TLR6_DASNO
ID TLR6_DASNO Reviewed; 789 AA.
AC Q0ZUL9;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 22-AUG-2006, sequence version 1.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Toll-like receptor 6;
DE AltName: CD_antigen=CD286;
DE Flags: Precursor;
GN Name=TLR6;
OS Dasypus novemcinctus (Nine-banded armadillo).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Xenarthra; Cingulata; Dasypodidae; Dasypus.
OX NCBI_TaxID=9361;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Adams J.E., Pena M.T., Gillis T.P., Williams D.L., Adams L.B., Truman R.W.;
RT "TLR-6 in Dasypus novemcinctus.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
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: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
CC TLR4: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 -!- SIMILARITY: Belongs to the Toll-like receptor family. {ECO:0000305}.
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}.
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DR EMBL; DQ113655; AAZ52552.1; -; mRNA.
DR RefSeq; NP_001268236.1; NM_001281307.1.
DR AlphaFoldDB; Q0ZUL9; -.
DR SMR; Q0ZUL9; -.
DR GeneID; 100913181; -.
DR KEGG; dnm:100913181; -.
DR CTD; 10333; -.
DR HOGENOM; CLU_006000_3_0_1; -.
DR OrthoDB; 282372at2759; -.
DR TreeFam; TF351113; -.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0045121; C:membrane raft; ISS:UniProtKB.
DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
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:0004888; F:transmembrane signaling receptor activity; IEA:InterPro.
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; IEA:UniProtKB-KW.
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 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; 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; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT CHAIN 32..789
FT /note="Toll-like receptor 6"
FT /id="PRO_0000253756"
FT TOPO_DOM 32..587
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 588..608
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 609..789
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 639..780
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT CARBOHYD 144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 186
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 214
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 372
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 433
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 519
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 117..139
FT /evidence="ECO:0000250"
FT DISULFID 235..265
FT /evidence="ECO:0000250"
FT DISULFID 348..373
FT /evidence="ECO:0000250"
FT DISULFID 423..446
FT /evidence="ECO:0000250"
SQ SEQUENCE 789 AA; 91379 MW; 81CB96D6B3C5C00C CRC64;
MTKDKEPIVK NFHLVCIVTL IVGTIIQFSD ADEFAIDMSK TGLTHVPKDL PPKTKVLDMS
QNYLSELQIS DISFLSGLKI LVLSHNRLQL LDLSVFKFNQ DLEYLDLSHN QLKKMSCHPF
VNLKHLDLSF NDFDSLPICK EFGNLTQLDF LGLSATKLQQ LDLLPIAHLH LNCILLDLKG
YYVKQNETES LQILNTKKLH LVFHTGSFFS VQVNMSVNTL GCLEMTNIKL NDKNCYFLMK
FLLELTKGPS LLNFTLNHME TTWKCLVRVF QFLWTKPVEY LNIYNLTIVD DINKEYFIYC
KTALKALKIE HITKTVFIFS WSSLYTLFSE MNIMMLSITD TPFIHMLCPK TRSTFKFLDF
TQNVFTDSIF ENCSTLVELE TLILQKNGLK DLFKIGLMTK GMPSLEILDL SWNSLVFNRQ
RKCIWVGSIL MLNMSSNLLT DLVFRCLPPR VTVLDLHNNR IMSIPKDVTS LETLQELNIA
FNSLTDLPGC GTFSSLSVLI IDYNLISHPS TDFIQSCQNI TSIKAGKNPF QCTCDLREFI
KTISQMSSEV VKDWPDSYKC DYPESYKGTL LQDFHISQLS CSTSLLTVTI GATMLVLVVT
VTFLCIYLDL PWYIRMVYQW TQTRRRARNI PLEELQRTLQ FHAFISYSGH DSAWVKTELL
PNLEKEDIQI CLHERNFVPG KSIIENIINF IEKSYKSIFV LSPNFVQSEW CHYELYFAHH
NLFHEAFDNL ILILLEPIPQ YSIPNNYHKL KSLIAQRTYL EWPKEKSKHG LFWANLRAAI
NIKLMEEKK
