TLR4_MOUSE
ID TLR4_MOUSE Reviewed; 835 AA.
AC Q9QUK6; Q9D691; Q9QZF5; Q9Z203;
DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=Toll-like receptor 4;
DE AltName: CD_antigen=CD284;
DE Flags: Precursor;
GN Name=Tlr4; Synonyms=Lps;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=C3H/HeJ;
RX PubMed=10087992; DOI=10.1006/bcmd.1998.0201;
RA Poltorak A., Smirnova I., He X., Liu M.-Y., Van Huffel C., Birdwell D.,
RA Alejos E., Silva M., Du X., Thompson P., Chan E.K.L., Ledesma J., Roe B.,
RA Clifton S., Vogel S.N., Beutler B.;
RT "Genetic and physical mapping of the Lps locus: identification of the Toll-
RT 4 receptor as a candidate gene in the critical region.";
RL Blood Cells Mol. Dis. 24:340-355(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND VARIANT LPS-TOLERANT HIS-712.
RC STRAIN=C3H/HeJ;
RX PubMed=9851930; DOI=10.1126/science.282.5396.2085;
RA Poltorak A., He X., Smirnova I., Liu M.-Y., Van Huffel C., Du X.,
RA Birdwell D., Alejos E., Silva M., Galanos C., Freudenberg M.,
RA Ricciardi-Castagnoli P., Layton B., Beutler B.;
RT "Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in
RT Tlr4 gene.";
RL Science 282:2085-2088(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND VARIANT LPS-TOLERANT HIS-712.
RC STRAIN=C57BL/6J;
RX PubMed=9989976; DOI=10.1084/jem.189.4.615;
RA Qureshi S.T., Lariviere L., Leveque G., Clermont S., Moore K.J., Gros P.,
RA Malo D.;
RT "Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4).";
RL J. Exp. Med. 189:615-625(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Macrophage;
RX PubMed=10548109; DOI=10.1038/44605;
RA Underhill D.M., Ozinsky A., Hajjar A.M., Stevens A., Wilson C.B.,
RA Bassetti M., Aderem A.;
RT "The Toll-like receptor 2 is recruited to macrophage phagosomes and
RT discriminates between pathogens.";
RL Nature 401:811-815(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASN-94; ILE-209; GLY-219;
RP ILE-254; LEU-423; SER-477; ALA-516; ASP-593; ILE-600; VAL-607; ILE-637;
RP HIS-761 AND LYS-811.
RC STRAIN=Various strains;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-154.
RC STRAIN=C57BL/6J; TISSUE=Skin;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [7]
RP FUNCTION.
RX PubMed=10952994; DOI=10.1074/jbc.m007386200;
RA Rhee S.H., Hwang D.;
RT "Murine Toll-like receptor 4 confers lipopolysaccharide responsiveness as
RT determined by activation of NF kappa B and expression of the inducible
RT cyclooxygenase.";
RL J. Biol. Chem. 275:34035-34040(2000).
RN [8]
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 [9]
RP INTERACTION WITH CNPY3.
RX PubMed=18780723; DOI=10.1093/intimm/dxn098;
RA Kiyokawa T., Akashi-Takamura S., Shibata T., Matsumoto F., Nishitani C.,
RA Kuroki Y., Seto Y., Miyake K.;
RT "A single base mutation in the PRAT4A gene reveals differential interaction
RT of PRAT4A with Toll-like receptors.";
RL Int. Immunol. 20:1407-1415(2008).
RN [10]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=20133493; DOI=10.1093/intimm/dxq005;
RA Tsukamoto H., Fukudome K., Takao S., Tsuneyoshi N., Kimoto M.;
RT "Lipopolysaccharide-binding protein-mediated Toll-like receptor 4
RT dimerization enables rapid signal transduction against lipopolysaccharide
RT stimulation on membrane-associated CD14-expressing cells.";
RL Int. Immunol. 22:271-280(2010).
RN [11]
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 [12]
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 [13]
RP FUNCTION.
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 [14]
RP INTERACTION WITH CEACAM1.
RX PubMed=22496641; DOI=10.1371/journal.ppat.1002597;
RA Lu R., Pan H., Shively J.E.;
RT "CEACAM1 negatively regulates IL-1beta production in LPS activated
RT neutrophils by recruiting SHP-1 to a SYK-TLR4-CEACAM1 complex.";
RL PLoS Pathog. 8:E1002597-E1002597(2012).
RN [15]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=23812099; DOI=10.1038/ni.2639;
RA Sheedy F.J., Grebe A., Rayner K.J., Kalantari P., Ramkhelawon B.,
RA Carpenter S.B., Becker C.E., Ediriweera H.N., Mullick A.E., Golenbock D.T.,
RA Stuart L.M., Latz E., Fitzgerald K.A., Moore K.J.;
RT "CD36 coordinates NLRP3 inflammasome activation by facilitating
RT intracellular nucleation of soluble ligands into particulate ligands in
RT sterile inflammation.";
RL Nat. Immunol. 14:812-820(2013).
RN [16]
RP FUNCTION, AND INTERACTION WITH TIRAP AND TICAM2.
RX PubMed=24380872; DOI=10.1093/intimm/dxt071;
RA Tanimura N., Saitoh S., Ohto U., Akashi-Takamura S., Fujimoto Y.,
RA Fukase K., Shimizu T., Miyake K.;
RT "The attenuated inflammation of MPL is due to the lack of CD14-dependent
RT tight dimerization of the TLR4/MD2 complex at the plasma membrane.";
RL Int. Immunol. 26:307-314(2014).
RN [17]
RP INTERACTION WITH SMPDL3B.
RX PubMed=26095358; DOI=10.1016/j.celrep.2015.05.006;
RA Heinz L.X., Baumann C.L., Koeberlin M.S., Snijder B., Gawish R., Shui G.,
RA Sharif O., Aspalter I.M., Mueller A.C., Kandasamy R.K., Breitwieser F.P.,
RA Pichlmair A., Bruckner M., Rebsamen M., Blueml S., Karonitsch T.,
RA Fauster A., Colinge J., Bennett K.L., Knapp S., Wenk M.R.,
RA Superti-Furga G.;
RT "The lipid-modifying enzyme SMPDL3B negatively regulates innate immunity.";
RL Cell Rep. 11:1919-1928(2015).
RN [18]
RP INTERACTION WITH WDFY1 AND TICAM1.
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 [19]
RP IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH SCIMP, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND PHOSPHORYLATION.
RX PubMed=28098138; DOI=10.1038/ncomms14133;
RA Luo L., Bokil N.J., Wall A.A., Kapetanovic R., Lansdaal N.M., Marceline F.,
RA Burgess B.J., Tong S.J., Guo Z., Alexandrov K., Ross I.L., Hibbs M.L.,
RA Stow J.L., Sweet M.J.;
RT "SCIMP is a transmembrane non-TIR TLR adaptor that promotes proinflammatory
RT cytokine production from macrophages.";
RL Nat. Commun. 8:14133-14133(2017).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.84 ANGSTROMS) OF 27-625 IN COMPLEX WITH LY96,
RP DISULFIDE BOND, AND GLYCOSYLATION AT ASN-34; ASN-75; ASN-172; ASN-204;
RP ASN-237; ASN-307; ASN-492; ASN-524 AND ASN-572.
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 [21]
RP X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS) OF 22-627 IN COMPLEX WITH LY96,
RP SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-172; ASN-204; ASN-524
RP AND ASN-572.
RX PubMed=22532668; DOI=10.1073/pnas.1201193109;
RA Ohto U., Fukase K., Miyake K., Shimizu T.;
RT "Structural basis of species-specific endotoxin sensing by innate immune
RT receptor TLR4/MD-2.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:7421-7426(2012).
CC -!- FUNCTION: Cooperates with LY96 and CD14 to mediate the innate immune
CC response to bacterial lipopolysaccharide (LPS) (PubMed:9851930,
CC PubMed:9989976, PubMed:20133493). Acts via MYD88, TIRAP and TRAF6,
CC leading to NF-kappa-B activation, cytokine secretion and the
CC inflammatory response (PubMed:24380872). Also involved in LPS-
CC independent inflammatory responses triggered by free fatty acids, such
CC as palmitate. In complex with TLR6, promotes sterile inflammation in
CC monocytes/macrophages in response to oxidized low-density lipoprotein
CC (oxLDL) or amyloid-beta 42. In this context, the initial signal is
CC provided by oxLDL- or amyloid-beta 42-binding to CD36. This event
CC 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(-) (By similarity).
CC Activated by the signaling pathway regulator NMI which acts as damage-
CC associated molecular patterns (DAMPs) in response to cell injury or
CC pathogen invasion, therefore promoting nuclear factor NF-kappa-B
CC activation (By similarity). {ECO:0000250|UniProtKB:O00206,
CC ECO:0000269|PubMed:10952994, ECO:0000269|PubMed:17478729,
CC ECO:0000269|PubMed:20037584, ECO:0000269|PubMed:20133493,
CC ECO:0000269|PubMed:23812099, ECO:0000269|PubMed:24380872,
CC ECO:0000269|PubMed:9851930, ECO:0000269|PubMed:9989976}.
CC -!- SUBUNIT: Belongs to the lipopolysaccharide (LPS) receptor, a multi-
CC protein complex containing at least CD14, LY96 and TLR4
CC (PubMed:24380872). Binding to bacterial LPS leads to homodimerization
CC (PubMed:20133493, PubMed:24380872, PubMed:22532668). Interacts with
CC LY96 via the extracellular domain (PubMed:17803912, PubMed:22532668).
CC Interacts with MYD88 (via the TIR domain). Interacts with TICAM2 and
CC TIRAP (PubMed:24380872). Interacts with NOX4 (By similarity). Interacts
CC with CNPY3 and HSP90B1; this interaction is required for proper folding
CC in the endoplasmic reticulum (PubMed:18780723, PubMed:20865800).
CC Interacts with MAP3K21; this interaction leads to negative regulation
CC of TLR4 signaling (By similarity). Interacts with CD36, following CD36
CC stimulation by oxLDL or amyloid-beta 42, and forms a heterodimer with
CC TLR6. The trimeric complex is internalized and triggers inflammatory
CC response. LYN kinase activity facilitates TLR4-TLR6 heterodimerization
CC and signal initiation (By similarity). Interacts with TICAM1 in
CC response to LPS in a WDFY1-dependent manner (PubMed:25736436).
CC Interacts with WDFY1 in response to LPS (PubMed:25736436). Interacts
CC with SMPDL3B (PubMed:26095358). Interacts with CEACAM1; upon
CC lipopolysaccharide stimulation, forms a complex including TLR4 and the
CC phosphorylated form of SYK and CEACAM1, which in turn, recruits PTPN6
CC that dephosphorylates SYK, reducing the production of reactive oxygen
CC species (ROS) and lysosome disruption, which in turn, reduces the
CC activity of the inflammasome (PubMed:22496641). Interacts with RFTN1;
CC the interaction occurs in response to lipopolysaccharide stimulation
CC (By similarity). Interacts with SCIMP; the interaction occurs in
CC response to lipopolysaccharide stimulation and is enhanced by
CC phosphorylation of SCIMP by LYN (PubMed:28098138). This interaction
CC facilitates the phosphorylation of TLR4 by LYN which elicits a
CC selective cytokine response in macrophages (PubMed:28098138). Interacts
CC with TRAF3IP3 (By similarity). Interacts with TREM1; this interaction
CC enhances TLR4-mediated inflammatory response (By similarity).
CC {ECO:0000250|UniProtKB:O00206, ECO:0000269|PubMed:17803912,
CC ECO:0000269|PubMed:18780723, ECO:0000269|PubMed:20133493,
CC ECO:0000269|PubMed:20865800, ECO:0000269|PubMed:22496641,
CC ECO:0000269|PubMed:22532668, ECO:0000269|PubMed:24380872,
CC ECO:0000269|PubMed:25736436, ECO:0000269|PubMed:26095358,
CC ECO:0000269|PubMed:28098138}.
CC -!- INTERACTION:
CC Q9QUK6; Q9JHF9: Ly96; NbExp=8; IntAct=EBI-1534575, EBI-1534566;
CC Q9QUK6; P22366: Myd88; NbExp=2; IntAct=EBI-1534575, EBI-525108;
CC Q9QUK6; Q91Y57: Siglec12; NbExp=3; IntAct=EBI-1534575, EBI-16826475;
CC Q9QUK6; Q3U0V2: Tradd; NbExp=3; IntAct=EBI-1534575, EBI-1544032;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20133493,
CC ECO:0000269|PubMed:28098138}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:20133493}. Early endosome
CC {ECO:0000250|UniProtKB:O00206}. Cell projection, ruffle
CC {ECO:0000269|PubMed:28098138}. Note=Upon complex formation with CD36
CC and TLR6, internalized through dynamin-dependent endocytosis.
CC Colocalizes with RFTN1 at cell membrane and then together with RFTN1
CC moves to endosomes, upon lipopolysaccharide stimulation.
CC {ECO:0000250|UniProtKB:O00206}.
CC -!- TISSUE SPECIFICITY: Expressed in macrophages (at protein level)
CC (PubMed:28098138). Highly expressed in heart, spleen, lung and muscle.
CC Lower levels are found in liver and kidney (PubMed:23812099).
CC {ECO:0000269|PubMed:23812099, ECO:0000269|PubMed:28098138}.
CC -!- DOMAIN: The TIR domain mediates interaction with NOX4.
CC {ECO:0000250|UniProtKB:O00206}.
CC -!- PTM: Phosphorylated on tyrosine residues by LYN after binding
CC lipopolysaccharide. {ECO:0000269|PubMed:28098138}.
CC -!- POLYMORPHISM: Interstrain analysis reveals that TLR4 is a polymorphic
CC protein and that the extracellular domain is far more variable than the
CC cytoplasmic domain, which is variable at the C-terminal.
CC {ECO:0000305|PubMed:11104518}.
CC -!- DISEASE: Note=The protein is encoded by the Lps locus, an important
CC susceptibility locus, influencing the propensity to develop a
CC disseminated Gram-negative infection. {ECO:0000269|PubMed:9851930,
CC ECO:0000269|PubMed:9989976}.
CC -!- DISRUPTION PHENOTYPE: Animals with a double knockout of APOE and TLR4,
CC fed a Western diet for 12 weeks, have less aortic plaque formation than
CC single APOE knockout mice. They also show lower serum concentrations of
CC IL1A, ILB and IL18. {ECO:0000269|PubMed:23812099}.
CC -!- SIMILARITY: Belongs to the Toll-like receptor family. {ECO:0000305}.
CC -!- CAUTION: In some plant proteins and in human SARM1, the TIR domain has
CC NAD(+) hydrolase (NADase) activity (By similarity). However, despite
CC the presence of the catalytic Asp residue, the isolated TIR domain of
CC human TLR4 lacks NADase activity (By similarity). Based on this, it is
CC unlikely that Toll-like receptors have NADase activity.
CC {ECO:0000250|UniProtKB:O00206, ECO:0000305}.
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DR EMBL; AF095353; AAC99411.1; -; mRNA.
DR EMBL; AF110133; AAD29272.1; -; mRNA.
DR EMBL; AF185285; AAF04278.1; -; mRNA.
DR EMBL; AF177767; AAF05317.1; -; Genomic_DNA.
DR EMBL; AK014533; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS18271.1; -.
DR RefSeq; NP_067272.1; NM_021297.3.
DR PDB; 2Z64; X-ray; 2.84 A; A=27-625.
DR PDB; 3VQ1; X-ray; 2.70 A; A/B=22-627.
DR PDB; 3VQ2; X-ray; 2.48 A; A/B=22-627.
DR PDB; 5IJB; X-ray; 2.91 A; A/B=26-544.
DR PDB; 5IJC; X-ray; 2.57 A; A/B=26-544.
DR PDB; 5IJD; X-ray; 2.70 A; A/B=26-544.
DR PDB; 7MLM; X-ray; 2.10 A; A=26-544.
DR PDBsum; 2Z64; -.
DR PDBsum; 3VQ1; -.
DR PDBsum; 3VQ2; -.
DR PDBsum; 5IJB; -.
DR PDBsum; 5IJC; -.
DR PDBsum; 5IJD; -.
DR PDBsum; 7MLM; -.
DR AlphaFoldDB; Q9QUK6; -.
DR SMR; Q9QUK6; -.
DR BioGRID; 204224; 24.
DR DIP; DIP-38573N; -.
DR IntAct; Q9QUK6; 15.
DR MINT; Q9QUK6; -.
DR STRING; 10090.ENSMUSP00000045770; -.
DR BindingDB; Q9QUK6; -.
DR ChEMBL; CHEMBL1795167; -.
DR GlyGen; Q9QUK6; 14 sites.
DR iPTMnet; Q9QUK6; -.
DR PhosphoSitePlus; Q9QUK6; -.
DR MaxQB; Q9QUK6; -.
DR PaxDb; Q9QUK6; -.
DR PRIDE; Q9QUK6; -.
DR ProteomicsDB; 259208; -.
DR Antibodypedia; 3410; 1889 antibodies from 51 providers.
DR DNASU; 21898; -.
DR Ensembl; ENSMUST00000048096; ENSMUSP00000045770; ENSMUSG00000039005.
DR GeneID; 21898; -.
DR KEGG; mmu:21898; -.
DR UCSC; uc008thv.1; mouse.
DR CTD; 7099; -.
DR MGI; MGI:96824; Tlr4.
DR VEuPathDB; HostDB:ENSMUSG00000039005; -.
DR eggNOG; KOG4641; Eukaryota.
DR GeneTree; ENSGT00940000160778; -.
DR HOGENOM; CLU_006000_5_0_1; -.
DR InParanoid; Q9QUK6; -.
DR OMA; CKHSAER; -.
DR OrthoDB; 282372at2759; -.
DR PhylomeDB; Q9QUK6; -.
DR TreeFam; TF351113; -.
DR Reactome; R-MMU-140534; Caspase activation via Death Receptors in the presence of ligand.
DR Reactome; R-MMU-166016; Toll Like Receptor 4 (TLR4) Cascade.
DR Reactome; R-MMU-166166; MyD88-independent TLR4 cascade.
DR Reactome; R-MMU-2562578; TRIF-mediated programmed cell death.
DR Reactome; R-MMU-5686938; Regulation of TLR by endogenous ligand.
DR Reactome; R-MMU-936964; Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
DR Reactome; R-MMU-937041; IKK complex recruitment mediated by RIP1.
DR Reactome; R-MMU-937072; TRAF6-mediated induction of TAK1 complex within TLR4 complex.
DR Reactome; R-MMU-9707616; Heme signaling.
DR Reactome; R-MMU-975163; IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
DR BioGRID-ORCS; 21898; 2 hits in 73 CRISPR screens.
DR EvolutionaryTrace; Q9QUK6; -.
DR PRO; PR:Q9QUK6; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q9QUK6; protein.
DR Bgee; ENSMUSG00000039005; Expressed in lumbar dorsal root ganglion and 142 other tissues.
DR ExpressionAtlas; Q9QUK6; baseline and differential.
DR Genevisible; Q9QUK6; MM.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISO:MGI.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISO:MGI.
DR GO; GO:0046696; C:lipopolysaccharide receptor complex; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0001891; C:phagocytic cup; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0043235; C:receptor complex; IDA:UniProtKB.
DR GO; GO:0001726; C:ruffle; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0001530; F:lipopolysaccharide binding; ISO:MGI.
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:0043548; F:phosphatidylinositol 3-kinase binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:InterPro.
DR GO; GO:0002218; P:activation of innate immune response; IMP:MGI.
DR GO; GO:0007250; P:activation of NF-kappaB-inducing kinase activity; NAS:UniProtKB.
DR GO; GO:0014002; P:astrocyte development; IMP:MGI.
DR GO; GO:0042100; P:B cell proliferation; IMP:MGI.
DR GO; GO:0002322; P:B cell proliferation involved in immune response; IMP:MGI.
DR GO; GO:1904646; P:cellular response to amyloid-beta; ISO:MGI.
DR GO; GO:0071346; P:cellular response to interferon-gamma; ISO:MGI.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:ARUK-UCL.
DR GO; GO:0071223; P:cellular response to lipoteichoic acid; IMP:MGI.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0140052; P:cellular response to oxidised low-density lipoprotein particle stimulus; IGI:ARUK-UCL.
DR GO; GO:0036120; P:cellular response to platelet-derived growth factor stimulus; IMP:BHF-UCL.
DR GO; GO:0042742; P:defense response to bacterium; ISO:MGI.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:MGI.
DR GO; GO:0032497; P:detection of lipopolysaccharide; IDA:UniProtKB.
DR GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; ISO:MGI.
DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; ISO:MGI.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IDA:MGI.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IDA:MGI.
DR GO; GO:0007252; P:I-kappaB phosphorylation; IMP:MGI.
DR GO; GO:0006954; P:inflammatory response; IMP:BHF-UCL.
DR GO; GO:0045087; P:innate immune response; TAS:BHF-UCL.
DR GO; GO:0002758; P:innate immune response-activating signal transduction; ISO:MGI.
DR GO; GO:0060729; P:intestinal epithelial structure maintenance; IMP:BHF-UCL.
DR GO; GO:0007254; P:JNK cascade; IDA:MGI.
DR GO; GO:0006691; P:leukotriene metabolic process; ISO:MGI.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:UniProtKB.
DR GO; GO:0046651; P:lymphocyte proliferation; IMP:MGI.
DR GO; GO:0042116; P:macrophage activation; ISS:UniProtKB.
DR GO; GO:0045576; P:mast cell activation; NAS:UniProtKB.
DR GO; GO:0045342; P:MHC class II biosynthetic process; IMP:MGI.
DR GO; GO:0001774; P:microglial cell activation; ISO:MGI.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; IGI:ARUK-UCL.
DR GO; GO:0120163; P:negative regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IMP:BHF-UCL.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IMP:BHF-UCL.
DR GO; GO:0032700; P:negative regulation of interleukin-17 production; IMP:BHF-UCL.
DR GO; GO:0032707; P:negative regulation of interleukin-23 production; IMP:BHF-UCL.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IMP:BHF-UCL.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:BHF-UCL.
DR GO; GO:0006809; P:nitric oxide biosynthetic process; IMP:MGI.
DR GO; GO:0002537; P:nitric oxide production involved in inflammatory response; IMP:MGI.
DR GO; GO:0070427; P:nucleotide-binding oligomerization domain containing 1 signaling pathway; IDA:MGI.
DR GO; GO:0070431; P:nucleotide-binding oligomerization domain containing 2 signaling pathway; IDA:MGI.
DR GO; GO:0006909; P:phagocytosis; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IMP:MGI.
DR GO; GO:1903974; P:positive regulation of cellular response to macrophage colony-stimulating factor stimulus; ISO:MGI.
DR GO; GO:2000343; P:positive regulation of chemokine (C-X-C motif) ligand 2 production; ISO:MGI.
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; IGI:ARUK-UCL.
DR GO; GO:0043388; P:positive regulation of DNA binding; ISO:MGI.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:MGI.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IGI:ARUK-UCL.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; IDA:BHF-UCL.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; IDA:BHF-UCL.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IMP: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; IDA:BHF-UCL.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IDA:BHF-UCL.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IDA:UniProtKB.
DR GO; GO:0032736; P:positive regulation of interleukin-13 production; NAS:UniProtKB.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:MGI.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:MGI.
DR GO; GO:0050671; P:positive regulation of lymphocyte proliferation; IMP:MGI.
DR GO; GO:0043032; P:positive regulation of macrophage activation; IGI:ARUK-UCL.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IDA:MGI.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IMP:BHF-UCL.
DR GO; GO:1904466; P:positive regulation of matrix metallopeptidase secretion; ISO:MGI.
DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; IMP:MGI.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IMP:MGI.
DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; IDA:BHF-UCL.
DR GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; IDA:UniProtKB.
DR GO; GO:0070430; P:positive regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway; IDA:MGI.
DR GO; GO:0070434; P:positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway; IDA:MGI.
DR GO; GO:1903223; P:positive regulation of oxidative stress-induced neuron death; IGI:ARUK-UCL.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
DR GO; GO:0010572; P:positive regulation of platelet activation; IMP:BHF-UCL.
DR GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; IMP:ARUK-UCL.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:BHF-UCL.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:BHF-UCL.
DR GO; GO:0032874; P:positive regulation of stress-activated MAPK cascade; IDA:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:BHF-UCL.
DR GO; GO:0002730; P:regulation of dendritic cell cytokine production; IDA:MGI.
DR GO; GO:0050727; P:regulation of inflammatory response; IMP:BHF-UCL.
DR GO; GO:0051930; P:regulation of sensory perception of pain; ISO:MGI.
DR GO; GO:0032680; P:regulation of tumor necrosis factor production; ISO:MGI.
DR GO; GO:0009617; P:response to bacterium; IMP:MGI.
DR GO; GO:0045471; P:response to ethanol; ISO:MGI.
DR GO; GO:0070542; P:response to fatty acid; ISO:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; IMP:MGI.
DR GO; GO:0006979; P:response to oxidative stress; ISO:MGI.
DR GO; GO:0051403; P:stress-activated MAPK cascade; IDA:MGI.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IDA:UniProtKB.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; ISO:MGI.
DR GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; IGI:ARUK-UCL.
DR GO; GO:0002246; P:wound healing involved in inflammatory response; IMP:BHF-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; 2.
DR Pfam; PF01582; TIR; 1.
DR PIRSF; PIRSF037595; Toll-like_receptor; 1.
DR SMART; SM00369; LRR_TYP; 8.
DR SMART; SM00082; LRRCT; 1.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF52200; SSF52200; 1.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cell projection; Disease variant;
KW Disulfide bond; Endosome; Glycoprotein; Immunity; Inflammatory response;
KW Innate immunity; Leucine-rich repeat; Membrane; NAD; Receptor;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..835
FT /note="Toll-like receptor 4"
FT /id="PRO_0000034723"
FT TOPO_DOM 26..638
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 639..659
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 660..835
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 54..75
FT /note="LRR 1"
FT REPEAT 78..99
FT /note="LRR 2"
FT REPEAT 102..123
FT /note="LRR 3"
FT REPEAT 126..147
FT /note="LRR 4"
FT REPEAT 150..171
FT /note="LRR 5"
FT REPEAT 175..198
FT /note="LRR 6"
FT REPEAT 204..224
FT /note="LRR 7"
FT REPEAT 226..247
FT /note="LRR 8"
FT REPEAT 248..269
FT /note="LRR 9"
FT REPEAT 329..349
FT /note="LRR 10"
FT REPEAT 350..370
FT /note="LRR 11"
FT REPEAT 372..392
FT /note="LRR 12"
FT REPEAT 398..420
FT /note="LRR 13"
FT REPEAT 421..442
FT /note="LRR 14"
FT REPEAT 446..467
FT /note="LRR 15"
FT REPEAT 470..490
FT /note="LRR 16"
FT REPEAT 495..516
FT /note="LRR 17"
FT REPEAT 519..540
FT /note="LRR 18"
FT REPEAT 543..564
FT /note="LRR 19"
FT DOMAIN 576..627
FT /note="LRRCT"
FT DOMAIN 670..813
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT REGION 670..835
FT /note="Interaction with SCIMP"
FT /evidence="ECO:0000269|PubMed:28098138"
FT CARBOHYD 34
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17803912"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17803912"
FT CARBOHYD 172
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17803912"
FT CARBOHYD 204
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17803912"
FT CARBOHYD 237
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17803912"
FT CARBOHYD 307
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17803912"
FT CARBOHYD 492
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17803912"
FT CARBOHYD 495
FT /note="N-linked (GlcNAc...) asparagine"
FT CARBOHYD 524
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17803912"
FT CARBOHYD 572
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17803912"
FT CARBOHYD 575
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 613
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 621
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 622
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 28..39
FT /evidence="ECO:0000269|PubMed:17803912"
FT DISULFID 280..304
FT /evidence="ECO:0000269|PubMed:17803912"
FT DISULFID 388..389
FT /evidence="ECO:0000269|PubMed:17803912"
FT DISULFID 580..606
FT /evidence="ECO:0000269|PubMed:17803912"
FT DISULFID 582..625
FT /evidence="ECO:0000269|PubMed:17803912"
FT VARIANT 94
FT /note="D -> N (in strain: KK/HLJ)"
FT /evidence="ECO:0000269|PubMed:11104518"
FT VARIANT 209
FT /note="M -> I (in strain: A/J, BALB/cJ, P/J, SODL/EI, SEA/
FT GNJ, NZW/LACJ and VM/DK)"
FT /evidence="ECO:0000269|PubMed:11104518"
FT VARIANT 219
FT /note="D -> G (in strain: SEA/GNJ)"
FT /evidence="ECO:0000269|PubMed:11104518"
FT VARIANT 254
FT /note="V -> I (in strain: A/J, BALB/cJ and SEA/GNJ)"
FT /evidence="ECO:0000269|PubMed:11104518"
FT VARIANT 423
FT /note="Q -> L (in strain: SEA/GNJ)"
FT /evidence="ECO:0000269|PubMed:11104518"
FT VARIANT 477
FT /note="A -> S (in strain: P/J)"
FT /evidence="ECO:0000269|PubMed:11104518"
FT VARIANT 516
FT /note="T -> A (in strain: LP/J)"
FT /evidence="ECO:0000269|PubMed:11104518"
FT VARIANT 593
FT /note="E -> D (in strain: A/J, BALB/cJ, P/J, SODL/EI, SEA/
FT GNJ, NZW/LACJ and VM/DK)"
FT /evidence="ECO:0000269|PubMed:11104518"
FT VARIANT 600
FT /note="N -> I (in strain: KK/HLJ)"
FT /evidence="ECO:0000269|PubMed:11104518"
FT VARIANT 607
FT /note="A -> V (in strain: P/J)"
FT /evidence="ECO:0000269|PubMed:11104518"
FT VARIANT 637
FT /note="V -> I (in strain: P/J)"
FT /evidence="ECO:0000269|PubMed:11104518"
FT VARIANT 712
FT /note="P -> H (in Lps-tolerant mice)"
FT /evidence="ECO:0000269|PubMed:9851930,
FT ECO:0000269|PubMed:9989976"
FT VARIANT 761
FT /note="R -> H (in strain: A/J, BALB/cJ, SODL/EI, SEA/GNJ,
FT NZW/LACJ and VM/DK)"
FT /evidence="ECO:0000269|PubMed:11104518"
FT VARIANT 811
FT /note="N -> K (in strain: P/J)"
FT /evidence="ECO:0000269|PubMed:11104518"
FT CONFLICT 87..154
FT /note="CEIETIEDKAWHGLHHLSNLILTGNPIQSFSPGSFSGLTSLENLVAVETKLA
FT SLESFPIGQLITLKKL -> EMNTESKSSEAHALALSHILSPCQPSRRKLRVKLGSLSY
FT QRAEEGVRSSEIGYSCLHVDTRHDINAVD (in Ref. 6)"
FT /evidence="ECO:0000305"
FT STRAND 29..32
FT /evidence="ECO:0007829|PDB:7MLM"
FT TURN 33..35
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:2Z64"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:5IJD"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:7MLM"
FT TURN 70..75
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 81..83
FT /evidence="ECO:0007829|PDB:7MLM"
FT TURN 94..99
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:7MLM"
FT TURN 118..123
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 129..131
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 140..143
FT /evidence="ECO:0007829|PDB:3VQ2"
FT STRAND 153..155
FT /evidence="ECO:0007829|PDB:7MLM"
FT HELIX 168..171
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 178..180
FT /evidence="ECO:0007829|PDB:7MLM"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:7MLM"
FT HELIX 195..199
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:7MLM"
FT TURN 219..224
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 226..234
FT /evidence="ECO:0007829|PDB:7MLM"
FT HELIX 239..247
FT /evidence="ECO:0007829|PDB:7MLM"
FT TURN 248..251
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 253..260
FT /evidence="ECO:0007829|PDB:7MLM"
FT HELIX 273..281
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 282..289
FT /evidence="ECO:0007829|PDB:7MLM"
FT HELIX 297..301
FT /evidence="ECO:0007829|PDB:7MLM"
FT HELIX 303..305
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 309..315
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 331..337
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 353..358
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 375..377
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 380..382
FT /evidence="ECO:0007829|PDB:2Z64"
FT STRAND 384..388
FT /evidence="ECO:0007829|PDB:7MLM"
FT HELIX 391..394
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 401..403
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 408..412
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 424..426
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 430..434
FT /evidence="ECO:0007829|PDB:7MLM"
FT TURN 435..443
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 449..451
FT /evidence="ECO:0007829|PDB:7MLM"
FT TURN 462..467
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 473..475
FT /evidence="ECO:0007829|PDB:7MLM"
FT HELIX 482..484
FT /evidence="ECO:0007829|PDB:7MLM"
FT TURN 489..492
FT /evidence="ECO:0007829|PDB:5IJD"
FT STRAND 498..500
FT /evidence="ECO:0007829|PDB:7MLM"
FT TURN 511..516
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 522..524
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 532..534
FT /evidence="ECO:0007829|PDB:2Z64"
FT HELIX 535..538
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 546..548
FT /evidence="ECO:0007829|PDB:3VQ2"
FT STRAND 557..559
FT /evidence="ECO:0007829|PDB:3VQ2"
FT HELIX 561..563
FT /evidence="ECO:0007829|PDB:3VQ2"
FT STRAND 570..572
FT /evidence="ECO:0007829|PDB:3VQ2"
FT HELIX 582..584
FT /evidence="ECO:0007829|PDB:3VQ1"
FT HELIX 585..588
FT /evidence="ECO:0007829|PDB:3VQ2"
FT TURN 589..593
FT /evidence="ECO:0007829|PDB:3VQ2"
FT STRAND 594..600
FT /evidence="ECO:0007829|PDB:3VQ2"
FT HELIX 601..603
FT /evidence="ECO:0007829|PDB:3VQ2"
FT STRAND 608..610
FT /evidence="ECO:0007829|PDB:2Z64"
FT HELIX 616..618
FT /evidence="ECO:0007829|PDB:2Z64"
SQ SEQUENCE 835 AA; 95519 MW; 9C83B59F9A220C17 CRC64;
MMPPWLLART LIMALFFSCL TPGSLNPCIE VVPNITYQCM DQKLSKVPDD IPSSTKNIDL
SFNPLKILKS YSFSNFSELQ WLDLSRCEIE TIEDKAWHGL HHLSNLILTG NPIQSFSPGS
FSGLTSLENL VAVETKLASL ESFPIGQLIT LKKLNVAHNF IHSCKLPAYF SNLTNLVHVD
LSYNYIQTIT VNDLQFLREN PQVNLSLDMS LNPIDFIQDQ AFQGIKLHEL TLRGNFNSSN
IMKTCLQNLA GLHVHRLILG EFKDERNLEI FEPSIMEGLC DVTIDEFRLT YTNDFSDDIV
KFHCLANVSA MSLAGVSIKY LEDVPKHFKW QSLSIIRCQL KQFPTLDLPF LKSLTLTMNK
GSISFKKVAL PSLSYLDLSR NALSFSGCCS YSDLGTNSLR HLDLSFNGAI IMSANFMGLE
ELQHLDFQHS TLKRVTEFSA FLSLEKLLYL DISYTNTKID FDGIFLGLTS LNTLKMAGNS
FKDNTLSNVF ANTTNLTFLD LSKCQLEQIS WGVFDTLHRL QLLNMSHNNL LFLDSSHYNQ
LYSLSTLDCS FNRIETSKGI LQHFPKSLAF FNLTNNSVAC ICEHQKFLQW VKEQKQFLVN
VEQMTCATPV EMNTSLVLDF NNSTCYMYKT IISVSVVSVI VVSTVAFLIY HFYFHLILIA
GCKKYSRGES IYDAFVIYSS QNEDWVRNEL VKNLEEGVPR FHLCLHYRDF IPGVAIAANI
IQEGFHKSRK VIVVVSRHFI QSRWCIFEYE IAQTWQFLSS RSGIIFIVLE KVEKSLLRQQ
VELYRLLSRN TYLEWEDNPL GRHIFWRRLK NALLDGKASN PEQTAEEEQE TATWT
