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SLC4A4: Wikis


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Solute carrier family 4, sodium bicarbonate cotransporter, member 4
Symbols SLC4A4; DKFZp781H1314; HNBC1; KNBC; NBC1; NBC2; SLC4A5; hhNMC; pNBC
External IDs OMIM603345 MGI1927555 HomoloGene55776 GeneCards: SLC4A4 Gene
RNA expression pattern
PBB GE SLC4A4 203908 at tn.png
PBB GE SLC4A4 210738 s at tn.png
PBB GE SLC4A4 210739 x at tn.png
More reference expression data
Species Human Mouse
Entrez 8671 54403
Ensembl ENSG00000080493 ENSMUSG00000060961
UniProt Q9Y6R1 O88343
RefSeq (mRNA) NM_003759 NM_018760
RefSeq (protein) NP_003750 NP_061230
Location (UCSC) Chr 4:
72.27 - 72.66 Mb
Chr 5:
90.01 - 90.31 Mb
PubMed search [1] [2]

Electrogenic sodium bicarbonate cotransporter 1 is a protein that in humans is encoded by the SLC4A4 gene.[1][2][3]

Sodium bicarbonate cotransporters (NBCs) mediate the coupled movement of sodium and bicarbonate ions across the plasma membrane of many cells. This is an electrogenic process with an apparent stoichiometry of 3 bicarbonate ions per sodium ion. Sodium bicarbonate cotransport is involved in bicarbonate secretion/absorption and intracellular pH regulation. Romero and Boron (1999) reviewed NBCs. Soleimani and Burnham (2000) reviewed NBCs and their regulation in physiologic and pathophysiologic states.[supplied by OMIM][3]


See also

Splice Variants

NBCe1-A aka kNBC1 (mainly expressed in the kidney)

NBCe1-B aka pNBC1 (expressed in the pancreas and elsewhere)

NBCe1-C (expressed in the brain)


The renal SLC4A4 gene product NBCe1-A is specifically expressed in the basolateral membranes of proximal tubule epithelia


  1. ^ Burnham CE, Amlal H, Wang Z, Shull GE, Soleimani M (Aug 1997). "Cloning and functional expression of a human kidney Na+:HCO3- cotransporter". J Biol Chem 272 (31): 19111-4. PMID 9235899.  
  2. ^ Abuladze N, Lee I, Newman D, Hwang J, Boorer K, Pushkin A, Kurtz I (Aug 1998). "Molecular cloning, chromosomal localization, tissue distribution, and functional expression of the human pancreatic sodium bicarbonate cotransporter". J Biol Chem 273 (28): 17689-95. PMID 9651366.  
  3. ^ a b "Entrez Gene: SLC4A4 solute carrier family 4, sodium bicarbonate cotransporter, member 4".  

Further reading

  • Romero MF, Boron WF (1999). "Electrogenic Na+/HCO3- cotransporters: cloning and physiology.". Annu. Rev. Physiol. 61: 699–723. doi:10.1146/annurev.physiol.61.1.699. PMID 10099707.  
  • Soleimani M, Burnham CE (2000). "Physiologic and molecular aspects of the Na+:HCO3- cotransporter in health and disease processes.". Kidney Int. 57 (2): 371–84. doi:10.1046/j.1523-1755.2000.00857.x. PMID 10652014.  
  • Choi I, Romero MF, Khandoudi N, et al. (1999). "Cloning and characterization of a human electrogenic Na+-HCO-3 cotransporter isoform (hhNBC).". Am. J. Physiol. 276 (3 Pt 1): C576–84. PMID 10069984.  
  • Igarashi T, Inatomi J, Sekine T, et al. (1999). "Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities.". Nat. Genet. 23 (3): 264–6. doi:10.1038/15440. PMID 10545938.  
  • Pushkin A, Yip KP, Clark I, et al. (2000). "NBC3 expression in rabbit collecting duct: colocalization with vacuolar H+-ATPase.". Am. J. Physiol. 277 (6 Pt 2): F974–81. PMID 10600945.  
  • Park K, Hurley PT, Roussa E, et al. (2002). "Expression of a sodium bicarbonate cotransporter in human parotid salivary glands.". Arch. Oral Biol. 47 (1): 1–9. doi:10.1016/S0003-9969(01)00098-X. PMID 11743927.  
  • Gross E, Hawkins K, Pushkin A, et al. (2002). "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. (Lond.) 537 (Pt 3): 659–65. doi:10.1113/jphysiol.2001.012956. PMID 11744745.  
  • Gross E, Pushkin A, Abuladze N, et al. (2003). "Regulation of the sodium bicarbonate cotransporter kNBC1 function: role of Asp(986), Asp(988) and kNBC1-carbonic anhydrase II binding.". J. Physiol. (Lond.) 544 (Pt 3): 679–85. doi:10.1113/jphysiol.2002.029777. PMID 12411514.  
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.  
  • Tatishchev S, Abuladze N, Pushkin A, et al. (2003). "Identification of membrane topography of the electrogenic sodium bicarbonate cotransporter pNBC1 by in vitro transcription/translation.". Biochemistry 42 (3): 755–65. doi:10.1021/bi026826q. PMID 12534288.  
  • Gross E, Fedotoff O, Pushkin A, et al. (2004). "Phosphorylation-induced modulation of pNBC1 function: distinct roles for the amino- and carboxy-termini.". J. Physiol. (Lond.) 549 (Pt 3): 673–82. doi:10.1113/jphysiol.2003.042226. PMID 12730338.  
  • Sun XC, Bonanno JA (2003). "Identification and cloning of the Na/HCO(3-) cotransporter (NBC) in human corneal endothelium.". Exp. Eye Res. 77 (3): 287–95. doi:10.1016/S0014-4835(03)00150-7. PMID 12907161.  
  • Yamada H, Yamazaki S, Moriyama N, et al. (2003). "Localization of NBC-1 variants in human kidney and renal cell carcinoma.". Biochem. Biophys. Res. Commun. 310 (4): 1213–8. doi:10.1016/j.bbrc.2003.09.147. PMID 14559244.  
  • Alvarez BV, Loiselle FB, Supuran CT, et al. (2003). "Direct extracellular interaction between carbonic anhydrase IV and the human NBC1 sodium/bicarbonate co-transporter.". Biochemistry 42 (42): 12321–9. doi:10.1021/bi0353124. PMID 14567693.  
  • Becker HM, Deitmer JW (2004). "Voltage dependence of H+ buffering mediated by sodium bicarbonate cotransport expressed in Xenopus oocytes.". J. Biol. Chem. 279 (27): 28057–62. doi:10.1074/jbc.M402401200. PMID 15123668.  
  • Pushkin A, Abuladze N, Gross E, et al. (2005). "Molecular mechanism of kNBC1-carbonic anhydrase II interaction in proximal tubule cells.". J. Physiol. (Lond.) 559 (Pt 1): 55–65. doi:10.1113/jphysiol.2004.065110. PMID 15218065.  

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



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