Q2EEY0

SS
Gene name
TLR9
Protein name
Toll-like receptor 9
Names
CD antigen CD289
Species
Equus caballus (Horse)
KEGG Pathway
ecb:100009693
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)

441-470 (Z-loop) SS

Target domain

24-806 (LRR domains)

Relief mechanism

Cleavage

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

7 structures for Q2EEY0

Entry ID Method Resolution Chain Position Source
3WPB X-ray 240 A A 26-817 PDB
3WPC X-ray 160 A A/B 26-817 PDB
3WPD X-ray 275 A A 26-817 PDB
5Y3J X-ray 181 A A/B 26-819 PDB
5Y3K X-ray 270 A A/B 26-819 PDB
5Y3L X-ray 260 A A/B 26-819 PDB
AF-Q2EEY0-F1 Predicted AlphaFoldDB

No variants for Q2EEY0

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q2EEY0

No associated diseases with Q2EEY0

5 regional properties for Q2EEY0

Type Name Position InterPro Accession
domain Protein kinase domain 25 - 279 IPR000719
domain NAF domain 362 - 430 IPR004041
active_site Serine/threonine-protein kinase, active site 143 - 155 IPR008271
binding_site Protein kinase, ATP binding site 31 - 54 IPR017441
domain NAF/FISL domain 359 - 383 IPR018451

Functions

Description
EC Number
Subcellular Localization
  • Endoplasmic reticulum membrane ; Single-pass type I membrane protein
  • Endosome
  • Lysosome
  • Cytoplasmic vesicle
  • Cytoplasmic vesicle, phagosome
  • Cell membrane
  • Cytoplasm
  • Nucleus
  • Relocalizes from endoplasmic reticulum to endosome and lysosome upon stimulation with agonist
  • Exit from the ER requires UNC93B1
  • Endolysosomal localization is required for proteolytic cleavage and subsequent activation
  • Intracellular localization of the active receptor may prevent from responding to self nucleic acid
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

7 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
endolysosome An transient hybrid organelle formed by fusion of a late endosome with a lysosome, and in which active degradation takes place.
endoplasmic reticulum membrane The lipid bilayer surrounding the endoplasmic reticulum.
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.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
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
identical protein binding Binding to an identical protein or proteins.
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.

17 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.
defense response to virus Reactions triggered in response to the presence of a virus that act to protect the cell or organism.
inflammatory response The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages.
innate immune response Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
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 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-6 production Any process that activates or increases the frequency, rate, or extent of interleukin-6 production.
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 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 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 differentiation Any process that modulates the frequency, rate or extent of B cell differentiation.
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.

10 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
Q9NR96 TLR9 Toll-like receptor 9 Homo sapiens (Human) EV
Q9NYK1 TLR7 Toll-like receptor 7 Homo sapiens (Human) EV
Q9EQU3 Tlr9 Toll-like receptor 9 Mus musculus (Mouse) SS
P58681 Tlr7 Toll-like receptor 7 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
MGPCHGALQP LSLLVQAAML AVALAQGTLP PFLPCELQPH GLVNCNWLFL KSVPHFSAAA
70 80 90 100 110 120
PRDNVTSLSL LSNRIHHLHD SDFAQLSNLQ KLNLKWNCPP AGLSPMHFPC HMTIEPNTFL
130 140 150 160 170 180
AVPTLEELNL SYNGITTVPA LPSSLVSLIL SRTNILQLDP TSLTGLHALR FLYMDGNCYY
190 200 210 220 230 240
KNPCGRALEV APGALLGLGN LTHLSLKYNN LTTVPRSLPP SLEYLLLSYN HIVTLAPEDL
250 260 270 280 290 300
ANLTALRVLD VGGNCRRCDH ARNPCVECPH KFPQLHSDTF SHLSRLEGLV LKDSSLYQLN
310 320 330 340 350 360
PRWFRGLGNL TVLDLSENFL YDCITKTKAF QGLAQLRRLN LSFNYHKKVS FAHLTLAPSF
370 380 390 400 410 420
GSLLSLQELD MHGIFFRSLS QKTLQPLARL PMLQRLYLQM NFINQAQLGI FKDFPGLRYI
430 440 450 460 470 480
DLSDNRISGA VEPVATTGEV DGGKKVWLTS RDLTPGPLDT PSSEDFMPSC KNLSFTLDLS
490 500 510 520 530 540
RNNLVTVQPE MFAQLSRLQC LRLSHNSISQ AVNGSQFVPL TSLQVLDLSH NKLDLYHGRS
550 560 570 580 590 600
FTELPRLEAL DLSYNSQPFS MRGVGHNLSF VAQLPTLRYL SLAHNGIHSR VSQQLCSTSL
610 620 630 640 650 660
WALDFSGNSL SQMWAEGDLY LRFFQGLRSL IRLDLSQNRL HTLLPCTLGN LPKSLQLLRL
670 680 690 700 710 720
RNNYLAFFNW SSLTLLPNLE TLDLAGNQLK ALSNGSLPSG TQLQRLDVSR NSIIFVVPGF
730 740 750 760 770 780
FALATRLREL NLSANALRTV EPSWFGFLAG SLEVLDVSAN PLHCACGAAF VDFLLQVQAA
790 800 810 820 830 840
VPGLPSRVKC GSPGQLQGRS IFAQDLRLCL DESLSWDCFG LSLLVVALGL AMPMLHHLCG
850 860 870 880 890 900
WDLWYCFHLG LAWLPRRGWQ RGADALSYDA FVVFDKAQSA VADWVYNELR VRLEERRGRR
910 920 930 940 950 960
ALRLCLEERD WLPGKTLFEN LWASVYSSRK MLFVLAHTDQ VSGLLRASFL LAQQRLLEDR
970 980 990 1000 1010 1020
KDVVVLVILS PDARRSRYVR LRQRLCRQSV LFWPHQPSGQ RSFWAQLGMA LTRDNRHFYN
1030
QNFCRGPTMA E