regulated proteins (GRP78 and GRP94) in hearts and fore-limb buds of mouse embryos exposed to hypoglycemia in vitro. Barnes, J.A., Smoak, I.W., Branch, S. Cell Stress Chaperones (1999) [Pubmed]
  10. Overexpression of the stress protein Grp94 reduces cardiomyocyte necrosis due to calcium overload and simulated ischemia. Vitadello, M., Penzo, D., Petronilli, V., Michieli, G., Gomirato, S., Menabò, R., Di Lisa, F., Gorza, L. FASEB J. (2003) [Pubmed]
  11. Identification of a human homologue of the murine tumor rejection antigen GP96. Srivastava, P.K., Old, L.J. Cancer Res. (1989) [Pubmed]
  12. GRP94/gp96 elicits ERK activation in murine macrophages. A role for endotoxin contamination in NF-kappa B activation and nitric oxide production. Reed, R.C., Berwin, B., Baker, J.P., Nicchitta, C.V. J. Biol. Chem. (2003) [Pubmed]
  13. Retroviral insertions in Evi12, a novel common virus integration site upstream of Tra1/Grp94, frequently coincide with insertions in the gene encoding the peripheral cannabinoid receptor Cnr2. Valk, P.J., Vankan, Y., Joosten, M., Jenkins, N.A., Copeland, N.G., Löwenberg, B., Delwel, R. J. Virol. (1999) [Pubmed]
  14. Radicicol-sensitive peptide binding to the N-terminal portion of GRP94. Vogen, S., Gidalevitz, T., Biswas, C., Simen, B.B., Stein, E., Gulmen, F., Argon, Y. J. Biol. Chem. (2002) [Pubmed]
  15. Localization and significance of molecular chaperones, heat shock protein 1, and tumor rejection antigen gp96 in the male reproductive tract and during capacitation and acrosome reaction. Asquith, K.L., Harman, A.J., McLaughlin, E.A., Nixon, B., Aitken, R.J. Biol. Reprod. (2005) [Pubmed]
  16. Cell surface targeting of heat shock protein gp96 induces dendritic cell maturation and antitumor immunity. Zheng, H., Dai, J., Stoilova, D., Li, Z. J. Immunol. (2001) [Pubmed]
  17. Evidence that glycoprotein 96 (B2), a stress protein, functions as a Th2-specific costimulatory molecule. Banerjee, P.P., Vinay, D.S., Mathew, A., Raje, M., Parekh, V., Prasad, D.V., Kumar, A., Mitra, D., Mishra, G.C. J. Immunol. (2002) [Pubmed]
  18. Purification of multiple heat shock proteins from a single tumor sample. Ménoret, A., Bell, G. J. Immunol. Methods (2000) [Pubmed]
  19. ERp99, an abundant, conserved glycoprotein of the endoplasmic reticulum, is homologous to the 90-kDa heat shock protein (hsp90) and the 94-kDa glucose regulated protein (GRP94). Mazzarella, R.A., Green, M. J. Biol. Chem. (1987) [Pubmed]
  20. Receptor mediated and fluid phase pathways for internalization of the ER Hsp90 chaperone GRP94 in murine macrophages. Wassenberg, J.J., Dezfulian, C., Nicchitta, C.V. J. Cell. Sci. (1999) [Pubmed]
  21. Ethanol-responsive genes in neural cells include the 78-kilodalton glucose-regulated protein (GRP78) and 94-kilodalton glucose-regulated protein (GRP94) molecular chaperones. Miles, M.F., Wilke, N., Elliot, M., Tanner, W., Shah, S. Mol. Pharmacol. (1994) [Pubmed]
  22. Brefeldin A, thapsigargin, and AIF4- stimulate the accumulation of GRP78 mRNA in a cycloheximide dependent manner, whilst induction by hypoxia is independent of protein synthesis. Price, B.D., Mannheim-Rodman, L.A., Calderwood, S.K. J. Cell. Physiol. (1992) [Pubmed]
  23. Glial expression of the 90-kDa heat shock protein (HSP90) and the 94-kDa glucose-regulated protein (GRP94) following an excitotoxic lesion in the mouse hippocampus. Jeon, G.S., Park, S.W., Kim, D.W., Seo, J.H., Cho, J., Lim, S.Y., Kim, S.D., Cho, S.S. Glia (2004) [Pubmed]
  24. Heat shock proteins as "danger signals": eukaryotic Hsp60 enhances and accelerates antigen-specific IFN-gamma production in T cells. Breloer, M., Dorner, B., Moré, S.H., Roderian, T., Fleischer, B., von Bonin, A. Eur. J. Immunol. (2001) [Pubmed]
  25. Glycoprotein 96 can chaperone both MHC class I- and class II-restricted epitopes for in vivo presentation, but selectively primes CD8+ T cell effector function. Doody, A.D., Kovalchin, J.T., Mihalyo, M.A., Hagymasi, A.T., Drake, C.G., Adler, A.J. J. Immunol. (2004) [Pubmed]
  26. Rapid degradation of an unassembled immunoglobulin light chain is mediated by a serine protease and occurs in a pre-Golgi compartment. Gardner, A.M., Aviel, S., Argon, Y. J. Biol. Chem. (1993) [Pubmed]
  27. The 170-kDa glucose-regulated stress protein is an endoplasmic reticulum protein that binds immunoglobulin. Lin, H.Y., Masso-Welch, P., Di, Y.P., Cai, J.W., Shen, J.W., Subjeck, J.R. Mol. Biol. Cell (1993) [Pubmed]
WikiGenes - Universities