TLR6_BOVIN
ID TLR6_BOVIN Reviewed; 793 AA.
AC Q704V6; B5T272; B5T275; B5T276; Q3BK20; Q706D2;
DT 15-JUN-2010, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 25-MAY-2022, entry version 111.
DE RecName: Full=Toll-like receptor 6 {ECO:0000312|EMBL:CAF06197.1};
DE AltName: CD_antigen=CD286 {ECO:0000250|UniProtKB:Q9Y2C9};
DE Flags: Precursor;
GN Name=TLR6 {ECO:0000312|EMBL:CAF06197.1};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1] {ECO:0000312|EMBL:AAY40896.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=16701904; DOI=10.1016/j.vetimm.2006.03.007;
RA Werling D., Piercy J., Coffey T.J.;
RT "Expression of TOLL-like receptors (TLR) by bovine antigen-presenting
RT cells-potential role in pathogen discrimination?";
RL Vet. Immunol. Immunopathol. 112:2-11(2006).
RN [2] {ECO:0000305, ECO:0000312|EMBL:ACH92795.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASN-214.
RC STRAIN=Angus {ECO:0000312|EMBL:ACH92795.1},
RC Charolais {ECO:0000312|EMBL:ACH92798.1},
RC Holstein {ECO:0000312|EMBL:ACH92799.1}, and
RC Limousin {ECO:0000312|EMBL:ACH92800.1};
RX PubMed=18639626; DOI=10.1016/j.ygeno.2008.06.005;
RA Seabury C.M., Womack J.E.;
RT "Analysis of sequence variability and protein domain architectures for
RT bovine peptidoglycan recognition protein 1 and Toll-like receptors 2 and
RT 6.";
RL Genomics 92:235-245(2008).
RN [3] {ECO:0000312|EMBL:CAF06197.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC TISSUE=Mammary gland {ECO:0000312|EMBL:CAF02015.1};
RA Yang W., Weikard R., Zerbe H., Seyfert H.M.;
RT "Structure and tissue-specific expression the bovine TLR6-encoding gene.";
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305, ECO:0000312|EMBL:CAJ35083.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 165-422, TISSUE SPECIFICITY, AND VARIANT
RP ASN-214.
RC TISSUE=Semen {ECO:0000269|PubMed:16950576};
RX PubMed=16950576; DOI=10.1016/j.gene.2006.06.027;
RA Opsal M.A., Vage D.I., Hayes B., Berget I., Lien S.;
RT "Genomic organization and transcript profiling of the bovine toll-like
RT receptor gene cluster TLR6-TLR1-TLR10.";
RL Gene 384:45-50(2006).
CC -!- FUNCTION: Participates in the innate immune response to Gram-positive
CC bacteria and fungi. Specifically recognizes diacylated and, to a lesser
CC extent, triacylated lipopeptides. In response to diacylated
CC lipopeptides, forms the activation cluster TLR2:TLR6:CD14:CD36, this
CC cluster triggers signaling from the cell surface and subsequently is
CC targeted to the Golgi in a lipid-raft dependent pathway. Acts via MYD88
CC and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the
CC inflammatory response. Recognizes mycoplasmal macrophage-activating
CC lipopeptide-2kD (MALP-2), soluble tuberculosis factor (STF), phenol-
CC soluble modulin (PSM) and B.burgdorferi outer surface protein A
CC lipoprotein (OspA-L) cooperatively with TLR2. In complex with TLR4,
CC promotes sterile inflammation in monocytes/macrophages in response to
CC oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42. In this
CC context, the initial signal is provided by oxLDL- or amyloid-beta 42-
CC binding to CD36. This event induces the formation of a heterodimer of
CC TLR4 and TLR6, which is rapidly internalized and triggers inflammatory
CC response, leading to the NF-kappa-B-dependent production of CXCL1,
CC CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5
CC cytokine, via TICAM1 signaling pathway, as well as IL1B secretion.
CC {ECO:0000250|UniProtKB:Q9EPW9, ECO:0000250|UniProtKB:Q9Y2C9}.
CC -!- SUBUNIT: Homodimer (via cytoplasmic TIR domain) (By similarity).
CC Heterodimer with TLR2 via their respective extracellular domains. Binds
CC MYD88 via their respective TIR domains (By similarity). Interacts with
CC CD36, following CD36 stimulation by oxLDL or amyloid-beta 42, and forms
CC a heterodimer with TLR4. The trimeric complex is internalized and
CC triggers inflammatory response. LYN kinase activity facilitates TLR4-
CC TLR6 heterodimerization and signal initiation (By similarity). The
CC heterodimer TLR2:TLR6 interacts with CD14 and CD36 in response to
CC triacylated lipopeptides. {ECO:0000250|UniProtKB:Q9EPW9,
CC ECO:0000250|UniProtKB:Q9Y2C9}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9Y2C9};
CC Single-pass type I membrane protein {ECO:0000255}. Cytoplasmic vesicle,
CC phagosome membrane {ECO:0000250|UniProtKB:Q9EPW9}; Single-pass type I
CC membrane protein {ECO:0000255}. Membrane raft
CC {ECO:0000250|UniProtKB:Q9Y2C9}. Golgi apparatus
CC {ECO:0000250|UniProtKB:Q9Y2C9}. Note=Upon complex formation with CD36
CC and TLR4, internalized through dynamin-dependent endocytosis. Does not
CC reside in lipid rafts before stimulation but accumulates increasingly
CC in the raft upon the presence of the microbial ligand. In response to
CC diacylated lipoproteins, TLR2:TLR6 heterodimers are recruited in lipid
CC rafts, this recruitment determine the intracellular targeting to the
CC Golgi apparatus. {ECO:0000250|UniProtKB:Q9Y2C9}.
CC -!- TISSUE SPECIFICITY: Highest expression levels seen in blood and lymph
CC node, intermediate expression seen in spleen and lowest expression seen
CC in the liver, lung and udder cistern. {ECO:0000269|PubMed:16950576}.
CC -!- SIMILARITY: Belongs to the Toll-like receptor family. {ECO:0000255}.
CC -!- CAUTION: In some plant proteins and in human SARM1, the TIR domain has
CC NAD(+) hydrolase (NADase) activity (By similarity). However, despite
CC the presence of the catalytic Asp residue, the isolated TIR domain of
CC human TLR4 lacks NADase activity (By similarity). Based on this, it is
CC unlikely that Toll-like receptors have NADase activity.
CC {ECO:0000250|UniProtKB:O00206, ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAJ35083.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AY487803; AAY40896.1; -; mRNA.
DR EMBL; EU746466; ACH92795.1; -; Genomic_DNA.
DR EMBL; EU746469; ACH92798.1; -; Genomic_DNA.
DR EMBL; EU746470; ACH92799.1; -; Genomic_DNA.
DR EMBL; EU746471; ACH92800.1; -; Genomic_DNA.
DR EMBL; AJ618974; CAF02015.1; -; mRNA.
DR EMBL; AJ620670; CAF06197.1; -; Genomic_DNA.
DR EMBL; AM113851; CAJ35083.1; ALT_FRAME; mRNA.
DR RefSeq; NP_001001159.1; NM_001001159.1.
DR AlphaFoldDB; Q704V6; -.
DR SMR; Q704V6; -.
DR STRING; 9913.ENSBTAP00000035880; -.
DR PaxDb; Q704V6; -.
DR GeneID; 407237; -.
DR KEGG; bta:407237; -.
DR CTD; 10333; -.
DR eggNOG; KOG4641; Eukaryota.
DR InParanoid; Q704V6; -.
DR OrthoDB; 282372at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0035355; C:Toll-like receptor 2-Toll-like receptor 6 protein complex; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0071723; F:lipopeptide binding; IBA:GO_Central.
DR GO; GO:0050135; F:NAD(P)+ nucleosidase activity; IEA:UniProtKB-EC.
DR GO; GO:0061809; F:NAD+ nucleotidase, cyclic ADP-ribose generating; IEA:UniProtKB-EC.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0035663; F:Toll-like receptor 2 binding; IBA:GO_Central.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:InterPro.
DR GO; GO:0071221; P:cellular response to bacterial lipopeptide; IBA:GO_Central.
DR GO; GO:0071726; P:cellular response to diacyl bacterial lipopeptide; ISS:UniProtKB.
DR GO; GO:0042496; P:detection of diacyl bacterial lipopeptide; IEA:InterPro.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; IEA:InterPro.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISS:UniProtKB.
DR GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; ISS:UniProtKB.
DR GO; GO:0034150; P:toll-like receptor 6 signaling pathway; IEA:InterPro.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; IBA:GO_Central.
DR Gene3D; 3.40.50.10140; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR000483; Cys-rich_flank_reg_C.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR027187; TLR6.
DR InterPro; IPR017241; Toll-like_receptor.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR PANTHER; PTHR24365; PTHR24365; 1.
DR PANTHER; PTHR24365:SF422; PTHR24365:SF422; 1.
DR Pfam; PF13855; LRR_8; 1.
DR Pfam; PF01463; LRRCT; 1.
DR Pfam; PF01582; TIR; 1.
DR PIRSF; PIRSF037595; Toll-like_receptor; 1.
DR SMART; SM00369; LRR_TYP; 5.
DR SMART; SM00082; LRRCT; 1.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF52200; SSF52200; 1.
DR PROSITE; PS51450; LRR; 10.
DR PROSITE; PS50104; TIR; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cytoplasmic vesicle; Disulfide bond; Glycoprotein;
KW Golgi apparatus; Immunity; Inflammatory response; Innate immunity;
KW Leucine-rich repeat; Membrane; NAD; Receptor; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..793
FT /note="Toll-like receptor 6"
FT /evidence="ECO:0000255"
FT /id="PRO_0000394670"
FT TOPO_DOM 24..584
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 585..605
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 606..793
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 54..77
FT /note="LRR 1"
FT REPEAT 78..101
FT /note="LRR 2"
FT REPEAT 102..122
FT /note="LRR 3"
FT REPEAT 123..147
FT /note="LRR 4"
FT REPEAT 148..168
FT /note="LRR 5"
FT REPEAT 169..196
FT /note="LRR 6"
FT REPEAT 197..219
FT /note="LRR 7"
FT REPEAT 220..250
FT /note="LRR 8"
FT REPEAT 251..277
FT /note="LRR 9"
FT REPEAT 278..303
FT /note="LRR 10"
FT REPEAT 304..330
FT /note="LRR 11"
FT REPEAT 331..354
FT /note="LRR 12"
FT REPEAT 355..378
FT /note="LRR 13"
FT REPEAT 379..404
FT /note="LRR 14"
FT REPEAT 405..428
FT /note="LRR 15"
FT REPEAT 429..449
FT /note="LRR 16"
FT REPEAT 450..473
FT /note="LRR 17"
FT REPEAT 474..495
FT /note="LRR 18"
FT REPEAT 496..519
FT /note="LRR 19"
FT DOMAIN 520..575
FT /note="LRRCT"
FT DOMAIN 640..781
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT CARBOHYD 63
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 253
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 285
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 359
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 423
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 434
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 117..140
FT /evidence="ECO:0000250"
FT DISULFID 235..265
FT /evidence="ECO:0000250"
FT DISULFID 348..373
FT /evidence="ECO:0000250"
FT DISULFID 424..447
FT /evidence="ECO:0000250"
FT VARIANT 214
FT /note="D -> N (in strain: Angus, Charolais, Holstein and
FT Limousin)"
FT /evidence="ECO:0000269|PubMed:16950576,
FT ECO:0000269|PubMed:18639626"
FT CONFLICT 221
FT /note="G -> A (in Ref. 1; CAF02015/AAY40896)"
FT /evidence="ECO:0000305"
FT CONFLICT 259
FT /note="V -> M (in Ref. 2; ACH92795/ACH92799/ACH92800/
FT ACH92798 and 4; CAJ35083)"
FT /evidence="ECO:0000305"
FT CONFLICT 503..504
FT /note="EH -> DY (in Ref. 2; ACH92795/ACH92799/ACH92800/
FT ACH92798)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 793 AA; 90927 MW; C11C26009F8E3668 CRC64;
MIKDKESPIR SCHFVYIVAL VFGTIIQFSD ESEFVVDMSK TSLIHVPKDL PPKTKVLDLS
QNNISELHLS DISFLSGLRV LRLSHNRIQG LDISIFKFNH DLEYLDLSHN QLQKISCHPI
TTTLKHLDLS FNDFDALPIC KEFGNLTQLN FLGLSATKLQ QLDLLPIAHL HLSCILLDLE
DYMKENKKES LQILNTKKLH LVFHPNSFFS VQVDISANSL GCLQLTNIKL NDYNCQVLLK
FLSGLTGGPT LLNFTLNHVE TTWKCLVKVF QFLWPKPIEY LNIYNLTIVE SIDEEVFTYY
KTTLKALKIE HITNKVFIFS QTALYTVFSE MNILMLTISD TRFIHMLCPQ EPSTFKFLNF
TQNSFTDSVF QNCDTLARLE TLILQKNELK DLFKTSLMTK DMLSLETLDV SWNSLEYDRS
NGNCSWVGSI VVLNLSSNAL TDSVFRCLPP RIKVLDLHNN RIRSIPKDVT GLETLQELNL
ASNSLAHLPG CGIFSSLSIL IIEHNSISNP SADFFQSCQK IRSLKAGNNP FQCSCELRDF
IQSVGQVSSD VVEGWPESYK CDYPESYKGT PLKDFQVSEL SCNTALLIIT IVVPGLVLAV
AVTVLCIYLD LPWYLRMVCQ WTQTRRRARN VPLEELQRTL QFHAFISYSE HDSAWVKNEL
IPNLEKEDIR ICLHERNFVA GKSIVENIIN CIEKSYKSIF VLSPNFVQSE WCHYELYFAH
HNLFHEGSDN LILILLDPIP QYSIPSSYHK LRALMAQRTY LEWPKEKSKH GLFWANLRAS
INIKLMEKAA EIH
