InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: TLR3

Summary

InnateDB Protein

IDBP-47296.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TLR3

Protein Name

toll-like receptor 3

Synonyms

CD283; IIAE2;

Species

Homo sapiens

Ensembl Protein

ENSP00000296795

InnateDB Gene

IDBG-47294 (TLR3)

Protein Structure

UniProt Annotation

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. TLR3 is a nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter TRIF/TICAM1, leading to NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and the inflammatory response. {ECO:0000269PubMed:12471095, ECO:0000269PubMed:12539043, ECO:0000269PubMed:16043704, ECO:0000269PubMed:16144834, ECO:0000269PubMed:16720699, ECO:0000269PubMed:16858407, ECO:0000269PubMed:17178723, ECO:0000269PubMed:18172197, ECO:0000269PubMed:22611194}.

Subcellular Localization

Endoplasmic reticulum membrane; Single-pass type I membrane protein. Endosome membrane.

Disease Associations

Herpes simplex encephalitis 2 (HSE2) [MIM:613002]: A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. HSE is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome. {ECO:0000269PubMed:17872438}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. TLR3 mutations predispose otherwise healthy individuals to isolated herpes simplex encephalitis through a mechanism that involves impaired IFNs production and reduced immune defense against viral infection in the central nervous system.

Tissue Specificity

Expressed at high level in placenta and pancreas. Also detected in CD11c+ immature dendritic cells. Only expressed in dendritic cells and not in other leukocytes, including monocyte precursors. TLR3 is the TLR that is expressed most strongly in the brain, especially in astrocytes, glia, and neurons. {ECO:0000269PubMed:17085778}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 42 experimentally validated interaction(s) in this database.
They are also associated with 7 interaction(s) predicted by orthology.

Experimentally validated
Total	42 [view]
Protein-Protein	38 [view]
Protein-DNA	4 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	7 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003725	double-stranded RNA binding
GO:0004872	receptor activity
GO:0004888	transmembrane signaling receptor activity
GO:0005515	protein binding

Biological Process

GO:0001774	microglial cell activation
GO:0001934	positive regulation of protein phosphorylation
GO:0002224	toll-like receptor signaling pathway
GO:0002282	microglial cell activation involved in immune response
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0006952	defense response
GO:0006954	inflammatory response
GO:0006972	hyperosmotic response
GO:0007165	signal transduction
GO:0007249	I-kappaB kinase/NF-kappaB signaling
GO:0007250	activation of NF-kappaB-inducing kinase activity
GO:0007252	I-kappaB phosphorylation
GO:0008584	male gonad development
GO:0009597	detection of virus
GO:0009615	response to virus
GO:0032481	positive regulation of type I interferon production
GO:0032722	positive regulation of chemokine production
GO:0032728	positive regulation of interferon-beta production
GO:0032735	positive regulation of interleukin-12 production
GO:0032755	positive regulation of interleukin-6 production
GO:0032757	positive regulation of interleukin-8 production
GO:0032760	positive regulation of tumor necrosis factor production
GO:0034123	positive regulation of toll-like receptor signaling pathway
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0034346	positive regulation of type III interferon production
GO:0035458	cellular response to interferon-beta
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0035690	cellular response to drug
GO:0042346	positive regulation of NF-kappaB import into nucleus
GO:0042742	defense response to bacterium
GO:0043065	positive regulation of apoptotic process
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043330	response to exogenous dsRNA
GO:0043331	response to dsRNA
GO:0045078	positive regulation of interferon-gamma biosynthetic process
GO:0045080	positive regulation of chemokine biosynthetic process
GO:0045087	innate immune response (InnateDB)
GO:0045356	positive regulation of interferon-alpha biosynthetic process
GO:0045359	positive regulation of interferon-beta biosynthetic process
GO:0045671	negative regulation of osteoclast differentiation
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046330	positive regulation of JNK cascade
GO:0050729	positive regulation of inflammatory response
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0051607	defense response to virus
GO:0071260	cellular response to mechanical stimulus
GO:0071346	cellular response to interferon-gamma
GO:0071359	cellular response to dsRNA
GO:0071360	cellular response to exogenous dsRNA
GO:0097191	extrinsic apoptotic signaling pathway
GO:0097527	necroptotic signaling pathway

Cellular Component

GO:0000139	Golgi membrane
GO:0005622	intracellular
GO:0005737	cytoplasm
GO:0005765	lysosomal membrane
GO:0005789	endoplasmic reticulum membrane
GO:0005887	integral component of plasma membrane
GO:0009986	cell surface
GO:0010008	endosome membrane
GO:0016020	membrane
GO:0036020	endolysosome membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000157 Toll/interleukin-1 receptor homology (TIR) domain
IPR000483 Cysteine-rich flanking region, C-terminal
IPR001611 Leucine-rich repeat
IPR003591 Leucine-rich repeat, typical subtype

PFAM

PF01582
PF13676
PF01463
PF00560
PF13504
PF13855

PRINTS

PIRSF

SMART

SM00255
SM00082
SM00369

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

O15455