Electrogenic sodium bicarbonate cotransporter 1

Last updated
SLC4A4
Identifiers
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
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001098484
NM_001134742
NM_003759

RefSeq (protein)

NP_001091954
NP_001128214
NP_003750

Location (UCSC) Chr 4: 71.19 – 71.57 Mb Chr 5: 89.03 – 89.39 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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]

Contents

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 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

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

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

Related Research Articles

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<span class="mw-page-title-main">Cotransporter</span> Type of membrane transport proteins

Cotransporters are a subcategory of membrane transport proteins (transporters) that couple the favorable movement of one molecule with its concentration gradient and unfavorable movement of another molecule against its concentration gradient. They enable coupled or cotransport and include antiporters and symporters. In general, cotransporters consist of two out of the three classes of integral membrane proteins known as transporters that move molecules and ions across biomembranes. Uniporters are also transporters but move only one type of molecule down its concentration gradient and are not classified as cotransporters.

The Na–K–Cl cotransporter (NKCC) is a transport protein that aids in the secondary active transport of sodium, potassium, and chloride into cells. In humans there are two isoforms of this membrane transport protein, NKCC1 and NKCC2, encoded by two different genes. Two isoforms of the NKCC1/Slc12a2 gene result from keeping or skipping exon 21 in the final gene product.

<span class="mw-page-title-main">Sodium-chloride symporter</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Sodium/glucose cotransporter 2</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">Sodium-hydrogen antiporter 3 regulator 1</span> Protein-coding gene in the species Homo sapiens

Sodium-hydrogen antiporter 3 regulator 1 is a regulator of Sodium-hydrogen antiporter 3. It is encoded by the gene SLC9A3R1. It is also known as ERM Binding Protein 50 (EBP50) or Na+/H+ Exchanger Regulatory Factor (NHERF1). It is believed to interact via long-range allostery, involving significant protein dynamics.

<span class="mw-page-title-main">Sodium–hydrogen antiporter 3</span> Protein-coding gene in the species Homo sapiens

Sodium–hydrogen antiporter 3 also known as sodium–hydrogen exchanger 3 (NHE3) or solute carrier family 9 member 3 (SLC9A3) is a protein that in humans is encoded by the SLC9A3 gene.

<span class="mw-page-title-main">Sodium bicarbonate cotransporter 3</span> Protein-coding gene in the species Homo sapiens

Sodium bicarbonate cotransporter 3 is a protein which in humans is encoded by the SLC4A7 gene.

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<span class="mw-page-title-main">Anion exchange protein 3</span> Protein-coding gene in the species Homo sapiens

Anion exchange protein 3 is a membrane transport protein that in humans is encoded by the SLC4A3 gene. AE3 is functionally similar to the Band 3 Cl/HCO3 exchange protein but it is expressed primarily in brain neurons and in the heart. Like AE2 its activity is sensitive to pH. AE3 mutations have been linked to seizures.

<span class="mw-page-title-main">Sodium–hydrogen antiporter 2</span> Protein-coding gene in the species Homo sapiens

Sodium–hydrogen exchanger 2 is a protein that in humans is encoded by the SLC9A2 gene.

<span class="mw-page-title-main">SLC26A6</span> Protein-coding gene in the species Homo sapiens

Solute carrier family 26 member 6 is a protein that in humans is encoded by the SLC26A6 gene. It is an anion-exchanger expressed in the apical membrane of the kidney proximal tubule, the apical membranes of the duct cells in the pancreas, and the villi of the duodenum.

<span class="mw-page-title-main">Electroneutral sodium bicarbonate exchanger 1</span> Protein-coding gene in the species Homo sapiens

Electroneutral sodium bicarbonate exchanger 1 is a protein that in humans is encoded by the SLC4A8 gene.

<span class="mw-page-title-main">Sodium-dependent phosphate transport protein 1</span> Protein-coding gene in the species Homo sapiens

Sodium-dependent phosphate transport protein 1 is a protein that in humans is encoded by the SLC17A1 gene.

<span class="mw-page-title-main">SLC13A3</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">SLC13A2</span> Protein-coding gene in the species Homo sapiens

Solute carrier family 13 member 2 is a protein that is encoded in humans by the SLC13A2 gene.

<span class="mw-page-title-main">Electrogenic sodium bicarbonate cotransporter 4</span> Protein-coding gene in the species Homo sapiens

Electrogenic sodium bicarbonate cotransporter 4 is a protein that in humans is encoded by the SLC4A5 gene.

Walter F. Boron is an American scientist and the 72nd president of the American Physiological Society. He was Secretary-General of the International Union of Physiological Sciences. Additionally, Boron is co-editor, along with Emile L. Boulpaep, of the textbook Medical Physiology and Concise Medical Physiology. He is a former editor-in-chief of two leading physiology journals, Physiological Reviews and Physiology.

<span class="mw-page-title-main">Organic anion transporter 1</span> Protein-coding gene in the species Homo sapiens

The organic anion transporter 1 (OAT1) also known as solute carrier family 22 member 6 (SLC22A6) is a protein that in humans is encoded by the SLC22A6 gene. It is a member of the organic anion transporter (OAT) family of proteins. OAT1 is a transmembrane protein that is expressed in the brain, the placenta, the eyes, smooth muscles, and the basolateral membrane of proximal tubular cells of the kidneys. It plays a central role in renal organic anion transport. Along with OAT3, OAT1 mediates the uptake of a wide range of relatively small and hydrophilic organic anions from plasma into the cytoplasm of the proximal tubular cells of the kidneys. From there, these substrates are transported into the lumen of the nephrons of the kidneys for excretion. OAT1 homologs have been identified in rats, mice, rabbits, pigs, flounders, and nematodes.

The anion exchanger family is a member of the large APC superfamily of secondary carriers. Members of the AE family are generally responsible for the transport of anions across cellular barriers, although their functions may vary. All of them exchange bicarbonate. Characterized protein members of the AE family are found in plants, animals, insects and yeast. Uncharacterized AE homologues may be present in bacteria. Animal AE proteins consist of homodimeric complexes of integral membrane proteins that vary in size from about 900 amino acyl residues to about 1250 residues. Their N-terminal hydrophilic domains may interact with cytoskeletal proteins and therefore play a cell structural role. Some of the currently characterized members of the AE family can be found in the Transporter Classification Database.

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:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  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. 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.
  9. 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.
  10. 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.
  11. 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

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