Homo sapiens Gene: TLR8
Summary
InnateDB Gene IDBG-44288.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol TLR8
Gene Name toll-like receptor 8
Synonyms
Species Homo sapiens
Ensembl Gene ENSG00000101916
Encoded Proteins
toll-like receptor 8
toll-like receptor 8
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
TLR8 expression and function is highly up-regulated in colonic epithelium from patients with active inflammatory bowel disease (IBD), suggesting that TLR8 signalling is important in the pathogenesis of IBD.
Toll-like receptor 8 (TLR8), 7 and 9 form a functional subgroup within the TLR family that recognizes pathogen-associated molecular patterns in endosomal/lysosomal compartments.
TLR8 and TLR7 bind single-stranded RNA, stimulating dendritic cells (DCs) and macrophages to secrete interferon-alpha and pro-inflammatory, as well as regulatory, cytokines.
TLR8 signalling strongly promotes inflammatory lipid mediator biosynthesis, providing novel insights on innate immune response to viral infections.
TLR8 is activated in human monocytic cells following Helicobacter pylori phagocytosis and TLR8 single nucleotide polymorphism play a role in the modulation of TLR8-dependent microbicidal response of infected macrophages.
TLR7 and TLR8 are translocated from the endoplasmic reticulum to the endosome in the presence of antiphospholipid antibodies, as a consequence, plasmacytoid dendritic cells become dramatically sensitized to TLR7/8 agonists and this may play a role in systemic autoimmunity.
TLR8 binding of HIV ssRNA induces endosomal acidification and chromatin remodeling at the TNF-alpha promoter to promote TNF-alpha release in infected macrophages.
TLR8 binds to exosomal MIR21 and MIR29A secreted by tumour cells and initiates a prometastatic inflammatory response.
TLR8 plays a pathogenic role in disease whereby its expression is increased in patients with systemic arthritis and is correlated with the elevation of IL1B levels and disease status.
TLR8 binds degradation products of single-stranded RNA at two distinct sites. One site prefers uridine mononucleosides and the other site prefers short oligonucleotides.
TLR8-dependent detection of bacterial RNA is critical for triggering monocyte activation in response to infection with Streptococcus pyogenes.
InnateDB Annotation from Orthologs
Summary
[Mus musculus] Tlr7 and Tlr8 are translocated from the endoplasmic reticulum to the endosome in the presence of antiphospholipid antibodies, as a consequence, plasmacytoid dendritic cells become dramatically sensitized to Tlr7/8 agonists and this may play a role in systemic autoimmunity.
[Mus musculus] Tlr8 binding of HIV ssRNA induces endosomal acidification and chromatin remodeling at the TNF-alpha promoter to promote TNF-alpha release in infected macrophages. (Demonstrated in human)
Entrez Gene
Summary 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]
Gene Information
Type Protein coding
Genomic Location Chromosome X:12906620-12923169
Strand Forward strand
Band p22.2
Transcripts
ENST00000218032 ENSP00000218032
ENST00000311912 ENSP00000312082
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 15 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.
Experimentally validated
Total 15 [view]
Protein-Protein 8 [view]
Protein-DNA 4 [view]
Protein-RNA 3 [view]
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 3 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0003677 DNA binding
GO:0003723 RNA binding
GO:0003725 double-stranded RNA binding
GO:0003727 single-stranded RNA binding
GO:0004872 receptor activity
GO:0005515 protein binding
GO:0008144 drug binding
Biological Process
GO:0001774 microglial cell activation
GO:0002224 toll-like receptor signaling pathway
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 (InnateDB)
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:0051607 defense response to virus
GO:0071260 cellular response to mechanical stimulus
Cellular Component
GO:0000139 Golgi membrane
GO:0005789 endoplasmic reticulum membrane
GO:0010008 endosome membrane
GO:0016021 integral component of membrane
GO:0036020 endolysosome membrane
Orthologs
Species
Mus musculus
Gene ID
Gene Order
Method
Confidence
Comments
Low
Tentative data, uncurated. RBBH derived.
Pathways
NETPATH
REACTOME
MyD88 dependent cascade initiated on endosome pathway
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
Toll Like Receptor 9 (TLR9) Cascade pathway
Innate Immune System pathway
Toll-Like Receptors Cascades pathway
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
Immune System pathway
Trafficking and processing of endosomal TLR pathway
TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling pathway
KEGG
Toll-like receptor signaling pathway pathway
INOH
PID BIOCARTA
PID NCI
Cross-References
SwissProt Q9NR97
TrEMBL B4DLJ2 Q8NC00
UniProt Splice Variant
Entrez Gene 51311
UniGene Hs.660543
RefSeq NM_016610 NM_138636 XM_005274543
HUGO HGNC:15632
OMIM 300366
CCDS CCDS14152 CCDS14153
HPRD
IMGT
EMBL AB445666 AC005859 AC139705 AF245703 AF246971 AK075117 AK297024 AY358296 BC101076 BC101077 CH471074 DQ023132 DQ023133 DQ023134 DQ023135 DQ023136 DQ023137 DQ023138 DQ023139 DQ023140
GenPept AAF64061 AAF78036 AAI01077 AAI01078 AAQ88663 AAZ95433 AAZ95434 AAZ95435 AAZ95436 AAZ95437 AAZ95438 AAZ95439 AAZ95440 AAZ95441 BAC11412 BAG55063 BAG59554 EAW98808 EAW98809
RNA Seq Atlas 51311