GO:0015125 bile acid transmembrane transporter activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0015125 (bile acid transmembrane transporter activity) is a molecular function that enables the transfer of bile acids across biological membranes.
• Bile acids are steroid carboxylic acids present in bile as sodium salts of glycine or taurine amides; their transport is essential for bile secretion, lipid digestion, and metabolic signaling.
• Key transporters include the bile/arsenite/riboflavin transporter (BART) superfamily members and other membrane proteins that mediate bile acid flux.
• Disruption of bile acid transport contributes to progressive familial intrahepatic cholestasis (PFIC) and other cholestatic liver diseases.
• Bile acid transporters are implicated in metabolic adaptation in lean NAFLD and in autophagy regulation in hepatic metabolism.
• Secondary bile acids such as lithocholic acid can modulate ion channels like CFTR, linking bile acid transport to epithelial physiology.
Description
Bile acid transmembrane transporter activity (GO:0015125) is a molecular function that enables the movement of bile acids from one side of a membrane to the other. Bile acids are steroid carboxylic acids that occur in bile, where they are present as sodium salts of their amides with glycine or taurine. This transport activity is fundamental to bile secretion, enterohepatic circulation, and the regulation of lipid and glucose metabolism. Researchers study this term to understand how bile acids are absorbed, distributed, and excreted, and how defects in these processes lead to disease. The BART superfamily represents one class of transporters capable of bile acid transport, highlighting the evolutionary diversity of these membrane proteins. In addition, secondary bile acids such as lithocholic acid can influence the expression and activity of other membrane proteins, including CFTR, demonstrating the broad physiological impact of bile acid transport. Understanding GO:0015125 is therefore critical for dissecting liver physiology, metabolic disease, and potential therapeutic targets.
bile acid transmembrane transporter activity At A Glance
| GO ID | GO:0015125 |
|---|---|
| GO term | bile acid transmembrane transporter activity |
| Ontology | molecular_function |
| Synonym | none |
| Major function | Enables the transfer of bile acids from one side of a membrane to the other |
| Substrates | Bile acids (steroid carboxylic acids) as sodium salts of glycine or taurine amides |
| Related superfamily | Bile/arsenite/riboflavin transporter (BART) superfamily |
| Disease relevance | Progressive familial intrahepatic cholestasis, NAFLD, cholestasis |
What Is GO:0015125?
GO:0015125 describes the molecular function of enabling the transfer of bile acids across a membrane. Bile acids are a group of steroid carboxylic acids found in bile, typically as sodium salts of their amides with glycine or taurine. This activity is essential for bile formation, fat digestion, and the enterohepatic circulation of bile acids.
Why Is bile acid transmembrane transporter activity Important in Cell Biology?
Bile acid transmembrane transporter activity is essential for bile secretion, lipid absorption, and metabolic homeostasis. Defects in bile acid transport underlie severe cholestatic liver diseases such as progressive familial intrahepatic cholestasis (PFIC). Moreover, bile acid transporters are implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), including lean NAFLD, where metabolic adaptation is shaped by differential bile acid handling. The activity also intersects with autophagy regulation in hepatic metabolism, suggesting broader roles in cellular stress responses. Secondary bile acids like lithocholic acid can modulate ion channels such as CFTR, linking bile acid transport to epithelial function. Thus, studying GO:0015125 provides insights into liver physiology, metabolic disease, and potential therapeutic targets.
• Essential for bile formation and secretion.
• Critical for enterohepatic circulation and lipid digestion.
• Dysfunction causes progressive familial intrahepatic cholestasis (PFIC).
• Implicated in lean NAFLD and metabolic adaptation.
• Linked to autophagy regulation in hepatic metabolism.
• Secondary bile acids modulate CFTR expression and activity.
• BART superfamily members exemplify diverse bile acid transporters.
• Potential target for cholestatic and metabolic liver diseases.
• Relevant to drug metabolism and detoxification.
• Key to understanding bile acid signaling in energy homeostasis.
Molecular Mechanism of bile acid transmembrane transporter activity
Substrate Recognition and Binding
In simple terms: The transporter first grabs the bile acid molecule.
Bile acid transporters recognize specific bile acids, which are steroid carboxylic acids present as sodium salts of glycine or taurine amides. The BART superfamily includes transporters that can handle bile acids along with other substrates like arsenite and riboflavin, indicating broad substrate specificity. Binding likely involves electrostatic interactions with the negatively charged bile acid and hydrophobic interactions with the steroid core.
Transmembrane Translocation
In simple terms: The transporter moves the bile acid across the membrane.
Once bound, the transporter undergoes conformational changes to shuttle the bile acid from one side of the membrane to the other. This process may be coupled to ion gradients or ATP hydrolysis, although the exact mechanism varies among transporters. The activity is essential for bile secretion and enterohepatic circulation.
Regulation by Cellular Signals
In simple terms: The cell can speed up or slow down bile acid transport.
Bile acid transport is regulated by factors such as autophagy, which modulates hepatic metabolism. In lean NAFLD, differential metabolic adaptation affects bile acid handling. Secondary bile acids like lithocholic acid can influence the expression and activity of membrane proteins such as CFTR, indirectly affecting transport.
Physiological Integration
In simple terms: Bile acid transport works together with other liver functions.
Bile acid transporters coordinate with bile secretion, lipid digestion, and metabolic signaling. Defects in these transporters lead to cholestatic diseases like PFIC. The BART superfamily highlights the evolutionary conservation of bile acid transport mechanisms.
Key Genes Involved in GO:0015125 bile acid transmembrane transporter activity
The following genes encode proteins with bile acid transmembrane transporter activity or related functions, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| ABCB11 | Bile acid export pump | PFIC2, cholestasis |
| ABCB4 | Phosphatidylcholine floppase | PFIC3, bile formation |
| ATP8B1 | Aminophospholipid flippase | PFIC1, cholestasis |
| SLC10A1 | Sodium-taurocholate cotransporting polypeptide | Bile acid uptake |
| SLC10A2 | Ileal bile acid transporter | Enterohepatic circulation |
| BART | Bile/arsenite/riboflavin transporter | Bile acid transport superfamily |
| CFTR | Chloride channel | Modulated by lithocholic acid |
| FATP5 | Fatty acid transport protein 5 | MASH, lipid composition |
| TMEM158 | Transmembrane protein 158 | ICC metastasis |
| ATG genes | Autophagy regulation | Hepatic metabolism |
| NR1H4 | Farnesoid X receptor | Bile acid signaling |
| SLC51A | Organic solute transporter alpha | Bile acid efflux |
| SLC51B | Organic solute transporter beta | Bile acid efflux |
| ABCC2 | Multidrug resistance protein 2 | Bile acid conjugation |
| ABCC3 | Multidrug resistance protein 3 | Bile acid transport |
| ABCC4 | Multidrug resistance protein 4 | Bile acid transport |
| OSTα/β | Organic solute transporter | Bile acid transport |
| ASBT | Apical sodium-dependent bile acid transporter | Bile acid absorption |
How Is bile acid transmembrane transporter activity Regulated?
Bile acid transmembrane transporter activity is regulated at multiple levels. Autophagy modulates hepatic metabolism and can influence bile acid transport. In lean NAFLD, metabolic adaptation leads to differential regulation of bile acid handling. The farnesoid X receptor (NR1H4) is a nuclear receptor that senses bile acids and regulates genes involved in bile acid transport and metabolism. Additionally, secondary bile acids such as lithocholic acid can affect the expression and activity of membrane proteins like CFTR, indirectly impacting bile acid transport.
bile acid transmembrane transporter activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ABCB11 | PFIC2 | Knockout mouse, patient-derived organoids |
| ABCB4 | PFIC3 | Knockout mouse, cell lines |
| ATP8B1 | PFIC1 | Knockout mouse, iPSC-derived hepatocytes |
| CFTR | Cystic fibrosis, epithelial function | Colonic epithelial cells, knockout models |
| FATP5 | MASH | Knockout mouse, overexpression cell lines |
Progressive Familial Intrahepatic Cholestasis (PFIC)
PFIC is a group of inherited cholestatic liver diseases caused by mutations in genes encoding bile acid transporters, such as ABCB11, ABCB4, and ATP8B1. These mutations impair bile acid transport, leading to bile acid accumulation, liver damage, and progressive cholestasis.
Lean NAFLD
Lean NAFLD is a distinct entity characterized by metabolic adaptation that includes altered bile acid transport and signaling. Differential regulation of bile acid transporters may contribute to the pathogenesis of lean NAFLD.
Cystic Fibrosis and Epithelial Function
The secondary bile acid lithocholic acid inhibits CFTR expression and activity in colonic epithelial cells, linking bile acid transport to epithelial ion transport and cystic fibrosis.
Metabolic Dysfunction-Associated Steatohepatitis (MASH)
FATP5 deficiency alleviates MASH by remodeling hepatic lipid composition and suppressing ferroptosis, indicating a role for bile acid transport in MASH pathogenesis.
From bile acid transmembrane transporter activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of ABCB11 cause cholestasis? | ABCB11 knockout mouse |
| How does lithocholic acid affect CFTR? | CFTR-expressing colonic epithelial cells treated with LCA |
| What is the role of FATP5 in MASH? | FATP5 knockout mouse and overexpression cell lines |
| How does autophagy regulate bile acid transport? | Autophagy-deficient hepatic cell lines |
| What is the impact of bile acid transport on lean NAFLD? | Lean NAFLD mouse models and patient samples |
| Can BART superfamily members transport bile acids? | Heterologous expression in Xenopus oocytes or HEK293 cells |
How to Study the bile acid transmembrane transporter activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Radiolabeled bile acid uptake | Transport activity | Characterizing transporter kinetics |
| RNA-seq | Gene expression | Identifying regulated transporters in disease |
| Proteomics | Protein abundance and modifications | Quantifying transporter levels |
| Immunofluorescence | Protein localization | Tissue distribution of transporters |
| CRISPR knockout screens | Gene function | Discovering regulators of bile acid transport |
| Patch-clamp | Ion channel activity | Assessing CFTR modulation by bile acids |
| Organoid culture | Physiological transport | Modeling cholestasis and NAFLD |
Transport Assays
Radiolabeled or fluorescent bile acid uptake assays in cell lines or membrane vesicles can directly measure bile acid transmembrane transporter activity. These assays are used to characterize substrate specificity and kinetics.
Gene Expression Analysis
RNA-seq and qPCR can quantify expression of bile acid transporter genes in liver or intestinal tissues, providing insights into regulation in health and disease.
Proteomics and Imaging
Mass spectrometry-based proteomics and immunofluorescence can localize and quantify bile acid transporters in cells and tissues, revealing changes in disease models.
CRISPR Screening
Genome-wide CRISPR knockout screens can identify genes that regulate bile acid transport and sensitivity to bile acids, uncovering novel therapeutic targets.
How CRISPR Can Be Used to Study GO:0015125 bile acid transmembrane transporter activity
Knockout
CRISPR knockout of bile acid transporter genes such as ABCB11 or SLC10A1 in cell lines or mice can model cholestatic diseases and reveal compensatory mechanisms.
Point Mutation
Introducing patient-specific point mutations in genes like ABCB4 or ATP8B1 via CRISPR can replicate PFIC phenotypes and test genotype-phenotype correlations.
Knock-in
Knock-in of tagged versions of bile acid transporters (e.g., GFP-ABCB11) allows live-cell imaging and proteomic analysis of transporter dynamics.
Overexpression
CRISPR activation or cDNA overexpression of bile acid transporters can enhance transport activity, useful for studying substrate specificity and drug interactions.
How EDITGENE Supports bile acid transmembrane transporter activity Research
Researchers studying bile acid transmembrane transporter activity-related genes often need to determine whether a candidate gene is causally involved in bile acid transport, cholestasis, or metabolic disease. EDITGENE provides comprehensive CRISPR-based services to create knockout, point-mutation, knock-in, and overexpression cell models, as well as CRISPR library screening and bioinformatics support, enabling rigorous functional studies of GO:0015125.
Contact EDITGENE today to design your custom CRISPR model for bile acid transmembrane transporter activity research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CEACAM1 Knockout HEK293 Cell Line | EDJ-KQ268 | Human | 634 | Details Get a Quote |
| ABCB11 Knockout HEK293 Cell Line | EDJ-KQ2032 | Human | 8647 | Details Get a Quote |
| SLCO1B1 Knockout HEK293 Cell Line | EDJ-KQ2079 | Human | 10599 | Details Get a Quote |
| SLC10A1 Knockout HEK293 Cell Line | EDJ-KQ2393 | Human | 6554 | Details Get a Quote |
| AKR1C4 Knockout HEK293 Cell Line | EDJ-KQ4264 | Human | 1109 | Details Get a Quote |
| SLC51A Knockout HEK293 Cell Line | EDJ-KQ4632 | Human | 200931 | Details Get a Quote |
| SLCO1A2 Knockout HEK293 Cell Line | EDJ-KQ5806 | Human | 6579 | Details Get a Quote |
| SLCO1C1 Knockout HEK293 Cell Line | EDJ-KQ11370 | Human | 53919 | Details Get a Quote |
| SLCO1B1 Knockout A-549 Cell Line | EDJ-KQ22162 | Human | 10599 | Details Get a Quote |
| SLCO1B1 Knockout HeLa Cell Line | EDJ-KQ22163 | Human | 10599 | Details Get a Quote |
| AKR1C4 Knockout A-549 Cell Line | EDJ-KQ26745 | Human | 1109 | Details Get a Quote |
| SLC51A Knockout A-549 Cell Line | EDJ-KQ27313 | Human | 200931 | Details Get a Quote |
| SLC51A Knockout HCT 116 Cell Line | EDJ-KQ27314 | Human | 200931 | Details Get a Quote |
| SLC51A Knockout HeLa Cell Line | EDJ-KQ27315 | Human | 200931 | Details Get a Quote |
| SLCO1C1 Knockout HeLa Cell Line | EDJ-KQ39560 | Human | 53919 | Details Get a Quote |
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Frequently Asked Questions About bile acid transmembrane transporter activity
What is bile acid transmembrane transporter activity?
It is a molecular function (GO:0015125) that enables the transfer of bile acids across membranes, essential for bile secretion and metabolism.
What genes are involved in bile acid transmembrane transporter activity?
Key genes include ABCB11, ABCB4, ATP8B1, SLC10A1, SLC10A2, and BART superfamily members.
How is bile acid transmembrane transporter activity regulated?
It is regulated by autophagy, metabolic adaptation, and nuclear receptors like FXR, as well as secondary bile acids.
What diseases are associated with defects in bile acid transport?
Progressive familial intrahepatic cholestasis (PFIC), lean NAFLD, and MASH are associated with bile acid transport defects.
What methods are used to study bile acid transmembrane transporter activity?
Transport assays, RNA-seq, proteomics, imaging, and CRISPR screens are commonly used.
Can CRISPR be used to model bile acid transport diseases?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are valuable for studying PFIC and NAFLD.
What is the role of BART superfamily in bile acid transport?
The BART superfamily includes transporters capable of bile acid transport, along with arsenite and riboflavin.
How does lithocholic acid affect CFTR?
Lithocholic acid inhibits CFTR expression and activity in colonic epithelial cells, linking bile acid transport to epithelial function.
What is the link between bile acid transport and autophagy?
Autophagy regulates hepatic metabolism and can influence bile acid transport.
What experimental models are suitable for studying bile acid transport?
Knockout mice, patient-derived organoids, and CRISPR-edited cell lines are suitable models.
Conclusion
Bile acid transmembrane transporter activity (GO:0015125) is a critical molecular function for bile acid homeostasis, lipid metabolism, and liver physiology. Its dysfunction is linked to cholestatic diseases, NAFLD, and metabolic disorders. Understanding the genes, mechanisms, and regulation of bile acid transport provides opportunities for therapeutic intervention. EDITGENE offers comprehensive CRISPR services to accelerate research in this field.
References
- 1. Byrnes K et al.. 2022. Therapeutic regulation of autophagy in hepatic metabolism.. Acta Pharm Sin B 12(1):33-49 PMID: 35127371
- 2. Srivastava A. 2014. Progressive familial intrahepatic cholestasis.. J Clin Exp Hepatol 4(1):25-36 PMID: 25755532
- 3. Chen F et al.. 2020. Lean NAFLD: A Distinct Entity Shaped by Differential Metabolic Adaptation.. Hepatology 71(4):1213-1227 PMID: 31442319
- 4. Curley CE et al.. 2026. The secondary bile acid, lithocholic acid, inhibits cystic fibrosis transmembrane conductance regulator expression and activity in colonic epithelial cells.. Am J Physiol Gastrointest Liver Physiol 330(2):G110-G122 PMID: 41452581
- 5. Liu Y et al.. 2025. FATP5 deficiency alleviates MASH via remodeling hepatic lipid composition to suppress ferroptosis.. Free Radic Biol Med 240:170-182 PMID: 40840619
- 6. Hundt M et al.. 2026. Physiology, Bile Secretion.. PMID: 29262229
- 7. Mansour NM et al.. 2007. The bile/arsenite/riboflavin transporter (BART) superfamily.. FEBS J 274(3):612-29 PMID: 17288550
- 8. Chen P et al.. 2026. TMEM158 promotes ICC metastasis via inducing lactic acid mediated reduction of actin skeleton stiffness of ICC cells.. J Adv Res 79:751-768 PMID: 40220896
