UniProt functional annotation for Q99MB1



	UniProt functional annotation for Q99MB1

UniProt code: Q99MB1.

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. TLR3 is a nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter TRIF/TICAM1, leading to NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and the inflammatory response (By similarity). {ECO:0000250, ECO:0000269|PubMed:14993594}.

Subunit: Monomer and homodimer; dimerization is triggered by ligand- binding, the signaling unit is composed of one ds-RNA of around 40 bp and two TLR3 molecules, and lateral clustering of signaling units along the length of the ds-RNA ligand is required for TLR3 signal transduction. Interacts (via transmembrane domain) with UNC93B1; the interaction is required for transport from the ER to the endosomes (PubMed:33432245). Interacts with SRC; upon binding of double-stranded RNA (By similarity). Interacts with TICAM1 (via the TIR domain) in response to poly(I:C) and this interaction is enhanced in the presence of WDFY1 (PubMed:25736436). The tyrosine-phosphorylated form (via TIR domain) interacts with WDFY1 (via WD repeat 2) in response to poly(I:C) (PubMed:25736436). {ECO:0000250|UniProtKB:O15455, ECO:0000269|PubMed:25736436, ECO:0000269|PubMed:33432245}.

Subcellular location: Endoplasmic reticulum membrane; Single-pass type I membrane protein. Endosome membrane {ECO:0000250|UniProtKB:O15455}. Early endosome {ECO:0000250|UniProtKB:O15455}.

Tissue specificity: Highly expressed in lung. After intraperitoneal injection of lipopolysaccharide, highly expressed in brain, heart, kidney, liver, lung and spleen.

Domain: ds-RNA binding is mediated by LRR 1 to 3, and LRR 17 to 18.

Ptm: TLR3 signaling requires a proteolytic cleavage mediated by cathepsins CTSB and CTSH, the cleavage occurs between amino acids 252 and 346. The cleaved form of TLR3 is the predominant form found in endosomes (By similarity). {ECO:0000250}.

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. TLR3 is a nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter TRIF/TICAM1, leading to NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and the inflammatory response (By similarity). {ECO:0000250, ECO:0000269\|PubMed:14993594}.


Subunit:		Monomer and homodimer; dimerization is triggered by ligand- binding, the signaling unit is composed of one ds-RNA of around 40 bp and two TLR3 molecules, and lateral clustering of signaling units along the length of the ds-RNA ligand is required for TLR3 signal transduction. Interacts (via transmembrane domain) with UNC93B1; the interaction is required for transport from the ER to the endosomes (PubMed:33432245). Interacts with SRC; upon binding of double-stranded RNA (By similarity). Interacts with TICAM1 (via the TIR domain) in response to poly(I:C) and this interaction is enhanced in the presence of WDFY1 (PubMed:25736436). The tyrosine-phosphorylated form (via TIR domain) interacts with WDFY1 (via WD repeat 2) in response to poly(I:C) (PubMed:25736436). {ECO:0000250\|UniProtKB:O15455, ECO:0000269\|PubMed:25736436, ECO:0000269\|PubMed:33432245}.
Subcellular location:		Endoplasmic reticulum membrane; Single-pass type I membrane protein. Endosome membrane {ECO:0000250\|UniProtKB:O15455}. Early endosome {ECO:0000250\|UniProtKB:O15455}.
Tissue specificity:		Highly expressed in lung. After intraperitoneal injection of lipopolysaccharide, highly expressed in brain, heart, kidney, liver, lung and spleen.
Domain:		ds-RNA binding is mediated by LRR 1 to 3, and LRR 17 to 18.
Ptm:		TLR3 signaling requires a proteolytic cleavage mediated by cathepsins CTSB and CTSH, the cleavage occurs between amino acids 252 and 346. The cleaved form of TLR3 is the predominant form found in endosomes (By similarity). {ECO:0000250}.
Similarity:		Belongs to the Toll-like receptor family. {ECO:0000305}.