Heat shock protein HSP 90-alpha (HSP90AA1)
The protein contains 732 amino acids for an estimated molecular weight of 84660 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 that is linked to its ATPase activity which is essential for its chaperone 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:11274138, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155, PubMed:12526792). 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 (PubMed:29127155). 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). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription mach (updated: Feb. 10, 2021)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
- 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.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- 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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| dbSNP:rs8005905 |
Biological Process
Activation of innate immune response
Axon extension
Axon guidance
Cellular response to heat
Cellular response to virus
Central nervous system neuron axonogenesis
Chaperone-mediated autophagy
Chaperone-mediated protein complex assembly
Ciliary basal body-plasma membrane docking
Cytokine-mediated signaling pathway
ERBB2 signaling pathway
Establishment of cell polarity
Fc-gamma receptor signaling pathway involved in phagocytosis
G2/M transition of mitotic cell cycle
Innate immune response
Mitochondrial transport
Mitotic cell cycle
Neutrophil degranulation
Nitric oxide metabolic process
Obsolete cofactor metabolic process
Organelle organization
Positive regulation of cellular protein catabolic process
Positive regulation of defense response to virus by host
Positive regulation of interferon-beta production
Positive regulation of nitric oxide biosynthetic process
Positive regulation of peptidyl-serine phosphorylation
Positive regulation of protein kinase B signaling
Positive regulation of protein phosphorylation
Positive regulation of protein polymerization
Positive regulation of tau-protein kinase activity
Positive regulation of telomerase activity
Protein folding
Protein insertion into mitochondrial outer membrane
Protein refolding
Protein stabilization
Protein unfolding
Receptor-mediated endocytosis
Regulation of apoptotic process
Regulation of cellular protein localization
Regulation of cellular response to heat
Regulation of G2/M transition of mitotic cell cycle
Regulation of necroptotic process
Regulation of nitric-oxide synthase activity
Regulation of protein ubiquitination
Regulation of protein-containing complex assembly
Response to antibiotic
Response to cold
Response to heat
Response to unfolded protein
Signal transduction
Small molecule metabolic process
Telomerase holoenzyme complex assembly
Telomere maintenance via telomerase
Tetrahydrobiopterin metabolic process
Vascular endothelial growth factor receptor signaling pathway
Viral process
Cellular Component
Axonal growth cone
Cell surface
Cytoplasm
Cytosol
Dendritic growth cone
Endocytic vesicle lumen
Extracellular exosome
Extracellular region
Ficolin-1-rich granule lumen
Lysosomal lumen
Melanosome
Membrane
Mitochondrion
Myelin sheath
Neuronal cell body
Nucleoplasm
Nucleus
Perinuclear region of cytoplasm
Plasma membrane
Protein complex
Protein-containing complex
Ruffle membrane
Secretory granule lumen
Molecular Function
ATP binding
ATPase
ATPase activity, coupled
Disordered domain specific binding
DNA polymerase binding
GTPase binding
Histone deacetylase binding
Identical protein binding
MHC class II protein complex binding
Nitric-oxide synthase regulator activity
Nucleotide binding
Poly(A) RNA binding
Protein folding chaperone
Protein homodimerization activity
Protein tyrosine kinase activity
Protein tyrosine kinase binding
RNA binding
Scaffold protein binding
Tau protein binding
TPR domain binding
Ubiquitin protein ligase binding
Unfolded protein binding
The reference OMIM entry for this protein is 140571
Heat-shock protein, 90-kd, alpha, class a, member 1; hsp90aa1
Heat-shock 90-kd protein 1, alpha, formerly; hspca, formerly
Hspc1
Hsp90a
Hsp89-alpha; hsp89a
Heat-shock 90-kd protein 1, alpha-like 4; hspcal4
Lipopolysaccharide-associated pr
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, an inducible form, and HSP90AB1 (140572), a constitutive form. Other HSP90 proteins are found in endoplasmic reticulum (HSP90B1; 191175) and mitochondria (TRAP1; 606219) (Chen et al., 2005).CLONING
In humans, 2 distinct HSP90 cDNA clones were identified that hybrid-select different mRNA transcripts encoding 2 members of the HSP90 family. These were called HSP89-alpha and HSP89-beta (Hickey et al., 1986; Simon et al., 1987). By database analysis, Chen et al. (2005) identified several HSP90AA1 variants encoding proteins of 413, 635, 732, and 854 amino acids. Like other HSP90 proteins, the 732-amino acid HSP90AA1 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 854-amino acid HSP90AA1 isoform has an N-terminal extension compared with the 732-amino acid isoform, but is otherwise identical. - Chimeric CD47/HSP90AA1 Transcript By screening a T-lymphoblastic leukemia cell line (CEM) cDNA library with a probe originally isolated from a pancreatic cancer cDNA library, Schweinfest et al. (1998) cloned a variant of HSPCA that they designated HSP89-alpha-delta-N. The deduced 539-amino acid variant protein has a calculated molecular mass of about 63 kD. It has a unique 30-amino acid N terminus instead of the 223-amino acid ATP/geldanamycin-binding domain found at the N terminus of full-length HSPCA, which contains 732 amino acids. RT-PCR analysis detected expression of the variant in CEM cells and several pancreatic cell lines, as well as in normal pancreatic tissue. In vitro transcription/translation produced a protein with an apparent molecular mass of about 70 kD. Chen et al. (2005) determined that the HSP89-alpha-delta-N transcript, which they called HSP90N, is a chimera, with the first 105 bp of the coding sequence derived from the CD47 gene (601028) on chromosome 3q13.2, and the remaining coding sequence derived from HSP90AA1.GENE FUNCTION
Stepanova et al. (1996) found that CDC37 (605065) and HSP90 associate preferentially with the fraction of CDK4 (123829) not bound to D-type cyclins. Pharmacologic inactivation of CDC37/HSP90 function leads to reduced stability of CDK4. CD14 (158120) and lipopolysaccharide (LPS)-binding protein (LBP; 151990) are major receptors for LPS; however, binding analyses and TNF production assays have suggested the presence of additional cell surface receptors, designated LPS-associated proteins (LAPs), that are distinct from CD14, LBP, and the Toll-like receptors (see TLR4; 603030). Using affinity chromatography, peptide mass fingerprinting, and fluorescence resonance energy transfer, Triantafilou et al. (2001) identified 4 diverse proteins, heat-shock cognate protein (HSPA8; 600816), HSP90A, chemokine receptor CXCR4 (162643), and growth/differentiation factor-5 (GDF5; 601146), on monocytes that form an activation cluster after LP ... More on the omim web site
Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
April 27, 2018: 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
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 140571 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed