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Protein

Toll-like receptor 6

Gene

TLR6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Participates in the innate immune response to Gram-positive bacteria and fungi. Specifically recognizes diacylated and, to a lesser extent, triacylated lipopeptides (PubMed:20037584). In response to diacylated lipopeptides, forms the activation cluster TLR2:TLR6:CD14:CD36, this cluster triggers signaling from the cell surface and subsequently is targeted to the Golgi in a lipid-raft dependent pathway (PubMed:16880211). Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Recognizes mycoplasmal macrophage-activating lipopeptide-2kD (MALP-2), soluble tuberculosis factor (STF), phenol-soluble modulin (PSM) and B.burgdorferi outer surface protein A lipoprotein (OspA-L) cooperatively with TLR2 (PubMed:11441107). In complex with TLR4, promotes sterile inflammation in monocytes/macrophages in response to oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42. In this context, the initial signal is provided by oxLDL- or amyloid-beta 42-binding to CD36. This event induces the formation of a heterodimer of TLR4 and TLR6, which is rapidly internalized and triggers inflammatory response, leading to the NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion (PubMed:11441107, PubMed:20037584).3 Publications

GO - Molecular functioni

  • identical protein binding Source: UniProtKB
  • lipopeptide binding Source: UniProtKB
  • protein heterodimerization activity Source: ARUK-UCL
  • signaling receptor activity Source: ProtInc
  • signaling receptor binding Source: ARUK-UCL
  • Toll-like receptor 2 binding Source: UniProtKB
  • transmembrane signaling receptor activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionReceptor
Biological processImmunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-HSA-1236974 ER-Phagosome pathway
R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-5602498 MyD88 deficiency (TLR2/4)
R-HSA-5603041 IRAK4 deficiency (TLR2/4)
R-HSA-5686938 Regulation of TLR by endogenous ligand

Names & Taxonomyi

Protein namesi
Recommended name:
Toll-like receptor 6
Alternative name(s):
CD_antigen: CD286
Gene namesi
Name:TLR6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000174130.12
HGNCiHGNC:16711 TLR6
MIMi605403 gene
neXtProtiNX_Q9Y2C9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini32 – 586ExtracellularSequence analysisAdd BLAST555
Transmembranei587 – 607HelicalSequence analysisAdd BLAST21
Topological domaini608 – 796CytoplasmicSequence analysisAdd BLAST189

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi678F → A: Does not inhibit homodimer formation. 1 Publication1
Mutagenesisi712C → R: Inhibits homodimer formation. 1 Publication1
Mutagenesisi716L → R: Inhibits homodimer formation. 1 Publication1

Organism-specific databases

DisGeNETi10333
OpenTargetsiENSG00000174130
PharmGKBiPA38183

Chemistry databases

ChEMBLiCHEMBL3301399

Polymorphism and mutation databases

BioMutaiTLR6
DMDMi296452933

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31Sequence analysisAdd BLAST31
ChainiPRO_000003473132 – 796Toll-like receptor 6Add BLAST765

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi117 ↔ 139By similarity
Glycosylationi144N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi186N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi214N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi235 ↔ 265By similarity
Glycosylationi253N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi285N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi348 ↔ 373By similarity
Glycosylationi359N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi423N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi424 ↔ 447By similarity
Glycosylationi434N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi583N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9Y2C9
PeptideAtlasiQ9Y2C9
PRIDEiQ9Y2C9

PTM databases

iPTMnetiQ9Y2C9
PhosphoSitePlusiQ9Y2C9

Expressioni

Tissue specificityi

Detected in monocytes, CD11c+ immature dendritic cells, plasmacytoid pre-dendritic cells and dermal microvessel endothelial cells.

Gene expression databases

BgeeiENSG00000174130
CleanExiHS_TLR6
ExpressionAtlasiQ9Y2C9 baseline and differential
GenevisibleiQ9Y2C9 HS

Organism-specific databases

HPAiHPA062733

Interactioni

Subunit structurei

Homodimer (via cytoplasmic TIR domain) (PubMed:25088687). Heterodimer with TLR2 via their respective extracellular domains (PubMed:16880211). Binds MYD88 via their respective TIR domains (Probable). Interacts with CD36, following CD36 stimulation by oxLDL or amyloid-beta 42, and forms a heterodimer with TLR4. The trimeric complex is internalized and triggers inflammatory response. LYN kinase activity facilitates TLR4:TLR6 heterodimerization and signal initiation (PubMed:20037584). The heterodimer TLR2:TLR6 interacts with CD14 and CD36 in response to triacylated lipopeptides (PubMed:16880211).Curated3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
TLR4O002062EBI-13940779,EBI-528701

GO - Molecular functioni

  • identical protein binding Source: UniProtKB
  • protein heterodimerization activity Source: ARUK-UCL
  • signaling receptor binding Source: ARUK-UCL
  • Toll-like receptor 2 binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115616, 3 interactors
IntActiQ9Y2C9, 4 interactors
STRINGi9606.ENSP00000371376

Structurei

Secondary structure

1796
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi642 – 647Combined sources6
Helixi650 – 652Combined sources3
Helixi653 – 658Combined sources6
Helixi660 – 666Combined sources7
Helixi674 – 677Combined sources4
Helixi684 – 694Combined sources11
Beta strandi695 – 702Combined sources8
Helixi704 – 709Combined sources6
Helixi711 – 717Combined sources7
Helixi722 – 724Combined sources3
Beta strandi725 – 727Combined sources3
Beta strandi731 – 737Combined sources7
Helixi741 – 743Combined sources3
Helixi749 – 757Combined sources9
Helixi772 – 780Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4OM7X-ray2.20A/B640-796[»]
ProteinModelPortaliQ9Y2C9
SMRiQ9Y2C9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati54 – 77LRR 1Add BLAST24
Repeati78 – 101LRR 2Add BLAST24
Repeati102 – 122LRR 3Add BLAST21
Repeati123 – 147LRR 4Add BLAST25
Repeati148 – 168LRR 5Add BLAST21
Repeati169 – 196LRR 6Add BLAST28
Repeati197 – 219LRR 7Add BLAST23
Repeati220 – 250LRR 8Add BLAST31
Repeati251 – 277LRR 9Add BLAST27
Repeati278 – 303LRR 10Add BLAST26
Repeati304 – 330LRR 11Add BLAST27
Repeati331 – 354LRR 12Add BLAST24
Repeati355 – 378LRR 13Add BLAST24
Repeati379 – 404LRR 14Add BLAST26
Repeati405 – 429LRR 15Add BLAST25
Repeati430 – 450LRR 16Add BLAST21
Repeati451 – 474LRR 17Add BLAST24
Repeati475 – 496LRR 18Add BLAST22
Repeati497 – 520LRR 19Add BLAST24
Domaini521 – 575LRRCTAdd BLAST55
Domaini640 – 784TIRPROSITE-ProRule annotationAdd BLAST145

Sequence similaritiesi

Belongs to the Toll-like receptor family.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4641 Eukaryota
COG4886 LUCA
GeneTreeiENSGT00760000119006
HOGENOMiHOG000008676
HOVERGENiHBG023180
InParanoidiQ9Y2C9
KOiK10169
OMAiWPKPVEY
OrthoDBiEOG091G0356
PhylomeDBiQ9Y2C9
TreeFamiTF351113

Family and domain databases

Gene3Di3.40.50.10140, 1 hit
3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000483 Cys-rich_flank_reg_C
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR000157 TIR_dom
IPR027187 TLR6
IPR035897 Toll_tir_struct_dom_sf
PANTHERiPTHR24365:SF422 PTHR24365:SF422, 1 hit
PfamiView protein in Pfam
PF13855 LRR_8, 2 hits
PF01463 LRRCT, 1 hit
PF01582 TIR, 1 hit
SMARTiView protein in SMART
SM00369 LRR_TYP, 5 hits
SM00082 LRRCT, 1 hit
SM00255 TIR, 1 hit
SUPFAMiSSF52200 SSF52200, 1 hit
PROSITEiView protein in PROSITE
PS51450 LRR, 9 hits
PS50104 TIR, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y2C9-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTKDKEPIVK SFHFVCLMII IVGTRIQFSD GNEFAVDKSK RGLIHVPKDL
60 70 80 90 100
PLKTKVLDMS QNYIAELQVS DMSFLSELTV LRLSHNRIQL LDLSVFKFNQ
110 120 130 140 150
DLEYLDLSHN QLQKISCHPI VSFRHLDLSF NDFKALPICK EFGNLSQLNF
160 170 180 190 200
LGLSAMKLQK LDLLPIAHLH LSYILLDLRN YYIKENETES LQILNAKTLH
210 220 230 240 250
LVFHPTSLFA IQVNISVNTL GCLQLTNIKL NDDNCQVFIK FLSELTRGST
260 270 280 290 300
LLNFTLNHIE TTWKCLVRVF QFLWPKPVEY LNIYNLTIIE SIREEDFTYS
310 320 330 340 350
KTTLKALTIE HITNQVFLFS QTALYTVFSE MNIMMLTISD TPFIHMLCPH
360 370 380 390 400
APSTFKFLNF TQNVFTDSIF EKCSTLVKLE TLILQKNGLK DLFKVGLMTK
410 420 430 440 450
DMPSLEILDV SWNSLESGRH KENCTWVESI VVLNLSSNML TDSVFRCLPP
460 470 480 490 500
RIKVLDLHSN KIKSVPKQVV KLEALQELNV AFNSLTDLPG CGSFSSLSVL
510 520 530 540 550
IIDHNSVSHP SADFFQSCQK MRSIKAGDNP FQCTCELREF VKNIDQVSSE
560 570 580 590 600
VLEGWPDSYK CDYPESYRGS PLKDFHMSEL SCNITLLIVT IGATMLVLAV
610 620 630 640 650
TVTSLCIYLD LPWYLRMVCQ WTQTRRRARN IPLEELQRNL QFHAFISYSE
660 670 680 690 700
HDSAWVKSEL VPYLEKEDIQ ICLHERNFVP GKSIVENIIN CIEKSYKSIF
710 720 730 740 750
VLSPNFVQSE WCHYELYFAH HNLFHEGSNN LILILLEPIP QNSIPNKYHK
760 770 780 790
LKALMTQRTY LQWPKEKSKR GLFWANIRAA FNMKLTLVTE NNDVKS
Length:796
Mass (Da):91,880
Last modified:May 18, 2010 - v2
Checksum:i9ACEAEC084CB466C
GO
Isoform 2 (identifier: Q9Y2C9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     383-698: Missing.

Note: No experimental confirmation available.
Show »
Length:480
Mass (Da):55,828
Checksum:i5AAB534C449E2D9B
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_057289120I → T2 PublicationsCorresponds to variant dbSNP:rs5743808Ensembl.1
Natural variantiVAR_066352128L → V Impairs the ability to induce NF-kappa-B activation. 1 PublicationCorresponds to variant dbSNP:rs137853178EnsemblClinVar.1
Natural variantiVAR_057290194L → P Impairs the ability to induce NF-kappa-B activation. 1 PublicationCorresponds to variant dbSNP:rs5743809Ensembl.1
Natural variantiVAR_066353210A → G1 PublicationCorresponds to variant dbSNP:rs137853180EnsemblClinVar.1
Natural variantiVAR_066354210A → T1 PublicationCorresponds to variant dbSNP:rs137853179EnsemblClinVar.1
Natural variantiVAR_057291247R → K1 PublicationCorresponds to variant dbSNP:rs35220466Ensembl.1
Natural variantiVAR_063110249S → P5 PublicationsCorresponds to variant dbSNP:rs5743810Ensembl.1
Natural variantiVAR_066355283I → V1 PublicationCorresponds to variant dbSNP:rs137853181EnsemblClinVar.1
Natural variantiVAR_057292327V → M2 PublicationsCorresponds to variant dbSNP:rs3796508Ensembl.1
Natural variantiVAR_057293345H → Y. Corresponds to variant dbSNP:rs5743813Ensembl.1
Natural variantiVAR_057294427V → A1 PublicationCorresponds to variant dbSNP:rs5743815Ensembl.1
Natural variantiVAR_066356442D → A1 PublicationCorresponds to variant dbSNP:rs137853182EnsemblClinVar.1
Natural variantiVAR_057295465V → I1 PublicationCorresponds to variant dbSNP:rs5743816Ensembl.1
Natural variantiVAR_057296474A → T1 PublicationCorresponds to variant dbSNP:rs5743817Ensembl.1
Natural variantiVAR_066357474A → V Impairs the ability to induce NF-kappa-B activation. 1 Publication1
Natural variantiVAR_066358592G → V1 PublicationCorresponds to variant dbSNP:rs75244616Ensembl.1
Natural variantiVAR_066359690N → T Impairs the ability to induce NF-kappa-B activation. 1 PublicationCorresponds to variant dbSNP:rs114855575Ensembl.1
Natural variantiVAR_066360708Q → H Impairs the ability to induce NF-kappa-B activation. 1 PublicationCorresponds to variant dbSNP:rs137853183EnsemblClinVar.1
Natural variantiVAR_057297783M → V. Corresponds to variant dbSNP:rs5743822Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056851383 – 698Missing in isoform 2. 1 PublicationAdd BLAST316

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020807 mRNA Translation: BAA78631.1
AB445652 mRNA Translation: BAG55049.1
EU170528 Genomic DNA Translation: ABW37063.1
EU170529 Genomic DNA Translation: ABW37064.1
EU170531 Genomic DNA Translation: ABW37066.1
EU170532 Genomic DNA Translation: ABW37067.1
EU170533 Genomic DNA Translation: ABW37068.1
EU170534 Genomic DNA Translation: ABW37069.1
EU170536 Genomic DNA Translation: ABW37071.1
EU195537 Genomic DNA Translation: ABY67113.1
EU195538 Genomic DNA Translation: ABY67114.1
EU195539 Genomic DNA Translation: ABY67115.1
EU195541 Genomic DNA Translation: ABY67117.1
EU195542 Genomic DNA Translation: ABY67118.1
EU195543 Genomic DNA Translation: ABY67119.1
EU195544 Genomic DNA Translation: ABY67120.1
EU195545 Genomic DNA Translation: ABY67121.1
EU195546 Genomic DNA Translation: ABY67122.1
EU195547 Genomic DNA Translation: ABY67123.1
EU195548 Genomic DNA Translation: ABY67124.1
EU195550 Genomic DNA Translation: ABY67126.1
EU195551 Genomic DNA Translation: ABY67127.1
EU195553 Genomic DNA Translation: ABY67129.1
EU195554 Genomic DNA Translation: ABY67130.1
EU195555 Genomic DNA Translation: ABY67131.1
EU195557 Genomic DNA Translation: ABY67133.1
AC108044 Genomic DNA No translation available.
CH471069 Genomic DNA Translation: EAW92902.1
BC111755 mRNA Translation: AAI11756.1
CCDSiCCDS3446.1 [Q9Y2C9-1]
RefSeqiNP_006059.2, NM_006068.4 [Q9Y2C9-1]
XP_005262694.1, XM_005262637.4 [Q9Y2C9-1]
XP_011511914.1, XM_011513612.2 [Q9Y2C9-1]
XP_011511915.1, XM_011513613.2 [Q9Y2C9-1]
XP_011511916.1, XM_011513614.2 [Q9Y2C9-1]
UniGeneiHs.575090
Hs.743572

Genome annotation databases

EnsembliENST00000381950; ENSP00000371376; ENSG00000174130 [Q9Y2C9-1]
ENST00000436693; ENSP00000389600; ENSG00000174130 [Q9Y2C9-1]
ENST00000610323; ENSP00000480266; ENSG00000174130 [Q9Y2C9-2]
GeneIDi10333
KEGGihsa:10333
UCSCiuc010ifg.3 human [Q9Y2C9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTLR6_HUMAN
AccessioniPrimary (citable) accession number: Q9Y2C9
Secondary accession number(s): B3Y640
, B6CH35, B6RFS4, B6RFS5, Q2NKL3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: May 18, 2010
Last modified: May 23, 2018
This is version 167 of the entry and version 2 of the sequence. See 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 4
    Human chromosome 4: 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. SIMILARITY comments
    Index of protein domains and families

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