Affinage

SLC10A2

Ileal sodium/bile acid cotransporter · UniProt Q12908

Length
348 aa
Mass
37.7 kDa
Annotated
2026-06-10
95 papers in source corpus 38 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC10A2 (ASBT) is the apical sodium-dependent bile acid cotransporter that drives reclamation of bile acids from the intestinal lumen, and loss-of-function mutations in it cause primary bile acid malabsorption (PMID:9109432). The transporter adopts a 7-transmembrane topology with an exofacial N-terminus and cytosolic C-terminus (PMID:16411770), and homology to a high-resolution bacterial structure organizes the protein into a sodium-bearing core domain and a panel domain between which substrate binds in an inward-facing cavity (PMID:21976025); sodium binding shifts the conformational equilibrium toward this inward-facing state to favor cytoplasmic substrate release (PMID:33359100). Systematic cysteine-scanning of individual helices has mapped function onto specific helices: TM1, TM3, TM4, and TM7 line the substrate translocation pathway and undergo substrate-dependent conformational changes (PMID:16899538, PMID:18311924, PMID:19653651, PMID:21646357), while TM2 and TM3 residues form the sodium binding/translocation route (PMID:24045943), with EL1 residues Asp-122 sensing Na+ and Asp-124 recognizing the 7α-OH of bile acids (PMID:18508772). ASBT functions as a non-covalent homodimer/oligomer (PMID:29198943) and transports a defined panel of bile acids, including taurolithocholic acid shared across the SLC10 family (PMID:34079822). Surface expression and activity are tuned post-translationally by N-glycosylation required for stability (PMID:25855079), lipid raft association (PMID:18063707), PKC-mediated Ser335 phosphorylation (PMID:39310206), Src family kinase tyrosine phosphorylation that protects against proteasomal degradation (PMID:31194565), ubiquitin-proteasome turnover (PMID:24498857), and apical insertion dependent on the ATP8B1-CDC50A flippase heterodimer (PMID:25239307). Gene expression is governed by a transcriptional network including HNF1α and PPARα (PMID:12055195), the glucocorticoid receptor (PMID:14684580), CDX1/CDX2 (PMID:22016432), KLF9 (PMID:35105957), the FXR→SHP→FTF bile acid feedback cascade (PMID:15591588), KDM6B-mediated chromatin activation (PMID:41387297), and microbiota-dependent suppression through GATA4 (PMID:26022694). Functionally, ASBT-mediated bile acid uptake in the distal ileum activates CFTR-dependent Cl- secretion (PMID:16037545).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1997 High

    Established that SLC10A2 dysfunction directly causes a human disease by showing that specific missense mutations abolish bile acid transport without disrupting protein expression or membrane trafficking.

    Evidence Site-directed mutagenesis and taurocholate uptake assays in transfected COS cells with disease-associated alleles

    PMID:9109432

    Open questions at the time
    • Did not resolve the structural basis of the affected residues
    • Did not define the transport mechanism or sodium stoichiometry
  2. 2004 Medium

    Resolved the membrane architecture of the transporter, supporting a 7-transmembrane topology and an initial 3D model of the bile acid binding domain.

    Evidence N-glycosylation scanning mutagenesis, homology modeling, and cholic acid docking

    PMID:15350125

    Open questions at the time
    • Model not experimentally confirmed by structure
    • Topology of cytosolic loops not fully resolved
  3. 2006 High

    Definitively settled the topology debate by confirming a 7TM model and refuting the alternative 9TM configuration, and identified TM7 as part of the substrate translocation pathway.

    Evidence Dual epitope-insertion mutagenesis with confocal imaging, plus cysteine-scanning SCAM of TM7 with substrate protection in COS-1 cells

    PMID:16411770 PMID:16899538

    Open questions at the time
    • Did not localize sodium binding sites
    • Functional roles of other helices unaddressed
  4. 2008 High

    Dissected which helices and residues form the substrate path versus the sodium path, identifying Asp-122 as a Na+ sensor and Asp-124 as a 7α-OH bile acid recognition residue.

    Evidence Cysteine-scanning/SCAM of EL1 and TM4 with substrate-specificity and sodium-sensitivity kinetics

    PMID:18311924 PMID:18508772

    Open questions at the time
    • Did not provide a holistic structural model integrating all helices
    • Number and exact coordination of both Na+ ions not fully defined
  5. 2009 High

    Extended the translocation-pathway map to TM3 and identified residues forming the substrate exit route, and demonstrated PKCζ-dependent post-translational control of surface expression.

    Evidence SCAM of TM3 with kinetic analysis; PKC isoform-selective pharmacology and membrane fractionation in Caco-2 cells

    PMID:19571234 PMID:19653651

    Open questions at the time
    • Direct phosphorylation target of PKCζ not defined here
    • Vesicular recycling machinery not identified
  6. 2011 High

    Provided the structural framework for the elevator mechanism via a substrate-bound bacterial homologue crystal structure, while helix-level mutagenesis assigned TM1 to both sodium co-transport and folding.

    Evidence X-ray crystallography of ASBT_NM with taurocholate; SCAM of TM1 with sodium/substrate kinetics and proteasome-inhibitor folding rescue

    PMID:21646357 PMID:21976025

    Open questions at the time
    • Structure is of a bacterial monomer, not human ASBT
    • Oligomeric state of human transporter unresolved at this point
  7. 2013 Medium

    Completed the helix-by-helix functional map by assigning TM2 to the sodium pathway and TM5 to helix-helix packing rather than direct translocation.

    Evidence SCAM/mutagenesis of TM2 and TM5 with sodium kinetics, conservative substitutions, and 3D modeling

    PMID:23815591 PMID:24045943

    Open questions at the time
    • TM5 not tested by direct SCAM accessibility
    • Inter-helix dynamics during transport not directly observed
  8. 2017 High

    Resolved the oligomeric organization of the human transporter, demonstrating functional non-covalent homodimers/oligomers independent of cysteine residues.

    Evidence Cross-linking, reciprocal co-IP of differentially tagged constructs, and dominant-negative functional assays

    PMID:29198943

    Open questions at the time
    • Dimer interface residues not mapped
    • Apparent conflict with monomeric bacterial homologue not reconciled
  9. 2021 High

    Defined the sodium-driven conformational mechanism of the homologue and benchmarked human ASBT substrate/inhibitor selectivity within the SLC10 family.

    Evidence SDAF and DEER EPR on ASBT_NM; comparative substrate/inhibitor profiling of NTCP, ASBT, SOAT in stable HEK293 cells

    PMID:33359100 PMID:34079822

    Open questions at the time
    • Conformational dynamics not measured on human ASBT directly
    • Structural basis of inhibitor selectivity unresolved
  10. 2024 Medium

    Identified Ser335 as the predominant PKC phosphosite controlling ASBT activity, providing site-level resolution of post-translational regulation.

    Evidence Parallel reaction monitoring targeted mass spectrometry with kinase modulation and uptake assays

    PMID:39310206

    Open questions at the time
    • Responsible PKC isoform at Ser335 not definitively assigned
    • Single study, mechanism linking phosphorylation to activity unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse post-translational inputs (glycosylation, raft association, tyrosine/serine phosphorylation, ubiquitination, flippase-dependent insertion) are coordinated in vivo, and a high-resolution structure of human ASBT, remain to be established.
  • No human ASBT structure in the corpus
  • Integration of competing regulatory signals not modeled
  • Dimer interface and physiological role of oligomerization undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0140104 molecular carrier activity 3 GO:0008289 lipid binding 2
Localization
GO:0005886 plasma membrane 5
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-382551 Transport of small molecules 3
Partners
ATP8B1CDC50A

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Loss-of-function mutations in SLC10A2 (L243P, T262M, and double mutant L243P/T262M) abolish taurocholate and bile acid transport without affecting transporter protein expression or trafficking to the plasma membrane, establishing that these residues are critical for transport activity. A171S had no effect on transport. A frame-shift mutation (646insG) also abolished transport in transfected COS cells. Site-directed mutagenesis, transfection in COS cells, taurocholate uptake assays, protein expression/trafficking analysis The Journal of clinical investigation High 9109432
2011 Crystal structure of the bacterial homologue of ASBT from Neisseria meningitidis (ASBT_NM) at 2.2 Å reveals two inverted structural repeats of five transmembrane helices, a core domain harboring two sodium ions, and a 'panel' domain. Taurocholate substrate is bound between the core and panel domains in an inward-facing hydrophobic cavity, suggesting a transport mechanism involving movements between these domains. X-ray crystallography at 2.2 Å resolution with substrate taurocholate co-crystallized Nature High 21976025
2004 Membrane topology of hASBT determined by N-glycosylation scanning mutagenesis supports a 7-transmembrane domain configuration, with extracellular loops 1 and 3 containing glycosylation-accessible reporter sites. A 3D model was built and site-directed mutagenesis of the predicted bile acid binding domain (including P290S pathological mutation) validated the model. N-glycosylation scanning mutagenesis, 3D homology modeling, site-directed mutagenesis, cholic acid docking Biochemistry Medium 15350125
2006 Dual label epitope insertion scanning mutagenesis confirmed a 7-transmembrane topology for hASBT, with extracellular loops 1 (residues 99-130), 2 (180-191), and 3 (253-287) and cytosolic localization of loops in the 7TM model. N-terminus is exofacial and C-terminus is cytosolic. This refutes the previously proposed 9TM model. Dual label epitope (HA and FLAG) insertion mutagenesis, cell surface biotinylation, confocal microscopy in permeabilized and non-permeabilized COS-1 and MDCK cells Biochemistry High 16411770
2006 Cysteine-scanning mutagenesis of TM7 of hASBT showed that TM7 lines the substrate translocation pathway. Residues in the extracellular half of TM7 are accessible to membrane-impermeant MTSES and MTSET, while the entire TM7 length is accessible to MTSEA. Substrate co-application significantly amended MTSEA sensitivity, consistent with conformational changes during transport. Loss-of-function mutants T289C, Y293C, Q297C, and A301C are MTS-inaccessible, suggesting a structural role. Cysteine-scanning mutagenesis, SCAM (substituted cysteine accessibility method) with MTSEA/MTSET/MTSES in COS-1 cells, taurocholate uptake assay Molecular pharmacology High 16899538
2005 Cysteine scanning mutagenesis identified C51A/T, C105A/T, C144A, and C255A/T as loss-of-function mutations in hASBT, and C74A/T abolishes cell surface expression suggesting a role in protein folding/trafficking. C270A remains functional and insensitive to polar MTS reagents but shows decreased K_T and J_max with cholyl- and chenodeoxycholyl-MTS conjugates, implicating C270 in a putative substrate binding domain. Ala/Thr scanning mutagenesis of all Cys residues, MTS bile acid conjugate affinity inactivators, taurocholate transport assays Biochemistry High 15952798
2008 Conserved residue Asp-122 in extracellular loop 1 of ASBT functions as a Na+ sensor (binding one of two co-transported Na+ ions), and Asp-124 interacts with 7α-OH groups of bile acids. Neutralization of charge at Asp-120 and Asp-122 abolishes transport, while D124A yields a functionally active transporter with low affinity for common bile acids except deoxycholic acid (which lacks a 7α-OH group). Cysteine-scanning mutagenesis of EL1 residues V99-S126, thiol modification, taurocholate uptake assay, in silico modeling The Journal of biological chemistry High 18508772
2008 Cysteine-scanning mutagenesis of TM4 (21 amino acids) of hASBT showed that primarily the cytosolic half is solvent-accessible via MTSES and MTSET modification, implicating it in substrate translocation. TM4 mutants were not sensitive to equilibrative sodium conditions, ruling out a direct role for TM4 in sodium translocation. Cysteine-scanning mutagenesis of TM4, MTS reagent accessibility (MTSES/MTSET), cell surface expression assays, taurocholate uptake Biochemistry High 18311924
2009 Cysteine-scanning mutagenesis of TM3 (V127-T149) showed that the cytosolic half forms portions of the substrate exit route. Residues S128C and L145C-T149C are solvent-accessible and show significant loss of taurocholate affinity. P142 is structurally and functionally important during the transport cycle (P142C mutation severely decreases activity). Cysteine-scanning mutagenesis of TM3, SCAM with MTS reagents, kinetic analysis (K_T and J_max) for taurocholate Biochemistry High 19653651
2011 Cysteine-scanning mutagenesis of TM1 (I29-G50) showed that TM1 plays a pivotal role in hASBT function and stability. G50 is involved in protein folding (G50C/A expression rescued by MG132 and cyclosporine A but not FK506). Residues L30, L38, T39, and M46 participate in sodium co-transport, while L34, T36, and L38 show temperature-dependent substrate protection from MTSET, indicating conformational changes in TM1 during transport. Cysteine-scanning mutagenesis, SCAM with MTSET, proteasome inhibitor rescue (MG132), cyclosporine A treatment, kinetic analysis The Journal of biological chemistry High 21646357
2013 Cysteine-scanning mutagenesis of TM2 (systematic approach) showed that TM2 is inaccessible to membrane-impermeant MTSET, indicating it does not directly form the bile acid translocation pathway. Kinetic studies identified residues Q75, F76, M79, G83, L86, F90, and D91 as sodium-sensitive, and computational analysis suggests D91 coordinates sodium during transport. TM2 residues likely form the sodium binding and translocation pathway together with TM3 residues. Cysteine-scanning mutagenesis of TM2, MTSET accessibility, sodium dependence kinetics, computational analysis The Journal of biological chemistry High 24045943
2013 Cysteine-scanning mutagenesis of TM5 showed that residues G197 and G201 form a GxxxG motif important for helix-helix interactions with TM4 (interacting with G179 and P175), and G212 interacts with G237 in a GxxxG domain in TM6. TM5 residues are critical for ASBT function but are not directly involved in substrate translocation pathway. Cysteine-scanning mutagenesis of TM5, alanine conservative mutations, cell surface expression, taurocholate uptake, 3D modeling Biochemistry Medium 23815591
2002 The human ASBT gene promoter contains three functional HNF1α recognition sites essential for expression, and a DR1 motif ~1.6 kb upstream that binds PPARα/RXR heterodimer. PPARα ligands (WY14643, ciprofibrate) transactivate ASBT promoter constructs in Caco2 cells; targeted mutagenesis of the DR1 motif abolished PPARα responsiveness. Ciprofibrate treatment of SK-ChA cholangiocytes increased ASBT mRNA. Promoter-reporter (luciferase) assays, targeted mutagenesis of DR1 motif, EMSA, PPARα ligand treatment, mRNA analysis The Journal of biological chemistry High 12055195
2004 Human ASBT is transactivated by the glucocorticoid receptor (GR). Two glucocorticoid response elements (IR3 elements, inverted hexanucleotide repeats) in the ASBT promoter confer inducibility by GR and dexamethasone. These elements bind GR in EMSA. In vivo, budesonide treatment increased ASBT protein expression in healthy volunteers. Luciferase reporter assays with GR co-expression, EMSA, western blot of human ileal biopsies, in vivo budesonide treatment Gut High 14684580
2005 FXR-activating bile acids repress rabbit ASBT expression via the cascade FXR→SHP→FTF. A cis-acting FTF binding element in the rabbit ASBT promoter (-1166/-1158) mediates this regulation. FTF stimulates ASBT promoter 4-fold; increasing SHP protein inhibits FTF-dependent transactivation. Only FXR-activating ligands (DCA, CDCA, CA) repress ASBT; non-FXR ligands (UDCA, UCA) do not. In vivo rabbit feeding experiments, 5'-flanking ASBT promoter cloning, luciferase reporter assays in Caco-2 cells, SHP overexpression, FTF site deletion mutagenesis American journal of physiology. Gastrointestinal and liver physiology High 15591588
2011 CDX1 and CDX2 transcription factors transcriptionally activate the human ASBT promoter. Six CDX binding sites within the ASBT promoter were verified by EMSA in vitro and chromatin immunoprecipitation in living cells. siRNA knockdown of CDX1/2 reduced ASBT mRNA expression in intestinal cells. siRNA knockdown, luciferase reporter assays, EMSA, chromatin immunoprecipitation (ChIP), real-time PCR in human biopsies American journal of physiology. Gastrointestinal and liver physiology High 22016432
2009 PKCζ (an atypical PKC isoform) mediates posttranscriptional regulation of ileal ASBT function and membrane expression. PMA (PKC activator) inhibits ASBT-mediated taurocholate uptake in Caco-2 cells; inhibition is blocked by bisindolylmaleimide I (PKC inhibitor) and myristoylated PKCζ pseudosubstrate peptide but not by Ca2+ chelation or PI3K inhibition. PMA decreases transporter V_max and reduces ASBT plasma membrane content, suggesting vesicular recycling. Taurocholate uptake assay in Caco-2 cells, PKC inhibitors (bisindolylmaleimide I, PKCζ pseudosubstrate), kinetic analysis (V_max), plasma membrane fractionation/immunoblot American journal of physiology. Gastrointestinal and liver physiology Medium 19571234
2007 ASBT associates with lipid raft microdomains in plasma membrane. Depletion of membrane cholesterol with methyl-β-cyclodextrin (MβCD) disrupts lipid raft association of ASBT and significantly reduces ASBT activity (decreased V_max) without altering plasma membrane expression. Cholesterol repletion with MβCD-cholesterol complexes restores activity. Optiprep density gradient flotation of lipid rafts, MβCD cholesterol depletion, taurocholate uptake kinetics, plasma membrane expression by biotinylation in HEK-293 cells stably transfected with ASBT, Caco-2 cells, and human ileal brush-border membrane vesicles American journal of physiology. Gastrointestinal and liver physiology Medium 18063707
2010 EGCG (epigallocatechin-3-gallate) inhibits ASBT activity by displacing ASBT from lipid raft fractions of the plasma membrane into detergent-soluble fractions, reducing V_max without changing total ASBT content on plasma membrane. Inhibition of PKC, PI3K, and MAPK pathways did not block EGCG effect. Taurocholate uptake assay, kinetic analysis, Optiprep density gradient fractionation, plasma membrane biotinylation, pathway inhibitor studies in HEK-293/ASBT cells and Caco-2 American journal of physiology. Gastrointestinal and liver physiology Medium 20056894
2012 Enteropathogenic E. coli (EPEC) inhibits ileal ASBT function via its type-III secretion system (TTSS) and bundle-forming pili. Mutations in escN, espA, espB, espD (TTSS components) and BFP (pili) gene ablate EPEC inhibitory effects on ASBT. EPEC inhibition is associated with decreased V_max and reduced ASBT plasma membrane levels, and is blocked by protein tyrosine phosphatase inhibitors. Taurocholate uptake in Caco-2 and HEK-293/ASBT cells infected with EPEC and TTSS/BFP mutant strains, kinetic analysis, plasma membrane expression, tyrosine phosphatase inhibitors American journal of physiology. Gastrointestinal and liver physiology Medium 22403793
2014 The lipid flippase heterodimer ATP8B1-CDC50A is essential for apical membrane insertion and surface expression of SLC10A2/ASBT in intestinal Caco-2 cells. ATP8B1 depletion strongly impairs SLC10A2-mediated bile salt uptake and reduces apical membrane localization of SLC10A2, caused by impaired apical membrane insertion (not reduced synthesis). Endogenous ATP8B1 exists in a functional heterodimer with CDC50A in Caco-2 cells. siRNA depletion of ATP8B1 in Caco-2 cells, bile salt uptake assay, apical membrane biotinylation, co-immunoprecipitation of ATP8B1-CDC50A, fecal bile salt analysis from PFIC1 patients Biochimica et biophysica acta High 25239307
2014 Resveratrol promotes ASBT protein degradation via the ubiquitin-proteasome pathway in a SIRT1-independent manner. Proteasome inhibitors MG132 and lactacystin, and ubiquitin inhibitor LDN57444, reverse RSV-mediated ASBT inhibition. Immunoprecipitation revealed high levels of ubiquitinated ASBT after RSV treatment. The effect is specific to ASBT; NTCP, OSTα, and ABCG1 are unaffected. Phosphorylation at the corresponding residues of rat Ser335/Thr339 does not contribute to RSV-mediated degradation. Proteasome inhibitor rescue assays, ubiquitin inhibitor, co-immunoprecipitation for ubiquitinated ASBT, site-directed mutagenesis of phosphorylation sites, transporter expression/function assays The Biochemical journal Medium 24498857
2015 N-glycosylation of ASBT is essential for function and protein stability but not for targeting to the plasma membrane. Fully mature N-acetylglucosamine-rich ASBT (41 kDa band) and core mannose-rich glycoprotein (35 kDa band) are present. The N10Q glycosylation-deficient mutant reaches the plasma membrane but has reduced half-life and increased trypsin susceptibility. High glucose increases mature glycosylated ASBT along with increased ASBT function. Tunicamycin treatment, PNGase F and Endo H glycosidase treatment, N10Q mutant expression, pulse-chase/half-life analysis, protease susceptibility assay, taurocholate uptake American journal of physiology. Cell physiology Medium 25855079
2017 hASBT forms functional non-covalent homodimers and higher-order oligomers, independent of endogenous cysteine residues. Chemical cross-linking and co-immunoprecipitation of differentially tagged (HA, FLAG) wild-type and cysteine-less hASBT confirmed dimerization. Cysteine-less hASBT showed dominant-negative effect when co-expressed with wild-type hASBT, validating functional heterodimerization/oligomerization. Site-directed mutagenesis (all 13 cysteines mutated stepwise), chemical cross-linking, co-immunoprecipitation of HA-/FLAG-tagged species, dominant-negative functional assay Biochimica et biophysica acta. Biomembranes High 29198943
2019 Tyrosine phosphorylation mediated by Src family kinases (SFKs) regulates surface expression, function, and stability of hASBT. SFK inhibition (PP2) reduces hASBT function and surface expression, rescued by proteasome inhibitor MG132, indicating dephosphorylation leads to proteasome-dependent degradation. Five intracellular tyrosine residues (Y148, Y216, Y308, Y311, Y337) individually alter ASBT function without changing total cellular expression; sequential mutation of all five renders ASBT nonfunctional with diminished expression. SFK inhibitor PP2, PTP inhibitor orthovanadate, proteasome inhibitor MG132, site-directed mutagenesis of five intracellular Tyr residues, taurocholate transport assays, surface expression measurements Molecular pharmaceutics Medium 31194565
2024 PKC regulates hASBT activity by phosphorylation at Ser335, established as the predominant phosphosite. Parallel reaction monitoring targeted mass spectrometry identified phosphorylation at Thr330, Ser334, and Ser335, with Ser335 being dominant. A proportional relationship between Ser335 phosphorylation level and ASBT bile acid uptake activity was demonstrated. Parallel reaction monitoring (PRM) targeted mass spectrometry, kinase inhibitor/activator treatments, phosphorylation site-specific analysis, bile acid uptake activity assay ACS omega Medium 39310206
2005 ASBT-mediated bile salt (taurocholate) absorption in the distal ileum triggers CFTR activation and consequent Cl- secretion. TC-evoked Cl- secretion was abrogated in Cftr-null mice, blocked by a selective ASBT inhibitor, and was restricted to the distal ileum. The mechanism involves CFTR channel gating modulation rather than changes in driving force, and is independent of cAMP/cGMP signaling. Short circuit current measurements across ileal tissue, Cftr-null mice, cGMP-dependent kinase II-null mice, ASBT inhibitor, neurotransmitter/prostaglandin suppression, nystatin permeabilization, H89 (PKA inhibitor) American journal of physiology. Gastrointestinal and liver physiology High 16037545
2015 Gut microbiota suppresses intestinal Asbt expression via the transcription factor Gata4. In germ-free or antibiotic-treated mice, Asbt expression increased in the ileum and extended more proximally in the small intestine. Genetic inactivation of either Asbt or Gata4 prevented most metabolic effects of antibiotic treatment on bile acid homeostasis, establishing Gata4 as a mediator of microbiota-dependent Asbt suppression. Germ-free and antibiotic-treated mouse models, Asbt-KO mice, intestinal-specific Gata4-iKO mice, gene expression analysis, metabolic profiling Journal of hepatology High 26022694
2009 Mutational analysis of conserved uncharged polar residues and proline in mouse Slc10a2 (Thr130-Pro142 region) revealed that T130A causes loss of cell surface localization, P142V abolishes almost all transport activity, and T134A affects taurocholic acid affinity. This region contains residues involved in substrate interaction, function, and cellular localization. Site-directed mutagenesis of conserved residues in mouse Slc10a2, taurocholic acid uptake assay, cell surface localization assessment Bioscience, biotechnology, and biochemistry Medium 19584562
2013 Mutational analysis of conserved proline and uncharged polar residues in mouse Slc10a2 (Pro107-Ser128 region) revealed that P107N/L impairs cell surface localization, S126A completely impairs cellular expression, S112A abolishes transport activity while maintaining surface expression, and T110A/S128A mutations enhance membrane expression. Tyr117 mutations show reduced activity proportional to side chain van der Waals volume. Site-directed mutagenesis, taurocholate uptake assay, cell surface localization assessment in heterologous expression system BMC physiology Medium 23374508
2011 SLC10A2 coding region variants 292G>A and 431G>A show partially impaired taurocholate transport in vitro, and a novel variant 790A>G shows near complete loss of taurocholate transport, without affecting protein expression or cell surface trafficking. PCR-based temperature gradient capillary electrophoresis (TGCE) for SNP identification, heterologous expression, taurocholate transport assay, western blot, immunofluorescence confocal microscopy Journal of gastroenterology and hepatology Medium 21649730
2021 Systematic comparative transport experiments with NTCP, ASBT, and SOAT using stably transfected HEK293 cells identified taurolithocholic acid (TLC) as the first common substrate of all three SLC10 carriers (K_m values: NTCP 18.4 μM, ASBT 5.9 μM, SOAT 19.3 μM). Lithocholic acid was the only bile acid not transported by any. Troglitazone, BSP, and erythrosine B were pan-SLC10 inhibitors, while cyclosporine A, irbesartan, and others only inhibited NTCP and SOAT but not ASBT. Stably transfected HEK293 cells (NTCP-, ASBT-, SOAT-), transport assays with >20 substrates, inhibition experiments Frontiers in molecular biosciences Medium 34079822
2021 The bacterial ASBT homologue ASBT_NM is a monomer (not a dimer or trimer as expected for elevator-type transporters). Na+ ions shift the conformational equilibrium toward the inward-facing state, facilitating cytoplasmic uptake of substrate. Site-directed alkylation monitored by in-gel fluorescence (SDAF) and DEER EPR spectroscopy validated the conformational states. Site-directed alkylation with in-gel fluorescence (SDAF), crosslinking experiments, DEER (double electron-electron resonance) EPR spectroscopy Journal of molecular biology High 33359100
2010 Ileal SLC10A2 mRNA and protein levels are significantly increased by antibiotic-mediated reduction of enterobacteria in mice (FXR-independent), with increased bile acid concentrations in portal blood. Re-administration of taurodeoxycholic acid or cholic acid (enterobacteria-biotransformed bile acids) to antibiotic-treated mice decreased ileal SLC10A2 expression, suggesting that enterobacteria-mediated bile acid biotransformation modulates SLC10A2 expression. Antibiotic treatment of C57BL/6N and FXR-null mice, ileal SLC10A2 mRNA/protein measurement, portal blood bile acid measurement, bile acid re-administration experiments The Journal of pharmacology and experimental therapeutics Medium 20884752
2010 ASBT expression and promoter activity are significantly decreased by insulin in Caco-2 cells. In streptozotocin-induced diabetic rats, ASBT mRNA and protein are significantly elevated, and ileal Na+-dependent taurocholate uptake is increased. Insulin treatment of diabetic rats reversed increased ASBT protein expression to control levels. STZ-induced diabetes in rats, Western blot, real-time qRT-PCR, isolated intestinal epithelial cell taurocholate uptake, Caco-2 promoter activity assays with insulin treatment American journal of physiology. Gastrointestinal and liver physiology Medium 20651004
2022 KDM6B histone demethylase directly transcriptionally activates SLC10A2; KDM6B loss increases H3K27me3 repression at the SLC10A2 promoter, activating the ERK/AP-1 pathway and CXCL/CXCR2-dependent MDSC recruitment in colorectal cancer. Intestinal epithelial-specific KDM6B deletion mouse model, ChIP for H3K27me3 at SLC10A2 promoter, ERK/AP-1 pathway analysis, MDSC recruitment assays Advanced science Medium 41387297
2022 Transcription factor KLF9 promotes intestinal Asbt expression in the terminal ileum to enhance bile acid absorption. Klf9 knockout mice show increased bile acids in gallbladder and feces with decreased serum BA levels; intestine-specific Klf9 deletion recapitulates this phenotype. Klf9 transgenic mice show the opposite. Biochemical and molecular assays confirmed KLF9 directly promotes Asbt expression. Systemic Klf9-/- mice, intestine-specific Klf9vil-/- mice, intestinal Klf9 transgenic mice, biochemical/molecular/functional assays for Asbt expression and bile acid homeostasis Acta pharmacologica Sinica High 35105957
2023 Apple-derived extracellular vesicles (APEVs) downregulate ASBT/SLC10A2 expression indirectly by reducing RARα/NR1B1 protein expression. APEVs decrease binding of RARα to the SLC10A2 promoter. MicroRNAs in APEVs reduce NR1B1 mRNA stability by targeting its 3'UTR, and apple microRNA mimics suppress NR1B1 mRNA expression. Proteomics, RARα binding to SLC10A2 promoter assay, NR1B1-3'UTR reporter assay, apple microRNA mimic transfection, ASBT expression and uptake activity Drug metabolism and pharmacokinetics Low 37517353

Source papers

Stage 0 corpus · 95 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2). The Journal of clinical investigation 282 9109432
2011 Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT. Nature 225 21976025
2004 Human ileal bile acid transporter gene ASBT (SLC10A2) is transactivated by the glucocorticoid receptor. Gut 167 14684580
2006 Apical sodium dependent bile acid transporter (ASBT, SLC10A2): a potential prodrug target. Molecular pharmaceutics 133 16749855
2015 Gut microbiota inhibit Asbt-dependent intestinal bile acid reabsorption via Gata4. Journal of hepatology 102 26022694
2021 ABO blood group and COVID-19: a review on behalf of the ISBT COVID-19 Working Group. Vox sanguinis 100 33578447
2002 Human apical sodium-dependent bile salt transporter gene (SLC10A2) is regulated by the peroxisome proliferator-activated receptor alpha. The Journal of biological chemistry 88 12055195
1996 Practical guidelines for process validation and process control of white cell-reduced blood components: report of the Biomedical Excellence for Safer Transfusion (BEST) Working Party of the International Society of Blood Transfusion (ISBT). Transfusion 88 8607148
2011 Genetic polymorphisms in Na+-taurocholate co-transporting polypeptide (NTCP) and ileal apical sodium-dependent bile acid transporter (ASBT) and ethnic comparisons of functional variants of NTCP among Asian populations. Xenobiotica; the fate of foreign compounds in biological systems 84 21341987
2005 FXR-activating ligands inhibit rabbit ASBT expression via FXR-SHP-FTF cascade. American journal of physiology. Gastrointestinal and liver physiology 74 15591588
2020 ASBT(SLC10A2): A promising target for treatment of diseases and drug discovery. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 68 33035828
2017 An important intestinal transporter that regulates the enterohepatic circulation of bile acids and cholesterol homeostasis: The apical sodium-dependent bile acid transporter (SLC10A2/ASBT). Clinics and research in hepatology and gastroenterology 66 28336180
2005 Adaptive regulation of the ileal apical sodium dependent bile acid transporter (ASBT) in patients with obstructive cholestasis. Gut 62 16150853
2004 Topology scanning and putative three-dimensional structure of the extracellular binding domains of the apical sodium-dependent bile acid transporter (SLC10A2). Biochemistry 58 15350125
2022 Maralixibat for the treatment of PFIC: Long-term, IBAT inhibition in an open-label, Phase 2 study. Hepatology communications 51 35507739
2015 Slc10a2-null mice uncover colon cancer-promoting actions of endogenous fecal bile acids. Carcinogenesis 48 26210740
2010 Green tea catechin EGCG inhibits ileal apical sodium bile acid transporter ASBT. American journal of physiology. Gastrointestinal and liver physiology 44 20056894
2006 Membrane topology of human ASBT (SLC10A2) determined by dual label epitope insertion scanning mutagenesis. New evidence for seven transmembrane domains. Biochemistry 41 16411770
2010 Enterobacteria modulate intestinal bile acid transport and homeostasis through apical sodium-dependent bile acid transporter (SLC10A2) expression. The Journal of pharmacology and experimental therapeutics 40 20884752
2007 Modulation of ileal bile acid transporter (ASBT) activity by depletion of plasma membrane cholesterol: association with lipid rafts. American journal of physiology. Gastrointestinal and liver physiology 39 18063707
2015 Enhanced antitumour drug delivery to cholangiocarcinoma through the apical sodium-dependent bile acid transporter (ASBT). Journal of controlled release : official journal of the Controlled Release Society 38 26278512
2016 BAT117213: Ileal bile acid transporter (IBAT) inhibition as a treatment for pruritus in primary biliary cirrhosis: study protocol for a randomised controlled trial. BMC gastroenterology 35 27431238
2022 Bile Acid Conjugation on Solid Nanoparticles Enhances ASBT-Mediated Endocytosis and Chylomicron Pathway but Weakens the Transcytosis by Inducing Transport Flow in a Cellular Negative Feedback Loop. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 34 35652273
2014 The lipid flippase heterodimer ATP8B1-CDC50A is essential for surface expression of the apical sodium-dependent bile acid transporter (SLC10A2/ASBT) in intestinal Caco-2 cells. Biochimica et biophysica acta 34 25239307
2017 Roles of Ileal ASBT and OSTα-OSTβ in Regulating Bile Acid Signaling. Digestive diseases (Basel, Switzerland) 32 28249269
2012 Inhibition of intestinal bile acid transporter Slc10a2 improves triglyceride metabolism and normalizes elevated plasma glucose levels in mice. PloS one 32 22662222
2006 Transmembrane domain VII of the human apical sodium-dependent bile acid transporter ASBT (SLC10A2) lines the substrate translocation pathway. Molecular pharmacology 32 16899538
2005 Activation of CFTR by ASBT-mediated bile salt absorption. American journal of physiology. Gastrointestinal and liver physiology 32 16037545
2018 A novel ASBT inhibitor, IMB17-15, repressed nonalcoholic fatty liver disease development in high-fat diet-fed Syrian golden hamsters. Acta pharmacologica Sinica 31 30573812
2022 Systemic ASBT inactivation protects against liver damage in obstructive cholestasis in mice. JHEP reports : innovation in hepatology 30 36160754
2011 Barley intake induces bile acid excretion by reduced expression of intestinal ASBT and NPC1L1 in C57BL/6J mice. Journal of agricultural and food chemistry 30 21591702
2009 A variant of the SLC10A2 gene encoding the apical sodium-dependent bile acid transporter is a risk factor for gallstone disease. PloS one 30 19823678
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 30 15952798
2001 Analysis of the ileal bile acid transporter gene, SLC10A2, in subjects with familial hypertriglyceridemia. Arteriosclerosis, thrombosis, and vascular biology 30 11742882
2012 Enteropathogenic Escherichia coli inhibits ileal sodium-dependent bile acid transporter ASBT. American journal of physiology. Gastrointestinal and liver physiology 29 22403793
2014 Prednisolone increases enterohepatic cycling of bile acids by induction of Asbt and promotes reverse cholesterol transport. Journal of hepatology 28 24681341
2018 Bexarotene inhibits the viability of non-small cell lung cancer cells via slc10a2/PPARγ/PTEN/mTOR signaling pathway. BMC cancer 26 29642873
2011 Functional characterization of genetic variants in the apical sodium-dependent bile acid transporter (ASBT; SLC10A2). Journal of gastroenterology and hepatology 26 21649730
2009 Modulation of ileal apical Na+-dependent bile acid transporter ASBT by protein kinase C. American journal of physiology. Gastrointestinal and liver physiology 26 19571234
2021 Substrate Specificities and Inhibition Pattern of the Solute Carrier Family 10 Members NTCP, ASBT and SOAT. Frontiers in molecular biosciences 25 34079822
2014 Resveratrol promotes degradation of the human bile acid transporter ASBT (SLC10A2). The Biochemical journal 23 24498857
2012 Evolution of substrate specificity for the bile salt transporter ASBT (SLC10A2). Journal of lipid research 22 22669917
2015 N-glycosylation is essential for ileal ASBT function and protection against proteases. American journal of physiology. Cell physiology 21 25855079
2011 Regulation of the gene encoding the intestinal bile acid transporter ASBT by the caudal-type homeobox proteins CDX1 and CDX2. American journal of physiology. Gastrointestinal and liver physiology 21 22016432
2018 Reduced adiposity by compensatory WAT browning upon iBAT removal in mice. Biochemical and biophysical research communications 18 29775611
2008 Cytosolic half of transmembrane domain IV of the human bile acid transporter hASBT (SLC10A2) forms part of the substrate translocation pathway. Biochemistry 18 18311924
2009 Mutation screening of apical sodium-dependent bile acid transporter (SLC10A2): novel haplotype block including six newly identified variants linked to reduced expression. Human genetics 17 19184108
1994 Review of the problems involved in using enzymes in blood group serology--provision of freeze-dried ICSH/ISBT protease enzyme and anti-D reference standards. International Council for Standardization in Haematology. International Society of Blood Transfusion. Vox sanguinis 17 7975466
2018 Do the Effects of Resveratrol on Thermogenic and Oxidative Capacities in IBAT and Skeletal Muscle Depend on Feeding Conditions? Nutrients 16 30301195
2017 Human bile acid transporter ASBT (SLC10A2) forms functional non-covalent homodimers and higher order oligomers. Biochimica et biophysica acta. Biomembranes 16 29198943
2008 Conserved aspartic acid residues lining the extracellular loop 1 of sodium-coupled bile acid transporter ASBT Interact with Na+ and 7alpha-OH moieties on the ligand cholestane skeleton. The Journal of biological chemistry 16 18508772
2020 Attenuation of the Hepatoprotective Effects of Ileal Apical Sodium Dependent Bile Acid Transporter (ASBT) Inhibition in Choline-Deficient L-Amino Acid-Defined (CDAA) Diet-Fed Mice. Frontiers in medicine 15 32158763
2011 Transmembrane helix 1 contributes to substrate translocation and protein stability of bile acid transporter SLC10A2. The Journal of biological chemistry 14 21646357
1982 The effects of pre- and postweaning dietary protein levels of mitochondrial metabolism in developing liver and interscapular brown adipose tissue (IBAT) in rats. The Journal of nutrition 14 7097364
2023 tDCS Regulates ASBT-3-OxoLCA-PLOD2-PTEN Signaling Pathway to Confer Neuroprotection Following Rat Cerebral Ischemia-Reperfusion Injury. Molecular neurobiology 13 37477767
2019 Tyrosine Phosphorylation Regulates Plasma Membrane Expression and Stability of the Human Bile Acid Transporter ASBT (SLC10A2). Molecular pharmaceutics 13 31194565
2010 Ileal apical Na+-dependent bile acid transporter ASBT is upregulated in rats with diabetes mellitus induced by low doses of streptozotocin. American journal of physiology. Gastrointestinal and liver physiology 13 20651004
2009 The cytosolic half of helix III forms the substrate exit route during permeation events of the sodium/bile acid cotransporter ASBT. Biochemistry 13 19653651
2023 Apple-derived extracellular vesicles modulate the expression of human intestinal bile acid transporter ASBT/SLC10A2 via downregulation of transcription factor RARα. Drug metabolism and pharmacokinetics 12 37517353
2013 Transmembrane domain V plays a stabilizing role in the function of human bile acid transporter SLC10A2. Biochemistry 12 23815591
1998 Report on the 1997 International Society of Blood Transfusion Workshop for Genotyping of Platelet Alloantigens. Platelet and Granulocyte Workshop ISBT. Transfusion medicine (Oxford, England) 12 9675789
2024 Coordinated ASBT and EGFR Mechanisms for Optimized Liraglutide Nanoformulation Absorption in the GI Tract. International journal of nanomedicine 11 38544951
2024 Exposure of Mice to a PFAS Mixture and Outcomes Related to Circulating Lipids, Bile Acid Excretion, and the Intestinal Transporter ASBT. Environmental health perspectives 11 39177951
2012 The JR blood group system (ISBT 032): molecular characterization of three new null alleles. Transfusion 11 23066723
2024 Pulsatilla decoction alleviates DSS-induced UC by activating FXR-ASBT pathways to ameliorate disordered bile acids homeostasis. Frontiers in pharmacology 10 38974033
2021 SLC10A2 deficiency-induced congenital chronic bile acid diarrhea and stunting. Molecular genetics & genomic medicine 10 34192422
1987 The Yt blood group system (ISBT No. 011). Genetic studies. Vox sanguinis 10 3477904
2022 Transcription factor Klf9 controls bile acid reabsorption and enterohepatic circulation in mice via promoting intestinal Asbt expression. Acta pharmacologica Sinica 9 35105957
2020 Mechanism of Asbt (Slc10a2)-related bile acid malabsorption in diarrhea after pelvic radiation. International journal of radiation biology 9 31900034
2017 Irinotecan-induced bile acid malabsorption is associated with down-regulation of ileal Asbt (Slc10a2) in mice. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 9 28288854
2013 Homologue gene of bile acid transporters ntcp, asbt, and ost-alpha in rainbow trout Oncorhynchus mykiss: tissue expression, effect of fasting, and response to bile acid administration. Fish physiology and biochemistry 9 24026769
2013 Transmembrane domain II of the human bile acid transporter SLC10A2 coordinates sodium translocation. The Journal of biological chemistry 9 24045943
2023 Enhancing oral bioavailability of insulin through bilosomes: Implication of charge and chain length on apical sodium-dependent bile acid transporter (ASBT) uptake. International journal of biological macromolecules 8 37640185
2011 Effects of SLC10A2 variant rs9514089 on gallstone risk and serum cholesterol levels- meta-analysis of three independent cohorts. BMC medical genetics 8 22093174
2007 Implementation of ISBT 128, a quality system, a standardized bar code labeling of blood products worldwide, electronic transfusion pathway: four years of experience in Norway. Transfusion 8 17725733
2010 ISBT 128: a global information standard. Cell and tissue banking 7 20652420
2020 Adenosine A2A receptor activation prevents DOCA-salt induced hypertensive cardiac remodeling via iBAT. Biochemical and biophysical research communications 6 32087969
2017 Altered expression of the Olr59, Ethe1, and Slc10a2 genes in the liver of F344 rats by neonatal thyroid hormone disruption. Journal of applied toxicology : JAT 6 28299817
2009 Mutational analysis of uncharged polar residues and proline in the distal one-third (Thr130-Pro142) of the highly conserved region of mouse Slc10a2. Bioscience, biotechnology, and biochemistry 6 19584562
2024 Efficacy and safety of 3-dimensional printing noncoplanar template (3D-PNCT)-assisted high-dose-rate interstitial brachytherapy (HDR-ISBT) for reirradiation of recurrent cervical cancer: a prospective cohort. Journal of gynecologic oncology 5 38991947
2024 Determination of Site-Specific Phosphorylation Occupancy Using Targeted Mass Spectrometry Reveals the Regulation of Human Apical Bile Acid Transporter, ASBT. ACS omega 5 39310206
2021 Dissecting the Conformational Dynamics of the Bile Acid Transporter Homologue ASBTNM. Journal of molecular biology 5 33359100
2017 iBAT sympathetic innervation is not required for body weight loss induced by central leptin delivery. American journal of physiology. Endocrinology and metabolism 5 29089334
2013 Importance of uncharged polar residues and proline in the proximal two-thirds (Pro107-Ser128) of the highly conserved region of mouse ileal Na+-dependent bile acid transporter, Slc10a2, in transport activity and cellular expression. BMC physiology 5 23374508
2024 Smooth muscle contractile responses to bile acids in mouse ileum require TGR5 but not ASBT. Frontiers in neurology 4 38721114
2024 Novel Expression of Apical Bile Acid Transport (ASBT) More Proximally Than Distal Ileum Contributing to Enhanced Intestinal Bile Acid Absorption in Obesity. International journal of molecular sciences 3 39519005
2023 Apple juice relieves loperamide-induced constipation in rats by downregulating the intestinal apical sodium-dependent bile acid transporter ASBT. Food & function 3 37129213
2025 The KDM6B/SLC10A2 Axis Suppresses MDSCs Recruitment via ERK/AP-1 Signaling in Colorectal Cancer. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2 41387297
2024 Exploring odevixibat's efficacy in alagille syndrome: insights from recent clinical trials and IBAT inhibitor experiences. Expert opinion on pharmacotherapy 2 39155775
2023 N-carbamoyl aspartate reduced body weight by stimulating the thermogenesis of iBAT. Biochemical and biophysical research communications 2 37163935
2023 Exploiting Apical Sodium-Dependent Bile Acid Transporter (ASBT)-Mediated Endocytosis with Multi-Functional Deoxycholic Acid Grafted Alginate Amide Nanoparticles as an Oral Insulin Delivery System. Pharmaceutical research 2 38114803
2011 The ISBT 700 series of low-incidence and 901 series of high-incidence blood group antigens. Immunohematology 2 22646068
2024 Patterns of red blood cell utilization: Harnessing electronic health records data from the Information Standard for Blood and Transplant (ISBT) 128 system within the Biologics Effectiveness and Safety (BEST) initiative. Transfusion 1 38689458
2025 Homozygosity for a variant in SLC10A2 and infancy onset severe fat-soluble vitamin deficiency due to bile acid malabsorption. JPGN reports 0 40814585
2025 Stage-dependent effects of systemic ASBT inhibition in a cholestasis-induced cholemic nephropathy mouse model. JHEP reports : innovation in hepatology 0 41321935

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