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Heat shock protein 90kDa beta member 1 (HSP90B1), known also as endoplasmin, gp96, grp94, or ERp99, is a chaperone protein that in humans is encoded by the HSP90B1 gene.[1][2]

HSP90B1 is an HSP90 paralogue that is found in the endoplasmic reticulum. It plays critical roles in folding proteins in the secretory pathway such as Toll-like receptors and integrins.[3][4] It has been implicated as an essential immune chaperone to regulate both innate and adaptive immunity.[5] Tumor-derived HSP90B1 (vitespen) has entered clinical trials for cancer immunotherapy.[6][7][8][9]

grp94 has been shown to be a target for treatment of a plethora of diseases such as glaucoma, multiple myeloma , and metastatic cancer. grp94 includes 5 distinct amino acids in its primary sequence which creates 2 unique sub-pockets, S1 and S2. These sub-pockets have been utilized in current research in order to inhibit the chaperone since its client proteins seem to be up-regulated in cancer cells. [10]


  1. Maki RG, Old LJ, Srivastava PK (August 1990). "Human homologue of murine tumor rejection antigen gp96: 5'-regulatory and coding regions and relationship to stress-induced proteins". Proceedings of the National Academy of Sciences of the United States of America. 87 (15): 5658–62. doi:10.1073/pnas.87.15.5658. PMC 54386. PMID 2377606.
  2. Chen B, Piel WH, Gui L, Bruford E, Monteiro A (December 2005). "The HSP90 family of genes in the human genome: insights into their divergence and evolution". Genomics. 86 (6): 627–37. doi:10.1016/j.ygeno.2005.08.012. PMID 16269234.
  3. Randow F, Seed B (October 2001). "Endoplasmic reticulum chaperone gp96 is required for innate immunity but not cell viability". Nature Cell Biology. 3 (10): 891–6. doi:10.1038/ncb1001-891. PMID 11584270.
  4. Yang Y, Liu B, Dai J, Srivastava PK, Zammit DJ, Lefrançois L, Li Z (February 2007). "Heat shock protein gp96 is a master chaperone for toll-like receptors and is important in the innate function of macrophages". Immunity. 26 (2): 215–26. doi:10.1016/j.immuni.2006.12.005. PMC 2847270. PMID 17275357.,
  5. Schild H, Rammensee HG (August 2000). "gp96--the immune system's Swiss army knife". Nature Immunology. 1 (2): 100–1. doi:10.1038/77770. PMID 11248798.
  6. Wood CG, Mulders P (August 2009). "Vitespen: a preclinical and clinical review". Future Oncology. 5 (6): 763–74. doi:10.2217/fon.09.46. PMID 19663726.
  7. Tosti G, di Pietro A, Ferrucci PF, Testori A (November 2009). "HSPPC-96 vaccine in metastatic melanoma patients: from the state of the art to a possible future". Expert Review of Vaccines. 8 (11): 1513–26. doi:10.1586/erv.09.108. PMID 19863242.
  8. "NCT00293423". ClinicalTrials.gov, United States National Institutes of Health. Retrieved 2010-04-10. GP96 Heat Shock Protein-Peptide Complex Vaccine in Treating Patients With Recurrent or Progressive Glioma
  9. Bloch O, Crane CA, Fuks Y, Kaur R, Aghi MK, Berger MS, Butowski NA, Chang SM, Clarke JL, McDermott MW, Prados MD, Sloan AE, Bruce JN, Parsa AT (January 2014). "Heat-shock protein peptide complex-96 vaccination for recurrent glioblastoma: a phase II, single-arm trial". Neuro-Oncology. 16 (2): 274–9. doi:10.1093/neuonc/not203. PMC 3895386. PMID 24335700.
  10. Khandelwal A, Crowley VM, Blagg BS (October 2017). "Resorcinol-Based Grp94-Selective Inhibitors". ACS Medicinal Chemistry Letters. 8 (10): 1013–1018. doi:10.1021/acsmedchemlett.7b00193. PMC 5641966. PMID 29057043.

Further reading