TLR5_HUMAN
ID TLR5_HUMAN Reviewed; 858 AA.
AC O60602; B1AZ05; B3Y633; B9VJ63; D1CS80; D3DTB8; O15456; Q32MI2; Q32MI3;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 4.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Toll-like receptor 5;
DE AltName: Full=Toll/interleukin-1 receptor-like protein 3;
DE Flags: Precursor;
GN Name=TLR5; Synonyms=TIL3;
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], AND VARIANTS LEU-616 AND LEU-822.
RC TISSUE=Leukocyte, and Prostate;
RX PubMed=9596645;
RA Chaudhary P.M., Ferguson C., Nguyen V., Nguyen O., Massa H.F., Eby M.,
RA Jasmin A., Trask B.J., Hood L., Nelson P.S.;
RT "Cloning and characterization of two Toll/Interleukin-1 receptor-like genes
RT TIL3 and TIL4: evidence for a multi-gene receptor family in humans.";
RL Blood 91:4020-4027(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-822.
RC TISSUE=Macrophage;
RA Seya T., Tsukada H.;
RT "Homo sapiens TLR5.";
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT LEU-822.
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], AND VARIANT LEU-822.
RX PubMed=19179655; DOI=10.1093/molbev/msp018;
RA Wlasiuk G., Khan S., Switzer W.M., Nachman M.W.;
RT "A history of recurrent positive selection at the toll-like receptor 5 in
RT primates.";
RL Mol. Biol. Evol. 26:937-949(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS PHE-644 AND LEU-822.
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT LEU-822.
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-822.
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 NUCLEOTIDE SEQUENCE [MRNA] OF 494-858, AND VARIANT LEU-822.
RC TISSUE=CNS;
RX PubMed=9435236; DOI=10.1073/pnas.95.2.588;
RA Rock F.L., Hardiman G., Timans J.C., Kastelein R.A., Bazan J.F.;
RT "A family of human receptors structurally related to Drosophila Toll.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:588-593(1998).
RN [10]
RP PROTEIN SEQUENCE OF 21-35.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [11]
RP TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=11489966; DOI=10.4049/jimmunol.167.4.1882;
RA Gewirtz A.T., Navas T.A., Lyons S., Godowski P.J., Madara J.L.;
RT "Cutting edge: bacterial flagellin activates basolaterally expressed TLR5
RT to induce epithelial proinflammatory gene expression.";
RL J. Immunol. 167:1882-1885(2001).
RN [12]
RP FUNCTION.
RX PubMed=11323673; DOI=10.1038/35074106;
RA Hayashi F., Smith K.D., Ozinsky A., Hawn T.R., Yi E.C., Goodlett D.R.,
RA Eng J.K., Akira S., Underhill D.M., Aderem A.;
RT "The innate immune response to bacterial flagellin is mediated by Toll-like
RT receptor 5.";
RL Nature 410:1099-1103(2001).
RN [13]
RP ASSOCIATION WITH RESISTANCE TO SLEB1, AND VARIANTS SER-592 AND LEU-616.
RX PubMed=16027372; DOI=10.1073/pnas.0501165102;
RA Hawn T.R., Wu H., Grossman J.M., Hahn B.H., Tsao B.P., Aderem A.;
RT "A stop codon polymorphism of Toll-like receptor 5 is associated with
RT resistance to systemic lupus erythematosus.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:10593-10597(2005).
RN [14]
RP PHOSPHORYLATION AT TYR-798.
RX PubMed=17157808; DOI=10.1016/j.bbrc.2006.11.132;
RA Ivison S.M., Khan M.A., Graham N.R., Bernales C.Q., Kaleem A.,
RA Tirling C.O., Cherkasov A., Steiner T.S.;
RT "A phosphorylation site in the Toll-like receptor 5 TIR domain is required
RT for inflammatory signalling in response to flagellin.";
RL Biochem. Biophys. Res. Commun. 352:936-941(2007).
RN [15]
RP PHOSPHORYLATION AT SER-805.
RX PubMed=17442957; DOI=10.4049/jimmunol.178.9.5735;
RA Ivison S.M., Graham N.R., Bernales C.Q., Kifayet A., Ng N., Shobab L.A.,
RA Steiner T.S.;
RT "Protein kinase D interaction with TLR5 is required for inflammatory
RT signaling in response to bacterial flagellin.";
RL J. Immunol. 178:5735-5743(2007).
RN [16]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=18490781; DOI=10.4049/jimmunol.180.11.7764;
RA Blohmke C.J., Victor R.E., Hirschfeld A.F., Elias I.M., Hancock D.G.,
RA Lane C.R., Davidson A.G., Wilcox P.G., Smith K.D., Overhage J.,
RA Hancock R.E., Turvey S.E.;
RT "Innate immunity mediated by TLR5 as a novel antiinflammatory target for
RT cystic fibrosis lung disease.";
RL J. Immunol. 180:7764-7773(2008).
RN [17]
RP FUNCTION, INTERACTION WITH TICAM1 AND MYD88, AND SUBCELLULAR LOCATION.
RX PubMed=20855887; DOI=10.1074/jbc.m110.158394;
RA Choi Y.J., Im E., Chung H.K., Pothoulakis C., Rhee S.H.;
RT "TRIF mediates Toll-like receptor 5-induced signaling in intestinal
RT epithelial cells.";
RL J. Biol. Chem. 285:37570-37578(2010).
RN [18]
RP POLYMORPHISM, AND INVOLVEMENT IN RESISTANCE TO MELIOIDOSIS.
RX PubMed=23447684; DOI=10.4049/jimmunol.1202974;
RA West T.E., Chantratita N., Chierakul W., Limmathurotsakul D.,
RA Wuthiekanun V., Myers N.D., Emond M.J., Wurfel M.M., Hawn T.R.,
RA Peacock S.J., Skerrett S.J.;
RT "Impaired TLR5 functionality is associated with survival in melioidosis.";
RL J. Immunol. 190:3373-3379(2013).
RN [19]
RP INTERACTION WITH UNC93B1, AND SUBCELLULAR LOCATION.
RX PubMed=24778236; DOI=10.1073/pnas.1322838111;
RA Huh J.W., Shibata T., Hwang M., Kwon E.H., Jang M.S., Fukui R., Kanno A.,
RA Jung D.J., Jang M.H., Miyake K., Kim Y.M.;
RT "UNC93B1 is essential for the plasma membrane localization and signaling of
RT Toll-like receptor 5.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:7072-7077(2014).
RN [20]
RP FUNCTION.
RX PubMed=29934223; DOI=10.1016/j.ijmm.2018.06.004;
RA Bielaszewska M., Marejkova M., Bauwens A., Kunsmann-Prokscha L.,
RA Mellmann A., Karch H.;
RT "Enterohemorrhagic Escherichia coli O157 outer membrane vesicles induce
RT interleukin 8 production in human intestinal epithelial cells by signaling
RT via Toll-like receptors TLR4 and TLR5 and activation of the nuclear factor
RT NF-kappaB.";
RL Int. J. Med. Microbiol. 308:882-889(2018).
RN [21]
RP STRUCTURE BY ELECTRON MICROSCOPY (26.0 ANGSTROMS) OF 23-858, GLYCOSYLATION
RP AT ASN-37; ASN-46; ASN-245; ASN-342; ASN-422; ASN-595 AND ASN-598,
RP DISULFIDE BONDS, LRR REPEATS, AND SUBUNIT.
RX PubMed=22173220; DOI=10.1016/j.jsb.2011.12.002;
RA Zhou K., Kanai R., Lee P., Wang H.W., Modis Y.;
RT "Toll-like receptor 5 forms asymmetric dimers in the absence of
RT flagellin.";
RL J. Struct. Biol. 177:402-409(2012).
RN [22]
RP VARIANTS 392-ARG--SER-858 DEL; SER-592 AND LEU-616.
RX PubMed=14623910; DOI=10.1084/jem.20031220;
RA Hawn T.R., Verbon A., Lettinga K.D., Zhao L.P., Li S.S., Laws R.J.,
RA Skerrett S.J., Beutler B., Schroeder L., Nachman A., Ozinsky A.,
RA Smith K.D., Aderem A.;
RT "A common dominant TLR5 stop codon polymorphism abolishes flagellin
RT signaling and is associated with susceptibility to legionnaires' disease.";
RL J. Exp. Med. 198:1563-1572(2003).
CC -!- FUNCTION: Pattern recognition receptor (PRR) located on the cell
CC surface that participates in the activation of innate immunity and
CC inflammatory response (PubMed:11323673, PubMed:18490781). Recognizes
CC small molecular motifs named pathogen-associated molecular pattern
CC (PAMPs) expressed by pathogens and microbe-associated molecular
CC patterns (MAMPs) usually expressed by resident microbiota
CC (PubMed:29934223). Upon ligand binding such as bacterial flagellins,
CC recruits intracellular adapter proteins MYD88 and TRIF leading to NF-
CC kappa-B activation, cytokine secretion and induction of the
CC inflammatory response (PubMed:20855887, PubMed:11489966). Plays thereby
CC an important role in the relationship between the intestinal epithelium
CC and enteric microbes and contributes to the gut microbiota composition
CC throughout life (By similarity). {ECO:0000250|UniProtKB:Q9JLF7,
CC ECO:0000269|PubMed:11323673, ECO:0000269|PubMed:11489966,
CC ECO:0000269|PubMed:18490781, ECO:0000269|PubMed:20855887,
CC ECO:0000269|PubMed:29934223}.
CC -!- SUBUNIT: Homodimer (PubMed:22173220). Interacts with MYD88 (via TIR
CC domain) (PubMed:20855887). Interacts with TICAM1 (via TIR domain)
CC (PubMed:20855887). Interacts with UNC93B1; this interaction is
CC essential for proper TLR5 localization to the plasma membrane
CC (PubMed:24778236). {ECO:0000269|PubMed:20855887,
CC ECO:0000269|PubMed:22173220, ECO:0000269|PubMed:24778236}.
CC -!- INTERACTION:
CC O60602; PRO_0000000092 [P05067]: APP; NbExp=3; IntAct=EBI-3505951, EBI-821758;
CC O60602; PRO_0000000093 [P05067]: APP; NbExp=3; IntAct=EBI-3505951, EBI-2431589;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:24778236};
CC Single-pass type I membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Highly expressed on the basolateral surface of
CC intestinal epithelia (PubMed:11489966). Expressed also in other cells
CC such as lung epithelial cells (PubMed:11489966, PubMed:18490781).
CC {ECO:0000269|PubMed:11489966, ECO:0000269|PubMed:18490781}.
CC -!- PTM: Phosphorylated at Ser-805 by PKD/PRKD1; phosphorylation induces
CC the production of inflammatory cytokines. {ECO:0000269|PubMed:17157808,
CC ECO:0000269|PubMed:17442957}.
CC -!- PTM: Phosphorylated at Tyr-798 upon flagellin binding; required for
CC signaling. {ECO:0000269|PubMed:17157808, ECO:0000269|PubMed:17442957}.
CC -!- POLYMORPHISM: Individuals with a common stop codon polymorphism in
CC position 392 are unable to mediate flagellin signaling. This
CC polymorphism acts in a dominant fashion and is associated with
CC susceptibility to pneumonia caused by Legionella pneumophila
CC [MIM:608556]. It also provides protection against systemic lupus
CC erythematosus.
CC -!- POLYMORPHISM: A nonsense TLR5 polymorphism, resulting in p.Arg392Ter,
CC confers resistance to melioidosis [MIM:615557], an infection caused by
CC the Gram-negative, flagellated soil saprophyte Burkholderia
CC pseudomallei. Carriers of this hypofunctional TLR5 variant may generate
CC impaired inflammatory responses during melioidosis infection that
CC result in reduced organ failure and lower mortality.
CC -!- DISEASE: Systemic lupus erythematosus 1 (SLEB1) [MIM:601744]: A
CC chronic, relapsing, inflammatory, and often febrile multisystemic
CC disorder of connective tissue, characterized principally by involvement
CC of the skin, joints, kidneys and serosal membranes. It is of unknown
CC etiology, but is thought to represent a failure of the regulatory
CC mechanisms of the autoimmune system. The disease is marked by a wide
CC range of system dysfunctions, an elevated erythrocyte sedimentation
CC rate, and the formation of LE cells in the blood or bone marrow.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the Toll-like receptor family. {ECO:0000305}.
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DR EMBL; AF051151; AAC34376.1; -; mRNA.
DR EMBL; AB060695; BAB43955.1; -; mRNA.
DR EMBL; AB445645; BAG55042.1; -; mRNA.
DR EMBL; FJ556976; ACM69019.1; -; Genomic_DNA.
DR EMBL; FJ556977; ACM69020.1; -; Genomic_DNA.
DR EMBL; FJ556979; ACM69022.1; -; Genomic_DNA.
DR EMBL; FJ556980; ACM69023.1; -; Genomic_DNA.
DR EMBL; FJ556987; ACM69030.1; -; Genomic_DNA.
DR EMBL; FJ556989; ACM69032.1; -; Genomic_DNA.
DR EMBL; DQ026408; AAZ17463.1; -; Genomic_DNA.
DR EMBL; DQ026409; AAZ17464.1; -; Genomic_DNA.
DR EMBL; DQ026415; AAZ17469.1; -; Genomic_DNA.
DR EMBL; AL929091; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471100; EAW93262.1; -; Genomic_DNA.
DR EMBL; CH471100; EAW93263.1; -; Genomic_DNA.
DR EMBL; BC109118; AAI09119.1; -; mRNA.
DR EMBL; BC109119; AAI09120.1; -; mRNA.
DR EMBL; U88881; AAC34136.1; -; mRNA.
DR CCDS; CCDS31033.1; -.
DR RefSeq; NP_003259.2; NM_003268.5.
DR RefSeq; XP_005273298.2; XM_005273241.4.
DR RefSeq; XP_005273299.2; XM_005273242.4.
DR RefSeq; XP_005273300.2; XM_005273243.4.
DR RefSeq; XP_006711567.1; XM_006711504.3.
DR RefSeq; XP_006711568.1; XM_006711505.3.
DR RefSeq; XP_006711569.1; XM_006711506.3.
DR RefSeq; XP_011508239.1; XM_011509937.2.
DR RefSeq; XP_016857697.1; XM_017002208.1.
DR PDB; 3J0A; EM; 26.00 A; A/B=23-858.
DR PDBsum; 3J0A; -.
DR AlphaFoldDB; O60602; -.
DR SMR; O60602; -.
DR BioGRID; 112955; 25.
DR IntAct; O60602; 21.
DR MINT; O60602; -.
DR STRING; 9606.ENSP00000440643; -.
DR BindingDB; O60602; -.
DR ChEMBL; CHEMBL2176839; -.
DR GlyGen; O60602; 7 sites.
DR iPTMnet; O60602; -.
DR PhosphoSitePlus; O60602; -.
DR BioMuta; TLR5; -.
DR jPOST; O60602; -.
DR MassIVE; O60602; -.
DR PaxDb; O60602; -.
DR PeptideAtlas; O60602; -.
DR PRIDE; O60602; -.
DR ProteomicsDB; 49480; -.
DR Antibodypedia; 2711; 957 antibodies from 44 providers.
DR DNASU; 7100; -.
DR Ensembl; ENST00000540964.5; ENSP00000440643.1; ENSG00000187554.14.
DR GeneID; 7100; -.
DR KEGG; hsa:7100; -.
DR UCSC; uc001hnw.3; human.
DR CTD; 7100; -.
DR DisGeNET; 7100; -.
DR GeneCards; TLR5; -.
DR HGNC; HGNC:11851; TLR5.
DR HPA; ENSG00000187554; Tissue enhanced (ovary).
DR MalaCards; TLR5; -.
DR MIM; 109100; phenotype.
DR MIM; 601744; phenotype.
DR MIM; 603031; gene.
DR MIM; 608556; phenotype.
DR MIM; 615557; phenotype.
DR neXtProt; NX_O60602; -.
DR PharmGKB; PA36553; -.
DR VEuPathDB; HostDB:ENSG00000187554; -.
DR eggNOG; KOG4641; Eukaryota.
DR HOGENOM; CLU_006000_4_1_1; -.
DR InParanoid; O60602; -.
DR OrthoDB; 282372at2759; -.
DR PhylomeDB; O60602; -.
DR TreeFam; TF351113; -.
DR PathwayCommons; O60602; -.
DR Reactome; R-HSA-168176; Toll Like Receptor 5 (TLR5) Cascade.
DR Reactome; R-HSA-5602680; MyD88 deficiency (TLR5).
DR Reactome; R-HSA-5603037; IRAK4 deficiency (TLR5).
DR Reactome; R-HSA-975871; MyD88 cascade initiated on plasma membrane.
DR SignaLink; O60602; -.
DR SIGNOR; O60602; -.
DR BioGRID-ORCS; 7100; 9 hits in 1011 CRISPR screens.
DR GeneWiki; TLR_5; -.
DR GenomeRNAi; 7100; -.
DR Pharos; O60602; Tbio.
DR PRO; PR:O60602; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; O60602; protein.
DR Bgee; ENSG00000187554; Expressed in monocyte and 168 other tissues.
DR ExpressionAtlas; O60602; baseline and differential.
DR Genevisible; O60602; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005149; F:interleukin-1 receptor binding; IPI:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:InterPro.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; IEA:InterPro.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; IEA:InterPro.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:BHF-UCL.
DR GO; GO:0034123; P:positive regulation of toll-like receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0034146; P:toll-like receptor 5 signaling pathway; IEA:InterPro.
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; -; 3.
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; IPR027176; TLR5.
DR InterPro; IPR017241; Toll-like_receptor.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR PANTHER; PTHR24365; PTHR24365; 1.
DR PANTHER; PTHR24365:SF525; PTHR24365:SF525; 1.
DR Pfam; PF13855; LRR_8; 5.
DR Pfam; PF01582; TIR; 1.
DR PIRSF; PIRSF037595; Toll-like_receptor; 1.
DR SMART; SM00369; LRR_TYP; 9.
DR SMART; SM00082; LRRCT; 1.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF52200; SSF52200; 1.
DR PROSITE; PS51450; LRR; 12.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Immunity; Inflammatory response; Innate immunity;
KW Leucine-rich repeat; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Signal; Systemic lupus erythematosus;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 21..858
FT /note="Toll-like receptor 5"
FT /id="PRO_0000034729"
FT TOPO_DOM 21..639
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 640..660
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 661..858
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 45..68
FT /note="LRR 1"
FT /evidence="ECO:0000269|PubMed:22173220"
FT REPEAT 71..93
FT /note="LRR 2"
FT /evidence="ECO:0000269|PubMed:22173220"
FT REPEAT 95..117
FT /note="LRR 3"
FT /evidence="ECO:0000269|PubMed:22173220"
FT REPEAT 120..143
FT /note="LRR 4"
FT /evidence="ECO:0000269|PubMed:22173220"
FT REPEAT 146..166
FT /note="LRR 5"
FT /evidence="ECO:0000269|PubMed:22173220"
FT REPEAT 171..192
FT /note="LRR 6"
FT /evidence="ECO:0000269|PubMed:22173220"
FT REPEAT 197..211
FT /note="LRR 7"
FT /evidence="ECO:0000269|PubMed:22173220"
FT REPEAT 214..229
FT /note="LRR 8"
FT /evidence="ECO:0000269|PubMed:22173220"
FT REPEAT 234..235
FT /note="LRR 9"
FT /evidence="ECO:0000269|PubMed:22173220"
FT REPEAT 260..284
FT /note="LRR 11"
FT /evidence="ECO:0000269|PubMed:22173220"
FT REPEAT 289..301
FT /note="LRR 12"
FT /evidence="ECO:0000269|PubMed:22173220"
FT REPEAT 313..334
FT /note="LRR 13"
FT /evidence="ECO:0000269|PubMed:22173220"
FT REPEAT 337..355
FT /note="LRR 14"
FT /evidence="ECO:0000269|PubMed:22173220"
FT REPEAT 385..401
FT /note="LRR 16"
FT /evidence="ECO:0000269|PubMed:22173220"
FT REPEAT 412..431
FT /note="LRR 17"
FT /evidence="ECO:0000269|PubMed:22173220"
FT REPEAT 449..470
FT /note="LRR 18"
FT /evidence="ECO:0000269|PubMed:22173220"
FT REPEAT 474..495
FT /note="LRR 19"
FT /evidence="ECO:0000269|PubMed:22173220"
FT REPEAT 503..524
FT /note="LRR 20"
FT /evidence="ECO:0000269|PubMed:22173220"
FT REPEAT 527..546
FT /note="LRR 21"
FT /evidence="ECO:0000269|PubMed:22173220"
FT REPEAT 549..567
FT /note="LRR 22"
FT /evidence="ECO:0000269|PubMed:22173220"
FT DOMAIN 579..631
FT /note="LRRCT"
FT DOMAIN 691..836
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT MOD_RES 798
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:17157808"
FT MOD_RES 805
FT /note="Phosphoserine; by PKD/PRKD1"
FT /evidence="ECO:0000269|PubMed:17442957"
FT CARBOHYD 37
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22173220"
FT CARBOHYD 46
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22173220"
FT CARBOHYD 245
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22173220"
FT CARBOHYD 342
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22173220"
FT CARBOHYD 422
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22173220"
FT CARBOHYD 595
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22173220"
FT CARBOHYD 598
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22173220"
FT DISULFID 583..610
FT /evidence="ECO:0000269|PubMed:22173220"
FT DISULFID 585..629
FT /evidence="ECO:0000269|PubMed:22173220"
FT VARIANT 82
FT /note="T -> I (in dbSNP:rs764535)"
FT /id="VAR_032455"
FT VARIANT 112
FT /note="P -> A (in dbSNP:rs5744166)"
FT /id="VAR_032456"
FT VARIANT 143
FT /note="N -> T (in dbSNP:rs5744167)"
FT /id="VAR_061856"
FT VARIANT 181
FT /note="Q -> K (in dbSNP:rs45528236)"
FT /id="VAR_061857"
FT VARIANT 392..858
FT /note="Missing (in 10% of the population; abolishes
FT flagellin signaling; associated with resistance to SLEB1)"
FT /evidence="ECO:0000269|PubMed:14623910"
FT /id="VAR_018398"
FT VARIANT 592
FT /note="N -> S (in dbSNP:rs2072493)"
FT /evidence="ECO:0000269|PubMed:14623910,
FT ECO:0000269|PubMed:16027372"
FT /id="VAR_018399"
FT VARIANT 616
FT /note="F -> L (in dbSNP:rs5744174)"
FT /evidence="ECO:0000269|PubMed:14623910,
FT ECO:0000269|PubMed:16027372, ECO:0000269|PubMed:9596645"
FT /id="VAR_018400"
FT VARIANT 644
FT /note="I -> F (in dbSNP:rs5744175)"
FT /evidence="ECO:0000269|PubMed:19924287"
FT /id="VAR_070457"
FT VARIANT 769
FT /note="L -> F (in dbSNP:rs56243703)"
FT /id="VAR_061858"
FT VARIANT 822
FT /note="F -> L (in dbSNP:rs7512943)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:18810425, ECO:0000269|PubMed:19179655,
FT ECO:0000269|PubMed:19924287, ECO:0000269|PubMed:9435236,
FT ECO:0000269|PubMed:9596645, ECO:0000269|Ref.2,
FT ECO:0000269|Ref.7"
FT /id="VAR_047454"
FT CONFLICT 231
FT /note="L -> V (in Ref. 1; AAC34376)"
FT /evidence="ECO:0000305"
FT CONFLICT 352
FT /note="Y -> C (in Ref. 1; AAC34376)"
FT /evidence="ECO:0000305"
FT CONFLICT 387
FT /note="Q -> R (in Ref. 8; AAI09120)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 858 AA; 97834 MW; 9EE0AB6EEFEA9051 CRC64;
MGDHLDLLLG VVLMAGPVFG IPSCSFDGRI AFYRFCNLTQ VPQVLNTTER LLLSFNYIRT
VTASSFPFLE QLQLLELGSQ YTPLTIDKEA FRNLPNLRIL DLGSSKIYFL HPDAFQGLFH
LFELRLYFCG LSDAVLKDGY FRNLKALTRL DLSKNQIRSL YLHPSFGKLN SLKSIDFSSN
QIFLVCEHEL EPLQGKTLSF FSLAANSLYS RVSVDWGKCM NPFRNMVLEI LDVSGNGWTV
DITGNFSNAI SKSQAFSLIL AHHIMGAGFG FHNIKDPDQN TFAGLARSSV RHLDLSHGFV
FSLNSRVFET LKDLKVLNLA YNKINKIADE AFYGLDNLQV LNLSYNLLGE LYSSNFYGLP
KVAYIDLQKN HIAIIQDQTF KFLEKLQTLD LRDNALTTIH FIPSIPDIFL SGNKLVTLPK
INLTANLIHL SENRLENLDI LYFLLRVPHL QILILNQNRF SSCSGDQTPS ENPSLEQLFL
GENMLQLAWE TELCWDVFEG LSHLQVLYLN HNYLNSLPPG VFSHLTALRG LSLNSNRLTV
LSHNDLPANL EILDISRNQL LAPNPDVFVS LSVLDITHNK FICECELSTF INWLNHTNVT
IAGPPADIYC VYPDSFSGVS LFSLSTEGCD EEEVLKSLKF SLFIVCTVTL TLFLMTILTV
TKFRGFCFIC YKTAQRLVFK DHPQGTEPDM YKYDAYLCFS SKDFTWVQNA LLKHLDTQYS
DQNRFNLCFE ERDFVPGENR IANIQDAIWN SRKIVCLVSR HFLRDGWCLE AFSYAQGRCL
SDLNSALIMV VVGSLSQYQL MKHQSIRGFV QKQQYLRWPE DFQDVGWFLH KLSQQILKKE
KEKKKDNNIP LQTVATIS
