ID   TLR3_MOUSE              Reviewed;         905 AA.
AC   Q99MB1; Q91ZM4;
DT   31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT   31-JAN-2002, sequence version 2.
DT   27-MAR-2024, entry version 194.
DE   RecName: Full=Toll-like receptor 3 {ECO:0000305};
DE   AltName: CD_antigen=CD283;
DE   Flags: Precursor;
GN   Name=Tlr3 {ECO:0000312|MGI:MGI:2156367};
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 [MRNA].
RC   STRAIN=129/Sv;
RX   PubMed=11607032; DOI=10.1038/35099560;
RA   Alexopoulou L., Holt A.C., Medzhitov R., Flavell R.A.;
RT   "Recognition of double-stranded RNA and activation of NF-kappaB by Toll-
RT   like receptor 3.";
RL   Nature 413:732-738(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=BALB/c X NIH; TISSUE=Macrophage;
RA   Applequist S.E., Ljunggren H.G.;
RT   "Molecular cloning of mouse Toll-like receptor 3 cDNA.";
RL   Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Spinal ganglion;
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   [4]
RP   FUNCTION IN CYTOMEGALOVIRUS INFECTION.
RX   PubMed=14993594; DOI=10.1073/pnas.0400525101;
RA   Tabeta K., Georgel P., Janssen E., Du X., Hoebe K., Crozat K., Mudd S.,
RA   Shamel L., Sovath S., Goode J., Alexopoulou L., Flavell R.A., Beutler B.;
RT   "Toll-like receptors 9 and 3 as essential components of innate immune
RT   defense against mouse cytomegalovirus infection.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:3516-3521(2004).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH UNC93B1.
RX   PubMed=17452530; DOI=10.1083/jcb.200612056;
RA   Brinkmann M.M., Spooner E., Hoebe K., Beutler B., Ploegh H.L., Kim Y.M.;
RT   "The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9
RT   is crucial for TLR signaling.";
RL   J. Cell Biol. 177:265-275(2007).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Spleen;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [7]
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   [8]
RP   FUNCTION, UBIQUITINATION BY RNF170, AND MUTAGENESIS OF LYS-766.
RX   PubMed=31076723; DOI=10.1038/s41423-019-0236-y;
RA   Song X., Liu S., Wang W., Ma Z., Cao X., Jiang M.;
RT   "E3 ubiquitin ligase RNF170 inhibits innate immune responses by targeting
RT   and degrading TLR3 in murine cells.";
RL   Cell. Mol. Immunol. 17:865-874(2020).
RN   [9]
RP   X-RAY CRYSTALLOGRAPHY (2.66 ANGSTROMS) OF 28-704 IN COMPLEX WITH DS-RNA,
RP   SUBUNIT, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-71; ASN-197; ASN-253;
RP   ASN-276; ASN-292; ASN-399; ASN-414; ASN-425; ASN-508; ASN-663 AND ASN-668.
RX   PubMed=18420935; DOI=10.1126/science.1155406;
RA   Liu L., Botos I., Wang Y., Leonard J.N., Shiloach J., Segal D.M.,
RA   Davies D.R.;
RT   "Structural basis of toll-like receptor 3 signaling with double-stranded
RT   RNA.";
RL   Science 320:379-381(2008).
RN   [10] {ECO:0007744|PDB:7C77}
RP   STRUCTURE BY ELECTRON MICROSCOPY (3.30 ANGSTROMS) IN COMPLEX WITH UNC93B1,
RP   AND INTERACTION WITH UNC93B1.
RX   PubMed=33432245; DOI=10.1038/s41594-020-00542-w;
RA   Ishida H., Asami J., Zhang Z., Nishizawa T., Shigematsu H., Ohto U.,
RA   Shimizu T.;
RT   "Cryo-EM structures of Toll-like receptors in complex with UNC93B1.";
RL   Nat. Struct. Mol. Biol. 28:173-180(2021).
CC   -!- FUNCTION: Key component of innate and adaptive immunity. TLRs (Toll-
CC       like receptors) control host immune response against pathogens through
CC       recognition of molecular patterns specific to microorganisms. TLR3 is a
CC       nucleotide-sensing TLR which is activated by double-stranded RNA, a
CC       sign of viral infection. Acts via the adapter TRIF/TICAM1, leading to
CC       NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion
CC       and the inflammatory response (By similarity). {ECO:0000250,
CC       ECO:0000269|PubMed:14993594}.
CC   -!- SUBUNIT: Monomer and homodimer; dimerization is triggered by ligand-
CC       binding, the signaling unit is composed of one ds-RNA of around 40 bp
CC       and two TLR3 molecules, and lateral clustering of signaling units along
CC       the length of the ds-RNA ligand is required for TLR3 signal
CC       transduction. Interacts (via transmembrane domain) with UNC93B1; the
CC       interaction is required for transport from the ER to the endosomes
CC       (PubMed:33432245). Interacts with SRC; upon binding of double-stranded
CC       RNA (By similarity). Interacts with TICAM1 (via the TIR domain) in
CC       response to poly(I:C) and this interaction is enhanced in the presence
CC       of WDFY1 (PubMed:25736436). The tyrosine-phosphorylated form (via TIR
CC       domain) interacts with WDFY1 (via WD repeat 2) in response to poly(I:C)
CC       (PubMed:25736436). Ubiquitinated by RNF170 at Lys-766 via 'Lys-48'-
CC       linked ubiquitin chains; leading to TLR3 proteasomal degradation
CC       (PubMed:31076723). {ECO:0000250|UniProtKB:O15455,
CC       ECO:0000269|PubMed:25736436, ECO:0000269|PubMed:31076723,
CC       ECO:0000269|PubMed:33432245}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type
CC       I membrane protein. Endosome membrane {ECO:0000250|UniProtKB:O15455}.
CC       Early endosome {ECO:0000250|UniProtKB:O15455}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in lung. After intraperitoneal
CC       injection of lipopolysaccharide, highly expressed in brain, heart,
CC       kidney, liver, lung and spleen.
CC   -!- DOMAIN: ds-RNA binding is mediated by LRR 1 to 3, and LRR 17 to 18.
CC   -!- PTM: TLR3 signaling requires a proteolytic cleavage mediated by
CC       cathepsins CTSB and CTSH, the cleavage occurs between amino acids 252
CC       and 346. The cleaved form of TLR3 is the predominant form found in
CC       endosomes (By similarity). {ECO:0000250}.
CC   -!- PTM: Ubiquitinated by TRIM3; leading to recognition and sorting of
CC       polyubiquitinated TLR3 by the ESCRT complexes. Ubiquitinated by ZNRF1
CC       via 'Lys-63'-linked ubiquitin chains; leading to TLR3 lysosomal
CC       trafficking and degradation. {ECO:0000250|UniProtKB:O15455}.
CC   -!- SIMILARITY: Belongs to the Toll-like receptor family. {ECO:0000305}.
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; AF420279; AAL27007.1; -; mRNA.
DR   EMBL; AF355152; AAK26117.1; -; mRNA.
DR   EMBL; AK083977; BAC39082.1; -; mRNA.
DR   CCDS; CCDS22278.1; -.
DR   RefSeq; NP_569054.2; NM_126166.4.
DR   RefSeq; XP_006509341.1; XM_006509278.3.
DR   RefSeq; XP_006509342.1; XM_006509279.2.
DR   RefSeq; XP_006509343.1; XM_006509280.2.
DR   RefSeq; XP_006509344.1; XM_006509281.3.
DR   RefSeq; XP_006509345.1; XM_006509282.3.
DR   RefSeq; XP_006509346.1; XM_006509283.3.
DR   PDB; 3CIG; X-ray; 2.66 A; A=28-704.
DR   PDB; 3CIY; X-ray; 3.41 A; A/B=28-704.
DR   PDB; 7C77; EM; 3.30 A; A=1-905.
DR   PDB; 7DA7; EM; 3.47 A; A/B=28-698.
DR   PDB; 7DAS; EM; 3.64 A; A/B=28-698.
DR   PDB; 7WM4; EM; 3.20 A; C/D/E/F=26-705.
DR   PDBsum; 3CIG; -.
DR   PDBsum; 3CIY; -.
DR   PDBsum; 7C77; -.
DR   PDBsum; 7DA7; -.
DR   PDBsum; 7DAS; -.
DR   PDBsum; 7WM4; -.
DR   AlphaFoldDB; Q99MB1; -.
DR   EMDB; EMD-30294; -.
DR   EMDB; EMD-30624; -.
DR   EMDB; EMD-30626; -.
DR   EMDB; EMD-32599; -.
DR   SMR; Q99MB1; -.
DR   BioGRID; 228338; 13.
DR   IntAct; Q99MB1; 1.
DR   STRING; 10090.ENSMUSP00000034056; -.
DR   ChEMBL; CHEMBL2146340; -.
DR   GlyCosmos; Q99MB1; 15 sites, No reported glycans.
DR   GlyGen; Q99MB1; 15 sites.
DR   iPTMnet; Q99MB1; -.
DR   PhosphoSitePlus; Q99MB1; -.
DR   MaxQB; Q99MB1; -.
DR   PaxDb; 10090-ENSMUSP00000034056; -.
DR   ProteomicsDB; 259207; -.
DR   ABCD; Q99MB1; 10 sequenced antibodies.
DR   Antibodypedia; 17502; 1231 antibodies from 48 providers.
DR   DNASU; 142980; -.
DR   Ensembl; ENSMUST00000034056.12; ENSMUSP00000034056.5; ENSMUSG00000031639.13.
DR   Ensembl; ENSMUST00000167106.3; ENSMUSP00000126556.2; ENSMUSG00000031639.13.
DR   Ensembl; ENSMUST00000209772.2; ENSMUSP00000147738.2; ENSMUSG00000031639.13.
DR   GeneID; 142980; -.
DR   KEGG; mmu:142980; -.
DR   UCSC; uc009loy.1; mouse.
DR   AGR; MGI:2156367; -.
DR   CTD; 7098; -.
DR   MGI; MGI:2156367; Tlr3.
DR   VEuPathDB; HostDB:ENSMUSG00000031639; -.
DR   eggNOG; KOG4641; Eukaryota.
DR   GeneTree; ENSGT00940000159678; -.
DR   HOGENOM; CLU_006000_4_1_1; -.
DR   InParanoid; Q99MB1; -.
DR   OMA; CKDVAPF; -.
DR   OrthoDB; 3428126at2759; -.
DR   PhylomeDB; Q99MB1; -.
DR   TreeFam; TF325595; -.
DR   BioGRID-ORCS; 142980; 4 hits in 76 CRISPR screens.
DR   ChiTaRS; Tlr3; mouse.
DR   EvolutionaryTrace; Q99MB1; -.
DR   PRO; PR:Q99MB1; -.
DR   Proteomes; UP000000589; Chromosome 8.
DR   RNAct; Q99MB1; Protein.
DR   Bgee; ENSMUSG00000031639; Expressed in conjunctival fornix and 212 other cell types or tissues.
DR   ExpressionAtlas; Q99MB1; baseline and differential.
DR   GO; GO:0009986; C:cell surface; ISO:MGI.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0005769; C:early endosome; ISO:MGI.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProt.
DR   GO; GO:0003725; F:double-stranded RNA binding; ISS:UniProtKB.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0038187; F:pattern recognition receptor activity; IDA:MGI.
DR   GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR   GO; GO:0004888; F:transmembrane signaling receptor activity; IDA:UniProt.
DR   GO; GO:0071360; P:cellular response to exogenous dsRNA; IDA:MGI.
DR   GO; GO:0035458; P:cellular response to interferon-beta; IEA:Ensembl.
DR   GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR   GO; GO:0071346; P:cellular response to type II interferon; IEA:Ensembl.
DR   GO; GO:0098586; P:cellular response to virus; IMP:MGI.
DR   GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR   GO; GO:0006952; P:defense response; IMP:MGI.
DR   GO; GO:0051607; P:defense response to virus; IGI:MGI.
DR   GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISO:MGI.
DR   GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR   GO; GO:0090594; P:inflammatory response to wounding; IDA:UniProt.
DR   GO; GO:0045087; P:innate immune response; TAS:BHF-UCL.
DR   GO; GO:0007254; P:JNK cascade; IDA:MGI.
DR   GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR   GO; GO:0000165; P:MAPK cascade; IMP:MGI.
DR   GO; GO:0001774; P:microglial cell activation; ISO:MGI.
DR   GO; GO:0097527; P:necroptotic signaling pathway; ISO:MGI.
DR   GO; GO:0045766; P:positive regulation of angiogenesis; IGI:BHF-UCL.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl.
DR   GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IDA:MGI.
DR   GO; GO:0032722; P:positive regulation of chemokine production; IMP:MGI.
DR   GO; GO:1900017; P:positive regulation of cytokine production involved in inflammatory response; IDA:UniProt.
DR   GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR   GO; GO:0032727; P:positive regulation of interferon-alpha production; ISS:UniProtKB.
DR   GO; GO:0032728; P:positive regulation of interferon-beta production; IDA:BHF-UCL.
DR   GO; GO:0032735; P:positive regulation of interleukin-12 production; IDA: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; ISO:MGI.
DR   GO; GO:0046330; P:positive regulation of JNK cascade; IDA:MGI.
DR   GO; GO:0060907; P:positive regulation of macrophage cytokine production; IDA:MGI.
DR   GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; ISO: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:0032481; P:positive regulation of type I interferon production; IDA:MGI.
DR   GO; GO:0032729; P:positive regulation of type II interferon production; ISS:UniProtKB.
DR   GO; GO:0034346; P:positive regulation of type III interferon production; IDA:MGI.
DR   GO; GO:0002730; P:regulation of dendritic cell cytokine production; IDA:MGI.
DR   GO; GO:0043331; P:response to dsRNA; ISO:MGI.
DR   GO; GO:0043330; P:response to exogenous dsRNA; IMP:MGI.
DR   GO; GO:0009615; P:response to virus; IMP:MGI.
DR   GO; GO:0034138; P:toll-like receptor 3 signaling pathway; ISO:MGI.
DR   GO; GO:0002224; P:toll-like receptor signaling pathway; ISO:MGI.
DR   GO; GO:0034343; P:type III interferon production; IDA:MGI.
DR   Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1.
DR   Gene3D; 3.40.50.10140; Toll/interleukin-1 receptor homology (TIR) domain; 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; IPR041015; TLR3_TMD.
DR   InterPro; IPR017241; Toll-like_receptor.
DR   InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR   PANTHER; PTHR24365; TOLL-LIKE RECEPTOR; 1.
DR   PANTHER; PTHR24365:SF524; TOLL-LIKE RECEPTOR 3; 1.
DR   Pfam; PF00560; LRR_1; 1.
DR   Pfam; PF13855; LRR_8; 6.
DR   Pfam; PF01582; TIR; 1.
DR   Pfam; PF17968; Tlr3_TMD; 1.
DR   PRINTS; PR00019; LEURICHRPT.
DR   SMART; SM00365; LRR_SD22; 7.
DR   SMART; SM00369; LRR_TYP; 16.
DR   SMART; SM00082; LRRCT; 1.
DR   SMART; SM00255; TIR; 1.
DR   SUPFAM; SSF52058; L domain-like; 2.
DR   SUPFAM; SSF52200; Toll/Interleukin receptor TIR domain; 1.
DR   PROSITE; PS51450; LRR; 18.
DR   PROSITE; PS50104; TIR; 1.
DR   Genevisible; Q99MB1; MM.
PE   1: Evidence at protein level;
KW   3D-structure; Disulfide bond; Endoplasmic reticulum; Endosome;
KW   Glycoprotein; Immunity; Inflammatory response; Innate immunity;
KW   Isopeptide bond; Leucine-rich repeat; Membrane; Phosphoprotein; Receptor;
KW   Reference proteome; Repeat; RNA-binding; Signal; Transmembrane;
KW   Transmembrane helix; Ubl conjugation.
FT   SIGNAL          1..25
FT                   /evidence="ECO:0000255"
FT   CHAIN           26..905
FT                   /note="Toll-like receptor 3"
FT                   /id="PRO_0000034716"
FT   TOPO_DOM        26..705
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        706..726
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        727..905
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          26..52
FT                   /note="LRRNT"
FT   REPEAT          53..74
FT                   /note="LRR 1"
FT   REPEAT          77..98
FT                   /note="LRR 2"
FT   REPEAT          101..122
FT                   /note="LRR 3"
FT   REPEAT          125..146
FT                   /note="LRR 4"
FT   REPEAT          149..170
FT                   /note="LRR 5"
FT   REPEAT          173..196
FT                   /note="LRR 6"
FT   REPEAT          199..220
FT                   /note="LRR 7"
FT   REPEAT          250..271
FT                   /note="LRR 8"
FT   REPEAT          276..297
FT                   /note="LRR 9"
FT   REPEAT          300..321
FT                   /note="LRR 10"
FT   REPEAT          324..345
FT                   /note="LRR 11"
FT   REPEAT          357..378
FT                   /note="LRR 12"
FT   REPEAT          381..401
FT                   /note="LRR 13"
FT   REPEAT          409..430
FT                   /note="LRR 14"
FT   REPEAT          433..454
FT                   /note="LRR 15"
FT   REPEAT          458..479
FT                   /note="LRR 16"
FT   REPEAT          482..502
FT                   /note="LRR 17"
FT   REPEAT          508..529
FT                   /note="LRR 18"
FT   REPEAT          532..553
FT                   /note="LRR 19"
FT   REPEAT          564..585
FT                   /note="LRR 20"
FT   REPEAT          588..609
FT                   /note="LRR 21"
FT   REPEAT          612..633
FT                   /note="LRR 22"
FT   DOMAIN          646..699
FT                   /note="LRRCT"
FT   DOMAIN          755..898
FT                   /note="TIR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT   MOD_RES         760
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:O15455"
FT   MOD_RES         859
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:O15455"
FT   CARBOHYD        53
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        58
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        71
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:18420935"
FT   CARBOHYD        125
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        197
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:18420935"
FT   CARBOHYD        248
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        253
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:18420935"
FT   CARBOHYD        276
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:18420935"
FT   CARBOHYD        292
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:18420935"
FT   CARBOHYD        399
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:18420935"
FT   CARBOHYD        414
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:18420935"
FT   CARBOHYD        425
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:18420935"
FT   CARBOHYD        508
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:18420935"
FT   CARBOHYD        663
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:18420935"
FT   CARBOHYD        668
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:18420935"
FT   DISULFID        29..38
FT                   /evidence="ECO:0000269|PubMed:18420935"
FT   DISULFID        96..123
FT                   /evidence="ECO:0000269|PubMed:18420935"
FT   DISULFID        650..678
FT                   /evidence="ECO:0000269|PubMed:18420935"
FT   DISULFID        652..697
FT                   /evidence="ECO:0000269|PubMed:18420935"
FT   CROSSLNK        766
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000250|UniProtKB:O15455"
FT   CROSSLNK        813
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000250|UniProtKB:O15455"
FT   CROSSLNK        832
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000250|UniProtKB:O15455"
FT   CONFLICT        670
FT                   /note="S -> F (in Ref. 2; AAK26117)"
FT                   /evidence="ECO:0000305"
FT   STRAND          33..35
FT                   /evidence="ECO:0007829|PDB:7WM4"
FT   STRAND          55..58
FT                   /evidence="ECO:0007829|PDB:7WM4"
FT   TURN            69..72
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   TURN            74..77
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          79..82
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   HELIX           94..98
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          104..106
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   HELIX           117..120
FT                   /evidence="ECO:0007829|PDB:7WM4"
FT   STRAND          128..130
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   TURN            143..146
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          152..154
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          167..169
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          176..178
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   HELIX           190..195
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          199..204
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   TURN            215..220
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          221..224
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          226..228
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   HELIX           236..246
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          247..249
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          253..255
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          262..264
FT                   /evidence="ECO:0007829|PDB:3CIY"
FT   TURN            266..269
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   HELIX           270..272
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          279..281
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   TURN            292..297
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          303..305
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   TURN            316..321
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          327..329
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          339..341
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   TURN            349..354
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          360..362
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   TURN            373..378
FT                   /evidence="ECO:0007829|PDB:3CIY"
FT   STRAND          384..386
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          391..393
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          395..397
FT                   /evidence="ECO:0007829|PDB:7WM4"
FT   TURN            399..402
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   HELIX           403..405
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          412..414
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   TURN            425..430
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          436..438
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          445..447
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   HELIX           451..453
FT                   /evidence="ECO:0007829|PDB:7WM4"
FT   STRAND          461..463
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          468..471
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   TURN            474..479
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          485..487
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          493..495
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          498..500
FT                   /evidence="ECO:0007829|PDB:7WM4"
FT   TURN            502..505
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          511..513
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   TURN            524..529
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          535..537
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   HELIX           544..547
FT                   /evidence="ECO:0007829|PDB:7C77"
FT   STRAND          551..554
FT                   /evidence="ECO:0007829|PDB:7C77"
FT   STRAND          567..569
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   TURN            580..585
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          591..593
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   TURN            604..609
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          615..617
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   HELIX           628..635
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          639..642
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   HELIX           652..664
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          668..671
FT                   /evidence="ECO:0007829|PDB:7C77"
FT   HELIX           672..675
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          677..681
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   HELIX           682..684
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   HELIX           689..691
FT                   /evidence="ECO:0007829|PDB:3CIG"
FT   STRAND          695..697
FT                   /evidence="ECO:0007829|PDB:7C77"
FT   TURN            698..700
FT                   /evidence="ECO:0007829|PDB:7C77"
FT   HELIX           703..726
FT                   /evidence="ECO:0007829|PDB:7C77"
SQ   SEQUENCE   905 AA;  103671 MW;  8EA6DBA9818E14B4 CRC64;
     MKGCSSYLMY SFGGLLSLWI LLVSSTNQCT VRYNVADCSH LKLTHIPDDL PSNITVLNLT
     HNQLRRLPPT NFTRYSQLAI LDAGFNSISK LEPELCQILP LLKVLNLQHN ELSQISDQTF
     VFCTNLTELD LMSNSIHKIK SNPFKNQKNL IKLDLSHNGL SSTKLGTGVQ LENLQELLLA
     KNKILALRSE ELEFLGNSSL RKLDLSSNPL KEFSPGCFQT IGKLFALLLN NAQLNPHLTE
     KLCWELSNTS IQNLSLANNQ LLATSESTFS GLKWTNLTQL DLSYNNLHDV GNGSFSYLPS
     LRYLSLEYNN IQRLSPRSFY GLSNLRYLSL KRAFTKQSVS LASHPNIDDF SFQWLKYLEY
     LNMDDNNIPS TKSNTFTGLV SLKYLSLSKT FTSLQTLTNE TFVSLAHSPL LTLNLTKNHI
     SKIANGTFSW LGQLRILDLG LNEIEQKLSG QEWRGLRNIF EIYLSYNKYL QLSTSSFALV
     PSLQRLMLRR VALKNVDISP SPFRPLRNLT ILDLSNNNIA NINEDLLEGL ENLEILDFQH
     NNLARLWKRA NPGGPVNFLK GLSHLHILNL ESNGLDEIPV GVFKNLFELK SINLGLNNLN
     KLEPFIFDDQ TSLRSLNLQK NLITSVEKDV FGPPFQNLNS LDMRFNPFDC TCESISWFVN
     WINQTHTNIS ELSTHYLCNT PHHYYGFPLK LFDTSSCKDS APFELLFIIS TSMLLVFILV
     VLLIHIEGWR ISFYWNVSVH RILGFKEIDT QAEQFEYTAY IIHAHKDRDW VWEHFSPMEE
     QDQSLKFCLE ERDFEAGVLG LEAIVNSIKR SRKIIFVITH HLLKDPLCRR FKVHHAVQQA
     IEQNLDSIIL IFLQNIPDYK LNHALCLRRG MFKSHCILNW PVQKERINAF HHKLQVALGS
     RNSAH
//