Heat shock protein HSP 90-beta (HSP90AB1)

The protein contains 724 amino acids for an estimated molecular weight of 83264 Da.

 

Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:16478993, PubMed:19696785). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself. Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:27295069, PubMed:26991466). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. They first alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic mod (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, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 99%
Model score: 155

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VariantDescription
dbSNP:rs11538975

Biological Process

Axon extension GO Logo
Axon guidance GO Logo
Cellular response to drug GO Logo
Cellular response to heat GO Logo
Cellular response to interleukin-4 GO Logo
Cellular response to organic cyclic compound GO Logo
Central nervous system neuron axonogenesis GO Logo
Chaperone-mediated protein complex assembly GO Logo
Establishment of cell polarity GO Logo
Fc-gamma receptor signaling pathway involved in phagocytosis GO Logo
Innate immune response GO Logo
Negative regulation of cell cycle arrest GO Logo
Negative regulation of complement-dependent cytotoxicity GO Logo
Negative regulation of neuron apoptotic process GO Logo
Negative regulation of proteasomal protein catabolic process GO Logo
Negative regulation of proteasomal ubiquitin-dependent protein catabolic process GO Logo
Negative regulation of protein metabolic process GO Logo
Negative regulation of transforming growth factor beta activation GO Logo
Neutrophil degranulation GO Logo
Nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway GO Logo
Placenta development GO Logo
Positive regulation of cell differentiation GO Logo
Positive regulation of cell size GO Logo
Positive regulation of cyclin-dependent protein kinase activity GO Logo
Positive regulation of nitric oxide biosynthetic process GO Logo
Positive regulation of peptidyl-serine phosphorylation GO Logo
Positive regulation of phosphoprotein phosphatase activity GO Logo
Positive regulation of protein binding GO Logo
Positive regulation of protein import into nucleus GO Logo
Positive regulation of protein import into nucleus, translocation GO Logo
Positive regulation of protein kinase B signaling GO Logo
Positive regulation of protein localization to cell surface GO Logo
Positive regulation of protein serine/threonine kinase activity GO Logo
Positive regulation of tau-protein kinase activity GO Logo
Positive regulation of telomerase activity GO Logo
Positive regulation of transforming growth factor beta receptor signaling pathway GO Logo
Protein folding GO Logo
Protein stabilization GO Logo
Purinergic nucleotide receptor signaling pathway GO Logo
Regulation of cellular protein localization GO Logo
Regulation of cellular response to heat GO Logo
Regulation of interferon-gamma-mediated signaling pathway GO Logo
Regulation of protein ubiquitination GO Logo
Regulation of type I interferon-mediated signaling pathway GO Logo
Response to cocaine GO Logo
Response to drug GO Logo
Response to salt stress GO Logo
Response to unfolded protein GO Logo
Supramolecular fiber organization GO Logo
Telomerase holoenzyme complex assembly GO Logo
Telomere maintenance via telomerase GO Logo
Virion attachment to host cell GO Logo
Xenobiotic metabolic process GO Logo

The reference OMIM entry for this protein is 140572

Heat-shock protein, 90-kd, alpha, class b, member 1; hsp90ab1
Heat-shock 90-kd protein 1, beta, formerly; hspcb, formerly
Hspc2
Hsp90b

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. There are 2 major cytosolic HSP90 proteins, HSP90AA1 (140571), an inducible form, and HSP90AB1, a constitutive form. Other HSP90 proteins are found in endoplasmic reticulum (HSP90B1; 191175) and mitochondria (TRAP1; 606219) (Chen et al., 2005).

CLONING

By database analysis, Chen et al. (2005) identified several HSP90AB1 variants encoding proteins of 571, 632, 724, and 737 amino acids. Like other HSP90 proteins, the 724-amino acid HSP90AB1 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 a 4-helical cytokine motif, a gln-rich region, and a C-terminal MEEVD motif characteristic of cytosolic HSP90 proteins. The 737-amino acid HSP90AB1 isoform is identical to the 724-amino acid isoform except for a short C-terminal extension.

GENE STRUCTURE

Rebbe et al. (1989) determined the complete genomic sequence of the HSP90B gene, including 1,102 bp upstream of the transcription initiation site. The gene consists of 12 exons and 11 introns. The exons range in size from 99 to 396 bp and the introns from 91 to 1,433 bp. Chen et al. (2005) also determined that the HSP90AB1 gene contains 12 exons.

MAPPING

By PCR amplification from a panel of hybrid cell lines, Durkin et al. (1993) mapped the HSPCB gene to chromosome 6 near the TCTE1 gene (186975) at 6p21. They were able to differentiate the structural gene from pseudogenes by designing primers from intronic sequences. By designing primers that bracket an intron, they were able to map 2 HSPCB pseudogenes, one to chromosome 4 and the other to chromosome 15. Saito et al. (1992) isolated 68 new RFLP markers on human chromosome 6, of which 64 were localized on chromosomal bands by fluorescence in situ hybridization. Takahashi et al. (1994) found that one of these markers, cloned into a cosmid vector and located at the D6S182 locus, contained the sequence corresponding to the 5-prime upstream region of the HSP90B gene. This strongly suggested that the gene is located at 6p12 inasmuch as the cosmid clone had been mapped to that band by Saito et al. (1992). By genomic sequence analysis, Chen et al. (2005) mapped the HSP90AB1 gene to chromosome 6p21.1. They identified HSP90AB pseudogenes on chromosomes 4p15.33 (HSP90AB2P), 4q22.1 (HSP90AB3P), 15q21.3 (HSP90AB4P), 3p12.3 (HSP90AB5P), and 13q32.1 (HSP90AB6P).

NOMENCLATURE

Chen et al. (2005) provided a revised nomenclature system for the HSP90 gene family. Under this system, the root HSP90A indicates cytosolic HSP90, HSP90B indicates endoplasmic reticulum HSP90, and TRAP indicates mitochondrial HSP90. HSP90A was divided into 2 classes, with HSP90AA representing conventional HSP90-alpha, and HSP90AB representing HSP90-beta. The number following the root/class represents the gene in that class, and a 'P' at the end indicates a putative pseudogene. ... 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.

Feb. 10, 2018: 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 140572 was added.

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