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TLR4
HPA
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  • TLR4
PROTEIN SUMMARY GENE INFORMATION RNA DATA ANTIBODY DATA
GENERAL INFORMATIONi

General description of the gene and the encoded protein(s) using information from HGNC and Ensembl, as well as predictions made by the Human Protein Atlas project.

Gene namei

Official gene symbol, which is typically a short form of the gene name, according to HGNC.

TLR4
Synonyms ARMD10, CD284, hToll, TLR-4
Gene descriptioni

Full gene name according to HGNC.

Toll like receptor 4
Protein classi

Assigned HPA protein class(es) for the encoded protein(s).

CD markers
FDA approved drug targets
Human disease related genes
Transporters
Predicted locationi

All transcripts of all genes have been analyzed regarding the location(s) of corresponding protein based on prediction methods for signal peptides and transmembrane regions.

  • Genes with at least one transcript predicted to encode a secreted protein, according to prediction methods or to UniProt location data, have been further annotated and classified with the aim to determine if the corresponding protein(s) are secreted or actually retained in intracellular locations or membrane-attached.

  • Remaining genes, with no transcript predicted to encode a secreted protein, will be assigned the prediction-based location(s).

The annotated location overrules the predicted location, so that a gene encoding a predicted secreted protein that has been annotated as intracellular will have intracellular as the final location.

Membrane, Intracellular
Protein evidence Evidence at protein level (all genes)
GENE INFORMATIONi

Gene information from Ensembl and Entrez, as well as links to available gene identifiers are displayed here. Information was retrieved from Ensembl if not indicated otherwise.

Chromosome 9
Cytoband q33.1
Chromosome location (bp) 117704175 - 117724735
Number of transcriptsi

Number of protein-coding transcripts from the gene as defined by Ensembl.

3
Ensembl ENSG00000136869 (version 109)
Entrez gene 7099
HGNC HGNC:11850
UniProt O00206 (UniProt - Evidence at protein level)
neXtProt NX_O00206
GeneCards TLR4
Antibodypedia TLR4 antibodies


PROTEIN FUNCTION
Protein function (UniProt)i

Useful information about the protein provided by UniProt.

Transmembrane receptor that functions as a pattern recognition receptor recognizing pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) to induce innate immune responses via downstream signaling pathways 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. At the plasma membrane, cooperates with LY96 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) 11. Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+) 12. Mechanistically, acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response 13, 14, 15, 16, 17. Alternatively, CD14-mediated TLR4 internalization via endocytosis is associated with the initiation of a MYD88-independent signaling via the TICAM1-TBK1-IRF3 axis leading to type I interferon production 18. In addition to the secretion of proinflammatory cytokines, initiates the activation of NLRP3 inflammasome and formation of a positive feedback loop between autophagy and NF-kappa-B signaling cascade 19. In complex with TLR6, promotes inflammation in monocytes/macrophages by associating with TLR6 and the receptor CD86 20. Upon ligand binding, such as oxLDL or amyloid-beta 42, the TLR4:TLR6 complex is internalized and triggers inflammatory response, leading to NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway 21. In myeloid dendritic cells, vesicular stomatitis virus glycoprotein G but not LPS promotes the activation of IRF7, leading to type I IFN production in a CD14-dependent manner 22, 23. Required for the migration-promoting effects of ZG16B/PAUF on pancreatic cancer cells.... show less
Molecular function (UniProt)i

Keywords assigned by UniProt to proteins due to their particular molecular function.

Receptor
Biological process (UniProt)i

Keywords assigned by UniProt to proteins because they are involved in a particular biological process.

Immunity, Inflammatory response, Innate immunity
Ligand (UniProt)i

Keywords assigned by UniProt to proteins because they bind, are associated with, or whose activity is dependent of some molecule.

NAD
Gene summary (Entrez)i

Useful information about the gene from Entrez

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. In silico studies have found a particularly strong binding of surface TLR4 with the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease-2019 (COVID-19). This receptor has also 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, and with susceptibility to age-related macular degeneration. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2020]... show less
PROTEIN INFORMATIONi

The protein information section displays alternative protein-coding transcripts (splice variants) encoded by this gene according to the Ensembl database.

The Splice variant identifier links to the Ensembl website protein summary for the selected splice variant. The data in the Swissprot and TrEMBL columns links to corresponding pages in the UniProt database.

The protein classes assigned to this protein are shown if expanding the data in the protein class column. Parent protein classes are in bold font and subclasses are listed under the parent class.

The length of the protein (amino acid residues according to Ensembl), molecular mass (kDalton), predicted signal peptide and number of predicted transmembrane region(s) according to in-house majority decision methods based on sets of predictors are also reported.
Splice variant SwissProt TrEMBL Protein class Gene ontology Length & mass Signal peptide
(predicted)
Transmembrane regions
(predicted)
TLR4-201
ENSP00000363089
ENST00000355622
O00206
[Direct mapping] Toll-like receptor 4
Show all
CD markers
Transporters
   Accessory Factors Involved in Transport
Predicted membrane proteins
   Prediction method-based
   Membrane proteins predicted by MDM
   MEMSAT3 predicted membrane proteins
   MEMSAT-SVM predicted membrane proteins
   Phobius predicted membrane proteins
   SCAMPI predicted membrane proteins
   SPOCTOPUS predicted membrane proteins
   THUMBUP predicted membrane proteins
   TMHMM predicted membrane proteins
   # TM segments-based
   1TM proteins predicted by MDM
FDA approved drug targets
   Small molecule drugs
Human disease related genes
   Nervous system diseases
   Eye disease
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
   DeepTMHMM predicted membrane proteins
Show all
GO:0001530 [lipopolysaccharide binding]
GO:0001540 [amyloid-beta binding]
GO:0001726 [ruffle]
GO:0001875 [lipopolysaccharide immune receptor activity]
GO:0001891 [phagocytic cup]
GO:0002218 [activation of innate immune response]
GO:0002224 [toll-like receptor signaling pathway]
GO:0002246 [wound healing involved in inflammatory response]
GO:0002322 [B cell proliferation involved in immune response]
GO:0002376 [immune system process]
GO:0002537 [nitric oxide production involved in inflammatory response]
GO:0002730 [regulation of dendritic cell cytokine production]
GO:0002755 [MyD88-dependent toll-like receptor signaling pathway]
GO:0004888 [transmembrane signaling receptor activity]
GO:0005102 [signaling receptor binding]
GO:0005515 [protein binding]
GO:0005737 [cytoplasm]
GO:0005768 [endosome]
GO:0005769 [early endosome]
GO:0005794 [Golgi apparatus]
GO:0005886 [plasma membrane]
GO:0006809 [nitric oxide biosynthetic process]
GO:0006909 [phagocytosis]
GO:0006954 [inflammatory response]
GO:0006955 [immune response]
GO:0007165 [signal transduction]
GO:0007249 [I-kappaB kinase/NF-kappaB signaling]
GO:0007252 [I-kappaB phosphorylation]
GO:0007254 [JNK cascade]
GO:0009605 [response to external stimulus]
GO:0009617 [response to bacterium]
GO:0009897 [external side of plasma membrane]
GO:0009986 [cell surface]
GO:0010008 [endosome membrane]
GO:0010572 [positive regulation of platelet activation]
GO:0010628 [positive regulation of gene expression]
GO:0014002 [astrocyte development]
GO:0014911 [positive regulation of smooth muscle cell migration]
GO:0016020 [membrane]
GO:0016021 [integral component of membrane]
GO:0016046 [detection of fungus]
GO:0030890 [positive regulation of B cell proliferation]
GO:0031663 [lipopolysaccharide-mediated signaling pathway]
GO:0032496 [response to lipopolysaccharide]
GO:0032497 [detection of lipopolysaccharide]
GO:0032689 [negative regulation of interferon-gamma production]
GO:0032700 [negative regulation of interleukin-17 production]
GO:0032707 [negative regulation of interleukin-23 production]
GO:0032715 [negative regulation of interleukin-6 production]
GO:0032720 [negative regulation of tumor necrosis factor production]
GO:0032722 [positive regulation of chemokine production]
GO:0032727 [positive regulation of interferon-alpha production]
GO:0032728 [positive regulation of interferon-beta production]
GO:0032729 [positive regulation of interferon-gamma production]
GO:0032731 [positive regulation of interleukin-1 beta production]
GO:0032732 [positive regulation of interleukin-1 production]
GO:0032733 [positive regulation of interleukin-10 production]
GO:0032735 [positive regulation of interleukin-12 production]
GO:0032755 [positive regulation of interleukin-6 production]
GO:0032757 [positive regulation of interleukin-8 production]
GO:0032760 [positive regulation of tumor necrosis factor production]
GO:0032874 [positive regulation of stress-activated MAPK cascade]
GO:0034142 [toll-like receptor 4 signaling pathway]
GO:0035666 [TRIF-dependent toll-like receptor signaling pathway]
GO:0036120 [cellular response to platelet-derived growth factor stimulus]
GO:0038023 [signaling receptor activity]
GO:0042088 [T-helper 1 type immune response]
GO:0042100 [B cell proliferation]
GO:0042116 [macrophage activation]
GO:0042742 [defense response to bacterium]
GO:0042802 [identical protein binding]
GO:0042995 [cell projection]
GO:0043032 [positive regulation of macrophage activation]
GO:0043123 [positive regulation of I-kappaB kinase/NF-kappaB signaling]
GO:0043235 [receptor complex]
GO:0043406 [positive regulation of MAP kinase activity]
GO:0045087 [innate immune response]
GO:0045342 [MHC class II biosynthetic process]
GO:0045348 [positive regulation of MHC class II biosynthetic process]
GO:0045429 [positive regulation of nitric oxide biosynthetic process]
GO:0045671 [negative regulation of osteoclast differentiation]
GO:0045944 [positive regulation of transcription by RNA polymerase II]
GO:0046330 [positive regulation of JNK cascade]
GO:0046651 [lymphocyte proliferation]
GO:0046696 [lipopolysaccharide receptor complex]
GO:0046982 [protein heterodimerization activity]
GO:0048471 [perinuclear region of cytoplasm]
GO:0048661 [positive regulation of smooth muscle cell proliferation]
GO:0050135 [NAD(P)+ nucleosidase activity]
GO:0050671 [positive regulation of lymphocyte proliferation]
GO:0050727 [regulation of inflammatory response]
GO:0050729 [positive regulation of inflammatory response]
GO:0050829 [defense response to Gram-negative bacterium]
GO:0051092 [positive regulation of NF-kappaB transcription factor activity]
GO:0051403 [stress-activated MAPK cascade]
GO:0051770 [positive regulation of nitric-oxide synthase biosynthetic process]
GO:0060729 [intestinal epithelial structure maintenance]
GO:0060907 [positive regulation of macrophage cytokine production]
GO:0061809 [NAD+ nucleotidase, cyclic ADP-ribose generating]
GO:0070371 [ERK1 and ERK2 cascade]
GO:0070373 [negative regulation of ERK1 and ERK2 cascade]
GO:0070374 [positive regulation of ERK1 and ERK2 cascade]
GO:0070427 [nucleotide-binding oligomerization domain containing 1 signaling pathway]
GO:0070430 [positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway]
GO:0070431 [nucleotide-binding oligomerization domain containing 2 signaling pathway]
GO:0070434 [positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway]
GO:0071222 [cellular response to lipopolysaccharide]
GO:0071223 [cellular response to lipoteichoic acid]
GO:0071260 [cellular response to mechanical stimulus]
GO:0071346 [cellular response to interferon-gamma]
GO:0120163 [negative regulation of cold-induced thermogenesis]
GO:0140052 [cellular response to oxidised low-density lipoprotein particle stimulus]
GO:1900017 [positive regulation of cytokine production involved in inflammatory response]
GO:1900227 [positive regulation of NLRP3 inflammasome complex assembly]
GO:1901224 [positive regulation of NIK/NF-kappaB signaling]
GO:1903223 [positive regulation of oxidative stress-induced neuron death]
GO:1903428 [positive regulation of reactive oxygen species biosynthetic process]
GO:1903974 [positive regulation of cellular response to macrophage colony-stimulating factor stimulus]
GO:1904466 [positive regulation of matrix metallopeptidase secretion]
GO:1904646 [cellular response to amyloid-beta]
GO:2000343 [positive regulation of chemokine (C-X-C motif) ligand 2 production]
Show all
839 aa
95.7 kDa
Yes 1
TLR4-202
ENSP00000377997
ENST00000394487
O00206
[Direct mapping] Toll-like receptor 4
Show all
CD markers
Transporters
   Accessory Factors Involved in Transport
Predicted membrane proteins
   Prediction method-based
   Membrane proteins predicted by MDM
   MEMSAT3 predicted membrane proteins
   MEMSAT-SVM predicted membrane proteins
   Phobius predicted membrane proteins
   SCAMPI predicted membrane proteins
   SPOCTOPUS predicted membrane proteins
   THUMBUP predicted membrane proteins
   TMHMM predicted membrane proteins
   # TM segments-based
   1TM proteins predicted by MDM
FDA approved drug targets
   Small molecule drugs
Human disease related genes
   Nervous system diseases
   Eye disease
Mapped to neXtProt
   neXtProt - Evidence at protein level
Protein evidence (Kim et al 2014)
   DeepTMHMM predicted membrane proteins
Show all
GO:0001530 [lipopolysaccharide binding]
GO:0001540 [amyloid-beta binding]
GO:0001726 [ruffle]
GO:0001875 [lipopolysaccharide immune receptor activity]
GO:0001891 [phagocytic cup]
GO:0002224 [toll-like receptor signaling pathway]
GO:0002376 [immune system process]
GO:0002755 [MyD88-dependent toll-like receptor signaling pathway]
GO:0004888 [transmembrane signaling receptor activity]
GO:0005102 [signaling receptor binding]
GO:0005515 [protein binding]
GO:0005737 [cytoplasm]
GO:0005768 [endosome]
GO:0005769 [early endosome]
GO:0005794 [Golgi apparatus]
GO:0005886 [plasma membrane]
GO:0006909 [phagocytosis]
GO:0006954 [inflammatory response]
GO:0006955 [immune response]
GO:0007165 [signal transduction]
GO:0007252 [I-kappaB phosphorylation]
GO:0009605 [response to external stimulus]
GO:0009897 [external side of plasma membrane]
GO:0009986 [cell surface]
GO:0010008 [endosome membrane]
GO:0010572 [positive regulation of platelet activation]
GO:0010628 [positive regulation of gene expression]
GO:0016020 [membrane]
GO:0016021 [integral component of membrane]
GO:0016046 [detection of fungus]
GO:0031663 [lipopolysaccharide-mediated signaling pathway]
GO:0032496 [response to lipopolysaccharide]
GO:0032497 [detection of lipopolysaccharide]
GO:0032689 [negative regulation of interferon-gamma production]
GO:0032700 [negative regulation of interleukin-17 production]
GO:0032707 [negative regulation of interleukin-23 production]
GO:0032715 [negative regulation of interleukin-6 production]
GO:0032720 [negative regulation of tumor necrosis factor production]
GO:0032722 [positive regulation of chemokine production]
GO:0032727 [positive regulation of interferon-alpha production]
GO:0032728 [positive regulation of interferon-beta production]
GO:0032729 [positive regulation of interferon-gamma production]
GO:0032731 [positive regulation of interleukin-1 beta production]
GO:0032732 [positive regulation of interleukin-1 production]
GO:0032733 [positive regulation of interleukin-10 production]
GO:0032735 [positive regulation of interleukin-12 production]
GO:0032755 [positive regulation of interleukin-6 production]
GO:0032757 [positive regulation of interleukin-8 production]
GO:0032760 [positive regulation of tumor necrosis factor production]
GO:0035666 [TRIF-dependent toll-like receptor signaling pathway]
GO:0038023 [signaling receptor activity]
GO:0042088 [T-helper 1 type immune response]
GO:0042116 [macrophage activation]
GO:0042742 [defense response to bacterium]
GO:0042802 [identical protein binding]
GO:0042995 [cell projection]
GO:0043032 [positive regulation of macrophage activation]
GO:0043235 [receptor complex]
GO:0043406 [positive regulation of MAP kinase activity]
GO:0045087 [innate immune response]
GO:0045429 [positive regulation of nitric oxide biosynthetic process]
GO:0045671 [negative regulation of osteoclast differentiation]
GO:0045944 [positive regulation of transcription by RNA polymerase II]
GO:0046696 [lipopolysaccharide receptor complex]
GO:0046982 [protein heterodimerization activity]
GO:0048471 [perinuclear region of cytoplasm]
GO:0050135 [NAD(P)+ nucleosidase activity]
GO:0050729 [positive regulation of inflammatory response]
GO:0050829 [defense response to Gram-negative bacterium]
GO:0051092 [positive regulation of NF-kappaB transcription factor activity]
GO:0051770 [positive regulation of nitric-oxide synthase biosynthetic process]
GO:0060729 [intestinal epithelial structure maintenance]
GO:0061809 [NAD+ nucleotidase, cyclic ADP-ribose generating]
GO:0070373 [negative regulation of ERK1 and ERK2 cascade]
GO:0071222 [cellular response to lipopolysaccharide]
GO:0071260 [cellular response to mechanical stimulus]
GO:0071346 [cellular response to interferon-gamma]
GO:0120163 [negative regulation of cold-induced thermogenesis]
GO:0140052 [cellular response to oxidised low-density lipoprotein particle stimulus]
GO:1900017 [positive regulation of cytokine production involved in inflammatory response]
GO:1900227 [positive regulation of NLRP3 inflammasome complex assembly]
GO:1901224 [positive regulation of NIK/NF-kappaB signaling]
GO:1903223 [positive regulation of oxidative stress-induced neuron death]
GO:1903428 [positive regulation of reactive oxygen species biosynthetic process]
GO:1903974 [positive regulation of cellular response to macrophage colony-stimulating factor stimulus]
GO:1904466 [positive regulation of matrix metallopeptidase secretion]
GO:1904646 [cellular response to amyloid-beta]
GO:2000343 [positive regulation of chemokine (C-X-C motif) ligand 2 production]
Show all
799 aa
91.3 kDa
No 1
TLR4-203
ENSP00000496429
ENST00000472304
A0A2R8Y7P4
[Direct mapping] Toll-like receptor 4
Show all
   Secreted proteins predicted by MDSEC
   Phobius predicted secreted proteins
   SPOCTOPUS predicted secreted proteins
   DeepSig predicted secreted proteins
Predicted intracellular proteins
Human disease related genes
   Nervous system diseases
   Eye disease
Show all
32 aa
3.5 kDa
Yes 0

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