Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Toll-like receptor 4

Gene

Tlr4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) (PubMed:9851930, PubMed:9989976, PubMed:20133493). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:24380872). Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate. 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- (By similarity).By similarity8 Publications

GO - Molecular functioni

GO - Biological processi

  • activation of innate immune response Source: MGI
  • activation of MAPK activity Source: BHF-UCL
  • activation of NF-kappaB-inducing kinase activity Source: UniProtKB
  • astrocyte development Source: MGI
  • B cell proliferation involved in immune response Source: MGI
  • cellular response to lipopolysaccharide Source: BHF-UCL
  • cellular response to lipoteichoic acid Source: MGI
  • cellular response to mechanical stimulus Source: Ensembl
  • defense response to Gram-negative bacterium Source: MGI
  • detection of lipopolysaccharide Source: BHF-UCL
  • I-kappaB phosphorylation Source: MGI
  • innate immune response Source: BHF-UCL
  • interferon-gamma production Source: MGI
  • interleukin-1 beta secretion Source: UniProtKB
  • intestinal epithelial structure maintenance Source: BHF-UCL
  • lipopolysaccharide-mediated signaling pathway Source: MGI
  • macrophage activation Source: UniProtKB
  • mast cell activation Source: UniProtKB
  • MyD88-dependent toll-like receptor signaling pathway Source: InterPro
  • negative regulation of ERK1 and ERK2 cascade Source: BHF-UCL
  • negative regulation of interferon-gamma production Source: BHF-UCL
  • negative regulation of interleukin-17 production Source: BHF-UCL
  • negative regulation of interleukin-23 production Source: BHF-UCL
  • negative regulation of interleukin-6 production Source: BHF-UCL
  • negative regulation of tumor necrosis factor production Source: BHF-UCL
  • nitric oxide production involved in inflammatory response Source: MGI
  • positive regulation of B cell proliferation Source: MGI
  • positive regulation of chemokine production Source: BHF-UCL
  • positive regulation of ERK1 and ERK2 cascade Source: MGI
  • positive regulation of gene expression Source: MGI
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: MGI
  • positive regulation of interferon-alpha production Source: BHF-UCL
  • positive regulation of interferon-beta biosynthetic process Source: MGI
  • positive regulation of interferon-beta production Source: BHF-UCL
  • positive regulation of interferon-gamma production Source: BHF-UCL
  • positive regulation of interleukin-10 production Source: BHF-UCL
  • positive regulation of interleukin-12 biosynthetic process Source: MGI
  • positive regulation of interleukin-12 production Source: BHF-UCL
  • positive regulation of interleukin-13 biosynthetic process Source: UniProtKB
  • positive regulation of interleukin-1 biosynthetic process Source: UniProtKB
  • positive regulation of interleukin-1 production Source: BHF-UCL
  • positive regulation of interleukin-6 biosynthetic process Source: UniProtKB
  • positive regulation of interleukin-6 production Source: BHF-UCL
  • positive regulation of interleukin-8 biosynthetic process Source: MGI
  • positive regulation of interleukin-8 production Source: MGI
  • positive regulation of JNK cascade Source: MGI
  • positive regulation of lymphocyte proliferation Source: MGI
  • positive regulation of macrophage cytokine production Source: MGI
  • positive regulation of MHC class II biosynthetic process Source: MGI
  • positive regulation of NF-kappaB import into nucleus Source: MGI
  • positive regulation of NF-kappaB transcription factor activity Source: MGI
  • positive regulation of nitric oxide biosynthetic process Source: MGI
  • positive regulation of nitric-oxide synthase biosynthetic process Source: BHF-UCL
  • positive regulation of NLRP3 inflammasome complex assembly Source: UniProtKB
  • positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway Source: MGI
  • positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway Source: MGI
  • positive regulation of platelet activation Source: BHF-UCL
  • positive regulation of stress-activated MAPK cascade Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of tumor necrosis factor biosynthetic process Source: MGI
  • positive regulation of tumor necrosis factor production Source: BHF-UCL
  • regulation of cytokine secretion Source: InterPro
  • regulation of dendritic cell cytokine production Source: MGI
  • regulation of inflammatory response Source: BHF-UCL
  • response to bacterium Source: MGI
  • response to lipopolysaccharide Source: MGI
  • toll-like receptor 4 signaling pathway Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-MMU-166016. Toll Like Receptor 4 (TLR4) Cascade.
R-MMU-166166. MyD88-independent TLR3/TLR4 cascade.

Names & Taxonomyi

Protein namesi
Recommended name:
Toll-like receptor 4
Alternative name(s):
CD_antigen: CD284
Gene namesi
Name:Tlr4
Synonyms:Lps
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:96824. Tlr4.

Subcellular locationi

  • Cell membrane 1 Publication; Single-pass type I membrane protein 1 Publication

  • Note: Upon complex formation with CD36 and TLR6, internalized through dynamin-dependent endocytosis.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini26 – 638613ExtracellularSequence analysisAdd
BLAST
Transmembranei639 – 65921HelicalSequence analysisAdd
BLAST
Topological domaini660 – 835176CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

The protein is encoded by the Lps locus, an important susceptibility locus, influencing the propensity to develop a disseminated Gram-negative infection.

Disruption phenotypei

Animals with a double knockout of APOE and TLR4, fed a Western diet for 12 weeks, have less aortic plaque formation than single APOE knockout mice. They also show lower serum concentrations of IL1A, ILB and IL18.1 Publication

Keywords - Diseasei

Disease mutation

Chemistry

ChEMBLiCHEMBL3038514.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2525Sequence analysisAdd
BLAST
Chaini26 – 835810Toll-like receptor 4PRO_0000034723Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi28 ↔ 391 Publication
Glycosylationi34 – 341N-linked (GlcNAc...)1 Publication
Glycosylationi75 – 751N-linked (GlcNAc...)1 Publication
Glycosylationi172 – 1721N-linked (GlcNAc...)1 Publication
Glycosylationi204 – 2041N-linked (GlcNAc...)1 Publication
Glycosylationi237 – 2371N-linked (GlcNAc...)1 Publication
Disulfide bondi280 ↔ 3041 Publication
Glycosylationi307 – 3071N-linked (GlcNAc...)1 Publication
Disulfide bondi388 ↔ 3891 Publication
Glycosylationi492 – 4921N-linked (GlcNAc...)1 Publication
Glycosylationi495 – 4951N-linked (GlcNAc...)
Glycosylationi524 – 5241N-linked (GlcNAc...)1 Publication
Glycosylationi572 – 5721N-linked (GlcNAc...)1 Publication
Glycosylationi575 – 5751N-linked (GlcNAc...)Sequence analysis
Disulfide bondi580 ↔ 6061 Publication
Disulfide bondi582 ↔ 6251 Publication
Glycosylationi613 – 6131N-linked (GlcNAc...)Sequence analysis
Glycosylationi621 – 6211N-linked (GlcNAc...)Sequence analysis
Glycosylationi622 – 6221N-linked (GlcNAc...)Sequence analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ9QUK6.
PaxDbiQ9QUK6.
PRIDEiQ9QUK6.

PTM databases

PhosphoSiteiQ9QUK6.

Expressioni

Tissue specificityi

Highly expressed in heart, spleen, lung and muscle. Lower levels are found in liver and kidney. Expressed in macrophages.1 Publication

Gene expression databases

BgeeiQ9QUK6.
CleanExiMM_TLR4.
ExpressionAtlasiQ9QUK6. baseline and differential.
GenevisibleiQ9QUK6. MM.

Interactioni

Subunit structurei

Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, LY96 and TLR4 (PubMed:24380872). Binding to bacterial LPS leads to homodimerization (PubMed:20133493, PubMed:24380872, PubMed:22532668). Interacts with LY96 via the extracellular domain (PubMed:17803912, PubMed:22532668). Interacts with MYD88 (via the TIR domain). Interacts with TICAM2 and TIRAP (PubMed:24380872). Interacts with NOX4 (By similarity). Interacts with CNPY3 and HSP90B1; this interaction is required for proper folding in the endoplasmic reticulum (PubMed:18780723, PubMed:20865800). Interacts with MLK4; this interaction leads to negative regulation of TLR4 signaling (By similarity). 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 (By similarity). Interacts with TICAM1 in response to LPS in a WDFY1-dependent manner (PubMed:25736436). Interacts with WDFY1 in response to LPS (PubMed:25736436). Interacts with SMPDL3B (PubMed:26095358).By similarity8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Ly96Q9JHF93EBI-1534575,EBI-1534566

Protein-protein interaction databases

BioGridi204224. 24 interactions.
DIPiDIP-38573N.
IntActiQ9QUK6. 8 interactions.
STRINGi10090.ENSMUSP00000045770.

Chemistry

BindingDBiQ9QUK6.

Structurei

Secondary structure

1
835
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi29 – 324Combined sources
Turni33 – 353Combined sources
Beta strandi36 – 383Combined sources
Beta strandi40 – 423Combined sources
Beta strandi49 – 513Combined sources
Beta strandi57 – 593Combined sources
Turni70 – 756Combined sources
Beta strandi81 – 833Combined sources
Turni94 – 996Combined sources
Beta strandi105 – 1073Combined sources
Turni118 – 1214Combined sources
Beta strandi129 – 1313Combined sources
Beta strandi140 – 1434Combined sources
Beta strandi153 – 1553Combined sources
Helixi168 – 1714Combined sources
Beta strandi178 – 1803Combined sources
Turni191 – 1944Combined sources
Helixi195 – 1995Combined sources
Beta strandi206 – 2083Combined sources
Turni219 – 2246Combined sources
Beta strandi226 – 2349Combined sources
Helixi239 – 2479Combined sources
Turni248 – 2514Combined sources
Beta strandi253 – 2608Combined sources
Helixi273 – 2764Combined sources
Helixi279 – 2813Combined sources
Beta strandi282 – 2898Combined sources
Helixi297 – 3004Combined sources
Helixi303 – 3053Combined sources
Beta strandi309 – 3157Combined sources
Beta strandi331 – 3377Combined sources
Beta strandi353 – 3586Combined sources
Beta strandi375 – 3773Combined sources
Beta strandi380 – 3823Combined sources
Beta strandi383 – 3886Combined sources
Helixi391 – 3944Combined sources
Beta strandi401 – 4033Combined sources
Beta strandi408 – 4125Combined sources
Beta strandi424 – 4263Combined sources
Beta strandi430 – 4345Combined sources
Turni435 – 4439Combined sources
Beta strandi449 – 4513Combined sources
Turni462 – 4676Combined sources
Beta strandi473 – 4753Combined sources
Helixi482 – 4843Combined sources
Turni489 – 4924Combined sources
Beta strandi498 – 5003Combined sources
Turni511 – 5166Combined sources
Beta strandi522 – 5243Combined sources
Beta strandi532 – 5343Combined sources
Helixi535 – 5373Combined sources
Turni538 – 5403Combined sources
Beta strandi546 – 5483Combined sources
Beta strandi557 – 5593Combined sources
Helixi561 – 5633Combined sources
Beta strandi570 – 5723Combined sources
Helixi582 – 5843Combined sources
Helixi585 – 5884Combined sources
Turni589 – 5935Combined sources
Beta strandi594 – 6007Combined sources
Helixi601 – 6033Combined sources
Beta strandi608 – 6103Combined sources
Helixi616 – 6183Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2Z64X-ray2.84A27-625[»]
3VQ1X-ray2.70A/B22-627[»]
3VQ2X-ray2.48A/B22-627[»]
5IJBX-ray2.91A/B27-544[»]
5IJCX-ray2.57A/B27-544[»]
5IJDX-ray2.70A/B27-544[»]
ProteinModelPortaliQ9QUK6.
SMRiQ9QUK6. Positions 27-814.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9QUK6.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati54 – 7522LRR 1Add
BLAST
Repeati78 – 9922LRR 2Add
BLAST
Repeati102 – 12322LRR 3Add
BLAST
Repeati126 – 14722LRR 4Add
BLAST
Repeati150 – 17122LRR 5Add
BLAST
Repeati175 – 19824LRR 6Add
BLAST
Repeati204 – 22421LRR 7Add
BLAST
Repeati226 – 24722LRR 8Add
BLAST
Repeati248 – 26922LRR 9Add
BLAST
Repeati329 – 34921LRR 10Add
BLAST
Repeati350 – 37021LRR 11Add
BLAST
Repeati372 – 39221LRR 12Add
BLAST
Repeati398 – 42023LRR 13Add
BLAST
Repeati421 – 44222LRR 14Add
BLAST
Repeati446 – 46722LRR 15Add
BLAST
Repeati470 – 49021LRR 16Add
BLAST
Repeati495 – 51622LRR 17Add
BLAST
Repeati519 – 54022LRR 18Add
BLAST
Repeati543 – 56422LRR 19Add
BLAST
Domaini576 – 62752LRRCTAdd
BLAST
Domaini670 – 816147TIRPROSITE-ProRule annotationAdd
BLAST

Domaini

The TIR domain mediates interaction with NOX4.By similarity

Sequence similaritiesi

Belongs to the Toll-like receptor family.Curated
Contains 19 LRR (leucine-rich) repeats.Curated
Contains 1 LRRCT domain.Curated
Contains 1 TIR domain.PROSITE-ProRule annotation

Keywords - Domaini

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

Phylogenomic databases

eggNOGiKOG4641. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00760000119006.
HOGENOMiHOG000037951.
HOVERGENiHBG018823.
InParanoidiQ9QUK6.
KOiK10160.
OMAiSVACICE.
OrthoDBiEOG7ZKS9G.
PhylomeDBiQ9QUK6.
TreeFamiTF351113.

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
3.80.10.10. 4 hits.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000157. TIR_dom.
IPR027168. TLR4.
[Graphical view]
PANTHERiPTHR24365:SF230. PTHR24365:SF230. 2 hits.
PfamiPF00560. LRR_1. 1 hit.
PF13855. LRR_8. 2 hits.
PF01582. TIR. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 8 hits.
SM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
SSF52200. SSF52200. 1 hit.
PROSITEiPS50104. TIR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9QUK6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMPPWLLART LIMALFFSCL TPGSLNPCIE VVPNITYQCM DQKLSKVPDD
60 70 80 90 100
IPSSTKNIDL SFNPLKILKS YSFSNFSELQ WLDLSRCEIE TIEDKAWHGL
110 120 130 140 150
HHLSNLILTG NPIQSFSPGS FSGLTSLENL VAVETKLASL ESFPIGQLIT
160 170 180 190 200
LKKLNVAHNF IHSCKLPAYF SNLTNLVHVD LSYNYIQTIT VNDLQFLREN
210 220 230 240 250
PQVNLSLDMS LNPIDFIQDQ AFQGIKLHEL TLRGNFNSSN IMKTCLQNLA
260 270 280 290 300
GLHVHRLILG EFKDERNLEI FEPSIMEGLC DVTIDEFRLT YTNDFSDDIV
310 320 330 340 350
KFHCLANVSA MSLAGVSIKY LEDVPKHFKW QSLSIIRCQL KQFPTLDLPF
360 370 380 390 400
LKSLTLTMNK GSISFKKVAL PSLSYLDLSR NALSFSGCCS YSDLGTNSLR
410 420 430 440 450
HLDLSFNGAI IMSANFMGLE ELQHLDFQHS TLKRVTEFSA FLSLEKLLYL
460 470 480 490 500
DISYTNTKID FDGIFLGLTS LNTLKMAGNS FKDNTLSNVF ANTTNLTFLD
510 520 530 540 550
LSKCQLEQIS WGVFDTLHRL QLLNMSHNNL LFLDSSHYNQ LYSLSTLDCS
560 570 580 590 600
FNRIETSKGI LQHFPKSLAF FNLTNNSVAC ICEHQKFLQW VKEQKQFLVN
610 620 630 640 650
VEQMTCATPV EMNTSLVLDF NNSTCYMYKT IISVSVVSVI VVSTVAFLIY
660 670 680 690 700
HFYFHLILIA GCKKYSRGES IYDAFVIYSS QNEDWVRNEL VKNLEEGVPR
710 720 730 740 750
FHLCLHYRDF IPGVAIAANI IQEGFHKSRK VIVVVSRHFI QSRWCIFEYE
760 770 780 790 800
IAQTWQFLSS RSGIIFIVLE KVEKSLLRQQ VELYRLLSRN TYLEWEDNPL
810 820 830
GRHIFWRRLK NALLDGKASN PEQTAEEEQE TATWT
Length:835
Mass (Da):95,519
Last modified:May 1, 2000 - v1
Checksum:i9C83B59F9A220C17
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti87 – 15468CEIET…TLKKL → EMNTESKSSEAHALALSHIL SPCQPSRRKLRVKLGSLSYQ RAEEGVRSSEIGYSCLHVDT RHDINAVD (PubMed:16141072).CuratedAdd
BLAST

Polymorphismi

Interstrain analyzes reveals that TLR4 is a polymorphic protein and that the extracellular domain is far more variable than the cytoplasmic domain, which is variable at the C-terminal.1 Publication

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti94 – 941D → N in strain: KK/HLJ. 1 Publication
Natural varianti209 – 2091M → I in strain: A/J, BALB/cJ, P/J, SODL/EI, SEA/GNJ, NZW/LACJ and VM/DK. 1 Publication
Natural varianti219 – 2191D → G in strain: SEA/GNJ. 1 Publication
Natural varianti254 – 2541V → I in strain: A/J, BALB/cJ and SEA/GNJ. 1 Publication
Natural varianti423 – 4231Q → L in strain: SEA/GNJ. 1 Publication
Natural varianti477 – 4771A → S in strain: P/J. 1 Publication
Natural varianti516 – 5161T → A in strain: LP/J. 1 Publication
Natural varianti593 – 5931E → D in strain: A/J, BALB/cJ, P/J, SODL/EI, SEA/GNJ, NZW/LACJ and VM/DK. 1 Publication
Natural varianti600 – 6001N → I in strain: KK/HLJ. 1 Publication
Natural varianti607 – 6071A → V in strain: P/J. 1 Publication
Natural varianti637 – 6371V → I in strain: P/J. 1 Publication
Natural varianti712 – 7121P → H in Lps-tolerant mice. 2 Publications
Natural varianti761 – 7611R → H in strain: A/J, BALB/cJ, SODL/EI, SEA/GNJ, NZW/LACJ and VM/DK. 1 Publication
Natural varianti811 – 8111N → K in strain: P/J. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF095353 mRNA. Translation: AAC99411.1.
AF110133 mRNA. Translation: AAD29272.1.
AF185285 mRNA. Translation: AAF04278.1.
AF177767 Genomic DNA. Translation: AAF05317.1.
AK014533 mRNA. No translation available.
CCDSiCCDS18271.1.
RefSeqiNP_067272.1. NM_021297.3.
UniGeneiMm.38049.

Genome annotation databases

EnsembliENSMUST00000048096; ENSMUSP00000045770; ENSMUSG00000039005.
GeneIDi21898.
KEGGimmu:21898.
UCSCiuc008thv.1. mouse.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF095353 mRNA. Translation: AAC99411.1.
AF110133 mRNA. Translation: AAD29272.1.
AF185285 mRNA. Translation: AAF04278.1.
AF177767 Genomic DNA. Translation: AAF05317.1.
AK014533 mRNA. No translation available.
CCDSiCCDS18271.1.
RefSeqiNP_067272.1. NM_021297.3.
UniGeneiMm.38049.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2Z64X-ray2.84A27-625[»]
3VQ1X-ray2.70A/B22-627[»]
3VQ2X-ray2.48A/B22-627[»]
5IJBX-ray2.91A/B27-544[»]
5IJCX-ray2.57A/B27-544[»]
5IJDX-ray2.70A/B27-544[»]
ProteinModelPortaliQ9QUK6.
SMRiQ9QUK6. Positions 27-814.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204224. 24 interactions.
DIPiDIP-38573N.
IntActiQ9QUK6. 8 interactions.
STRINGi10090.ENSMUSP00000045770.

Chemistry

BindingDBiQ9QUK6.
ChEMBLiCHEMBL3038514.

PTM databases

PhosphoSiteiQ9QUK6.

Proteomic databases

MaxQBiQ9QUK6.
PaxDbiQ9QUK6.
PRIDEiQ9QUK6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000048096; ENSMUSP00000045770; ENSMUSG00000039005.
GeneIDi21898.
KEGGimmu:21898.
UCSCiuc008thv.1. mouse.

Organism-specific databases

CTDi7099.
MGIiMGI:96824. Tlr4.

Phylogenomic databases

eggNOGiKOG4641. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00760000119006.
HOGENOMiHOG000037951.
HOVERGENiHBG018823.
InParanoidiQ9QUK6.
KOiK10160.
OMAiSVACICE.
OrthoDBiEOG7ZKS9G.
PhylomeDBiQ9QUK6.
TreeFamiTF351113.

Enzyme and pathway databases

ReactomeiR-MMU-166016. Toll Like Receptor 4 (TLR4) Cascade.
R-MMU-166166. MyD88-independent TLR3/TLR4 cascade.

Miscellaneous databases

EvolutionaryTraceiQ9QUK6.
PROiQ9QUK6.
SOURCEiSearch...

Gene expression databases

BgeeiQ9QUK6.
CleanExiMM_TLR4.
ExpressionAtlasiQ9QUK6. baseline and differential.
GenevisibleiQ9QUK6. MM.

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
3.80.10.10. 4 hits.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000157. TIR_dom.
IPR027168. TLR4.
[Graphical view]
PANTHERiPTHR24365:SF230. PTHR24365:SF230. 2 hits.
PfamiPF00560. LRR_1. 1 hit.
PF13855. LRR_8. 2 hits.
PF01582. TIR. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 8 hits.
SM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
SSF52200. SSF52200. 1 hit.
PROSITEiPS50104. TIR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Genetic and physical mapping of the Lps locus: identification of the Toll-4 receptor as a candidate gene in the critical region."
    Poltorak A., Smirnova I., He X., Liu M.-Y., Van Huffel C., Birdwell D., Alejos E., Silva M., Du X., Thompson P., Chan E.K.L., Ledesma J., Roe B., Clifton S., Vogel S.N., Beutler B.
    Blood Cells Mol. Dis. 24:340-355(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: C3H/HeJ.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, VARIANT LPS-TOLERANT HIS-712.
    Strain: C3H/HeJ.
  3. "Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4)."
    Qureshi S.T., Lariviere L., Leveque G., Clermont S., Moore K.J., Gros P., Malo D.
    J. Exp. Med. 189:615-625(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, VARIANT LPS-TOLERANT HIS-712.
    Strain: C57BL/6J.
  4. "The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens."
    Underhill D.M., Ozinsky A., Hajjar A.M., Stevens A., Wilson C.B., Bassetti M., Aderem A.
    Nature 401:811-815(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Macrophage.
  5. "Phylogenetic variation and polymorphism at the Toll-like receptor 4 locus (TLR4)."
    Smirnova I., Poltorak A., Chan E.K.L., McBride C., Beutler B.
    Genome Biol. 1:RESEARCH002.1-RESEARCH002.10(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ASN-94; ILE-209; GLY-219; ILE-254; LEU-423; SER-477; ALA-516; ASP-593; ILE-600; VAL-607; ILE-637; HIS-761 AND LYS-811.
    Strain: Various strains.
  6. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-154.
    Strain: C57BL/6J.
    Tissue: Skin.
  7. "Murine Toll-like receptor 4 confers lipopolysaccharide responsiveness as determined by activation of NF kappa B and expression of the inducible cyclooxygenase."
    Rhee S.H., Hwang D.
    J. Biol. Chem. 275:34035-34040(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity."
    Kim F., Pham M., Luttrell I., Bannerman D.D., Tupper J., Thaler J., Hawn T.R., Raines E.W., Schwartz M.W.
    Circ. Res. 100:1589-1596(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "A single base mutation in the PRAT4A gene reveals differential interaction of PRAT4A with Toll-like receptors."
    Kiyokawa T., Akashi-Takamura S., Shibata T., Matsumoto F., Nishitani C., Kuroki Y., Seto Y., Miyake K.
    Int. Immunol. 20:1407-1415(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CNPY3.
  10. "Lipopolysaccharide-binding protein-mediated Toll-like receptor 4 dimerization enables rapid signal transduction against lipopolysaccharide stimulation on membrane-associated CD14-expressing cells."
    Tsukamoto H., Fukudome K., Takao S., Tsuneyoshi N., Kimoto M.
    Int. Immunol. 22:271-280(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBUNIT, SUBCELLULAR LOCATION.
  11. "Folding of Toll-like receptors by the HSP90 paralogue gp96 requires a substrate-specific cochaperone."
    Liu B., Yang Y., Qiu Z., Staron M., Hong F., Li Y., Wu S., Li Y., Hao B., Bona R., Han D., Li Z.
    Nat. Commun. 1:79-79(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HSP90B1.
  12. Erratum
    Liu B., Yang Y., Qiu Z., Staron M., Hong F., Li Y., Wu S., Li Y., Hao B., Bona R., Han D., Li Z.
    Nat. Commun. 3:653-653(2012)
  13. "CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer."
    Stewart C.R., Stuart L.M., Wilkinson K., van Gils J.M., Deng J., Halle A., Rayner K.J., Boyer L., Zhong R., Frazier W.A., Lacy-Hulbert A., El Khoury J., Golenbock D.T., Moore K.J.
    Nat. Immunol. 11:155-161(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  14. "CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation."
    Sheedy F.J., Grebe A., Rayner K.J., Kalantari P., Ramkhelawon B., Carpenter S.B., Becker C.E., Ediriweera H.N., Mullick A.E., Golenbock D.T., Stuart L.M., Latz E., Fitzgerald K.A., Moore K.J.
    Nat. Immunol. 14:812-820(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.
  15. "The attenuated inflammation of MPL is due to the lack of CD14-dependent tight dimerization of the TLR4/MD2 complex at the plasma membrane."
    Tanimura N., Saitoh S., Ohto U., Akashi-Takamura S., Fujimoto Y., Fukase K., Shimizu T., Miyake K.
    Int. Immunol. 26:307-314(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH TIRAP AND TICAM2.
  16. Cited for: INTERACTION WITH SMPDL3B.
  17. "WDFY1 mediates TLR3/4 signaling by recruiting TRIF."
    Hu Y.H., Zhang Y., Jiang L.Q., Wang S., Lei C.Q., Sun M.S., Shu H.B., Liu Y.
    EMBO Rep. 16:447-455(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH WDFY1 AND TICAM1.
  18. "Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran."
    Kim H.M., Park B.S., Kim J.-I., Kim S.E., Lee J., Oh S.C., Enkhbayar P., Matsushima N., Lee H., Yoo O.J., Lee J.-O.
    Cell 130:906-917(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.84 ANGSTROMS) OF 27-625 IN COMPLEX WITH LY96, DISULFIDE BOND, GLYCOSYLATION AT ASN-34; ASN-75; ASN-172; ASN-204; ASN-237; ASN-307; ASN-492; ASN-524 AND ASN-572.
  19. "Structural basis of species-specific endotoxin sensing by innate immune receptor TLR4/MD-2."
    Ohto U., Fukase K., Miyake K., Shimizu T.
    Proc. Natl. Acad. Sci. U.S.A. 109:7421-7426(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS) OF 22-627 IN COMPLEX WITH LY96, SUBUNIT, DISULFIDE BONDS, GLYCOSYLATION AT ASN-172; ASN-204; ASN-524 AND ASN-572.

Entry informationi

Entry nameiTLR4_MOUSE
AccessioniPrimary (citable) accession number: Q9QUK6
Secondary accession number(s): Q9D691, Q9QZF5, Q9Z203
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: May 1, 2000
Last modified: June 8, 2016
This is version 149 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.