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Reviewed, UniProtKB/Swiss-Prot O00206 (TLR4_HUMAN)

Last modified July 7, 2009. Version 94. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Toll-like receptor 4
Alternative name(s):
    hToll
    CD_antigen=CD284
Gene names
Name: TLR4
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length839 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

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.

Subunit structure

Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, LY96 and TLR4. Interacts with LY96 via the extracellular domain. Interacts with MYD88 and TIRAP via their respective TIR domains. Interacts with NOX4. Ref.14

Subcellular location

Membrane; Single-pass type I membrane protein.

Tissue specificity

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

Domain

The TIR domain mediates interaction with NOX4.

Post-translational modification

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. Ref.13 Ref.15

Polymorphism

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

Involvement in disease

Genetic variation in TLR4 is associated with age-related macular degeneration type 10 (ARMD10) [MIM:611488]. ARMD is 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.

Sequence similarities

Belongs to the Toll-like receptor family.

Contains 21 LRR (leucine-rich) repeats.

Contains 1 TIR domain.

Ontologies

Keywords
   Biological processImmune response
Inflammatory response
Innate immunity
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseAge-related macular degeneration
   DomainLeucine-rich repeat
Repeat
Signal
Transmembrane
   Molecular functionReceptor
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Gene Ontology (GO)
   Biological processI-kappaB kinase/NF-kappaB cascade

Inferred from Experiment. Source: Reactome

T-helper 1 type immune response

Non-traceable author statement. Source: UniProtKB

defense response to Gram-negative bacterium

Inferred by curator. Source: UniProtKB

detection of fungus

Non-traceable author statement. Source: UniProtKB

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

macrophage activation Ref.4

Inferred from mutant phenotype. Source: UniProtKB

negative regulation of osteoclast differentiation

Non-traceable author statement. Source: UniProtKB

positive regulation of interleukin-12 biosynthetic process

Inferred from direct assay. Source: UniProtKB

positive regulation of interleukin-8 biosynthetic process

Inferred from direct assay. Source: UniProtKB

positive regulation of platelet activation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of tumor necrosis factor biosynthetic process

Inferred from direct assay. Source: UniProtKB

response to lipopolysaccharide

Inferred by curator. Source: UniProtKB

   Cellular componentexternal side of plasma membrane

Inferred from direct assay. Source: UniProtKB

integral to plasma membrane

Inferred from direct assay. Source: UniProtKB

lipopolysaccharide receptor complex

Non-traceable author statement. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay. Source: UniProtKB

   Molecular functionlipopolysaccharide binding Ref.4

Non-traceable author statement. Source: UniProtKB

protein binding

Inferred from physical interaction. Source: IntAct

transmembrane receptor activity

Non-traceable author statement. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TIRAPP587531EBI-528701,EBI-528644

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O00206-1)

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.
Isoform 2 (identifier: O00206-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-40: Missing.
Isoform 3 (identifier: O00206-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-200: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Ref.11
Chain24 – 839816Toll-like receptor 4
PRO_0000034722

Regions

Topological domain24 – 631608Extracellular Potential
Transmembrane632 – 65221 Potential
Topological domain653 – 839187Cytoplasmic Potential
Repeat52 – 7625LRR 1
Repeat77 – 10024LRR 2
Repeat101 – 12424LRR 3
Repeat128 – 14922LRR 4
Repeat150 – 17324LRR 5
Repeat174 – 19724LRR 6
Repeat203 – 22523LRR 7
Repeat228 – 25225LRR 8
Repeat277 – 30327LRR 9
Repeat307 – 33024LRR 10
Repeat332 – 35019LRR 11
Repeat351 – 37222LRR 12
Repeat373 – 39826LRR 13
Repeat400 – 42122LRR 14
Repeat422 – 44524LRR 15
Repeat447 – 46923LRR 16
Repeat470 – 49425LRR 17
Repeat495 – 51824LRR 18
Repeat520 – 54122LRR 19
Repeat543 – 56624LRR 20
Repeat568 – 59225LRR 21
Domain672 – 818147TIR

Amino acid modifications

Glycosylation351N-linked (GlcNAc...) Ref.13 Ref.15
Glycosylation1731N-linked (GlcNAc...) Ref.13 Ref.15
Glycosylation2051N-linked (GlcNAc...) Ref.13 Ref.15
Glycosylation2821N-linked (GlcNAc...) Ref.13
Glycosylation3091N-linked (GlcNAc...) Ref.13
Glycosylation4971N-linked (GlcNAc...) Ref.13
Glycosylation5261N-linked (GlcNAc...) Ref.13
Glycosylation5751N-linked (GlcNAc...) Ref.13
Glycosylation6241N-linked (GlcNAc...) Ref.13
Glycosylation6301N-linked (GlcNAc...) Potential
Disulfide bond29 ↔ 40 Ref.15
Disulfide bond281 ↔ 306
Disulfide bond390 ↔ 391
Disulfide bond583 ↔ 609
Disulfide bond585 ↔ 627

Natural variations

Alternative sequence1 – 200200Missing in isoform 3.
VSP_035793
Alternative sequence1 – 4040Missing in isoform 2.
VSP_035794
Natural variant1751T → A: dbSNP rs16906079.
VAR_021977
Natural variant1881Q → R: dbSNP rs5030713. Ref.17
VAR_018729
Natural variant2461C → S: dbSNP rs5030714. Ref.17
VAR_018730
Natural variant2991D → G in allele TLR4*B; reduced LPS-response; associated with an increased risk for ARMD10 in Caucasian patients carriers. dbSNP rs4986790.
VAR_012739
Natural variant3061C → W: dbSNP rs2770145.
VAR_047563
Natural variant3101V → G: dbSNP rs2770144.
VAR_047564
Natural variant3291N → S: dbSNP rs5030715. Ref.17
VAR_018731
Natural variant3421F → Y: dbSNP rs5031050.
VAR_020334
Natural variant3851L → F: dbSNP rs11536884.
VAR_037668
Natural variant3991T → I in allele TLR4*B; reduced LPS-response. dbSNP rs4986791. Ref.17 Ref.3 Ref.4
VAR_012740
Natural variant4001S → N: dbSNP rs4987233.
VAR_020335
Natural variant4431F → L: dbSNP rs5030716. Ref.17
VAR_018732
Natural variant4741E → K: dbSNP rs5030718. Ref.17
VAR_018733
Natural variant5101Q → H: dbSNP rs5030719. Ref.17
VAR_018734
Natural variant6941K → R: dbSNP rs5030722. Ref.17
VAR_018735
Natural variant7631R → H: dbSNP rs5030723. Ref.17
VAR_018736
Natural variant8341Q → H Ref.17
VAR_018737

Experimental info

Mutagenesis5261N → A: Abolishes LPS-response and prevents the cell surface expression. Ref.13
Mutagenesis5751N → A: Abolishes LPS-response and prevents the cell surface expression. Ref.13
Mutagenesis6971E → R: Abolishes LPS-response. Ref.12
Mutagenesis7101R → E: Abolishes LPS-response. Ref.12
Mutagenesis7111D → K: Abolishes LPS-response. Ref.12
Mutagenesis7141P → H, R or E: Abolishes MYD88-binding and LPS-response. Ref.12
Sequence conflict731S → R in ABU41664. Ref.10
Sequence conflict4001S → C in BAF82742. Ref.6
Sequence conflict5811F → S in BAG64706. Ref.6

Secondary structure

..................................................................................................... 839
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 1, 1998. Version 2.
Checksum: 92C48F55821133E8

FASTA83995,680
        10         20         30         40         50         60 
MMSASRLAGT LIPAMAFLSC VRPESWEPCV EVVPNITYQC MELNFYKIPD NLPFSTKNLD 

        70         80         90        100        110        120 
LSFNPLRHLG SYSFFSFPEL QVLDLSRCEI QTIEDGAYQS LSHLSTLILT GNPIQSLALG 

       130        140        150        160        170        180 
AFSGLSSLQK LVAVETNLAS LENFPIGHLK TLKELNVAHN LIQSFKLPEY FSNLTNLEHL 

       190        200        210        220        230        240 
DLSSNKIQSI YCTDLRVLHQ MPLLNLSLDL SLNPMNFIQP GAFKEIRLHK LTLRNNFDSL 

       250        260        270        280        290        300 
NVMKTCIQGL AGLEVHRLVL GEFRNEGNLE KFDKSALEGL CNLTIEEFRL AYLDYYLDDI 

       310        320        330        340        350        360 
IDLFNCLTNV SSFSLVSVTI ERVKDFSYNF GWQHLELVNC KFGQFPTLKL KSLKRLTFTS 

       370        380        390        400        410        420 
NKGGNAFSEV DLPSLEFLDL SRNGLSFKGC CSQSDFGTTS LKYLDLSFNG VITMSSNFLG 

       430        440        450        460        470        480 
LEQLEHLDFQ HSNLKQMSEF SVFLSLRNLI YLDISHTHTR VAFNGIFNGL SSLEVLKMAG 

       490        500        510        520        530        540 
NSFQENFLPD IFTELRNLTF LDLSQCQLEQ LSPTAFNSLS SLQVLNMSHN NFFSLDTFPY 

       550        560        570        580        590        600 
KCLNSLQVLD YSLNHIMTSK KQELQHFPSS LAFLNLTQND FACTCEHQSF LQWIKDQRQL 

       610        620        630        640        650        660 
LVEVERMECA TPSDKQGMPV LSLNITCQMN KTIIGVSVLS VLVVSVVAVL VYKFYFHLML 

       670        680        690        700        710        720 
LAGCIKYGRG ENIYDAFVIY SSQDEDWVRN ELVKNLEEGV PPFQLCLHYR DFIPGVAIAA 

       730        740        750        760        770        780 
NIIHEGFHKS RKVIVVVSQH FIQSRWCIFE YEIAQTWQFL SSRAGIIFIV LQKVEKTLLR 

       790        800        810        820        830 
QQVELYRLLS RNTYLEWEDS VLGRHIFWRR LRKALLDGKS WNPEGTVGTG CNWQEATSI 

« Hide

Isoform 2.

Checksum: 82F70995E7F2AF9D
Show »

FASTA79991,296
Isoform 3.

Checksum: 23C1406CE32427EC
Show »

FASTA63973,301

References

« Hide 'large scale' references
[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: 9237759] [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: 9435236] [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: 11104518] [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: 10835634] [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: 18810425] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[6]"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. expand/collapse author list , 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: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
Tissue: Hippocampus, Kidney and Uterus.
[7]"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. expand/collapse author list , 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: 15164053] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Cerebellum.
[10]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.
[11]"Signal peptide prediction based on analysis of experimentally verified cleavage sites."
Zhang Z., Henzel W.J.
Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract]
Cited for: PROTEIN SEQUENCE OF 24-38.
[12]"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: 11081518] [Abstract]
Cited for: MUTAGENESIS OF GLU-697; ARG-710; ASP-711 AND PRO-714.
[13]"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: 11706042] [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.
[14]"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: 15356101] [Abstract]
Cited for: INTERACTION WITH NOX4.
[15]"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: 17803912] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 27-228, DISULFIDE BONDS, GLYCOSYLATION AT ASN-35; ASN-173 AND ASN-205.
[16]"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: 19252480] [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.
[17]"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: 11514453] [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.
[18]"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: 15829498] [Abstract]
Cited for: VARIANT GLY-299, ASSSOCIATION WITH ARMD SUSCEPTIBILITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

U93091 mRNA. Translation: AAC80227.1.
AB445638 mRNA. Translation: BAG55035.1.
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.
IPIIPI00008673.
IPI00374265.
IPI00914904.
RefSeqNP_612564.1.
UniGeneHs.174312

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
2Z62X-ray1.70A27-228[»]
2Z63X-ray2.00A27-527[»]
2Z65X-ray2.70A/B27-228[»]
2Z66X-ray1.90A/B/C/D380-627[»]
3FXIX-ray3.10A/B27-631[»]
ModBaseSearch...

Protein-protein interaction databases

IntActO00206. 5 interactions.

PTM databases

PhosphoSiteO00206.

Proteomic databases

PRIDEO00206.

Genome annotation databases

EnsemblENSG00000136869. Homo sapiens. [Contig view]
GeneID7099.
KEGGhsa:7099.
UCSCuc004bjz.1. human.

Organism-specific databases

GeneCardsGC09P119506.
H-InvDBHIX0034835.
HGNCHGNC:11850. TLR4.
HPACAB004025.
MIM603030. gene+phenotype.
611488. phenotype.
PharmGKBPA36552.
GenAtlasSearch...

Phylogenomic databases

HOGENOMO00206.
HOVERGENO00206.
OMAO00206. LAGLEVH.

Enzyme and pathway databases

ReactomeREACT_6900. Signaling in Immune system.
REACT_6968. Mal Cascade.

Gene expression databases

ArrayExpressO00206.
BgeeO00206.
GermOnlineENSG00000136869. Homo sapiens.

Family and domain databases

InterProIPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000483. LRR_C.
IPR000157. Toll-Interleukin_rcpt.
IPR017241. Toll-like_receptor.
[Graphical view]
PfamPF00560. LRR_1. 6 hits.
PF01463. LRRCT. 1 hit.
PF01582. TIR. 1 hit.
[Graphical view]
PIRSFPIRSF037595. Toll-like_receptor. 1 hit.
SMARTSM00369. LRR_TYP. 2 hits.
SM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
PROSITEPS50104. TIR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio27773.
SOURCESearch...

Entry information

Entry nameTLR4_HUMAN
AccessionPrimary (citable) accession number: O00206
Secondary accession number(s): A8K1Y8 expand/collapse secondary AC list , A9XLP9, A9XLQ0, A9XLQ1, B4E194, Q5VZI8, Q5VZI9, Q9UK78, Q9UM57
Entry history
Integrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: January 1, 1998
Last modified: July 7, 2009
This is version 94 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

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 polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

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

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents