UniProt functional annotation for P17181



	UniProt functional annotation for P17181

UniProt code: P17181.

Organism: Homo sapiens (Human).

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

Function: Component of the receptor for type I interferons, including interferons alpha, IFNB1 and IFNW1 (PubMed:2153461, PubMed:7665574, PubMed:10049744, PubMed:14532120, PubMed:15337770, PubMed:21854986). Functions in general as heterodimer with IFNAR2 (PubMed:7665574, PubMed:10049744, PubMed:21854986). Type I interferon binding activates the JAK-STAT signaling cascade, and triggers tyrosine phosphorylation of a number of proteins including JAKs, TYK2, STAT proteins and the IFNR alpha- and beta-subunits themselves (PubMed:7665574, PubMed:21854986, PubMed:32972995). Can form an active IFNB1 receptor by itself and activate a signaling cascade that does not involve activation of the JAK-STAT pathway (By similarity). {ECO:0000250|UniProtKB:P33896, ECO:0000269|PubMed:10049744, ECO:0000269|PubMed:14532120, ECO:0000269|PubMed:15337770, ECO:0000269|PubMed:19561067, ECO:0000269|PubMed:2153461, ECO:0000269|PubMed:32972995, ECO:0000269|PubMed:7665574, ECO:0000305|PubMed:21854986}.

Subunit: Heterodimer with IFNAR2 (PubMed:7665574, PubMed:10049744, PubMed:21854986). Interacts with STAT1 and STAT2; the interaction requires its phosphorylation at Tyr-466 (PubMed:9121453). Interacts with TYK2 (PubMed:7526154, PubMed:15337770, PubMed:24704786). Interacts (serine-phosphorylated form) with FBXW11, the substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (PubMed:14532120, PubMed:15337770, PubMed:18056411). Interacts with SHMT2; this promotes interaction with ABRAXAS2 and the BRISC complex (PubMed:24075985). {ECO:0000269|PubMed:10049744, ECO:0000269|PubMed:14532120, ECO:0000269|PubMed:15337770, ECO:0000269|PubMed:18056411, ECO:0000269|PubMed:21854986, ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:24704786, ECO:0000269|PubMed:7526154, ECO:0000269|PubMed:7665574, ECO:0000269|PubMed:9121453}.

Subcellular location: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:14532120, ECO:0000269|PubMed:18056411, ECO:0000269|PubMed:2153461, ECO:0000305|PubMed:7665574}; Single-pass type I membrane protein {ECO:0000305}. Late endosome {ECO:0000269|PubMed:18056411, ECO:0000305|PubMed:14532120}. Lysosome {ECO:0000269|PubMed:18056411, ECO:0000305|PubMed:14532120}. Note=Interferon binding triggers internalization of the receptor from the cell membrane into endosomes and then into lysosomes. {ECO:0000269|PubMed:14532120, ECO:0000269|PubMed:18056411}.

Tissue specificity: IFN receptors are present in all tissues and even on the surface of most IFN-resistant cells. Isoform 1, isoform 2 and isoform 3 are expressed in the IFN-alpha sensitive myeloma cell line U266B1. Isoform 2 and isoform 3 are expressed in the IFN-alpha resistant myeloma cell line U266R. Isoform 1 is not expressed in IFN- alpha resistant myeloma cell line U266R. {ECO:0000269|PubMed:8307198}.

Ptm: Ubiquitinated, leading to its internalization and degradation (PubMed:14532120, PubMed:15337770). Polyubiquitinated via 'Lys-48'- linked and 'Lys-63'-linked ubiquitin chains, leading to receptor internalization and lysosomal degradation (PubMed:18056411). The 'Lys- 63'-linked ubiquitin chains are cleaved off by the BRISC complex (PubMed:24075985). {ECO:0000269|PubMed:14532120, ECO:0000269|PubMed:15337770, ECO:0000269|PubMed:18056411, ECO:0000269|PubMed:24075985}.

Ptm: Phosphorylated on serine residues in response to interferon binding; this promotes interaction with FBXW11 and ubiquitination (PubMed:14532120, PubMed:15337770, PubMed:24075985). Phosphorylated on tyrosine residues by TYK2 tyrosine kinase (PubMed:7526154). Phosphorylated on tyrosine residues in response to interferon (PubMed:10049744). {ECO:0000269|PubMed:10049744, ECO:0000269|PubMed:14532120, ECO:0000269|PubMed:15337770, ECO:0000269|PubMed:7526154}.

Ptm: Palmitoylation at Cys-463 is required for the activation of STAT1 and STAT2. {ECO:0000269|PubMed:19561067}.

Miscellaneous: [Isoform 2]: Incomplete sequence. {ECO:0000305}.

Miscellaneous: [Isoform 3]: Incomplete sequence. {ECO:0000305}.

Similarity: Belongs to the type II cytokine receptor family. {ECO:0000305}.

Sequence caution: Sequence=AAH02590.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={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:		Component of the receptor for type I interferons, including interferons alpha, IFNB1 and IFNW1 (PubMed:2153461, PubMed:7665574, PubMed:10049744, PubMed:14532120, PubMed:15337770, PubMed:21854986). Functions in general as heterodimer with IFNAR2 (PubMed:7665574, PubMed:10049744, PubMed:21854986). Type I interferon binding activates the JAK-STAT signaling cascade, and triggers tyrosine phosphorylation of a number of proteins including JAKs, TYK2, STAT proteins and the IFNR alpha- and beta-subunits themselves (PubMed:7665574, PubMed:21854986, PubMed:32972995). Can form an active IFNB1 receptor by itself and activate a signaling cascade that does not involve activation of the JAK-STAT pathway (By similarity). {ECO:0000250\|UniProtKB:P33896, ECO:0000269\|PubMed:10049744, ECO:0000269\|PubMed:14532120, ECO:0000269\|PubMed:15337770, ECO:0000269\|PubMed:19561067, ECO:0000269\|PubMed:2153461, ECO:0000269\|PubMed:32972995, ECO:0000269\|PubMed:7665574, ECO:0000305\|PubMed:21854986}.


Subunit:		Heterodimer with IFNAR2 (PubMed:7665574, PubMed:10049744, PubMed:21854986). Interacts with STAT1 and STAT2; the interaction requires its phosphorylation at Tyr-466 (PubMed:9121453). Interacts with TYK2 (PubMed:7526154, PubMed:15337770, PubMed:24704786). Interacts (serine-phosphorylated form) with FBXW11, the substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (PubMed:14532120, PubMed:15337770, PubMed:18056411). Interacts with SHMT2; this promotes interaction with ABRAXAS2 and the BRISC complex (PubMed:24075985). {ECO:0000269\|PubMed:10049744, ECO:0000269\|PubMed:14532120, ECO:0000269\|PubMed:15337770, ECO:0000269\|PubMed:18056411, ECO:0000269\|PubMed:21854986, ECO:0000269\|PubMed:24075985, ECO:0000269\|PubMed:24704786, ECO:0000269\|PubMed:7526154, ECO:0000269\|PubMed:7665574, ECO:0000269\|PubMed:9121453}.
Subcellular location:		[Isoform 1]: Cell membrane {ECO:0000269\|PubMed:14532120, ECO:0000269\|PubMed:18056411, ECO:0000269\|PubMed:2153461, ECO:0000305\|PubMed:7665574}; Single-pass type I membrane protein {ECO:0000305}. Late endosome {ECO:0000269\|PubMed:18056411, ECO:0000305\|PubMed:14532120}. Lysosome {ECO:0000269\|PubMed:18056411, ECO:0000305\|PubMed:14532120}. Note=Interferon binding triggers internalization of the receptor from the cell membrane into endosomes and then into lysosomes. {ECO:0000269\|PubMed:14532120, ECO:0000269\|PubMed:18056411}.
Tissue specificity:		IFN receptors are present in all tissues and even on the surface of most IFN-resistant cells. Isoform 1, isoform 2 and isoform 3 are expressed in the IFN-alpha sensitive myeloma cell line U266B1. Isoform 2 and isoform 3 are expressed in the IFN-alpha resistant myeloma cell line U266R. Isoform 1 is not expressed in IFN- alpha resistant myeloma cell line U266R. {ECO:0000269\|PubMed:8307198}.
Ptm:		Ubiquitinated, leading to its internalization and degradation (PubMed:14532120, PubMed:15337770). Polyubiquitinated via 'Lys-48'- linked and 'Lys-63'-linked ubiquitin chains, leading to receptor internalization and lysosomal degradation (PubMed:18056411). The 'Lys- 63'-linked ubiquitin chains are cleaved off by the BRISC complex (PubMed:24075985). {ECO:0000269\|PubMed:14532120, ECO:0000269\|PubMed:15337770, ECO:0000269\|PubMed:18056411, ECO:0000269\|PubMed:24075985}.
Ptm:		Phosphorylated on serine residues in response to interferon binding; this promotes interaction with FBXW11 and ubiquitination (PubMed:14532120, PubMed:15337770, PubMed:24075985). Phosphorylated on tyrosine residues by TYK2 tyrosine kinase (PubMed:7526154). Phosphorylated on tyrosine residues in response to interferon (PubMed:10049744). {ECO:0000269\|PubMed:10049744, ECO:0000269\|PubMed:14532120, ECO:0000269\|PubMed:15337770, ECO:0000269\|PubMed:7526154}.
Ptm:		Palmitoylation at Cys-463 is required for the activation of STAT1 and STAT2. {ECO:0000269\|PubMed:19561067}.
Miscellaneous:		[Isoform 2]: Incomplete sequence. {ECO:0000305}.
Miscellaneous:		[Isoform 3]: Incomplete sequence. {ECO:0000305}.
Similarity:		Belongs to the type II cytokine receptor family. {ECO:0000305}.
Sequence caution:		Sequence=AAH02590.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};