PPP3R1 Human
Description
Molecular Structure and Function
PPP3R1 comprises 170 amino acids and belongs to the calcineurin regulatory subunit family . As part of the calcineurin complex, it confers calcium sensitivity by binding calcium ions through EF-hand motifs, enabling activation of the catalytic subunit (e.g., PPP3CA/CB/CC) . Key functional partners include:
PPP3R1 facilitates dephosphorylation of substrates like NFAT (Nuclear Factor of Activated T-cells), enabling their nuclear translocation to regulate genes involved in immune response, cardiac development, and neuronal plasticity .
Clinical Significance
PPP3R1 dysregulation is implicated in multiple diseases:
Neurodegenerative Disorders
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The SNP rs1868402 in PPP3R1 correlates with accelerated Alzheimer’s disease progression .
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Reduced PPP3R1 expression disrupts calcineurin-NFAT signaling, exacerbating synaptic dysfunction .
Cardiovascular Pathologies
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Hypercholesterolemia downregulates PPP3R1 protein (but not mRNA) via miR-30 family miRNAs, contributing to cardiac dysfunction .
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PPP3R1 depletion in dilated cardiomyopathy impairs calcium handling, promoting arrhythmias .
Immunosuppression
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PPP3R1 polymorphisms (rs875, rs4347819, rs7560138) influence tacrolimus efficacy in transplant patients by altering calcineurin-NFAT pathway activity .
Cellular Senescence and Aging
PPP3R1 drives senescence by depolarizing membranes, increasing Ca²⁺ influx, and activating stress-response pathways. In mesenchymal stem cells (MSCs), PPP3R1 overexpression elevates reactive oxygen species (ROS) and β-galactosidase activity, hallmarks of senescence . Age-dependent PPP3R1 upregulation in murine BMSCs further underscores its role in aging .
Tissue Expression and Research Tools
PPP3R1 is ubiquitously expressed, with high levels in:
| Tissue | Expression Level (nTPM) |
|---|---|
| Cerebral Cortex | 15.2 |
| Lymph Node | 12.8 |
| Heart | 8.5 |
Recombinant PPP3R1 protein (≥90% purity) is commercially available for studies on calcineurin signaling and drug screening .
Therapeutic and Diagnostic Potential
Product Specs
Q&A
Basic Research Questions
What experimental approaches validate PPP3R1's role in calcium signaling pathways?
PPP3R1 (calcineurin B subunit) regulates calcium-dependent phosphatase activity. To study this:
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Use calcium flux assays (e.g., Fura-2AM imaging) paired with calcineurin activity kits to measure PPP3R1-dependent dephosphorylation events .
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Combine RNAi knockdown in neuronal cell lines with electrophysiological recordings to assess synaptic vesicle release dynamics .
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Validate findings using Ppp3r1 conditional knockout mice, analyzing hippocampal calcium-regulated exocytosis pathways via RNA-seq and immunohistochemistry .
How do researchers analyze PPP3R1 expression changes in Alzheimer’s disease (AD) cohorts?
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Process postmortem brain RNA-seq data (e.g., GEO datasets like GSE63060) with pipelines like DESeq2 to identify differentially expressed genes (DEGs) between AD and controls .
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Stratify cohorts by Braak tangle stage and correlate PPP3R1 protein levels (via Western blot) with clinical dementia ratings (CDR) .
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Validate using in situ hybridization in hippocampal sections to localize expression changes to specific neuronal subpopulations .
What functional enrichment methods identify PPP3R1-associated pathways?
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Perform Gene Ontology (GO) and KEGG analysis on co-expressed genes (e.g., STRING DB) to highlight calcium-regulated exocytosis and synaptic vesicle transport .
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Conduct GSEA (Gene Set Enrichment Analysis) using MSigDB’s synaptic transmission gene sets to quantify pathway activation in PPP3R1-low vs. high cohorts .
Advanced Research Questions
How to resolve contradictions in PPP3R1’s disease associations across studies?
What multi-omics strategies elucidate PPP3R1’s role in tau pathology?
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Integrate ATAC-seq (chromatin accessibility) and ChIP-seq (H3K27ac) data from AD brains to identify PPP3R1-linked regulatory elements near MAPT (tau) .
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Perform phosphoproteomics on Ppp3r1 KO mice to quantify tau hyperphosphorylation (e.g., p-tau Ser202/Thr205) .
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Validate using spatial transcriptomics in hippocampal subregions to map PPP3R1-tau colocalization .
How to design CRISPR screens for PPP3R1 interactors in neurodegeneration models?
Methodological Considerations Table
Product Science Overview
Protein Phosphatase 3 is composed of two subunits:
- Catalytic Subunit (PPP3CA): This subunit is responsible for the enzyme’s phosphatase activity. It binds to calmodulin in the presence of calcium ions, which activates the enzyme.
- Regulatory Subunit (PPP3R1): This subunit, also known as Calcineurin B, binds calcium ions and is essential for the enzyme’s activation and stability.
The alpha isozyme of the regulatory subunit (PPP3R1) is one of the isoforms that can be found in humans. It is involved in the regulation of the catalytic subunit’s activity and ensures the proper functioning of the enzyme.
Calcineurin is involved in several critical cellular pathways:
- T-Cell Activation: Calcineurin dephosphorylates the nuclear factor of activated T-cells (NFAT), allowing it to enter the nucleus and initiate the transcription of interleukin-2 (IL-2) and other cytokines, which are vital for T-cell proliferation and immune response.
- Neuronal Signaling: Calcineurin modulates synaptic plasticity and memory formation by dephosphorylating various substrates involved in neurotransmission.
- Muscle Development: Calcineurin plays a role in muscle fiber type differentiation and hypertrophy by regulating the transcription of muscle-specific genes.
The recombinant form of Protein Phosphatase 3, Regulatory Subunit, Alpha Isozyme, is produced using recombinant DNA technology. This involves cloning the gene encoding the protein into an expression vector, which is then introduced into a host cell (such as E. coli or mammalian cells). The host cells express the protein, which is subsequently purified for research or therapeutic use.
Recombinant Protein Phosphatase 3, Regulatory Subunit, Alpha Isozyme, is widely used in research to study its role in various cellular processes and diseases. It is also used in drug discovery and development, particularly in the context of immunosuppressive therapies. Calcineurin inhibitors, such as cyclosporine and tacrolimus, are commonly used to prevent organ transplant rejection by inhibiting T-cell activation.
