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Protein

Toll-like receptor 4

Gene

TLR4

Organism
Homo sapiens (Human)
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). 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 Ni2+. Responses triggered by Ni2+ require non-conserved histidines and are, therefore, species-specific (PubMed:20711192). Both M.tuberculosis HSP70 (dnaK) and HSP65 (groEL-2) act via this protein to stimulate NF-kappa-B expression (PubMed:15809303). 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).7 Publications

GO - Molecular functioni

  • lipopolysaccharide binding Source: UniProtKB
  • lipopolysaccharide receptor activity Source: UniProtKB
  • receptor activity Source: ProtInc
  • transmembrane signaling receptor activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

BioCyciZFISH:ENSG00000136869-MONOMER.
ReactomeiR-HSA-1236974. ER-Phagosome pathway.
R-HSA-140534. Ligand-dependent caspase activation.
R-HSA-166016. Toll Like Receptor 4 (TLR4) Cascade.
R-HSA-166058. MyD88:Mal cascade initiated on plasma membrane.
R-HSA-166166. MyD88-independent TLR3/TLR4 cascade.
R-HSA-2562578. TRIF-mediated programmed cell death.
R-HSA-5602498. MyD88 deficiency (TLR2/4).
R-HSA-5603041. IRAK4 deficiency (TLR2/4).
R-HSA-5686938. Regulation of TLR by endogenous ligand.
R-HSA-936964. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
R-HSA-937041. IKK complex recruitment mediated by RIP1.
R-HSA-937072. TRAF6 mediated induction of TAK1 complex.
SignaLinkiO00206.
SIGNORiO00206.

Names & Taxonomyi

Protein namesi
Recommended name:
Toll-like receptor 4
Alternative name(s):
hToll
CD_antigen: CD284
Gene namesi
Name:TLR4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:11850. TLR4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 631ExtracellularSequence analysisAdd BLAST608
Transmembranei632 – 652HelicalSequence analysisAdd BLAST21
Topological domaini653 – 839CytoplasmicSequence analysisAdd BLAST187

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • cytoplasm Source: BHF-UCL
  • endosome membrane Source: Reactome
  • external side of plasma membrane Source: BHF-UCL
  • integral component of plasma membrane Source: UniProtKB
  • intrinsic component of plasma membrane Source: UniProtKB
  • lipopolysaccharide receptor complex Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi431H → A: Partially diminishes NF-kappa-B activation induced by Ni(2+). Strongly reduces NF-kappa-B activation induced by Ni(2+); when associated with A-456 or A-458. 1 Publication1
Mutagenesisi456H → A: Partially diminishes NF-kappa-B activation induced by Ni(2+). Strongly reduces NF-kappa-B activation induced by Ni(2+); when associated with A-431. Suppresses NF-kappa-B activation induced by Ni(2+); when associated with A-458. 1 Publication1
Mutagenesisi458H → A: Partially diminishes NF-kappa-B activation induced by Ni(2+). Strongly reduces NF-kappa-B activation induced by Ni(2+); when associated with A-431. Suppresses NF-kappa-B activation induced by Ni(2+); when associated with A-456. 1 Publication1
Mutagenesisi526N → A: Abolishes LPS-response and prevents the cell surface expression. 1 Publication1
Mutagenesisi575N → A: Abolishes LPS-response and prevents the cell surface expression. 1 Publication1
Mutagenesisi697E → R: Abolishes LPS-response. 1 Publication1
Mutagenesisi710R → E: Abolishes LPS-response. 1 Publication1
Mutagenesisi711D → K: Abolishes LPS-response. 1 Publication1
Mutagenesisi714P → H, R or E: Abolishes MYD88-binding and LPS-response. 1 Publication1

Keywords - Diseasei

Age-related macular degeneration

Organism-specific databases

DisGeNETi7099.
MalaCardsiTLR4.
OpenTargetsiENSG00000136869.
Orphaneti117. Behcet disease.
PharmGKBiPA36552.

Chemistry databases

ChEMBLiCHEMBL5255.
DrugBankiDB01183. Naloxone.

Polymorphism and mutation databases

BioMutaiTLR4.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 231 PublicationAdd BLAST23
ChainiPRO_000003472224 – 839Toll-like receptor 4Add BLAST816

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi29 ↔ 402 Publications
Glycosylationi35N-linked (GlcNAc...)3 Publications1
Glycosylationi173N-linked (GlcNAc...)4 Publications1
Glycosylationi205N-linked (GlcNAc...)3 Publications1
Disulfide bondi281 ↔ 3061 Publication
Glycosylationi282N-linked (GlcNAc...)1 Publication1
Glycosylationi309N-linked (GlcNAc...)1 Publication1
Disulfide bondi390 ↔ 3911 Publication
Glycosylationi497N-linked (GlcNAc...)2 Publications1
Glycosylationi526N-linked (GlcNAc...)2 Publications1
Glycosylationi575N-linked (GlcNAc...)2 Publications1
Disulfide bondi583 ↔ 6091 Publication
Disulfide bondi585 ↔ 6271 Publication
Glycosylationi624N-linked (GlcNAc...)1 Publication1
Glycosylationi630N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

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.4 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO00206.
PeptideAtlasiO00206.
PRIDEiO00206.

PTM databases

iPTMnetiO00206.
PhosphoSitePlusiO00206.

Expressioni

Tissue specificityi

Highly expressed in placenta, spleen and peripheral blood leukocytes. Detected in monocytes, macrophages, dendritic cells and several types of T-cells.2 Publications

Gene expression databases

BgeeiENSG00000136869.
GenevisibleiO00206. HS.

Organism-specific databases

HPAiCAB004025.
HPA049174.

Interactioni

Subunit structurei

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). Interacts with SMPDL3B (By similarity). Interacts with CEACAM1; upon lipopolysaccharide stimulation, forms a complex including TLR4 and the phosphorylated form of SYK and CEACAM1, which in turn, recruits PTPN6 that dephosphorylates SYK, reducing the production of reactive oxygen species (ROS) and lysosome disruption, which in turn, reduces the activity of the inflammasome (By similarity).By similarity9 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
O765523EBI-528701,EBI-3870694From a different organism.
LY96Q9Y6Y95EBI-528701,EBI-1539247
MYD88Q998362EBI-528701,EBI-447677
NOX4Q9NPH54EBI-528701,EBI-11301574
TICAM2Q86XR72EBI-528701,EBI-525927
TIRAPP587535EBI-528701,EBI-528644

Protein-protein interaction databases

BioGridi112954. 30 interactors.
DIPiDIP-34769N.
IntActiO00206. 16 interactors.
MINTiMINT-3981856.
STRINGi9606.ENSP00000363089.

Chemistry databases

BindingDBiO00206.

Structurei

Secondary structure

1839
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi29 – 33Combined sources5
Turni34 – 36Combined sources3
Beta strandi37 – 39Combined sources3
Beta strandi50 – 52Combined sources3
Beta strandi58 – 60Combined sources3
Turni71 – 76Combined sources6
Beta strandi81 – 84Combined sources4
Turni95 – 100Combined sources6
Beta strandi106 – 108Combined sources3
Beta strandi115 – 117Combined sources3
Turni119 – 124Combined sources6
Beta strandi130 – 132Combined sources3
Helixi141 – 143Combined sources3
Turni145 – 148Combined sources4
Beta strandi154 – 156Combined sources3
Helixi169 – 173Combined sources5
Beta strandi179 – 181Combined sources3
Helixi192 – 195Combined sources4
Helixi196 – 199Combined sources4
Beta strandi206 – 209Combined sources4
Turni220 – 225Combined sources6
Beta strandi227 – 235Combined sources9
Helixi242 – 248Combined sources7
Turni249 – 252Combined sources4
Beta strandi254 – 262Combined sources9
Turni274 – 277Combined sources4
Helixi278 – 282Combined sources5
Beta strandi283 – 292Combined sources10
Beta strandi295 – 298Combined sources4
Turni301 – 304Combined sources4
Helixi305 – 307Combined sources3
Beta strandi311 – 317Combined sources7
Beta strandi319 – 322Combined sources4
Helixi324 – 327Combined sources4
Beta strandi333 – 339Combined sources7
Beta strandi341 – 344Combined sources4
Beta strandi355 – 360Combined sources6
Beta strandi377 – 379Combined sources3
Beta strandi387 – 392Combined sources6
Helixi393 – 396Combined sources4
Beta strandi403 – 405Combined sources3
Beta strandi410 – 419Combined sources10
Beta strandi426 – 428Combined sources3
Beta strandi432 – 437Combined sources6
Turni438 – 445Combined sources8
Beta strandi451 – 453Combined sources3
Turni464 – 469Combined sources6
Beta strandi475 – 477Combined sources3
Helixi484 – 486Combined sources3
Beta strandi500 – 502Combined sources3
Turni513 – 518Combined sources6
Beta strandi524 – 526Combined sources3
Helixi538 – 540Combined sources3
Beta strandi548 – 550Combined sources3
Beta strandi560 – 563Combined sources4
Beta strandi573 – 575Combined sources3
Helixi585 – 587Combined sources3
Helixi588 – 596Combined sources9
Helixi597 – 600Combined sources4
Helixi604 – 606Combined sources3
Beta strandi608 – 612Combined sources5
Helixi613 – 615Combined sources3
Beta strandi617 – 619Combined sources3
Helixi620 – 622Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Z62X-ray1.70A27-228[»]
2Z63X-ray2.00A27-527[»]
2Z65X-ray2.70A/B27-228[»]
2Z66X-ray1.90A/B/C/D381-627[»]
3FXIX-ray3.10A/B27-631[»]
3UL7X-ray2.37A28-226[»]
3UL8X-ray2.50A27-228[»]
3UL9X-ray2.45A28-228[»]
3ULAX-ray3.60A/C27-228[»]
4G8AX-ray2.40A/B23-629[»]
ProteinModelPortaliO00206.
SMRiO00206.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00206.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati55 – 76LRR 1Add BLAST22
Repeati79 – 100LRR 2Add BLAST22
Repeati103 – 124LRR 3Add BLAST22
Repeati127 – 148LRR 4Add BLAST22
Repeati151 – 172LRR 5Add BLAST22
Repeati176 – 199LRR 6Add BLAST24
Repeati205 – 225LRR 7Add BLAST21
Repeati227 – 247LRR 8Add BLAST21
Repeati331 – 351LRR 9Add BLAST21
Repeati352 – 373LRR 10Add BLAST22
Repeati374 – 394LRR 11Add BLAST21
Repeati400 – 422LRR 12Add BLAST23
Repeati423 – 444LRR 13Add BLAST22
Repeati448 – 456LRR 149
Repeati472 – 495LRR 15Add BLAST24
Repeati497 – 518LRR 16Add BLAST22
Repeati521 – 542LRR 17Add BLAST22
Repeati545 – 565LRR 18Add BLAST21
Domaini579 – 629LRRCTAdd BLAST51
Domaini672 – 818TIRPROSITE-ProRule annotationAdd BLAST147

Domaini

The TIR domain mediates interaction with NOX4.1 Publication

Sequence similaritiesi

Belongs to the Toll-like receptor family.Curated
Contains 18 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.
HOVERGENiHBG018823.
InParanoidiO00206.
KOiK10160.
OMAiIYCKDLQ.
OrthoDBiEOG091G01RC.
PhylomeDBiO00206.
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.
PfamiPF13516. LRR_6. 1 hit.
PF13855. LRR_8. 3 hits.
PF01582. TIR. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 11 hits.
SM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF52200. SSF52200. 1 hit.
PROSITEiPS51450. LRR. 11 hits.
PS50104. TIR. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O00206-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MMSASRLAGT LIPAMAFLSC VRPESWEPCV EVVPNITYQC MELNFYKIPD
60 70 80 90 100
NLPFSTKNLD LSFNPLRHLG SYSFFSFPEL QVLDLSRCEI QTIEDGAYQS
110 120 130 140 150
LSHLSTLILT GNPIQSLALG AFSGLSSLQK LVAVETNLAS LENFPIGHLK
160 170 180 190 200
TLKELNVAHN LIQSFKLPEY FSNLTNLEHL DLSSNKIQSI YCTDLRVLHQ
210 220 230 240 250
MPLLNLSLDL SLNPMNFIQP GAFKEIRLHK LTLRNNFDSL NVMKTCIQGL
260 270 280 290 300
AGLEVHRLVL GEFRNEGNLE KFDKSALEGL CNLTIEEFRL AYLDYYLDDI
310 320 330 340 350
IDLFNCLTNV SSFSLVSVTI ERVKDFSYNF GWQHLELVNC KFGQFPTLKL
360 370 380 390 400
KSLKRLTFTS NKGGNAFSEV DLPSLEFLDL SRNGLSFKGC CSQSDFGTTS
410 420 430 440 450
LKYLDLSFNG VITMSSNFLG LEQLEHLDFQ HSNLKQMSEF SVFLSLRNLI
460 470 480 490 500
YLDISHTHTR VAFNGIFNGL SSLEVLKMAG NSFQENFLPD IFTELRNLTF
510 520 530 540 550
LDLSQCQLEQ LSPTAFNSLS SLQVLNMSHN NFFSLDTFPY KCLNSLQVLD
560 570 580 590 600
YSLNHIMTSK KQELQHFPSS LAFLNLTQND FACTCEHQSF LQWIKDQRQL
610 620 630 640 650
LVEVERMECA TPSDKQGMPV LSLNITCQMN KTIIGVSVLS VLVVSVVAVL
660 670 680 690 700
VYKFYFHLML LAGCIKYGRG ENIYDAFVIY SSQDEDWVRN ELVKNLEEGV
710 720 730 740 750
PPFQLCLHYR DFIPGVAIAA NIIHEGFHKS RKVIVVVSQH FIQSRWCIFE
760 770 780 790 800
YEIAQTWQFL SSRAGIIFIV LQKVEKTLLR QQVELYRLLS RNTYLEWEDS
810 820 830
VLGRHIFWRR LRKALLDGKS WNPEGTVGTG CNWQEATSI
Length:839
Mass (Da):95,680
Last modified:January 1, 1998 - v2
Checksum:i92C48F55821133E8
GO
Isoform 2 (identifier: O00206-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-40: Missing.

Show »
Length:799
Mass (Da):91,296
Checksum:i82F70995E7F2AF9D
GO
Isoform 3 (identifier: O00206-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-200: Missing.

Note: No experimental confirmation available.
Show »
Length:639
Mass (Da):73,301
Checksum:i23C1406CE32427EC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti73S → R in ABU41664 (Ref. 11) Curated1
Sequence conflicti400S → C in BAF82742 (PubMed:14702039).Curated1
Sequence conflicti581F → S in BAG64706 (PubMed:14702039).Curated1

Polymorphismi

Allele TLR4*B (Gly-299, Ile-399) is associated with a blunted response to inhaled LPS.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021977175T → A.Corresponds to variant rs16906079dbSNPEnsembl.1
Natural variantiVAR_018729188Q → R.1 PublicationCorresponds to variant rs5030713dbSNPEnsembl.1
Natural variantiVAR_018730246C → S.1 PublicationCorresponds to variant rs5030714dbSNPEnsembl.1
Natural variantiVAR_074187287E → D.1 Publication1
Natural variantiVAR_012739299D → G in allele TLR4*B; reduced LPS-response; associated with an increased risk for age-related macular degeneration in Caucasian carriers. 5 PublicationsCorresponds to variant rs4986790dbSNPEnsembl.1
Natural variantiVAR_047563306C → W.Corresponds to variant rs2770145dbSNPEnsembl.1
Natural variantiVAR_047564310V → G.Corresponds to variant rs2770144dbSNPEnsembl.1
Natural variantiVAR_018731329N → S.1 PublicationCorresponds to variant rs5030715dbSNPEnsembl.1
Natural variantiVAR_020334342F → Y.Corresponds to variant rs5031050dbSNPEnsembl.1
Natural variantiVAR_037668385L → F.Corresponds to variant rs11536884dbSNPEnsembl.1
Natural variantiVAR_012740399T → I in allele TLR4*B; reduced LPS-response. 4 PublicationsCorresponds to variant rs4986791dbSNPEnsembl.1
Natural variantiVAR_020335400S → N.Corresponds to variant rs4987233dbSNPEnsembl.1
Natural variantiVAR_018732443F → L.1 PublicationCorresponds to variant rs5030716dbSNPEnsembl.1
Natural variantiVAR_018733474E → K.1 PublicationCorresponds to variant rs5030718dbSNPEnsembl.1
Natural variantiVAR_018734510Q → H.1 PublicationCorresponds to variant rs5030719dbSNPEnsembl.1
Natural variantiVAR_018735694K → R.1 PublicationCorresponds to variant rs5030722dbSNPEnsembl.1
Natural variantiVAR_018736763R → H.1 PublicationCorresponds to variant rs5030723dbSNPEnsembl.1
Natural variantiVAR_018737834Q → H.1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0357931 – 200Missing in isoform 3. 1 PublicationAdd BLAST200
Alternative sequenceiVSP_0357941 – 40Missing in isoform 2. 2 PublicationsAdd BLAST40

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U93091 mRNA. Translation: AAC80227.1.
AB445638 mRNA. Translation: BAG55035.1.
DQ018107 Genomic DNA. Translation: AAY82267.1.
DQ018108 Genomic DNA. Translation: AAY82268.1.
DQ018109 Genomic DNA. Translation: AAY82269.1.
AK290053 mRNA. Translation: BAF82742.1.
AK293068 mRNA. Translation: BAF85757.1.
AK303730 mRNA. Translation: BAG64706.1.
AL160272 Genomic DNA. Translation: CAH72618.1.
AL160272 Genomic DNA. Translation: CAH72619.1.
CH471090 Genomic DNA. Translation: EAW87448.1.
CH471090 Genomic DNA. Translation: EAW87451.1.
BC117422 mRNA. Translation: AAI17423.1.
EF535831 Genomic DNA. Translation: ABU41662.1.
EF535832 Genomic DNA. Translation: ABU41663.1.
EF535833 Genomic DNA. Translation: ABU41664.1.
AF177765 Genomic DNA. Translation: AAF05316.1.
AF177766 Genomic DNA. Translation: AAF07823.1.
AF172171, AF172169, AF172170 Genomic DNA. Translation: AAF89753.1.
U88880 mRNA. Translation: AAC34135.1.
CCDSiCCDS6818.1. [O00206-1]
RefSeqiNP_003257.1. NM_003266.3. [O00206-2]
NP_612564.1. NM_138554.4. [O00206-1]
NP_612567.1. NM_138557.2. [O00206-3]
UniGeneiHs.174312.

Genome annotation databases

EnsembliENST00000355622; ENSP00000363089; ENSG00000136869. [O00206-1]
ENST00000394487; ENSP00000377997; ENSG00000136869. [O00206-2]
GeneIDi7099.
KEGGihsa:7099.
UCSCiuc004bjz.5. human. [O00206-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Protein Spotlight

Zips, necklaces and mobile telephones - Issue 134 of December 2011

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U93091 mRNA. Translation: AAC80227.1.
AB445638 mRNA. Translation: BAG55035.1.
DQ018107 Genomic DNA. Translation: AAY82267.1.
DQ018108 Genomic DNA. Translation: AAY82268.1.
DQ018109 Genomic DNA. Translation: AAY82269.1.
AK290053 mRNA. Translation: BAF82742.1.
AK293068 mRNA. Translation: BAF85757.1.
AK303730 mRNA. Translation: BAG64706.1.
AL160272 Genomic DNA. Translation: CAH72618.1.
AL160272 Genomic DNA. Translation: CAH72619.1.
CH471090 Genomic DNA. Translation: EAW87448.1.
CH471090 Genomic DNA. Translation: EAW87451.1.
BC117422 mRNA. Translation: AAI17423.1.
EF535831 Genomic DNA. Translation: ABU41662.1.
EF535832 Genomic DNA. Translation: ABU41663.1.
EF535833 Genomic DNA. Translation: ABU41664.1.
AF177765 Genomic DNA. Translation: AAF05316.1.
AF177766 Genomic DNA. Translation: AAF07823.1.
AF172171, AF172169, AF172170 Genomic DNA. Translation: AAF89753.1.
U88880 mRNA. Translation: AAC34135.1.
CCDSiCCDS6818.1. [O00206-1]
RefSeqiNP_003257.1. NM_003266.3. [O00206-2]
NP_612564.1. NM_138554.4. [O00206-1]
NP_612567.1. NM_138557.2. [O00206-3]
UniGeneiHs.174312.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2Z62X-ray1.70A27-228[»]
2Z63X-ray2.00A27-527[»]
2Z65X-ray2.70A/B27-228[»]
2Z66X-ray1.90A/B/C/D381-627[»]
3FXIX-ray3.10A/B27-631[»]
3UL7X-ray2.37A28-226[»]
3UL8X-ray2.50A27-228[»]
3UL9X-ray2.45A28-228[»]
3ULAX-ray3.60A/C27-228[»]
4G8AX-ray2.40A/B23-629[»]
ProteinModelPortaliO00206.
SMRiO00206.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112954. 30 interactors.
DIPiDIP-34769N.
IntActiO00206. 16 interactors.
MINTiMINT-3981856.
STRINGi9606.ENSP00000363089.

Chemistry databases

BindingDBiO00206.
ChEMBLiCHEMBL5255.
DrugBankiDB01183. Naloxone.

PTM databases

iPTMnetiO00206.
PhosphoSitePlusiO00206.

Polymorphism and mutation databases

BioMutaiTLR4.

Proteomic databases

PaxDbiO00206.
PeptideAtlasiO00206.
PRIDEiO00206.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000355622; ENSP00000363089; ENSG00000136869. [O00206-1]
ENST00000394487; ENSP00000377997; ENSG00000136869. [O00206-2]
GeneIDi7099.
KEGGihsa:7099.
UCSCiuc004bjz.5. human. [O00206-1]

Organism-specific databases

CTDi7099.
DisGeNETi7099.
GeneCardsiTLR4.
HGNCiHGNC:11850. TLR4.
HPAiCAB004025.
HPA049174.
MalaCardsiTLR4.
MIMi603030. gene.
neXtProtiNX_O00206.
OpenTargetsiENSG00000136869.
Orphaneti117. Behcet disease.
PharmGKBiPA36552.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4641. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00760000119006.
HOVERGENiHBG018823.
InParanoidiO00206.
KOiK10160.
OMAiIYCKDLQ.
OrthoDBiEOG091G01RC.
PhylomeDBiO00206.
TreeFamiTF351113.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000136869-MONOMER.
ReactomeiR-HSA-1236974. ER-Phagosome pathway.
R-HSA-140534. Ligand-dependent caspase activation.
R-HSA-166016. Toll Like Receptor 4 (TLR4) Cascade.
R-HSA-166058. MyD88:Mal cascade initiated on plasma membrane.
R-HSA-166166. MyD88-independent TLR3/TLR4 cascade.
R-HSA-2562578. TRIF-mediated programmed cell death.
R-HSA-5602498. MyD88 deficiency (TLR2/4).
R-HSA-5603041. IRAK4 deficiency (TLR2/4).
R-HSA-5686938. Regulation of TLR by endogenous ligand.
R-HSA-936964. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
R-HSA-937041. IKK complex recruitment mediated by RIP1.
R-HSA-937072. TRAF6 mediated induction of TAK1 complex.
SignaLinkiO00206.
SIGNORiO00206.

Miscellaneous databases

EvolutionaryTraceiO00206.
GeneWikiiTLR_4.
GenomeRNAii7099.
PROiO00206.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136869.
GenevisibleiO00206. HS.

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.
PfamiPF13516. LRR_6. 1 hit.
PF13855. LRR_8. 3 hits.
PF01582. TIR. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 11 hits.
SM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF52200. SSF52200. 1 hit.
PROSITEiPS51450. LRR. 11 hits.
PS50104. TIR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTLR4_HUMAN
AccessioniPrimary (citable) accession number: O00206
Secondary accession number(s): A8K1Y8
, A9XLP9, A9XLQ0, A9XLQ1, B4E194, D1CS52, D1CS53, Q5VZI8, Q5VZI9, Q9UK78, Q9UM57
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: January 1, 1998
Last modified: November 2, 2016
This is version 176 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

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 (Ni2+). Ni2+ 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 Ni2+. A mouse model of contact allergy to Ni2+ in which TLR4-deficient mice expresses human TLR4 has been proposed.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  8. 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.