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   27-MAR-2024, entry version 172.
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).
RN   [7]
RP   MUTAGENESIS OF TYR-264.
RX   PubMed=35477763; DOI=10.1038/s41586-022-04642-z;
RA   Brown G.J., Canete P.F., Wang H., Medhavy A., Bones J., Roco J.A., He Y.,
RA   Qin Y., Cappello J., Ellyard J.I., Bassett K., Shen Q., Burgio G.,
RA   Zhang Y., Turnbull C., Meng X., Wu P., Cho E., Miosge L.A., Andrews T.D.,
RA   Field M.A., Tvorogov D., Lopez A.F., Babon J.J., Lopez C.A.,
RA   Gonzalez-Murillo A., Garulo D.C., Pascual V., Levy T., Mallack E.J.,
RA   Calame D.G., Lotze T., Lupski J.R., Ding H., Ullah T.R., Walters G.D.,
RA   Koina M.E., Cook M.C., Shen N., de Lucas Collantes C., Corry B.,
RA   Gantier M.P., Athanasopoulos V., Vinuesa C.G.;
RT   "TLR7 gain-of-function genetic variation causes human lupus.";
RL   Nature 605:349-356(2022).
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; 3.
DR   IntAct; P58681; 2.
DR   STRING; 10090.ENSMUSP00000107787; -.
DR   BindingDB; P58681; -.
DR   ChEMBL; CHEMBL6085; -.
DR   GuidetoPHARMACOLOGY; 1757; -.
DR   GlyCosmos; P58681; 12 sites, No reported glycans.
DR   GlyGen; P58681; 12 sites.
DR   iPTMnet; P58681; -.
DR   PhosphoSitePlus; P58681; -.
DR   PaxDb; 10090-ENSMUSP00000061853; -.
DR   PeptideAtlas; P58681; -.
DR   ProteomicsDB; 259516; -.
DR   Antibodypedia; 8500; 1072 antibodies from 45 providers.
DR   DNASU; 170743; -.
DR   Ensembl; ENSMUST00000060719.12; ENSMUSP00000061853.6; ENSMUSG00000044583.14.
DR   Ensembl; ENSMUST00000112161.8; ENSMUSP00000107787.2; ENSMUSG00000044583.14.
DR   Ensembl; ENSMUST00000112164.2; ENSMUSP00000107789.2; ENSMUSG00000044583.14.
DR   GeneID; 170743; -.
DR   KEGG; mmu:170743; -.
DR   UCSC; uc009uwz.2; mouse.
DR   AGR; MGI:2176882; -.
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; 5356114at2759; -.
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 77 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 70 other cell types or tissues.
DR   ExpressionAtlas; P58681; baseline and differential.
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: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:0007249; P:canonical NF-kappaB signal transduction; ISS:UniProtKB.
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:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR   GO; GO:0045087; P:innate immune response; ISS:UniProtKB.
DR   GO; GO:0007254; P:JNK cascade; IMP:MGI.
DR   GO; GO:0000165; P:MAPK cascade; IMP:MGI.
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: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 non-canonical NF-kappaB signal transduction; ISO:MGI.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:MGI.
DR   GO; GO:0032729; P:positive regulation of type II interferon production; ISS:UniProtKB.
DR   GO; GO:0001932; P:regulation of protein phosphorylation; IGI:MGI.
DR   GO; GO:0070305; P:response to cGMP; ISS:UniProtKB.
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; 3.80.10.10; Ribonuclease Inhibitor; 1.
DR   Gene3D; 3.40.50.10140; Toll/interleukin-1 receptor homology (TIR) domain; 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; IPR035897; Toll_tir_struct_dom_sf.
DR   PANTHER; PTHR47410:SF2; TOLL-LIKE RECEPTOR 7; 1.
DR   PANTHER; PTHR47410; TOLL-LIKE RECEPTOR 7-RELATED; 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   PRINTS; PR00019; LEURICHRPT.
DR   SMART; SM00364; LRR_BAC; 4.
DR   SMART; SM00365; LRR_SD22; 8.
DR   SMART; SM00369; LRR_TYP; 12.
DR   SMART; SM00082; LRRCT; 1.
DR   SMART; SM00255; TIR; 1.
DR   SUPFAM; SSF52058; L domain-like; 1.
DR   SUPFAM; SSF52047; RNI-like; 1.
DR   SUPFAM; SSF52200; Toll/Interleukin receptor TIR domain; 1.
DR   PROSITE; PS51450; LRR; 19.
DR   PROSITE; PS50104; TIR; 1.
DR   Genevisible; P58681; MM.
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"
FT   MUTAGEN         264
FT                   /note="Y->H: In kika; mice develop autoimmunity with
FT                   splenomegaly, multiple autoantibodies, and increased total
FT                   and activated B cells, germinal centers, plasma cells and
FT                   memory CD4+ T cells."
FT                   /evidence="ECO:0000269|PubMed:35477763"
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
//