HMR1_BOVIN
ID HMR1_BOVIN Reviewed; 336 AA.
AC C1ITJ8; F1MVL8;
DT 19-FEB-2014, integrated into UniProtKB/Swiss-Prot.
DT 26-MAY-2009, sequence version 1.
DT 03-AUG-2022, entry version 91.
DE RecName: Full=Major histocompatibility complex class I-related gene protein;
DE Short=MHC class I-related gene protein;
DE AltName: Full=Class I histocompatibility antigen-like protein;
DE Flags: Precursor;
GN Name=MR1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND SUBCELLULAR LOCATION.
RX PubMed=19416870; DOI=10.1073/pnas.0903196106;
RA Huang S., Martin E., Kim S., Yu L., Soudais C., Fremont D.H., Lantz O.,
RA Hansen T.H.;
RT "MR1 antigen presentation to mucosal-associated invariant T cells was
RT highly conserved in evolution.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:8290-8295(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Van Rhijn I.;
RT "Ruminant MR1 and MAIT cells.";
RL Submitted (AUG-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Hereford;
RX PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D.,
RA Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT "A whole-genome assembly of the domestic cow, Bos taurus.";
RL Genome Biol. 10:R42.01-R42.10(2009).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.86 ANGSTROMS) OF 19-295 IN COMPLEX WITH B2M AND
RP HUMAN T-CELL RECEPTOR, AND DISULFIDE BONDS.
RX PubMed=23613577; DOI=10.1073/pnas.1222678110;
RA Lopez-Sagaseta J., Dulberger C.L., Crooks J.E., Parks C.D., Luoma A.M.,
RA McFedries A., Van Rhijn I., Saghatelian A., Adams E.J.;
RT "The molecular basis for Mucosal-Associated Invariant T cell recognition of
RT MR1 proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:E1771-E1778(2013).
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 metabolite antigen
CC (By similarity). Forms reversible covalent Schiff base complexes with
CC the microbial metabolite, which serve 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 (By similarity). MR1-B2M heterodimer (via alpha-helices)
CC interacts with TCR (via CDR domains) (PubMed:23613577).
CC {ECO:0000250|UniProtKB:Q95460, ECO:0000269|PubMed:23613577}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19416870};
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 -!- 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 -!- SIMILARITY: Belongs to the MHC class I family. {ECO:0000305}.
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DR EMBL; EU792881; ACH56827.1; -; mRNA.
DR EMBL; FJ028657; ACN18277.1; -; mRNA.
DR EMBL; DAAA02043522; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; DAAA02043523; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001177227.1; NM_001190298.1.
DR PDB; 4IIQ; X-ray; 2.86 A; C=19-295.
DR PDB; 4L8S; X-ray; 2.90 A; C=19-295.
DR PDB; 4L9L; X-ray; 3.40 A; C=19-295.
DR PDB; 4LCC; X-ray; 3.26 A; C=19-295.
DR PDBsum; 4IIQ; -.
DR PDBsum; 4L8S; -.
DR PDBsum; 4L9L; -.
DR PDBsum; 4LCC; -.
DR AlphaFoldDB; C1ITJ8; -.
DR SMR; C1ITJ8; -.
DR STRING; 9913.ENSBTAP00000013095; -.
DR PaxDb; C1ITJ8; -.
DR PRIDE; C1ITJ8; -.
DR Ensembl; ENSBTAT00000013095; ENSBTAP00000013095; ENSBTAG00000009924.
DR GeneID; 506206; -.
DR KEGG; bta:506206; -.
DR CTD; 3140; -.
DR VEuPathDB; HostDB:ENSBTAG00000009924; -.
DR VGNC; VGNC:31595; MR1.
DR eggNOG; ENOG502RQEK; Eukaryota.
DR GeneTree; ENSGT01040000240396; -.
DR HOGENOM; CLU_047501_0_1_1; -.
DR InParanoid; C1ITJ8; -.
DR OMA; HVEHCGL; -.
DR OrthoDB; 912212at2759; -.
DR TreeFam; TF336617; -.
DR Proteomes; UP000009136; Chromosome 16.
DR Bgee; ENSBTAG00000009924; Expressed in monocyte and 106 other tissues.
DR ExpressionAtlas; C1ITJ8; baseline and differential.
DR GO; GO:0031901; C:early endosome membrane; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
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; ISS:UniProtKB.
DR GO; GO:0042612; C:MHC class I protein complex; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0030881; F:beta-2-microglobulin binding; ISS:UniProtKB.
DR GO; GO:0042608; F:T cell receptor binding; ISS:UniProtKB.
DR GO; GO:0002474; P:antigen processing and presentation of peptide antigen via MHC class I; IEA:UniProtKB-KW.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; ISS:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0002854; P:positive regulation of T cell mediated cytotoxicity directed against tumor cell target; ISS:UniProtKB.
DR GO; GO:0033077; P:T cell differentiation in thymus; ISS:UniProtKB.
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 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disulfide bond; Endoplasmic reticulum;
KW Endosome; Glycoprotein; Golgi apparatus; Immunity; Immunoglobulin domain;
KW Innate immunity; Membrane; MHC I; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..18
FT /evidence="ECO:0000250"
FT CHAIN 19..336
FT /note="Major histocompatibility complex class I-related
FT gene protein"
FT /id="PRO_0000425531"
FT TOPO_DOM 19..298
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 299..319
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 320..336
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 199..295
FT /note="Ig-like C1-type"
FT REGION 19..197
FT /note="Ligand-binding"
FT /evidence="ECO:0000250"
FT REGION 19..105
FT /note="Alpha-1"
FT REGION 106..197
FT /note="Alpha-2"
FT REGION 198..289
FT /note="Alpha-3"
FT REGION 290..298
FT /note="Connecting peptide"
FT /evidence="ECO:0000250"
FT BINDING 27
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 27
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 42
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 42
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 61
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 61
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 112
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 112
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 170
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 170
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 171
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 171
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 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000305"
FT DISULFID 116..179
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:23613577"
FT DISULFID 218..274
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:23613577"
FT STRAND 21..30
FT /evidence="ECO:0007829|PDB:4IIQ"
FT STRAND 39..46
FT /evidence="ECO:0007829|PDB:4IIQ"
FT STRAND 49..58
FT /evidence="ECO:0007829|PDB:4IIQ"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:4IIQ"
FT HELIX 66..69
FT /evidence="ECO:0007829|PDB:4IIQ"
FT HELIX 74..101
FT /evidence="ECO:0007829|PDB:4IIQ"
FT STRAND 109..118
FT /evidence="ECO:0007829|PDB:4IIQ"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:4IIQ"
FT STRAND 124..132
FT /evidence="ECO:0007829|PDB:4IIQ"
FT STRAND 135..141
FT /evidence="ECO:0007829|PDB:4IIQ"
FT TURN 142..145
FT /evidence="ECO:0007829|PDB:4IIQ"
FT STRAND 146..153
FT /evidence="ECO:0007829|PDB:4IIQ"
FT HELIX 154..163
FT /evidence="ECO:0007829|PDB:4IIQ"
FT HELIX 165..176
FT /evidence="ECO:0007829|PDB:4IIQ"
FT HELIX 178..189
FT /evidence="ECO:0007829|PDB:4IIQ"
FT HELIX 191..194
FT /evidence="ECO:0007829|PDB:4IIQ"
FT STRAND 201..206
FT /evidence="ECO:0007829|PDB:4IIQ"
FT STRAND 215..226
FT /evidence="ECO:0007829|PDB:4IIQ"
FT STRAND 229..234
FT /evidence="ECO:0007829|PDB:4IIQ"
FT STRAND 241..245
FT /evidence="ECO:0007829|PDB:4L8S"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:4IIQ"
FT STRAND 256..263
FT /evidence="ECO:0007829|PDB:4IIQ"
FT STRAND 272..280
FT /evidence="ECO:0007829|PDB:4IIQ"
FT STRAND 282..288
FT /evidence="ECO:0007829|PDB:4IIQ"
SQ SEQUENCE 336 AA; 38894 MW; D0501CC96F59A2C1 CRC64;
MMLLLPLIIV LMMKLSDART HSLRYFRLGI SEPGYGIPEF ISAGYVDSHP ITMYNSVSQL
KEPRALWMEE NLAPDHWERY TQLLRGWQQA FKVELKQLQH HYNHSGFHTY QRMIGCELLE
DGSITGFLQY AYDGQDFLIF NKDTLSWMAM DNVADIIRRV WEANRHELQY QKNWLEEECI
AWLKRFLEYG KDALQRTEPP KVRVNHKETF PGITTLYCRA YGFYPPEISI NWMKNGEEIF
QDTDYGGILP SGDGTYQTWV SVELDPQNGD IYSCHVEHGG VHMVLQGFQE SETILLVVKA
VGFIVLAIAL AGVGILAWRK RPRGKNKVIC LSTPEH
