GO:0008271 secondary active sulfate transmembrane transporter activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0008271 describes secondary active sulfate transmembrane transporter activity, a molecular function that moves sulfate across membranes using chemiosmotic energy rather than ATP hydrolysis.
• Sulfate transporters in this class include symporters and antiporters that bind sulfate and undergo conformational changes to transfer it up its concentration gradient.
• Key genes include SLC26A1, SLC26A2, SLC26A3, SLC26A4, SLC26A6, SLC26A7, SLC26A8, SLC26A9, SLC26A11, SLC13A1, SLC13A4, and SLC25A10, many of which are linked to human disease.
• The STAS domain is critical for the function and biogenesis of sulfate transporters, and mutations in this domain impair transport activity.
• Charged amino acid residues within transmembrane helices are essential for sulfate transport, as shown by mutagenesis of SHST1.
• Secondary active sulfate transport is regulated by IRBIT, which modulates ion channels and transporters.
Description
Secondary active sulfate transmembrane transporter activity (GO:0008271) is a molecular function that enables the transfer of sulfate across a membrane using a chemiosmotic source of energy, rather than direct ATP hydrolysis. This activity is essential for sulfate homeostasis in cells and organisms, influencing processes such as sulfation of macromolecules, detoxification, and bone development. Researchers study this term to understand how sulfate is absorbed, distributed, and utilized in health and disease. The transporters involved are often members of the SLC26 and SLC13 families, which are expressed in various tissues including kidney, liver, intestine, and cartilage.
secondary active sulfate transmembrane transporter activity At A Glance
| GO ID | GO:0008271 |
|---|---|
| GO term | secondary active sulfate transmembrane transporter activity |
| Ontology | molecular_function |
| Synonym | secondary active sulphate transmembrane transporter activity; sulfate porter activity; sulphate porter activity |
| Major function | Secondary active transfer of sulfate across a membrane using chemiosmotic energy |
| Transport type | Symporters and antiporters |
| Directionality | Works equally well in either direction |
| Energy source | Chemiosmotic source of energy |
What Is GO:0008271?
According to the Gene Ontology, GO:0008271 enables the secondary active transfer of sulfate from one side of a membrane to the other. Secondary active transport is the transfer of a solute across a membrane, up its concentration gradient. The transporter binds the solute and undergoes a series of conformational changes. Transport works equally well in either direction and is driven by a chemiosmotic source of energy. Secondary active transporters include symporters and antiporters. Synonyms include secondary active sulphate transmembrane transporter activity, sulfate porter activity, and sulphate porter activity.
Why Is secondary active sulfate transmembrane transporter activity Important in Cell Biology?
Secondary active sulfate transmembrane transporter activity is crucial for maintaining sulfate homeostasis, which is required for the sulfation of proteins, lipids, and glycosaminoglycans, as well as for detoxification and bone mineralization. Dysfunction of these transporters is associated with human diseases such as chondrodysplasias, due to impaired sulfate uptake in cartilage. Understanding this activity helps researchers develop therapeutic strategies for disorders of sulfate metabolism and transport.
• Maintains sulfate homeostasis in cells and tissues.
• Enables sulfation of macromolecules, including glycosaminoglycans and proteins.
• Supports detoxification processes in the liver.
• Critical for bone and cartilage development.
• Mutations in sulfate transporters cause chondrodysplasias and other diseases.
• Regulated by IRBIT, which modulates ion channels and transporters.
• Involved in kidney and intestinal sulfate reabsorption.
• Target for research in cancer and metabolic disorders.
• Provides a model for studying secondary active transport mechanisms.
• Potential therapeutic target for diseases of sulfate metabolism.
What Happens During secondary active sulfate transmembrane transporter activity?
Substrate Binding and Conformational Change
In simple terms: The transporter grabs sulfate and changes shape to move it across the membrane.
The transporter binds sulfate and undergoes a series of conformational changes to transfer it across the membrane, driven by a chemiosmotic source of energy. This process is essential for moving sulfate up its concentration gradient.
Symport and Antiport Mechanisms
In simple terms: Some transporters move sulfate together with another ion, while others exchange it for a different ion.
Secondary active transporters include symporters and antiporters, which couple sulfate transport to the movement of other ions or solutes. For example, SLC26A6 functions as a sulfate/chloride exchanger.
Role of Transmembrane Helices
In simple terms: Specific parts of the transporter protein are important for moving sulfate.
Charged amino acid residues within transmembrane helices are critical for sulfate transport, as demonstrated by mutagenesis studies of the sulfate transporter SHST1.
STAS Domain Function
In simple terms: A special domain helps the transporter work and fold properly.
The STAS domain is important for the function and biogenesis of sulfate transporters, and random mutagenesis has shown that it is required for transport activity.
Key Genes Involved in GO:0008271 secondary active sulfate transmembrane transporter activity
The following genes encode proteins with secondary active sulfate transmembrane transporter activity or are closely related to this function.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SLC26A1 | Sulfate transporter in liver and kidney | Studied for sulfate homeostasis and detoxification |
| SLC26A2 | Sulfate transporter in cartilage | Mutations cause chondrodysplasias |
| SLC26A3 | Chloride/sulfate exchanger in intestine | Linked to congenital chloride diarrhea |
| SLC26A4 | Iodide/chloride/sulfate transporter | Mutations cause Pendred syndrome |
| SLC26A6 | Sulfate/chloride exchanger | Involved in intestinal and renal sulfate transport |
| SLC26A7 | Sulfate transporter in kidney | Potential role in acid-base balance |
| SLC26A8 | Sulfate transporter in testis | Required for sperm function |
| SLC26A9 | Chloride/sulfate transporter | Associated with airway diseases |
| SLC26A11 | Sulfate transporter in brain | Potential role in neuronal sulfate homeostasis |
| SLC13A1 | Sodium/sulfate cotransporter | Important for renal sulfate reabsorption |
| SLC13A4 | Sodium/sulfate cotransporter | Expressed in placenta and brain |
| SLC25A10 | Mitochondrial sulfate transporter | Involved in mitochondrial sulfate metabolism |
| SHST1 | Plant sulfate transporter | Model for studying transmembrane helix interactions |
| IRBIT | Regulator of ion channels and transporters | Modulates sulfate transporter activity |
How Is secondary active sulfate transmembrane transporter activity Regulated?
Secondary active sulfate transmembrane transporter activity is regulated by IRBIT, a protein that interacts with ion channels and transporters to modulate their activity. Additionally, the STAS domain is essential for the function and biogenesis of sulfate transporters, and mutations in this domain can impair transport.
secondary active sulfate transmembrane transporter activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SLC26A2 | Chondrodysplasias | Knockout mouse or patient-derived iPSCs |
| SLC26A4 | Pendred syndrome | Knock-in mouse models |
| SLC26A3 | Congenital chloride diarrhea | Intestinal organoids |
| SLC26A6 | Kidney stone disease | Knockout mice |
| SLC13A1 | Sulfate homeostasis disorders | Cell lines with overexpression |
Chondrodysplasias
Mutations in SLC26A2, a sulfate transporter, cause chondrodysplasias due to impaired sulfate uptake in cartilage, leading to defective sulfation of proteoglycans.
Pendred Syndrome
Mutations in SLC26A4, which encodes pendrin, a sulfate transporter, are associated with Pendred syndrome, characterized by hearing loss and goiter.
Congenital Chloride Diarrhea
SLC26A3 mutations cause congenital chloride diarrhea, a disorder of intestinal ion transport where sulfate transport may also be affected.
From secondary active sulfate transmembrane transporter activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of SLC26A2 affect cartilage development? | Knockout mouse |
| Does a specific mutation in SLC26A4 impair sulfate transport? | Point mutation knock-in |
| Can overexpression of SLC26A6 rescue sulfate transport? | Overexpression cell line |
| Where is SLC26A1 localized in liver cells? | Tagged knock-in |
| Does IRBIT regulate SLC26A4 activity? | Knockout of IRBIT in cell lines |
| What is the role of STAS domain in sulfate transport? | Random mutagenesis and knock-in |
How to Study the secondary active sulfate transmembrane transporter activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Radioactive sulfate uptake | Transport activity | Functional characterization of transporters |
| Site-directed mutagenesis | Effect of mutations on transport | Identifying critical residues |
| RNA-seq | Gene expression levels | Tissue-specific expression profiling |
| Co-immunoprecipitation | Protein-protein interactions | Identifying regulators like IRBIT |
| Immunofluorescence | Subcellular localization | Determining membrane localization |
| Patch clamp | Ion currents | Electrophysiological characterization |
| CRISPR knockout | Loss-of-function phenotypes | Studying gene function in disease models |
Transport Assays
Radioactive sulfate uptake assays are used to measure secondary active sulfate transport activity in cells expressing specific transporters.
Mutagenesis Studies
Site-directed mutagenesis of transmembrane helices and the STAS domain helps identify residues critical for sulfate transport.
Expression Profiling
RNA-seq and qPCR can determine the expression patterns of sulfate transporters in different tissues and disease states.
Protein Interaction Studies
Co-immunoprecipitation and yeast two-hybrid assays can identify regulators such as IRBIT that interact with sulfate transporters.
How CRISPR Can Be Used to Study GO:0008271 secondary active sulfate transmembrane transporter activity
Knockout
CRISPR knockout of sulfate transporter genes such as SLC26A2 can model chondrodysplasias and reveal compensatory mechanisms.
Point Mutation
Introducing disease-associated point mutations (e.g., in SLC26A4) via CRISPR allows study of transport defects at the molecular level.
Knock-in
Knock-in of tagged versions of sulfate transporters enables localization and interaction studies in native contexts.
Overexpression
CRISPR activation or cDNA overexpression can increase sulfate transport activity to study downstream effects on sulfation and metabolism.
How EDITGENE Supports secondary active sulfate transmembrane transporter activity Research
Researchers studying secondary active sulfate transmembrane transporter activity-related genes often need to determine whether a candidate gene is causally involved in sulfate transport and disease. EDITGENE provides comprehensive CRISPR services to create precise cell models for functional studies.
Contact EDITGENE today to design your custom CRISPR model for secondary active sulfate transmembrane transporter activity research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC26A4 Knockout HEK293 Cell Line | EDJ-KQ2080 | Human | 5172 | Details Get a Quote |
| UCP2 Knockout HEK293 Cell Line | EDJ-KQ2339 | Human | 7351 | Details Get a Quote |
| SLC26A2 Knockout HEK293 Cell Line | EDJ-KQ2573 | Human | 1836 | Details Get a Quote |
| SLC26A3 Knockout HEK293 Cell Line | EDJ-KQ4476 | Human | 1811 | Details Get a Quote |
| SLC13A1 Knockout HEK293 Cell Line | EDJ-KQ5788 | Human | 6561 | Details Get a Quote |
| SLC26A1 Knockout HEK293 Cell Line | EDJ-KQ7191 | Human | 10861 | Details Get a Quote |
| SLC26A5 Knockout HEK293 Cell Line | EDJ-KQ15319 | Human | 375611 | Details Get a Quote |
| SLC26A6 Knockout HEK293 Cell Line | EDJ-KQ15320 | Human | 65010 | Details Get a Quote |
| SLC26A11 Knockout HEK293 Cell Line | EDJ-KQ15321 | Human | 284129 | Details Get a Quote |
| SLC26A1 Knockout HCT 116 Cell Line | EDJ-KQ32133 | Human | 10861 | Details Get a Quote |
| SLC26A6 Knockout A-549 Cell Line | EDJ-KQ46026 | Human | 65010 | Details Get a Quote |
| SLC26A6 Knockout HCT 116 Cell Line | EDJ-KQ46027 | Human | 65010 | Details Get a Quote |
| SLC26A6 Knockout HeLa Cell Line | EDJ-KQ46028 | Human | 65010 | Details Get a Quote |
| SLC26A11 Knockout A-549 Cell Line | EDJ-KQ46029 | Human | 284129 | Details Get a Quote |
| SLC26A11 Knockout HCT 116 Cell Line | EDJ-KQ46030 | Human | 284129 | Details Get a Quote |
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Frequently Asked Questions About secondary active sulfate transmembrane transporter activity
What is secondary active sulfate transmembrane transporter activity?
It is a molecular function (GO:0008271) that moves sulfate across membranes using chemiosmotic energy, often via symporters or antiporters.
What genes are involved in secondary active sulfate transport?
Key genes include SLC26A1, SLC26A2, SLC26A3, SLC26A4, SLC26A6, SLC13A1, and others.
How is sulfate transported across membranes?
Sulfate is transported by secondary active transporters that bind sulfate and undergo conformational changes, driven by ion gradients.
What diseases are linked to sulfate transporter mutations?
Mutations in SLC26A2 cause chondrodysplasias, and SLC26A4 mutations cause Pendred syndrome.
What is the role of the STAS domain in sulfate transporters?
The STAS domain is essential for the function and biogenesis of sulfate transporters.
How can I study sulfate transport in the lab?
Use radioactive sulfate uptake assays, mutagenesis, and CRISPR knockout models.
What is IRBIT and how does it relate to sulfate transport?
IRBIT is a regulator of ion channels and transporters, including sulfate transporters.
Are there animal models for sulfate transport diseases?
Yes, knockout mice for SLC26A2 and other transporters model chondrodysplasias and related disorders.
What are the synonyms for GO:0008271?
Synonyms include secondary active sulphate transmembrane transporter activity, sulfate porter activity, and sulphate porter activity.
How does secondary active sulfate transport differ from primary active transport?
Secondary active transport uses chemiosmotic energy, while primary active transport directly uses ATP.
Conclusion
Secondary active sulfate transmembrane transporter activity (GO:0008271) is a fundamental molecular function that maintains sulfate homeostasis and supports diverse physiological processes. Dysregulation of these transporters leads to diseases such as chondrodysplasias and Pendred syndrome, making them important therapeutic targets. Continued research using CRISPR models and advanced methods will further elucidate their mechanisms and roles in disease.
References
- 2. Pajor AM. 1999. Sodium-coupled transporters for Krebs cycle intermediates.. Annu Rev Physiol 61:663-82 PMID: 10099705
- 3. Shelden MC et al.. 2003. Interactions between charged amino acid residues within transmembrane helices in the sulfate transporter SHST1.. Biochemistry 42(44):12941-9 PMID: 14596609
- 4. Ando H et al.. 2014. IRBIT: a regulator of ion channels and ion transporters.. Biochim Biophys Acta 1843(10):2195-204 PMID: 24518248
- 5. Shi Y et al.. 2024. 5-Aminolevulinic Acid (5-ALA)-Induced Drought Resistance in Maize Seedling Root at Physiological and Transcriptomic Levels.. Int J Mol Sci 25(23) PMID: 39684675
- 6. Bissig M et al.. 1994. Functional expression cloning of the canalicular sulfate transport system of rat hepatocytes.. J Biol Chem 269(4):3017-21 PMID: 8300633
- 7. Bassot C et al.. 2017. Mapping pathogenic mutations suggests an innovative structural model for the pendrin (SLC26A4) transmembrane domain.. Biochimie 132:109-120 PMID: 27771369
- 8. Shibagaki N et al.. 2006. The role of the STAS domain in the function and biogenesis of a sulfate transporter as probed by random mutagenesis.. J Biol Chem 281(32):22964-73 PMID: 16754669
