HSP90B1

HSP90B1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4NH9
Identifiers
Aliases	HSP90B1 , ECGP, GP96, GRP94, HEL-S-125m, HEL35, TRA1, heat shock protein 90kDa beta family member 1, heat shock protein 90 beta family member 1
External IDs	OMIM: 191175; MGI: 98817; HomoloGene: 2476; GeneCards: HSP90B1; OMA:HSP90B1 - orthologs
Gene location (Human) Chr. Chromosome 12 (human) [1] Band 12q23.3 Start 103,930,107 bp [1] End 103,953,931 bp [1]
Gene location (Mouse) Chr. Chromosome 10 (mouse) [2] Band 10 C1|10 43.05 cM Start 86,526,073 bp [2] End 86,541,373 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of thyroid gland left lobe of thyroid gland corpus epididymis pericardium islet of Langerhans anterior pituitary tendon of biceps brachii pylorus Achilles tendon caput epididymis Top expressed in tail of embryo genital tubercle migratory enteric neural crest cell medullary collecting duct abdominal wall dermis spermatocyte renal corpuscle supraoptic nucleus seminal vesicula More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding calcium ion binding unfolded protein binding low-density lipoprotein particle receptor binding protein binding RNA binding protein phosphatase binding ATP binding Cellular component cytosol endocytic vesicle lumen endoplasmic reticulum lumen endoplasmic reticulum membrane membrane focal adhesion extracellular matrix melanosome plasma membrane endoplasmic reticulum chaperone complex extracellular region midbody endoplasmic reticulum perinuclear region of cytoplasm extracellular exosome nucleus protein-containing complex collagen-containing extracellular matrix Biological process response to hypoxia response to stress protein folding in endoplasmic reticulum negative regulation of apoptotic process receptor-mediated endocytosis response to endoplasmic reticulum stress toll-like receptor signaling pathway regulation of phosphoprotein phosphatase activity ATF6-mediated unfolded protein response actin rod assembly retrograde protein transport, ER to cytosol sequestering of calcium ion protein folding ubiquitin-dependent ERAD pathway protein transport cellular response to ATP post-translational protein modification cytokine-mediated signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7184 22027 Ensembl ENSG00000166598 ENSMUSG00000020048 UniProt P14625 P08113 RefSeq (mRNA) NM_003299 NM_011631 RefSeq (protein) NP_003290 NP_035761 Location (UCSC) Chr 12: 103.93 – 103.95 Mb Chr 10: 86.53 – 86.54 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. ^{[5] [6]}

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. ^{[7] [8]} It has been implicated as an essential immune chaperone to regulate both innate and adaptive immunity. ^[9] Tumor-derived HSP90B1 (vitespen) has entered clinical trials for cancer immunotherapy. ^{[10] [11] [12] [13]}

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. ^[14]

References

1. GRCh38: Ensembl release 89: ENSG00000166598 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020048 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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. Bibcode:1990PNAS...87.5658M. doi: 10.1073/pnas.87.15.5658 . PMC   54386 . PMID   2377606.
6. 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.
7. 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. S2CID   26559580.
8. 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.,
9. 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. S2CID   29571184.
10. 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.
11. 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. S2CID   207223461.
12. "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
13. 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.
14. 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

• Srivastava P (2001). "Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses". Annual Review of Immunology. 20 (1): 395–425. doi:10.1146/annurev.immunol.20.100301.064801. PMID   11861608.
• Li Z, Dai J, Zheng H, Liu B, Caudill M (March 2002). "An integrated view of the roles and mechanisms of heat shock protein gp96-peptide complex in eliciting immune response". Frontiers in Bioscience. 7 (4): d731–51. doi:10.2741/A808. PMID   11861214.
• Dollins DE, Warren JJ, Immormino RM, Gewirth DT (October 2007). "Structures of GRP94-nucleotide complexes reveal mechanistic differences between the hsp90 chaperones". Molecular Cell. 28 (1): 41–56. doi:10.1016/j.molcel.2007.08.024. PMC   2094010 . PMID   17936703.
• Kaul SC, Taira K, Pereira-Smith OM, Wadhwa R (2003). "Mortalin: present and prospective". Experimental Gerontology. 37 (10–11): 1157–64. doi:10.1016/S0531-5565(02)00135-3. PMID   12470827. S2CID   44450296.
• Schaiff WT, Hruska KA, McCourt DW, Green M, Schwartz BD (September 1992). "HLA-DR associates with specific stress proteins and is retained in the endoplasmic reticulum in invariant chain negative cells". The Journal of Experimental Medicine. 176 (3): 657–66. doi:10.1084/jem.176.3.657. PMC   2119345 . PMID   1512535.
• Zolnierowicz S, Work C, Hutchison K, Fox IH (April 1990). "Partial separation of platelet and placental adenosine receptors from adenosine A2-like binding protein". Molecular Pharmacology. 37 (4): 554–9. PMID   2325637.
• Hutchison KA, Nevins B, Perini F, Fox IH (May 1990). "Soluble and membrane-associated human low-affinity adenosine binding protein (adenotin): properties and homology with mammalian and avian stress proteins". Biochemistry. 29 (21): 5138–44. doi:10.1021/bi00473a020. PMID   2378869.
• Chang SC, Erwin AE, Lee AS (May 1989). "Glucose-regulated protein (GRP94 and GRP78) genes share common regulatory domains and are coordinately regulated by common trans-acting factors". Molecular and Cellular Biology. 9 (5): 2153–62. doi:10.1128/mcb.9.5.2153. PMC   363009 . PMID   2546060.
• Anderson SL, Shen T, Lou J, Xing L, Blachere NE, Srivastava PK, Rubin BY (October 1994). "The endoplasmic reticular heat shock protein gp96 is transcriptionally upregulated in interferon-treated cells". The Journal of Experimental Medicine. 180 (4): 1565–9. doi:10.1084/jem.180.4.1565. PMC   2191700 . PMID   7523574.
• Bruneau N, Lombardo D (June 1995). "Chaperone function of a Grp 94-related protein for folding and transport of the pancreatic bile salt-dependent lipase". The Journal of Biological Chemistry. 270 (22): 13524–33. doi: 10.1074/jbc.270.22.13524 . PMID   7768954.
• Chavany C, Mimnaugh E, Miller P, Bitton R, Nguyen P, Trepel J, Whitesell L, Schnur R, Moyer J, Neckers L (March 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. 271 (9): 4974–7. doi: 10.1074/jbc.271.9.4974 . PMID   8617772.
• Kuznetsov G, Chen LB, Nigam SK (January 1997). "Multiple molecular chaperones complex with misfolded large oligomeric glycoproteins in the endoplasmic reticulum". The Journal of Biological Chemistry. 272 (5): 3057–63. doi: 10.1074/jbc.272.5.3057 . PMID   9006956.
• Hoshino T, Wang J, Devetten MP, Iwata N, Kajigaya S, Wise RJ, Liu JM, Youssoufian H (June 1998). "Molecular chaperone GRP94 binds to the Fanconi anemia group C protein and regulates its intracellular expression". Blood. 91 (11): 4379–86. doi:10.1182/blood.v91.11.4379. PMID   9596688.
• Linnik KM, Herscovitz H (August 1998). "Multiple molecular chaperones interact with apolipoprotein B during its maturation. The network of endoplasmic reticulum-resident chaperones (ERp72, GRP94, calreticulin, and BiP) interacts with apolipoprotein b regardless of its lipidation state". The Journal of Biological Chemistry. 273 (33): 21368–73. doi: 10.1074/jbc.273.33.21368 . PMID   9694898.
• Delom F, Lejeune PJ, Vinet L, Carayon P, Mallet B (February 1999). "Involvement of oxidative reactions and extracellular protein chaperones in the rescue of misassembled thyroglobulin in the follicular lumen". Biochemical and Biophysical Research Communications. 255 (2): 438–43. doi:10.1006/bbrc.1999.0229. PMID   10049727.
• Reddy RK, Lu J, Lee AS (October 1999). "The endoplasmic reticulum chaperone glycoprotein GRP94 with Ca(2+)-binding and antiapoptotic properties is a novel proteolytic target of calpain during etoposide-induced apoptosis". The Journal of Biological Chemistry. 274 (40): 28476–83. doi: 10.1074/jbc.274.40.28476 . PMID   10497210.
• Roher N, Sarno S, Miró F, Ruzzene M, Llorens F, Meggio F, Itarte E, Pinna LA, Plana M (September 2001). "The carboxy-terminal domain of Grp94 binds to protein kinase CK2 alpha but not to CK2 holoenzyme". FEBS Letters. 505 (1): 42–6. doi: 10.1016/S0014-5793(01)02781-8 . PMID   11557039. S2CID   52949128.
• Vabulas RM, Braedel S, Hilf N, Singh-Jasuja H, Herter S, Ahmad-Nejad P, Kirschning CJ, Da Costa C, Rammensee HG, Wagner H, Schild H (June 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. 277 (23): 20847–53. doi: 10.1074/jbc.M200425200 . PMID   11912201.
• Shin HJ, Kim SS, Cho YH, Lee SG, Rho HM (March 2002). "Host cell proteins binding to the encapsidation signal epsilon in hepatitis B virus RNA". Archives of Virology. 147 (3): 471–91. doi: 10.1007/s007050200001 . PMID   11958450. S2CID   23653290.