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SLC10 family of sodium-bile acid co-transporters C
Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Overview
The SLC10 family transport bile acids, sulphated solutes, and other xenobiotics in a sodium-dependent manner. The founding members, SLC10A1 (NTCP) and SLC10A2 (ASBT) function, along with members of the ABC transporter family (MDR1/ABCB1, BSEP/ABCB11 and MRP2/ABCC2) and the organic solute transporter obligate heterodimer OSTα:OSTβ (SLC51), to maintain the enterohepatic circulation of bile acids [5,17]. SLC10A6 (SOAT) functions as a sodium-dependent transporter of sulphated solutes including sulfphated steroids and bile acids [8,10]. Transport function has not yet been demonstrated for the 4 remaining members of the SLC10 family, SLC10A3 (P3), SLC10A4 (P4), SLC10A5 (P5), and SLC10A7 (P7), and the identity of their endogenous substrates remain unknown [7,10,13,20]. Members of the SLC10 family are predicted to have seven transmembrane domains with an extracellular N-terminus and cytoplasmic C-terminus [1,14].
Transporters
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NTCP (Sodium/bile acid and sulphated solute cotransporter 1 / SLC10A1) C Show summary »« Hide summary
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ASBT (Sodium/bile acid and sulphated solute cotransporter 2 / SLC10A2) C Show summary »« Hide summary
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P3 (Sodium/bile acid and sulphated solute cotransporter 3 / SLC10A3) Show summary »« Hide summary
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P4 (Sodium/bile acid and sulphated solute cotransporter 4 / SLC10A4) Show summary »« Hide summary
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P5 (Sodium/bile acid and sulphated solute cotransporter 5 / SLC10A5) Show summary »« Hide summary
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SOAT (Sodium/bile acid and sulphated solute cotransporter 6 / SLC10A6) C Show summary »« Hide summary
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P7 (Sodium/bile acid and sulphated solute cotransporter 7 / SLC10A7) Show summary »« Hide summary
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Further reading
* Key recommended reading is highlighted with an asterisk
Alrefai WA, Gill RK. (2007) Bile acid transporters: structure, function, regulation and pathophysiological implications. Pharm Res, 24 (10): 1803-23. [PMID:17404808]
* Anwer MS, Stieger B. (2014) Sodium-dependent bile salt transporters of the SLC10A transporter family: more than solute transporters. Pflugers Arch, 466 (1): 77-89. [PMID:24196564]
Borges K. (2013) Slc10A4 - what do we know about the function of this "secret ligand carrier" protein?. Exp Neurol, 248: 258-61. [PMID:23810836]
* Claro da Silva T, Polli JE, Swaan PW. (2013) The solute carrier family 10 (SLC10): beyond bile acid transport. Mol Aspects Med, 34 (2-3): 252-69. [PMID:23506869]
* Dawson PA. (2017) Roles of Ileal ASBT and OSTα-OSTβ in Regulating Bile Acid Signaling. Dig Dis, 35 (3): 261-266. [PMID:28249269]
Dawson PA, Lan T, Rao A. (2009) Bile acid transporters. J Lipid Res, 50 (12): 2340-57. [PMID:19498215]
Döring B, Lütteke T, Geyer J, Petzinger E. (2012) The SLC10 carrier family: transport functions and molecular structure. Curr Top Membr, 70: 105-68. [PMID:23177985]
Geyer J, Wilke T, Petzinger E. (2006) The solute carrier family SLC10: more than a family of bile acid transporters regarding function and phylogenetic relationships. Naunyn Schmiedebergs Arch Pharmacol, 372 (6): 413-31. [PMID:16541252]
Hagenbuch B, Dawson P. (2004) The sodium bile salt cotransport family SLC10. Pflugers Arch, 447 (5): 566-70. [PMID:12851823]
Klaassen CD, Aleksunes LM. (2010) Xenobiotic, bile acid, and cholesterol transporters: function and regulation. Pharmacol Rev, 62 (1): 1-96. [PMID:20103563]
Kosters A, Karpen SJ. (2008) Bile acid transporters in health and disease. Xenobiotica, 38 (7-8): 1043-71. [PMID:18668439]
* Zwicker BL, Agellon LB. (2013) Transport and biological activities of bile acids. Int J Biochem Cell Biol, 45 (7): 1389-98. [PMID:23603607]
References
1. Banerjee A, Swaan PW. (2006) Membrane topology of human ASBT (SLC10A2) determined by dual label epitope insertion scanning mutagenesis. New evidence for seven transmembrane domains. Biochemistry, 45 (3): 943-53. [PMID:16411770]
2. Bhat BG, Rapp SR, Beaudry JA, Napawan N, Butteiger DN, Hall KA, Null CL, Luo Y, Keller BT. (2003) Inhibition of ileal bile acid transport and reduced atherosclerosis in apoE-/- mice by SC-435. J Lipid Res, 44 (9): 1614-21. [PMID:12810816]
3. Burger S, Döring B, Hardt M, Beuerlein K, Gerstberger R, Geyer J. (2011) Co-expression studies of the orphan carrier protein Slc10a4 and the vesicular carriers VAChT and VMAT2 in the rat central and peripheral nervous system. Neuroscience, 193: 109-21. [PMID:21742018]
4. Craddock AL, Love MW, Daniel RW, Kirby LC, Walters HC, Wong MH, Dawson PA. (1998) Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter. Am J Physiol, 274 (1 Pt 1): G157-69. [PMID:9458785]
5. Dawson PA, Lan T, Rao A. (2009) Bile acid transporters. J Lipid Res, 50 (12): 2340-57. [PMID:19498215]
6. Dong Z, Ekins S, Polli JE. (2013) Structure-activity relationship for FDA approved drugs as inhibitors of the human sodium taurocholate cotransporting polypeptide (NTCP). Mol Pharm, 10 (3): 1008-19. [PMID:23339484]
7. Fernandes CF, Godoy JR, Döring B, Cavalcanti MC, Bergmann M, Petzinger E, Geyer J. (2007) The novel putative bile acid transporter SLC10A5 is highly expressed in liver and kidney. Biochem Biophys Res Commun, 361 (1): 26-32. [PMID:17632081]
8. Geyer J, Döring B, Meerkamp K, Ugele B, Bakhiya N, Fernandes CF, Godoy JR, Glatt H, Petzinger E. (2007) Cloning and functional characterization of human sodium-dependent organic anion transporter (SLC10A6). J Biol Chem, 282 (27): 19728-41. [PMID:17491011]
9. Geyer J, Fernandes CF, Döring B, Burger S, Godoy JR, Rafalzik S, Hübschle T, Gerstberger R, Petzinger E. (2008) Cloning and molecular characterization of the orphan carrier protein Slc10a4: expression in cholinergic neurons of the rat central nervous system. Neuroscience, 152 (4): 990-1005. [PMID:18355966]
10. Geyer J, Godoy JR, Petzinger E. (2004) Identification of a sodium-dependent organic anion transporter from rat adrenal gland. Biochem Biophys Res Commun, 316 (2): 300-6. [PMID:15020217]
11. Gillberg P-G, Graffner H, Starke I. (2013) Ibat inhibitors for the treatment of liver diseases. Patent number: US20130225511A1. Assignee: Albireo AB. Priority date: 08/11/2010. Publication date: 29/08/2013.
12. Gillberg P-G, Graffner H, Starke I. (2017) IBAT inhibitors for the treatment of liver disease. Patent number: US9694018B1. Assignee: Albireo AB. Priority date: 08/11/2010. Publication date: 04/07/2017.
13. Godoy JR, Fernandes C, Döring B, Beuerlein K, Petzinger E, Geyer J. (2007) Molecular and phylogenetic characterization of a novel putative membrane transporter (SLC10A7), conserved in vertebrates and bacteria. Eur J Cell Biol, 86 (8): 445-60. [PMID:17628207]
14. Hallén S, Brändén M, Dawson PA, Sachs G. (1999) Membrane insertion scanning of the human ileal sodium/bile acid co-transporter. Biochemistry, 38 (35): 11379-88. [PMID:10471288]
15. Huang HC, Tremont SJ, Lee LF, Keller BT, Carpenter AJ, Wang CC, Banerjee SC, Both SR, Fletcher T, Garland DJ et al.. (2005) Discovery of potent, nonsystemic apical sodium-codependent bile acid transporter inhibitors (Part 2). J Med Chem, 48 (18): 5853-68. [PMID:16134951]
16. Kim RB, Leake B, Cvetkovic M, Roden MM, Nadeau J, Walubo A, Wilkinson GR. (1999) Modulation by drugs of human hepatic sodium-dependent bile acid transporter (sodium taurocholate cotransporting polypeptide) activity. J Pharmacol Exp Ther, 291 (3): 1204-9. [PMID:10565843]
17. Klaassen CD, Aleksunes LM. (2010) Xenobiotic, bile acid, and cholesterol transporters: function and regulation. Pharmacol Rev, 62 (1): 1-96. [PMID:20103563]
18. Meier PJ, Eckhardt U, Schroeder A, Hagenbuch B, Stieger B. (1997) Substrate specificity of sinusoidal bile acid and organic anion uptake systems in rat and human liver. Hepatology, 26 (6): 1667-77. [PMID:9398014]
19. Tollefson MB, Kolodziej SA, Fletcher TR, Vernier WF, Beaudry JA, Keller BT, Reitz DB. (2003) A novel class of apical sodium co-dependent bile acid transporter inhibitors: the 1,2-benzothiazepines. Bioorg Med Chem Lett, 13 (21): 3727-30. [PMID:14552767]
20. Visser WE, Wong WS, van Mullem AA, Friesema EC, Geyer J, Visser TJ. (2010) Study of the transport of thyroid hormone by transporters of the SLC10 family. Mol Cell Endocrinol, 315 (1-2): 138-45. [PMID:19682536]
21. Weinman SA, Carruth MW, Dawson PA. (1998) Bile acid uptake via the human apical sodium-bile acid cotransporter is electrogenic. J Biol Chem, 273 (52): 34691-5. [PMID:9856990]
22. Wu Y, Aquino CJ, Cowan DJ, Anderson DL, Ambroso JL, Bishop MJ, Boros EE, Chen L, Cunningham A, Dobbins RL et al.. (2013) Discovery of a highly potent, nonabsorbable apical sodium-dependent bile acid transporter inhibitor (GSK2330672) for treatment of type 2 diabetes. J Med Chem, 56 (12): 5094-114. [PMID:23678871]
How to cite this family page
Database page citation:
SLC10 family of sodium-bile acid co-transporters. Accessed on 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=182.
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Fabbro D, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Transporters. Br J Pharmacol. 180 Suppl 2:S374-469.
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License
Heterologously expressed SLC10A4 [9] or SLC10A7 [13] failed to exhibit significant transport of taurocholic acid, pregnenolone sulphate, dehydroepiandrosterone sulphate or choline. SLC10A4 has recently been suggested to associate with neuronal vesicles [3].