SLC4A4

SLC4A4
Identifiers
AliasesSLC4A4, HNBC1, KNBC, NBC1, NBC2, NBCe1-A, SLC4A5, hhNMC, pNBC, kNBC1, solute carrier family 4 member 4
External IDsMGI: 1927555 HomoloGene: 55776 GeneCards: SLC4A4
Gene location (Human)
Chr.Chromosome 4 (human)[1]
Band4q13.3Start71,186,757 bp[1]
End71,572,087 bp[1]
RNA expression pattern




More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

8671

54403

Ensembl

ENSG00000080493

ENSMUSG00000060961

UniProt

Q9Y6R1

O88343

RefSeq (mRNA)

NM_001098484
NM_001134742
NM_003759

RefSeq (protein)

NP_001091954
NP_001128214
NP_003750

Location (UCSC)Chr 4: 71.19 – 71.57 MbChr 5: 88.89 – 89.24 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Electrogenic sodium bicarbonate cotransporter 1 is a membrane transport protein that in humans is encoded by the SLC4A4 gene.[5][6][7]

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][7]

Clinical significance

NBCe1 may participate in regulation of brain extracellular space pH. Some mutations in NBCe1 have been associated with Familial hemiplegic migraine.[8] Other NBCe1 mutations disrupt kidney bicarbonate transport and cause proximal renal tubular acidosis.[9]

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

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000080493 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000060961 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:".
  4. ↑ "Mouse PubMed Reference:".
  5. ↑ 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. doi:10.1074/jbc.272.31.19111. PMID 9235899.
  6. ↑ 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. doi:10.1074/jbc.273.28.17689. PMID 9651366.
  7. 1 2 "Entrez Gene: SLC4A4 solute carrier family 4, sodium bicarbonate cotransporter, member 4".
  8. ↑ Suzuki M, Van Paesschen W, Stalmans I, Horita S, Yamada H, Bergmans BA, Legius E, Riant F, De Jonghe P, Li Y, Sekine T, Igarashi T, Fujimoto I, Mikoshiba K, Shimadzu M, Shiohara M, Braverman N, Al-Gazali L, Fujita T, Seki G (September 2010). "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. doi:10.1073/pnas.1008705107. PMC 2936614. PMID 20798035.
  9. ↑ Zhu Q, Kao L, Azimov R, Newman D, Liu W, Pushkin A, Abuladze N, Kurtz I (April 2010). "Topological location and structural importance of the NBCe1-A residues mutated in proximal renal tubular acidosis". J. Biol. Chem. 285 (18): 13416–26. doi:10.1074/jbc.M109.093286. PMC 2859501. PMID 20197274.

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 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. doi:10.1113/jphysiol.2001.012956. PMC 2278987. PMID 11744745.
  • Gross E, Pushkin A, Abuladze N, et al. (2003). "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. doi:10.1113/jphysiol.2002.029777. PMC 2290621. 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. PMC 139241. 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. 549 (Pt 3): 673–82. doi:10.1113/jphysiol.2003.042226. PMC 2342979. 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. 559 (Pt 1): 55–65. doi:10.1113/jphysiol.2004.065110. PMC 1665076. PMID 15218065.

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