TLR9_MOUSE
ID TLR9_MOUSE Reviewed; 1032 AA.
AC Q9EQU3; F8VPN5; Q4L0K3; Q4L0K4; Q99MF2; Q99MQ8;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 3.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Toll-like receptor 9;
DE AltName: CD_antigen=CD289;
DE Flags: Precursor;
GN Name=Tlr9;
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].
RX PubMed=11130078; DOI=10.1038/35047123;
RA Hemmi H., Takeuchi O., Kawai T., Kaisho T., Sato S., Sanjo H.,
RA Matsumoto M., Hoshino K., Wagner H., Takeda K., Akira S.;
RT "A Toll-like receptor recognizes bacterial DNA.";
RL Nature 408:740-745(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Macrophage;
RX PubMed=11470918; DOI=10.1073/pnas.161293498;
RA Bauer S.M., Kirschning C.J., Hacker H., Redecke V., Hausmann S., Akira S.,
RA Wagner H., Lipford G.B.;
RT "Human TLR9 confers responsiveness to bacterial DNA via species-specific
RT CpG motif recognition.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:9237-9242(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RX PubMed=11867692;
RA Chuang T.-H., Lee J., Kline L., Mathison J.C., Ulevitch R.J.;
RT "Toll-like receptor 9 mediates CpG-DNA signaling.";
RL J. Leukoc. Biol. 71:538-544(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-964, FUNCTION, TISSUE SPECIFICITY,
RP INDUCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=BALB/cJ, and C57BL/6J;
RX PubMed=17474149; DOI=10.1002/eji.200636562;
RA Anderson A.E., Worku M.L., Khamri W., Bamford K.B., Walker M.M.,
RA Thursz M.R.;
RT "TLR9 polymorphisms determine murine lymphocyte responses to Helicobacter:
RT results from a genome-wide scan.";
RL Eur. J. Immunol. 37:1548-1561(2007).
RN [6]
RP FUNCTION IN CYTOMEGALOVIRUS INFECTION, AND MUTAGENESIS OF LEU-499.
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 [7]
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 [8]
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 [9]
RP SUBCELLULAR LOCATION.
RX PubMed=18305481; DOI=10.1038/nature06726;
RA Kim Y.M., Brinkmann M.M., Paquet M.E., Ploegh H.L.;
RT "UNC93B1 delivers nucleotide-sensing toll-like receptors to
RT endolysosomes.";
RL Nature 452:234-238(2008).
RN [10]
RP FUNCTION, INTERACTION WITH MYD88, SUBCELLULAR LOCATION, AND PROTEOLYTIC
RP CLEAVAGE.
RX PubMed=18820679; DOI=10.1038/nature07405;
RA Ewald S.E., Lee B.L., Lau L., Wickliffe K.E., Shi G.P., Chapman H.A.,
RA Barton G.M.;
RT "The ectodomain of Toll-like receptor 9 is cleaved to generate a functional
RT receptor.";
RL Nature 456:658-662(2008).
RN [11]
RP FUNCTION, INTERACTION WITH UNC93B1, SUBCELLULAR LOCATION, PROTEOLYTIC
RP CLEAVAGE, AND 3D-STRUCTURE MODELING OF THE ECTODOMAIN.
RX PubMed=18931679; DOI=10.1038/ni.1669;
RA Park B., Brinkmann M.M., Spooner E., Lee C.C., Kim Y.M., Ploegh H.L.;
RT "Proteolytic cleavage in an endolysosomal compartment is required for
RT activation of Toll-like receptor 9.";
RL Nat. Immunol. 9:1407-1414(2008).
RN [12]
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 [13]
RP INTERACTION WITH CNPY3 AND 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 [14]
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 [15]
RP FUNCTION, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=21402738; DOI=10.1084/jem.20100682;
RA Ewald S.E., Engel A., Lee J., Wang M., Bogyo M., Barton G.M.;
RT "Nucleic acid recognition by Toll-like receptors is coupled to stepwise
RT processing by cathepsins and asparagine endopeptidase.";
RL J. Exp. Med. 208:643-651(2011).
RN [16]
RP INTERACTION WITH CD300LH.
RX PubMed=21940676; DOI=10.4049/jimmunol.1003806;
RA Wu Y., Zhu X., Li N., Chen T., Yang M., Yao M., Liu X., Jin B., Wang X.,
RA Cao X.;
RT "CMRF-35-like molecule 3 preferentially promotes TLR9-triggered
RT proinflammatory cytokine production in macrophages by enhancing TNF
RT receptor-associated factor 6 ubiquitination.";
RL J. Immunol. 187:4881-4889(2011).
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 SUBCELLULAR LOCATION.
RX PubMed=25917084; DOI=10.4049/jimmunol.1402006;
RA Kimura T., Endo S., Inui M., Saitoh S., Miyake K., Takai T.;
RT "Endoplasmic Protein Nogo-B (RTN4-B) Interacts with GRAMD4 and Regulates
RT TLR9-Mediated Innate Immune Responses.";
RL J. Immunol. 194:5426-5436(2015).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 26-818 OF UNLIGANDED REDUCED
RP GLYCOSYLATION MUTANT AND IN COMPLEXES WITH INHIBITORY DNA, FUNCTION,
RP GLYCOSYLATION AT ASN-210; ASN-332 AND ASN-732, DISULFIDE BONDS, AND
RP MUTAGENESIS OF TRP-47; ARG-74; SER-104; PHE-108; TYR-132; HIS-152; TYR-179;
RP TYR-229; HIS-642; PHE-668 AND ASN-695.
RX PubMed=25686612; DOI=10.1038/nature14138;
RA Ohto U., Shibata T., Tanji H., Ishida H., Krayukhina E., Uchiyama S.,
RA Miyake K., Shimizu T.;
RT "Structural basis of CpG and inhibitory DNA recognition by Toll-like
RT receptor 9.";
RL Nature 520:702-705(2015).
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. TLR9 is a
CC nucleotide-sensing TLR which is activated by unmethylated cytidine-
CC phosphate-guanosine (CpG) dinucleotides. Acts via MYD88 and TRAF6,
CC leading to NF-kappa-B activation, cytokine secretion and the
CC inflammatory response (PubMed:18931679, PubMed:21402738,
CC PubMed:14993594, PubMed:17474149, PubMed:25686612, PubMed:18820679).
CC Plays a role in defense against systemic mouse cytomegalovirus
CC infection (PubMed:14993594). Controls lymphocyte response to
CC Helicobacter infection (PubMed:17474149). Upon CpG stimulation, induces
CC B-cell proliferation, activation, survival and antibody production (By
CC similarity). {ECO:0000250|UniProtKB:Q9NR96,
CC ECO:0000269|PubMed:14993594, ECO:0000269|PubMed:17474149,
CC ECO:0000269|PubMed:18820679, ECO:0000269|PubMed:18931679,
CC ECO:0000269|PubMed:21402738, ECO:0000269|PubMed:25686612}.
CC -!- SUBUNIT: Monomer and homodimer. Exists as a monomer in the absence of
CC unmethylated cytidine-phosphate-guanosine (CpG) ligand. Proteolytic
CC processing of an insertion loop (Z-loop) is required for
CC homodimerization upon binding to the unmethylated CpG ligand leading to
CC its activation (By similarity). Interacts with MYD88 via their
CC respective TIR domains (PubMed:18820679). Interacts with BTK (By
CC similarity). Interacts (via transmembrane domain) with UNC93B1
CC (PubMed:17452530, PubMed:18931679). Interacts with CD300LH; the
CC interaction may promote full activation of TLR9-triggered innate
CC responses (PubMed:21940676). Interacts with CNPY3 and HSP90B1; this
CC interaction is required for proper folding in the endoplasmic reticulum
CC (PubMed:18780723, PubMed:20865800). Interacts with SMPDL3B
CC (PubMed:26095358). {ECO:0000250|UniProtKB:Q2EEY0,
CC ECO:0000250|UniProtKB:Q9NR96, ECO:0000269|PubMed:17452530,
CC ECO:0000269|PubMed:18780723, ECO:0000269|PubMed:18820679,
CC ECO:0000269|PubMed:18931679, ECO:0000269|PubMed:20865800,
CC ECO:0000269|PubMed:21940676, ECO:0000269|PubMed:26095358}.
CC -!- INTERACTION:
CC Q9EQU3; P11507: Atp2a2; Xeno; NbExp=4; IntAct=EBI-9979528, EBI-916319;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:18305481}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:18305481}. Endosome {ECO:0000269|PubMed:18305481,
CC ECO:0000269|PubMed:25917084}. Lysosome {ECO:0000269|PubMed:18305481,
CC ECO:0000269|PubMed:18820679, ECO:0000269|PubMed:25917084}. Cytoplasmic
CC vesicle, phagosome {ECO:0000269|PubMed:18305481,
CC ECO:0000269|PubMed:18820679}. Note=Relocalizes from endoplasmic
CC reticulum to endosome and lysosome upon stimulation with agonist
CC (PubMed:18305481). Exit from the ER requires UNC93B1 (PubMed:18820679).
CC Endolysosomal localization is required for proteolytic cleavage and
CC subsequent activation (PubMed:18931679, PubMed:18820679). Intracellular
CC localization of the active receptor may prevent from responding to self
CC nucleic acid (PubMed:18820679). {ECO:0000269|PubMed:18305481,
CC ECO:0000269|PubMed:18820679, ECO:0000269|PubMed:18931679}.
CC -!- TISSUE SPECIFICITY: Expressed in the basolateral region of gastric
CC epithelial cells with high levels detected in antrum and body mucosa
CC (at protein level). Detected in spleen and stomach at higher levels in
CC C57BL/6 mice than BALB/C. {ECO:0000269|PubMed:17474149}.
CC -!- INDUCTION: Following Helicobacter infection, down-regulated in C57BL/6
CC mice and up-regulated in BALB/C mice. {ECO:0000269|PubMed:17474149}.
CC -!- PTM: Activated by proteolytic cleavage of the flexible loop between
CC repeats LRR14 and LRR15 within the ectodomain (PubMed:18931679,
CC PubMed:18820679). Cleavage requires UNC93B1 (PubMed:18820679).
CC Proteolytically processed by first removing the majority of the
CC ectodomain by either asparagine endopeptidase (AEP) or a cathepsin
CC followed by a trimming event that is solely cathepsin mediated and
CC required for optimal receptor signaling (PubMed:21402738).
CC {ECO:0000269|PubMed:18820679, ECO:0000269|PubMed:18931679,
CC ECO:0000269|PubMed:21402738}.
CC -!- DISRUPTION PHENOTYPE: Reduced proliferation of lymphocytes, reduced
CC interferon-gamma production by splenocytes and reduced neutrophil
CC numbers following Helicobacter infection.
CC {ECO:0000269|PubMed:17474149}.
CC -!- SIMILARITY: Belongs to the Toll-like receptor family. {ECO:0000305}.
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DR EMBL; AB045181; BAB19260.1; -; mRNA.
DR EMBL; AF348140; AAK29625.1; -; mRNA.
DR EMBL; AF314224; AAK28488.1; -; mRNA.
DR EMBL; AC164430; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AY649790; AAU04980.1; -; Genomic_DNA.
DR EMBL; AY649791; AAU04981.1; -; Genomic_DNA.
DR CCDS; CCDS40755.1; -.
DR RefSeq; NP_112455.2; NM_031178.2.
DR PDB; 3WPF; X-ray; 1.96 A; A=26-818.
DR PDB; 3WPG; X-ray; 2.25 A; A=26-818.
DR PDB; 3WPH; X-ray; 2.33 A; A=26-818.
DR PDB; 3WPI; X-ray; 2.25 A; A=26-818.
DR PDB; 4QDH; X-ray; 2.40 A; A/B=480-753.
DR PDB; 5ZLN; X-ray; 2.30 A; A/B=26-818.
DR PDBsum; 3WPF; -.
DR PDBsum; 3WPG; -.
DR PDBsum; 3WPH; -.
DR PDBsum; 3WPI; -.
DR PDBsum; 4QDH; -.
DR PDBsum; 5ZLN; -.
DR AlphaFoldDB; Q9EQU3; -.
DR SMR; Q9EQU3; -.
DR BioGRID; 219897; 2.
DR CORUM; Q9EQU3; -.
DR IntAct; Q9EQU3; 28.
DR MINT; Q9EQU3; -.
DR STRING; 10090.ENSMUSP00000082207; -.
DR BindingDB; Q9EQU3; -.
DR ChEMBL; CHEMBL6128; -.
DR GlyGen; Q9EQU3; 18 sites.
DR iPTMnet; Q9EQU3; -.
DR PhosphoSitePlus; Q9EQU3; -.
DR SwissPalm; Q9EQU3; -.
DR EPD; Q9EQU3; -.
DR MaxQB; Q9EQU3; -.
DR PaxDb; Q9EQU3; -.
DR PeptideAtlas; Q9EQU3; -.
DR PRIDE; Q9EQU3; -.
DR ProteomicsDB; 258897; -.
DR ABCD; Q9EQU3; 1 sequenced antibody.
DR DNASU; 81897; -.
DR Ensembl; ENSMUST00000062241; ENSMUSP00000082207; ENSMUSG00000045322.
DR GeneID; 81897; -.
DR KEGG; mmu:81897; -.
DR UCSC; uc009rjh.1; mouse.
DR CTD; 54106; -.
DR MGI; MGI:1932389; Tlr9.
DR VEuPathDB; HostDB:ENSMUSG00000045322; -.
DR eggNOG; KOG4641; Eukaryota.
DR GeneTree; ENSGT00940000162493; -.
DR HOGENOM; CLU_006000_2_0_1; -.
DR InParanoid; Q9EQU3; -.
DR OMA; LSWDCFG; -.
DR OrthoDB; 263937at2759; -.
DR PhylomeDB; Q9EQU3; -.
DR TreeFam; TF325595; -.
DR Reactome; R-MMU-109704; PI3K Cascade.
DR Reactome; R-MMU-1679131; Trafficking and processing of endosomal TLR.
DR Reactome; R-MMU-168138; Toll Like Receptor 9 (TLR9) Cascade.
DR BioGRID-ORCS; 81897; 2 hits in 70 CRISPR screens.
DR PRO; PR:Q9EQU3; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q9EQU3; protein.
DR Bgee; ENSMUSG00000045322; Expressed in animal zygote and 36 other tissues.
DR Genevisible; Q9EQU3; MM.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0032009; C:early phagosome; IDA:UniProtKB.
DR GO; GO:0036019; C:endolysosome; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0045335; C:phagocytic vesicle; IGI:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0005149; F:interleukin-1 receptor binding; ISO:MGI.
DR GO; GO:0038187; F:pattern recognition receptor activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0035197; F:siRNA binding; ISS:UniProtKB.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:InterPro.
DR GO; GO:0045322; F:unmethylated CpG binding; ISS:UniProtKB.
DR GO; GO:0002218; P:activation of innate immune response; IDA:UniProtKB.
DR GO; GO:1902350; P:cellular response to chloroquine; IDA:MGI.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0071248; P:cellular response to metal ion; IEA:Ensembl.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; ISO:MGI.
DR GO; GO:0051607; P:defense response to virus; IGI:MGI.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:0007252; P:I-kappaB phosphorylation; ISO:MGI.
DR GO; GO:0006955; P:immune response; IMP:MGI.
DR GO; GO:0045087; P:innate immune response; TAS:BHF-UCL.
DR GO; GO:0030277; P:maintenance of gastrointestinal epithelium; IMP: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:0002755; P:MyD88-dependent toll-like receptor signaling pathway; IPI:UniProtKB.
DR GO; GO:1901895; P:negative regulation of ATPase-coupled calcium transmembrane transporter activity; ISO:MGI.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IGI:MGI.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IMP:BHF-UCL.
DR GO; GO:0032717; P:negative regulation of interleukin-8 production; ISO:MGI.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; ISO:MGI.
DR GO; GO:0010508; P:positive regulation of autophagy; IEA:Ensembl.
DR GO; GO:0050871; P:positive regulation of B cell activation; ISS:UniProtKB.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; ISS:UniProtKB.
DR GO; GO:0032722; P:positive regulation of chemokine production; ISO:MGI.
DR GO; GO:0001819; P:positive regulation of cytokine production; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; ISO:MGI.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0002639; P:positive regulation of immunoglobulin production; ISS:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IEA:InterPro.
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:0032729; P:positive regulation of interferon-gamma production; ISS:UniProtKB.
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:BHF-UCL.
DR GO; GO:0032741; P:positive regulation of interleukin-18 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:0043507; P:positive regulation of JUN kinase activity; ISO:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0034165; P:positive regulation of toll-like receptor 9 signaling pathway; IMP:UniProtKB.
DR GO; GO:0034123; P:positive regulation of toll-like receptor signaling pathway; 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:0050864; P:regulation of B cell activation; IGI:MGI.
DR GO; GO:0045577; P:regulation of B cell differentiation; ISS:UniProtKB.
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:0001932; P:regulation of protein phosphorylation; IDA:MGI.
DR GO; GO:0034163; P:regulation of toll-like receptor 9 signaling pathway; ISS:UniProtKB.
DR GO; GO:0002237; P:response to molecule of bacterial origin; TAS:BHF-UCL.
DR GO; GO:0009615; P:response to virus; IMP:MGI.
DR GO; GO:0034162; P:toll-like receptor 9 signaling pathway; IEA:InterPro.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; IBA:GO_Central.
DR Gene3D; 3.40.50.10140; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR041283; LRR_12.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR027181; TLR9.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR PANTHER; PTHR47410:SF3; PTHR47410:SF3; 1.
DR Pfam; PF18837; LRR_12; 1.
DR Pfam; PF13855; LRR_8; 2.
DR Pfam; PF01582; TIR; 1.
DR SMART; SM00369; LRR_TYP; 15.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF52200; SSF52200; 1.
DR PROSITE; PS51450; LRR; 16.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasmic vesicle; Disulfide bond; Endoplasmic reticulum;
KW Endosome; Glycoprotein; Immunity; Inflammatory response; Innate immunity;
KW Leucine-rich repeat; Lysosome; Membrane; Receptor; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..1032
FT /note="Toll-like receptor 9"
FT /id="PRO_0000034738"
FT TOPO_DOM 26..818
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 819..839
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 840..1032
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 62..85
FT /note="LRR 1"
FT REPEAT 87..110
FT /note="LRR 2"
FT REPEAT 122..147
FT /note="LRR 3"
FT REPEAT 150..166
FT /note="LRR 4"
FT REPEAT 167..190
FT /note="LRR 5"
FT REPEAT 198..221
FT /note="LRR 6"
FT REPEAT 223..242
FT /note="LRR 7"
FT REPEAT 243..268
FT /note="LRR 8"
FT REPEAT 283..306
FT /note="LRR 9"
FT REPEAT 308..332
FT /note="LRR 10"
FT REPEAT 333..356
FT /note="LRR 11"
FT REPEAT 363..386
FT /note="LRR 12"
FT REPEAT 390..413
FT /note="LRR 13"
FT REPEAT 415..440
FT /note="LRR 14"
FT REPEAT 471..495
FT /note="LRR 15"
FT REPEAT 497..520
FT /note="LRR 16"
FT REPEAT 521..544
FT /note="LRR 17"
FT REPEAT 546..573
FT /note="LRR 18"
FT REPEAT 575..599
FT /note="LRR 19"
FT REPEAT 601..623
FT /note="LRR 20"
FT REPEAT 628..651
FT /note="LRR 21"
FT REPEAT 653..676
FT /note="LRR 22"
FT REPEAT 677..700
FT /note="LRR 23"
FT REPEAT 702..724
FT /note="LRR 24"
FT REPEAT 725..748
FT /note="LRR 25"
FT REPEAT 750..773
FT /note="LRR 26"
FT DOMAIN 868..1013
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT REGION 430..462
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 47..51
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT BINDING 72..77
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT BINDING 95..109
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT BINDING 132
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT BINDING 179..181
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT BINDING 208
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT CARBOHYD 64
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 129
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 147
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 200
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 210
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPF"
FT CARBOHYD 242
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 300
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 332
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPF, ECO:0007744|PDB:3WPH"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 495
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 514
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 568
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 670
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 695
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 700
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 732
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPF, ECO:0007744|PDB:3WPG,
FT ECO:0007744|PDB:3WPH, ECO:0007744|PDB:3WPI"
FT CARBOHYD 752
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 35..45
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPF, ECO:0007744|PDB:3WPG,
FT ECO:0007744|PDB:3WPH, ECO:0007744|PDB:3WPI"
FT DISULFID 98..110
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPF, ECO:0007744|PDB:3WPG,
FT ECO:0007744|PDB:3WPH, ECO:0007744|PDB:3WPI"
FT DISULFID 178..184
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPF, ECO:0007744|PDB:3WPG,
FT ECO:0007744|PDB:3WPH, ECO:0007744|PDB:3WPI"
FT DISULFID 255..268
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPF, ECO:0007744|PDB:3WPG,
FT ECO:0007744|PDB:3WPH, ECO:0007744|PDB:3WPI"
FT DISULFID 258..265
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPF, ECO:0007744|PDB:3WPG,
FT ECO:0007744|PDB:3WPH, ECO:0007744|PDB:3WPI"
FT DISULFID 471..501
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPF, ECO:0007744|PDB:3WPG,
FT ECO:0007744|PDB:3WPH, ECO:0007744|PDB:3WPI"
FT DISULFID 765..791
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPF, ECO:0007744|PDB:3WPG,
FT ECO:0007744|PDB:3WPH, ECO:0007744|PDB:3WPI"
FT DISULFID 767..810
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPF, ECO:0007744|PDB:3WPG,
FT ECO:0007744|PDB:3WPH, ECO:0007744|PDB:3WPI"
FT MUTAGEN 47
FT /note="W->A: Significantly decreased NF-kappa-B
FT activation."
FT /evidence="ECO:0000269|PubMed:25686612"
FT MUTAGEN 74
FT /note="R->A: Significantly decreased NF-kappa-B
FT activation."
FT /evidence="ECO:0000269|PubMed:25686612"
FT MUTAGEN 104
FT /note="S->A: Significantly decreased NF-kappa-B
FT activation."
FT /evidence="ECO:0000269|PubMed:25686612"
FT MUTAGEN 108
FT /note="F->A: Significantly decreased NF-kappa-B
FT activation."
FT /evidence="ECO:0000269|PubMed:25686612"
FT MUTAGEN 132
FT /note="Y->A: Significantly decreased NF-kappa-B
FT activation."
FT /evidence="ECO:0000269|PubMed:25686612"
FT MUTAGEN 152
FT /note="H->A: Significantly decreased NF-kappa-B
FT activation."
FT /evidence="ECO:0000269|PubMed:25686612"
FT MUTAGEN 179
FT /note="Y->A: Significantly decreased NF-kappa-B
FT activation."
FT /evidence="ECO:0000269|PubMed:25686612"
FT MUTAGEN 229
FT /note="Y->A: Significantly decreased NF-kappa-B
FT activation."
FT /evidence="ECO:0000269|PubMed:25686612"
FT MUTAGEN 499
FT /note="L->P: Highly susceptible to mouse cytomegalovirus
FT infection. Shows low level of cytokine induction and
FT natural killer activation on viral infection."
FT /evidence="ECO:0000269|PubMed:14993594"
FT MUTAGEN 642
FT /note="H->A: Loss of NF-kappa-B activation."
FT /evidence="ECO:0000269|PubMed:25686612"
FT MUTAGEN 668
FT /note="F->A: Significantly decreased NF-kappa-B
FT activation."
FT /evidence="ECO:0000269|PubMed:25686612"
FT MUTAGEN 695
FT /note="N->A: Significantly decreased NF-kappa-B
FT activation."
FT /evidence="ECO:0000269|PubMed:25686612"
FT CONFLICT 325
FT /note="T -> N (in Ref. 1; BAB19260, 2; AAK29625, 3;
FT AAK28488 and 5; AAU04980)"
FT /evidence="ECO:0000305"
FT CONFLICT 378
FT /note="L -> S (in Ref. 1; BAB19260, 2; AAK29625, 3;
FT AAK28488 and 5; AAU04980)"
FT /evidence="ECO:0000305"
FT CONFLICT 554
FT /note="S -> G (in Ref. 3; AAK28488)"
FT /evidence="ECO:0000305"
FT CONFLICT 562
FT /note="M -> I (in Ref. 3; AAK28488)"
FT /evidence="ECO:0000305"
FT CONFLICT 573
FT /note="T -> A (in Ref. 2; AAK29625, 3; AAK28488 and 5;
FT AAU04980)"
FT /evidence="ECO:0000305"
FT CONFLICT 579
FT /note="Q -> H (in Ref. 2; AAK29625, 3; AAK28488 and 5;
FT AAU04980)"
FT /evidence="ECO:0000305"
FT CONFLICT 867
FT /note="T -> A (in Ref. 2; AAK29625, 3; AAK28488 and 5;
FT AAU04980)"
FT /evidence="ECO:0000305"
FT CONFLICT 897
FT /note="E -> G (in Ref. 3; AAK28488)"
FT /evidence="ECO:0000305"
FT TURN 31..34
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 35..38
FT /evidence="ECO:0007829|PDB:3WPF"
FT TURN 39..41
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 67..69
FT /evidence="ECO:0007829|PDB:3WPF"
FT TURN 80..83
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 84..86
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 90..93
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:3WPI"
FT TURN 116..121
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 147..149
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 160..163
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:3WPF"
FT TURN 192..197
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 223..226
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 237..239
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 247..250
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 254..256
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 258..260
FT /evidence="ECO:0007829|PDB:5ZLN"
FT STRAND 269..272
FT /evidence="ECO:0007829|PDB:3WPF"
FT TURN 277..282
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 288..290
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 301..304
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 312..314
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 321..324
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 329..332
FT /evidence="ECO:0007829|PDB:3WPI"
FT STRAND 338..340
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 347..349
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 358..362
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 368..370
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 377..379
FT /evidence="ECO:0007829|PDB:3WPF"
FT TURN 381..384
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 385..387
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 395..397
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 408..412
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 413..416
FT /evidence="ECO:0007829|PDB:3WPI"
FT STRAND 419..421
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 467..471
FT /evidence="ECO:0007829|PDB:5ZLN"
FT STRAND 473..475
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 477..479
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 490..493
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 501..503
FT /evidence="ECO:0007829|PDB:3WPF"
FT TURN 517..520
FT /evidence="ECO:0007829|PDB:3WPH"
FT STRAND 526..528
FT /evidence="ECO:0007829|PDB:3WPF"
FT TURN 539..544
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 550..552
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 558..561
FT /evidence="ECO:0007829|PDB:5ZLN"
FT HELIX 570..574
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 580..582
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 590..592
FT /evidence="ECO:0007829|PDB:5ZLN"
FT STRAND 597..600
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 603..605
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 611..615
FT /evidence="ECO:0007829|PDB:3WPF"
FT TURN 620..626
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 633..635
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 646..650
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 658..660
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 671..676
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 682..684
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 706..708
FT /evidence="ECO:0007829|PDB:3WPF"
FT TURN 719..724
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 730..732
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 743..745
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 747..751
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 754..757
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 771..777
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 779..781
FT /evidence="ECO:0007829|PDB:3WPF"
FT TURN 783..788
FT /evidence="ECO:0007829|PDB:3WPF"
FT STRAND 789..794
FT /evidence="ECO:0007829|PDB:3WPF"
FT TURN 795..797
FT /evidence="ECO:0007829|PDB:3WPF"
FT HELIX 807..809
FT /evidence="ECO:0007829|PDB:3WPF"
SQ SEQUENCE 1032 AA; 116412 MW; C13A7888588CE297 CRC64;
MVLRRRTLHP LSLLVQAAVL AETLALGTLP AFLPCELKPH GLVDCNWLFL KSVPRFSAAA
SCSNITRLSL ISNRIHHLHN SDFVHLSNLR QLNLKWNCPP TGLSPLHFSC HMTIEPRTFL
AMRTLEELNL SYNGITTVPR LPSSLVNLSL SHTNILVLDA NSLAGLYSLR VLFMDGNCYY
KNPCTGAVKV TPGALLGLSN LTHLSLKYNN LTKVPRQLPP SLEYLLVSYN LIVKLGPEDL
ANLTSLRVLD VGGNCRRCDH APNPCIECGQ KSLHLHPETF HHLSHLEGLV LKDSSLHTLN
SSWFQGLVNL SVLDLSENFL YESITHTNAF QNLTRLRKLN LSFNYRKKVS FARLHLASSF
KNLVSLQELN MNGIFFRLLN KYTLRWLADL PKLHTLHLQM NFINQAQLSI FGTFRALRFV
DLSDNRISGP STLSEATPEE ADDAEQEELL SADPHPAPLS TPASKNFMDR CKNFKFTMDL
SRNNLVTIKP EMFVNLSRLQ CLSLSHNSIA QAVNGSQFLP LTNLQVLDLS HNKLDLYHWK
SFSELPQLQA LDLSYNSQPF SMKGIGHNFS FVTHLSMLQS LSLAHNDIHT RVSSHLNSNS
VRFLDFSGNG MGRMWDEGGL YLHFFQGLSG LLKLDLSQNN LHILRPQNLD NLPKSLKLLS
LRDNYLSFFN WTSLSFLPNL EVLDLAGNQL KALTNGTLPN GTLLQKLDVS SNSIVSVVPA
FFALAVELKE VNLSHNILKT VDRSWFGPIV MNLTVLDVRS NPLHCACGAA FVDLLLEVQT
KVPGLANGVK CGSPGQLQGR SIFAQDLRLC LDEVLSWDCF GLSLLAVAVG MVVPILHHLC
GWDVWYCFHL CLAWLPLLAR SRRSAQTLPY DAFVVFDKAQ SAVADWVYNE LRVRLEERRG
RRALRLCLED RDWLPGQTLF ENLWASIYGS RKTLFVLAHT DRVSGLLRTS FLLAQQRLLE
DRKDVVVLVI LRPDAHRSRY VRLRQRLCRQ SVLFWPQQPN GQGGFWAQLS TALTRDNRHF
YNQNFCRGPT AE
