UniProt functional annotation for Q9EQU3



	UniProt functional annotation for Q9EQU3

UniProt code: Q9EQU3.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

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 (PubMed:18931679, PubMed:21402738, PubMed:14993594, PubMed:17474149, PubMed:25686612, PubMed:18820679). Plays a role in defense against systemic mouse cytomegalovirus infection (PubMed:14993594). Controls lymphocyte response to Helicobacter infection (PubMed:17474149). Upon CpG stimulation, induces B-cell proliferation, activation, survival and antibody production (By similarity). {ECO:0000250|UniProtKB:Q9NR96, ECO:0000269|PubMed:14993594, ECO:0000269|PubMed:17474149, ECO:0000269|PubMed:18820679, ECO:0000269|PubMed:18931679, ECO:0000269|PubMed:21402738, ECO:0000269|PubMed:25686612}.

Subunit: Monomer and homodimer. Exists as a monomer in the absence of unmethylated cytidine-phosphate-guanosine (CpG) ligand. Proteolytic processing of an insertion loop (Z-loop) is required for homodimerization upon binding to the unmethylated CpG ligand leading to its activation (By similarity). Interacts with MYD88 via their respective TIR domains (PubMed:18820679). Interacts with BTK (By similarity). Interacts (via transmembrane domain) with UNC93B1 (PubMed:17452530, PubMed:18931679). Interacts with CD300LH; the interaction may promote full activation of TLR9-triggered innate responses (PubMed:21940676). Interacts with CNPY3 and HSP90B1; this interaction is required for proper folding in the endoplasmic reticulum (PubMed:18780723, PubMed:20865800). Interacts with SMPDL3B (PubMed:26095358). {ECO:0000250|UniProtKB:Q2EEY0, ECO:0000250|UniProtKB:Q9NR96, ECO:0000269|PubMed:17452530, ECO:0000269|PubMed:18780723, ECO:0000269|PubMed:18820679, ECO:0000269|PubMed:18931679, ECO:0000269|PubMed:20865800, ECO:0000269|PubMed:21940676, ECO:0000269|PubMed:26095358}.

Subcellular location: Endoplasmic reticulum membrane {ECO:0000269|PubMed:18305481}; Single-pass type I membrane protein {ECO:0000269|PubMed:18305481}. Endosome {ECO:0000269|PubMed:18305481, ECO:0000269|PubMed:25917084}. Lysosome {ECO:0000269|PubMed:18305481, ECO:0000269|PubMed:18820679, ECO:0000269|PubMed:25917084}. Cytoplasmic vesicle, phagosome {ECO:0000269|PubMed:18305481, ECO:0000269|PubMed:18820679}. Note=Relocalizes from endoplasmic reticulum to endosome and lysosome upon stimulation with agonist (PubMed:18305481). Exit from the ER requires UNC93B1 (PubMed:18820679). Endolysosomal localization is required for proteolytic cleavage and subsequent activation (PubMed:18931679, PubMed:18820679). Intracellular localization of the active receptor may prevent from responding to self nucleic acid (PubMed:18820679). {ECO:0000269|PubMed:18305481, ECO:0000269|PubMed:18820679, ECO:0000269|PubMed:18931679}.

Tissue specificity: Expressed in the basolateral region of gastric epithelial cells with high levels detected in antrum and body mucosa (at protein level). Detected in spleen and stomach at higher levels in C57BL/6 mice than BALB/C. {ECO:0000269|PubMed:17474149}.

Induction: Following Helicobacter infection, down-regulated in C57BL/6 mice and up-regulated in BALB/C mice. {ECO:0000269|PubMed:17474149}.

Ptm: Activated by proteolytic cleavage of the flexible loop between repeats LRR14 and LRR15 within the ectodomain (PubMed:18931679, PubMed:18820679). Cleavage requires UNC93B1 (PubMed:18820679). Proteolytically processed by first removing the majority of the ectodomain by either asparagine endopeptidase (AEP) or a cathepsin followed by a trimming event that is solely cathepsin mediated and required for optimal receptor signaling (PubMed:21402738). {ECO:0000269|PubMed:18820679, ECO:0000269|PubMed:18931679, ECO:0000269|PubMed:21402738}.

Disruption phenotype: Reduced proliferation of lymphocytes, reduced interferon-gamma production by splenocytes and reduced neutrophil numbers following Helicobacter infection. {ECO:0000269|PubMed:17474149}.

Similarity: Belongs to the Toll-like receptor family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



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 (PubMed:18931679, PubMed:21402738, PubMed:14993594, PubMed:17474149, PubMed:25686612, PubMed:18820679). Plays a role in defense against systemic mouse cytomegalovirus infection (PubMed:14993594). Controls lymphocyte response to Helicobacter infection (PubMed:17474149). Upon CpG stimulation, induces B-cell proliferation, activation, survival and antibody production (By similarity). {ECO:0000250\|UniProtKB:Q9NR96, ECO:0000269\|PubMed:14993594, ECO:0000269\|PubMed:17474149, ECO:0000269\|PubMed:18820679, ECO:0000269\|PubMed:18931679, ECO:0000269\|PubMed:21402738, ECO:0000269\|PubMed:25686612}.


Subunit:		Monomer and homodimer. Exists as a monomer in the absence of unmethylated cytidine-phosphate-guanosine (CpG) ligand. Proteolytic processing of an insertion loop (Z-loop) is required for homodimerization upon binding to the unmethylated CpG ligand leading to its activation (By similarity). Interacts with MYD88 via their respective TIR domains (PubMed:18820679). Interacts with BTK (By similarity). Interacts (via transmembrane domain) with UNC93B1 (PubMed:17452530, PubMed:18931679). Interacts with CD300LH; the interaction may promote full activation of TLR9-triggered innate responses (PubMed:21940676). Interacts with CNPY3 and HSP90B1; this interaction is required for proper folding in the endoplasmic reticulum (PubMed:18780723, PubMed:20865800). Interacts with SMPDL3B (PubMed:26095358). {ECO:0000250\|UniProtKB:Q2EEY0, ECO:0000250\|UniProtKB:Q9NR96, ECO:0000269\|PubMed:17452530, ECO:0000269\|PubMed:18780723, ECO:0000269\|PubMed:18820679, ECO:0000269\|PubMed:18931679, ECO:0000269\|PubMed:20865800, ECO:0000269\|PubMed:21940676, ECO:0000269\|PubMed:26095358}.
Subcellular location:		Endoplasmic reticulum membrane {ECO:0000269\|PubMed:18305481}; Single-pass type I membrane protein {ECO:0000269\|PubMed:18305481}. Endosome {ECO:0000269\|PubMed:18305481, ECO:0000269\|PubMed:25917084}. Lysosome {ECO:0000269\|PubMed:18305481, ECO:0000269\|PubMed:18820679, ECO:0000269\|PubMed:25917084}. Cytoplasmic vesicle, phagosome {ECO:0000269\|PubMed:18305481, ECO:0000269\|PubMed:18820679}. Note=Relocalizes from endoplasmic reticulum to endosome and lysosome upon stimulation with agonist (PubMed:18305481). Exit from the ER requires UNC93B1 (PubMed:18820679). Endolysosomal localization is required for proteolytic cleavage and subsequent activation (PubMed:18931679, PubMed:18820679). Intracellular localization of the active receptor may prevent from responding to self nucleic acid (PubMed:18820679). {ECO:0000269\|PubMed:18305481, ECO:0000269\|PubMed:18820679, ECO:0000269\|PubMed:18931679}.
Tissue specificity:		Expressed in the basolateral region of gastric epithelial cells with high levels detected in antrum and body mucosa (at protein level). Detected in spleen and stomach at higher levels in C57BL/6 mice than BALB/C. {ECO:0000269\|PubMed:17474149}.
Induction:		Following Helicobacter infection, down-regulated in C57BL/6 mice and up-regulated in BALB/C mice. {ECO:0000269\|PubMed:17474149}.
Ptm:		Activated by proteolytic cleavage of the flexible loop between repeats LRR14 and LRR15 within the ectodomain (PubMed:18931679, PubMed:18820679). Cleavage requires UNC93B1 (PubMed:18820679). Proteolytically processed by first removing the majority of the ectodomain by either asparagine endopeptidase (AEP) or a cathepsin followed by a trimming event that is solely cathepsin mediated and required for optimal receptor signaling (PubMed:21402738). {ECO:0000269\|PubMed:18820679, ECO:0000269\|PubMed:18931679, ECO:0000269\|PubMed:21402738}.
Disruption phenotype:		Reduced proliferation of lymphocytes, reduced interferon-gamma production by splenocytes and reduced neutrophil numbers following Helicobacter infection. {ECO:0000269\|PubMed:17474149}.
Similarity:		Belongs to the Toll-like receptor family. {ECO:0000305}.