Q9EQU3
SS
Gene name |
Tlr9 |
Protein name |
Toll-like receptor 9 |
Names |
CD antigen CD289 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:81897 |
EC number |
|
Protein Class |
|
Descriptions
TLR9 (Toll-like receptor 9) plays a key role in the innate immune system in response to unmethylated CpG DNA. After stimulation of cells with CpG DNA, TLR9 redistributes from the endoplasmic reticulum to lysosomes, where a signaling cascade is triggered by recruitment of the MyD88 adaptor molecule. TLR9 is a type I transmembrane protein characterized by an extracellular leucine-rich repeat (LRR) domain, a transmembrane helix, and an intracellular Toll/interleukin-1 receptor (TIR) homology domain. TLR9 undergoes proteolytic cleavage, executed by cysteine proteases, in the endolysosomal compartment, and molecular modeling shows that the cleavage sites are situated between LRR14 and LRR15, as being part of a flexible loop that could render TLR9 susceptible to proteolysis. On a molar basis, the C-terminal cleavage fragment of TLR9 binds CpG DNA more strongly than does full-length TLR9, although full-length TLR9 binds CpG DNA. The broadly specific inhibitor z-FA-fmk is most effective at blocking the cleavage and, accordingly, abrogated TNF production in cells exposed to the TLR9 agonist CpG DNA.
Autoinhibitory domains (AIDs)
Target domain |
24-807 (LRR domains) |
Relief mechanism |
Cleavage |
Assay |
|
Accessory elements
No accessory elements
References
- Tanji H et al. (2016) "Autoinhibition and relief mechanism by the proteolytic processing of Toll-like receptor 8", Proceedings of the National Academy of Sciences of the United States of America, 113, 3012-7
- Park B et al. (2008) "Proteolytic cleavage in an endolysosomal compartment is required for activation of Toll-like receptor 9", Nature immunology, 9, 1407-14
Autoinhibited structure
Activated structure
64 variants for Q9EQU3
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3389065157 | 23 | T>N | No | EVA | |
| rs3389077775 | 39 | P>S | No | EVA | |
| rs3547506825 | 66 | T>P | No | EVA | |
| rs3389067855 | 100 | P>A | No | EVA | |
| rs3389070339 | 124 | T>I | No | EVA | |
| rs3389070349 | 167 | Y>N | No | EVA | |
| rs864256436 | 183 | P>L | No | EVA | |
| rs864256436 | 183 | P>R | No | EVA | |
| rs253875008 | 227 | V>L | No | EVA | |
| rs261271014 | 229 | Y>N | No | EVA | |
| rs30071511 | 325 | T>N | No | EVA | |
| rs3389070427 | 332 | N>K | No | EVA | |
| rs3547501728 | 337 | R>C | No | EVA | |
| rs30281144 | 360 | F>L | No | EVA | |
| rs3389069746 | 370 | N>K | No | EVA | |
| rs30033068 | 378 | L>S | No | EVA | |
| rs3389069681 | 393 | L>F | No | EVA | |
| rs3389044229 | 401 | N>K | No | EVA | |
| rs3400632281 | 404 | N>I | No | EVA | |
| rs1133742676 | 406 | A>V | No | EVA | |
| rs230927150 | 433 | L>V | No | EVA | |
| rs249980814 | 437 | T>A | No | EVA | |
| rs3389073492 | 438 | P>S | No | EVA | |
| rs3389067902 | 446 | Q>E | No | EVA | |
| rs3389070578 | 477 | T>I | No | EVA | |
| rs3389013522 | 490 | P>L | No | EVA | |
| rs3389013522 | 490 | P>Q | No | EVA | |
| rs245516143 | 498 | R>C | No | EVA | |
| rs3400682040 | 570 | S>N | No | EVA | |
| rs3400430824 | 571 | F>* | No | EVA | |
| rs6351546 | 573 | T>A | No | EVA | |
| rs6351573 | 579 | Q>H | No | EVA | |
| rs3389070393 | 582 | S>I | No | EVA | |
| rs224194769 | 587 | D>G | No | EVA | |
| rs231062015 | 613 | R>H | No | EVA | |
| rs3389048485 | 648 | N>K | No | EVA | |
| rs3389070423 | 680 | L>M | No | EVA | |
| rs3389077738 | 684 | D>Y | No | EVA | |
| rs3389065173 | 705 | Q>* | No | EVA | |
| rs3389078613 | 716 | S>Y | No | EVA | |
| rs3389078594 | 755 | V>D | No | EVA | |
| rs3389073490 | 762 | P>S | No | EVA | |
| rs3389070593 | 773 | D>N | No | EVA | |
| rs3400540235 | 797 | L>P | No | EVA | |
| rs3400540260 | 799 | G>V | No | EVA | |
| rs3400430814 | 811 | L>R | No | EVA | |
| rs3389065133 | 826 | A>G | No | EVA | |
| rs223744921 | 834 | P>A | No | EVA | |
| rs240350356 | 841 | G>R | No | EVA | |
| rs240350356 | 841 | G>S | No | EVA | |
| rs3507932408 | 865 | A>T | No | EVA | |
| rs50188335 | 867 | T>A | No | EVA | |
| rs3389073520 | 906 | L>V | No | EVA | |
| rs3389044225 | 938 | A>T | No | EVA | |
| rs3389057307 | 952 | L>P | No | EVA | |
| rs3400774370 | 965 | V>A | No | EVA | |
| rs3389069694 | 980 | Y>N | No | EVA | |
| rs3400638599 | 998 | Q>K | No | EVA | |
| rs3400682093 | 1000 | N>T | No | EVA | |
| rs3400612595 | 1002 | Q>P | No | EVA | |
| rs3400638589 | 1007 | A>G | No | EVA | |
| rs3400727620 | 1009 | L>M | No | EVA | |
| rs3389013538 | 1023 | Q>R | No | EVA | |
| rs3389068050 | 1024 | N>K | No | EVA |
No associated diseases with Q9EQU3
9 regional properties for Q9EQU3
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | SH3 domain | 225 - 293 | IPR001452 |
| domain | PDZ domain | 140 - 219 | IPR001478 |
| domain | L27 domain | 8 - 121 | IPR004172 |
| domain | Guanylate kinase-like domain | 350 - 537 | IPR008144 |
| domain | Guanylate kinase/L-type calcium channel beta subunit | 349 - 540 | IPR008145 |
| domain | L27 domain, C-terminal | 12 - 63 | IPR014775-1 |
| domain | L27 domain, C-terminal | 69 - 120 | IPR014775-2 |
| conserved_site | Guanylate kinase, conserved site | 385 - 402 | IPR020590 |
| domain | MPP2, SH3 domain | 229 - 287 | IPR035602 |
Functions
10 GO annotations of cellular component
| Name | Definition |
|---|---|
| apical plasma membrane | The region of the plasma membrane located at the apical end of the cell. |
| basolateral plasma membrane | The region of the plasma membrane that includes the basal end and sides of the cell. Often used in reference to animal polarized epithelial membranes, where the basal membrane is the part attached to the extracellular matrix, or in plant cells, where the basal membrane is defined with respect to the zygotic axis. |
| early phagosome | A membrane-bounded intracellular vesicle as initially formed upon the ingestion of particulate material by phagocytosis. |
| endolysosome | An transient hybrid organelle formed by fusion of a late endosome with a lysosome, and in which active degradation takes place. |
| endoplasmic reticulum | The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached). |
| endoplasmic reticulum membrane | The lipid bilayer surrounding the endoplasmic reticulum. |
| endosome | A vacuole to which materials ingested by endocytosis are delivered. |
| lysosome | A small lytic vacuole that has cell cycle-independent morphology found in most animal cells and that contains a variety of hydrolases, most of which have their maximal activities in the pH range 5-6. The contained enzymes display latency if properly isolated. About 40 different lysosomal hydrolases are known and lysosomes have a great variety of morphologies and functions. |
| phagocytic vesicle | A membrane-bounded intracellular vesicle that arises from the ingestion of particulate material by phagocytosis. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
5 GO annotations of molecular function
| Name | Definition |
|---|---|
| interleukin-1 receptor binding | Binding to an interleukin-1 receptor. |
| pattern recognition receptor activity | Combining with a pathogen-associated molecular pattern (PAMP), a structure conserved among microbial species to initiate an innate immune response. |
| protein homodimerization activity | Binding to an identical protein to form a homodimer. |
| siRNA binding | Binding to a small interfering RNA, a 21-23 nucleotide RNA that is processed from double stranded RNA (dsRNA) by an RNAse enzyme. |
| unmethylated CpG binding | Binding to uan nmethylated CpG motif. Unmethylated CpG dinucleotides are often associated with gene promoters. |
49 GO annotations of biological process
| Name | Definition |
|---|---|
| activation of innate immune response | Any process that initiates an innate immune response. Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens. Examples of this process include activation of the hypersensitive response of Arabidopsis thaliana and activation of any NOD or TLR signaling pathway in vertebrate species. |
| canonical NF-kappaB signal transduction | The process in which a signal is passed on to downstream components within the cell through the I-kappaB-kinase (IKK)-dependent activation of NF-kappaB. The cascade begins with activation of a trimeric IKK complex (consisting of catalytic kinase subunits IKKalpha and/or IKKbeta, and the regulatory scaffold protein NEMO) and ends with the regulation of transcription of target genes by NF-kappaB. In a resting state, NF-kappaB dimers are bound to I-kappaB proteins, sequestering NF-kappaB in the cytoplasm. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing the NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription. |
| cellular response to chloroquine | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a chloroquine stimulus. |
| cellular response to lipopolysaccharide | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria. |
| cellular response to metal ion | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a metal ion stimulus. |
| defense response to Gram-negative bacterium | Reactions triggered in response to the presence of a Gram-negative bacterium that act to protect the cell or organism. |
| defense response to virus | Reactions triggered in response to the presence of a virus that act to protect the cell or organism. |
| detection of molecule of bacterial origin | The series of events in which a stimulus from a molecule of bacterial origin is received and converted into a molecular signal. |
| immune response | Any immune system process that functions in the calibrated response of an organism to a potential internal or invasive threat. |
| innate immune response | Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens. |
| maintenance of gastrointestinal epithelium | Protection of epithelial surfaces of the gastrointestinal tract from proteolytic and caustic digestive agents. |
| male gonad development | The process whose specific outcome is the progression of the male gonad over time, from its formation to the mature structure. |
| microglial cell activation | The change in morphology and behavior of a microglial cell resulting from exposure to a cytokine, chemokine, cellular ligand, or soluble factor. |
| MyD88-dependent toll-like receptor signaling pathway | A toll-like receptor signaling pathway in which the MyD88 adaptor molecule mediates transduction of the signal. Toll-like receptors directly bind pattern motifs from a variety of microbial sources to initiate an innate immune response. |
| negative regulation of ERK1 and ERK2 cascade | Any process that stops, prevents, or reduces the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade. |
| positive regulation of autophagy | Any process that activates, maintains or increases the rate of autophagy. Autophagy is the process in which cells digest parts of their own cytoplasm. |
| positive regulation of B cell activation | Any process that activates or increases the frequency, rate or extent of B cell activation. |
| positive regulation of B cell proliferation | Any process that activates or increases the rate or extent of B cell proliferation. |
| positive regulation of canonical NF-kappaB signal transduction | Any process that activates or increases the frequency, rate or extent of I-kappaB kinase/NF-kappaB signaling. |
| positive regulation of chemokine production | Any process that activates or increases the frequency, rate, or extent of chemokine production. |
| positive regulation of cytokine production | Any process that activates or increases the frequency, rate or extent of production of a cytokine. |
| positive regulation of granulocyte macrophage colony-stimulating factor production | Any process that activates or increases the frequency, rate, or extent of granulocyte macrophage colony-stimulating factor production. |
| positive regulation of immunoglobulin production | Any process that activates or increases the frequency, rate, or extent of immunoglobulin production. |
| positive regulation of interferon-alpha production | Any process that activates or increases the frequency, rate, or extent of interferon-alpha production. |
| positive regulation of interferon-beta production | Any process that activates or increases the frequency, rate, or extent of interferon-beta production. |
| positive regulation of interleukin-10 production | Any process that activates or increases the frequency, rate, or extent of interleukin-10 production. |
| positive regulation of interleukin-12 production | Any process that activates or increases the frequency, rate, or extent of interleukin-12 production. |
| positive regulation of interleukin-18 production | Any process that activates or increases the frequency, rate, or extent of interleukin-18 production. |
| positive regulation of interleukin-6 production | Any process that activates or increases the frequency, rate, or extent of interleukin-6 production. |
| positive regulation of interleukin-8 production | Any process that activates or increases the frequency, rate, or extent of interleukin-8 production. |
| positive regulation of intestinal epithelial cell development | Any process that activates or increases the frequency, rate or extent of intestinal epithelial cell development. |
| positive regulation of JNK cascade | Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the JNK cascade. |
| positive regulation of MAPK cascade | Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the MAPK cascade. |
| positive regulation of NF-kappaB transcription factor activity | Any process that activates or increases the frequency, rate or extent of activity of the transcription factor NF-kappaB. |
| positive regulation of non-canonical NF-kappaB signal transduction | Any process that activates or increases the frequency, rate or extent of NIK/NF-kappaB signaling. |
| positive regulation of toll-like receptor 9 signaling pathway | Any process that activates or increases the frequency, rate, or extent of toll-like receptor 9 signaling pathway. |
| positive regulation of transcription by RNA polymerase II | Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. |
| positive regulation of tumor necrosis factor production | Any process that activates or increases the frequency, rate or extent of tumor necrosis factor production. |
| positive regulation of type II interferon production | Any process that activates or increases the frequency, rate, or extent of interferon-gamma production. Interferon-gamma is also known as type II interferon. |
| regulation of B cell activation | Any process that modulates the frequency, rate or extent of B cell activation. |
| regulation of B cell differentiation | Any process that modulates the frequency, rate or extent of B cell differentiation. |
| regulation of dendritic cell cytokine production | Any process that modulates the frequency, rate, or extent of dendritic cell cytokine production. |
| regulation of inflammatory response | Any process that modulates the frequency, rate or extent of the inflammatory response, the immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. |
| regulation of protein phosphorylation | Any process that modulates the frequency, rate or extent of addition of phosphate groups into an amino acid in a protein. |
| regulation of toll-like receptor 9 signaling pathway | Any process that modulates the frequency, rate, or extent of toll-like receptor 9 signaling pathway. |
| response to molecule of bacterial origin | Any process that results in a change in state or activity of an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus by molecules of bacterial origin such as peptides derived from bacterial flagellin. |
| response to virus | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a virus. |
| toll-like receptor 9 signaling pathway | The series of molecular signals initiated by a ligand binding to the endolysosomal toll-like receptor 9. |
| toll-like receptor signaling pathway | The series of molecular signals initiated by a ligand binding to a toll-like receptor of a target cell. Toll-like receptors directly bind pattern motifs from a variety of microbial sources to initiate an innate immune response. |
11 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q5I2M5 | TLR9 | Toll-like receptor 9 | Bos taurus (Bovine) | SS |
| Q5I2M7 | TLR9 | Toll-like receptor 9 | Felis catus (Cat) (Felis silvestris catus) | SS |
| Q5I2M8 | TLR9 | Toll-like receptor 9 | Canis lupus familiaris (Dog) (Canis familiaris) | SS |
| P08953 | Tl | Protein toll | Drosophila melanogaster (Fruit fly) | PR |
| Q2EEY0 | TLR9 | Toll-like receptor 9 | Equus caballus (Horse) | SS |
| Q9NYK1 | TLR7 | Toll-like receptor 7 | Homo sapiens (Human) | EV |
| Q9NR96 | TLR9 | Toll-like receptor 9 | Homo sapiens (Human) | EV |
| P58681 | Tlr7 | Toll-like receptor 7 | Mus musculus (Mouse) | SS |
| P58682 | Tlr8 | Toll-like receptor 8 | Mus musculus (Mouse) | SS |
| Q5I2M3 | TLR9 | Toll-like receptor 9 | Sus scrofa (Pig) | SS |
| A5H2Z9 | Tlr7 | Toll-like receptor 7 | Rattus norvegicus (Rat) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MVLRRRTLHP | LSLLVQAAVL | AETLALGTLP | AFLPCELKPH | GLVDCNWLFL | KSVPRFSAAA |
| 70 | 80 | 90 | 100 | 110 | 120 |
| SCSNITRLSL | ISNRIHHLHN | SDFVHLSNLR | QLNLKWNCPP | TGLSPLHFSC | HMTIEPRTFL |
| 130 | 140 | 150 | 160 | 170 | 180 |
| AMRTLEELNL | SYNGITTVPR | LPSSLVNLSL | SHTNILVLDA | NSLAGLYSLR | VLFMDGNCYY |
| 190 | 200 | 210 | 220 | 230 | 240 |
| KNPCTGAVKV | TPGALLGLSN | LTHLSLKYNN | LTKVPRQLPP | SLEYLLVSYN | LIVKLGPEDL |
| 250 | 260 | 270 | 280 | 290 | 300 |
| ANLTSLRVLD | VGGNCRRCDH | APNPCIECGQ | KSLHLHPETF | HHLSHLEGLV | LKDSSLHTLN |
| 310 | 320 | 330 | 340 | 350 | 360 |
| SSWFQGLVNL | SVLDLSENFL | YESITHTNAF | QNLTRLRKLN | LSFNYRKKVS | FARLHLASSF |
| 370 | 380 | 390 | 400 | 410 | 420 |
| KNLVSLQELN | MNGIFFRLLN | KYTLRWLADL | PKLHTLHLQM | NFINQAQLSI | FGTFRALRFV |
| 430 | 440 | 450 | 460 | 470 | 480 |
| DLSDNRISGP | STLSEATPEE | ADDAEQEELL | SADPHPAPLS | TPASKNFMDR | CKNFKFTMDL |
| 490 | 500 | 510 | 520 | 530 | 540 |
| SRNNLVTIKP | EMFVNLSRLQ | CLSLSHNSIA | QAVNGSQFLP | LTNLQVLDLS | HNKLDLYHWK |
| 550 | 560 | 570 | 580 | 590 | 600 |
| SFSELPQLQA | LDLSYNSQPF | SMKGIGHNFS | FVTHLSMLQS | LSLAHNDIHT | RVSSHLNSNS |
| 610 | 620 | 630 | 640 | 650 | 660 |
| VRFLDFSGNG | MGRMWDEGGL | YLHFFQGLSG | LLKLDLSQNN | LHILRPQNLD | NLPKSLKLLS |
| 670 | 680 | 690 | 700 | 710 | 720 |
| LRDNYLSFFN | WTSLSFLPNL | EVLDLAGNQL | KALTNGTLPN | GTLLQKLDVS | SNSIVSVVPA |
| 730 | 740 | 750 | 760 | 770 | 780 |
| FFALAVELKE | VNLSHNILKT | VDRSWFGPIV | MNLTVLDVRS | NPLHCACGAA | FVDLLLEVQT |
| 790 | 800 | 810 | 820 | 830 | 840 |
| KVPGLANGVK | CGSPGQLQGR | SIFAQDLRLC | LDEVLSWDCF | GLSLLAVAVG | MVVPILHHLC |
| 850 | 860 | 870 | 880 | 890 | 900 |
| GWDVWYCFHL | CLAWLPLLAR | SRRSAQTLPY | DAFVVFDKAQ | SAVADWVYNE | LRVRLEERRG |
| 910 | 920 | 930 | 940 | 950 | 960 |
| RRALRLCLED | RDWLPGQTLF | ENLWASIYGS | RKTLFVLAHT | DRVSGLLRTS | FLLAQQRLLE |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| DRKDVVVLVI | LRPDAHRSRY | VRLRQRLCRQ | SVLFWPQQPN | GQGGFWAQLS | TALTRDNRHF |
| 1030 | |||||
| YNQNFCRGPT | AE |