HSP90B1

Heat shock protein 90kDa beta (Grp94), member 1

PDB rendering based on 1qy5.

Available structures
PDB	1qy5, 1qy8, 1qye, 1u0y, 1yt2

Identifiers

Symbols

HSP90B1; ECGP; GP96; GRP94; TRA1

External IDs

OMIM: 191175 MGI: 98817 HomoloGene: 2476 GeneCards: HSP90B1 Gene

Gene Ontology
Molecular function	• nucleotide binding • RNA binding • calcium ion binding • protein binding • ATP binding • protein phosphatase binding • virion binding • low-density lipoprotein particle receptor binding • unfolded protein binding
Cellular component	• endoplasmic reticulum • endoplasmic reticulum • endoplasmic reticulum lumen • endoplasmic reticulum membrane • microsome • cytosol • midbody • melanosome • plasma membrane part • perinuclear region of cytoplasm
Biological process	• response to hypoxia • protein folding • anti-apoptosis • anti-apoptosis • protein transport • ER-associated protein catabolic process • actin rod assembly • regulation of phosphoprotein phosphatase activity • sequestering of calcium ion • cellular response to ATP
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 12:
104.32 – 104.34 Mb

Chr 10:
86.15 – 86.17 Mb

PubMed search

[1]

[2]

Heat shock protein 90kDa beta member 1 (HSP90B1), known also as endoplasmin, gp96, grp94 and 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. It has been implicated as an essential immune chaperone to regulate both innate and adaptive immunity.^[3] Tumor-derived HSP90B1 (vitespen) has entered clinical trials for cancer immunotherapy.^[4]^[5]^[6]

References

^ 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". Proc. Natl. Acad. Sci. U.S.A. 87 (15): 5658–62. doi:10.1073/pnas.87.15.5658. PMC 54386. PMID 2377606. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=54386.
^ 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.
^ Schild H, Rammensee HG (August 2000). "gp96--the immune system's Swiss army knife". Nat. Immunol. 1 (2): 100–1. doi:10.1038/77770. PMID 11248798.
^ Wood CG, Mulders P (August 2009). "Vitespen: a preclinical and clinical review". Future Oncol 5 (6): 763–74. doi:10.2217/fon.09.46. PMID 19663726.
^ 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 Rev Vaccines 8 (11): 1513–26. doi:10.1586/erv.09.108. PMID 19863242.
^ "NCT00293423". ClinicalTrials.gov, United States National Institutes of Health. http://clinicaltrials.gov/ct2/show/NCT00293423. Retrieved 2010-04-10. "GP96 Heat Shock Protein-Peptide Complex Vaccine in Treating Patients With Recurrent or Progressive Glioma"

Srivastava P (2001). "Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses.". Annu Rev Immunol. 20 (1): 395–425. doi:10.1146/annurev.immunol.20.100301.064801. PMID 11861608.
Li Z, Dai J, Zheng H, et al. (2002). "An integrated view of the roles and mechanisms of heat shock protein gp96-peptide complex in eliciting immune response.". Front. Biosci. 7: d731–51. PMID 11861214.
Randow F, Seed B (2001). "Endoplasmic reticulum chaperone gp96 is required for innate immunity but not cell viability.". Nat. Cell Biol. 3 (10): 891–6. doi:10.1038/ncb1001-891. PMID 11584270.
Yang Y, et al. (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): 215–226. doi:10.1016/j.immuni.2006.12.005. PMC 2847270. PMID 17275357. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2847270.
Dollins DE, et al. (2007). "Structures of GRP94-nucleotide complexes reveal mechanistic differences between the hsp90 chaperones.". Mol Cell 28 (1): 41–56. doi:10.1016/j.molcel.2007.08.024. PMC 2094010. PMID 17936703. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2094010.
Kaul SC, Taira K, Pereira-Smith OM, Wadhwa R (2003). "Mortalin: present and prospective.". Exp. Gerontol. 37 (10-11): 1157–64. doi:10.1016/S0531-5565(02)00135-3. PMID 12470827.
Schaiff WT, Hruska KA, McCourt DW, et al. (1992). "HLA-DR associates with specific stress proteins and is retained in the endoplasmic reticulum in invariant chain negative cells.". J. Exp. Med. 176 (3): 657–66. doi:10.1084/jem.176.3.657. PMC 2119345. PMID 1512535. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2119345.
Zolnierowicz S, Work C, Hutchison K, Fox IH (1990). "Partial separation of platelet and placental adenosine receptors from adenosine A2-like binding protein.". Mol. Pharmacol. 37 (4): 554–9. PMID 2325637.
Hutchison KA, Nevins B, Perini F, Fox IH (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 (1989). "Glucose-regulated protein (GRP94 and GRP78) genes share common regulatory domains and are coordinately regulated by common trans-acting factors.". Mol. Cell. Biol. 9 (5): 2153–62. PMC 363009. PMID 2546060. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=363009.
Anderson SL, Shen T, Lou J, et al. (1994). "The endoplasmic reticular heat shock protein gp96 is transcriptionally upregulated in interferon-treated cells.". J. Exp. Med. 180 (4): 1565–9. doi:10.1084/jem.180.4.1565. PMC 2191700. PMID 7523574. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2191700.
Bruneau N, Lombardo D (1995). "Chaperone function of a Grp 94-related protein for folding and transport of the pancreatic bile salt-dependent lipase.". J. Biol. Chem. 270 (22): 13524–33. doi:10.1074/jbc.270.22.13524. PMID 7768954.
Chavany C, Mimnaugh E, Miller P, et al. (1996). "p185erbB2 binds to GRP94 in vivo. Dissociation of the p185erbB2/GRP94 heterocomplex by benzoquinone ansamycins precedes depletion of p185erbB2.". J. Biol. Chem. 271 (9): 4974–7. doi:10.1074/jbc.271.9.4974. PMID 8617772.
Kuznetsov G, Chen LB, Nigam SK (1997). "Multiple molecular chaperones complex with misfolded large oligomeric glycoproteins in the endoplasmic reticulum.". J. Biol. Chem. 272 (5): 3057–63. doi:10.1074/jbc.272.5.3057. PMID 9006956.
Hoshino T, Wang J, Devetten MP, et al. (1998). "Molecular chaperone GRP94 binds to the Fanconi anemia group C protein and regulates its intracellular expression.". Blood 91 (11): 4379–86. PMID 9596688.
Linnik KM, Herscovitz H (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.". J. Biol. Chem. 273 (33): 21368–73. doi:10.1074/jbc.273.33.21368. PMID 9694898.
Delom F, Lejeune PJ, Vinet L, et al. (1999). "Involvement of oxidative reactions and extracellular protein chaperones in the rescue of misassembled thyroglobulin in the follicular lumen.". Biochem. Biophys. Res. Commun. 255 (2): 438–43. doi:10.1006/bbrc.1999.0229. PMID 10049727.
Reddy RK, Lu J, Lee AS (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.". J. Biol. Chem. 274 (40): 28476–83. doi:10.1074/jbc.274.40.28476. PMID 10497210.
Roher N, Sarno S, Miró F, et al. (2001). "The carboxy-terminal domain of Grp94 binds to protein kinase CK2 alpha but not to CK2 holoenzyme.". FEBS Lett. 505 (1): 42–6. doi:10.1016/S0014-5793(01)02781-8. PMID 11557039.
Vabulas RM, Braedel S, Hilf N, et al. (2002). "The endoplasmic reticulum-resident heat shock protein Gp96 activates dendritic cells via the Toll-like receptor 2/4 pathway.". J. Biol. Chem. 277 (23): 20847–53. doi:10.1074/jbc.M200425200. PMID 11912201.
Shin HJ, Kim SS, Cho YH, et al. (2002). "Host cell proteins binding to the encapsidation signal epsilon in hepatitis B virus RNA.". Arch. Virol. 147 (3): 471–91. doi:10.1007/s007050200001. PMID 11958450.

PDB gallery

1qy5: Crystal Structure of the N-domain of the ER Hsp90 chaperone GRP94 in complex with the specific ligand NECA

1qy8: Crystal Structure of the N-domain of the ER Hsp90 chaperone GRP94 in complex with Radicicol

1qye: Crystal Structure of the N-domain of the ER Hsp90 chaperone GRP94 in complex with 2-chlorodideoxyadenosine

1u0y: N-Domain Of Grp94, with the Charged Domain, In Complex With the Novel Ligand N-Propyl Carboxyamido Adenosine

1yt2: Crystal Structure of the Unliganded Form of GRP94, the ER Hsp90: Basis for Nucleotide-Induced Conformational Change, GRP94N APO CRYSTAL

Posttranslational modification

Chaperones/
protein folding

Heat shock proteins/ Chaperonins	Hsp10/GroES (Early pregnancy factor) · Hsp27 · Hsp47 · HSP60/GroEL Hsp40/DnaJ (A1, A2, A3, B1, B2, B11, B4, B6, B9, C1, C3, C5, C6, C7, C10, C11, C13, C14, C19) Hsp70 (1A, 1B, 1L, 2, 4, 4L, 5, 6, 7, 8, 9, 12A, 14) Hsp90 (α₁, α₂, β, ER, TRAP1)

Other	Alpha crystallin · Clusterin · Survival of motor neuron (SMN1, SMN2)

Protein targeting

Signal peptide

Ubiquitin

E1 Ubiquitin-activating enzyme (UBA1, UBA2, UBA3, UBA5, UBA6, UBA7, ATG7, NAE1, SAE1)

E2 Ubiquitin-conjugating enzyme (A • B • C • D1, D2, D3 • E1, E2, E3 • G1, G2 • H • I • J1, J2 • K • L1, L2, L3, L4, L6 • M • N • O • Q1, Q2 • R1 (CDC34), R2 • S • V1, V2 • Z)

E3 Ubiquitin ligase (VHL, Cullin, CBL, MDM2, FANCL, UBR1)

Deubiquitinating enzyme: Ataxin 3 • USP6 • CYLD

ATG3 • BIRC6 • UFC1

Other

SUMO protein

see also posttranslational modification disorders
B bsyn: dna (repl, cycl, reco, repr) · tscr (fact, tcrg, nucl, rnat, rept, ptts) · tltn (risu, pttl, nexn) · dnab, rnab/runp · stru (domn, 1°, 2°, 3°, 4°)

HSP90B1

References

Further reading