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Protein

Toll-like receptor 4

Gene

Tlr4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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. 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.By similarity

GO - Molecular functioni

  • lipopolysaccharide binding Source: RGD
  • lipopolysaccharide receptor activity Source: UniProtKB
  • phosphatidylinositol 3-kinase binding Source: RGD
  • receptor activity Source: RGD
  • transmembrane signaling receptor activity Source: InterPro

GO - Biological processi

  • cellular response to lipopolysaccharide Source: RGD
  • cellular response to mechanical stimulus Source: RGD
  • cellular response to retinoic acid Source: RGD
  • defense response to Gram-negative bacterium Source: InterPro
  • detection of lipopolysaccharide Source: UniProtKB
  • immunoglobulin mediated immune response Source: RGD
  • inflammatory response Source: RGD
  • innate immune response Source: RGD
  • innate immune response-activating signal transduction Source: RGD
  • leukotriene metabolic process Source: RGD
  • microglial cell activation Source: RGD
  • MyD88-dependent toll-like receptor signaling pathway Source: InterPro
  • positive regulation of apoptotic process Source: RGD
  • positive regulation of DNA binding Source: RGD
  • positive regulation of inflammatory response Source: RGD
  • positive regulation of NF-kappaB transcription factor activity Source: RGD
  • positive regulation of peptidyl-tyrosine phosphorylation Source: RGD
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: RGD
  • regulation of cytokine secretion Source: InterPro
  • regulation of sensory perception of pain Source: RGD
  • response to activity Source: RGD
  • response to ethanol Source: RGD
  • response to fatty acid Source: RGD
  • response to glucocorticoid Source: RGD
  • response to gold nanoparticle Source: RGD
  • response to hypoxia Source: RGD
  • response to insulin Source: RGD
  • response to lipopolysaccharide Source: RGD
  • response to morphine Source: RGD
  • response to oxidative stress Source: RGD
  • response to progesterone Source: RGD
  • response to retinoic acid Source: RGD
  • response to toxic substance Source: RGD
  • skeletal muscle contraction Source: RGD
  • toll-like receptor 4 signaling pathway Source: InterPro
  • toll-like receptor signaling pathway Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Names & Taxonomyi

Protein namesi
Recommended name:
Toll-like receptor 4
Short name:
Toll4
Alternative name(s):
CD_antigen: CD284
Gene namesi
Name:Tlr4
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Unplaced

Organism-specific databases

RGDi3870. Tlr4.

Subcellular locationi

  • Cell membrane By similarity; Single-pass type I membrane protein By similarity

  • 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

  • cell surface Source: RGD
  • cytoplasm Source: RGD
  • integral component of plasma membrane Source: RGD
  • lipopolysaccharide receptor complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2525Sequence AnalysisAdd
BLAST
Chaini26 – 835810Toll-like receptor 4PRO_0000034728Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi28 ↔ 39By similarity
Glycosylationi34 – 341N-linked (GlcNAc...)Sequence Analysis
Glycosylationi43 – 431N-linked (GlcNAc...)Sequence Analysis
Glycosylationi75 – 751N-linked (GlcNAc...)Sequence Analysis
Glycosylationi172 – 1721N-linked (GlcNAc...)Sequence Analysis
Glycosylationi204 – 2041N-linked (GlcNAc...)Sequence Analysis
Glycosylationi237 – 2371N-linked (GlcNAc...)Sequence Analysis
Glycosylationi248 – 2481N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi280 ↔ 304By similarity
Glycosylationi281 – 2811N-linked (GlcNAc...)Sequence Analysis
Glycosylationi307 – 3071N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi388 ↔ 389By similarity
Glycosylationi492 – 4921N-linked (GlcNAc...)Sequence Analysis
Glycosylationi495 – 4951N-linked (GlcNAc...)Sequence Analysis
Glycosylationi524 – 5241N-linked (GlcNAc...)Sequence Analysis
Glycosylationi572 – 5721N-linked (GlcNAc...)Sequence Analysis
Glycosylationi575 – 5751N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi580 ↔ 606By similarity
Disulfide bondi582 ↔ 625By similarity
Glycosylationi622 – 6221N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PRIDEiQ9QX05.

Expressioni

Gene expression databases

GenevestigatoriQ9QX05.

Interactioni

Subunit structurei

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 and HSP90B1; this interaction 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.By similarity

Structurei

3D structure databases

ProteinModelPortaliQ9QX05.
SMRiQ9QX05. Positions 27-625.
ModBaseiSearch...
MobiDBiSearch...

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
Repeati372 – 38110LRR 9
Repeati398 – 42023LRR 10Add
BLAST
Repeati421 – 44222LRR 11Add
BLAST
Repeati446 – 46722LRR 12Add
BLAST
Repeati470 – 49122LRR 13Add
BLAST
Repeati495 – 51622LRR 14Add
BLAST
Repeati519 – 54022LRR 15Add
BLAST
Repeati543 – 56422LRR 16Add
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 16 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

eggNOGiNOG249751.
HOGENOMiHOG000037951.
HOVERGENiHBG018823.
InParanoidiQ9QX05.
KOiK10160.
PhylomeDBiQ9QX05.

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR001611. Leu-rich_rpt.
IPR000157. TIR_dom.
IPR027168. TLR4.
[Graphical view]
PANTHERiPTHR24365:SF230. PTHR24365:SF230. 1 hit.
PfamiPF13855. LRR_8. 3 hits.
PF01582. TIR. 1 hit.
[Graphical view]
SMARTiSM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF52200. SSF52200. 1 hit.
PROSITEiPS51450. LRR. 13 hits.
PS50104. TIR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q9QX05-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMPLLHLAGT LIMALFLSCL RPGSLNPCIE VLPNITYQCM DQNLSKIPHD
60 70 80 90 100
IPYSTKNLDL SFNPLKILRS YSFTNFSQLQ WLDLSRCEIE TIEDKAWHGL
110 120 130 140 150
NQLSTLVLTG NPIKSFSPGS FSGLTNLENL VAVETKMTSL EGFHIGQLIS
160 170 180 190 200
LKKLNVAHNL IHSFKLPEYF SNLTNLEHVD LSYNYIQTIS VKDLQFLREN
210 220 230 240 250
PQVNLSLDLS LNPIDSIQAQ AFQGIRLHEL TLRSNFNSSN VLKMCLQNMT
260 270 280 290 300
GLHVHRLILG EFKNERNLES FDRSVMEGLC NVSIDEFRLT YINHFSDDIY
310 320 330 340 350
NLNCLANISA MSFTGVHIKH IADVPRHFKW QSLSIIRCHL KPFPKLSLPF
360 370 380 390 400
LKSWTLTTNR EDISFGQLAL PSLRYLDLSR NAMSFRGCCS YSDFGTNNLK
410 420 430 440 450
YLDLSFNGVI LMSANFMGLE ELEYLDFQHS TLKKVTEFSV FLSLEKLLYL
460 470 480 490 500
DISYTNTKID FDGIFLGLIS LNTLKMAGNS FKDNTLSNVF TNTTNLTFLD
510 520 530 540 550
LSKCQLEQIS RGVFDTLYRL QLLNMSHNNL LFLDPSHYKQ LYSLRTLDCS
560 570 580 590 600
FNRIETSKGI LQHFPKSLAV FNLTNNSVAC ICEYQNFLQW VKDQKMFLVN
610 620 630 640 650
VEQMKCASPI DMKASLVLDF TNSTCYIYKT IISVSVVSVL VVATVAFLIY
660 670 680 690 700
HFYFHLILIA GCKKYSRGES IYDAFVIYSS QNEDWVRNEL VKNLEEGVPR
710 720 730 740 750
FQLCLHYRDF IPGVAIAANI IQEGFHKSRK VIVVVSRHFI QSRWCIFEYE
760 770 780 790 800
IAQTWQFLSS RSGIIFIVLE KVEKSLLRQQ VELYRLLSRN TYLEWEDNAL
810 820 830
GRHIFWRRLK KALLDGKALN PDETSEEEQE ATTLT
Length:835
Mass (Da):96,072
Last modified:May 1, 2000 - v1
Checksum:iDF5E16A30851E3A0
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF057025 mRNA. Translation: AAC13313.1.
RefSeqiNP_062051.1. NM_019178.1.
UniGeneiRn.14534.

Genome annotation databases

GeneIDi29260.
KEGGirno:29260.
UCSCiRGD:3870. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF057025 mRNA. Translation: AAC13313.1.
RefSeqiNP_062051.1. NM_019178.1.
UniGeneiRn.14534.

3D structure databases

ProteinModelPortaliQ9QX05.
SMRiQ9QX05. Positions 27-625.
ModBaseiSearch...
MobiDBiSearch...

Proteomic databases

PRIDEiQ9QX05.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi29260.
KEGGirno:29260.
UCSCiRGD:3870. rat.

Organism-specific databases

CTDi7099.
RGDi3870. Tlr4.

Phylogenomic databases

eggNOGiNOG249751.
HOGENOMiHOG000037951.
HOVERGENiHBG018823.
InParanoidiQ9QX05.
KOiK10160.
PhylomeDBiQ9QX05.

Miscellaneous databases

NextBioi608584.
PROiQ9QX05.

Gene expression databases

GenevestigatoriQ9QX05.

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR001611. Leu-rich_rpt.
IPR000157. TIR_dom.
IPR027168. TLR4.
[Graphical view]
PANTHERiPTHR24365:SF230. PTHR24365:SF230. 1 hit.
PfamiPF13855. LRR_8. 3 hits.
PF01582. TIR. 1 hit.
[Graphical view]
SMARTiSM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF52200. SSF52200. 1 hit.
PROSITEiPS51450. LRR. 13 hits.
PS50104. TIR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium."
    Frantz S., Kobzik L., Kim Y.-D., Fukazawa R., Medzhitov R., Lee R.T., Kelly R.A.
    J. Clin. Invest. 104:271-280(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
    Tissue: Heart.

Entry informationi

Entry nameiTLR4_RAT
AccessioniPrimary (citable) accession number: Q9QX05
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: May 1, 2000
Last modified: April 1, 2015
This is version 118 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

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.