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Gene Review

SLC4A7  -  solute carrier family 4, sodium...

Homo sapiens

Synonyms: BT, Bicarbonate transporter, Electroneutral Na/HCO(3) cotransporter, NBC2, NBC2B, ...
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Disease relevance of SLC4A7

  • NBC2 may be a major regulator of extracellular pH of retina where light stimulation produces an extracellular alkalization and may contribute as a solute transporter to the prevention of retinal detachment [1].

High impact information on SLC4A7


Biological context of SLC4A7

  • NBC2 and NBC3 have a wider tissue distribution than NBC1, are electroneutral, and are involved with cell pH regulation [4].
  • Haplotype analysis in a second family refined the interval to a 3.4-cM region that includes the candidate genes TOP2B and SLC4A7 [5].
  • Mapping of the human NBC3 (SLC4A7) gene to chromosome 3p22 [6].
  • Although PKA decreased NBC3 transport activity, it did so independently of the NBC3/CAII interaction and did not involve phosphorylation of NBC3Ct [7].
  • We further propose that enhanced expression of NBC-3 in severe acid stress could play an important role in cell survival by mediating the influx of HCO-3 into the cells [8].

Anatomical context of SLC4A7

  • Expression studies in oocytes indicated that NBC-3 mediates Na-dependent HCO3- cotransport [9].
  • Although NBC3 immunoreactivity was also detected in submandibular gland acinar cells and in the ducts of both glands, it is unlikely that NBC3 plays any role in pH(i) regulation [10].
  • Cotransfection of HEK-293 cells with NBC3 and CAII recruited CAII to the plasma membrane [7].
  • NBC-3 is highly expressed in brain and spinal column, with moderate levels in trachea, thyroid, and kidney [8].
  • Used together, CDDP and ETP showed a synergistic effect against cell growth on only 1 cell line (SBC-3), additive effects on 6 (SBC-2, SBC-5, Lu130, Lu134AH, Lu135T and H69) and an antagonistic effect on 1 (SBC-1) [11].

Associations of SLC4A7 with chemical compounds

  • We have recently cloned and characterized a unique sodium bicarbonate cotransporter, NBC3, which unlike other members of the NBC family, is ethylisopropylamiloride (EIPA) inhibitable, DIDS insensitive, and electroneutral (A. Pushkin, N. Abuladze, I. Lee, D. Newman, J. Hwang, and I. Kurtz. J. Biol. Chem. 274: 16569-16575, 1999) [12].
  • RESULTS: IC50 values for SBC-2, -3, -4, and -7 cells of antimicrotubule agents were markedly lower than those of doxorubicin, etoposide, and cisplatin [13].
  • The results showed that the well differentiated TCC cell lines, RT4, SBC-2, and SBC-7, did not possess the capacity to internalize BCG, which was associated with an inability to upregulate IL-6 synthesis when stimulated with BCG [14].
  • Effect of SiO2 and zeolite surfaces on the excited triplet state of benzophenone, BT; a spectroscopic and kinetic study [15].

Other interactions of SLC4A7

  • The best characterized members are the SLC4A4 and SLC4A7 [16].
  • The genes TOP2B and SLC4A7 and five other characterized genes that map within the critical interval have been investigated and excluded from having a pathogenic role in HSNI with cough and GER [5].

Analytical, diagnostic and therapeutic context of SLC4A7


  1. Molecular cloning of a new sodium bicarbonate cotransporter cDNA from human retina. Ishibashi, K., Sasaki, S., Marumo, F. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  2. The cystic fibrosis transmembrane conductance regulator interacts with and regulates the activity of the HCO3- salvage transporter human Na+-HCO3- cotransport isoform 3. Park, M., Ko, S.B., Choi, J.Y., Muallem, G., Thomas, P.J., Pushkin, A., Lee, M.S., Kim, J.Y., Lee, M.G., Muallem, S., Kurtz, I. J. Biol. Chem. (2002) [Pubmed]
  3. Cloning, tissue distribution, genomic organization, and functional characterization of NBC3, a new member of the sodium bicarbonate cotransporter family. Pushkin, A., Abuladze, N., Lee, I., Newman, D., Hwang, J., Kurtz, I. J. Biol. Chem. (1999) [Pubmed]
  4. Na+:HCO(3-) cotransporters (NBC): cloning and characterization. Soleimani, M., Burnham, C.E. J. Membr. Biol. (2001) [Pubmed]
  5. Transcript map of the candidate region for HSNI with cough and gastroesophageal reflux on chromosome 3p and exclusion of candidate genes. Kok, C., Kennerson, M.L., Myers, S.J., Nicholson, G.A. Neurogenetics (2004) [Pubmed]
  6. Mapping of the human NBC3 (SLC4A7) gene to chromosome 3p22. Pushkin, A., Abuladze, N., Lee, I., Newman, D., Hwang, J., Kurtz, I. Genomics (1999) [Pubmed]
  7. Regulation of the human NBC3 Na+/HCO3- cotransporter by carbonic anhydrase II and PKA. Loiselle, F.B., Morgan, P.E., Alvarez, B.V., Casey, J.R. Am. J. Physiol., Cell Physiol. (2004) [Pubmed]
  8. Characterization of Na+/HCO-3 cotransporter isoform NBC-3. Amlal, H., Burnham, C.E., Soleimani, M. Am. J. Physiol. (1999) [Pubmed]
  9. Mouse Na+: HCO3- cotransporter isoform NBC-3 (kNBC-3): cloning, expression, and renal distribution. Wang, Z., Conforti, L., Petrovic, S., Amlal, H., Burnham, C.E., Soleimani, M. Kidney Int. (2001) [Pubmed]
  10. Expression of the Na+-HCO3- cotransporter and its role in pHi regulation in guinea pig salivary glands. Li, J., Koo, N.Y., Cho, I.H., Kwon, T.H., Choi, S.Y., Lee, S.J., Oh, S.B., Kim, J.S., Park, K. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  11. In vitro and in vivo effects of cisplatin and etoposide in combination on small cell lung cancer cell lines. Kondo, H., Kanzawa, F., Nishio, K., Saito, S., Saijo, N. Jpn. J. Cancer Res. (1994) [Pubmed]
  12. NBC3 expression in rabbit collecting duct: colocalization with vacuolar H+-ATPase. Pushkin, A., Yip, K.P., Clark, I., Abuladze, N., Kwon, T.H., Tsuruoka, S., Schwartz, G.J., Nielsen, S., Kurtz, I. Am. J. Physiol. (1999) [Pubmed]
  13. In vitro evaluation of antimicrotubule agents in human small-cell lung cancer cell lines. Ikubo, S., Takigawa, N., Ueoka, H., Kiura, K., Tabata, M., Shibayama, T., Chikamori, M., Aoe, K., Matsushita, A., Harada, M. Anticancer Res. (1999) [Pubmed]
  14. BCG-induced interleukin-6 upregulation and BCG internalization in well and poorly differentiated human bladder cancer cell lines. Bevers, R.F., de Boer, E.C., Kurth, K.H., Schamhart, D.H. Eur. Cytokine Netw. (1998) [Pubmed]
  15. Effect of SiO2 and zeolite surfaces on the excited triplet state of benzophenone, BT; a spectroscopic and kinetic study. Thomas, J.K. Photochem. Photobiol. Sci. (2004) [Pubmed]
  16. Sodium coupled bicarbonate transporters in the kidney, an update. Aalkjaer, C., Frische, S., Leipziger, J., Nielsen, S., Praetorius, J. Acta Physiol. Scand. (2004) [Pubmed]
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