MR1 — Major histocompatibility complex, class I-related
MR1 belongs to a gene co-expression module in 2 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.
MR1's module in each cell type
| Cell type | Module | Shares the module with | |
|---|---|---|---|
| CD4⁺ T cells | Membrane Trafficking Protein processing & ER | B4GALT1, BTF3L4, CELF1, CLTC, CSNK1G3, CTBS, DERL2, DYNC1LI2 +23 more | View in SCUBA |
| Macrophages | Lysosomal Hydrolase Program Lysosomal & pahgocytosis | AMDHD2, ARL6IP5, ARPIN, ARSA, CD81, CLDN7, CLEC2B, COMT +35 more | View in SCUBA |
About the gene
| Synonyms | HLALS |
|---|---|
| Chromosome | 1: 181033374-181061938 |
| Predicted location | Intracellular, Membrane |
| Essential gene | No |
| Protein class | FDA approved drug targets, Predicted intracellular proteins, Predicted membrane proteins |
| Biological process | Immunity, Innate immunity |
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 TRAV1.2 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 TRAV1-2-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. 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. 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. Allele MR1*01: Presents microbial-derived metabolite 5-OP-RU to semi-invariant TRAV1.2-TRAJ33-TRBV6.1 (A-F7) TCR on MAIT cells. 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. Displays moderate binding affinity toward tumor- enriched pyridoxal and pyridoxal 5'-phosphate antigens. Allele MR1*04: Presents tumor-enriched metabolite pyridoxal to pan-cancer 7.G5 TCR on T cells enabling preferential recognition of cancer cells. May act as an alloantigen.
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.