Heat shock 70 kDa protein 1-like (HSPA1L)
The protein contains 641 amino acids for an estimated molecular weight of 70375 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). Positive regulator of PRKN translocation to damaged mitochondria (PubMed:24270810). (updated: Jan. 31, 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.
- 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
Binding of sperm to zona pellucida
Cellular response to heat
Cellular response to unfolded protein
Chaperone cofactor-dependent protein refolding
Positive regulation of protein targeting to mitochondrion
Protein refolding
Regulation of cellular response to heat
Response to unfolded protein
Vesicle-mediated transport
The reference OMIM entry for this protein is 140559
Heat-shock 70-kd protein-like 1; hspa1l
Heat-shock protein, 70-kd, homologous
Hsp70-hom
Hsp70-1l
Hsp70t
CLONING
The human HSP70, or HSPA, multigene family encodes several highly conserved 70-kD heat-shock proteins that vary in their inducibility in response to metabolic stress. Sargent et al. (1989) identified the HSP70-HOM gene as a region with similarity to HSP70-1 (HSPA1A; 140550) that was located approximately 4 kb telomeric to HSP70-1 in the class III region of the major histocompatibility complex on 6p21.3. Milner and Campbell (1990) defined this homologous region as a gene of the HSP70 family. They found that the HSP70-HOM gene lacks introns. The predicted 641-amino acid HSP70-HOM protein is 90%, 84%, and 79% identical to the HSP70-1, HSC70 (HSPA8; 600816), and HSP70B-prime (HSPA6; 140555) proteins, respectively; the sequences differ most in the C-terminal 100 amino acids. Northern blot analysis of HeLa cell RNA detected an approximately 3-kb HSP70-HOM transcript that was expressed constitutively at a low level but was not induced by heat shock.GENE FUNCTION
Hasson et al. (2013) elucidated regulators that have an impact on parkin (PARK2; 602544) translocation to damaged mitochondria with genomewide small interfering RNA (siRNA) screens coupled to high-content microscopy. Screening yielded gene candidates involved in diverse cellular processes that were subsequently validated in low-throughput assays. This led to characterization of TOMM7 (607980) as essential for stabilizing PINK1 (608309) on the outer mitochondrial membrane following mitochondrial damage. Hasson et al. (2013) also discovered that HSPA1L and BAG4 (603884) have mutually opposing roles in the regulation of parkin translocation. The screens revealed that SIAH3 (615609), found to localize to mitochondria, inhibits PINK1 accumulation after mitochondrial insult, reducing parkin translocation.MOLECULAR GENETICS
Milner and Campbell (1992) investigated the presence of sequence variation in the HSP70-HOM gene among different HLA haplotypes. They identified a T-to-C transition in a number of haplotypes that results in a met-to-thr substitution at position 493 (M493T), which is located within the proposed peptide-binding site of HSP70 proteins. Abacavir is a commonly used nucleoside analog with potent antiviral activity against HIV-1. Approximately 5 to 9% of patients treated with abacavir develop a hypersensitivity reaction characterized by multisystem involvement that can be fatal in rare cases (Mallal et al., 2002; Hetherington et al., 2002). Martin et al. (2004) reported that the combination of HLA-B*5701 (see 142830) and a haplotypic M493T polymorphism of HSP70-HOM is highly predictive of abacavir hypersensitivity. Spagnolo et al. (2007) found a strong association between the HSP70-HOM dbSNP rs2075800 G allele and uveitis in patients with sarcoidosis (181000). Their study included 270 white patients with sarcoidosis, including 88 with sarcoid-related uveitis; 347 matched control subjects; and 181 patients with idiopathic interior or intermediate uveitis. The HSPA1L dbSNP rs2075800 G allele frequency was higher in the sarcoid-uveitis group than in both the sarcoid-nonuveitis and control groups (83% vs 71%, OR, 2.00, P(c) = 0.01; and 83% vs 66%, OR, 2.45, P(c) = 0.00005, respectively). Similar results were observed when considering the carriage frequency of the associated haplotype (HSP70 haplotype 2) across the 3 study groups. In addition, the association was specific sarcoidosis, as the carriage of the G allele discriminated between sarc ... 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 HSPA1L
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 140559 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed