Hemoglobin subunit gamma-2 (HBG2)
The protein contains 147 amino acids for an estimated molecular weight of 16126 Da.
Gamma chains make up the fetal hemoglobin F, in combination with alpha chains. (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.
- 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.
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The reference OMIM entry for this protein is 142250
Hemoglobin, gamma g; hbg2
Hemoglobin--gamma locus, 136 glycine
DESCRIPTION
The HBG2 and HBG1 (142200) genes encode the gamma chain of hemoglobin, which combines with 2 alpha chains (HBA1; 141800) (alpha-2/gamma-2) to form fetal hemoglobin. The 2 chains differ by a single amino acid at codon 136: HBG1 contains an alanine at codon 136, whereas HBG2 contains a glycine at codon 136 (Schroeder et al., 1968).CLONING
Fritsch et al. (1980) isolated clones corresponding to the HBG1 and HBG2 genes as part of the beta-like globin gene cluster (HBB; 141900).GENE STRUCTURE
Chen et al. (2008) identified a silencing element in the HBG2 promoter between nucleotides -675 and -526. There is a GATA motif from nucleotides -569 to -544 that binds the GATA1 (305371) transcription factor and results in silencing of the gene in adults. This motif is uniquely conserved in simian primates, who also have a fetal pattern of gamma-globin gene expression.GENE FUNCTION
Schroeder et al. (1968) provided evidence for the existence of 2 types of gamma polypeptide chains, determined presumably by separate cistrons. Although not distinguishable by most of the physical methods used, sequencing has shown at least 1 amino acid difference: at position 136, one type has glycine (G-gamma; HBG2) and the second type has alanine (A-gamma; HBG1; 142200). Presumably the 2 loci arose by gene duplication. Each mutation occurs, apparently, in only 1 of the gamma cistrons; e.g., the mutation of Hb F(Malta) is in the glycine-136 cistron. Huisman et al. (1972) concluded that there are usually 4 gamma structural loci, 2 on each autosome. In the heterozygote, gamma-G chain variants contribute either about one-fourth or one-eighth and the gamma-A chain variants either about one-eighth or one-sixteenth of the total HbF. The 4 postulated gamma loci, 2 gamma-G loci termed M and L by these workers, and 2 gamma-A loci likewise termed M and L, produce gamma chains in an approximate ratio of 4:2:2:1. By a direct method involving hybridization of complementary DNA to total human DNA, Old et al. (1976) demonstrated that man has 2 gamma-globin genes per haploid genome. The ratio of G-gamma to A-gamma is fairly constant (about 7:3) during the fetal period. The ratio declines progressively during the postnatal gamma-to-beta switch, leading to an average value of 2:3 in the small residual amount of HbF detectable in normal adult blood. This switch in gamma ratio seems to occur by the same mechanism as the gamma-beta switch (Comi et al., 1980). For a discussion of the regulatory region of hemoglobin gamma, see 142200. Foley et al. (2002) demonstrated that synthesis of STAT3-beta (102582) by erythroleukemia and primary erythroid progenitor cells treated with IL6 (147620) silences gamma-globin expression. They identified the STAT3-like binding sequence in the promoter region of both the A-gamma and G-gamma hemoglobins.MOLECULAR GENETICS
Persons with 3 gamma-chain genes have been found (Trent et al., 1981); this is not accompanied by hematologic abnormalities (Thein et al., 1984). In the family studied by Thein et al. (1984), restriction enzyme analysis indicated that the 3 gamma genes were 2 G-gamma and an A-gamma, arranged 5-prime to 3-prime, respectively. In the course of a survey of infants with gene-specific probes, Fei et al. (1988) found a black infant with 5 gamma-globin genes. They concluded that the 3 genes located between the 5-prime G-gamma and the 3-prime A-gamma genes were G-gamma genes with a possi ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
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 142250 was added.
Feb. 25, 2016: Protein entry updated
Automatic update: model status changed