Reviewed, UniProtKB/Swiss-Prot O00206 (TLR4_HUMAN)

Names and origin

Protein names

Recommended name:
    Toll-like receptor 4
Alternative name(s):
    hToll
    CD_antigen=CD284

Gene names

Name:

TLR4

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	839 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Immune response Inflammatory response Innate immunity
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Age-related macular degeneration
Domain	Leucine-rich repeat Repeat Signal Transmembrane
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	I-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 component	external 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 function	lipopolysaccharide 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
TIRAP	P58753	1	EBI-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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 23

23

Ref.11

Chain

24 – 839

816

Toll-like receptor 4

PRO_0000034722

Regions

Topological domain

24 – 631

608

Extracellular Potential

Transmembrane

632 – 652

21

Potential

Topological domain

653 – 839

187

Cytoplasmic Potential

Repeat

52 – 76

25

LRR 1

Repeat

77 – 100

24

LRR 2

Repeat

101 – 124

24

LRR 3

Repeat

128 – 149

22

LRR 4

Repeat

150 – 173

24

LRR 5

Repeat

174 – 197

24

LRR 6

Repeat

203 – 225

23

LRR 7

Repeat

228 – 252

25

LRR 8

Repeat

277 – 303

27

LRR 9

Repeat

307 – 330

24

LRR 10

Repeat

332 – 350

19

LRR 11

Repeat

351 – 372

22

LRR 12

Repeat

373 – 398

26

LRR 13

Repeat

400 – 421

22

LRR 14

Repeat

422 – 445

24

LRR 15

Repeat

447 – 469

23

LRR 16

Repeat

470 – 494

25

LRR 17

Repeat

495 – 518

24

LRR 18

Repeat

520 – 541

22

LRR 19

Repeat

543 – 566

24

LRR 20

Repeat

568 – 592

25

LRR 21

Domain

672 – 818

147

TIR

Amino acid modifications

Glycosylation

35

1

N-linked (GlcNAc...) Ref.13 Ref.15

Glycosylation

173

1

N-linked (GlcNAc...) Ref.13 Ref.15

Glycosylation

205

1

N-linked (GlcNAc...) Ref.13 Ref.15

Glycosylation

282

1

N-linked (GlcNAc...) Ref.13

Glycosylation

309

1

N-linked (GlcNAc...) Ref.13

Glycosylation

497

1

N-linked (GlcNAc...) Ref.13

Glycosylation

526

1

N-linked (GlcNAc...) Ref.13

Glycosylation

575

1

N-linked (GlcNAc...) Ref.13

Glycosylation

624

1

N-linked (GlcNAc...) Ref.13

Glycosylation

630

1

N-linked (GlcNAc...) Potential

Disulfide bond

29 ↔ 40

Ref.15

Disulfide bond

281 ↔ 306

Disulfide bond

390 ↔ 391

Disulfide bond

583 ↔ 609

Disulfide bond

585 ↔ 627

Natural variations

Alternative sequence

1 – 200

200

Missing in isoform 3.

VSP_035793

Alternative sequence

1 – 40

40

Missing in isoform 2.

VSP_035794

Natural variant

175

1

T → A: dbSNP rs16906079.

VAR_021977

Natural variant

188

1

Q → R: dbSNP rs5030713. Ref.17

VAR_018729

Natural variant

246

1

C → S: dbSNP rs5030714. Ref.17

VAR_018730

Natural variant

299

1

D → G in allele TLR4*B; reduced LPS-response; associated with an increased risk for ARMD10 in Caucasian patients carriers. dbSNP rs4986790.

VAR_012739

Natural variant

306

1

C → W: dbSNP rs2770145.

VAR_047563

Natural variant

310

1

V → G: dbSNP rs2770144.

VAR_047564

Natural variant

329

1

N → S: dbSNP rs5030715. Ref.17

VAR_018731

Natural variant

342

1

F → Y: dbSNP rs5031050.

VAR_020334

Natural variant

385

1

L → F: dbSNP rs11536884.

VAR_037668

Natural variant

399

1

T → I in allele TLR4*B; reduced LPS-response. dbSNP rs4986791. Ref.17 Ref.3 Ref.4

VAR_012740

Natural variant

400

1

S → N: dbSNP rs4987233.

VAR_020335

Natural variant

443

1

F → L: dbSNP rs5030716. Ref.17

VAR_018732

Natural variant

474

1

E → K: dbSNP rs5030718. Ref.17

VAR_018733

Natural variant

510

1

Q → H: dbSNP rs5030719. Ref.17

VAR_018734

Natural variant

694

1

K → R: dbSNP rs5030722. Ref.17

VAR_018735

Natural variant

763

1

R → H: dbSNP rs5030723. Ref.17

VAR_018736

Natural variant

834

1

Q → H Ref.17

VAR_018737

Experimental info

Mutagenesis

526

1

N → A: Abolishes LPS-response and prevents the cell surface expression. Ref.13

Mutagenesis

575

1

N → A: Abolishes LPS-response and prevents the cell surface expression. Ref.13

Mutagenesis

697

1

E → R: Abolishes LPS-response. Ref.12

Mutagenesis

710

1

R → E: Abolishes LPS-response. Ref.12

Mutagenesis

711

1

D → K: Abolishes LPS-response. Ref.12

Mutagenesis

714

1

P → H, R or E: Abolishes MYD88-binding and LPS-response. Ref.12

Sequence conflict

73

1

S → R in ABU41664. Ref.10

Sequence conflict

400

1

S → C in BAF82742. Ref.6

Sequence conflict

581

1

F → S in BAG64706. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

839

Helix Strand Turn

Details...

Beta strand

29 – 33

5

Turn

34 – 36

3

Beta strand

37 – 39

3

Beta strand

50 – 52

3

Beta strand

58 – 60

3

Turn

71 – 76

6

Beta strand

81 – 84

4

Turn

95 – 100

6

Beta strand

106 – 108

3

Turn

119 – 124

6

Beta strand

130 – 132

3

Beta strand

154 – 156

3

Helix

169 – 173

5

Beta strand

179 – 181

3

Helix

192 – 195

4

Helix

196 – 199

4

Beta strand

206 – 209

4

Beta strand

228 – 232

5

Turn

237 – 239

3

Beta strand

244 – 246

3

Turn

255 – 258

4

Helix

259 – 265

7

Turn

274 – 277

4

Helix

278 – 282

5

Beta strand

283 – 292

10

Beta strand

295 – 298

4

Turn

301 – 304

4

Helix

305 – 307

3

Beta strand

311 – 317

7

Beta strand

333 – 339

7

Beta strand

355 – 360

6

Beta strand

377 – 379

3

Beta strand

386 – 392

7

Helix

393 – 396

4

Beta strand

403 – 405

3

Beta strand

410 – 419

10

Beta strand

426 – 428

3

Beta strand

432 – 436

5

Turn

442 – 445

4

Beta strand

451 – 453

3

Turn

464 – 469

6

Beta strand

475 – 477

3

Helix

484 – 486

3

Beta strand

500 – 502

3

Turn

513 – 518

6

Beta strand

524 – 526

3

Turn

537 – 542

6

Beta strand

548 – 575

28

Turn

585 – 588

4

Helix

589 – 593

5

Helix

597 – 600

4

Helix

604 – 606

3

Beta strand

608 – 612

5

Helix

613 – 615

3

Helix

620 – 622

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 1, 1998. Version 2. Checksum: 92C48F55821133E8	FASTA	839	95,680
	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
	Isoform 2. Checksum: 82F70995E7F2AF9D	FASTA	799	91,296
	10 20 30 40 50 60 MELNFYKIPD NLPFSTKNLD LSFNPLRHLG SYSFFSFPEL QVLDLSRCEI QTIEDGAYQS 70 80 90 100 110 120 LSHLSTLILT GNPIQSLALG AFSGLSSLQK LVAVETNLAS LENFPIGHLK TLKELNVAHN 130 140 150 160 170 180 LIQSFKLPEY FSNLTNLEHL DLSSNKIQSI YCTDLRVLHQ MPLLNLSLDL SLNPMNFIQP 190 200 210 220 230 240 GAFKEIRLHK LTLRNNFDSL NVMKTCIQGL AGLEVHRLVL GEFRNEGNLE KFDKSALEGL 250 260 270 280 290 300 CNLTIEEFRL AYLDYYLDDI IDLFNCLTNV SSFSLVSVTI ERVKDFSYNF GWQHLELVNC 310 320 330 340 350 360 KFGQFPTLKL KSLKRLTFTS NKGGNAFSEV DLPSLEFLDL SRNGLSFKGC CSQSDFGTTS 370 380 390 400 410 420 LKYLDLSFNG VITMSSNFLG LEQLEHLDFQ HSNLKQMSEF SVFLSLRNLI YLDISHTHTR 430 440 450 460 470 480 VAFNGIFNGL SSLEVLKMAG NSFQENFLPD IFTELRNLTF LDLSQCQLEQ LSPTAFNSLS 490 500 510 520 530 540 SLQVLNMSHN NFFSLDTFPY KCLNSLQVLD YSLNHIMTSK KQELQHFPSS LAFLNLTQND 550 560 570 580 590 600 FACTCEHQSF LQWIKDQRQL LVEVERMECA TPSDKQGMPV LSLNITCQMN KTIIGVSVLS 610 620 630 640 650 660 VLVVSVVAVL VYKFYFHLML LAGCIKYGRG ENIYDAFVIY SSQDEDWVRN ELVKNLEEGV 670 680 690 700 710 720 PPFQLCLHYR DFIPGVAIAA NIIHEGFHKS RKVIVVVSQH FIQSRWCIFE YEIAQTWQFL 730 740 750 760 770 780 SSRAGIIFIV LQKVEKTLLR QQVELYRLLS RNTYLEWEDS VLGRHIFWRR LRKALLDGKS 790 WNPEGTVGTG CNWQEATSI
	Isoform 3. Checksum: 23C1406CE32427EC	FASTA	639	73,301
	10 20 30 40 50 60 MPLLNLSLDL SLNPMNFIQP GAFKEIRLHK LTLRNNFDSL NVMKTCIQGL AGLEVHRLVL 70 80 90 100 110 120 GEFRNEGNLE KFDKSALEGL CNLTIEEFRL AYLDYYLDDI IDLFNCLTNV SSFSLVSVTI 130 140 150 160 170 180 ERVKDFSYNF GWQHLELVNC KFGQFPTLKL KSLKRLTFTS NKGGNAFSEV DLPSLEFLDL 190 200 210 220 230 240 SRNGLSFKGC CSQSDFGTTS LKYLDLSFNG VITMSSNFLG LEQLEHLDFQ HSNLKQMSEF 250 260 270 280 290 300 SVFLSLRNLI YLDISHTHTR VAFNGIFNGL SSLEVLKMAG NSFQENFLPD IFTELRNLTF 310 320 330 340 350 360 LDLSQCQLEQ LSPTAFNSLS SLQVLNMSHN NFFSLDTFPY KCLNSLQVLD YSLNHIMTSK 370 380 390 400 410 420 KQELQHFPSS LAFLNLTQND FACTCEHQSF LQWIKDQRQL LVEVERMECA TPSDKQGMPV 430 440 450 460 470 480 LSLNITCQMN KTIIGVSVLS VLVVSVVAVL VYKFYFHLML LAGCIKYGRG ENIYDAFVIY 490 500 510 520 530 540 SSQDEDWVRN ELVKNLEEGV PPFQLCLHYR DFIPGVAIAA NIIHEGFHKS RKVIVVVSQH 550 560 570 580 590 600 FIQSRWCIFE YEIAQTWQFL SSRAGIIFIV LQKVEKTLLR QQVELYRLLS RNTYLEWEDS 610 620 630 VLGRHIFWRR LRKALLDGKS WNPEGTVGTG CNWQEATSI

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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

EMBLGenBankDDBJ

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.

IPI

IPI00008673.
IPI00374265.
IPI00914904.

RefSeq

NP_612564.1.

UniGene

Hs.174312

3D structure databases

PDBPDBe

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	380-627	[»]
3FXI	X-ray	3.10	A/B	27-631	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O00206. 5 interactions.

PTM databases

PhosphoSite

O00206.

Proteomic databases

PRIDE

O00206.

Genome annotation databases

Ensembl

ENSG00000136869. Homo sapiens. [Contig view]

GeneID

7099.

KEGG

hsa:7099.

UCSC

uc004bjz.1. human.

Organism-specific databases

GeneCards

GC09P119506.

H-InvDB

HIX0034835.

HGNC

HGNC:11850. TLR4.

HPA

CAB004025.

MIM

603030. gene+phenotype.
611488. phenotype.

PharmGKB

PA36552.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O00206.

HOVERGEN

O00206.

OMA

O00206. LAGLEVH.

Enzyme and pathway databases

Reactome

REACT_6900. Signaling in Immune system.
REACT_6968. Mal Cascade.

Gene expression databases

ArrayExpress

O00206.

Bgee

O00206.

GermOnline

ENSG00000136869. Homo sapiens.

Family and domain databases

InterPro

IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000483. LRR_C.
IPR000157. Toll-Interleukin_rcpt.
IPR017241. Toll-like_receptor.
[Graphical view]

Pfam

PF00560. LRR_1. 6 hits.
PF01463. LRRCT. 1 hit.
PF01582. TIR. 1 hit.
[Graphical view]

PIRSF

PIRSF037595. Toll-like_receptor. 1 hit.

SMART

SM00369. LRR_TYP. 2 hits.
SM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]

PROSITE

PS50104. TIR. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

27773.

SOURCE

Search...

Entry information

Entry name

TLR4_HUMAN

Accession

Primary (citable) accession number: O00206
Secondary accession number(s): A8K1Y8 , 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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)