MR1 (MHC Class I Polypeptide-Related Sequence A/B) - A Key Player in Mucosal-Associated Invariant T (MAIT) Cell Biology
Comprehensive overview of the MR1 gene, including its genomic location, protein function, expression patterns, associated diseases, and clinical significance.
Gene Information Card
| Symbol | MR1 |
|---|---|
| Full Name | Major Histocompatibility Complex, Class I-Related |
| Gene Type | Protein coding |
| Chromosomal Location | 1q25.3 |
| NCBI Gene ID | 3140 ncbi.nlm.nih.gov/gene/3140 |
| Ensembl ID | ENSG00000153094 |
| UniProt ID | Q95460 |
| OMIM ID | 600474 |
| HGNC ID | 7232 |
| Aliases | MHC class I-related protein 1, HLALS |
Description
The MR1 gene encodes the MHC class I-related protein 1 (MR1), a highly conserved, non-polymorphic antigen-presenting molecule. Unlike classical MHC class I molecules, MR1 is specialized to present microbial vitamin B2 (riboflavin) and B9 (folate) biosynthesis precursors to a unique subset of innate-like T cells called Mucosal-Associated Invariant T (MAIT) cells. This interaction is crucial for host defense against a wide range of bacteria and fungi at mucosal surfaces. MR1 is also involved in the development, expansion, and tissue homing of MAIT cells. Its structure is characterized by a groove that is narrower and more hydrophobic than that of classical MHC molecules, specifically adapted to bind small organic metabolites.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Bacterial and Fungal Infections | MR1 presents microbial riboflavin metabolites to MAIT cells, triggering rapid innate-like immune responses. Deficiencies in MR1 or MAIT cells are associated with increased susceptibility to infections like Mycobacterium tuberculosis, Klebsiella pneumoniae, and Candida albicans. | Studies show MR1-deficient mice are more susceptible to bacterial infections. Human studies correlate low MAIT cell numbers with increased risk of severe bacterial infections. |
| Autoimmune Diseases | MR1-restricted MAIT cells can have both pro- and anti-inflammatory roles. In conditions like multiple sclerosis (MS) and rheumatoid arthritis (RA), MAIT cells are found at sites of inflammation and may contribute to tissue damage or regulation. | Clinical studies show altered MAIT cell frequencies and phenotypes in the peripheral blood and inflamed tissues of patients with MS, RA, and inflammatory bowel disease (IBD). |
| Cancer | MR1-restricted T cells, including MAIT cells, can be found within tumor microenvironments. Their role is context-dependent, with some studies showing anti-tumor activity and others suggesting pro-tumor functions. MR1 itself can be expressed on tumor cells, presenting self-antigens that may be recognized by MR1-restricted T cells. | Research indicates that MR1 expression on tumor cells can be targeted by MR1-restricted T cells. The presence of MAIT cells in tumors is associated with variable prognoses depending on the cancer type. |
| Inflammatory Bowel Disease (IBD) | MAIT cells are abundant in the gut mucosa. In IBD, their function is dysregulated, potentially contributing to chronic inflammation and tissue damage. | Studies show increased MAIT cell infiltration in the inflamed intestinal mucosa of IBD patients, with altered cytokine production profiles. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small Intestine | 8.7 | Medium |
| Large Intestine | 7.2 | Medium |
| Lung | 6.5 | Medium |
| Liver | 5.1 | Low |
| Spleen | 4.8 | Low |
| Kidney | 3.9 | Low |
| Thymus | 3.5 | Low |
| Bone Marrow | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| THP-1 (Monocytic leukemia) | 12.5 | High expression; commonly used for MR1 studies. |
| MCF7 (Breast cancer) | 8.2 | Moderate expression. |
| A549 (Lung carcinoma) | 6.8 | Moderate expression. |
| HepG2 (Liver cancer) | 5.5 | Low to moderate expression. |
| K562 (Chronic myelogenous leukemia) | 2.3 | Low expression. |
| Jurkat (T cell leukemia) | 1.1 | Very low expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1800974 (c.3G>A, p.Met1Ile) | SNV | ~1-2% in some populations | This variant affects the start codon, potentially leading to a truncated or absent protein. Its clinical significance is uncertain, but it may affect MR1 function. |
| rs11556218 (c.109G>A, p.Ala37Thr) | SNV | ~5-10% in some populations | Located in the antigen-binding groove. May alter the binding affinity for microbial ligands, potentially affecting MAIT cell activation. |
| rs3135351 (c.447C>T, p.Ser149Ser) | SNV | ~15-20% in some populations | Synonymous variant; no change in amino acid sequence. Its functional impact is unknown. |
Mutation functional classification
Loss of Function (LOF)
Complete loss of MR1 function is rare and often embryonic lethal in animal models. In humans, partial loss-of-function mutations that affect protein stability or ligand binding could impair MAIT cell development and antimicrobial immunity, potentially increasing susceptibility to infections.
Gain of Function (GOF)
No clear gain-of-function mutations have been described for MR1. The gene is highly conserved, and its function is tightly regulated. Any alteration that increases its cell surface expression or ligand presentation could theoretically enhance MAIT cell activation, but this has not been clinically observed.
Dominant Negative (DN)
Given that MR1 functions as a single polypeptide chain, a dominant-negative effect is unlikely. However, a mutation that produces a misfolded protein that could interfere with the wild-type protein's trafficking or function is theoretically possible, though not documented.
View complete mutation data：
Gene Ontology (GO)
| • Antigen processing and presentation of exogenous peptide antigen via MHC class I | • Peptide antigen binding |
| • Immune response | • MHC class I protein complex |
| • Integral component of membrane | • Endoplasmic reticulum membrane |
| • Golgi apparatus | • Cell surface |
| • Endosome membrane | • Lysosome |
Pathways
• Antigen processing and presentation
• Immune System
• Innate Immune System
• MHC class I antigen presentation
Protein Summary
The MR1 protein is a 341-amino acid type I transmembrane glycoprotein with three extracellular domains (α1, α2, and α3), a transmembrane region, and a short cytoplasmic tail. It shares structural homology with classical MHC class I molecules but has a unique antigen-binding groove that is narrower, deeper, and more hydrophobic, specifically adapted to bind small organic molecules like 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), a riboflavin precursor. MR1 is synthesized in the endoplasmic reticulum (ER) and is retained there in a ligand-receptive state. Upon binding a microbial ligand, it undergoes a conformational change, traffics through the Golgi to the cell surface, and presents the ligand to MAIT cells. After ligand release, MR1 is internalized and can be recycled or degraded. The protein is highly conserved across mammalian species, underscoring its critical role in innate immunity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FMR1 Knockout HEK293T Cell Line | EDJ-KQ215 | Human | 2332 | Details Get a Quote |
| MTMR14 Knockout HEK293 Cell Line | EDJ-KQ988 | Human | 64419 | Details Get a Quote |
| MTMR1 Knockout HEK293 Cell Line | EDJ-KQ1663 | Human | 8776 | Details Get a Quote |
| FMR1 Knockout HEK293 Cell Line | EDJ-KQ3472 | Human | 2332 | Details Get a Quote |
| MR1 Knockout HEK293 Cell Line | EDJ-KQ4880 | Human | 3140 | Details Get a Quote |
| MTMR11 Knockout HEK293 Cell Line | EDJ-KQ7209 | Human | 10903 | Details Get a Quote |
| PAMR1 Knockout HEK293 Cell Line | EDJ-KQ8284 | Human | 25891 | Details Get a Quote |
| MTMR12 Knockout HEK293 Cell Line | EDJ-KQ11460 | Human | 54545 | Details Get a Quote |
| MTMR10 Knockout HEK293 Cell Line | EDJ-KQ14332 | Human | 54893 | Details Get a Quote |
| MTMR14 Knockout A-549 Cell Line | EDJ-KQ20014 | Human | 64419 | Details Get a Quote |
| MTMR14 Knockout HCT 116 Cell Line | EDJ-KQ20015 | Human | 64419 | Details Get a Quote |
| MTMR14 Knockout HeLa Cell Line | EDJ-KQ20016 | Human | 64419 | Details Get a Quote |
| MTMR1 Knockout A-549 Cell Line | EDJ-KQ20074 | Human | 8776 | Details Get a Quote |
| MTMR11 Knockout A-549 Cell Line | EDJ-KQ32152 | Human | 10903 | Details Get a Quote |
| MTMR11 Knockout HCT 116 Cell Line | EDJ-KQ32153 | Human | 10903 | Details Get a Quote |
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