Ammonium transporter Rh type A (RHAG)
The protein contains 409 amino acids for an estimated molecular weight of 44198 Da.
Associated with rhesus blood group antigen expression (PubMed:19744193). May be part of an oligomeric complex which is likely to have a transport or channel function in the erythrocyte membrane (PubMed:11062476, PubMed:11861637). Involved in ammonia transport across the erythrocyte membrane (PubMed:21849667, PubMed:22012326). Seems to act in monovalent cation transport (PubMed:18931342, PubMed:21849667). (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.
- 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.
- 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 predicted to be membranous by TOPCONS.
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Biological Process
Ammonium transmembrane transport
Ammonium transport
Bicarbonate transport
Carbon dioxide transmembrane transport
Carbon dioxide transport
Cellular ion homeostasis
Erythrocyte development
Inorganic cation transmembrane transport
Monovalent inorganic cation transport
Multicellular organismal iron ion homeostasis
Organic cation transport
Small molecule metabolic process
Transmembrane transport
The reference OMIM entry for this protein is 180297
Rhesus blood group-associated glycoprotein; rhag
Rhesus associated polypeptide, 50-kd; rh50a
Rh2
DESCRIPTION
The Rh blood group antigens (111700) are associated with human erythrocyte membrane proteins of approximately 30 kD, the so-called Rh30 polypeptides. Heterogeneously glycosylated membrane proteins of 50 and 45 kD, the Rh50 glycoproteins, are coprecipitated with the Rh30 polypeptides on immunoprecipitation with anti-Rh-specific mono- and polyclonal antibodies. The Rh antigens appear to exist as a multisubunit complex of CD47 (601028), LW (111250), and glycophorin B (111740), and play a critical role in the Rh50 glycoprotein.CLONING
Ridgwell et al. (1992) isolated cDNA clones representing a member of the Rh50 glycoprotein family, the Rh50A glycoprotein. They used PCR with degenerate primers based on the N-terminal amino acid sequence of the Rh50 glycoproteins and human genomic DNA as a template. The cDNA clones containing the full coding sequence of the Rh50A glycoprotein predicted a 409-amino acid N-glycosylated membrane protein with up to 12 transmembrane domains. It showed clear similarity to the Rh30A protein in both amino acid sequence and predicted topology. The findings were considered consistent with the possibility that the Rh30 and Rh50 groups of proteins are different subunits of an oligomeric complex which is likely to have a transport or channel function in the erythrocyte membrane.GENE STRUCTURE
Huang (1998) determined the intron/exon structure of the Rh50 gene. The structure of the Rh50 gene is nearly identical to that of the Rh30 gene. Of the 10 exons assigned, conservation of size and sequence was confined mainly to the region from exons 2 to 9, suggesting that RH50 and RH30 were formed as 2 separate genetic loci from a common ancestor via a transchromosomal insertion event.GENE FUNCTION
The absence of the RhAG and Rh proteins in Rh(null) individuals leads to morphologic and functional abnormalities of erythrocytes, known as the Rh-deficiency syndrome. The RhAG and Rh polypeptides are erythroid-specific transmembrane proteins belonging to the same family (36% identity). Marini et al. (1997) and Matassi et al. (1998) found significant sequence similarity between the Rh family proteins, especially RhAG, and Mep/Amt ammonium transporters. Marini et al. (2000) showed that RhAG and also RhGK (605381), a human homolog expressed in kidney cells only, function as ammonium transport proteins when expressed in yeast. Both specifically complement the growth defect of a yeast mutant deficient in ammonium uptake. Moreover, ammonium efflux assays and growth tests in the presence of toxic concentrations of the analog methylammonium indicated that RhAG and RhGK also promote ammonium export. The results provided the first experimental evidence for a direct role of RhAG and RhGK in ammonium transport and were of high interest, because no specific ammonium transport system had been previously characterized in human. Westhoff et al. (2002) used the Xenopus oocyte expression system to determine the function of Rh and RhAG proteins. They demonstrated expression of fully glycosylated RhAG protein and provided the first direct evidence for RhAG-mediated ammonium uptake. Ripoche et al. (2004) assayed transport in red blood cells and ghosts from human and mouse genetic variants with defects in RhAG or other components of the Rh complex. They found that the rate constant for methylammonium or ammonium transport directly correlated with the amount of functional RhAG and was unaffected by the ... More on the omim web site
Feb. 5, 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 16, 2016: Protein entry updated
Automatic update: OMIM entry 180297 was added.