Protein-coding gene in the species Homo sapiens
Ileal sodium/bile acid cotransporter , also known as apical sodium–bile acid transporter (ASBT ) and ileal bile acid transporter (IBAT ), is a bile acid:sodium symporter protein that in humans is encoded by the SLC10A2 gene .[5] [6]
ASBT/IBAT is most highly expressed in the ileum , where it is found on the brush border membrane of enterocytes . It is responsible for the initial uptake of bile acids , particularly conjugated bile acids, from the intestine as part of their enterohepatic circulation .[7]
As a drug target Several medications to inhibit IBAT are under development . They include elobixibat , under development for the treatment of constipation and irritable bowel syndrome ,[8] volixibat , under development for the treatment of nonalcoholic steatohepatitis .[9]
See also References
^ a b c GRCh38: Ensembl release 89: ENSG00000125255 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000023073 – 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 .^ Wong MH, Rao PN, Pettenati MJ, Dawson PA (May 1996). "Localization of the ileal sodium-bile acid cotransporter gene (SLC10A2) to human chromosome 13q33". Genomics . 33 (3): 538–40. doi :10.1006/geno.1996.0233 . PMID 8661017 . ^ "Entrez Gene: SLC10A2 solute carrier family 10 (sodium/bile acid cotransporter family), member 2" .^ Dawson PA (2011). "Role of the Intestinal Bile Acid Transporters in Bile Acid and Drug Disposition". Drug Transporters . Handbook of Experimental Pharmacology. Vol. 201. pp. 169–203. doi :10.1007/978-3-642-14541-4_4 . ISBN 978-3-642-14540-7 PMC 3249407 PMID 21103970 . ^ Acosta A, Camilleri M (July 2014). "Elobixibat and its potential role in chronic idiopathic constipation" . Therapeutic Advances in Gastroenterology . 7 (4): 167–75. doi :10.1177/1756283X14528269 . PMC 4107709 PMID 25057297 . ^ Chitnis D (2016-08-03), "FDA grants fast track status to volixibat" , Internal Medicine News Digital Network , retrieved 2016-08-14 .
Further reading
Shneider BL (April 2001). "Intestinal bile acid transport: biology, physiology, and pathophysiology" . Journal of Pediatric Gastroenterology and Nutrition . 32 (4): 407–17. doi :10.1097/00005176-200104000-00002 PMID 11396803 . Balakrishnan A, Polli JE (2006). "Apical sodium dependent bile acid transporter (ASBT, SLC10A2): a potential prodrug target" . Molecular Pharmaceutics . 3 (3): 223–30. doi :10.1021/mp060022d . PMC 2796132 PMID 16749855 . Wong MH, Oelkers P, Dawson PA (November 1995). "Identification of a mutation in the ileal sodium-dependent bile acid transporter gene that abolishes transport activity" . The Journal of Biological Chemistry . 270 (45): 27228–34. doi :10.1074/jbc.270.45.27228 PMID 7592981 . Oelkers P, Kirby LC, Heubi JE, Dawson PA (April 1997). "Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2)" . The Journal of Clinical Investigation . 99 (8): 1880–7. doi :10.1172/JCI119355 . PMC 508012 PMID 9109432 . Craddock AL, Love MW, Daniel RW, Kirby LC, Walters HC, Wong MH, Dawson PA (January 1998). "Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter". The American Journal of Physiology . 274 (1 Pt 1): G157-69. doi :10.1152/ajpgi.1998.274.1.G157 . PMID 9458785 . Montagnani M, Love MW, Rössel P, Dawson PA, Qvist P (October 2001). "Absence of dysfunctional ileal sodium-bile acid cotransporter gene mutations in patients with adult-onset idiopathic bile acid malabsorption". Scandinavian Journal of Gastroenterology . 36 (10): 1077–80. doi :10.1080/003655201750422693 . PMID 11589382 . S2CID 218908622 . Love MW, Craddock AL, Angelin B, Brunzell JD, Duane WC, Dawson PA (December 2001). "Analysis of the ileal bile acid transporter gene, SLC10A2, in subjects with familial hypertriglyceridemia" . Arteriosclerosis, Thrombosis, and Vascular Biology . 21 (12): 2039–45. doi :10.1161/hq1201.100262 PMID 11742882 . Jung D, Fried M, Kullak-Ublick GA (August 2002). "Human apical sodium-dependent bile salt transporter gene (SLC10A2) is regulated by the peroxisome proliferator-activated receptor alpha" . The Journal of Biological Chemistry . 277 (34): 30559–66. doi :10.1074/jbc.M203511200 PMID 12055195 . Zelcer N, Saeki T, Bot I, Kuil A, Borst P (January 2003). "Transport of bile acids in multidrug-resistance-protein 3-overexpressing cells co-transfected with the ileal Na+-dependent bile-acid transporter" . The Biochemical Journal . 369 (Pt 1): 23–30. doi :10.1042/BJ20021081 . PMC 1223054 PMID 12220224 . Neimark E, Chen F, Li X, Shneider BL (July 2004). "Bile acid-induced negative feedback regulation of the human ileal bile acid transporter" . Hepatology . 40 (1): 149–56. doi :10.1002/hep.20295 PMID 15239098 . Xia X, Roundtree M, Merikhi A, Lu X, Shentu S, Lesage G (October 2004). "Degradation of the apical sodium-dependent bile acid transporter by the ubiquitin-proteasome pathway in cholangiocytes" . The Journal of Biological Chemistry . 279 (43): 44931–7. doi :10.1074/jbc.M400969200 PMID 15304498 . Zhang EY, Phelps MA, Banerjee A, Khantwal CM, Chang C, Helsper F, Swaan PW (September 2004). "Topology scanning and putative three-dimensional structure of the extracellular binding domains of the apical sodium-dependent bile acid transporter (SLC10A2)". Biochemistry . 43 (36): 11380–92. doi :10.1021/bi049270a . PMID 15350125 . Banerjee A, Ray A, Chang C, Swaan PW (June 2005). "Site-directed mutagenesis and use of bile acid-MTS conjugates to probe the role of cysteines in the human apical sodium-dependent bile acid transporter (SLC10A2)". Biochemistry . 44 (24): 8908–17. doi :10.1021/bi050553s . PMID 15952798 . Nakahara M, Furuya N, Takagaki K, Sugaya T, Hirota K, Fukamizu A, Kanda T, Fujii H, Sato R (December 2005). "Ileal bile acid-binding protein, functionally associated with the farnesoid X receptor or the ileal bile acid transporter, regulates bile acid activity in the small intestine" . The Journal of Biological Chemistry . 280 (51): 42283–9. doi :10.1074/jbc.M507454200 PMID 16230354 . Bergheim I, Harsch S, Mueller O, Schimmel S, Fritz P, Stange EF (January 2006). "Apical sodium bile acid transporter and ileal lipid binding protein in gallstone carriers" . Journal of Lipid Research . 47 (1): 42–50. doi :10.1194/jlr.M500215-JLR200 PMID 16237211 . Banerjee A, Swaan PW (January 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. doi :10.1021/bi052202j . PMC 2525805 PMID 16411770 .
This article incorporates text from the United States National Library of Medicine , which is in the public domain .
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