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 symporterprotein that in humans is encoded by the SLC10A2gene.[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]
^ abcGRCh38: Ensembl release 89: ENSG00000125255 – Ensembl, May 2017
^ abcGRCm38: 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. ISBN978-3-642-14540-7. PMC3249407. 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. PMC4107709. PMID 25057297.
^Chitnis D (2016-08-03), "FDA grants fast track status to volixibat", Internal Medicine News Digital Network, retrieved 2016-08-14.
Further readingedit
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. PMC2796132. 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. PMC508012. 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. PMC1223054. 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. PMC2525805. PMID 16411770.
ileal, sodium, bile, acid, cotransporter, also, known, apical, sodium, bile, acid, transporter, asbt, ileal, bile, acid, transporter, ibat, bile, acid, sodium, symporter, protein, that, humans, encoded, slc10a2, gene, slc10a2identifiersaliasesslc10a2, asbt, ib. 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 SLC10A2IdentifiersAliasesSLC10A2 ASBT IBAT ISBT NTCP2 PBAM solute carrier family 10 member 2 Ileal bile acid transporter PBAM1External IDsOMIM 601295 MGI 1201406 HomoloGene 390 GeneCards SLC10A2Gene location Human Chr Chromosome 13 human 1 Band13q33 1Start103 043 998 bp 1 End103 066 417 bp 1 Gene location Mouse Chr Chromosome 8 mouse 2 Band8 A1 1 8 2 16 cMStart5 133 219 bp 2 End5 155 351 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed injejunal mucosaduodenumkidney tubuleglomerulusmetanephric glomeruluskidneygallbladderamniotic fluidrenal medullalower lobe of lungTop expressed inproximal tubulekidneyileumPaneth cellleft lobe of liverintestinal villusjejunumspermatidleft colonduodenumMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionsymporter activity bile acid sodium symporter activityCellular componentintegral component of membrane microvillus plasma membrane integral component of plasma membrane apical plasma membrane membraneBiological procession transport transmembrane transport bile acid and bile salt transport sodium ion transport response to bacteriumSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez655520494EnsemblENSG00000125255ENSMUSG00000023073UniProtQ12908P70172RefSeq mRNA NM 000452NM 011388RefSeq protein NP 000443NP 035518Location UCSC Chr 13 103 04 103 07 MbChr 8 5 13 5 16 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse 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 Contents 1 As a drug target 2 See also 3 References 4 Further readingAs a drug target editSeveral medications to inhibit IBAT are under development They include elobixibat under development for the treatment of constipation and irritable bowel syndrome 8 and volixibat under development for the treatment of nonalcoholic steatohepatitis 9 See also editSolute carrier familyReferences edit 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 editShneider 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 Rossel 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 nbsp This membrane protein related article is a stub You 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