GO:1903810 L-histidine import across plasma membrane: Transport Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1903810 describes the directed movement of L-histidine from outside a cell, across the plasma membrane, and into the cytosol.
• L-histidine import is a carrier-mediated process, and mechanistic studies of related transporters show that substrate translocation involves conformational changes driven by salt-bridge dynamics and ion release [1,5].
• The process is distinct from outer-membrane transport steps, which have been resolved for colicin E1 import in Escherichia coli.
• Related transport proteins, such as HRG-1-related heme transporters, illustrate how topologically conserved residues can direct substrate movement across membranes.
• Mitochondrial protein import requires sequential action of two hsp70 complexes, providing a paradigm for how multi-step import systems are organized.
• Bidirectional translocation mechanisms can be dissected genetically, as shown by a FocA variant that imports formate poorly but retains formic acid efflux.
Description
GO:1903810, L-histidine import across plasma membrane, is a biological process term that defines the directed movement of L-histidine from outside a cell, across the plasma membrane, and into the cytosol. L-histidine is a proteinogenic amino acid and a precursor for histamine and other metabolites, so its uptake across the plasma membrane is a point of control for cellular metabolism and signaling. The term is therefore relevant to researchers studying amino acid homeostasis, membrane transport, and metabolic disease. Mechanistic understanding of related transport systems has advanced through structural and biochemical studies of membrane transporters. For example, structural analysis of P(IB-4)-type ATPases has revealed ion-release mechanisms that underlie transport cycles, and studies of the membrane transporter GlpT have shown that salt-bridge dynamics control substrate-induced conformational change. These findings provide a general framework for how carriers can couple substrate binding to movement across the membrane. Additional context comes from studies of outer-membrane import, such as the initial steps of colicin E1 import in Escherichia coli, and from work on heme transport by HRG-1-related proteins, where topologically conserved residues direct substrate movement. Together, these studies illustrate the diversity of transport mechanisms that can inform research on L-histidine import.
L-histidine import across plasma membrane At A Glance
| GO ID | GO:1903810 |
|---|---|
| GO term | L-histidine import across plasma membrane |
| Ontology | biological_process |
| Synonym | histidine import; L-histidine import; L-histidine import into cell |
| Definition | The directed movement of L-histidine from outside of a cell, across the plasma membrane and into the cytosol. |
| Major function | Carrier-mediated uptake of L-histidine into the cytosol |
| Directionality | Import (extracellular to intracellular) |
| Compartment | Plasma membrane and cytosol |
What Is GO:1903810?
GO:1903810 is defined as the directed movement of L-histidine from outside of a cell, across the plasma membrane and into the cytosol. In other words, it covers the step in which L-histidine is recognized on the extracellular side, translocated through the plasma membrane, and released into the intracellular compartment. This term is a biological process and is distinct from terms describing transport across organellar membranes or outer membranes. Related synonyms include histidine import, L-histidine import, and L-histidine import into cell.
Why Is L-histidine import across plasma membrane Important in Cell Biology?
L-histidine import across the plasma membrane is important because it supplies a proteinogenic amino acid and a precursor for histamine and other metabolites, and because transport steps are often rate-limiting for cellular responses to nutrient availability. Mechanistic studies of related transporters have shown that substrate translocation depends on precise conformational changes, including salt-bridge dynamics and ion-release steps. Understanding these mechanisms can help researchers interpret how mutations or expression changes in transport proteins affect cellular metabolism. In addition, import pathways are relevant to microbial and host interactions, as illustrated by studies of outer-membrane import and by work on metal and heme transport proteins [3,7].
• Supplies L-histidine for protein synthesis and for synthesis of histamine and related metabolites.
• Represents a point of control for amino acid homeostasis at the plasma membrane.
• Mechanistic studies of related transporters reveal conformational changes driven by salt-bridge dynamics.
• Structural work on P(IB-4)-type ATPases provides a framework for understanding ion-release steps in transport.
• Outer-membrane import studies, such as colicin E1 import, illustrate how transport can be resolved step by step.
• Heme transport by HRG-1-related proteins shows how conserved residues direct substrate movement.
• Mitochondrial protein import demonstrates the importance of sequential complexes in import pathways.
• Bidirectional translocation can be dissected genetically, as shown for FocA variants.
• Metal-binding motifs in transport proteins can influence substrate handling, as seen for CopM and OprC.
• Plastidic ATP/ADP transporter expression in bacteria provides a model for functional expression of transport proteins.
What Happens During L-histidine import across plasma membrane?
Substrate recognition at the plasma membrane
In simple terms: The transporter first recognizes L-histidine on the outside of the cell.
The process begins when L-histidine is available on the extracellular side of the plasma membrane. Transport proteins must distinguish L-histidine from related amino acids and metabolites. Studies of related transporters have shown that substrate recognition is coupled to local structural changes, including salt-bridge rearrangements that control conformational transitions. In addition, work on heme transport by HRG-1-related proteins has identified topologically conserved residues that direct substrate movement, providing a general principle for how recognition sites can be organized.
Conformational change and translocation
In simple terms: The transporter changes shape to move L-histidine across the membrane.
After recognition, the transporter undergoes conformational changes that move the substrate across the lipid bilayer. Structural and biochemical studies of P(IB-4)-type ATPases have revealed ion-release mechanisms that are coupled to transport cycles. Similarly, salt-bridge dynamics in the membrane transporter GlpT control substrate-induced conformational change. These findings support a model in which local electrostatic interactions govern the transition between outward-facing and inward-facing states.
Release into the cytosol
In simple terms: L-histidine is released inside the cell.
The final step of GO:1903810 is the release of L-histidine into the cytosol. This step requires that the substrate-binding site open to the intracellular side and that the substrate be discharged. Mechanistic studies of related transport systems have shown that release can be coupled to ion movements or to changes in protein conformation. The overall directionality of the process is import, from outside the cell to the cytosol.
Distinction from outer-membrane and organellar import
In simple terms: This term is specifically about crossing the plasma membrane, not other membranes.
GO:1903810 is restricted to import across the plasma membrane. It does not describe outer-membrane transport steps, such as the initial steps of colicin E1 import across the outer membrane of Escherichia coli, nor does it describe mitochondrial protein import, which requires sequential action of two hsp70 complexes. Researchers should therefore use this term only for plasma membrane-to-cytosol movement of L-histidine.
Key Genes Involved in GO:1903810 L-histidine import across plasma membrane
The following genes and proteins are relevant to L-histidine import across plasma membrane and to related transport processes, based on published studies of membrane transport mechanisms.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SLC15A4 | Peptide/histidine transporter family member | Candidate for histidine and peptide transport studies |
| SLC15A3 | Peptide/histidine transporter family member | Candidate for endosomal and plasma membrane transport studies |
| SLC7A1 | Cationic amino acid transporter | Model for amino acid transport mechanism |
| SLC7A2 | Cationic amino acid transporter | Model for substrate recognition studies |
| SLC3A2 | Heavy chain partner for amino acid transporters | Relevant to heteromeric transporter assembly |
| SLC6A14 | Amino acid transporter | Model for broad-specificity amino acid uptake |
| SLC38A2 | Sodium-coupled amino acid transporter | Model for nutrient-responsive transport |
| SLC38A3 | Sodium-coupled amino acid transporter | Model for amino acid homeostasis |
| SLC36A1 | Proton-coupled amino acid transporter | Model for pH-dependent transport |
| SLC43A1 | Amino acid transporter | Model for large neutral amino acid transport |
| SLC43A2 | Amino acid transporter | Model for large neutral amino acid transport |
| HRG-1 | Heme transport protein | Illustrates conserved residues in substrate movement |
| GlpT | Glycerol-3-phosphate transporter | Model for salt-bridge dynamics in transport |
| FocA | Formate transporter | Model for bidirectional translocation mechanisms |
| CopM | Metallophore | Model for metal-binding motifs in transport |
| OprC | Outer membrane protein | Model for metal transport interactions |
| P(IB-4)-type ATPase | Ion-transporting ATPase | Model for ion-release mechanisms |
| Hsp70 | Chaperone | Model for sequential import complexes |
How Is L-histidine import across plasma membrane Regulated?
Regulation of L-histidine import across the plasma membrane is expected to occur at the level of transporter expression, localization, and activity, although the specific regulators for this term are not defined by the QuickGO entry. Mechanistic studies of related transporters indicate that activity can be controlled by conformational equilibria and electrostatic interactions, such as salt-bridge dynamics, and by ion-release steps in ATP-driven transporters. In addition, nutrient-responsive transport systems can be regulated by substrate availability and by cellular metabolic state, as suggested by studies of amino acid and nucleotide transporters.
L-histidine import across plasma membrane and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SLC15A4 | Amino acid and peptide transport biology | Knockout cell model |
| SLC7A1 | Cationic amino acid transport biology | Point-mutation cell model |
| SLC38A2 | Nutrient-responsive transport biology | Overexpression cell model |
| HRG-1 | Heme transport biology | Knock-in reporter model |
| GlpT | Membrane transport mechanism | Bacterial expression model |
Amino acid transport and metabolic disease
Altered amino acid transport can affect cellular metabolism and nutrient sensing. Studies of related transport proteins have shown that mutations or expression changes can alter substrate handling. Although specific disease associations for GO:1903810 are not defined by the QuickGO entry, research on amino acid transporters provides a framework for investigating metabolic phenotypes.
Transport proteins and microbial interactions
Outer-membrane import studies, such as the initial steps of colicin E1 import in Escherichia coli, illustrate how transport pathways can be exploited by microbial factors. Related work on metal transport proteins, including CopM and OprC, shows how metal-binding motifs influence transport and host-microbe interactions.
Transport mechanisms in cancer and neurological research
Membrane transporters are frequently studied in cancer and neurological contexts because they influence nutrient availability and signaling. Mechanistic insights from transporters such as GlpT and P(IB-4)-type ATPases can guide hypothesis-driven research on L-histidine import in these disease areas.
From L-histidine import across plasma membrane-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is a candidate gene required for L-histidine import? | Knockout cell model |
| Does a specific residue control substrate recognition? | Point-mutation cell model |
| Can a tagged transporter be tracked in live cells? | Tagged knock-in cell model |
| Does overexpression increase L-histidine uptake? | Overexpression cell model |
| Which genes modify L-histidine import? | CRISPR library screening |
| What pathways are altered by transport loss? | Transcriptomic and proteomic profiling |
How to Study the L-histidine import across plasma membrane Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Radiolabeled transport assay | Uptake of L-histidine | Functional validation of candidate transporters |
| Structural biology | Protein conformation and substrate binding | Mechanistic studies of transport proteins |
| Mutagenesis | Residue-specific effects on transport | Testing salt-bridge and binding-site hypotheses |
| Genetic variant analysis | Separation of import and efflux | Dissecting bidirectional translocation |
| Heterologous expression | Function of transport proteins in a new host | Characterizing candidate transporters |
| Comparative sequence analysis | Conserved residues and motifs | Identifying functional sites |
| Outer-membrane import assays | Steps in membrane translocation | Studying import pathways |
| Metal-binding assays | Interactions with metal ions | Analyzing transport protein motifs |
Transport assays
Transport assays measure the movement of L-histidine across the plasma membrane. Related studies have used functional expression systems to characterize transport proteins, as shown for a plastidic ATP/ADP transporter expressed in Escherichia coli. Such assays can be adapted to test candidate genes for L-histidine import.
Structural and biochemical analysis
Structural studies of P(IB-4)-type ATPases have revealed ion-release mechanisms, and biochemical studies of GlpT have shown how salt-bridge dynamics control conformational change. These approaches can inform mechanistic work on L-histidine transporters.
Genetic dissection of transport
Genetic variants can separate import from efflux, as demonstrated for a FocA variant that is incapable of formate import but retains formic acid efflux. Similar strategies can be used to dissect L-histidine import.
Comparative and evolutionary analysis
Comparative studies of transport proteins, including HRG-1-related proteins and outer-membrane import systems, can identify conserved residues and mechanistic principles relevant to L-histidine import.
How CRISPR Can Be Used to Study GO:1903810 L-histidine import across plasma membrane
Knockout
CRISPR knockout can be used to delete candidate genes and test whether L-histidine import is reduced. This approach is analogous to genetic dissection studies of transport proteins, such as the analysis of FocA variants.
Point Mutation
Point mutations can be introduced to test specific residues predicted to be involved in substrate recognition or conformational change. This strategy is supported by studies showing that salt-bridge dynamics control substrate-induced conformational change in GlpT.
Knock-in
Knock-in of tags or reporters allows visualization and biochemical isolation of transport proteins. Similar approaches have been used to study heme transport by HRG-1-related proteins.
Overexpression
Overexpression can be used to increase transport activity and test whether a candidate gene is sufficient to enhance L-histidine import. Heterologous expression of a plastidic ATP/ADP transporter in Escherichia coli provides a precedent for functional expression of transport proteins.
How EDITGENE Supports L-histidine import across plasma membrane Research
Researchers studying L-histidine import across plasma membrane-related genes often need to determine whether a candidate gene is causally involved in transport, whether specific residues control substrate recognition, and whether expression changes alter cellular phenotypes. EDITGENE provides CRISPR-based cell models and screening services to address these questions with publication-ready rigor.
Contact EDITGENE today to design your custom CRISPR model for L-histidine import across plasma membrane research.
Frequently Asked Questions About L-histidine import across plasma membrane
What is L-histidine import across plasma membrane?
It is the directed movement of L-histidine from outside a cell, across the plasma membrane, and into the cytosol, corresponding to GO:1903810.
What is the GO ID for L-histidine import across plasma membrane?
The GO ID is GO:1903810.
What genes are involved in L-histidine import across plasma membrane?
Candidate genes include amino acid transporter families such as SLC15A4, SLC7A1, and SLC38A2, although specific assignments require experimental validation.
What is the definition of GO:1903810?
The directed movement of L-histidine from outside of a cell, across the plasma membrane and into the cytosol.
How is L-histidine import across plasma membrane studied?
It can be studied using transport assays, structural biology, mutagenesis, heterologous expression, and CRISPR-based genetic models [1,5,8].
Is L-histidine import across plasma membrane the same as outer-membrane import?
No. GO:1903810 specifically describes import across the plasma membrane, not outer-membrane transport steps such as colicin E1 import.
What mechanisms drive L-histidine import?
Related transporters use conformational changes, salt-bridge dynamics, and ion-release steps to move substrates across membranes [1,5].
Can CRISPR be used to study L-histidine import?
Yes. Knockout, point-mutation, knock-in, and overexpression models can test the role of candidate genes and residues in transport.
What diseases are linked to amino acid transport?
Altered amino acid transport can affect metabolic and nutrient-sensing pathways, and transport proteins are studied in cancer and neurological research.
What model systems are suitable for L-histidine import research?
Suitable models include knockout, point-mutation, knock-in, tagged knock-in, and overexpression cell models, as well as CRISPR library screening.
Conclusion
GO:1903810, L-histidine import across plasma membrane, defines a specific transport step that supplies L-histidine to the cytosol. Mechanistic insights from related transporters, including salt-bridge dynamics and ion-release mechanisms, provide a framework for studying this process. CRISPR-based cell models and screening approaches offer practical routes to test candidate genes and residues involved in L-histidine import.
References
- 1. Grønberg C et al.. 2021. Structure and ion-release mechanism of P(IB-4)-type ATPases.. Elife 10 PMID: 34951590
- 2. Masi M et al.. 2007. Initial steps of colicin E1 import across the outer membrane of Escherichia coli.. J Bacteriol 189(7):2667-76 PMID: 17277071
- 3. Yuan X et al.. 2012. Topologically conserved residues direct heme transport in HRG-1-related proteins.. J Biol Chem 287(7):4914-24 PMID: 22174408
- 4. Horst M et al.. 1997. Sequential action of two hsp70 complexes during protein import into mitochondria.. EMBO J 16(8):1842-9 PMID: 9155010
- 5. Law CJ et al.. 2008. Salt-bridge dynamics control substrate-induced conformational change in the membrane transporter GlpT.. J Mol Biol 378(4):828-39 PMID: 18395745
- 6. Kammel M et al.. 2025. A FocA variant incapable of formate import but retaining formic acid efflux highlights the distinct mechanisms governing bidirectional formate translocation.. Microb Physiol PMID: 40931489
- 7. Hecel A et al.. 2025. Thiol, His-His Motif, and the Battle over Cu(II) in the Relationship of CopM Metallophore and OprC Outer Membrane Protein.. Inorg Chem 64(6):2936-2950 PMID: 39914813
- 8. Tjaden J et al.. 1998. Expression of a plastidic ATP/ADP transporter gene in Escherichia coli leads to a functional adenine nucleotide transport system in the bacterial cytoplasmic membrane.. J Biol Chem 273(16):9630-6 PMID: 9545295
