GO:0002134 UTP binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0002134 (UTP binding) is a molecular function defined as binding to uridine 5'-triphosphate (UTP), a pyrimidine ribonucleotide that serves as an RNA building block and a signaling molecule.
• UTP-binding proteins include metabolic enzymes such as E. coli aspartate carbamoyltransferase, where UTP binds to low-affinity CTP sites to synergistically inhibit the enzyme.
• UTP activates G protein-coupled P2Y2 and P2Y4 receptors, which mediate purinergic signaling in inflammation and other processes [3, 6].
• UTP is also bound by RNA-processing factors such as Pwp2, which mediates UTP-B assembly, and by transcriptional U three proteins (t-UTPs) like hALP that regulate RNA polymerase I transcription [7, 8].
• Chemical proteomic profiling has identified numerous UTP-binding proteins in human cells, highlighting the broad scope of UTP-dependent functions.
• Dysregulation of UTP-binding proteins is linked to inflammation, metabolic disorders, and cancer, making them potential therapeutic targets [3, 6].
Description
Uridine 5'-triphosphate (UTP) is a pyrimidine nucleotide that serves as a substrate for RNA synthesis and as an extracellular signaling molecule. The Gene Ontology term GO:0002134, UTP binding, describes the molecular function of selectively interacting with UTP. This function is critical for diverse cellular processes, including nucleotide metabolism, RNA processing, and purinergic signaling [1, 4, 7]. Researchers study UTP binding to understand how cells sense and respond to nucleotide levels, and to identify targets for diseases such as inflammation and cancer [3, 6]. The binding of UTP to proteins can be specific, as seen in E. coli aspartate carbamoyltransferase where UTP binds to low-affinity CTP sites to synergistically inhibit the enzyme in the presence of CTP. In eukaryotes, UTP-binding proteins participate in ribosome assembly and transcription, exemplified by Pwp2 and hALP [7, 8]. Chemical proteomic profiling has revealed a wide array of UTP-binding proteins in human cells, underscoring the importance of this molecular function.
UTP binding At A Glance
| GO ID | GO:0002134 |
|---|---|
| GO term | UTP binding |
| Ontology | molecular_function |
| Synonym | None |
| Major function | Binding to uridine 5'-triphosphate (UTP) |
| Related processes | RNA synthesis, purinergic signaling, nucleotide metabolism |
| Example proteins | P2Y2, P2Y4, aspartate carbamoyltransferase, Pwp2, hALP |
| Disease relevance | Inflammation, cancer, metabolic disorders |
What Is GO:0002134?
UTP binding (GO:0002134) is the molecular function of binding to uridine 5'-triphosphate (UTP), a ribonucleotide consisting of uracil, ribose, and three phosphate groups. This binding can be non-covalent and reversible, and it may serve structural, regulatory, or catalytic roles in proteins. The term encompasses any protein that interacts with UTP, including enzymes, receptors, and RNA-binding proteins [1, 3, 4, 7].
Why Is UTP binding Important in Cell Biology?
UTP binding is fundamental to cellular function because UTP is not only a building block of RNA but also a signaling molecule. Proteins that bind UTP regulate key processes such as RNA transcription, ribosome assembly, and extracellular nucleotide signaling [1, 7, 8]. Dysregulation of these proteins can lead to diseases including inflammation and cancer, making UTP-binding proteins attractive targets for drug discovery [3, 6].
• UTP is a substrate for RNA synthesis, and its binding to RNA polymerases and transcription factors is essential for gene expression.
• UTP-binding proteins like Pwp2 are required for ribosome assembly, linking UTP binding to protein synthesis.
• Extracellular UTP activates P2Y2 and P2Y4 receptors, which mediate inflammation and immune responses [3, 6].
• UTP binding to metabolic enzymes such as aspartate carbamoyltransferase regulates pyrimidine biosynthesis.
• Chemical proteomics has identified many UTP-binding proteins, revealing new roles in cellular metabolism.
• UTP-binding proteins are potential drug targets for inflammatory diseases and cancer [3, 6].
• UTP binding can be studied using biochemical assays, structural biology, and CRISPR-based models [1, 3].
• Understanding UTP binding helps elucidate mechanisms of nucleotide sensing and signaling [2, 3].
What Happens During UTP binding?
UTP as a substrate for RNA synthesis
In simple terms: UTP is used as a building block to make RNA.
During transcription, UTP binds to RNA polymerases and is incorporated into growing RNA strands. This binding is essential for the synthesis of all RNA molecules, including messenger RNA, ribosomal RNA, and transfer RNA.
UTP binding in purinergic signaling
In simple terms: UTP can act as a signal outside cells by binding to receptors.
Extracellular UTP binds to P2Y2 and P2Y4 receptors, which are G protein-coupled receptors. This binding activates intracellular signaling cascades that regulate inflammation, cell proliferation, and migration [3, 6].
UTP binding in ribosome assembly
In simple terms: UTP helps assemble the machinery that makes proteins.
In the nucleolus, UTP-binding proteins such as Pwp2 are part of the UTP-B complex, which is required for the assembly of small ribosomal subunits. Pwp2 mediates UTP-B assembly via two structurally independent domains.
UTP binding in transcriptional regulation
In simple terms: UTP-binding proteins can control how genes are turned on.
The transcriptional U three protein hALP binds and acetylates upstream binding factor (UBF), activating RNA polymerase I transcription. This links UTP binding to ribosomal RNA synthesis and cell growth.
UTP binding in metabolic regulation
In simple terms: UTP can tell enzymes to slow down or speed up.
In E. coli, UTP binds to the low-affinity CTP sites of aspartate carbamoyltransferase, synergistically inhibiting the enzyme in the presence of CTP. This feedback regulation controls pyrimidine biosynthesis.
Key Genes Involved in GO:0002134 UTP binding
The following genes and proteins are representative examples of UTP-binding proteins, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| P2RY2 | UTP-activated G protein-coupled receptor | Inflammation, cancer, drug target |
| P2RY4 | UTP-activated G protein-coupled receptor | Inflammation, cancer, drug target |
| PYR1 (aspartate carbamoyltransferase) | Bacterial enzyme inhibited by UTP | Model for allosteric regulation |
| PWP2 | Mediates UTP-B assembly in ribosome biogenesis | Ribosomopathy, cancer |
| hALP | Transcriptional U three protein, activates RNA pol I | Ribosome biogenesis, cancer |
| UTP-B complex components | Ribosome assembly | Ribosomopathy |
| Ectonucleotidases | Regulate extracellular UTP levels | Inflammation |
| UTP-binding proteins (proteomics) | Various cellular functions | Chemical proteomics |
| P2Y2 receptor | UTP signaling | Inflammation |
| P2Y4 receptor | UTP signaling | Inflammation |
| Aspartate carbamoyltransferase | Pyrimidine biosynthesis | Allosteric regulation |
| Pwp2 | UTP-B assembly | Ribosome biogenesis |
| hALP | RNA pol I transcription | Transcription regulation |
| UTP-binding proteins in frog semicircular canal | Phosphoinositidase C activation | Sensory signaling |
| UDP-glucose related proteins | Proinsulin degradation | Diabetes |
How Is UTP binding Regulated?
UTP binding can be regulated by cellular UTP concentrations, which fluctuate with metabolic state and extracellular signaling. For example, ectonucleotidases hydrolyze extracellular UTP, thereby terminating receptor activation. Intracellular UTP levels are controlled by pyrimidine biosynthesis and salvage pathways, and allosteric enzymes like aspartate carbamoyltransferase are feedback-inhibited by UTP. Additionally, post-translational modifications of UTP-binding proteins, such as acetylation of hALP, can modulate their activity.
UTP binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| P2RY2 | Inflammation | Knockout mouse, overexpression cell line |
| P2RY4 | Inflammation | Knockout mouse, overexpression cell line |
| PWP2 | Ribosomopathy, cancer | Knockout cell line, knock-in mutation |
| hALP | Cancer | Knockout cell line, overexpression |
| Aspartate carbamoyltransferase | Metabolic disorders | Point mutation in bacterial model |
UTP binding in inflammation
Extracellular UTP activates P2Y2 and P2Y4 receptors, promoting inflammatory responses. Ectonucleotidases regulate UTP levels, and their dysregulation is associated with acute and chronic inflammation [3, 6].
UTP binding in cancer
UTP-binding proteins involved in ribosome biogenesis, such as Pwp2 and hALP, are overexpressed in some cancers, contributing to increased protein synthesis and cell proliferation [7, 8].
UTP binding in metabolic disorders
UTP binding to enzymes like aspartate carbamoyltransferase regulates pyrimidine biosynthesis, and its dysregulation can affect nucleotide balance and metabolic disorders.
UTP binding in sensory signaling
In frog semicircular canal, UTP binding activates phosphoinositidase C, suggesting a role in sensory signaling.
From UTP binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does P2RY2 mediate UTP-induced inflammation? | P2RY2 knockout mouse |
| What is the role of Pwp2 in ribosome assembly? | PWP2 knockout cell line |
| How does hALP acetylation affect RNA pol I transcription? | hALP point mutant knock-in |
| Can UTP binding be targeted in cancer? | Overexpression of UTP-binding proteins in cancer cell lines |
| What is the effect of UTP on metabolic enzymes? | Point mutation in aspartate carbamoyltransferase |
| How do ectonucleotidases regulate UTP signaling? | Knockout of ectonucleotidases in cell lines |
How to Study the UTP binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Chemical proteomics | UTP-binding proteins | Identifying novel UTP binders |
| Mutagenesis | Ligand binding and activation | P2Y receptor studies |
| X-ray crystallography | 3D structure of UTP-protein complexes | Pwp2 structure |
| Enzymatic assays | Enzyme activity | Aspartate carbamoyltransferase |
| RNA-seq | Gene expression changes | Knockout studies |
| Ribo-seq | Translation efficiency | Ribosome assembly studies |
| CRISPR screening | Gene essentiality | Identifying UTP-binding protein functions |
| Immunoprecipitation | Protein-protein interactions | UTP-B complex assembly |
Chemical proteomics for UTP-binding proteins
Chemical proteomic profiling using UTP-based probes can identify UTP-binding proteins in human cells. This method combines affinity enrichment with mass spectrometry to reveal the UTP interactome.
Mutagenesis and pharmacological studies
Site-directed mutagenesis of P2Y2 and P2Y4 receptors combined with pharmacological assays can elucidate ligand binding and activation mechanisms.
Structural biology
X-ray crystallography and cryo-EM can determine the structures of UTP-binding proteins, such as Pwp2 domains, revealing how UTP is recognized.
Biochemical assays
Enzymatic assays measuring aspartate carbamoyltransferase activity in the presence of UTP and CTP can reveal allosteric regulation.
How CRISPR Can Be Used to Study GO:0002134 UTP binding
Knockout
CRISPR knockout of UTP-binding genes such as P2RY2, P2RY4, or PWP2 can reveal their roles in inflammation, signaling, and ribosome assembly. Knockout cell lines are valuable for studying loss-of-function phenotypes [3, 7].
Point Mutation
Introducing point mutations in UTP-binding proteins, such as in the ligand-binding pocket of P2Y2, can dissect the molecular determinants of UTP binding and activation.
Knock-in
Knock-in of tagged UTP-binding proteins (e.g., GFP or HA tags) allows for localization and interaction studies. This is useful for tracking Pwp2 or hALP in live cells [7, 8].
Overexpression
Overexpression of UTP-binding proteins like hALP or P2Y2 can model gain-of-function effects in cancer and inflammation, and can be used for drug screening [3, 8].
How EDITGENE Supports UTP binding Research
Researchers studying UTP binding-related genes often need to determine whether a candidate gene is causally involved in a specific cellular process or disease. EDITGENE provides comprehensive CRISPR services to create precise cell models for such investigations.
Contact EDITGENE today to design your custom CRISPR model for UTP binding research.
Frequently Asked Questions About UTP binding
What is UTP binding?
UTP binding is the molecular function of selectively interacting with uridine 5'-triphosphate (UTP), a nucleotide involved in RNA synthesis and signaling.
What genes are involved in UTP binding?
Genes encoding UTP-binding proteins include P2RY2, P2RY4, PWP2, and hALP, among others [3, 7, 8].
What is GO:0002134?
GO:0002134 is the Gene Ontology term for UTP binding, a molecular function.
How is UTP binding studied?
UTP binding is studied using chemical proteomics, mutagenesis, structural biology, and biochemical assays [1, 3, 4, 7].
What diseases are associated with UTP binding?
UTP binding is linked to inflammation, cancer, and metabolic disorders [3, 6, 7, 8].
What are P2Y2 and P2Y4 receptors?
P2Y2 and P2Y4 are G protein-coupled receptors activated by UTP, involved in inflammation and signaling.
What is the role of UTP in ribosome assembly?
UTP is required for the assembly of ribosomal subunits, mediated by proteins like Pwp2.
Can UTP binding be targeted therapeutically?
Yes, UTP-binding proteins are potential drug targets for inflammatory diseases and cancer [3, 6].
What is the UTP-B complex?
The UTP-B complex is a group of proteins involved in ribosome assembly, including Pwp2.
How does UTP regulate enzyme activity?
UTP can act as an allosteric inhibitor, as seen in E. coli aspartate carbamoyltransferase.
Conclusion
UTP binding (GO:0002134) is a fundamental molecular function with diverse roles in RNA synthesis, signaling, and metabolism. Understanding the proteins that bind UTP provides insights into cellular regulation and disease mechanisms. CRISPR-based models are powerful tools for dissecting the functions of UTP-binding proteins and developing targeted therapies.
References
- 1. Liu Y et al.. 2021. Chemical proteomic profiling of UTP-binding proteins in human cells.. Anal Chim Acta 1168:338607 PMID: 34052001
- 2. Teixeira M et al.. 2000. UTP binding and phosphoinositidase C activation in ampulla from frog semicircular canal.. Am J Physiol Regul Integr Comp Physiol 279(3):R803-12 PMID: 10956237
- 3. Attah IY et al.. 2020. Ligand binding and activation of UTP-activated G protein-coupled P2Y(2) and P2Y(4) receptors elucidated by mutagenesis, pharmacological and computational studies.. Biochim Biophys Acta Gen Subj 1864(3):129501 PMID: 31812541
- 4. Zhang Y et al.. 1991. The synergistic inhibition of Escherichia coli aspartate carbamoyltransferase by UTP in the presence of CTP is due to the binding of UTP to the low affinity CTP sites.. J Biol Chem 266(33):22154-8 PMID: 1939236
- 6. Giuliani AL et al.. 2020. Ectonucleotidases in Acute and Chronic Inflammation.. Front Pharmacol 11:619458 PMID: 33613285
- 7. Boissier F et al.. 2017. Pwp2 mediates UTP-B assembly via two structurally independent domains.. Sci Rep 7(1):3169 PMID: 28600509
- 8. Kong R et al.. 2011. hALP, a novel transcriptional U three protein (t-UTP), activates RNA polymerase I transcription by binding and acetylating the upstream binding factor (UBF).. J Biol Chem 286(9):7139-48 PMID: 21177859
