HSP90B1

{{Short description|Protein-coding gene in the species Homo sapiens}} {{Infobox_gene}} '''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.<ref name="pmid2377606">{{cite journal | vauthors = Maki RG, Old LJ, Srivastava PK | title = Human homologue of murine tumor rejection antigen gp96: 5'-regulatory and coding regions and relationship to stress-induced proteins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 87 | issue = 15 | pages = 5658–62 | date = August 1990 | pmid = 2377606 | pmc = 54386 | doi = 10.1073/pnas.87.15.5658 | bibcode = 1990PNAS...87.5658M | doi-access = free }}</ref><ref name="pmid16269234">{{cite journal | vauthors = Chen B, Piel WH, Gui L, Bruford E, Monteiro A | title = The HSP90 family of genes in the human genome: insights into their divergence and evolution | journal = Genomics | volume = 86 | issue = 6 | pages = 627–37 | date = December 2005 | pmid = 16269234 | doi = 10.1016/j.ygeno.2005.08.012 | doi-access = free }}</ref>

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.<ref name="pmid11584270">{{cite journal | vauthors = Randow F, Seed B | title = Endoplasmic reticulum chaperone gp96 is required for innate immunity but not cell viability | journal = Nature Cell Biology | volume = 3 | issue = 10 | pages = 891–6 | date = October 2001 | pmid = 11584270 | doi = 10.1038/ncb1001-891 | s2cid = 26559580 }}</ref><ref name="pmid17275357">{{cite journal | vauthors = Yang Y, Liu B, Dai J, Srivastava PK, Zammit DJ, Lefrançois L, Li Z | title = Heat shock protein gp96 is a master chaperone for toll-like receptors and is important in the innate function of macrophages | journal = Immunity | volume = 26 | issue = 2 | pages = 215–26 | date = February 2007 | pmid = 17275357 | pmc = 2847270 | doi = 10.1016/j.immuni.2006.12.005 }},</ref> It has been implicated as an essential immune chaperone to regulate both innate and adaptive immunity.<ref name="pmid11248798">{{cite journal | vauthors = Schild H, Rammensee HG | title = gp96--the immune system's Swiss army knife | journal = Nature Immunology | volume = 1 | issue = 2 | pages = 100–1 | date = August 2000 | pmid = 11248798 | doi = 10.1038/77770 | s2cid = 29571184 }}</ref> Tumor-derived HSP90B1 (vitespen) has entered clinical trials for cancer immunotherapy.<ref name="pmid19663726">{{cite journal | vauthors = Wood CG, Mulders P | title = Vitespen: a preclinical and clinical review | journal = Future Oncology | volume = 5 | issue = 6 | pages = 763–74 | date = August 2009 | pmid = 19663726 | doi = 10.2217/fon.09.46 }}</ref><ref name="pmid19863242">{{cite journal | vauthors = Tosti G, di Pietro A, Ferrucci PF, Testori A | title = HSPPC-96 vaccine in metastatic melanoma patients: from the state of the art to a possible future | journal = Expert Review of Vaccines | volume = 8 | issue = 11 | pages = 1513–26 | date = November 2009 | pmid = 19863242 | doi = 10.1586/erv.09.108 | s2cid = 207223461 }}</ref><ref name="NCT00293423_ClinicalTrials.gov">{{cite web | url = http://clinicaltrials.gov/ct2/show/NCT00293423 | title = NCT00293423 | publisher = ClinicalTrials.gov, United States National Institutes of Health | quote = GP96 Heat Shock Protein-Peptide Complex Vaccine in Treating Patients With Recurrent or Progressive Glioma | access-date = 2010-04-10 }}</ref><ref>{{cite journal | vauthors = 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 | title = Heat-shock protein peptide complex-96 vaccination for recurrent glioblastoma: a phase II, single-arm trial | journal = Neuro-Oncology | volume = 16 | issue = 2 | pages = 274–9 | date = January 2014 | pmid = 24335700 | doi = 10.1093/neuonc/not203 | pmc = 3895386 }}</ref>

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.<ref>{{cite journal | vauthors = Khandelwal A, Crowley VM, Blagg BS | title = Resorcinol-Based Grp94-Selective Inhibitors | language = EN | journal = ACS Medicinal Chemistry Letters | volume = 8 | issue = 10 | pages = 1013–1018 | date = October 2017 | pmid = 29057043 | pmc = 5641966 | doi = 10.1021/acsmedchemlett.7b00193 }}</ref>

== References == {{Reflist}}

== Further reading == {{refbegin | 2}} * {{cite journal | vauthors = Srivastava P | title = Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses | journal = Annual Review of Immunology | volume = 20 | issue = 1 | pages = 395–425 | year = 2001 | pmid = 11861608 | doi = 10.1146/annurev.immunol.20.100301.064801 }} * {{cite journal | vauthors = Li Z, Dai J, Zheng H, Liu B, Caudill M | title = An integrated view of the roles and mechanisms of heat shock protein gp96-peptide complex in eliciting immune response | journal = Frontiers in Bioscience | volume = 7 | issue = 4| pages = d731–51 | date = March 2002 | pmid = 11861214 | doi = 10.2741/A808 }} * {{cite journal | vauthors = Dollins DE, Warren JJ, Immormino RM, Gewirth DT | title = Structures of GRP94-nucleotide complexes reveal mechanistic differences between the hsp90 chaperones | journal = Molecular Cell | volume = 28 | issue = 1 | pages = 41–56 | date = October 2007 | pmid = 17936703 | pmc = 2094010 | doi = 10.1016/j.molcel.2007.08.024 }} * {{cite journal | vauthors = Kaul SC, Taira K, Pereira-Smith OM, Wadhwa R | title = Mortalin: present and prospective | journal = Experimental Gerontology | volume = 37 | issue = 10–11 | pages = 1157–64 | year = 2003 | pmid = 12470827 | doi = 10.1016/S0531-5565(02)00135-3 | s2cid = 44450296 }} * {{cite journal | vauthors = Schaiff WT, Hruska KA, McCourt DW, Green M, Schwartz BD | title = HLA-DR associates with specific stress proteins and is retained in the endoplasmic reticulum in invariant chain negative cells | journal = The Journal of Experimental Medicine | volume = 176 | issue = 3 | pages = 657–66 | date = September 1992 | pmid = 1512535 | pmc = 2119345 | doi = 10.1084/jem.176.3.657 }} * {{cite journal | vauthors = Zolnierowicz S, Work C, Hutchison K, Fox IH | title = Partial separation of platelet and placental adenosine receptors from adenosine A2-like binding protein | journal = Molecular Pharmacology | volume = 37 | issue = 4 | pages = 554–9 | date = April 1990 | pmid = 2325637 }} * {{cite journal | vauthors = Hutchison KA, Nevins B, Perini F, Fox IH | title = Soluble and membrane-associated human low-affinity adenosine binding protein (adenotin): properties and homology with mammalian and avian stress proteins | journal = Biochemistry | volume = 29 | issue = 21 | pages = 5138–44 | date = May 1990 | pmid = 2378869 | doi = 10.1021/bi00473a020 }} * {{cite journal | vauthors = Chang SC, Erwin AE, Lee AS | title = Glucose-regulated protein (GRP94 and GRP78) genes share common regulatory domains and are coordinately regulated by common trans-acting factors | journal = Molecular and Cellular Biology | volume = 9 | issue = 5 | pages = 2153–62 | date = May 1989 | pmid = 2546060 | pmc = 363009 | doi = 10.1128/mcb.9.5.2153}} * {{cite journal | vauthors = Anderson SL, Shen T, Lou J, Xing L, Blachere NE, Srivastava PK, Rubin BY | title = The endoplasmic reticular heat shock protein gp96 is transcriptionally upregulated in interferon-treated cells | journal = The Journal of Experimental Medicine | volume = 180 | issue = 4 | pages = 1565–9 | date = October 1994 | pmid = 7523574 | pmc = 2191700 | doi = 10.1084/jem.180.4.1565 }} * {{cite journal | vauthors = Bruneau N, Lombardo D | title = Chaperone function of a Grp 94-related protein for folding and transport of the pancreatic bile salt-dependent lipase | journal = The Journal of Biological Chemistry | volume = 270 | issue = 22 | pages = 13524–33 | date = June 1995 | pmid = 7768954 | doi = 10.1074/jbc.270.22.13524 | doi-access = free }} * {{cite journal | vauthors = Chavany C, Mimnaugh E, Miller P, Bitton R, Nguyen P, Trepel J, Whitesell L, Schnur R, Moyer J, Neckers L | title = p185erbB2 binds to GRP94 in vivo. Dissociation of the p185erbB2/GRP94 heterocomplex by benzoquinone ansamycins precedes depletion of p185erbB2 | journal = The Journal of Biological Chemistry | volume = 271 | issue = 9 | pages = 4974–7 | date = March 1996 | pmid = 8617772 | doi = 10.1074/jbc.271.9.4974 | doi-access = free }} * {{cite journal | vauthors = Kuznetsov G, Chen LB, Nigam SK | title = Multiple molecular chaperones complex with misfolded large oligomeric glycoproteins in the endoplasmic reticulum | journal = The Journal of Biological Chemistry | volume = 272 | issue = 5 | pages = 3057–63 | date = January 1997 | pmid = 9006956 | doi = 10.1074/jbc.272.5.3057 | doi-access = free }} * {{cite journal | vauthors = Hoshino T, Wang J, Devetten MP, Iwata N, Kajigaya S, Wise RJ, Liu JM, Youssoufian H | title = Molecular chaperone GRP94 binds to the Fanconi anemia group C protein and regulates its intracellular expression | journal = Blood | volume = 91 | issue = 11 | pages = 4379–86 | date = June 1998 | pmid = 9596688 | doi = 10.1182/blood.v91.11.4379}} * {{cite journal | vauthors = Linnik KM, Herscovitz H | title = 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 | journal = The Journal of Biological Chemistry | volume = 273 | issue = 33 | pages = 21368–73 | date = August 1998 | pmid = 9694898 | doi = 10.1074/jbc.273.33.21368 | doi-access = free }} * {{cite journal | vauthors = Delom F, Lejeune PJ, Vinet L, Carayon P, Mallet B | title = Involvement of oxidative reactions and extracellular protein chaperones in the rescue of misassembled thyroglobulin in the follicular lumen | journal = Biochemical and Biophysical Research Communications | volume = 255 | issue = 2 | pages = 438–43 | date = February 1999 | pmid = 10049727 | doi = 10.1006/bbrc.1999.0229 }} * {{cite journal | vauthors = Reddy RK, Lu J, Lee AS | title = The endoplasmic reticulum chaperone glycoprotein GRP94 with Ca(2+)-binding and antiapoptotic properties is a novel proteolytic target of calpain during etoposide-induced apoptosis | journal = The Journal of Biological Chemistry | volume = 274 | issue = 40 | pages = 28476–83 | date = October 1999 | pmid = 10497210 | doi = 10.1074/jbc.274.40.28476 | doi-access = free }} * {{cite journal | vauthors = Roher N, Sarno S, Miró F, Ruzzene M, Llorens F, Meggio F, Itarte E, Pinna LA, Plana M | title = The carboxy-terminal domain of Grp94 binds to protein kinase CK2 alpha but not to CK2 holoenzyme | journal = FEBS Letters | volume = 505 | issue = 1 | pages = 42–6 | date = September 2001 | pmid = 11557039 | doi = 10.1016/S0014-5793(01)02781-8 | s2cid = 52949128 | doi-access = free }} * {{cite journal | vauthors = 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 | title = The endoplasmic reticulum-resident heat shock protein Gp96 activates dendritic cells via the Toll-like receptor 2/4 pathway | journal = The Journal of Biological Chemistry | volume = 277 | issue = 23 | pages = 20847–53 | date = June 2002 | pmid = 11912201 | doi = 10.1074/jbc.M200425200 | doi-access = free }} * {{cite journal | vauthors = Shin HJ, Kim SS, Cho YH, Lee SG, Rho HM | title = Host cell proteins binding to the encapsidation signal epsilon in hepatitis B virus RNA | journal = Archives of Virology | volume = 147 | issue = 3 | pages = 471–91 | date = March 2002 | pmid = 11958450 | doi = 10.1007/s007050200001 | s2cid = 23653290 | doi-access = free }} {{refend}} {{PDB Gallery|geneid=7184}}

{{Chaperones}}

Category:Molecular chaperones Category:Endoplasmic reticulum resident proteins Category:Long stubs with short prose

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