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Entry version 192 (13 Feb 2019)
Sequence version 1 (01 Jan 1998)
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Protein

Toll-like receptor 3

Gene

TLR3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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. 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.9 Publications

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionReceptor, RNA-binding
Biological processImmunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-1679131 Trafficking and processing of endosomal TLR
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade
R-HSA-168927 TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-1810476 RIP-mediated NFkB activation via ZBP1
R-HSA-5602410 TLR3 deficiency - HSE
R-HSA-5602415 UNC93B1 deficiency - HSE
R-HSA-5602566 TICAM1 deficiency - HSE
R-HSA-5602571 TRAF3 deficiency - HSE
R-HSA-9013957 TLR3-mediated TICAM1-dependent programmed cell death
R-HSA-9013973 TICAM1-dependent activation of IRF3/IRF7
R-HSA-9014325 TICAM1,TRAF6-dependent induction of TAK1 complex

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
O15455

SIGNOR Signaling Network Open Resource

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SIGNORi
O15455

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Toll-like receptor 3
Alternative name(s):
CD_antigen: CD283
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:TLR3
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 4

Organism-specific databases

Eukaryotic Pathogen Database Resources

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EuPathDBi
HostDB:ENSG00000164342.12

Human Gene Nomenclature Database

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HGNCi
HGNC:11849 TLR3

Online Mendelian Inheritance in Man (OMIM)

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MIMi
603029 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_O15455

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>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 & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini24 – 704LumenalSequence analysisAdd BLAST681
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei705 – 725HelicalSequence analysisAdd BLAST21
Topological domaini726 – 904CytoplasmicSequence analysisAdd BLAST179

Keywords - Cellular componenti

Endoplasmic reticulum, Endosome, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Encephalopathy, acute, infection-induced, Herpes-specific, 2 (IIAE2)1 Publication
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.
Disease descriptionA rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. It 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.
See also OMIM:613002
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_054887554P → S in IIAE2; causes TLR3 deficiency and predisposition to herpes simplex encephalitis. 1 PublicationCorresponds to variant dbSNP:rs121434431EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi95C → A: Reduced response to ds-RNA. 1 Publication1
Mutagenesisi122C → A: Reduced response to ds-RNA. 1 Publication1
Mutagenesisi196N → G: Reduced expression levels; when associated with R-247. 1 Publication1
Mutagenesisi247N → R: Reduced response to ds-RNA. Reduced expression levels; when associated with G-196. 1 Publication1
Mutagenesisi539H → A: No effect. 1 Publication1
Mutagenesisi539H → E: Loss of RNA binding. Constitutive activation of NF-kappa-B. 1 Publication1
Mutagenesisi541N → A: Loss of RNA binding. Abolishes activation of NF-kappa-B. 1 Publication1
Mutagenesisi759Y → F: Reduced activation of NF-kappa-B in response to ds-RNA. Reduced induction of IL-8 in response to ds-RNA. Loss of interaction with WDFY1. 2 Publications1
Mutagenesisi858Y → F: Loss of interaction with WDFY1. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNET

More...
DisGeNETi
7098

MalaCards human disease database

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MalaCardsi
TLR3
MIMi613002 phenotype

Open Targets

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OpenTargetsi
ENSG00000164342

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
1930 Herpes simplex virus encephalitis

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA36551

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL1075113

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
TLR3

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 231 PublicationAdd BLAST23
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000003471524 – 904Toll-like receptor 3Add BLAST881

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi28 ↔ 37
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi52N-linked (GlcNAc...) asparagine3 Publications1
Glycosylationi57N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi70N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi95 ↔ 122
Glycosylationi124N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi196N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi247N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi252N-linked (GlcNAc...) asparagine3 Publications1
Glycosylationi265N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi275N-linked (GlcNAc...) asparagine3 Publications1
Glycosylationi291N-linked (GlcNAc...) asparagine3 Publications1
Glycosylationi398N-linked (GlcNAc...) asparagine3 Publications1
Glycosylationi413N-linked (GlcNAc...) asparagine3 Publications1
Glycosylationi507N-linked (GlcNAc...) asparagine3 Publications1
Glycosylationi636N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi649 ↔ 677
Disulfide bondi651 ↔ 696
Glycosylationi662N-linked (GlcNAc...) asparagineSequence analysis1
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei759Phosphotyrosine1 Publication1
Modified residuei858Phosphotyrosine1 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Heavily N-glycosylated, except on that part of the surface of the ectodomain that is involved in ligand binding.4 Publications
TLR3 signaling requires a proteolytic cleavage mediated by cathepsins CTSB and CTSH, the cleavage occurs between amino acids 252 and 346. The cleaved form of TLR3 is the predominant form found in endosomes.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
O15455

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
O15455

MaxQB - The MaxQuant DataBase

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MaxQBi
O15455

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
O15455

PeptideAtlas

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PeptideAtlasi
O15455

PRoteomics IDEntifications database

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PRIDEi
O15455

ProteomicsDB human proteome resource

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ProteomicsDBi
48678

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
O15455

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
O15455

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

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.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000164342 Expressed in 179 organ(s), highest expression level in placenta

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
O15455 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
O15455 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
CAB025658

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Monomer and homodimer; dimerization is triggered by ligand-binding, the signaling unit is composed of one ds-RNA of around 40 bp and two TLR3 molecules, and lateral clustering of signaling units along the length of the ds-RNA ligand is required for TLR3 signal transduction. Interacts (via transmembrane domain) with UNC93B1; the interaction is required for transport from the ER to the endosomes. Interacts with SRC; upon binding of double-stranded RNA. Interacts with TICAM1 (via the TIR domain) in response to poly(I:C) and this interaction is enhanced in the presence of WDFY1 (PubMed:25736436). The tyrosine-phosphorylated form (via TIR domain) interacts with WDFY1 (via WD repeat 2) in response to poly(I:C) (PubMed:25736436).8 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
112953, 32 interactors

Database of interacting proteins

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DIPi
DIP-29660N

Protein interaction database and analysis system

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IntActi
O15455, 14 interactors

Molecular INTeraction database

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MINTi
O15455

STRING: functional protein association networks

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STRINGi
9606.ENSP00000296795

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1904
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ZIWX-ray2.10A27-700[»]
2A0ZX-ray2.40A22-703[»]
2MK9NMR-A/B698-730[»]
2MKANMR-A/B/C698-730[»]
3ULUX-ray3.52A22-702[»]
3ULVX-ray3.52A22-702[»]
5GS0X-ray3.27A/B27-697[»]

Protein Model Portal of the PSI-Nature Structural Biology Knowledgebase

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ProteinModelPortali
O15455

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
O15455

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
O15455

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini24 – 51LRRNTAdd BLAST28
<p>This subsection of the ‘Family and Domains’ section indicates the positions and types of repeated sequence motifs or repeated domains within the protein.<p><a href='/help/repeat' target='_top'>More...</a></p>Repeati52 – 73LRR 1Add BLAST22
Repeati76 – 97LRR 2Add BLAST22
Repeati100 – 121LRR 3Add BLAST22
Repeati124 – 145LRR 4Add BLAST22
Repeati148 – 168LRR 5Add BLAST21
Repeati172 – 193LRR 6Add BLAST22
Repeati198 – 219LRR 7Add BLAST22
Repeati222 – 244LRR 8Add BLAST23
Repeati249 – 270LRR 9Add BLAST22
Repeati275 – 296LRR 10Add BLAST22
Repeati299 – 320LRR 11Add BLAST22
Repeati323 – 344LRR 12Add BLAST22
Repeati356 – 377LRR 13Add BLAST22
Repeati380 – 400LRR 14Add BLAST21
Repeati408 – 429LRR 15Add BLAST22
Repeati432 – 454LRR 16Add BLAST23
Repeati465 – 486LRR 17Add BLAST22
Repeati507 – 528LRR 18Add BLAST22
Repeati531 – 552LRR 19Add BLAST22
Repeati563 – 584LRR 20Add BLAST22
Repeati587 – 608LRR 21Add BLAST22
Repeati611 – 632LRR 22Add BLAST22
Domaini645 – 698LRRCTAdd BLAST54
Domaini754 – 896TIRPROSITE-ProRule annotationAdd BLAST143

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

ds-RNA binding is mediated by LRR 1 to 3, and LRR 17 to 18.

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the Toll-like receptor family.Curated

Keywords - Domaini

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

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG4641 Eukaryota
COG4886 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000159678

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000251618

The HOVERGEN Database of Homologous Vertebrate Genes

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HOVERGENi
HBG023181

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
O15455

KEGG Orthology (KO)

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KOi
K05401

Identification of Orthologs from Complete Genome Data

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OMAi
NKYLQLT

Database of Orthologous Groups

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OrthoDBi
737804at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
O15455

TreeFam database of animal gene trees

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TreeFami
TF325595

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
3.40.50.10140, 1 hit
3.80.10.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View 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
IPR027173 TLR3
IPR035897 Toll_tir_struct_dom_sf

The PANTHER Classification System

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PANTHERi
PTHR44599 PTHR44599, 1 hit

Pfam protein domain database

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Pfami
View protein in Pfam
PF13516 LRR_6, 1 hit
PF13855 LRR_8, 6 hits
PF01582 TIR, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00369 LRR_TYP, 16 hits
SM00082 LRRCT, 1 hit
SM00255 TIR, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF52200 SSF52200, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS51450 LRR, 19 hits
PS50104 TIR, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: O15455-1) [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
MRQTLPCIYF WGGLLPFGML CASSTTKCTV SHEVADCSHL KLTQVPDDLP
60 70 80 90 100
TNITVLNLTH NQLRRLPAAN FTRYSQLTSL DVGFNTISKL EPELCQKLPM
110 120 130 140 150
LKVLNLQHNE LSQLSDKTFA FCTNLTELHL MSNSIQKIKN NPFVKQKNLI
160 170 180 190 200
TLDLSHNGLS STKLGTQVQL ENLQELLLSN NKIQALKSEE LDIFANSSLK
210 220 230 240 250
KLELSSNQIK EFSPGCFHAI GRLFGLFLNN VQLGPSLTEK LCLELANTSI
260 270 280 290 300
RNLSLSNSQL STTSNTTFLG LKWTNLTMLD LSYNNLNVVG NDSFAWLPQL
310 320 330 340 350
EYFFLEYNNI QHLFSHSLHG LFNVRYLNLK RSFTKQSISL ASLPKIDDFS
360 370 380 390 400
FQWLKCLEHL NMEDNDIPGI KSNMFTGLIN LKYLSLSNSF TSLRTLTNET
410 420 430 440 450
FVSLAHSPLH ILNLTKNKIS KIESDAFSWL GHLEVLDLGL NEIGQELTGQ
460 470 480 490 500
EWRGLENIFE IYLSYNKYLQ LTRNSFALVP SLQRLMLRRV ALKNVDSSPS
510 520 530 540 550
PFQPLRNLTI LDLSNNNIAN INDDMLEGLE KLEILDLQHN NLARLWKHAN
560 570 580 590 600
PGGPIYFLKG LSHLHILNLE SNGFDEIPVE VFKDLFELKI IDLGLNNLNT
610 620 630 640 650
LPASVFNNQV SLKSLNLQKN LITSVEKKVF GPAFRNLTEL DMRFNPFDCT
660 670 680 690 700
CESIAWFVNW INETHTNIPE LSSHYLCNTP PHYHGFPVRL FDTSSCKDSA
710 720 730 740 750
PFELFFMINT SILLIFIFIV LLIHFEGWRI SFYWNVSVHR VLGFKEIDRQ
760 770 780 790 800
TEQFEYAAYI IHAYKDKDWV WEHFSSMEKE DQSLKFCLEE RDFEAGVFEL
810 820 830 840 850
EAIVNSIKRS RKIIFVITHH LLKDPLCKRF KVHHAVQQAI EQNLDSIILV
860 870 880 890 900
FLEEIPDYKL NHALCLRRGM FKSHCILNWP VQKERIGAFR HKLQVALGSK

NSVH
Length:904
Mass (Da):103,829
Last modified:January 1, 1998 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i034E05ECA7A4D2F7
GO
Isoform 2 (identifier: O15455-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-277: Missing.

Note: No experimental confirmation available.
Show »
Length:627
Mass (Da):72,937
Checksum:i0D376D88306EBEFC
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RA51D6RA51_HUMAN
Toll-like receptor 3, isoform CRA_b
TLR3 hCG_1787812
351Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti290G → R in BAG36884 (PubMed:14702039).Curated1
Sequence conflicti575D → N in AAH94737 (PubMed:15489334).Curated1
Sequence conflicti605V → A in BAG36884 (PubMed:14702039).Curated1
Sequence conflicti663E → G in BAG36884 (PubMed:14702039).Curated1

<p>This subsection of the ‘Sequence’ section provides information on polymorphic variants. If the variant is associated with a disease state, the description of the latter can be found in the <a href="http://www.uniprot.org/manual/involvement_in_disease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismi

The Phe-412 allele (dbSNP:rs3775291) occurs with a frequency of 30% in populations with European and Asian ancestry, and confers some natural resistance to HIV-1 infection.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_052361284N → I. Corresponds to variant dbSNP:rs5743316Ensembl.1
Natural variantiVAR_052362307Y → D. Corresponds to variant dbSNP:rs5743317EnsemblClinVar.1
Natural variantiVAR_021976412L → F4 PublicationsCorresponds to variant dbSNP:rs3775291EnsemblClinVar.1
Natural variantiVAR_054887554P → S in IIAE2; causes TLR3 deficiency and predisposition to herpes simplex encephalitis. 1 PublicationCorresponds to variant dbSNP:rs121434431EnsemblClinVar.1
Natural variantiVAR_024664737S → T. Corresponds to variant dbSNP:rs5743318EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0541881 – 277Missing in isoform 2. 1 PublicationAdd BLAST277

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
U88879 mRNA Translation: AAC34134.1
DQ445682 mRNA Translation: ABE01399.1
AB445631 mRNA Translation: BAG55028.1
DQ360814 Genomic DNA Translation: ABC86908.1
DQ360815 Genomic DNA Translation: ABC86909.1
DQ360816 Genomic DNA Translation: ABC86910.1
AK302143 mRNA Translation: BAH13636.1
AK314208 mRNA Translation: BAG36884.1
AC104070 Genomic DNA No translation available.
CH471056 Genomic DNA Translation: EAX04628.1
BC094737 mRNA Translation: AAH94737.1
BC096333 mRNA Translation: AAH96333.1
BC096334 mRNA Translation: AAH96334.1
BC096335 mRNA Translation: AAH96335.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS3846.1 [O15455-1]

NCBI Reference Sequences

More...
RefSeqi
NP_003256.1, NM_003265.2 [O15455-1]
XP_016864066.1, XM_017008577.1

UniGene gene-oriented nucleotide sequence clusters

More...
UniGenei
Hs.657724

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000296795; ENSP00000296795; ENSG00000164342 [O15455-1]
ENST00000504367; ENSP00000423684; ENSG00000164342 [O15455-2]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
7098

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:7098

UCSC genome browser

More...
UCSCi
uc003iyq.4 human [O15455-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

TLR3base

TLR3 mutation db

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U88879 mRNA Translation: AAC34134.1
DQ445682 mRNA Translation: ABE01399.1
AB445631 mRNA Translation: BAG55028.1
DQ360814 Genomic DNA Translation: ABC86908.1
DQ360815 Genomic DNA Translation: ABC86909.1
DQ360816 Genomic DNA Translation: ABC86910.1
AK302143 mRNA Translation: BAH13636.1
AK314208 mRNA Translation: BAG36884.1
AC104070 Genomic DNA No translation available.
CH471056 Genomic DNA Translation: EAX04628.1
BC094737 mRNA Translation: AAH94737.1
BC096333 mRNA Translation: AAH96333.1
BC096334 mRNA Translation: AAH96334.1
BC096335 mRNA Translation: AAH96335.1
CCDSiCCDS3846.1 [O15455-1]
RefSeqiNP_003256.1, NM_003265.2 [O15455-1]
XP_016864066.1, XM_017008577.1
UniGeneiHs.657724

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ZIWX-ray2.10A27-700[»]
2A0ZX-ray2.40A22-703[»]
2MK9NMR-A/B698-730[»]
2MKANMR-A/B/C698-730[»]
3ULUX-ray3.52A22-702[»]
3ULVX-ray3.52A22-702[»]
5GS0X-ray3.27A/B27-697[»]
ProteinModelPortaliO15455
SMRiO15455
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112953, 32 interactors
DIPiDIP-29660N
IntActiO15455, 14 interactors
MINTiO15455
STRINGi9606.ENSP00000296795

Chemistry databases

ChEMBLiCHEMBL1075113

PTM databases

iPTMnetiO15455
PhosphoSitePlusiO15455

Polymorphism and mutation databases

BioMutaiTLR3

Proteomic databases

EPDiO15455
jPOSTiO15455
MaxQBiO15455
PaxDbiO15455
PeptideAtlasiO15455
PRIDEiO15455
ProteomicsDBi48678

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000296795; ENSP00000296795; ENSG00000164342 [O15455-1]
ENST00000504367; ENSP00000423684; ENSG00000164342 [O15455-2]
GeneIDi7098
KEGGihsa:7098
UCSCiuc003iyq.4 human [O15455-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
7098
DisGeNETi7098
EuPathDBiHostDB:ENSG00000164342.12

GeneCards: human genes, protein and diseases

More...
GeneCardsi
TLR3
HGNCiHGNC:11849 TLR3
HPAiCAB025658
MalaCardsiTLR3
MIMi603029 gene
613002 phenotype
neXtProtiNX_O15455
OpenTargetsiENSG00000164342
Orphaneti1930 Herpes simplex virus encephalitis
PharmGKBiPA36551

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG4641 Eukaryota
COG4886 LUCA
GeneTreeiENSGT00940000159678
HOGENOMiHOG000251618
HOVERGENiHBG023181
InParanoidiO15455
KOiK05401
OMAiNKYLQLT
OrthoDBi737804at2759
PhylomeDBiO15455
TreeFamiTF325595

Enzyme and pathway databases

ReactomeiR-HSA-1679131 Trafficking and processing of endosomal TLR
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade
R-HSA-168927 TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-1810476 RIP-mediated NFkB activation via ZBP1
R-HSA-5602410 TLR3 deficiency - HSE
R-HSA-5602415 UNC93B1 deficiency - HSE
R-HSA-5602566 TICAM1 deficiency - HSE
R-HSA-5602571 TRAF3 deficiency - HSE
R-HSA-9013957 TLR3-mediated TICAM1-dependent programmed cell death
R-HSA-9013973 TICAM1-dependent activation of IRF3/IRF7
R-HSA-9014325 TICAM1,TRAF6-dependent induction of TAK1 complex
SignaLinkiO15455
SIGNORiO15455

Miscellaneous databases

EvolutionaryTraceiO15455

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
TLR_3

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
7098

Protein Ontology

More...
PROi
PR:O15455

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000164342 Expressed in 179 organ(s), highest expression level in placenta
ExpressionAtlasiO15455 baseline and differential
GenevisibleiO15455 HS

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
IPR027173 TLR3
IPR035897 Toll_tir_struct_dom_sf
PANTHERiPTHR44599 PTHR44599, 1 hit
PfamiView protein in Pfam
PF13516 LRR_6, 1 hit
PF13855 LRR_8, 6 hits
PF01582 TIR, 1 hit
SMARTiView protein in SMART
SM00369 LRR_TYP, 16 hits
SM00082 LRRCT, 1 hit
SM00255 TIR, 1 hit
SUPFAMiSSF52200 SSF52200, 1 hit
PROSITEiView protein in PROSITE
PS51450 LRR, 19 hits
PS50104 TIR, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiTLR3_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: O15455
Secondary accession number(s): B2RAI7
, B7Z7K0, E6Y0F0, E6Y0F1, E9PGH4, Q4VAL2, Q504W0
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: January 1, 1998
Last modified: February 13, 2019
This is version 192 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  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. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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