ID TLR2_HUMAN Reviewed; 784 AA. AC O60603; B3Y612; D1CS45; D1CS48; D1CS49; O15454; Q8NI00; DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1998, sequence version 1. DT 13-FEB-2019, entry version 208. DE RecName: Full=Toll-like receptor 2; DE AltName: Full=Toll/interleukin-1 receptor-like protein 4; DE AltName: CD_antigen=CD282; DE Flags: Precursor; GN Name=TLR2; Synonyms=TIL4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Leukocyte, and Prostate; RX PubMed=9596645; RA Chaudhary P.M., Ferguson C., Nguyen V., Nguyen O., Massa H.F., Eby M., RA Jasmin A., Trask B.J., Hood L., Nelson P.S.; RT "Cloning and characterization of two Toll/Interleukin-1 receptor-like RT genes TIL3 and TIL4: evidence for a multi-gene receptor family in RT humans."; RL Blood 91:4020-4027(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9435236; DOI=10.1073/pnas.95.2.588; RA Rock F.L., Hardiman G., Timans J.C., Kastelein R.A., Bazan J.F.; RT "A family of human receptors structurally related to Drosophila RT Toll."; RL Proc. Natl. Acad. Sci. U.S.A. 95:588-593(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND RESPONSE TO LIPOPOLYSACCHARIDE. RC TISSUE=Fetal lung; RX PubMed=9751057; DOI=10.1038/26239; RA Yang R.-B., Mark M.R., Gray A.M., Huang A., Xie M.-H., Zhang M., RA Goddard A.D., Wood W.I., Gurney A.L., Godowski P.J.; RT "Toll-like receptor-2 mediates lipopolysaccharide-induced cellular RT signalling."; RL Nature 395:284-288(1998). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=18810425; DOI=10.1007/s00251-008-0332-0; RA Nakajima T., Ohtani H., Satta Y., Uno Y., Akari H., Ishida T., RA Kimura A.; RT "Natural selection in the TLR-related genes in the course of primate RT evolution."; RL Immunogenetics 60:727-735(2008). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS HIS-631 AND GLN-753. RX PubMed=19924287; DOI=10.1371/journal.pone.0007803; RA Georgel P., Macquin C., Bahram S.; RT "The heterogeneous allelic repertoire of human Toll-Like receptor RT (TLR) genes."; RL PLoS ONE 4:E7803-E7803(2009). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Blood; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-586. RA Zhang L., Yu W.B., Ma Y.Y.; RT "Cloning and sequencing of extracellular domain and its N-terminal and RT C-terminal fragments of Toll-like receptor 2."; RL Di 4 Jun Yi Da Xue Xue Bao 23:1085-1089(2002). RN [9] RP FUNCTION. RC TISSUE=T-cell; RX PubMed=10426995; DOI=10.1126/science.285.5428.732; RA Brightbill H.D., Libraty D.H., Krutzik S.R., Yang R.B., Belisle J.T., RA Bleharski J.R., Maitland M., Norgard M.V., Plevy S.E., Smale S.T., RA Brennan P.J., Bloom B.R., Godowski P.J., Modlin R.L.; RT "Host defense mechanisms triggered by microbial lipoproteins through RT Toll-like receptors."; RL Science 285:732-736(1999). RN [10] RP FUNCTION. RX PubMed=10426996; DOI=10.1126/science.285.5428.736; RA Aliprantis A.O., Yang R.-B., Mark M.R., Suggett S., Devaux B., RA Radolf J.D., Klimpel G.R., Godowski P.J., Zychlinsky A.; RT "Cell activation and apoptosis by bacterial lipoproteins through Toll- RT like receptor-2."; RL Science 285:736-739(1999). RN [11] RP FUNCTION. RX PubMed=11441107; DOI=10.4049/jimmunol.167.2.987; RA Bulut Y., Faure E., Thomas L., Equils O., Arditi M.; RT "Cooperation of Toll-like receptor 2 and 6 for cellular activation by RT soluble tuberculosis factor and Borrelia burgdorferi outer surface RT protein A lipoprotein: role of Toll-interacting protein and IL-1 RT receptor signaling molecules in Toll-like receptor 2 signaling."; RL J. Immunol. 167:987-994(2001). RN [12] RP INTERACTION WITH TICAM1. RX PubMed=12471095; DOI=10.4049/jimmunol.169.12.6668; RA Yamamoto M., Sato S., Mori K., Hoshino K., Takeuchi O., Takeda K., RA Akira S.; RT "A novel Toll/IL-1 receptor domain-containing adapter that RT preferentially activates the IFN-beta promoter in the Toll-like RT receptor signaling."; RL J. Immunol. 169:6668-6672(2002). RN [13] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CD14; CD36; TLR1 RP AND TLR6. RX PubMed=16880211; DOI=10.1074/jbc.M602794200; RA Triantafilou M., Gamper F.G., Haston R.M., Mouratis M.A., Morath S., RA Hartung T., Triantafilou K.; RT "Membrane sorting of toll-like receptor (TLR)-2/6 and TLR2/1 RT heterodimers at the cell surface determines heterotypic associations RT with CD36 and intracellular targeting."; RL J. Biol. Chem. 281:31002-31011(2006). RN [14] RP GLYCOSYLATION AT ASN-114; ASN-199 AND ASN-442, AND MUTAGENESIS OF RP ASN-114; ASN-199; THR-416 AND ASN-442. RX PubMed=15173186; DOI=10.1074/jbc.M403830200; RA Weber A.N., Morse M.A., Gay N.J.; RT "Four N-linked glycosylation sites in human toll-like receptor 2 RT cooperate to direct efficient biosynthesis and secretion."; RL J. Biol. Chem. 279:34589-34594(2004). RN [15] RP FUNCTION. RX PubMed=15809303; DOI=10.1074/jbc.M411379200; RA Bulut Y., Michelsen K.S., Hayrapetian L., Naiki Y., Spallek R., RA Singh M., Arditi M.; RT "Mycobacterium tuberculosis heat shock proteins use diverse Toll-like RT receptor pathways to activate pro-inflammatory signals."; RL J. Biol. Chem. 280:20961-20967(2005). RN [16] RP FUNCTION. RC TISSUE=Monocyte; RX PubMed=16622205; DOI=10.1128/IAI.74.5.2686-2696.2006; RA Jung S.B., Yang C.S., Lee J.S., Shin A.R., Jung S.S., Son J.W., RA Harding C.V., Kim H.J., Park J.K., Paik T.H., Song C.H., Jo E.K.; RT "The mycobacterial 38-kilodalton glycolipoprotein antigen activates RT the mitogen-activated protein kinase pathway and release of RT proinflammatory cytokines through Toll-like receptors 2 and 4 in human RT monocytes."; RL Infect. Immun. 74:2686-2696(2006). RN [17] RP FUNCTION. 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 RT dendritic cells to lipoproteins of Mycobacterium tuberculosis."; RL Cell. Immunol. 258:29-37(2009). RN [18] RP FUNCTION, AND INTERACTION WITH M.BOVIS MPB83 AND M.TUBERCULOSIS ESXA. RX PubMed=20800577; DOI=10.1016/j.bbrc.2010.08.085; RA Chambers M.A., Whelan A.O., Spallek R., Singh M., Coddeville B., RA Guerardel Y., Elass E.; RT "Non-acylated Mycobacterium bovis glycoprotein MPB83 binds to TLR1/2 RT and stimulates production of matrix metalloproteinase 9."; RL Biochem. Biophys. Res. Commun. 400:403-408(2010). RN [19] RP FUNCTION. RC TISSUE=T-cell; RX PubMed=21078852; DOI=10.1128/IAI.00806-10; RA Lancioni C.L., Li Q., Thomas J.J., Ding X., Thiel B., Drage M.G., RA Pecora N.D., Ziady A.G., Shank S., Harding C.V., Boom W.H., RA Rojas R.E.; RT "Mycobacterium tuberculosis lipoproteins directly regulate human RT memory CD4(+) T cell activation via Toll-like receptors 1 and 2."; RL Infect. Immun. 79:663-673(2011). RN [20] RP INTERACTION WITH ATG16L1. RX PubMed=23376921; DOI=10.1038/emboj.2013.8; RA Boada-Romero E., Letek M., Fleischer A., Pallauf K., Ramon-Barros C., RA Pimentel-Muinos F.X.; RT "TMEM59 defines a novel ATG16L1-binding motif that promotes local RT activation of LC3."; RL EMBO J. 32:566-582(2013). RN [21] RP UBIQUITINATION AT LYS-754, AND MUTAGENESIS OF LYS-709; LYS-714; RP 742-LYS--LYS-743; LYS-751 AND LYS-754. 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 [22] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 639-784, AND MUTAGENESIS. RX PubMed=11081518; DOI=10.1038/35040600; RA Xu Y., Tao X., Shen B., Horng T., Medzhitov R., Manley J.L., Tong L.; RT "Structural basis for signal transduction by the Toll/interleukin-1 RT receptor domains."; RL Nature 408:111-115(2000). RN [23] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-509 IN COMPLEX WITH TLR1 RP AND BACTERIAL LIPOPEPTIDE ANALOG, DISULFIDE BONDS, GLYCOSYLATION AT RP ASN-114; ASN-199; ASN-414 AND ASN-442, AND FUNCTION. 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 RT a tri-acylated lipopeptide."; RL Cell 130:1071-1082(2007). RN [24] RP VARIANT TRP-677, AND ASSOCIATION WITH LEPROSIS. RX PubMed=11476982; DOI=10.1111/j.1574-695X.2001.tb01586.x; RA Kang T.-J., Chae G.-T.; RT "Detection of Toll-like receptor 2 (TLR2) mutation in the lepromatous RT leprosy patients."; RL FEMS Immunol. Med. Microbiol. 31:53-58(2001). RN [25] RP VARIANT TRP-677, AND ASSOCIATION WITH LEPROSIS. RX PubMed=12646604; DOI=10.4049/jimmunol.170.7.3451; RA Bochud P.-Y., Hawn T.R., Aderem A.; RT "A Toll-like receptor 2 polymorphism that is associated with RT lepromatous leprosy is unable to mediate mycobacterial signaling."; RL J. Immunol. 170:3451-3454(2003). RN [26] RP VARIANTS ASP-89; ILE-411; HIS-571; HIS-631; ARG-636 AND GLN-753, AND RP CHARACTERIZATION OF VARIANTS ILE-411; HIS-631 AND GLN-753. RX PubMed=21618349; DOI=10.1002/humu.21486; RA Ben-Ali M., Corre B., Manry J., Barreiro L.B., Quach H., Boniotto M., RA Pellegrini S., Quintana-Murci L.; RT "Functional characterization of naturally occurring genetic variants RT in the human TLR1-2-6 gene family."; RL Hum. Mutat. 32:643-652(2011). CC -!- FUNCTION: Cooperates with LY96 to mediate the innate immune CC response to bacterial lipoproteins and other microbial cell wall CC components. Cooperates with TLR1 or TLR6 to mediate the innate CC immune response to bacterial lipoproteins or lipopeptides CC (PubMed:21078852, PubMed:17889651). Acts via MYD88 and TRAF6, CC leading to NF-kappa-B activation, cytokine secretion and the CC inflammatory response. May also activate immune cells and promote CC apoptosis in response to the lipid moiety of lipoproteins CC (PubMed:10426995, PubMed:10426996). Recognizes mycoplasmal CC macrophage-activating lipopeptide-2kD (MALP-2), soluble CC tuberculosis factor (STF), phenol-soluble modulin (PSM) and CC B.burgdorferi outer surface protein A lipoprotein (OspA-L) CC cooperatively with TLR6 (PubMed:11441107). Stimulation of CC monocytes in vitro with M.tuberculosis PstS1 induces p38 MAPK and CC ERK1/2 activation primarily via this receptor, but also partially CC via TLR4 (PubMed:16622205). MAPK activation in response to CC bacterial peptidoglycan also occurs via this receptor CC (PubMed:16622205). Acts as a receptor for M.tuberculosis CC lipoproteins LprA, LprG, LpqH and PstS1, some lipoproteins are CC dependent on other coreceptors (TLR1, CD14 and/or CD36); the CC lipoproteins act as agonists to modulate antigen presenting cell CC functions in response to the pathogen (PubMed:19362712). CC M.tuberculosis HSP70 (dnaK) but not HSP65 (groEL-2) acts via this CC protein to stimulate NF-kappa-B expression (PubMed:15809303). CC Recognizes M.tuberculosis major T-antigen EsxA (ESAT-6) which CC inhibits downstream MYD88-dependent signaling (shown in mouse) (By CC similarity). Forms activation clusters composed of several CC receptors depending on the ligand, these clusters trigger CC signaling from the cell surface and subsequently are targeted to CC the Golgi in a lipid-raft dependent pathway. Forms the cluster CC TLR2:TLR6:CD14:CD36 in response to diacylated lipopeptides and CC TLR2:TLR1:CD14 in response to triacylated lipopeptides CC (PubMed:16880211). Required for normal uptake of M.tuberculosis, a CC process that is inhibited by M.tuberculosis LppM (By similarity). CC {ECO:0000250|UniProtKB:Q9QUN7, ECO:0000269|PubMed:10426995, CC ECO:0000269|PubMed:10426996, ECO:0000269|PubMed:11441107, CC ECO:0000269|PubMed:15809303, ECO:0000269|PubMed:16622205, CC ECO:0000269|PubMed:16880211, ECO:0000269|PubMed:17889651, CC ECO:0000269|PubMed:19362712, ECO:0000269|PubMed:21078852}. CC -!- SUBUNIT: Interacts with LY96, TLR1 and TLR6 (via extracellular CC domain) (PubMed:17889651). TLR2 seems to exist in heterodimers CC with either TLR1 or TLR6 before stimulation by the ligand. The CC heterodimers form bigger oligomers in response to their CC corresponding ligands as well as further heterotypic associations CC with other receptors such as CD14 and/or CD36 (PubMed:16880211). CC Binds MYD88 (via TIR domain). Interacts with TICAM1 CC (PubMed:12471095). Interacts with CNPY3 (By similarity). Interacts CC with ATG16L1 (PubMed:23376921). Interacts with PPP1R11 (By CC similarity). {ECO:0000250|UniProtKB:Q9QUN7, CC ECO:0000269|PubMed:12471095, ECO:0000269|PubMed:16880211, CC ECO:0000269|PubMed:17889651, ECO:0000269|PubMed:23376921}. CC -!- SUBUNIT: (Microbial infection) Interacts with M.tuberculosis EsxA. CC {ECO:0000269|PubMed:20800577}. CC -!- SUBUNIT: (Microbial infection) Interacts with M.bovis MPB83. CC {ECO:0000269|PubMed:20800577}. CC -!- INTERACTION: CC Self; NbExp=4; IntAct=EBI-973722, EBI-973722; CC P61073:CXCR4; NbExp=3; IntAct=EBI-973722, EBI-489411; CC P00533:EGFR; NbExp=2; IntAct=EBI-973722, EBI-297353; CC C3PTT6:PAUF; NbExp=3; IntAct=EBI-973722, EBI-3505892; CC Q15399:TLR1; NbExp=3; IntAct=EBI-973722, EBI-9009517; CC Q9BXR5:TLR10; NbExp=3; IntAct=EBI-973722, EBI-16825459; CC Q9Y2C9:TLR6; NbExp=4; IntAct=EBI-973722, EBI-13940779; CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q9QUN7}; CC Single-pass type I membrane protein {ECO:0000255}. Cytoplasmic CC vesicle, phagosome membrane {ECO:0000250|UniProtKB:Q9QUN7}; CC Single-pass type I membrane protein {ECO:0000255}. Membrane raft CC {ECO:0000269|PubMed:16880211}. Note=Does not reside in lipid rafts CC before stimulation but accumulates increasingly in the raft upon CC the presence of the microbial ligand. In response to diacylated CC lipoproteins, TLR2:TLR6 heterodimers are recruited in lipid rafts, CC this recruitment determines the intracellular targeting to the CC Golgi apparatus. Triacylated lipoproteins induce the same CC mechanism for TLR2:TLR1 heterodimers. CC {ECO:0000269|PubMed:16880211}. CC -!- TISSUE SPECIFICITY: Highly expressed in peripheral blood CC leukocytes, in particular in monocytes, in bone marrow, lymph node CC and in spleen. Also detected in lung and in fetal liver. Levels CC are low in other tissues. CC -!- DOMAIN: Ester-bound lipid substrates are bound through a crevice CC formed between the LRR 11 and LRR 12. {ECO:0000250}. CC -!- DOMAIN: The ATG16L1-binding motif mediates interaction with CC ATG16L1. {ECO:0000269|PubMed:23376921}. CC -!- PTM: Glycosylation of Asn-442 is critical for secretion of the N- CC terminal ectodomain of TLR2. {ECO:0000269|PubMed:15173186, CC ECO:0000269|PubMed:17889651}. CC -!- PTM: Ubiquitinated at Lys-754 by PPP1R11, leading to its CC degradation (PubMed:27805901). Deubiquitinated by USP2 (By CC similarity). {ECO:0000250|UniProtKB:Q9QUN7, CC ECO:0000269|PubMed:27805901}. CC -!- POLYMORPHISM: Genetic variations in TLR2 are associated with CC susceptibility to leprosy [MIM:246300]. Leprosy is a chronic CC disease associated with depressed cellular (but not humoral) CC immunity, the bacterium requires a lower temperature than 37 CC degrees Celsius and thrives particularly in peripheral Schwann CC cells and macrophages. The Trp-677 polymorphism in the CC intracellular domain of TLR2 has a role in susceptibility to CC lepromatous leprosy. Wild-type TLR2 mediates CD14-enhanced CC Mycobacterium leprae-dependent activation of NFKB1, but TLR2 CC containing the Trp-677 polymorphism did not. The impaired function CC of the Trp-677 polymorphism provides a molecular mechanism for the CC poor cellular immune response associated with lepromatous leprosy. CC {ECO:0000269|PubMed:11476982, ECO:0000269|PubMed:12646604}. CC -!- SIMILARITY: Belongs to the Toll-like receptor family. CC {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AF051152; AAC34377.1; -; mRNA. DR EMBL; U88878; AAC34133.1; -; mRNA. DR EMBL; AB445624; BAG55021.1; -; mRNA. DR EMBL; DQ012265; AAY85644.1; -; mRNA. DR EMBL; DQ012266; AAY85645.1; -; mRNA. DR EMBL; DQ012267; AAY85646.1; -; mRNA. DR EMBL; DQ012268; AAY85647.1; -; mRNA. DR EMBL; DQ012269; AAY85648.1; -; mRNA. DR EMBL; DQ012270; AAY85649.1; -; mRNA. DR EMBL; DQ012271; AAY85650.1; -; mRNA. DR EMBL; CH471056; EAX04952.1; -; Genomic_DNA. DR EMBL; CH471056; EAX04953.1; -; Genomic_DNA. DR EMBL; BC033756; AAH33756.1; -; mRNA. DR EMBL; AF502291; AAM23001.1; -; mRNA. DR CCDS; CCDS3784.1; -. DR RefSeq; NP_001305716.1; NM_001318787.1. DR RefSeq; NP_001305718.1; NM_001318789.1. DR RefSeq; NP_001305719.1; NM_001318790.1. DR RefSeq; NP_001305720.1; NM_001318791.1. DR RefSeq; NP_001305722.1; NM_001318793.1. DR RefSeq; NP_001305724.1; NM_001318795.1. DR RefSeq; NP_001305725.1; NM_001318796.1. DR RefSeq; NP_003255.2; NM_003264.4. DR RefSeq; XP_011530517.1; XM_011532215.2. DR RefSeq; XP_011530518.1; XM_011532216.2. DR RefSeq; XP_016864062.1; XM_017008573.1. DR RefSeq; XP_016864063.1; XM_017008574.1. DR RefSeq; XP_016864064.1; XM_017008575.1. DR RefSeq; XP_016864065.1; XM_017008576.1. DR UniGene; Hs.519033; -. DR PDB; 1FYW; X-ray; 3.00 A; A=636-784. DR PDB; 1FYX; X-ray; 2.80 A; A=636-784. DR PDB; 1O77; X-ray; 3.20 A; A/B/C/D/E=639-784. DR PDB; 2Z7X; X-ray; 2.10 A; A=27-506. DR PDB; 2Z80; X-ray; 1.80 A; A/B=1-284. DR PDBsum; 1FYW; -. DR PDBsum; 1FYX; -. DR PDBsum; 1O77; -. DR PDBsum; 2Z7X; -. DR PDBsum; 2Z80; -. DR ProteinModelPortal; O60603; -. DR SMR; O60603; -. DR BioGrid; 112952; 27. DR CORUM; O60603; -. DR DIP; DIP-35138N; -. DR IntAct; O60603; 28. DR MINT; O60603; -. DR STRING; 9606.ENSP00000260010; -. DR BindingDB; O60603; -. DR ChEMBL; CHEMBL4163; -. DR DrugBank; DB00045; OspA lipoprotein. DR DrugBank; DB03963; S-(Dimethylarsenic)Cysteine. DR DrugBank; DB05475; SCV-07. DR GuidetoPHARMACOLOGY; 1752; -. DR GlyConnect; 1816; -. DR iPTMnet; O60603; -. DR PhosphoSitePlus; O60603; -. DR SwissPalm; O60603; -. DR BioMuta; TLR2; -. DR EPD; O60603; -. DR jPOST; O60603; -. DR PaxDb; O60603; -. DR PeptideAtlas; O60603; -. DR PRIDE; O60603; -. DR ProteomicsDB; 49481; -. DR DNASU; 7097; -. DR Ensembl; ENST00000260010; ENSP00000260010; ENSG00000137462. DR Ensembl; ENST00000642580; ENSP00000495339; ENSG00000137462. DR Ensembl; ENST00000642700; ENSP00000494425; ENSG00000137462. DR Ensembl; ENST00000644308; ENSP00000496321; ENSG00000137462. DR GeneID; 7097; -. DR KEGG; hsa:7097; -. DR UCSC; uc063aif.1; human. DR CTD; 7097; -. DR DisGeNET; 7097; -. DR EuPathDB; HostDB:ENSG00000137462.6; -. DR GeneCards; TLR2; -. DR HGNC; HGNC:11848; TLR2. DR HPA; HPA060231; -. DR HPA; HPA071546; -. DR MalaCards; TLR2; -. DR MIM; 246300; phenotype. DR MIM; 603028; gene. DR neXtProt; NX_O60603; -. DR OpenTargets; ENSG00000137462; -. DR PharmGKB; PA36550; -. DR eggNOG; KOG4641; Eukaryota. DR eggNOG; COG4886; LUCA. DR GeneTree; ENSGT00940000156323; -. DR HOGENOM; HOG000110611; -. DR HOVERGEN; HBG108574; -. DR InParanoid; O60603; -. DR KO; K10159; -. DR OMA; IPQRFCK; -. DR OrthoDB; 282372at2759; -. DR PhylomeDB; O60603; -. DR TreeFam; TF351113; -. DR Reactome; R-HSA-1236974; ER-Phagosome pathway. DR Reactome; R-HSA-1461957; Beta defensins. DR Reactome; R-HSA-166058; MyD88:MAL(TIRAP) cascade initiated on plasma membrane. DR Reactome; R-HSA-168179; Toll Like Receptor TLR1:TLR2 Cascade. DR Reactome; R-HSA-168188; Toll Like Receptor TLR6:TLR2 Cascade. DR Reactome; R-HSA-5602498; MyD88 deficiency (TLR2/4). DR Reactome; R-HSA-5603041; IRAK4 deficiency (TLR2/4). DR Reactome; R-HSA-5686938; Regulation of TLR by endogenous ligand. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR SignaLink; O60603; -. DR EvolutionaryTrace; O60603; -. DR GeneWiki; TLR_2; -. DR GenomeRNAi; 7097; -. DR PRO; PR:O60603; -. DR Proteomes; UP000005640; Chromosome 4. DR Bgee; ENSG00000137462; Expressed in 158 organ(s), highest expression level in blood. DR ExpressionAtlas; O60603; baseline and differential. DR Genevisible; O60603; HS. DR GO; GO:0044297; C:cell body; IEA:Ensembl. DR GO; GO:0042995; C:cell projection; IEA:Ensembl. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central. DR GO; GO:0031226; C:intrinsic component of plasma membrane; IDA:UniProtKB. DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB. DR GO; GO:0030670; C:phagocytic vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL. DR GO; GO:0030667; C:secretory granule membrane; TAS:Reactome. DR GO; GO:0035354; C:Toll-like receptor 1-Toll-like receptor 2 protein complex; IDA:MGI. DR GO; GO:0001540; F:amyloid-beta binding; IDA:ARUK-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0001530; F:lipopolysaccharide binding; IDA:UniProtKB. DR GO; GO:0001875; F:lipopolysaccharide receptor activity; TAS:UniProtKB. DR GO; GO:0042834; F:peptidoglycan binding; IDA:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; IDA:MGI. DR GO; GO:0044877; F:protein-containing complex binding; IPI:ARUK-UCL. DR GO; GO:0008329; F:signaling pattern recognition receptor activity; IDA:UniProtKB. DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc. DR GO; GO:0035325; F:Toll-like receptor binding; IPI:UniProtKB. DR GO; GO:0042497; F:triacyl lipopeptide binding; IDA:MGI. DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc. DR GO; GO:0001775; P:cell activation; IDA:AgBase. DR GO; GO:0071221; P:cellular response to bacterial lipopeptide; TAS:BHF-UCL. DR GO; GO:0071726; P:cellular response to diacyl bacterial lipopeptide; IDA:UniProtKB. DR GO; GO:0071346; P:cellular response to interferon-gamma; IDA:UniProtKB. DR GO; GO:0071223; P:cellular response to lipoteichoic acid; IDA:MGI. DR GO; GO:0071727; P:cellular response to triacyl bacterial lipopeptide; IDA:UniProtKB. DR GO; GO:0032289; P:central nervous system myelin formation; IEA:Ensembl. DR GO; GO:0002374; P:cytokine secretion involved in immune response; IMP:CACAO. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB. DR GO; GO:0042496; P:detection of diacyl bacterial lipopeptide; IDA:MGI. DR GO; GO:0042495; P:detection of triacyl bacterial lipopeptide; IDA:MGI. DR GO; GO:0007252; P:I-kappaB phosphorylation; IDA:BHF-UCL. DR GO; GO:0006955; P:immune response; TAS:ProtInc. DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central. DR GO; GO:0045087; P:innate immune response; TAS:BHF-UCL. DR GO; GO:0032613; P:interleukin-10 production; IDA:CACAO. DR GO; GO:0007612; P:learning; ISS:ARUK-UCL. DR GO; GO:0006691; P:leukotriene metabolic process; IEA:Ensembl. DR GO; GO:0014005; P:microglia development; ISS:ARUK-UCL. DR GO; GO:0001774; P:microglial cell activation; IEA:Ensembl. DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:0050765; P:negative regulation of phagocytosis; ISS:ARUK-UCL. DR GO; GO:0051964; P:negative regulation of synapse assembly; ISS:ARUK-UCL. DR GO; GO:0043312; P:neutrophil degranulation; TAS:Reactome. DR GO; GO:0046209; P:nitric oxide metabolic process; IEA:Ensembl. DR GO; GO:1903974; P:positive regulation of cellular response to macrophage colony-stimulating factor stimulus; IDA:UniProtKB. DR GO; GO:0032722; P:positive regulation of chemokine production; IDA:BHF-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB. DR GO; GO:0050729; P:positive regulation of inflammatory response; IC:BHF-UCL. DR GO; GO:0032728; P:positive regulation of interferon-beta production; ISS:BHF-UCL. DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IEA:Ensembl. DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISS:BHF-UCL. DR GO; GO:0032741; P:positive regulation of interleukin-18 production; ISS: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; IDA:BHF-UCL. DR GO; GO:2000484; P:positive regulation of interleukin-8 secretion; IGI:ARUK-UCL. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB. DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IDA:BHF-UCL. DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; ISS:BHF-UCL. DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IEA:Ensembl. DR GO; GO:0034123; P:positive regulation of toll-like receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:BHF-UCL. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:BHF-UCL. DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IMP:BHF-UCL. DR GO; GO:0070542; P:response to fatty acid; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0032868; P:response to insulin; IEA:Ensembl. DR GO; GO:0032570; P:response to progesterone; IEA:Ensembl. DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:UniProtKB. DR GO; GO:0034134; P:toll-like receptor 2 signaling pathway; IEA:InterPro. DR GO; GO:0002224; P:toll-like receptor signaling pathway; IBA:GO_Central. DR GO; GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome. DR GO; GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome. DR GO; GO:0032640; P:tumor necrosis factor production; ISS:ARUK-UCL. 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; IPR035897; Toll_tir_struct_dom_sf. DR PANTHER; PTHR24365:SF17; PTHR24365:SF17; 1. DR Pfam; PF13855; LRR_8; 2. DR Pfam; PF01463; LRRCT; 1. DR Pfam; PF01582; TIR; 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; 11. DR PROSITE; PS50104; TIR; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Cytoplasmic vesicle; Disulfide bond; KW Glycoprotein; Immunity; Inflammatory response; Innate immunity; KW Isopeptide bond; Leucine-rich repeat; Membrane; Polymorphism; KW Receptor; Reference proteome; Repeat; Signal; Transmembrane; KW Transmembrane helix; Ubl conjugation. FT SIGNAL 1 20 {ECO:0000255}. FT CHAIN 21 784 Toll-like receptor 2. FT /FTId=PRO_0000034710. FT TOPO_DOM 21 588 Extracellular. {ECO:0000255}. FT TRANSMEM 589 609 Helical. {ECO:0000255}. FT TOPO_DOM 610 784 Cytoplasmic. {ECO:0000255}. FT REPEAT 54 77 LRR 1. FT REPEAT 78 101 LRR 2. FT REPEAT 102 125 LRR 3. FT REPEAT 126 150 LRR 4. FT REPEAT 151 175 LRR 5. FT REPEAT 176 199 LRR 6. FT REPEAT 200 223 LRR 7. FT REPEAT 224 250 LRR 8. FT REPEAT 251 278 LRR 9. FT REPEAT 279 308 LRR 10. FT REPEAT 309 337 LRR 11. FT REPEAT 338 361 LRR 12. FT REPEAT 362 388 LRR 13. FT REPEAT 389 414 LRR 14. FT REPEAT 415 437 LRR 15. FT REPEAT 438 457 LRR 16. FT REPEAT 458 478 LRR 17. FT REPEAT 479 500 LRR 18. FT REPEAT 501 524 LRR 19. FT DOMAIN 525 579 LRRCT. FT DOMAIN 639 784 TIR. {ECO:0000255|PROSITE- FT ProRule:PRU00204}. FT MOTIF 761 778 ATG16L1-binding motif. FT SITE 349 349 Interaction with bacterial lipopeptide. FT CARBOHYD 114 114 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:15173186, FT ECO:0000269|PubMed:17889651}. FT CARBOHYD 199 199 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:15173186, FT ECO:0000269|PubMed:17889651}. FT CARBOHYD 414 414 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:17889651}. FT CARBOHYD 442 442 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:15173186, FT ECO:0000269|PubMed:17889651}. FT DISULFID 30 36 {ECO:0000269|PubMed:17889651}. FT DISULFID 353 382 {ECO:0000269|PubMed:17889651}. FT DISULFID 432 454 {ECO:0000269|PubMed:17889651}. FT CROSSLNK 754 754 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000269|PubMed:27805901}. FT VARIANT 89 89 N -> D (in dbSNP:rs137853176). FT {ECO:0000269|PubMed:21618349}. FT /FTId=VAR_066349. FT VARIANT 411 411 T -> I (reduces TLR2-mediated NF-kappa-B FT activation; dbSNP:rs5743699). FT {ECO:0000269|PubMed:21618349}. FT /FTId=VAR_026765. FT VARIANT 571 571 R -> H (in dbSNP:rs61735277). FT {ECO:0000269|PubMed:21618349}. FT /FTId=VAR_066350. FT VARIANT 579 579 R -> H (in dbSNP:rs5743703). FT /FTId=VAR_026766. FT VARIANT 631 631 P -> H (reduces TLR2-mediated NF-kappa-B FT activation; dbSNP:rs5743704). FT {ECO:0000269|PubMed:19924287, FT ECO:0000269|PubMed:21618349}. FT /FTId=VAR_024663. FT VARIANT 636 636 S -> R (in dbSNP:rs137853177). FT {ECO:0000269|PubMed:21618349}. FT /FTId=VAR_066351. FT VARIANT 677 677 R -> W (in dbSNP:rs121917864). FT {ECO:0000269|PubMed:11476982, FT ECO:0000269|PubMed:12646604}. FT /FTId=VAR_031236. FT VARIANT 715 715 Y -> N (in dbSNP:rs5743706). FT /FTId=VAR_052360. FT VARIANT 753 753 R -> Q (reduces TLR2-mediated NF-kappa-B FT activation; dbSNP:rs5743708). FT {ECO:0000269|PubMed:19924287, FT ECO:0000269|PubMed:21618349}. FT /FTId=VAR_031237. FT MUTAGEN 114 114 N->S: Prevents addition of N-glycans. FT Reduces secretion of the N-terminal FT ectodomain. FT {ECO:0000269|PubMed:15173186}. FT MUTAGEN 199 199 N->D: Prevents addition of N-glycans. FT Reduces secretion of the N-terminal FT ectodomain. FT {ECO:0000269|PubMed:15173186}. FT MUTAGEN 416 416 T->A: Prevents addition of N-glycans. FT Reduces secretion of the N-terminal FT ectodomain. FT {ECO:0000269|PubMed:15173186}. FT MUTAGEN 442 442 N->D: Prevents addition of N-glycans. FT Prevents secretion of the N-terminal FT ectodomain. FT {ECO:0000269|PubMed:15173186}. FT MUTAGEN 681 681 P->F: Abolishes the interaction with FT MYD88. No effect on oligomerization or on FT the structure of the TIR domain. FT {ECO:0000269|PubMed:11081518}. FT MUTAGEN 709 709 K->R: Reduced protein stability. FT {ECO:0000269|PubMed:27805901}. FT MUTAGEN 714 714 K->R: Reduced protein stability. FT {ECO:0000269|PubMed:27805901}. FT MUTAGEN 742 743 KK->RR: Reduced protein stability. FT {ECO:0000269|PubMed:27805901}. FT MUTAGEN 751 751 K->R: Reduced protein stability. FT {ECO:0000269|PubMed:27805901}. FT MUTAGEN 754 754 K->R: Loss of PPP1R11-mediated FT ubiquitination and degradation. FT {ECO:0000269|PubMed:27805901}. FT CONFLICT 59 59 L -> Q (in Ref. 8; AAM23001). FT {ECO:0000305}. FT CONFLICT 68 68 S -> C (in Ref. 8; AAM23001). FT {ECO:0000305}. FT CONFLICT 726 726 D -> E (in Ref. 2; AAC34133). FT {ECO:0000305}. FT STRAND 34 37 {ECO:0000244|PDB:2Z80}. FT STRAND 56 58 {ECO:0000244|PDB:2Z80}. FT TURN 69 74 {ECO:0000244|PDB:2Z80}. FT STRAND 80 82 {ECO:0000244|PDB:2Z80}. FT TURN 93 98 {ECO:0000244|PDB:2Z80}. FT STRAND 104 106 {ECO:0000244|PDB:2Z80}. FT HELIX 117 120 {ECO:0000244|PDB:2Z80}. FT STRAND 127 130 {ECO:0000244|PDB:2Z80}. FT STRAND 137 139 {ECO:0000244|PDB:2Z80}. FT STRAND 153 161 {ECO:0000244|PDB:2Z80}. FT TURN 167 172 {ECO:0000244|PDB:2Z80}. FT STRAND 175 183 {ECO:0000244|PDB:2Z80}. FT TURN 191 196 {ECO:0000244|PDB:2Z80}. FT STRAND 198 206 {ECO:0000244|PDB:2Z80}. FT HELIX 213 220 {ECO:0000244|PDB:2Z80}. FT TURN 221 223 {ECO:0000244|PDB:2Z80}. FT STRAND 224 231 {ECO:0000244|PDB:2Z80}. FT STRAND 253 258 {ECO:0000244|PDB:2Z80}. FT STRAND 260 262 {ECO:0000244|PDB:2Z7X}. FT HELIX 263 274 {ECO:0000244|PDB:2Z80}. FT STRAND 281 283 {ECO:0000244|PDB:2Z80}. FT STRAND 288 291 {ECO:0000244|PDB:2Z7X}. FT STRAND 311 316 {ECO:0000244|PDB:2Z7X}. FT HELIX 322 324 {ECO:0000244|PDB:2Z7X}. FT HELIX 329 334 {ECO:0000244|PDB:2Z7X}. FT STRAND 340 346 {ECO:0000244|PDB:2Z7X}. FT HELIX 353 358 {ECO:0000244|PDB:2Z7X}. FT STRAND 364 366 {ECO:0000244|PDB:2Z7X}. FT HELIX 374 380 {ECO:0000244|PDB:2Z7X}. FT STRAND 391 393 {ECO:0000244|PDB:2Z7X}. FT HELIX 402 408 {ECO:0000244|PDB:2Z7X}. FT HELIX 409 411 {ECO:0000244|PDB:2Z7X}. FT STRAND 417 419 {ECO:0000244|PDB:2Z7X}. FT STRAND 440 442 {ECO:0000244|PDB:2Z7X}. FT STRAND 460 463 {ECO:0000244|PDB:2Z7X}. FT STRAND 481 483 {ECO:0000244|PDB:2Z7X}. FT HELIX 495 497 {ECO:0000244|PDB:2Z7X}. FT STRAND 503 505 {ECO:0000244|PDB:2Z7X}. FT HELIX 518 520 {ECO:0000244|PDB:2Z7X}. FT STRAND 527 529 {ECO:0000244|PDB:2Z7X}. FT HELIX 539 544 {ECO:0000244|PDB:2Z7X}. FT TURN 545 547 {ECO:0000244|PDB:2Z7X}. FT STRAND 548 550 {ECO:0000244|PDB:2Z7X}. FT STRAND 641 646 {ECO:0000244|PDB:1FYX}. FT HELIX 649 651 {ECO:0000244|PDB:1FYX}. FT HELIX 652 656 {ECO:0000244|PDB:1FYX}. FT HELIX 658 663 {ECO:0000244|PDB:1FYX}. FT STRAND 666 668 {ECO:0000244|PDB:1FYX}. FT STRAND 672 674 {ECO:0000244|PDB:1FYX}. FT HELIX 675 678 {ECO:0000244|PDB:1FYX}. FT STRAND 681 683 {ECO:0000244|PDB:1FYX}. FT HELIX 685 695 {ECO:0000244|PDB:1FYX}. FT STRAND 696 703 {ECO:0000244|PDB:1FYX}. FT HELIX 705 711 {ECO:0000244|PDB:1FYX}. FT HELIX 713 716 {ECO:0000244|PDB:1FYX}. FT TURN 717 719 {ECO:0000244|PDB:1O77}. FT HELIX 720 722 {ECO:0000244|PDB:1O77}. FT TURN 723 725 {ECO:0000244|PDB:1FYW}. FT HELIX 726 728 {ECO:0000244|PDB:1FYX}. FT STRAND 733 738 {ECO:0000244|PDB:1FYX}. FT TURN 742 744 {ECO:0000244|PDB:1FYX}. FT HELIX 750 758 {ECO:0000244|PDB:1FYX}. FT STRAND 761 763 {ECO:0000244|PDB:1FYX}. FT HELIX 768 770 {ECO:0000244|PDB:1FYX}. FT HELIX 771 783 {ECO:0000244|PDB:1FYX}. SQ SEQUENCE 784 AA; 89838 MW; 7DBE6B24CF1FAF8B CRC64; MPHTLWMVWV LGVIISLSKE ESSNQASLSC DRNGICKGSS GSLNSIPSGL TEAVKSLDLS NNRITYISNS DLQRCVNLQA LVLTSNGINT IEEDSFSSLG SLEHLDLSYN YLSNLSSSWF KPLSSLTFLN LLGNPYKTLG ETSLFSHLTK LQILRVGNMD TFTKIQRKDF AGLTFLEELE IDASDLQSYE PKSLKSIQNV SHLILHMKQH ILLLEIFVDV TSSVECLELR DTDLDTFHFS ELSTGETNSL IKKFTFRNVK ITDESLFQVM KLLNQISGLL ELEFDDCTLN GVGNFRASDN DRVIDPGKVE TLTIRRLHIP RFYLFYDLST LYSLTERVKR ITVENSKVFL VPCLLSQHLK SLEYLDLSEN LMVEEYLKNS ACEDAWPSLQ TLILRQNHLA SLEKTGETLL TLKNLTNIDI SKNSFHSMPE TCQWPEKMKY LNLSSTRIHS VTGCIPKTLE ILDVSNNNLN LFSLNLPQLK ELYISRNKLM TLPDASLLPM LLVLKISRNA ITTFSKEQLD SFHTLKTLEA GGNNFICSCE FLSFTQEQQA LAKVLIDWPA NYLCDSPSHV RGQQVQDVRL SVSECHRTAL VSGMCCALFL LILLTGVLCH RFHGLWYMKM MWAWLQAKRK PRKAPSRNIC YDAFVSYSER DAYWVENLMV QELENFNPPF KLCLHKRDFI PGKWIIDNII DSIEKSHKTV FVLSENFVKS EWCKYELDFS HFRLFDENND AAILILLEPI EKKAIPQRFC KLRKIMNTKT YLEWPMDEAQ REGFWVNLRA AIKS //