Blood group Rh(D) polypeptide (RHD)
The protein contains 417 amino acids for an estimated molecular weight of 45211 Da.
May be part of an oligomeric complex which is likely to have a transport or channel function in the erythrocyte membrane. (updated: April 1, 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.
- 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.
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, is predicted to be membranous by TOPCONS.
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No binding partner found
Biological Process
Ammonium transmembrane transport
Organic cation transport
Peptide biosynthetic process
The reference OMIM entry for this protein is 111680
Rhesus blood group, d antigen; rhd
Blood group--rhesus system d polypeptide
Individuals are classified as Rh-positive and Rh-negative according to the presence or the absence of the major D antigen on the surface of their erythrocytes, but more than 46 other antigens, including those of the CcEe series, have been identified (Issitt, 1989). By Southern blot analysis, Colin et al. (1991) showed that the Rh 'locus' is composed of 2 homologous structural genes, one encoding the Rh D polypeptide and the other encoding both the Cc and the Ee polypeptides (111700). Alternative splicing of a primary transcript was considered the likely mechanism of the encoding of the Cc and Ee polypeptides by a single gene (Le Van Kim et al., 1992). Le Van Kim et al. (1992) cloned cDNAs for representing the RHD gene. They found that the predicted translation product is a 417-amino acid protein of molecular mass 45,500 with a membrane organization of 13 bipolar-spanning domains similar to that of the polypeptide encoded by the CcEe gene. The D and CeEe polypeptides differ by 36 amino acids (8.4% divergence), but the NH2- and COOH-terminal regions of the 2 proteins are well conserved. The sequence homology supports the concept that the genes evolve by duplication of a common ancestral gene. It is evident that the controversy between Wiener (1944), who espoused the existence of a single gene with multiple epitopic sites, and the Fisher-Race school (Race, 1944), which held to the existence of 2 closely linked genes, has now been resolved with the conclusion that each view was partially right and partially wrong. None of the 3 researchers survived to see the definitive resolution of the issue. Arce et al. (1993) likewise cloned the RHD gene. Bennett et al. (1993) demonstrated that DNA testing can be used to determine RhD type in chorionic villus samples or amniotic cells. An RhD-negative woman whose partner is heterozygous may have preexisting anti-RhD antibodies that may or may not affect a subsequent fetus, depending on whether it is heterozygous. A safe method of determining fetal RhD type early in pregnancy would eliminate the risks to an RhD-negative fetus of fetal blood sampling or serial amniocenteses. Cartron (1994) provided a comprehensive review of the molecular genetics of the Rh blood group antigens. These antigens are carried by a family of nonglycosylated hydrophobic transmembrane proteins of 30 to 32 kD, which are missing from the red cells of rare Rh-null individuals. The Rh proteins are erythroid-specific and share no sequence homology with any known protein. The RhD and non-D proteins exhibit 92% sequence identity. The RHD and RHCE (111700) genes are organized in tandem on 1p36-p34 and presumably originated by duplication of a common ancestral gene. This concept is supported by the identification of RH-like genes in nonhuman primates. The C/c and E/e proteins are presumably produced through alternative splicing of a pre-messenger RNA; most RhD-negative haplotypes represent absence of the RHD gene and the presence of only 1 structural gene, RHCE. The correlation between the blood group D epitopes and the amino acid polymorphism of the Rh proteins had not been established, but in the case of the RHCE gene, the polymorphism ser103-to-pro had been shown to be responsible for the C/c specificity (111700.0002) and pro226-to-ala for the E/e specificity (111700.0001). Gene conversion appears to be the principal mechanism responsible for polymorphism and gene diversity in the RH system; however, gene deletions have also been ident ... 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
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for RHD
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 111680 was added.