Slc12a3

Summary

Gene Symbol: Slc12a3
Description: solute carrier family 12 member 3
Alias: NCC, TSC, solute carrier family 12 member 3, Na-Cl symporter, solute carrier family 12 (sodium/chloride transporter), member 3, solute carrier family 12 (sodium/chloride transporters), member 3, thiazide-sensitive Na-Cl cotransporter, thiazide-sensitive sodium-chloride cotransporter
Species: rat
Products:     Slc12a3

Top Publications

  1. Ruete M, Carrizo L, Bocanegra M, Valles P. Altered renal expression of Na(+) transporters and ROMK in protein-deprived rats. Nephron Physiol. 2009;111:p17-29 pubmed publisher
    ..The abundance of the aldosterone-regulated Na(+)-Cl(-) cotransporter (NCC) and epithelial Na(+) channel (ENaC) was higher in the LP group and was associated with higher plasma aldosterone ..
  2. Chee K, Vorontsova I, Lim J, Kistler J, Donaldson P. Expression of the sodium potassium chloride cotransporter (NKCC1) and sodium chloride cotransporter (NCC) and their effects on rat lens transparency. Mol Vis. 2010;16:800-12 pubmed
    To characterize the expression patterns of the Na+-K+-Cl(-) cotransporter (NKCC) 1 and NKCC2, and the Na+-Cl(-) cotransporter (NCC) in the rat lens and to determine if they play a role in regulating lens volume and transparency.
  3. Gamba G, Miyanoshita A, Lombardi M, Lytton J, Lee W, Hediger M, et al. Molecular cloning, primary structure, and characterization of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in kidney. J Biol Chem. 1994;269:17713-22 pubmed
    ..These proteins establish a new family of Na(+)-(K+)-Cl- cotransporters. ..
  4. Taniyama Y, Sato K, Sugawara A, Uruno A, Ikeda Y, Kudo M, et al. Renal tubule-specific transcription and chromosomal localization of rat thiazide-sensitive Na-Cl cotransporter gene. J Biol Chem. 2001;276:26260-8 pubmed
    The molecular mechanism underlying the renal expression localization of the thiazide-sensitive Na-Cl cotransporter (TSC) gene was studied. The TSC gene was localized to chromosome 19p12-14...
  5. Pacheco Alvarez D, Cristóbal P, Meade P, Moreno E, Vazquez N, Munoz E, et al. The Na+:Cl- cotransporter is activated and phosphorylated at the amino-terminal domain upon intracellular chloride depletion. J Biol Chem. 2006;281:28755-63 pubmed
    ..that has two major branches with inverse physiological functions and regulation: sodium-driven cotransporters (NCC and NKCC1/2) that mediate cellular Cl(-) influx are activated by phosphorylation, whereas potassium-driven ..
  6. Frindt G, Yang L, Uchida S, Weinstein A, Palmer L. Responses of distal nephron Na+ transporters to acute volume depletion and hyperkalemia. Am J Physiol Renal Physiol. 2017;313:F62-F73 pubmed publisher
    ..effects appeared as alterations in the expression of protein for the distal nephron Na+ transporters NCC and ENaC...
  7. Rosenbaek L, Kortenoeven M, Aroankins T, Fenton R. Phosphorylation decreases ubiquitylation of the thiazide-sensitive cotransporter NCC and subsequent clathrin-mediated endocytosis. J Biol Chem. 2014;289:13347-61 pubmed publisher
    The thiazide-sensitive sodium chloride cotransporter, NCC, is the major NaCl transport protein in the distal convoluted tubule (DCT)...
  8. Stuiver M, Lainez S, Will C, Terryn S, Gunzel D, Debaix H, et al. CNNM2, encoding a basolateral protein required for renal Mg2+ handling, is mutated in dominant hypomagnesemia. Am J Hum Genet. 2011;88:333-43 pubmed publisher
    ..The mutations found in CNNM2, its observed sensitivity to extracellular Mg(2+), and its basolateral localization signify a critical role for CNNM2 in epithelial Mg(2+) transport. ..
  9. Sandberg M, Maunsbach A, McDonough A. Redistribution of distal tubule Na+-Cl- cotransporter (NCC) in response to a high-salt diet. Am J Physiol Renal Physiol. 2006;291:F503-8 pubmed
    The distal convoluted tubule (DCT) apical Na(+)-Cl(-) cotransporter (NCC) is responsible for the reabsorption of 5-10% of filtered NaCl and is the target for thiazide diuretics...
  10. Tiwari S, Packer R, Hu X, Sugimura Y, Verbalis J, Ecelbarger C. Increased renal alpha-ENaC and NCC abundance and elevated blood pressure are independent of hyperaldosteronism in vasopressin escape. Am J Physiol Renal Physiol. 2006;291:F49-57 pubmed
    ..abundance of the alpha-subunit of the epithelial sodium channel (ENaC), the thiazide-sensitive Na-Cl cotransporter (NCC), and the 70-kDa band of gamma-ENaC (Song J, Hu X, Khan O, Tian Y, Verbalis JG, and Ecelbarger CA...

Detail Information

Publications38

  1. Ruete M, Carrizo L, Bocanegra M, Valles P. Altered renal expression of Na(+) transporters and ROMK in protein-deprived rats. Nephron Physiol. 2009;111:p17-29 pubmed publisher
    ..The abundance of the aldosterone-regulated Na(+)-Cl(-) cotransporter (NCC) and epithelial Na(+) channel (ENaC) was higher in the LP group and was associated with higher plasma aldosterone ..
  2. Chee K, Vorontsova I, Lim J, Kistler J, Donaldson P. Expression of the sodium potassium chloride cotransporter (NKCC1) and sodium chloride cotransporter (NCC) and their effects on rat lens transparency. Mol Vis. 2010;16:800-12 pubmed
    To characterize the expression patterns of the Na+-K+-Cl(-) cotransporter (NKCC) 1 and NKCC2, and the Na+-Cl(-) cotransporter (NCC) in the rat lens and to determine if they play a role in regulating lens volume and transparency.
  3. Gamba G, Miyanoshita A, Lombardi M, Lytton J, Lee W, Hediger M, et al. Molecular cloning, primary structure, and characterization of two members of the mammalian electroneutral sodium-(potassium)-chloride cotransporter family expressed in kidney. J Biol Chem. 1994;269:17713-22 pubmed
    ..These proteins establish a new family of Na(+)-(K+)-Cl- cotransporters. ..
  4. Taniyama Y, Sato K, Sugawara A, Uruno A, Ikeda Y, Kudo M, et al. Renal tubule-specific transcription and chromosomal localization of rat thiazide-sensitive Na-Cl cotransporter gene. J Biol Chem. 2001;276:26260-8 pubmed
    The molecular mechanism underlying the renal expression localization of the thiazide-sensitive Na-Cl cotransporter (TSC) gene was studied. The TSC gene was localized to chromosome 19p12-14...
  5. Pacheco Alvarez D, Cristóbal P, Meade P, Moreno E, Vazquez N, Munoz E, et al. The Na+:Cl- cotransporter is activated and phosphorylated at the amino-terminal domain upon intracellular chloride depletion. J Biol Chem. 2006;281:28755-63 pubmed
    ..that has two major branches with inverse physiological functions and regulation: sodium-driven cotransporters (NCC and NKCC1/2) that mediate cellular Cl(-) influx are activated by phosphorylation, whereas potassium-driven ..
  6. Frindt G, Yang L, Uchida S, Weinstein A, Palmer L. Responses of distal nephron Na+ transporters to acute volume depletion and hyperkalemia. Am J Physiol Renal Physiol. 2017;313:F62-F73 pubmed publisher
    ..effects appeared as alterations in the expression of protein for the distal nephron Na+ transporters NCC and ENaC...
  7. Rosenbaek L, Kortenoeven M, Aroankins T, Fenton R. Phosphorylation decreases ubiquitylation of the thiazide-sensitive cotransporter NCC and subsequent clathrin-mediated endocytosis. J Biol Chem. 2014;289:13347-61 pubmed publisher
    The thiazide-sensitive sodium chloride cotransporter, NCC, is the major NaCl transport protein in the distal convoluted tubule (DCT)...
  8. Stuiver M, Lainez S, Will C, Terryn S, Gunzel D, Debaix H, et al. CNNM2, encoding a basolateral protein required for renal Mg2+ handling, is mutated in dominant hypomagnesemia. Am J Hum Genet. 2011;88:333-43 pubmed publisher
    ..The mutations found in CNNM2, its observed sensitivity to extracellular Mg(2+), and its basolateral localization signify a critical role for CNNM2 in epithelial Mg(2+) transport. ..
  9. Sandberg M, Maunsbach A, McDonough A. Redistribution of distal tubule Na+-Cl- cotransporter (NCC) in response to a high-salt diet. Am J Physiol Renal Physiol. 2006;291:F503-8 pubmed
    The distal convoluted tubule (DCT) apical Na(+)-Cl(-) cotransporter (NCC) is responsible for the reabsorption of 5-10% of filtered NaCl and is the target for thiazide diuretics...
  10. Tiwari S, Packer R, Hu X, Sugimura Y, Verbalis J, Ecelbarger C. Increased renal alpha-ENaC and NCC abundance and elevated blood pressure are independent of hyperaldosteronism in vasopressin escape. Am J Physiol Renal Physiol. 2006;291:F49-57 pubmed
    ..abundance of the alpha-subunit of the epithelial sodium channel (ENaC), the thiazide-sensitive Na-Cl cotransporter (NCC), and the 70-kDa band of gamma-ENaC (Song J, Hu X, Khan O, Tian Y, Verbalis JG, and Ecelbarger CA...
  11. Lagnaz D, Arroyo J, Chavez Canales M, Vazquez N, Rizzo F, Spirlì A, et al. WNK3 abrogates the NEDD4-2-mediated inhibition of the renal Na+-Cl- cotransporter. Am J Physiol Renal Physiol. 2014;307:F275-86 pubmed publisher
    ..WNK3 and the ubiquitin-protein ligase NEDD4-2 are key regulators of the thiazide-sensitive Na+-Cl- cotransporter (NCC), WNK3 as an activator and NEDD2-4 as an inhibitor...
  12. Wyse B, Ali N, Ellison D. Interaction with grp58 increases activity of the thiazide-sensitive Na-Cl cotransporter. Am J Physiol Renal Physiol. 2002;282:F424-30 pubmed
    The thiazide-sensitive sodium-chloride cotransporter (NCC) is expressed by distal convoluted tubule cells of the mammalian kidney...
  13. Lee D, Riquier A, Yang L, Leong P, Maunsbach A, McDonough A. Acute hypertension provokes acute trafficking of distal tubule Na-Cl cotransporter (NCC) to subapical cytoplasmic vesicles. Am J Physiol Renal Physiol. 2009;296:F810-8 pubmed publisher
    ..Distal convoluted tubule Na(+)-Cl(-) cotransporter (NCC) is regulated by trafficking between the apical plasma membrane (APM) and subapical cytoplasmic vesicles (SCV)...
  14. Hoover R, Poch E, Monroy A, Vazquez N, Nishio T, Gamba G, et al. N-Glycosylation at two sites critically alters thiazide binding and activity of the rat thiazide-sensitive Na(+):Cl(-) cotransporter. J Am Soc Nephrol. 2003;14:271-82 pubmed
    ..that the mutants displayed drastically decreased thiazide-sensitive (22)Na(+) uptake compared with wild-type NCC. Analysis of enhanced green fluorescence protein (EGFP)-tagged cotransporters demonstrated that this decrease in ..
  15. Yu Z, Serra A, Sauter D, Loffing J, Ackermann D, Frey F, et al. Sodium retention in rats with liver cirrhosis is associated with increased renal abundance of NaCl cotransporter (NCC). Nephrol Dial Transplant. 2005;20:1833-41 pubmed
    ..Renal protein content of ENaC subunits, ubiquitin-protein-ligase Nedd4-2 and NaCl cotransporter (NCC) were assessed by western blot...
  16. Komers R, Rogers S, Oyama T, Xu B, Yang C, McCormick J, et al. Enhanced phosphorylation of Na(+)-Cl- co-transporter in experimental metabolic syndrome: role of insulin. Clin Sci (Lond). 2012;123:635-47 pubmed publisher
    In the present study, we investigated the activity of the thiazide-sensitive NCC (Na(+)-Cl(-) co-transporter) in experimental metabolic syndrome and the role of insulin in NCC activation...
  17. Turban S, Wang X, Knepper M. Regulation of NHE3, NKCC2, and NCC abundance in kidney during aldosterone escape phenomenon: role of NO. Am J Physiol Renal Physiol. 2003;285:F843-51 pubmed
    ..occurs largely as a result of a marked suppression of the abundance of the thiazide-sensitive Na-Cl cotransporter (NCC) of the distal convoluted tubule but have also demonstrated a paradoxical increase in the protein abundance of the ..
  18. San Cristobal P, Ponce Coria J, Vazquez N, Bobadilla N, Gamba G. WNK3 and WNK4 amino-terminal domain defines their effect on the renal Na+-Cl- cotransporter. Am J Physiol Renal Physiol. 2008;295:F1199-206 pubmed publisher
    Loss of physiological regulation of the renal thiazide-sensitive Na+-Cl- cotransporter (NCC) by mutant WNK1 or WNK4 results in pseudohypoaldosteronism type II (PHAII) characterized by arterial hypertension and hyperkalemia...
  19. Kunchaparty S, Palcso M, Berkman J, Velazquez H, Desir G, Bernstein P, et al. Defective processing and expression of thiazide-sensitive Na-Cl cotransporter as a cause of Gitelman's syndrome. Am J Physiol. 1999;277:F643-9 pubmed
  20. Tovar Palacio C, Bobadilla N, Cortes P, Plata C, de los Heros P, Vazquez N, et al. Ion and diuretic specificity of chimeric proteins between apical Na(+)-K(+)-2Cl(-) and Na(+)-Cl(-) cotransporters. Am J Physiol Renal Physiol. 2004;287:F570-7 pubmed
    ..Thus NH(2)-terminal and COOH-terminal domains do not play a role in defining these properties. A similar conclusion can be suggested for the Na(+)-Cl(-) cotransporter. ..
  21. Kobayashi K, Uchida S, Mizutani S, Sasaki S, Marumo F. Intrarenal and cellular localization of CLC-K2 protein in the mouse kidney. J Am Soc Nephrol. 2001;12:1327-34 pubmed
    ..These aspects of CLC-K2 localization suggest that CLC-K2 is important in Cl(-) transport in the distal nephron segments. ..
  22. Riancho J, Saro G, Sañudo C, Izquierdo M, Zarrabeitia M. Gitelman syndrome: genetic and expression analysis of the thiazide-sensitive sodium-chloride transporter in blood cells. Nephrol Dial Transplant. 2006;21:217-20 pubmed
    Gitelman syndrome is caused by mutations of the SLC12A3 gene, which encodes the thiazide-sensitive NaCl transporter NCCT...
  23. Verlander J, Miller R, Frank A, Royaux I, Kim Y, Weiner I. Localization of the ammonium transporter proteins RhBG and RhCG in mouse kidney. Am J Physiol Renal Physiol. 2003;284:F323-37 pubmed
    ..These findings suggest that RhBG and RhCG may play important and cell-specific roles in ammonium transport and signaling in these regions of the kidney. ..
  24. Matayoshi T, Kamide K, Takiuchi S, Yoshii M, Miwa Y, Takami Y, et al. The thiazide-sensitive Na(+)-Cl(-) cotransporter gene, C1784T, and adrenergic receptor-beta3 gene, T727C, may be gene polymorphisms susceptible to the antihypertensive effect of thiazide diuretics. Hypertens Res. 2004;27:821-33 pubmed
    ..Forty-eight SNPs in 17 genes (ADD1, GNB3, TSC [SLC12A3], MLR [NR3C2], NCX1 [SLC8A1], WNK1, WNK4, AGT, ACE, AT1 [AGTR1], CYP11B2, ADRB1, ADRB2, ADRB3, ADRA1A, ADRA1B, ..
  25. Capasso G, Rizzo M, Garavaglia M, Trepiccione F, Zacchia M, Mugione A, et al. Upregulation of apical sodium-chloride cotransporter and basolateral chloride channels is responsible for the maintenance of salt-sensitive hypertension. Am J Physiol Renal Physiol. 2008;295:F556-67 pubmed publisher
    ..005) for Na+-Cl- (NCC) in distal convoluted tubules (DCT)...
  26. Moreno E, Cristóbal P, Rivera M, Vazquez N, Bobadilla N, Gamba G. Affinity-defining domains in the Na-Cl cotransporter: a different location for Cl- and thiazide binding. J Biol Chem. 2006;281:17266-75 pubmed
    The thiazide-sensitive Na+-Cl- cotransporter (NCC) is the major pathway for salt reabsorption in the distal convoluted tubule, serves as a receptor for thiazide-type diuretics, and is involved in inherited diseases associated with ..
  27. Faroqui S, Sheriff S, Amlal H. Metabolic acidosis has dual effects on sodium handling by rat kidney. Am J Physiol Renal Physiol. 2006;291:F322-31 pubmed
    ..67 meq/l) after 5d of CMA. The protein abundance of the cortical Na-Cl cotransporter (NCC) remained unchanged at 24 h, but increased significantly (P < 0.01) after 5d of CMA...
  28. Rinehart J, Kahle K, de los Heros P, Vazquez N, Meade P, Wilson F, et al. WNK3 kinase is a positive regulator of NKCC2 and NCC, renal cation-Cl- cotransporters required for normal blood pressure homeostasis. Proc Natl Acad Sci U S A. 2005;102:16777-82 pubmed
    ..SLC12A family, we used coexpression studies in Xenopus oocytes to investigate the effect of WNK3 on NCC and NKCC2, related kidney-specific transporters that mediate apical NaCl reabsorption in the thick ascending limb ..
  29. Sandberg M, Riquier A, Pihakaski Maunsbach K, McDonough A, Maunsbach A. ANG II provokes acute trafficking of distal tubule Na+-Cl(-) cotransporter to apical membrane. Am J Physiol Renal Physiol. 2007;293:F662-9 pubmed
    The distal convoluted tubule (DCT) Na+-Cl(-) cotransporter (NCC), the target of thiazide diuretics, is responsible for the reabsorption of 5-10% of filtered NaCl...
  30. West C, McDonough A, Masilamani S, Verlander J, Baylis C. Renal NCC is unchanged in the midpregnant rat and decreased in the late pregnant rat despite avid renal Na+ retention. Am J Physiol Renal Physiol. 2015;309:F63-70 pubmed publisher
    ..In the present study, we investigated the aldosterone-responsive Na(+)-Cl(-) cotransporter (NCC) in mid- and late pregnant rats compared with virgin rats...
  31. Mutig K, Saritas T, Uchida S, Kahl T, Borowski T, Paliege A, et al. Short-term stimulation of the thiazide-sensitive Na+-Cl- cotransporter by vasopressin involves phosphorylation and membrane translocation. Am J Physiol Renal Physiol. 2010;298:F502-9 pubmed publisher
    ..The Na+-Cl- cotransporter (NCC) of DCT is activated by luminal trafficking and phosphorylation at conserved NH2-terminal residues...
  32. Walsh K, Kuwabara J, Shim J, Wainford R. Norepinephrine-evoked salt-sensitive hypertension requires impaired renal sodium chloride cotransporter activity in Sprague-Dawley rats. Am J Physiol Regul Integr Comp Physiol. 2016;310:R115-24 pubmed publisher
    Recent studies have implicated a role of norepinephrine (NE) in the activation of the sodium chloride cotransporter (NCC) to drive the development of salt-sensitive hypertension...
  33. Matsuo A, Katsuya T, Ishikawa K, Sugimoto K, Iwashima Y, Yamamoto K, et al. G2736A polymorphism of thiazide-sensitive Na-Cl cotransporter gene predisposes to hypertension in young women. J Hypertens. 2004;22:2123-7 pubmed
    The thiazide-sensitive Na-Cl cotransporter (TSC) is located in the distal renal tubules...
  34. Rojas Vega L, Reyes Castro L, Ramírez V, Bautista Pérez R, Rafael C, Castañeda Bueno M, et al. Ovarian hormones and prolactin increase renal NaCl cotransporter phosphorylation. Am J Physiol Renal Physiol. 2015;308:F799-808 pubmed publisher
    ..Accordingly, a dimorphic regulation of the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC) has been reported, with a higher activity in females than in males...
  35. Akiyama K, Miyashita T, Mori T, Inamoto R, Mori N. Expression of thiazide-sensitive Na+-Cl- cotransporter in the rat endolymphatic sac. Biochem Biophys Res Commun. 2008;371:649-53 pubmed publisher
    ..The thiazide-sensitive Na(+), Cl(-) cotransporter (TSC) is an electroneutral cotransporter specific to the kidney that plays an important role in absorption of NaCl in ..
  36. Blankenstein K, Borschewski A, Labes R, Paliege A, Boldt C, McCormick J, et al. Calcineurin inhibitor cyclosporine A activates renal Na-K-Cl cotransporters via local and systemic mechanisms. Am J Physiol Renal Physiol. 2017;312:F489-F501 pubmed publisher
    ..Na-K-2Cl cotransporter (NKCC2) of the thick ascending limb and the thiazide-sensitive Na-Cl cotransporter (NCC) of the distal convoluted tubule upon calcineurin inhibition using cyclosporin A (CsA)...
  37. Kaneko H, Putzier I, Frings S, Kaupp U, Gensch T. Chloride accumulation in mammalian olfactory sensory neurons. J Neurosci. 2004;24:7931-8 pubmed
    ..Cl(-) accumulation provides OSNs with the driving force for the depolarizing Cl(-) current that is the basis of the low-noise receptor current in these neurons. ..
  38. Acuña R, Martínez de la Maza L, Ponce Coria J, Vazquez N, Ortal Vite P, Pacheco Alvarez D, et al. Rare mutations in SLC12A1 and SLC12A3 protect against hypertension by reducing the activity of renal salt cotransporters. J Hypertens. 2011;29:475-83 pubmed publisher
    Screening for variants in SLC12A1 and SLC12A3 genes, encoding the renal Na:Cl (NCC) and Na:K:2Cl (NKCC2) cotransporters, respectively, in 3125 members of the Framingham Heart Study (FHS) revealed that carrying a rare mutation in one of ..