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O00206

- TLR4_HUMAN

UniProt

O00206 - TLR4_HUMAN

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Protein

Toll-like receptor 4

Gene

TLR4

Organism
Homo sapiens (Human)
Status
Reviewed - 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. 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. 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.3 Publications

GO - Molecular functioni

  1. lipopolysaccharide binding Source: UniProtKB
  2. lipopolysaccharide receptor activity Source: UniProtKB
  3. receptor activity Source: ProtInc
  4. transmembrane signaling receptor activity Source: UniProtKB

GO - Biological processi

  1. activation of MAPK activity Source: BHF-UCL
  2. B cell proliferation involved in immune response Source: Ensembl
  3. cellular response to lipopolysaccharide Source: BHF-UCL
  4. cellular response to lipoteichoic acid Source: Ensembl
  5. cellular response to mechanical stimulus Source: UniProtKB
  6. defense response to bacterium Source: UniProtKB
  7. defense response to Gram-negative bacterium Source: BHF-UCL
  8. detection of fungus Source: UniProtKB
  9. detection of lipopolysaccharide Source: UniProtKB
  10. I-kappaB kinase/NF-kappaB signaling Source: Reactome
  11. I-kappaB phosphorylation Source: BHF-UCL
  12. immune response Source: ProtInc
  13. innate immune response Source: BHF-UCL
  14. interferon-gamma production Source: Ensembl
  15. intestinal epithelial structure maintenance Source: BHF-UCL
  16. lipopolysaccharide-mediated signaling pathway Source: MGI
  17. macrophage activation Source: UniProtKB
  18. MyD88-dependent toll-like receptor signaling pathway Source: Reactome
  19. MyD88-independent toll-like receptor signaling pathway Source: Reactome
  20. negative regulation of ERK1 and ERK2 cascade Source: BHF-UCL
  21. negative regulation of interferon-gamma production Source: BHF-UCL
  22. negative regulation of interleukin-17 production Source: BHF-UCL
  23. negative regulation of interleukin-23 production Source: BHF-UCL
  24. negative regulation of interleukin-6 production Source: BHF-UCL
  25. negative regulation of osteoclast differentiation Source: UniProtKB
  26. negative regulation of tumor necrosis factor production Source: BHF-UCL
  27. nitric oxide production involved in inflammatory response Source: Ensembl
  28. positive regulation of B cell proliferation Source: Ensembl
  29. positive regulation of chemokine production Source: BHF-UCL
  30. positive regulation of ERK1 and ERK2 cascade Source: Ensembl
  31. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  32. positive regulation of inflammatory response Source: BHF-UCL
  33. positive regulation of interferon-alpha production Source: BHF-UCL
  34. positive regulation of interferon-beta biosynthetic process Source: Ensembl
  35. positive regulation of interferon-beta production Source: BHF-UCL
  36. positive regulation of interferon-gamma production Source: BHF-UCL
  37. positive regulation of interleukin-10 production Source: BHF-UCL
  38. positive regulation of interleukin-12 biosynthetic process Source: UniProtKB
  39. positive regulation of interleukin-12 production Source: BHF-UCL
  40. positive regulation of interleukin-1 production Source: BHF-UCL
  41. positive regulation of interleukin-6 production Source: BHF-UCL
  42. positive regulation of interleukin-8 biosynthetic process Source: UniProtKB
  43. positive regulation of interleukin-8 production Source: BHF-UCL
  44. positive regulation of JNK cascade Source: Ensembl
  45. positive regulation of macrophage cytokine production Source: Ensembl
  46. positive regulation of MHC class II biosynthetic process Source: Ensembl
  47. positive regulation of NF-kappaB import into nucleus Source: BHF-UCL
  48. positive regulation of NF-kappaB transcription factor activity Source: MGI
  49. positive regulation of nitric oxide biosynthetic process Source: Ensembl
  50. positive regulation of nitric-oxide synthase biosynthetic process Source: BHF-UCL
  51. positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway Source: Ensembl
  52. positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway Source: Ensembl
  53. positive regulation of platelet activation Source: BHF-UCL
  54. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  55. positive regulation of tumor necrosis factor biosynthetic process Source: UniProtKB
  56. positive regulation of tumor necrosis factor production Source: BHF-UCL
  57. regulation of cytokine secretion Source: InterPro
  58. response to lipopolysaccharide Source: BHF-UCL
  59. T-helper 1 type immune response Source: UniProtKB
  60. toll-like receptor 2 signaling pathway Source: Reactome
  61. toll-like receptor 3 signaling pathway Source: Reactome
  62. toll-like receptor 4 signaling pathway Source: Reactome
  63. toll-like receptor signaling pathway Source: Reactome
  64. toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
  65. toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
  66. TRIF-dependent toll-like receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiREACT_150361. TRIF-mediated programmed cell death.
REACT_25148. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
REACT_25351. TRAF6 mediated induction of TAK1 complex.
REACT_25374. IKK complex recruitment mediated by RIP1.
REACT_6788. MyD88:Mal cascade initiated on plasma membrane.
REACT_6894. Toll Like Receptor 4 (TLR4) Cascade.
SignaLinkiO00206.

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
ProteomesiUP000005640: Chromosome 9

Organism-specific databases

HGNCiHGNC:11850. TLR4.

Subcellular locationi

Cell membrane; Single-pass type I membrane protein
Note: Upon complex formation with CD36 and TLR6, internalized through dynamin-dependent endocytosis.1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini24 – 631608ExtracellularSequence AnalysisAdd
BLAST
Transmembranei632 – 65221HelicalSequence AnalysisAdd
BLAST
Topological domaini653 – 839187CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cytoplasm Source: BHF-UCL
  2. endosome membrane Source: Reactome
  3. external side of plasma membrane Source: BHF-UCL
  4. integral component of plasma membrane Source: UniProtKB
  5. lipopolysaccharide receptor complex Source: UniProtKB
  6. perinuclear region of cytoplasm Source: UniProtKB
  7. plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Macular degeneration, age-related, 10 (ARMD10) [MIM:611488]: A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti299 – 2991D → G in allele TLR4*B; reduced LPS-response; associated with an increased risk for ARMD10 in Caucasian patients carriers. 5 Publications
Corresponds to variant rs4986790 [ dbSNP | Ensembl ].
VAR_012739

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi431 – 4311H → 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
Mutagenesisi456 – 4561H → 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
Mutagenesisi458 – 4581H → 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
Mutagenesisi526 – 5261N → A: Abolishes LPS-response and prevents the cell surface expression. 1 Publication
Mutagenesisi575 – 5751N → A: Abolishes LPS-response and prevents the cell surface expression. 1 Publication
Mutagenesisi697 – 6971E → R: Abolishes LPS-response. 1 Publication
Mutagenesisi710 – 7101R → E: Abolishes LPS-response. 1 Publication
Mutagenesisi711 – 7111D → K: Abolishes LPS-response. 1 Publication
Mutagenesisi714 – 7141P → H, R or E: Abolishes MYD88-binding and LPS-response. 1 Publication

Keywords - Diseasei

Age-related macular degeneration

Organism-specific databases

MIMi603030. gene+phenotype.
611488. phenotype.
Orphaneti117. Behcet disease.
PharmGKBiPA36552.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 23231 PublicationAdd
BLAST
Chaini24 – 839816Toll-like receptor 4PRO_0000034722Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi29 ↔ 40
Glycosylationi35 – 351N-linked (GlcNAc...)3 Publications
Glycosylationi173 – 1731N-linked (GlcNAc...)4 Publications
Glycosylationi205 – 2051N-linked (GlcNAc...)3 Publications
Disulfide bondi281 ↔ 306
Glycosylationi282 – 2821N-linked (GlcNAc...)1 Publication
Glycosylationi309 – 3091N-linked (GlcNAc...)1 Publication
Disulfide bondi390 ↔ 391
Glycosylationi497 – 4971N-linked (GlcNAc...)2 Publications
Glycosylationi526 – 5261N-linked (GlcNAc...)2 Publications
Glycosylationi575 – 5751N-linked (GlcNAc...)2 Publications
Disulfide bondi583 ↔ 609
Disulfide bondi585 ↔ 627
Glycosylationi624 – 6241N-linked (GlcNAc...)1 Publication
Glycosylationi630 – 6301N-linked (GlcNAc...)Sequence Analysis

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.
PRIDEiO00206.

PTM databases

PhosphoSiteiO00206.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiO00206.
ExpressionAtlasiO00206. baseline and differential.
GenevestigatoriO00206.

Organism-specific databases

HPAiCAB004025.

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 (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. 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.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
O765523EBI-528701,EBI-3870694From a different organism.
LY96Q9Y6Y93EBI-528701,EBI-1539247
TIRAPP587532EBI-528701,EBI-528644

Protein-protein interaction databases

BioGridi112954. 30 interactions.
DIPiDIP-34769N.
IntActiO00206. 14 interactions.
MINTiMINT-3981856.

Structurei

Secondary structure

1
839
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi29 – 335Combined sources
Turni34 – 363Combined sources
Beta strandi37 – 393Combined sources
Beta strandi50 – 523Combined sources
Beta strandi58 – 603Combined sources
Turni71 – 766Combined sources
Beta strandi81 – 844Combined sources
Turni95 – 1006Combined sources
Beta strandi106 – 1083Combined sources
Beta strandi115 – 1173Combined sources
Turni119 – 1246Combined sources
Beta strandi130 – 1323Combined sources
Helixi141 – 1433Combined sources
Turni145 – 1484Combined sources
Beta strandi154 – 1563Combined sources
Helixi169 – 1735Combined sources
Beta strandi179 – 1813Combined sources
Helixi192 – 1954Combined sources
Helixi196 – 1994Combined sources
Beta strandi206 – 2094Combined sources
Turni220 – 2256Combined sources
Beta strandi227 – 2359Combined sources
Helixi242 – 2487Combined sources
Turni249 – 2524Combined sources
Beta strandi254 – 2629Combined sources
Turni274 – 2774Combined sources
Helixi278 – 2825Combined sources
Beta strandi283 – 29210Combined sources
Beta strandi295 – 2984Combined sources
Turni301 – 3044Combined sources
Helixi305 – 3073Combined sources
Beta strandi311 – 3177Combined sources
Beta strandi319 – 3224Combined sources
Helixi324 – 3274Combined sources
Beta strandi333 – 3397Combined sources
Beta strandi341 – 3444Combined sources
Beta strandi355 – 3606Combined sources
Beta strandi377 – 3793Combined sources
Beta strandi387 – 3926Combined sources
Helixi393 – 3964Combined sources
Beta strandi403 – 4053Combined sources
Beta strandi410 – 41910Combined sources
Beta strandi426 – 4283Combined sources
Beta strandi432 – 4376Combined sources
Turni438 – 4458Combined sources
Beta strandi451 – 4533Combined sources
Turni464 – 4696Combined sources
Beta strandi475 – 4773Combined sources
Helixi484 – 4863Combined sources
Beta strandi500 – 5023Combined sources
Turni513 – 5186Combined sources
Beta strandi524 – 5263Combined sources
Helixi538 – 5403Combined sources
Beta strandi548 – 5503Combined sources
Beta strandi560 – 5634Combined sources
Beta strandi573 – 5753Combined sources
Helixi585 – 5873Combined sources
Helixi588 – 5969Combined sources
Helixi597 – 6004Combined sources
Helixi604 – 6063Combined sources
Beta strandi608 – 6125Combined sources
Helixi613 – 6153Combined sources
Beta strandi617 – 6193Combined sources
Helixi620 – 6223Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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. Positions 23-816.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00206.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati55 – 7622LRR 1Add
BLAST
Repeati79 – 10022LRR 2Add
BLAST
Repeati103 – 12422LRR 3Add
BLAST
Repeati127 – 14822LRR 4Add
BLAST
Repeati151 – 17222LRR 5Add
BLAST
Repeati176 – 19924LRR 6Add
BLAST
Repeati205 – 22521LRR 7Add
BLAST
Repeati227 – 24721LRR 8Add
BLAST
Repeati331 – 35121LRR 9Add
BLAST
Repeati352 – 37322LRR 10Add
BLAST
Repeati374 – 39421LRR 11Add
BLAST
Repeati400 – 42223LRR 12Add
BLAST
Repeati423 – 44422LRR 13Add
BLAST
Repeati448 – 4569LRR 14
Repeati472 – 49524LRR 15Add
BLAST
Repeati497 – 51822LRR 16Add
BLAST
Repeati521 – 54222LRR 17Add
BLAST
Repeati545 – 56521LRR 18Add
BLAST
Domaini579 – 62951LRRCTAdd
BLAST
Domaini672 – 818147TIRPROSITE-ProRule annotationAdd
BLAST

Domaini

The TIR domain mediates interaction with NOX4.

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

eggNOGiNOG249751.
GeneTreeiENSGT00760000119006.
HOVERGENiHBG018823.
InParanoidiO00206.
KOiK10160.
OMAiPESWDPC.
OrthoDBiEOG7ZKS9G.
PhylomeDBiO00206.
TreeFamiTF351113.

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR001611. Leu-rich_rpt.
IPR025875. Leu-rich_rpt_4.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000157. TIR_dom.
IPR027168. TLR4.
IPR017241. Toll-like_receptor.
[Graphical view]
PANTHERiPTHR24365:SF230. PTHR24365:SF230. 1 hit.
PfamiPF12799. LRR_4. 1 hit.
PF13855. LRR_8. 2 hits.
PF01582. TIR. 1 hit.
[Graphical view]
PIRSFiPIRSF037595. Toll-like_receptor. 1 hit.
SMARTiSM00369. LRR_TYP. 2 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. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti73 – 731S → R in ABU41664. 1 PublicationCurated
Sequence conflicti400 – 4001S → C in BAF82742. (PubMed:14702039)Curated
Sequence conflicti581 – 5811F → S in BAG64706. (PubMed:14702039)Curated

Polymorphismi

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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti175 – 1751T → A.
Corresponds to variant rs16906079 [ dbSNP | Ensembl ].
VAR_021977
Natural varianti188 – 1881Q → R.1 Publication
Corresponds to variant rs5030713 [ dbSNP | Ensembl ].
VAR_018729
Natural varianti246 – 2461C → S.1 Publication
Corresponds to variant rs5030714 [ dbSNP | Ensembl ].
VAR_018730
Natural varianti299 – 2991D → G in allele TLR4*B; reduced LPS-response; associated with an increased risk for ARMD10 in Caucasian patients carriers. 5 Publications
Corresponds to variant rs4986790 [ dbSNP | Ensembl ].
VAR_012739
Natural varianti306 – 3061C → W.
Corresponds to variant rs2770145 [ dbSNP | Ensembl ].
VAR_047563
Natural varianti310 – 3101V → G.
Corresponds to variant rs2770144 [ dbSNP | Ensembl ].
VAR_047564
Natural varianti329 – 3291N → S.1 Publication
Corresponds to variant rs5030715 [ dbSNP | Ensembl ].
VAR_018731
Natural varianti342 – 3421F → Y.
Corresponds to variant rs5031050 [ dbSNP | Ensembl ].
VAR_020334
Natural varianti385 – 3851L → F.
Corresponds to variant rs11536884 [ dbSNP | Ensembl ].
VAR_037668
Natural varianti399 – 3991T → I in allele TLR4*B; reduced LPS-response. 4 Publications
Corresponds to variant rs4986791 [ dbSNP | Ensembl ].
VAR_012740
Natural varianti400 – 4001S → N.
Corresponds to variant rs4987233 [ dbSNP | Ensembl ].
VAR_020335
Natural varianti443 – 4431F → L.1 Publication
Corresponds to variant rs5030716 [ dbSNP | Ensembl ].
VAR_018732
Natural varianti474 – 4741E → K.1 Publication
Corresponds to variant rs5030718 [ dbSNP | Ensembl ].
VAR_018733
Natural varianti510 – 5101Q → H.1 Publication
Corresponds to variant rs5030719 [ dbSNP | Ensembl ].
VAR_018734
Natural varianti694 – 6941K → R.1 Publication
Corresponds to variant rs5030722 [ dbSNP | Ensembl ].
VAR_018735
Natural varianti763 – 7631R → H.1 Publication
Corresponds to variant rs5030723 [ dbSNP | Ensembl ].
VAR_018736
Natural varianti834 – 8341Q → H.1 Publication
VAR_018737

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 200200Missing in isoform 3. 1 PublicationVSP_035793Add
BLAST
Alternative sequencei1 – 4040Missing in isoform 2. 2 PublicationsVSP_035794Add
BLAST

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.4. 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 .
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 ]
UniGenei Hs.174312.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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 [» ]
ProteinModelPortali O00206.
SMRi O00206. Positions 23-816.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112954. 30 interactions.
DIPi DIP-34769N.
IntActi O00206. 14 interactions.
MINTi MINT-3981856.

Chemistry

BindingDBi O00206.
ChEMBLi CHEMBL3038512.
DrugBanki DB01183. Naloxone.
GuidetoPHARMACOLOGYi 1754.

PTM databases

PhosphoSitei O00206.

Proteomic databases

PaxDbi O00206.
PRIDEi O00206.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000355622 ; ENSP00000363089 ; ENSG00000136869 . [O00206-1 ]
ENST00000394487 ; ENSP00000377997 ; ENSG00000136869 . [O00206-2 ]
GeneIDi 7099.
KEGGi hsa:7099.
UCSCi uc004bjz.4. human. [O00206-1 ]

Organism-specific databases

CTDi 7099.
GeneCardsi GC09P120466.
HGNCi HGNC:11850. TLR4.
HPAi CAB004025.
MIMi 603030. gene+phenotype.
611488. phenotype.
neXtProti NX_O00206.
Orphaneti 117. Behcet disease.
PharmGKBi PA36552.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG249751.
GeneTreei ENSGT00760000119006.
HOVERGENi HBG018823.
InParanoidi O00206.
KOi K10160.
OMAi PESWDPC.
OrthoDBi EOG7ZKS9G.
PhylomeDBi O00206.
TreeFami TF351113.

Enzyme and pathway databases

Reactomei REACT_150361. TRIF-mediated programmed cell death.
REACT_25148. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
REACT_25351. TRAF6 mediated induction of TAK1 complex.
REACT_25374. IKK complex recruitment mediated by RIP1.
REACT_6788. MyD88:Mal cascade initiated on plasma membrane.
REACT_6894. Toll Like Receptor 4 (TLR4) Cascade.
SignaLinki O00206.

Miscellaneous databases

EvolutionaryTracei O00206.
GeneWikii TLR_4.
GenomeRNAii 7099.
NextBioi 27773.
PROi O00206.
SOURCEi Search...

Gene expression databases

Bgeei O00206.
ExpressionAtlasi O00206. baseline and differential.
Genevestigatori O00206.

Family and domain databases

Gene3Di 3.40.50.10140. 1 hit.
InterProi IPR000483. Cys-rich_flank_reg_C.
IPR001611. Leu-rich_rpt.
IPR025875. Leu-rich_rpt_4.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000157. TIR_dom.
IPR027168. TLR4.
IPR017241. Toll-like_receptor.
[Graphical view ]
PANTHERi PTHR24365:SF230. PTHR24365:SF230. 1 hit.
Pfami PF12799. LRR_4. 1 hit.
PF13855. LRR_8. 2 hits.
PF01582. TIR. 1 hit.
[Graphical view ]
PIRSFi PIRSF037595. Toll-like_receptor. 1 hit.
SMARTi SM00369. LRR_TYP. 2 hits.
SM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view ]
SUPFAMi SSF52200. SSF52200. 1 hit.
PROSITEi PS51450. LRR. 11 hits.
PS50104. TIR. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "A human homologue of the Drosophila Toll protein signals activation of adaptive immunity."
    Medzhitov R., Preston-Hurlburt P., Janeway C.A. Jr.
    Nature 388:394-397(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Spleen.
  2. "A family of human receptors structurally related to Drosophila Toll."
    Rock F.L., Hardiman G., Timans J.C., Kastelein R.A., Bazan J.F.
    Proc. Natl. Acad. Sci. U.S.A. 95:588-593(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
    Tissue: Fetal liver, Lung and Placenta.
  3. "Phylogenetic variation and polymorphism at the Toll-like receptor 4 locus (TLR4)."
    Smirnova I., Poltorak A., Chan E.K.L., McBride C., Beutler B.
    Genome Biol. 1:RESEARCH002.1-RESEARCH002.10(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-299 AND ILE-399.
  4. "TLR4 mutations are associated with endotoxin hyporesponsiveness in humans."
    Arbour N.C., Lorenz E., Schutte B.C., Zabner J., Kline J.N., Jones M., Frees K., Watt J.L., Schwartz D.A.
    Nat. Genet. 25:187-191(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-299 AND ILE-399.
  5. "Natural selection in the TLR-related genes in the course of primate evolution."
    Nakajima T., Ohtani H., Satta Y., Uno Y., Akari H., Ishida T., Kimura A.
    Immunogenetics 60:727-735(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  6. "The heterogeneous allelic repertoire of human Toll-Like receptor (TLR) genes."
    Georgel P., Macquin C., Bahram S.
    PLoS ONE 4:E7803-E7803(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-299 AND ILE-399.
  7. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
    Tissue: Hippocampus, Kidney and Uterus.
  8. "DNA sequence and analysis of human chromosome 9."
    Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L.
    , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
    Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  9. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  10. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Cerebellum.
  11. Liu Z., Li N., Wang J., Xiao W.
    Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-86.
  12. "Signal peptide prediction based on analysis of experimentally verified cleavage sites."
    Zhang Z., Henzel W.J.
    Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 24-38.
  13. "Structural basis for signal transduction by the Toll/interleukin-1 receptor domains."
    Xu Y., Tao X., Shen B., Horng T., Medzhitov R., Manley J.L., Tong L.
    Nature 408:111-115(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF GLU-697; ARG-710; ASP-711 AND PRO-714.
  14. "MD-2 and TLR4 N-linked glycosylations are important for a functional lipopolysaccharide receptor."
    da Silva Correia J., Ulevitch R.J.
    J. Biol. Chem. 277:1845-1854(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION AT ASN-35; ASN-173; ASN-205; ASN-282; ASN-309; ASN-497; ASN-526; ASN-575 AND ASN-624, MUTAGENESIS OF ASN-526 AND ASN-575.
  15. "Direct interaction of TLR4 with NAD(P)H oxidase 4 isozyme is essential for lipopolysaccharide-induced production of reactive oxygen species and activation of NF-kappa B."
    Park H.S., Jung H.Y., Park E.Y., Kim J., Lee W.J., Bae Y.S.
    J. Immunol. 173:3589-3593(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NOX4.
  16. "Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity."
    Kim F., Pham M., Luttrell I., Bannerman D.D., Tupper J., Thaler J., Hawn T.R., Raines E.W., Schwartz M.W.
    Circ. Res. 100:1589-1596(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  17. "Folding of Toll-like receptors by the HSP90 paralogue gp96 requires a substrate-specific cochaperone."
    Liu B., Yang Y., Qiu Z., Staron M., Hong F., Li Y., Wu S., Li Y., Hao B., Bona R., Han D., Li Z.
    Nat. Commun. 1:79-79(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HSP90B1.
  18. Erratum
    Liu B., Yang Y., Qiu Z., Staron M., Hong F., Li Y., Wu S., Li Y., Hao B., Bona R., Han D., Li Z.
    Nat. Commun. 3:653-653(2012)
  19. "CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer."
    Stewart C.R., Stuart L.M., Wilkinson K., van Gils J.M., Deng J., Halle A., Rayner K.J., Boyer L., Zhong R., Frazier W.A., Lacy-Hulbert A., El Khoury J., Golenbock D.T., Moore K.J.
    Nat. Immunol. 11:155-161(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH CD36 AND TLR6, SUBCELLULAR LOCATION.
  20. Cited for: FUNCTION, MUTAGENESIS OF HIS-431; HIS-456 AND HIS-458, INVOLVEMENT IN CONTACT ALLERGY TO NICKEL.
  21. "MLK4 has negative effect on TLR4 signaling."
    Seit-Nebi A., Cheng W., Xu H., Han J.
    Cell. Mol. Immunol. 9:27-33(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MLK4.
  22. "Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran."
    Kim H.M., Park B.S., Kim J.-I., Kim S.E., Lee J., Oh S.C., Enkhbayar P., Matsushima N., Lee H., Yoo O.J., Lee J.-O.
    Cell 130:906-917(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 27-228, DISULFIDE BONDS, GLYCOSYLATION AT ASN-35; ASN-173 AND ASN-205.
  23. "The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex."
    Park B.S., Song D.H., Kim H.M., Choi B.-S., Lee H., Lee J.-O.
    Nature 458:1191-1195(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 27-631 IN COMPLEX WITH LY96 AND LIPOPOLYSACCHARIDE, DISULFIDE BONDS, GLYCOSYLATION AT ASN-173; ASN-205; ASN-497 AND ASN-526 AND ASN-575.
  24. "Structure-based rational design of a Toll-like receptor 4 (TLR4) decoy receptor with high binding affinity for a target protein."
    Han J., Kim H.J., Lee S.C., Hong S., Park K., Jeon Y.H., Kim D., Cheong H.K., Kim H.S.
    PLoS ONE 7:E30929-E30929(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.37 ANGSTROMS) OF 28-228, GLYCOSYLATION AT ASN-35 AND ASN-173, DISULFIDE BONDS.
  25. "Excess of rare amino acid polymorphisms in the Toll-like receptor 4 in humans."
    Smirnova I., Hamblin M.T., McBride C., Beutler B., Di Rienzo A.
    Genetics 158:1657-1664(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS ARG-188; SER-246; GLY-299; SER-329; ILE-399; LEU-443; LYS-474; HIS-510; ARG-694; HIS-763 AND HIS-834.
  26. "Toll-like receptor 4 variant D299G is associated with susceptibility to age-related macular degeneration."
    Zareparsi S., Buraczynska M., Branham K.E.H., Shah S., Eng D., Li M., Pawar H., Yashar B.M., Moroi S.E., Lichter P.R., Petty H.R., Richards J.E., Abecasis G.R., Elner V.M., Swaroop A.
    Hum. Mol. Genet. 14:1449-1455(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT GLY-299, ASSOCIATION WITH ARMD SUSCEPTIBILITY.

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: October 29, 2014
This is version 155 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.

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

External Data

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