Sodium/bile acid cotransporter
| SLC10A1 | |||
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Gene ontology | |||
| Molecular function | |||
| Cellular component | |||
| Biological process | |||
| Sources:Amigo / QuickGO | |||
Ensembl | |||||||||
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| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 14: 69.78 – 69.8 Mb | Chr 12: 81 – 81.02 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Sodium/bile acid cotransporter also known as the
Structure
Sodium/bile acid cotransporters are integral membrane glycoproteins. Human NTCP contains 349 amino acids and has a mass of 56 kDa.[7]
Function
As a cotransporter, NTCP binds two sodium ions and one (conjugated)
Hepatitis virus entry
NTCP is a cell surface receptor necessary for the entry of
SLC10A1-deficiency
Individuals that lack functional NTCP have been identified.[11] These individuals display highly elevated bile salt levels in plasma, but without a clear phenotype. In areas of the world with a high prevalence of HBV, there are multiple individuals who carry the NTCP p.S267F polymorphism on both alleles; this makes NTCP inactive as a bile acid transporter, but provides protection against HBV infection.[12]
NTCP-deficient mice have also been created. These mice have reduced hepatic bile salt uptake but plasma bile salt levels are less clearly elevated, as the rodent-specific OATP1a/1b transporters provide can partially replace the function of NTCP.[13] Nevertheless, this NTCP-knockout animal model pointed to possible additional (non-HBV) aspects of NTCP-deficiency. NTCP-deficient mice are partially protected against the problems associated with a high-calorie diet, including excessive weight gain[14] and to liver damage in cholestasis.[15] These effects of NTCP deficiency have not yet been replicated in humans.
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000100652 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021135 – 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.
- ^ "Entrez Gene: SLC10A1 solute carrier family 10 (sodium/bile acid cotransporter family), member 1".
- PMID 8132774.
- ^ PMID 24557582.
- PMID 23150796.
- ^ H. Spreitzer (14 September 2015). "Neue Wirkstoffe – Myrcludex B". Österreichische Apothekerzeitung (in German) (19/2015): 12.
- PMID 35312737.
- PMID 24867799.
- S2CID 205895418.
- PMID 25641256.
- PMID 31237863.
- PMID 29572910.
Further reading
- Trauner M, Boyer JL (April 2003). "Bile salt transporters: molecular characterization, function, and regulation". Physiological Reviews. 83 (2): 633–671. S2CID 5911966.
- Shiao T, Iwahashi M, Fortune J, Quattrochi L, Bowman S, Wick M, et al. (October 2000). "Structural and functional characterization of liver cell-specific activity of the human sodium/taurocholate cotransporter". Genomics. 69 (2): 203–213. 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): 673–679. 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): 7253–7266. 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): 7213–7222. 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–G761. S2CID 1101720.
- 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–G985. S2CID 633434.
- Chen HL, Chen HL, Liu YJ, Feng CH, Wu CY, Shyu MK, et al. (September 2005). "Developmental expression of canalicular transporter genes in human liver". Journal of Hepatology. 43 (3): 472–477. 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): 33687–33692. 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. 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): 445–450. S2CID 46522965.
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