Q5I2M7

SS
Gene name
TLR9
Protein name
Toll-like receptor 9
Names
CD antigen CD289
Species
Felis catus (Cat) (Felis silvestris catus)
KEGG Pathway
fca:493839
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

1 structures for Q5I2M7

Entry ID Method Resolution Chain Position Source
AF-Q5I2M7-F1 Predicted AlphaFoldDB

No variants for Q5I2M7

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q5I2M7

No associated diseases with Q5I2M7

17 regional properties for Q5I2M7

Type Name Position InterPro Accession
domain SNF2, N-terminal 721 - 1000 IPR000330
domain Chromo/chromo shadow domain 468 - 556 IPR000953-1
domain Chromo/chromo shadow domain 592 - 649 IPR000953-2
domain Helicase, C-terminal 1028 - 1195 IPR001650
domain Zinc finger, PHD-type 347 - 390 IPR001965-1
domain Zinc finger, PHD-type 420 - 463 IPR001965-2
conserved_site DNA/RNA helicase, ATP-dependent, DEAH-box type, conserved site 844 - 853 IPR002464
domain CHD subfamily II, SANT-like domain 1374 - 1533 IPR009462
domain Domain of unknown function DUF1087 1297 - 1361 IPR009463
domain CHD, C-terminal 2 1731 - 1876 IPR012957
domain CHD, N-terminal 153 - 203 IPR012958
domain Helicase superfamily 1/2, ATP-binding domain 698 - 910 IPR014001
conserved_site Zinc finger, PHD-type, conserved site 348 - 389 IPR019786
domain Zinc finger, PHD-finger 345 - 392 IPR019787-1
domain Zinc finger, PHD-finger 418 - 465 IPR019787-2
domain Chromo domain 595 - 644 IPR023780
domain Chromodomain-helicase-DNA-binding protein 5, DEAH-box helicase domain 702 - 933 IPR028727

Functions

Description
EC Number
Subcellular Localization
  • Endoplasmic reticulum membrane ; Single-pass type I membrane protein
  • Endosome
  • Lysosome
  • Cytoplasmic vesicle, phagosome
  • 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
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.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

4 GO annotations of molecular function

Name Definition
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.

18 GO annotations of biological process

Name Definition
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 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.
regulation of nitrogen compound metabolic process Any process that modulates the frequency, rate or extent of the chemical reactions and pathways involving nitrogen or nitrogenous compounds.
regulation of primary metabolic process Any process that modulates the frequency, rate or extent of the chemical reactions and pathways within a cell or an organism involving those compounds formed as a part of the normal anabolic and catabolic processes. These processes take place in most, if not all, cells of the organism.
regulation of toll-like receptor 9 signaling pathway Any process that modulates the frequency, rate, or extent of toll-like receptor 9 signaling pathway.
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
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
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
MGPCHGALHP LSLLVQAAAL AVALAQGTLP AFLPCELQRH GLVNCDWLFL KSVPHFSAAA
70 80 90 100 110 120
PRGNVTSLSL YSNRIHHLHD SDFVHLSSLR RLNLKWNCPP ASLSPMHFPC HMTIEPHTFL
130 140 150 160 170 180
AVPTLEELNL SYNSITTVPA LPSSLVSLSL SRTNILVLDP ANLAGLHSLR FLFLDGNCYY
190 200 210 220 230 240
KNPCPQALQV APGALLGLGN LTHLSLKYNN LTAVPRGLPP SLEYLLLSYN HIITLAPEDL
250 260 270 280 290 300
ANLTALRVLD VGGNCRRCDH ARNPCMECPK GFPHLHPDTF SHLNHLEGLV LKDSSLYNLN
310 320 330 340 350 360
PRWFHALGNL MVLDLSENFL YDCITKTTAF QGLAQLRRLN LSFNYHKKVS FAHLHLAPSF
370 380 390 400 410 420
GSLLSLQQLD MHGIFFRSLS ETTLRSLVHL PMLQSLHLQM NFINQAQLSI FGAFPGLRYV
430 440 450 460 470 480
DLSDNRISGA MELAAATGEV DGGERVRLPS GDLALGPPGT PSSEGFMPGC KTLNFTLDLS
490 500 510 520 530 540
RNNLVTIQPE MFARLSRLQC LLLSRNSISQ AVNGSQFMPL TSLQVLDLSH NKLDLYHGRS
550 560 570 580 590 600
FTELPRLEAL DLSYNSQPFS MQGVGHNLSF VAQLPALRYL SLAHNDIHSR VSQQLCSASL
610 620 630 640 650 660
RALDFSGNAL SRMWAEGDLY LHFFRGLRSL VRLDLSQNRL HTLLPRTLDN LPKSLRLLRL
670 680 690 700 710 720
RDNYLAFFNW SSLVLLPRLE ALDLAGNQLK ALSNGSLPNG TQLQRLDLSS NSISFVASSF
730 740 750 760 770 780
FALATRLREL NLSANALKTV EPSWFGSLAG TLKVLDVTGN PLHCACGAAF VDFLLEVQAA
790 800 810 820 830 840
VPGLPGHVKC GSPGQLQGRS IFAQDLRLCL DEALSWDCFG LSLLTVALGL AVPMLHHLCG
850 860 870 880 890 900
WDLWYCFHLC LAWLPRRGRR RGADALPYDA FVVFDKAQSA VADWVYNELR VRLEERRGRR
910 920 930 940 950 960
ALRLCLEERD WLPGKTLFEN LWASVYSSRK MLFVLAHTDR VSGLLRASFL LAQQRLLEDR
970 980 990 1000 1010 1020
KDVVVLVILR PDAHRSRYVR LRQRLCRQSV LLWPHQPSGQ RSFWAQLGTA LTRDNQHFYN
1030
QNFCRGPTTA E