Stomatin, properly known as 'erythrocyte membrane protein 7.2b' (if you can handle that one) is a 32kD integral membrane protein found in the red cell membrane. Lande and others in San Francisco (Lande et al, 1982: PubMed, 7174793) were the first to notice that this protein was missing from the membrane in overhydrated hereditary stomatocytosis and this is confirmed by others (Eber et al, 1989; Stewart et al, 1992). We now know the sequence of this protein and the gene (Hiebl-Dirschmied et al, 1991; Stewart et al, 1992), but we do not really understand what it does. It is found in virtually all human tissues (Gallagher et al, 1995a, Fricke et al 2003) and in very many animals, including simple flatworms and many bacteria: it seems to be basic in biology. The human genomic (Gallagher & Forget, 1995a; Unfried et al, 1995) and murine (Gallagher et al, 1995b) genes have been isolated. The human gene maps to chromosome 9q32-34 (Gallagher et al, 1993; Westberg et al, 1993). Prohaska and others have found that the stomatin protein molecules seems to assemble together like bricks (Snyers et al, 1998); and that it is linked up to the scaffolding ('cytoskeleton') of the cell (Snyers et al, 1997); and that it is assocuiated with the cholesterol+sphingomyelin-rich material of the cell membrane, possibly forming isolated domains commonly known as 'rafts' ((Snyers et al, 1999; Mairhofer et al, 2002) .
Three similar genes (mec-2 (Huang et al, 1995), unc-24 (Barnes et al, 1996), unc-1) coding for similar proteins have been found in a worm, Caenorhabditis elegans. Mutations in these genes all cause some kind of problem with the nervous system of the animal, and some mutations in one (unc-1) cause abnormal susceptibility to anaesthetics (Rajaram et al, 1998). A further homologue has been found in nitrogen fixing bacteria (You et al, 1998). The importance of this protein in the human nervous system is not yet known.
In one context, one of these stomatin-like genes (mec-2) is implicated in a process that controls a channel that conducts the cation sodium (Na+), known as ENaC (Canessa et al 1995). Recenet evidence strongly supports the idea that stomatin-like proteins play a direct role in the activity of ENaC (Goodman et al 2002).
It should be stressed again that the stomatin gene in overhydrated HSt is normal (Fricke et al 2003). No disease that is definitely caused by a mutation in the human gene has yet been described, although this group, with Prof Delaunay in France, has identified a French child who showed a very unpleasant, inherited, multi-system disease associated with abnormal splicing in the stomatin gene (Argent et al, 2003).
Since stomatin was first cloned, a series of other stomatin-like proteins have been found (Seidel et al, 1998; Wang et al, 2000). A form of recessively inherited nephrotic syndrome is caused by mutations in 'podocin', a basement membrane protein (Boute et al, 2000). Stomatin is similar to the flottilins (Bickel et al, 1997) and to prohibitin (Ikonen et al 1995).
Mouse gene by Gallagher et al (MMUMPEPB3)
Murine cDNA sequence. (Gallagher et al) MM17297
Murine cDNA (Schlegel et al) MMEPB72
Rat expressed sequence tag AA859080
Genbank
EMBL consensus
EST consensus
Protein at Swissprot P27105
Around exon 1 HSEPB72E1
Around exons 2-7 HSEPB72EX
mec-2 CE26735
unc-24 CE42013
Zebrafish BRY13473
Rhizobium etli homologue AF034831
Argent, A., Chetty, M.C., Fricke, B., Bertrand, Y., Philippe, N., Khogal, S., von During, M., Delaunay, J. & Stewart, G. (2003). A family showing recessively-inherited multi-system pathology with aberrant splicing of the erythrocyte Band 7.2b ('stomatin') gene. Journal of Inherited Metabolic Disease: In Press.
Barnes, T., Jin, Y., Horvitz, H., Ruvkun, G. & Hekimi, S. (1996) The Caenorhabditis elegans behavioral gene unc-24 encodes a novel bipartite protein similar to both erythrocyte protein Band 7.2 (stomatin) and nonspecific lipid transfer protein. Journal of Neurochemistry, 67, 46-57. PubMed
Bickel, P.E., Scherer, P.E., Schnitzer, J.E., Oh, P., Lisanti, M.P. & Lodish, H.F. (1997). Flotillin and epidermal surface antigen define a new family of caveolae- associated integral membrane proteins. J Biol Chem 272(21): 13793-802. PubMed
Boute, N., Gribouval, O., Roselli, S., Benessy, F., Lee, H., Fuchshuber, A., Dahan, K., Gubler, M.C., Niaudet, P. & Antignac, C. (2000). NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nature Genetics 24(4): 349-54. PubMed
Canessa, C., Horisberger, J.-D., & Rossier, B. (1995). Epithelial sodium channel related to proteins involved in neurodegeneration. Nature. 1993 Feb 11;361:504. PubMed
Eber, S.W., Lande, W.M., Iarocci, T.A., Mentzer, W.M., Hohn, P., Wiley, J.S. & Schroter, W. (1989) Hereditary stomatocytosis: consistent association with an integral membrane protein deficiency. Br. J. Haematol., 72, 452-455. PubMed
Fricke, B., Argent, A.C., Chetty, M.C., Pizzey, A.R., Turner, E.J., Ho, M.M., Iolascon, A.M., Von Duering, M. & Stewart, G.W. (2003). The 'stomatin' gene and protein in overhydrated hereditary stomatocytosis. Blood 102: 2268-2277. PubMed
Fricke, B., Stewart, G.W., K. Treharne, K., Mehta, A., Knöpfle, G., Friedrichs, N., Müller, K.-M. & von Düring, M. (2003). Stomatin-like immunoreactivity in ciliated cells of the human airway epithelium. Anatomy and Embryology 207: 1-7. PubMed
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Gallagher, P.G., Upender, M., Ward, D.C. & Forget, B.G. (1993) 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, 167-9. PubMed
Goodman, M.B., Ernstrom, G.G., Chelur, D.S., O'Hagan, R., Yao, C.A. & Chalfie, M. (2002). MEC-2 regulates C. elegans DEG/ENaC channels needed for mechanosensation. Nature 415(6875): 1039-42. PubMed
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Huang, M., Gu, G., Ferguson, E. & Chalfie, M. (1995) A stomatin-like protein necessary for mechanosensation in C. elegans. Nature, 378, 292-295. PubMed
Ikonen, E., Fiedler, K., Parton, R.G. & Simons, K. (1995). Prohibitin, an antiproliferative protein, is localized to mitochondria. FEBS Lett 358(3): 273-7. PubMed
Lande, W.M., Thiemann, P.W. & Mentzer, W.M. (1982) Missing band 7 membrane protein in two patients with high Na, low K erythrocytes. J. Clin. Invest., 70, 1273-1280. PubMed
Mairhofer, M., Steiner, M., Mosgoeller, W., Prohaska, R. & Salzer, U. (2002). Stomatin is a major lipid-raft component of platelet alpha granules. Blood 100(3): 897-904. PubMed
Rajaram, S., Sedenskey, M. & Morgan, P. (1998) Unc-1: a stomatin homologue controls sensitivity to vlotile anesthetics in C. elegans. Proceedings of the National Academy of Science (USA), 95, 8761-8766. PubMed
Seidel, G. & Prohaska, R. (1998). Molecular cloning of hSLP-1, a novel human brain-specific member of the band 7/MEC-2 family similar to Caenorhabditis elegans UNC-24. Gene 225(1-2): 23-9. PubMed
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Snyers, L., Thines-Sempoux, D. & Prohaska, R. (1997) Colocalization of stomatin (band 7.2b) and actin microfilaments in UAC epithelial cells. European Journal Cell Biology, 73, 281-285. PubMed
Snyers, L., Umlauf, E. & Prohaska, R. (1998) Oligomeric nature of the integral membrane protein stomatin. Journal of Biological Chemistry, 273, 17221-17226. PubMed
Stewart, G.W., Hepworth-Jones, B.E., Keen, J.N., Dash, B.C.J., Argent, A.C. & Casimir, C.M. (1992) Isolation of cDNA coding for a ubiquitous membrane protein deficient in high Na, low K stomatocytic erythrocytes. Blood, 79, 1593-1601.
Unfried, I., Entler, B. & Prohaska, R. (1995) The organization of the gene (EPB72) encoding the human erythrocyte band 7 integral membrane protein (protein 7.2b). Genomics, 30, 521-528. PubMed
Wang, Y. & Morrow, J.S. (2000). Identification and characterization of human SLP-2, a novel homologue of stomatin (band 7.2b) present in erythrocytes and other tissues. J Biol Chem 275(11): 8062-71. PubMed
Westberg, J., Entler, B., Prohaska, R. & Schroder, J. (1993) The gene coding for erythrocyte membrane protein band 7.2b (EPB7.2) is located in band q34.1 of human chromosome 9. Cytogenetics and Cellular Genetics, 63, 241-243. PubMed
You, Z., Gao, X., Ho, M.M. & Borthakur, D. (1998) A stomatin-like protein encoded by the slp gene of Rhizobium etli is required for nodulation competitiveness on the common bean. Microbiology, 144, 2619 -2627. PubMed