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Aliases for TLR4 Gene

Aliases for TLR4 Gene

  • Toll Like Receptor 4 2 3
  • Toll-Like Receptor 4 2 5
  • HToll 3 4
  • Homolog Of Drosophila Toll 3
  • CD284 Antigen 4
  • ARMD10 3
  • CD284 3
  • TLR-4 3
  • TOLL 3

External Ids for TLR4 Gene

Previous GeneCards Identifiers for TLR4 Gene

  • GC09P111571
  • GC09P112113
  • GC09P113920
  • GC09P115842
  • GC09P117546
  • GC09P119506
  • GC09P120466
  • GC09P090084

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 colorectal cancer. Among its related pathways are A-beta Pathways: Uptake and Degradation and Immune System. 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 (PubMed:9237759, PubMed:10835634). 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 (PubMed:20711192). 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).

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 (heterodimers have been reported) and are found on immune cells; macrophages, B lymphocytes and mast cells.

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

Regulatory Elements for TLR4 Gene

Promoters for TLR4 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around TLR4 on UCSC Golden Path with GeneCards custom track

Genomic Location for TLR4 Gene

Chromosome:
9
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

Genes around TLR4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TLR4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TLR4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence 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 (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 MLK4; 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).
    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.
  • Glycosylation at Asn 35, Asn 173, Asn 205, Asn 282, Asn 309, Asn 497, Asn 526, Asn 575, Asn 624, and Asn 630
  • Modification sites at PhosphoSitePlus

Other Protein References for TLR4 Gene

Antibody Products

No data available for DME Specific Peptides for TLR4 Gene

Domains & Families for TLR4 Gene

Gene Families for TLR4 Gene

Graphical View of Domain Structure for InterPro Entry

O00206

UniProtKB/Swiss-Prot:

TLR4_HUMAN :
  • The TIR domain mediates interaction with NOX4.
  • Belongs to the Toll-like receptor family.
  • Contains 18 LRR (leucine-rich) repeats.
Domain:
  • The TIR domain mediates interaction with NOX4.
  • Contains 1 LRRCT domain.
  • Contains 1 TIR domain.
Family:
  • Belongs to the Toll-like receptor family.
Similarity:
  • Contains 18 LRR (leucine-rich) repeats.
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 (PubMed:9237759, PubMed:10835634). 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 (PubMed:20711192). 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).
genes like me logo Genes that share phenotypes with TLR4: view

Human Phenotype Ontology for TLR4 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TLR4 Gene

MGI Knock Outs for TLR4:

Animal Model Products

Inhibitory RNA Products

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Gene Ontology (GO) - Molecular Function , Transcription Factor Targets 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
endosome 5
plasma membrane 5
nucleus 4
cytosol 3
extracellular 3
cytoskeleton 2
endoplasmic reticulum 2
lysosome 2
mitochondrion 2
peroxisome 2
vacuole 2
golgi apparatus 1

Gene Ontology (GO) - Cellular Components for TLR4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0009897 external side of plasma membrane IDA 16514062
genes like me logo Genes that share ontologies with TLR4: view

Pathways & Interactions for TLR4 Gene

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

SIGNOR curated interactions for TLR4 Gene

Activates:
Is activated by:

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 IEA --
GO:0002224 toll-like receptor signaling pathway IEA,IBA --
GO:0002537 nitric oxide production involved in inflammatory response IEA --
GO:0002730 regulation of dendritic cell cytokine production IEA --
genes like me logo Genes that share ontologies with TLR4: view

Drugs & Compounds for TLR4 Gene

(79) Drugs for TLR4 Gene - From: Novoseek, IUPHAR, DGIdb, ClinicalTrials, DrugBank, PharmGKB, and Tocris

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Paclitaxel Approved Pharma inhibitor, Biomarker, binder Tubulin and Bcl2 inhibitor, Taxanes 2621
Tacrolimus Approved, Investigational Pharma 1023
Imiquimod Approved, Investigational Pharma Agonist TLR-7 agonist,immunomodulator with antiviral and antitumor activity, Toll-like receptor 7 (TLR7) agonist 131
Naloxone Approved Pharma Antagonist, Target, inhibitor 221
Methotrexate Approved Pharma Folate antagonist,inhibits DFHR, Cytotoxic agent 1444

(56) Additional Compounds for TLR4 Gene - From: Novoseek, HMDB, and Tocris

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Dodecanoic acid
  • 1-Undecanecarboxylate
  • 1-Undecanecarboxylic acid
  • ABL
  • Aliphat No. 4
  • Dodecanoate
143-07-7
Pam3CSK4
112208-00-1
Poly(I:C)
24939-03-5
RWJ 21757
121288-39-9

(5) Tocris Compounds for TLR4 Gene

Compound Action Cas Number
Imiquimod Toll-like receptor 7 (TLR7) agonist 99011-02-6
Pam3CSK4 TLR1/2 agonist; induces cytokine production 112208-00-1
Poly(I:C) TLR3 agonist 24939-03-5
Resiquimod Toll-like receptor 7 (TLR7) agonist 144875-48-9
RWJ 21757 Toll-like receptor 7 (TLR7) agonist 121288-39-9
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:

Inhibitory RNA Products

Flow Cytometry Products

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 (x15.3).

Protein differential expression in normal tissues from HIPED for TLR4 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (18.1), Testis (14.9), Liver (13.5), Heart (12.5), and Monocytes (8.7).

Integrated Proteomics: protein expression in normal tissues and cell lines 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 expression patterns with TLR4: view

Protein tissue co-expression partners for TLR4 Gene

- Elite partner

Primer Products

In Situ Assay Products

Orthologs for TLR4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for TLR4 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia TLR4 35
  • 81.58 (n)
  • 76.48 (a)
TLR4 36
  • 76 (a)
OneToOne
dog
(Canis familiaris)
Mammalia TLR4 35
  • 82.28 (n)
  • 74.33 (a)
TLR4 36
  • 74 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Tlr4 35
  • 75.16 (n)
  • 67.84 (a)
Tlr4 16
Tlr4 36
  • 67 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia TLR4 35
  • 99.76 (n)
  • 99.64 (a)
TLR4 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Tlr4 35
  • 75.19 (n)
  • 67.11 (a)
oppossum
(Monodelphis domestica)
Mammalia TLR4 36
  • 55 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TLR4 36
  • 53 (a)
OneToOne
chicken
(Gallus gallus)
Aves TLR4 35
  • 55.84 (n)
  • 46.69 (a)
TLR4 36
  • 45 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TLR4 36
  • 44 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii tlr4ba 35
  • 50.6 (n)
  • 40.3 (a)
tlr4al 36
  • 38 (a)
OneToMany
tlr4ba 36
  • 39 (a)
OneToMany
tlr4bb 36
  • 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

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
rs4986790 - 117,713,024(+) CGATG(A/G)TATTA reference, missense
rs4986791 - 117,713,324(+) GACAA(C/T)CAGCC reference, missense
rs5030713 - 117,712,691(+) GATTC(A/G/T)AAGTA reference, missense, utr-variant-5-prime
rs5030714 - 117,712,865(+) AACTT(C/G)TATTC reference, missense
rs5030715 - 117,713,114(+) TTATA(A/C/G)TTTCG reference, missense

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

Variation tolerance for TLR4 Gene

Residual Variation Intolerance Score: 87.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.17; 61.75% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for TLR4 Gene

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

Disorders for TLR4 Gene

MalaCards: The human disease database

(97) MalaCards diseases for TLR4 Gene - From: OMIM, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
macular degeneration, age-related, 10
  • armd10
colorectal cancer
  • colorectal cancer, somatic
pertussis
  • bordetella infection
anterior uveitis
  • iridocyclitis
pyelonephritis
- elite association - COSMIC cancer census association via MalaCards
Search TLR4 in MalaCards View complete list of genes associated with diseases

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.

Relevant External Links for TLR4

Genetic Association Database (GAD)
TLR4
Human Genome Epidemiology (HuGE) Navigator
TLR4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
TLR4
genes like me logo Genes that share disorders with TLR4: view

No data available for Genatlas for TLR4 Gene

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 48 67
  2. Toll-like receptor 4 and inducible nitric oxide synthase gene polymorphisms are associated with Type 2 diabetes. (PMID: 19395279) Bagarolli R.A. … Saad S.T. (J. Diabetes Complicat. 2010) 3 23
  3. A functional nonsynonymous toll-like receptor 4 gene polymorphism is associated with metabolic syndrome, surrogates of insulin resistance, and syndromes of lipid accumulation. (PMID: 19922963) Steinhardt A.P. … Taverna M.J. (Metab. Clin. Exp. 2010) 3 23
  4. Enhanced TLR4 endothelial cell immunohistochemical expression in symptomatic carotid atherosclerotic plaques. (PMID: 20001205) Katsargyris A. … Klonaris C. (Expert Opin. Ther. Targets 2010) 3 23
  5. Adipocyte-mononuclear cell interaction, Toll-like receptor 4 activation, and high glucose synergistically up-regulate osteopontin expression via an interleukin 6-mediated mechanism. (PMID: 20007708) Samuvel D.J. … Huang Y. (J. Biol. Chem. 2010) 3 23

Products for TLR4 Gene

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