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UniProtKB - O00206 (TLR4_HUMAN)

Entry version 216 (07 Apr 2021)
Sequence version 2 (01 Jan 1998)
Previous versions | rss
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Protein

Toll-like receptor 4

Gene

TLR4

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

Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) (PubMed:27022195). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:9237759, PubMed:10835634, PubMed:27022195,PubMed:21393102). Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni2+. Responses triggered by Ni2+ require non-conserved histidines and are, therefore, species-specific (PubMed:20711192). Both M.tuberculosis HSP70 (dnaK) and HSP65 (groEL-2) act via this protein to stimulate NF-kappa-B expression (PubMed:15809303). In complex with TLR6, promotes sterile inflammation in monocytes/macrophages in response to oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42. In this context, the initial signal is provided by oxLDL- or amyloid-beta 42-binding to CD36. This event induces the formation of a heterodimer of TLR4 and TLR6, which is rapidly internalized and triggers inflammatory response, leading to the NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion. Binds electronegative LDL (LDL-) and mediates the cytokine release induced by LDL- (PubMed:23880187). Stimulation of monocytes in vitro with M.tuberculosis PstS1 induces p38 MAPK and ERK1/2 activation primarily via TLR2, but also partially via this receptor (PubMed:16622205, PubMed:10835634, PubMed:15809303, PubMed:17478729, PubMed:20037584, PubMed:20711192, PubMed:23880187, PubMed:27022195, PubMed:9237759). Activated by the signaling pathway regulator NMI which acts as damage-associated molecular patterns (DAMPs) in response to cell injury or pathogen invasion, therefore promoting nuclear factor NF-kappa-B activation (PubMed:29038465).10 Publications

Miscellaneous

His-456 and His-458 are found in TLR4 of human and several other primate species and may be responsible for inflammatory responses triggered by nickel (Ni2+). Ni2+ may cross-link the two receptor monomers through specific histidines, triggering the formation of a dimer that structurally resembles that induced by LPS. This process may be the basis for the development of contact allergy to Ni2+. A mouse model of contact allergy to Ni2+ in which TLR4-deficient mice expresses human TLR4 has been proposed.1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei750PROSITE-ProRule annotation1

<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

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<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 functionHydrolase, Receptor
Biological processImmunity, Inflammatory response, Innate immunity
LigandNAD

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		O00206

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-1236974, ER-Phagosome pathway
R-HSA-140534, Caspase activation via Death Receptors in the presence of ligand
R-HSA-166016, Toll Like Receptor 4 (TLR4) Cascade
R-HSA-166058, MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-166166, MyD88-independent TLR4 cascade
R-HSA-2562578, TRIF-mediated programmed cell death
R-HSA-5602498, MyD88 deficiency (TLR2/4)
R-HSA-5603041, IRAK4 deficiency (TLR2/4)
R-HSA-5686938, Regulation of TLR by endogenous ligand
R-HSA-936964, Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
R-HSA-937041, IKK complex recruitment mediated by RIP1
R-HSA-937072, TRAF6-mediated induction of TAK1 complex within TLR4 complex
R-HSA-975163, IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation

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

More...SignaLinki		O00206

SIGNOR Signaling Network Open Resource

More...SIGNORi		O00206

Protein family/group databases

Transport Classification Database

More...TCDBi		8.A.43.1.9, the neat-domain containing methaemoglobin heme sequestration (n-mhs) family

<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%5Fand%5Ftaxonomy%5Fsection">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 4 (EC:3.2.2.6PROSITE-ProRule annotation)
Alternative name(s):
hToll
CD_antigen: CD284
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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:TLR4
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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%5Fand%5Ftaxonomy%5Fsection">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%5Fand%5Ftaxonomy%5Fsection">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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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%5Fmanual">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 9

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:11850, TLR4

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		603030, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_O00206

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000136869.13

<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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'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 – 631ExtracellularSequence analysisAdd BLAST608
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'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>Transmembranei632 – 652HelicalSequence analysisAdd BLAST21
Topological domaini653 – 839CytoplasmicSequence analysisAdd BLAST187

Keywords - Cellular componenti

Cell membrane, Cell projection, 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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'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>Mutagenesisi431H → A: Partially diminishes NF-kappa-B activation induced by Ni(2+). Strongly reduces NF-kappa-B activation induced by Ni(2+); when associated with A-456 or A-458. 1 Publication1
Mutagenesisi456H → A: Partially diminishes NF-kappa-B activation induced by Ni(2+). Strongly reduces NF-kappa-B activation induced by Ni(2+); when associated with A-431. Suppresses NF-kappa-B activation induced by Ni(2+); when associated with A-458. 1 Publication1
Mutagenesisi458H → A: Partially diminishes NF-kappa-B activation induced by Ni(2+). Strongly reduces NF-kappa-B activation induced by Ni(2+); when associated with A-431. Suppresses NF-kappa-B activation induced by Ni(2+); when associated with A-456. 1 Publication1
Mutagenesisi526N → A: Abolishes LPS-response and prevents the cell surface expression. 1 Publication1
Mutagenesisi575N → A: Abolishes LPS-response and prevents the cell surface expression. 1 Publication1
Mutagenesisi697E → R: Abolishes LPS-response. 1 Publication1
Mutagenesisi710R → E: Abolishes LPS-response. 1 Publication1
Mutagenesisi711D → K: Abolishes LPS-response. 1 Publication1
Mutagenesisi714P → H, R or E: Abolishes MYD88-binding and LPS-response. 1 Publication1

Keywords - Diseasei

Age-related macular degeneration

Organism-specific databases

DisGeNET

More...DisGeNETi		7099

MalaCards human disease database

More...MalaCardsi		TLR4

Open Targets

More...OpenTargetsi		ENSG00000136869

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

More...Orphaneti		117, Behcet disease

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA36552

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		O00206, Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL5255

Drug and drug target database

More...DrugBanki		DB02767, (R)-3-hydroxytetradecanoic acid
DB00924, Cyclobenzaprine
DB06447, E5531
DB04933, Eritoran
DB05475, Golotimod
DB03017, Lauric acid
DB13615, Mifamurtide
DB08231, Myristic acid
DB01183, Naloxone
DB11193, Papain

DrugCentral

More...DrugCentrali		O00206

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		1754

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		TLR4

<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 or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000003472224 – 839Toll-like receptor 4Add BLAST816

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 bondi29 ↔ 402 Publications
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">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>Glycosylationi35N-linked (GlcNAc...) asparagine3 Publications1
Glycosylationi173N-linked (GlcNAc...) asparagine4 Publications1
Glycosylationi205N-linked (GlcNAc...) asparagine3 Publications1
Disulfide bondi281 ↔ 3061 Publication
Glycosylationi282N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi309N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi390 ↔ 3911 Publication
Glycosylationi497N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi526N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi575N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi583 ↔ 6091 Publication
Disulfide bondi585 ↔ 6271 Publication
Glycosylationi624N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi630N-linked (GlcNAc...) asparagineSequence analysis1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">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

N-glycosylated. Glycosylation of Asn-526 and Asn-575 seems to be necessary for the expression of TLR4 on the cell surface and the LPS-response. Likewise, mutants lacking two or more of the other N-glycosylation sites were deficient in interaction with LPS.4 Publications
Phosphorylated on tyrosine residues by LYN after binding lipopolysaccharide.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		O00206

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

More...PaxDbi		O00206

PeptideAtlas

More...PeptideAtlasi		O00206

PRoteomics IDEntifications database

More...PRIDEi		O00206

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		47779 [O00206-1]
47780 [O00206-2]
47781 [O00206-3]

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		O00206, 10 sites

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		O00206

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

More...PhosphoSitePlusi		O00206

<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

Highly expressed in placenta, spleen and peripheral blood leukocytes (PubMed:9435236, PubMed:9237759). Detected in monocytes, macrophages, dendritic cells and several types of T-cells (PubMed:9237759, PubMed:27022195).3 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000136869, Expressed in leukocyte and 198 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		O00206, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		O00206, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000136869, Low tissue specificity

<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%5Fsection">'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%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, LY96 and TLR4 (PubMed:11274165). Binding to bacterial LPS leads to homodimerization.

Interacts with LY96 via the extracellular domain (PubMed:17803912, PubMed:19252480).

Interacts with MYD88 and TIRAP via their respective TIR domains (By similarity).

Interacts with TICAM2 (PubMed:14519765, PubMed:25736436).

Interacts with NOX4 (PubMed:15356101).

Interacts with CNPY3 (By similarity).

Interacts with HSP90B1. The interaction with both CNPY3 and HSP90B1 is required for proper folding in the endoplasmic reticulum.

Interacts with MAP3K21; this interaction leads to negative regulation of TLR4 signaling (PubMed:21602844).

Interacts with CD36, following CD36 stimulation by oxLDL or amyloid-beta 42, and forms a heterodimer with TLR6 (PubMed:20037584). The trimeric complex is internalized and triggers inflammatory response. LYN kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation.

Interacts with TICAM1 in response to LPS in a WDFY1-dependent manner (PubMed:25736436).

Interacts with WDFY1 in response to LPS (By similarity).

Interacts with SMPDL3B (By similarity).

Interacts with CEACAM1; upon lipopolysaccharide stimulation, forms a complex including TLR4 and the phosphorylated form of SYK and CEACAM1, which in turn, recruits PTPN6 that dephosphorylates SYK, reducing the production of reactive oxygen species (ROS) and lysosome disruption, which in turn, reduces the activity of the inflammasome (By similarity).

Interacts with RFTN1; the interaction occurs in response to lipopolysaccharide stimulation (PubMed:27022195).

Interacts with SCIMP; the interaction occurs in response to lipopolysaccharide stimulation and is enhanced by phosphorylation of SCIMP by LYN (By similarity). This interaction facilitates the phosphorylation of TLR4 by LYN which elicits a selective cytokine response in macrophages (By similarity).

Interacts with TRAF3IP3 (PubMed:30573680).

Interacts with TREM1; this interaction enhances TLR4-mediated inflammatory response (PubMed:21393102, PubMed:17098818).

By similarity13 Publications

(Microbial infection) In case of infection, interacts with uropathogenic E.coli protein TcpC.

1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">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="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		112954, 36 interactors

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		O00206

Database of interacting proteins

More...DIPi		DIP-34769N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

More...ELMi		O00206

Protein interaction database and analysis system

More...IntActi		O00206, 31 interactors

Molecular INTeraction database

More...MINTi		O00206

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000363089

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		O00206

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		O00206, protein

<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

1839
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

More...SMRi		O00206

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		O00206

<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 '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>Repeati55 – 76LRR 1Add BLAST22
Repeati79 – 100LRR 2Add BLAST22
Repeati103 – 124LRR 3Add BLAST22
Repeati127 – 148LRR 4Add BLAST22
Repeati151 – 172LRR 5Add BLAST22
Repeati176 – 199LRR 6Add BLAST24
Repeati205 – 225LRR 7Add BLAST21
Repeati227 – 247LRR 8Add BLAST21
Repeati331 – 351LRR 9Add BLAST21
Repeati352 – 373LRR 10Add BLAST22
Repeati374 – 394LRR 11Add BLAST21
Repeati400 – 422LRR 12Add BLAST23
Repeati423 – 444LRR 13Add BLAST22
Repeati448 – 456LRR 149
Repeati472 – 495LRR 15Add BLAST24
Repeati497 – 518LRR 16Add BLAST22
Repeati521 – 542LRR 17Add BLAST22
Repeati545 – 565LRR 18Add BLAST21
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">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>Domaini579 – 629LRRCTAdd BLAST51
Domaini672 – 815TIRPROSITE-ProRule annotationAdd BLAST144

<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

The TIR domain mediates interaction with NOX4.1 Publication
The TIR domain mediates NAD+ hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity.PROSITE-ProRule annotation

<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

More...eggNOGi		KOG4641, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00940000160778

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_006000_5_0_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		O00206

Identification of Orthologs from Complete Genome Data

More...OMAi		AHNLIHS

Database of Orthologous Groups

More...OrthoDBi		282372at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		O00206

TreeFam database of animal gene trees

More...TreeFami		TF351113

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		3.40.50.10140, 1 hit
3.80.10.10, 1 hit

Integrated resource of protein families, domains and functional sites

More...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
IPR017241, Toll-like_receptor
IPR035897, Toll_tir_struct_dom_sf

The PANTHER Classification System

More...PANTHERi		PTHR24365, PTHR24365, 1 hit

Pfam protein domain database

More...Pfami		View protein in Pfam
PF13855, LRR_8, 3 hits
PF01582, TIR, 1 hit

PIRSF; a whole-protein classification database

More...PIRSFi		PIRSF037595, Toll-like_receptor, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00369, LRR_TYP, 11 hits
SM00082, LRRCT, 1 hit
SM00255, TIR, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF52200, SSF52200, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS51450, LRR, 11 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%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">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%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">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 3 <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. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: O00206-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali 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
MMSASRLAGT LIPAMAFLSC VRPESWEPCV EVVPNITYQC MELNFYKIPD 
        60         70         80         90        100
NLPFSTKNLD LSFNPLRHLG SYSFFSFPEL QVLDLSRCEI QTIEDGAYQS 
       110        120        130        140        150
LSHLSTLILT GNPIQSLALG AFSGLSSLQK LVAVETNLAS LENFPIGHLK 
       160        170        180        190        200
TLKELNVAHN LIQSFKLPEY FSNLTNLEHL DLSSNKIQSI YCTDLRVLHQ 
       210        220        230        240        250
MPLLNLSLDL SLNPMNFIQP GAFKEIRLHK LTLRNNFDSL NVMKTCIQGL 
       260        270        280        290        300
AGLEVHRLVL GEFRNEGNLE KFDKSALEGL CNLTIEEFRL AYLDYYLDDI 
       310        320        330        340        350
IDLFNCLTNV SSFSLVSVTI ERVKDFSYNF GWQHLELVNC KFGQFPTLKL 
       360        370        380        390        400
KSLKRLTFTS NKGGNAFSEV DLPSLEFLDL SRNGLSFKGC CSQSDFGTTS 
       410        420        430        440        450
LKYLDLSFNG VITMSSNFLG LEQLEHLDFQ HSNLKQMSEF SVFLSLRNLI 
       460        470        480        490        500
YLDISHTHTR VAFNGIFNGL SSLEVLKMAG NSFQENFLPD IFTELRNLTF 
       510        520        530        540        550
LDLSQCQLEQ LSPTAFNSLS SLQVLNMSHN NFFSLDTFPY KCLNSLQVLD 
       560        570        580        590        600
YSLNHIMTSK KQELQHFPSS LAFLNLTQND FACTCEHQSF LQWIKDQRQL 
       610        620        630        640        650
LVEVERMECA TPSDKQGMPV LSLNITCQMN KTIIGVSVLS VLVVSVVAVL 
       660        670        680        690        700
VYKFYFHLML LAGCIKYGRG ENIYDAFVIY SSQDEDWVRN ELVKNLEEGV 
       710        720        730        740        750
PPFQLCLHYR DFIPGVAIAA NIIHEGFHKS RKVIVVVSQH FIQSRWCIFE 
       760        770        780        790        800
YEIAQTWQFL SSRAGIIFIV LQKVEKTLLR QQVELYRLLS RNTYLEWEDS 
       810        820        830 
VLGRHIFWRR LRKALLDGKS WNPEGTVGTG CNWQEATSI
Length:839
Mass (Da):95,680
Last modified:January 1, 1998 - v2
<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:i92C48F55821133E8
GO
Isoform 2 (identifier: O00206-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-40: Missing.

Show »
Length:799
Mass (Da):91,296
Checksum:i82F70995E7F2AF9D
GO
Isoform 3 (identifier: O00206-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-200: Missing.

Show »
Length:639
Mass (Da):73,301
Checksum:i23C1406CE32427EC
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
A0A2R8Y7P4A0A2R8Y7P4_HUMAN
Toll-like receptor 4
TLR4
32Annotation score:

Annotation score:1 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 conflicti73S → R in ABU41664 (Ref. 11) Curated1
Sequence conflicti400S → C in BAF82742 (PubMed:14702039).Curated1
Sequence conflicti581F → S in BAG64706 (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%5Fin%5Fdisease">'Involvement in disease'</a> subsection.<p><a href='/help/polymorphism' target='_top'>More...</a></p>Polymorphismi

Allele TLR4*B (Gly-299, Ile-399) is associated with a blunted response to inhaled LPS.1 Publication

Natural variant

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_021977175T → A. Corresponds to variant dbSNP:rs16906079Ensembl.1
Natural variantiVAR_018729188Q → R1 PublicationCorresponds to variant dbSNP:rs5030713Ensembl.1
Natural variantiVAR_018730246C → S1 PublicationCorresponds to variant dbSNP:rs5030714Ensembl.1
Natural variantiVAR_074187287E → D1 Publication1
Natural variantiVAR_012739299D → G in allele TLR4*B; reduced LPS-response; associated with an increased risk for age-related macular degeneration in Caucasian carriers. 5 PublicationsCorresponds to variant dbSNP:rs4986790EnsemblClinVar.1
Natural variantiVAR_047563306C → W. Corresponds to variant dbSNP:rs2770145Ensembl.1
Natural variantiVAR_047564310V → G. Corresponds to variant dbSNP:rs2770144Ensembl.1
Natural variantiVAR_018731329N → S1 PublicationCorresponds to variant dbSNP:rs5030715Ensembl.1
Natural variantiVAR_020334342F → Y. Corresponds to variant dbSNP:rs5031050Ensembl.1
Natural variantiVAR_037668385L → F. Corresponds to variant dbSNP:rs11536884Ensembl.1
Natural variantiVAR_012740399T → I in allele TLR4*B; reduced LPS-response. 4 PublicationsCorresponds to variant dbSNP:rs4986791EnsemblClinVar.1
Natural variantiVAR_020335400S → N. Corresponds to variant dbSNP:rs4987233Ensembl.1
Natural variantiVAR_018732443F → L1 PublicationCorresponds to variant dbSNP:rs5030716Ensembl.1
Natural variantiVAR_018733474E → K1 PublicationCorresponds to variant dbSNP:rs5030718Ensembl.1
Natural variantiVAR_018734510Q → H1 PublicationCorresponds to variant dbSNP:rs5030719Ensembl.1
Natural variantiVAR_018735694K → R1 PublicationCorresponds to variant dbSNP:rs5030722Ensembl.1
Natural variantiVAR_018736763R → H1 PublicationCorresponds to variant dbSNP:rs5030723Ensembl.1
Natural variantiVAR_018737834Q → H1 Publication1

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_0357931 – 200Missing in isoform 3. 1 PublicationAdd BLAST200
Alternative sequenceiVSP_0357941 – 40Missing in isoform 2. 2 PublicationsAdd BLAST40

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
U93091 mRNA Translation: AAC80227.1
AB445638 mRNA Translation: BAG55035.1
DQ018107 Genomic DNA Translation: AAY82267.1
DQ018108 Genomic DNA Translation: AAY82268.1
DQ018109 Genomic DNA Translation: AAY82269.1
AK290053 mRNA Translation: BAF82742.1
AK293068 mRNA Translation: BAF85757.1
AK303730 mRNA Translation: BAG64706.1
AL160272 Genomic DNA No translation available.
CH471090 Genomic DNA Translation: EAW87448.1
CH471090 Genomic DNA Translation: EAW87451.1
BC117422 mRNA Translation: AAI17423.1
EF535831 Genomic DNA Translation: ABU41662.1
EF535832 Genomic DNA Translation: ABU41663.1
EF535833 Genomic DNA Translation: ABU41664.1
AF177765 Genomic DNA Translation: AAF05316.1
AF177766 Genomic DNA Translation: AAF07823.1
AF172171, AF172169, AF172170 Genomic DNA Translation: AAF89753.1
U88880 mRNA Translation: AAC34135.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS6818.1 [O00206-1]

NCBI Reference Sequences

More...RefSeqi		NP_003257.1, NM_003266.3 [O00206-2]
NP_612564.1, NM_138554.4 [O00206-1]
NP_612567.1, NM_138557.2 [O00206-3]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000355622; ENSP00000363089; ENSG00000136869 [O00206-1]
ENST00000394487; ENSP00000377997; ENSG00000136869 [O00206-2]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		7099

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:7099

UCSC genome browser

More...UCSCi		uc004bjz.5, human [O00206-1]

Keywords - Coding sequence diversityi

Alternative splicing

<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%5Freferences%5Fsection">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

Protein Spotlight

Zips, necklaces and mobile telephones - Issue 134 of December 2011

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U93091 mRNA Translation: AAC80227.1
AB445638 mRNA Translation: BAG55035.1
DQ018107 Genomic DNA Translation: AAY82267.1
DQ018108 Genomic DNA Translation: AAY82268.1
DQ018109 Genomic DNA Translation: AAY82269.1
AK290053 mRNA Translation: BAF82742.1
AK293068 mRNA Translation: BAF85757.1
AK303730 mRNA Translation: BAG64706.1
AL160272 Genomic DNA No translation available.
CH471090 Genomic DNA Translation: EAW87448.1
CH471090 Genomic DNA Translation: EAW87451.1
BC117422 mRNA Translation: AAI17423.1
EF535831 Genomic DNA Translation: ABU41662.1
EF535832 Genomic DNA Translation: ABU41663.1
EF535833 Genomic DNA Translation: ABU41664.1
AF177765 Genomic DNA Translation: AAF05316.1
AF177766 Genomic DNA Translation: AAF07823.1
AF172171, AF172169, AF172170 Genomic DNA Translation: AAF89753.1
U88880 mRNA Translation: AAC34135.1
CCDSiCCDS6818.1 [O00206-1]
RefSeqiNP_003257.1, NM_003266.3 [O00206-2]
NP_612564.1, NM_138554.4 [O00206-1]
NP_612567.1, NM_138557.2 [O00206-3]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Z62X-ray1.70A27-228[»]
2Z63X-ray2.00A27-527[»]
2Z65X-ray2.70A/B27-228[»]
2Z66X-ray1.90A/B/C/D381-627[»]
3FXIX-ray3.10A/B27-631[»]
3UL7X-ray2.37A28-226[»]
3UL8X-ray2.50A27-228[»]
3UL9X-ray2.45A28-228[»]
3ULAX-ray3.60A/C27-228[»]
4G8AX-ray2.40A/B23-629[»]
5NAMNMR-A623-670[»]
5NAONMR-A623-657[»]
SMRiO00206
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi112954, 36 interactors
CORUMiO00206
DIPiDIP-34769N
ELMiO00206
IntActiO00206, 31 interactors
MINTiO00206
STRINGi9606.ENSP00000363089

Chemistry databases

BindingDBiO00206
ChEMBLiCHEMBL5255
DrugBankiDB02767, (R)-3-hydroxytetradecanoic acid
DB00924, Cyclobenzaprine
DB06447, E5531
DB04933, Eritoran
DB05475, Golotimod
DB03017, Lauric acid
DB13615, Mifamurtide
DB08231, Myristic acid
DB01183, Naloxone
DB11193, Papain
DrugCentraliO00206
GuidetoPHARMACOLOGYi1754

Protein family/group databases

TCDBi8.A.43.1.9, the neat-domain containing methaemoglobin heme sequestration (n-mhs) family

PTM databases

GlyGeniO00206, 10 sites
iPTMnetiO00206
PhosphoSitePlusiO00206

Genetic variation databases

BioMutaiTLR4

Proteomic databases

MassIVEiO00206
PaxDbiO00206
PeptideAtlasiO00206
PRIDEiO00206
ProteomicsDBi47779 [O00206-1]
47780 [O00206-2]
47781 [O00206-3]

Protocols and materials databases

ABCD curated depository of sequenced antibodies

More...ABCDi		O00206, 21 sequenced antibodies

Antibodypedia a portal for validated antibodies

More...Antibodypediai		3410, 1864 antibodies

Genome annotation databases

EnsembliENST00000355622; ENSP00000363089; ENSG00000136869 [O00206-1]
ENST00000394487; ENSP00000377997; ENSG00000136869 [O00206-2]
GeneIDi7099
KEGGihsa:7099
UCSCiuc004bjz.5, human [O00206-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		7099
DisGeNETi7099

GeneCards: human genes, protein and diseases

More...GeneCardsi		TLR4
HGNCiHGNC:11850, TLR4
HPAiENSG00000136869, Low tissue specificity
MalaCardsiTLR4
MIMi603030, gene
neXtProtiNX_O00206
OpenTargetsiENSG00000136869
Orphaneti117, Behcet disease
PharmGKBiPA36552
VEuPathDBiHostDB:ENSG00000136869.13

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG4641, Eukaryota
GeneTreeiENSGT00940000160778
HOGENOMiCLU_006000_5_0_1
InParanoidiO00206
OMAiAHNLIHS
OrthoDBi282372at2759
PhylomeDBiO00206
TreeFamiTF351113

Enzyme and pathway databases

PathwayCommonsiO00206
ReactomeiR-HSA-1236974, ER-Phagosome pathway
R-HSA-140534, Caspase activation via Death Receptors in the presence of ligand
R-HSA-166016, Toll Like Receptor 4 (TLR4) Cascade
R-HSA-166058, MyD88:MAL(TIRAP) cascade initiated on plasma membrane
R-HSA-166166, MyD88-independent TLR4 cascade
R-HSA-2562578, TRIF-mediated programmed cell death
R-HSA-5602498, MyD88 deficiency (TLR2/4)
R-HSA-5603041, IRAK4 deficiency (TLR2/4)
R-HSA-5686938, Regulation of TLR by endogenous ligand
R-HSA-936964, Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
R-HSA-937041, IKK complex recruitment mediated by RIP1
R-HSA-937072, TRAF6-mediated induction of TAK1 complex within TLR4 complex
R-HSA-975163, IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation
SignaLinkiO00206
SIGNORiO00206

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		7099, 5 hits in 985 CRISPR screens
EvolutionaryTraceiO00206

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		TLR_4

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

More...GenomeRNAii		7099
PharosiO00206, Tchem

Protein Ontology

More...PROi		PR:O00206
RNActiO00206, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000136869, Expressed in leukocyte and 198 other tissues
ExpressionAtlasiO00206, baseline and differential
GenevisibleiO00206, 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
IPR017241, Toll-like_receptor
IPR035897, Toll_tir_struct_dom_sf
PANTHERiPTHR24365, PTHR24365, 1 hit
PfamiView protein in Pfam
PF13855, LRR_8, 3 hits
PF01582, TIR, 1 hit
PIRSFiPIRSF037595, Toll-like_receptor, 1 hit
SMARTiView protein in SMART
SM00369, LRR_TYP, 11 hits
SM00082, LRRCT, 1 hit
SM00255, TIR, 1 hit
SUPFAMiSSF52200, SSF52200, 1 hit
PROSITEiView protein in PROSITE
PS51450, LRR, 11 hits
PS50104, TIR, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		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 nameiTLR4_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: O00206
Secondary accession number(s): A8K1Y8
, A9XLP9, A9XLQ0, A9XLQ1, B4E194, D1CS52, D1CS53, Q5VZI8, Q5VZI9, Q9UK78, Q9UM57
<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%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: January 1, 1998
Last modified: April 7, 2021
This is version 216 of the entry and version 2 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, Direct protein sequencing, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  3. Human entries with genetic variants
    List of human entries with genetic variants
  4. Human variants curated from literature reports
    Index of human variants curated from literature reports
  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. SIMILARITY comments
    Index of protein domains and families
  8. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
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