Q5I2M5

SS
Gene name
TLR9
Protein name
Toll-like receptor 9
Names
CD antigen CD289
Species
Bos taurus (Bovine)
KEGG Pathway
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)

440-469 (Z-loop) SS

Target domain

23-804 (LRR domains)

Relief mechanism

Cleavage

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

3 structures for Q5I2M5

Entry ID Method Resolution Chain Position Source
3WPE X-ray 238 A A 25-815 PDB
5Y3M X-ray 250 A A/B 25-817 PDB
AF-Q5I2M5-F1 Predicted AlphaFoldDB

No variants for Q5I2M5

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q5I2M5

No associated diseases with Q5I2M5

25 regional properties for Q5I2M5

Type Name Position InterPro Accession
domain Toll/interleukin-1 receptor homology (TIR) domain 864 - 1009 IPR000157
repeat Leucine-rich repeat 123 - 144 IPR001611-1
repeat Leucine-rich repeat 273 - 317 IPR001611-2
repeat Leucine-rich repeat 474 - 508 IPR001611-3
repeat Leucine-rich repeat 509 - 553 IPR001611-4
repeat Leucine-rich repeat 627 - 649 IPR001611-5
repeat Leucine-rich repeat 700 - 760 IPR001611-6
repeat Leucine-rich repeat, typical subtype 62 - 84 IPR003591-1
repeat Leucine-rich repeat, typical subtype 121 - 143 IPR003591-2
repeat Leucine-rich repeat, typical subtype 197 - 218 IPR003591-3
repeat Leucine-rich repeat, typical subtype 219 - 241 IPR003591-4
repeat Leucine-rich repeat, typical subtype 282 - 305 IPR003591-5
repeat Leucine-rich repeat, typical subtype 306 - 331 IPR003591-6
repeat Leucine-rich repeat, typical subtype 332 - 352 IPR003591-7
repeat Leucine-rich repeat, typical subtype 362 - 385 IPR003591-8
repeat Leucine-rich repeat, typical subtype 389 - 412 IPR003591-9
repeat Leucine-rich repeat, typical subtype 469 - 492 IPR003591-10
repeat Leucine-rich repeat, typical subtype 493 - 515 IPR003591-11
repeat Leucine-rich repeat, typical subtype 518 - 541 IPR003591-12
repeat Leucine-rich repeat, typical subtype 542 - 565 IPR003591-13
repeat Leucine-rich repeat, typical subtype 572 - 596 IPR003591-14
repeat Leucine-rich repeat, typical subtype 625 - 648 IPR003591-15
repeat Leucine-rich repeat, typical subtype 674 - 697 IPR003591-16
repeat Leucine-rich repeat, typical subtype 723 - 745 IPR003591-17
repeat Leucine-rich repeat unit 392 - 421 IPR041283

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.

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.

6 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
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
Q2EEY0 TLR9 Toll-like receptor 9 Equus caballus (Horse) SS
Q9NR96 TLR9 Toll-like receptor 9 Homo sapiens (Human) EV
Q9EQU3 Tlr9 Toll-like receptor 9 Mus musculus (Mouse) SS
Q5I2M3 TLR9 Toll-like receptor 9 Sus scrofa (Pig) SS
10 20 30 40 50 60
MGPYCAPHPL SLLVQAAALA AALAEGTLPA FLPCELQPHG QVDCNWLFLK SVPHFSAGAP
70 80 90 100 110 120
RANVTSLSLI SNRIHHLHDS DFVHLSNLRV LNLKWNCPPA GLSPMHFPCR MTIEPNTFLA
130 140 150 160 170 180
VPTLEELNLS YNGITTVPAL PSSLVSLSLS HTSILVLGPT HFTGLHALRF LYMDGNCYYM
190 200 210 220 230 240
NPCPRALEVA PGALLGLGNL THLSLKYNNL TEVPRRLPPS LDTLLLSYNH IVTLAPEDLA
250 260 270 280 290 300
NLTALRVLDV GGNCRRCDHA RNPCRECPKN FPKLHPDTFS HLSRLEGLVL KDSSLYKLEK
310 320 330 340 350 360
DWFRGLGRLQ VLDLSENFLY DYITKTTIFN DLTQLRRLNL SFNYHKKVSF AHLHLASSFG
370 380 390 400 410 420
SLVSLEKLDM HGIFFRSLTN ITLQSLTRLP KLQSLHLQLN FINQAQLSIF GAFPSLLFVD
430 440 450 460 470 480
LSDNRISGAA TPAAALGEVD SRVEVWRLPR GLAPGPLDAV SSKDFMPSCN LNFTLDLSRN
490 500 510 520 530 540
NLVTIQQEMF TRLSRLQCLR LSHNSISQAV NGSQFVPLTS LRVLDLSHNK LDLYHGRSFT
550 560 570 580 590 600
ELPQLEALDL SYNSQPFSMQ GVGHNLSFVA QLPSLRYLSL AHNGIHSRVS QKLSSASLRA
610 620 630 640 650 660
LDFSGNSLSQ MWAEGDLYLC FFKGLRNLVQ LDLSENHLHT LLPRHLDNLP KSLRQLRLRD
670 680 690 700 710 720
NNLAFFNWSS LTVLPRLEAL DLAGNQLKAL SNGSLPPGIR LQKLDVSSNS IGFVIPGFFV
730 740 750 760 770 780
RATRLIELNL SANALKTVDP SWFGSLAGTL KILDVSANPL HCACGAAFVD FLLERQEAVP
790 800 810 820 830 840
GLSRRVTCGS PGQLQGRSIF TQDLRLCLDE TLSLDCFGLS LLMVALGLAV PMLHHLCGWD
850 860 870 880 890 900
LWYCFHLCLA HLPRRRRQRG EDTLLYDAVV VFDKVQSAVA DWVYNELRVQ LEERRGRRAL
910 920 930 940 950 960
RLCLEERDWL PGKTLFENLW ASVYSSRKTM FVLDHTDRVS GLLRASFLLA QQRLLEDRKD
970 980 990 1000 1010 1020
VVVLVILRPA AYRSRYVRLR QRLCRQSVLL WPHQPSGQGS FWANLGIALT RDNRHFYNRN
FCRGPTTAE