PPP1R3A Antibody
Description
What Is PPP1R3A Antibody?
PPP1R3A antibody is a laboratory tool designed to detect and study the protein phosphatase 1 regulatory subunit 3A (PPP1R3A), a glycogen-targeting subunit of protein phosphatase 1 (PP1). This regulatory subunit plays critical roles in glycogen metabolism, muscle contractility, and calcium homeostasis by directing PP1 to dephosphorylate substrates like glycogen synthase (GS) and glycogen phosphorylase (GP) . Antibodies targeting PPP1R3A are widely used in research to investigate its expression, localization, and functional interactions in diseases such as type 2 diabetes, heart failure, and atrial fibrillation .
General Properties
Functional Domains
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Glycogen-binding domain: Facilitates PP1 targeting to glycogen particles .
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Sarcoplasmic reticulum (SR) binding: Mediates localization to SR membranes in muscle cells .
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PP1c-binding domain: Directs phosphatase activity toward glycogen-metabolizing enzymes .
Role in Metabolic Disorders
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Glycogen Synthesis: PPP1R3A deficiency reduces muscle glycogen content by impairing PP1-mediated dephosphorylation of GS and GP. A prevalent PPP1R3A FS mutation (C1984ΔAG) causes premature termination of the protein, leading to reduced glycogen storage in humans and mice .
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Type 2 Diabetes: Impaired insulin-stimulated glycogen synthesis in PPP1R3A FS carriers suggests a potential link to insulin resistance and diabetes pathogenesis .
Cardiac Function and Disease
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Atrial Fibrillation (AF): PPP1R3A downregulation in human atria correlates with aberrant sarcoplasmic reticulum (SR) calcium release and increased AF susceptibility. Knockout mice show reduced PP1 binding to RyR2 and phospholamban (PLN), leading to hyperphosphorylation and SR calcium leakage .
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Heart Failure: PPP1R3A knockdown in cardiomyocytes attenuates hypertrophy and restores oxidative metabolism by modulating pyruvate dehydrogenase kinase (PDK2) and glucose transporters (GLUT1/4) .
Bone and Tendon Biology
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Osteogenesis: PPP1R3A inhibits osteogenic differentiation in tendon cells. Knockdown increases alkaline phosphatase activity and osteochondral markers (e.g., OCN, Sox9), suggesting regulatory roles in calcium homeostasis .
Validation and Performance
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Specificity: Antibodies are validated using siRNA knockdown, gene knockout models, and peptide-blocking assays .
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Key Findings:
Technical Considerations
Product Specs
Target Background
- A variant in the PPP1R3A gene has been associated with type 2 diabetes. PMID: 29948331
- In univariate analyses, TP53, PPP1R3A, and KMT2B were found to be significantly more frequently mutated in interval cancers than in screen-detected cancers. PMID: 27587435
- Research suggests that hScrib acts as a scaffold to integrate the control of the PP1gamma and ERK signaling pathways, providing an explanation for how disruptions in hScrib localization can contribute to the development of human malignancy. PMID: 23359326
- Studies have shown that a combined effect of Asp905 and BMI increases the risk of type 2 diabetes, and the Asp905Tyr and ARE polymorphism of the PPP1R3 gene are not major diabetogenic gene variants in the Chinese population. PMID: 11793847
- G(M) promotes glycogen storage and inversely regulates glycogen synthase and glycogen phosphorylase activities. Notably, the synthase phosphatase activity of G(M)-PP1 is inhibited by glycogen. PMID: 12941760
- In the largest cohort of nondiabetic subjects (Caucasian, n = 112), the presence of the deletion allele (ARE-2) was associated with insulin resistance and hyperandrogenemia. PMID: 15181086
- Inactivation of the PPP1R3 gene has been linked to tumor progression and metastasis of colorectal cancers. PMID: 15870946
- PPP1R3A C1984DeltaAG (stop codon 668) is the most prevalent mutation that directly impairs glycogen synthesis and decreases glycogen levels in human skeletal muscle. It is present in approximately 1 in 70 UK whites. PMID: 18232732
