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O00206

- TLR4_HUMAN

UniProt

O00206 - TLR4_HUMAN

Protein

Toll-like receptor 4

Gene

TLR4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 154 (01 Oct 2014)
      Sequence version 2 (01 Jan 1998)
      Previous versions | rss
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    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.2 Publications

    GO - Molecular functioni

    1. lipopolysaccharide binding Source: UniProtKB
    2. lipopolysaccharide receptor activity Source: UniProtKB
    3. protein binding Source: UniProtKB
    4. receptor activity Source: ProtInc
    5. 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

    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

    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

    Keywords - Cellular componenti

    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

    ArrayExpressiO00206.
    BgeeiO00206.
    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.By similarity4 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. 13 interactions.
    MINTiMINT-3981856.

    Structurei

    Secondary structure

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

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.

    Topological domain

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

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei632 – 65221HelicalSequence AnalysisAdd
    BLAST

    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.
    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

    MMSASRLAGT LIPAMAFLSC VRPESWEPCV EVVPNITYQC MELNFYKIPD    50
    NLPFSTKNLD LSFNPLRHLG SYSFFSFPEL QVLDLSRCEI QTIEDGAYQS 100
    LSHLSTLILT GNPIQSLALG AFSGLSSLQK LVAVETNLAS LENFPIGHLK 150
    TLKELNVAHN LIQSFKLPEY FSNLTNLEHL DLSSNKIQSI YCTDLRVLHQ 200
    MPLLNLSLDL SLNPMNFIQP GAFKEIRLHK LTLRNNFDSL NVMKTCIQGL 250
    AGLEVHRLVL GEFRNEGNLE KFDKSALEGL CNLTIEEFRL AYLDYYLDDI 300
    IDLFNCLTNV SSFSLVSVTI ERVKDFSYNF GWQHLELVNC KFGQFPTLKL 350
    KSLKRLTFTS NKGGNAFSEV DLPSLEFLDL SRNGLSFKGC CSQSDFGTTS 400
    LKYLDLSFNG VITMSSNFLG LEQLEHLDFQ HSNLKQMSEF SVFLSLRNLI 450
    YLDISHTHTR VAFNGIFNGL SSLEVLKMAG NSFQENFLPD IFTELRNLTF 500
    LDLSQCQLEQ LSPTAFNSLS SLQVLNMSHN NFFSLDTFPY KCLNSLQVLD 550
    YSLNHIMTSK KQELQHFPSS LAFLNLTQND FACTCEHQSF LQWIKDQRQL 600
    LVEVERMECA TPSDKQGMPV LSLNITCQMN KTIIGVSVLS VLVVSVVAVL 650
    VYKFYFHLML LAGCIKYGRG ENIYDAFVIY SSQDEDWVRN ELVKNLEEGV 700
    PPFQLCLHYR DFIPGVAIAA NIIHEGFHKS RKVIVVVSQH FIQSRWCIFE 750
    YEIAQTWQFL SSRAGIIFIV LQKVEKTLLR QQVELYRLLS RNTYLEWEDS 800
    VLGRHIFWRR LRKALLDGKS WNPEGTVGTG CNWQEATSI 839
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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:
    PDBe
    RCSB PDB
    PDBj
    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. 13 interactions.
    MINTi MINT-3981856.

    Chemistry

    BindingDBi O00206.
    ChEMBLi CHEMBL3038512.
    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.
    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

    ArrayExpressi O00206.
    Bgeei O00206.
    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

    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. Cited for: FUNCTION, MUTAGENESIS OF HIS-431; HIS-456 AND HIS-458, INVOLVEMENT IN CONTACT ALLERGY TO NICKEL.
    20. "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.
    21. "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.
    22. "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.
    23. "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.
    24. "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.
    25. "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 1, 2014
    This is version 154 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

    Dasty 3