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Q9Y2C9 (TLR6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Toll-like receptor 6
Alternative name(s):
CD_antigen=CD286
Gene names
Name:TLR6
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length796 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Participates in the innate immune response to Gram-positive bacteria and fungi. Specifically recognizes diacylated and, to a lesser extent, triacylated lipopeptides. 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. Ref.6

Subunit structure

Binds MYD88 via their respective TIR domains. Heterodimer with TLR2 via their respective extracellular domains By similarity.

Subcellular location

Cell membrane; Single-pass type I membrane protein By similarity. Cytoplasmic vesiclephagosome membrane; Single-pass type I membrane protein By similarity.

Tissue specificity

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

Sequence similarities

Belongs to the Toll-like receptor family.

Contains 19 LRR (leucine-rich) repeats.

Contains 1 LRRCT domain.

Contains 1 TIR domain.

Ontologies

Keywords
   Biological processImmunity
Inflammatory response
Innate immunity
   Cellular componentCell membrane
Cytoplasmic vesicle
Membrane
   Coding sequence diversityPolymorphism
   DomainLeucine-rich repeat
Repeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionReceptor
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processMyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

T-helper 1 type immune response

Inferred by curator PubMed 11686851. Source: UniProtKB

activation of NF-kappaB-inducing kinase activity

Non-traceable author statement Ref.1. Source: UniProtKB

cellular response to diacyl bacterial lipopeptide

Inferred from direct assay PubMed 19931471. Source: MGI

defense response to bacterium

Traceable author statement PubMed 10426995. Source: ProtInc

detection of diacyl bacterial lipopeptide

Inferred from direct assay PubMed 19931471. Source: MGI

detection of triacyl bacterial lipopeptide

Inferred from electronic annotation. Source: InterPro

immune response

Traceable author statement PubMed 10426995. Source: ProtInc

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Traceable author statement. Source: Reactome

microglial cell activation involved in immune response

Inferred from electronic annotation. Source: Ensembl

nitric oxide metabolic process

Inferred from electronic annotation. Source: Ensembl

pathogen-associated molecular pattern dependent induction by symbiont of host innate immune response

Inferred from electronic annotation. Source: Ensembl

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from direct assay Ref.1. Source: MGI

positive regulation of JUN kinase activity

Inferred from direct assay Ref.1. Source: MGI

positive regulation of interleukin-6 biosynthetic process

Inferred from sequence or structural similarity PubMed 12077222. Source: UniProtKB

regulation of cytokine secretion

Inferred from electronic annotation. Source: InterPro

signal transduction

Traceable author statement Ref.1. Source: ProtInc

toll-like receptor 1 signaling pathway

Inferred from electronic annotation. Source: InterPro

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentToll-like receptor 2-Toll-like receptor 6 protein complex

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

phagocytic vesicle membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functiondiacyl lipopeptide binding

Inferred from electronic annotation. Source: Ensembl

lipopeptide binding

Inferred from sequence or structural similarity PubMed 11431423. Source: UniProtKB

receptor activity

Traceable author statement PubMed 10426995. Source: ProtInc

transmembrane signaling receptor activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3131 Potential
Chain32 – 796765Toll-like receptor 6
PRO_0000034731

Regions

Topological domain32 – 586555Extracellular Potential
Transmembrane587 – 60721Helical; Potential
Topological domain608 – 796189Cytoplasmic Potential
Repeat54 – 7724LRR 1
Repeat78 – 10124LRR 2
Repeat102 – 12221LRR 3
Repeat123 – 14725LRR 4
Repeat148 – 16821LRR 5
Repeat169 – 19628LRR 6
Repeat197 – 21923LRR 7
Repeat220 – 25031LRR 8
Repeat251 – 27727LRR 9
Repeat278 – 30326LRR 10
Repeat304 – 33027LRR 11
Repeat331 – 35424LRR 12
Repeat355 – 37824LRR 13
Repeat379 – 40426LRR 14
Repeat405 – 42925LRR 15
Repeat430 – 45021LRR 16
Repeat451 – 47424LRR 17
Repeat475 – 49622LRR 18
Repeat497 – 52024LRR 19
Domain521 – 57555LRRCT
Domain640 – 784145TIR

Amino acid modifications

Glycosylation1441N-linked (GlcNAc...) Potential
Glycosylation1861N-linked (GlcNAc...) Potential
Glycosylation2141N-linked (GlcNAc...) Potential
Glycosylation2531N-linked (GlcNAc...) Potential
Glycosylation2851N-linked (GlcNAc...) Potential
Glycosylation3591N-linked (GlcNAc...) Potential
Glycosylation4231N-linked (GlcNAc...) Potential
Glycosylation4341N-linked (GlcNAc...) Potential
Glycosylation5831N-linked (GlcNAc...) Potential
Disulfide bond117 ↔ 139 By similarity
Disulfide bond235 ↔ 265 By similarity
Disulfide bond348 ↔ 373 By similarity
Disulfide bond424 ↔ 447 By similarity

Natural variations

Natural variant1201I → T. Ref.3 Ref.7
Corresponds to variant rs5743808 [ dbSNP | Ensembl ].
VAR_057289
Natural variant1281L → V Impairs the ability to induce NF-kappa-B activation. Ref.7
Corresponds to variant rs137853178 [ dbSNP | Ensembl ].
VAR_066352
Natural variant1941L → P Impairs the ability to induce NF-kappa-B activation. Ref.7
Corresponds to variant rs5743809 [ dbSNP | Ensembl ].
VAR_057290
Natural variant2101A → G. Ref.7
VAR_066353
Natural variant2101A → T. Ref.7
VAR_066354
Natural variant2471R → K. Ref.7
Corresponds to variant rs35220466 [ dbSNP | Ensembl ].
VAR_057291
Natural variant2491S → P. Ref.2 Ref.3 Ref.4 Ref.7
Corresponds to variant rs5743810 [ dbSNP | Ensembl ].
VAR_063110
Natural variant2831I → V. Ref.7
VAR_066355
Natural variant3271V → M. Ref.3 Ref.7
Corresponds to variant rs3796508 [ dbSNP | Ensembl ].
VAR_057292
Natural variant3451H → Y.
Corresponds to variant rs5743813 [ dbSNP | Ensembl ].
VAR_057293
Natural variant4271V → A. Ref.7
Corresponds to variant rs5743815 [ dbSNP | Ensembl ].
VAR_057294
Natural variant4421D → A. Ref.7
VAR_066356
Natural variant4651V → I. Ref.7
Corresponds to variant rs5743816 [ dbSNP | Ensembl ].
VAR_057295
Natural variant4741A → T. Ref.7
Corresponds to variant rs35762983 [ dbSNP | Ensembl ].
VAR_057296
Natural variant4741A → V Impairs the ability to induce NF-kappa-B activation. Ref.7
VAR_066357
Natural variant5921G → V. Ref.7
Corresponds to variant rs75244616 [ dbSNP | Ensembl ].
VAR_066358
Natural variant6901N → T Impairs the ability to induce NF-kappa-B activation. Ref.7
Corresponds to variant rs114855575 [ dbSNP | Ensembl ].
VAR_066359
Natural variant7081Q → H Impairs the ability to induce NF-kappa-B activation. Ref.7
Corresponds to variant rs137853183 [ dbSNP | Ensembl ].
VAR_066360
Natural variant7831M → V.
Corresponds to variant rs5743822 [ dbSNP | Ensembl ].
VAR_057297

Sequences

Sequence LengthMass (Da)Tools
Q9Y2C9 [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: 9ACEAEC084CB466C

FASTA79691,880
        10         20         30         40         50         60 
MTKDKEPIVK SFHFVCLMII IVGTRIQFSD GNEFAVDKSK RGLIHVPKDL PLKTKVLDMS 

        70         80         90        100        110        120 
QNYIAELQVS DMSFLSELTV LRLSHNRIQL LDLSVFKFNQ DLEYLDLSHN QLQKISCHPI 

       130        140        150        160        170        180 
VSFRHLDLSF NDFKALPICK EFGNLSQLNF LGLSAMKLQK LDLLPIAHLH LSYILLDLRN 

       190        200        210        220        230        240 
YYIKENETES LQILNAKTLH LVFHPTSLFA IQVNISVNTL GCLQLTNIKL NDDNCQVFIK 

       250        260        270        280        290        300 
FLSELTRGST LLNFTLNHIE TTWKCLVRVF QFLWPKPVEY LNIYNLTIIE SIREEDFTYS 

       310        320        330        340        350        360 
KTTLKALTIE HITNQVFLFS QTALYTVFSE MNIMMLTISD TPFIHMLCPH APSTFKFLNF 

       370        380        390        400        410        420 
TQNVFTDSIF EKCSTLVKLE TLILQKNGLK DLFKVGLMTK DMPSLEILDV SWNSLESGRH 

       430        440        450        460        470        480 
KENCTWVESI VVLNLSSNML TDSVFRCLPP RIKVLDLHSN KIKSVPKQVV KLEALQELNV 

       490        500        510        520        530        540 
AFNSLTDLPG CGSFSSLSVL IIDHNSVSHP SADFFQSCQK MRSIKAGDNP FQCTCELREF 

       550        560        570        580        590        600 
VKNIDQVSSE VLEGWPDSYK CDYPESYRGS PLKDFHMSEL SCNITLLIVT IGATMLVLAV 

       610        620        630        640        650        660 
TVTSLCIYLD LPWYLRMVCQ WTQTRRRARN IPLEELQRNL QFHAFISYSE HDSAWVKSEL 

       670        680        690        700        710        720 
VPYLEKEDIQ ICLHERNFVP GKSIVENIIN CIEKSYKSIF VLSPNFVQSE WCHYELYFAH 

       730        740        750        760        770        780 
HNLFHEGSNN LILILLEPIP QNSIPNKYHK LKALMTQRTY LQWPKEKSKR GLFWANIRAA 

       790 
FNMKLTLVTE NNDVKS 

« Hide

References

« Hide 'large scale' references
[1]"TLR6: a novel member of an expanding Toll-like receptor family."
Takeuchi O., Kawai T., Sanjo H., Copeland N.G., Gilbert D.J., Jenkins N.A., Takeda K., Akira S.
Gene 231:59-65(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Placenta.
[2]"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], VARIANT PRO-249.
[3]"The novel allele of toll-like receptor 6 gene."
Liu Z., Xiao W., Wang J., Li N., Tai Y.
Submitted (OCT-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-120 AND PRO-249; MET-327.
[4]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT PRO-249.
[5]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].
[6]"Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling."
Bulut Y., Faure E., Thomas L., Equils O., Arditi M.
J. Immunol. 167:987-994(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Functional characterization of naturally occurring genetic variants in the human TLR1-2-6 gene family."
Ben-Ali M., Corre B., Manry J., Barreiro L.B., Quach H., Boniotto M., Pellegrini S., Quintana-Murci L.
Hum. Mutat. 32:643-652(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS THR-120; VAL-128; PRO-194; THR-210; GLY-210; LYS-247; PRO-249; VAL-283; MET-327; ALA-427; ALA-442; ILE-465; THR-474; VAL-474; VAL-592; THR-690 AND HIS-708, CHARACTERIZATION OF VARIANTS VAL-128; PRO-194; VAL-474; THR-690 AND HIS-708.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS3446.1.
RefSeqNP_006059.2. NM_006068.4.
XP_005262693.1. XM_005262636.1.
XP_005262694.1. XM_005262637.2.
UniGeneHs.575090.
Hs.743572.

3D structure databases

ProteinModelPortalQ9Y2C9.
SMRQ9Y2C9. Positions 33-786.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115616. 1 interaction.
STRING9606.ENSP00000371376.

PTM databases

PhosphoSiteQ9Y2C9.

Polymorphism databases

DMDM296452933.

Proteomic databases

MaxQBQ9Y2C9.
PaxDbQ9Y2C9.
PRIDEQ9Y2C9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000381950; ENSP00000371376; ENSG00000174130.
ENST00000436693; ENSP00000389600; ENSG00000174130.
GeneID10333.
KEGGhsa:10333.
UCSCuc003gtm.3. human.

Organism-specific databases

CTD10333.
GeneCardsGC04M038828.
H-InvDBHIX0004160.
HGNCHGNC:16711. TLR6.
MIM605403. gene.
neXtProtNX_Q9Y2C9.
PharmGKBPA38183.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG272762.
HOGENOMHOG000008676.
HOVERGENHBG023180.
InParanoidQ9Y2C9.
KOK10169.
OMASDTPFIH.
OrthoDBEOG7GN2M5.
PhylomeDBQ9Y2C9.
TreeFamTF351113.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressQ9Y2C9.
BgeeQ9Y2C9.
CleanExHS_TLR6.
GenevestigatorQ9Y2C9.

Family and domain databases

Gene3D3.40.50.10140. 1 hit.
InterProIPR000483. Cys-rich_flank_reg_C.
IPR001611. Leu-rich_rpt.
IPR000157. TIR_dom.
IPR027187. TLR6.
IPR017241. Toll-like_receptor.
[Graphical view]
PANTHERPTHR24365:SF23. PTHR24365:SF23. 1 hit.
PfamPF13855. LRR_8. 2 hits.
PF01463. LRRCT. 1 hit.
PF01582. TIR. 1 hit.
[Graphical view]
PIRSFPIRSF037595. Toll-like_receptor. 1 hit.
SMARTSM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMSSF52200. SSF52200. 1 hit.
PROSITEPS51450. LRR. 9 hits.
PS50104. TIR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSTLR6. human.
GeneWikiTLR6.
GenomeRNAi10333.
NextBio39189.
PROQ9Y2C9.
SOURCESearch...

Entry information

Entry nameTLR6_HUMAN
AccessionPrimary (citable) accession number: Q9Y2C9
Secondary accession number(s): B3Y640 expand/collapse secondary AC list , B6CH35, B6RFS4, B6RFS5
Entry history
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: May 18, 2010
Last modified: July 9, 2014
This is version 132 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries