TLR2_MOUSE
ID TLR2_MOUSE Reviewed; 784 AA.
AC Q9QUN7; Q3U400; Q9DBC4;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Toll-like receptor 2;
DE AltName: CD_antigen=CD282;
DE Flags: Precursor;
GN Name=Tlr2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND MUTAGENESIS OF PRO-681.
RX PubMed=10548109; DOI=10.1038/44605;
RA Underhill D.M., Ozinsky A., Hajjar A.M., Stevens A., Wilson C.B.,
RA Bassetti M., Aderem A.;
RT "The Toll-like receptor 2 is recruited to macrophage phagosomes and
RT discriminates between pathogens.";
RL Nature 401:811-815(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Macrophage;
RX PubMed=10358136;
RA Heine H., Kirschning C.J., Lien E., Monks B.G., Rothe M., Golenbock D.T.;
RT "Cells that carry a null allele for Toll-like receptor 2 are capable of
RT responding to endotoxin.";
RL J. Immunol. 162:6971-6975(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Macrophage;
RX PubMed=10666214;
RA Matsuguchi T., Takagi K., Musikacharoen T., Yoshikai Y.;
RT "Gene expressions of lipopolysaccharide receptors, Toll-like receptors 2
RT and 4, are differently regulated in mouse T lymphocytes.";
RL Blood 95:1378-1385(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Adipocyte;
RX PubMed=10823826; DOI=10.1074/jbc.m002137200;
RA Lin Y., Lee H., Berg A.H., Lisanti M.P., Shapiro L., Scherer P.E.;
RT "The lipopolysaccharide-activated Toll-like receptor (TLR)-4 induces
RT synthesis of the closely related receptor TLR-2 in adipocytes.";
RL J. Biol. Chem. 275:24255-24263(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Liver;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP PROTEIN SEQUENCE OF 405-413 AND 754-759, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [7]
RP SUBCELLULAR LOCATION.
RC STRAIN=BALB/cJ; TISSUE=Macrophage;
RX PubMed=11095740; DOI=10.1073/pnas.250476497;
RA Ozinsky A., Underhill D.M., Fontenot J.D., Hajjar A.M., Smith K.D.,
RA Wilson C.B., Schroeder L., Aderem A.;
RT "The repertoire for pattern recognition of pathogens by the innate immune
RT system is defined by cooperation between Toll-like receptors.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:13766-13771(2000).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15690042; DOI=10.1038/nature03253;
RA Hoebe K., Georgel P., Rutschmann S., Du X., Mudd S., Crozat K., Sovath S.,
RA Shamel L., Hartung T., Zaehringer U., Beutler B.;
RT "CD36 is a sensor of diacylglycerides.";
RL Nature 433:523-527(2005).
RN [9]
RP FUNCTION, AND INTERACTION WITH M.TUBERCULOSIS ESXA.
RX PubMed=17486091; DOI=10.1038/ni1468;
RA Pathak S.K., Basu S., Basu K.K., Banerjee A., Pathak S., Bhattacharyya A.,
RA Kaisho T., Kundu M., Basu J.;
RT "Direct extracellular interaction between the early secreted antigen ESAT-6
RT of Mycobacterium tuberculosis and TLR2 inhibits TLR signaling in
RT macrophages.";
RL Nat. Immunol. 8:610-618(2007).
RN [10]
RP ERRATUM OF PUBMED:17486091.
RX PubMed=25689444; DOI=10.1038/ni0315-326b;
RA Pathak S.K., Basu S., Basu K.K., Banerjee A., Pathak S., Bhattacharyya A.,
RA Kaisho T., Kundu M., Basu J.;
RT "Corrigendum: Direct extracellular interaction between the early secreted
RT antigen ESAT-6 of Mycobacterium tuberculosis and TLR2 inhibits TLR
RT signaling in macrophages.";
RL Nat. Immunol. 16:326-326(2015).
RN [11]
RP INTERACTION WITH CNPY3.
RX PubMed=18780723; DOI=10.1093/intimm/dxn098;
RA Kiyokawa T., Akashi-Takamura S., Shibata T., Matsumoto F., Nishitani C.,
RA Kuroki Y., Seto Y., Miyake K.;
RT "A single base mutation in the PRAT4A gene reveals differential interaction
RT of PRAT4A with Toll-like receptors.";
RL Int. Immunol. 20:1407-1415(2008).
RN [12]
RP FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Macrophage;
RX PubMed=19362712; DOI=10.1016/j.cellimm.2009.03.008;
RA Drage M.G., Pecora N.D., Hise A.G., Febbraio M., Silverstein R.L.,
RA Golenbock D.T., Boom W.H., Harding C.V.;
RT "TLR2 and its co-receptors determine responses of macrophages and dendritic
RT cells to lipoproteins of Mycobacterium tuberculosis.";
RL Cell. Immunol. 258:29-37(2009).
RN [13]
RP INTERACTION WITH STAPHYLOCOCCUS AUREUS SUPERANTIGEN-LIKE PROTEIN 3
RP (MICROBIAL INFECTION).
RX PubMed=22665377; DOI=10.1128/iai.00399-12;
RA Yokoyama R., Itoh S., Kamoshida G., Takii T., Fujii S., Tsuji T.,
RA Onozaki K.;
RT "Staphylococcal superantigen-like protein 3 binds to the Toll-like receptor
RT 2 extracellular domain and inhibits cytokine production induced by
RT Staphylococcus aureus, cell wall component, or lipopeptides in murine
RT macrophages.";
RL Infect. Immun. 80:2816-2825(2012).
RN [14]
RP FUNCTION, AND INTERACTION WITH M.TUBERCULOSIS MPT83 (MICROBIAL INFECTION).
RC TISSUE=Macrophage;
RX PubMed=22174456; DOI=10.4049/jimmunol.1102177;
RA Chen S.T., Li J.Y., Zhang Y., Gao X., Cai H.;
RT "Recombinant MPT83 derived from Mycobacterium tuberculosis induces cytokine
RT production and upregulates the function of mouse macrophages through
RT TLR2.";
RL J. Immunol. 188:668-677(2012).
RN [15]
RP FUNCTION.
RC TISSUE=Macrophage;
RX PubMed=27220037; DOI=10.1111/cmi.12619;
RA Deboosere N., Iantomasi R., Queval C.J., Song O.R., Deloison G., Jouny S.,
RA Debrie A.S., Chamaillard M., Nigou J., Cohen-Gonsaud M., Locht C.,
RA Brodin P., Veyron-Churlet R.;
RT "LppM impact on the colonization of macrophages by Mycobacterium
RT tuberculosis.";
RL Cell. Microbiol. 0:0-0(2016).
RN [16]
RP UBIQUITINATION AT LYS-754, DEUBIQUITINATION, AND INTERACTION WITH PPP1R11.
RX PubMed=27805901; DOI=10.7554/elife.18496;
RA McKelvey A.C., Lear T.B., Dunn S.R., Evankovich J., Londino J.D.,
RA Bednash J.S., Zhang Y., McVerry B.J., Liu Y., Chen B.B.;
RT "RING finger E3 ligase PPP1R11 regulates TLR2 signaling and innate
RT immunity.";
RL Elife 5:0-0(2016).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 27-506, DISULFIDE BONDS, AND
RP GLYCOSYLATION AT ASN-147; ASN-414 AND ASN-442.
RX PubMed=17889651; DOI=10.1016/j.cell.2007.09.008;
RA Jin M.S., Kim S.E., Heo J.Y., Lee M.E., Kim H.M., Paik S.-G., Lee H.,
RA Lee J.-O.;
RT "Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a
RT tri-acylated lipopeptide.";
RL Cell 130:1071-1082(2007).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 1-506 IN COMPLEX WITH TLR6 AND
RP LIPOPEPTIDE, DISULFIDE BONDS, GLYCOSYLATION AT ASN-147; ASN-414 AND
RP ASN-442, FUNCTION, LRR REPEATS, AND SUBUNIT.
RX PubMed=19931471; DOI=10.1016/j.immuni.2009.09.018;
RA Kang J.Y., Nan X., Jin M.S., Youn S.J., Ryu Y.H., Mah S., Han S.H., Lee H.,
RA Paik S.G., Lee J.O.;
RT "Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like
RT receptor 6 heterodimer.";
RL Immunity 31:873-884(2009).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 25-589, GLYCOSYLATION AT ASN-414
RP AND ASN-442, AND INTERACTION WITH STAPHYLOCOCCAL SUPERANTIGEN-LIKE PROTEIN
RP 3.
RX PubMed=26283364; DOI=10.1073/pnas.1502026112;
RA Koymans K.J., Feitsma L.J., Brondijk T.H., Aerts P.C., Lukkien E.,
RA Loessl P., van Kessel K.P., de Haas C.J., van Strijp J.A., Huizinga E.G.;
RT "Structural basis for inhibition of TLR2 by staphylococcal superantigen-
RT like protein 3 (SSL3).";
RL Proc. Natl. Acad. Sci. U.S.A. 112:11018-11023(2015).
CC -!- FUNCTION: Cooperates with LY96 to mediate the innate immune response to
CC bacterial lipoproteins and other microbial cell wall components.
CC Cooperates with TLR1 or TLR6 to mediate the innate immune response to
CC bacterial lipoproteins or lipopeptides. Acts via MYD88 and TRAF6,
CC leading to NF-kappa-B activation, cytokine secretion and the
CC inflammatory response (By similarity) (PubMed:15690042). May also
CC promote apoptosis in response to lipoproteins (By similarity). Forms
CC activation clusters composed of several receptors depending on the
CC ligand, these clusters trigger signaling from the cell surface and
CC subsequently are targeted to the Golgi in a lipid-raft dependent
CC pathway. Forms the cluster TLR2:TLR6:CD14:CD36 in response to
CC diacylated lipopeptides and TLR2:TLR1:CD14 in response to triacylated
CC lipopeptides (By similarity). Recognizes M.tuberculosis major T-antigen
CC EsxA (ESAT-6) which inhibits downstream MYD88-dependent signaling
CC (PubMed:17486091). Acts as the major receptor for M.tuberculosis
CC lipoproteins LprA, LprG, LpqH and PhoS1 (pstS1), in conjunction with
CC TLR1 and for some but not all lipoproteins CD14 and/or CD36. The
CC lipoproteins act as agonists to modulate antigen presenting cell
CC functions in response to the pathogen (PubMed:19362712). Recombinant
CC MPT83 from M.tuberculosis stimulates secretion of cytokines (TNF-alpha,
CC IL-6 and IL-12p40) by mouse macrophage cell lines in a TLR2-dependent
CC fashion, which leads to increased host innate immunity responses
CC against the bacterium (PubMed:22174456). Lung macrophages which express
CC low levels of TLR2 respond poorly to stimulation by M.tuberculosis LpqH
CC (PubMed:19362712). Required for normal uptake of M.tuberculosis, a
CC process that is inhibited by M.tuberculosis LppM (PubMed:27220037).
CC Interacts with TICAM2 (By similarity). {ECO:0000250|UniProtKB:O60603,
CC ECO:0000269|PubMed:15690042, ECO:0000269|PubMed:17486091,
CC ECO:0000269|PubMed:19362712, ECO:0000269|PubMed:22174456,
CC ECO:0000269|PubMed:27220037}.
CC -!- SUBUNIT: Interacts with LY96, TLR1 and TLR6 (via extracellular domain).
CC TLR2 seems to exist in heterodimers with either TLR1 or TLR6 before
CC stimulation by the ligand (PubMed:19931471). The heterodimers form
CC bigger oligomers in response to their corresponding ligands as well as
CC further heterotypic associations with other receptors such as CD14
CC and/or CD36 (By similarity). Binds MYD88 (via TIR domain). Interacts
CC with TICAM1 (By similarity). Interacts with CNPY3 (PubMed:18780723).
CC Interacts with ATG16L1 (By similarity). Interacts with non-modified
CC M.tuberculosis protein MPT83 (PubMed:22174456). Interacts with PPP1R11
CC (PubMed:27805901). {ECO:0000250|UniProtKB:O60603,
CC ECO:0000269|PubMed:18780723, ECO:0000269|PubMed:19931471,
CC ECO:0000269|PubMed:22174456, ECO:0000269|PubMed:27805901}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Staphylococcus aureus
CC protein SSL3; this interaction inhibits TLR2-mediated cytokine
CC production. {ECO:0000269|PubMed:22665377, ECO:0000269|PubMed:26283364}.
CC -!- INTERACTION:
CC Q9QUN7; P22366: Myd88; NbExp=2; IntAct=EBI-3505834, EBI-525108;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11095740};
CC Single-pass type I membrane protein {ECO:0000255}. Cytoplasmic vesicle,
CC phagosome membrane {ECO:0000269|PubMed:11095740}; Single-pass type I
CC membrane protein {ECO:0000255}. Membrane raft
CC {ECO:0000250|UniProtKB:O60603}. Note=Does not reside in lipid rafts
CC before stimulation but accumulates increasingly in the raft upon the
CC presence of the microbial ligand. In response to diacylated
CC lipoproteins, TLR2:TLR6 heterodimers are recruited in lipid rafts, this
CC recruitment determine the intracellular targeting to the Golgi
CC apparatus. Triacylated lipoproteins induce the same mechanism for
CC TLR2:TLR1 heterodimers. {ECO:0000250|UniProtKB:O60603}.
CC -!- TISSUE SPECIFICITY: Detected in a macrophage cell line, smooth muscle,
CC lung, spleen, thymus, brain and adipose tissue. Cell surface expression
CC detected in lung alveolar macrophages, dendritic macrophages and at
CC lower levels in lung macrophages (at protein level) (PubMed:19362712).
CC {ECO:0000269|PubMed:19362712}.
CC -!- DOMAIN: Ester-bound lipid substrates are bound through a crevice formed
CC between the LRR 11 and LRR 12.
CC -!- DOMAIN: The ATG16L1-binding motif mediates interaction with ATG16L1.
CC {ECO:0000250}.
CC -!- PTM: Ubiquitinated at Lys-754 by PPP1R11, leading to its degradation.
CC Deubiquitinated by USP2. {ECO:0000269|PubMed:27805901}.
CC -!- PTM: Glycosylation of Asn-442 is critical for secretion of the N-
CC terminal ectodomain of TLR2. {ECO:0000250|UniProtKB:O60603}.
CC -!- DISRUPTION PHENOTYPE: Mutants succumb to Staphylococcus aureus
CC infection within 5 days. {ECO:0000269|PubMed:15690042}.
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; AF185284; AAF04277.1; -; mRNA.
DR EMBL; AF124741; AAD46481.1; -; mRNA.
DR EMBL; AF216289; AAF28345.1; -; mRNA.
DR EMBL; AF165189; AAD49335.1; -; mRNA.
DR EMBL; AK005043; BAB23770.1; -; mRNA.
DR EMBL; AK154504; BAE32635.1; -; mRNA.
DR CCDS; CCDS17435.1; -.
DR RefSeq; NP_036035.3; NM_011905.3.
DR PDB; 2Z81; X-ray; 1.80 A; A=27-506.
DR PDB; 2Z82; X-ray; 2.60 A; A=27-506.
DR PDB; 3A79; X-ray; 2.90 A; A=1-506.
DR PDB; 3A7B; X-ray; 2.53 A; A=1-506.
DR PDB; 3A7C; X-ray; 2.40 A; A=1-506.
DR PDB; 5D3I; X-ray; 3.20 A; A=25-589.
DR PDBsum; 2Z81; -.
DR PDBsum; 2Z82; -.
DR PDBsum; 3A79; -.
DR PDBsum; 3A7B; -.
DR PDBsum; 3A7C; -.
DR PDBsum; 5D3I; -.
DR AlphaFoldDB; Q9QUN7; -.
DR SMR; Q9QUN7; -.
DR DIP; DIP-61222N; -.
DR IntAct; Q9QUN7; 12.
DR MINT; Q9QUN7; -.
DR STRING; 10090.ENSMUSP00000029623; -.
DR BindingDB; Q9QUN7; -.
DR ChEMBL; CHEMBL1075106; -.
DR GuidetoPHARMACOLOGY; 1752; -.
DR GlyGen; Q9QUN7; 3 sites.
DR iPTMnet; Q9QUN7; -.
DR PhosphoSitePlus; Q9QUN7; -.
DR SwissPalm; Q9QUN7; -.
DR MaxQB; Q9QUN7; -.
DR PaxDb; Q9QUN7; -.
DR PeptideAtlas; Q9QUN7; -.
DR PRIDE; Q9QUN7; -.
DR ProteomicsDB; 258894; -.
DR ABCD; Q9QUN7; 23 sequenced antibodies.
DR DNASU; 24088; -.
DR GeneID; 24088; -.
DR KEGG; mmu:24088; -.
DR CTD; 7097; -.
DR MGI; MGI:1346060; Tlr2.
DR eggNOG; KOG4641; Eukaryota.
DR InParanoid; Q9QUN7; -.
DR OrthoDB; 282372at2759; -.
DR PhylomeDB; Q9QUN7; -.
DR Reactome; R-MMU-1461957; Beta defensins.
DR Reactome; R-MMU-5686938; Regulation of TLR by endogenous ligand.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 24088; 2 hits in 72 CRISPR screens.
DR EvolutionaryTrace; Q9QUN7; -.
DR PRO; PR:Q9QUN7; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9QUN7; protein.
DR GO; GO:0044297; C:cell body; ISO:MGI.
DR GO; GO:0042995; C:cell projection; ISO:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISO:MGI.
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; IDA:MGI.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0035354; C:Toll-like receptor 1-Toll-like receptor 2 protein complex; ISO:MGI.
DR GO; GO:0035355; C:Toll-like receptor 2-Toll-like receptor 6 protein complex; IPI:MGI.
DR GO; GO:0001540; F:amyloid-beta binding; IDA:ARUK-UCL.
DR GO; GO:0042498; F:diacyl lipopeptide binding; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0071723; F:lipopeptide binding; ISO:MGI.
DR GO; GO:0001530; F:lipopolysaccharide binding; ISO:MGI.
DR GO; GO:0070891; F:lipoteichoic acid binding; IDA:MGI.
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:0038187; F:pattern recognition receptor activity; ISO:MGI.
DR GO; GO:0042834; F:peptidoglycan binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:ARUK-UCL.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0035325; F:Toll-like receptor binding; ISO:MGI.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:InterPro.
DR GO; GO:0042497; F:triacyl lipopeptide binding; IDA:MGI.
DR GO; GO:0001775; P:cell activation; ISO:MGI.
DR GO; GO:0002752; P:cell surface pattern recognition receptor signaling pathway; IMP:MGI.
DR GO; GO:0071221; P:cellular response to bacterial lipopeptide; IMP:MGI.
DR GO; GO:0071726; P:cellular response to diacyl bacterial lipopeptide; ISS:UniProtKB.
DR GO; GO:0071346; P:cellular response to interferon-gamma; ISO:MGI.
DR GO; GO:0071223; P:cellular response to lipoteichoic acid; IMP:MGI.
DR GO; GO:0071224; P:cellular response to peptidoglycan; IMP:MGI.
DR GO; GO:0071727; P:cellular response to triacyl bacterial lipopeptide; ISS:UniProtKB.
DR GO; GO:0032289; P:central nervous system myelin formation; ISO:MGI.
DR GO; GO:0006952; P:defense response; IMP:MGI.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:MGI.
DR GO; GO:0042496; P:detection of diacyl bacterial lipopeptide; ISO:MGI.
DR GO; GO:0042495; P:detection of triacyl bacterial lipopeptide; ISO:MGI.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IMP:MGI.
DR GO; GO:0007252; P:I-kappaB phosphorylation; ISO:MGI.
DR GO; GO:0006954; P:inflammatory response; ISO:MGI.
DR GO; GO:0045087; P:innate immune response; TAS:BHF-UCL.
DR GO; GO:0007612; P:learning; IGI:ARUK-UCL.
DR GO; GO:0050900; P:leukocyte migration; IMP:MGI.
DR GO; GO:0006691; P:leukotriene metabolic process; ISO:MGI.
DR GO; GO:0014005; P:microglia development; IGI:ARUK-UCL.
DR GO; GO:0001774; P:microglial cell activation; ISO:MGI.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; IGI:MGI.
DR GO; GO:0030837; P:negative regulation of actin filament polymerization; IGI:ARUK-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0032695; P:negative regulation of interleukin-12 production; IMP:MGI.
DR GO; GO:0032700; P:negative regulation of interleukin-17 production; IMP:MGI.
DR GO; GO:0050765; P:negative regulation of phagocytosis; IMP:ARUK-UCL.
DR GO; GO:0051964; P:negative regulation of synapse assembly; IGI:ARUK-UCL.
DR GO; GO:1990266; P:neutrophil migration; IMP:MGI.
DR GO; GO:0038061; P:NIK/NF-kappaB signaling; IMP:MGI.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IMP:MGI.
DR GO; GO:0046209; P:nitric oxide metabolic process; ISO:MGI.
DR GO; GO:1903974; P:positive regulation of cellular response to macrophage colony-stimulating factor stimulus; ISO:MGI.
DR GO; GO:0032722; P:positive regulation of chemokine production; IMP:MGI.
DR GO; GO:0001819; P:positive regulation of cytokine production; IGI:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IGI:ARUK-UCL.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; IDA:BHF-UCL.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IGI:ARUK-UCL.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISO:MGI.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IDA:BHF-UCL.
DR GO; GO:0032741; P:positive regulation of interleukin-18 production; IDA:BHF-UCL.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:BHF-UCL.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:MGI.
DR GO; GO:0002687; P:positive regulation of leukocyte migration; IMP:MGI.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IDA:MGI.
DR GO; GO:1904466; P:positive regulation of matrix metallopeptidase secretion; ISO:MGI.
DR GO; GO:1902624; P:positive regulation of neutrophil migration; IMP:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IMP:MGI.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IMP:MGI.
DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; ISO:MGI.
DR GO; GO:0034123; P:positive regulation of toll-like receptor signaling pathway; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:BHF-UCL.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISO:MGI.
DR GO; GO:1904417; P:positive regulation of xenophagy; IMP:MGI.
DR GO; GO:0002730; P:regulation of dendritic cell cytokine production; IDA:MGI.
DR GO; GO:0032493; P:response to bacterial lipoprotein; ISO:MGI.
DR GO; GO:0009617; P:response to bacterium; IMP:MGI.
DR GO; GO:0070542; P:response to fatty acid; ISO:MGI.
DR GO; GO:0002238; P:response to molecule of fungal origin; IMP:MGI.
DR GO; GO:0032494; P:response to peptidoglycan; IMP:MGI.
DR GO; GO:0034134; P:toll-like receptor 2 signaling pathway; IEA:InterPro.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; ISO:MGI.
DR GO; GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; ISO:MGI.
DR GO; GO:0098792; P:xenophagy; IMP:MGI.
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; IPR027185; TLR2.
DR InterPro; IPR017241; Toll-like_receptor.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR PANTHER; PTHR24365; PTHR24365; 1.
DR PANTHER; PTHR24365:SF17; PTHR24365:SF17; 1.
DR Pfam; PF13855; LRR_8; 2.
DR Pfam; PF01582; TIR; 1.
DR PIRSF; PIRSF037595; Toll-like_receptor; 1.
DR SMART; SM00369; LRR_TYP; 7.
DR SMART; SM00082; LRRCT; 1.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF52200; SSF52200; 1.
DR PROSITE; PS51450; LRR; 9.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytoplasmic vesicle;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Immunity;
KW Inflammatory response; Innate immunity; Isopeptide bond;
KW Leucine-rich repeat; Membrane; NAD; Receptor; Reference proteome; Repeat;
KW Signal; Transmembrane; Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..784
FT /note="Toll-like receptor 2"
FT /id="PRO_0000034712"
FT TOPO_DOM 25..587
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 588..608
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 609..784
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 54..77
FT /note="LRR 1"
FT /evidence="ECO:0000269|PubMed:19931471"
FT REPEAT 78..101
FT /note="LRR 2"
FT /evidence="ECO:0000269|PubMed:19931471"
FT REPEAT 102..125
FT /note="LRR 3"
FT /evidence="ECO:0000269|PubMed:19931471"
FT REPEAT 126..150
FT /note="LRR 4"
FT /evidence="ECO:0000269|PubMed:19931471"
FT REPEAT 151..175
FT /note="LRR 5"
FT /evidence="ECO:0000269|PubMed:19931471"
FT REPEAT 176..199
FT /note="LRR 6"
FT /evidence="ECO:0000269|PubMed:19931471"
FT REPEAT 200..223
FT /note="LRR 7"
FT /evidence="ECO:0000269|PubMed:19931471"
FT REPEAT 224..250
FT /note="LRR 8"
FT /evidence="ECO:0000269|PubMed:19931471"
FT REPEAT 251..278
FT /note="LRR 9"
FT /evidence="ECO:0000269|PubMed:19931471"
FT REPEAT 279..308
FT /note="LRR 10"
FT /evidence="ECO:0000269|PubMed:19931471"
FT REPEAT 309..337
FT /note="LRR 11"
FT /evidence="ECO:0000269|PubMed:19931471"
FT REPEAT 338..361
FT /note="LRR 12"
FT /evidence="ECO:0000269|PubMed:19931471"
FT REPEAT 362..388
FT /note="LRR 13"
FT /evidence="ECO:0000269|PubMed:19931471"
FT REPEAT 389..414
FT /note="LRR 14"
FT /evidence="ECO:0000269|PubMed:19931471"
FT REPEAT 415..437
FT /note="LRR 15"
FT /evidence="ECO:0000269|PubMed:19931471"
FT REPEAT 438..457
FT /note="LRR 16"
FT /evidence="ECO:0000269|PubMed:19931471"
FT REPEAT 458..478
FT /note="LRR 17"
FT /evidence="ECO:0000269|PubMed:19931471"
FT REPEAT 479..500
FT /note="LRR 18"
FT /evidence="ECO:0000269|PubMed:19931471"
FT REPEAT 501..524
FT /note="LRR 19"
FT /evidence="ECO:0000269|PubMed:19931471"
FT DOMAIN 525..576
FT /note="LRRCT"
FT DOMAIN 639..782
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT MOTIF 761..778
FT /note="ATG16L1-binding motif"
FT SITE 349
FT /note="Interaction with bacterial lipopeptide"
FT /evidence="ECO:0000250"
FT CARBOHYD 147
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17889651,
FT ECO:0000269|PubMed:19931471, ECO:0000269|PubMed:26283364"
FT CARBOHYD 414
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17889651,
FT ECO:0000269|PubMed:19931471, ECO:0000269|PubMed:26283364"
FT CARBOHYD 442
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17889651,
FT ECO:0000269|PubMed:19931471, ECO:0000269|PubMed:26283364"
FT DISULFID 30..36
FT DISULFID 353..382
FT DISULFID 432..454
FT CROSSLNK 754
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:27805901"
FT MUTAGEN 681
FT /note="P->H: Abolishes MYD88-binding and response to
FT microbial cell wall components."
FT /evidence="ECO:0000269|PubMed:10548109"
FT CONFLICT 59
FT /note="L -> P (in Ref. 5; BAB23770)"
FT /evidence="ECO:0000305"
FT CONFLICT 82
FT /note="I -> M (in Ref. 5; BAB23770)"
FT /evidence="ECO:0000305"
FT STRAND 34..37
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:3A79"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 71..74
FT /evidence="ECO:0007829|PDB:3A7C"
FT STRAND 80..82
FT /evidence="ECO:0007829|PDB:2Z81"
FT TURN 93..98
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:2Z81"
FT HELIX 117..120
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 153..161
FT /evidence="ECO:0007829|PDB:2Z81"
FT TURN 167..172
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 175..183
FT /evidence="ECO:0007829|PDB:2Z81"
FT TURN 191..196
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 198..206
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 208..210
FT /evidence="ECO:0007829|PDB:2Z81"
FT HELIX 213..219
FT /evidence="ECO:0007829|PDB:2Z81"
FT TURN 221..223
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 224..231
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:3A7C"
FT STRAND 253..258
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 260..262
FT /evidence="ECO:0007829|PDB:2Z81"
FT HELIX 263..270
FT /evidence="ECO:0007829|PDB:2Z81"
FT HELIX 271..275
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 281..286
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 288..290
FT /evidence="ECO:0007829|PDB:2Z81"
FT TURN 299..301
FT /evidence="ECO:0007829|PDB:2Z81"
FT HELIX 304..306
FT /evidence="ECO:0007829|PDB:3A7C"
FT STRAND 311..316
FT /evidence="ECO:0007829|PDB:2Z81"
FT HELIX 322..324
FT /evidence="ECO:0007829|PDB:2Z81"
FT HELIX 330..334
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 340..346
FT /evidence="ECO:0007829|PDB:2Z81"
FT HELIX 353..358
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 364..366
FT /evidence="ECO:0007829|PDB:2Z81"
FT HELIX 374..380
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 391..393
FT /evidence="ECO:0007829|PDB:2Z81"
FT HELIX 402..408
FT /evidence="ECO:0007829|PDB:2Z81"
FT HELIX 409..411
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 417..419
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 440..442
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 460..463
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 481..483
FT /evidence="ECO:0007829|PDB:2Z81"
FT HELIX 495..497
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 503..505
FT /evidence="ECO:0007829|PDB:2Z81"
FT HELIX 518..521
FT /evidence="ECO:0007829|PDB:2Z81"
FT STRAND 527..529
FT /evidence="ECO:0007829|PDB:2Z81"
FT HELIX 539..544
FT /evidence="ECO:0007829|PDB:2Z81"
FT HELIX 549..553
FT /evidence="ECO:0007829|PDB:5D3I"
FT TURN 556..561
FT /evidence="ECO:0007829|PDB:5D3I"
FT STRAND 564..567
FT /evidence="ECO:0007829|PDB:5D3I"
FT TURN 568..572
FT /evidence="ECO:0007829|PDB:5D3I"
SQ SEQUENCE 784 AA; 89449 MW; 606D56BF85F320A2 CRC64;
MLRALWLFWI LVAITVLFSK RCSAQESLSC DASGVCDGRS RSFTSIPSGL TAAMKSLDLS
FNKITYIGHG DLRACANLQV LILKSSRINT IEGDAFYSLG SLEHLDLSDN HLSSLSSSWF
GPLSSLKYLN LMGNPYQTLG VTSLFPNLTN LQTLRIGNVE TFSEIRRIDF AGLTSLNELE
IKALSLRNYQ SQSLKSIRDI HHLTLHLSES AFLLEIFADI LSSVRYLELR DTNLARFQFS
PLPVDEVSSP MKKLAFRGSV LTDESFNELL KLLRYILELS EVEFDDCTLN GLGDFNPSES
DVVSELGKVE TVTIRRLHIP QFYLFYDLST VYSLLEKVKR ITVENSKVFL VPCSFSQHLK
SLEFLDLSEN LMVEEYLKNS ACKGAWPSLQ TLVLSQNHLR SMQKTGEILL TLKNLTSLDI
SRNTFHPMPD SCQWPEKMRF LNLSSTGIRV VKTCIPQTLE VLDVSNNNLD SFSLFLPRLQ
ELYISRNKLK TLPDASLFPV LLVMKIRENA VSTFSKDQLG SFPKLETLEA GDNHFVCSCE
LLSFTMETPA LAQILVDWPD SYLCDSPPRL HGHRLQDARP SVLECHQAAL VSGVCCALLL
LILLVGALCH HFHGLWYLRM MWAWLQAKRK PKKAPCRDVC YDAFVSYSEQ DSHWVENLMV
QQLENSDPPF KLCLHKRDFV PGKWIIDNII DSIEKSHKTV FVLSENFVRS EWCKYELDFS
HFRLFDENND AAILVLLEPI ERKAIPQRFC KLRKIMNTKT YLEWPLDEGQ QEVFWVNLRT
AIKS
