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 24-JAN-2024, entry version 235. DE RecName: Full=Toll-like receptor 2 {ECO:0000305}; DE AltName: Full=Toll/interleukin-1 receptor-like protein 4; DE AltName: CD_antigen=CD282; DE Flags: Precursor; GN Name=TLR2 {ECO:0000312|HGNC:HGNC:11848}; Synonyms=TIL4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC 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 genes RT TIL3 and TIL4: evidence for a multi-gene receptor family in 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 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., 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 (TLR) RT 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., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., 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 project: RT 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 C- RT 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 Toll- RT 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., Radolf J.D., RA Klimpel G.R., Godowski P.J., Zychlinsky A.; RT "Cell activation and apoptosis by bacterial lipoproteins through Toll-like RT 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 protein RT A lipoprotein: role of Toll-interacting protein and IL-1 receptor signaling RT 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 preferentially RT activates the IFN-beta promoter in the Toll-like receptor signaling."; RL J. Immunol. 169:6668-6672(2002). RN [13] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CD14; CD36; TLR1 AND RP 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 heterodimers RT at the cell surface determines heterotypic associations with CD36 and RT 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 ASN-114; RP 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 cooperate RT 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., Singh M., RA 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 the RT mitogen-activated protein kinase pathway and release of proinflammatory RT cytokines through Toll-like receptors 2 and 4 in human monocytes."; RL Infect. Immun. 74:2686-2696(2006). RN [17] RP INTERACTION WITH TIRAP. RX PubMed=17322885; DOI=10.1038/ng1976; RA Khor C.C., Chapman S.J., Vannberg F.O., Dunne A., Murphy C., Ling E.Y., RA Frodsham A.J., Walley A.J., Kyrieleis O., Khan A., Aucan C., Segal S., RA Moore C.E., Knox K., Campbell S.J., Lienhardt C., Scott A., Aaby P., RA Sow O.Y., Grignani R.T., Sillah J., Sirugo G., Peshu N., Williams T.N., RA Maitland K., Davies R.J.O., Kwiatkowski D.P., Day N.P., Yala D., RA Crook D.W., Marsh K., Berkley J.A., O'Neill L.A.J., Hill A.V.S.; RT "A Mal functional variant is associated with protection against invasive RT pneumococcal disease, bacteremia, malaria and tuberculosis."; RL Nat. Genet. 39:523-528(2007). RN [18] 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 dendritic RT cells to lipoproteins of Mycobacterium tuberculosis."; RL Cell. Immunol. 258:29-37(2009). RN [19] RP FUNCTION, AND INTERACTION WITH M.BOVIS MPB83 AND M.TUBERCULOSIS ESXA RP (MICROBIAL INFECTION). 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 and RT stimulates production of matrix metalloproteinase 9."; RL Biochem. Biophys. Res. Commun. 400:403-408(2010). RN [20] 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., Rojas R.E.; RT "Mycobacterium tuberculosis lipoproteins directly regulate human memory RT CD4(+) T cell activation via Toll-like receptors 1 and 2."; RL Infect. Immun. 79:663-673(2011). RN [21] 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 [22] 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 [23] RP INTERACTION WITH TICAM2. RX PubMed=25385819; DOI=10.4049/jimmunol.1401605; RA Stack J., Doyle S.L., Connolly D.J., Reinert L.S., O'Keeffe K.M., RA McLoughlin R.M., Paludan S.R., Bowie A.G.; RT "TRAM is required for TLR2 endosomal signaling to type I IFN induction."; RL J. Immunol. 193:6090-6102(2014). RN [24] 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 [25] RP INDUCTION BY SARS-COV-2 INFECTION. RX PubMed=34133077; DOI=10.15252/emmm.202114150; RA Theobald S.J., Simonis A., Georgomanolis T., Kreer C., Zehner M., RA Eisfeld H.S., Albert M.C., Chhen J., Motameny S., Erger F., Fischer J., RA Malin J.J., Graeb J., Winter S., Pouikli A., David F., Boell B., RA Koehler P., Vanshylla K., Gruell H., Suarez I., Hallek M., Faetkenheuer G., RA Jung N., Cornely O.A., Lehmann C., Tessarz P., Altmueller J., Nuernberg P., RA Kashkar H., Klein F., Koch M., Rybniker J.; RT "Long-lived macrophage reprogramming drives spike protein-mediated RT inflammasome activation in COVID-19."; RL EMBO Mol. Med. 0:0-0(2021). RN [26] 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 [27] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-509 IN COMPLEX WITH TLR1 AND RP BACTERIAL LIPOPEPTIDE ANALOG, DISULFIDE BONDS, GLYCOSYLATION AT ASN-114; RP 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 a RT tri-acylated lipopeptide."; RL Cell 130:1071-1082(2007). RN [28] 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 [29] 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 lepromatous RT leprosy is unable to mediate mycobacterial signaling."; RL J. Immunol. 170:3451-3454(2003). RN [30] 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 in the RT human TLR1-2-6 gene family."; RL Hum. Mutat. 32:643-652(2011). 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 (PubMed:21078852, CC PubMed:17889651). Acts via MYD88 and TRAF6, leading to NF-kappa-B CC activation, cytokine secretion and the inflammatory response. May also CC activate immune cells and promote apoptosis in response to the lipid CC moiety of lipoproteins (PubMed:10426995, PubMed:10426996). Recognizes CC mycoplasmal 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 monocytes in CC vitro with M.tuberculosis PstS1 induces p38 MAPK and ERK1/2 activation CC primarily via this receptor, but also partially via TLR4 CC (PubMed:16622205). MAPK activation in response to bacterial CC peptidoglycan also occurs via this receptor (PubMed:16622205). Acts as CC a receptor for M.tuberculosis lipoproteins LprA, LprG, LpqH and PstS1, CC some lipoproteins are dependent on other coreceptors (TLR1, CD14 and/or CC CD36); the lipoproteins act as agonists to modulate antigen presenting CC cell 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 inhibits CC downstream MYD88-dependent signaling (shown in mouse) (By similarity). CC Forms activation clusters composed of several receptors depending on CC the 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 (PubMed:16880211). Required for normal uptake of CC M.tuberculosis, a process that is inhibited by M.tuberculosis LppM (By CC similarity). {ECO:0000250|UniProtKB:Q9QUN7, CC ECO:0000269|PubMed:10426995, ECO:0000269|PubMed:10426996, CC ECO:0000269|PubMed:11441107, ECO:0000269|PubMed:15809303, CC ECO:0000269|PubMed:16622205, ECO:0000269|PubMed:16880211, CC ECO:0000269|PubMed:17889651, ECO:0000269|PubMed:19362712, CC ECO:0000269|PubMed:21078852}. CC -!- SUBUNIT: Interacts with LY96, TLR1 and TLR6 (via extracellular domain) CC (PubMed:17889651). TLR2 seems to exist in heterodimers with either TLR1 CC or TLR6 before stimulation by the ligand. The heterodimers form bigger CC oligomers in response to their corresponding ligands as well as further CC heterotypic associations with other receptors such as CD14 and/or CD36 CC (PubMed:16880211). Binds MYD88 (via TIR domain). Interacts with TICAM1 CC (PubMed:12471095). Interacts with CNPY3 (By similarity). Interacts with CC ATG16L1 (PubMed:23376921). Interacts with PPP1R11 (By similarity). CC Interacts with TICAM2 (PubMed:25385819). Interacts with TIRAP CC (PubMed:17322885). {ECO:0000250|UniProtKB:Q9QUN7, CC ECO:0000269|PubMed:12471095, ECO:0000269|PubMed:16880211, CC ECO:0000269|PubMed:17322885, ECO:0000269|PubMed:17889651, CC ECO:0000269|PubMed:23376921, ECO:0000269|PubMed:25385819}. 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 -!- SUBUNIT: (Microbial infection) Interacts with Staphylococcus aureus CC protein SSL5. {ECO:0000269|PubMed:22665377}. CC -!- INTERACTION: CC O60603; P61073: CXCR4; NbExp=3; IntAct=EBI-973722, EBI-489411; CC O60603; P00533: EGFR; NbExp=3; IntAct=EBI-973722, EBI-297353; CC O60603; Q99836: MYD88; NbExp=4; IntAct=EBI-973722, EBI-447677; CC O60603; C3PTT6: PAUF; NbExp=3; IntAct=EBI-973722, EBI-3505892; CC O60603; Q15399: TLR1; NbExp=3; IntAct=EBI-973722, EBI-9009517; CC O60603; Q9BXR5: TLR10; NbExp=3; IntAct=EBI-973722, EBI-16825459; CC O60603; O60603: TLR2; NbExp=4; IntAct=EBI-973722, EBI-973722; CC O60603; Q9Y2C9: TLR6; NbExp=5; IntAct=EBI-973722, EBI-13940779; CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q9QUN7}; Single- CC pass type I membrane protein {ECO:0000255}. Cytoplasmic vesicle, CC phagosome membrane {ECO:0000250|UniProtKB:Q9QUN7}; Single-pass type I CC 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 the CC presence of the microbial ligand. In response to diacylated CC lipoproteins, TLR2:TLR6 heterodimers are recruited in lipid rafts, this CC recruitment determines the intracellular targeting to the Golgi CC apparatus. Triacylated lipoproteins induce the same mechanism for CC TLR2:TLR1 heterodimers. {ECO:0000269|PubMed:16880211}. CC -!- TISSUE SPECIFICITY: Highly expressed in peripheral blood leukocytes, in CC particular in monocytes, in bone marrow, lymph node and in spleen. Also CC detected in lung and in fetal liver. Levels are low in other tissues. CC -!- INDUCTION: (Microbial infection) In macrophages, induced by SARS-CoV-2 CC infection. {ECO:0000269|PubMed:34133077}. CC -!- DOMAIN: Ester-bound lipid substrates are bound through a crevice formed CC between the LRR 11 and LRR 12. {ECO:0000250}. CC -!- DOMAIN: The ATG16L1-binding motif mediates interaction with ATG16L1. CC {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 degradation CC (PubMed:27805901). Deubiquitinated by USP2 (By similarity). CC {ECO:0000250|UniProtKB:Q9QUN7, ECO:0000269|PubMed:27805901}. CC -!- POLYMORPHISM: Genetic variations in TLR2 are associated with CC susceptibility to leprosy [MIM:246300]. Leprosy is a chronic disease CC associated with depressed cellular (but not humoral) immunity, the CC bacterium requires a lower temperature than 37 degrees Celsius and CC thrives particularly in peripheral Schwann cells and macrophages. The CC Trp-677 polymorphism in the intracellular domain of TLR2 has a role in CC susceptibility to lepromatous leprosy. Wild-type TLR2 mediates CD14- CC enhanced Mycobacterium leprae-dependent activation of NFKB1, but TLR2 CC containing the Trp-677 polymorphism did not. The impaired function of CC the Trp-677 polymorphism provides a molecular mechanism for the poor CC 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. {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}. 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 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 PDB; 6NIG; X-ray; 2.35 A; A/B/C/D=1-507. DR PDB; 8AR0; NMR; -; A=580-629. DR PDBsum; 1FYW; -. DR PDBsum; 1FYX; -. DR PDBsum; 1O77; -. DR PDBsum; 2Z7X; -. DR PDBsum; 2Z80; -. DR PDBsum; 6NIG; -. DR PDBsum; 8AR0; -. DR AlphaFoldDB; O60603; -. DR SMR; O60603; -. DR BioGRID; 112952; 41. DR ComplexPortal; CPX-2524; TLR2-TLR10 toll-like receptor complex. DR ComplexPortal; CPX-892; TLR2-TLR6 toll-like receptor complex. DR ComplexPortal; CPX-893; TLR1-TLR2 toll-like receptor complex. DR CORUM; O60603; -. DR DIP; DIP-35138N; -. DR IntAct; O60603; 41. DR MINT; O60603; -. DR STRING; 9606.ENSP00000260010; -. DR BindingDB; O60603; -. DR ChEMBL; CHEMBL4163; -. DR DrugBank; DB00210; Adapalene. DR DrugBank; DB05475; Golotimod. DR DrugBank; DB00045; Lyme disease vaccine (recombinant OspA). DR DrugBank; DB16474; Pam2csk4. DR DrugBank; DB03963; S-(Dimethylarsenic)Cysteine. DR DrugBank; DB11601; Tuberculin purified protein derivative. DR GuidetoPHARMACOLOGY; 1752; -. DR TCDB; 8.A.43.1.16; the neat-domain containing methaemoglobin heme sequestration (n-mhs) family. DR GlyConnect; 1816; 6 N-Linked glycans (2 sites). DR GlyCosmos; O60603; 4 sites, 9 glycans. DR GlyGen; O60603; 4 sites, 9 N-linked glycans (2 sites). DR iPTMnet; O60603; -. DR PhosphoSitePlus; O60603; -. DR SwissPalm; O60603; -. DR BioMuta; TLR2; -. DR EPD; O60603; -. DR jPOST; O60603; -. DR MassIVE; O60603; -. DR PaxDb; 9606-ENSP00000260010; -. DR PeptideAtlas; O60603; -. DR ProteomicsDB; 49481; -. DR ABCD; O60603; 4 sequenced antibodies. DR Antibodypedia; 16689; 1532 antibodies from 49 providers. DR DNASU; 7097; -. DR Ensembl; ENST00000260010.6; ENSP00000260010.6; ENSG00000137462.9. DR Ensembl; ENST00000642580.1; ENSP00000495339.1; ENSG00000137462.9. DR Ensembl; ENST00000642700.2; ENSP00000494425.1; ENSG00000137462.9. DR Ensembl; ENST00000643501.2; ENSP00000496208.2; ENSG00000137462.9. DR Ensembl; ENST00000646219.2; ENSP00000496676.2; ENSG00000137462.9. DR Ensembl; ENST00000646900.2; ENSP00000493968.2; ENSG00000137462.9. DR GeneID; 7097; -. DR KEGG; hsa:7097; -. DR MANE-Select; ENST00000642700.2; ENSP00000494425.1; NM_001318789.2; NP_001305718.1. DR UCSC; uc063aif.1; human. DR AGR; HGNC:11848; -. DR CTD; 7097; -. DR DisGeNET; 7097; -. DR GeneCards; TLR2; -. DR HGNC; HGNC:11848; TLR2. DR HPA; ENSG00000137462; Tissue enhanced (bone marrow, lymphoid tissue). DR MalaCards; TLR2; -. DR MIM; 246300; phenotype. DR MIM; 603028; gene. DR neXtProt; NX_O60603; -. DR OpenTargets; ENSG00000137462; -. DR PharmGKB; PA36550; -. DR VEuPathDB; HostDB:ENSG00000137462; -. DR eggNOG; KOG4641; Eukaryota. DR GeneTree; ENSGT00940000156323; -. DR HOGENOM; CLU_006000_3_0_1; -. DR InParanoid; O60603; -. DR OMA; NRDICYD; -. DR OrthoDB; 21383at2759; -. DR PhylomeDB; O60603; -. DR TreeFam; TF351113; -. DR PathwayCommons; O60603; -. 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 Reactome; R-HSA-9637628; Modulation by Mtb of host immune system. DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses. DR SignaLink; O60603; -. DR SIGNOR; O60603; -. DR BioGRID-ORCS; 7097; 9 hits in 1165 CRISPR screens. DR EvolutionaryTrace; O60603; -. DR GeneWiki; TLR_2; -. DR GenomeRNAi; 7097; -. DR Pharos; O60603; Tchem. DR PRO; PR:O60603; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; O60603; Protein. DR Bgee; ENSG00000137462; Expressed in monocyte and 140 other cell types or tissues. DR ExpressionAtlas; O60603; baseline and differential. 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: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:UniProtKB. DR GO; GO:0043235; C:receptor complex; IPI:ComplexPortal. 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:0035355; C:Toll-like receptor 2-Toll-like receptor 6 protein complex; IPI:ComplexPortal. 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 immune receptor activity; TAS: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:0038187; F:pattern recognition receptor activity; IDA:UniProtKB. DR GO; GO:0042834; F:peptidoglycan binding; IDA:UniProtKB. 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; IPI:UniProtKB. DR GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:InterPro. DR GO; GO:0042497; F:triacyl lipopeptide binding; IDA:MGI. DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc. 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: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:0071346; P:cellular response to type II interferon; IDA:UniProtKB. DR GO; GO:0032289; P:central nervous system myelin formation; IEA:Ensembl. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB. DR GO; GO:0051607; P:defense response to virus; IEP:ARUK-UCL. 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: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: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: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; IGI:ARUK-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:1904466; P:positive regulation of matrix metallopeptidase secretion; IGI:ARUK-UCL. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB. DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; ISS:BHF-UCL. DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; IDA:BHF-UCL. DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IEA:Ensembl. 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:ARUK-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; IDA:BHF-UCL. DR GO; GO:0002224; P:toll-like receptor signaling pathway; IDA:ComplexPortal. DR GO; GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; IDA:ComplexPortal. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1. DR Gene3D; 3.40.50.10140; Toll/interleukin-1 receptor homology (TIR) domain; 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; IPR017241; Toll-like_receptor. DR InterPro; IPR035897; Toll_tir_struct_dom_sf. DR PANTHER; PTHR24365; TOLL-LIKE RECEPTOR; 1. DR PANTHER; PTHR24365:SF17; TOLL-LIKE RECEPTOR 2; 1. DR Pfam; PF00560; LRR_1; 1. DR Pfam; PF13855; LRR_8; 2. DR Pfam; PF01463; LRRCT; 1. DR Pfam; PF01582; TIR; 1. DR PIRSF; PIRSF037595; Toll-like_receptor; 1. DR PRINTS; PR01537; INTRLKN1R1F. DR PRINTS; PR00019; LEURICHRPT. DR SMART; SM00364; LRR_BAC; 4. DR SMART; SM00369; LRR_TYP; 7. DR SMART; SM00082; LRRCT; 1. DR SMART; SM00255; TIR; 1. DR SUPFAM; SSF52058; L domain-like; 1. DR SUPFAM; SSF52047; RNI-like; 1. DR SUPFAM; SSF52200; Toll/Interleukin receptor TIR domain; 1. DR PROSITE; PS51450; LRR; 11. DR PROSITE; PS50104; TIR; 1. DR Genevisible; O60603; HS. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasmic vesicle; 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..20 FT /evidence="ECO:0000255" FT CHAIN 21..784 FT /note="Toll-like receptor 2" FT /id="PRO_0000034710" FT TOPO_DOM 21..588 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 589..609 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 610..784 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..125 FT /note="LRR 3" FT REPEAT 126..150 FT /note="LRR 4" FT REPEAT 151..175 FT /note="LRR 5" FT REPEAT 176..199 FT /note="LRR 6" FT REPEAT 200..223 FT /note="LRR 7" FT REPEAT 224..250 FT /note="LRR 8" FT REPEAT 251..278 FT /note="LRR 9" FT REPEAT 279..308 FT /note="LRR 10" FT REPEAT 309..337 FT /note="LRR 11" FT REPEAT 338..361 FT /note="LRR 12" FT REPEAT 362..388 FT /note="LRR 13" FT REPEAT 389..414 FT /note="LRR 14" FT REPEAT 415..437 FT /note="LRR 15" FT REPEAT 438..457 FT /note="LRR 16" FT REPEAT 458..478 FT /note="LRR 17" FT REPEAT 479..500 FT /note="LRR 18" FT REPEAT 501..524 FT /note="LRR 19" FT DOMAIN 525..579 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 CARBOHYD 114 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:15173186, FT ECO:0000269|PubMed:17889651" FT CARBOHYD 199 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:15173186, FT ECO:0000269|PubMed:17889651" FT CARBOHYD 414 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:17889651" FT CARBOHYD 442 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:15173186, FT ECO:0000269|PubMed:17889651" FT DISULFID 30..36 FT /evidence="ECO:0000269|PubMed:17889651" FT DISULFID 353..382 FT /evidence="ECO:0000269|PubMed:17889651" FT DISULFID 432..454 FT /evidence="ECO:0000269|PubMed:17889651" FT CROSSLNK 754 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:27805901" FT VARIANT 89 FT /note="N -> D (in dbSNP:rs137853176)" FT /evidence="ECO:0000269|PubMed:21618349" FT /id="VAR_066349" FT VARIANT 411 FT /note="T -> I (reduces TLR2-mediated NF-kappa-B activation; FT dbSNP:rs5743699)" FT /evidence="ECO:0000269|PubMed:21618349" FT /id="VAR_026765" FT VARIANT 571 FT /note="R -> H (in dbSNP:rs61735277)" FT /evidence="ECO:0000269|PubMed:21618349" FT /id="VAR_066350" FT VARIANT 579 FT /note="R -> H (in dbSNP:rs5743703)" FT /id="VAR_026766" FT VARIANT 631 FT /note="P -> H (reduces TLR2-mediated NF-kappa-B activation; FT dbSNP:rs5743704)" FT /evidence="ECO:0000269|PubMed:19924287, FT ECO:0000269|PubMed:21618349" FT /id="VAR_024663" FT VARIANT 636 FT /note="S -> R (in dbSNP:rs137853177)" FT /evidence="ECO:0000269|PubMed:21618349" FT /id="VAR_066351" FT VARIANT 677 FT /note="R -> W (in dbSNP:rs121917864)" FT /evidence="ECO:0000269|PubMed:11476982, FT ECO:0000269|PubMed:12646604" FT /id="VAR_031236" FT VARIANT 715 FT /note="Y -> N (in dbSNP:rs5743706)" FT /id="VAR_052360" FT VARIANT 753 FT /note="R -> Q (reduces TLR2-mediated NF-kappa-B activation; FT dbSNP:rs5743708)" FT /evidence="ECO:0000269|PubMed:19924287, FT ECO:0000269|PubMed:21618349" FT /id="VAR_031237" FT MUTAGEN 114 FT /note="N->S: Prevents addition of N-glycans. Reduces FT secretion of the N-terminal ectodomain." FT /evidence="ECO:0000269|PubMed:15173186" FT MUTAGEN 199 FT /note="N->D: Prevents addition of N-glycans. Reduces FT secretion of the N-terminal ectodomain." FT /evidence="ECO:0000269|PubMed:15173186" FT MUTAGEN 416 FT /note="T->A: Prevents addition of N-glycans. Reduces FT secretion of the N-terminal ectodomain." FT /evidence="ECO:0000269|PubMed:15173186" FT MUTAGEN 442 FT /note="N->D: Prevents addition of N-glycans. Prevents FT secretion of the N-terminal ectodomain." FT /evidence="ECO:0000269|PubMed:15173186" FT MUTAGEN 681 FT /note="P->F: Abolishes the interaction with MYD88. No FT effect on oligomerization or on the structure of the TIR FT domain." FT /evidence="ECO:0000269|PubMed:11081518" FT MUTAGEN 709 FT /note="K->R: Reduced protein stability." FT /evidence="ECO:0000269|PubMed:27805901" FT MUTAGEN 714 FT /note="K->R: Reduced protein stability." FT /evidence="ECO:0000269|PubMed:27805901" FT MUTAGEN 742..743 FT /note="KK->RR: Reduced protein stability." FT /evidence="ECO:0000269|PubMed:27805901" FT MUTAGEN 751 FT /note="K->R: Reduced protein stability." FT /evidence="ECO:0000269|PubMed:27805901" FT MUTAGEN 754 FT /note="K->R: Loss of PPP1R11-mediated ubiquitination and FT degradation." FT /evidence="ECO:0000269|PubMed:27805901" FT CONFLICT 59 FT /note="L -> Q (in Ref. 8; AAM23001)" FT /evidence="ECO:0000305" FT CONFLICT 68 FT /note="S -> C (in Ref. 8; AAM23001)" FT /evidence="ECO:0000305" FT CONFLICT 726 FT /note="D -> E (in Ref. 2; AAC34133)" FT /evidence="ECO:0000305" FT STRAND 34..37 FT /evidence="ECO:0007829|PDB:2Z80" FT STRAND 56..58 FT /evidence="ECO:0007829|PDB:2Z80" FT TURN 69..74 FT /evidence="ECO:0007829|PDB:2Z80" FT STRAND 80..82 FT /evidence="ECO:0007829|PDB:2Z80" FT TURN 93..98 FT /evidence="ECO:0007829|PDB:2Z80" FT STRAND 104..106 FT /evidence="ECO:0007829|PDB:2Z80" FT HELIX 117..120 FT /evidence="ECO:0007829|PDB:2Z80" FT STRAND 127..130 FT /evidence="ECO:0007829|PDB:2Z80" FT STRAND 137..139 FT /evidence="ECO:0007829|PDB:2Z80" FT STRAND 153..161 FT /evidence="ECO:0007829|PDB:2Z80" FT TURN 167..172 FT /evidence="ECO:0007829|PDB:2Z80" FT STRAND 175..183 FT /evidence="ECO:0007829|PDB:2Z80" FT TURN 191..196 FT /evidence="ECO:0007829|PDB:2Z80" FT STRAND 198..206 FT /evidence="ECO:0007829|PDB:2Z80" FT STRAND 208..210 FT /evidence="ECO:0007829|PDB:6NIG" FT HELIX 213..220 FT /evidence="ECO:0007829|PDB:2Z80" FT TURN 221..223 FT /evidence="ECO:0007829|PDB:2Z80" FT STRAND 224..231 FT /evidence="ECO:0007829|PDB:2Z80" FT STRAND 253..258 FT /evidence="ECO:0007829|PDB:2Z80" FT STRAND 260..262 FT /evidence="ECO:0007829|PDB:2Z7X" FT HELIX 263..274 FT /evidence="ECO:0007829|PDB:2Z80" FT STRAND 281..283 FT /evidence="ECO:0007829|PDB:2Z80" FT STRAND 288..291 FT /evidence="ECO:0007829|PDB:2Z7X" FT TURN 300..302 FT /evidence="ECO:0007829|PDB:6NIG" FT STRAND 311..316 FT /evidence="ECO:0007829|PDB:2Z7X" FT HELIX 322..324 FT /evidence="ECO:0007829|PDB:2Z7X" FT HELIX 329..334 FT /evidence="ECO:0007829|PDB:2Z7X" FT STRAND 340..346 FT /evidence="ECO:0007829|PDB:2Z7X" FT HELIX 353..358 FT /evidence="ECO:0007829|PDB:2Z7X" FT STRAND 364..366 FT /evidence="ECO:0007829|PDB:2Z7X" FT HELIX 374..380 FT /evidence="ECO:0007829|PDB:2Z7X" FT STRAND 391..393 FT /evidence="ECO:0007829|PDB:2Z7X" FT HELIX 402..408 FT /evidence="ECO:0007829|PDB:2Z7X" FT HELIX 409..411 FT /evidence="ECO:0007829|PDB:2Z7X" FT STRAND 417..419 FT /evidence="ECO:0007829|PDB:2Z7X" FT STRAND 440..442 FT /evidence="ECO:0007829|PDB:2Z7X" FT STRAND 460..463 FT /evidence="ECO:0007829|PDB:2Z7X" FT STRAND 481..483 FT /evidence="ECO:0007829|PDB:2Z7X" FT HELIX 495..497 FT /evidence="ECO:0007829|PDB:2Z7X" FT STRAND 503..505 FT /evidence="ECO:0007829|PDB:2Z7X" FT HELIX 518..520 FT /evidence="ECO:0007829|PDB:2Z7X" FT STRAND 527..529 FT /evidence="ECO:0007829|PDB:2Z7X" FT HELIX 539..544 FT /evidence="ECO:0007829|PDB:2Z7X" FT TURN 545..547 FT /evidence="ECO:0007829|PDB:2Z7X" FT STRAND 548..550 FT /evidence="ECO:0007829|PDB:2Z7X" FT HELIX 586..611 FT /evidence="ECO:0007829|PDB:8AR0" FT HELIX 613..627 FT /evidence="ECO:0007829|PDB:8AR0" FT STRAND 641..646 FT /evidence="ECO:0007829|PDB:1FYX" FT HELIX 649..651 FT /evidence="ECO:0007829|PDB:1FYX" FT HELIX 652..656 FT /evidence="ECO:0007829|PDB:1FYX" FT HELIX 658..663 FT /evidence="ECO:0007829|PDB:1FYX" FT STRAND 666..668 FT /evidence="ECO:0007829|PDB:1FYX" FT STRAND 672..674 FT /evidence="ECO:0007829|PDB:1FYX" FT HELIX 675..678 FT /evidence="ECO:0007829|PDB:1FYX" FT STRAND 681..683 FT /evidence="ECO:0007829|PDB:1FYX" FT HELIX 685..695 FT /evidence="ECO:0007829|PDB:1FYX" FT STRAND 696..703 FT /evidence="ECO:0007829|PDB:1FYX" FT HELIX 705..711 FT /evidence="ECO:0007829|PDB:1FYX" FT HELIX 713..716 FT /evidence="ECO:0007829|PDB:1FYX" FT TURN 717..719 FT /evidence="ECO:0007829|PDB:1O77" FT HELIX 720..722 FT /evidence="ECO:0007829|PDB:1O77" FT TURN 723..725 FT /evidence="ECO:0007829|PDB:1FYW" FT HELIX 726..728 FT /evidence="ECO:0007829|PDB:1FYX" FT STRAND 733..738 FT /evidence="ECO:0007829|PDB:1FYX" FT TURN 742..744 FT /evidence="ECO:0007829|PDB:1FYX" FT HELIX 750..758 FT /evidence="ECO:0007829|PDB:1FYX" FT STRAND 761..763 FT /evidence="ECO:0007829|PDB:1FYX" FT HELIX 768..770 FT /evidence="ECO:0007829|PDB:1FYX" FT HELIX 771..783 FT /evidence="ECO:0007829|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 //