HMR1_RAT
ID HMR1_RAT Reviewed; 343 AA.
AC O19477;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 129.
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; Synonyms=Hlals;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 25-342, AND TISSUE SPECIFICITY.
RC STRAIN=Lewis.1W;
RX PubMed=9553154; DOI=10.1007/s002510050385;
RA Walter L., Guenther E.;
RT "Isolation and molecular characterization of the rat MR1 homologue, a non-
RT MHC-linked class I-related gene.";
RL Immunogenetics 47:477-482(1998).
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 -!- TISSUE SPECIFICITY: Expressed in kidney, liver, testis, spleen, thymus,
CC brain, and heart. {ECO:0000269|PubMed:9553154}.
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 -!- POLYMORPHISM: Does not appear to be polymorphic.
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}.
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DR EMBL; AABR03084784; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Y13972; CAA74305.1; -; mRNA.
DR RefSeq; NP_001094105.1; NM_001100635.1.
DR AlphaFoldDB; O19477; -.
DR SMR; O19477; -.
DR STRING; 10116.ENSRNOP00000004694; -.
DR GlyGen; O19477; 1 site.
DR PaxDb; O19477; -.
DR PRIDE; O19477; -.
DR GeneID; 25119; -.
DR KEGG; rno:25119; -.
DR UCSC; RGD:1593291; rat.
DR CTD; 3140; -.
DR RGD; 1593291; Mr1.
DR eggNOG; ENOG502RQEK; Eukaryota.
DR HOGENOM; CLU_047501_0_1_1; -.
DR InParanoid; O19477; -.
DR OrthoDB; 912212at2759; -.
DR PhylomeDB; O19477; -.
DR TreeFam; TF336617; -.
DR PRO; PR:O19477; -.
DR Proteomes; UP000002494; Unplaced.
DR Genevisible; O19477; RN.
DR GO; GO:0031901; C:early endosome membrane; ISO:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0042612; C:MHC class I protein complex; IEA:UniProtKB-KW.
DR GO; GO:0030881; F:beta-2-microglobulin binding; ISO:RGD.
DR GO; GO:0042608; F:T cell receptor binding; ISO:RGD.
DR GO; GO:0019884; P:antigen processing and presentation of exogenous antigen; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0033077; P:T cell differentiation in thymus; ISO:RGD.
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 Cell membrane; Disulfide bond; Endoplasmic reticulum; Endosome;
KW 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:0000255"
FT CHAIN 19..343
FT /note="Major histocompatibility complex class I-related
FT gene protein"
FT /id="PRO_0000344446"
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..343
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 204..286
FT /note="Ig-like C1-type"
FT REGION 19..105
FT /note="Alpha-1"
FT /evidence="ECO:0000250"
FT REGION 106..197
FT /note="Alpha-2"
FT /evidence="ECO:0000250"
FT REGION 198..289
FT /note="Alpha-3"
FT /evidence="ECO:0000250"
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:0000255"
FT DISULFID 116..179
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 218..274
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT CONFLICT 284
FT /note="V -> I (in Ref. 2; CAA74305)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 343 AA; 39571 MW; 2D1AC536F7E5A626 CRC64;
MMFLLPFLTV FLAKQSHTRT HSLRYFRLAI SDPGPGVPEF ISVGYVDSHP ITTYDSVTRQ
KEPRAPWMAE NLAPDHWERY TQLLRGWQRT FQTELRHLQR HYNHSGLHTY QRMIGCELLE
DGSTTGFLQY AYDGQDFIVF DKDTLSWLAM DNVAHITKRA WEANLHELQY QKNWLEEECI
AWLKRFLEYG SDALERTEHP VVRTTRKETF PGITTLFCRA HGFYPPEISM IWKKNGEEIV
QEVDYGGVLP SGDGTYQMWV SVDLDPQTKD IYSCHVEHCG LQMVLEAPQE SGNTLLVANT
ISGTIILIIV LAGVGALIWR RRSREPKEVM YQPTQVNEGS SPS
