UniProt functional annotation for Q9NR97



	UniProt functional annotation for Q9NR97

UniProt code: Q9NR97.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Endosomal receptor that plays a key role in innate and adaptive immunity (PubMed:25297876, PubMed:32433612). Controls host immune response against pathogens through recognition of RNA degradation products specific to microorganisms that are initially processed by RNASET2 (PubMed:31778653). Recognizes GU-rich single- stranded RNA (GU-rich RNA) derived from SARS-CoV-2, SARS-CoV-1 and HIV- 1 viruses (PubMed:33718825). Upon binding to agonists, undergoes dimerization that brings TIR domains from the two molecules into direct contact, leading to the recruitment of TIR-containing downstream adapter MYD88 through homotypic interaction (PubMed:23520111, PubMed:25599397, PubMed:26929371, PubMed:33718825). In turn, the Myddosome signaling complex is formed involving IRAK4, IRAK1, TRAF6, TRAF3 leading to activation of downstream transcription factors NF- kappa-B and IRF7 to induce proinflammatory cytokines and interferons, respectively (PubMed:16737960, PubMed:17932028, PubMed:29155428). {ECO:0000269|PubMed:16737960, ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:23520111, ECO:0000269|PubMed:25297876, ECO:0000269|PubMed:25599397, ECO:0000269|PubMed:26929371, ECO:0000269|PubMed:29155428, ECO:0000269|PubMed:31778653, ECO:0000269|PubMed:32433612, ECO:0000269|PubMed:33718825}.

Activity regulation: Activated by RNAs having enough uridines. {ECO:0000269|PubMed:25599397, ECO:0000269|PubMed:26929371}.

Subunit: Homodimer (PubMed:23520111, PubMed:25599397, PubMed:26929371, PubMed:29155428). Interacts with MYD88 via their respective TIR domains (Probable). Interacts with UNC93B1 (By similarity). Interacts with BTK (PubMed:17932028). Interacts with SMPDL3B (By similarity). {ECO:0000250|UniProtKB:P58682, ECO:0000269|PubMed:17932028, ECO:0000269|PubMed:23520111, ECO:0000269|PubMed:25599397, ECO:0000269|PubMed:26929371, ECO:0000269|PubMed:29155428, ECO:0000305}.

Subcellular location: Endosome membrane {ECO:0000269|PubMed:25297876}; Single-pass type I membrane protein {ECO:0000250}. Note=Endosomal localization confers distinctive proteolytic processing. {ECO:0000269|PubMed:25297876}.

Tissue specificity: Expressed in myeloid dendritic cells, monocytes, and monocyte-derived dendritic cells. {ECO:0000269|PubMed:33718825}.

Ptm: Ubiquitinated by RNF216; leading to degradation by the proteasome. {ECO:0000269|PubMed:31385713}.

Ptm: Proteolytic processing occurs in monocytes and monocyte-derived macrophages by both furin-like proprotein convertase and cathepsins (PubMed:25297876). The cleavage is necessary for dimer formation and subsequent activation (PubMed:26929371). {ECO:0000269|PubMed:25297876, ECO:0000269|PubMed:26929371}.

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

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Endosomal receptor that plays a key role in innate and adaptive immunity (PubMed:25297876, PubMed:32433612). Controls host immune response against pathogens through recognition of RNA degradation products specific to microorganisms that are initially processed by RNASET2 (PubMed:31778653). Recognizes GU-rich single- stranded RNA (GU-rich RNA) derived from SARS-CoV-2, SARS-CoV-1 and HIV- 1 viruses (PubMed:33718825). Upon binding to agonists, undergoes dimerization that brings TIR domains from the two molecules into direct contact, leading to the recruitment of TIR-containing downstream adapter MYD88 through homotypic interaction (PubMed:23520111, PubMed:25599397, PubMed:26929371, PubMed:33718825). In turn, the Myddosome signaling complex is formed involving IRAK4, IRAK1, TRAF6, TRAF3 leading to activation of downstream transcription factors NF- kappa-B and IRF7 to induce proinflammatory cytokines and interferons, respectively (PubMed:16737960, PubMed:17932028, PubMed:29155428). {ECO:0000269\|PubMed:16737960, ECO:0000269\|PubMed:17932028, ECO:0000269\|PubMed:23520111, ECO:0000269\|PubMed:25297876, ECO:0000269\|PubMed:25599397, ECO:0000269\|PubMed:26929371, ECO:0000269\|PubMed:29155428, ECO:0000269\|PubMed:31778653, ECO:0000269\|PubMed:32433612, ECO:0000269\|PubMed:33718825}.


Activity regulation:		Activated by RNAs having enough uridines. {ECO:0000269\|PubMed:25599397, ECO:0000269\|PubMed:26929371}.
Subunit:		Homodimer (PubMed:23520111, PubMed:25599397, PubMed:26929371, PubMed:29155428). Interacts with MYD88 via their respective TIR domains (Probable). Interacts with UNC93B1 (By similarity). Interacts with BTK (PubMed:17932028). Interacts with SMPDL3B (By similarity). {ECO:0000250\|UniProtKB:P58682, ECO:0000269\|PubMed:17932028, ECO:0000269\|PubMed:23520111, ECO:0000269\|PubMed:25599397, ECO:0000269\|PubMed:26929371, ECO:0000269\|PubMed:29155428, ECO:0000305}.
Subcellular location:		Endosome membrane {ECO:0000269\|PubMed:25297876}; Single-pass type I membrane protein {ECO:0000250}. Note=Endosomal localization confers distinctive proteolytic processing. {ECO:0000269\|PubMed:25297876}.
Tissue specificity:		Expressed in myeloid dendritic cells, monocytes, and monocyte-derived dendritic cells. {ECO:0000269\|PubMed:33718825}.
Ptm:		Ubiquitinated by RNF216; leading to degradation by the proteasome. {ECO:0000269\|PubMed:31385713}.
Ptm:		Proteolytic processing occurs in monocytes and monocyte-derived macrophages by both furin-like proprotein convertase and cathepsins (PubMed:25297876). The cleavage is necessary for dimer formation and subsequent activation (PubMed:26929371). {ECO:0000269\|PubMed:25297876, ECO:0000269\|PubMed:26929371}.
Similarity:		Belongs to the Toll-like receptor family. {ECO:0000305}.