UniProt functional annotation for Q6R5N8



	UniProt functional annotation for Q6R5N8

UniProt code: Q6R5N8.

Organism: Mus musculus (Mouse).

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

Function: Component of innate and adaptive immunity that recognizes and binds 23S rRNA from bacteria. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Specifically binds the 5'-CGGAAAGACC-3' sequence on bacterial 23S rRNA, a sequence also bound by MLS group antibiotics (including erythromycin). May also recognize vesicular stomatitis virus; however, these data require additional evidences. {ECO:0000269|PubMed:21131352, ECO:0000269|PubMed:22821982, ECO:0000269|PubMed:22896636}.

Catalytic activity: Reaction=H2O + NAD(+) = ADP-D-ribose + H(+) + nicotinamide; Xref=Rhea:RHEA:16301, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:57967; EC=3.2.2.6; Evidence={ECO:0000255|PROSITE-ProRule:PRU00204}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16302; Evidence={ECO:0000255|PROSITE-ProRule:PRU00204};

Subunit: Binds MYD88 via their respective TIR domains (By similarity). Interacts with UNC93B1. {ECO:0000250, ECO:0000269|PubMed:17452530}.

Subcellular location: Endosome membrane {ECO:0000269|PubMed:22896636}; Single-pass type I membrane protein {ECO:0000269|PubMed:22896636}.

Domain: The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity. {ECO:0000255|PROSITE-ProRule:PRU00204}.

Miscellaneous: The sequence 23S rRNA from clinical isolates of erythromycin-resistant S.aureus is methylated and is not recognized by Tlr13 anymore, suggesting a link between antibiotic resistance and evasion from Tlr13 recognition. 23S rRNA modifications generating resistance toward MLS antibiotics preventing recognition of bacteria from Tlr13. These data may also explain why Tlr13 is not conserved in human: human may instead possess a related rRNA-sensing pattern recognition receptor that has evolved to recognize species that can hide from Tlr13 owing to rRNA modifications (PubMed:22821982). {ECO:0000305|PubMed:22821982}.

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

Sequence caution: Sequence=BAE41528.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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:		Component of innate and adaptive immunity that recognizes and binds 23S rRNA from bacteria. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Specifically binds the 5'-CGGAAAGACC-3' sequence on bacterial 23S rRNA, a sequence also bound by MLS group antibiotics (including erythromycin). May also recognize vesicular stomatitis virus; however, these data require additional evidences. {ECO:0000269\|PubMed:21131352, ECO:0000269\|PubMed:22821982, ECO:0000269\|PubMed:22896636}.


Catalytic activity:		Reaction=H2O + NAD(+) = ADP-D-ribose + H(+) + nicotinamide; Xref=Rhea:RHEA:16301, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:57967; EC=3.2.2.6; Evidence={ECO:0000255\|PROSITE-ProRule:PRU00204}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16302; Evidence={ECO:0000255\|PROSITE-ProRule:PRU00204};
Subunit:		Binds MYD88 via their respective TIR domains (By similarity). Interacts with UNC93B1. {ECO:0000250, ECO:0000269\|PubMed:17452530}.
Subcellular location:		Endosome membrane {ECO:0000269\|PubMed:22896636}; Single-pass type I membrane protein {ECO:0000269\|PubMed:22896636}.
Domain:		The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity. {ECO:0000255\|PROSITE-ProRule:PRU00204}.
Miscellaneous:		The sequence 23S rRNA from clinical isolates of erythromycin-resistant S.aureus is methylated and is not recognized by Tlr13 anymore, suggesting a link between antibiotic resistance and evasion from Tlr13 recognition. 23S rRNA modifications generating resistance toward MLS antibiotics preventing recognition of bacteria from Tlr13. These data may also explain why Tlr13 is not conserved in human: human may instead possess a related rRNA-sensing pattern recognition receptor that has evolved to recognize species that can hide from Tlr13 owing to rRNA modifications (PubMed:22821982). {ECO:0000305\|PubMed:22821982}.
Similarity:		Belongs to the Toll-like receptor family. {ECO:0000305}.
Sequence caution:		Sequence=BAE41528.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};