SLC10A1: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''Sodium/bile acid cotransporter''' also known as the [[sodium|Na]]<sup>+</sup>-[[taurocholate]] [[cotransport]]ing [[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]].<ref name="entrez">{{cite web | title = Entrez Gene: SLC10A1 solute carrier family 10 (sodium/bile acid cotransporter family), member 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6554| accessdate = }}</ref><ref name="pmid8132774">{{cite journal | vauthors = Hagenbuch B, Meier PJ | title = Molecular cloning, chromosomal localization, and functional characterization of a human liver Na+/bile acid cotransporter | journal = The Journal of Clinical Investigation | volume = 93 | issue = 3 | pages = 1326–31 | date = March 1994 | pmid = 8132774 | pmc = 294097 | doi = 10.1172/JCI117091 }}</ref>
| update_page = yes
 
| require_manual_inspection = no
==Structure==
| update_protein_box = yes
Sodium/bile acid [[cotransporter]]s are integral membrane glycoproteins. Human NTCP contains 349 amino acids and has a mass of 56 kDa.<ref name="Watashi2014"/>
| update_summary = yes
 
| update_citations = yes
== Function ==
}}
[[Bile acid:sodium symporter]]s participate in the [[enterohepatic circulation]] of [[bile acid]]s. 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 ([[SLC10A2|ileal sodium/bile acid cotransporter]]).  The other is this protein and is expressed in the [[basolateral membrane]]s of hepatocytes (NTCP).<ref name="Watashi2014"/>


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
As a cotransporter, NTCP binds two sodium ions and one (conjugated) [[bile salt]] molecule, thereby providing an [[liver|hepatic]] influx of bile salts. Other transported molecules include [[steroid hormone]]s, [[thyroid hormone]]s and various [[xenobiotic]]s:<ref name="Watashi2014"/>
{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = Solute carrier family 10 (sodium/bile acid cotransporter family), member 1
| HGNCid = 10905
| Symbol = SLC10A1
| AltSymbols =; NTCP; NTCP1
| OMIM = 182396
| ECnumber = 
| Homologene = 31126
| MGIid = 97379
| GeneAtlas_image1 = PBB_GE_SLC10A1_207185_at_tn.png
| Function = {{GNF_GO|id=GO:0008508 |text = bile acid:sodium symporter activity}} {{GNF_GO|id=GO:0015293 |text = symporter activity}} {{GNF_GO|id=GO:0031402 |text = sodium ion binding}}
| Component = {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}} {{GNF_GO|id=GO:0016020 |text = membrane}}
| Process = {{GNF_GO|id=GO:0006811 |text = ion transport}} {{GNF_GO|id=GO:0006814 |text = sodium ion transport}} {{GNF_GO|id=GO:0015711 |text = organic anion transport}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 6554
    | Hs_Ensembl = ENSG00000100652
    | Hs_RefseqProtein = NP_003040
    | Hs_RefseqmRNA = NM_003049
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 14
    | Hs_GenLoc_start = 69312305
    | Hs_GenLoc_end = 69333707
    | Hs_Uniprot = Q14973
    | Mm_EntrezGene = 20493
    | Mm_Ensembl = ENSMUSG00000021135
    | Mm_RefseqmRNA = NM_011387
    | Mm_RefseqProtein = NP_035517
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 12
    | Mm_GenLoc_start = 81872040
    | Mm_GenLoc_end = 81887553
    | Mm_Uniprot = O35940
  }}
}}
'''Solute carrier family 10 (sodium/bile acid cotransporter family), member 1''', also known as '''SLC10A1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: SLC10A1 solute carrier family 10 (sodium/bile acid cotransporter family), member 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6554| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
===Hepatitis virus entry===
{{PBB_Summary
NTCP is a cell surface receptor necessary for the entry of [[hepatitis B virus|hepatitis B]] and [[hepatitis D virus]].<ref>{{cite journal | vauthors = 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 | title = Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus | journal = eLife | volume = 1 | pages = e00049 | date = November 2012 | pmid = 23150796 | pmc = 3485615 | doi = 10.7554/eLife.00049 }}</ref> This entry mechanism is inhibited by [[myrcludex B]],<ref name="Spreitzer">{{cite journal| author = H. Spreitzer| date = 14 September 2015| title = Neue Wirkstoffe – Myrcludex B| journal = Österreichische Apothekerzeitung| issue = 19/2015| page = 12| language = German}}</ref> [[cyclosporin A]], [[progesterone]], [[propranolol]], [[bosentan]], [[ezetimibe]], as well as NTCP [[Substrate (biochemistry)|substrate]]s like [[taurocholate]], [[tauroursodeoxycholate]] and [[bromosulfophthalein]].<ref name="Watashi2014"/>
| section_title =  
| summary_text = Sodium/bile acid cotransporters are integral membrane glycoproteins that participate in the enterohepatic circulation of bile acids. Two homologous transporters are involved in the reabsorption of bile acids, one absorbing from the intestinal lumen, the bile duct, and the kidney with an apical localization (SLC10A2; MIM 601295), and the other being found in the basolateral membranes of hepatocytes (SLC10A1).[supplied by OMIM]<ref name="entrez">{{cite web | title = Entrez Gene: SLC10A1 solute carrier family 10 (sodium/bile acid cotransporter family), member 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6554| accessdate = }}</ref>
}}


==See also==
== See also ==
* [[Solute carrier family]]
* [[Solute carrier family]]


==References==
== References ==
{{reflist|2}}
{{reflist|33em|refs=
<ref name="Watashi2014">{{cite journal | vauthors = Watashi K, Urban S, Li W, Wakita T | title = NTCP and beyond: opening the door to unveil hepatitis B virus entry | journal = International Journal of Molecular Sciences | volume = 15 | issue = 2 | pages = 2892–905 | date = February 2014 | pmid = 24557582 | pmc = 3958888 | doi = 10.3390/ijms15022892 }}</ref>
}}


==Further reading==
== Further reading ==
{{refbegin | 2}}
{{refbegin|33em}}
{{PBB_Further_reading
* {{cite journal | vauthors = Trauner M, Boyer JL | title = Bile salt transporters: molecular characterization, function, and regulation | journal = Physiological Reviews | volume = 83 | issue = 2 | pages = 633–71 | date = April 2003 | pmid = 12663868 | doi = 10.1152/physrev.00027.2002 }}
| citations =
* {{cite journal | vauthors = Shiao T, Iwahashi M, Fortune J, Quattrochi L, Bowman S, Wick M, Qadri I, Simon FR | title = Structural and functional characterization of liver cell-specific activity of the human sodium/taurocholate cotransporter | journal = Genomics | volume = 69 | issue = 2 | pages = 203–13 | date = October 2000 | pmid = 11031103 | doi = 10.1006/geno.2000.6329 }}
*{{cite journal | author=Trauner M, Boyer JL |title=Bile salt transporters: molecular characterization, function, and regulation. |journal=Physiol. Rev. |volume=83 |issue= 2 |pages= 633-71 |year= 2003 |pmid= 12663868 |doi= 10.1152/physrev.00027.2002 }}
* {{cite journal | vauthors = Müller O, Schalla C, Scheibner J, Stange EF, Fuchs M | title = Expression of liver plasma membrane transporters in gallstone-susceptible and gallstone-resistant mice | journal = The Biochemical Journal | volume = 361 | issue = Pt 3 | pages = 673–9 | date = February 2002 | pmid = 11802798 | pmc = 1222351 | doi = 10.1042/0264-6021:3610673 }}
*{{cite journal | author=Hagenbuch B, Meier PJ |title=Molecular cloning, chromosomal localization, and functional characterization of a human liver Na+/bile acid cotransporter. |journal=J. Clin. Invest. |volume=93 |issue= 3 |pages= 1326-31 |year= 1994 |pmid= 8132774 |doi=  }}
* {{cite journal | vauthors = Hallén S, Mareninova O, Brändén M, Sachs G | title = Organization of the membrane domain of the human liver sodium/bile acid cotransporter | journal = Biochemistry | volume = 41 | issue = 23 | pages = 7253–66 | date = June 2002 | pmid = 12044156 | doi = 10.1021/bi012152s }}
*{{cite journal  | author=Shiao T, Iwahashi M, Fortune J, ''et al.'' |title=Structural and functional characterization of liver cell-specific activity of the human sodium/taurocholate cotransporter. |journal=Genomics |volume=69 |issue= 2 |pages= 203-13 |year= 2001 |pmid= 11031103 |doi= 10.1006/geno.2000.6329 }}
* {{cite journal | vauthors = Ho RH, Leake BF, Roberts RL, Lee W, Kim RB | title = Ethnicity-dependent polymorphism in Na+-taurocholate cotransporting polypeptide (SLC10A1) reveals a domain critical for bile acid substrate recognition | journal = The Journal of Biological Chemistry | volume = 279 | issue = 8 | pages = 7213–22 | date = February 2004 | pmid = 14660639 | doi = 10.1074/jbc.M305782200 }}
*{{cite journal | author=Müller O, Schalla C, Scheibner J, ''et al.'' |title=Expression of liver plasma membrane transporters in gallstone-susceptible and gallstone-resistant mice. |journal=Biochem. J. |volume=361 |issue= Pt 3 |pages= 673-9 |year= 2002 |pmid= 11802798 |doi= }}
* {{cite journal | vauthors = Jung D, Hagenbuch B, Fried M, Meier PJ, Kullak-Ublick GA | title = Role of liver-enriched transcription factors and nuclear receptors in regulating the human, mouse, and rat NTCP gene | journal = American Journal of Physiology. Gastrointestinal and Liver Physiology | volume = 286 | issue = 5 | pages = G752–61 | date = May 2004 | pmid = 14701722 | doi = 10.1152/ajpgi.00456.2003 }}
*{{cite journal | author=Hallén S, Mareninova O, Brändén M, Sachs G |title=Organization of the membrane domain of the human liver sodium/bile acid cotransporter. |journal=Biochemistry |volume=41 |issue= 23 |pages= 7253-66 |year= 2002 |pmid= 12044156 |doi=  }}
* {{cite journal | vauthors = Alrefai WA, Sarwar Z, Tyagi S, Saksena S, Dudeja PK, Gill RK | title = Cholesterol modulates human intestinal sodium-dependent bile acid transporter | journal = American Journal of Physiology. Gastrointestinal and Liver Physiology | volume = 288 | issue = 5 | pages = G978–85 | date = May 2005 | pmid = 15604201 | doi = 10.1152/ajpgi.00379.2004 }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |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 }}
* {{cite journal | vauthors = Chen HL, Chen HL, Liu YJ, Feng CH, Wu CY, Shyu MK, Yuan RH, Chang MH | title = Developmental expression of canalicular transporter genes in human liver | journal = Journal of Hepatology | volume = 43 | issue = 3 | pages = 472–7 | date = September 2005 | pmid = 15922475 | doi = 10.1016/j.jhep.2005.02.030 }}
*{{cite journal | author=Ho RH, Leake BF, Roberts RL, ''et al.'' |title=Ethnicity-dependent polymorphism in Na+-taurocholate cotransporting polypeptide (SLC10A1) reveals a domain critical for bile acid substrate recognition. |journal=J. Biol. Chem. |volume=279 |issue= 8 |pages= 7213-22 |year= 2004 |pmid= 14660639 |doi= 10.1074/jbc.M305782200 }}
* {{cite journal | vauthors = Anwer MS, Gillin H, Mukhopadhyay S, Balasubramaniyan N, Suchy FJ, Ananthanarayanan M | title = Dephosphorylation of Ser-226 facilitates plasma membrane retention of Ntcp | journal = The Journal of Biological Chemistry | volume = 280 | issue = 39 | pages = 33687–92 | date = September 2005 | pmid = 16027164 | doi = 10.1074/jbc.M502151200 }}
*{{cite journal | author=Jung D, Hagenbuch B, Fried M, ''et al.'' |title=Role of liver-enriched transcription factors and nuclear receptors in regulating the human, mouse, and rat NTCP gene. |journal=Am. J. Physiol. Gastrointest. Liver Physiol. |volume=286 |issue= 5 |pages= G752-61 |year= 2004 |pmid= 14701722 |doi= 10.1152/ajpgi.00456.2003 }}
* {{cite journal | vauthors = Eloranta JJ, Jung D, Kullak-Ublick GA | title = 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 | journal = Molecular Endocrinology | volume = 20 | issue = 1 | pages = 65–79 | date = January 2006 | pmid = 16123152 | doi = 10.1210/me.2005-0159 }}
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
* {{cite journal | vauthors = Dias V, Ribeiro V | title = The expression of the solute carriers NTCP and OCT-1 is regulated by cholesterol in HepG2 cells | journal = Fundamental & Clinical Pharmacology | volume = 21 | issue = 4 | pages = 445–50 | date = August 2007 | pmid = 17635184 | doi = 10.1111/j.1472-8206.2007.00517.x }}
*{{cite journal  | author=Alrefai WA, Sarwar Z, Tyagi S, ''et al.'' |title=Cholesterol modulates human intestinal sodium-dependent bile acid transporter. |journal=Am. J. Physiol. Gastrointest. Liver Physiol. |volume=288 |issue= 5 |pages= G978-85 |year= 2005 |pmid= 15604201 |doi= 10.1152/ajpgi.00379.2004 }}
*{{cite journal | author=Chen HL, Chen HL, Liu YJ, ''et al.'' |title=Developmental expression of canalicular transporter genes in human liver. |journal=J. Hepatol. |volume=43 |issue= 3 |pages= 472-7 |year= 2005 |pmid= 15922475 |doi= 10.1016/j.jhep.2005.02.030 }}
*{{cite journal | author=Anwer MS, Gillin H, Mukhopadhyay S, ''et al.'' |title=Dephosphorylation of Ser-226 facilitates plasma membrane retention of Ntcp. |journal=J. Biol. Chem. |volume=280 |issue= 39 |pages= 33687-92 |year= 2005 |pmid= 16027164 |doi= 10.1074/jbc.M502151200 }}
*{{cite journal | author=Eloranta JJ, Jung D, Kullak-Ublick GA |title=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. |journal=Mol. Endocrinol. |volume=20 |issue= 1 |pages= 65-79 |year= 2006 |pmid= 16123152 |doi= 10.1210/me.2005-0159 }}
*{{cite journal | author=Dias V, Ribeiro V |title=The expression of the solute carriers NTCP and OCT-1 is regulated by cholesterol in HepG2 cells. |journal=Fundamental & clinical pharmacology |volume=21 |issue= 4 |pages= 445-50 |year= 2007 |pmid= 17635184 |doi= 10.1111/j.1472-8206.2007.00517.x }}
}}
{{refend}}
{{refend}}


{{membrane-protein-stub}}
{{NLM content}}
{{NLM content}}
{{Membrane transport proteins}}
{{Membrane transport proteins}}
[[Category:Solute carrier family]]
[[Category:Solute carrier family]]
{{WikiDoc Sources}}
 
{{membrane-protein-stub}}

Latest revision as of 06:25, 11 September 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

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.

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