Biology:SLC4A4
 Generic protein structure example |
Electrogenic sodium bicarbonate cotransporter 1 is a membrane transport protein that in humans is encoded by the SLC4A4 gene.[1][2][3]
Function
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]
Clinical significance
NBCe1 may participate in regulation of brain extracellular space pH. Some mutations in NBCe1 have been associated with Familial hemiplegic migraine.[4] Other NBCe1 mutations disrupt kidney bicarbonate transport and cause proximal renal tubular acidosis.[5]
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)
Distribution
The renal SLC4A4 gene product NBCe1-A is specifically expressed in the basolateral membranes of proximal tubule epithelia.
See also
References
- ↑ "Cloning and functional expression of a human kidney Na+:HCO3- cotransporter". J Biol Chem 272 (31): 19111–4. Aug 1997. doi:10.1074/jbc.272.31.19111. PMID 9235899.
- ↑ "Molecular cloning, chromosomal localization, tissue distribution, and functional expression of the human pancreatic sodium bicarbonate cotransporter". J Biol Chem 273 (28): 17689–95. Aug 1998. doi:10.1074/jbc.273.28.17689. PMID 9651366.
- ↑ 3.0 3.1 "Entrez Gene: SLC4A4 solute carrier family 4, sodium bicarbonate cotransporter, member 4". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8671.
- ↑ "Defective membrane expression of the Na(+)-HCO(3)(-) cotransporter NBCe1 is associated with familial migraine". Proc. Natl. Acad. Sci. U.S.A. 107 (36): 15963–8. September 2010. doi:10.1073/pnas.1008705107. PMID 20798035.
- ↑ "Topological location and structural importance of the NBCe1-A residues mutated in proximal renal tubular acidosis". J. Biol. Chem. 285 (18): 13416–26. April 2010. doi:10.1074/jbc.M109.093286. PMID 20197274.
Further reading
- "Electrogenic Na+/HCO3- cotransporters: cloning and physiology.". Annu. Rev. Physiol. 61: 699–723. 1999. doi:10.1146/annurev.physiol.61.1.699. PMID 10099707.
- "Physiologic and molecular aspects of the Na+:HCO3- cotransporter in health and disease processes.". Kidney Int. 57 (2): 371–84. 2000. doi:10.1046/j.1523-1755.2000.00857.x. PMID 10652014.
- "Cloning and characterization of a human electrogenic Na+-HCO-3 cotransporter isoform (hhNBC).". Am. J. Physiol. 276 (3 Pt 1): C576–84. 1999. PMID 10069984.
- "Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities.". Nat. Genet. 23 (3): 264–6. 1999. doi:10.1038/15440. PMID 10545938.
- "NBC3 expression in rabbit collecting duct: colocalization with vacuolar H+-ATPase.". Am. J. Physiol. 277 (6 Pt 2): F974–81. 2000. PMID 10600945.
- "Expression of a sodium bicarbonate cotransporter in human parotid salivary glands.". Arch. Oral Biol. 47 (1): 1–9. 2002. doi:10.1016/S0003-9969(01)00098-X. PMID 11743927.
- "Phosphorylation of Ser982 in the sodium bicarbonate cotransporter kNBC1 shifts the HCO3−: Na+ stoichiometry from 3:1 to 2:1 in murine proximal tubule cells". J. Physiol. 537 (Pt 3): 659–65. 2002. doi:10.1113/jphysiol.2001.012956. PMID 11744745.
- "Regulation of the sodium bicarbonate cotransporter kNBC1 function: role of Asp986, Asp988 and kNBC1-carbonic anhydrase II binding". J. Physiol. 544 (Pt 3): 679–85. 2003. doi:10.1113/jphysiol.2002.029777. PMID 12411514.
- "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. 2003. doi:10.1073/pnas.242603899. PMID 12477932.
- "Identification of membrane topography of the electrogenic sodium bicarbonate cotransporter pNBC1 by in vitro transcription/translation". Biochemistry 42 (3): 755–65. 2003. doi:10.1021/bi026826q. PMID 12534288.
- "Phosphorylation-induced modulation of pNBC1 function: distinct roles for the amino- and carboxy-termini". J. Physiol. 549 (Pt 3): 673–82. 2004. doi:10.1113/jphysiol.2003.042226. PMID 12730338.
- "Identification and cloning of the Na/HCO(3-) cotransporter (NBC) in human corneal endothelium". Exp. Eye Res. 77 (3): 287–95. 2003. doi:10.1016/S0014-4835(03)00150-7. PMID 12907161.
- "Localization of NBC-1 variants in human kidney and renal cell carcinoma". Biochem. Biophys. Res. Commun. 310 (4): 1213–8. 2003. doi:10.1016/j.bbrc.2003.09.147. PMID 14559244.
- "Direct extracellular interaction between carbonic anhydrase IV and the human NBC1 sodium/bicarbonate co-transporter". Biochemistry 42 (42): 12321–9. 2003. doi:10.1021/bi0353124. PMID 14567693.
- "Voltage dependence of H+ buffering mediated by sodium bicarbonate cotransport expressed in Xenopus oocytes". J. Biol. Chem. 279 (27): 28057–62. 2004. doi:10.1074/jbc.M402401200. PMID 15123668.
- "Molecular mechanism of kNBC1—carbonic anhydrase II interaction in proximal tubule cells". J. Physiol. 559 (Pt 1): 55–65. 2005. 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.
 |
