Toll-like receptor 8

Details

Name
Toll-like receptor 8
Synonyms
Not Available
Gene Name
TLR8
UniProtKB Entry
Q9NR97Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0006790|Toll-like receptor 8
MENMFLQSSMLTCIFLLISGSCELCAEENFSRSYPCDEKKQNDSVIAECSNRRLQEVPQT
VGKYVTELDLSDNFITHITNESFQGLQNLTKINLNHNPNVQHQNGNPGIQSNGLNITDGA
FLNLKNLRELLLEDNQLPQIPSGLPESLTELSLIQNNIYNITKEGISRLINLKNLYLAWN
CYFNKVCEKTNIEDGVFETLTNLELLSLSFNSLSHVPPKLPSSLRKLFLSNTQIKYISEE
DFKGLINLTLLDLSGNCPRCFNAPFPCVPCDGGASINIDRFAFQNLTQLRYLNLSSTSLR
KINAAWFKNMPHLKVLDLEFNYLVGEIASGAFLTMLPRLEILDLSFNYIKGSYPQHINIS
RNFSKLLSLRALHLRGYVFQELREDDFQPLMQLPNLSTINLGINFIKQIDFKLFQNFSNL
EIIYLSENRISPLVKDTRQSYANSSSFQRHIRKRRSTDFEFDPHSNFYHFTRPLIKPQCA
AYGKALDLSLNSIFFIGPNQFENLPDIACLNLSANSNAQVLSGTEFSAIPHVKYLDLTNN
RLDFDNASALTELSDLEVLDLSYNSHYFRIAGVTHHLEFIQNFTNLKVLNLSHNNIYTLT
DKYNLESKSLVELVFSGNRLDILWNDDDNRYISIFKGLKNLTRLDLSLNRLKHIPNEAFL
NLPASLTELHINDNMLKFFNWTLLQQFPRLELLDLRGNKLLFLTDSLSDFTSSLRTLLLS
HNRISHLPSGFLSEVSSLKHLDLSSNLLKTINKSALETKTTTKLSMLELHGNPFECTCDI
GDFRRWMDEHLNVKIPRLVDVICASPGDQRGKSIVSLELTTCVSDVTAVILFFFTFFITT
MVMLAALAHHLFYWDVWFIYNVCLAKVKGYRSLSTSQTFYDAYISYDTKDASVTDWVINE
LRYHLEESRDKNVLLCLEERDWDPGLAIIDNLMQSINQSKKTVFVLTKKYAKSWNFKTAF
YLALQRLMDENMDVIIFILLEPVLQHSQYLRLRQRICKSSILQWPDNPKAEGLFWQTLRN
VVLTENDSRYNNMYVDSIKQY
Number of residues
1041
Molecular Weight
119826.82
Theoretical pI
6.63
GO Classification
Functions
identical protein binding / pattern recognition receptor activity / signaling receptor activity
Processes
canonical NF-kappaB signal transduction / negative regulation of interleukin-12 production / positive regulation of canonical NF-kappaB signal transduction / positive regulation of interferon-alpha production / positive regulation of interferon-beta production / positive regulation of interleukin-1 beta production / positive regulation of interleukin-6 production / positive regulation of interleukin-8 production / positive regulation of type II interferon production
Components
external side of plasma membrane / plasma membrane
General Function
Endosomal receptor that plays a key role in innate and adaptive immunity (PubMed:25297876, PubMed:32433612). Controls host immune response against pathogens through recognition of RNA degradation products specific to microorganisms that are initially processed by RNASET2 (PubMed:31778653). Recognizes GU-rich single-stranded RNA (GU-rich RNA) derived from SARS-CoV-2, SARS-CoV-1 and HIV-1 viruses (PubMed:33718825). Upon binding to agonists, undergoes dimerization that brings TIR domains from the two molecules into direct contact, leading to the recruitment of TIR-containing downstream adapter MYD88 through homotypic interaction (PubMed:23520111, PubMed:25599397, PubMed:26929371, PubMed:33718825). In turn, the Myddosome signaling complex is formed involving IRAK4, IRAK1, TRAF6, TRAF3 leading to activation of downstream transcription factors NF-kappa-B and IRF7 to induce pro-inflammatory cytokines and interferons, respectively (PubMed:16737960, PubMed:17932028, PubMed:29155428)
Specific Function
Dna binding
Pfam Domain Function
Signal Regions
1-26
Transmembrane Regions
828-848
Cellular Location
Endosome membrane
Gene sequence
>lcl|BSEQ0017129|Toll-like receptor 8 (TLR8)
ATGAAGGAGTCATCTTTGCAAAATAGCTCCTGCAGCCTGGGAAAGGAGACTAAAAAGGAA
AACATGTTCCTTCAGTCGTCAATGCTGACCTGCATTTTCCTGCTAATATCTGGTTCCTGT
GAGTTATGCGCCGAAGAAAATTTTTCTAGAAGCTATCCTTGTGATGAGAAAAAGCAAAAT
GACTCAGTTATTGCAGAGTGCAGCAATCGTCGACTACAGGAAGTTCCCCAAACGGTGGGC
AAATATGTGACAGAACTAGACCTGTCTGATAATTTCATCACACACATAACGAATGAATCA
TTTCAAGGGCTGCAAAATCTCACTAAAATAAATCTAAACCACAACCCCAATGTACAGCAC
CAGAACGGAAATCCCGGTATACAATCAAATGGCTTGAATATCACAGACGGGGCATTCCTC
AACCTAAAAAACCTAAGGGAGTTACTGCTTGAAGACAACCAGTTACCCCAAATACCCTCT
GGTTTGCCAGAGTCTTTGACAGAACTTAGTCTAATTCAAAACAATATATACAACATAACT
AAAGAGGGCATTTCAAGACTTATAAACTTGAAAAATCTCTATTTGGCCTGGAACTGCTAT
TTTAACAAAGTTTGCGAGAAAACTAACATAGAAGATGGAGTATTTGAAACGCTGACAAAT
TTGGAGTTGCTATCACTATCTTTCAATTCTCTTTCACACGTGCCACCCAAACTGCCAAGC
TCCCTACGCAAACTTTTTCTGAGCAACACCCAGATCAAATACATTAGTGAAGAAGATTTC
AAGGGATTGATAAATTTAACATTACTAGATTTAAGCGGGAACTGTCCGAGGTGCTTCAAT
GCCCCATTTCCATGCGTGCCTTGTGATGGTGGTGCTTCAATTAATATAGATCGTTTTGCT
TTTCAAAACTTGACCCAACTTCGATACCTAAACCTCTCTAGCACTTCCCTCAGGAAGATT
AATGCTGCCTGGTTTAAAAATATGCCTCATCTGAAGGTGCTGGATCTTGAATTCAACTAT
TTAGTGGGAGAAATAGCCTCTGGGGCATTTTTAACGATGCTGCCCCGCTTAGAAATACTT
GACTTGTCTTTTAACTATATAAAGGGGAGTTATCCACAGCATATTAATATTTCCAGAAAC
TTCTCTAAACTTTTGTCTCTACGGGCATTGCATTTAAGAGGTTATGTGTTCCAGGAACTC
AGAGAAGATGATTTCCAGCCCCTGATGCAGCTTCCAAACTTATCGACTATCAACTTGGGT
ATTAATTTTATTAAGCAAATCGATTTCAAACTTTTCCAAAATTTCTCCAATCTGGAAATT
ATTTACTTGTCAGAAAACAGAATATCACCGTTGGTAAAAGATACCCGGCAGAGTTATGCA
AATAGTTCCTCTTTTCAACGTCATATCCGGAAACGACGCTCAACAGATTTTGAGTTTGAC
CCACATTCGAACTTTTATCATTTCACCCGTCCTTTAATAAAGCCACAATGTGCTGCTTAT
GGAAAAGCCTTAGATTTAAGCCTCAACAGTATTTTCTTCATTGGGCCAAACCAATTTGAA
AATCTTCCTGACATTGCCTGTTTAAATCTGTCTGCAAATAGCAATGCTCAAGTGTTAAGT
GGAACTGAATTTTCAGCCATTCCTCATGTCAAATATTTGGATTTGACAAACAATAGACTA
GACTTTGATAATGCTAGTGCTCTTACTGAATTGTCCGACTTGGAAGTTCTAGATCTCAGC
TATAATTCACACTATTTCAGAATAGCAGGCGTAACACATCATCTAGAATTTATTCAAAAT
TTCACAAATCTAAAAGTTTTAAACTTGAGCCACAACAACATTTATACTTTAACAGATAAG
TATAACCTGGAAAGCAAGTCCCTGGTAGAATTAGTTTTCAGTGGCAATCGCCTTGACATT
TTGTGGAATGATGATGACAACAGGTATATCTCCATTTTCAAAGGTCTCAAGAATCTGACA
CGTCTGGATTTATCCCTTAATAGGCTGAAGCACATCCCAAATGAAGCATTCCTTAATTTG
CCAGCGAGTCTCACTGAACTACATATAAATGATAATATGTTAAAGTTTTTTAACTGGACA
TTACTCCAGCAGTTTCCTCGTCTCGAGTTGCTTGACTTACGTGGAAACAAACTACTCTTT
TTAACTGATAGCCTATCTGACTTTACATCTTCCCTTCGGACACTGCTGCTGAGTCATAAC
AGGATTTCCCACCTACCCTCTGGCTTTCTTTCTGAAGTCAGTAGTCTGAAGCACCTCGAT
TTAAGTTCCAATCTGCTAAAAACAATCAACAAATCCGCACTTGAAACTAAGACCACCACC
AAATTATCTATGTTGGAACTACACGGAAACCCCTTTGAATGCACCTGTGACATTGGAGAT
TTCCGAAGATGGATGGATGAACATCTGAATGTCAAAATTCCCAGACTGGTAGATGTCATT
TGTGCCAGTCCTGGGGATCAAAGAGGGAAGAGTATTGTGAGTCTGGAGCTAACAACTTGT
GTTTCAGATGTCACTGCAGTGATATTATTTTTCTTCACGTTCTTTATCACCACCATGGTT
ATGTTGGCTGCCCTGGCTCACCATTTGTTTTACTGGGATGTTTGGTTTATATATAATGTG
TGTTTAGCTAAGGTAAAAGGCTACAGGTCTCTTTCCACATCCCAAACTTTCTATGATGCT
TACATTTCTTATGACACCAAAGATGCCTCTGTTACTGACTGGGTGATAAATGAGCTGCGC
TACCACCTTGAAGAGAGCCGAGACAAAAACGTTCTCCTTTGTCTAGAGGAGAGGGATTGG
GACCCGGGATTGGCCATCATCGACAACCTCATGCAGAGCATCAACCAAAGCAAGAAAACA
GTATTTGTTTTAACCAAAAAATATGCAAAAAGCTGGAACTTTAAAACAGCTTTTTACTTG
GCTTTGCAGAGGCTAATGGATGAGAACATGGATGTGATTATATTTATCCTGCTGGAGCCA
GTGTTACAGCATTCTCAGTATTTGAGGCTACGGCAGCGGATCTGTAAGAGCTCCATCCTC
CAGTGGCCTGACAACCCGAAGGCAGAAGGCTTGTTTTGGCAAACTCTGAGAAATGTGGTC
TTGACTGAAAATGATTCACGGTATAACAATATGTATGTCGATTCCATTAAGCAATACTAA
Chromosome Location
X
Locus
Xp22.2
External Identifiers
ResourceLink
UniProtKB IDQ9NR97
UniProtKB Entry NameTLR8_HUMAN
GenBank Gene IDBC101077
GeneCard IDTLR8
GenAtlas IDTLR8
HGNC IDHGNC:15632
PDB ID(s)3W3G, 3W3J, 3W3K, 3W3L, 3W3M, 3W3N, 3WN4, 4QBZ, 4QC0, 4R07, 4R08, 4R09, 4R0A, 4R6A, 5AWA, 5AWB, 5AWC, 5AWD, 5AZ5, 5HDH, 5WYX, 5WYZ, 5Z14, 5Z15, 6KYA, 6TY5, 6V9U, 6WML, 6ZJZ, 7CRF, 7R52, 7R53, 7R54, 7RC9, 7YTX, 8PFI
KEGG IDhsa:51311
IUPHAR/Guide To Pharmacology ID1758
NCBI Gene ID51311
General References
  1. Du X, Poltorak A, Wei Y, Beutler B: Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Eur Cytokine Netw. 2000 Sep;11(3):362-71. [Article]
  2. Chuang TH, Ulevitch RJ: Cloning and characterization of a sub-family of human toll-like receptors: hTLR7, hTLR8 and hTLR9. Eur Cytokine Netw. 2000 Sep;11(3):372-8. [Article]
  3. Nakajima T, Ohtani H, Satta Y, Uno Y, Akari H, Ishida T, Kimura A: Natural selection in the TLR-related genes in the course of primate evolution. Immunogenetics. 2008 Dec;60(12):727-35. doi: 10.1007/s00251-008-0332-0. Epub 2008 Sep 23. [Article]
  4. Georgel P, Macquin C, Bahram S: The heterogeneous allelic repertoire of human toll-like receptor (TLR) genes. PLoS One. 2009 Nov 17;4(11):e7803. doi: 10.1371/journal.pone.0007803. [Article]
  5. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70. Epub 2003 Sep 15. [Article]
  6. Ross MT, Grafham DV, Coffey AJ, Scherer S, McLay K, Muzny D, Platzer M, Howell GR, Burrows C, Bird CP, Frankish A, Lovell FL, Howe KL, Ashurst JL, Fulton RS, Sudbrak R, Wen G, Jones MC, Hurles ME, Andrews TD, Scott CE, Searle S, Ramser J, Whittaker A, Deadman R, Carter NP, Hunt SE, Chen R, Cree A, Gunaratne P, Havlak P, Hodgson A, Metzker ML, Richards S, Scott G, Steffen D, Sodergren E, Wheeler DA, Worley KC, Ainscough R, Ambrose KD, Ansari-Lari MA, Aradhya S, Ashwell RI, Babbage AK, Bagguley CL, Ballabio A, Banerjee R, Barker GE, Barlow KF, Barrett IP, Bates KN, Beare DM, Beasley H, Beasley O, Beck A, Bethel G, Blechschmidt K, Brady N, Bray-Allen S, Bridgeman AM, Brown AJ, Brown MJ, Bonnin D, Bruford EA, Buhay C, Burch P, Burford D, Burgess J, Burrill W, Burton J, Bye JM, Carder C, Carrel L, Chako J, Chapman JC, Chavez D, Chen E, Chen G, Chen Y, Chen Z, Chinault C, Ciccodicola A, Clark SY, Clarke G, Clee CM, Clegg S, Clerc-Blankenburg K, Clifford K, Cobley V, Cole CG, Conquer JS, Corby N, Connor RE, David R, Davies J, Davis C, Davis J, Delgado O, Deshazo D, Dhami P, Ding Y, Dinh H, Dodsworth S, Draper H, Dugan-Rocha S, Dunham A, Dunn M, Durbin KJ, Dutta I, Eades T, Ellwood M, Emery-Cohen A, Errington H, Evans KL, Faulkner L, Francis F, Frankland J, Fraser AE, Galgoczy P, Gilbert J, Gill R, Glockner G, Gregory SG, Gribble S, Griffiths C, Grocock R, Gu Y, Gwilliam R, Hamilton C, Hart EA, Hawes A, Heath PD, Heitmann K, Hennig S, Hernandez J, Hinzmann B, Ho S, Hoffs M, Howden PJ, Huckle EJ, Hume J, Hunt PJ, Hunt AR, Isherwood J, Jacob L, Johnson D, Jones S, de Jong PJ, Joseph SS, Keenan S, Kelly S, Kershaw JK, Khan Z, Kioschis P, Klages S, Knights AJ, Kosiura A, Kovar-Smith C, Laird GK, Langford C, Lawlor S, Leversha M, Lewis L, Liu W, Lloyd C, Lloyd DM, Loulseged H, Loveland JE, Lovell JD, Lozado R, Lu J, Lyne R, Ma J, Maheshwari M, Matthews LH, McDowall J, McLaren S, McMurray A, Meidl P, Meitinger T, Milne S, Miner G, Mistry SL, Morgan M, Morris S, Muller I, Mullikin JC, Nguyen N, Nordsiek G, Nyakatura G, O'Dell CN, Okwuonu G, Palmer S, Pandian R, Parker D, Parrish J, Pasternak S, Patel D, Pearce AV, Pearson DM, Pelan SE, Perez L, Porter KM, Ramsey Y, Reichwald K, Rhodes S, Ridler KA, Schlessinger D, Schueler MG, Sehra HK, Shaw-Smith C, Shen H, Sheridan EM, Shownkeen R, Skuce CD, Smith ML, Sotheran EC, Steingruber HE, Steward CA, Storey R, Swann RM, Swarbreck D, Tabor PE, Taudien S, Taylor T, Teague B, Thomas K, Thorpe A, Timms K, Tracey A, Trevanion S, Tromans AC, d'Urso M, Verduzco D, Villasana D, Waldron L, Wall M, Wang Q, Warren J, Warry GL, Wei X, West A, Whitehead SL, Whiteley MN, Wilkinson JE, Willey DL, Williams G, Williams L, Williamson A, Williamson H, Wilming L, Woodmansey RL, Wray PW, Yen J, Zhang J, Zhou J, Zoghbi H, Zorilla S, Buck D, Reinhardt R, Poustka A, Rosenthal A, Lehrach H, Meindl A, Minx PJ, Hillier LW, Willard HF, Wilson RK, Waterston RH, Rice CM, Vaudin M, Coulson A, Nelson DL, Weinstock G, Sulston JE, Durbin R, Hubbard T, Gibbs RA, Beck S, Rogers J, Bentley DR: The DNA sequence of the human X chromosome. Nature. 2005 Mar 17;434(7031):325-37. [Article]
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  8. Doyle SL, Jefferies CA, Feighery C, O'Neill LA: Signaling by Toll-like receptors 8 and 9 requires Bruton's tyrosine kinase. J Biol Chem. 2007 Dec 21;282(51):36953-60. Epub 2007 Oct 11. [Article]
  9. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. [Article]
  10. Tanji H, Ohto U, Shibata T, Miyake K, Shimizu T: Structural reorganization of the Toll-like receptor 8 dimer induced by agonistic ligands. Science. 2013 Mar 22;339(6126):1426-9. doi: 10.1126/science.1229159. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Toll-like receptor 8 (Humans)protein
primary
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
ResiquimodinvestigationalyestargetmodulatorDetails
Imiquimodapproved, investigationalunknowntargetagonistDetails
AfimetoraninvestigationalyestargetantagonistDetails
SelgantolimodinvestigationalyestargetagonistDetails
MotolimodinvestigationalyestargetmodulatorDetails