ID:TLR9_HUMAN DESCRIPTION: RecName: Full=Toll-like receptor 9; AltName: CD_antigen=CD289; Flags: Precursor; FUNCTION: Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR9 is a nucleotide-sensing TLR which is activated by unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Controls lymphocyte response to Helicobacter infection. SUBUNIT: Interacts with MYD88 via their respective TIR domains (By similarity). Interacts (via transmembrane domain) with UNC93B1 (By similarity). Interacts with CD300LH; the interaction may promote full activation of TLR9-triggered innate responses (By similarity). Interacts with BTK. Interacts with CNPY3 and HSP90B1; this interaction is required for proper folding in the endoplasmic reticulum. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Single-pass type I membrane protein (By similarity). Endosome (By similarity). Lysosome (By similarity). Cytoplasmic vesicle, phagosome (By similarity). Note=Relocalizes from endoplasmic reticulum to endosome and lysosome upon stimulation with agonist (By similarity). TISSUE SPECIFICITY: Highly expressed in spleen, lymph node, tonsil and peripheral blood leukocytes, especially in plasmacytoid pre- dendritic cells. Levels are much lower in monocytes and CD11c+ immature dendritic cells. Also detected in lung and liver. SIMILARITY: Belongs to the Toll-like receptor family. SIMILARITY: Contains 26 LRR (leucine-rich) repeats. SIMILARITY: Contains 1 TIR domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
SCOP Domains: 52047 - RNI-like 52058 - L domain-like 52075 - Outer arm dynein light chain 1 52200 - Toll/Interleukin receptor TIR domain
ModBase Predicted Comparative 3D Structure on Q9NR96
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0002224 toll-like receptor signaling pathway GO:0002237 response to molecule of bacterial origin GO:0002376 immune system process GO:0002639 positive regulation of immunoglobulin production GO:0002755 MyD88-dependent toll-like receptor signaling pathway GO:0006954 inflammatory response GO:0007165 signal transduction GO:0007252 I-kappaB phosphorylation GO:0007409 axonogenesis GO:0010628 positive regulation of gene expression GO:0030277 maintenance of gastrointestinal epithelium GO:0030890 positive regulation of B cell proliferation GO:0032088 negative regulation of NF-kappaB transcription factor activity GO:0032640 tumor necrosis factor production GO:0032715 negative regulation of interleukin-6 production GO:0032717 negative regulation of interleukin-8 production GO:0032722 positive regulation of chemokine production GO:0032725 positive regulation of granulocyte macrophage colony-stimulating factor production GO:0032728 positive regulation of interferon-beta production GO:0032733 positive regulation of interleukin-10 production GO:0032735 positive regulation of interleukin-12 production GO:0032741 positive regulation of interleukin-18 production GO:0032755 positive regulation of interleukin-6 production GO:0032757 positive regulation of interleukin-8 production GO:0032760 positive regulation of tumor necrosis factor production GO:0034122 negative regulation of toll-like receptor signaling pathway GO:0034123 positive regulation of toll-like receptor signaling pathway GO:0034162 toll-like receptor 9 signaling pathway GO:0034163 regulation of toll-like receptor 9 signaling pathway GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process GO:0042742 defense response to bacterium GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0043410 positive regulation of MAPK cascade GO:0043507 positive regulation of JUN kinase activity GO:0045078 positive regulation of interferon-gamma biosynthetic process GO:0045087 innate immune response GO:0045356 positive regulation of interferon-alpha biosynthetic process GO:0045359 positive regulation of interferon-beta biosynthetic process GO:0045577 regulation of B cell differentiation GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0046330 positive regulation of JNK cascade GO:0050707 regulation of cytokine secretion GO:0050729 positive regulation of inflammatory response GO:0050829 defense response to Gram-negative bacterium GO:0050871 positive regulation of B cell activation GO:0051092 positive regulation of NF-kappaB transcription factor activity GO:0051770 positive regulation of nitric-oxide synthase biosynthetic process GO:1901224 positive regulation of NIK/NF-kappaB signaling GO:1901895 negative regulation of calcium-transporting ATPase activity
EU831898 - Synthetic construct Homo sapiens clone HAIB:100066927; DKFZo004G0522 toll-like receptor 9 protein (TLR9) gene, encodes complete protein. BC032713 - Homo sapiens toll-like receptor 9, mRNA (cDNA clone MGC:45083 IMAGE:5495717), complete cds. AK303285 - Homo sapiens cDNA FLJ56277 complete cds, highly similar to Toll-like receptor 9 precursor. AF259263 - Homo sapiens toll-like receptor 9 form B (TLR9) mRNA, complete cds; alternatively spliced. AF259262 - Homo sapiens toll-like receptor 9 form A (TLR9) mRNA, complete cds; alternatively spliced. JD123161 - Sequence 104185 from Patent EP1572962. JD413104 - Sequence 394128 from Patent EP1572962. AF245704 - Homo sapiens toll-like receptor 9 (TLR9) mRNA, complete cds. JD260187 - Sequence 241211 from Patent EP1572962. JD419498 - Sequence 400522 from Patent EP1572962. AB045180 - Homo sapiens TLR9 mRNA for toll-like receptor 9, complete cds. JD452381 - Sequence 433405 from Patent EP1572962. JD255004 - Sequence 236028 from Patent EP1572962. AY359085 - Homo sapiens clone DNA119714 TLR9 (UNQ5798) mRNA, complete cds. JD386508 - Sequence 367532 from Patent EP1572962. AB445673 - Homo sapiens TLR9 mRNA for toll-like receptor 9, complete cds. EU831821 - Synthetic construct Homo sapiens clone HAIB:100066850; DKFZo008G0521 toll-like receptor 9 protein (TLR9) gene, encodes complete protein. AF246972 - Homo sapiens toll-like receptor 9 (TLR9) mRNA, partial cds. AF246973 - Homo sapiens toll-like receptor 9 (TLR9) mRNA, partial cds, alternatively spliced. AF246974 - Homo sapiens toll-like receptor 9 (TLR9) mRNA, partial cds, alternatively spliced. JD428099 - Sequence 409123 from Patent EP1572962. JD041707 - Sequence 22731 from Patent EP1572962. JD191874 - Sequence 172898 from Patent EP1572962. JD302860 - Sequence 283884 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q9NR96 (Reactome details) participates in the following event(s):
R-HSA-1679589 Engulfed CpG DNA binds to endosomal full-length TLR9 R-HSA-1678920 TLR processing at low pH R-HSA-1678981 TLR9 processing at neutral pH R-HSA-1678923 TLR folding by chaperones GP96 and CNPY3 R-HSA-1679098 Engulfed CpG DNA binds to endosomal N-ter TLR9 dimer R-HSA-187895 Engulfed CpG DNA binds to endosomal C-ter TLR9 R-HSA-188002 Rab5-mediated recruitment of class III PI3K to TLR9 R-HSA-1678944 Folded full-length TLR7/8/9 dissociates from the GP96:CNPY3 complex R-HSA-1678921 Full-length TLR3/7/8/9 binds to UNC93B1 R-HSA-975175 MyD88 interacts with the activated TLR receptor 7, 8 or 9 R-HSA-109699 PI3K-containing complexes phosphorylate PIP2 to PIP3 R-HSA-975156 IRAK4 binds to the activated TLR7/8 or 9 receptor:MyD88 complex R-HSA-975098 MyD88 oligomerization within the complex of activated TLR 7/8 or 9 : MyD88 R-HSA-975115 IRAK1/or IRAK2 binds to the activated IRAK4 :MyD88:activated TLR 7/8 or 9. R-HSA-975100 Dissociation of hp-IRAK1/or IRAK2:TRAF6-oligomer from the p-IRAK4 :oligo-Myd88:activated TLR7/8 or 9 complex R-HSA-975170 IRAK4 autophosphorylation in the complex with MyD88:activated TLR 7/8 or 9 R-HSA-975125 Multiple IRAK1 autophosphorylation steps within the complex pIRAK4:MyD88:activated TLR7/8 or 9 R-HSA-975134 Second phosphorylation of IRAK1 by IRAK4 bound to MyD88: activated TLR 7/8 or 9 R-HSA-975180 First phosphorylation of IRAK1 by IRAK4 bound to MyD88:activated TLR 7/8 or 9 R-HSA-975160 Phosphorylation of IRAK2 bound to the activated IRAK4:MyD88 oligomer:activated TLR 7/8 or 9 R-HSA-975111 TRAF6 binds to hp- IRAK1/or p-IRAK2:p-IRAK4:MyD88:activated TLR7/8 or 9 R-HSA-975188 TRAF6 interacts with IRF7 upon TLR7/8 or 9 activation R-HSA-975106 Phosphorylation and release of IRF7 upon TLR7/8 or 9 activation R-HSA-975118 TRAF6 ubiquitinqtes IRF7 in a K63-dependent manner following TLR7/8 or 9 stimulation R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade R-HSA-1679131 Trafficking and processing of endosomal TLR R-HSA-168898 Toll-Like Receptors Cascades R-HSA-168249 Innate Immune System R-HSA-168256 Immune System R-HSA-975155 MyD88 dependent cascade initiated on endosome R-HSA-109704 PI3K Cascade R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade R-HSA-112399 IRS-mediated signalling R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation R-HSA-74751 Insulin receptor signalling cascade R-HSA-2428928 IRS-related events triggered by IGF1R R-HSA-74752 Signaling by Insulin receptor R-HSA-2428924 IGF1R signaling cascade R-HSA-975110 TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling R-HSA-9006934 Signaling by Receptor Tyrosine Kinases R-HSA-2404192 Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) R-HSA-162582 Signal Transduction
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
