ID TLR7_HUMAN Reviewed; 1049 AA. AC Q9NYK1; D1CS69; Q9NR98; DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 02-OCT-2024, entry version 204. DE RecName: Full=Toll-like receptor 7 {ECO:0000305}; DE Flags: Precursor; GN Name=TLR7 {ECO:0000312|HGNC:HGNC:15631}; ORFNames=UNQ248/PRO285; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Placenta; RX PubMed=11022119; RA Du X., Poltorak A., Wei Y., Beutler B.; RT "Three novel mammalian Toll-like receptors: gene structure, expression, and RT evolution."; RL Eur. Cytokine Netw. 11:362-371(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Placenta; RX PubMed=11022120; RA Chuang T.-H., Ulevitch R.J.; RT "Cloning and characterization of a sub-family of human Toll-like receptors: RT hTLR7, hTLR8 and hTLR9."; RL Eur. Cytokine Netw. 11:372-378(2000). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-11. RX PubMed=19924287; DOI=10.1371/journal.pone.0007803; RA Georgel P., Macquin C., Bahram S.; RT "The heterogeneous allelic repertoire of human Toll-Like receptor (TLR) RT genes."; RL PLoS ONE 4:E7803-E7803(2009). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=12975309; DOI=10.1101/gr.1293003; RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.; RT "The secreted protein discovery initiative (SPDI), a large-scale effort to RT identify novel human secreted and transmembrane proteins: a bioinformatics RT assessment."; RL Genome Res. 13:2265-2270(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=12738885; DOI=10.1073/pnas.0631696100; RA Lee J., Chuang T.H., Redecke V., She L., Pitha P.M., Carson D.A., Raz E., RA Cottam H.B.; RT "Molecular basis for the immunostimulatory activity of guanine nucleoside RT analogs: activation of Toll-like receptor 7."; RL Proc. Natl. Acad. Sci. U.S.A. 100:6646-6651(2003). RN [7] 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 [8] RP FUNCTION. RX PubMed=18250417; DOI=10.4049/jimmunol.180.4.2117; RA Gantier M.P., Tong S., Behlke M.A., Xu D., Phipps S., Foster P.S., RA Williams B.R.; RT "TLR7 is involved in sequence-specific sensing of single-stranded RNAs in RT human macrophages."; RL J. Immunol. 180:2117-2124(2008). RN [9] RP FUNCTION, SUBUNIT, AND DOMAIN. RX PubMed=27742543; DOI=10.1016/j.immuni.2016.09.011; RA Zhang Z., Ohto U., Shibata T., Krayukhina E., Taoka M., Yamauchi Y., RA Tanji H., Isobe T., Uchiyama S., Miyake K., Shimizu T.; RT "Structural Analysis Reveals that Toll-like Receptor 7 Is a Dual Receptor RT for Guanosine and Single-Stranded RNA."; RL Immunity 45:737-748(2016). RN [10] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=31608988; DOI=10.1002/eji.201948151; RA Davenne T., Bridgeman A., Rigby R.E., Rehwinkel J.; RT "Deoxyguanosine is a TLR7 agonist."; RL Eur. J. Immunol. 50:56-62(2020). RN [11] RP FUNCTION. RX PubMed=32433612; DOI=10.1038/s41586-020-2282-0; RA Heinz L.X., Lee J., Kapoor U., Kartnig F., Sedlyarov V., Papakostas K., RA Cesar-Razquin A., Essletzbichler P., Goldmann U., Stefanovic A., RA Bigenzahn J.W., Scorzoni S., Pizzagalli M.D., Bensimon A., Mueller A.C., RA King F.J., Li J., Girardi E., Mbow M.L., Whitehurst C.E., Rebsamen M., RA Superti-Furga G.; RT "TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9."; RL Nature 581:316-322(2020). RN [12] RP FUNCTION, INVOLVEMENT IN IMD74, VARIANT IMD74 PHE-795, CHARACTERIZATION OF RP VARIANT IMD74 PHE-795, AND ACTIVITY REGULATION. RX PubMed=32706371; DOI=10.1001/jama.2020.13719; RA van der Made C.I., Simons A., Schuurs-Hoeijmakers J., van den Heuvel G., RA Mantere T., Kersten S., van Deuren R.C., Steehouwer M., RA van Reijmersdal S.V., Jaeger M., Hofste T., Astuti G., RA Corominas Galbany J., van der Schoot V., van der Hoeven H., RA Hagmolen Of Ten Have W., Klijn E., van den Meer C., Fiddelaers J., RA de Mast Q., Bleeker-Rovers C.P., Joosten L.A.B., Yntema H.G., Gilissen C., RA Nelen M., van der Meer J.W.M., Brunner H.G., Netea M.G., RA van de Veerdonk F.L., Hoischen A.; RT "Presence of Genetic Variants Among Young Men With Severe COVID-19."; RL JAMA 324:663-673(2020). RN [13] RP INVOLVEMENT IN SLEB17, VARIANTS SLEB17 GLY-28; HIS-264 AND LEU-507, RP CHARACTERIZATION OF VARIANTS SLEB17 GLY-28; HIS-264 AND LEU-507, FUNCTION, RP AND ACTIVITY REGULATION. 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). RN [14] {ECO:0007744|PDB:7CYN} RP STRUCTURE BY ELECTRON MICROSCOPY (4.20 ANGSTROMS) IN COMPLEX WITH UNC93B1, RP AND INTERACTION WITH UNC93B1. RX PubMed=33432245; DOI=10.1038/s41594-020-00542-w; RA Ishida H., Asami J., Zhang Z., Nishizawa T., Shigematsu H., Ohto U., RA Shimizu T.; RT "Cryo-EM structures of Toll-like receptors in complex with UNC93B1."; RL Nat. Struct. Mol. Biol. 28:173-180(2021). CC -!- FUNCTION: Endosomal receptor that plays a key role in innate and CC adaptive immunity (PubMed:14976261, PubMed:32433612). Controls host CC immune response against pathogens through recognition of uridine- CC containing single strand RNAs (ssRNAs) of viral origin or guanosine CC analogs (PubMed:12738885, PubMed:27742543, PubMed:31608988, CC PubMed:32706371, PubMed:35477763). Upon binding to agonists, undergoes CC dimerization that brings TIR domains from the two molecules into direct CC contact, leading to the recruitment of TIR-containing downstream CC adapter MYD88 through homotypic interaction (PubMed:27742543). In turn, CC 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:27742543, PubMed:32706371). CC {ECO:0000269|PubMed:12738885, ECO:0000269|PubMed:14976261, CC ECO:0000269|PubMed:27742543, ECO:0000269|PubMed:31608988, CC ECO:0000269|PubMed:32433612, ECO:0000269|PubMed:32706371, CC ECO:0000269|PubMed:35477763}. CC -!- ACTIVITY REGULATION: Activated by guanosine analogs including CC deoxyguanosine, 7-thia-8-oxoguanosine or 7-deazaguanosine in a RNA- CC independent manner. Activated by imiquimod (PubMed:32706371). CC {ECO:0000269|PubMed:12738885, ECO:0000269|PubMed:31608988, CC ECO:0000269|PubMed:32706371, ECO:0000269|PubMed:35477763}. CC -!- SUBUNIT: Homodimer (PubMed:27742543). Interacts with MYD88 via their CC respective TIR domains (Probable). Interacts with UNC93B1 CC (PubMed:33432245). Interacts with SMPDL3B (By similarity). CC {ECO:0000250|UniProtKB:P58681, ECO:0000269|PubMed:27742543, CC ECO:0000269|PubMed:33432245, ECO:0000305}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:P58681}; Single-pass type I membrane protein CC {ECO:0000250|UniProtKB:P58681}. Endosome CC {ECO:0000250|UniProtKB:P58681}. Lysosome CC {ECO:0000250|UniProtKB:P58681}. Cytoplasmic vesicle, phagosome CC {ECO:0000250|UniProtKB:P58681}. Note=Relocalizes from endoplasmic CC reticulum to endosome and lysosome upon stimulation with agonist. CC {ECO:0000250|UniProtKB:P58681}. CC -!- TISSUE SPECIFICITY: Detected in brain, placenta, spleen, stomach, small CC intestine, lung and in plasmacytoid pre-dendritic cells. Expressed in CC peripheral mononuclear blood cells (PubMed:32706371). CC {ECO:0000269|PubMed:32706371}. CC -!- DOMAIN: Contains two binding domains, first site for small ligands and CC second site for ssRNA. {ECO:0000269|PubMed:27742543}. CC -!- DISEASE: Immunodeficiency 74, COVID19-related, X-linked (IMD74) CC [MIM:301051]: An X-linked recessive immunologic disorder characterized CC by impaired type I and type II interferon responses due to defective CC TLR7 signaling. Individuals with TLR7 deficiency develop severe CC respiratory insufficiency in response to infection with SARS-CoV-2 CC coronavirus. Death from respiratory failure may occur. CC {ECO:0000269|PubMed:32706371}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Systemic lupus erythematosus 17 (SLEB17) [MIM:301080]: A form CC of systemic lupus erythematosus, a chronic, relapsing, inflammatory, CC and often febrile multisystemic disorder of connective tissue, CC characterized principally by involvement of the skin, joints, kidneys CC and serosal membranes. The disease is marked by a wide range of system CC dysfunctions, an elevated erythrocyte sedimentation rate, and the CC formation of LE cells in the blood or bone marrow. SLEB17 is an X- CC linked dominant form characterized by onset of systemic CC autoinflammatory symptoms in the first decades of life. CC {ECO:0000269|PubMed:35477763}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the Toll-like receptor family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF240467; AAF60188.1; -; mRNA. DR EMBL; AF245702; AAF78035.1; -; mRNA. DR EMBL; DQ022185; AAZ99026.1; -; Genomic_DNA. DR EMBL; AY358292; AAQ88659.1; -; mRNA. DR EMBL; BC033651; AAH33651.1; -; mRNA. DR CCDS; CCDS14151.1; -. DR RefSeq; NP_057646.1; NM_016562.3. DR PDB; 7CYN; EM; 4.20 A; A/B=1-1049. DR PDBsum; 7CYN; -. DR AlphaFoldDB; Q9NYK1; -. DR EMDB; EMD-30501; -. DR SMR; Q9NYK1; -. DR BioGRID; 119436; 28. DR IntAct; Q9NYK1; 18. DR STRING; 9606.ENSP00000370034; -. DR BindingDB; Q9NYK1; -. DR ChEMBL; CHEMBL5936; -. DR DrugBank; DB16580; Afimetoran. DR DrugBank; DB05127; ANA971. DR DrugBank; DB05475; Golotimod. DR DrugBank; DB01611; Hydroxychloroquine. DR DrugBank; DB00724; Imiquimod. DR DrugBank; DB04860; Isatoribine. DR DrugBank; DB06530; Resiquimod. DR DrugBank; DB06329; RG-7795. DR DrugCentral; Q9NYK1; -. DR GuidetoPHARMACOLOGY; 1757; -. DR GlyCosmos; Q9NYK1; 14 sites, No reported glycans. DR GlyGen; Q9NYK1; 14 sites. DR iPTMnet; Q9NYK1; -. DR PhosphoSitePlus; Q9NYK1; -. DR BioMuta; TLR7; -. DR DMDM; 20140876; -. DR jPOST; Q9NYK1; -. DR MassIVE; Q9NYK1; -. DR PaxDb; 9606-ENSP00000370034; -. DR PeptideAtlas; Q9NYK1; -. DR ProteomicsDB; 83240; -. DR Antibodypedia; 8500; 1104 antibodies from 45 providers. DR DNASU; 51284; -. DR Ensembl; ENST00000380659.4; ENSP00000370034.3; ENSG00000196664.5. DR GeneID; 51284; -. DR KEGG; hsa:51284; -. DR MANE-Select; ENST00000380659.4; ENSP00000370034.3; NM_016562.4; NP_057646.1. DR UCSC; uc004cvc.4; human. DR AGR; HGNC:15631; -. DR CTD; 51284; -. DR DisGeNET; 51284; -. DR GeneCards; TLR7; -. DR HGNC; HGNC:15631; TLR7. DR HPA; ENSG00000196664; Tissue enhanced (placenta). DR MalaCards; TLR7; -. DR MIM; 300365; gene. DR MIM; 301051; phenotype. DR MIM; 301080; phenotype. DR neXtProt; NX_Q9NYK1; -. DR OpenTargets; ENSG00000196664; -. DR Orphanet; 536; Systemic lupus erythematosus. DR PharmGKB; PA38008; -. DR VEuPathDB; HostDB:ENSG00000196664; -. DR eggNOG; KOG4641; Eukaryota. DR GeneTree; ENSGT00940000159771; -. DR HOGENOM; CLU_006000_2_0_1; -. DR InParanoid; Q9NYK1; -. DR OMA; CNSKYLR; -. DR OrthoDB; 5356114at2759; -. DR PhylomeDB; Q9NYK1; -. DR TreeFam; TF325595; -. DR PathwayCommons; Q9NYK1; -. DR Reactome; R-HSA-1679131; Trafficking and processing of endosomal TLR. DR Reactome; R-HSA-168181; Toll Like Receptor 7/8 (TLR7/8) Cascade. DR Reactome; R-HSA-5686938; Regulation of TLR by endogenous ligand. DR Reactome; R-HSA-9679191; Potential therapeutics for SARS. DR Reactome; R-HSA-9692916; SARS-CoV-1 activates/modulates innate immune responses. DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses. DR Reactome; R-HSA-975110; TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling. DR Reactome; R-HSA-975138; TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation. DR Reactome; R-HSA-975155; MyD88 dependent cascade initiated on endosome. DR Reactome; R-HSA-9824856; Defective regulation of TLR7 by endogenous ligand. DR Reactome; R-HSA-9833110; RSV-host interactions. DR SignaLink; Q9NYK1; -. DR SIGNOR; Q9NYK1; -. DR BioGRID-ORCS; 51284; 11 hits in 774 CRISPR screens. DR ChiTaRS; TLR7; human. DR GeneWiki; TLR_7; -. DR GenomeRNAi; 51284; -. DR Pharos; Q9NYK1; Tclin. DR PRO; PR:Q9NYK1; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; Q9NYK1; protein. DR Bgee; ENSG00000196664; Expressed in monocyte and 117 other cell types or tissues. DR ExpressionAtlas; Q9NYK1; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0032009; C:early phagosome; ISS:UniProtKB. DR GO; GO:0036020; C:endolysosome membrane; TAS:Reactome. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0005768; C:endosome; ISS:UniProtKB. DR GO; GO:0010008; C:endosome membrane; TAS:Reactome. DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome. DR GO; GO:0005764; C:lysosome; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL. DR GO; GO:0043235; C:receptor complex; IDA:MGI. DR GO; GO:0003725; F:double-stranded RNA binding; IDA: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; ISS:UniProtKB. DR GO; GO:0007249; P:canonical NF-kappaB signal transduction; IMP:UniProtKB. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB. DR GO; GO:0098586; P:cellular response to virus; IEA:Ensembl. DR GO; GO:0051607; P:defense response to virus; IMP:UniProtKB. DR GO; GO:0007252; P:I-kappaB phosphorylation; IDA:BHF-UCL. DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW. DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB. DR GO; GO:0007254; P:JNK cascade; IEA:Ensembl. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IDA:GO_Central. DR GO; GO:0032722; P:positive regulation of chemokine production; IDA:BHF-UCL. DR GO; GO:0050729; P:positive regulation of inflammatory response; IC:BHF-UCL. DR GO; GO:0032727; P:positive regulation of interferon-alpha production; IDA:UniProtKB. DR GO; GO:0032728; P:positive regulation of interferon-beta production; IDA:UniProtKB. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IBA:GO_Central. DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:BHF-UCL. DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IEA:Ensembl. DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0032729; P:positive regulation of type II interferon production; IDA:UniProtKB. DR GO; GO:0001932; P:regulation of protein phosphorylation; IEA:Ensembl. DR GO; GO:0070305; P:response to cGMP; IMP:UniProtKB. DR GO; GO:0034154; P:toll-like receptor 7 signaling pathway; IDA:GO_Central. 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; 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; PF13855; LRR_8; 3. DR Pfam; PF01582; TIR; 1. DR PRINTS; PR00019; LEURICHRPT. DR SMART; SM00365; LRR_SD22; 9. DR SMART; SM00369; LRR_TYP; 12. DR SMART; SM00082; LRRCT; 1. DR SMART; SM00255; TIR; 1. DR SUPFAM; SSF52058; L domain-like; 3. DR SUPFAM; SSF52200; Toll/Interleukin receptor TIR domain; 1. DR PROSITE; PS51450; LRR; 18. DR PROSITE; PS50104; TIR; 1. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasmic vesicle; Disease variant; Endoplasmic reticulum; KW Endosome; Glycoprotein; Immunity; Inflammatory response; Innate immunity; KW Leucine-rich repeat; Lysosome; Membrane; Proteomics identification; KW Receptor; Reference proteome; Repeat; Signal; Systemic lupus erythematosus; KW Transmembrane; Transmembrane helix. FT SIGNAL 1..26 FT /evidence="ECO:0000255" FT CHAIN 27..1049 FT /note="Toll-like receptor 7" FT /id="PRO_0000034733" FT TOPO_DOM 27..839 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 840..860 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 861..1049 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REPEAT 43..64 FT /note="LRR 1" FT REPEAT 65..87 FT /note="LRR 2" FT REPEAT 110..126 FT /note="LRR 3" FT REPEAT 127..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..275 FT /note="LRR 9" FT REPEAT 289..312 FT /note="LRR 10" FT REPEAT 314..337 FT /note="LRR 11" FT REPEAT 339..368 FT /note="LRR 12" FT REPEAT 369..392 FT /note="LRR 13" FT REPEAT 396..419 FT /note="LRR 14" FT REPEAT 421..443 FT /note="LRR 15" FT REPEAT 492..515 FT /note="LRR 16" FT REPEAT 516..540 FT /note="LRR 17" FT REPEAT 541..564 FT /note="LRR 18" FT REPEAT 566..588 FT /note="LRR 19" FT REPEAT 595..618 FT /note="LRR 20" FT REPEAT 619..644 FT /note="LRR 21" FT REPEAT 649..672 FT /note="LRR 22" FT REPEAT 674..697 FT /note="LRR 23" FT REPEAT 698..721 FT /note="LRR 24" FT REPEAT 723..745 FT /note="LRR 25" FT REPEAT 746..769 FT /note="LRR 26" FT REPEAT 772..795 FT /note="LRR 27" FT DOMAIN 889..1033 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 202 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 361 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 413 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 488 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 523 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 534 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 590 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 679 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 720 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 799 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VARIANT 11 FT /note="Q -> L (in dbSNP:rs179008)" FT /evidence="ECO:0000269|PubMed:19924287" FT /id="VAR_034554" FT VARIANT 28 FT /note="R -> G (in SLEB17; increased NFKB1 activation after FT stimulation with guanosine and ssRNA; dbSNP:rs2147245261)" FT /evidence="ECO:0000269|PubMed:35477763" FT /id="VAR_087534" FT VARIANT 264 FT /note="Y -> H (in SLEB17; increased NFKB1 activation after FT stimulation with cGMP; dbSNP:rs2147245558)" FT /evidence="ECO:0000269|PubMed:35477763" FT /id="VAR_087535" FT VARIANT 448 FT /note="A -> V (in dbSNP:rs5743781)" FT /id="VAR_024665" FT VARIANT 507 FT /note="F -> L (in SLEB17; increased NFKB1 activation after FT stimulation with cGMP; dbSNP:rs2147245859)" FT /evidence="ECO:0000269|PubMed:35477763" FT /id="VAR_087536" FT VARIANT 795 FT /note="V -> F (in IMD74; no enhanced expression after FT stimulation by imiquimod; defective up-regulation of type I FT IFN-related genes; decreased expression of IFNG; FT dbSNP:rs200553089)" FT /evidence="ECO:0000269|PubMed:32706371" FT /id="VAR_084629" FT CONFLICT 725 FT /note="L -> H (in Ref. 2; AAF78035)" FT /evidence="ECO:0000305" FT CONFLICT 738 FT /note="L -> P (in Ref. 2; AAF78035)" FT /evidence="ECO:0000305" SQ SEQUENCE 1049 AA; 120922 MW; 8C701E9E437F2721 CRC64; MVFPMWTLKR QILILFNIIL ISKLLGARWF PKTLPCDVTL DVPKNHVIVD CTDKHLTEIP GGIPTNTTNL TLTINHIPDI SPASFHRLDH LVEIDFRCNC VPIPLGSKNN MCIKRLQIKP RSFSGLTYLK SLYLDGNQLL EIPQGLPPSL QLLSLEANNI FSIRKENLTE LANIEILYLG QNCYYRNPCY VSYSIEKDAF LNLTKLKVLS LKDNNVTAVP TVLPSTLTEL YLYNNMIAKI QEDDFNNLNQ LQILDLSGNC PRCYNAPFPC APCKNNSPLQ IPVNAFDALT ELKVLRLHSN SLQHVPPRWF KNINKLQELD LSQNFLAKEI GDAKFLHFLP SLIQLDLSFN FELQVYRASM NLSQAFSSLK SLKILRIRGY VFKELKSFNL SPLHNLQNLE VLDLGTNFIK IANLSMFKQF KRLKVIDLSV NKISPSGDSS EVGFCSNART SVESYEPQVL EQLHYFRYDK YARSCRFKNK EASFMSVNES CYKYGQTLDL SKNSIFFVKS SDFQHLSFLK CLNLSGNLIS QTLNGSEFQP LAELRYLDFS NNRLDLLHST AFEELHKLEV LDISSNSHYF QSEGITHMLN FTKNLKVLQK LMMNDNDISS STSRTMESES LRTLEFRGNH LDVLWREGDN RYLQLFKNLL KLEELDISKN SLSFLPSGVF DGMPPNLKNL SLAKNGLKSF SWKKLQCLKN LETLDLSHNQ LTTVPERLSN CSRSLKNLIL KNNQIRSLTK YFLQDAFQLR YLDLSSNKIQ MIQKTSFPEN VLNNLKMLLL HHNRFLCTCD AVWFVWWVNH TEVTIPYLAT DVTCVGPGAH KGQSVISLDL YTCELDLTNL ILFSLSISVS LFLMVMMTAS HLYFWDVWYI YHFCKAKIKG YQRLISPDCC YDAFIVYDTK DPAVTEWVLA ELVAKLEDPR EKHFNLCLEE RDWLPGQPVL ENLSQSIQLS KKTVFVMTDK YAKTENFKIA FYLSHQRLMD EKVDVIILIF LEKPFQKSKF LQLRKRLCGS SVLEWPTNPQ AHPYFWQCLK NALATDNHVA YSQVFKETV //