Q9Y2C9 (TLR6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Toll-like receptor 6

Alternative name(s):
CD_antigen=CD286

Gene names

Name:

TLR6

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	796 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	Participates in the innate immune response to Gram-positive bacteria and fungi. 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 TLR2 via their respective extracellular domains. Binds MYD88 via their respective TIR domains By similarity.
Subcellular location	Cell membrane; Single-pass type I membrane protein By similarity. Cytoplasmic vesicle › phagosome 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 12 LRR (leucine-rich) repeats. Contains 1 LRRCT domain. Contains 1 TIR domain.

Ontologies

Keywords
Biological process	Immunity Inflammatory response Innate immunity
Cellular component	Cell membrane Cytoplasmic vesicle Membrane
Coding sequence diversity	Polymorphism
Domain	Leucine-rich repeat Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	MyD88-dependent toll-like receptor signaling pathway Traceable author statement. Source: Reactome T-helper 1 type immune response Inferred by curator. Source: UniProtKB Toll signaling pathway Traceable author statement. Source: Reactome 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. Source: MGI defense response to bacterium Traceable author statement. Source: ProtInc detection of diacyl bacterial lipopeptide Inferred from direct assay. Source: MGI inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Traceable author statement. Source: Reactome positive regulation of I-kappaB kinase/NF-kappaB cascade 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. Source: UniProtKB toll-like receptor 1 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 2 signaling pathway Traceable author statement. Source: Reactome toll-like receptor 4 signaling pathway Traceable author statement. Source: Reactome
Cellular component	integral to plasma membrane Traceable author statement. Source: ProtInc phagocytic vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	transmembrane signaling receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 31	31	Potential
	Chain	32 – 796	765	Toll-like receptor 6		PRO_0000034731
Regions
	Topological domain	32 – 586	555	Extracellular Potential
	Transmembrane	587 – 607	21	Helical; Potential
	Topological domain	608 – 796	189	Cytoplasmic Potential
	Repeat	53 – 74	22	LRR 1
	Repeat	77 – 97	21	LRR 2
	Repeat	101 – 122	22	LRR 3
	Repeat	123 – 143	21	LRR 4
	Repeat	147 – 168	22	LRR 5
	Repeat	177 – 198	22	LRR 6
	Repeat	378 – 399	22	LRR 7
	Repeat	404 – 425	22	LRR 8
	Repeat	429 – 449	21	LRR 9
	Repeat	451 – 472	22	LRR 10
	Repeat	474 – 495	22	LRR 11
	Repeat	496 – 517	22	LRR 12
	Domain	529 – 584	56	LRRCT
	Domain	640 – 784	145	TIR
Amino acid modifications
	Glycosylation	144	1	N-linked (GlcNAc...) Potential
	Glycosylation	186	1	N-linked (GlcNAc...) Potential
	Glycosylation	214	1	N-linked (GlcNAc...) Potential
	Glycosylation	253	1	N-linked (GlcNAc...) Potential
	Glycosylation	285	1	N-linked (GlcNAc...) Potential
	Glycosylation	359	1	N-linked (GlcNAc...) Potential
	Glycosylation	423	1	N-linked (GlcNAc...) Potential
	Glycosylation	434	1	N-linked (GlcNAc...) Potential
	Glycosylation	583	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	120	1	I → T. Ref.3 Ref.7 Corresponds to variant rs5743808 [ dbSNP | Ensembl ].		VAR_057289
	Natural variant	128	1	L → V Impairs the ability to induce NF-kappa-B activation. Ref.7		VAR_066352
	Natural variant	194	1	L → P Impairs the ability to induce NF-kappa-B activation. Ref.7 Corresponds to variant rs5743809 [ dbSNP | Ensembl ].		VAR_057290
	Natural variant	210	1	A → G. Ref.7		VAR_066353
	Natural variant	210	1	A → T. Ref.7		VAR_066354
	Natural variant	247	1	R → K. Ref.7 Corresponds to variant rs35220466 [ dbSNP | Ensembl ].		VAR_057291
	Natural variant	249	1	S → P. Ref.2 Ref.3 Ref.4 Ref.7 Corresponds to variant rs5743810 [ dbSNP | Ensembl ].		VAR_063110
	Natural variant	283	1	I → V. Ref.7		VAR_066355
	Natural variant	327	1	V → M. Ref.3 Ref.7 Corresponds to variant rs3796508 [ dbSNP | Ensembl ].		VAR_057292
	Natural variant	345	1	H → Y. Corresponds to variant rs5743813 [ dbSNP | Ensembl ].		VAR_057293
	Natural variant	427	1	V → A. Ref.7 Corresponds to variant rs5743815 [ dbSNP | Ensembl ].		VAR_057294
	Natural variant	442	1	D → A. Ref.7		VAR_066356
	Natural variant	465	1	V → I. Ref.7 Corresponds to variant rs5743816 [ dbSNP | Ensembl ].		VAR_057295
	Natural variant	474	1	A → T. Ref.7 Corresponds to variant rs35762983 [ dbSNP | Ensembl ].		VAR_057296
	Natural variant	474	1	A → V Impairs the ability to induce NF-kappa-B activation. Ref.7		VAR_066357
	Natural variant	592	1	G → V. Ref.7		VAR_066358
	Natural variant	690	1	N → T Impairs the ability to induce NF-kappa-B activation. Ref.7		VAR_066359
	Natural variant	708	1	Q → H Impairs the ability to induce NF-kappa-B activation. Ref.7		VAR_066360
	Natural variant	783	1	M → V. Corresponds to variant rs5743822 [ dbSNP | Ensembl ].		VAR_057297

Sequences

	Sequence		Length	Mass (Da)
	Q9Y2C9 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: 9ACEAEC084CB466C	FASTA	796	91,880
	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

References

	« Hide 'large scale' referencesShow '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: 10231569] [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: 18810425] [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. , 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: 15815621] [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. , 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: 11441107] [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: 21618349] [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.
IPI	IPI00294125.
RefSeq	NP_006059.2. NM_006068.4.
UniGene	Hs.575090.
3D structure databases
ProteinModelPortal	Q9Y2C9.
SMR	Q9Y2C9. Positions 33-573, 630-786.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9Y2C9.
PTM databases
PhosphoSite	Q9Y2C9.
Polymorphism databases
DMDM	296452933.
Proteomic databases
PRIDE	Q9Y2C9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000381950; ENSP00000371376; ENSG00000174130. ENST00000436693; ENSP00000389600; ENSG00000174130.
GeneID	10333.
KEGG	hsa:10333.
UCSC	uc003gtm.2. human.
Organism-specific databases
CTD	10333.
GeneCards	GC04M038828.
H-InvDB	HIX0031342.
HGNC	HGNC:16711. TLR6.
MIM	605403. gene.
neXtProt	NX_Q9Y2C9.
PharmGKB	PA38183.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG12467.
GeneTree	ENSGT00600000084264.
HOGENOM	HBG444147.
HOVERGEN	HBG023180.
InParanoid	Q9Y2C9.
OMA	SDTPFIH.
OrthoDB	EOG4SBDXJ.
PhylomeDB	Q9Y2C9.
Enzyme and pathway databases
Reactome	REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q9Y2C9.
Bgee	Q9Y2C9.
CleanEx	HS_TLR6.
Genevestigator	Q9Y2C9.
GermOnline	ENSG00000174130. Homo sapiens.
Family and domain databases
InterPro	IPR000483. Cys-rich_flank_reg_C. IPR004075. IL1_rcpt_1. IPR001611. Leu-rich_rpt. IPR000157. TIR_dom. IPR017241. Toll-like_receptor. [Graphical view]
KO	K10169.
Pfam	PF01463. LRRCT. 1 hit. PF01582. TIR. 1 hit. [Graphical view]
PIRSF	PIRSF037595. Toll-like_receptor. 1 hit.
PRINTS	PR01537. INTRLKN1R1F.
SMART	SM00082. LRRCT. 1 hit. SM00255. TIR. 1 hit. [Graphical view]
SUPFAM	SSF52200. TIR. 1 hit.
PROSITE	PS51450. LRR. 9 hits. PS50104. TIR. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	39189.
SOURCE	Search...

Entry information

Entry name

TLR6_HUMAN

Accession

Primary (citable) accession number: Q9Y2C9
Secondary accession number(s): B3Y640 , B6CH35, B6RFS4, B6RFS5

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 31, 2002
Last sequence update:	May 18, 2010
Last modified:	January 25, 2012
This is version 109 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.