MR1: A Potential Drug Target for MHC Class I (G3140)

Target Name: MR1

NCBI ID: G3140

Other Name(s): Major histocompatibility complex class I-related gene protein | Major histocompatibility complex class I-related gene protein (isoform 1) | MHC class I-like antigen MR-1 | Class I histocompatibility antigen-like protein | MHC class I-related protein | MHC class I-related gene protein | Major histocompatibility complex, class I-like sequence | major histocompatibility complex, class I-like sequence | MHC class-I related-gene protein | major histocompatibility complex, class I-related | Major histocompatibility complex, class I-related, transcript variant 1 | MR1 variant 1 | HMR1_HUMAN | HLALS

MR1: A Potential Drug Target for MHC Class I

The Major Histocompatibility Complex (MHC) is a crucial immune system protein that plays a vital role in protecting the body against foreign substances like viruses, bacteria, and cancer cells. MHC class I is one of the MHC proteins that are responsible for presenting antigens to T-cells, which are the primary immune cells that recognize and respond to these antigens.

Research has identified a potential drug target for MHC class I, called MR1. MR1 is a protein that is expressed in many different tissues throughout the body, including the brain, lungs, heart, kidneys, and intestines. It is also involved in several cellular processes that are important for maintaining tissue homeostasis and has been implicated in a number of diseases, including cancer, autoimmune disorders, and neurodegenerative diseases.

One of the things that makes MR1 an attractive drug target is its ability to interact with a variety of different drugs. For example, studies have shown that MR1 can be stabilized by certain chemotherapy drugs, such as taxanes, which can be used to treat breast and ovarian cancers. Additionally, MR1 has been shown to be involved in the regulation of cell death, which makes it a potential target for drugs that are used to treat neurodegenerative diseases.

Another potential mechanism by which MR1 may be targeted by drugs is its role in the regulation of inflammation. Studies have shown that MR1 is involved in the production of pro-inflammatory cytokines, which can contribute to the inflammatory response that occurs in response to infection or injury. By targeting MR1, drugs may be able to reduce the production of these cytokines and improve the body's ability to control inflammation.

In addition to its potential clinical applications, MR1 is also an important protein that is involved in many fundamental cellular processes. Its role in tissue homeostasis, as well as its involvement in the regulation of cell death and inflammation, makes it an important target for researchers who are studying the mechanisms of immune system function and disease.

Overall, MR1 is a protein that has the potential to be a drug target for a variety of different diseases. Its involvement in the regulation of immune system function and tissue homeostasis makes it an attractive target for drugs that are used to treat a wide range of conditions, from cancer and autoimmune disorders to neurodegenerative diseases. Further research is needed to fully understand the mechanisms of MR1 and its potential as a drug target.

Protein Name: Major Histocompatibility Complex, Class I-related

Functions: Antigen-presenting molecule specialized in displaying microbial pyrimidine-based metabolites to alpha-beta T cell receptors (TCR) on innate-type mucosal-associated invariant T (MAIT) cells (PubMed:23051753, PubMed:26795251, PubMed:12794138, PubMed:19416870, PubMed:22692454, PubMed:23846752). In complex with B2M preferentially presents riboflavin-derived metabolites to semi-invariant TRAV1-2 TCRs on MAIT cells, guiding immune surveillance of the microbial metabolome at mucosal epithelial barriers (PubMed:26795251, PubMed:24695216, PubMed:20581831). Signature pyrimidine-based microbial antigens are generated via non-enzymatic condensation of metabolite intermediates of the riboflavin pathway with by-products arising from other metabolic pathways such as glycolysis. Typical potent antigenic metabolites are 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU) and 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), products of condensation of 5-amino-6-D-ribityaminouracil (5-A-RU) with glyoxal or methylglyoxal by-products, respectively (PubMed:24695216). May present microbial antigens to various TRAV1-2-negative MAIT cell subsets, providing for unique recognition of diverse microbes, including pathogens that do not synthesize riboflavin (PubMed:27527800, PubMed:31113973). Upon antigen recognition, elicits rapid innate-type MAIT cell activation to eliminate pathogenic microbes by directly killing infected cells (PubMed:24695216, PubMed:27527800, PubMed:23846752). During T cell development, drives thymic selection and post-thymic terminal differentiation of MAIT cells in a process dependent on commensal microflora (By similarity). Acts as an immune sensor of cancer cell metabolome (PubMed:31959982). May present a tumor-specific or -associated metabolite essential for cancer cell survival to a pan-cancer TCR consisting of TRAV38.2-DV8*TRAJ31 alpha chain paired with a TRBV25.1*TRBJ2.3 beta chain on a non-MAIT CD8-positive T cell clone (MC.7.G5), triggering T cell-mediated killing of a wide range of cancer cell types (PubMed:31959982)

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