Protein: HMR1_HUMAN
Sequence: MGELMAFLLPLIIVLMVKHSDSRTHSLRYFRLGVSDPIHGVPEFISVGYVDSHPITTYDSVTRQKEPRAPWMAENLAPDHWERYTQLLRGWQQMFKVELKRLQRHYNHSGSHTYQRMIGCELLEDGSTTGFLQYAYDGQDFLIFNKDTLSWLAVDNVAHTIKQAWEANQHELLYQKNWLEEECIAWLKRFLEYGKDTLQRTEPPLVRVNRKETFPGVTALFCKAHGFYPPEIYMTWMKNGEEIVQEIDYGDILPSGDGTYQAWASIELDPQSSNLYSCHVEHCGVHMVLQVPQESETIPLVMKAVSGSIVLVIVLAGVGVLVWRRRPREQNGAIYLPTPDR
What is the function of this protein?
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: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).
What are the official names of this protein?
Major histocompatibility complex class I-related gene protein, MHC class I-related gene protein, Class I histocompatibility antigen-like protein.
What is the protein family that this protein belongs to?
Belongs to the MHC class I family.
What are the subcellular locations of this protein?
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. SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass membrane protein. SUBCELLULAR LOCATION: [Isoform 3]: Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane; Single-pass membrane protein. 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. SUBCELLULAR LOCATION: [Isoform 4]: Secreted.