UniProtKB - O00206 (TLR4_HUMAN)
Toll-like receptor 4
TLR4
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,PubMed:21393102).
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, PubMed:10835634, PubMed:15809303, PubMed:17478729, PubMed:20037584, PubMed:20711192, PubMed:23880187, PubMed:27022195, PubMed:9237759).
Activated by the signaling pathway regulator NMI which acts as damage-associated molecular patterns (DAMPs) in response to cell injury or pathogen invasion, therefore promoting nuclear factor NF-kappa-B activation (PubMed:29038465).
10 PublicationsMiscellaneous
Caution
GO - Molecular functioni
- amyloid-beta binding Source: ARUK-UCL
- identical protein binding Source: IntAct
- lipopolysaccharide binding Source: BHF-UCL
- lipopolysaccharide immune receptor activity Source: UniProtKB
- NAD(P)+ nucleosidase activity Source: UniProtKB-EC
- NAD+ nucleotidase, cyclic ADP-ribose generating Source: UniProtKB-EC
- protein heterodimerization activity Source: ARUK-UCL
- signaling receptor activity Source: GO_Central
- signaling receptor binding Source: ARUK-UCL
- transmembrane signaling receptor activity Source: UniProtKB
GO - Biological processi
- activation of innate immune response Source: Ensembl
- astrocyte development Source: Ensembl
- B cell proliferation involved in immune response Source: Ensembl
- cellular response to amyloid-beta Source: ComplexPortal
- cellular response to interferon-gamma Source: UniProtKB
- cellular response to lipopolysaccharide Source: UniProtKB
- cellular response to lipoteichoic acid Source: Ensembl
- cellular response to mechanical stimulus Source: UniProtKB
- cellular response to oxidised low-density lipoprotein particle stimulus Source: ComplexPortal
- cellular response to platelet-derived growth factor stimulus Source: Ensembl
- defense response to bacterium Source: ARUK-UCL
- defense response to Gram-negative bacterium Source: GO_Central
- detection of fungus Source: UniProtKB
- detection of lipopolysaccharide Source: UniProtKB
- I-kappaB phosphorylation Source: BHF-UCL
- immune response Source: ProtInc
- inflammatory response Source: GO_Central
- innate immune response Source: BHF-UCL
- intestinal epithelial structure maintenance Source: BHF-UCL
- lipopolysaccharide-mediated signaling pathway Source: MGI
- macrophage activation Source: UniProtKB
- MyD88-dependent toll-like receptor signaling pathway Source: ComplexPortal
- negative regulation of cold-induced thermogenesis Source: YuBioLab
- 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 osteoclast differentiation Source: UniProtKB
- negative regulation of tumor necrosis factor production Source: BHF-UCL
- nitric oxide production involved in inflammatory response Source: Ensembl
- phagocytosis Source: UniProtKB
- positive regulation of B cell proliferation Source: Ensembl
- positive regulation of cellular response to macrophage colony-stimulating factor stimulus Source: UniProtKB
- positive regulation of chemokine (C-X-C motif) ligand 2 production Source: ARUK-UCL
- positive regulation of chemokine production Source: BHF-UCL
- positive regulation of cytokine production involved in inflammatory response Source: ARUK-UCL
- positive regulation of ERK1 and ERK2 cascade Source: Ensembl
- positive regulation of gene expression Source: UniProtKB
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
- positive regulation of inflammatory response Source: ARUK-UCL
- positive regulation of interferon-alpha production Source: BHF-UCL
- 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 production Source: UniProtKB
- positive regulation of interleukin-1 beta production Source: UniProtKB
- positive regulation of interleukin-1 production Source: BHF-UCL
- positive regulation of interleukin-6 production Source: BHF-UCL
- positive regulation of interleukin-8 production Source: UniProtKB
- positive regulation of JNK cascade Source: Ensembl
- positive regulation of macrophage activation Source: ARUK-UCL
- positive regulation of macrophage cytokine production Source: Ensembl
- positive regulation of MAP kinase activity Source: BHF-UCL
- positive regulation of matrix metallopeptidase secretion Source: ARUK-UCL
- positive regulation of MHC class II biosynthetic process Source: Ensembl
- positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
- positive regulation of NIK/NF-kappaB signaling Source: BHF-UCL
- positive regulation of nitric oxide biosynthetic process Source: ARUK-UCL
- 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: Ensembl
- positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway Source: Ensembl
- positive regulation of oxidative stress-induced neuron death Source: ARUK-UCL
- positive regulation of platelet activation Source: BHF-UCL
- positive regulation of reactive oxygen species biosynthetic process Source: ARUK-UCL
- positive regulation of smooth muscle cell migration Source: Ensembl
- positive regulation of smooth muscle cell proliferation Source: Ensembl
- positive regulation of transcription by RNA polymerase II Source: BHF-UCL
- positive regulation of tumor necrosis factor production Source: UniProtKB
- regulation of dendritic cell cytokine production Source: Ensembl
- response to lipopolysaccharide Source: MGI
- T-helper 1 type immune response Source: UniProtKB
- toll-like receptor 4 signaling pathway Source: Ensembl
- toll-like receptor signaling pathway Source: ComplexPortal
- TRIF-dependent toll-like receptor signaling pathway Source: ARUK-UCL
- wound healing involved in inflammatory response Source: Ensembl
Keywordsi
Molecular function | Receptor |
Biological process | Immunity, Inflammatory response, Innate immunity |
Ligand | NAD |
Enzyme and pathway databases
PathwayCommonsi | O00206 |
Reactomei | R-HSA-1236974, ER-Phagosome pathway R-HSA-140534, Caspase activation via Death Receptors in the presence of ligand R-HSA-166016, Toll Like Receptor 4 (TLR4) Cascade R-HSA-166058, MyD88:MAL(TIRAP) 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-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-9707616, Heme signaling R-HSA-975163, IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation |
SignaLinki | O00206 |
SIGNORi | O00206 |
Protein family/group databases
TCDBi | 8.A.43.1.9, the neat-domain containing methaemoglobin heme sequestration (n-mhs) family |
Names & Taxonomyi
Protein namesi | Recommended name: Toll-like receptor 4Alternative name(s): hToll CD_antigen: CD284 |
Gene namesi | Name:TLR4 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:11850, TLR4 |
MIMi | 603030, gene |
neXtProti | NX_O00206 |
VEuPathDBi | HostDB:ENSG00000136869 |
Subcellular locationi
Endosome
- Early endosome 1 Publication
Plasma membrane
- Cell membrane 6 Publications; Single-pass type I membrane protein 1 Publication
Other locations
- ruffle By similarity
Note: Upon complex formation with CD36 and TLR6, internalized through dynamin-dependent endocytosis (PubMed:20037584). Colocalizes with RFTN1 at cell membrane and then together with RFTN1 moves to endosomes, upon lipopolysaccharide stimulation.1 Publication
Endosome
- early endosome Source: UniProtKB-SubCell
- endosome membrane Source: Reactome
Golgi apparatus
- Golgi apparatus Source: HPA
Plasma Membrane
- external side of plasma membrane Source: BHF-UCL
- integral component of plasma membrane Source: UniProtKB
- intrinsic component of plasma membrane Source: UniProtKB
- phagocytic cup Source: UniProtKB
- plasma membrane Source: UniProtKB
Other locations
- cell surface Source: UniProtKB
- cytoplasm Source: BHF-UCL
- lipopolysaccharide receptor complex Source: UniProtKB
- perinuclear region of cytoplasm Source: UniProtKB
- receptor complex Source: ARUK-UCL
- ruffle Source: UniProtKB-SubCell
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 24 – 631 | ExtracellularSequence analysisAdd BLAST | 608 | |
Transmembranei | 632 – 652 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 653 – 839 | CytoplasmicSequence analysisAdd BLAST | 187 |
Keywords - Cellular componenti
Cell membrane, Cell projection, Endosome, MembranePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 431 | H → 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 Publication | 1 | |
Mutagenesisi | 456 | H → 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 Publication | 1 | |
Mutagenesisi | 458 | H → 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 Publication | 1 | |
Mutagenesisi | 526 | N → A: Abolishes LPS-response and prevents the cell surface expression. 1 Publication | 1 | |
Mutagenesisi | 575 | N → A: Abolishes LPS-response and prevents the cell surface expression. 1 Publication | 1 | |
Mutagenesisi | 697 | E → R: Abolishes LPS-response. 1 Publication | 1 | |
Mutagenesisi | 710 | R → E: Abolishes LPS-response. 1 Publication | 1 | |
Mutagenesisi | 711 | D → K: Abolishes LPS-response. 1 Publication | 1 | |
Mutagenesisi | 714 | P → H, R or E: Abolishes MYD88-binding and LPS-response. 1 Publication | 1 |
Keywords - Diseasei
Age-related macular degenerationOrganism-specific databases
DisGeNETi | 7099 |
MalaCardsi | TLR4 |
OpenTargetsi | ENSG00000136869 |
Orphaneti | 117, Behcet disease |
PharmGKBi | PA36552 |
Miscellaneous databases
Pharosi | O00206, Tchem |
Chemistry databases
ChEMBLi | CHEMBL5255 |
DrugBanki | DB02767, (R)-3-hydroxytetradecanoic acid DB00924, Cyclobenzaprine DB06447, E5531 DB04933, Eritoran DB05475, Golotimod DB03017, Lauric acid DB13615, Mifamurtide DB08231, Myristic acid DB01183, Naloxone DB11193, Papain |
DrugCentrali | O00206 |
GuidetoPHARMACOLOGYi | 1754 |
Genetic variation databases
BioMutai | TLR4 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 23 | 1 PublicationAdd BLAST | 23 | |
ChainiPRO_0000034722 | 24 – 839 | Toll-like receptor 4Add BLAST | 816 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 29 ↔ 40 | 2 Publications | ||
Glycosylationi | 35 | N-linked (GlcNAc...) asparagine3 Publications | 1 | |
Glycosylationi | 173 | N-linked (GlcNAc...) asparagine4 Publications | 1 | |
Glycosylationi | 205 | N-linked (GlcNAc...) asparagine3 Publications | 1 | |
Disulfide bondi | 281 ↔ 306 | 1 Publication | ||
Glycosylationi | 282 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 309 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 390 ↔ 391 | 1 Publication | ||
Glycosylationi | 497 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Glycosylationi | 526 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Glycosylationi | 575 | N-linked (GlcNAc...) asparagine2 Publications | 1 | |
Disulfide bondi | 583 ↔ 609 | 1 Publication | ||
Disulfide bondi | 585 ↔ 627 | 1 Publication | ||
Glycosylationi | 624 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 630 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
MassIVEi | O00206 |
PaxDbi | O00206 |
PeptideAtlasi | O00206 |
PRIDEi | O00206 |
ProteomicsDBi | 47779 [O00206-1] 47780 [O00206-2] 47781 [O00206-3] |
PTM databases
GlyGeni | O00206, 10 sites |
iPTMneti | O00206 |
PhosphoSitePlusi | O00206 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000136869, Expressed in leukocyte and 199 other tissues |
ExpressionAtlasi | O00206, baseline and differential |
Genevisiblei | O00206, HS |
Organism-specific databases
HPAi | ENSG00000136869, Low tissue specificity |
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).
Interacts with SCIMP; the interaction occurs in response to lipopolysaccharide stimulation and is enhanced by phosphorylation of SCIMP by LYN (By similarity). This interaction facilitates the phosphorylation of TLR4 by LYN which elicits a selective cytokine response in macrophages (By similarity).
Interacts with TRAF3IP3 (PubMed:30573680).
Interacts with TREM1; this interaction enhances TLR4-mediated inflammatory response (PubMed:21393102, PubMed:17098818).
By similarity13 Publications(Microbial infection) In case of infection, interacts with uropathogenic E.coli protein TcpC.
1 PublicationBinary interactionsi
O00206
Isoform 1 [O00206-1]
With | #Exp. | IntAct |
---|---|---|
LY96 [Q9Y6Y9] | 5 | EBI-15745059,EBI-1539247 |
DERP2 [P49278] from Dermatophagoides pteronyssinus. | 3 | EBI-15745059,EBI-15745025 |
GO - Molecular functioni
- identical protein binding Source: IntAct
- protein heterodimerization activity Source: ARUK-UCL
- signaling receptor binding Source: ARUK-UCL
Protein-protein interaction databases
BioGRIDi | 112954, 41 interactors |
ComplexPortali | CPX-2545, LY96-TLR4 toll-like receptor complex CPX-945, TLR4-TLR6 toll-like receptor complex |
CORUMi | O00206 |
DIPi | DIP-34769N |
ELMi | O00206 |
IntActi | O00206, 33 interactors |
MINTi | O00206 |
STRINGi | 9606.ENSP00000363089 |
Chemistry databases
BindingDBi | O00206 |
Miscellaneous databases
RNActi | O00206, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | O00206 |
SMRi | O00206 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O00206 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 55 – 76 | LRR 1Add BLAST | 22 | |
Repeati | 79 – 100 | LRR 2Add BLAST | 22 | |
Repeati | 103 – 124 | LRR 3Add BLAST | 22 | |
Repeati | 127 – 148 | LRR 4Add BLAST | 22 | |
Repeati | 151 – 172 | LRR 5Add BLAST | 22 | |
Repeati | 176 – 199 | LRR 6Add BLAST | 24 | |
Repeati | 205 – 225 | LRR 7Add BLAST | 21 | |
Repeati | 227 – 247 | LRR 8Add BLAST | 21 | |
Repeati | 331 – 351 | LRR 9Add BLAST | 21 | |
Repeati | 352 – 373 | LRR 10Add BLAST | 22 | |
Repeati | 374 – 394 | LRR 11Add BLAST | 21 | |
Repeati | 400 – 422 | LRR 12Add BLAST | 23 | |
Repeati | 423 – 444 | LRR 13Add BLAST | 22 | |
Repeati | 448 – 456 | LRR 14 | 9 | |
Repeati | 472 – 495 | LRR 15Add BLAST | 24 | |
Repeati | 497 – 518 | LRR 16Add BLAST | 22 | |
Repeati | 521 – 542 | LRR 17Add BLAST | 22 | |
Repeati | 545 – 565 | LRR 18Add BLAST | 21 | |
Domaini | 579 – 629 | LRRCTAdd BLAST | 51 | |
Domaini | 672 – 815 | TIRPROSITE-ProRule annotationAdd BLAST | 144 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG4641, Eukaryota |
GeneTreei | ENSGT00940000160778 |
HOGENOMi | CLU_006000_5_0_1 |
InParanoidi | O00206 |
OMAi | CKHSAER |
OrthoDBi | 282372at2759 |
PhylomeDBi | O00206 |
TreeFami | TF351113 |
Family and domain databases
Gene3Di | 3.40.50.10140, 1 hit 3.80.10.10, 1 hit |
InterProi | View 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 IPR017241, Toll-like_receptor IPR035897, Toll_tir_struct_dom_sf |
PANTHERi | PTHR24365, PTHR24365, 1 hit |
Pfami | View protein in Pfam PF13855, LRR_8, 3 hits PF01582, TIR, 1 hit |
PIRSFi | PIRSF037595, Toll-like_receptor, 1 hit |
SMARTi | View protein in SMART SM00369, LRR_TYP, 11 hits SM00082, LRRCT, 1 hit SM00255, TIR, 1 hit |
SUPFAMi | SSF52200, SSF52200, 1 hit |
PROSITEi | View protein in PROSITE PS51450, LRR, 11 hits PS50104, TIR, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA0A2R8Y7P4 | A0A2R8Y7P4_HUMAN | Toll-like receptor 4 | TLR4 | 32 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 73 | S → R in ABU41664 (Ref. 11) Curated | 1 | |
Sequence conflicti | 400 | S → C in BAF82742 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 581 | F → S in BAG64706 (PubMed:14702039).Curated | 1 |
Polymorphismi
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_021977 | 175 | T → A. Corresponds to variant dbSNP:rs16906079Ensembl. | 1 | |
Natural variantiVAR_018729 | 188 | Q → R1 PublicationCorresponds to variant dbSNP:rs5030713Ensembl. | 1 | |
Natural variantiVAR_018730 | 246 | C → S1 PublicationCorresponds to variant dbSNP:rs5030714Ensembl. | 1 | |
Natural variantiVAR_074187 | 287 | E → D1 Publication | 1 | |
Natural variantiVAR_012739 | 299 | D → 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_047563 | 306 | C → W. Corresponds to variant dbSNP:rs2770145Ensembl. | 1 | |
Natural variantiVAR_047564 | 310 | V → G. Corresponds to variant dbSNP:rs2770144Ensembl. | 1 | |
Natural variantiVAR_018731 | 329 | N → S1 PublicationCorresponds to variant dbSNP:rs5030715Ensembl. | 1 | |
Natural variantiVAR_020334 | 342 | F → Y. Corresponds to variant dbSNP:rs5031050Ensembl. | 1 | |
Natural variantiVAR_037668 | 385 | L → F. Corresponds to variant dbSNP:rs11536884Ensembl. | 1 | |
Natural variantiVAR_012740 | 399 | T → I in allele TLR4*B; reduced LPS-response. 4 PublicationsCorresponds to variant dbSNP:rs4986791EnsemblClinVar. | 1 | |
Natural variantiVAR_020335 | 400 | S → N. Corresponds to variant dbSNP:rs4987233Ensembl. | 1 | |
Natural variantiVAR_018732 | 443 | F → L1 PublicationCorresponds to variant dbSNP:rs5030716Ensembl. | 1 | |
Natural variantiVAR_018733 | 474 | E → K1 PublicationCorresponds to variant dbSNP:rs5030718Ensembl. | 1 | |
Natural variantiVAR_018734 | 510 | Q → H1 PublicationCorresponds to variant dbSNP:rs5030719Ensembl. | 1 | |
Natural variantiVAR_018735 | 694 | K → R1 PublicationCorresponds to variant dbSNP:rs5030722Ensembl. | 1 | |
Natural variantiVAR_018736 | 763 | R → H1 PublicationCorresponds to variant dbSNP:rs5030723Ensembl. | 1 | |
Natural variantiVAR_018737 | 834 | Q → H1 Publication | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_035793 | 1 – 200 | Missing in isoform 3. 1 PublicationAdd BLAST | 200 | |
Alternative sequenceiVSP_035794 | 1 – 40 | Missing in isoform 2. 2 PublicationsAdd BLAST | 40 |
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 |
CCDSi | CCDS6818.1 [O00206-1] |
RefSeqi | NP_003257.1, NM_003266.3 [O00206-2] NP_612564.1, NM_138554.4 [O00206-1] NP_612567.1, NM_138557.2 [O00206-3] |
Genome annotation databases
Ensembli | ENST00000355622.8; ENSP00000363089.5; ENSG00000136869.16 ENST00000394487.5; ENSP00000377997.4; ENSG00000136869.16 [O00206-2] |
GeneIDi | 7099 |
KEGGi | hsa:7099 |
MANE-Selecti | ENST00000355622.8; ENSP00000363089.5; NM_138554.5; NP_612564.1 |
UCSCi | uc004bjz.5, human [O00206-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar 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 |
CCDSi | CCDS6818.1 [O00206-1] |
RefSeqi | NP_003257.1, NM_003266.3 [O00206-2] NP_612564.1, NM_138554.4 [O00206-1] NP_612567.1, NM_138557.2 [O00206-3] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2Z62 | X-ray | 1.70 | A | 27-228 | [»] | |
2Z63 | X-ray | 2.00 | A | 27-527 | [»] | |
2Z65 | X-ray | 2.70 | A/B | 27-228 | [»] | |
2Z66 | X-ray | 1.90 | A/B/C/D | 381-627 | [»] | |
3FXI | X-ray | 3.10 | A/B | 27-631 | [»] | |
3UL7 | X-ray | 2.37 | A | 28-226 | [»] | |
3UL8 | X-ray | 2.50 | A | 27-228 | [»] | |
3UL9 | X-ray | 2.45 | A | 28-228 | [»] | |
3ULA | X-ray | 3.60 | A/C | 27-228 | [»] | |
4G8A | X-ray | 2.40 | A/B | 23-629 | [»] | |
5NAM | NMR | - | A | 623-670 | [»] | |
5NAO | NMR | - | A | 623-657 | [»] | |
AlphaFoldDBi | O00206 | |||||
SMRi | O00206 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 112954, 41 interactors |
ComplexPortali | CPX-2545, LY96-TLR4 toll-like receptor complex CPX-945, TLR4-TLR6 toll-like receptor complex |
CORUMi | O00206 |
DIPi | DIP-34769N |
ELMi | O00206 |
IntActi | O00206, 33 interactors |
MINTi | O00206 |
STRINGi | 9606.ENSP00000363089 |
Chemistry databases
BindingDBi | O00206 |
ChEMBLi | CHEMBL5255 |
DrugBanki | DB02767, (R)-3-hydroxytetradecanoic acid DB00924, Cyclobenzaprine DB06447, E5531 DB04933, Eritoran DB05475, Golotimod DB03017, Lauric acid DB13615, Mifamurtide DB08231, Myristic acid DB01183, Naloxone DB11193, Papain |
DrugCentrali | O00206 |
GuidetoPHARMACOLOGYi | 1754 |
Protein family/group databases
TCDBi | 8.A.43.1.9, the neat-domain containing methaemoglobin heme sequestration (n-mhs) family |
PTM databases
GlyGeni | O00206, 10 sites |
iPTMneti | O00206 |
PhosphoSitePlusi | O00206 |
Genetic variation databases
BioMutai | TLR4 |
Proteomic databases
MassIVEi | O00206 |
PaxDbi | O00206 |
PeptideAtlasi | O00206 |
PRIDEi | O00206 |
ProteomicsDBi | 47779 [O00206-1] 47780 [O00206-2] 47781 [O00206-3] |
Protocols and materials databases
ABCDi | O00206, 25 sequenced antibodies |
Antibodypediai | 3410, 1901 antibodies from 51 providers |
DNASUi | 7099 |
Genome annotation databases
Ensembli | ENST00000355622.8; ENSP00000363089.5; ENSG00000136869.16 ENST00000394487.5; ENSP00000377997.4; ENSG00000136869.16 [O00206-2] |
GeneIDi | 7099 |
KEGGi | hsa:7099 |
MANE-Selecti | ENST00000355622.8; ENSP00000363089.5; NM_138554.5; NP_612564.1 |
UCSCi | uc004bjz.5, human [O00206-1] |
Organism-specific databases
CTDi | 7099 |
DisGeNETi | 7099 |
GeneCardsi | TLR4 |
HGNCi | HGNC:11850, TLR4 |
HPAi | ENSG00000136869, Low tissue specificity |
MalaCardsi | TLR4 |
MIMi | 603030, gene |
neXtProti | NX_O00206 |
OpenTargetsi | ENSG00000136869 |
Orphaneti | 117, Behcet disease |
PharmGKBi | PA36552 |
VEuPathDBi | HostDB:ENSG00000136869 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4641, Eukaryota |
GeneTreei | ENSGT00940000160778 |
HOGENOMi | CLU_006000_5_0_1 |
InParanoidi | O00206 |
OMAi | CKHSAER |
OrthoDBi | 282372at2759 |
PhylomeDBi | O00206 |
TreeFami | TF351113 |
Enzyme and pathway databases
PathwayCommonsi | O00206 |
Reactomei | R-HSA-1236974, ER-Phagosome pathway R-HSA-140534, Caspase activation via Death Receptors in the presence of ligand R-HSA-166016, Toll Like Receptor 4 (TLR4) Cascade R-HSA-166058, MyD88:MAL(TIRAP) 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-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-9707616, Heme signaling R-HSA-975163, IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation |
SignaLinki | O00206 |
SIGNORi | O00206 |
Miscellaneous databases
BioGRID-ORCSi | 7099, 6 hits in 1065 CRISPR screens |
EvolutionaryTracei | O00206 |
GeneWikii | TLR_4 |
GenomeRNAii | 7099 |
Pharosi | O00206, Tchem |
PROi | PR:O00206 |
RNActi | O00206, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000136869, Expressed in leukocyte and 199 other tissues |
ExpressionAtlasi | O00206, baseline and differential |
Genevisiblei | O00206, HS |
Family and domain databases
Gene3Di | 3.40.50.10140, 1 hit 3.80.10.10, 1 hit |
InterProi | View 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 IPR017241, Toll-like_receptor IPR035897, Toll_tir_struct_dom_sf |
PANTHERi | PTHR24365, PTHR24365, 1 hit |
Pfami | View protein in Pfam PF13855, LRR_8, 3 hits PF01582, TIR, 1 hit |
PIRSFi | PIRSF037595, Toll-like_receptor, 1 hit |
SMARTi | View protein in SMART SM00369, LRR_TYP, 11 hits SM00082, LRRCT, 1 hit SM00255, TIR, 1 hit |
SUPFAMi | SSF52200, SSF52200, 1 hit |
PROSITEi | View protein in PROSITE PS51450, LRR, 11 hits PS50104, TIR, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | TLR4_HUMAN | |
Accessioni | O00206Primary (citable) accession number: O00206 Secondary accession number(s): A8K1Y8 Q9UM57 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 11, 2002 |
Last sequence update: | January 1, 1998 | |
Last modified: | May 25, 2022 | |
This is version 220 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Direct protein sequencing, Reference proteomeDocuments
- Human cell differentiation molecules
CD nomenclature of surface proteins of human leucocytes and list of entries - Human chromosome 9
Human chromosome 9: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Protein Spotlight
Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries