MR1
entrez
3140
canonical
uniprot
Q95460
canonical
ensembl
ENSG00000153029
resolver
ensp
ENSP00000282990
resolver
ensp
ENSP00000356551
resolver
ensp
ENSP00000356552
resolver
ensp
ENSP00000388504
resolver
ensp
ENSP00000477563
resolver
ensp
ENSP00000478976
resolver
enst
ENST00000617803
resolver
genesymbol
MR1
resolver
hgnc
HGNC:4975
resolver
uniprot
A0A8C8PVM5
resolver
uniprot
A8K2V9
resolver
uniprot
B4E3B1
resolver
uniprot
O97985
resolver
uniprot
O97986
resolver
uniprot
Q53GM1
resolver
uniprot
Q95HB8
resolver
uniprot
Q9MY23
resolver
uniprot
Q9NPL2
resolver
uniprot
Q9TQB3
resolver
uniprot
Q9TQB9
resolver
uniprot
Q9TQK3
resolver
uniprot_entry
A0A8C8PVM5_HUMAN
resolver
uniprot_entry
HMR1_HUMAN
resolver
uniprot_sec
A8K2V9
resolver
uniprot_sec
B4E3B1
resolver
uniprot_sec
O97985
resolver
uniprot_sec
O97986
resolver
uniprot_sec
Q53GM1
resolver
uniprot_sec
Q95HB8
resolver
uniprot_sec
Q9MY23
resolver
uniprot_sec
Q9NPL2
resolver
uniprot_sec
Q9TQB3
resolver
uniprot_sec
Q9TQB9
resolver
uniprot_sec
Q9TQK3
resolver
activity_regulation
ACTIVITY REGULATION: 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:23846752, 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). {ECO:0000269|PubMed:28166217}.
uniprot
proteins
amino_acid_sequence
MGELMAFLLPLIIVLMVKHSDSRTHSLRYFRLGVSDPIHGVPEFISVGYVDSHPITTYDSVTRQKEPRAPWMAENLAPDHWERYTQLLRGWQQMFKVELKRLQRHYNHSGSHTYQRMIGCELLEDGSTTGFLQYAYDGQDFLIFNKDTLSWLAVDNVAHTIKQAWEANQHELLYQKNWLEEECIAWLKRFLEYGKDTLQRTEPPLVRVNRKETFPGVTALFCKAHGFYPPEIYMTWMKNGEEIVQEIDYGDILPSGDGTYQAWASIELDPQSSNLYSCHVEHCGVHMVLQVPQESETIPLVMKAVSGSIVLVIVLAGVGVLVWRRRPREQNGAIYLPTPDR
uniprot
proteins
function
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 (PubMed:19416870, PubMed:23457030, PubMed:22692454, PubMed:23051753, PubMed:24101382, PubMed:23846752, PubMed:26795251). 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:20581831, PubMed:24101382, PubMed:24695216, PubMed:26795251). 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, PubMed:32958637, PubMed:32709702). 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:23846752, PubMed:24695216, PubMed:27527800). 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). {ECO:0000250|UniProtKB:Q8HWB0, ECO:0000269|PubMed:19416870, ECO:0000269|PubMed:20581831, ECO:0000269|PubMed:22692454, ECO:0000269|PubMed:23051753, ECO:0000269|PubMed:23846752, ECO:0000269|PubMed:24101382, ECO:0000269|PubMed:24695216, ECO:0000269|PubMed:26795251, ECO:0000269|PubMed:27527800, ECO:0000269|PubMed:31113973, ECO:0000269|PubMed:31959982, ECO:0000269|PubMed:32709702, ECO:0000269|PubMed:32958637}.; FUNCTION: Allele MR1*01: Presents microbial-derived metabolite 5-OP-RU to semi-invariant TRAV1.2-TRAJ33-TRBV6.1 (A-F7) TCR on MAIT cells (PubMed:39589872). 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 (PubMed:39701104). Displays moderate binding affinity toward tumor-enriched pyridoxal and pyridoxal 5'-phosphate antigens (PubMed:39589872). {ECO:0000269|PubMed:39589872, ECO:0000269|PubMed:39701104}.; FUNCTION: 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. {ECO:0000269|PubMed:39445059, ECO:0000269|PubMed:39589872}.
uniprot
proteins
mass_dalton
39366
uniprot
proteins
mutagenesis
MUTAGEN 65; /note="K->A: Associates with B2M and translocates to plasma membrane in the absence of 6-FP. Refolds and adopts a stable structural conformation in the absence of ligand in vitro. Impairs recognition by pan-cancer TCR, MC.7.G5. Loss of pyridoxal binding."; /evidence="ECO:0000269|PubMed:24101382, ECO:0000269|PubMed:27043408, ECO:0000269|PubMed:31959982, ECO:0000269|PubMed:39589872"; MUTAGEN 65; /note="K->R: Fails to refold in the presence of 6-FP. Impairs the association with B2M and translocation to the plasma membrane."; /evidence="ECO:0000269|PubMed:23051753, ECO:0000269|PubMed:27043408"; MUTAGEN 72; /note="M->P: Markedly decreases expression at the cell surface likely due to protein misfolding."; /evidence="ECO:0000269|PubMed:35725941"; MUTAGEN 105; /note="H->P: Markedly decreases expression at the cell surface likely due to protein misfolding."; /evidence="ECO:0000269|PubMed:35725941"; MUTAGEN 169; /note="Q->L: Able to activate mouse MAIT cells (xeno-reactivity)."; /evidence="ECO:0000269|PubMed:19416870"; MUTAGEN 175; /note="Q->P: Markedly decreases expression at the cell surface likely due to protein misfolding."; /evidence="ECO:0000269|PubMed:35725941
uniprot
proteins
post_translational_modification
PTM: N-glycosylated. {ECO:0000269|PubMed:12794138, ECO:0000269|PubMed:27043408}.
uniprot
proteins
protein_family
MHC class I family
uniprot
proteins
pubmed
11019920
uniprot
proteins
pubmed
12794138
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
18068122
uniprot
proteins
pubmed
19416870
uniprot
proteins
pubmed
19760593
uniprot
proteins
pubmed
20581831
uniprot
proteins
pubmed
22692454
uniprot
proteins
pubmed
23051753
uniprot
proteins
pubmed
23457030
uniprot
proteins
pubmed
23846752
uniprot
proteins
pubmed
24101382
uniprot
proteins
pubmed
24695216
uniprot
proteins
pubmed
26795251
uniprot
proteins
pubmed
27043408
uniprot
proteins
pubmed
27527800
uniprot
proteins
pubmed
28166217
uniprot
proteins
pubmed
31113973
uniprot
proteins
pubmed
31959982
uniprot
proteins
pubmed
32130899
uniprot
proteins
pubmed
32709702
uniprot
proteins
pubmed
32958637
uniprot
proteins
pubmed
34351076
uniprot
proteins
pubmed
35725941
uniprot
proteins
pubmed
39445059
uniprot
proteins
pubmed
39589872
uniprot
proteins
pubmed
39701104
uniprot
proteins
pubmed
7624800
uniprot
proteins
pubmed
9780177
uniprot
proteins
pubmed
9784382
uniprot
proteins
sequence_length
341
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12794138, ECO:0000269|PubMed:18068122, ECO:0000269|PubMed:27043408, ECO:0000269|PubMed:32958637}; Single-pass type I membrane protein. Endoplasmic reticulum membrane {ECO:0000269|PubMed:18068122, ECO:0000269|PubMed:27043408, ECO:0000269|PubMed:32958637}; Single-pass type I membrane protein {ECO:0000255}. Golgi apparatus membrane {ECO:0000269|PubMed:18068122}; Single-pass type I membrane protein {ECO:0000255}. Early endosome membrane {ECO:0000269|PubMed:27043408}; Single-pass type I membrane protein {ECO:0000255}. Late endosome membrane {ECO:0000269|PubMed:18068122, ECO:0000269|PubMed:27043408}; Single-pass type I membrane protein {ECO:0000255}. 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. {ECO:0000269|PubMed:27043408}.; SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:23457030}; Single-pass type I membrane protein {ECO:0000255}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:23457030}; Single-pass membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Isoform 3]: Cell membrane {ECO:0000269|PubMed:23457030}; Single-pass type I membrane protein {ECO:0000255}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:23457030}; Single-pass membrane protein {ECO:0000255}. Note=The larger proportion remains in the ER in an immature state. The subset that reach cell surface does it through a B2M-independent pathway. {ECO:0000269|PubMed:23457030}.; SUBCELLULAR LOCATION: [Isoform 4]: Secreted {ECO:0000303|PubMed:9780177}.
uniprot
proteins
transmembrane_region
TRANSMEM 303..323; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins