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Aliases for TLR4 Gene

Aliases for TLR4 Gene

  • Toll-Like Receptor 4 2 3
  • ARMD10 3 6
  • HToll 3 4
  • Homolog Of Drosophila Toll 3
  • CD284 Antigen 4
  • CD284 3
  • TLR-4 3
  • TOLL 3

External Ids for TLR4 Gene

Summaries for TLR4 Gene

Entrez Gene Summary for TLR4 Gene

  • The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This receptor has been implicated in signal transduction events induced by lipopolysaccharide (LPS) found in most gram-negative bacteria. Mutations in this gene have been associated with differences in LPS responsiveness. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

GeneCards Summary for TLR4 Gene

TLR4 (Toll-Like Receptor 4) is a Protein Coding gene. Diseases associated with TLR4 include macular degeneration, age-related, 10 and behcets disease. Among its related pathways are PI3K-Akt signaling pathway and Proteoglycans in cancer. GO annotations related to this gene include receptor activity and lipopolysaccharide binding. An important paralog of this gene is TLR6.

UniProtKB/Swiss-Prot for TLR4 Gene

  • Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+). Responses triggered by Ni(2+) require non-conserved histidines and are, therefore, species-specific. 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.

Tocris Summary for TLR4 Gene

  • Toll-like receptors (TLRs) are single transmembrane cell-surface receptors, which have a key role in the innate immune system. TLRs generally exist as homodimers (although TLR2-TLR6 heterodimers have been reported) and are found on immune cells such as macrophages, B lymphocytes and mast cells. Toll-like receptors are activated by molecules associated with biological threat and are highly specific towards evolutionary conserved entities on microbes, such as bacterial cell-surface lipopolysaccharides, flagella and unmethylated CpG islands. It has been suggested that some toll-like receptors may have endogenous ligands, such as Hsp60 and fibrinogen, and this has promoted speculation that endogenous toll-like receptor activators may have a pathological role in autoimmune disease. Activation of toll-like receptors initiates downstream signaling cascades, initially via the adapter molecules MyD88, Trap, Trif and Tram, which converge on the PI 3-K and NF-kappaB pathways and regulate intracellular kinases and gene expression. This can stimulate an inflammatory and/or antigen-specific immune response. The signaling cascade coupled to toll-like receptor activation is very similar to that of interleukin-1 receptor (IL-1R) activation.

Gene Wiki entry for TLR4 Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TLR4 Gene

Genomics for TLR4 Gene

Genomic Location for TLR4 Gene

Start:
117,704,175 bp from pter
End:
117,717,491 bp from pter
Size:
13,317 bases
Orientation:
Plus strand

Genomic View for TLR4 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for TLR4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TLR4 Gene

Regulatory Elements for TLR4 Gene

Proteins for TLR4 Gene

  • Protein details for TLR4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O00206-TLR4_HUMAN
    Recommended name:
    Toll-like receptor 4
    Protein Accession:
    O00206
    Secondary Accessions:
    • A8K1Y8
    • A9XLP9
    • A9XLQ0
    • A9XLQ1
    • B4E194
    • D1CS52
    • D1CS53
    • Q5VZI8
    • Q5VZI9
    • Q9UK78
    • Q9UM57

    Protein attributes for TLR4 Gene

    Size:
    839 amino acids
    Molecular mass:
    95680 Da
    Quaternary structure:
    • Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, LY96 and TLR4. Binding to bacterial LPS leads to homodimerization. Interacts with LY96 via the extracellular domain. Interacts with MYD88 and TIRAP via their respective TIR domains. Interacts with NOX4. 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 MLK4; this interaction leads to negative regulation of TLR4 signaling. Interacts with CD36, following CD36 stimulation by oxLDL or amyloid-beta 42, and forms a heterodimer with TLR6. The trimeric complex is internalized and triggers inflammatory response. LYN kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation.
    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 (Ni(2+)). Ni(2+) 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 Ni(2+). A mouse model of contact allergy to Ni(2+) in which TLR4-deficient mice expresses human TLR4 has been proposed

    Three dimensional structures from OCA and Proteopedia for TLR4 Gene

    Alternative splice isoforms for TLR4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TLR4 Gene

Proteomics data for TLR4 Gene at MOPED

Post-translational modifications for TLR4 Gene

  • 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.
  • Modification sites at PhosphoSitePlus
  • Glycosylation at Asn35, Asn173, Asn205, Asn282, Asn309, Asn497, Asn526, Asn575, Asn624, and Asn630

Other Protein References for TLR4 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

No data available for DME Specific Peptides for TLR4 Gene

Domains for TLR4 Gene

Gene Families for TLR4 Gene

HGNC:
  • CD :CD molecules
IUPHAR :

UniProtKB/Swiss-Prot:

TLR4_HUMAN
Domain:
  • The TIR domain mediates interaction with NOX4:
    • O00206
  • Contains 1 LRRCT domain.:
    • O00206
  • Contains 1 TIR domain.:
    • O00206
Family:
  • Belongs to the Toll-like receptor family.:
    • O00206
Similarity:
  • Contains 18 LRR (leucine-rich) repeats.:
    • O00206
genes like me logo Genes that share domains with TLR4: view

Function for TLR4 Gene

Molecular function for TLR4 Gene

GENATLAS Biochemistry: Drosophila transmembrane receptor Toll homolog 4,specifically expressed in placenta,and on cells of the immune system binding directly to TLR2 and essential component of liposaccharides (LPS) receptor,inducing the LPS signaling pathway
UniProtKB/Swiss-Prot Function: Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+). Responses triggered by Ni(2+) require non-conserved histidines and are, therefore, species-specific. 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.

Gene Ontology (GO) - Molecular Function for TLR4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001530 lipopolysaccharide binding NAS 10835634
GO:0001875 lipopolysaccharide receptor activity IDA 19252480
GO:0004872 receptor activity TAS 10426995
GO:0004888 transmembrane signaling receptor activity NAS 11970998
GO:0005515 protein binding IPI 11441107
genes like me logo Genes that share ontologies with TLR4: view
genes like me logo Genes that share phenotypes with TLR4: view

Animal Models for TLR4 Gene

MGI Knock Outs for TLR4:

miRNA for TLR4 Gene

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for TLR4 Gene

Localization for TLR4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TLR4 Gene

Cell membrane; Single-pass type I membrane protein. Note=Upon complex formation with CD36 and TLR6, internalized through dynamin-dependent endocytosis. {ECO:0000269 PubMed:20037584}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for TLR4 Gene COMPARTMENTS Subcellular localization image for TLR4 gene
Compartment Confidence
plasma membrane 5
endosome 4
extracellular 3
nucleus 3
cytoskeleton 2
cytosol 2
endoplasmic reticulum 2
golgi apparatus 2
lysosome 2
vacuole 2
mitochondrion 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for TLR4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IDA 19740627
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane IDA 15027902
GO:0009897 external side of plasma membrane IDA 16514062
GO:0010008 endosome membrane TAS --
genes like me logo Genes that share ontologies with TLR4: view

Pathways for TLR4 Gene

genes like me logo Genes that share pathways with TLR4: view

Gene Ontology (GO) - Biological Process for TLR4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000187 activation of MAPK activity ISS --
GO:0002218 activation of innate immune response --
GO:0002224 toll-like receptor signaling pathway TAS --
GO:0002322 B cell proliferation involved in immune response IEA --
GO:0002537 nitric oxide production involved in inflammatory response IEA --
genes like me logo Genes that share ontologies with TLR4: view

Compounds for TLR4 Gene

(5) Tocris Compounds for TLR4 Gene

Compound Action Cas Number
Imiquimod Toll-like receptor 7 (TLR7) agonist [99011-02-6]
Pam2CSK4 TLR2/6 agonist; induces TNF-alpha production [868247-72-7]
Pam3CSK4 TLR1/2 agonist; induces cytokine production [112208-00-1]
Poly(I:C) TLR3 agonist [42424-50-0]
Resiquimod Toll-like receptor 7 (TLR7) agonist [144875-48-9]

(3) Drugbank Compounds for TLR4 Gene

Compound Synonyms Cas Number Type Actions PubMed IDs
3-Hydroxy-Myristic Acid
target
MYRISTIC ACID
target
Naloxone
  • EN 1530 Base
465-65-6 target inhibitor

(2) IUPHAR Ligand for TLR4 Gene

Ligand Type Action Affinity Pubmed IDs
taxol Agonist Agonist 5.3
LPS Agonist Agonist

(95) Novoseek inferred chemical compound relationships for TLR4 Gene

Compound -log(P) Hits PubMed IDs
lipoteichoic acid 83.8 45
endotoxin 81.3 164
peptidoglycan 80.9 75
poly(i-c) 73.7 15
flagellin 73.5 26

(3) PharmGKB related drug/compound annotations for TLR4 Gene

Drug/compound Annotation
folic acid CA
methotrexate CA
pravastatin CA
genes like me logo Genes that share compounds with TLR4: view

Transcripts for TLR4 Gene

Unigene Clusters for TLR4 Gene

Toll-like receptor 4:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for TLR4 Gene

ExUns: 1a · 1b · 1c ^ 2 ^ 3a · 3b ^ 4a · 4b · 4c
SP1: -
SP2: - -
SP3: - - -
SP4:

Relevant External Links for TLR4 Gene

GeneLoc Exon Structure for
TLR4
ECgene alternative splicing isoforms for
TLR4

Expression for TLR4 Gene

mRNA expression in normal human tissues for TLR4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for TLR4 Gene

This gene is overexpressed in Whole Blood (15.3).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, and MOPED for TLR4 Gene

SOURCE GeneReport for Unigene cluster for TLR4 Gene Hs.174312

mRNA Expression by UniProt/SwissProt for TLR4 Gene

O00206-TLR4_HUMAN
Tissue specificity: Highly expressed in placenta, spleen and peripheral blood leukocytes. Detected in monocytes, macrophages, dendritic cells and several types of T-cells
genes like me logo Genes that share expressions with TLR4: view

Orthologs for TLR4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for TLR4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TLR4 36
  • 99.76 (n)
  • 99.64 (a)
TLR4 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia TLR4 36
  • 81.58 (n)
  • 76.48 (a)
TLR4 37
  • 76 (a)
OneToOne
dog
(Canis familiaris)
Mammalia TLR4 36
  • 82.28 (n)
  • 74.33 (a)
TLR4 37
  • 74 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Tlr4 36
  • 75.16 (n)
  • 67.84 (a)
Tlr4 16
Tlr4 37
  • 67 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia TLR4 37
  • 55 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TLR4 37
  • 53 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Tlr4 36
  • 75.19 (n)
  • 67.11 (a)
chicken
(Gallus gallus)
Aves TLR4 36
  • 55.84 (n)
  • 46.69 (a)
TLR4 37
  • 45 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TLR4 37
  • 44 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii tlr4al 37
  • 38 (a)
OneToMany
tlr4ba 36
  • 50.6 (n)
  • 40.3 (a)
tlr4ba 37
  • 39 (a)
OneToMany
tlr4bb 37
  • 38 (a)
OneToMany
Species with no ortholog for TLR4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for TLR4 Gene

ENSEMBL:
Gene Tree for TLR4 (if available)
TreeFam:
Gene Tree for TLR4 (if available)

Paralogs for TLR4 Gene

Paralogs for TLR4 Gene

Selected SIMAP similar genes for TLR4 Gene using alignment to 10 proteins:

genes like me logo Genes that share paralogs with TLR4: view

Variants for TLR4 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for TLR4 Gene

O00206-TLR4_HUMAN
Allele TLR4*B (Gly-299, Ile-399) is associated with a blunted response to inhaled LPS

Sequence variations from dbSNP and Humsavar for TLR4 Gene

SNP ID Clin Chr 09 pos Sequence Context AA Info Type MAF
rs760361 -- 117,704,404(+) GGTCA(A/G)ACGGT utr-variant-5-prime
rs760363 -- 117,704,418(+) AGCAA(A/G)CCACG utr-variant-5-prime
rs1057309 -- 117,715,172(+) GTCTA(A/G)TGGCT utr-variant-3-prime
rs1057310 -- 117,715,233(+) CTCGA(A/G)CATGT utr-variant-3-prime
rs1057312 -- 117,715,560(+) GGCTA(G/T)AGGCA utr-variant-3-prime

Structural Variations from Database of Genomic Variants (DGV) for TLR4 Gene

Variant ID Type Subtype PubMed ID
nsv7434 OTHER Inversion 18451855
nsv831706 CNV Gain 17160897

Relevant External Links for TLR4 Gene

HapMap Linkage Disequilibrium report
TLR4
Human Gene Mutation Database (HGMD)
TLR4

Disorders for TLR4 Gene

(2) OMIM Diseases for TLR4 Gene (603030)

UniProtKB/Swiss-Prot

TLR4_HUMAN
  • Macular degeneration, age-related, 10 (ARMD10) [MIM:611488]: A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

(93) Novoseek inferred disease relationships for TLR4 Gene

Disease -log(P) Hits PubMed IDs
inflammation 74.6 123
necrosis 73.4 109
gram-negative bacterial infections 73 11
sepsis 67 89
bacterial infections 66.3 31

Relevant External Links for TLR4

Genetic Association Database (GAD)
TLR4
Human Genome Epidemiology (HuGE) Navigator
TLR4
genes like me logo Genes that share disorders with TLR4: view

Publications for TLR4 Gene

  1. Toll-like receptor 4 variant D299G is associated with susceptibility to age-related macular degeneration. (PMID: 15829498) Zareparsi S. … Swaroop A. (Hum. Mol. Genet. 2005) 3 4 23 49
  2. Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn's disease: phenotype-genotype correlations. (PMID: 15770725) Lakatos P.L. … Ferenci P. (World J. Gastroenterol. 2005) 3 23 49
  3. Toll-like receptor 4 gene Asp299Gly polymorphism is associated with reductions in vascular inflammation, angiographic coronary artery disease, and clinical diabetes. (PMID: 15632890) Kolek M.J. … Anderson J.L. (Am. Heart J. 2004) 3 23 49
  4. Association between polymorphisms in the Toll-like receptor 4, CD14, and CARD15/NOD2 and inflammatory bowel disease in the Greek population. (PMID: 15655821) Gazouli M. … Gorgoulis V.G. (World J. Gastroenterol. 2005) 3 23 49
  5. Variation in the toll-like receptor 4 gene and susceptibility to myocardial infarction. (PMID: 15864121) Holloway J.W. … Ye S. (Pharmacogenet. Genomics 2005) 3 23 49

Products for TLR4 Gene

  • Addgene plasmids for TLR4

Sources for TLR4 Gene

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