GO:0015191 L-methionine transmembrane transporter activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0015191 describes the molecular function of moving L-methionine across a membrane, a process essential for protein synthesis, methylation, and redox balance.
• L-methionine transport is mediated by several transporter families, including the y+L system (SLC7A7) that also transports cationic amino acids.
• In shrimp hepatopancreas, L-methionine shares a Na+/K+-dependent transporter with L-leucine and L-phenylalanine, indicating conserved broad-specificity amino acid transporters.
• Bacterial transporters such as YhjE in Escherichia coli K-12 contribute to branched-chain amino acid uptake and can influence methionine-related metabolism.
• L-methionine exhibits anti-biofilm activity against Pseudomonas aeruginosa, and this activity is enhanced by the CFTR potentiator ivacaftor, linking transport to cystic fibrosis research.
• Dysregulation of methionine transport may impact liver disease, as autophagy and lipid droplet dynamics intersect with methionine metabolism and FATP5 deficiency alters hepatic lipid composition.
Description
L-methionine transmembrane transporter activity (GO:0015191) is a molecular function that enables the transfer of L-methionine from one side of a membrane to the other. L-methionine is an essential amino acid that serves as the initiator of protein synthesis and a precursor for S-adenosylmethionine, the principal methyl donor in cells. Because methionine cannot be synthesized de novo in humans, its uptake across the plasma membrane and organellar membranes is critical for normal physiology. Transporters that mediate this activity are therefore central to amino acid homeostasis and are implicated in a range of biological processes, from protein translation to redox regulation. In this article, we explore the mechanistic, genetic, and disease-related aspects of GO:0015191, drawing on verified literature to provide a research-grade overview for scientists and AI-driven knowledge systems.
L-methionine transmembrane transporter activity At A Glance
| GO ID | GO:0015191 |
|---|---|
| GO term | L-methionine transmembrane transporter activity |
| Ontology | molecular_function |
| Synonym | L-methionine transporter activity |
| Major function | Enables the transfer of L-methionine from one side of a membrane to the other |
| Substrate | L-methionine (2-amino-4-(methylthio)butanoic acid) |
| Directionality | Transmembrane, can be coupled to ion gradients |
| Related transporters | SLC7A7 (y+LAT1), SLC3A2 (4F2hc), bacterial YhjE |
| Disease relevance | Lysinuric protein intolerance, cystic fibrosis, liver disease |
What Is GO:0015191?
GO:0015191, L-methionine transmembrane transporter activity, is defined as the transfer of L-methionine (2-amino-4-(methylthio)butanoic acid) from one side of a membrane to the other. This activity is a molecular function that facilitates the movement of this specific amino acid across lipid bilayers, often against its concentration gradient, using energy from ion gradients or ATP hydrolysis. It is synonymous with L-methionine transporter activity and is distinct from general amino acid permease activities that do not discriminate L-methionine as a primary substrate.
Why Is L-methionine transmembrane transporter activity Important in Cell Biology?
L-methionine transmembrane transporter activity is fundamental to cellular metabolism because methionine is an essential amino acid required for protein synthesis initiation and for the generation of S-adenosylmethionine, the universal methyl donor. Defects in methionine transport can lead to imbalances in amino acid pools, affecting processes such as autophagy, lipid metabolism, and redox homeostasis. In pathogens, methionine transport influences biofilm formation and virulence, as shown by the anti-biofilm activity of L-methionine against Pseudomonas aeruginosa. Moreover, mutations in transporters like SLC7A7 cause lysinuric protein intolerance, a rare inherited disorder, highlighting the clinical importance of this activity. Understanding GO:0015191 is therefore relevant for basic cell biology, infectious disease, and inherited metabolic disorders.
• Essential for protein synthesis: methionine is the initiating amino acid in translation, and its transport ensures adequate intracellular supply.
• Supports methylation reactions: methionine is converted to S-adenosylmethionine, which methylates DNA, RNA, proteins, and lipids.
• Maintains redox balance: methionine and its derivatives participate in antioxidant defense, influencing ferroptosis sensitivity.
• Influences autophagy and lipid droplet dynamics: methionine metabolism intersects with autophagy and liver disease progression.
• Contributes to pathogen virulence: L-methionine transport affects biofilm formation in Pseudomonas aeruginosa.
• Linked to inherited disorders: mutations in SLC7A7 cause lysinuric protein intolerance, a disorder of amino acid transport.
• Target for anti-infective strategies: modulating methionine transport can enhance antimicrobial efficacy.
• Relevant to metabolic engineering: bacterial transporters like YhjE can be manipulated for amino acid production.
• Affects nutrient sensing: amino acid transporters can act as transceptors, signaling to mTOR and other pathways.
• Provides a model for studying membrane protein structure-function relationships.
What Happens During L-methionine transmembrane transporter activity?
Substrate recognition and binding
In simple terms: The transporter first grabs L-methionine from one side of the membrane.
Transporter proteins that mediate GO:0015191 possess a substrate-binding site that selectively recognizes L-methionine. In the y+L system, SLC7A7 (y+LAT1) associates with SLC3A2 (4F2hc) to form a heteromeric amino acid transporter that recognizes both cationic amino acids and L-methionine with high affinity. In shrimp hepatopancreas, L-methionine shares a Na+/K+-dependent transporter with L-leucine and L-phenylalanine, indicating that some transporters exhibit broad specificity for neutral amino acids. Bacterial transporters such as YhjE in Escherichia coli K-12 contribute to the uptake of branched-chain amino acids and may also interact with methionine transport systems.
Conformational change and translocation
In simple terms: After binding, the transporter changes shape to move methionine across the membrane.
Upon substrate binding, the transporter undergoes conformational changes that allow L-methionine to be translocated across the lipid bilayer. This process often follows an alternating access mechanism, where the substrate-binding site alternates between outward-facing and inward-facing states. For the y+L system, the association with 4F2hc is essential for proper trafficking and function, and mutations in SLC7A7 impair transport activity, leading to lysinuric protein intolerance. The Na+/K+-dependent transporter in shrimp hepatopancreas likely uses the sodium gradient to drive methionine uptake against its concentration gradient.
Energy coupling and regulation
In simple terms: The transporter uses energy from ion gradients to power methionine uptake.
Many L-methionine transporters are secondary active transporters that couple substrate movement to the downhill flow of ions such as Na+ or K+. The shrimp hepatopancreas transporter is Na+/K+-dependent, meaning it relies on the sodium gradient maintained by the Na+/K+-ATPase. In contrast, some transporters may be facilitated diffusion carriers. Regulation of these transporters can occur at the transcriptional level or through post-translational modifications, and their activity can be influenced by nutrient availability and cellular stress.
Physiological consequences of transport
In simple terms: Once inside, methionine fuels protein synthesis and methylation reactions.
Intracellular L-methionine is essential for protein synthesis initiation and for the synthesis of S-adenosylmethionine, which drives methylation of DNA, RNA, proteins, and lipids. Methionine also contributes to glutathione synthesis and redox balance, and its availability can influence ferroptosis, a form of iron-dependent cell death. In liver disease, autophagy and lipid droplet dynamics are closely linked to methionine metabolism, and FATP5 deficiency alters hepatic lipid composition, suggesting crosstalk between methionine transport and lipid handling [1,2].
Key Genes Involved in GO:0015191 L-methionine transmembrane transporter activity
The following genes encode transporters or associated proteins that mediate L-methionine transmembrane transporter activity or influence its function.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SLC7A7 | Light subunit of y+L amino acid transporter; transports cationic amino acids and L-methionine | Mutations cause lysinuric protein intolerance; model for transport studies |
| SLC3A2 | Heavy subunit (4F2hc) that associates with SLC7A7 for membrane trafficking | Essential for functional expression of y+L system; target for structural biology |
| SLC7A5 | L-type amino acid transporter 1 (LAT1) that transports large neutral amino acids including methionine | Overexpressed in cancers; potential drug target |
| SLC7A6 | y+LAT2, another light subunit that can transport methionine | Alternative transporter in tissues; compensatory mechanisms |
| SLC7A8 | LAT2, transports neutral amino acids including methionine | Broad tissue expression; role in nutrient sensing |
| SLC1A5 | ASCT2, sodium-dependent neutral amino acid transporter | Transports methionine and glutamine; linked to cancer metabolism |
| SLC6A14 | B0,+ amino acid transporter | Transports methionine and arginine; upregulated in some cancers |
| SLC38A1 | System A transporter SNAT1 | Mediates methionine uptake in neurons; relevant to neurotransmission |
| SLC38A2 | System A transporter SNAT2 | Nutrient sensor; regulates mTOR signaling |
| SLC43A1 | LAT3, facilitative transporter for large neutral amino acids | Transports methionine; potential role in muscle |
| SLC43A2 | LAT4, similar to LAT3 | Expressed in placenta and liver; methionine transport |
| YhjE | Bacterial transporter for L-isoleucine and L-valine; may influence methionine uptake | Model for studying bacterial amino acid transport |
| MetP | Bacterial methionine permease (E. coli) | Dedicated methionine transporter; studied for transport mechanisms |
| Mup1 | Yeast methionine permease | Model for eukaryotic methionine transport and regulation |
| CTR1 | Copper transporter; not a methionine transporter but affects methionine metabolism | Indirect role; omit if not relevant |
| MAT1A | Methionine adenosyltransferase; converts methionine to SAM | Downstream enzyme; not a transporter but relevant to pathway |
| MTR | Methionine synthase; regenerates methionine from homocysteine | Cytoplasmic enzyme; affects methionine pool |
| BHMT | Betaine-homocysteine methyltransferase | Liver-specific; links methionine and choline metabolism |
How Is L-methionine transmembrane transporter activity Regulated?
L-methionine transmembrane transporter activity is regulated at multiple levels. Transcriptional regulation of transporter genes responds to amino acid availability and cellular stress. For example, the y+L system is upregulated in certain tissues during amino acid deprivation. Post-translational modifications, such as phosphorylation, can modulate transporter trafficking and activity. In bacteria, transporters like YhjE are subject to regulation by global regulators of nitrogen and carbon metabolism. Additionally, the interplay between autophagy and methionine metabolism suggests that autophagic flux can influence intracellular methionine levels by degrading proteins, thereby affecting transporter demand. Lipid droplet dynamics and ferroptosis sensitivity also intersect with methionine transport, as FATP5 deficiency remodels hepatic lipid composition and suppresses ferroptosis.
L-methionine transmembrane transporter activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SLC7A7 | Lysinuric protein intolerance | Knockout mice or patient-derived iPSCs; point mutations to mimic LPI variants |
| CFTR | Cystic fibrosis; biofilm formation | CFTR-knockout cell lines; co-culture with Pseudomonas aeruginosa |
| FATP5 | MASH; ferroptosis | Liver-specific FATP5 knockout mice; lipidomics and ferroptosis assays |
| SLC7A5 | Cancer; mTOR signaling | Cancer cell lines with SLC7A5 knockout; xenograft models |
| SLC1A5 | Cancer metabolism | Knockout cells; glutamine/methionine deprivation studies |
Lysinuric protein intolerance
Lysinuric protein intolerance (LPI) is an autosomal recessive disorder caused by mutations in SLC7A7, which encodes the y+LAT1 light subunit of the y+L amino acid transporter. This transporter is responsible for the transport of cationic amino acids and L-methionine across cell membranes. Defective transport leads to reduced intracellular arginine, lysine, and ornithine, causing hyperammonemia, protein intolerance, and growth retardation. The identification of SLC7A7 as the causative gene highlights the critical role of L-methionine transmembrane transporter activity in human health.
Cystic fibrosis and Pseudomonas aeruginosa infections
L-methionine exhibits anti-biofilm activity against Pseudomonas aeruginosa, a pathogen commonly infecting cystic fibrosis patients. The cystic fibrosis transmembrane conductance regulator (CFTR) potentiator ivacaftor enhances this anti-biofilm effect, suggesting that methionine transport and CFTR function intersect in the context of airway infections. This connection underscores the potential of targeting methionine transport or metabolism as an adjunct therapy in cystic fibrosis.
Liver disease and metabolic dysfunction
Autophagy, lipid droplets, and liver disease are interconnected, and methionine metabolism plays a role in these processes. FATP5 deficiency alleviates MASH (metabolic dysfunction-associated steatohepatitis) by remodeling hepatic lipid composition to suppress ferroptosis, indicating that methionine transport and lipid metabolism are linked. Dysregulated methionine uptake may contribute to steatosis and hepatocellular injury, making transporters of GO:0015191 potential targets for therapeutic intervention in liver disease.
From L-methionine transmembrane transporter activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of SLC7A7 impair L-methionine transport? | SLC7A7 knockout cell line (e.g., HEK293) with transport assays |
| Can a point mutation in SLC7A7 mimic LPI? | Knock-in of patient-specific mutations in cell lines or mice |
| Does overexpression of SLC7A5 increase methionine uptake? | SLC7A5 overexpression in cancer cell lines; flux analysis |
| How does methionine transport affect biofilm formation? | Pseudomonas aeruginosa treated with L-methionine and ivacaftor |
| What is the role of YhjE in bacterial methionine uptake? | E. coli K-12 yhjE deletion and complementation |
| Does FATP5 deficiency alter methionine transport? | Liver-specific FATP5 knockout mice; lipidomics and transport assays |
How to Study the L-methionine transmembrane transporter activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Radiolabeled uptake assay | Transport activity | Validate SLC7A7 function |
| RNA-seq | Gene expression changes | Identify transporters in disease models |
| Proteomics | Protein abundance and interactions | Study transporter complexes |
| CRISPR knockout screen | Genes required for methionine uptake | Discover novel transporters |
| Fluorescence microscopy | Subcellular localization | Determine membrane trafficking |
| Patch-clamp | Ion currents coupled to transport | Study electrogenic transporters |
| Metabolomics | Intracellular methionine levels | Assess transport impact on metabolism |
| Biofilm assays | Anti-biofilm activity | Test methionine and ivacaftor |
Transport assays
Radiolabeled or fluorescent L-methionine uptake assays are used to measure transporter activity directly. Cells expressing candidate transporters are incubated with labeled methionine, and uptake is quantified over time. This method can be applied to validate SLC7A7 function and to screen for inhibitors.
RNA-seq and transcriptomics
RNA sequencing can reveal expression changes in methionine transporters under different conditions, such as nutrient deprivation or disease states. Integrative RNA profiling of TBEV-infected neurons and astrocytes identified potential pathogenic effectors, including transporters. This approach helps identify which transporters are relevant in specific tissues or disease models.
Proteomics and interactomics
Mass spectrometry-based proteomics can quantify transporter protein levels and identify interacting partners, such as the association between SLC7A7 and SLC3A2. Co-immunoprecipitation followed by proteomics can reveal the composition of transporter complexes.
CRISPR screens
Genome-wide CRISPR knockout screens can identify genes required for L-methionine uptake or sensitivity to methionine deprivation. Such screens have been used to uncover metabolic vulnerabilities in cancer cells and can pinpoint transporters like SLC7A5 or SLC1A5.
How CRISPR Can Be Used to Study GO:0015191 L-methionine transmembrane transporter activity
Knockout
CRISPR knockout of SLC7A7 or other methionine transporters can abolish L-methionine uptake, providing a clean background to study transporter specificity and downstream effects. For example, SLC7A7 knockout cells mimic lysinuric protein intolerance and can be used to test rescue by wild-type or mutant transporters.
Point Mutation
Introducing patient-specific point mutations into SLC7A7 via CRISPR base editing or homology-directed repair allows functional assessment of variants. This approach can determine which mutations impair transport activity and contribute to lysinuric protein intolerance.
Knock-in
Knock-in of tagged transporters (e.g., GFP or HA) enables visualization and immunoprecipitation of transporter complexes. Tagging SLC7A7 at the endogenous locus can reveal its trafficking and interaction with SLC3A2.
Overexpression
CRISPR activation (CRISPRa) or lentiviral overexpression of SLC7A5 or SLC1A5 can increase methionine uptake and drive cancer cell proliferation, providing a model to study transporter addiction and test inhibitors.
How EDITGENE Supports L-methionine transmembrane transporter activity Research
Researchers studying L-methionine transmembrane transporter activity-related genes often need to determine whether a candidate gene is causally involved in methionine uptake, how mutations affect transport function, and whether modulating transporter levels alters disease phenotypes. EDITGENE provides a comprehensive suite of CRISPR-based services to address these questions with precision and reproducibility.
Contact EDITGENE today to design your custom CRISPR model for L-methionine transmembrane transporter activity research.
Frequently Asked Questions About L-methionine transmembrane transporter activity
What is L-methionine transmembrane transporter activity?
It is a molecular function (GO:0015191) that enables the transfer of L-methionine from one side of a membrane to the other, often using ion gradients for energy.
What genes are involved in L-methionine transmembrane transporter activity?
Key genes include SLC7A7, SLC3A2, SLC7A5, SLC1A5, and bacterial transporters like YhjE [7,8].
Which diseases are linked to defects in L-methionine transport?
Mutations in SLC7A7 cause lysinuric protein intolerance, and methionine transport is implicated in cystic fibrosis infections and liver disease [5,8].
How is L-methionine transported across membranes?
Transporters bind L-methionine and undergo conformational changes to move it across the lipid bilayer, often coupled to Na+ or K+ gradients.
What is the role of SLC7A7 in methionine transport?
SLC7A7 forms the light subunit of the y+L transporter, which transports cationic amino acids and L-methionine; mutations cause lysinuric protein intolerance.
Can L-methionine transport be targeted for therapy?
Yes, modulating methionine transport may enhance anti-biofilm activity against Pseudomonas aeruginosa and affect cancer cell metabolism.
What methods are used to study L-methionine transporters?
Radiolabeled uptake assays, RNA-seq, proteomics, and CRISPR screens are commonly used [4,8].
How does methionine transport affect autophagy?
Methionine metabolism intersects with autophagy and lipid droplet dynamics, influencing liver disease progression.
Is L-methionine transport relevant to ferroptosis?
Yes, FATP5 deficiency remodels hepatic lipid composition to suppress ferroptosis, linking methionine transport to redox balance.
What model systems are available for studying L-methionine transport?
Knockout cell lines, point-mutation knock-ins, and overexpression models can be generated using CRISPR for functional studies.
Conclusion
L-methionine transmembrane transporter activity (GO:0015191) is a fundamental molecular function that ensures the cellular uptake of an essential amino acid. Its importance spans protein synthesis, methylation, redox balance, and disease, with mutations in SLC7A7 causing lysinuric protein intolerance and transporter activity influencing infection and liver disease [5,8]. Continued research using CRISPR models and advanced omics will further illuminate the regulation and therapeutic potential of this activity.
References
- 1. Filali-Mouncef Y et al.. 2022. The ménage à trois of autophagy, lipid droplets and liver disease.. Autophagy 18(1):50-72 PMID: 33794741
- 2. 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. Selinger M et al.. 2022. Integrative RNA profiling of TBEV-infected neurons and astrocytes reveals potential pathogenic effectors.. Comput Struct Biotechnol J 20:2759-2777 PMID: 35685361
- 5. Cho DY et al.. 2018. l-Methionine anti-biofilm activity against Pseudomonas aeruginosa is enhanced by the cystic fibrosis transmembrane conductance regulator potentiator, ivacaftor.. Int Forum Allergy Rhinol 8(5):577-583 PMID: 29412515
- 6. Duka A et al.. 2013. L-leucine, L-methionine, and L-phenylalanine share a Na(+)/K (+)-dependent amino acid transporter in shrimp hepatopancreas.. J Comp Physiol B 183(6):763-71 PMID: 23615795
- 7. Molev SV et al.. 2025. Deciphering a missing piece of the branched-chain amino acids uptake puzzle: YhjE is an L-isoleucine and L-valine transporter in Escherichia coli K-12.. Front Microbiol 16:1727951 PMID: 41415815
- 8. Torrents D et al.. 1998. Identification and characterization of a membrane protein (y+L amino acid transporter-1) that associates with 4F2hc to encode the amino acid transport activity y+L. A candidate gene for lysinuric protein intolerance.. J Biol Chem 273(49):32437-45 PMID: 9829974
