SGCD Human
Description
Molecular Structure and Properties
The recombinant SGCD Human protein is produced in E. coli as a non-glycosylated polypeptide with a molecular mass of 28 kDa. Key structural features include:
The protein’s sequence includes conserved domains critical for interactions with other sarcoglycans (e.g., α, β, γ) and dystrophin .
Biological Function
SGCD is integral to the DGC, which anchors the cytoskeleton to the extracellular matrix, protecting muscle fibers during contraction. Key roles include:
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Sarcolemmal Stabilization: Prevents muscle cell membrane damage during mechanical stress .
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Cardiac Muscle Integrity: Maintains heart muscle function; defects linked to dilated cardiomyopathy (DCM) .
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Melanocyte Regulation: Expression modulated by MITF in melanocytic cells .
Clinical Associations
Mutations in SGCD are implicated in two primary disorders:
Table 1: Clinical Conditions Linked to SGCD
Key Mutations:
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p.A131P (homozygous): Causes severe LGMD2F in consanguineous families .
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p.S151A (heterozygous): Controversially linked to DCM; conflicting evidence on penetrance .
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p.Arg97* (nonsense): Truncated protein; triggers nonsense-mediated decay .
4.1. Genetic and Molecular Insights
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Sarcoglycan Complex Dynamics: Mutations disrupt the tetramer formation (α-β-γ-δ), destabilizing the DGC .
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Gene-Environment Interactions: The SGCD GG genotype may protect against systolic hypertension in low-discrimination environments .
4.2. Controversies in DCM Pathogenesis
The p.S151A variant has sparked debate:
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Pro-DCM Evidence: Linked to fatal DCM in some families (e.g., heart failure, transplantation) .
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Counter-Evidence: No cardiac symptoms observed in consanguineous families with this mutation .
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Mechanistic Studies: Mouse models (heterozygous S151A) show mild cardiac phenotypes, suggesting modifier genes may influence outcomes .
Genetic and Diagnostic Resources
Product Specs
Q&A
Here’s a structured collection of FAQs tailored for researchers studying SGCD in human disease contexts, incorporating methodological insights and data from recent studies:
What is the role of δ-sarcoglycan (SGCD) in human cardiomyopathies and muscular dystrophies?
The SGCD gene encodes a critical component of the dystrophin-glycoprotein complex (DGC), which stabilizes muscle membranes during contraction. Mutations in SGCD disrupt the sarcoglycan complex, leading to:
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Cardiomyopathy: Loss of δ-sarcoglycan causes secondary depletion of α-, β-, and γ-sarcoglycan in cardiac tissue, resulting in systolic dysfunction, myocardial degeneration, and sudden death in animal models .
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Limb-Girdle Muscular Dystrophy Type 2F (LGMD2F): Homozygous nonsense mutations (e.g., p.Arg97*) induce premature stop codons, triggering nonsense-mediated decay or truncated protein production, leading to progressive muscle weakness and cardiomyopathy .
Methodological Insight: Use immunohistochemistry to assess sarcoglycan complex integrity in patient biopsies or model systems. Quantify protein levels via Western blot .
Which experimental models best recapitulate SGCD-associated pathologies?
Methodological Insight: Prioritize pigs for translational studies of structural cardiac pathology and mice for early functional deficits .
How do contradictions in SGCD−/− cardiac function data arise, and how can they be resolved?
Studies report conflicting results on ejection fraction and contractility in SGCD−/− models due to:
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Genetic modifiers: Background strains (e.g., Ltbp4, Annexin6) influence phenotype severity .
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Experimental design:
Methodological Insight: Standardize genetic backgrounds and use ex vivo assays (e.g., β-adrenergic stimulation tests) to isolate cardiomyocyte-specific deficits .
What gene therapy strategies show promise for SGCD-related diseases?
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Claudin-5 virotherapy: AAV6-mediated delivery restores cardiac contractility in Sgcd−/− mice by improving membrane stability .
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CRISPR/Cas9 editing: Not yet tested for SGCD but successful in other sarcoglycanopathies (e.g., SGCB).
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Read-through agents: Potential to bypass nonsense mutations (e.g., p.Arg97*), though efficacy depends on mutation position .
Methodological Insight: Combine functional assays (e.g., force measurements in AAV-treated muscles) with histopathology to validate therapy efficacy .
How can multi-omics approaches clarify SGCD mutation pathogenicity?
Methodological Insight: Use trio-based sequencing to distinguish pathogenic mutations from benign variants in consanguineous families .
Data Contradiction Analysis
Issue: Variable ejection fraction findings in SGCD−/− mice .
Resolution Framework:
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Control for genetic modifiers: Backcross models to uniform genetic backgrounds.
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Standardize functional assays: Use high-fidelity pressure-volume loops in vivo and length-tension relationships ex vivo.
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Longitudinal monitoring: Track disease progression from pre-symptomatic to late stages.
Example: A study using isolated cardiac muscles (sarcomere length = 2.2 μm) revealed significant contractile deficits in Sgcd−/− mice, resolving discrepancies from prior unloaded cardiomyocyte experiments .
Experimental Design Table for SGCD Studies
Product Science Overview
Sarcoglycan Delta is a transmembrane glycoprotein with a small intracellular domain and a single transmembrane hydrophobic domain . It shows about 70% identity at the amino acid level to both human and rabbit gamma-sarcoglycan (SGCG) . The protein is expressed most abundantly in skeletal and cardiac muscle .
The gene encoding Sarcoglycan Delta is located on chromosome 5q33. The protein’s gene ID is 6444, and its UniProt ID is Q92629 . Mutations in this gene have been associated with autosomal recessive limb-girdle muscular dystrophy (LGMD) and dilated cardiomyopathy . These mutations can lead to the disruption of the sarcoglycan complex, resulting in muscle weakness and degeneration.
Recombinant Human Sarcoglycan Delta is typically produced in E. coli and is often tagged with a His-tag for purification purposes . The recombinant protein is used in various research applications, including ELISA, Western Blot (WB), and Immunoprecipitation (IP) . The biological activity of the recombinant protein is determined by its binding ability in functional assays .
Recombinant Sarcoglycan Delta is valuable in studying the molecular mechanisms underlying muscular dystrophies and cardiomyopathies. It is also used to investigate the interactions within the dystrophin-glycoprotein complex and to develop potential therapeutic strategies for muscle-related diseases .
