Heat shock cognate 71 kDa protein (HSPA8)
The protein contains 646 amino acids for an estimated molecular weight of 70898 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 (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488). This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488, PubMed:12526792). The co-chaperones have been shown to not only regulate different steps of the ATPase cycle of HSP70, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation (PubMed:21150129, PubMed:21148293, PubMed:24732912, PubMed:27916661, PubMed:23018488, PubMed:12526792). The affinity of HSP70 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. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchang (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:rs11551602 | |
| dbSNP:rs11551598 |
Biological Process
ATP metabolic process
Axo-dendritic transport
Axon guidance
Cellular response to heat
Cellular response to starvation
Cellular response to unfolded protein
Chaperone cofactor-dependent protein refolding
Chaperone-mediated autophagy
Chaperone-mediated autophagy translocation complex disassembly
Chemical synaptic transmission
Clathrin coat disassembly
Cytokine-mediated signaling pathway
Gene expression
Late endosomal microautophagy
Membrane organization
MRNA splicing, via spliceosome
Negative regulation of supramolecular fiber organization
Negative regulation of transcription, DNA-templated
Neurotransmitter secretion
Neutrophil degranulation
Obsolete chaperone-mediated protein transport involved in chaperone-mediated autophagy
Positive regulation by host of viral genome replication
Positive regulation of mRNA splicing, via spliceosome
Post-Golgi vesicle-mediated transport
Protein folding
Protein methylation
Protein refolding
Protein targeting to lysosome involved in chaperone-mediated autophagy
Regulation of cell cycle
Regulation of cellular response to heat
Regulation of mRNA stability
Regulation of postsynapse organization
Regulation of protein complex stability
Regulation of protein import
Regulation of protein stability
Regulation of protein-containing complex assembly
Response to unfolded protein
RNA splicing
Slow axonal transport
Transcription, DNA-templated
Vesicle-mediated transport
Viral process
Cellular Component
Autophagosome
Axon
Blood microparticle
Chaperone complex
Clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane
Cytoplasm
Cytosol
Dendrite
Extracellular exosome
Extracellular matrix
Extracellular region
Extracellular space
Ficolin-1-rich granule lumen
Focal adhesion
Glutamatergic synapse
Glycinergic synapse
Intracellular anatomical structure
Intracellular ribonucleoprotein complex
Late endosome
Lumenal side of lysosomal membrane
Lysosomal lumen
Lysosomal membrane
Lysosome
Melanosome
Membrane
Myelin sheath
Nucleolus
Nucleoplasm
Nucleus
Perinuclear region of cytoplasm
Photoreceptor ribbon synapse
Plasma membrane
Postsynaptic cytosol
Postsynaptic specialization membrane
Presynapse
Presynaptic cytosol
Prp19 complex
Ribonucleoprotein complex
Secretory granule lumen
Spliceosomal complex
Terminal bouton
Molecular Function
ATP binding
ATPase
ATPase activity, coupled
C3HC4-type RING finger domain binding
Cadherin binding
Chaperone binding
Clathrin-uncoating ATPase activity
Enzyme binding
G protein-coupled receptor binding
Heat shock protein binding
MHC class II protein complex binding
Misfolded protein binding
Phosphatidylserine binding
Poly(A) RNA binding
Protein folding chaperone
Protein-macromolecule adaptor activity
RNA binding
Ubiquitin protein ligase binding
Unfolded protein binding
The reference OMIM entry for this protein is 600816
Heat-shock 70-kd protein 8; hspa8
Heat-shock cognate protein, 71-kd; hsc71
Hsp73
Hsc70
Heat-shock 70-kd protein 10, formerly; hspa10, formerly
Lipopolysaccharide-associated protein 1; lap1
Lps-associated protein 1
CLONING
The family of approximately 70-kD heat-shock proteins, HSP70 (see 140550), contains both heat-inducible and constitutively expressed members, the latter of which are sometimes called heat-shock cognate proteins (HSCs). By screening a human genomic library with Drosophila hsp70 and hsc70 cDNAs, Dworniczak and Mirault (1987) isolated the HSPA8 gene, which they called HSC70. Using HSPA8 genomic sequence to screen a human cDNA library derived from a hepatic metastasis that originated from a pancreatic gastrinoma, the authors cloned HSPA8 cDNAs. The HSPA8 gene contains 9 exons and spans 5 kb. The deduced HSPA8 protein has 646 amino acids and a predicted molecular mass of 70,899 Da. In vitro translation of HSPA8 RNA produced a polypeptide that migrated as a 71-kD protein in SDS-polyacrylamide gels. HSPA8 RNA and protein were moderately abundant in unstressed HeLa cells and were only minimally induced by heat. Dworniczak and Mirault (1987) noted that HSPA8 is likely the constitutively expressed 71-kD heat-shock protein that is identical to uncoating ATPase (Ungewickell, 1985; Chappell et al., 1986), an enzyme that releases clathrin from coated vesicles. They identified 2 distinct HSPA8-related processed pseudogenes.GENE FUNCTION
Tavaria et al. (1995) stated that HSPA8 (also known as HSP73) plays an important role in cells by transiently associating with nascent polypeptides to facilitate correct folding. The protein folding process involves other constitutively expressed heat-shock proteins, such as HSP60 (HSPD1; 118190), HSP90 (HSPCA; 140571), and GRP78 (138120), which have collectively been termed chaperones. Chaperones are also involved in maintaining proteins in a semifolded state that enables translocation through the mitochondrial and endoplasmic reticulum membranes. HSP73 also functions as an ATPase in the disassembly of clathrin-coated vesicles during transport of membrane components through the cell. Using a yeast 2-hybrid assay, Hohfeld et al. (1995) showed that rat Hip (ST13; 606796) bound Hsc70. One Hip oligomer bound the ATPase domains of at least 2 Hsc70 molecules, and binding was dependent on activation of the Hsc70 ATPase by Hsp40 (DNAJB1; 604572). Hip stabilized the ADP-bound form of Hsc70, which had a high affinity for a test protein substrate. Hohfeld et al. (1995) concluded that HIP contributes to interactions of HSC70 with target proteins through its own chaperone activity. Cytokine and protooncogene mRNAs are rapidly degraded through AU-rich elements in the 3-prime untranslated region. Rapid decay involves AU-rich binding protein AUF1, which complexes with heat-shock proteins HSC70 and HSP70, translation initiation factor EIF4G (600495), and poly(A)-binding protein (PABP, or PABPC1; 604679). AU-rich mRNA decay is associated with displacement of EIF4G from AUF1, ubiquitination of AUF1, and degradation of AUF1 by proteasomes. Induction of HSP70 by heat shock, downregulation of the ubiquitin-proteasome network, or inactivation of ubiquitinating enzyme E1 (314370), all result in HSP70 sequestration of AUF1 in the perinucleus-nucleus, and all 3 processes block decay of AU-rich mRNAs and AUF1 protein. These results link the rapid degradation of cytokine mRNAs to the ubiquitin-proteasome pathway (Larola et al., 1999). BIM (BCL2L11; 603827) is an apoptotic factor that regulates total blood cell number. Matsui et al. (2007) uncovered a molecular mechanism for cytokine-mediated posttranscriptional reg ... 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
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 600816 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed