TLR2_HUMAN
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 03-AUG-2022, entry version 227.
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 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 [18]
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 [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., 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 [20]
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 [21]
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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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). {ECO:0000250|UniProtKB:Q9QUN7,
CC ECO:0000269|PubMed:12471095, ECO:0000269|PubMed:16880211,
CC ECO:0000269|PubMed:17889651, ECO:0000269|PubMed:23376921,
CC 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}.
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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 PDBsum; 1FYW; -.
DR PDBsum; 1FYX; -.
DR PDBsum; 1O77; -.
DR PDBsum; 2Z7X; -.
DR PDBsum; 2Z80; -.
DR PDBsum; 6NIG; -.
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; 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 GlyGen; O60603; 4 sites, 7 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; O60603; -.
DR PeptideAtlas; O60603; -.
DR PRIDE; O60603; -.
DR ProteomicsDB; 49481; -.
DR ABCD; O60603; 4 sequenced antibodies.
DR Antibodypedia; 16689; 1407 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 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 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; 282372at2759; -.
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 1081 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 138 other tissues.
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; IDA:ARUK-UCL.
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: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: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: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:0002755; P:MyD88-dependent toll-like receptor signaling pathway; IEA:InterPro.
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: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: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; IEA:InterPro.
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; 3.40.50.10140; -; 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; PF01463; LRRCT; 1.
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; 11.
DR PROSITE; PS50104; TIR; 1.
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 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
