GO:0015245 fatty acid transmembrane transporter activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0015245 (fatty acid transmembrane transporter activity) is a molecular_function term describing proteins that move fatty acids across biological membranes.
• Key protein families include CD36/SR-B2, the FATP/SLC27 family, and FABPpm, which together govern cellular fatty acid uptake and homeostasis.
• FATP5 (SLC27A5) couples fatty acid transport to activation and is linked to hepatic lipid remodeling and ferroptosis suppression in MASH.
• CD36 is a master regulator of fatty acid homeostasis and a therapeutic target in HER2-positive breast cancer [5,8].
• E. coli FadD exemplifies how fatty acyl-CoA synthetase activity is required for transmembrane movement and activation of exogenous long-chain fatty acids.
• Studying this term requires transport assays, lipidomics, and CRISPR models that dissect transport versus activation functions [3,4,8].
Description
GO:0015245, fatty acid transmembrane transporter activity, is a Gene Ontology molecular_function term that enables the transfer of fatty acids from one side of a membrane to the other. Fatty acids are aliphatic monocarboxylic acids liberated from naturally occurring fats and oils by hydrolysis, and their movement across membranes is fundamental to energy metabolism, membrane biogenesis, and signaling. Researchers study this activity because dysregulated fatty acid uptake contributes to metabolic disease, cancer, and ferroptosis-related pathology [3,5]. The term is distinct from fatty acid activation or intracellular trafficking; it specifically captures the membrane-spanning transport step. Experimental evidence from bacterial and mammalian systems shows that transport can be coupled to activation, as seen with E. coli FadD, where residues in the ATP/AMP signature motif are required for both enzyme activity and fatty acid transport. In mammals, CD36 (SR-B2) is recognized as a master regulator of cellular fatty acid homeostasis, coordinating uptake with downstream metabolic fate. Understanding GO:0015245 therefore provides a mechanistic entry point for interrogating lipid-related disease and for designing targeted interventions [3,5,8].
fatty acid transmembrane transporter activity At A Glance
| GO ID | GO:0015245 |
|---|---|
| GO term | fatty acid transmembrane transporter activity |
| Ontology | molecular_function |
| Synonym | fatty acid transporter activity; fatty-acyl group transporter activity; fatty acyl transporter activity; peroxisomal fatty acyl transporter |
| Major function | Transfer of fatty acids across a membrane from one side to the other |
| Representative proteins | CD36/SR-B2, FATP/SLC27 family members, FABPpm, and bacterial FadD |
| Coupled activity | Can be functionally coupled to fatty acyl-CoA synthetase activity, as shown for E. coli FadD |
| Disease relevance | Metabolic dysfunction-associated steatohepatitis, HER2-positive breast cancer, and ferroptosis-related pathology |
What Is GO:0015245?
GO:0015245 describes the molecular function of enabling the transfer of fatty acids from one side of a membrane to the other. Fatty acids are aliphatic monocarboxylic acids liberated from naturally occurring fats and oils by hydrolysis. The term encompasses fatty acid transporter activity, fatty-acyl group transporter activity, fatty acyl transporter activity, and peroxisomal fatty acyl transporter activity. It is a molecular_function in the Gene Ontology and is distinct from enzymatic activation, binding, or intracellular lipid transport.
Why Is fatty acid transmembrane transporter activity Important in Cell Biology?
Fatty acid transmembrane transporter activity is important because it controls the first committed step of cellular fatty acid utilization, influencing energy production, membrane lipid composition, and lipid signaling. In metabolic disease, altered transport contributes to hepatic lipid remodeling and ferroptosis sensitivity, as shown for FATP5 deficiency in MASH. In cancer, CD36-mediated fatty acid uptake supports tumor growth and therapy resistance, making it a target in HER2-positive breast cancer. Because transport can be coupled to activation, as demonstrated for E. coli FadD, the activity also informs how cells coordinate uptake with metabolic activation. These features make GO:0015245 a high-value term for both mechanistic and translational research [3,5,8].
• Controls the first committed step of cellular fatty acid utilization and energy metabolism.
• Shapes membrane lipid composition and lipid signaling.
• Links to metabolic dysfunction-associated steatohepatitis through FATP5 and ferroptosis.
• Supports cancer growth and therapy resistance via CD36 in HER2-positive breast cancer.
• Provides a model for coupled transport and activation through bacterial FadD.
• Enables dissection of peroxisomal fatty acyl transport in lipid metabolism.
• Informs drug discovery targeting CD36 and related transporters.
• Connects to human health through L-carnitine and fatty acid oxidation pathways.
• Offers a mechanistic basis for understanding statin and ryanodine receptor modulation.
• Supports CRISPR-based functional genomics of lipid uptake [3,5,8].
Mechanism, Genes and Research Methods of fatty acid transmembrane transporter activity
Substrate recognition and membrane association
In simple terms: The transporter first recognizes fatty acids at the membrane surface.
Fatty acid transmembrane transporter activity begins with substrate recognition at the membrane interface, where proteins such as CD36/SR-B2 bind long-chain fatty acids and facilitate their transfer. In bacteria, E. coli FadD requires specific amino acid residues within the ATP/AMP signature motif for enzyme activity and fatty acid transport, indicating that substrate handling is structurally constrained. This step is distinct from simple diffusion and involves protein-mediated recognition [4,8].
Transmembrane transfer and coupling to activation
In simple terms: The fatty acid is moved across the membrane and can be activated at the same time.
Following recognition, the fatty acid is transferred across the lipid bilayer. In E. coli, FadD couples transmembrane movement with activation of exogenous long-chain fatty acids, demonstrating that transport and fatty acyl-CoA synthetase activity can be functionally linked. In mammals, CD36 coordinates uptake with downstream metabolic fate, acting as a master regulator of cellular fatty acid homeostasis. This coupling ensures that transported fatty acids are efficiently directed into metabolic pathways [4,8].
Peroxisomal and organellar fatty acyl transport
In simple terms: Fatty acids also need to cross membranes of organelles such as peroxisomes.
The term includes peroxisomal fatty acyl transporter activity, reflecting the need to move fatty acyl groups across organellar membranes. This is essential for fatty acid oxidation and lipid remodeling. FATP5 (SLC27A5) is a hepatic transporter that influences lipid composition and ferroptosis sensitivity, illustrating how organellar and cellular transport intersect with disease.
Regulation by metabolic and hormonal signals
In simple terms: The activity of these transporters is tuned by the cell's metabolic state.
Fatty acid transport is regulated in response to metabolic and hormonal cues. CD36 is a master regulator whose expression and localization adjust cellular fatty acid homeostasis. L-carnitine, which is significant for human health, supports fatty acid oxidation and indirectly reflects the importance of transport in energy metabolism. Statins and ryanodine receptor modulation further illustrate how pharmacological agents can influence lipid-related membrane proteins. These regulatory layers ensure that fatty acid uptake matches cellular demand [6,7,8].
Key Genes Involved in GO:0015245 fatty acid transmembrane transporter activity
The following genes and proteins are experimentally linked to fatty acid transmembrane transporter activity or its coupled processes.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CD36 | Master regulator of cellular fatty acid homeostasis; facilitates fatty acid uptake | Target in HER2-positive breast cancer and metabolic disease [5,8] |
| SLC27A5 (FATP5) | Hepatic fatty acid transport and activation; influences lipid composition | Deficiency alleviates MASH via remodeling hepatic lipid composition to suppress ferroptosis |
| FadD | Bacterial fatty acyl-CoA synthetase required for transmembrane movement and activation of exogenous long-chain fatty acids | Model for coupled transport and activation; ATP/AMP signature motif residues are essential |
| FABPpm | Membrane fatty acid binding protein involved in fatty acid transport | Studied in cellular fatty acid uptake |
| SLC27A1 (FATP1) | Fatty acid transport protein family member | Implicated in cellular fatty acid uptake |
| SLC27A2 (FATP2) | Fatty acid transport protein family member | Linked to lipid metabolism |
| SLC27A4 (FATP4) | Fatty acid transport protein family member | Studied in fatty acid transport |
| ACSL1 | Acyl-CoA synthetase that activates long-chain fatty acids | Coupled to transport and activation |
| ACSL3 | Acyl-CoA synthetase | Related to fatty acid activation |
| ACSL4 | Acyl-CoA synthetase | Linked to ferroptosis and lipid metabolism |
| CPT1A | Carnitine palmitoyltransferase 1A; mitochondrial fatty acid oxidation | Connects transport to oxidation; L-carnitine significance |
| CPT2 | Carnitine palmitoyltransferase 2 | Fatty acid oxidation pathway |
| SLC25A20 | Carnitine-acylcarnitine translocase | Mitochondrial fatty acid transport |
| TRPV1 | Capsaicin receptor; not a fatty acid transporter but modulated by lipid ligands | Illustrates lipid-protein interactions |
| RYR1 | Ryanodine receptor; modulated by statin triplets | Example of membrane protein regulation by lipids |
| HMGCR | Statin target; cholesterol synthesis | Indirectly linked to lipid metabolism |
| SLC22A5 | Carnitine transporter | L-carnitine transport for fatty acid oxidation |
How Is fatty acid transmembrane transporter activity Regulated?
Fatty acid transmembrane transporter activity is regulated at multiple levels. CD36, a master regulator of cellular fatty acid homeostasis, adjusts its expression and membrane localization in response to metabolic state. L-carnitine availability influences fatty acid oxidation and reflects the integration of transport with mitochondrial metabolism. Pharmacological agents such as statins can modulate membrane proteins, as shown by cryo-electron microscopy of ryanodine receptor activation by statin triplets. In bacteria, the ATP/AMP signature motif of FadD is required for enzyme activity and fatty acid transport, indicating that nucleotide binding regulates coupled transport. These mechanisms ensure that fatty acid uptake is matched to cellular demand and metabolic context [4,6,7,8].
fatty acid transmembrane transporter activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SLC27A5 (FATP5) | MASH and ferroptosis suppression | Knockout mouse or hepatocyte KO |
| CD36 | HER2-positive breast cancer and therapy resistance | Knockout or overexpression in breast cancer cell lines |
| FadD | Bacterial fatty acid transport and activation | Point mutation of ATP/AMP signature motif |
| CPT1A | Fatty acid oxidation disorders | Knock-in of patient variants |
| SLC22A5 | Carnitine transport deficiency | Knockout cell model |
Metabolic dysfunction-associated steatohepatitis (MASH)
FATP5 deficiency alleviates MASH via remodeling hepatic lipid composition to suppress ferroptosis, directly linking fatty acid transport to liver disease pathology. This suggests that modulating fatty acid transmembrane transporter activity could be therapeutically relevant in MASH.
HER2-positive breast cancer
CD36-mediated fatty acid uptake supports tumor biology, and selective CD36 inhibitors have been identified to potentiate HER2-targeted therapy in HER2-positive breast cancer. This positions fatty acid transmembrane transporter activity as a target in precision oncology.
Ferroptosis-related pathology
Altered fatty acid transport and lipid composition influence ferroptosis sensitivity, as shown in MASH models where FATP5 deficiency suppresses ferroptosis. This connects GO:0015245 to cell death pathways and lipid peroxidation.
Metabolic and cardiovascular implications
CD36 as a master regulator of fatty acid homeostasis is relevant to metabolic and cardiovascular conditions, and L-carnitine is significant for human health through fatty acid oxidation [6,8]. Statin effects on membrane proteins further illustrate pharmacological intersections.
From fatty acid transmembrane transporter activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of FATP5 alter hepatic lipid composition and ferroptosis? | SLC27A5 knockout hepatocytes or mouse models |
| Can CD36 inhibition potentiate HER2-targeted therapy? | CD36 knockout or overexpression in HER2-positive breast cancer cells |
| Which residues are required for coupled transport and activation? | Point mutations in the ATP/AMP signature motif of FadD |
| How does CD36 localization affect fatty acid homeostasis? | Tagged knock-in of CD36 for imaging |
| What is the role of carnitine transport in fatty acid oxidation? | SLC22A5 knockout or knock-in models |
| How do statins modulate membrane protein function? | Point mutation or knock-in of ryanodine receptor |
How to Study the fatty acid transmembrane transporter activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Radiolabeled fatty acid uptake | Transport rate across membranes | Assessing GO:0015245 activity |
| Lipidomics | Membrane and cellular lipid composition | FATP5 deficiency in MASH |
| CRISPR knockout | Gene requirement for fatty acid uptake | CD36 in breast cancer |
| CRISPR knock-in | Effect of specific mutations on transport | FadD ATP/AMP motif |
| Live-cell imaging | Transporter localization and dynamics | CD36 trafficking |
| Cryo-electron microscopy | Structural basis of membrane protein regulation | Statin-ryanodine receptor interaction |
| Metabolomics | Flux through fatty acid oxidation | L-carnitine and CPT1A |
| Protein interaction assays | Binding partners of transporters | CD36 and FABPpm |
Transport assays
Direct measurement of fatty acid transmembrane transporter activity uses radiolabeled or fluorescent fatty acid uptake assays in cells and membrane vesicles. These assays distinguish transport from binding and activation, as demonstrated for E. coli FadD.
Lipidomics and metabolomics
Mass spectrometry-based lipidomics quantifies changes in lipid composition following manipulation of transporters such as FATP5, revealing remodeling that suppresses ferroptosis. Metabolomics can trace fatty acid flux into oxidation pathways.
CRISPR functional genomics
CRISPR knockout and knock-in screens identify genes required for fatty acid uptake and homeostasis. CD36 and FATP5 are validated targets in cancer and MASH models [3,5].
Imaging and protein interaction
Tagged knock-in and live-cell imaging visualize transporter localization and trafficking, as with CD36. Cryo-electron microscopy can resolve membrane protein regulation by ligands such as statins.
How CRISPR Can Be Used to Study GO:0015245 fatty acid transmembrane transporter activity
Knockout
CRISPR knockout of SLC27A5 or CD36 eliminates fatty acid transmembrane transporter activity, enabling assessment of lipid remodeling and ferroptosis in MASH or cancer models [3,5]. Knockout of FadD in bacteria abolishes coupled transport and activation.
Point Mutation
Point mutations in the ATP/AMP signature motif of FadD disrupt enzyme activity and fatty acid transport, providing residue-level insight into GO:0015245. Similar approaches can test CD36 or FATP5 functional domains.
Knock-in
Knock-in of tagged CD36 allows visualization of transporter localization and trafficking in live cells. Knock-in of disease-associated variants in CPT1A or SLC22A5 can model fatty acid oxidation disorders.
Overexpression
Overexpression of CD36 or FATP5 increases fatty acid uptake and can drive lipid accumulation or therapy resistance, as seen in HER2-positive breast cancer models [5,8]. Overexpression of FadD in E. coli enhances transport and activation of exogenous fatty acids.
How EDITGENE Supports fatty acid transmembrane transporter activity Research
Researchers studying fatty acid transmembrane transporter activity-related genes often need to determine whether a candidate gene is causally involved in fatty acid uptake, lipid remodeling, or disease phenotypes. EDITGENE provides publication-ready CRISPR models and screening services to dissect these mechanisms with precision.
Contact EDITGENE today to design your custom CRISPR model for fatty acid transmembrane transporter activity research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
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| SLC27A4 Knockout HEK293 Cell Line | EDJ-KQ3094 | Human | 10999 | Details Get a Quote |
| SLC27A1 Knockout HEK293 Cell Line | EDJ-KQ3543 | Human | 376497 | Details Get a Quote |
| SLC43A3 Knockout HEK293 Cell Line | EDJ-KQ3679 | Human | 29015 | Details Get a Quote |
| SLC27A2 Knockout HEK293 Cell Line | EDJ-KQ6607 | Human | 11001 | Details Get a Quote |
| SLC27A5 Knockout HEK293 Cell Line | EDJ-KQ7238 | Human | 10998 | Details Get a Quote |
| SLC27A6 Knockout HEK293 Cell Line | EDJ-KQ8943 | Human | 28965 | Details Get a Quote |
| MFSD2A Knockout HEK293 Cell Line | EDJ-KQ10231 | Human | 84879 | Details Get a Quote |
| SLC27A5 Knockout A-549 Cell Line | EDJ-KQ32216 | Human | 10998 | Details Get a Quote |
| MFSD2A Knockout HeLa Cell Line | EDJ-KQ36165 | Human | 84879 | Details Get a Quote |
| SLC27A4 Knockout A-549 Cell Line | EDJ-KQ24411 | Human | 10999 | Details Get a Quote |
| SLC27A4 Knockout HCT 116 Cell Line | EDJ-KQ24412 | Human | 10999 | Details Get a Quote |
| SLC27A4 Knockout HeLa Cell Line | EDJ-KQ24413 | Human | 10999 | Details Get a Quote |
| SLC27A1 Knockout A-549 Cell Line | EDJ-KQ25390 | Human | 376497 | Details Get a Quote |
| SLC27A1 Knockout HCT 116 Cell Line | EDJ-KQ25391 | Human | 376497 | Details Get a Quote |
| SLC27A1 Knockout HeLa Cell Line | EDJ-KQ25392 | Human | 376497 | Details Get a Quote |
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Frequently Asked Questions About fatty acid transmembrane transporter activity
What is GO:0015245?
GO:0015245 is the Gene Ontology molecular_function term for fatty acid transmembrane transporter activity, enabling the transfer of fatty acids from one side of a membrane to the other.
What genes are involved in fatty acid transmembrane transporter activity?
Key genes include CD36, SLC27A5 (FATP5), FABPpm, and the SLC27A family, as well as bacterial FadD [3,4,5,8].
How is fatty acid transmembrane transporter activity measured?
It is measured using radiolabeled or fluorescent fatty acid uptake assays, lipidomics, and CRISPR-based functional screens [3,4,5].
What diseases are linked to fatty acid transmembrane transporter activity?
It is linked to MASH, HER2-positive breast cancer, ferroptosis-related pathology, and metabolic disorders [3,5,8].
What is the role of CD36 in fatty acid transport?
CD36 (SR-B2) is a master regulator of cellular fatty acid homeostasis and a therapeutic target in HER2-positive breast cancer [5,8].
How does FATP5 affect liver disease?
FATP5 deficiency alleviates MASH via remodeling hepatic lipid composition to suppress ferroptosis.
Can CRISPR be used to study fatty acid transporters?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are used to dissect transporter function [3,4,5,8].
What is the difference between fatty acid transport and activation?
Transport moves fatty acids across membranes, while activation converts them to fatty acyl-CoA; these can be coupled, as in E. coli FadD.
What is peroxisomal fatty acyl transporter activity?
It is a synonym for GO:0015245, reflecting transport of fatty acyl groups across peroxisomal membranes.
Why is L-carnitine relevant to fatty acid transport?
L-carnitine is significant for human health and supports fatty acid oxidation, connecting transport to mitochondrial metabolism.
Conclusion
GO:0015245 fatty acid transmembrane transporter activity is a central molecular function governing cellular fatty acid uptake and homeostasis. Its key mediators, including CD36 and FATP5, are linked to MASH, cancer, and ferroptosis, making the term highly relevant for disease research [3,5,8]. Coupled transport and activation, exemplified by E. coli FadD, further highlight the mechanistic complexity of this activity. CRISPR-based models and lipidomic methods provide robust tools to dissect these pathways and identify therapeutic targets [3,4,5,8].
References
- 1. Yang F et al.. 2017. Understand spiciness: mechanism of TRPV1 channel activation by capsaicin.. Protein Cell 8(3):169-177 PMID: 28044278
- 3. 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
- 4. Weimar JD et al.. 2002. Functional role of fatty acyl-coenzyme A synthetase in the transmembrane movement and activation of exogenous long-chain fatty acids. Amino acid residues within the ATP/AMP signature motif of Escherichia coli FadD are required for enzyme activity and fatty acid transport.. J Biol Chem 277(33):29369-76 PMID: 12034706
- 5. Castagnoli L et al.. 2025. Identification of new selective CD36 inhibitors to potentiate HER2-targeted therapy in HER2-positive breast cancer.. Sci Rep 15(1):28709 PMID: 40770043
- 6. Adeva-Andany MM et al.. 2017. Significance of l-carnitine for human health.. IUBMB Life 69(8):578-594 PMID: 28653367
- 7. Molinarolo S et al.. 2025. Cryo-electron microscopy reveals sequential binding and activation of Ryanodine Receptors by statin triplets.. Nat Commun 16(1):11508 PMID: 41266329
- 8. Glatz JFC et al.. 2022. CD36 (SR-B2) as master regulator of cellular fatty acid homeostasis.. Curr Opin Lipidol 33(2):103-111 PMID: 35125400
