UniProt functional annotation for C1ITJ8



	UniProt functional annotation for C1ITJ8

UniProt code: C1ITJ8.

Organism: Bos taurus (Bovine).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; Bovinae; Bos.

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 TCRs on MAIT cells, guiding immune surveillance of the microbial metabolome at mucosal epithelial barriers (By similarity). 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 (By similarity). May present microbial antigens to various 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 (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 on a non-MAIT CD8-positive T cell clone, triggering T cell-mediated killing of a wide range of cancer cell types (By similarity). {ECO:0000250|UniProtKB:Q8HWB0, ECO:0000250|UniProtKB:Q95460}.

Subunit: Heterotrimer that consists of MR1, B2M and metabolite antigen (By similarity). Forms reversible covalent Schiff base complexes with the microbial metabolite, which serve as a molecular switch triggering complete folding, stable association with B2M and translocation of the ternary complex from endoplasmic reticulum to the plasma membrane. On antigen-presenting cells, the ternary complex interacts with TCR on CD8-positive T cells. 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 (By similarity). MR1-B2M heterodimer (via alpha-helices) interacts with TCR (via CDR domains) (PubMed:23613577). {ECO:0000250|UniProtKB:Q95460, ECO:0000269|PubMed:23613577}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:19416870}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q95460}. Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q95460}; Single- pass type I membrane protein {ECO:0000255}. Golgi apparatus membrane {ECO:0000250|UniProtKB:Q95460}; Single-pass type I membrane protein {ECO:0000255}. Early endosome membrane {ECO:0000250|UniProtKB:Q95460}; Single-pass type I membrane protein {ECO:0000255}. Late endosome membrane {ECO:0000250|UniProtKB:Q95460}; 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:0000250|UniProtKB:Q95460}.

Domain: The alpha-1 domain is a structural part of antigen-binding cleft. {ECO:0000250|UniProtKB:Q95460}.

Domain: The alpha-2 domain is a structural part of antigen-binding cleft. {ECO:0000250|UniProtKB:Q95460}.

Ptm: N-glycosylated. {ECO:0000250|UniProtKB:Q95460}.

Similarity: Belongs to the MHC class I family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Bos taurus (Bovine).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; Bovinae; Bos.



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 TCRs on MAIT cells, guiding immune surveillance of the microbial metabolome at mucosal epithelial barriers (By similarity). 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 (By similarity). May present microbial antigens to various 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 (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 on a non-MAIT CD8-positive T cell clone, triggering T cell-mediated killing of a wide range of cancer cell types (By similarity). {ECO:0000250\|UniProtKB:Q8HWB0, ECO:0000250\|UniProtKB:Q95460}.


Subunit:		Heterotrimer that consists of MR1, B2M and metabolite antigen (By similarity). Forms reversible covalent Schiff base complexes with the microbial metabolite, which serve as a molecular switch triggering complete folding, stable association with B2M and translocation of the ternary complex from endoplasmic reticulum to the plasma membrane. On antigen-presenting cells, the ternary complex interacts with TCR on CD8-positive T cells. 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 (By similarity). MR1-B2M heterodimer (via alpha-helices) interacts with TCR (via CDR domains) (PubMed:23613577). {ECO:0000250\|UniProtKB:Q95460, ECO:0000269\|PubMed:23613577}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:19416870}; Single-pass type I membrane protein {ECO:0000250\|UniProtKB:Q95460}. Endoplasmic reticulum membrane {ECO:0000250\|UniProtKB:Q95460}; Single- pass type I membrane protein {ECO:0000255}. Golgi apparatus membrane {ECO:0000250\|UniProtKB:Q95460}; Single-pass type I membrane protein {ECO:0000255}. Early endosome membrane {ECO:0000250\|UniProtKB:Q95460}; Single-pass type I membrane protein {ECO:0000255}. Late endosome membrane {ECO:0000250\|UniProtKB:Q95460}; 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:0000250\|UniProtKB:Q95460}.
Domain:		The alpha-1 domain is a structural part of antigen-binding cleft. {ECO:0000250\|UniProtKB:Q95460}.
Domain:		The alpha-2 domain is a structural part of antigen-binding cleft. {ECO:0000250\|UniProtKB:Q95460}.
Ptm:		N-glycosylated. {ECO:0000250\|UniProtKB:Q95460}.
Similarity:		Belongs to the MHC class I family. {ECO:0000305}.