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Protein

Toll-like receptor 8

Gene

TLR8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.2 Publications

GO - Molecular functioni

  • DNA binding Source: UniProtKB
  • double-stranded RNA binding Source: UniProtKB
  • drug binding Source: Ensembl
  • identical protein binding Source: IntAct
  • RNA binding Source: UniProtKB
  • signaling receptor activity Source: UniProtKB
  • single-stranded RNA binding Source: UniProtKB
  • transmembrane signaling receptor activity Source: InterPro

GO - Biological processi

  • cellular response to mechanical stimulus Source: UniProtKB
  • defense response to virus Source: UniProtKB
  • I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • immunoglobulin mediated immune response Source: UniProtKB
  • inflammatory response Source: GO_Central
  • innate immune response Source: UniProtKB
  • microglial cell activation Source: Ensembl
  • MyD88-dependent toll-like receptor signaling pathway Source: InterPro
  • negative regulation of interleukin-12 secretion Source: CAFA
  • positive regulation of innate immune response Source: UniProtKB
  • positive regulation of interferon-alpha biosynthetic process Source: UniProtKB
  • positive regulation of interferon-beta biosynthetic process Source: UniProtKB
  • positive regulation of interferon-gamma biosynthetic process Source: UniProtKB
  • positive regulation of interleukin-1 beta secretion Source: CAFA
  • positive regulation of interleukin-6 secretion Source: CAFA
  • positive regulation of interleukin-8 biosynthetic process Source: UniProtKB
  • regulation of protein phosphorylation Source: Ensembl
  • response to virus Source: UniProtKB
  • toll-like receptor 8 signaling pathway Source: CAFA
  • toll-like receptor 9 signaling pathway Source: Reactome
  • toll-like receptor signaling pathway Source: Reactome

Keywordsi

Molecular functionReceptor
Biological processImmunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-1679131 Trafficking and processing of endosomal TLR
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-975110 TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-975155 MyD88 dependent cascade initiated on endosome

Names & Taxonomyi

Protein namesi
Recommended name:
Toll-like receptor 8
Alternative name(s):
CD_antigen: CD288
Gene namesi
Name:TLR8
ORF Names:UNQ249/PRO286
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000101916.11
HGNCiHGNC:15632 TLR8
MIMi300366 gene
neXtProtiNX_Q9NR97

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini27 – 827ExtracellularSequence analysisAdd BLAST801
Transmembranei828 – 848HelicalSequence analysisAdd BLAST21
Topological domaini849 – 1041CytoplasmicSequence analysisAdd BLAST193

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi348Y → A: Abolishes activation of NF-kappa-B. 1 Publication1
Mutagenesisi378V → A: Increases activation of NF-kappa-B. 1 Publication1
Mutagenesisi405F → A: Abolishes activation of NF-kappa-B. 1 Publication1
Mutagenesisi520V → A: Strongly decreases activation of NF-kappa-B. 1 Publication1
Mutagenesisi543D → A: Abolishes activation of NF-kappa-B. 1 Publication1
Mutagenesisi574T → A: Strongly decreases activation of NF-kappa-B. 1 Publication1

Organism-specific databases

DisGeNETi51311
OpenTargetsiENSG00000101916
PharmGKBiPA38009

Chemistry databases

ChEMBLiCHEMBL5805
DrugBankiDB00724 Imiquimod
GuidetoPHARMACOLOGYi1758

Polymorphism and mutation databases

BioMutaiTLR8
DMDMi20140873

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
ChainiPRO_000003473527 – 1041Toll-like receptor 8Add BLAST1015

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi29N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi36 ↔ 491 Publication
Glycosylationi42N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi80N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi88N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi115N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi160N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi181 ↔ 1871 Publication
Glycosylationi247N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi257 ↔ 2701 Publication
Disulfide bondi260 ↔ 2671 Publication
Glycosylationi285N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi293N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi358N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi362N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi395N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi416N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi443N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi479 ↔ 5091 Publication
Glycosylationi511N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi546N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi582N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi590N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi640N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi680N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi752N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi776 ↔ 8031 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9NR97
PeptideAtlasiQ9NR97
PRIDEiQ9NR97
ProteomicsDBi82313

PTM databases

iPTMnetiQ9NR97
PhosphoSitePlusiQ9NR97

Expressioni

Tissue specificityi

Detected in brain, heart, lung, liver, placenta, in monocytes, and at lower levels in CD11c+ immature dendritic cells.

Gene expression databases

BgeeiENSG00000101916
CleanExiHS_TLR8
GenevisibleiQ9NR97 HS

Organism-specific databases

HPAiHPA001608

Interactioni

Subunit structurei

Interacts with MYD88 via their respective TIR domains. Interacts with UNC93B1 (By similarity). Homodimer. Interacts with BTK. Interacts with SMPDL3B (By similarity).By similarity2 Publications

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi119462, 1 interactor
DIPiDIP-61413N
IntActiQ9NR97, 7 interactors
STRINGi9606.ENSP00000218032

Chemistry databases

BindingDBiQ9NR97

Structurei

Secondary structure

11041
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi37 – 39Combined sources3
Beta strandi42 – 44Combined sources3
Beta strandi46 – 48Combined sources3
Beta strandi66 – 69Combined sources4
Turni80 – 85Combined sources6
Beta strandi91 – 93Combined sources3
Beta strandi96 – 98Combined sources3
Turni118 – 123Combined sources6
Beta strandi129 – 131Combined sources3
Beta strandi149 – 152Combined sources4
Helixi163 – 166Combined sources4
Beta strandi174 – 176Combined sources3
Beta strandi179 – 181Combined sources3
Beta strandi183 – 185Combined sources3
Turni194 – 199Combined sources6
Beta strandi205 – 207Combined sources3
Beta strandi225 – 228Combined sources4
Turni241 – 244Combined sources4
Beta strandi250 – 252Combined sources3
Helixi271 – 273Combined sources3
Turni280 – 285Combined sources6
Beta strandi291 – 293Combined sources3
Helixi304 – 307Combined sources4
Beta strandi315 – 317Combined sources3
Beta strandi320 – 322Combined sources3
Helixi324 – 329Combined sources6
Helixi331 – 335Combined sources5
Beta strandi341 – 343Combined sources3
Helixi361 – 365Combined sources5
Beta strandi371 – 373Combined sources3
Beta strandi380 – 382Combined sources3
Helixi384 – 390Combined sources7
Beta strandi398 – 400Combined sources3
Helixi411 – 416Combined sources6
Beta strandi417 – 419Combined sources3
Beta strandi421 – 424Combined sources4
Beta strandi459 – 461Combined sources3
Beta strandi467 – 469Combined sources3
Helixi477 – 480Combined sources4
Beta strandi485 – 487Combined sources3
Turni498 – 503Combined sources6
Beta strandi508 – 511Combined sources4
Turni525 – 528Combined sources4
Beta strandi533 – 536Combined sources4
Turni547 – 552Combined sources6
Beta strandi558 – 560Combined sources3
Helixi565 – 568Combined sources4
Turni571 – 573Combined sources3
Helixi578 – 582Combined sources5
Beta strandi588 – 590Combined sources3
Beta strandi599 – 601Combined sources3
Beta strandi607 – 609Combined sources3
Beta strandi612 – 614Combined sources3
Helixi620 – 623Combined sources4
Beta strandi626 – 629Combined sources4
Turni630 – 637Combined sources8
Beta strandi638 – 640Combined sources3
Beta strandi643 – 645Combined sources3
Helixi656 – 660Combined sources5
Beta strandi667 – 670Combined sources4
Helixi681 – 686Combined sources6
Beta strandi692 – 694Combined sources3
Helixi707 – 709Combined sources3
Beta strandi716 – 718Combined sources3
Turni729 – 733Combined sources5
Beta strandi734 – 737Combined sources4
Beta strandi740 – 742Combined sources3
Helixi753 – 756Combined sources4
Beta strandi758 – 760Combined sources3
Beta strandi765 – 768Combined sources4
Helixi778 – 780Combined sources3
Helixi781 – 789Combined sources9
Turni790 – 792Combined sources3
Helixi798 – 800Combined sources3
Beta strandi801 – 806Combined sources6
Turni807 – 811Combined sources5
Helixi814 – 816Combined sources3
Helixi819 – 822Combined sources4

3D structure databases

ProteinModelPortaliQ9NR97
SMRiQ9NR97
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati126 – 147LRR 11 PublicationAdd BLAST22
Repeati148 – 168LRR 21 PublicationAdd BLAST21
Repeati171 – 193LRR 31 PublicationAdd BLAST23
Repeati202 – 223LRR 41 PublicationAdd BLAST22
Repeati224 – 244LRR 51 PublicationAdd BLAST21
Repeati247 – 268LRR 61 PublicationAdd BLAST22
Repeati288 – 309LRR 71 PublicationAdd BLAST22
Repeati312 – 334LRR 81 PublicationAdd BLAST23
Repeati338 – 360LRR 91 PublicationAdd BLAST23
Repeati368 – 389LRR 101 PublicationAdd BLAST22
Repeati395 – 416LRR 111 PublicationAdd BLAST22
Repeati419 – 440LRR 121 PublicationAdd BLAST22
Repeati482 – 503LRR 131 PublicationAdd BLAST22
Repeati506 – 527LRR 141 PublicationAdd BLAST22
Repeati531 – 551LRR 151 PublicationAdd BLAST21
Repeati555 – 577LRR 161 PublicationAdd BLAST23
Repeati585 – 606LRR 171 PublicationAdd BLAST22
Repeati609 – 630LRR 181 PublicationAdd BLAST22
Repeati640 – 661LRR 191 PublicationAdd BLAST22
Repeati665 – 685LRR 201 PublicationAdd BLAST21
Repeati689 – 710LRR 211 PublicationAdd BLAST22
Repeati713 – 734LRR 221 PublicationAdd BLAST22
Repeati737 – 758LRR 231 PublicationAdd BLAST22
Domaini772 – 824LRRCTAdd BLAST53
Domaini878 – 1025TIRPROSITE-ProRule annotationAdd BLAST148

Sequence similaritiesi

Belongs to the Toll-like receptor family.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4641 Eukaryota
COG4886 LUCA
GeneTreeiENSGT00760000119006
HOGENOMiHOG000230468
HOVERGENiHBG018601
InParanoidiQ9NR97
KOiK10170
OMAiWPDNPKA
OrthoDBiEOG091G014D
PhylomeDBiQ9NR97
TreeFamiTF351113

Family and domain databases

Gene3Di3.40.50.10140, 1 hit
3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000483 Cys-rich_flank_reg_C
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR000157 TIR_dom
IPR027175 TLR8
IPR035897 Toll_tir_struct_dom_sf
PANTHERiPTHR44312:SF2 PTHR44312:SF2, 1 hit
PfamiView protein in Pfam
PF13855 LRR_8, 5 hits
PF01582 TIR, 1 hit
SMARTiView protein in SMART
SM00369 LRR_TYP, 15 hits
SM00082 LRRCT, 1 hit
SM00255 TIR, 1 hit
SUPFAMiSSF52200 SSF52200, 1 hit
PROSITEiView protein in PROSITE
PS51450 LRR, 20 hits
PS50104 TIR, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NR97-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MENMFLQSSM LTCIFLLISG SCELCAEENF SRSYPCDEKK QNDSVIAECS
60 70 80 90 100
NRRLQEVPQT VGKYVTELDL SDNFITHITN ESFQGLQNLT KINLNHNPNV
110 120 130 140 150
QHQNGNPGIQ SNGLNITDGA FLNLKNLREL LLEDNQLPQI PSGLPESLTE
160 170 180 190 200
LSLIQNNIYN ITKEGISRLI NLKNLYLAWN CYFNKVCEKT NIEDGVFETL
210 220 230 240 250
TNLELLSLSF NSLSHVPPKL PSSLRKLFLS NTQIKYISEE DFKGLINLTL
260 270 280 290 300
LDLSGNCPRC FNAPFPCVPC DGGASINIDR FAFQNLTQLR YLNLSSTSLR
310 320 330 340 350
KINAAWFKNM PHLKVLDLEF NYLVGEIASG AFLTMLPRLE ILDLSFNYIK
360 370 380 390 400
GSYPQHINIS RNFSKLLSLR ALHLRGYVFQ ELREDDFQPL MQLPNLSTIN
410 420 430 440 450
LGINFIKQID FKLFQNFSNL EIIYLSENRI SPLVKDTRQS YANSSSFQRH
460 470 480 490 500
IRKRRSTDFE FDPHSNFYHF TRPLIKPQCA AYGKALDLSL NSIFFIGPNQ
510 520 530 540 550
FENLPDIACL NLSANSNAQV LSGTEFSAIP HVKYLDLTNN RLDFDNASAL
560 570 580 590 600
TELSDLEVLD LSYNSHYFRI AGVTHHLEFI QNFTNLKVLN LSHNNIYTLT
610 620 630 640 650
DKYNLESKSL VELVFSGNRL DILWNDDDNR YISIFKGLKN LTRLDLSLNR
660 670 680 690 700
LKHIPNEAFL NLPASLTELH INDNMLKFFN WTLLQQFPRL ELLDLRGNKL
710 720 730 740 750
LFLTDSLSDF TSSLRTLLLS HNRISHLPSG FLSEVSSLKH LDLSSNLLKT
760 770 780 790 800
INKSALETKT TTKLSMLELH GNPFECTCDI GDFRRWMDEH LNVKIPRLVD
810 820 830 840 850
VICASPGDQR GKSIVSLELT TCVSDVTAVI LFFFTFFITT MVMLAALAHH
860 870 880 890 900
LFYWDVWFIY NVCLAKVKGY RSLSTSQTFY DAYISYDTKD ASVTDWVINE
910 920 930 940 950
LRYHLEESRD KNVLLCLEER DWDPGLAIID NLMQSINQSK KTVFVLTKKY
960 970 980 990 1000
AKSWNFKTAF YLALQRLMDE NMDVIIFILL EPVLQHSQYL RLRQRICKSS
1010 1020 1030 1040
ILQWPDNPKA EGLFWQTLRN VVLTENDSRY NNMYVDSIKQ Y
Length:1,041
Mass (Da):119,828
Last modified:October 1, 2000 - v1
Checksum:i39A38B60629291C8
GO
Isoform 2 (identifier: Q9NR97-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MKESSLQNSSCSLGKETKK

Show »
Length:1,059
Mass (Da):121,764
Checksum:i27803D560E09D7BF
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti217P → S in AAF64061 (PubMed:11022119).Curated1
Sequence conflicti328A → V in AAQ88663 (PubMed:12975309).Curated1
Sequence conflicti366L → P in AAF64061 (PubMed:11022119).Curated1
Sequence conflicti410D → N in AAZ95439 (PubMed:19924287).Curated1
Sequence conflicti867V → I in AAF64061 (PubMed:11022119).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02466710M → V. Corresponds to variant dbSNP:rs5744077Ensembl.1
Natural variantiVAR_052363715R → Q. Corresponds to variant dbSNP:rs5744082Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0534121M → MKESSLQNSSCSLGKETKK in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF246971 mRNA Translation: AAF64061.1
AF245703 mRNA Translation: AAF78036.1
AB445666 mRNA Translation: BAG55063.1
DQ023132 Genomic DNA Translation: AAZ95433.1
DQ023133 Genomic DNA Translation: AAZ95434.1
DQ023134 Genomic DNA Translation: AAZ95435.1
DQ023135 Genomic DNA Translation: AAZ95436.1
DQ023136 Genomic DNA Translation: AAZ95437.1
DQ023137 Genomic DNA Translation: AAZ95438.1
DQ023138 Genomic DNA Translation: AAZ95439.1
DQ023139 Genomic DNA Translation: AAZ95440.1
DQ023140 Genomic DNA Translation: AAZ95441.1
CH471074 Genomic DNA Translation: EAW98808.1
AY358296 mRNA Translation: AAQ88663.1
AC005859 Genomic DNA No translation available.
AC139705 Genomic DNA No translation available.
CH471074 Genomic DNA Translation: EAW98809.1
BC101076 mRNA Translation: AAI01077.1
BC101077 mRNA Translation: AAI01078.1
CCDSiCCDS14152.1 [Q9NR97-1]
CCDS14153.1 [Q9NR97-2]
RefSeqiNP_057694.2, NM_016610.3 [Q9NR97-2]
NP_619542.1, NM_138636.5 [Q9NR97-1]
XP_011543831.1, XM_011545529.1 [Q9NR97-2]
XP_011543832.1, XM_011545530.2 [Q9NR97-2]
UniGeneiHs.660543

Genome annotation databases

EnsembliENST00000218032; ENSP00000218032; ENSG00000101916 [Q9NR97-1]
ENST00000311912; ENSP00000312082; ENSG00000101916 [Q9NR97-2]
GeneIDi51311
KEGGihsa:51311
UCSCiuc004cvd.4 human [Q9NR97-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTLR8_HUMAN
AccessioniPrimary (citable) accession number: Q9NR97
Secondary accession number(s): B3Y654
, D1CS70, D1CS76, Q495P4, Q6UXL6, Q9NYG9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: October 1, 2000
Last modified: June 20, 2018
This is version 167 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

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