Alternative titles; symbols
HGNC Approved Gene Symbol: STOM
Cytogenetic location: 9q33.2 Genomic coordinates (GRCh38): 9:121,338,987-121,370,250 (from NCBI)
Erythrocyte surface protein band 7.2 is a 29,000-kD integral membrane protein that is exposed on the cytoplasmic surface of the membrane and is susceptible to phosphorylation by a cAMP-dependent protein kinase. The same protein can be demonstrated in human cell lines of epithelial and lymphoid origin, notably in HeLa cells. Hiebl-Dirschmied et al. (1991), therefore, could screen HeLa cell cDNA expression libraries with antibodies to the protein in order to isolate cDNA clones, determine the nucleotide sequence, and study the structure of the protein. HeLa and bone marrow cell-derived sequences were identical, except for one nucleotide; the deduced sequence of 287 amino acids was confirmed by sequence identity with peptides of the erythroid protein. Structural analysis assigned band 7 protein to the type Ib transmembrane proteins.
Gallagher et al. (1995) cloned the mouse band 7.2b cDNA and studied its tissue-specific expression. They isolated 2,873 bp of cDNA with an open reading frame of 852 bp. The predicted protein was 284 amino acids with a molecular mass of 31 kD. They detected a wide pattern of expression, with high levels of mRNA in heart, liver, skeletal muscle, and testis but low levels in lung, brain, and spleen. Models of the predicted protein structure showed a short NH2-terminal head, a strongly hydrophobic 28-amino acid stretch presumably encoding a single membrane-spanning domain, and a large domain composed of beta sheet and alpha helix. Database searching showed no significant homology of other proteins to either the human or the murine band 7.2b.
Gallagher and Forget (1995) determined the sequence of the full-length human band 7.2b cDNA, characterized the genomic structure of the EPB72 gene, studied its pattern of expression in different tissues, and characterized the promoter of the gene. The promoter directed high-level expression of a reporter gene in both erythroid and non-erythroid cells.
Gallagher and Forget (1995) determined that the EPB72 gene is composed of 7 exons distributed over 40 kb of DNA. Its promoter was identified as lacking a TATA box and to be GC-rich.
Unfried et al. (1995) showed that the human EPB72 gene contains 7 exons spanning about 30 kb. Two polyadenylation signals were found in the 3-prime UTR accounting for the 3.2- and 3.3-kb RNAs that are observed in Northern blots.
Westberg et al. (1993) used a cDNA clone coding for stomatin to determine the chromosomal localization of the EPB72 gene. They assigned the gene to human chromosome 9 by Southern blot analysis of somatic cell hybrids. By analysis of hybrid cells containing only parts of chromosome 9, they regionalized the assignment to 9q34.1, proximal to the breakpoint that creates the Philadelphia chromosome of chronic myeloid leukemia (CML; 608232) and, therefore, proximal to the Abelson oncogene (189980). Using fluorescence in situ hybridization, Gallagher et al. (1993) likewise mapped the EPB72 gene to 9q33-q34. They showed that EPB72 was not translocated with the 3-prime end of the ABL gene in the Philadelphia chromosome, suggesting that the EPB72 gene is centromeric to the ABL gene. Pilz et al. (1994) demonstrated that the homologous gene is located on mouse chromosome 2.
Using fluorescence in situ hybridization, Gallagher et al. (1995) mapped the murine band 7.2b gene to chromosome 2, at the border of the distal region of 2B and proximal region of C1, syntenic to 9q, the location of the human homolog.
Montel-Hagen et al. (2008) stated that, of all human cell lineages, erythrocytes express the highest level of glucose transporter-1 (GLUT1, or SLC2A1; 138140), with more than 200,000 molecules per cell. They showed that GLUT1 preferentially transported L-dehydroascorbic acid (DHA) rather than glucose in human erythrocytes. This switch from glucose to DHA was associated with induction of stomatin. Accordingly, in a patient with overhydrated hereditary stomatocytosis (185000), a disorder characterized by low stomatin levels, DHA transport was decreased by 50%, while glucose uptake was significantly increased. Montel-Hagen et al. (2008) found that erythrocyte-specific GLUT1 expression and DHA transport are specific traits of vitamin C-deficient mammalian species, encompassing only higher primates, guinea pigs, and fruit bats. Adult mouse erythrocytes expressed Glut4 (SLC2A4; 138190) rather than Glut1 and did not transport DHA. Montel-Hagen et al. (2008) concluded that induction of GLUT1 and stomatin during erythroid differentiation is a compensatory mechanism in mammals unable to synthesize vitamin C.
To examine the relationship between erythrocyte membrane protein 7.2b deficiency and the hemolytic anemia of human hereditary stomatocytosis, Zhu et al. (1999) created 7.2b knockout mice by standard gene targeting approaches. Despite a complete absence of protein 7.2b in homozygous knockout mice, there was no hemolytic anemia, and mouse red blood cells were normal in morphology, cell indices, hydration status, monovalent cation content, and ability to translocate lipids. Thus, their experiments suggested that 7.2b deficiency plays no direct role in the etiology of stomatocytosis and excluded any role of this protein as a mediator of cation transport in red blood cells.
Gallagher, P. G., Forget, B. G. Structure, organization, and expression of the band 7.2b gene, a candidate gene for hereditary hydrocytosis. J. Biol. Chem. 270: 26358-26363, 1995. [PubMed: 7592848] [Full Text: https://doi.org/10.1074/jbc.270.44.26358]
Gallagher, P. G., Romana, M., Lieman, J. H., Ward, D. C. cDNA structure, tissue-specific expression, and chromosomal localization of the murine band 7.2b gene. Blood 86: 359-365, 1995. [PubMed: 7540886]
Gallagher, P. G., Upender, M., Ward, D. C., Forget, B. G. The gene for human erythrocyte membrane protein band 7.2 (EPB72) maps to 9q33-q34 centromeric to the Philadelphia chromosome translocation breakpoint region. Genomics 18: 167-169, 1993. [PubMed: 8276411] [Full Text: https://doi.org/10.1006/geno.1993.1449]
Hiebl-Dirschmied, C. M., Entler, B., Glotzmann, C., Maurer-Fogy, I., Stratowa, C., Prohaska, R. Cloning and nucleotide sequence of cDNA encoding human erythrocyte band 7 integral membrane protein. Biochim. Biophys. Acta 1090: 123-124, 1991. [PubMed: 1883838] [Full Text: https://doi.org/10.1016/0167-4781(91)90047-p]
Montel-Hagen, A., Kinet, S., Manel, N., Mongellaz, C., Prohaska, R., Battini, J.-L., Delaunay, J., Sitbon, M., Taylor, N. Erythrocyte Glut1 triggers dehydroascorbic acid uptake in mammals unable to synthesize vitamin C. Cell 132: 1039-1048, 2008. [PubMed: 18358815] [Full Text: https://doi.org/10.1016/j.cell.2008.01.042]
Pilz, A., Prohaska, R., Peters, J., Abbott, C. Genetic linkage analysis of the Ak1, Col5a1, Epb7.2, Fpgs, Grp78, Pbx3, and Notch1 genes in the region of mouse chromosome 2 homologous to human chromosome 9q. Genomics 21: 104-109, 1994. [PubMed: 8088777] [Full Text: https://doi.org/10.1006/geno.1994.1230]
Unfried, I., Entler, B., Prohaska, R. The organization of the gene (EPB72) encoding the human erythrocyte band 7 integral membrane protein (protein 7.2b). Genomics 30: 521-528, 1995. [PubMed: 8825639] [Full Text: https://doi.org/10.1006/geno.1995.1273]
Westberg, J. A., Entler, B., Prohaska, R., Schroder, J. P. The gene coding for erythrocyte protein band 7.2b (EPB72) is located in band q34.1 of human chromosome 9. Cytogenet. Cell Genet. 63: 241-243, 1993. [PubMed: 8500356] [Full Text: https://doi.org/10.1159/000133542]
Zhu, Y., Paszty, C., Turetsky, T., Tsai, S., Kuypers, F. A., Lee, G., Cooper, P., Gallagher, P. G., Stevens, M. E., Rubin, E., Mohandas, N., Mentzer, W. C. Stomatocytosis is absent in 'stomatin'-deficient murine red blood cells. Blood 93: 2404-2410, 1999. [PubMed: 10090952]