ID TLR3_HUMAN Reviewed; 904 AA. AC O15455; B2RAI7; B7Z7K0; E6Y0F0; E6Y0F1; E9PGH4; Q4VAL2; Q504W0; DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 13-FEB-2019, entry version 192. DE RecName: Full=Toll-like receptor 3; DE AltName: CD_antigen=CD283; DE Flags: Precursor; GN Name=TLR3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). 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 RT Toll."; RL Proc. Natl. Acad. Sci. U.S.A. 95:588-593(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Neuron; RX PubMed=17085778; DOI=10.1385/JMN:29:3:185; RA Lafon M., Megret F., Lafage M., Prehaud C.; RT "The innate immune facet of brain: human neurons express TLR-3 and RT sense viral dsRNA."; RL J. Mol. Neurosci. 29:185-194(2006). RN [3] 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., RA Kimura A.; RT "Natural selection in the TLR-related genes in the course of primate RT evolution."; RL Immunogenetics 60:727-735(2008). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT PHE-412. RA Macquin C., Bahram S.; RT "TLR polymorphism."; RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP PHE-412. RC TISSUE=Testis, and Thymus; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 4."; RL Nature 434:724-731(2005). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] 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 RT verified cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [10] RP FUNCTION, AND INTERACTION WITH TICAM1. RX PubMed=12471095; DOI=10.4049/jimmunol.169.12.6668; RA Yamamoto M., Sato S., Mori K., Hoshino K., Takeuchi O., Takeda K., RA Akira S.; RT "A novel Toll/IL-1 receptor domain-containing adapter that RT preferentially activates the IFN-beta promoter in the Toll-like RT receptor signaling."; RL J. Immunol. 169:6668-6672(2002). RN [11] RP FUNCTION, AND INTERACTION WITH TICAM1. RC TISSUE=Lung; RX PubMed=12539043; DOI=10.1038/ni886; RA Oshiumi H., Matsumoto M., Funami K., Akazawa T., Seya T.; RT "TICAM-1, an adapter molecule that participates in Toll-like receptor RT 3 mediated interferon-beta induction."; RL Nat. Immunol. 4:161-167(2003). RN [12] RP FUNCTION, SUBUNIT, AND MUTAGENESIS OF CYS-95; CYS-122; ASN-196 AND RP ASN-247. RX PubMed=16144834; DOI=10.1074/jbc.M507163200; RA de Bouteiller O., Merck E., Hasan U.A., Hubac S., Benguigui B., RA Trinchieri G., Bates E.E., Caux C.; RT "Recognition of double-stranded RNA by human toll-like receptor 3 and RT downstream receptor signaling requires multimerization and an acidic RT pH."; RL J. Biol. Chem. 280:38133-38145(2005). RN [13] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH SRC. RX PubMed=16858407; DOI=10.1038/sj.emboj.7601222; RA Johnsen I.B., Nguyen T.T., Ringdal M., Tryggestad A.M., Bakke O., RA Lien E., Espevik T., Anthonsen M.W.; RT "Toll-like receptor 3 associates with c-Src tyrosine kinase on RT endosomes to initiate antiviral signaling."; RL EMBO J. 25:3335-3346(2006). RN [14] RP FUNCTION, AND MUTAGENESIS OF HIS-539 AND ASN-541. RX PubMed=16720699; DOI=10.1073/pnas.0603245103; RA Bell J.K., Askins J., Hall P.R., Davies D.R., Segal D.M.; RT "The dsRNA binding site of human Toll-like receptor 3."; RL Proc. Natl. Acad. Sci. U.S.A. 103:8792-8797(2006). RN [15] RP PHOSPHORYLATION AT TYR-759 AND TYR-858, FUNCTION, AND MUTAGENESIS OF RP TYR-759. RX PubMed=17178723; DOI=10.1074/jbc.C600226200; RA Sarkar S.N., Elco C.P., Peters K.L., Chattopadhyay S., Sen G.C.; RT "Two tyrosine residues of Toll-like receptor 3 trigger different steps RT of NF-kappa B activation."; RL J. Biol. Chem. 282:3423-3427(2007). RN [16] RP FUNCTION, DOUBLE-STRANDED RNA-BINDING, AND HOMODIMERIZATION. RX PubMed=18172197; DOI=10.1073/pnas.0710779105; RA Leonard J.N., Ghirlando R., Askins J., Bell J.K., Margulies D.H., RA Davies D.R., Segal D.M.; RT "The TLR3 signaling complex forms by cooperative receptor RT dimerization."; RL Proc. Natl. Acad. Sci. U.S.A. 105:258-263(2008). RN [17] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-52 AND ASN-57. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of RT multiple enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [18] RP FUNCTION, PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION, AND RP INTERACTION WITH UNC93B1. RX PubMed=22611194; DOI=10.1073/pnas.1115091109; RA Garcia-Cattaneo A., Gobert F.X., Muller M., Toscano F., Flores M., RA Lescure A., Del Nery E., Benaroch P.; RT "Cleavage of Toll-like receptor 3 by cathepsins B and H is essential RT for signaling."; RL Proc. Natl. Acad. Sci. U.S.A. 109:9053-9058(2012). RN [19] RP INTERACTION WITH WDFY1 AND TICAM1, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF TYR-759 AND TYR-858. 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 [20] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 22-703, FUNCTION, DISULFIDE RP BONDS, SUBUNIT, GLYCOSYLATION AT ASN-52; ASN-70; ASN-196; ASN-252; RP ASN-265; ASN-275; ASN-291; ASN-398; ASN-413; ASN-507 AND ASN-636, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=16043704; DOI=10.1073/pnas.0505077102; RA Bell J.K., Botos I., Hall P.R., Askins J., Shiloach J., Segal D.M., RA Davies D.R.; RT "The molecular structure of the Toll-like receptor 3 ligand-binding RT domain."; RL Proc. Natl. Acad. Sci. U.S.A. 102:10976-10980(2005). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 27-700, DISULFIDE BONDS, AND RP GLYCOSYLATION AT ASN-124; ASN-252; ASN-275; ASN-291; ASN-398; ASN-413 RP AND ASN-507. RX PubMed=15961631; DOI=10.1126/science.1115253; RA Choe J., Kelker M.S., Wilson I.A.; RT "Crystal structure of human toll-like receptor 3 (TLR3) ectodomain."; RL Science 309:581-585(2005). RN [22] RP X-RAY CRYSTALLOGRAPHY (3.52 ANGSTROMS) OF 22-702 IN COMPLEX WITH RP ANTIBODY, DISULFIDE BONDS, SUBUNIT, DS-RNA BINDING REGIONS, AND RP GLYCOSYLATION AT ASN-52; ASN-70; ASN-124; ASN-247; ASN-252; ASN-265; RP ASN-275; ASN-291; ASN-398; ASN-413 AND ASN-507. RX PubMed=22579623; DOI=10.1016/j.jmb.2012.05.006; RA Luo J., Obmolova G., Malia T.J., Wu S.J., Duffy K.E., Marion J.D., RA Bell J.K., Ge P., Zhou Z.H., Teplyakov A., Zhao Y., Lamb R.J., RA Jordan J.L., San Mateo L.R., Sweet R.W., Gilliland G.L.; RT "Lateral clustering of TLR3:dsRNA signaling units revealed by RT TLR3ecd:3Fabs quaternary structure."; RL J. Mol. Biol. 421:112-124(2012). RN [23] RP VARIANT IIAE2 SER-554. RX PubMed=17872438; DOI=10.1126/science.1139522; RA Zhang S.-Y., Jouanguy E., Ugolini S., Smahi A., Elain G., Romero P., RA Segal D., Sancho-Shimizu V., Lorenzo L., Puel A., Picard C., RA Chapgier A., Plancoulaine S., Titeux M., Cognet C., von Bernuth H., RA Ku C.-L., Casrouge A., Zhang X.-X., Barreiro L., Leonard J., RA Hamilton C., Lebon P., Heron B., Vallee L., Quintana-Murci L., RA Hovnanian A., Rozenberg F., Vivier E., Geissmann F., Tardieu M., RA Abel L., Casanova J.-L.; RT "TLR3 deficiency in patients with herpes simplex encephalitis."; RL Science 317:1522-1527(2007). RN [24] RP VARIANT PHE-412. RX PubMed=18753640; DOI=10.1056/NEJMoa0802437; RA Yang Z., Stratton C., Francis P.J., Kleinman M.E., Tan P.L., Gibbs D., RA Tong Z., Chen H., Constantine R., Yang X., Chen Y., Zeng J., Davey L., RA Ma X., Hau V.S., Wang C., Harmon J., Buehler J., Pearson E., Patel S., RA Kaminoh Y., Watkins S., Luo L., Zabriskie N.A., Bernstein P.S., RA Cho W., Schwager A., Hinton D.R., Klein M.L., Hamon S.C., Simmons E., RA Yu B., Campochiaro B., Sunness J.S., Campochiaro P., Jorde L., RA Parmigiani G., Zack D.J., Katsanis N., Ambati J., Zhang K.; RT "Toll-like receptor 3 and geographic atrophy in age-related macular RT degeneration."; RL N. Engl. J. Med. 359:1456-1463(2008). RN [25] RP ERRATUM. RA Yang Z., Stratton C., Francis P.J., Kleinman M.E., Tan P.L., Gibbs D., RA Tong Z., Chen H., Constantine R., Yang X., Chen Y., Zeng J., Davey L., RA Ma X., Hau V.S., Wang C., Harmon J., Buehler J., Pearson E., Patel S., RA Kaminoh Y., Watkins S., Luo L., Zabriskie N.A., Bernstein P.S., RA Cho W., Schwager A., Hinton D.R., Klein M.L., Hamon S.C., Simmons E., RA Yu B., Campochiaro B., Sunness J.S., Campochiaro P., Jorde L., RA Parmigiani G., Zack D.J., Katsanis N., Ambati J., Zhang K.; RL N. Engl. J. Med. 359:1859-1859(2008). RN [26] RP VARIANT PHE-412. RX PubMed=22174453; DOI=10.4049/jimmunol.1102179; RA Sironi M., Biasin M., Cagliani R., Forni D., De Luca M., Saulle I., RA Lo Caputo S., Mazzotta F., Macias J., Pineda J.A., Caruz A., RA Clerici M.; RT "A common polymorphism in TLR3 confers natural resistance to HIV-1 RT infection."; RL J. Immunol. 188:818-823(2012). CC -!- FUNCTION: Key component of innate and adaptive immunity. TLRs CC (Toll-like receptors) control host immune response against CC pathogens through recognition of molecular patterns specific to CC microorganisms. TLR3 is a nucleotide-sensing TLR which is CC activated by double-stranded RNA, a sign of viral infection. Acts CC via the adapter TRIF/TICAM1, leading to NF-kappa-B activation, CC IRF3 nuclear translocation, cytokine secretion and the CC inflammatory response. {ECO:0000269|PubMed:12471095, CC ECO:0000269|PubMed:12539043, ECO:0000269|PubMed:16043704, CC ECO:0000269|PubMed:16144834, ECO:0000269|PubMed:16720699, CC ECO:0000269|PubMed:16858407, ECO:0000269|PubMed:17178723, CC ECO:0000269|PubMed:18172197, ECO:0000269|PubMed:22611194}. CC -!- SUBUNIT: Monomer and homodimer; dimerization is triggered by CC ligand-binding, the signaling unit is composed of one ds-RNA of CC around 40 bp and two TLR3 molecules, and lateral clustering of CC signaling units along the length of the ds-RNA ligand is required CC for TLR3 signal transduction. Interacts (via transmembrane domain) CC with UNC93B1; the interaction is required for transport from the CC ER to the endosomes. Interacts with SRC; upon binding of double- CC stranded RNA. Interacts with TICAM1 (via the TIR domain) in CC response to poly(I:C) and this interaction is enhanced in the CC presence of WDFY1 (PubMed:25736436). The tyrosine-phosphorylated CC form (via TIR domain) interacts with WDFY1 (via WD repeat 2) in CC response to poly(I:C) (PubMed:25736436). CC {ECO:0000269|PubMed:12471095, ECO:0000269|PubMed:12539043, CC ECO:0000269|PubMed:16043704, ECO:0000269|PubMed:16144834, CC ECO:0000269|PubMed:16858407, ECO:0000269|PubMed:22579623, CC ECO:0000269|PubMed:22611194, ECO:0000269|PubMed:25736436}. CC -!- INTERACTION: CC Self; NbExp=5; IntAct=EBI-6116630, EBI-6116630; CC P27986:PIK3R1; NbExp=2; IntAct=EBI-6116630, EBI-79464; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass CC type I membrane protein. Endosome membrane. Early endosome CC {ECO:0000269|PubMed:25736436}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O15455-1; Sequence=Displayed; CC Name=2; CC IsoId=O15455-2; Sequence=VSP_054188; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Expressed at high level in placenta and CC pancreas. Also detected in CD11c+ immature dendritic cells. Only CC expressed in dendritic cells and not in other leukocytes, CC including monocyte precursors. TLR3 is the TLR that is expressed CC most strongly in the brain, especially in astrocytes, glia, and CC neurons. {ECO:0000269|PubMed:17085778}. CC -!- DOMAIN: ds-RNA binding is mediated by LRR 1 to 3, and LRR 17 to CC 18. CC -!- PTM: Heavily N-glycosylated, except on that part of the surface of CC the ectodomain that is involved in ligand binding. CC {ECO:0000269|PubMed:15961631, ECO:0000269|PubMed:16043704, CC ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:22579623}. CC -!- PTM: TLR3 signaling requires a proteolytic cleavage mediated by CC cathepsins CTSB and CTSH, the cleavage occurs between amino acids CC 252 and 346. The cleaved form of TLR3 is the predominant form CC found in endosomes. {ECO:0000269|PubMed:22611194}. CC -!- POLYMORPHISM: The Phe-412 allele (dbSNP:rs3775291) occurs with a CC frequency of 30% in populations with European and Asian ancestry, CC and confers some natural resistance to HIV-1 infection. CC -!- DISEASE: Encephalopathy, acute, infection-induced, Herpes- CC specific, 2 (IIAE2) [MIM:613002]: A rare complication of human CC herpesvirus 1 (HHV-1) infection, occurring in only a small CC minority of HHV-1 infected individuals. It is characterized by CC hemorrhagic necrosis of parts of the temporal and frontal lobes. CC Onset is over several days and involves fever, headache, seizures, CC stupor, and often coma, frequently with a fatal outcome. CC {ECO:0000269|PubMed:17872438}. Note=Disease susceptibility is CC associated with variations affecting the gene represented in this CC entry. TLR3 mutations predispose otherwise healthy individuals to CC isolated herpes simplex encephalitis through a mechanism that CC involves impaired IFNs production and reduced immune defense CC against viral infection in the central nervous system. CC -!- SIMILARITY: Belongs to the Toll-like receptor family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=TLR3base; Note=TLR3 mutation db; CC URL="http://structure.bmc.lu.se/idbase/TLR3base/"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; U88879; AAC34134.1; -; mRNA. DR EMBL; DQ445682; ABE01399.1; -; mRNA. DR EMBL; AB445631; BAG55028.1; -; mRNA. DR EMBL; DQ360814; ABC86908.1; -; Genomic_DNA. DR EMBL; DQ360815; ABC86909.1; -; Genomic_DNA. DR EMBL; DQ360816; ABC86910.1; -; Genomic_DNA. DR EMBL; AK302143; BAH13636.1; -; mRNA. DR EMBL; AK314208; BAG36884.1; -; mRNA. DR EMBL; AC104070; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471056; EAX04628.1; -; Genomic_DNA. DR EMBL; BC094737; AAH94737.1; -; mRNA. DR EMBL; BC096333; AAH96333.1; -; mRNA. DR EMBL; BC096334; AAH96334.1; -; mRNA. DR EMBL; BC096335; AAH96335.1; -; mRNA. DR CCDS; CCDS3846.1; -. [O15455-1] DR RefSeq; NP_003256.1; NM_003265.2. [O15455-1] DR RefSeq; XP_016864066.1; XM_017008577.1. DR UniGene; Hs.657724; -. DR PDB; 1ZIW; X-ray; 2.10 A; A=27-700. DR PDB; 2A0Z; X-ray; 2.40 A; A=22-703. DR PDB; 2MK9; NMR; -; A/B=698-730. DR PDB; 2MKA; NMR; -; A/B/C=698-730. DR PDB; 3ULU; X-ray; 3.52 A; A=22-702. DR PDB; 3ULV; X-ray; 3.52 A; A=22-702. DR PDB; 5GS0; X-ray; 3.27 A; A/B=27-697. DR PDBsum; 1ZIW; -. DR PDBsum; 2A0Z; -. DR PDBsum; 2MK9; -. DR PDBsum; 2MKA; -. DR PDBsum; 3ULU; -. DR PDBsum; 3ULV; -. DR PDBsum; 5GS0; -. DR ProteinModelPortal; O15455; -. DR SMR; O15455; -. DR BioGrid; 112953; 32. DR DIP; DIP-29660N; -. DR IntAct; O15455; 14. DR MINT; O15455; -. DR STRING; 9606.ENSP00000296795; -. DR ChEMBL; CHEMBL1075113; -. DR iPTMnet; O15455; -. DR PhosphoSitePlus; O15455; -. DR BioMuta; TLR3; -. DR EPD; O15455; -. DR jPOST; O15455; -. DR MaxQB; O15455; -. DR PaxDb; O15455; -. DR PeptideAtlas; O15455; -. DR PRIDE; O15455; -. DR ProteomicsDB; 48678; -. DR Ensembl; ENST00000296795; ENSP00000296795; ENSG00000164342. [O15455-1] DR Ensembl; ENST00000504367; ENSP00000423684; ENSG00000164342. [O15455-2] DR GeneID; 7098; -. DR KEGG; hsa:7098; -. DR UCSC; uc003iyq.4; human. [O15455-1] DR CTD; 7098; -. DR DisGeNET; 7098; -. DR EuPathDB; HostDB:ENSG00000164342.12; -. DR GeneCards; TLR3; -. DR HGNC; HGNC:11849; TLR3. DR HPA; CAB025658; -. DR MalaCards; TLR3; -. DR MIM; 603029; gene. DR MIM; 613002; phenotype. DR neXtProt; NX_O15455; -. DR OpenTargets; ENSG00000164342; -. DR Orphanet; 1930; Herpes simplex virus encephalitis. DR PharmGKB; PA36551; -. DR eggNOG; KOG4641; Eukaryota. DR eggNOG; COG4886; LUCA. DR GeneTree; ENSGT00940000159678; -. DR HOGENOM; HOG000251618; -. DR HOVERGEN; HBG023181; -. DR InParanoid; O15455; -. DR KO; K05401; -. DR OMA; NKYLQLT; -. DR OrthoDB; 737804at2759; -. DR PhylomeDB; O15455; -. DR TreeFam; TF325595; -. DR Reactome; R-HSA-1679131; Trafficking and processing of endosomal TLR. DR Reactome; R-HSA-168164; Toll Like Receptor 3 (TLR3) Cascade. DR Reactome; R-HSA-168927; TICAM1, RIP1-mediated IKK complex recruitment. DR Reactome; R-HSA-1810476; RIP-mediated NFkB activation via ZBP1. DR Reactome; R-HSA-5602410; TLR3 deficiency - HSE. DR Reactome; R-HSA-5602415; UNC93B1 deficiency - HSE. DR Reactome; R-HSA-5602566; TICAM1 deficiency - HSE. DR Reactome; R-HSA-5602571; TRAF3 deficiency - HSE. DR Reactome; R-HSA-9013957; TLR3-mediated TICAM1-dependent programmed cell death. DR Reactome; R-HSA-9013973; TICAM1-dependent activation of IRF3/IRF7. DR Reactome; R-HSA-9014325; TICAM1,TRAF6-dependent induction of TAK1 complex. DR SignaLink; O15455; -. DR SIGNOR; O15455; -. DR EvolutionaryTrace; O15455; -. DR GeneWiki; TLR_3; -. DR GenomeRNAi; 7098; -. DR PRO; PR:O15455; -. DR Proteomes; UP000005640; Chromosome 4. DR Bgee; ENSG00000164342; Expressed in 179 organ(s), highest expression level in placenta. DR ExpressionAtlas; O15455; baseline and differential. DR Genevisible; O15455; HS. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell. DR GO; GO:0036020; C:endolysosome membrane; TAS:Reactome. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0010008; C:endosome membrane; TAS:Reactome. DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome. DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc. DR GO; GO:0005622; C:intracellular; IDA:UniProtKB. DR GO; GO:0005765; C:lysosomal membrane; HDA:UniProtKB. DR GO; GO:0016020; C:membrane; NAS:UniProtKB. DR GO; GO:0003725; F:double-stranded RNA binding; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc. DR GO; GO:0004888; F:transmembrane signaling receptor activity; NAS:UniProtKB. DR GO; GO:0007250; P:activation of NF-kappaB-inducing kinase activity; NAS:UniProtKB. DR GO; GO:0097190; P:apoptotic signaling pathway; TAS:Reactome. DR GO; GO:0035690; P:cellular response to drug; IEA:Ensembl. DR GO; GO:0071360; P:cellular response to exogenous dsRNA; IEA:Ensembl. DR GO; GO:0035458; P:cellular response to interferon-beta; IEA:Ensembl. DR GO; GO:0071346; P:cellular response to interferon-gamma; IEA:Ensembl. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB. DR GO; GO:0042742; P:defense response to bacterium; TAS:ProtInc. DR GO; GO:0051607; P:defense response to virus; TAS:BHF-UCL. DR GO; GO:0009597; P:detection of virus; NAS:UniProtKB. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IDA:UniProtKB. DR GO; GO:0006972; P:hyperosmotic response; NAS:UniProtKB. DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; TAS:Reactome. DR GO; GO:0007252; P:I-kappaB phosphorylation; IDA:BHF-UCL. DR GO; GO:0045087; P:innate immune response; TAS:BHF-UCL. DR GO; GO:0008584; P:male gonad development; IEA:Ensembl. DR GO; GO:0001774; P:microglial cell activation; IEA:Ensembl. DR GO; GO:0002756; P:MyD88-independent toll-like receptor signaling pathway; TAS:Reactome. DR GO; GO:0070266; P:necroptotic process; TAS:Reactome. DR GO; GO:0097527; P:necroptotic signaling pathway; IDA:UniProtKB. DR GO; GO:0034128; P:negative regulation of MyD88-independent toll-like receptor signaling pathway; TAS:Reactome. DR GO; GO:0045671; P:negative regulation of osteoclast differentiation; NAS:UniProtKB. DR GO; GO:0045766; P:positive regulation of angiogenesis; IEA:Ensembl. DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl. DR GO; GO:0045080; P:positive regulation of chemokine biosynthetic process; IEA:Ensembl. DR GO; GO:0032722; P:positive regulation of chemokine production; IDA:BHF-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB. DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl. DR GO; GO:0050729; P:positive regulation of inflammatory response; IC:BHF-UCL. DR GO; GO:0045356; P:positive regulation of interferon-alpha biosynthetic process; IDA:UniProtKB. DR GO; GO:0045359; P:positive regulation of interferon-beta biosynthetic process; IDA:UniProtKB. DR GO; GO:0032728; P:positive regulation of interferon-beta production; ISS:BHF-UCL. DR GO; GO:0045078; P:positive regulation of interferon-gamma biosynthetic process; IDA:UniProtKB. DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISS:BHF-UCL. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:BHF-UCL. DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:BHF-UCL. DR GO; GO:0046330; P:positive regulation of JNK cascade; IEA:Ensembl. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IEA:Ensembl. DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IDA:BHF-UCL. DR GO; GO:0034123; P:positive regulation of toll-like receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:BHF-UCL. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:BHF-UCL. DR GO; GO:0034346; P:positive regulation of type III interferon production; IEA:Ensembl. DR GO; GO:0002730; P:regulation of dendritic cell cytokine production; IEA:Ensembl. DR GO; GO:0043330; P:response to exogenous dsRNA; IDA:MGI. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome. DR GO; GO:0002224; P:toll-like receptor signaling pathway; TAS:Reactome. DR GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome. 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; IPR027173; TLR3. DR InterPro; IPR035897; Toll_tir_struct_dom_sf. DR PANTHER; PTHR44599; PTHR44599; 1. DR Pfam; PF13516; LRR_6; 1. DR Pfam; PF13855; LRR_8; 6. DR Pfam; PF01582; TIR; 1. DR SMART; SM00369; LRR_TYP; 16. DR SMART; SM00082; LRRCT; 1. DR SMART; SM00255; TIR; 1. DR SUPFAM; SSF52200; SSF52200; 1. DR PROSITE; PS51450; LRR; 19. DR PROSITE; PS50104; TIR; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complete proteome; KW Direct protein sequencing; Disease mutation; Disulfide bond; KW Endoplasmic reticulum; Endosome; Glycoprotein; Immunity; KW Inflammatory response; Innate immunity; Leucine-rich repeat; Membrane; KW Phosphoprotein; Polymorphism; Receptor; Reference proteome; Repeat; KW RNA-binding; Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1 23 {ECO:0000269|PubMed:15340161}. FT CHAIN 24 904 Toll-like receptor 3. FT /FTId=PRO_0000034715. FT TOPO_DOM 24 704 Lumenal. {ECO:0000255}. FT TRANSMEM 705 725 Helical. {ECO:0000255}. FT TOPO_DOM 726 904 Cytoplasmic. {ECO:0000255}. FT DOMAIN 24 51 LRRNT. FT REPEAT 52 73 LRR 1. FT REPEAT 76 97 LRR 2. FT REPEAT 100 121 LRR 3. FT REPEAT 124 145 LRR 4. FT REPEAT 148 168 LRR 5. FT REPEAT 172 193 LRR 6. FT REPEAT 198 219 LRR 7. FT REPEAT 222 244 LRR 8. FT REPEAT 249 270 LRR 9. FT REPEAT 275 296 LRR 10. FT REPEAT 299 320 LRR 11. FT REPEAT 323 344 LRR 12. FT REPEAT 356 377 LRR 13. FT REPEAT 380 400 LRR 14. FT REPEAT 408 429 LRR 15. FT REPEAT 432 454 LRR 16. FT REPEAT 465 486 LRR 17. FT REPEAT 507 528 LRR 18. FT REPEAT 531 552 LRR 19. FT REPEAT 563 584 LRR 20. FT REPEAT 587 608 LRR 21. FT REPEAT 611 632 LRR 22. FT DOMAIN 645 698 LRRCT. FT DOMAIN 754 896 TIR. {ECO:0000255|PROSITE- FT ProRule:PRU00204}. FT MOD_RES 759 759 Phosphotyrosine. FT {ECO:0000269|PubMed:17178723}. FT MOD_RES 858 858 Phosphotyrosine. FT {ECO:0000269|PubMed:17178723}. FT CARBOHYD 52 52 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16043704, FT ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:22579623}. FT CARBOHYD 57 57 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:19159218}. FT CARBOHYD 70 70 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16043704, FT ECO:0000269|PubMed:22579623}. FT CARBOHYD 124 124 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:15961631, FT ECO:0000269|PubMed:22579623}. FT CARBOHYD 196 196 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16043704}. FT CARBOHYD 247 247 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:22579623}. FT CARBOHYD 252 252 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:15961631, FT ECO:0000269|PubMed:16043704, FT ECO:0000269|PubMed:22579623}. FT CARBOHYD 265 265 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16043704, FT ECO:0000269|PubMed:22579623}. FT CARBOHYD 275 275 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:15961631, FT ECO:0000269|PubMed:16043704, FT ECO:0000269|PubMed:22579623}. FT CARBOHYD 291 291 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:15961631, FT ECO:0000269|PubMed:16043704, FT ECO:0000269|PubMed:22579623}. FT CARBOHYD 398 398 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:15961631, FT ECO:0000269|PubMed:16043704, FT ECO:0000269|PubMed:22579623}. FT CARBOHYD 413 413 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:15961631, FT ECO:0000269|PubMed:16043704, FT ECO:0000269|PubMed:22579623}. FT CARBOHYD 507 507 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:15961631, FT ECO:0000269|PubMed:16043704, FT ECO:0000269|PubMed:22579623}. FT CARBOHYD 636 636 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:16043704}. FT CARBOHYD 662 662 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 28 37 FT DISULFID 95 122 FT DISULFID 649 677 FT DISULFID 651 696 FT VAR_SEQ 1 277 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_054188. FT VARIANT 284 284 N -> I (in dbSNP:rs5743316). FT /FTId=VAR_052361. FT VARIANT 307 307 Y -> D (in dbSNP:rs5743317). FT /FTId=VAR_052362. FT VARIANT 412 412 L -> F (in dbSNP:rs3775291). FT {ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:18753640, FT ECO:0000269|PubMed:22174453, FT ECO:0000269|Ref.4}. FT /FTId=VAR_021976. FT VARIANT 554 554 P -> S (in IIAE2; causes TLR3 deficiency FT and predisposition to herpes simplex FT encephalitis; dbSNP:rs121434431). FT {ECO:0000269|PubMed:17872438}. FT /FTId=VAR_054887. FT VARIANT 737 737 S -> T (in dbSNP:rs5743318). FT /FTId=VAR_024664. FT MUTAGEN 95 95 C->A: Reduced response to ds-RNA. FT {ECO:0000269|PubMed:16144834}. FT MUTAGEN 122 122 C->A: Reduced response to ds-RNA. FT {ECO:0000269|PubMed:16144834}. FT MUTAGEN 196 196 N->G: Reduced expression levels; when FT associated with R-247. FT {ECO:0000269|PubMed:16144834}. FT MUTAGEN 247 247 N->R: Reduced response to ds-RNA. Reduced FT expression levels; when associated with FT G-196. {ECO:0000269|PubMed:16144834}. FT MUTAGEN 539 539 H->A: No effect. FT {ECO:0000269|PubMed:16720699}. FT MUTAGEN 539 539 H->E: Loss of RNA binding. Constitutive FT activation of NF-kappa-B. FT {ECO:0000269|PubMed:16720699}. FT MUTAGEN 541 541 N->A: Loss of RNA binding. Abolishes FT activation of NF-kappa-B. FT {ECO:0000269|PubMed:16720699}. FT MUTAGEN 759 759 Y->F: Reduced activation of NF-kappa-B in FT response to ds-RNA. Reduced induction of FT IL-8 in response to ds-RNA. Loss of FT interaction with WDFY1. FT {ECO:0000269|PubMed:17178723, FT ECO:0000269|PubMed:25736436}. FT MUTAGEN 858 858 Y->F: Loss of interaction with WDFY1. FT {ECO:0000269|PubMed:25736436}. FT CONFLICT 290 290 G -> R (in Ref. 5; BAG36884). FT {ECO:0000305}. FT CONFLICT 575 575 D -> N (in Ref. 8; AAH94737). FT {ECO:0000305}. FT CONFLICT 605 605 V -> A (in Ref. 5; BAG36884). FT {ECO:0000305}. FT CONFLICT 663 663 E -> G (in Ref. 5; BAG36884). FT {ECO:0000305}. FT STRAND 31 36 {ECO:0000244|PDB:1ZIW}. FT STRAND 47 49 {ECO:0000244|PDB:2A0Z}. FT STRAND 54 57 {ECO:0000244|PDB:1ZIW}. FT HELIX 68 74 {ECO:0000244|PDB:1ZIW}. FT STRAND 78 81 {ECO:0000244|PDB:1ZIW}. FT HELIX 94 97 {ECO:0000244|PDB:1ZIW}. FT STRAND 103 105 {ECO:0000244|PDB:1ZIW}. FT STRAND 108 110 {ECO:0000244|PDB:5GS0}. FT TURN 118 121 {ECO:0000244|PDB:1ZIW}. FT STRAND 126 129 {ECO:0000244|PDB:1ZIW}. FT TURN 142 145 {ECO:0000244|PDB:1ZIW}. FT STRAND 151 153 {ECO:0000244|PDB:1ZIW}. FT STRAND 166 168 {ECO:0000244|PDB:1ZIW}. FT STRAND 175 177 {ECO:0000244|PDB:1ZIW}. FT HELIX 188 191 {ECO:0000244|PDB:1ZIW}. FT HELIX 192 194 {ECO:0000244|PDB:1ZIW}. FT STRAND 198 203 {ECO:0000244|PDB:1ZIW}. FT HELIX 216 219 {ECO:0000244|PDB:1ZIW}. FT STRAND 220 223 {ECO:0000244|PDB:1ZIW}. FT STRAND 225 227 {ECO:0000244|PDB:1ZIW}. FT HELIX 234 245 {ECO:0000244|PDB:1ZIW}. FT STRAND 252 254 {ECO:0000244|PDB:1ZIW}. FT TURN 265 268 {ECO:0000244|PDB:1ZIW}. FT HELIX 269 273 {ECO:0000244|PDB:1ZIW}. FT STRAND 278 280 {ECO:0000244|PDB:1ZIW}. FT TURN 291 296 {ECO:0000244|PDB:1ZIW}. FT STRAND 302 304 {ECO:0000244|PDB:1ZIW}. FT STRAND 310 313 {ECO:0000244|PDB:1ZIW}. FT TURN 315 320 {ECO:0000244|PDB:1ZIW}. FT STRAND 326 328 {ECO:0000244|PDB:1ZIW}. FT STRAND 338 340 {ECO:0000244|PDB:2A0Z}. FT TURN 348 353 {ECO:0000244|PDB:1ZIW}. FT STRAND 359 361 {ECO:0000244|PDB:1ZIW}. FT TURN 372 377 {ECO:0000244|PDB:1ZIW}. FT STRAND 383 385 {ECO:0000244|PDB:1ZIW}. FT TURN 398 401 {ECO:0000244|PDB:1ZIW}. FT HELIX 402 404 {ECO:0000244|PDB:1ZIW}. FT STRAND 411 413 {ECO:0000244|PDB:1ZIW}. FT TURN 424 429 {ECO:0000244|PDB:1ZIW}. FT STRAND 435 437 {ECO:0000244|PDB:1ZIW}. FT STRAND 444 446 {ECO:0000244|PDB:1ZIW}. FT HELIX 450 452 {ECO:0000244|PDB:1ZIW}. FT STRAND 460 462 {ECO:0000244|PDB:1ZIW}. FT STRAND 467 470 {ECO:0000244|PDB:1ZIW}. FT TURN 473 478 {ECO:0000244|PDB:1ZIW}. FT STRAND 484 486 {ECO:0000244|PDB:1ZIW}. FT TURN 501 504 {ECO:0000244|PDB:1ZIW}. FT STRAND 510 512 {ECO:0000244|PDB:1ZIW}. FT TURN 523 528 {ECO:0000244|PDB:1ZIW}. FT STRAND 534 536 {ECO:0000244|PDB:1ZIW}. FT HELIX 543 546 {ECO:0000244|PDB:1ZIW}. FT TURN 557 560 {ECO:0000244|PDB:1ZIW}. FT STRAND 566 568 {ECO:0000244|PDB:1ZIW}. FT TURN 579 584 {ECO:0000244|PDB:1ZIW}. FT STRAND 590 592 {ECO:0000244|PDB:1ZIW}. FT TURN 603 608 {ECO:0000244|PDB:1ZIW}. FT STRAND 614 616 {ECO:0000244|PDB:1ZIW}. FT HELIX 627 634 {ECO:0000244|PDB:1ZIW}. FT STRAND 638 641 {ECO:0000244|PDB:1ZIW}. FT STRAND 655 658 {ECO:0000244|PDB:1ZIW}. FT HELIX 671 674 {ECO:0000244|PDB:2A0Z}. FT STRAND 676 680 {ECO:0000244|PDB:2A0Z}. FT HELIX 688 690 {ECO:0000244|PDB:2A0Z}. FT HELIX 700 727 {ECO:0000244|PDB:2MK9}. SQ SEQUENCE 904 AA; 103829 MW; 034E05ECA7A4D2F7 CRC64; MRQTLPCIYF WGGLLPFGML CASSTTKCTV SHEVADCSHL KLTQVPDDLP TNITVLNLTH NQLRRLPAAN FTRYSQLTSL DVGFNTISKL EPELCQKLPM LKVLNLQHNE LSQLSDKTFA FCTNLTELHL MSNSIQKIKN NPFVKQKNLI TLDLSHNGLS STKLGTQVQL ENLQELLLSN NKIQALKSEE LDIFANSSLK KLELSSNQIK EFSPGCFHAI GRLFGLFLNN VQLGPSLTEK LCLELANTSI RNLSLSNSQL STTSNTTFLG LKWTNLTMLD LSYNNLNVVG NDSFAWLPQL EYFFLEYNNI QHLFSHSLHG LFNVRYLNLK RSFTKQSISL ASLPKIDDFS FQWLKCLEHL NMEDNDIPGI KSNMFTGLIN LKYLSLSNSF TSLRTLTNET FVSLAHSPLH ILNLTKNKIS KIESDAFSWL GHLEVLDLGL NEIGQELTGQ EWRGLENIFE IYLSYNKYLQ LTRNSFALVP SLQRLMLRRV ALKNVDSSPS PFQPLRNLTI LDLSNNNIAN INDDMLEGLE KLEILDLQHN NLARLWKHAN PGGPIYFLKG LSHLHILNLE SNGFDEIPVE VFKDLFELKI IDLGLNNLNT LPASVFNNQV SLKSLNLQKN LITSVEKKVF GPAFRNLTEL DMRFNPFDCT CESIAWFVNW INETHTNIPE LSSHYLCNTP PHYHGFPVRL FDTSSCKDSA PFELFFMINT SILLIFIFIV LLIHFEGWRI SFYWNVSVHR VLGFKEIDRQ TEQFEYAAYI IHAYKDKDWV WEHFSSMEKE DQSLKFCLEE RDFEAGVFEL EAIVNSIKRS RKIIFVITHH LLKDPLCKRF KVHHAVQQAI EQNLDSIILV FLEEIPDYKL NHALCLRRGM FKSHCILNWP VQKERIGAFR HKLQVALGSK NSVH //