ID   TLR8_HUMAN              Reviewed;        1041 AA.
AC   Q9NR97; B3Y654; D1CS70; D1CS76; Q495P4; Q6UXL6; Q9NYG9;
DT   31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   02-OCT-2024, entry version 203.
DE   RecName: Full=Toll-like receptor 8 {ECO:0000305};
DE   AltName: CD_antigen=CD288;
DE   Flags: Precursor;
GN   Name=TLR8 {ECO:0000312|HGNC:HGNC:15632}; ORFNames=UNQ249/PRO286;
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] (ISOFORM 2).
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] (ISOFORM 1).
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 [MRNA] (ISOFORM 1).
RX   PubMed=18810425; DOI=10.1007/s00251-008-0332-0;
RA   Nakajima T., Ohtani H., Satta Y., Uno Y., Akari H., Ishida T., Kimura A.;
RT   "Natural selection in the TLR-related genes in the course of primate
RT   evolution.";
RL   Immunogenetics 60:727-735(2008).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15772651; DOI=10.1038/nature03440;
RA   Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA   Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA   Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA   Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA   Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA   Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA   Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA   Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA   Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA   Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA   Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA   Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA   Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA   Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA   Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA   Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA   Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA   Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA   Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA   Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA   Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA   Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA   Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA   Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA   Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA   Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA   Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA   Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA   Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA   Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA   McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA   Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA   Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA   Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA   Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA   Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA   Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA   Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA   Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA   Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA   d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA   Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA   Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA   Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA   Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA   Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA   Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA   Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA   Rogers J., Bentley D.R.;
RT   "The DNA sequence of the human X chromosome.";
RL   Nature 434:325-337(2005).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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   [9]
RP   FUNCTION IN NF-KAPPA-B ACTIVATION.
RX   PubMed=16737960; DOI=10.1074/jbc.m512908200;
RA   Qin J., Yao J., Cui G., Xiao H., Kim T.W., Fraczek J., Wightman P.,
RA   Sato S., Akira S., Puel A., Casanova J.L., Su B., Li X.;
RT   "TLR8-mediated NF-kappaB and JNK activation are TAK1-independent and MEKK3-
RT   dependent.";
RL   J. Biol. Chem. 281:21013-21021(2006).
RN   [10]
RP   FUNCTION, AND INTERACTION WITH BTK.
RX   PubMed=17932028; DOI=10.1074/jbc.m707682200;
RA   Doyle S.L., Jefferies C.A., Feighery C., O'Neill L.A.;
RT   "Signaling by Toll-like receptors 8 and 9 requires Bruton's tyrosine
RT   kinase.";
RL   J. Biol. Chem. 282:36953-36960(2007).
RN   [11]
RP   GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-80 AND ASN-88.
RC   TISSUE=Liver;
RX   PubMed=19159218; DOI=10.1021/pr8008012;
RA   Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT   "Glycoproteomics analysis of human liver tissue by combination of multiple
RT   enzyme digestion and hydrazide chemistry.";
RL   J. Proteome Res. 8:651-661(2009).
RN   [12]
RP   FUNCTION, SUBCELLULAR LOCATION, AND CLEAVAGE.
RX   PubMed=25297876; DOI=10.4049/jimmunol.1401375;
RA   Ishii N., Funami K., Tatematsu M., Seya T., Matsumoto M.;
RT   "Endosomal localization of TLR8 confers distinctive proteolytic processing
RT   on human myeloid cells.";
RL   J. Immunol. 193:5118-5128(2014).
RN   [13]
RP   UBIQUITINATION BY RNF216.
RX   PubMed=31385713; DOI=10.1165/rcmb.2018-0373oc;
RA   Evankovich J., Lear T., Baldwin C., Chen Y., White V., Villandre J.,
RA   Londino J., Liu Y., McVerry B., Kitsios G.D., Mallampalli R.K., Chen B.B.;
RT   "Toll-Like Receptor 8 Stability is Regulated by Ring Finger 216 in response
RT   to circulating MicroRNAs.";
RL   Am. J. Respir. Cell Mol. Biol. 62:157-167(2020).
RN   [14]
RP   FUNCTION.
RX   PubMed=31778653; DOI=10.1016/j.cell.2019.11.001;
RA   Greulich W., Wagner M., Gaidt M.M., Stafford C., Cheng Y., Linder A.,
RA   Carell T., Hornung V.;
RT   "TLR8 Is a Sensor of RNase T2 Degradation Products.";
RL   Cell 179:1264-1275.E13(2019).
RN   [15]
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   [16]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=33718825; DOI=10.1016/j.isci.2021.102295;
RA   Campbell G.R., To R.K., Hanna J., Spector S.A.;
RT   "SARS-CoV-2, SARS-CoV-1, and HIV-1 derived ssRNA sequences activate the
RT   NLRP3 inflammasome in human macrophages through a non-classical pathway.";
RL   IScience 1:102295-102295(2021).
RN   [17]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 27-827 IN COMPLEXES WITH
RP   RESIQUIMOD AND OTHER SYNTHETIC AGONISTS, FUNCTION, SUBUNIT, LEUCINE-RICH
RP   REPEATS, MUTAGENESIS OF TYR-348; VAL-378; PHE-405; VAL-520; ASP-543 AND
RP   THR-574, GLYCOSYLATION AT ASN-293; ASN-395; ASN-511; ASN-546; ASN-590;
RP   ASN-640 AND ASN-680, AND DISULFIDE BONDS.
RX   PubMed=23520111; DOI=10.1126/science.1229159;
RA   Tanji H., Ohto U., Shibata T., Miyake K., Shimizu T.;
RT   "Structural reorganization of the Toll-like receptor 8 dimer induced by
RT   agonistic ligands.";
RL   Science 339:1426-1429(2013).
RN   [18]
RP   X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 27-827 IN COMPLEX WITH URIDINE,
RP   FUNCTION, SUBUNIT, ACTIVITY REGULATION, AND MUTAGENESIS OF TYR-348;
RP   PHE-405; ASP-543 AND THR-574.
RX   PubMed=25599397; DOI=10.1038/nsmb.2943;
RA   Tanji H., Ohto U., Shibata T., Taoka M., Yamauchi Y., Isobe T., Miyake K.,
RA   Shimizu T.;
RT   "Toll-like receptor 8 senses degradation products of single-stranded RNA.";
RL   Nat. Struct. Mol. Biol. 22:109-115(2015).
RN   [19]
RP   X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 27-827, SUBUNIT, MUTAGENESIS OF
RP   452-ARG--ARG-455, CLEAVAGE, AND ACTIVITY REGULATION.
RX   PubMed=26929371; DOI=10.1073/pnas.1516000113;
RA   Tanji H., Ohto U., Motoi Y., Shibata T., Miyake K., Shimizu T.;
RT   "Autoinhibition and relief mechanism by the proteolytic processing of Toll-
RT   like receptor 8.";
RL   Proc. Natl. Acad. Sci. U.S.A. 113:3012-3017(2016).
RN   [20]
RP   X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 27-827, SUBUNIT, AND FUNCTION.
RX   PubMed=29155428; DOI=10.1038/nchembio.2518;
RA   Zhang S., Hu Z., Tanji H., Jiang S., Das N., Li J., Sakaniwa K., Jin J.,
RA   Bian Y., Ohto U., Shimizu T., Yin H.;
RT   "Small-molecule inhibition of TLR8 through stabilization of its resting
RT   state.";
RL   Nat. Chem. Biol. 14:58-64(2018).
RN   [21]
RP   VARIANTS IMD98 LEU-432; LEU-494 AND ASP-572, CHARACTERIZATION OF VARIANTS
RP   IMD98 LEU-432; LEU-494 AND ASP-572, INVOLVEMENT IN IMD98, AND MUTAGENESIS
RP   OF ASP-543.
RX   PubMed=33512449; DOI=10.1182/blood.2020009620;
RA   Aluri J., Bach A., Kaviany S., Chiquetto Paracatu L., Kitcharoensakkul M.,
RA   Walkiewicz M.A., Putnam C.D., Shinawi M., Saucier N., Rizzi E.M.,
RA   Harmon M.T., Keppel M.P., Ritter M., Similuk M., Kulm E., Joyce M.,
RA   de Jesus A.A., Goldbach-Mansky R., Lee Y.S., Cella M., Kendall P.L.,
RA   Dinauer M.C., Bednarski J.J., Bemrich-Stolz C., Canna S.W., Abraham S.M.,
RA   Demczko M.M., Powell J., Jones S.M., Scurlock A.M., De Ravin S.S.,
RA   Bleesing J.J., Connelly J.A., Rao V.K., Schuettpelz L.G., Cooper M.A.;
RT   "Immunodeficiency and bone marrow failure with mosaic and germline TLR8
RT   gain of function.";
RL   Blood 137:2450-2462(2021).
RN   [22]
RP   VARIANT IMD98 VAL-572, AND CHARACTERIZATION OF VARIANT IMD98 VAL-572.
RX   PubMed=34981838; DOI=10.1002/ajh.26452;
RA   Fejtkova M., Sukova M., Hlozkova K., Skvarova Kramarzova K., Rackova M.,
RA   Jakubec D., Bakardjieva M., Bloomfield M., Klocperk A., Parackova Z.,
RA   Sediva A., Aluri J., Novakova M., Kalina T., Fronkova E., Hrusak O.,
RA   Malcova H., Sedlacek P., Liba Z., Kudr M., Stary J., Cooper M.A.,
RA   Svaton M., Kanderova V.;
RT   "TLR8/TLR7 dysregulation due to a novel TLR8 mutation causes severe
RT   autoimmune hemolytic anemia and autoinflammation in identical twins.";
RL   Am. J. Hematol. 97:338-351(2022).
CC   -!- FUNCTION: Endosomal receptor that plays a key role in innate and
CC       adaptive immunity (PubMed:25297876, PubMed:32433612). Controls host
CC       immune response against pathogens through recognition of RNA
CC       degradation products specific to microorganisms that are initially
CC       processed by RNASET2 (PubMed:31778653). Recognizes GU-rich single-
CC       stranded RNA (GU-rich RNA) derived from SARS-CoV-2, SARS-CoV-1 and HIV-
CC       1 viruses (PubMed:33718825). 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:23520111,
CC       PubMed:25599397, PubMed:26929371, PubMed:33718825). In turn, the
CC       Myddosome signaling complex is formed involving IRAK4, IRAK1, TRAF6,
CC       TRAF3 leading to activation of downstream transcription factors NF-
CC       kappa-B and IRF7 to induce pro-inflammatory cytokines and interferons,
CC       respectively (PubMed:16737960, PubMed:17932028, PubMed:29155428).
CC       {ECO:0000269|PubMed:16737960, ECO:0000269|PubMed:17932028,
CC       ECO:0000269|PubMed:23520111, ECO:0000269|PubMed:25297876,
CC       ECO:0000269|PubMed:25599397, ECO:0000269|PubMed:26929371,
CC       ECO:0000269|PubMed:29155428, ECO:0000269|PubMed:31778653,
CC       ECO:0000269|PubMed:32433612, ECO:0000269|PubMed:33718825}.
CC   -!- ACTIVITY REGULATION: Activated by RNAs having enough uridines.
CC       {ECO:0000269|PubMed:25599397, ECO:0000269|PubMed:26929371}.
CC   -!- SUBUNIT: Homodimer (PubMed:23520111, PubMed:25599397, PubMed:26929371,
CC       PubMed:29155428). Interacts with MYD88 via their respective TIR domains
CC       (Probable). Interacts with UNC93B1 (By similarity). Interacts with BTK
CC       (PubMed:17932028). Interacts with SMPDL3B (By similarity).
CC       {ECO:0000250|UniProtKB:P58682, ECO:0000269|PubMed:17932028,
CC       ECO:0000269|PubMed:23520111, ECO:0000269|PubMed:25599397,
CC       ECO:0000269|PubMed:26929371, ECO:0000269|PubMed:29155428, ECO:0000305}.
CC   -!- INTERACTION:
CC       Q9NR97; Q9H1C4: UNC93B1; NbExp=4; IntAct=EBI-16356363, EBI-4401271;
CC       Q9NR97-1; Q9NR97-1: TLR8; NbExp=4; IntAct=EBI-16041685, EBI-16041685;
CC   -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000269|PubMed:25297876};
CC       Single-pass type I membrane protein {ECO:0000250}. Note=Endosomal
CC       localization confers distinctive proteolytic processing.
CC       {ECO:0000269|PubMed:25297876}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9NR97-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9NR97-2; Sequence=VSP_053412;
CC   -!- TISSUE SPECIFICITY: Expressed in myeloid dendritic cells, monocytes,
CC       and monocyte-derived dendritic cells. {ECO:0000269|PubMed:33718825}.
CC   -!- PTM: Ubiquitinated by RNF216; leading to degradation by the proteasome.
CC       {ECO:0000269|PubMed:31385713}.
CC   -!- PTM: Proteolytic processing occurs in monocytes and monocyte-derived
CC       macrophages by both furin-like proprotein convertase and cathepsins
CC       (PubMed:25297876). The cleavage is necessary for dimer formation and
CC       subsequent activation (PubMed:26929371). {ECO:0000269|PubMed:25297876,
CC       ECO:0000269|PubMed:26929371}.
CC   -!- DISEASE: Immunodeficiency 98 with autoinflammation, X-linked (IMD98)
CC       [MIM:301078]: An X-linked disorder characterized by onset of recurrent
CC       infections associated with lymphoproliferation and autoinflammation in
CC       the first decade of life. Mostly males are affected; carrier females
CC       may have mild symptoms. Features include mouth ulcers, fever, poor
CC       early growth, hepatosplenomegaly, lymphadenopathy, polyarthritis, and
CC       non-infectious enteritis. {ECO:0000269|PubMed:33512449,
CC       ECO:0000269|PubMed:34981838}. 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}.
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DR   EMBL; AF246971; AAF64061.1; -; mRNA.
DR   EMBL; AF245703; AAF78036.1; -; mRNA.
DR   EMBL; AB445666; BAG55063.1; -; mRNA.
DR   EMBL; DQ023132; AAZ95433.1; -; Genomic_DNA.
DR   EMBL; DQ023133; AAZ95434.1; -; Genomic_DNA.
DR   EMBL; DQ023134; AAZ95435.1; -; Genomic_DNA.
DR   EMBL; DQ023135; AAZ95436.1; -; Genomic_DNA.
DR   EMBL; DQ023136; AAZ95437.1; -; Genomic_DNA.
DR   EMBL; DQ023137; AAZ95438.1; -; Genomic_DNA.
DR   EMBL; DQ023138; AAZ95439.1; -; Genomic_DNA.
DR   EMBL; DQ023139; AAZ95440.1; -; Genomic_DNA.
DR   EMBL; DQ023140; AAZ95441.1; -; Genomic_DNA.
DR   EMBL; CH471074; EAW98808.1; -; Genomic_DNA.
DR   EMBL; AY358296; AAQ88663.1; -; mRNA.
DR   EMBL; AC005859; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC139705; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471074; EAW98809.1; -; Genomic_DNA.
DR   EMBL; BC101076; AAI01077.1; -; mRNA.
DR   EMBL; BC101077; AAI01078.1; -; mRNA.
DR   CCDS; CCDS14152.1; -. [Q9NR97-1]
DR   CCDS; CCDS14153.1; -. [Q9NR97-2]
DR   RefSeq; NP_057694.2; NM_016610.3. [Q9NR97-2]
DR   RefSeq; NP_619542.1; NM_138636.5. [Q9NR97-1]
DR   RefSeq; XP_011543831.1; XM_011545529.1.
DR   RefSeq; XP_011543832.1; XM_011545530.2.
DR   PDB; 3W3G; X-ray; 2.30 A; A/B=27-827.
DR   PDB; 3W3J; X-ray; 2.00 A; A/B=27-827.
DR   PDB; 3W3K; X-ray; 2.30 A; A/B=27-827.
DR   PDB; 3W3L; X-ray; 2.33 A; A/B/C/D=27-827.
DR   PDB; 3W3M; X-ray; 2.70 A; A=27-827.
DR   PDB; 3W3N; X-ray; 2.10 A; A/B=27-827.
DR   PDB; 3WN4; X-ray; 1.81 A; A=27-827.
DR   PDB; 4QBZ; X-ray; 2.00 A; A/B=27-827.
DR   PDB; 4QC0; X-ray; 2.10 A; A/B=27-827.
DR   PDB; 4R07; X-ray; 2.00 A; A/B/C/D=27-827.
DR   PDB; 4R08; X-ray; 2.40 A; A/B/C/D=27-827.
DR   PDB; 4R09; X-ray; 2.62 A; A/B/C/D=27-827.
DR   PDB; 4R0A; X-ray; 1.90 A; A=27-827.
DR   PDB; 4R6A; X-ray; 2.10 A; A/B=27-827.
DR   PDB; 5AWA; X-ray; 2.20 A; A=27-827.
DR   PDB; 5AWB; X-ray; 2.10 A; A=27-827.
DR   PDB; 5AWC; X-ray; 2.50 A; A/B/C/D=27-827.
DR   PDB; 5AWD; X-ray; 2.05 A; A=27-827.
DR   PDB; 5AZ5; X-ray; 2.40 A; A/B/C/D=27-827.
DR   PDB; 5HDH; X-ray; 2.60 A; A=27-827.
DR   PDB; 5WYX; X-ray; 2.40 A; A/B=27-827.
DR   PDB; 5WYZ; X-ray; 2.30 A; A/B=27-827.
DR   PDB; 5Z14; X-ray; 2.80 A; A/B=27-827.
DR   PDB; 5Z15; X-ray; 2.90 A; A/B=27-827.
DR   PDB; 6KYA; X-ray; 2.89 A; A/B=27-827.
DR   PDB; 6TY5; X-ray; 2.79 A; A/B=27-827.
DR   PDB; 6V9U; X-ray; 2.65 A; A/B=27-827.
DR   PDB; 6WML; X-ray; 2.50 A; A/B/C/D=27-827.
DR   PDB; 6ZJZ; X-ray; 2.49 A; A/B=27-827.
DR   PDB; 7CRF; X-ray; 2.89 A; A/B=27-827.
DR   PDB; 7R52; X-ray; 2.94 A; A/B=27-827.
DR   PDB; 7R53; X-ray; 3.12 A; A/B=27-827.
DR   PDB; 7R54; X-ray; 2.84 A; A/B=27-827.
DR   PDB; 7RC9; X-ray; 2.76 A; A/B=27-827.
DR   PDB; 7YTX; X-ray; 2.90 A; A/B=27-827.
DR   PDB; 8PFI; X-ray; 2.79 A; A/B=27-827.
DR   PDBsum; 3W3G; -.
DR   PDBsum; 3W3J; -.
DR   PDBsum; 3W3K; -.
DR   PDBsum; 3W3L; -.
DR   PDBsum; 3W3M; -.
DR   PDBsum; 3W3N; -.
DR   PDBsum; 3WN4; -.
DR   PDBsum; 4QBZ; -.
DR   PDBsum; 4QC0; -.
DR   PDBsum; 4R07; -.
DR   PDBsum; 4R08; -.
DR   PDBsum; 4R09; -.
DR   PDBsum; 4R0A; -.
DR   PDBsum; 4R6A; -.
DR   PDBsum; 5AWA; -.
DR   PDBsum; 5AWB; -.
DR   PDBsum; 5AWC; -.
DR   PDBsum; 5AWD; -.
DR   PDBsum; 5AZ5; -.
DR   PDBsum; 5HDH; -.
DR   PDBsum; 5WYX; -.
DR   PDBsum; 5WYZ; -.
DR   PDBsum; 5Z14; -.
DR   PDBsum; 5Z15; -.
DR   PDBsum; 6KYA; -.
DR   PDBsum; 6TY5; -.
DR   PDBsum; 6V9U; -.
DR   PDBsum; 6WML; -.
DR   PDBsum; 6ZJZ; -.
DR   PDBsum; 7CRF; -.
DR   PDBsum; 7R52; -.
DR   PDBsum; 7R53; -.
DR   PDBsum; 7R54; -.
DR   PDBsum; 7RC9; -.
DR   PDBsum; 7YTX; -.
DR   PDBsum; 8PFI; -.
DR   AlphaFoldDB; Q9NR97; -.
DR   SMR; Q9NR97; -.
DR   BioGRID; 119462; 6.
DR   DIP; DIP-61413N; -.
DR   IntAct; Q9NR97; 9.
DR   STRING; 9606.ENSP00000312082; -.
DR   BindingDB; Q9NR97; -.
DR   ChEMBL; CHEMBL5805; -.
DR   DrugBank; DB16580; Afimetoran.
DR   DrugBank; DB00724; Imiquimod.
DR   DrugBank; DB06530; Resiquimod.
DR   DrugBank; DB16324; Selgantolimod.
DR   GuidetoPHARMACOLOGY; 1758; -.
DR   GlyCosmos; Q9NR97; 21 sites, No reported glycans.
DR   GlyGen; Q9NR97; 24 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9NR97; -.
DR   PhosphoSitePlus; Q9NR97; -.
DR   BioMuta; TLR8; -.
DR   DMDM; 20140873; -.
DR   CPTAC; CPTAC-2235; -.
DR   jPOST; Q9NR97; -.
DR   MassIVE; Q9NR97; -.
DR   PaxDb; 9606-ENSP00000312082; -.
DR   PeptideAtlas; Q9NR97; -.
DR   ProteomicsDB; 12724; -.
DR   ProteomicsDB; 82313; -. [Q9NR97-1]
DR   Antibodypedia; 458; 913 antibodies from 42 providers.
DR   DNASU; 51311; -.
DR   Ensembl; ENST00000218032.7; ENSP00000218032.7; ENSG00000101916.12. [Q9NR97-1]
DR   Ensembl; ENST00000311912.5; ENSP00000312082.5; ENSG00000101916.12. [Q9NR97-2]
DR   GeneID; 51311; -.
DR   KEGG; hsa:51311; -.
DR   MANE-Select; ENST00000218032.7; ENSP00000218032.7; NM_138636.5; NP_619542.1.
DR   UCSC; uc004cvd.4; human. [Q9NR97-1]
DR   AGR; HGNC:15632; -.
DR   CTD; 51311; -.
DR   DisGeNET; 51311; -.
DR   GeneCards; TLR8; -.
DR   HGNC; HGNC:15632; TLR8.
DR   HPA; ENSG00000101916; Tissue enhanced (lung, lymphoid tissue).
DR   MalaCards; TLR8; -.
DR   MIM; 300366; gene.
DR   MIM; 301078; phenotype.
DR   neXtProt; NX_Q9NR97; -.
DR   OpenTargets; ENSG00000101916; -.
DR   PharmGKB; PA38009; -.
DR   VEuPathDB; HostDB:ENSG00000101916; -.
DR   eggNOG; KOG4641; Eukaryota.
DR   GeneTree; ENSGT00940000160879; -.
DR   HOGENOM; CLU_006000_2_0_1; -.
DR   InParanoid; Q9NR97; -.
DR   OMA; LSWNCYF; -.
DR   OrthoDB; 5356114at2759; -.
DR   PhylomeDB; Q9NR97; -.
DR   TreeFam; TF351113; -.
DR   PathwayCommons; Q9NR97; -.
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-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR   SignaLink; Q9NR97; -.
DR   SIGNOR; Q9NR97; -.
DR   BioGRID-ORCS; 51311; 14 hits in 775 CRISPR screens.
DR   ChiTaRS; TLR8; human.
DR   EvolutionaryTrace; Q9NR97; -.
DR   GeneWiki; TLR8; -.
DR   GenomeRNAi; 51311; -.
DR   Pharos; Q9NR97; Tchem.
DR   PRO; PR:Q9NR97; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   RNAct; Q9NR97; protein.
DR   Bgee; ENSG00000101916; Expressed in monocyte and 124 other cell types or tissues.
DR   GO; GO:0036020; C:endolysosome membrane; TAS:Reactome.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR   GO; GO:0009897; C:external side of plasma membrane; IDA:CAFA.
DR   GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR   GO; GO:0003725; F:double-stranded RNA binding; IDA:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0038187; F:pattern recognition receptor activity; IBA:GO_Central.
DR   GO; GO:0003723; F:RNA binding; TAS:UniProtKB.
DR   GO; GO:0038023; F:signaling receptor activity; NAS:UniProtKB.
DR   GO; GO:0003727; F:single-stranded RNA binding; IDA:UniProtKB.
DR   GO; GO:0007249; P:canonical NF-kappaB signal transduction; IBA:GO_Central.
DR   GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
DR   GO; GO:0051607; P:defense response to virus; IDA:UniProtKB.
DR   GO; GO:0016064; P:immunoglobulin mediated immune response; TAS:UniProtKB.
DR   GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR   GO; GO:0045087; P:innate immune response; NAS:UniProtKB.
DR   GO; GO:0032695; P:negative regulation of interleukin-12 production; IDA:CAFA.
DR   GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IDA:UniProtKB.
DR   GO; GO:0045089; P:positive regulation of innate immune response; IDA:UniProtKB.
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:0032731; P:positive regulation of interleukin-1 beta production; IDA:UniProtKB.
DR   GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:CAFA.
DR   GO; GO:0032757; P:positive regulation of interleukin-8 production; IMP:UniProtKB.
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:0009615; P:response to virus; IDA:UniProtKB.
DR   GO; GO:0034158; P:toll-like receptor 8 signaling pathway; IDA: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; IPR032675; LRR_dom_sf.
DR   InterPro; IPR000157; TIR_dom.
DR   InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR   PANTHER; PTHR47410; TOLL-LIKE RECEPTOR 7-RELATED; 1.
DR   PANTHER; PTHR47410:SF1; TOLL-LIKE RECEPTOR 8; 1.
DR   Pfam; PF13855; LRR_8; 5.
DR   Pfam; PF01582; TIR; 1.
DR   SMART; SM00365; LRR_SD22; 9.
DR   SMART; SM00369; LRR_TYP; 15.
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; 20.
DR   PROSITE; PS50104; TIR; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Disease variant; Disulfide bond;
KW   Endosome; Glycoprotein; Immunity; Inflammatory response; Innate immunity;
KW   Leucine-rich repeat; Membrane; Proteomics identification; Receptor;
KW   Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix;
KW   Ubl conjugation.
FT   SIGNAL          1..26
FT                   /evidence="ECO:0000255"
FT   CHAIN           27..1041
FT                   /note="Toll-like receptor 8"
FT                   /id="PRO_0000034735"
FT   TOPO_DOM        27..827
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        828..848
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        849..1041
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REPEAT          126..147
FT                   /note="LRR 1"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          148..168
FT                   /note="LRR 2"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          171..193
FT                   /note="LRR 3"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          202..223
FT                   /note="LRR 4"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          224..244
FT                   /note="LRR 5"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          247..268
FT                   /note="LRR 6"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          288..309
FT                   /note="LRR 7"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          312..334
FT                   /note="LRR 8"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          338..360
FT                   /note="LRR 9"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          368..389
FT                   /note="LRR 10"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          395..416
FT                   /note="LRR 11"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          419..440
FT                   /note="LRR 12"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          482..503
FT                   /note="LRR 13"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          506..527
FT                   /note="LRR 14"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          531..551
FT                   /note="LRR 15"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          555..577
FT                   /note="LRR 16"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          585..606
FT                   /note="LRR 17"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          609..630
FT                   /note="LRR 18"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          640..661
FT                   /note="LRR 19"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          665..685
FT                   /note="LRR 20"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          689..710
FT                   /note="LRR 21"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          713..734
FT                   /note="LRR 22"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   REPEAT          737..758
FT                   /note="LRR 23"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   DOMAIN          772..824
FT                   /note="LRRCT"
FT   DOMAIN          878..1022
FT                   /note="TIR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT   CARBOHYD        29
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        42
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        80
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218"
FT   CARBOHYD        88
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:19159218"
FT   CARBOHYD        115
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        160
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        247
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        285
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        293
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   CARBOHYD        358
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        362
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        395
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   CARBOHYD        416
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        443
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        511
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   CARBOHYD        546
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   CARBOHYD        582
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        590
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   CARBOHYD        640
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   CARBOHYD        680
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   CARBOHYD        752
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        36..49
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   DISULFID        181..187
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   DISULFID        257..270
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   DISULFID        260..267
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   DISULFID        479..509
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   DISULFID        776..803
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   VAR_SEQ         1
FT                   /note="M -> MKESSLQNSSCSLGKETKK (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:11022119"
FT                   /id="VSP_053412"
FT   VARIANT         10
FT                   /note="M -> V (in dbSNP:rs5744077)"
FT                   /id="VAR_024667"
FT   VARIANT         432
FT                   /note="P -> L (in IMD98; gain-of-function variant resulting
FT                   in increased NF-kappa-B activation measured in a reporter
FT                   assay; dbSNP:rs2147258995)"
FT                   /evidence="ECO:0000269|PubMed:33512449"
FT                   /id="VAR_087088"
FT   VARIANT         494
FT                   /note="F -> L (in IMD98; gain-of-function variant resulting
FT                   in increased NF-kappa-B activation measured in a reporter
FT                   assay; dbSNP:rs2147259120)"
FT                   /evidence="ECO:0000269|PubMed:33512449"
FT                   /id="VAR_087089"
FT   VARIANT         572
FT                   /note="G -> D (in IMD98; gain-of-function variant resulting
FT                   in increased NF-kappa-B activation measured in a reporter
FT                   assay; dbSNP:rs1385657144)"
FT                   /evidence="ECO:0000269|PubMed:33512449"
FT                   /id="VAR_087090"
FT   VARIANT         572
FT                   /note="G -> V (in IMD98; increased NF-kappa-B activation
FT                   measured in a reporter assay; results in increased TLR8
FT                   protein degradation; dbSNP:rs1385657144)"
FT                   /evidence="ECO:0000269|PubMed:34981838"
FT                   /id="VAR_087091"
FT   VARIANT         715
FT                   /note="R -> Q (in dbSNP:rs5744082)"
FT                   /id="VAR_052363"
FT   MUTAGEN         348
FT                   /note="Y->A: Abolishes activation of NF-kappa-B."
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   MUTAGEN         348
FT                   /note="Y->A: Abolishes responses to both ssRNA and chemical
FT                   ligands."
FT                   /evidence="ECO:0000269|PubMed:25599397"
FT   MUTAGEN         378
FT                   /note="V->A: Increases activation of NF-kappa-B."
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   MUTAGEN         405
FT                   /note="F->A: Abolishes activation of NF-kappa-B."
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   MUTAGEN         405
FT                   /note="F->A: Abolishes responses to both ssRNA and chemical
FT                   ligands."
FT                   /evidence="ECO:0000269|PubMed:25599397"
FT   MUTAGEN         452..455
FT                   /note="RKRR->NQSN: Monomeric and inactive."
FT                   /evidence="ECO:0000269|PubMed:26929371"
FT   MUTAGEN         520
FT                   /note="V->A: Strongly decreases activation of NF-kappa-B."
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   MUTAGEN         543
FT                   /note="D->A: Abolishes activation of NF-kappa-B."
FT                   /evidence="ECO:0000269|PubMed:23520111,
FT                   ECO:0000269|PubMed:33512449"
FT   MUTAGEN         543
FT                   /note="D->A: Abolishes responses to both ssRNA and chemical
FT                   ligands."
FT                   /evidence="ECO:0000269|PubMed:25599397"
FT   MUTAGEN         574
FT                   /note="T->A: Abolishes responses to both ssRNA and chemical
FT                   ligands."
FT                   /evidence="ECO:0000269|PubMed:25599397"
FT   MUTAGEN         574
FT                   /note="T->A: Strongly decreases activation of NF-kappa-B."
FT                   /evidence="ECO:0000269|PubMed:23520111"
FT   CONFLICT        217
FT                   /note="P -> S (in Ref. 1; AAF64061)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        328
FT                   /note="A -> V (in Ref. 5; AAQ88663)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        366
FT                   /note="L -> P (in Ref. 1; AAF64061)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        410
FT                   /note="D -> N (in Ref. 4; AAZ95439)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        867
FT                   /note="V -> I (in Ref. 1; AAF64061)"
FT                   /evidence="ECO:0000305"
FT   STRAND          37..39
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          42..44
FT                   /evidence="ECO:0007829|PDB:4R0A"
FT   STRAND          46..48
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          66..69
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   TURN            80..85
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          91..93
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          96..98
FT                   /evidence="ECO:0007829|PDB:3W3J"
FT   TURN            118..123
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          129..131
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          149..152
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   HELIX           163..166
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          174..176
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          179..181
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          183..185
FT                   /evidence="ECO:0007829|PDB:5WYX"
FT   TURN            194..199
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          205..207
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          225..228
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          230..232
FT                   /evidence="ECO:0007829|PDB:7YTX"
FT   TURN            241..244
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          250..252
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          260..262
FT                   /evidence="ECO:0007829|PDB:6ZJZ"
FT   HELIX           271..273
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   TURN            280..285
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          291..293
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   HELIX           304..307
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          315..317
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          320..322
FT                   /evidence="ECO:0007829|PDB:3W3K"
FT   HELIX           324..329
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   HELIX           331..335
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          341..343
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   HELIX           361..365
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          371..373
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          380..382
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   HELIX           384..390
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          398..400
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          407..409
FT                   /evidence="ECO:0007829|PDB:6ZJZ"
FT   HELIX           411..416
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          417..419
FT                   /evidence="ECO:0007829|PDB:3W3N"
FT   STRAND          421..424
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          459..461
FT                   /evidence="ECO:0007829|PDB:4R07"
FT   STRAND          463..465
FT                   /evidence="ECO:0007829|PDB:6V9U"
FT   STRAND          467..469
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   HELIX           477..480
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          485..487
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          490..492
FT                   /evidence="ECO:0007829|PDB:6ZJZ"
FT   TURN            498..503
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          508..511
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   TURN            525..528
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          533..536
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   TURN            547..552
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          558..560
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   HELIX           565..568
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   TURN            571..573
FT                   /evidence="ECO:0007829|PDB:3W3G"
FT   HELIX           578..582
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          588..590
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          599..601
FT                   /evidence="ECO:0007829|PDB:5WYZ"
FT   STRAND          607..609
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          612..614
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   HELIX           620..623
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          626..629
FT                   /evidence="ECO:0007829|PDB:5HDH"
FT   TURN            630..637
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          638..640
FT                   /evidence="ECO:0007829|PDB:3W3M"
FT   STRAND          643..645
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   HELIX           656..660
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          667..670
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   HELIX           681..686
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          692..694
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   HELIX           707..709
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          716..718
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   TURN            729..733
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          734..737
FT                   /evidence="ECO:0007829|PDB:5AZ5"
FT   STRAND          740..742
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   HELIX           753..756
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          758..760
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          765..768
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   HELIX           778..780
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   HELIX           781..789
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   TURN            790..792
FT                   /evidence="ECO:0007829|PDB:4R0A"
FT   HELIX           798..800
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   STRAND          801..806
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   TURN            807..811
FT                   /evidence="ECO:0007829|PDB:3WN4"
FT   HELIX           814..816
FT                   /evidence="ECO:0007829|PDB:4QBZ"
FT   HELIX           819..821
FT                   /evidence="ECO:0007829|PDB:6ZJZ"
SQ   SEQUENCE   1041 AA;  119828 MW;  39A38B60629291C8 CRC64;
     MENMFLQSSM LTCIFLLISG SCELCAEENF SRSYPCDEKK QNDSVIAECS NRRLQEVPQT
     VGKYVTELDL SDNFITHITN ESFQGLQNLT KINLNHNPNV QHQNGNPGIQ SNGLNITDGA
     FLNLKNLREL LLEDNQLPQI PSGLPESLTE LSLIQNNIYN ITKEGISRLI NLKNLYLAWN
     CYFNKVCEKT NIEDGVFETL TNLELLSLSF NSLSHVPPKL PSSLRKLFLS NTQIKYISEE
     DFKGLINLTL LDLSGNCPRC FNAPFPCVPC DGGASINIDR FAFQNLTQLR YLNLSSTSLR
     KINAAWFKNM PHLKVLDLEF NYLVGEIASG AFLTMLPRLE ILDLSFNYIK GSYPQHINIS
     RNFSKLLSLR ALHLRGYVFQ ELREDDFQPL MQLPNLSTIN LGINFIKQID FKLFQNFSNL
     EIIYLSENRI SPLVKDTRQS YANSSSFQRH IRKRRSTDFE FDPHSNFYHF TRPLIKPQCA
     AYGKALDLSL NSIFFIGPNQ FENLPDIACL NLSANSNAQV LSGTEFSAIP HVKYLDLTNN
     RLDFDNASAL TELSDLEVLD LSYNSHYFRI AGVTHHLEFI QNFTNLKVLN LSHNNIYTLT
     DKYNLESKSL VELVFSGNRL DILWNDDDNR YISIFKGLKN LTRLDLSLNR LKHIPNEAFL
     NLPASLTELH INDNMLKFFN WTLLQQFPRL ELLDLRGNKL LFLTDSLSDF TSSLRTLLLS
     HNRISHLPSG FLSEVSSLKH LDLSSNLLKT INKSALETKT TTKLSMLELH GNPFECTCDI
     GDFRRWMDEH LNVKIPRLVD VICASPGDQR GKSIVSLELT TCVSDVTAVI LFFFTFFITT
     MVMLAALAHH LFYWDVWFIY NVCLAKVKGY RSLSTSQTFY DAYISYDTKD ASVTDWVINE
     LRYHLEESRD KNVLLCLEER DWDPGLAIID NLMQSINQSK KTVFVLTKKY AKSWNFKTAF
     YLALQRLMDE NMDVIIFILL EPVLQHSQYL RLRQRICKSS ILQWPDNPKA EGLFWQTLRN
     VVLTENDSRY NNMYVDSIKQ Y
//