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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
The '''''SLC10A2''''' (solute carrier family 10 member 2) [[gene]] in humans encodes the [[bile acid:sodium symporter]] known as the '''apical sodium–bile acid transporter''' (ASBT) or as the '''ileal bile acid transporter''' (IBAT).<ref name="pmid8661017">{{cite journal | vauthors = Wong MH, Rao PN, Pettenati MJ, Dawson PA | title = Localization of the ileal sodium-bile acid cotransporter gene (SLC10A2) to human chromosome 13q33 | journal = Genomics | volume = 33 | issue = 3 | pages = 538–40 | date = May 1996 | pmid = 8661017 | pmc =  | doi = 10.1006/geno.1996.0233 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: SLC10A2 solute carrier family 10 (sodium/bile acid cotransporter family), member 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6555| accessdate = }}</ref>
{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = Solute carrier family 10 (sodium/bile acid cotransporter family), member 2
| HGNCid = 10906
| Symbol = SLC10A2
| AltSymbols =; ASBT; ISBT; NTCP2
| OMIM = 601295
| ECnumber = 
| Homologene = 390
| MGIid = 1201406
| GeneAtlas_image1 = PBB_GE_SLC10A2_207095_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:0005886 |text = plasma membrane}} {{GNF_GO|id=GO:0005887 |text = integral to plasma 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 = 6555
    | Hs_Ensembl = ENSG00000125255
    | Hs_RefseqProtein = NP_000443
    | Hs_RefseqmRNA = NM_000452
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 13
    | Hs_GenLoc_start = 102494351
    | Hs_GenLoc_end = 102517197
    | Hs_Uniprot = Q12908
    | Mm_EntrezGene = 20494
    | Mm_Ensembl = ENSMUSG00000023073
    | Mm_RefseqmRNA = NM_011388
    | Mm_RefseqProtein = NP_035518
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 8
    | Mm_GenLoc_start = 5085595
    | Mm_GenLoc_end = 5105204
    | Mm_Uniprot = Q0VBB8
  }}
}}
'''Solute carrier family 10 (sodium/bile acid cotransporter family), member 2''', also known as '''SLC10A2''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: SLC10A2 solute carrier family 10 (sodium/bile acid cotransporter family), member 2| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6555| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
ASBT/IBAT is  most highly expressed in the [[ileum]], where it is found on the [[brush border]] membrane of [[enterocyte]]s.  It is responsible for the initial uptake of bile acids, particularly conjugated bile acids, from the intestine as part of their [[enterohepatic circulation]].<ref name="pmid21103970">{{cite journal | vauthors = Dawson PA | title = Role of the intestinal bile acid transporters in bile acid and drug disposition | journal = Handbook of Experimental Pharmacology | volume =  | issue = 201 | pages = 169–203 | year = 2011 | pmid = 21103970 | pmc = 3249407 | doi = 10.1007/978-3-642-14541-4_4 }}</ref>
{{PBB_Summary
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| summary_text =  
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==See also==
== As a drug target ==
 
Several [[pharmaceutical drug|medications]] to inhibit IBAT are under [[drug development|development]]. They include [[elobixibat]], under development for the treatment of [[constipation]] and [[irritable bowel syndrome]],<ref name="pmid25057297">{{cite journal | vauthors = Acosta A, Camilleri M | title = Elobixibat and its potential role in chronic idiopathic constipation | journal = Therapeutic Advances in Gastroenterology | volume = 7 | issue = 4 | pages = 167–75 | date = July 2014 | pmid = 25057297 | pmc = 4107709 | doi = 10.1177/1756283X14528269 }}</ref> and [[volixibat]], under development for the treatment of [[non-alcoholic fatty liver disease|nonalcoholic steatohepatitis]].<ref name="Chitnis_2016-08-03">{{Citation |last=Chitnis |first=Deepak | name-list-format = vanc |date=2016-08-03 |accessdate=2016-08-14 |title=FDA grants fast track status to volixibat |work=Internal Medicine News Digital Network |url=http://www.internalmedicinenews.com/index.php?id=514&tx_ttnews[tt_news]=529065&cHash=0318868cbd3098688c489deca5797e62 |postscript=.}}</ref>
 
== See also ==
* [[Solute carrier family]]
* [[Solute carrier family]]


==References==
== References ==
{{reflist|2}}
{{reflist}}
 
{{clear}}
==Further reading==
== Further reading ==
{{refbegin | 2}}
{{refbegin|33em}}
{{PBB_Further_reading
* {{cite journal | vauthors = Shneider BL | title = Intestinal bile acid transport: biology, physiology, and pathophysiology | journal = Journal of Pediatric Gastroenterology and Nutrition | volume = 32 | issue = 4 | pages = 407–17 | date = April 2001 | pmid = 11396803 | doi = 10.1097/00005176-200104000-00002 }}
| citations =
* {{cite journal | vauthors = Balakrishnan A, Polli JE | title = Apical sodium dependent bile acid transporter (ASBT, SLC10A2): a potential prodrug target | journal = Molecular Pharmaceutics | volume = 3 | issue = 3 | pages = 223–30 | year = 2006 | pmid = 16749855 | pmc = 2796132 | doi = 10.1021/mp060022d }}
*{{cite journal | author=Shneider BL |title=Intestinal bile acid transport: biology, physiology, and pathophysiology. |journal=J. Pediatr. Gastroenterol. Nutr. |volume=32 |issue= 4 |pages= 407-17 |year= 2001 |pmid= 11396803 |doi= }}
* {{cite journal | vauthors = Wong MH, Oelkers P, Dawson PA | title = Identification of a mutation in the ileal sodium-dependent bile acid transporter gene that abolishes transport activity | journal = The Journal of Biological Chemistry | volume = 270 | issue = 45 | pages = 27228–34 | date = November 1995 | pmid = 7592981 | doi = 10.1074/jbc.270.45.27228 }}
*{{cite journal | author=Balakrishnan A, Polli JE |title=Apical sodium dependent bile acid transporter (ASBT, SLC10A2): a potential prodrug target. |journal=Mol. Pharm. |volume=3 |issue= 3 |pages= 223-30 |year= 2006 |pmid= 16749855 |doi= 10.1021/mp060022d }}
* {{cite journal | vauthors = Oelkers P, Kirby LC, Heubi JE, Dawson PA | title = Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2) | journal = The Journal of Clinical Investigation | volume = 99 | issue = 8 | pages = 1880–7 | date = April 1997 | pmid = 9109432 | pmc = 508012 | doi = 10.1172/JCI119355 }}
*{{cite journal | author=Wong MH, Oelkers P, Dawson PA |title=Identification of a mutation in the ileal sodium-dependent bile acid transporter gene that abolishes transport activity. |journal=J. Biol. Chem. |volume=270 |issue= 45 |pages= 27228-34 |year= 1995 |pmid= 7592981 |doi= }}
* {{cite journal | vauthors = Craddock AL, Love MW, Daniel RW, Kirby LC, Walters HC, Wong MH, Dawson PA | title = Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter | journal = The American Journal of Physiology | volume = 274 | issue = 1 Pt 1 | pages = G157-69 | date = January 1998 | pmid = 9458785 | doi =  }}
*{{cite journal | author=Wong MH, Rao PN, Pettenati MJ, Dawson PA |title=Localization of the ileal sodium-bile acid cotransporter gene (SLC10A2) to human chromosome 13q33. |journal=Genomics |volume=33 |issue= 3 |pages= 538-40 |year= 1996 |pmid= 8661017 |doi= 10.1006/geno.1996.0233 }}
* {{cite journal | vauthors = Montagnani M, Love MW, Rössel P, Dawson PA, Qvist P | title = Absence of dysfunctional ileal sodium-bile acid cotransporter gene mutations in patients with adult-onset idiopathic bile acid malabsorption | journal = Scandinavian Journal of Gastroenterology | volume = 36 | issue = 10 | pages = 1077–80 | date = October 2001 | pmid = 11589382 | doi = 10.1080/003655201750422693 }}
*{{cite journal | author=Oelkers P, Kirby LC, Heubi JE, Dawson PA |title=Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2). |journal=J. Clin. Invest. |volume=99 |issue= 8 |pages= 1880-7 |year= 1997 |pmid= 9109432 |doi=  }}
* {{cite journal | vauthors = Love MW, Craddock AL, Angelin B, Brunzell JD, Duane WC, Dawson PA | title = Analysis of the ileal bile acid transporter gene, SLC10A2, in subjects with familial hypertriglyceridemia | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 21 | issue = 12 | pages = 2039–45 | date = December 2001 | pmid = 11742882 | doi = 10.1161/hq1201.100262 }}
*{{cite journal | author=Craddock AL, Love MW, Daniel RW, ''et al.'' |title=Expression and transport properties of the human ileal and renal sodium-dependent bile acid transporter. |journal=Am. J. Physiol. |volume=274 |issue= 1 Pt 1 |pages= G157-69 |year= 1998 |pmid= 9458785 |doi= }}
* {{cite journal | vauthors = Jung D, Fried M, Kullak-Ublick GA | title = Human apical sodium-dependent bile salt transporter gene (SLC10A2) is regulated by the peroxisome proliferator-activated receptor alpha | journal = The Journal of Biological Chemistry | volume = 277 | issue = 34 | pages = 30559–66 | date = August 2002 | pmid = 12055195 | doi = 10.1074/jbc.M203511200 }}
*{{cite journal | author=Montagnani M, Love MW, Rössel P, ''et al.'' |title=Absence of dysfunctional ileal sodium-bile acid cotransporter gene mutations in patients with adult-onset idiopathic bile acid malabsorption. |journal=Scand. J. Gastroenterol. |volume=36 |issue= 10 |pages= 1077-80 |year= 2002 |pmid= 11589382 |doi= }}
* {{cite journal | vauthors = Zelcer N, Saeki T, Bot I, Kuil A, Borst P | title = Transport of bile acids in multidrug-resistance-protein 3-overexpressing cells co-transfected with the ileal Na+-dependent bile-acid transporter | journal = The Biochemical Journal | volume = 369 | issue = Pt 1 | pages = 23–30 | date = January 2003 | pmid = 12220224 | pmc = 1223054 | doi = 10.1042/BJ20021081 }}
*{{cite journal | author=Love MW, Craddock AL, Angelin B, ''et al.'' |title=Analysis of the ileal bile acid transporter gene, SLC10A2, in subjects with familial hypertriglyceridemia. |journal=Arterioscler. Thromb. Vasc. Biol. |volume=21 |issue= 12 |pages= 2039-45 |year= 2002 |pmid= 11742882 |doi= }}
* {{cite journal | vauthors = Chumakov I, Blumenfeld M, Guerassimenko O, Cavarec L, Palicio M, Abderrahim H, Bougueleret L, Barry C, Tanaka H, La Rosa P, Puech A, Tahri N, Cohen-Akenine A, Delabrosse S, Lissarrague S, Picard FP, Maurice K, Essioux L, Millasseau P, Grel P, Debailleul V, Simon AM, Caterina D, Dufaure I, Malekzadeh K, Belova M, Luan JJ, Bouillot M, Sambucy JL, Primas G, Saumier M, Boubkiri N, Martin-Saumier S, Nasroune M, Peixoto H, Delaye A, Pinchot V, Bastucci M, Guillou S, Chevillon M, Sainz-Fuertes R, Meguenni S, Aurich-Costa J, Cherif D, Gimalac A, Van Duijn C, Gauvreau D, Ouellette G, Fortier I, Raelson J, Sherbatich T, Riazanskaia N, Rogaev E, Raeymaekers P, Aerssens J, Konings F, Luyten W, Macciardi F, Sham PC, Straub RE, Weinberger DR, Cohen N, Cohen D, Ouelette G, Realson J | display-authors = 6 | title = Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 21 | pages = 13675–80 | date = October 2002 | pmid = 12364586 | pmc = 129739 | doi = 10.1073/pnas.182412499 }}
*{{cite journal | author=Jung D, Fried M, Kullak-Ublick GA |title=Human apical sodium-dependent bile salt transporter gene (SLC10A2) is regulated by the peroxisome proliferator-activated receptor alpha. |journal=J. Biol. Chem. |volume=277 |issue= 34 |pages= 30559-66 |year= 2002 |pmid= 12055195 |doi= 10.1074/jbc.M203511200 }}
* {{cite journal | vauthors = Neimark E, Chen F, Li X, Shneider BL | title = Bile acid-induced negative feedback regulation of the human ileal bile acid transporter | journal = Hepatology | volume = 40 | issue = 1 | pages = 149–56 | date = July 2004 | pmid = 15239098 | doi = 10.1002/hep.20295 }}
*{{cite journal | author=Zelcer N, Saeki T, Bot I, ''et al.'' |title=Transport of bile acids in multidrug-resistance-protein 3-overexpressing cells co-transfected with the ileal Na+-dependent bile-acid transporter. |journal=Biochem. J. |volume=369 |issue= Pt 1 |pages= 23-30 |year= 2003 |pmid= 12220224 |doi= 10.1042/BJ20021081 }}
* {{cite journal | vauthors = Xia X, Roundtree M, Merikhi A, Lu X, Shentu S, Lesage G | title = Degradation of the apical sodium-dependent bile acid transporter by the ubiquitin-proteasome pathway in cholangiocytes | journal = The Journal of Biological Chemistry | volume = 279 | issue = 43 | pages = 44931–7 | date = October 2004 | pmid = 15304498 | doi = 10.1074/jbc.M400969200 }}
*{{cite journal  | author=Chumakov I, Blumenfeld M, Guerassimenko O, ''et al.'' |title=Genetic and physiological data implicating the new human gene G72 and the gene for D-amino acid oxidase in schizophrenia. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 21 |pages= 13675-80 |year= 2002 |pmid= 12364586 |doi= 10.1073/pnas.182412499 }}
* {{cite journal | vauthors = Zhang EY, Phelps MA, Banerjee A, Khantwal CM, Chang C, Helsper F, Swaan PW | title = Topology scanning and putative three-dimensional structure of the extracellular binding domains of the apical sodium-dependent bile acid transporter (SLC10A2) | journal = Biochemistry | volume = 43 | issue = 36 | pages = 11380–92 | date = September 2004 | pmid = 15350125 | doi = 10.1021/bi049270a }}
*{{cite journal | author=Dunham A, Matthews LH, Burton J, ''et al.'' |title=The DNA sequence and analysis of human chromosome 13. |journal=Nature |volume=428 |issue= 6982 |pages= 522-8 |year= 2004 |pmid= 15057823 |doi= 10.1038/nature02379 }}
* {{cite journal | vauthors = Banerjee A, Ray A, Chang C, Swaan PW | title = 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) | journal = Biochemistry | volume = 44 | issue = 24 | pages = 8908–17 | date = June 2005 | pmid = 15952798 | doi = 10.1021/bi050553s }}
*{{cite journal | author=Neimark E, Chen F, Li X, Shneider BL |title=Bile acid-induced negative feedback regulation of the human ileal bile acid transporter. |journal=Hepatology |volume=40 |issue= 1 |pages= 149-56 |year= 2004 |pmid= 15239098 |doi= 10.1002/hep.20295 }}
* {{cite journal | vauthors = Nakahara M, Furuya N, Takagaki K, Sugaya T, Hirota K, Fukamizu A, Kanda T, Fujii H, Sato R | title = 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 | journal = The Journal of Biological Chemistry | volume = 280 | issue = 51 | pages = 42283–9 | date = December 2005 | pmid = 16230354 | doi = 10.1074/jbc.M507454200 }}
*{{cite journal | author=Xia X, Roundtree M, Merikhi A, ''et al.'' |title=Degradation of the apical sodium-dependent bile acid transporter by the ubiquitin-proteasome pathway in cholangiocytes. |journal=J. Biol. Chem. |volume=279 |issue= 43 |pages= 44931-7 |year= 2004 |pmid= 15304498 |doi= 10.1074/jbc.M400969200 }}
* {{cite journal | vauthors = Bergheim I, Harsch S, Mueller O, Schimmel S, Fritz P, Stange EF | title = Apical sodium bile acid transporter and ileal lipid binding protein in gallstone carriers | journal = Journal of Lipid Research | volume = 47 | issue = 1 | pages = 42–50 | date = January 2006 | pmid = 16237211 | doi = 10.1194/jlr.M500215-JLR200 }}
*{{cite journal | author=Zhang EY, Phelps MA, Banerjee A, ''et al.'' |title=Topology scanning and putative three-dimensional structure of the extracellular binding domains of the apical sodium-dependent bile acid transporter (SLC10A2). |journal=Biochemistry |volume=43 |issue= 36 |pages= 11380-92 |year= 2004 |pmid= 15350125 |doi= 10.1021/bi049270a }}
* {{cite journal | vauthors = Banerjee A, Swaan PW | title = Membrane topology of human ASBT (SLC10A2) determined by dual label epitope insertion scanning mutagenesis. New evidence for seven transmembrane domains | journal = Biochemistry | volume = 45 | issue = 3 | pages = 943–53 | date = January 2006 | pmid = 16411770 | pmc = 2525805 | doi = 10.1021/bi052202j }}
*{{cite journal | author=Banerjee A, Ray A, Chang C, Swaan PW |title=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). |journal=Biochemistry |volume=44 |issue= 24 |pages= 8908-17 |year= 2005 |pmid= 15952798 |doi= 10.1021/bi050553s }}
*{{cite journal | author=Nakahara M, Furuya N, Takagaki K, ''et al.'' |title=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. |journal=J. Biol. Chem. |volume=280 |issue= 51 |pages= 42283-9 |year= 2006 |pmid= 16230354 |doi= 10.1074/jbc.M507454200 }}
*{{cite journal  | author=Bergheim I, Harsch S, Mueller O, ''et al.'' |title=Apical sodium bile acid transporter and ileal lipid binding protein in gallstone carriers. |journal=J. Lipid Res. |volume=47 |issue= 1 |pages= 42-50 |year= 2006 |pmid= 16237211 |doi= 10.1194/jlr.M500215-JLR200 }}
*{{cite journal  | author=Banerjee A, Swaan PW |title=Membrane topology of human ASBT (SLC10A2) determined by dual label epitope insertion scanning mutagenesis. New evidence for seven transmembrane domains. |journal=Biochemistry |volume=45 |issue= 3 |pages= 943-53 |year= 2006 |pmid= 16411770 |doi= 10.1021/bi052202j }}
}}
{{refend}}
{{refend}}


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[[Category:Solute carrier family]]
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Revision as of 06:25, 11 September 2017

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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
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The SLC10A2 (solute carrier family 10 member 2) gene in humans encodes the bile acid:sodium symporter known as the apical sodium–bile acid transporter (ASBT) or as the ileal bile acid transporter (IBAT).[1][2]

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.[3]

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,[4] and volixibat, under development for the treatment of nonalcoholic steatohepatitis.[5]

See also

References

  1. ↑ 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.
  2. ↑ "Entrez Gene: SLC10A2 solute carrier family 10 (sodium/bile acid cotransporter family), member 2".
  3. ↑ Dawson PA (2011). "Role of the intestinal bile acid transporters in bile acid and drug disposition". Handbook of Experimental Pharmacology (201): 169–203. doi:10.1007/978-3-642-14541-4_4. PMC 3249407. PMID 21103970.
  4. ↑ 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.
  5. ↑ Chitnis D (2016-08-03), "FDA grants fast track status to volixibat", Internal Medicine News Digital Network, retrieved 2016-08-14.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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