Endoplasmin (HSP90B1)

The protein contains 803 amino acids for an estimated molecular weight of 92469 Da.

 

Molecular chaperone that functions in the processing and transport of secreted proteins (By similarity). When associated with CNPY3, required for proper folding of Toll-like receptors (By similarity). Functions in endoplasmic reticulum associated degradation (ERAD) (PubMed:18264092). Has ATPase activity (By similarity). May participate in the unfolding of cytosolic leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1 to facilitate their translocation into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and secretion; the translocation process is mediated by the cargo receptor TMED10 (PubMed:32272059). (updated: Oct. 7, 2020)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology.


Interpro domains
Total structural coverage: 92%
Model score: 49

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The reference OMIM entry for this protein is 191175

Heat-shock protein, 90-kd, beta, 1; hsp90b1
Tumor rejection antigen 1
Tra1
Stress-inducible tumor rejection antigen gp96
Glucose-regulated protein, 94-kd; grp94

DESCRIPTION

HSP90 proteins are highly conserved molecular chaperones that have key roles in signal transduction, protein folding, protein degradation, and morphologic evolution. HSP90 proteins normally associate with other cochaperones and play important roles in folding newly synthesized proteins or stabilizing and refolding denatured proteins after stress. HSP90B1 is an endoplasmic reticulum HSP90 protein. Other HSP90 proteins are found in cytosol (see HSP90AA1; 140571) and mitochondria (TRAP1; 606219) (Chen et al., 2005).

CLONING

By screening a human teratocarcinoma cDNA library with mouse gp96, Maki et al. (1990) isolated a cDNA encoding TRA1, which they called GP96. The 803-amino acid protein, which is 96% homologous to the mouse sequence, contains a 21-amino acid signal peptide and 5 potential N-linked glycosylation sites. Northern blot analysis detected a 2.8-kb GP96 transcript in all tumor cell lines tested. Southern blot analysis suggested the presence 3 or 4 GP96-related genes per haploid genome. By database analysis, Chen et al. (2005) identified full-length HSP90B1 and several variants. Like other HSP90 proteins, the 803-amino acid HSP90B1 protein has a highly conserved N-terminal domain, a charged domain, a middle domain involved in ATPase activity, a second charged domain, and a C-terminal domain. It also has an incomplete 4-helical cytokine motif, a gln-rich region, and a signal peptide.

GENE FUNCTION

Using a mouse system, Binder et al. (2000) determined that the receptor for GP96 is CD91 (A2MR, or LRP1; 107770) and that A2M (103950), a protein found in blood, inhibits GP96 binding to CD91. Schild and Rammensee (2000) stated that GP96 has multiple functions, including chaperoning peptides to MHC class I molecules of dendritic cells and other antigen-presenting cells, as well as inducing dendritic cells to express costimulatory molecules such as B7 (CD80; 112203) and to produce cytokines IL12 (see 161560) and TNFA (191160). Using a mutagenesis screen, Randow and Seed (2001) identified a murine pre-B cell line that was unresponsive to lipopolysaccharide and deficient in Gp96. Lack of Gp96 was compatible with survival even under stress conditions and resulted in defective formation of a subset of surface receptors and retention of intracellular Toll-like receptors (TLRs), leading to unresponsiveness to microbial stimuli. Reintroduction of Gp96 restored surface expression of Tlr1 (601194), Tlr2 (603028), and Tlr4 (603030). Randow and Seed (2001) concluded that GP96 is required for maturation of a narrow set of client proteins and that it forms stable associations with these proteins. Rivoltini et al. (2003) showed that GP96 derived from metastatic human melanoma or colon carcinomas could present antigenic peptides to CD8 (see 186910)-positive T cells both in vivo and in vitro. Paris et al. (2005) found that GRP94 was upregulated in endothelial cells by hypoxia, and they identified 3 hypoxia-responsive elements (HRE) in the GRP94 promoter. Competition experiments demonstrated that HIF1 (see 603348) bound to the GRP94 HREs with high affinity. Using a ligand overlay approach, Cabanes et al. (2005) identified GP96 as a receptor for a Listeria monocytogenes virulence factor, Vip. The GP96-Vip interaction was critical for viral entry into mammalian cells and for infection in vivo. By coimmunoprecipitation, mass spectrum analysis, and fluorescence microscopy, Na et al. (2008) identified GP96 as a hum ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.

June 7, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 191175 was added.

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed