SLC10A1

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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Sodium/bile acid cotransporter also known as the Na+-taurocholate cotransporting polypeptide (NTCP) or liver bile acid transporter (LBAT) is a protein that in humans is encoded by the SLC10A1 (solute carrier family 10 member 1) gene.[1][2]

Structure

Sodium/bile acid cotransporters are integral membrane glycoproteins. Human NTCP contains 349 amino acids and has a mass of 56 kDa.[3]

Function

Bile acid:sodium symporters participate in the enterohepatic circulation of bile acids. Two homologous transporters are involved in the reabsorption of bile acids. One of these absorbs bile acids from the intestinal lumen, the bile duct, and the kidney with an apical localization (ileal sodium/bile acid cotransporter). The other is this protein and is expressed in the basolateral membranes of hepatocytes (NTCP).[3]

As a cotransporter, NTCP binds two sodium ions and one (conjugated) bile salt molecule, thereby providing an hepatic influx of bile salts. Other transported molecules include steroid hormones, thyroid hormones and various xenobiotics:[3]

Hepatitis virus entry

NTCP is a cell surface receptor necessary for the entry of hepatitis B and hepatitis D virus.[4] This entry mechanism is inhibited by myrcludex B,[5] cyclosporin A, progesterone, propranolol, bosentan, ezetimibe, as well as NTCP substrates like taurocholate, tauroursodeoxycholate and bromosulfophthalein.[3]

See also

References

  1. ↑ "Entrez Gene: SLC10A1 solute carrier family 10 (sodium/bile acid cotransporter family), member 1".
  2. ↑ Hagenbuch B, Meier PJ (March 1994). "Molecular cloning, chromosomal localization, and functional characterization of a human liver Na+/bile acid cotransporter". The Journal of Clinical Investigation. 93 (3): 1326–31. doi:10.1172/JCI117091. PMC 294097. PMID 8132774.
  3. ↑ 3.0 3.1 3.2 3.3 Watashi K, Urban S, Li W, Wakita T (February 2014). "NTCP and beyond: opening the door to unveil hepatitis B virus entry". International Journal of Molecular Sciences. 15 (2): 2892–905. doi:10.3390/ijms15022892. PMC 3958888. PMID 24557582.
  4. ↑ Yan H, Zhong G, Xu G, He W, Jing Z, Gao Z, Huang Y, Qi Y, Peng B, Wang H, Fu L, Song M, Chen P, Gao W, Ren B, Sun Y, Cai T, Feng X, Sui J, Li W (November 2012). "Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus". eLife. 1: e00049. doi:10.7554/eLife.00049. PMC 3485615. PMID 23150796.
  5. ↑ H. Spreitzer (14 September 2015). "Neue Wirkstoffe – Myrcludex B". Österreichische Apothekerzeitung (in German) (19/2015): 12.

Further reading

  • Trauner M, Boyer JL (April 2003). "Bile salt transporters: molecular characterization, function, and regulation". Physiological Reviews. 83 (2): 633–71. doi:10.1152/physrev.00027.2002. PMID 12663868.
  • Shiao T, Iwahashi M, Fortune J, Quattrochi L, Bowman S, Wick M, Qadri I, Simon FR (October 2000). "Structural and functional characterization of liver cell-specific activity of the human sodium/taurocholate cotransporter". Genomics. 69 (2): 203–13. doi:10.1006/geno.2000.6329. PMID 11031103.
  • Müller O, Schalla C, Scheibner J, Stange EF, Fuchs M (February 2002). "Expression of liver plasma membrane transporters in gallstone-susceptible and gallstone-resistant mice". The Biochemical Journal. 361 (Pt 3): 673–9. doi:10.1042/0264-6021:3610673. PMC 1222351. PMID 11802798.
  • Hallén S, Mareninova O, Brändén M, Sachs G (June 2002). "Organization of the membrane domain of the human liver sodium/bile acid cotransporter". Biochemistry. 41 (23): 7253–66. doi:10.1021/bi012152s. PMID 12044156.
  • Ho RH, Leake BF, Roberts RL, Lee W, Kim RB (February 2004). "Ethnicity-dependent polymorphism in Na+-taurocholate cotransporting polypeptide (SLC10A1) reveals a domain critical for bile acid substrate recognition". The Journal of Biological Chemistry. 279 (8): 7213–22. doi:10.1074/jbc.M305782200. PMID 14660639.
  • Jung D, Hagenbuch B, Fried M, Meier PJ, Kullak-Ublick GA (May 2004). "Role of liver-enriched transcription factors and nuclear receptors in regulating the human, mouse, and rat NTCP gene". American Journal of Physiology. Gastrointestinal and Liver Physiology. 286 (5): G752–61. doi:10.1152/ajpgi.00456.2003. PMID 14701722.
  • Alrefai WA, Sarwar Z, Tyagi S, Saksena S, Dudeja PK, Gill RK (May 2005). "Cholesterol modulates human intestinal sodium-dependent bile acid transporter". American Journal of Physiology. Gastrointestinal and Liver Physiology. 288 (5): G978–85. doi:10.1152/ajpgi.00379.2004. PMID 15604201.
  • Chen HL, Chen HL, Liu YJ, Feng CH, Wu CY, Shyu MK, Yuan RH, Chang MH (September 2005). "Developmental expression of canalicular transporter genes in human liver". Journal of Hepatology. 43 (3): 472–7. doi:10.1016/j.jhep.2005.02.030. PMID 15922475.
  • Anwer MS, Gillin H, Mukhopadhyay S, Balasubramaniyan N, Suchy FJ, Ananthanarayanan M (September 2005). "Dephosphorylation of Ser-226 facilitates plasma membrane retention of Ntcp". The Journal of Biological Chemistry. 280 (39): 33687–92. doi:10.1074/jbc.M502151200. PMID 16027164.
  • Eloranta JJ, Jung D, Kullak-Ublick GA (January 2006). "The human Na+-taurocholate cotransporting polypeptide gene is activated by glucocorticoid receptor and peroxisome proliferator-activated receptor-gamma coactivator-1alpha, and suppressed by bile acids via a small heterodimer partner-dependent mechanism". Molecular Endocrinology. 20 (1): 65–79. doi:10.1210/me.2005-0159. PMID 16123152.
  • Dias V, Ribeiro V (August 2007). "The expression of the solute carriers NTCP and OCT-1 is regulated by cholesterol in HepG2 cells". Fundamental & Clinical Pharmacology. 21 (4): 445–50. doi:10.1111/j.1472-8206.2007.00517.x. PMID 17635184.

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

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