TLR8

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]

TLR8 Gene(Protein Coding) Toll Like Receptor 8

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).

Biological Process cellular response to mechanical stimulusSource:UniProtKB1 Publication
Biological Process defense response to virusSource:UniProtKB1 Publication
Biological Process I-kappaB kinase/NF-kappaB signalingSource:UniProtKB1 Publication
Biological Process immunoglobulin mediated immune responseSource:UniProtKB1 Publication
Biological Process inflammatory responseSource:UniProtKB-KW
Biological Process innate immune responseSource:UniProtKB1 Publication
Biological Process MyD88-dependent toll-like receptor signaling pathwaySource:InterPro
Biological Process negative regulation of interleukin-12 productionSource:CAFA1 Publication
Biological Process positive regulation of innate immune responseSource:UniProtKB1 Publication
Biological Process positive regulation of interferon-alpha productionSource:UniProtKB1 Publication
Biological Process positive regulation of interferon-beta productionSource:UniProtKB1 Publication
Biological Process positive regulation of interferon-gamma productionSource:UniProtKB1 Publication
Biological Process positive regulation of interleukin-1 beta productionSource:UniProtKB1 Publication
Biological Process positive regulation of interleukin-6 productionSource:CAFA1 Publication
Biological Process positive regulation of interleukin-8 productionSource:UniProtKB1 Publication
Biological Process regulation of protein phosphorylationSource:Ensembl
Biological Process response to virusSource:UniProtKB1 Publication
Biological Process toll-like receptor 8 signaling pathwaySource:UniProtKB1 Publication
Biological Process toll-like receptor signaling pathwaySource:GO_Central1 Publication

Endosome membrane
Endosomal localization confers distinctive proteolytic processing.

Extracellular: 27-827
Helical: 828-848
Cytoplasmic: 849-1041

Ubiquitinated by RNF216; leading to degradation by the proteasome.
Proteolytic processing occurs in monocytes and monocyte-derived macrophages by both furin-like proprotein convertase and cathepsins (PubMed:25297876).
The cleavage is necessary for dimer formation and subsequent activation (PubMed:26929371).