The following text describes a protein:
Function:
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. In complex with B2M preferentially presents riboflavin-derived metabolites to semi-invariant TRAV1 TCRs on MAIT cells, guiding immune surveillance of the microbial metabolome at mucosal epithelial barriers. 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. May present microbial antigens to various TRAV1-negative MAIT cell subsets, providing for unique recognition of diverse microbes, including pathogens that do not synthesize riboflavin. Upon antigen recognition, elicits rapid innate-type MAIT cell activation to eliminate pathogenic microbes by directly killing infected cells (By similarity). During T cell development, drives thymic selection and post-thymic terminal differentiation of MAIT cells in a process dependent on commensal microflora. Acts as an immune sensor of cancer cell metabolome. May present a tumor-specific or -associated metabolite essential for cancer cell survival to a pan-cancer TCR on a non-MAIT CD8-positive T cell clone, triggering T cell-mediated killing of a wide range of cancer cell types (By similarity). May present tumor-enriched pyridoxal and pyridoxal 5'-phosphate antigens, enabling preferential recognition of cancer cells (By similarity). Presents nucleobase carbonyl adducts generated during oxidative stress. Captures M3Ade, a nucleobase adduct composed of one adenine modified by a malondialdehyde trimer, for recognition by MR1-restricted T cell clones expressing a polyclonal TCR repertoire (By similarity).
Miscellaneous:
MISCELLANEOUS: MR1 is detected in an open versus folded conformation. Only the folded MR1 conformer activates MAIT cells.
Subcellular Localization:
Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass type I membrane protein. Golgi apparatus membrane; Single-pass type I membrane protein. Early endosome membrane; Single-pass type I membrane protein. Late endosome membrane; Single-pass type I membrane protein. Note=In the absence of antigen remains within the endoplasmic reticulum where it acts as a metabolite sensor. Antigen binding triggers trafficking of the ternary complex to the plasma membrane. After presentation, most of these complexes are rapidly internalized and degraded via endocytosis. A small subset recycles via endosomes back to the plasma membrane and may thus acquire and present new antigens that do not efficiently reach the endoplasmic reticulum.
Domain:
The alpha-1 domain is a structural part of antigen-binding cleft; The alpha-2 domain is a structural part of antigen-binding cleft.
Sequence:
MMLLLPLLAVFLVKRSHTRTHSLRYFRLAVSDPGPVVPEFISVGYVDSHPITTYDSVTRQKEPKAPWMAENLAPDHWERYTQLLRGWQQTFKAELRHLQRHYNHSGLHTYQRMIGCELLEDGSTTGFLQYAYDGQDFIIFNKDTLSWLAMDYVAHITKQAWEANLHELQYQKNWLEEECIAWLKRFLEYGRDTLERTEHPVVRTTRKETFPGITTFFCRAHGFYPPEISMTWMKNGEEIAQEVDYGGVLPSGDGTYQTWLSVNLDPQSNDVYSCHVEHCGRQMVLEAPRESGDILRVSTISGTTILIIALAGVGVLIWRRSQELKEVMYQPTQVNEGSSPS