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MR1

MAIT (mucosal-associated invariant T-cells) lymphocytes represent a small population of T-cells primarily found in the gut. The protein encoded by this gene is an antigen-presenting molecule that presents metabolites of microbial vitamin B to MAITs. This presentation may activate the MAITs to regulate the amounts of specific types of bacteria in the gut. Several transcript variants encoding different isoforms have been found for this gene, and a pseudogene of it has been detected about 36 kbp upstream on the same chromosome.
Protein class

FDA approved drug targets

Predicted location

Intracellular, Membrane (different isoforms)

Single cell type specificity

Low cell type specificity

Immune cell specificity

Low immune cell specificity

Cell line specificity

Low cell line specificity

Interaction

Heterotrimer that consists of MR1, B2M and a metabolite antigen (PubMed:27043408, PubMed:23051753, PubMed:23846752, PubMed:24695216). Forms reversible covalent Schiff base complexes with the microbial metabolite, which serves as a molecular switch triggering complete folding, stable association with B2M and translocation of the ternary complex from endoplasmic reticulum to the plasma membrane (PubMed:27043408, PubMed:23051753, PubMed:23846752, PubMed:24695216). On antigen-presenting cells, the ternary complex interacts with TCR on CD8-positive T cells (PubMed:23846752, PubMed:24695216, PubMed:26795251). The molecular machinery involved in antigen processing remains unknown, but appears to be TAP1-TAP2 and proteasome-independent. Structurally, MR1-B2M heterodimer adopts a topology similar to classical MHC class I molecules, with alpha-1 and alpha-2 domains of MR1 forming the antigen-binding cleft composed of two alpha-helices resting on a floor of 7-stranded anti-parallel beta-pleated sheet (PubMed:23846752, PubMed:24695216, PubMed:26795251). The ribityl moiety of pyrimidine-based antigens is recognized by Tyr-95 residue in the CDR3 alpha loop of the invariant TRAV1-2 TCR (PubMed:23846752, PubMed:24695216, PubMed:26795251). [Isoform 3]: Homodimerizes and does not associate with B2M.

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