Heat shock 70 kDa protein 6 (HSPA6)
The protein contains 643 amino acids for an estimated molecular weight of 71028 Da.
Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release (PubMed:26865365). (updated: Dec. 20, 2017)
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.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- 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.
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Biological Process
Cellular response to heat
Cellular response to unfolded protein
Chaperone cofactor-dependent protein refolding
Neutrophil degranulation
Protein refolding
Response to unfolded protein
Vesicle-mediated transport
The reference OMIM entry for this protein is 140555
Heat-shock 70-kd protein 6; hspa6
Hsp70b-prime
CLONING
HSPA6 (HPS70B-prime) is a stress-induced heat-shock gene encoding a basic 70-kD protein. It is a close homolog of HSPA7 (140556), formerly designated HSP70B (Leung et al., 1990). Leung et al. (1992) stated that both HSPA6 and HSPA7 represent functional genes, as determined by analyses of mRNA from heat-shocked human cells using sequence-specific oligonucleotides. After heat shock at 45 degrees C, HSPA6 mRNA was detected in fibroblast, HeLa, and Daudi cells, whereas HSPA7 mRNA was detected only in fibroblasts. Parsian et al. (2000) found that HSPA6 and HSPA7 share 98% nucleotide identity through their putative coding regions. However, HSPA7 was predicted to lack protein-coding potential. Orthologs of HSPA6 and HSPA7 were not detected in mouse by Southern blot analysis.GENE FUNCTION
Using RT-PCR, Parsian et al. (2000) detected the expression of HSPA6 and HSPA7 only after heat shock in human W138 and HeLa cells. HSPA6 was more strongly expressed following heat shock.MAPPING
By hybridization analyses of a somatic cell hybrid DNA panel, Leung et al. (1992) found that HSPA6 and HSPA7 localize to 1q. A BamHI polymorphism in the HSPA7 gene was present in a predominantly Asian population. Grosz et al. (1992) concluded that bovine HSP70-4 is homologous to HSPA6 or HSPA7 because it is syntenic with amylase-1 (104700) and PGM1 (171900), both of which are on human chromosome 1. Using FISH, Parsian et al. (2000) mapped the HSPA6 and HSPA7 genes to within 5 to 10 Mb of each other on chromosome 1q23.1. Brzustowicz et al. (2002) stated that the HSPA6 and HSPA7 genes are located on chromosome 1q22, according to sequence data provided by the Human Genome Project, and are in close proximity to a susceptibility locus for schizophrenia (604906). ... More on the omim web site
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 25, 2017: Additional information
No protein expression data in P. Mayeux work for HSPA6
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 140555 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed