SLC4A4

Summary

Gene Symbol: SLC4A4
Description: solute carrier family 4 member 4
Alias: HNBC1, KNBC, NBC1, NBC2, NBCe1-A, SLC4A5, hhNMC, kNBC1, pNBC, electrogenic sodium bicarbonate cotransporter 1, Na(+)/HCO3(-) cotransporter, sodium bicarbonate cotransporter 1 (sodium bicarbonate cotransporter, kidney; sodium bicarbonate cotransporter, pancreas), solute carrier family 4 (sodium bicarbonate cotransporter), member 4, solute carrier family 4, sodium bicarbonate cotransporter, member 4, brain type, solute carrier family 4, sodium bicarbonate cotransporter, member 5
Species: human
Products:     SLC4A4

Top Publications

  1. Dinour D, Chang M, Satoh J, Smith B, Angle N, Knecht A, et al. A novel missense mutation in the sodium bicarbonate cotransporter (NBCe1/SLC4A4) causes proximal tubular acidosis and glaucoma through ion transport defects. J Biol Chem. 2004;279:52238-46 pubmed
    ..part by absorbing filtered bicarbonate in the proximal tubule via an electrogenic Na+/HCO3- cotransporter (NBCe1/SLC4A4). Recently, human genetics revealed that NBCe1 is the major renal contributor to this process...
  2. Gross E, Fedotoff O, Pushkin A, Abuladze N, Newman D, Kurtz I. Phosphorylation-induced modulation of pNBC1 function: distinct roles for the amino- and carboxy-termini. J Physiol. 2003;549:673-82 pubmed
    The human NBC1 (SLC4A4) gene encodes the electrogenic sodium bicarbonate cotransporters kNBC1 and pNBC1, which are highly expressed in the kidney and pancreas, respectively...
  3. Alvarez B, Loiselle F, Supuran C, Schwartz G, Casey J. Direct extracellular interaction between carbonic anhydrase IV and the human NBC1 sodium/bicarbonate co-transporter. Biochemistry. 2003;42:12321-9 pubmed publisher
    ..Electrogenic NBC1 catalyzes HCO(3)(-) fluxes in mammalian kidney, pancreas, and heart cells...
  4. Burnham C, Amlal H, Wang Z, Shull G, Soleimani M. Cloning and functional expression of a human kidney Na+:HCO3- cotransporter. J Biol Chem. 1997;272:19111-4 pubmed
    ..6-kilobase mRNA is highly expressed in kidney and pancreas, with detectable levels in brain. Functional studies in transiently transfected HEK-293 cells demonstrate that the cloned transporter mediates Na+:HCO3- cotransport. ..
  5. Abuladze N, Lee I, Newman D, Hwang J, Boorer K, Pushkin A, et al. Molecular cloning, chromosomal localization, tissue distribution, and functional expression of the human pancreatic sodium bicarbonate cotransporter. J Biol Chem. 1998;273:17689-95 pubmed
    ..differs at the N terminus from the recently cloned human sodium bicarbonate cotransporter isolated from kidney (kNBC) (Burnham, C. E., Amlal, H., Wang, Z., Shull, G. E., and Soleimani, M. (1997) J. Biol. Chem. 272, 19111-19114)...
  6. Shirakabe K, Priori G, Yamada H, Ando H, Horita S, Fujita T, et al. IRBIT, an inositol 1,4,5-trisphosphate receptor-binding protein, specifically binds to and activates pancreas-type Na+/HCO3- cotransporter 1 (pNBC1). Proc Natl Acad Sci U S A. 2006;103:9542-7 pubmed
    ..Of the two major splicing variants of NBC1, pancreas-type NBC1 (pNBC1) and kidney-type NBC1 (kNBC1), IRBIT was found to bind specifically to pNBC1 and not to bind to kNBC1...
  7. Chen L, Liu Y, Boron W. Role of an extracellular loop in determining the stoichiometry of Na+-HCO?? cotransporters. J Physiol. 2011;589:877-90 pubmed publisher
    ..Moreover, mutations and gene disruptions in NBC are linked to a wide range of pathologies. NBCe1 (SLC4A4) is electrogenic because it has an apparent Na+:HCO?? stoichiometry of 1:2 or 1:3, whereas NBCn1 (SLC4A7) is ..
  8. Ali N, Khan S, Yao H, Wang J. Biochars reduced the bioaccessibility and (bio)uptake of organochlorine pesticides and changed the microbial community dynamics in agricultural soils. Chemosphere. 2019;224:805-815 pubmed publisher
    ..sewage sludge biochar (SSBC), soybean straw biochar (SBBC), rice straw biochar (RSBC) and peanut shells biochar (PNBC)), on bioaccessible fractions of OCPs in a contaminated soil and their subsequent bioaccumulation into vegetables (..
  9. Alves A, Gregório S, Egger R, Fuentes J. Molecular and functional regionalization of bicarbonate secretion cascade in the intestine of the European sea bass (Dicentrarchus labrax). Comp Biochem Physiol A Mol Integr Physiol. 2019;233:53-64 pubmed publisher
    ..higher Na+/K+-ATPase activity, Cl- transepithelial transport and basolateral slc4a4, apical slc26a6 and slc26a3 expression levels...

More Information

Publications117 found, 100 shown here

  1. Sun P, Shen L, Zhang C, Du L, Wu X. Promoting the expansion and function of human corneal endothelial cells with an orbital adipose-derived stem cell-conditioned medium. Stem Cell Res Ther. 2017;8:287 pubmed publisher
    ..The CEC-relative markers zonula occludens-1 (ZO-1), Na+/K+ ATPase, N-cadherin, Col8a2, and SLC4A4 were expressed in HCECs cultured by OASC-CM...
  2. Vairamani K, Prasad V, Wang Y, Huang W, Chen Y, Medvedovic M, et al. NBCe1 Na+-HCO3- cotransporter ablation causes reduced apoptosis following cardiac ischemia-reperfusion injury in vivo. World J Cardiol. 2018;10:97-109 pubmed publisher
    ..An NBCe1 (Slc4a4 gene) conditional knockout mouse (KO) model was prepared by gene targeting...
  3. Virreira Bermudez M, Jin L, Djerbib S, De Deken X, Miot F, Massart C, et al. Expression, localization and regulation of the sodium bicarbonate cotransporter NBCe1 in the thyroid. Thyroid. 2018;: pubmed publisher
    ..is unknown, so this study investigated whether the rather ubiquitous sodium bicarbonate cotransporter NBCe1 (SLC4A4) might play this role...
  4. Mukaibo T, Munemasa T, George A, Tran D, Gao X, Herche J, et al. The apical anion exchanger Slc26a6 promotes oxalate secretion by murine submandibular gland acinar cells. J Biol Chem. 2018;293:6259-6268 pubmed publisher
    ..whereas two other anion exchangers known to be expressed in salivary gland acinar cells, Slc4a4 and Slc4a9, mediated little, if any, Cl-/oxalate exchange...
  5. Ruiz Jarabo I, Gregório S, Gaetano P, Trischitta F, Fuentes J. High rates of intestinal bicarbonate secretion in seawater tilapia (Oreochromis mossambicus). Comp Biochem Physiol A Mol Integr Physiol. 2017;207:57-64 pubmed publisher
    ..e. slc26a6, slc26a3, slc4a4 and v-type H-ATPase sub C in the intestine of tilapia acclimated to both seawater and freshwater...
  6. Kant S, Stopa E, Johanson C, Baird A, Silverberg G. Choroid plexus genes for CSF production and brain homeostasis are altered in Alzheimer's disease. Fluids Barriers CNS. 2018;15:34 pubmed publisher
    ..These included disruptions to ion transporters (e.g., the solute carrier gene SLC4A5, p = 0.004) and associated enzyme expressions (e.g., carbonic anhydrase CA4, p = 0...
  7. Khakipoor S, Ophoven C, Schrödl Häußel M, Feuerstein M, Heimrich B, Deitmer J, et al. TGF-β signaling directly regulates transcription and functional expression of the electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), via Smad4 in mouse astrocytes. Glia. 2017;65:1361-1375 pubmed publisher
    The electrogenic sodium bicarbonate cotransporter NBCe1 (SLC4A4) expressed in astrocytes regulates intracellular and extracellular pH...
  8. Yamazaki O, Yamada H, Suzuki M, Horita S, Shirai A, Nakamura M, et al. Functional characterization of nonsynonymous single nucleotide polymorphisms in the electrogenic Na+-HCO3- cotransporter NBCe1A. Pflugers Arch. 2011;461:249-59 pubmed publisher
    The electrogenic Na(+)-HCO(3)(-) cotransporter NBCe1 encoded by SLC4A4 plays essential roles in the regulation of intracellular/extracellular pH...
  9. Nakamura M, Satoh N, Suzuki M, Kume H, Homma Y, Seki G, et al. Stimulatory effect of insulin on renal proximal tubule sodium transport is preserved in type 2 diabetes with nephropathy. Biochem Biophys Res Commun. 2015;461:154-8 pubmed publisher
    ..In addition to hypoglycemia, insulin-induced renal sodium retention might also play a role in increased cardiovascular risk associated with intensive glycemic control in type 2 diabetic patients with nephropathy. ..
  10. Shahzad H, Giribabu N, Karim K, Kassim N, Muniandy S, Salleh N. Combinatorial effects of quercetin and sex-steroids on fluid and electrolytes' (Na+, Cl-, HCO3-) secretory mechanisms in the uterus of ovariectomised female Sprague-Dawley rats. PLoS ONE. 2017;12:e0172765 pubmed publisher
    ..In concordant, levels of CFTR, SLC4A4, ENaC (α, β and γ), Na+/K+-ATPase, GPα/β, AC and cAMP in the uterus increased following increased in the ..
  11. Gross E, Hawkins K, Pushkin A, Sassani P, Dukkipati R, Abuladze N, et al. Phosphorylation of Ser(982) in the sodium bicarbonate cotransporter kNBC1 shifts the HCO(3)(-) : Na(+) stoichiometry from 3 : 1 to 2 : 1 in murine proximal tubule cells. J Physiol. 2001;537:659-65 pubmed
    ..The electrogenic sodium bicarbonate cotransporter kNBC1 mediates basolateral sodium and bicarbonate efflux in the proximal tubule by coupling the transport of 1 Na(+) ..
  12. Ali N, Khan S, Li Y, Zheng N, Yao H. Influence of biochars on the accessibility of organochlorine pesticides and microbial community in contaminated soils. Sci Total Environ. 2018;647:551-560 pubmed publisher
    ..The soil was amended with four different kinds of biochars: sewage sludge biochar (SSBC), peanut shells biochar (PNBC), rice straw biochar (RSBC), and soybean straw biochar (SBBC)...
  13. Wen D, Yuan Y, Warner P, Wang B, Cornelius R, Wang France J, et al. Increased Epithelial Sodium Channel Activity Contributes to Hypertension Caused by Na+-HCO3- Cotransporter Electrogenic 2 Deficiency. Hypertension. 2015;66:68-74 pubmed publisher
    The gene SLC4A5 encodes the Na(+)-HCO3 (-) cotransporter electrogenic 2, which is located in the distal nephron...
  14. Wen D, Yuan Y, Cornelius R, Li H, Warner P, Wang B, et al. Deficient acid handling with distal RTA in the NBCe2 knockout mouse. Am J Physiol Renal Physiol. 2015;309:F523-30 pubmed publisher
    ..In the present study, we report that a mouse model lacking the electrogenic Na(+)-HCO3 (-) cotransporter [NBCe2/Slc4a5; NBCe2 knockout (KO) mice] developed dRTA after an oral acid challenge...
  15. Myers E, Marshall A, Parker M. The role of disease-linked residue glutamine-913 in support of the structure and function of the human electrogenic sodium/bicarbonate cotransporter NBCe1-A. Sci Rep. 2018;8:3066 pubmed publisher
    Mutations in the sodium bicarbonate cotransporter NBCe1 (SLC4A4) cause proximal renal tubular acidosis (pRTA). We recently described a novel pRTA mutation p.Gln913Arg (Q913R), inherited in compound heterozygous form with p...
  16. Horita S, Simsek E, Simsek T, Yildirim N, Ishiura H, Nakamura M, et al. SLC4A4 compound heterozygous mutations in exon-intron boundary regions presenting with severe proximal renal tubular acidosis and extrarenal symptoms coexisting with Turner's syndrome: a case report. BMC Med Genet. 2018;19:103 pubmed publisher
    Congenital NBCe1A deficiency with the SLC4A4 mutation causes severe proximal renal tubular acidosis, which often comprises extrarenal symptoms, such as intellectual disability and developmental delay, glaucoma, cataract and band ..
  17. Schrödl Häußel M, Theparambil S, Deitmer J, Roussa E. Regulation of functional expression of the electrogenic sodium bicarbonate cotransporter 1, NBCe1 (SLC4A4), in mouse astrocytes. Glia. 2015;63:1226-39 pubmed publisher
    The electrogenic sodium bicarbonate cotransporter NBCe1 (SLC4A4) is expressed in many cell types and is a major regulator of intracellular, and extracellular pH...
  18. Heidtmann H, Ruminot I, Becker H, Deitmer J. Inhibition of monocarboxylate transporter by N-cyanosulphonamide S0859. Eur J Pharmacol. 2015;762:344-9 pubmed publisher
    ..2008). First, for comparison, the electrogenic human NBCe1 (SLC4A4) was heterologously expressed in Xenopus laevis oocytes, where its transport activity was inhibited by S0859 with ..
  19. Azimov R, Abuladze N, Sassani P, Newman D, Kao L, Liu W, et al. G418-mediated ribosomal read-through of a nonsense mutation causing autosomal recessive proximal renal tubular acidosis. Am J Physiol Renal Physiol. 2008;295:F633-41 pubmed publisher
    Autosomal recessive proximal renal tubular acidosis is caused by mutations in the SLC4A4 gene encoding the electrogenic sodium bicarbonate cotransporter NBCe1-A...
  20. Praetorius J, Hager H, Nielsen S, Aalkjaer C, Friis U, Ainsworth M, et al. Molecular and functional evidence for electrogenic and electroneutral Na(+)-HCO(3)(-) cotransporters in murine duodenum. Am J Physiol Gastrointest Liver Physiol. 2001;280:G332-43 pubmed
    ..Proximal duodenal epithelial cells expressed mRNA encoding two electrogenic NBC1 isoforms and the electroneutral NBCn1...
  21. Yu Q, Liu X, Liu Y, Riederer B, Li T, Tian D, et al. Defective small intestinal anion secretion, dipeptide absorption, and intestinal failure in suckling NBCe1-deficient mice. Pflugers Arch. 2016;468:1419-32 pubmed publisher
    The electrogenic Na(+)HCO3 (-) cotransporter NBCe1 (Slc4a4) is strongly expressed in the basolateral enterocyte membrane in a villous/surface predominant fashion...
  22. Pushkin A, Abuladze N, Gross E, Newman D, Tatishchev S, Lee I, et al. Molecular mechanism of kNBC1-carbonic anhydrase II interaction in proximal tubule cells. J Physiol. 2004;559:55-65 pubmed
    ..carbonic anhydrase II (CAII) binds in vitro to the C-terminus of the electrogenic sodium bicarbonate cotransporter kNBC1 (kNBC1-ct)...
  23. Abuladze N, Azimov R, Newman D, Sassani P, Liu W, Tatishchev S, et al. Critical amino acid residues involved in the electrogenic sodium-bicarbonate cotransporter kNBC1-mediated transport. J Physiol. 2005;565:717-30 pubmed
    ..acids putatively involved in ion transport mediated by the predominant variant of NBC1 expressed in the kidney (kNBC1) were mutated to neutral and/or oppositely charged amino acids...
  24. Lee S, Boron W, Parker M. Relief of autoinhibition of the electrogenic Na-HCO(3) [corrected] cotransporter NBCe1-B: role of IRBIT vs.amino-terminal truncation. Am J Physiol Cell Physiol. 2012;302:C518-26 pubmed publisher
    Two maneuvers known to stimulate electrogenic sodium bicarbonate cotransporter 1 (NBCe1) activity are 1) deletion from the cytosolic amino-terminus (Nt) of NBCe1-C of an 87-amino acid sequence that contains an autoinhibitory domain (AID);..
  25. Dagilgan S, Dündar Yenilmez E, Tuli A, Urunsak I, Erdogan S. Evaluation of intracellular pH regulation and alkalosis defense mechanisms in preimplantation embryos. Theriogenology. 2015;83:1075-84 pubmed publisher
    ..All embryos expressed SLC4A2 and SLC4A4 coding for AE-2 and AE-4, but none expressed either AE-1 or AE-3...
  26. Yin K, Lei Y, Wen X, Lacruz R, Soleimani M, Kurtz I, et al. SLC26A Gene Family Participate in pH Regulation during Enamel Maturation. PLoS ONE. 2015;10:e0144703 pubmed publisher
    ..observed in Slc26a1-/- or Slc26a7-/- animals, absence of Slc26a1 or Slc26a7 results in up-regulation of Cftr, Ca2, Slc4a4, Slc4a9 and Slc26a9, all of which are involved in pH homeostasis, indicating that this might be a compensatory ..
  27. Niculescu A, Le Niculescu H, Levey D, Phalen P, Dainton H, ROSEBERRY K, et al. Precision medicine for suicidality: from universality to subtypes and personalization. Mol Psychiatry. 2017;22:1250-1273 pubmed publisher
    ..such as CLN5 and AK2), as well as reinforcement of ours and others previous findings in the field (such as SLC4A4 and SKA2)...
  28. Zhu Q, Kao L, Azimov R, Abuladze N, Newman D, Kurtz I. Interplay between disulfide bonding and N-glycosylation defines SLC4 Na+-coupled transporter extracellular topography. J Biol Chem. 2015;290:5391-404 pubmed publisher
    ..Moreover, the formation of this unique structure is critically dependent on the finely tuned interplay between disulfide bonding and N-glycosylation in the membrane processed NBCe1-A dimer. ..
  29. Cao L, Xia C, Shi Z, Wang N, Gu Z, Yu L, et al. Na+/HCO3- cotransporter is expressed on ? and ? cells during rat pancreatic development. World J Gastroenterol. 2016;22:9525-9533 pubmed
    ..the expression and localization of the electrogenic Na+/HCO3- cotransporter (NBC1) in rat pancreas during development...
  30. Christensen H, Barbuskaite D, Rojek A, Malte H, Christensen I, F chtbauer A, et al. The choroid plexus sodium-bicarbonate cotransporter NBCe2 regulates mouse cerebrospinal fluid pH. J Physiol. 2018;: pubmed publisher
    ..A novel strain of NBCe2 (Slc4a5) knockout (ko) mice was generated and validated...
  31. Espiritu D, Bernardo A, Arruda J. Role of NH(2) and COOH termini in targeting, stability, and activity of sodium bicarbonate cotransporter 1. Am J Physiol Renal Physiol. 2006;291:F588-96 pubmed
    Sodium bicarbonate cotransporter 1 (NBC1) mediates 80% of bicarbonate reabsorption by the kidney, but the molecular determinants for activity, targeting, and cell membrane stability are poorly understood...
  32. Liao J, Su X, Chen P, Wang X, Xu L, Li X, et al. Meta-analysis of genome-wide association studies in multiethnic Asians identifies two loci for age-related nuclear cataract. Hum Mol Genet. 2014;23:6119-28 pubmed publisher
    ..The results offer additional insights into the pathogenesis of nuclear cataract in Asians. ..
  33. Osis G, Handlogten M, Lee H, Hering Smith K, Huang W, Romero M, et al. Effect of NBCe1 deletion on renal citrate and 2-oxoglutarate handling. Physiol Rep. 2016;4: pubmed publisher
    The bicarbonate transporter, NBCe1 (SLC4A4), is necessary for at least two components of the proximal tubule contribution to acid-base homeostasis, filtered bicarbonate reabsorption, and ammonia metabolism...
  34. Chourasia T, D Cotta H, Baroiller J, Slosman T, Cnaani A. Effects of the acclimation to high salinity on intestinal ion and peptide transporters in two tilapia species that differ in their salinity tolerance. Comp Biochem Physiol A Mol Integr Physiol. 2018;218:16-23 pubmed publisher
    ..as well as expression levels of genes encoding two HCO3- and three peptide transporters (nbc1, slc26a6, slc15a1a, slc15a1b and slc15a2) were measured in three intestinal sections of these two species, grown in ..
  35. Li G, Khan S, Ibrahim M, Sun T, Tang J, Cotner J, et al. Biochars induced modification of dissolved organic matter (DOM) in soil and its impact on mobility and bioaccumulation of arsenic and cadmium. J Hazard Mater. 2018;348:100-108 pubmed publisher
    ..biochars pyrolysed from mushroom waste (MSBC), soybean straw (SBBC), sewage sludge (SSBC), peanut shells (PNBC) and rice straw (RSBC) at two pyrolysis temperatures (200 °C and 350 °C) were used to investigate ..
  36. Stumpff F. A look at the smelly side of physiology: transport of short chain fatty acids. Pflugers Arch. 2018;470:571-598 pubmed publisher
    ..Furthermore, protons can be basolaterally removed by NHE1 (SCL9A1) or NBCe1 (SLC4A4)...
  37. Theparambil S, Ruminot I, Schneider H, Shull G, Deitmer J. The electrogenic sodium bicarbonate cotransporter NBCe1 is a high-affinity bicarbonate carrier in cortical astrocytes. J Neurosci. 2014;34:1148-57 pubmed publisher
    The electrogenic sodium bicarbonate cotransporter NBCe1 (SLC4A4) is a robust regulator of intracellular H(+) and a significant base carrier in many cell types...
  38. Gildea J, Xu P, Carlson J, Gaglione R, Bigler Wang D, Kemp B, et al. The sodium-bicarbonate cotransporter NBCe2 (slc4a5) expressed in human renal proximal tubules shows increased apical expression under high-salt conditions. Am J Physiol Regul Integr Comp Physiol. 2015;309:R1447-59 pubmed publisher
    The electrogenic sodium bicarbonate cotransporter (NBCe2) is encoded by SLC4A5, variants of which have been associated with salt sensitivity of blood pressure, which affects 25% of the adult population...
  39. Michael K, Kreiss C, Hu M, Koschnick N, Bickmeyer U, Dupont S, et al. Adjustments of molecular key components of branchial ion and pH regulation in Atlantic cod (Gadus morhua) in response to ocean acidification and warming. Comp Biochem Physiol B Biochem Mol Biol. 2016;193:33-46 pubmed publisher
    ..Here, we characterized the regulation of transepithelial ion transporters (NKCC1, NBC1, SLC26A6, NHE1 and 2) and ATPases (Na(+)/K(+) ATPase and V-type H(+) ATPase) in gills of Atlantic cod (Gadus morhua)..
  40. McIntyre A, Hulikova A, Ledaki I, Snell C, Singleton D, Steers G, et al. Disrupting Hypoxia-Induced Bicarbonate Transport Acidifies Tumor Cells and Suppresses Tumor Growth. Cancer Res. 2016;76:3744-55 pubmed publisher
    ..The most robust and frequent inductions were of the sodium-driven bicarbonate transporters SLC4A4 and SLC4A9, which rely upon both HIF1? and HIF2? activity for their expression...
  41. Li H, Worrell R, Matthews J, Husseinzadeh H, Neumeier L, Petrovic S, et al. Identification of a carboxyl-terminal motif essential for the targeting of Na+-HCO-3 cotransporter NBC1 to the basolateral membrane. J Biol Chem. 2004;279:43190-7 pubmed
    The Na+-HCO3- cotransporter NBC1 is located exclusively on the basolateral membrane and mediates vectorial transport of bicarbonate in a number of epithelia, including kidney and pancreas...
  42. Handlogten M, Osis G, Lee H, Romero M, Verlander J, Weiner I. NBCe1 expression is required for normal renal ammonia metabolism. Am J Physiol Renal Physiol. 2015;309:F658-66 pubmed publisher
    ..addressed the role of the proximal tubule basolateral electrogenic Na(+)-coupled bicarbonate cotransporter (NBCe1; Slc4a4) in renal ammonia metabolism...
  43. Cheng H, Chang W, Hu Y, Hsieh B, Huang T, Chong I, et al. Arecoline Increases Glycolysis and Modulates pH Regulator Expression in HA22T/VGH Hepatoma Cells, Leading to Increase of Intracellular Ca2+, Reactive Oxygen Species, and Anoikis. J Cancer. 2017;8:3173-3182 pubmed publisher
    ..of pH regulators including monocarboxylate transporter 1 and 4 (MCT 1 and 4), sodium bicarbonate cotransporter 1 (NBC1), carbonic anhydrases (CA) IX and XII and vacuolar ATPase (V-ATPase) were down-regulated...
  44. Katzir Z, Dinour D, Reznik Wolf H, Nissenkorn A, Holtzman E. Familial pure proximal renal tubular acidosis--a clinical and genetic study. Nephrol Dial Transplant. 2008;23:1211-5 pubmed
    ..Objectives. We report a unique family with isolated pRTA. The aim of the project was to define the phenotype and to try to find the gene defect causing the disease...
  45. Shnitsar V, Li J, Li X, Calmettes C, Basu A, Casey J, et al. A substrate access tunnel in the cytosolic domain is not an essential feature of the solute carrier 4 (SLC4) family of bicarbonate transporters. J Biol Chem. 2013;288:33848-60 pubmed publisher
    ..Mutation of a conserved arginine residue (R298S) in the cytosolic domain of NBCe1 (SLC4A4) is linked to proximal renal tubular acidosis and results in impaired transport function, suggesting that the ..
  46. Taylor J, Sun Y, Barcelona de Mendoza V, Ifatunji M, Rafferty J, Fox E, et al. The combined effects of genetic risk and perceived discrimination on blood pressure among African Americans in the Jackson Heart Study. Medicine (Baltimore). 2017;96:e8369 pubmed publisher
    ..Most notably, there was a significant SNP?×?discrimination interaction for 2 SNPs on the SLC4A5 gene: rs3771724 (MLD: SBP P = .034, DBP P = .031; ED: DBP: P = .016) and rs1006502 (MLD: SBP P?=?.034, DBP P?=?...
  47. Hanzu F, Gasa R, Bulur N, Lybaert P, Gomis R, Malaisse W, et al. Expression of TMEM16A and SLC4A4 in human pancreatic islets. Cell Physiol Biochem. 2012;29:61-4 pubmed publisher
    ..may involve volume-regulated anion channels, including possibly TMEM16A, and the Na(+)-HCO(3)(-)-cotransporter SLC4A4. The present study was designed to explore the expression of both TMEM16A and SLC4A4 in human pancreatic islets...
  48. Smith J, Avery C, Evans D, Nalls M, Meng Y, Smith E, et al. Impact of ancestry and common genetic variants on QT interval in African Americans. Circ Cardiovasc Genet. 2012;5:647-55 pubmed publisher
    ..In addition, our genome-wide association study extends the association of polymorphisms at several loci associated with repolarization in individuals of European ancestry to include individuals of African ancestry. ..
  49. Wu X, Lund M, Sahana G, Guldbrandtsen B, Sun D, Zhang Q, et al. Association analysis for udder health based on SNP-panel and sequence data in Danish Holsteins. Genet Sel Evol. 2015;47:50 pubmed publisher
    ..The comparison between these candidate QTL regions and known genes suggested that NPFFR2, SLC4A4, DCK, LIFR, and EDN3 may be considered as candidate genes for mastitis susceptibility.
  50. Dieho K, van Baal J, Kruijt L, Bannink A, Schonewille J, Carreno D, et al. Effect of supplemental concentrate during the dry period or early lactation on rumen epithelium gene and protein expression in dairy cattle during the transition period. J Dairy Sci. 2017;100:7227-7245 pubmed publisher
    ..of epithelial transporter genes was not affected by day or treatment in the lactation experiment, except for NBC1. In the dry period experiment, expression of MCT1, NBC1, DRA, NHE2, NHE3, and UT-B generally decreased after ..
  51. Alsaif H, Khan A, Patel N, Alkuraya H, Hashem M, Abdulwahab F, et al. Congenital glaucoma and CYP1B1: an old story revisited. Hum Genet. 2018;: pubmed publisher
    ..inclusive of glaucoma, highlighting conditions that might phenotypically overlap with primary congenital glaucoma (SLC4A4, SLC4A11, CPAMD8, and KERA)...
  52. Khan S, Waqas M, Ding F, Shamshad I, Arp H, Li G. The influence of various biochars on the bioaccessibility and bioaccumulation of PAHs and potentially toxic elements to turnips (Brassica rapa L.). J Hazard Mater. 2015;300:243-253 pubmed publisher
    ..sewage sludge biochar (SSBC), soybean straw biochar (SBBC), rice straw biochar (RSBC) and peanut shell biochar (PNBC)...
  53. Felder R, Jose P, Xu P, Gildea J. The Renal Sodium Bicarbonate Cotransporter NBCe2: Is It a Major Contributor to Sodium and pH Homeostasis?. Curr Hypertens Rep. 2016;18:71 pubmed publisher
    ..This review will summarize our current understanding of the distribution and function of NBCe2 in the human kidney and how genetic variants of its gene, SLC4A5, contribute to salt sensitivity of blood pressure.
  54. Romero M, Boron W. Electrogenic Na+/HCO3- cotransporters: cloning and physiology. Annu Rev Physiol. 1999;61:699-723 pubmed
    ..For example, NBC occurs in pancreas, prostate, brain, heart, small and large intestine, stomach, and epididymis. Finally, there are at least two genes that encode NBC proteins. Possible future directions of research are discussed. ..
  55. Kristensen J, Kristensen M, Juel C. Expression of Na+/HCO3- co-transporter proteins (NBCs) in rat and human skeletal muscle. Acta Physiol Scand. 2004;182:69-76 pubmed
    ..One NBC protein (approximately 150 kDa) seems to be related to the kidney/pancreas/heart isoform NBC1, whereas the other protein (approximately 200 kDa) is related to the NBC4 isoform...
  56. Ruminot I, Gutierrez R, Peña Münzenmayer G, Añazco C, Sotelo Hitschfeld T, Lerchundi R, et al. NBCe1 mediates the acute stimulation of astrocytic glycolysis by extracellular K+. J Neurosci. 2011;31:14264-71 pubmed publisher
    ..The glycolytic response to K(+) was absent in astrocytes from NBCe1 null mice (Slc4a4) and was blocked by functional or pharmacological inhibition of the NBCe1...
  57. Kurtz I, Zhu Q. Structure, function, and regulation of the SLC4 NBCe1 transporter and its role in causing proximal renal tubular acidosis. Curr Opin Nephrol Hypertens. 2013;22:572-83 pubmed publisher
  58. Suzuki M, Vaisbich M, Yamada H, Horita S, Li Y, Sekine T, et al. Functional analysis of a novel missense NBC1 mutation and of other mutations causing proximal renal tubular acidosis. Pflugers Arch. 2008;455:583-93 pubmed
    Mutations in the Na(+)-HCO(3)(-) cotransporter NBC1 cause severe proximal tubular acidosis (pRTA) associated with ocular abnormalities...
  59. Gross P, Meye C. Proximal RTA: Are all the charts completed yet?. Nephrol Dial Transplant. 2008;23:1101-2 pubmed publisher
  60. Yang H, Kim E, Lee S, Park H, Cooper D, Rajbhandari I, et al. Mutation of Aspartate 555 of the Sodium/Bicarbonate Transporter SLC4A4/NBCe1 Induces Chloride Transport. J Biol Chem. 2009;284:15970-9 pubmed publisher
    To understand the mechanism for ion transport through the sodium/bicarbonate transporter SLC4A4 (NBCe1), we examined amino acid residues, within transmembrane domains, that are conserved among electrogenic Na/HCO(3) transporters but are ..
  61. Bae J, Koo N, Namkoong E, Davies A, Choi S, Shin Y, et al. Chaperone stress 70 protein (STCH) binds and regulates two acid/base transporters NBCe1-B and NHE1. J Biol Chem. 2013;288:6295-305 pubmed publisher
    ..We propose STCH may play a role in pHi regulation at times of cellular stress by enhancing the recovery from intracellular acidification. ..
  62. Guo L, Liu F, Chen S, Yang X, Huang J, He J, et al. Common variants in the Na(+)-coupled bicarbonate transporter genes and salt sensitivity of blood pressure: the GenSalt study. J Hum Hypertens. 2016;30:543-8 pubmed publisher
    ..model was used to assess the additive associations of 76 common variants in five NCBT genes, including SLC4A4, SLC4A5, SLC4A7, SLC4A8 and SLC4A10, with salt sensitivity phenotypes...
  63. Becker H, Deitmer J. Voltage dependence of H+ buffering mediated by sodium bicarbonate cotransport expressed in Xenopus oocytes. J Biol Chem. 2004;279:28057-62 pubmed
    ..Our results indicate that the electrogenic NBCe1 renders the cell membrane potential an effective regulator of intracellular H(+) buffering and acid/base-coupled metabolite transport. ..
  64. Chen L, Qin X, Moss F, Liu Y, Boron W. Effect of simultaneously replacing putative TM6 and TM12 of human NBCe1-A with those from NBCn1 on surface abundance in Xenopus oocytes. J Membr Biol. 2012;245:131-40 pubmed publisher
  65. Monazzami A, Rajabi H, Ghrakhanlou R, Yari K, Rahimi Z. Modulation of oxidative and glycolytic skeletal muscle fibers Na+/H+ exchanger1 (NHE1) and Na+/HCO3- co-transporter1 (NBC1) genes and proteins expression in type 2 diabetic rat (Streptozotocin + high fat diet) following long term endurance training. Cell Mol Biol (Noisy-le-grand). 2017;63:11-18 pubmed publisher
    ..The aim of present study was to investigate the effects of endurance training on muscle NHE1 and NBC1 genes and proteins expression in type 2 diabetic rats. Male wistar rats (n=30), 4 weeks old and 95.7±10...
  66. Huynh K, Jiang J, Abuladze N, Tsirulnikov K, Kao L, Shao X, et al. CryoEM structure of the human SLC4A4 sodium-coupled acid-base transporter NBCe1. Nat Commun. 2018;9:900 pubmed publisher
    ..Our data suggest that symporters and exchangers utilize comparable transport machinery and that subtle differences in their substrate-binding regions have very significant effects on their transport mode. ..
  67. Igarashi T, Inatomi J, Sekine T, Cha S, Kanai Y, Kunimi M, et al. Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities. Nat Genet. 1999;23:264-6 pubmed
  68. Li H, Szigligeti P, Worrell R, Matthews J, Conforti L, Soleimani M. Missense mutations in Na+:HCO3- cotransporter NBC1 show abnormal trafficking in polarized kidney cells: a basis of proximal renal tubular acidosis. Am J Physiol Renal Physiol. 2005;289:F61-71 pubmed
    The kidney Na(+):HCO(3)(-) cotransporter NBC1 is located exclusively on the basolateral membrane of kidney proximal tubule cells and is responsible for the reabsorption of majority of filtered bicarbonate...
  69. Kreindler J, Peters K, Frizzell R, Bridges R. Identification and membrane localization of electrogenic sodium bicarbonate cotransporters in Calu-3 cells. Biochim Biophys Acta. 2006;1762:704-10 pubmed
    ..These data suggest that these transporters contribute to regulated bicarbonate secretion across Calu-3 cells and perhaps human airway submucosal glands. ..
  70. Park K, Hurley P, Roussa E, Cooper G, Smith C, Thevenod F, et al. Expression of a sodium bicarbonate cotransporter in human parotid salivary glands. Arch Oral Biol. 2002;47:1-9 pubmed
    ..By reverse transcriptase-polymerase chain reaction, a full-length NBC1 clone was obtained showing more than 99% homology with the human pancreatic isoform hpNBC1...
  71. Yang Z, Alvarez B, Chakarova C, Jiang L, Karan G, Frederick J, et al. Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal photoreceptor degeneration. Hum Mol Genet. 2005;14:255-65 pubmed
    ..Here, we show that a functional complex of carbonic anhydrase 4 (CA4) and Na+/bicarbonate co-transporter 1 (NBC1) is specifically expressed in the choriocapillaris and that missense mutations in CA4 linked to autosomal dominant ..
  72. Dorfman R, Li W, Sun L, Lin F, Wang Y, Sandford A, et al. Modifier gene study of meconium ileus in cystic fibrosis: statistical considerations and gene mapping results. Hum Genet. 2009;126:763-78 pubmed publisher
    ..3 (HLOD = 3.19), with substantial heterogeneity. A candidate gene in the region, SLC4A4, provided preliminary evidence of association (p = 0.002), warranting further follow-up studies...
  73. Lee S, Boron W, Parker M. Substrate specificity of the electrogenic sodium/bicarbonate cotransporter NBCe1-A (SLC4A4, variant A) from humans and rabbits. Am J Physiol Renal Physiol. 2013;304:F883-99 pubmed publisher
    In the basolateral membrane of proximal-tubule cells, NBCe1-A (SLC4A4, variant A), operating with an apparent Na(+):HCO(3)(-) stoichiometry of 1:3, contributes to the reclamation of HCO(3)(-) from the glomerular filtrate, thereby ..
  74. Yamada H, Yamazaki S, Moriyama N, Hara C, Horita S, Enomoto Y, et al. Localization of NBC-1 variants in human kidney and renal cell carcinoma. Biochem Biophys Res Commun. 2003;310:1213-8 pubmed
    ..clarify these issues, immunohistochemical analysis was performed using the specific antibodies against kidney type (kNBC-1) and pancreatic type (pNBC-1) transporters...
  75. Perry C, Blaine J, Le H, Grichtchenko I. PMA- and ANG II-induced PKC regulation of the renal Na+-HCO3- cotransporter (hkNBCe1). Am J Physiol Renal Physiol. 2006;290:F417-27 pubmed
    ..3) Similar to proximal tubule, acute ANG II has a biphasic effect on hkNBCe1 coexpressed with AT(1B) in X. laevis oocytes. ..
  76. Li H, Li E, Neumeier L, Conforti L, Soleimani M. Identification of a novel signal in the cytoplasmic tail of the Na+:HCO3- cotransporter NBC1 that mediates basolateral targeting. Am J Physiol Renal Physiol. 2007;292:F1245-55 pubmed
    The Na(+):HCO(3)(-) cotransporter NBC1 (SLC4A4, variant A, kidney specific) is located exclusively on the basolateral membrane of epithelial cells, implying that this molecule has acquired specific signals for targeting to the basolateral ..
  77. Charoenphandhu N, Laohapitakworn S, Kraidith K, Nakkrasae L, Jongwattanapisan P, Tharabenjasin P, et al. Electrogenic Na?/HCO?? co-transporter-1 is essential for the parathyroid hormone-stimulated intestinal HCO?? secretion. Biochem Biophys Res Commun. 2011;409:775-9 pubmed publisher
    ..Therefore, the present results suggested that PTH stimulated intestinal HCO(3)(-) secretion, particularly in the ileum, by inducing the basolateral HCO(3)(-) uptake via NBCe1. ..
  78. Zhu Q, Liu W, Kao L, Azimov R, Newman D, Abuladze N, et al. Topology of NBCe1 protein transmembrane segment 1 and structural effect of proximal renal tubular acidosis (pRTA) S427L mutation. J Biol Chem. 2013;288:7894-906 pubmed publisher
    ..Our study provides novel structural insights into the pathogenic mechanism of S427L in mediating proximal renal tubular acidosis...
  79. Soleimani M, Burnham C. Physiologic and molecular aspects of the Na+:HCO3- cotransporter in health and disease processes. Kidney Int. 2000;57:371-84 pubmed
    ..Possible signals responsible for the regulation of NBCs in these conditions are examined. Furthermore, the possible role of this transporter in acid-base disorders (such as proximal renal tubular acidosis) is discussed. ..
  80. Gross E, Pushkin A, Abuladze N, Fedotoff O, Kurtz I. Regulation of the sodium bicarbonate cotransporter kNBC1 function: role of Asp(986), Asp(988) and kNBC1-carbonic anhydrase II binding. J Physiol. 2002;544:679-85 pubmed
    The HCO(3)(-) : Na(+) cotransport stoichiometry of the electrogenic sodium bicarbonate cotransporter kNBC1 determines the reversal potential (E(rev)) and thus the net direction of transport of these ions through the cotransporter...
  81. Espiritu D, Yang V, Bernardo A, Arruda J. Regulation of renal Na+/HCO3- cotransporter stimulation by CO2: role of phosphorylation, exocytosis and protein synthesis. J Membr Biol. 2004;199:39-49 pubmed
    The sodium bicarbonate cotransporter (NBC1) mediates bicarbonate reabsorption in the renal proximal tubule. NBC1 activity is stimulated by 10% CO2, however, the mechanism is poorly understood...
  82. Zhu Q, Azimov R, Kao L, Newman D, Liu W, Abuladze N, et al. NBCe1-A Transmembrane Segment 1 Lines the Ion Translocation Pathway. J Biol Chem. 2009;284:8918-29 pubmed publisher
    ..Our findings are suggestive of a delta(-) helical dipole at the C-terminal end of TM1 involving Thr-442 that plays a critical role in the function of the cotransporter. ..
  83. Zhu Q, Kao L, Azimov R, Newman D, Liu W, Pushkin A, et al. Topological location and structural importance of the NBCe1-A residues mutated in proximal renal tubular acidosis. J Biol Chem. 2010;285:13416-26 pubmed publisher
    ..Our findings demonstrate that the pRTA residues in NBCe1-A are buried in the protein complex/lipid bilayer where they perform important structural roles. ..
  84. Yang D, Li Q, So I, Huang C, Ando H, Mizutani A, et al. IRBIT governs epithelial secretion in mice by antagonizing the WNK/SPAK kinase pathway. J Clin Invest. 2011;121:956-65 pubmed publisher
    ..They also have implications for WNK/SPAK kinase-regulated processes involved in systemic fluid homeostasis, hypertension, and cystic fibrosis. ..
  85. Tsumuraya T, Matsushita M. COPA and SLC4A4 are required for cellular entry of arginine-rich peptides. PLoS ONE. 2014;9:e86639 pubmed publisher
    ..In this screening, we identified the cell membrane gene SLC4A4 and the trafficking regulator gene COPA, which also plays an important role in early endosome maturation...
  86. Choi I, Romero M, Khandoudi N, Bril A, Boron W. Cloning and characterization of a human electrogenic Na+-HCO-3 cotransporter isoform (hhNBC). Am J Physiol. 1999;276:C576-84 pubmed
    ..We conclude that hhNBC is an electrogenic Na+-HCO-3 cotransporter and that hkNBC is also electrogenic. ..
  87. Li H, Collier J, Shawki A, Rudra J, Li E, Mackenzie B, et al. Sequence- or position-specific mutations in the carboxyl-terminal FL motif of the kidney sodium bicarbonate cotransporter (NBC1) disrupt its basolateral targeting and alpha-helical structure. J Membr Biol. 2009;228:111-24 pubmed publisher
    The sodium-bicarbonate cotransporter NBC1 is targeted exclusively at the basolateral membrane. Mutagenesis of a dihydrophobic FL motif (residues 1013-1014) in the C-terminal domain disrupts the targeting of NBC1...
  88. Zhu Q, Shao X, Kao L, Azimov R, Weinstein A, Newman D, et al. Missense mutation T485S alters NBCe1-A electrogenicity causing proximal renal tubular acidosis. Am J Physiol Cell Physiol. 2013;305:C392-405 pubmed publisher
    Mutations in SLC4A4, the gene encoding the electrogenic Na(+)-HCO3(-) cotransporter NBCe1, cause severe proximal renal tubular acidosis (pRTA), growth retardation, decreased IQ, and eye and teeth abnormalities...
  89. Adams M, Kerlavage A, Fields C, Venter J. 3,400 new expressed sequence tags identify diversity of transcripts in human brain. Nat Genet. 1993;4:256-67 pubmed
    ..About half of the ESTs predicted to contain a protein-coding region have no matches in the public peptide databases and may represent new gene families. ..
  90. Toye A, Parker M, Daly C, Lu J, Virkki L, Pelletier M, et al. The human NBCe1-A mutant R881C, associated with proximal renal tubular acidosis, retains function but is mistargeted in polarized renal epithelia. Am J Physiol Cell Physiol. 2006;291:C788-801 pubmed
    The human electrogenic renal Na-HCO(3) cotransporter (NBCe1-A; SLC4A4) is localized to the basolateral membrane of proximal tubule cells...
  91. Zhu Q, Kao L, Azimov R, Abuladze N, Newman D, Pushkin A, et al. Structural and functional characterization of the C-terminal transmembrane region of NBCe1-A. J Biol Chem. 2010;285:37178-87 pubmed publisher
    ..Our findings suggest that the C-terminal transmembrane region of NBCe1-A is tightly folded with unique structural and functional features that differ from AE1. ..
  92. Yang H, Liang Y, Chen J, Chiang K, Chung C, Ho H, et al. Identification of IGF1, SLC4A4, WWOX, and SFMBT1 as hypertension susceptibility genes in Han Chinese with a genome-wide gene-based association study. PLoS ONE. 2012;7:e32907 pubmed publisher
    ..SLC4A4, which encodes the electrogenic sodium bicarbonate cotransporter 1, is associated with decreased body weight/size and abnormal ion homeostasis in mice...