PDIA4 Human
Description
Protein Folding and ER Stress
PDIA4 facilitates disulfide bond formation and rearrangement in nascent proteins, ensuring proper tertiary structure . It interacts with key ER chaperones:
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HSP90B1 (Endoplasmin): Collaborates in folding Toll-like receptors
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CALR (Calreticulin): Part of the calnexin/calreticulin quality control cycle
Metabolic Regulation
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Insulin Resistance (IR): Serum PDIA4 levels correlate with HOMA-2 IR (, ) and interleukin-6 (IL-6) (, ) .
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Diabetes: Knockdown reduces blood glucose and HbA1C in diabetic mice .
Table 1: Clinical Correlations of Serum PDIA4 Levels
| Parameter | Correlation (r) | P-value |
|---|---|---|
| BMI | 0.405 | < 0.001 |
| Waist Circumference | 0.39 | < 0.001 |
| HOMA-2IR | 0.274 | < 0.001 |
| IL-6 | 0.154 | 0.001 |
Cancer Chemoresistance
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Overexpressed in cisplatin-resistant lung adenocarcinoma cells .
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Inactivation restores mitochondrial apoptosis, enhancing chemotherapy efficacy .
Metabolic Diseases
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Obesity: Higher PDIA4 tertiles associate with elevated waist circumference, triglycerides, and blood pressure .
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Therapeutic Target: Metformin reduces ER stress by modulating PDIA4, improving insulin signaling in skeletal muscle .
Table 2: PDIA4 in Palmitate-Treated C2C12 Myotubes
| Condition | Effect on PDIA4 | Glucose Uptake |
|---|---|---|
| Palmitate + Insulin | ↑ 2.1-fold | ↓ 40% |
| PDIA4 Knockdown | ↓ 70% | ↑ 85% |
Interaction Network
PDIA4 partners with ER-resident proteins to manage proteostasis:
| Interaction Partner | Function | Score (STRING) |
|---|---|---|
| HSPA5 (BiP) | ER stress sensor | 0.990 |
| ERO1B | Oxidoreductase for PDI reoxidation | 0.984 |
| CANX (Calnexin) | Glycoprotein quality control | 0.931 |
Research Applications
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Recombinant PDIA4: Used in studying ER stress mechanisms (Cat# ENZ-246) .
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Biomarker Potential: Elevated serum levels predict metabolic syndrome progression .
Future Directions
Product Specs
FAIADEEDYA GEVKDLGLSE SGEDVNAAIL DESGKKFAME PEEFDSDTLR EFVTAFKKGK LKPVIKSQPV PKNNKGPVKV VVGKTFDSIV MDPKKDVLIE FYAPWCGHCK QLEPVYNSLA KKYKGQKGLV IAKMDATAND VPSDRYKVEG FPTIYFAPSG DKKNPVKFEG GDRDLEHLSK FIEEHATKLS RTKEEL.
Product Science Overview
PDIA4 is synthesized as a 625 amino acid precursor, which includes a 20 amino acid signal sequence and a mature chain of 605 amino acids . The enzyme contains three thioredoxin domains, which are critical for its oxidoreductase and chaperone activities . These domains facilitate the formation, isomerization, and reduction or oxidation of disulfide bonds in client proteins .
PDIA4 is primarily located in the endoplasmic reticulum (ER) lumen, where it assists in the proper folding of nascent proteins . It is a core component of the major histocompatibility complex class I (MHC I) peptide loading complex, functioning as an essential folding chaperone for TAPBP . Through its interaction with TAPBP, PDIA4 aids in the dynamic assembly of the MHC I complex with high-affinity antigens in the ER, playing a crucial role in antigen presentation to cytotoxic T cells in adaptive immunity .
Recent studies have highlighted the involvement of PDIA4 in various diseases, particularly in cancer. PDIA4 has been reported to be involved in carcinogenesis and the progression of glioblastoma, a type of brain cancer . Its role in maintaining protein homeostasis and regulating redox states makes it a potential target for therapeutic interventions in cancer treatment .
Human recombinant PDIA4 is produced using recombinant DNA technology, which involves inserting the human PDIA4 gene into a suitable expression system, such as bacteria or yeast, to produce the protein in large quantities. This recombinant protein is used in various research applications to study its structure, function, and role in disease processes .
