HMR1_PONPY
ID HMR1_PONPY Reviewed; 340 AA.
AC Q9BD50; Q95M21; Q9BD49;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Major histocompatibility complex class I-related gene protein;
DE AltName: Full=MHC class I-related gene protein;
DE Flags: Precursor;
GN Name=MR1;
OS Pongo pygmaeus (Bornean orangutan).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9600;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), AND
RP ALTERNATIVE SPLICING.
RX PubMed=11797097; DOI=10.1007/s00251-001-0380-1;
RA Parra-Cuadrado J.F., del Moral M.G., Garcia-Pavia P., Setien F.,
RA Martinez-Naves E.;
RT "Characterization of the MHC class I-related MR1 locus in nonhuman
RT primates.";
RL Immunogenetics 53:643-648(2001).
CC -!- FUNCTION: Antigen-presenting molecule specialized in displaying
CC microbial pyrimidine-based metabolites to alpha-beta T cell receptors
CC (TCR) on innate-type mucosal-associated invariant T (MAIT) cells. In
CC complex with B2M preferentially presents riboflavin-derived metabolites
CC to semi-invariant TCRs on MAIT cells, guiding immune surveillance of
CC the microbial metabolome at mucosal epithelial barriers (By
CC similarity). Signature pyrimidine-based microbial antigens are
CC generated via non-enzymatic condensation of metabolite intermediates of
CC the riboflavin pathway with by-products arising from other metabolic
CC pathways such as glycolysis. Typical potent antigenic metabolites are
CC 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU) and 5-(2-
CC oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU), products of
CC condensation of 5-amino-6-D-ribityaminouracil (5-A-RU) with glyoxal or
CC methylglyoxal by-products, respectively (By similarity). May present
CC microbial antigens to various MAIT cell subsets, providing for unique
CC recognition of diverse microbes, including pathogens that do not
CC synthesize riboflavin. Upon antigen recognition, elicits rapid innate-
CC type MAIT cell activation to eliminate pathogenic microbes by directly
CC killing infected cells (By similarity). During T cell development,
CC drives thymic selection and post-thymic terminal differentiation of
CC MAIT cells in a process dependent on commensal microflora (By
CC similarity). Acts as an immune sensor of cancer cell metabolome. May
CC present a tumor-specific or -associated metabolite essential for cancer
CC cell survival to a pan-cancer TCR on a non-MAIT CD8-positive T cell
CC clone, triggering T cell-mediated killing of a wide range of cancer
CC cell types (By similarity). {ECO:0000250|UniProtKB:Q8HWB0,
CC ECO:0000250|UniProtKB:Q95460}.
CC -!- SUBUNIT: Heterotrimer that consists of MR1, B2M and a metabolite
CC antigen. Forms reversible covalent Schiff base complexes with the
CC microbial metabolite, which serves as a molecular switch triggering
CC complete folding, stable association with B2M and translocation of the
CC ternary complex from endoplasmic reticulum to the plasma membrane. On
CC antigen-presenting cells, the ternary complex interacts with TCR on
CC CD8-positive T cells. The molecular machinery involved in antigen
CC processing remains unknown, but appears to be TAP1-TAP2 and proteasome-
CC independent. Structurally, MR1-B2M heterodimer adopts a topology
CC similar to classical MHC class I molecules, with alpha-1 and alpha-2
CC domains of MR1 forming the antigen-binding cleft composed of two alpha-
CC helices resting on a floor of 7-stranded anti-parallel beta-pleated
CC sheet. The ribityl moiety of pyrimidine-based antigens is recognized by
CC Tyr-95 residue in the CDR3 alpha loop of the invariant TRAV1-2 TCR.
CC {ECO:0000250|UniProtKB:Q95460}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q95460};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q95460}.
CC Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q95460}; Single-
CC pass type I membrane protein {ECO:0000255}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q95460}; Single-pass type I membrane protein
CC {ECO:0000255}. Early endosome membrane {ECO:0000250|UniProtKB:Q95460};
CC Single-pass type I membrane protein {ECO:0000255}. Late endosome
CC membrane {ECO:0000250|UniProtKB:Q95460}; Single-pass type I membrane
CC protein {ECO:0000255}. Note=In the absence of antigen remains within
CC the endoplasmic reticulum where it acts as a metabolite sensor. Antigen
CC binding triggers trafficking of the ternary complex to the plasma
CC membrane. After presentation, most of these complexes are rapidly
CC internalized and degraded via endocytosis. A small subset recycles via
CC endosomes back to the plasma membrane and may thus acquire and present
CC new antigens that do not efficiently reach the endoplasmic reticulum.
CC {ECO:0000250|UniProtKB:Q95460}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=MR1;
CC IsoId=Q9BD50-1; Sequence=Displayed;
CC Name=2; Synonyms=MR1B2;
CC IsoId=Q9BD50-2; Sequence=VSP_034761;
CC -!- DOMAIN: The alpha-1 domain is a structural part of antigen-binding
CC cleft. {ECO:0000250|UniProtKB:Q95460}.
CC -!- DOMAIN: The alpha-2 domain is a structural part of antigen-binding
CC cleft. {ECO:0000250|UniProtKB:Q95460}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q95460}.
CC -!- MISCELLANEOUS: MR1 is detected in an open versus folded conformation.
CC Only the folded MR1 conformer activates MAIT cells (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the MHC class I family. {ECO:0000305}.
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DR EMBL; AJ271828; CAC28215.1; -; mRNA.
DR EMBL; AJ271829; CAC28216.1; -; mRNA.
DR EMBL; AJ315656; CAC42232.1; -; Genomic_DNA.
DR AlphaFoldDB; Q9BD50; -.
DR SMR; Q9BD50; -.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042612; C:MHC class I protein complex; IEA:UniProtKB-KW.
DR GO; GO:0002474; P:antigen processing and presentation of peptide antigen via MHC class I; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.30.500.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003006; Ig/MHC_CS.
DR InterPro; IPR003597; Ig_C1-set.
DR InterPro; IPR011161; MHC_I-like_Ag-recog.
DR InterPro; IPR037055; MHC_I-like_Ag-recog_sf.
DR InterPro; IPR011162; MHC_I/II-like_Ag-recog.
DR InterPro; IPR001039; MHC_I_a_a1/a2.
DR Pfam; PF07654; C1-set; 1.
DR Pfam; PF00129; MHC_I; 1.
DR PRINTS; PR01638; MHCCLASSI.
DR SMART; SM00407; IGc1; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR SUPFAM; SSF54452; SSF54452; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS00290; IG_MHC; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; Disulfide bond; Endoplasmic reticulum;
KW Endosome; Glycoprotein; Golgi apparatus; Immunity; Immunoglobulin domain;
KW Innate immunity; Membrane; MHC I; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..340
FT /note="Major histocompatibility complex class I-related
FT gene protein"
FT /id="PRO_0000344445"
FT TOPO_DOM 23..302
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 303..323
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 324..340
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 203..294
FT /note="Ig-like C1-type"
FT REGION 23..109
FT /note="Alpha-1"
FT /evidence="ECO:0000250"
FT REGION 110..201
FT /note="Alpha-2"
FT /evidence="ECO:0000250"
FT REGION 202..293
FT /note="Alpha-3"
FT /evidence="ECO:0000250"
FT REGION 294..302
FT /note="Connecting peptide"
FT /evidence="ECO:0000250"
FT BINDING 31
FT /ligand="5-(2-oxoethylideneamino)-6-(D-ribitylamino)uracil"
FT /ligand_id="ChEBI:CHEBI:78397"
FT /ligand_note="pathogen-derived metabolite antigen"
FT /evidence="ECO:0000250|UniProtKB:Q95460"
FT BINDING 31
FT /ligand="5-(2-oxopropylideneamino)-6-(D-
FT ribitylamino)uracil"
FT /ligand_id="ChEBI:CHEBI:78398"
FT /ligand_note="pathogen-derived metabolite antigen"
FT /evidence="ECO:0000250|UniProtKB:Q95460"
FT BINDING 46
FT /ligand="5-(2-oxoethylideneamino)-6-(D-ribitylamino)uracil"
FT /ligand_id="ChEBI:CHEBI:78397"
FT /ligand_note="pathogen-derived metabolite antigen"
FT /evidence="ECO:0000250|UniProtKB:Q95460"
FT BINDING 46
FT /ligand="5-(2-oxopropylideneamino)-6-(D-
FT ribitylamino)uracil"
FT /ligand_id="ChEBI:CHEBI:78398"
FT /ligand_note="pathogen-derived metabolite antigen"
FT /evidence="ECO:0000250|UniProtKB:Q95460"
FT BINDING 65
FT /ligand="5-(2-oxoethylideneamino)-6-(D-ribitylamino)uracil"
FT /ligand_id="ChEBI:CHEBI:78397"
FT /ligand_note="pathogen-derived metabolite antigen"
FT /note="covalent"
FT /evidence="ECO:0000250|UniProtKB:Q95460"
FT BINDING 65
FT /ligand="5-(2-oxopropylideneamino)-6-(D-
FT ribitylamino)uracil"
FT /ligand_id="ChEBI:CHEBI:78398"
FT /ligand_note="pathogen-derived metabolite antigen"
FT /note="covalent"
FT /evidence="ECO:0000250|UniProtKB:Q95460"
FT BINDING 116
FT /ligand="5-(2-oxoethylideneamino)-6-(D-ribitylamino)uracil"
FT /ligand_id="ChEBI:CHEBI:78397"
FT /ligand_note="pathogen-derived metabolite antigen"
FT /evidence="ECO:0000250|UniProtKB:Q95460"
FT BINDING 116
FT /ligand="5-(2-oxopropylideneamino)-6-(D-
FT ribitylamino)uracil"
FT /ligand_id="ChEBI:CHEBI:78398"
FT /ligand_note="pathogen-derived metabolite antigen"
FT /evidence="ECO:0000250|UniProtKB:Q95460"
FT BINDING 174
FT /ligand="5-(2-oxoethylideneamino)-6-(D-ribitylamino)uracil"
FT /ligand_id="ChEBI:CHEBI:78397"
FT /ligand_note="pathogen-derived metabolite antigen"
FT /evidence="ECO:0000250|UniProtKB:Q95460"
FT BINDING 174
FT /ligand="5-(2-oxopropylideneamino)-6-(D-
FT ribitylamino)uracil"
FT /ligand_id="ChEBI:CHEBI:78398"
FT /ligand_note="pathogen-derived metabolite antigen"
FT /evidence="ECO:0000250|UniProtKB:Q95460"
FT BINDING 175
FT /ligand="5-(2-oxoethylideneamino)-6-(D-ribitylamino)uracil"
FT /ligand_id="ChEBI:CHEBI:78397"
FT /ligand_note="pathogen-derived metabolite antigen"
FT /evidence="ECO:0000250|UniProtKB:Q95460"
FT BINDING 175
FT /ligand="5-(2-oxopropylideneamino)-6-(D-
FT ribitylamino)uracil"
FT /ligand_id="ChEBI:CHEBI:78398"
FT /ligand_note="pathogen-derived metabolite antigen"
FT /evidence="ECO:0000250|UniProtKB:Q95460"
FT CARBOHYD 107
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 120..183
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 222..278
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT VAR_SEQ 203..294
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11797097"
FT /id="VSP_034761"
FT CONFLICT 63
FT /note="Q -> R (in Ref. 1; CAC42232)"
FT /evidence="ECO:0000305"
FT CONFLICT 163
FT /note="R -> Q (in Ref. 1; CAC42232)"
FT /evidence="ECO:0000305"
FT CONFLICT 173
FT /note="Q -> L (in Ref. 1; CAC42232)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 340 AA; 39375 MW; A893952B78725F17 CRC64;
MGELMAFLLP LIIVLMVKHS NSRTHSLRYF RLGVSDPIRG VPEFISVGYV DSHPITTYDS
VTQQKEPRAP WMAENLAPDH WERYTQLLRG WQQMFKVELK RLQRHYNHSG SHTYQRMIGC
ELLEDGSTTG FLQYAYDGQD FLIFNKDTLS WLAVDNVAHT IKRAWEANQH ELQYQKNWLE
EECIAWLKRF LEYGKDTLQR TEPPLVRVNR KETFPGVTTL FCKAHGFYPP EIYMTWMKNG
EEIVQEMDYG DILPSGDGTY QTWASFELDP QSSNLYSCHV EHCGVHMVLQ VPQESEAIPL
VMKAVSGSIV FVIVLTGVGV LVWRRRPREQ NGAVYLPTPD
