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Protein

Toll-like receptor 6

Gene

Tlr6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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:19931471). 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. 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. 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:20037584, PubMed:23812099).3 Publications

GO - Molecular functioni

  • diacyl lipopeptide binding Source: MGI
  • lipopeptide binding Source: UniProtKB
  • protein heterodimerization activity Source: MGI
  • Toll-like receptor 2 binding Source: MGI
  • transmembrane signaling receptor activity Source: GO_Central

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Names & Taxonomyi

Protein namesi
Recommended name:
Toll-like receptor 6
Alternative name(s):
CD_antigen: CD286
Gene namesi
Name:Tlr6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1341296. Tlr6.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini28 – 584557ExtracellularSequence analysisAdd
BLAST
Transmembranei585 – 60521HelicalSequence analysisAdd
BLAST
Topological domaini606 – 795190CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasmic vesicle, Golgi apparatus, Membrane

Pathology & Biotechi

Disruption phenotypei

Animals with a double knockout of APOE and TLR6, fed a Western diet for 12 weeks, have less aortic plaque formation than single APOE knockout mice. They also show lower serum concentrations of IL1A, ILB and IL18.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi680 – 6801P → H: Dominant negative mutant, blocks response to Gram-positive pathogens. 1 Publication

Chemistry

ChEMBLiCHEMBL3137289.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence analysisAdd
BLAST
Chaini28 – 795768Toll-like receptor 6PRO_0000034732Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi42 – 421N-linked (GlcNAc...)Sequence analysis
Glycosylationi114 – 1141N-linked (GlcNAc...)Sequence analysis
Disulfide bondi117 ↔ 1391 Publication
Glycosylationi144 – 1441N-linked (GlcNAc...)1 Publication
Glycosylationi195 – 1951N-linked (GlcNAc...)1 Publication
Glycosylationi214 – 2141N-linked (GlcNAc...)1 Publication
Disulfide bondi235 ↔ 2651 Publication
Glycosylationi253 – 2531N-linked (GlcNAc...)1 Publication
Glycosylationi285 – 2851N-linked (GlcNAc...)
Disulfide bondi348 ↔ 3731 Publication
Glycosylationi359 – 3591N-linked (GlcNAc...)1 Publication
Glycosylationi401 – 4011N-linked (GlcNAc...)1 Publication
Disulfide bondi424 ↔ 4471 Publication
Glycosylationi434 – 4341N-linked (GlcNAc...)1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ9EPW9.
PaxDbiQ9EPW9.
PRIDEiQ9EPW9.

PTM databases

iPTMnetiQ9EPW9.
PhosphoSiteiQ9EPW9.

Expressioni

Tissue specificityi

Detected in thymus, spleen, ovary and lung. Expressed in macrohpages.1 Publication

Gene expression databases

BgeeiENSMUSG00000051498.
CleanExiMM_TLR6.

Interactioni

Subunit structurei

Heterodimer with TLR2 via their respective extracellular domains (PubMed:19931471). 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 (By similarity). The heterodimer TLR2:TLR6 interacts with CD14 and CD36 in response to triacylated lipopeptides (By similarity).By similarityCurated1 Publication

GO - Molecular functioni

  • protein heterodimerization activity Source: MGI
  • Toll-like receptor 2 binding Source: MGI

Protein-protein interaction databases

IntActiQ9EPW9. 1 interaction.
STRINGi10090.ENSMUSP00000062096.

Structurei

Secondary structure

1
795
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi35 – 373Combined sources
Beta strandi56 – 583Combined sources
Helixi69 – 713Combined sources
Turni72 – 743Combined sources
Beta strandi80 – 823Combined sources
Turni93 – 986Combined sources
Beta strandi104 – 1063Combined sources
Beta strandi124 – 1274Combined sources
Helixi140 – 1445Combined sources
Beta strandi150 – 1545Combined sources
Turni160 – 1634Combined sources
Helixi164 – 1663Combined sources
Beta strandi171 – 18010Combined sources
Beta strandi185 – 1873Combined sources
Beta strandi190 – 1934Combined sources
Beta strandi196 – 2038Combined sources
Beta strandi205 – 2073Combined sources
Beta strandi214 – 22916Combined sources
Helixi235 – 24612Combined sources
Beta strandi252 – 26110Combined sources
Helixi263 – 27311Combined sources
Beta strandi276 – 28813Combined sources
Beta strandi306 – 3149Combined sources
Helixi321 – 3299Combined sources
Beta strandi334 – 3418Combined sources
Beta strandi357 – 3593Combined sources
Turni367 – 3726Combined sources
Beta strandi381 – 3833Combined sources
Helixi394 – 3974Combined sources
Turni398 – 4014Combined sources
Beta strandi407 – 4093Combined sources
Beta strandi432 – 4343Combined sources
Helixi442 – 4454Combined sources
Beta strandi453 – 4564Combined sources
Turni467 – 4704Combined sources
Beta strandi476 – 4794Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3A79X-ray2.90B1-482[»]
ProteinModelPortaliQ9EPW9.
SMRiQ9EPW9. Positions 33-781.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9EPW9.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati54 – 7724LRR 11 PublicationAdd
BLAST
Repeati78 – 10124LRR 21 PublicationAdd
BLAST
Repeati102 – 12524LRR 31 PublicationAdd
BLAST
Repeati126 – 15025LRR 41 PublicationAdd
BLAST
Repeati151 – 17525LRR 51 PublicationAdd
BLAST
Repeati176 – 19924LRR 61 PublicationAdd
BLAST
Repeati200 – 22324LRR 71 PublicationAdd
BLAST
Repeati224 – 25027LRR 81 PublicationAdd
BLAST
Repeati251 – 27828LRR 91 PublicationAdd
BLAST
Repeati279 – 30830LRR 101 PublicationAdd
BLAST
Repeati309 – 33729LRR 111 PublicationAdd
BLAST
Repeati338 – 36124LRR 121 PublicationAdd
BLAST
Repeati362 – 38827LRR 131 PublicationAdd
BLAST
Repeati389 – 41426LRR 141 PublicationAdd
BLAST
Repeati415 – 43723LRR 151 PublicationAdd
BLAST
Repeati438 – 45720LRR 161 PublicationAdd
BLAST
Repeati458 – 47821LRR 171 PublicationAdd
BLAST
Repeati479 – 50022LRR 181 PublicationAdd
BLAST
Repeati501 – 52424LRR 191 PublicationAdd
BLAST
Domaini525 – 57652LRRCTAdd
BLAST
Domaini640 – 784145TIRPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the Toll-like receptor family.Curated
Contains 19 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

eggNOGiKOG4641. Eukaryota.
COG4886. LUCA.
HOVERGENiHBG023180.
InParanoidiQ9EPW9.
KOiK10169.
PhylomeDBiQ9EPW9.

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
3.80.10.10. 2 hits.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR025875. Leu-rich_rpt_4.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000157. TIR_dom.
IPR027187. TLR6.
IPR017241. Toll-like_receptor.
[Graphical view]
PANTHERiPTHR24365:SF23. PTHR24365:SF23. 1 hit.
PfamiPF12799. LRR_4. 1 hit.
PF13855. LRR_8. 1 hit.
PF01582. TIR. 1 hit.
[Graphical view]
PIRSFiPIRSF037595. Toll-like_receptor. 1 hit.
SMARTiSM00369. LRR_TYP. 4 hits.
SM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
SSF52200. SSF52200. 1 hit.
PROSITEiPS51450. LRR. 10 hits.
PS50104. TIR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q9EPW9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSQDRKPIVG SFHFVCALAL IVGSMTPFSN ELESMVDYSN RNLTHVPKDL
60 70 80 90 100
PPRTKALSLS QNSISELRMP DISFLSELRV LRLSHNRIRS LDFHVFLFNQ
110 120 130 140 150
DLEYLDVSHN RLQNISCCPM ASLRHLDLSF NDFDVLPVCK EFGNLTKLTF
160 170 180 190 200
LGLSAAKFRQ LDLLPVAHLH LSCILLDLVS YHIKGGETES LQIPNTTVLH
210 220 230 240 250
LVFHPNSLFS VQVNMSVNAL GHLQLSNIKL NDENCQRLMT FLSELTRGPT
260 270 280 290 300
LLNVTLQHIE TTWKCSVKLF QFFWPRPVEY LNIYNLTITE RIDREEFTYS
310 320 330 340 350
ETALKSLMIE HVKNQVFLFS KEALYSVFAE MNIKMLSISD TPFIHMVCPP
360 370 380 390 400
SPSSFTFLNF TQNVFTDSVF QGCSTLKRLQ TLILQRNGLK NFFKVALMTK
410 420 430 440 450
NMSSLETLDV SLNSLNSHAY DRTCAWAESI LVLNLSSNML TGSVFRCLPP
460 470 480 490 500
KVKVLDLHNN RIMSIPKDVT HLQALQELNV ASNSLTDLPG CGAFSSLSVL
510 520 530 540 550
VIDHNSVSHP SEDFFQSCQN IRSLTAGNNP FQCTCELRDF VKNIGWVARE
560 570 580 590 600
VVEGWPDSYR CDYPESSKGT ALRDFHMSPL SCDTVLLTVT IGATMLVLAV
610 620 630 640 650
TGAFLCLYFD LPWYVRMLCQ WTQTRHRARH IPLEELQRNL QFHAFVSYSE
660 670 680 690 700
HDSAWVKNEL LPNLEKDDIR VCLHERNFVP GKSIVENIIN FIEKSYKAIF
710 720 730 740 750
VLSPHFIQSE WCHYELYFAH HNLFHEGSDN LILILLEPIL QNNIPSRYHK
760 770 780 790
LRALMAQRTY LEWPTEKGKR GLFWANLRAS FIMKLALVNE DDVKT
Length:795
Mass (Da):91,116
Last modified:January 31, 2002 - v2
Checksum:i34D8BD175A26C233
GO

Sequence cautioni

The sequence AAG38563 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAA78632 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti181 – 1811Y → H in BAA78632 (PubMed:10231569).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020808 mRNA. Translation: BAA78632.1. Different initiation.
AF314636 mRNA. Translation: AAG38563.1. Different initiation.
RefSeqiNP_035734.3. NM_011604.3.
XP_006503920.1. XM_006503857.2.
XP_006503921.1. XM_006503858.2.
XP_006503922.1. XM_006503859.2.
XP_006503923.1. XM_006503860.1.
XP_011239023.1. XM_011240721.1.
UniGeneiMm.42146.

Genome annotation databases

GeneIDi21899.
KEGGimmu:21899.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020808 mRNA. Translation: BAA78632.1. Different initiation.
AF314636 mRNA. Translation: AAG38563.1. Different initiation.
RefSeqiNP_035734.3. NM_011604.3.
XP_006503920.1. XM_006503857.2.
XP_006503921.1. XM_006503858.2.
XP_006503922.1. XM_006503859.2.
XP_006503923.1. XM_006503860.1.
XP_011239023.1. XM_011240721.1.
UniGeneiMm.42146.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3A79X-ray2.90B1-482[»]
ProteinModelPortaliQ9EPW9.
SMRiQ9EPW9. Positions 33-781.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9EPW9. 1 interaction.
STRINGi10090.ENSMUSP00000062096.

Chemistry

ChEMBLiCHEMBL3137289.

PTM databases

iPTMnetiQ9EPW9.
PhosphoSiteiQ9EPW9.

Proteomic databases

MaxQBiQ9EPW9.
PaxDbiQ9EPW9.
PRIDEiQ9EPW9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi21899.
KEGGimmu:21899.

Organism-specific databases

CTDi10333.
MGIiMGI:1341296. Tlr6.

Phylogenomic databases

eggNOGiKOG4641. Eukaryota.
COG4886. LUCA.
HOVERGENiHBG023180.
InParanoidiQ9EPW9.
KOiK10169.
PhylomeDBiQ9EPW9.

Miscellaneous databases

EvolutionaryTraceiQ9EPW9.
PROiQ9EPW9.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000051498.
CleanExiMM_TLR6.

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
3.80.10.10. 2 hits.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR025875. Leu-rich_rpt_4.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000157. TIR_dom.
IPR027187. TLR6.
IPR017241. Toll-like_receptor.
[Graphical view]
PANTHERiPTHR24365:SF23. PTHR24365:SF23. 1 hit.
PfamiPF12799. LRR_4. 1 hit.
PF13855. LRR_8. 1 hit.
PF01582. TIR. 1 hit.
[Graphical view]
PIRSFiPIRSF037595. Toll-like_receptor. 1 hit.
SMARTiSM00369. LRR_TYP. 4 hits.
SM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
SSF52200. SSF52200. 1 hit.
PROSITEiPS51450. LRR. 10 hits.
PS50104. TIR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTLR6_MOUSE
AccessioniPrimary (citable) accession number: Q9EPW9
Secondary accession number(s): Q9WTQ4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: January 31, 2002
Last modified: September 7, 2016
This is version 130 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.