SERPINA7 Human
Description
Introduction to SERPINA7 Human
SERPINA7 Human, encoded by the SERPINA7 gene, is a 44–55 kDa glycoprotein that primarily functions as thyroxine-binding globulin (TBG). It belongs to the serpin superfamily (clade A) and is synthesized in the liver. TBG is the primary transporter of thyroid hormones (T₃ and T₄) in the bloodstream, binding approximately 75% of circulating T₄ and 80% of T₃ . Despite its low plasma concentration compared to other transport proteins (e.g., transthyretin, albumin), TBG has the highest affinity for thyroid hormones .
Protein Structure
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Class: Serpin (serine protease inhibitor)
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Domain: Core β-sheet structure with an exposed reactive center loop (RCL)
Functional Role
Genetic and Molecular Insights
The SERPINA7 gene is located on the X chromosome (Xq22.3) and spans ~6.1 kb. Mutations in this gene cause thyroxine-binding globulin deficiency (TBG-CD) or excess (TBG-E), with distinct phenotypes:
Key Mutations and Phenotypes
Inheritance Patterns
Differential Diagnosis
| Condition | Total T₄/T₃ | Free T₄/T₃ | TBG Level |
|---|---|---|---|
| TBG-CD | Low | Normal | Very low (<10% normal) |
| Hypothyroidism | Low | Low | Normal/Elevated |
| TBG-E | High | Normal | Elevated (2–4× normal) |
Case Studies
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TBG-CD: A 61-year-old male with c.1114del mutation (exon 5) had TBG <1.42 μg/mL, leading to chronic misdiagnosis of hypothyroidism .
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TBG-PD: A novel p.Phe269Cysfs*18 mutation caused partial deficiency (TBG 5.16 μg/mL), mimicking mild hypothyroidism .
Genetic Diversity
Over 25 SERPINA7 mutations are documented, including:
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Splice-site mutations: Disrupt exon-intron boundaries (e.g., donor splice site in TBG-CD-Andrews) .
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Frameshifts: Premature stop codons (e.g., p.Leu372Phefs*23) .
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Missense variants: Altered T₄ binding (e.g., p.Glu74Lys in TBG-PD-Korea) .
Population-Specific Variants
Therapeutic and Diagnostic Applications
Product Specs
Thyroxine binding globulin, also called SERPINA7, is a protein produced by the liver that helps transport thyroid hormones in the blood. Changes in SERPINA7 levels can occur in various health conditions. Measuring SERPINA7 is important for understanding thyroid function by determining the levels of free T3 and T4 hormones. It binds to and carries the majority of T3 and T4 in the bloodstream. Typically, about 25% of Thyroxine binding globulin has a T3 or T4 hormone bound to it.
This is a purified protein, called SERPINA7, that is naturally found in human blood. It is approximately 55 kilodaltons in size.
It appears as a white powder that has been freeze-dried and sterilized through filtration.
The protein powder was freeze-dried from a solution containing 20mM NH4HCO3 and filtered through a 0.2 micrometer filter.
To reconstitute the freeze-dried SERPINA7 Human, dissolve it in a phosphate buffer solution containing 0.15M NaCl.
While SERPINA7 Human remains stable at room temperature for up to 3 weeks, it is recommended to store it between 2-8 degrees Celsius for long-term preservation.
The purity of this product is greater than 98%.
The donor of the starting material for this product has undergone testing and been confirmed negative for various viral infections including HIV-1, HIV-2, HCV, HBSAG, Parvovirus B19, Syphilis. Additional PCR testing confirms the absence of HIV, HBV, and HCV.
Human serum.
Q&A
What is the molecular structure and function of human SERPINA7?
SERPINA7 (Thyroxine-binding globulin, TBG) is a secreted 54 kDa glycoprotein that functions as a non-inhibitory member of the serpin family. Unlike most serpins that act as protease inhibitors, SERPINA7 specializes in binding and transporting thyroid hormones in plasma. It spans amino acids Ala21-Ala415 and is primarily expressed by the liver . Human SERPINA7 shares approximately 76% amino acid sequence identity with mouse SERPINA7 . The protein binds thyroxine (T4) and triiodothyronine (T3) with high affinity, regulating their bioavailability and half-life in circulation.
What experimental methods are recommended for detecting SERPINA7 protein?
For laboratory detection of SERPINA7, researchers should employ:
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Western blot analysis: Use PVDF membranes under reducing conditions with specific antibodies like Sheep Anti-Human Serpin A7/TBG. SERPINA7 appears as a band at approximately 55 kDa .
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Direct ELISA: Can be used for quantitative measurement, though cross-reactivity with other serpins (approximately 5% with Serpin A9) should be considered .
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Immunoassays: For clinical samples, techniques include immunoradiometric assay (IRMA), radioimmunoassay (RIA), and electrochemiluminescence immunoassay (ECLIA) .
What are the optimal storage conditions for SERPINA7 research reagents?
For maintaining antibody integrity when studying SERPINA7:
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Use manual defrost freezers and avoid repeated freeze-thaw cycles
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Store unopened reagents at -20°C to -70°C for up to 12 months
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After reconstitution, maintain at 2-8°C for up to 1 month under sterile conditions
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For long-term storage post-reconstitution, keep at -20°C to -70°C for up to 6 months
What is the genomic organization of the SERPINA7 gene and how should researchers approach sequencing?
The SERPINA7 gene consists of 4 exons and their intron-exon boundaries. For comprehensive genetic analysis:
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Extract genomic DNA from peripheral blood leukocytes using standard phenol-chloroform methods
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Design primers to amplify all exons (1-4) and exon-intron junctions
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Perform PCR amplification followed by direct DNA sequencing
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Use reference sequences NM_000354.6 (nucleotide) and NP_000345.2 (protein) for annotation
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Analyze variants using multiple databases including dbSNP, Clinvar, HGMD, gnomAD, and population-specific databases
What mutation types affect SERPINA7 and how are they classified?
SERPINA7 mutations manifest as:
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Complete deficiency (TBG-CD): Mutations causing absence of functional protein
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Partial deficiency (TBG-PD): Mutations reducing protein levels or function
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Variants with altered affinity: Mutations affecting hormone binding without changing protein levels
Classification follows the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines, using criteria such as population frequency, in silico predictions, and functional evidence .
What are the common pathogenic variants in SERPINA7 identified across populations?
Based on current research:
How do researchers distinguish between TBG deficiency and primary thyroid disorders?
Differential diagnosis requires a comprehensive approach:
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Thyroid function profile: Patients with TBG deficiency typically show low total T3 and T4 with normal free T3 (FT3), free T4 (FT4), and TSH levels
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TBG measurement: Direct measurement reveals low or undetectable levels (<10.90 μg/mL)
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Thyroid autoantibody testing: Negative results for anti-microsomal antibodies, thyroglobulin antibodies, and anti-TSH receptor antibodies
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Inheritance pattern analysis: Pedigree consistent with X-linked inheritance
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Genetic confirmation: Sequencing of SERPINA7 gene to identify pathogenic variants
What methodology should be employed when investigating novel SERPINA7 variants?
When characterizing novel variants:
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Perform in silico analysis using multiple predictive algorithms
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Assess population frequency in control databases (gnomAD, KRGDB)
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Analyze conservation across species
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Consider the variant's location within the protein structure
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Conduct functional studies to evaluate:
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Protein expression and secretion in cell models
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Protein stability in circulation
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Binding affinity for thyroid hormones
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How do SERPINA7 mutations affect protein trafficking and stability at the molecular level?
Different mutation types disrupt SERPINA7 through distinct mechanisms:
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Frameshift mutations: Often lead to premature stop codons and nonsense-mediated decay (e.g., p.Leu372Phefs23, p.Phe269Cysfs18)
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Missense mutations: May affect protein folding, secretion efficiency, or stability in circulation
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Regulatory region mutations: Can alter expression levels
Researchers should employ cell biology approaches to assess:
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Intracellular protein levels (by immunoblotting)
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Secretion efficiency (measuring intracellular versus secreted protein)
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Protein half-life in conditioned media
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Subcellular localization (by immunofluorescence or fractionation)
What experimental models are most appropriate for studying SERPINA7 function?
Researchers should consider:
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In vitro expression systems: Using wild-type and mutated SERPINA7 constructs in hepatic cell lines
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Primary hepatocyte cultures: For studying regulated expression
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Binding assays: To quantify hormone binding kinetics
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Patient-derived samples: Analyzing naturally occurring variants
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Recombinant protein production: For structural studies
When interpreting results, note that SERPINA7 gene regulation is influenced by factors including estrogen levels and developmental stage .
How can researchers address contradictory findings in SERPINA7 mutation analysis?
When confronting data inconsistencies:
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Consider X-chromosome inactivation effects in heterozygous females
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Evaluate the presence of multiple variants that may interact
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Account for environmental factors affecting TBG levels (e.g., pregnancy, estrogen therapy)
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Assess methodology differences between studies:
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Different reference ranges for TBG measurement
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Varying sensitivity of genetic screening techniques
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Classification criteria for partial versus complete deficiency
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Incorporate family studies to confirm segregation of variants with phenotype
What are emerging areas for investigation in SERPINA7 research?
Promising research directions include:
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Integration of structural biology approaches to understand mutation effects
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Development of high-throughput functional assays for variant classification
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Investigation of non-thyroid hormone transport functions
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Exploration of tissue-specific effects beyond circulating hormone levels
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Analysis of gene-environment interactions affecting SERPINA7 expression
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Utilization of genome editing techniques to model variants in cellular systems
What methodological approaches are needed to resolve outstanding questions in SERPINA7 biology?
Research advancement requires:
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Comprehensive population-specific mutation databases
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Standardized functional assays for variant classification
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Integration of clinical, biochemical, and genetic data
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Advanced structural modeling incorporating glycosylation effects
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Longitudinal studies of individuals with characterized mutations
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Development of reference materials for TBG measurement standardization
Product Science Overview
Serpin Peptidase Inhibitor, Clade A Member 7 (SERPINA7), also known as Thyroxine-Binding Globulin (TBG), is a protein encoded by the SERPINA7 gene. This protein is a member of the serpin superfamily, which is known for its role in inhibiting serine proteases. However, unlike many other serpins, SERPINA7 primarily functions as a hormone-binding protein rather than a protease inhibitor .
The primary function of SERPINA7 is to bind and transport thyroid hormones, including thyroxine (T4) and triiodothyronine (T3), in the bloodstream. By binding to these hormones, SERPINA7 regulates their availability and activity, ensuring that they are delivered to tissues in a controlled manner. This binding also protects the hormones from degradation and excretion .
Mutations in the SERPINA7 gene can lead to various thyroid hormone transport disorders. For example, Thyroxine-Binding Globulin Deficiency is a condition characterized by reduced levels of TBG, leading to altered thyroid hormone levels in the blood. Conversely, Thyroxine-Binding Globulin Excess results in elevated TBG levels, which can also affect thyroid hormone homeostasis .
