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{{Short description|Protein-coding gene in the species Homo sapiens}} |
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{{Infobox_gene}} |
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'''Electrogenic sodium bicarbonate cotransporter 1 |
'''Electrogenic sodium bicarbonate cotransporter 1''', '''sodium bicarbonate cotransporter''' is a [[membrane transport protein]] that in humans is encoded by the ''SLC4A4'' [[gene]].<ref name="pmid9235899">{{cite journal | vauthors = Burnham CE, Amlal H, Wang Z, Shull GE, Soleimani M | title = Cloning and functional expression of a human kidney Na+:HCO3- cotransporter | journal = J Biol Chem | volume = 272 | issue = 31 | pages = 19111–4 |date=Aug 1997 | pmid = 9235899 | doi =10.1074/jbc.272.31.19111 | doi-access = free }}</ref><ref name="pmid9651366">{{cite journal | vauthors = Abuladze N, Lee I, Newman D, Hwang J, Boorer K, Pushkin A, Kurtz I | title = Molecular cloning, chromosomal localization, tissue distribution, and functional expression of the human pancreatic sodium bicarbonate cotransporter | journal = J Biol Chem | volume = 273 | issue = 28 | pages = 17689–95 |date=Aug 1998 | pmid = 9651366 | doi =10.1074/jbc.273.28.17689 | doi-access = free }}</ref><ref name="entrez"/> |
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== Function == |
== Function == |
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Sodium bicarbonate [[cotransporter]]s (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 [[ |
Sodium bicarbonate [[cotransporter]]s (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 [[co-transport]] 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]<ref name="entrez">{{cite web | title = Entrez Gene: SLC4A4 solute carrier family 4, sodium bicarbonate cotransporter, member 4| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8671}}</ref> |
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== Clinical significance == |
== Clinical significance == |
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In brain, |
In the brain, the sodium bicarbonate transporter is predominantly expressed by [[astrocyte]]s.<ref>{{Cite journal|last1=Theparambil|first1=Shefeeq M.|last2=Hosford|first2=Patrick S.|last3=Ruminot|first3=Iván|last4=Kopach|first4=Olga|last5=Reynolds|first5=James R.|last6=Sandoval|first6=Pamela Y.|last7=Rusakov|first7=Dmitri A.|last8=Barros|first8=L. Felipe|last9=Gourine|first9=Alexander V.|date=2020-10-08|title=Astrocytes regulate brain extracellular pH via a neuronal activity-dependent bicarbonate shuttle|journal=Nature Communications|language=en|volume=11|issue=1|pages=5073|doi=10.1038/s41467-020-18756-3|pmid=33033238|pmc=7545092|bibcode=2020NatCo..11.5073T|issn=2041-1723|doi-access=free}}</ref> They may participate in regulation of brain [[extracellular space]] [[pH]].<ref>{{Cite journal|last1=Theparambil|first1=Shefeeq M.|last2=Hosford|first2=Patrick S.|last3=Ruminot|first3=Iván|last4=Kopach|first4=Olga|last5=Reynolds|first5=James R.|last6=Sandoval|first6=Pamela Y.|last7=Rusakov|first7=Dmitri A.|last8=Barros|first8=L. Felipe|last9=Gourine|first9=Alexander V.|date=2020-10-08|title=Astrocytes regulate brain extracellular pH via a neuronal activity-dependent bicarbonate shuttle|journal=Nature Communications|language=en|volume=11|issue=1|pages=5073|doi=10.1038/s41467-020-18756-3|pmid=33033238|pmc=7545092|bibcode=2020NatCo..11.5073T|issn=2041-1723|doi-access=free}}</ref> Some mutations in the gene have been associated with [[familial hemiplegic migraine]].<ref name="pmid20798035">{{cite journal | vauthors = 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 | title = Defective membrane expression of the Na(+)-HCO(3)(-) cotransporter NBCe1 is associated with familial migraine | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 107 | issue = 36 | pages = 15963–8 |date=September 2010 | pmid = 20798035 | pmc = 2936614 | doi = 10.1073/pnas.1008705107 | doi-access = free }}</ref> Other mutations disrupt kidney bicarbonate transport and cause [[proximal renal tubular acidosis]].<ref name="pmid20197274">{{cite journal | vauthors = Zhu Q, Kao L, Azimov R, Newman D, Liu W, Pushkin A, Abuladze N, Kurtz I | title = Topological location and structural importance of the NBCe1-A residues mutated in proximal renal tubular acidosis | journal = J. Biol. Chem. | volume = 285 | issue = 18 | pages = 13416–26 |date=April 2010 | pmid = 20197274 | pmc = 2859501 | doi = 10.1074/jbc.M109.093286 | doi-access = free }}</ref> |
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==[[Splice variant]]s== |
==[[Splice variant]]s== |
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*{{cite journal | vauthors=Romero MF, Boron WF |title=Electrogenic Na+/HCO3- cotransporters: cloning and physiology. |journal=Annu. Rev. Physiol. |volume=61 |pages= 699–723 |year= 1999 |pmid= 10099707 |doi= 10.1146/annurev.physiol.61.1.699 }} |
*{{cite journal | vauthors=Romero MF, Boron WF |title=Electrogenic Na+/HCO3- cotransporters: cloning and physiology. |journal=Annu. Rev. Physiol. |volume=61 |pages= 699–723 |year= 1999 |pmid= 10099707 |doi= 10.1146/annurev.physiol.61.1.699 }} |
||
*{{cite journal | vauthors=Soleimani M, Burnham CE |title=Physiologic and molecular aspects of the Na+:HCO3- cotransporter in health and disease processes. |journal=Kidney Int. |volume=57 |issue= 2 |pages= 371–84 |year= 2000 |pmid= 10652014 |doi= 10.1046/j.1523-1755.2000.00857.x |doi-access= free }} |
*{{cite journal | vauthors=Soleimani M, Burnham CE |title=Physiologic and molecular aspects of the Na+:HCO3- cotransporter in health and disease processes. |journal=Kidney Int. |volume=57 |issue= 2 |pages= 371–84 |year= 2000 |pmid= 10652014 |doi= 10.1046/j.1523-1755.2000.00857.x |doi-access= free }} |
||
*{{cite journal |vauthors=Choi I, Romero MF, Khandoudi N, etal |title=Cloning and characterization of a human electrogenic Na+-HCO-3 cotransporter isoform (hhNBC). |journal=Am. J. Physiol. |volume=276 |issue= 3 Pt 1 |pages= C576–84 |year= 1999 |pmid= 10069984 |doi= 10.1152/ajpcell.1999.276.3.C576}} |
*{{cite journal |vauthors=Choi I, Romero MF, Khandoudi N, etal |title=Cloning and characterization of a human electrogenic Na+-HCO-3 cotransporter isoform (hhNBC). |journal=Am. J. Physiol. |volume=276 |issue= 3 Pt 1 |pages= C576–84 |year= 1999 |pmid= 10069984 |doi= 10.1152/ajpcell.1999.276.3.C576|s2cid=23345395 }} |
||
*{{cite journal |vauthors=Igarashi T, Inatomi J, Sekine T, etal |title=Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities. |journal=Nat. Genet. |volume=23 |issue= 3 |pages= 264–6 |year= 1999 |pmid= 10545938 |doi= 10.1038/15440 |s2cid=547845 }} |
*{{cite journal |vauthors=Igarashi T, Inatomi J, Sekine T, etal |title=Mutations in SLC4A4 cause permanent isolated proximal renal tubular acidosis with ocular abnormalities. |journal=Nat. Genet. |volume=23 |issue= 3 |pages= 264–6 |year= 1999 |pmid= 10545938 |doi= 10.1038/15440 |s2cid=547845 }} |
||
*{{cite journal |vauthors=Pushkin A, Yip KP, Clark I, etal |title=NBC3 expression in rabbit collecting duct: colocalization with vacuolar H+-ATPase. |journal=Am. J. Physiol. |volume=277 |issue= 6 Pt 2 |pages= F974–81 |year= 2000 |pmid= 10600945 |doi= 10.1152/ajprenal.1999.277.6.F974}} |
*{{cite journal |vauthors=Pushkin A, Yip KP, Clark I, etal |title=NBC3 expression in rabbit collecting duct: colocalization with vacuolar H+-ATPase. |journal=Am. J. Physiol. |volume=277 |issue= 6 Pt 2 |pages= F974–81 |year= 2000 |pmid= 10600945 |doi= 10.1152/ajprenal.1999.277.6.F974|s2cid=4457223 }} |
||
*{{cite journal |vauthors=Park K, Hurley PT, Roussa E, etal |title=Expression of a sodium bicarbonate cotransporter in human parotid salivary glands. |journal=Arch. Oral Biol. |volume=47 |issue= 1 |pages= 1–9 |year= 2002 |pmid= 11743927 |doi=10.1016/S0003-9969(01)00098-X }} |
*{{cite journal |vauthors=Park K, Hurley PT, Roussa E, etal |title=Expression of a sodium bicarbonate cotransporter in human parotid salivary glands. |journal=Arch. Oral Biol. |volume=47 |issue= 1 |pages= 1–9 |year= 2002 |pmid= 11743927 |doi=10.1016/S0003-9969(01)00098-X }} |
||
*{{cite journal |vauthors=Gross E, Hawkins K, Pushkin A, etal |title=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 |journal=J. Physiol. |volume=537 |issue= Pt 3 |pages= 659–65 |year= 2002 |pmid= 11744745 |doi=10.1113/jphysiol.2001.012956 | pmc=2278987 }} |
*{{cite journal |vauthors=Gross E, Hawkins K, Pushkin A, etal |title=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 |journal=J. Physiol. |volume=537 |issue= Pt 3 |pages= 659–65 |year= 2002 |pmid= 11744745 |doi=10.1113/jphysiol.2001.012956 | pmc=2278987 }} |
||
*{{cite journal |vauthors=Gross E, Pushkin A, Abuladze N, etal |title=Regulation of the sodium bicarbonate cotransporter kNBC1 function: role of Asp986, Asp988 and kNBC1-carbonic anhydrase II binding |journal=J. Physiol. |volume=544 |issue= Pt 3 |pages= 679–85 |year= 2003 |pmid= 12411514 |doi=10.1113/jphysiol.2002.029777 | pmc=2290621 }} |
*{{cite journal |vauthors=Gross E, Pushkin A, Abuladze N, etal |title=Regulation of the sodium bicarbonate cotransporter kNBC1 function: role of Asp986, Asp988 and kNBC1-carbonic anhydrase II binding |journal=J. Physiol. |volume=544 |issue= Pt 3 |pages= 679–85 |year= 2003 |pmid= 12411514 |doi=10.1113/jphysiol.2002.029777 | pmc=2290621 }} |
||
*{{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |doi-access=free }} |
*{{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |bibcode=2002PNAS...9916899M |doi-access=free }} |
||
*{{cite journal |vauthors=Tatishchev S, Abuladze N, Pushkin A, etal |title=Identification of membrane topography of the electrogenic sodium bicarbonate cotransporter pNBC1 by in vitro transcription/translation |journal=Biochemistry |volume=42 |issue= 3 |pages= 755–65 |year= 2003 |pmid= 12534288 |doi= 10.1021/bi026826q }} |
*{{cite journal |vauthors=Tatishchev S, Abuladze N, Pushkin A, etal |title=Identification of membrane topography of the electrogenic sodium bicarbonate cotransporter pNBC1 by in vitro transcription/translation |journal=Biochemistry |volume=42 |issue= 3 |pages= 755–65 |year= 2003 |pmid= 12534288 |doi= 10.1021/bi026826q }} |
||
*{{cite journal |vauthors=Gross E, Fedotoff O, Pushkin A, etal |title=Phosphorylation-induced modulation of pNBC1 function: distinct roles for the amino- and carboxy-termini |journal=J. Physiol. |volume=549 |issue= Pt 3 |pages= 673–82 |year= 2004 |pmid= 12730338 |doi= 10.1113/jphysiol.2003.042226 | pmc=2342979 }} |
*{{cite journal |vauthors=Gross E, Fedotoff O, Pushkin A, etal |title=Phosphorylation-induced modulation of pNBC1 function: distinct roles for the amino- and carboxy-termini |journal=J. Physiol. |volume=549 |issue= Pt 3 |pages= 673–82 |year= 2004 |pmid= 12730338 |doi= 10.1113/jphysiol.2003.042226 | pmc=2342979 }} |
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Latest revision as of 20:01, 23 December 2023
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| Aliases | SLC4A4, HNBC1, KNBC, NBC1, NBC2, NBCe1-A, SLC4A5, hhNMC, pNBC, kNBC1, solute carrier family 4 member 4 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 603345 MGI: 1927555 HomoloGene: 55776 GeneCards: SLC4A4 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Electrogenic sodium bicarbonate cotransporter 1, sodium bicarbonate cotransporter is a membrane transport protein that in humans is encoded by the SLC4A4 gene.[5][6][7]
Function[edit]
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 co-transport 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[edit]
In the brain, the sodium bicarbonate transporter is predominantly expressed by astrocytes.[8] They may participate in regulation of brain extracellular space pH.[9] Some mutations in the gene have been associated with familial hemiplegic migraine.[10] Other mutations disrupt kidney bicarbonate transport and cause proximal renal tubular acidosis.[11]
Splice variants[edit]
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[edit]
The renal SLC4A4 gene product NBCe1-A is specifically expressed in the basolateral membranes of proximal tubule epithelia.
See also[edit]
References[edit]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000080493 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000060961 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ 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.
- ^ 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.
- ^ a b "Entrez Gene: SLC4A4 solute carrier family 4, sodium bicarbonate cotransporter, member 4".
- ^ Theparambil SM, Hosford PS, Ruminot I, Kopach O, Reynolds JR, Sandoval PY, Rusakov DA, Barros LF, Gourine AV (2020-10-08). "Astrocytes regulate brain extracellular pH via a neuronal activity-dependent bicarbonate shuttle". Nature Communications. 11 (1): 5073. Bibcode:2020NatCo..11.5073T. doi:10.1038/s41467-020-18756-3. ISSN 2041-1723. PMC 7545092. PMID 33033238.
- ^ Theparambil SM, Hosford PS, Ruminot I, Kopach O, Reynolds JR, Sandoval PY, Rusakov DA, Barros LF, Gourine AV (2020-10-08). "Astrocytes regulate brain extracellular pH via a neuronal activity-dependent bicarbonate shuttle". Nature Communications. 11 (1): 5073. Bibcode:2020NatCo..11.5073T. doi:10.1038/s41467-020-18756-3. ISSN 2041-1723. PMC 7545092. PMID 33033238.
- ^ 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.
- ^ 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[edit]
- 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. doi:10.1152/ajpcell.1999.276.3.C576. PMID 10069984. S2CID 23345395.
- 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. S2CID 547845.
- 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. doi:10.1152/ajprenal.1999.277.6.F974. PMID 10600945. S2CID 4457223.
- 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. Bibcode:2002PNAS...9916899M. 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. PMC 4106483. 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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