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Database: UniProt
Entry: O00206
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Original site: O00206 
ID   TLR4_HUMAN              Reviewed;         839 AA.
AC   O00206; A8K1Y8; A9XLP9; A9XLQ0; A9XLQ1; B4E194; D1CS52; D1CS53; Q5VZI8;
AC   Q5VZI9; Q9UK78; Q9UM57;
DT   11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 2.
DT   29-SEP-2021, entry version 218.
DE   RecName: Full=Toll-like receptor 4;
DE            EC=3.2.2.6 {ECO:0000255|PROSITE-ProRule:PRU00204};
DE   AltName: Full=hToll;
DE   AltName: CD_antigen=CD284;
DE   Flags: Precursor;
GN   Name=TLR4;
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] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP   TISSUE SPECIFICITY.
RC   TISSUE=Spleen;
RX   PubMed=9237759; DOI=10.1038/41131;
RA   Medzhitov R., Preston-Hurlburt P., Janeway C.A. Jr.;
RT   "A human homologue of the Drosophila Toll protein signals activation of
RT   adaptive immunity.";
RL   Nature 388:394-397(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC   TISSUE=Fetal liver, Lung, and Placenta;
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 [GENOMIC DNA], FUNCTION, VARIANTS GLY-299 AND ILE-399,
RP   CHARACTERIZATION OF VARIANTS GLY-299 AND ILE-399, AND POLYMORPHISM.
RX   PubMed=11104518; DOI=10.1186/gb-2000-1-1-research002;
RA   Smirnova I., Poltorak A., Chan E.K.L., McBride C., Beutler B.;
RT   "Phylogenetic variation and polymorphism at the Toll-like receptor 4 locus
RT   (TLR4).";
RL   Genome Biol. 1:RESEARCH002.1-RESEARCH002.10(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLY-299 AND ILE-399.
RX   PubMed=10835634; DOI=10.1038/76048;
RA   Arbour N.C., Lorenz E., Schutte B.C., Zabner J., Kline J.N., Jones M.,
RA   Frees K., Watt J.L., Schwartz D.A.;
RT   "TLR4 mutations are associated with endotoxin hyporesponsiveness in
RT   humans.";
RL   Nat. Genet. 25:187-191(2000).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLY-299 AND ILE-399.
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   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
RC   TISSUE=Hippocampus, Kidney, and Uterus;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164053; DOI=10.1038/nature02465;
RA   Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA   Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA   Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA   Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA   Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA   Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA   Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA   Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA   Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA   Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA   Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA   Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA   Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA   Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA   Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA   Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA   Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA   McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA   Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA   Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA   Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA   Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA   West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA   Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA   Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA   Dunham I.;
RT   "DNA sequence and analysis of human chromosome 9.";
RL   Nature 429:369-374(2004).
RN   [9]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [10]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Cerebellum;
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   [11]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-86.
RA   Liu Z., Li N., Wang J., Xiao W.;
RL   Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
RN   [12]
RP   PROTEIN SEQUENCE OF 24-38.
RX   PubMed=15340161; DOI=10.1110/ps.04682504;
RA   Zhang Z., Henzel W.J.;
RT   "Signal peptide prediction based on analysis of experimentally verified
RT   cleavage sites.";
RL   Protein Sci. 13:2819-2824(2004).
RN   [13]
RP   MUTAGENESIS OF GLU-697; ARG-710; ASP-711 AND PRO-714.
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   [14]
RP   SUBUNIT, AND SUBCELLULAR LOCATION.
RX   PubMed=11274165; DOI=10.1074/jbc.m009164200;
RA   da Silva Correia J., Soldau K., Christen U., Tobias P.S., Ulevitch R.J.;
RT   "Lipopolysaccharide is in close proximity to each of the proteins in its
RT   membrane receptor complex. transfer from CD14 to TLR4 and MD-2.";
RL   J. Biol. Chem. 276:21129-21135(2001).
RN   [15]
RP   GLYCOSYLATION AT ASN-35; ASN-173; ASN-205; ASN-282; ASN-309; ASN-497;
RP   ASN-526; ASN-575 AND ASN-624, AND MUTAGENESIS OF ASN-526 AND ASN-575.
RX   PubMed=11706042; DOI=10.1074/jbc.m109910200;
RA   da Silva Correia J., Ulevitch R.J.;
RT   "MD-2 and TLR4 N-linked glycosylations are important for a functional
RT   lipopolysaccharide receptor.";
RL   J. Biol. Chem. 277:1845-1854(2002).
RN   [16]
RP   INTERACTION WITH TICAM2.
RX   PubMed=14519765; DOI=10.1074/jbc.m305820200;
RA   Oshiumi H., Sasai M., Shida K., Fujita T., Matsumoto M., Seya T.;
RT   "TIR-containing adapter molecule (TICAM)-2, a bridging adapter recruiting
RT   to toll-like receptor 4 TICAM-1 that induces interferon-beta.";
RL   J. Biol. Chem. 278:49751-49762(2003).
RN   [17]
RP   INTERACTION WITH NOX4.
RX   PubMed=15356101; DOI=10.4049/jimmunol.173.6.3589;
RA   Park H.S., Jung H.Y., Park E.Y., Kim J., Lee W.J., Bae Y.S.;
RT   "Direct interaction of TLR4 with NAD(P)H oxidase 4 isozyme is essential for
RT   lipopolysaccharide-induced production of reactive oxygen species and
RT   activation of NF-kappa B.";
RL   J. Immunol. 173:3589-3593(2004).
RN   [18]
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   [19]
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   [20]
RP   INTERACTION WITH TREM1, AND SUBCELLULAR LOCATION.
RX   PubMed=17098818; DOI=10.1093/intimm/dxl119;
RA   Fortin C.F., Lesur O., Fulop T. Jr.;
RT   "Effects of TREM-1 activation in human neutrophils: activation of signaling
RT   pathways, recruitment into lipid rafts and association with TLR4.";
RL   Int. Immunol. 19:41-50(2007).
RN   [21]
RP   FUNCTION.
RX   PubMed=17478729; DOI=10.1161/circresaha.106.142851;
RA   Kim F., Pham M., Luttrell I., Bannerman D.D., Tupper J., Thaler J.,
RA   Hawn T.R., Raines E.W., Schwartz M.W.;
RT   "Toll-like receptor-4 mediates vascular inflammation and insulin resistance
RT   in diet-induced obesity.";
RL   Circ. Res. 100:1589-1596(2007).
RN   [22]
RP   INTERACTION WITH HSP90B1.
RX   PubMed=20865800; DOI=10.1038/ncomms1070;
RA   Liu B., Yang Y., Qiu Z., Staron M., Hong F., Li Y., Wu S., Li Y., Hao B.,
RA   Bona R., Han D., Li Z.;
RT   "Folding of Toll-like receptors by the HSP90 paralogue gp96 requires a
RT   substrate-specific cochaperone.";
RL   Nat. Commun. 1:79-79(2010).
RN   [23]
RP   FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TREM1.
RX   PubMed=21393102; DOI=10.1684/ecn.2011.0274;
RA   Arts R.J., Joosten L.A., Dinarello C.A., Kullberg B.J., van der Meer J.W.,
RA   Netea M.G.;
RT   "TREM-1 interaction with the LPS/TLR4 receptor complex.";
RL   Eur. Cytokine Netw. 22:11-14(2011).
RN   [24]
RP   ERRATUM OF PUBMED:20865800.
RA   Liu B., Yang Y., Qiu Z., Staron M., Hong F., Li Y., Wu S., Li Y., Hao B.,
RA   Bona R., Han D., Li Z.;
RL   Nat. Commun. 3:653-653(2012).
RN   [25]
RP   FUNCTION, INTERACTION WITH CD36 AND TLR6, AND SUBCELLULAR LOCATION.
RX   PubMed=20037584; DOI=10.1038/ni.1836;
RA   Stewart C.R., Stuart L.M., Wilkinson K., van Gils J.M., Deng J., Halle A.,
RA   Rayner K.J., Boyer L., Zhong R., Frazier W.A., Lacy-Hulbert A.,
RA   El Khoury J., Golenbock D.T., Moore K.J.;
RT   "CD36 ligands promote sterile inflammation through assembly of a Toll-like
RT   receptor 4 and 6 heterodimer.";
RL   Nat. Immunol. 11:155-161(2010).
RN   [26]
RP   FUNCTION, MUTAGENESIS OF HIS-431; HIS-456 AND HIS-458, AND INVOLVEMENT IN
RP   CONTACT ALLERGY TO NICKEL.
RX   PubMed=20711192; DOI=10.1038/ni.1919;
RA   Schmidt M., Raghavan B., Mueller V., Vogl T., Fejer G., Tchaptchet S.,
RA   Keck S., Kalis C., Nielsen P.J., Galanos C., Roth J., Skerra A.,
RA   Martin S.F., Freudenberg M.A., Goebeler M.;
RT   "Crucial role for human Toll-like receptor 4 in the development of contact
RT   allergy to nickel.";
RL   Nat. Immunol. 11:814-819(2010).
RN   [27]
RP   INTERACTION WITH MAP3K21.
RX   PubMed=21602844; DOI=10.1038/cmi.2011.15;
RA   Seit-Nebi A., Cheng W., Xu H., Han J.;
RT   "MLK4 has negative effect on TLR4 signaling.";
RL   Cell. Mol. Immunol. 9:27-33(2012).
RN   [28]
RP   FUNCTION.
RX   PubMed=23880187; DOI=10.1016/j.atherosclerosis.2013.05.011;
RA   Estruch M., Bancells C., Beloki L., Sanchez-Quesada J.L.,
RA   Ordonez-Llanos J., Benitez S.;
RT   "CD14 and TLR4 mediate cytokine release promoted by electronegative LDL in
RT   monocytes.";
RL   Atherosclerosis 229:356-362(2013).
RN   [29]
RP   INTERACTION WITH E.COLI PROTEIN TCPC (MICROBIAL INFECTION).
RX   PubMed=23569230; DOI=10.1073/pnas.1215770110;
RA   Snyder G.A., Cirl C., Jiang J., Chen K., Waldhuber A., Smith P.,
RA   Roemmler F., Snyder N., Fresquez T., Duerr S., Tjandra N., Miethke T.,
RA   Xiao T.S.;
RT   "Molecular mechanisms for the subversion of MyD88 signaling by TcpC from
RT   virulent uropathogenic Escherichia coli.";
RL   Proc. Natl. Acad. Sci. U.S.A. 110:6985-6990(2013).
RN   [30]
RP   INTERACTION WITH TICAM1 AND TICAM2.
RX   PubMed=25736436; DOI=10.15252/embr.201439637;
RA   Hu Y.H., Zhang Y., Jiang L.Q., Wang S., Lei C.Q., Sun M.S., Shu H.B.,
RA   Liu Y.;
RT   "WDFY1 mediates TLR3/4 signaling by recruiting TRIF.";
RL   EMBO Rep. 16:447-455(2015).
RN   [31]
RP   FUNCTION, INTERACTION WITH RFTN1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP   AND INDUCTION BY LPS.
RX   PubMed=27022195; DOI=10.4049/jimmunol.1501734;
RA   Tatematsu M., Yoshida R., Morioka Y., Ishii N., Funami K., Watanabe A.,
RA   Saeki K., Seya T., Matsumoto M.;
RT   "Raftlin controls lipopolysaccharide-induced TLR4 internalization and
RT   TICAM-1 signaling in a cell type-specific manner.";
RL   J. Immunol. 196:3865-3876(2016).
RN   [32]
RP   FUNCTION.
RX   PubMed=29038465; DOI=10.1038/s41467-017-00930-9;
RA   Xiahou Z., Wang X., Shen J., Zhu X., Xu F., Hu R., Guo D., Li H., Tian Y.,
RA   Liu Y., Liang H.;
RT   "NMI and IFP35 serve as proinflammatory DAMPs during cellular infection and
RT   injury.";
RL   Nat. Commun. 8:950-950(2017).
RN   [33]
RP   INTERACTION WITH TRAF3IP3.
RX   PubMed=30573680; DOI=10.1074/jbc.ra118.003137;
RA   Li Y., Guan J., Wang W., Hou C., Zhou L., Ma J., Cheng Y., Jiao S.,
RA   Zhou Z.;
RT   "TRAF3-interacting JNK-activating modulator promotes inflammation by
RT   stimulating translocation of Toll-like receptor 4 to lipid rafts.";
RL   J. Biol. Chem. 294:2744-2756(2019).
RN   [34]
RP   X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 27-228 IN COMPLEX WITH LY96,
RP   SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-35; ASN-173 AND ASN-205.
RX   PubMed=17803912; DOI=10.1016/j.cell.2007.08.002;
RA   Kim H.M., Park B.S., Kim J.-I., Kim S.E., Lee J., Oh S.C., Enkhbayar P.,
RA   Matsushima N., Lee H., Yoo O.J., Lee J.-O.;
RT   "Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist
RT   Eritoran.";
RL   Cell 130:906-917(2007).
RN   [35]
RP   X-RAY CRYSTALLOGRAPHY (3.1 ANGSTROMS) OF 27-631 IN COMPLEX WITH LY96 AND
RP   LIPOPOLYSACCHARIDE, SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-173;
RP   ASN-205; ASN-497 AND ASN-526 AND ASN-575.
RX   PubMed=19252480; DOI=10.1038/nature07830;
RA   Park B.S., Song D.H., Kim H.M., Choi B.-S., Lee H., Lee J.-O.;
RT   "The structural basis of lipopolysaccharide recognition by the TLR4-MD-2
RT   complex.";
RL   Nature 458:1191-1195(2009).
RN   [36]
RP   X-RAY CRYSTALLOGRAPHY (2.37 ANGSTROMS) OF 28-228, GLYCOSYLATION AT ASN-35
RP   AND ASN-173, AND DISULFIDE BONDS.
RX   PubMed=22363519; DOI=10.1371/journal.pone.0030929;
RA   Han J., Kim H.J., Lee S.C., Hong S., Park K., Jeon Y.H., Kim D.,
RA   Cheong H.K., Kim H.S.;
RT   "Structure-based rational design of a Toll-like receptor 4 (TLR4) decoy
RT   receptor with high binding affinity for a target protein.";
RL   PLoS ONE 7:E30929-E30929(2012).
RN   [37]
RP   VARIANTS ARG-188; SER-246; GLY-299; SER-329; ILE-399; LEU-443; LYS-474;
RP   HIS-510; ARG-694; HIS-763 AND HIS-834.
RX   PubMed=11514453;
RA   Smirnova I., Hamblin M.T., McBride C., Beutler B., Di Rienzo A.;
RT   "Excess of rare amino acid polymorphisms in the Toll-like receptor 4 in
RT   humans.";
RL   Genetics 158:1657-1664(2001).
RN   [38]
RP   VARIANT GLY-299, AND ASSOCIATION WITH ARMD SUSCEPTIBILITY.
RX   PubMed=15829498; DOI=10.1093/hmg/ddi154;
RA   Zareparsi S., Buraczynska M., Branham K.E.H., Shah S., Eng D., Li M.,
RA   Pawar H., Yashar B.M., Moroi S.E., Lichter P.R., Petty H.R., Richards J.E.,
RA   Abecasis G.R., Elner V.M., Swaroop A.;
RT   "Toll-like receptor 4 variant D299G is associated with susceptibility to
RT   age-related macular degeneration.";
RL   Hum. Mol. Genet. 14:1449-1455(2005).
RN   [39]
RP   VARIANT ASP-287.
RX   PubMed=25787250; DOI=10.1073/pnas.1503696112;
RA   Cromer M.K., Choi M., Nelson-Williams C., Fonseca A.L., Kunstman J.W.,
RA   Korah R.M., Overton J.D., Mane S., Kenney B., Malchoff C.D., Stalberg P.,
RA   Akerstroem G., Westin G., Hellman P., Carling T., Bjoerklund P.,
RA   Lifton R.P.;
RT   "Neomorphic effects of recurrent somatic mutations in Yin Yang 1 in
RT   insulin-producing adenomas.";
RL   Proc. Natl. Acad. Sci. U.S.A. 112:4062-4067(2015).
CC   -!- FUNCTION: Cooperates with LY96 and CD14 to mediate the innate immune
CC       response to bacterial lipopolysaccharide (LPS) (PubMed:27022195). Acts
CC       via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine
CC       secretion and the inflammatory response (PubMed:9237759,
CC       PubMed:10835634, PubMed:27022195,PubMed:21393102). Also involved in
CC       LPS-independent inflammatory responses triggered by free fatty acids,
CC       such as palmitate, and Ni(2+). Responses triggered by Ni(2+) require
CC       non-conserved histidines and are, therefore, species-specific
CC       (PubMed:20711192). Both M.tuberculosis HSP70 (dnaK) and HSP65 (groEL-2)
CC       act via this protein to stimulate NF-kappa-B expression
CC       (PubMed:15809303). In complex with TLR6, promotes sterile inflammation
CC       in monocytes/macrophages in response to oxidized low-density
CC       lipoprotein (oxLDL) or amyloid-beta 42. In this context, the initial
CC       signal is provided by oxLDL- or amyloid-beta 42-binding to CD36. This
CC       event induces the formation of a heterodimer of TLR4 and TLR6, which is
CC       rapidly internalized and triggers inflammatory response, leading to the
CC       NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via
CC       MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling
CC       pathway, as well as IL1B secretion. Binds electronegative LDL (LDL(-))
CC       and mediates the cytokine release induced by LDL(-) (PubMed:23880187).
CC       Stimulation of monocytes in vitro with M.tuberculosis PstS1 induces p38
CC       MAPK and ERK1/2 activation primarily via TLR2, but also partially via
CC       this receptor (PubMed:16622205, PubMed:10835634, PubMed:15809303,
CC       PubMed:17478729, PubMed:20037584, PubMed:20711192, PubMed:23880187,
CC       PubMed:27022195, PubMed:9237759). Activated by the signaling pathway
CC       regulator NMI which acts as damage-associated molecular patterns
CC       (DAMPs) in response to cell injury or pathogen invasion, therefore
CC       promoting nuclear factor NF-kappa-B activation (PubMed:29038465).
CC       {ECO:0000269|PubMed:10835634, ECO:0000269|PubMed:15809303,
CC       ECO:0000269|PubMed:16622205, ECO:0000269|PubMed:17478729,
CC       ECO:0000269|PubMed:20037584, ECO:0000269|PubMed:20711192,
CC       ECO:0000269|PubMed:23880187, ECO:0000269|PubMed:27022195,
CC       ECO:0000269|PubMed:29038465, ECO:0000269|PubMed:9237759}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + NAD(+) = ADP-D-ribose + H(+) + nicotinamide;
CC         Xref=Rhea:RHEA:16301, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:57967; EC=3.2.2.6;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU00204};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16302;
CC         Evidence={ECO:0000255|PROSITE-ProRule:PRU00204};
CC   -!- SUBUNIT: Belongs to the lipopolysaccharide (LPS) receptor, a multi-
CC       protein complex containing at least CD14, LY96 and TLR4
CC       (PubMed:11274165). Binding to bacterial LPS leads to homodimerization.
CC       Interacts with LY96 via the extracellular domain (PubMed:17803912,
CC       PubMed:19252480). Interacts with MYD88 and TIRAP via their respective
CC       TIR domains (By similarity). Interacts with TICAM2 (PubMed:14519765,
CC       PubMed:25736436). Interacts with NOX4 (PubMed:15356101). Interacts with
CC       CNPY3 (By similarity). Interacts with HSP90B1. The interaction with
CC       both CNPY3 and HSP90B1 is required for proper folding in the
CC       endoplasmic reticulum. Interacts with MAP3K21; this interaction leads
CC       to negative regulation of TLR4 signaling (PubMed:21602844). Interacts
CC       with CD36, following CD36 stimulation by oxLDL or amyloid-beta 42, and
CC       forms a heterodimer with TLR6 (PubMed:20037584). The trimeric complex
CC       is internalized and triggers inflammatory response. LYN kinase activity
CC       facilitates TLR4-TLR6 heterodimerization and signal initiation.
CC       Interacts with TICAM1 in response to LPS in a WDFY1-dependent manner
CC       (PubMed:25736436). Interacts with WDFY1 in response to LPS (By
CC       similarity). Interacts with SMPDL3B (By similarity). Interacts with
CC       CEACAM1; upon lipopolysaccharide stimulation, forms a complex including
CC       TLR4 and the phosphorylated form of SYK and CEACAM1, which in turn,
CC       recruits PTPN6 that dephosphorylates SYK, reducing the production of
CC       reactive oxygen species (ROS) and lysosome disruption, which in turn,
CC       reduces the activity of the inflammasome (By similarity). Interacts
CC       with RFTN1; the interaction occurs in response to lipopolysaccharide
CC       stimulation (PubMed:27022195). Interacts with SCIMP; the interaction
CC       occurs in response to lipopolysaccharide stimulation and is enhanced by
CC       phosphorylation of SCIMP by LYN (By similarity). This interaction
CC       facilitates the phosphorylation of TLR4 by LYN which elicits a
CC       selective cytokine response in macrophages (By similarity). Interacts
CC       with TRAF3IP3 (PubMed:30573680). Interacts with TREM1; this interaction
CC       enhances TLR4-mediated inflammatory response (PubMed:21393102,
CC       PubMed:17098818). {ECO:0000250|UniProtKB:Q9QUK6,
CC       ECO:0000269|PubMed:11274165, ECO:0000269|PubMed:14519765,
CC       ECO:0000269|PubMed:15356101, ECO:0000269|PubMed:17098818,
CC       ECO:0000269|PubMed:17803912, ECO:0000269|PubMed:19252480,
CC       ECO:0000269|PubMed:20037584, ECO:0000269|PubMed:20865800,
CC       ECO:0000269|PubMed:21393102, ECO:0000269|PubMed:21602844,
CC       ECO:0000269|PubMed:25736436, ECO:0000269|PubMed:27022195,
CC       ECO:0000269|PubMed:30573680}.
CC   -!- SUBUNIT: (Microbial infection) In case of infection, interacts with
CC       uropathogenic E.coli protein TcpC. {ECO:0000269|PubMed:23569230}.
CC   -!- INTERACTION:
CC       O00206; Q96A54: ADIPOR1; NbExp=2; IntAct=EBI-528701, EBI-1632076;
CC       O00206; Q9Y6Y9: LY96; NbExp=7; IntAct=EBI-528701, EBI-1539247;
CC       O00206; P11226: MBL2; NbExp=2; IntAct=EBI-528701, EBI-5325353;
CC       O00206; Q99836: MYD88; NbExp=4; IntAct=EBI-528701, EBI-447677;
CC       O00206; Q9NPH5: NOX4; NbExp=4; IntAct=EBI-528701, EBI-11301574;
CC       O00206; O15389: SIGLEC5; NbExp=2; IntAct=EBI-528701, EBI-750381;
CC       O00206; O43699-3: SIGLEC6; NbExp=2; IntAct=EBI-528701, EBI-12161783;
CC       O00206; Q9Y336: SIGLEC9; NbExp=2; IntAct=EBI-528701, EBI-12857926;
CC       O00206; Q86XR7: TICAM2; NbExp=3; IntAct=EBI-528701, EBI-525927;
CC       O00206; P58753: TIRAP; NbExp=6; IntAct=EBI-528701, EBI-528644;
CC       O00206; O00206: TLR4; NbExp=2; IntAct=EBI-528701, EBI-528701;
CC       O00206; Q9Y2C9: TLR6; NbExp=2; IntAct=EBI-528701, EBI-13940779;
CC       O00206; P24821: TNC; NbExp=4; IntAct=EBI-528701, EBI-9979894;
CC       O00206-1; Q9Y6Y9: LY96; NbExp=5; IntAct=EBI-15745059, EBI-1539247;
CC       O00206-1; P49278: DERP2; Xeno; NbExp=3; IntAct=EBI-15745059, EBI-15745025;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11274165,
CC       ECO:0000269|PubMed:17098818, ECO:0000269|PubMed:20037584,
CC       ECO:0000269|PubMed:21393102, ECO:0000269|PubMed:27022195,
CC       ECO:0000269|PubMed:9237759}; Single-pass type I membrane protein
CC       {ECO:0000269|PubMed:11274165}. Early endosome
CC       {ECO:0000269|PubMed:27022195}. Cell projection, ruffle
CC       {ECO:0000250|UniProtKB:Q9QUK6}. Note=Upon complex formation with CD36
CC       and TLR6, internalized through dynamin-dependent endocytosis
CC       (PubMed:20037584). Colocalizes with RFTN1 at cell membrane and then
CC       together with RFTN1 moves to endosomes, upon lipopolysaccharide
CC       stimulation. {ECO:0000269|PubMed:20037584}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=O00206-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O00206-2; Sequence=VSP_035794;
CC       Name=3;
CC         IsoId=O00206-3; Sequence=VSP_035793;
CC   -!- TISSUE SPECIFICITY: Highly expressed in placenta, spleen and peripheral
CC       blood leukocytes (PubMed:9435236, PubMed:9237759). Detected in
CC       monocytes, macrophages, dendritic cells and several types of T-cells
CC       (PubMed:9237759, PubMed:27022195). {ECO:0000269|PubMed:27022195,
CC       ECO:0000269|PubMed:9237759, ECO:0000269|PubMed:9435236}.
CC   -!- DOMAIN: The TIR domain mediates interaction with NOX4.
CC       {ECO:0000269|PubMed:15356101}.
CC   -!- DOMAIN: The TIR domain mediates NAD(+) hydrolase (NADase) activity.
CC       Self-association of TIR domains is required for NADase activity.
CC       {ECO:0000255|PROSITE-ProRule:PRU00204}.
CC   -!- PTM: N-glycosylated. Glycosylation of Asn-526 and Asn-575 seems to be
CC       necessary for the expression of TLR4 on the cell surface and the LPS-
CC       response. Likewise, mutants lacking two or more of the other N-
CC       glycosylation sites were deficient in interaction with LPS.
CC       {ECO:0000269|PubMed:11706042, ECO:0000269|PubMed:17803912,
CC       ECO:0000269|PubMed:19252480, ECO:0000269|PubMed:22363519}.
CC   -!- PTM: Phosphorylated on tyrosine residues by LYN after binding
CC       lipopolysaccharide. {ECO:0000250|UniProtKB:Q9QUK6}.
CC   -!- POLYMORPHISM: Allele TLR4*B (Gly-299, Ile-399) is associated with a
CC       blunted response to inhaled LPS. {ECO:0000269|PubMed:10835634}.
CC   -!- MISCELLANEOUS: His-456 and His-458 are found in TLR4 of human and
CC       several other primate species and may be responsible for inflammatory
CC       responses triggered by nickel (Ni(2+)). Ni(2+) may cross-link the two
CC       receptor monomers through specific histidines, triggering the formation
CC       of a dimer that structurally resembles that induced by LPS. This
CC       process may be the basis for the development of contact allergy to
CC       Ni(2+). A mouse model of contact allergy to Ni(2+) in which TLR4-
CC       deficient mice expresses human TLR4 has been proposed.
CC       {ECO:0000305|PubMed:20711192}.
CC   -!- SIMILARITY: Belongs to the Toll-like receptor family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=Zips, necklaces and mobile
CC       telephones - Issue 134 of December 2011;
CC       URL="https://web.expasy.org/spotlight/back_issues/134";
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DR   EMBL; U93091; AAC80227.1; -; mRNA.
DR   EMBL; AB445638; BAG55035.1; -; mRNA.
DR   EMBL; DQ018107; AAY82267.1; -; Genomic_DNA.
DR   EMBL; DQ018108; AAY82268.1; -; Genomic_DNA.
DR   EMBL; DQ018109; AAY82269.1; -; Genomic_DNA.
DR   EMBL; AK290053; BAF82742.1; -; mRNA.
DR   EMBL; AK293068; BAF85757.1; -; mRNA.
DR   EMBL; AK303730; BAG64706.1; -; mRNA.
DR   EMBL; AL160272; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471090; EAW87448.1; -; Genomic_DNA.
DR   EMBL; CH471090; EAW87451.1; -; Genomic_DNA.
DR   EMBL; BC117422; AAI17423.1; -; mRNA.
DR   EMBL; EF535831; ABU41662.1; -; Genomic_DNA.
DR   EMBL; EF535832; ABU41663.1; -; Genomic_DNA.
DR   EMBL; EF535833; ABU41664.1; -; Genomic_DNA.
DR   EMBL; AF177765; AAF05316.1; -; Genomic_DNA.
DR   EMBL; AF177766; AAF07823.1; -; Genomic_DNA.
DR   EMBL; AF172171; AAF89753.1; -; Genomic_DNA.
DR   EMBL; AF172169; AAF89753.1; JOINED; Genomic_DNA.
DR   EMBL; AF172170; AAF89753.1; JOINED; Genomic_DNA.
DR   EMBL; U88880; AAC34135.1; -; mRNA.
DR   CCDS; CCDS6818.1; -. [O00206-1]
DR   RefSeq; NP_003257.1; NM_003266.3. [O00206-2]
DR   RefSeq; NP_612564.1; NM_138554.4. [O00206-1]
DR   RefSeq; NP_612567.1; NM_138557.2. [O00206-3]
DR   PDB; 2Z62; X-ray; 1.70 A; A=27-228.
DR   PDB; 2Z63; X-ray; 2.00 A; A=27-527.
DR   PDB; 2Z65; X-ray; 2.70 A; A/B=27-228.
DR   PDB; 2Z66; X-ray; 1.90 A; A/B/C/D=381-627.
DR   PDB; 3FXI; X-ray; 3.10 A; A/B=27-631.
DR   PDB; 3UL7; X-ray; 2.37 A; A=28-226.
DR   PDB; 3UL8; X-ray; 2.50 A; A=27-228.
DR   PDB; 3UL9; X-ray; 2.45 A; A=28-228.
DR   PDB; 3ULA; X-ray; 3.60 A; A/C=27-228.
DR   PDB; 4G8A; X-ray; 2.40 A; A/B=23-629.
DR   PDB; 5NAM; NMR; -; A=623-670.
DR   PDB; 5NAO; NMR; -; A=623-657.
DR   PDBsum; 2Z62; -.
DR   PDBsum; 2Z63; -.
DR   PDBsum; 2Z65; -.
DR   PDBsum; 2Z66; -.
DR   PDBsum; 3FXI; -.
DR   PDBsum; 3UL7; -.
DR   PDBsum; 3UL8; -.
DR   PDBsum; 3UL9; -.
DR   PDBsum; 3ULA; -.
DR   PDBsum; 4G8A; -.
DR   PDBsum; 5NAM; -.
DR   PDBsum; 5NAO; -.
DR   SMR; O00206; -.
DR   BioGRID; 112954; 38.
DR   CORUM; O00206; -.
DR   DIP; DIP-34769N; -.
DR   ELM; O00206; -.
DR   IntAct; O00206; 33.
DR   MINT; O00206; -.
DR   STRING; 9606.ENSP00000363089; -.
DR   BindingDB; O00206; -.
DR   ChEMBL; CHEMBL5255; -.
DR   DrugBank; DB02767; (R)-3-hydroxytetradecanoic acid.
DR   DrugBank; DB00924; Cyclobenzaprine.
DR   DrugBank; DB06447; E5531.
DR   DrugBank; DB04933; Eritoran.
DR   DrugBank; DB05475; Golotimod.
DR   DrugBank; DB03017; Lauric acid.
DR   DrugBank; DB13615; Mifamurtide.
DR   DrugBank; DB08231; Myristic acid.
DR   DrugBank; DB01183; Naloxone.
DR   DrugBank; DB11193; Papain.
DR   DrugCentral; O00206; -.
DR   GuidetoPHARMACOLOGY; 1754; -.
DR   TCDB; 8.A.43.1.9; the neat-domain containing methaemoglobin heme sequestration (n-mhs) family.
DR   GlyGen; O00206; 10 sites.
DR   iPTMnet; O00206; -.
DR   PhosphoSitePlus; O00206; -.
DR   BioMuta; TLR4; -.
DR   MassIVE; O00206; -.
DR   PaxDb; O00206; -.
DR   PeptideAtlas; O00206; -.
DR   PRIDE; O00206; -.
DR   ProteomicsDB; 47779; -. [O00206-1]
DR   ProteomicsDB; 47780; -. [O00206-2]
DR   ProteomicsDB; 47781; -. [O00206-3]
DR   ABCD; O00206; 21 sequenced antibodies.
DR   Antibodypedia; 3410; 1895 antibodies.
DR   DNASU; 7099; -.
DR   Ensembl; ENST00000355622; ENSP00000363089; ENSG00000136869. [O00206-1]
DR   Ensembl; ENST00000394487; ENSP00000377997; ENSG00000136869. [O00206-2]
DR   GeneID; 7099; -.
DR   KEGG; hsa:7099; -.
DR   UCSC; uc004bjz.5; human. [O00206-1]
DR   CTD; 7099; -.
DR   DisGeNET; 7099; -.
DR   GeneCards; TLR4; -.
DR   HGNC; HGNC:11850; TLR4.
DR   HPA; ENSG00000136869; Low tissue specificity.
DR   MalaCards; TLR4; -.
DR   MIM; 603030; gene.
DR   neXtProt; NX_O00206; -.
DR   OpenTargets; ENSG00000136869; -.
DR   Orphanet; 117; Behcet disease.
DR   PharmGKB; PA36552; -.
DR   VEuPathDB; HostDB:ENSG00000136869; -.
DR   eggNOG; KOG4641; Eukaryota.
DR   GeneTree; ENSGT00940000160778; -.
DR   HOGENOM; CLU_006000_5_0_1; -.
DR   InParanoid; O00206; -.
DR   OMA; CLRPESW; -.
DR   OrthoDB; 282372at2759; -.
DR   PhylomeDB; O00206; -.
DR   TreeFam; TF351113; -.
DR   PathwayCommons; O00206; -.
DR   Reactome; R-HSA-1236974; ER-Phagosome pathway.
DR   Reactome; R-HSA-140534; Caspase activation via Death Receptors in the presence of ligand.
DR   Reactome; R-HSA-166016; Toll Like Receptor 4 (TLR4) Cascade.
DR   Reactome; R-HSA-166058; MyD88:MAL(TIRAP) cascade initiated on plasma membrane.
DR   Reactome; R-HSA-166166; MyD88-independent TLR4 cascade.
DR   Reactome; R-HSA-2562578; TRIF-mediated programmed cell death.
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-936964; Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
DR   Reactome; R-HSA-937041; IKK complex recruitment mediated by RIP1.
DR   Reactome; R-HSA-937072; TRAF6-mediated induction of TAK1 complex within TLR4 complex.
DR   Reactome; R-HSA-9707616; Heme signaling.
DR   Reactome; R-HSA-975163; IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
DR   SignaLink; O00206; -.
DR   SIGNOR; O00206; -.
DR   BioGRID-ORCS; 7099; 5 hits in 1007 CRISPR screens.
DR   EvolutionaryTrace; O00206; -.
DR   GeneWiki; TLR_4; -.
DR   GenomeRNAi; 7099; -.
DR   Pharos; O00206; Tchem.
DR   PRO; PR:O00206; -.
DR   Proteomes; UP000005640; Chromosome 9.
DR   RNAct; O00206; protein.
DR   Bgee; ENSG00000136869; Expressed in leukocyte and 199 other tissues.
DR   ExpressionAtlas; O00206; baseline and differential.
DR   Genevisible; O00206; HS.
DR   GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR   GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR   GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR   GO; GO:0009897; C:external side of plasma membrane; IDA:BHF-UCL.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR   GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR   GO; GO:0031226; C:intrinsic component of plasma membrane; IDA:UniProtKB.
DR   GO; GO:0046696; C:lipopolysaccharide receptor complex; IDA:UniProtKB.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR   GO; GO:0001891; C:phagocytic cup; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0043235; C:receptor complex; IPI:ARUK-UCL.
DR   GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR   GO; GO:0001540; F:amyloid-beta binding; IC:ARUK-UCL.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0001530; F:lipopolysaccharide binding; IMP:BHF-UCL.
DR   GO; GO:0001875; F:lipopolysaccharide immune receptor activity; IDA: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:0046982; F:protein heterodimerization activity; IPI:ARUK-UCL.
DR   GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR   GO; GO:0005102; F:signaling receptor binding; IPI:ARUK-UCL.
DR   GO; GO:0004888; F:transmembrane signaling receptor activity; NAS:UniProtKB.
DR   GO; GO:0002218; P:activation of innate immune response; IEA:Ensembl.
DR   GO; GO:0014002; P:astrocyte development; IEA:Ensembl.
DR   GO; GO:0002322; P:B cell proliferation involved in immune response; IEA:Ensembl.
DR   GO; GO:1904646; P:cellular response to amyloid-beta; IGI:ARUK-UCL.
DR   GO; GO:0071346; P:cellular response to interferon-gamma; IDA:UniProtKB.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:UniProtKB.
DR   GO; GO:0071223; P:cellular response to lipoteichoic acid; IEA:Ensembl.
DR   GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
DR   GO; GO:0140052; P:cellular response to oxidised low-density lipoprotein particle stimulus; ISS:ARUK-UCL.
DR   GO; GO:0042742; P:defense response to bacterium; IGI:ARUK-UCL.
DR   GO; GO:0050829; P:defense response to Gram-negative bacterium; IBA:GO_Central.
DR   GO; GO:0016046; P:detection of fungus; NAS:UniProtKB.
DR   GO; GO:0032497; P:detection of lipopolysaccharide; IDA:UniProtKB.
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:0060729; P:intestinal epithelial structure maintenance; ISS:BHF-UCL.
DR   GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IGI:MGI.
DR   GO; GO:0042116; P:macrophage activation; IMP:UniProtKB.
DR   GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; ISS:ARUK-UCL.
DR   GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR   GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISS:BHF-UCL.
DR   GO; GO:0032689; P:negative regulation of interferon-gamma production; ISS:BHF-UCL.
DR   GO; GO:0032700; P:negative regulation of interleukin-17 production; ISS:BHF-UCL.
DR   GO; GO:0032707; P:negative regulation of interleukin-23 production; ISS:BHF-UCL.
DR   GO; GO:0032715; P:negative regulation of interleukin-6 production; ISS:BHF-UCL.
DR   GO; GO:0045671; P:negative regulation of osteoclast differentiation; NAS:UniProtKB.
DR   GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISS:BHF-UCL.
DR   GO; GO:0002537; P:nitric oxide production involved in inflammatory response; IEA:Ensembl.
DR   GO; GO:0006909; P:phagocytosis; IDA:UniProtKB.
DR   GO; GO:0030890; P:positive regulation of B cell proliferation; IEA:Ensembl.
DR   GO; GO:1903974; P:positive regulation of cellular response to macrophage colony-stimulating factor stimulus; IDA:UniProtKB.
DR   GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; IMP:ARUK-UCL.
DR   GO; GO:0032722; P:positive regulation of chemokine production; IDA:BHF-UCL.
DR   GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; IMP:ARUK-UCL.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR   GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR   GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR   GO; GO:0050729; P:positive regulation of inflammatory response; IMP:ARUK-UCL.
DR   GO; GO:0032727; P:positive regulation of interferon-alpha production; ISS:BHF-UCL.
DR   GO; GO:0032728; P:positive regulation of interferon-beta production; ISS:BHF-UCL.
DR   GO; GO:0032729; P:positive regulation of interferon-gamma production; ISS:BHF-UCL.
DR   GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IDA:UniProtKB.
DR   GO; GO:0032732; P:positive regulation of interleukin-1 production; ISS:BHF-UCL.
DR   GO; GO:0032733; P:positive regulation of interleukin-10 production; ISS:BHF-UCL.
DR   GO; GO:0032735; P:positive regulation of interleukin-12 production; IDA:UniProtKB.
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:UniProtKB.
DR   GO; GO:0046330; P:positive regulation of JNK cascade; IEA:Ensembl.
DR   GO; GO:0043032; P:positive regulation of macrophage activation; ISS:ARUK-UCL.
DR   GO; GO:0060907; P:positive regulation of macrophage cytokine production; IEA:Ensembl.
DR   GO; GO:0043406; P:positive regulation of MAP kinase activity; ISS:BHF-UCL.
DR   GO; GO:1904466; P:positive regulation of matrix metallopeptidase secretion; IMP:ARUK-UCL.
DR   GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; IEA:Ensembl.
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:0045429; P:positive regulation of nitric oxide biosynthetic process; ISS:ARUK-UCL.
DR   GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; ISS:BHF-UCL.
DR   GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; ISS:UniProtKB.
DR   GO; GO:0070430; P:positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway; IEA:Ensembl.
DR   GO; GO:0070434; P:positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway; IEA:Ensembl.
DR   GO; GO:1903223; P:positive regulation of oxidative stress-induced neuron death; ISS:ARUK-UCL.
DR   GO; GO:0010572; P:positive regulation of platelet activation; ISS:BHF-UCL.
DR   GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; ISS:ARUK-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; IDA:UniProtKB.
DR   GO; GO:0002730; P:regulation of dendritic cell cytokine production; IEA:Ensembl.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IDA:MGI.
DR   GO; GO:0042088; P:T-helper 1 type immune response; NAS:UniProtKB.
DR   GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IEA:Ensembl.
DR   GO; GO:0002224; P:toll-like receptor signaling pathway; IBA:GO_Central.
DR   GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; 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; IPR017241; Toll-like_receptor.
DR   InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR   PANTHER; PTHR24365; PTHR24365; 1.
DR   Pfam; PF13855; LRR_8; 3.
DR   Pfam; PF01582; TIR; 1.
DR   PIRSF; PIRSF037595; Toll-like_receptor; 1.
DR   SMART; SM00369; LRR_TYP; 11.
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; Age-related macular degeneration; Alternative splicing;
KW   Cell membrane; Cell projection; Direct protein sequencing; Disulfide bond;
KW   Endosome; Glycoprotein; Hydrolase; Immunity; Inflammatory response;
KW   Innate immunity; Leucine-rich repeat; Membrane; NAD; Receptor;
KW   Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000269|PubMed:15340161"
FT   CHAIN           24..839
FT                   /note="Toll-like receptor 4"
FT                   /id="PRO_0000034722"
FT   TOPO_DOM        24..631
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        632..652
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        653..839
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REPEAT          55..76
FT                   /note="LRR 1"
FT   REPEAT          79..100
FT                   /note="LRR 2"
FT   REPEAT          103..124
FT                   /note="LRR 3"
FT   REPEAT          127..148
FT                   /note="LRR 4"
FT   REPEAT          151..172
FT                   /note="LRR 5"
FT   REPEAT          176..199
FT                   /note="LRR 6"
FT   REPEAT          205..225
FT                   /note="LRR 7"
FT   REPEAT          227..247
FT                   /note="LRR 8"
FT   REPEAT          331..351
FT                   /note="LRR 9"
FT   REPEAT          352..373
FT                   /note="LRR 10"
FT   REPEAT          374..394
FT                   /note="LRR 11"
FT   REPEAT          400..422
FT                   /note="LRR 12"
FT   REPEAT          423..444
FT                   /note="LRR 13"
FT   REPEAT          448..456
FT                   /note="LRR 14"
FT   REPEAT          472..495
FT                   /note="LRR 15"
FT   REPEAT          497..518
FT                   /note="LRR 16"
FT   REPEAT          521..542
FT                   /note="LRR 17"
FT   REPEAT          545..565
FT                   /note="LRR 18"
FT   DOMAIN          579..629
FT                   /note="LRRCT"
FT   DOMAIN          672..815
FT                   /note="TIR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT   ACT_SITE        750
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT   CARBOHYD        35
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11706042,
FT                   ECO:0000269|PubMed:17803912, ECO:0000269|PubMed:22363519"
FT   CARBOHYD        173
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11706042,
FT                   ECO:0000269|PubMed:17803912, ECO:0000269|PubMed:19252480,
FT                   ECO:0000269|PubMed:22363519"
FT   CARBOHYD        205
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11706042,
FT                   ECO:0000269|PubMed:17803912, ECO:0000269|PubMed:19252480"
FT   CARBOHYD        282
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11706042"
FT   CARBOHYD        309
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11706042"
FT   CARBOHYD        497
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11706042,
FT                   ECO:0000269|PubMed:19252480"
FT   CARBOHYD        526
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11706042,
FT                   ECO:0000269|PubMed:19252480"
FT   CARBOHYD        575
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11706042,
FT                   ECO:0000269|PubMed:19252480"
FT   CARBOHYD        624
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:11706042"
FT   CARBOHYD        630
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        29..40
FT                   /evidence="ECO:0000269|PubMed:17803912,
FT                   ECO:0000269|PubMed:19252480"
FT   DISULFID        281..306
FT                   /evidence="ECO:0000269|PubMed:19252480"
FT   DISULFID        390..391
FT                   /evidence="ECO:0000269|PubMed:19252480"
FT   DISULFID        583..609
FT                   /evidence="ECO:0000269|PubMed:19252480"
FT   DISULFID        585..627
FT                   /evidence="ECO:0000269|PubMed:19252480"
FT   VAR_SEQ         1..200
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_035793"
FT   VAR_SEQ         1..40
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039,
FT                   ECO:0000303|PubMed:9435236"
FT                   /id="VSP_035794"
FT   VARIANT         175
FT                   /note="T -> A (in dbSNP:rs16906079)"
FT                   /id="VAR_021977"
FT   VARIANT         188
FT                   /note="Q -> R (in dbSNP:rs5030713)"
FT                   /evidence="ECO:0000269|PubMed:11514453"
FT                   /id="VAR_018729"
FT   VARIANT         246
FT                   /note="C -> S (in dbSNP:rs5030714)"
FT                   /evidence="ECO:0000269|PubMed:11514453"
FT                   /id="VAR_018730"
FT   VARIANT         287
FT                   /note="E -> D"
FT                   /evidence="ECO:0000269|PubMed:25787250"
FT                   /id="VAR_074187"
FT   VARIANT         299
FT                   /note="D -> G (in allele TLR4*B; reduced LPS-response;
FT                   associated with an increased risk for age-related macular
FT                   degeneration in Caucasian carriers; dbSNP:rs4986790)"
FT                   /evidence="ECO:0000269|PubMed:10835634,
FT                   ECO:0000269|PubMed:11104518, ECO:0000269|PubMed:11514453,
FT                   ECO:0000269|PubMed:15829498, ECO:0000269|PubMed:19924287"
FT                   /id="VAR_012739"
FT   VARIANT         306
FT                   /note="C -> W (in dbSNP:rs2770145)"
FT                   /id="VAR_047563"
FT   VARIANT         310
FT                   /note="V -> G (in dbSNP:rs2770144)"
FT                   /id="VAR_047564"
FT   VARIANT         329
FT                   /note="N -> S (in dbSNP:rs5030715)"
FT                   /evidence="ECO:0000269|PubMed:11514453"
FT                   /id="VAR_018731"
FT   VARIANT         342
FT                   /note="F -> Y (in dbSNP:rs5031050)"
FT                   /id="VAR_020334"
FT   VARIANT         385
FT                   /note="L -> F (in dbSNP:rs11536884)"
FT                   /id="VAR_037668"
FT   VARIANT         399
FT                   /note="T -> I (in allele TLR4*B; reduced LPS-response;
FT                   dbSNP:rs4986791)"
FT                   /evidence="ECO:0000269|PubMed:10835634,
FT                   ECO:0000269|PubMed:11104518, ECO:0000269|PubMed:11514453,
FT                   ECO:0000269|PubMed:19924287"
FT                   /id="VAR_012740"
FT   VARIANT         400
FT                   /note="S -> N (in dbSNP:rs4987233)"
FT                   /id="VAR_020335"
FT   VARIANT         443
FT                   /note="F -> L (in dbSNP:rs5030716)"
FT                   /evidence="ECO:0000269|PubMed:11514453"
FT                   /id="VAR_018732"
FT   VARIANT         474
FT                   /note="E -> K (in dbSNP:rs5030718)"
FT                   /evidence="ECO:0000269|PubMed:11514453"
FT                   /id="VAR_018733"
FT   VARIANT         510
FT                   /note="Q -> H (in dbSNP:rs5030719)"
FT                   /evidence="ECO:0000269|PubMed:11514453"
FT                   /id="VAR_018734"
FT   VARIANT         694
FT                   /note="K -> R (in dbSNP:rs5030722)"
FT                   /evidence="ECO:0000269|PubMed:11514453"
FT                   /id="VAR_018735"
FT   VARIANT         763
FT                   /note="R -> H (in dbSNP:rs5030723)"
FT                   /evidence="ECO:0000269|PubMed:11514453"
FT                   /id="VAR_018736"
FT   VARIANT         834
FT                   /note="Q -> H"
FT                   /evidence="ECO:0000269|PubMed:11514453"
FT                   /id="VAR_018737"
FT   MUTAGEN         431
FT                   /note="H->A: Partially diminishes NF-kappa-B activation
FT                   induced by Ni(2+). Strongly reduces NF-kappa-B activation
FT                   induced by Ni(2+); when associated with A-456 or A-458."
FT                   /evidence="ECO:0000269|PubMed:20711192"
FT   MUTAGEN         456
FT                   /note="H->A: Partially diminishes NF-kappa-B activation
FT                   induced by Ni(2+). Strongly reduces NF-kappa-B activation
FT                   induced by Ni(2+); when associated with A-431. Suppresses
FT                   NF-kappa-B activation induced by Ni(2+); when associated
FT                   with A-458."
FT                   /evidence="ECO:0000269|PubMed:20711192"
FT   MUTAGEN         458
FT                   /note="H->A: Partially diminishes NF-kappa-B activation
FT                   induced by Ni(2+). Strongly reduces NF-kappa-B activation
FT                   induced by Ni(2+); when associated with A-431. Suppresses
FT                   NF-kappa-B activation induced by Ni(2+); when associated
FT                   with A-456."
FT                   /evidence="ECO:0000269|PubMed:20711192"
FT   MUTAGEN         526
FT                   /note="N->A: Abolishes LPS-response and prevents the cell
FT                   surface expression."
FT                   /evidence="ECO:0000269|PubMed:11706042"
FT   MUTAGEN         575
FT                   /note="N->A: Abolishes LPS-response and prevents the cell
FT                   surface expression."
FT                   /evidence="ECO:0000269|PubMed:11706042"
FT   MUTAGEN         697
FT                   /note="E->R: Abolishes LPS-response."
FT                   /evidence="ECO:0000269|PubMed:11081518"
FT   MUTAGEN         710
FT                   /note="R->E: Abolishes LPS-response."
FT                   /evidence="ECO:0000269|PubMed:11081518"
FT   MUTAGEN         711
FT                   /note="D->K: Abolishes LPS-response."
FT                   /evidence="ECO:0000269|PubMed:11081518"
FT   MUTAGEN         714
FT                   /note="P->H,R,E: Abolishes MYD88-binding and LPS-response."
FT                   /evidence="ECO:0000269|PubMed:11081518"
FT   CONFLICT        73
FT                   /note="S -> R (in Ref. 11; ABU41664)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        400
FT                   /note="S -> C (in Ref. 7; BAF82742)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        581
FT                   /note="F -> S (in Ref. 7; BAG64706)"
FT                   /evidence="ECO:0000305"
FT   STRAND          29..33
FT                   /evidence="ECO:0007829|PDB:2Z62"
FT   TURN            34..36
FT                   /evidence="ECO:0007829|PDB:2Z62"
FT   STRAND          37..39
FT                   /evidence="ECO:0007829|PDB:2Z62"
FT   STRAND          50..52
FT                   /evidence="ECO:0007829|PDB:2Z62"
FT   STRAND          58..60
FT                   /evidence="ECO:0007829|PDB:2Z62"
FT   TURN            71..76
FT                   /evidence="ECO:0007829|PDB:2Z62"
FT   STRAND          81..84
FT                   /evidence="ECO:0007829|PDB:2Z62"
FT   TURN            95..100
FT                   /evidence="ECO:0007829|PDB:2Z62"
FT   STRAND          106..108
FT                   /evidence="ECO:0007829|PDB:2Z62"
FT   STRAND          115..117
FT                   /evidence="ECO:0007829|PDB:3UL9"
FT   TURN            119..124
FT                   /evidence="ECO:0007829|PDB:2Z62"
FT   STRAND          130..132
FT                   /evidence="ECO:0007829|PDB:2Z62"
FT   HELIX           141..143
FT                   /evidence="ECO:0007829|PDB:3UL8"
FT   TURN            145..148
FT                   /evidence="ECO:0007829|PDB:3FXI"
FT   STRAND          154..156
FT                   /evidence="ECO:0007829|PDB:2Z62"
FT   HELIX           169..173
FT                   /evidence="ECO:0007829|PDB:2Z62"
FT   STRAND          179..181
FT                   /evidence="ECO:0007829|PDB:2Z62"
FT   HELIX           192..195
FT                   /evidence="ECO:0007829|PDB:2Z62"
FT   HELIX           196..199
FT                   /evidence="ECO:0007829|PDB:2Z62"
FT   STRAND          206..209
FT                   /evidence="ECO:0007829|PDB:2Z62"
FT   TURN            220..225
FT                   /evidence="ECO:0007829|PDB:2Z63"
FT   STRAND          227..235
FT                   /evidence="ECO:0007829|PDB:2Z63"
FT   HELIX           242..248
FT                   /evidence="ECO:0007829|PDB:2Z63"
FT   TURN            249..252
FT                   /evidence="ECO:0007829|PDB:2Z63"
FT   STRAND          254..262
FT                   /evidence="ECO:0007829|PDB:2Z63"
FT   TURN            274..277
FT                   /evidence="ECO:0007829|PDB:2Z63"
FT   HELIX           278..282
FT                   /evidence="ECO:0007829|PDB:2Z63"
FT   STRAND          283..292
FT                   /evidence="ECO:0007829|PDB:2Z63"
FT   STRAND          295..298
FT                   /evidence="ECO:0007829|PDB:2Z63"
FT   TURN            301..304
FT                   /evidence="ECO:0007829|PDB:2Z63"
FT   HELIX           305..307
FT                   /evidence="ECO:0007829|PDB:2Z63"
FT   STRAND          311..317
FT                   /evidence="ECO:0007829|PDB:2Z63"
FT   STRAND          319..322
FT                   /evidence="ECO:0007829|PDB:4G8A"
FT   HELIX           324..327
FT                   /evidence="ECO:0007829|PDB:4G8A"
FT   STRAND          333..339
FT                   /evidence="ECO:0007829|PDB:2Z63"
FT   STRAND          341..344
FT                   /evidence="ECO:0007829|PDB:4G8A"
FT   STRAND          355..360
FT                   /evidence="ECO:0007829|PDB:2Z63"
FT   STRAND          377..379
FT                   /evidence="ECO:0007829|PDB:2Z63"
FT   STRAND          387..392
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   HELIX           393..396
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   STRAND          403..405
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   STRAND          410..419
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   STRAND          426..428
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   STRAND          432..437
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   TURN            438..445
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   STRAND          451..453
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   TURN            464..469
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   STRAND          475..477
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   HELIX           484..486
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   STRAND          500..502
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   TURN            513..518
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   STRAND          524..526
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   HELIX           538..540
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   STRAND          548..550
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   STRAND          560..563
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   STRAND          573..575
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   HELIX           585..587
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   HELIX           588..596
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   HELIX           597..600
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   HELIX           604..606
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   STRAND          608..612
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   HELIX           613..615
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   STRAND          617..619
FT                   /evidence="ECO:0007829|PDB:3FXI"
FT   HELIX           620..622
FT                   /evidence="ECO:0007829|PDB:2Z66"
FT   STRAND          627..629
FT                   /evidence="ECO:0007829|PDB:5NAM"
FT   HELIX           630..662
FT                   /evidence="ECO:0007829|PDB:5NAM"
SQ   SEQUENCE   839 AA;  95680 MW;  92C48F55821133E8 CRC64;
     MMSASRLAGT LIPAMAFLSC VRPESWEPCV EVVPNITYQC MELNFYKIPD NLPFSTKNLD
     LSFNPLRHLG SYSFFSFPEL QVLDLSRCEI QTIEDGAYQS LSHLSTLILT GNPIQSLALG
     AFSGLSSLQK LVAVETNLAS LENFPIGHLK TLKELNVAHN LIQSFKLPEY FSNLTNLEHL
     DLSSNKIQSI YCTDLRVLHQ MPLLNLSLDL SLNPMNFIQP GAFKEIRLHK LTLRNNFDSL
     NVMKTCIQGL AGLEVHRLVL GEFRNEGNLE KFDKSALEGL CNLTIEEFRL AYLDYYLDDI
     IDLFNCLTNV SSFSLVSVTI ERVKDFSYNF GWQHLELVNC KFGQFPTLKL KSLKRLTFTS
     NKGGNAFSEV DLPSLEFLDL SRNGLSFKGC CSQSDFGTTS LKYLDLSFNG VITMSSNFLG
     LEQLEHLDFQ HSNLKQMSEF SVFLSLRNLI YLDISHTHTR VAFNGIFNGL SSLEVLKMAG
     NSFQENFLPD IFTELRNLTF LDLSQCQLEQ LSPTAFNSLS SLQVLNMSHN NFFSLDTFPY
     KCLNSLQVLD YSLNHIMTSK KQELQHFPSS LAFLNLTQND FACTCEHQSF LQWIKDQRQL
     LVEVERMECA TPSDKQGMPV LSLNITCQMN KTIIGVSVLS VLVVSVVAVL VYKFYFHLML
     LAGCIKYGRG ENIYDAFVIY SSQDEDWVRN ELVKNLEEGV PPFQLCLHYR DFIPGVAIAA
     NIIHEGFHKS RKVIVVVSQH FIQSRWCIFE YEIAQTWQFL SSRAGIIFIV LQKVEKTLLR
     QQVELYRLLS RNTYLEWEDS VLGRHIFWRR LRKALLDGKS WNPEGTVGTG CNWQEATSI
//
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