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

• In this work, we report that transient or stable expression of human NBC3 (hNBC3) in HEK cells resulted in a Na(+)-dependent, DIDS (4,4'-diisothiocyanostilbene-2,2'-disulfonic acid)- and 5-ethylisopropylamiloride-insensitive HCO(3)(-) transport [2].
• Glutathione S-transferase-EBP50 pulled down CFTR and hNBC3 from cell lysates when expressed individually and as a complex when expressed together [2].
• The NBC3 gene (SLC4A7) spans approximately 80 kb and is composed of 25 coding exons and 24 introns that are flanked by typical splice donor and acceptor sequences [3].
• Cloning, tissue distribution, genomic organization, and functional characterization of NBC3, a new member of the sodium bicarbonate cotransporter family [3].
• We report the cloning, sequence analysis, tissue distribution, genomic organization, and functional analysis of a new member of the sodium bicarbonate cotransporter (NBC) family, NBC3, from human skeletal muscle. mNBC3 encodes a 1214-residue polypeptide with 12 putative membrane-spanning domains [3].

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

• Northern blot analysis revealed that NBC-3 encodes a 4.4-kb mRNA with a tissue distribution pattern distinct from NBC-1 and NBC-2 [8].

References