RAET1G Human
Description
Functional Mechanisms
RAET1G serves as a ligand for the NKG2D receptor (KLRK1) on NK cells and CD8+ T-cells . Key functional aspects include:
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Immune Activation:
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Immune Evasion:
Expression Patterns
Normal Tissues (TMA analysis of 35 tissues) :
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Constitutive: Gut epithelium (colon), kidney tubules
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Low: Anterior pituitary, thyroid follicular cells
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Absent: Brain, lung, liver, reproductive organs
Cancer Expression (20 tumor types analyzed) :
| Tumor Type | Expression Frequency |
|---|---|
| Colorectal adenocarcinoma | 100% (5/5 cases) |
| Gastric adenocarcinoma | 83% (5/6 cases) |
| Ovarian serous carcinoma | 75% (3/4 cases) |
| Squamous cell carcinoma | 67% (lung/skin) |
| Hepatocellular carcinoma | 50% (2/4 cases) |
RAET1G1 shows 6-fold higher expression in tumors compared to matched normal tissues .
Clinical Implications
Therapeutic Potential:
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Target for NK cell-based immunotherapies due to tumor-restricted expression
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Recombinant RAET1G (PRO-1608) available for experimental studies
Diagnostic Applications:
Key Interaction Partners
| Interactor | Interaction Type | Biological Effect |
|---|---|---|
| NKG2D (KLRK1) | Receptor binding | Activates cytotoxic response |
| UL16 (HCMV) | Viral protein binding | Modulates immune evasion |
| HCST | Signal transduction | Enhances PI3K/GRB2 signaling |
| MICB | Co-expression | Synergistic NK cell activation |
Product Specs
Q&A
RAET1G (Retinoic Acid Early Transcript 1G) is a transmembrane NKG2D ligand with critical roles in immune surveillance. Below are structured FAQs addressing key research considerations, supported by experimental evidence from peer-reviewed studies.
Advanced Research Questions
How does RAET1G isoform switching impact immune evasion?
RAET1G2 (soluble splice variant):
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Lacks TM domain due to 100-bp exon 4 deletion
Methodological insight: Use CRISPR-Cas9 to delete exon 4 splice sites and assess NK cell function via CD107a degranulation assays.
What contradictions exist in RAET1G interaction data?
How does RAET1G trafficking differ from GPI-anchored ULBPs?
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Pulse-chase experiments: RAET1G surface expression peaks at 6 hr post-transfection vs. 4 hr for ULBP2 .
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Endocytosis: Antibody-bound RAET1G internalizes via clathrin-coated pits (blocked by dynasore, 80 μM) .
Methodological insight: Use pHrodo™ Red conjugates to track ligand internalization kinetics in live cells.
Functional Comparison of RAET1G with Other Ligands
| Feature | RAET1G | ULBP2 | MICA |
|---|---|---|---|
| Membrane anchor | TM + CYT | GPI | TM + CYT |
| Viral evasion | Binds UL16 | UL16-resistant | UL16-resistant |
| Tissue specificity | Colon, tumors | Broad | Epithelial |
| Soluble isoforms | RAET1G2 | None | MICA-129Exon5 |
Key Technical Recommendations
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Antibody validation: Confirm RAET1G specificity using CRISPR knockout controls in flow cytometry.
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Cytotoxicity assays: Include IL-2 (100 U/mL) during NK cell expansion to maintain NKG2D expression .
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Data interpretation: Account for RAET1G2’s decoy effects in tumor microenvironment studies by measuring soluble ligands via ELISA.
Product Science Overview
RAET1G is located on chromosome 6 and is part of a gene cluster. The gene encodes a protein that includes C-terminal transmembrane and cytoplasmic domains. However, these domains are removed through proteolytic processing, and the protein is subsequently tethered to the plasma membrane by a glycosylphosphatidylinositol (GPI)-anchor .
The RAET1G protein is one of several ligands for the natural killer group 2, member D (NKG2D) receptor. This receptor functions as an activating receptor in both innate and adaptive immunity. The interaction between RAET1G and NKG2D receptor mediates natural killer (NK) cell cytotoxicity, which is crucial for the immune response against tumors and virally infected cells .
RAET1G has multiple isoforms with distinct functions:
RAET1G is associated with various pathways, including the metabolism of proteins and the post-translational modification of GPI-anchored proteins. It is also linked to certain diseases, such as eunuchism . The protein’s role in immune response makes it a potential target for therapeutic interventions in cancer and infectious diseases.
