TLR7_MOUSE
ID TLR7_MOUSE Reviewed; 1050 AA.
AC P58681; Q923I1;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 31-JAN-2002, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Toll-like receptor 7;
DE Flags: Precursor;
GN Name=Tlr7;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Macrophage;
RA Heil F.J., Lipford G.B., Wagner H., Bauer S.M.;
RT "Molecular cloning of murine Toll-like receptor 7.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION.
RX PubMed=14976261; DOI=10.1126/science.1093616;
RA Diebold S.S., Kaisho T., Hemmi H., Akira S., Reis e Sousa C.;
RT "Innate antiviral responses by means of TLR7-mediated recognition of
RT single-stranded RNA.";
RL Science 303:1529-1531(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH UNC93B1.
RX PubMed=17452530; DOI=10.1083/jcb.200612056;
RA Brinkmann M.M., Spooner E., Hoebe K., Beutler B., Ploegh H.L., Kim Y.M.;
RT "The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9
RT is crucial for TLR signaling.";
RL J. Cell Biol. 177:265-275(2007).
RN [4]
RP SUBCELLULAR LOCATION.
RX PubMed=18305481; DOI=10.1038/nature06726;
RA Kim Y.M., Brinkmann M.M., Paquet M.E., Ploegh H.L.;
RT "UNC93B1 delivers nucleotide-sensing toll-like receptors to
RT endolysosomes.";
RL Nature 452:234-238(2008).
RN [5]
RP PROTEOLYTIC CLEAVAGE, AND FUNCTION.
RX PubMed=21402738; DOI=10.1084/jem.20100682;
RA Ewald S.E., Engel A., Lee J., Wang M., Bogyo M., Barton G.M.;
RT "Nucleic acid recognition by Toll-like receptors is coupled to stepwise
RT processing by cathepsins and asparagine endopeptidase.";
RL J. Exp. Med. 208:643-651(2011).
RN [6]
RP INTERACTION WITH SMPDL3B.
RX PubMed=26095358; DOI=10.1016/j.celrep.2015.05.006;
RA Heinz L.X., Baumann C.L., Koeberlin M.S., Snijder B., Gawish R., Shui G.,
RA Sharif O., Aspalter I.M., Mueller A.C., Kandasamy R.K., Breitwieser F.P.,
RA Pichlmair A., Bruckner M., Rebsamen M., Blueml S., Karonitsch T.,
RA Fauster A., Colinge J., Bennett K.L., Knapp S., Wenk M.R.,
RA Superti-Furga G.;
RT "The lipid-modifying enzyme SMPDL3B negatively regulates innate immunity.";
RL Cell Rep. 11:1919-1928(2015).
CC -!- FUNCTION: Endosomal receptor that plays a key role in innate and
CC adaptive immunity. Controls host immune response against pathogens
CC through recognition of uridine-containing single strand RNAs (ssRNAs)
CC of viral origin or guanosine analogs (PubMed:21402738). Upon binding to
CC agonists, undergoes dimerization that brings TIR domains from the two
CC molecules into direct contact, leading to the recruitment of TIR-
CC containing downstream adapter MYD88 through homotypic interaction. In
CC turn, the Myddosome signaling complex is formed involving IRAK4, IRAK1,
CC TRAF6, TRAF3 leading to activation of downstream transcription factors
CC NF-kappa-B and IRF7 to induce pro-inflammatory cytokines and
CC interferons, respectively (PubMed:14976261) (By similarity).
CC {ECO:0000250|UniProtKB:Q9NYK1, ECO:0000269|PubMed:14976261,
CC ECO:0000269|PubMed:21402738}.
CC -!- ACTIVITY REGULATION: Activated by guanosine analogs including
CC deoxyguanosine, 7-thia-8-oxoguanosine or 7-deazaguanosine in a RNA-
CC independent manner. {ECO:0000250|UniProtKB:Q9NYK1}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with MYD88 via their
CC respective TIR domains (Probable). Interacts with UNC93B1
CC (PubMed:17452530). Interacts with SMPDL3B (PubMed:26095358).
CC {ECO:0000250|UniProtKB:Q9NYK1, ECO:0000269|PubMed:17452530,
CC ECO:0000269|PubMed:26095358, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000269|PubMed:18305481}.
CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:18305481}; Single-
CC pass type I membrane protein {ECO:0000269|PubMed:18305481}. Lysosome
CC {ECO:0000269|PubMed:18305481}. Cytoplasmic vesicle, phagosome
CC {ECO:0000269|PubMed:18305481}. Note=Relocalizes from endoplasmic
CC reticulum to endosome and lysosome upon stimulation with agonist.
CC -!- DOMAIN: Contains two binding domains, first site for small ligands and
CC second site for ssRNA. {ECO:0000250|UniProtKB:Q9NYK1}.
CC -!- PTM: The first cleavage is performed by asparagine endopeptidase or
CC cathepsin family members. This initial cleavage event is followed by a
CC trimming event that is solely cathepsin mediated and required for
CC optimal receptor signaling. {ECO:0000269|PubMed:21402738}.
CC -!- SIMILARITY: Belongs to the Toll-like receptor family. {ECO:0000305}.
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DR EMBL; AY035889; AAK62676.1; -; mRNA.
DR CCDS; CCDS30531.1; -.
DR CCDS; CCDS72469.1; -.
DR RefSeq; NP_001277684.1; NM_001290755.1.
DR RefSeq; NP_001277685.1; NM_001290756.1.
DR RefSeq; NP_001277686.1; NM_001290757.1.
DR RefSeq; NP_573474.1; NM_133211.4.
DR RefSeq; XP_011246087.1; XM_011247785.1.
DR RefSeq; XP_011246088.1; XM_011247786.1.
DR AlphaFoldDB; P58681; -.
DR SMR; P58681; -.
DR BioGRID; 228409; 2.
DR IntAct; P58681; 2.
DR STRING; 10090.ENSMUSP00000061853; -.
DR BindingDB; P58681; -.
DR ChEMBL; CHEMBL6085; -.
DR GuidetoPHARMACOLOGY; 1757; -.
DR GlyGen; P58681; 12 sites.
DR iPTMnet; P58681; -.
DR PhosphoSitePlus; P58681; -.
DR PaxDb; P58681; -.
DR PeptideAtlas; P58681; -.
DR PRIDE; P58681; -.
DR ProteomicsDB; 259516; -.
DR Antibodypedia; 8500; 1008 antibodies from 45 providers.
DR DNASU; 170743; -.
DR Ensembl; ENSMUST00000060719; ENSMUSP00000061853; ENSMUSG00000044583.
DR Ensembl; ENSMUST00000112161; ENSMUSP00000107787; ENSMUSG00000044583.
DR Ensembl; ENSMUST00000112164; ENSMUSP00000107789; ENSMUSG00000044583.
DR GeneID; 170743; -.
DR KEGG; mmu:170743; -.
DR UCSC; uc009uwz.2; mouse.
DR CTD; 51284; -.
DR MGI; MGI:2176882; Tlr7.
DR VEuPathDB; HostDB:ENSMUSG00000044583; -.
DR eggNOG; KOG4641; Eukaryota.
DR GeneTree; ENSGT00940000159771; -.
DR HOGENOM; CLU_006000_2_0_1; -.
DR InParanoid; P58681; -.
DR OMA; CNSKYLR; -.
DR OrthoDB; 303561at2759; -.
DR PhylomeDB; P58681; -.
DR TreeFam; TF325595; -.
DR Reactome; R-MMU-1679131; Trafficking and processing of endosomal TLR.
DR Reactome; R-MMU-168181; Toll Like Receptor 7/8 (TLR7/8) Cascade.
DR BioGRID-ORCS; 170743; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Tlr7; mouse.
DR PRO; PR:P58681; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; P58681; protein.
DR Bgee; ENSMUSG00000044583; Expressed in stroma of bone marrow and 68 other tissues.
DR ExpressionAtlas; P58681; baseline and differential.
DR Genevisible; P58681; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0032009; C:early phagosome; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0003725; F:double-stranded RNA binding; ISS:UniProtKB.
DR GO; GO:0038187; F:pattern recognition receptor activity; IBA:GO_Central.
DR GO; GO:0003727; F:single-stranded RNA binding; IMP:UniProtKB.
DR GO; GO:0035197; F:siRNA binding; IMP:UniProtKB.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:InterPro.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0098586; P:cellular response to virus; IMP:MGI.
DR GO; GO:0051607; P:defense response to virus; IMP:UniProtKB.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:0007252; P:I-kappaB phosphorylation; ISO:MGI.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0007254; P:JNK cascade; IMP:MGI.
DR GO; GO:0000165; P:MAPK cascade; IMP:MGI.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; IEA:InterPro.
DR GO; GO:0032722; P:positive regulation of chemokine production; ISO:MGI.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; IMP:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; ISS:UniProtKB.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISS:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:MGI.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISS:UniProtKB.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IDA:MGI.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IGI:MGI.
DR GO; GO:0034154; P:toll-like receptor 7 signaling pathway; IMP:UniProtKB.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; IBA:GO_Central.
DR Gene3D; 3.40.50.10140; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR000483; Cys-rich_flank_reg_C.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR041283; LRR_12.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR026880; TLR7.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR PANTHER; PTHR47410:SF2; PTHR47410:SF2; 1.
DR Pfam; PF00560; LRR_1; 1.
DR Pfam; PF18837; LRR_12; 1.
DR Pfam; PF13855; LRR_8; 4.
DR Pfam; PF01582; TIR; 1.
DR SMART; SM00369; LRR_TYP; 12.
DR SMART; SM00082; LRRCT; 1.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF52200; SSF52200; 1.
DR PROSITE; PS51450; LRR; 19.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW Cytoplasmic vesicle; Endoplasmic reticulum; Endosome; Glycoprotein;
KW Immunity; Inflammatory response; Innate immunity; Leucine-rich repeat;
KW Lysosome; Membrane; Receptor; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..1050
FT /note="Toll-like receptor 7"
FT /id="PRO_0000034734"
FT TOPO_DOM 27..837
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 838..858
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 859..1050
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 42..64
FT /note="LRR 1"
FT REPEAT 65..87
FT /note="LRR 2"
FT REPEAT 89..111
FT /note="LRR 3"
FT REPEAT 126..149
FT /note="LRR 4"
FT REPEAT 151..170
FT /note="LRR 5"
FT REPEAT 171..195
FT /note="LRR 6"
FT REPEAT 203..226
FT /note="LRR 7"
FT REPEAT 228..247
FT /note="LRR 8"
FT REPEAT 248..273
FT /note="LRR 9"
FT REPEAT 275..289
FT /note="LRR 10"
FT REPEAT 290..312
FT /note="LRR 11"
FT REPEAT 314..337
FT /note="LRR 12"
FT REPEAT 339..364
FT /note="LRR 13"
FT REPEAT 369..392
FT /note="LRR 14"
FT REPEAT 396..419
FT /note="LRR 15"
FT REPEAT 421..443
FT /note="LRR 16"
FT REPEAT 493..516
FT /note="LRR 17"
FT REPEAT 517..542
FT /note="LRR 18"
FT REPEAT 543..565
FT /note="LRR 19"
FT REPEAT 567..589
FT /note="LRR 20"
FT REPEAT 596..619
FT /note="LRR 21"
FT REPEAT 620..645
FT /note="LRR 22"
FT REPEAT 650..673
FT /note="LRR 23"
FT REPEAT 675..698
FT /note="LRR 24"
FT REPEAT 699..722
FT /note="LRR 25"
FT REPEAT 724..746
FT /note="LRR 26"
FT REPEAT 747..770
FT /note="LRR 27"
FT REPEAT 773..796
FT /note="LRR 28"
FT DOMAIN 890..1034
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT CARBOHYD 66
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 69
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 167
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 190
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 215
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 387
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 524
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 535
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 591
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 680
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 721
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 800
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1050 AA; 121837 MW; 495B75DEE849D8EE CRC64;
MVFSMWTRKR QILIFLNMLL VSRVFGFRWF PKTLPCEVKV NIPEAHVIVD CTDKHLTEIP
EGIPTNTTNL TLTINHIPSI SPDSFRRLNH LEEIDLRCNC VPVLLGSKAN VCTKRLQIRP
GSFSGLSDLK ALYLDGNQLL EIPQDLPSSL HLLSLEANNI FSITKENLTE LVNIETLYLG
QNCYYRNPCN VSYSIEKDAF LVMRNLKVLS LKDNNVTAVP TTLPPNLLEL YLYNNIIKKI
QENDFNNLNE LQVLDLSGNC PRCYNVPYPC TPCENNSPLQ IHDNAFNSLT ELKVLRLHSN
SLQHVPPTWF KNMRNLQELD LSQNYLAREI EEAKFLHFLP NLVELDFSFN YELQVYHASI
TLPHSLSSLE NLKILRVKGY VFKELKNSSL SVLHKLPRLE VLDLGTNFIK IADLNIFKHF
ENLKLIDLSV NKISPSEESR EVGFCPNAQT SVDRHGPQVL EALHYFRYDE YARSCRFKNK
EPPSFLPLNA DCHIYGQTLD LSRNNIFFIK PSDFQHLSFL KCLNLSGNTI GQTLNGSELW
PLRELRYLDF SNNRLDLLYS TAFEELQSLE VLDLSSNSHY FQAEGITHML NFTKKLRLLD
KLMMNDNDIS TSASRTMESD SLRILEFRGN HLDVLWRAGD NRYLDFFKNL FNLEVLDISR
NSLNSLPPEV FEGMPPNLKN LSLAKNGLKS FFWDRLQLLK HLEILDLSHN QLTKVPERLA
NCSKSLTTLI LKHNQIRQLT KYFLEDALQL RYLDISSNKI QVIQKTSFPE NVLNNLEMLV
LHHNRFLCNC DAVWFVWWVN HTDVTIPYLA TDVTCVGPGA HKGQSVISLD LYTCELDLTN
LILFSVSISS VLFLMVVMTT SHLFFWDMWY IYYFWKAKIK GYQHLQSMES CYDAFIVYDT
KNSAVTEWVL QELVAKLEDP REKHFNLCLE ERDWLPGQPV LENLSQSIQL SKKTVFVMTQ
KYAKTESFKM AFYLSHQRLL DEKVDVIILI FLEKPLQKSK FLQLRKRLCR SSVLEWPANP
QAHPYFWQCL KNALTTDNHV AYSQMFKETV
