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UniProtKB - O00206 (TLR4_HUMAN)

Protein

Toll-like receptor 4

Gene

TLR4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) (PubMed:27022195). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:9237759, PubMed:10835634, PubMed:27022195). 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). Stimulation of monocytes in vitro with M.tuberculosis PstS1 induces p38 MAPK and ERK1/2 activation primarily via TLR2, but also partially via this receptor (PubMed:16622205).9 Publications

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

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • lipopolysaccharide binding Source: BHF-UCL
  • lipopolysaccharide receptor activity Source: UniProtKB
  • protein heterodimerization activity Source: ARUK-UCL
  • signaling receptor activity Source: ProtInc
  • signaling receptor binding Source: ARUK-UCL
  • transmembrane signaling receptor activity Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionReceptor
Biological processImmunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-1236974 ER-Phagosome pathway
R-HSA-140534 via Death Receptors in the presence of ligand
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade
R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane
R-HSA-166166 MyD88-independent 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-9014325 TICAM1,TRAF6-dependent induction of TAK1 complex
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 within TLR4 complex
R-HSA-975163 IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation
SignaLinkiO00206
SIGNORiO00206

Protein family/group databases

TCDBi8.A.43.1.9 the neat-domain containing methaemoglobin heme sequestration (n-mhs) family

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000136869.13
HGNCiHGNC:11850 TLR4
MIMi603030 gene
neXtProtiNX_O00206

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

Keywords - Cellular componenti

Cell membrane, Endosome, 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
DrugBankiDB02767 3-Hydroxy-Myristic Acid
DB04933 Eritoran
DB03017 Lauric Acid
DB08231 MYRISTIC ACID
DB01183 Naloxone
DB05475 SCV-07

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...) asparagine3 Publications1
Glycosylationi173N-linked (GlcNAc...) asparagine4 Publications1
Glycosylationi205N-linked (GlcNAc...) asparagine3 Publications1
Disulfide bondi281 ↔ 3061 Publication
Glycosylationi282N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi309N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi390 ↔ 3911 Publication
Glycosylationi497N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi526N-linked (GlcNAc...) asparagine2 Publications1
Glycosylationi575N-linked (GlcNAc...) asparagine2 Publications1
Disulfide bondi583 ↔ 6091 Publication
Disulfide bondi585 ↔ 6271 Publication
Glycosylationi624N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi630N-linked (GlcNAc...) asparagineSequence 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
ProteomicsDBi47779
47780 [O00206-2]
47781 [O00206-3]

PTM databases

iPTMnetiO00206
PhosphoSitePlusiO00206

Expressioni

Tissue specificityi

Highly expressed in placenta, spleen and peripheral blood leukocytes (PubMed:9435236, PubMed:9237759). Detected in monocytes, macrophages, dendritic cells and several types of T-cells (PubMed:9237759, PubMed:27022195).3 Publications

Gene expression databases

BgeeiENSG00000136869 Expressed in 185 organ(s), highest expression level in leukocyte
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 MAP3K21; 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). Interacts with RFTN1; the interaction occurs in response to lipopolysaccharide stimulation (PubMed:27022195).By similarity10 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi112954, 31 interactors
CORUMiO00206
DIPiDIP-34769N
ELMiO00206
IntActiO00206, 30 interactors
MINTiO00206
STRINGi9606.ENSP00000363089

Chemistry databases

BindingDBiO00206

Structurei

Secondary structure

1839
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

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

Phylogenomic databases

eggNOGiKOG4641 Eukaryota
COG4886 LUCA
GeneTreeiENSGT00760000119006
HOVERGENiHBG018823
InParanoidiO00206
KOiK10160
OMAiEDWVRNE
OrthoDBiEOG091G01RC
PhylomeDBiO00206
TreeFamiTF351113

Family and domain databases

Gene3Di3.40.50.10140, 1 hit
3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000483 Cys-rich_flank_reg_C
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR000157 TIR_dom
IPR027168 TLR4
IPR035897 Toll_tir_struct_dom_sf
PANTHERiPTHR44568 PTHR44568, 1 hit
PfamiView protein in Pfam
PF13516 LRR_6, 1 hit
PF13855 LRR_8, 3 hits
PF01582 TIR, 1 hit
SMARTiView protein in SMART
SM00369 LRR_TYP, 11 hits
SM00082 LRRCT, 1 hit
SM00255 TIR, 1 hit
SUPFAMiSSF52200 SSF52200, 1 hit
PROSITEiView protein in PROSITE
PS51450 LRR, 11 hits
PS50104 TIR, 1 hit

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

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A2R8Y7P4A0A2R8Y7P4_HUMAN
Toll-like receptor 4
TLR4
32Annotation score:

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 dbSNP:rs16906079Ensembl.1
Natural variantiVAR_018729188Q → R1 PublicationCorresponds to variant dbSNP:rs5030713Ensembl.1
Natural variantiVAR_018730246C → S1 PublicationCorresponds to variant dbSNP:rs5030714Ensembl.1
Natural variantiVAR_074187287E → D1 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 dbSNP:rs4986790EnsemblClinVar.1
Natural variantiVAR_047563306C → W. Corresponds to variant dbSNP:rs2770145Ensembl.1
Natural variantiVAR_047564310V → G. Corresponds to variant dbSNP:rs2770144Ensembl.1
Natural variantiVAR_018731329N → S1 PublicationCorresponds to variant dbSNP:rs5030715Ensembl.1
Natural variantiVAR_020334342F → Y. Corresponds to variant dbSNP:rs5031050Ensembl.1
Natural variantiVAR_037668385L → F. Corresponds to variant dbSNP:rs11536884Ensembl.1
Natural variantiVAR_012740399T → I in allele TLR4*B; reduced LPS-response. 4 PublicationsCorresponds to variant dbSNP:rs4986791EnsemblClinVar.1
Natural variantiVAR_020335400S → N. Corresponds to variant dbSNP:rs4987233Ensembl.1
Natural variantiVAR_018732443F → L1 PublicationCorresponds to variant dbSNP:rs5030716Ensembl.1
Natural variantiVAR_018733474E → K1 PublicationCorresponds to variant dbSNP:rs5030718Ensembl.1
Natural variantiVAR_018734510Q → H1 PublicationCorresponds to variant dbSNP:rs5030719Ensembl.1
Natural variantiVAR_018735694K → R1 PublicationCorresponds to variant dbSNP:rs5030722Ensembl.1
Natural variantiVAR_018736763R → H1 PublicationCorresponds to variant dbSNP:rs5030723Ensembl.1
Natural variantiVAR_018737834Q → H1 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 No translation available.
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]
ENST00000645071; ENSP00000494590; ENSG00000136869 [O00206-1]
GeneIDi7099
KEGGihsa:7099
UCSCiuc004bjz.5 human [O00206-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

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 No translation available.
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[»]
5NAMNMR-A623-670[»]
5NAONMR-A623-657[»]
ProteinModelPortaliO00206
SMRiO00206
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112954, 31 interactors
CORUMiO00206
DIPiDIP-34769N
ELMiO00206
IntActiO00206, 30 interactors
MINTiO00206
STRINGi9606.ENSP00000363089

Chemistry databases

BindingDBiO00206
ChEMBLiCHEMBL5255
DrugBankiDB02767 3-Hydroxy-Myristic Acid
DB04933 Eritoran
DB03017 Lauric Acid
DB08231 MYRISTIC ACID
DB01183 Naloxone
DB05475 SCV-07

Protein family/group databases

TCDBi8.A.43.1.9 the neat-domain containing methaemoglobin heme sequestration (n-mhs) family

PTM databases

iPTMnetiO00206
PhosphoSitePlusiO00206

Polymorphism and mutation databases

BioMutaiTLR4

Proteomic databases

PaxDbiO00206
PeptideAtlasiO00206
PRIDEiO00206
ProteomicsDBi47779
47780 [O00206-2]
47781 [O00206-3]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000355622; ENSP00000363089; ENSG00000136869 [O00206-1]
ENST00000394487; ENSP00000377997; ENSG00000136869 [O00206-2]
ENST00000645071; ENSP00000494590; ENSG00000136869 [O00206-1]
GeneIDi7099
KEGGihsa:7099
UCSCiuc004bjz.5 human [O00206-1]

Organism-specific databases

CTDi7099
DisGeNETi7099
EuPathDBiHostDB:ENSG00000136869.13
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
OMAiEDWVRNE
OrthoDBiEOG091G01RC
PhylomeDBiO00206
TreeFamiTF351113

Enzyme and pathway databases

ReactomeiR-HSA-1236974 ER-Phagosome pathway
R-HSA-140534 via Death Receptors in the presence of ligand
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade
R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane
R-HSA-166166 MyD88-independent 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-9014325 TICAM1,TRAF6-dependent induction of TAK1 complex
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 within TLR4 complex
R-HSA-975163 IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation
SignaLinkiO00206
SIGNORiO00206

Miscellaneous databases

EvolutionaryTraceiO00206
GeneWikiiTLR_4
GenomeRNAii7099
PROiPR:O00206
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136869 Expressed in 185 organ(s), highest expression level in leukocyte
GenevisibleiO00206 HS

Family and domain databases

Gene3Di3.40.50.10140, 1 hit
3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000483 Cys-rich_flank_reg_C
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR000157 TIR_dom
IPR027168 TLR4
IPR035897 Toll_tir_struct_dom_sf
PANTHERiPTHR44568 PTHR44568, 1 hit
PfamiView protein in Pfam
PF13516 LRR_6, 1 hit
PF13855 LRR_8, 3 hits
PF01582 TIR, 1 hit
SMARTiView protein in SMART
SM00369 LRR_TYP, 11 hits
SM00082 LRRCT, 1 hit
SM00255 TIR, 1 hit
SUPFAMiSSF52200 SSF52200, 1 hit
PROSITEiView protein in PROSITE
PS51450 LRR, 11 hits
PS50104 TIR, 1 hit
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 historyiIntegrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: January 1, 1998
Last modified: October 10, 2018
This is version 197 of the entry and version 2 of the sequence. See 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

Keywords - Technical termi

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

Documents

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