TLR4_HUMAN
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 03-AUG-2022, entry version 221.
DE RecName: Full=Toll-like receptor 4;
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 LACK OF NADASE ACTIVITY.
RX PubMed=28334607; DOI=10.1016/j.neuron.2017.02.022;
RA Essuman K., Summers D.W., Sasaki Y., Mao X., DiAntonio A., Milbrandt J.;
RT "The SARM1 Toll/Interleukin-1 receptor domain possesses intrinsic NAD+
RT cleavage activity that promotes pathological axonal degeneration.";
RL Neuron 93:1334-1343(2017).
RN [34]
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 [35]
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 [36]
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 [37]
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 [38]
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; DOI=10.1093/genetics/158.4.1657;
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 [39]
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 [40]
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 -!- 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 -!- 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 -!- CAUTION: In some plant proteins and in human SARM1, the TIR domain has
CC NAD(+) hydrolase (NADase) activity (PubMed:28334607). However, despite
CC the presence of the catalytic Asp residue, the isolated TIR domain of
CC human TLR4 lacks NADase activity (PubMed:28334607). Based on this, it
CC is unlikely that Toll-like receptors have NADase activity.
CC {ECO:0000269|PubMed:28334607, 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 AlphaFoldDB; O00206; -.
DR SMR; O00206; -.
DR BioGRID; 112954; 41.
DR ComplexPortal; CPX-2545; LY96-TLR4 toll-like receptor complex.
DR ComplexPortal; CPX-945; TLR4-TLR6 toll-like receptor complex.
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; 25 sequenced antibodies.
DR Antibodypedia; 3410; 1889 antibodies from 51 providers.
DR DNASU; 7099; -.
DR Ensembl; ENST00000355622.8; ENSP00000363089.5; ENSG00000136869.16. [O00206-1]
DR Ensembl; ENST00000394487.5; ENSP00000377997.4; ENSG00000136869.16. [O00206-2]
DR GeneID; 7099; -.
DR KEGG; hsa:7099; -.
DR MANE-Select; ENST00000355622.8; ENSP00000363089.5; NM_138554.5; NP_612564.1.
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; CKHSAER; -.
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; 6 hits in 1065 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 monocyte and 154 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; IDA:ComplexPortal.
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; IDA:ComplexPortal.
DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IEA:Ensembl.
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:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl.
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:0007254; P:JNK cascade; IEA:Ensembl.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IGI:MGI.
DR GO; GO:0042116; P:macrophage activation; IMP:UniProtKB.
DR GO; GO:0045342; P:MHC class II biosynthetic process; IEA:Ensembl.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; IDA:ComplexPortal.
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:0006809; P:nitric oxide biosynthetic process; IEA:Ensembl.
DR GO; GO:0002537; P:nitric oxide production involved in inflammatory response; IEA:Ensembl.
DR GO; GO:0070427; P:nucleotide-binding oligomerization domain containing 1 signaling pathway; IEA:Ensembl.
DR GO; GO:0070431; P:nucleotide-binding oligomerization domain containing 2 signaling pathway; 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:0014911; P:positive regulation of smooth muscle cell migration; IEA:Ensembl.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; 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; IDA:ComplexPortal.
DR GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; ISS:ARUK-UCL.
DR GO; GO:0002246; P:wound healing involved in inflammatory response; IEA:Ensembl.
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; Immunity; Inflammatory response; Innate immunity;
KW Leucine-rich repeat; Membrane; NAD; Receptor; Reference proteome; Repeat;
KW 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 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
