Heat shock 70 kDa protein 1B (HSPA1B)
The protein contains 641 amino acids for an estimated molecular weight of 70052 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 co-chaperones have been shown to not only regulate different steps of the ATPase cycle, but they also have an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote degradation. 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. The co-chaperones are of three types: J-domain co-chaperones such as HSP40s (stimulate ATPase hydrolysis by HSP70), the nucleotide exchange factors (NEF) such as BAG1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby pr (updated: Oct. 10, 2018)
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.
- 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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| Variant | Description |
|---|---|
| empty | |
| dbSNP:rs538280104 | |
| dbSNP:rs483638 |
No binding partner found
Biological Process
ATP metabolic process
Cellular heat acclimation
Cellular response to heat
Cellular response to oxidative stress
Cellular response to unfolded protein
Chaperone cofactor-dependent protein refolding
MRNA catabolic process
Negative regulation of apoptotic process
Negative regulation of cell death
Negative regulation of cell growth
Negative regulation of cell population proliferation
Negative regulation of extrinsic apoptotic signaling pathway in absence of ligand
Negative regulation of inclusion body assembly
Negative regulation of protein ubiquitination
Neutrophil degranulation
Positive regulation of erythrocyte differentiation
Positive regulation of gene expression
Positive regulation of interleukin-8 production
Positive regulation of microtubule nucleation
Positive regulation of NF-kappaB transcription factor activity
Positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway
Positive regulation of proteasomal ubiquitin-dependent protein catabolic process
Positive regulation of tumor necrosis factor-mediated signaling pathway
Protein refolding
Protein stabilization
Regulation of cellular response to heat
Regulation of mitotic spindle assembly
Regulation of protein ubiquitination
Response to unfolded protein
Vesicle-mediated transport
Cellular Component
Aggresome
Blood microparticle
Centriole
Centrosome
Cytoplasm
Cytosol
Endoplasmic reticulum
Extracellular exosome
Extracellular region
Ficolin-1-rich granule lumen
Focal adhesion
Inclusion body
Mitochondrion
Nuclear speck
Nucleoplasm
Nucleus
Perinuclear region of cytoplasm
Plasma membrane
Protein-containing complex
Ribonucleoprotein complex
Vesicle
Molecular Function
ATP binding
ATPase
ATPase activity, coupled
C3HC4-type RING finger domain binding
Enzyme binding
G protein-coupled receptor binding
Heat shock protein binding
Histone deacetylase binding
Misfolded protein binding
Protein folding chaperone
Protein N-terminus binding
RNA binding
Signaling receptor binding
Ubiquitin protein ligase binding
Unfolded protein binding
Virus receptor activity
The reference OMIM entry for this protein is 140550
Heat-shock 70-kd protein 1a; hspa1a
Heat-shock 70-kd protein 1; hspa1
Heat-shock protein, 70-kd, 1
Hsp70-1
Hsp70-1a
Hsp72
Heat-shock 70-kd protein, inducible; hsp70i
CLONING
A number of organisms, such as Drosophila, respond to elevated temperature by synthesizing a small number of specific proteins. This phenomenon occurs also in yeast and in cultured HeLa cells. Exposure of HeLa cells to a temperature of 45 degrees C for 10 minutes leads to an increased synthesis of at least 3 sets of proteins with molecular masses of about 100,000, 72,000-74,000, and 37,000 daltons (Slater et al., 1981). The phenomenon is blocked by actinomycin D, suggesting transcriptional control. In vitro translation of cytoplasmic RNA from heat-shocked cells, followed by 2-D gel analysis of the translation products, shows that the major 72,000- to 74,000-dalton band consists of 7 polypeptides, designated alpha, alpha-prime, beta, gamma, delta, epsilon, and zeta. The increase in synthesis of the heat-shock proteins begins soon after heat treatment but does not reach a maximum until 2 hours later. The pattern of induction suggests coordinate regulation. To study this, Cato et al. (1981) cloned the cDNA sequences encoding the beta, gamma, delta, and epsilon heat-shock polypeptides. Hickey et al. (1986) isolated cDNA clones representing at least 5 distinct heat-inducible mRNAs in human cells. Milner and Campbell (1990) determined that the HSPA1A gene encodes a predicted 641-amino acid protein. By Northern blot analysis of HeLa cell RNA, they detected an approximately 2.4-kb HSPA1A transcript that was constitutively expressed at low levels and was induced following heat shock.GENE FUNCTION
While the function of the ubiquitous, highly conserved heat-shock proteins was unknown, an intriguing relationship between expression of heat-shock proteins and transformation had been observed. Pelham (1986) speculated on the function of heat-shock proteins. 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 (601324), which complexes with heat-shock proteins HSC70 (600816) and HSP70, translation initiation factor EIF4G (600495), and poly(A)-binding protein (604679). AU-rich mRNA decay is associated with displacement of EIF4G from AUF1, ubiquitination of AUF1, and degradation of AUF1 by proteasomes. Laroia et al. (1999) found that 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. During adenovirus late infection, or heat shock of cells, translation of most capped cellular mRNAs is inhibited and adenovirus late mRNAs are translated by a mechanism called ribosome shunting. In shunting, ribosomes are loaded onto mRNA by a cap-dependent process, but then shunt or bypass large segments of the mRNA before initiating translation at a downstream AUG. Ribosome shunting is mediated by the 5-prime noncoding region of adenovirus mRNAs, called the tripartite leader, which shares striking complementarity to 18S rRNAs. Yueh and Schneider (2000) found that the 5-prime noncoding region of human HSP70 mRNA contains an element related to the adenovirus tripartite leader sequence. This element promoted ribosome shunting for HSP70 expression during heat shock when cap-dependent protein synthesis was blocked. Unfold ... More on the omim web site
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 140550 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).