Alpha-hemoglobin-stabilizing protein (AHSP)
The protein contains 102 amino acids for an estimated molecular weight of 11840 Da.
Acts as a chaperone to prevent the harmful aggregation of alpha-hemoglobin during normal erythroid cell development. Specifically protects free alpha-hemoglobin from precipitation. It is predicted to modulate pathological states of alpha-hemoglobin excess such as beta-thalassemia. (updated: March 4, 2015)
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.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| dbSNP:rs36018996 |
The reference OMIM entry for this protein is 605821
Erythroid-associated factor; eraf
Erythroid differentiation-related factor; edrf
Alpha-hemoglobin stabilizing protein; ahsp
CLONING
The EDRF gene expresses a transcript that is confined to the erythroid lineage and is downregulated in transmissible spongiform encephalopathies (TSEs). To identify molecular markers of TSEs in noncentral nervous system tissues, Miele et al. (2001) compared gene expression in spleens of scrapie-infected and uninfected mice. Miele et al. (2001) used the differential display RT-PCR procedure to specifically identify genes differentially expressed as a result of TSE infection. They identified 1 cDNA representing a transcript that clearly showed a decrease in expression level in spleens from scrapie-infected C57BL mice. This sequence, called 'erythroid differentiation-related factor' (EDRF), represents a transcript of approximately 0.5 kb with a predicted open reading frame (ORF) of 102 amino acids. Northern blot analysis of RNA isolated from spleens of scrapie-infected and control mice confirmed that levels of EDRF transcript are dramatically decreased at the terminal stages of disease. The effect on EDRF transcript levels in spleen is first evident during the early stages of disease and becomes more pronounced with progression of disease. Northern blot analysis of RNA from spleens of both mice and hamsters infected with a number of different strains of TSE agents confirmed the substantial decrease in levels of EDRF transcript. In mice, EDRF is normally expressed only in spleen, bone marrow, and blood, with highest levels in bone marrow. Northern blot analysis of human tissue revealed that EDRF expression was confined to blood and bone marrow, with no expression detectable in spleen. Reduced EDRF expression was also detected in BSE-infected cattle and scrapie-infected sheep. EDRF expression is confined to the erythroid lineage, with higher levels of expression in blast-forming (BFU-E), colony-forming (CFU-E), and maturing erythroid (TER-119+) cells. By using a screen for genes induced by the essential erythroid transcription factor GATA1 (305371), Kihm et al. (2002) identified the ERAF protein as one that stabilizes free alpha-hemoglobin and renamed it 'alpha-hemoglobin stabilizing protein,' or AHSP, on the basis of this function. AHSP is an abundant erythroid-specific protein that forms a stable complex with free alpha-hemoglobin but not with beta-hemoglobin or hemoglobin A (alpha2-beta2). Moreover, AHSP specifically protects free alpha-hemoglobin from precipitation in solution and in live cells. Kihm et al. (2002) predicted that AHSP gene dosage would modulate pathologic states of alpha-hemoglobin excess such as beta-thalassemia. Although beta-thalassemia is considered to be a classic monogenic disease, there is considerable clinical variability between patients who inherit identical mutations in the beta-globin gene (HBB; 141900), suggesting that there may be a variety of genetic determinants influencing the clinical phenotype. It has been proposed that alleles altering the levels or function of AHSP might account for some of the clinical variability observed in patients with beta-thalassemia (Kihm et al., 2002; Luzatto and Notaro, 2002). To address this hypothesis, Viprakasit et al. (2004) studied 120 Thai patients with Hb E (141900.0071) with mild, moderate, or severe clinical phenotypes. Using gene mapping, direct genomic sequencing, and extended haplotype analysis, they found no mutation or specific association between haplotypes of AHSP and disease severity in these patients, suggesting that AHSP is not a disease ... More on the omim web site
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 16, 2016: Protein entry updated
Automatic update: OMIM entry 605821 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed