IFNAR1
entrez
3454
canonical
uniprot
P17181
canonical
ensembl
ENSG00000142166
resolver
ensp
ENSP00000270139
resolver
ensp
ENSP00000498654
resolver
ensp
ENSP00000514786
resolver
ensp
ENSP00000515373
resolver
ensp
ENSP00000684764
resolver
enst
ENST00000700084
resolver
enst
ENST00000703557
resolver
genesymbol
IFNAR1
resolver
genesymbol_syn
IFNAR
resolver
hgnc
HGNC:5432
resolver
uniprot
A0A8V8TQK8
resolver
uniprot
A0A994J6F6
resolver
uniprot
B2R6L9
resolver
uniprot
B4DNT3
resolver
uniprot
D3DSF0
resolver
uniprot
Q53GW9
resolver
uniprot
Q53H11
resolver
uniprot
Q6PKD7
resolver
uniprot
Q7M4L2
resolver
uniprot
Q8WTZ2
resolver
uniprot_entry
A0A8V8TQK8_HUMAN
resolver
uniprot_entry
A0A994J6F6_HUMAN
resolver
uniprot_entry
INAR1_HUMAN
resolver
uniprot_sec
B2R6L9
resolver
uniprot_sec
B4DNT3
resolver
uniprot_sec
D3DSF0
resolver
uniprot_sec
Q53GW9
resolver
uniprot_sec
Q53H11
resolver
uniprot_sec
Q6PKD7
resolver
uniprot_sec
Q7M4L2
resolver
uniprot_sec
Q8WTZ2
resolver
amino_acid_sequence
MMVVLLGATTLVLVAVAPWVLSAAAGGKNLKSPQKVEVDIIDDNFILRWNRSDESVGNVTFSFDYQKTGMDNWIKLSGCQNITSTKCNFSSLKLNVYEEIKLRIRAEKENTSSWYEVDSFTPFRKAQIGPPEVHLEAEDKAIVIHISPGTKDSVMWALDGLSFTYSLVIWKNSSGVEERIENIYSRHKIYKLSPETTYCLKVKAALLTSWKIGVYSPVHCIKTTVENELPPPENIEVSVQNQNYVLKWDYTYANMTFQVQWLHAFLKRNPGNHLYKWKQIPDCENVKTTQCVFPQNVFQKGIYLLRVQASDGNNTSFWSEEIKFDTEIQAFLLPPVFNIRSLSDSFHIYIGAPKQSGNTPVIQDYPLIYEIIFWENTSNAERKIIEKKTDVTVPNLKPLTVYCVKARAHTMDEKLNKSSVFSDAVCEKTKPGNTSKIWLIVGICIALFALPFVIYAAKVFLRCINYVFFPSLKPSSSIDEYFSEQPLKNLLLSTSEEQIEKCFIIENISTIATVEETNQTDEDHKKYSSQTSQDSGNYSNEDESESKTSEELQQDFV
uniprot
proteins
disease_involvement
DISEASE: Immunodeficiency 106, susceptibility to viral infections (IMD106) [MIM:619935]: An autosomal recessive immunologic disorder characterized by increased susceptibility to viral infections beginning in infancy or early childhood. IMD106 affected individuals may demonstrate adverse reactions to vaccination with live attenuated viral vaccines, most notably measles, mumps and rubella (MMR) and yellow fever vaccines. A subset of IMD106 patients develop severe reactions, including excessive hyperinflammatory response, encephalopathy, acute respiratory distress syndrome, and multiorgan failure. IMD106 may also predispose to severe respiratory infection with SARS-CoV-2. {ECO:0000269|PubMed:31270247, ECO:0000269|PubMed:33252644, ECO:0000269|PubMed:35442418}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Together with IFNAR2, forms the heterodimeric receptor for type I interferons (including interferons alpha, beta, epsilon, omega and kappa) (PubMed:10049744, PubMed:14532120, PubMed:15337770, PubMed:2153461, PubMed:21854986, PubMed:24075985, PubMed:31270247, PubMed:33252644, PubMed:35442418, PubMed:7813427). Type I interferon binding activates the JAK-STAT signaling cascade, resulting in transcriptional activation or repression of interferon-regulated genes that encode the effectors of the interferon response (PubMed:10049744, PubMed:21854986, PubMed:7665574). Mechanistically, type I interferon-binding brings the IFNAR1 and IFNAR2 subunits into close proximity with one another, driving their associated Janus kinases (JAKs) (TYK2 bound to IFNAR1 and JAK1 bound to IFNAR2) to cross-phosphorylate one another (PubMed:21854986, PubMed:32972995, PubMed:7665574, PubMed:7813427). The activated kinases phosphorylate specific tyrosine residues on the intracellular domains of IFNAR1 and IFNAR2, forming docking sites for the STAT transcription factors (PubMed:21854986, PubMed:32972995, PubMed:7526154, PubMed:7665574, PubMed:7813427). STAT proteins are then phosphorylated by the JAKs, promoting their translocation into the nucleus to regulate expression of interferon-regulated genes (PubMed:19561067, PubMed:21854986, PubMed:32972995, PubMed:7665574, PubMed:7813427, PubMed:9121453). Can also act independently of IFNAR2: 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:21854986, ECO:0000269|PubMed:24075985, ECO:0000269|PubMed:31270247, ECO:0000269|PubMed:32972995, ECO:0000269|PubMed:33252644, ECO:0000269|PubMed:35442418, ECO:0000269|PubMed:7526154, ECO:0000269|PubMed:7665574, ECO:0000269|PubMed:7813427, ECO:0000269|PubMed:9121453}.
uniprot
proteins
mass_dalton
63525
uniprot
proteins
mutagenesis
MUTAGEN 466; /note="Y->F: Impairs internalization in response to interferon."; /evidence="ECO:0000269|PubMed:18056411"; MUTAGEN 491..492; /note="LL->AA: Impairs interaction with TYK2."; /evidence="ECO:0000269|PubMed:24704786"; MUTAGEN 496..497; /note="EE->AA: Impairs interaction with TYK2."; /evidence="ECO:0000269|PubMed:24704786"; MUTAGEN 500; /note="E->A: Impairs interaction with TYK2."; /evidence="ECO:0000269|PubMed:24704786"; MUTAGEN 501; /note="K->R: Mildly reduces ubiquitination. Nearly abolishes ubiquitination and subsequent degradation; when associated with 525-R-R-526."; /evidence="ECO:0000269|PubMed:15337770"; MUTAGEN 525..526; /note="KK->RR: Reduces ubiquitination. Nearly abolishes ubiquitination and subsequent degradation; when associated with R-501."; /evidence="ECO:0000269|PubMed:15337770"; MUTAGEN 535; /note="S->A: Abolishes interaction with FBXW11 and decreases ubiquitination."; /evidence="ECO:0000269|PubMed:14532120, ECO:0000269|PubMed:15337770"; MUTAGEN 535; /note="S->A: Abolishes phosphorylation at this site and interaction with SHMT2."; /evidence="ECO:0000269|PubMed:24075985"; MUTAGEN 539; /note="S->A: Abolishes interaction with FBXW11 and decreases ubiquitination."; /evidence="ECO:0000269|PubMed:15337770
uniprot
proteins
post_translational_modification
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 tyrosine residues in response to interferon-binding: phosphorylation by TYK2 tyrosine kinase creates docking sites for STAT proteins (PubMed:10049744, PubMed:7526154). Phosphorylated on serine residues in response to interferon binding; this promotes interaction with FBXW11 and ubiquitination (PubMed:14532120, PubMed:15337770, PubMed:24075985). {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}.
uniprot
proteins
protein_family
Type II cytokine receptor family
uniprot
proteins
pubmed
10049744
uniprot
proteins
pubmed
10830953
uniprot
proteins
pubmed
1370833
uniprot
proteins
pubmed
14532120
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15337770
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
18056411
uniprot
proteins
pubmed
19349973
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19561067
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
2153461
uniprot
proteins
pubmed
21854986
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24075985
uniprot
proteins
pubmed
24704786
uniprot
proteins
pubmed
31270247
uniprot
proteins
pubmed
32972995
uniprot
proteins
pubmed
33252644
uniprot
proteins
pubmed
33811647
uniprot
proteins
pubmed
35442418
uniprot
proteins
pubmed
7526154
uniprot
proteins
pubmed
7665574
uniprot
proteins
pubmed
7813427
uniprot
proteins
pubmed
8307198
uniprot
proteins
pubmed
9121453
uniprot
proteins
sequence_length
557
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:14532120, ECO:0000269|PubMed:18056411, ECO:0000269|PubMed:2153461, ECO:0000269|PubMed:35442418, 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}.
uniprot
proteins
transmembrane_region
TRANSMEM 437..457; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins