Human Gene TLR8 (uc004cve.3) Description and Page Index
  Description: Homo sapiens toll-like receptor 8 (TLR8), mRNA.
RefSeq Summary (NM_138636): The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This gene is predominantly expressed in lung and peripheral blood leukocytes, and lies in close proximity to another family member, TLR7, on chromosome X. [provided by RefSeq, Jul 2008].
Transcript (Including UTRs)
   Position: hg19 chrX:12,924,739-12,941,288 Size: 16,550 Total Exon Count: 2 Strand: +
Coding Region
   Position: hg19 chrX:12,924,826-12,940,285 Size: 15,460 Coding Exon Count: 2 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chrX:12,924,739-12,941,288)mRNA (may differ from genome)Protein (1041 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
OMIMPubMedReactomeStanford SOURCETreefamUniProtKB

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Toll-like receptor 8; AltName: CD_antigen=CD288; Flags: Precursor;
FUNCTION: 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.
SUBUNIT: Interacts with MYD88 via their respective TIR domains. Interacts with UNC93B1 (By similarity). Interacts with BTK.
SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein (By similarity).
TISSUE SPECIFICITY: Detected in brain, heart, lung, liver, placenta, in monocytes, and at lower levels in CD11c+ immature dendritic cells.
SIMILARITY: Belongs to the Toll-like receptor family.
SIMILARITY: Contains 23 LRR (leucine-rich) repeats.
SIMILARITY: Contains 1 LRRCT domain.
SIMILARITY: Contains 1 TIR domain.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): TLR8
CDC HuGE Published Literature: TLR8
Positive Disease Associations: Celiac disease , HIV Infections
Related Studies:
  1. Celiac disease
    Dubois ,et al. Nat Genet 2010, Multiple common variants for celiac disease influencing immune gene expression , Nature genetics 2010 42- 4 : 295-302. [PubMed 20190752]
  2. HIV Infections
    D-Y Oh , et al. The Journal of infectious diseases 2008 198(5):701-9, A functional toll-like receptor 8 variant is associated with HIV disease restriction., The Journal of infectious diseases 2008 198(5):701-9. [PubMed 18605904]
    This first report of a functional TLR8 variant associated with a different clinical course of an RNA viral disease may have implications for the individual risk assessment of patients infected with HIV and other RNA viruses as well as for future HIV vacci

-  MalaCards Disease Associations
  MalaCards Gene Search: TLR8
Diseases sorted by gene-association score: crimean-congo hemorrhagic fever (11), superficial basal cell carcinoma (8), viral infectious disease (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
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-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 24.66 RPKM in Whole Blood
Total median expression: 43.80 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -18.0087-0.207 Picture PostScript Text
3' UTR -292.751003-0.292 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000483 - Cys-rich_flank_reg_C
IPR001611 - Leu-rich_rpt
IPR003591 - Leu-rich_rpt_typical-subtyp
IPR000157 - TIR_dom

Pfam Domains:
PF00560 - Leucine Rich Repeat
PF01582 - TIR domain
PF13306 - Leucine rich repeats (6 copies)
PF13855 - Leucine rich repeat

SCOP Domains:
52047 - RNI-like
52058 - L domain-like
52075 - Outer arm dynein light chain 1
52200 - Toll/Interleukin receptor TIR domain

ModBase Predicted Comparative 3D Structure on Q9NR97
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003677 DNA binding
GO:0003723 RNA binding
GO:0003725 double-stranded RNA binding
GO:0003727 single-stranded RNA binding
GO:0004888 transmembrane signaling receptor activity
GO:0008144 drug binding
GO:0038023 signaling receptor activity
GO:0042802 identical protein binding

Biological Process:
GO:0001774 microglial cell activation
GO:0001932 regulation of protein phosphorylation
GO:0002224 toll-like receptor signaling pathway
GO:0002376 immune system process
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0006954 inflammatory response
GO:0007165 signal transduction
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0009615 response to virus
GO:0016064 immunoglobulin mediated immune response
GO:0034158 toll-like receptor 8 signaling pathway
GO:0034162 toll-like receptor 9 signaling pathway
GO:0045078 positive regulation of interferon-gamma biosynthetic process
GO:0045087 innate immune response
GO:0045089 positive regulation of innate immune response
GO:0045356 positive regulation of interferon-alpha biosynthetic process
GO:0045359 positive regulation of interferon-beta biosynthetic process
GO:0045416 positive regulation of interleukin-8 biosynthetic process
GO:0050707 regulation of cytokine secretion
GO:0050718 positive regulation of interleukin-1 beta secretion
GO:0051607 defense response to virus
GO:0071260 cellular response to mechanical stimulus
GO:2000778 positive regulation of interleukin-6 secretion
GO:2001183 negative regulation of interleukin-12 secretion

Cellular Component:
GO:0000139 Golgi membrane
GO:0005789 endoplasmic reticulum membrane
GO:0005887 integral component of plasma membrane
GO:0009897 external side of plasma membrane
GO:0010008 endosome membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0036020 endolysosome membrane

-  Descriptions from all associated GenBank mRNAs
  AK314240 - Homo sapiens cDNA, FLJ94985.
AF246971 - Homo sapiens Toll-like receptor 8 (TLR8) mRNA, complete cds.
LP895634 - Sequence 498 from Patent EP3253886.
JD110360 - Sequence 91384 from Patent EP1572962.
AY358296 - Homo sapiens clone DNA42663 TLR8 (UNQ249) mRNA, complete cds.
BC101074 - Homo sapiens toll-like receptor 8, mRNA (cDNA clone MGC:119598 IMAGE:40008787), complete cds.
BC101075 - Homo sapiens toll-like receptor 8, mRNA (cDNA clone MGC:119599 IMAGE:40008788), complete cds.
BC101076 - Homo sapiens toll-like receptor 8, mRNA (cDNA clone MGC:119600 IMAGE:40008792), complete cds.
BC101077 - Homo sapiens toll-like receptor 8, mRNA (cDNA clone MGC:119601 IMAGE:40008793), complete cds.
AF245703 - Homo sapiens toll-like receptor 8 (TLR8) mRNA, complete cds.
JD171756 - Sequence 152780 from Patent EP1572962.
JD171757 - Sequence 152781 from Patent EP1572962.
KJ898881 - Synthetic construct Homo sapiens clone ccsbBroadEn_08275 TLR8 gene, encodes complete protein.
AB445666 - Homo sapiens TLR8 mRNA for toll-like receptor 8, complete cds.
AK307562 - Homo sapiens cDNA, FLJ97510.
AK297024 - Homo sapiens cDNA FLJ56817 complete cds, highly similar to Toll-like receptor 8 precursor.
AK075117 - Homo sapiens cDNA FLJ90636 fis, clone PLACE1003737, highly similar to Toll-like receptor 8 precursor.
JD022865 - Sequence 3889 from Patent EP1572962.
JD035332 - Sequence 16356 from Patent EP1572962.
JD028572 - Sequence 9596 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04620 - Toll-like receptor signaling pathway

Reactome (by CSHL, EBI, and GO)

Protein Q9NR97 (Reactome details) participates in the following event(s):

R-HSA-1678923 TLR folding by chaperones GP96 and CNPY3
R-HSA-1678944 Folded full-length TLR7/8/9 dissociates from the GP96:CNPY3 complex
R-HSA-167983 Ligand binds to TLR7 or TLR8
R-HSA-1678921 Full-length TLR3/7/8/9 binds to UNC93B1
R-HSA-975175 MyD88 interacts with the activated TLR receptor 7, 8 or 9
R-HSA-975156 IRAK4 binds to the activated TLR7/8 or 9 receptor:MyD88 complex
R-HSA-975098 MyD88 oligomerization within the complex of activated TLR 7/8 or 9 : MyD88
R-HSA-975115 IRAK1/or IRAK2 binds to the activated IRAK4 :MyD88:activated TLR 7/8 or 9.
R-HSA-975100 Dissociation of hp-IRAK1/or IRAK2:TRAF6-oligomer from the p-IRAK4 :oligo-Myd88:activated TLR7/8 or 9 complex
R-HSA-975170 IRAK4 autophosphorylation in the complex with MyD88:activated TLR 7/8 or 9
R-HSA-975125 Multiple IRAK1 autophosphorylation steps within the complex pIRAK4:MyD88:activated TLR7/8 or 9
R-HSA-975134 Second phosphorylation of IRAK1 by IRAK4 bound to MyD88: activated TLR 7/8 or 9
R-HSA-975180 First phosphorylation of IRAK1 by IRAK4 bound to MyD88:activated TLR 7/8 or 9
R-HSA-975160 Phosphorylation of IRAK2 bound to the activated IRAK4:MyD88 oligomer:activated TLR 7/8 or 9
R-HSA-975111 TRAF6 binds to hp- IRAK1/or p-IRAK2:p-IRAK4:MyD88:activated TLR7/8 or 9
R-HSA-975188 TRAF6 interacts with IRF7 upon TLR7/8 or 9 activation
R-HSA-975106 Phosphorylation and release of IRF7 upon TLR7/8 or 9 activation
R-HSA-975118 TRAF6 ubiquitinqtes IRF7 in a K63-dependent manner following TLR7/8 or 9 stimulation
R-HSA-1679131 Trafficking and processing of endosomal TLR
R-HSA-168898 Toll-Like Receptors Cascades
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade
R-HSA-168249 Innate Immune System
R-HSA-168256 Immune System
R-HSA-975155 MyD88 dependent cascade initiated on endosome
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-975110 TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling

-  Other Names for This Gene
  Alternate Gene Symbols: B3Y654, NM_138636, NP_619542, Q495P4, Q6UXL6, Q9NR97, Q9NYG9, TLR8_HUMAN, UNQ249/PRO286
UCSC ID: uc004cve.3
RefSeq Accession: NM_138636
Protein: Q9NR97 (aka TLR8_HUMAN)
CCDS: CCDS14152.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_138636.4
exon count: 2CDS single in 3' UTR: no RNA size: 4216
ORF size: 3126CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 6427.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
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-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.