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Gene Review

Slc4a1  -  solute carrier family 4 (anion exchanger),...

Mus musculus

Synonyms: AE 1, Ae1, Anion exchange protein 1, Anion exchanger 1, Band 3 anion transport protein, ...
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Disease relevance of Slc4a1


Psychiatry related information on Slc4a1


High impact information on Slc4a1

  • Our report establishes an evolutionarily conserved role for band 3 in erythroid-specific cell division and illustrates the concept of cell-specific adaptation for mitosis [6].
  • Plasma aldosterone is increased in NHE3-deficient mice, and expression of both renin and the AE1 (Slc4a1) Cl-/HCO3- exchanger mRNAs are induced in kidney [7].
  • To assess the biological consequences of band 3 deficiency, we have selectively inactivated erythroid but not kidney band 3 by gene targeting in mice [8].
  • Remarkably, the band 3-/- red blood cells assembled normal membrane skeleton thus challenging the notion that the presence of band 3 is required for the stable biogenesis of membrane skeleton [8].
  • Anion exchanger 1 (band 3) is required to prevent erythrocyte membrane surface loss but not to form the membrane skeleton [9].

Chemical compound and disease context of Slc4a1


Biological context of Slc4a1

  • The AE1/2 changes and altered intracellular pH regulation likely account, at least in part, for the ion transport defects and hyperproliferation [13].
  • Hematologic and survival data from C3H, CAST/Ei F2 wan homozygotes support the hypothesis that genetic modifiers significantly influence the band-3 null HS phenotype [1].
  • While there was a significant correlation between transgene copy number and the amount of gamma-globin mRNA in all 18 lines, the transgene mRNAs initiated upstream of the start site of the endogenous AE1 mRNA [14].
  • Variegated expression from the murine band 3 (AE1) promoter in transgenic mice is associated with mRNA transcript initiation at upstream start sites and can be suppressed by the addition of the chicken beta-globin 5' HS4 insulator element [14].
  • The section adjacent to the putative membrane-associated segment is 33% identical in amino acid sequence to the amino-terminal, cytoplasmic domain of band 3 [15].

Anatomical context of Slc4a1

  • The availability of band 3-/- mice offers a unique opportunity to investigate the role of erythroid band 3 in the regulation of membrane-skeletal interactions, anion transport and the invasion and growth of malaria parasite into red blood cells [8].
  • Based on these findings and other published evidence, we propose that band 3 plays a chaperone-like role, which is necessary for the recruitment of GPA to the red blood cell plasma membrane [2].
  • AE1 mRNA was transcribed at a higher level and maintained at a higher steady-state level than either ankyrin or beta-spectrin in mouse fetal liver cells [14].
  • Cloning and characterization of a murine band 3-related cDNA from kidney and from a lymphoid cell line [15].
  • Mutation of Cys-861 to serine or methionine caused no significant changes of band 3-mediated anion exchange as measured after expression of the appropriate cRNAs in Xenopus oocytes [16].

Associations of Slc4a1 with chemical compounds

  • Anion transport function of mouse erythroid band 3 protein (AE1) does not require acylation of cysteine residue 861 [16].
  • The amino-acid sequence of murine band 3, deduced from the nucleotide sequence of a complementary DNA clone, confirms that this integral membrane glycoprotein is composed of two major structural domains which correlate with its dual functions as the anchor for the erythrocyte cytoskeleton and as a plasma membrane anion antiporter [17].
  • The steady-state level of band 3 mRNA increases markedly following dimethyl sulfoxide-induced differentiation, but the pattern of transcription initiation does not vary. mRNA from anemic and normal mouse spleen exhibits the same pattern, with the addition of another transcript whose 5' end maps to position -260 [18].
  • Based on these observations, we postulate that the high mortality of band 3 null mice may be related to a hypercoagulable state, which appears to originate from changes in the phospholipid composition of the membrane leading to PS exposure on the outer leaflet [3].
  • Antibiotic treatment markedly decreased colon inflammation and ion transporter AE1/2 mistargeting, indicating that luminal bacteria play an important role in the observed phenotype [19].

Physical interactions of Slc4a1


Regulatory relationships of Slc4a1

  • These data establish that the band 3 gene is expressed in kidney as well as in erythroid cells and suggest the presence of tissue-specific alternate promoter elements within the first exon of the band 3 gene [18].
  • The AE1 gene is expressed in erythrocytes and the A-type intercalated cells of the kidney distal collecting duct [22].
  • Loss of rotational mobility of band 3 proteins in human erythrocyte membranes induced by antibodies to glycophorin A [23].
  • Thus, a parasite-induced modification of band 3 promotes adhesion and induces antigenic changes in the P. falciparum-infected erythrocyte [24].

Other interactions of Slc4a1

  • The other, far amino-terminal section of B3RP has no correspondent in the band 3 sequence [15].
  • Levels of beta-spectrin, ankyrin, and band 3 mRNA, but not alpha-spectrin, were decreased in EKLF-deficient fetal liver RNA [25].
  • During this time we observe increases in transcriptional activity for 5-aminolevulinic acid synthase, carbonic anhydrase form II, and band 3 coordinate with the large increase in beta-globin gene transcription [26].
  • Other changes subsequent to intense Epo stimulation, like increased betaminor/alpha-globin chain synthesis ratio, reduced levels of alpha chains and immunoglobulins bound to membranes, improved spectrin/band 3 ratio, increased red blood cell survival, and improved erythropoiesis appeared as consequences of increased betaminor-globin mRNA levels [27].
  • The cells lose their cell-surface fibronectin receptors and accumulate red cell-specific membrane proteins, such as band 3, in amounts comparable to those in erythrocytes [28].

Analytical, diagnostic and therapeutic context of Slc4a1


  1. Identification of quantitative trait loci that modify the severity of hereditary spherocytosis in wan, a new mouse model of band-3 deficiency. Peters, L.L., Swearingen, R.A., Andersen, S.G., Gwynn, B., Lambert, A.J., Li, R., Lux, S.E., Churchill, G.A. Blood (2004) [Pubmed]
  2. Complete deficiency of glycophorin A in red blood cells from mice with targeted inactivation of the band 3 (AE1) gene. Hassoun, H., Hanada, T., Lutchman, M., Sahr, K.E., Palek, J., Hanspal, M., Chishti, A.H. Blood (1998) [Pubmed]
  3. Targeted inactivation of murine band 3 (AE1) gene produces a hypercoagulable state causing widespread thrombosis in vivo. Hassoun, H., Wang, Y., Vassiliadis, J., Lutchman, M., Palek, J., Aish, L., Aish, I.S., Liu, S.C., Chishti, A.H. Blood (1998) [Pubmed]
  4. Erythroid phosphatidyl serine exposure is not predictive of thrombotic risk in mice with hemolytic anemia. Wandersee, N.J., Tait, J.F., Barker, J.E. Blood Cells Mol. Dis. (2000) [Pubmed]
  5. Posttranslational changes in band 3 in adult and aging brain following treatment with ergoloid mesylates, comparison to changes observed in Alzheimer's disease. Cover, C.C., Poulin, J.E., Gustafson, M.R., Wyant, T., Gamble, D.N., Kay, M.M. Life Sci. (1996) [Pubmed]
  6. Cell-specific mitotic defect and dyserythropoiesis associated with erythroid band 3 deficiency. Paw, B.H., Davidson, A.J., Zhou, Y., Li, R., Pratt, S.J., Lee, C., Trede, N.S., Brownlie, A., Donovan, A., Liao, E.C., Ziai, J.M., Drejer, A.H., Guo, W., Kim, C.H., Gwynn, B., Peters, L.L., Chernova, M.N., Alper, S.L., Zapata, A., Wickramasinghe, S.N., Lee, M.J., Lux, S.E., Fritz, A., Postlethwait, J.H., Zon, L.I. Nat. Genet. (2003) [Pubmed]
  7. Renal and intestinal absorptive defects in mice lacking the NHE3 Na+/H+ exchanger. Schultheis, P.J., Clarke, L.L., Meneton, P., Miller, M.L., Soleimani, M., Gawenis, L.R., Riddle, T.M., Duffy, J.J., Doetschman, T., Wang, T., Giebisch, G., Aronson, P.S., Lorenz, J.N., Shull, G.E. Nat. Genet. (1998) [Pubmed]
  8. Targeted disruption of the murine erythroid band 3 gene results in spherocytosis and severe haemolytic anaemia despite a normal membrane skeleton. Southgate, C.D., Chishti, A.H., Mitchell, B., Yi, S.J., Palek, J. Nat. Genet. (1996) [Pubmed]
  9. Anion exchanger 1 (band 3) is required to prevent erythrocyte membrane surface loss but not to form the membrane skeleton. Peters, L.L., Shivdasani, R.A., Liu, S.C., Hanspal, M., John, K.M., Gonzalez, J.M., Brugnara, C., Gwynn, B., Mohandas, N., Alper, S.L., Orkin, S.H., Lux, S.E. Cell (1996) [Pubmed]
  10. Thymidine incorporation in nucleoside transport-deficient lymphoma cells. Aronow, B., Ullman, B. J. Biol. Chem. (1985) [Pubmed]
  11. Role of the nucleoside transport function in the transport and salvage of purine nucleobases. Aronow, B., Ullman, B. J. Biol. Chem. (1986) [Pubmed]
  12. Biosynthesis of erythrocyte membrane protein band 3 in DMSO-induced Friend erythroleukemia cells. Sabban, E.L., Sabatini, D.D., Marchesi, V.T., Adesnik, M. J. Cell. Physiol. (1980) [Pubmed]
  13. Keratins modulate colonocyte electrolyte transport via protein mistargeting. Toivola, D.M., Krishnan, S., Binder, H.J., Singh, S.K., Omary, M.B. J. Cell Biol. (2004) [Pubmed]
  14. Variegated expression from the murine band 3 (AE1) promoter in transgenic mice is associated with mRNA transcript initiation at upstream start sites and can be suppressed by the addition of the chicken beta-globin 5' HS4 insulator element. Frazar, T.F., Weisbein, J.L., Anderson, S.M., Cline, A.P., Garrett, L.J., Felsenfeld, G., Gallagher, P.G., Bodine, D.M. Mol. Cell. Biol. (2003) [Pubmed]
  15. Cloning and characterization of a murine band 3-related cDNA from kidney and from a lymphoid cell line. Alper, S.L., Kopito, R.R., Libresco, S.M., Lodish, H.F. J. Biol. Chem. (1988) [Pubmed]
  16. Anion transport function of mouse erythroid band 3 protein (AE1) does not require acylation of cysteine residue 861. Kang, D., Karbach, D., Passow, H. Biochim. Biophys. Acta (1994) [Pubmed]
  17. Primary structure and transmembrane orientation of the murine anion exchange protein. Kopito, R.R., Lodish, H.F. Nature (1985) [Pubmed]
  18. Multiple tissue-specific sites of transcriptional initiation of the mouse anion antiport gene in erythroid and renal cells. Kopito, R.R., Andersson, M.A., Lodish, H.F. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  19. Keratin-8-deficient mice develop chronic spontaneous Th2 colitis amenable to antibiotic treatment. Habtezion, A., Toivola, D.M., Butcher, E.C., Omary, M.B. J. Cell. Sci. (2005) [Pubmed]
  20. Identification of a band-3 binding site near the N-terminus of erythrocyte membrane protein 4.2. Rybicki, A.C., Musto, S., Schwartz, R.S. Biochem. J. (1995) [Pubmed]
  21. Evidence for an anion exchanger in the mouse lacrimal gland acinar cell membrane. Ozawa, T., Saito, Y., Nishiyama, A. J. Membr. Biol. (1988) [Pubmed]
  22. Identification of the proximal erythroid promoter region of the mouse anion exchanger gene. Sahr, K.E., Daniels, B.P., Hanspal, M. Blood (1996) [Pubmed]
  23. Loss of rotational mobility of band 3 proteins in human erythrocyte membranes induced by antibodies to glycophorin A. Che, A., Cherry, R.J. Biophys. J. (1995) [Pubmed]
  24. Band 3 clustering promotes the exposure of neoantigens in Plasmodium falciparum-infected erythrocytes. Winograd, E., Prudhomme, J.G., Sherman, I.W. Mol. Biochem. Parasitol. (2005) [Pubmed]
  25. Major erythrocyte membrane protein genes in EKLF-deficient mice. Nilson, D.G., Sabatino, D.E., Bodine, D.M., Gallagher, P.G. Exp. Hematol. (2006) [Pubmed]
  26. Specific pattern of gene expression during induction of mouse erythroleukemia cells. Fraser, P.J., Curtis, P.J. Genes Dev. (1987) [Pubmed]
  27. betaMinor-globin messenger RNA accumulation in reticulocytes governs improved erythropoiesis in beta thalassemic mice after erythropoietin complementary DNA electrotransfer in muscles. Samakoglu, S., Fattori, E., Lamartina, S., Toniatti, C., Stockholm, D., Heard, J.M., Bohl, D. Blood (2001) [Pubmed]
  28. Maturation of murine erythroleukemia cells committed to differentiation requires protein kinase C. GuptaRoy, B., Cohen, C.M. J. Biol. Chem. (1992) [Pubmed]
  29. Anion transport in oocytes of Xenopus laevis induced by expression of mouse erythroid band 3 protein--encoding cRNA and of a cRNA derivative obtained by site-directed mutagenesis at the stilbene disulfonate binding site. Bartel, D., Lepke, S., Layh-Schmitt, G., Legrum, B., Passow, H. EMBO J. (1989) [Pubmed]
  30. Defective assembly of membrane proteins in erythroid precursors of beta-thalassemic mice. Yuan, J., Rubin, E., Aljurf, M., Ma, L., Schrier, S.L. Blood (1994) [Pubmed]
  31. Temporal synthesis of band 3 oligomers during terminal maturation of mouse erythroblasts. Dimers and tetramers exist in the membrane as preformed stable species. Hanspal, M., Golan, D.E., Smockova, Y., Yi, S.J., Cho, M.R., Liu, S.C., Palek, J. Blood (1998) [Pubmed]
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