Q95460A8K2V9B4E3B1O97985O97986Q53GM1Q95HB8Q9MY23Q9NPL2Q9TQB3Q9TQB9Q9TQK3HMR1_HUMANMajor histocompatibility complex class I-related gene proteinMHC class I-related gene proteinClass I histocompatibility antigen-like proteinMR1Homo sapiensHumanEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomoA gene outside the human MHC related to classical HLA class I genes.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)TISSUE SPECIFICITYA study on the polymorphism of human MHC class I-related MR1 gene and identification of an MR1-like pseudogene.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)POLYMORPHISMComplete sequencing and characterization of 21,243 full-length human cDNAs.NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 5)NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)The DNA sequence and biological annotation of human chromosome 1.NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)Genomics, isoforms, expression, and phylogeny of the MHC class I-related MR1 gene.NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-11NUCLEOTIDE SEQUENCE [MRNA] OF 5-341 (ISOFORM 3)NUCLEOTIDE SEQUENCE [MRNA] OF 6-229 (ISOFORM 4)ALTERNATIVE SPLICINGTISSUE SPECIFICITYExpanded genomic organization of conserved mammalian MHC class I-related genes, human MR1 and its murine ortholog.NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 8-341Unrelated expression patterns of MHC class Ia, Ib and TCRA molecules.NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 23-109VARIANT ARG-39Biochemical features of the MHC-related protein 1 consistent with an immunological function.FUNCTIONSUBCELLULAR LOCATIONSIGNAL SEQUENCE CLEAVAGE SITEGLYCOSYLATION AT ASN-107INTERACTION WITH B2MMUTAGENESIS OF CYS-283CAUTIONNovel MHC class I-related molecule MR1 affects MHC class I expression in 293T cells.SUBCELLULAR LOCATIONINTERACTION WITH B2MThe MHC-related protein 1 (MR1) is expressed by a subpopulation of CD38+, IgA+ cells in the human intestinal mucosa.TISSUE SPECIFICITYMR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution.FUNCTIONMUTAGENESIS OF GLN-169Antimicrobial activity of mucosal-associated invariant T cells.FUNCTIONMR1B, a natural spliced isoform of the MHC-related 1 protein, is expressed as homodimers at the cell surface and activates MAIT cells.SUBCELLULAR LOCATION (ISOFORMS 1 AND 3)SUBUNIT (ISOFORM 3)CAUTIONHuman thymic MR1-restricted MAIT cells are innate pathogen-reactive effectors that adapt following thymic egress.FUNCTIONTISSUE SPECIFICITYHuman TRAV1-2-negative MR1-restricted T cells detect S. pyogenes and alternatives to MAIT riboflavin-based antigens.FUNCTIONThe intracellular pathway for the presentation of vitamin B-related antigens by the antigen-presenting molecule MR1.INTERACTION WITH B2M AND VITAMIN B METABOLITESUBCELLULAR LOCATIONTISSUE SPECIFICITYGLYCOSYLATIONMUTAGENESIS OF LYS-65Diverse MR1-restricted T cells in mice and humans.FUNCTIONGenome-wide CRISPR-Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1.FUNCTIONMUTAGENESIS OF LYS-65MR1 presents microbial vitamin B metabolites to MAIT cells.X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 23-292 IN COMPLEX WITH B2M AND METABOLITE ANTIGENANTIGEN-BINDING SITEDISULFIDE BONDSFUNCTIONMUTAGENESIS OF LYS-65Recognition of vitamin B metabolites by mucosal-associated invariant T cells.X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 23-292 IN COMPLEX WITH B2M AND METABOLITE ANTIGENANTIGEN-BINDING SITESDOMAININTERACTION WITH TCRFUNCTIONT-cell activation by transitory neo-antigens derived from distinct microbial pathways.X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 23-292 IN COMPLEXES WITH B2M AND METABOLITE ANTIGENSDISULFIDE BONDANTIGEN-BINDING SITESDOMAINFUNCTIONINTERACTION WITH TCRDiversity of T Cells Restricted by the MHC Class I-Related Molecule MR1 Facilitates Differential Antigen Recognition.X-RAY CRYSTALLOGRAPHY (1.97 ANGSTROMS) OF 23-292 IN COMPLEX WITH B2M AND METABOLITE ANTIGENDISULFIDE BONDANTIGEN-BINDING SITESDOMAINFUNCTIONINTERACTION WITH TCRDrugs and drug-like molecules can modulate the function of mucosal-associated invariant T cells.X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 23-292 IN COMPLEX WITH B2M AND DRUGACTIVITY REGULATIONAntigen-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).Usually inhibited by pterin-based metabolites such as 6-formylpterin (6-FP, a product of folic acid photodegradation). 6-FP competitively inhibits MAIT cell activation by 5-OP-RU (PubMed:28166217). Modulated by commonly prescribed anti-inflammatory drug metabolites. Inhibited by salicilates such as 3-formylsalicylic and 5-formylsalicylic acids. Activated by diclofenac and/or its hydroxy metabolites (PubMed:28166217).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 3Homodimerizes and does not associate with B2M.Q95460Q969F0false3Q95460-1P61769false3Q95460-2O95674false3Q95460-2Q07325false3Q95460-2P54852false3Q95460-2Q7Z2K6false3Q95460-2Q969F0false3Q95460-2Q8N3T1false3Q95460-2Q9NZG7false3Cell membraneSingle-pass type I membrane proteinEndoplasmic reticulum membraneSingle-pass type I membrane proteinGolgi apparatus membraneSingle-pass type I membrane proteinEarly endosome membraneSingle-pass type I membrane proteinLate endosome membraneSingle-pass type I membrane proteinIn 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.Isoform 1Cell membraneSingle-pass type I membrane proteinEndoplasmic reticulum membraneSingle-pass membrane proteinIsoform 3Cell membraneSingle-pass type I membrane proteinEndoplasmic reticulum membraneSingle-pass membrane proteinThe larger proportion remains in the ER in an immature state. The subset that reach cell surface does it through a B2M-independent pathway.Isoform 4SecretedQ95460-11MR1AQ95460-22Q95460-33MR1BMR1DQ95460-44MR1CQ95460-55Ubiquitous (PubMed:7624800, PubMed:9780177). Low expression is detected in peripheral blood B cells, T cells, monocytes and in bronchial epithelial cells (at protein level) (PubMed:27043408). Expressed in plasmablasts or plasma B cells in the lamina propria of ileum, appendix and colon (at protein level) (PubMed:19760593). Highly expressed on a subset of CD45-positive CD3-positive thymocytes (at protein level) (PubMed:22692454).The alpha-1 domain is a structural part of antigen-binding cleft.The alpha-2 domain is a structural part of antigen-binding cleft.N-glycosylated.Several individuals from different ethnic background were analyzed for polymorphism. MR1 was identical in all individuals analyzed, except one. MR1 is not polymorphic.Belongs to the MHC class I family.Reported to be associated with components of the peptide-loading complex, TAPBP, CALR, CANX and PDIA3 (PubMed:23457030, PubMed:12794138). This association in primary cells and its functional relevance is disputable, given that antigen presentation and MAIT cell activation is shown to be TAP1-TAP2 and proteasome-independent.Truncated N-terminus.3D-structureAlternative splicingCell membraneDisulfide bondEndoplasmic reticulumEndosomeGlycoproteinGolgi apparatusImmunityImmunoglobulin domainInnate immunityMembraneMHC IReference proteomeSecretedSignalTransmembraneTransmembrane helix5-(2-oxoethylideneamino)-6-(D-ribitylamino)uracilpathogen-derived metabolite antigen5-(2-oxopropylideneamino)-6-(D-ribitylamino)uracilpathogen-derived metabolite antigen5-(2-oxoethylideneamino)-6-(D-ribitylamino)uracilpathogen-derived metabolite antigen5-(2-oxopropylideneamino)-6-(D-ribitylamino)uracilpathogen-derived metabolite antigen5-(2-oxoethylideneamino)-6-(D-ribitylamino)uracilpathogen-derived metabolite antigen5-(2-oxopropylideneamino)-6-(D-ribitylamino)uracilpathogen-derived metabolite antigen5-(2-oxoethylideneamino)-6-(D-ribitylamino)uracilpathogen-derived metabolite antigen5-(2-oxopropylideneamino)-6-(D-ribitylamino)uracilpathogen-derived metabolite antigen5-(2-oxoethylideneamino)-6-(D-ribitylamino)uracilpathogen-derived metabolite antigen5-(2-oxopropylideneamino)-6-(D-ribitylamino)uracilpathogen-derived metabolite antigen5-(2-oxoethylideneamino)-6-(D-ribitylamino)uracilpathogen-derived metabolite antigen5-(2-oxopropylideneamino)-6-(D-ribitylamino)uracilpathogen-derived metabolite antigenEPPLVRVNRKETFPGVTALGKEKEKASFPHCLNNCFYTHRRQAVKAKRQLCGMVRGLPMGELMAFLLPLIIVLMVKHSDSRTHSLRYFRLGVSDPIHGVPEFISVGYVDSHPITTYDSVTRQKEPRAPWMAENLAPDHWERYTQLLRGWQQMFKVELKRLQRHYNHSGSHTYQRMIGCELLEDGSTTGFLQYAYDGQDFLIFNKDTLSWLAVDNVAHTIKQAWEANQHELLYQKNWLEEECIAWLKRFLEYGKDTLQRTEPPLVRVNRKETFPGVTALFCKAHGFYPPEIYMTWMKNGEEIVQEIDYGDILPSGDGTYQAWASIELDPQSSNLYSCHVEHCGVHMVLQVPQESETIPLVMKAVSGSIVLVIVLAGVGVLVWRRRPREQNGAIYLPTPDR
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