Affinage

IFNAR2

Interferon alpha/beta receptor 2 · UniProt P48551

Length
515 aa
Mass
57.8 kDa
Annotated
2026-06-10
53 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IFNAR2 is the high-affinity ligand-binding subunit of the heterodimeric type I interferon receptor and is essential and non-redundant for IFN-alpha/beta signaling in human antiviral immunity (PMID:10339405, PMID:26424569). Its extracellular domain binds IFNalpha2 with 1:1 stoichiometry and ~10 nM affinity through a defined epitope centered on hot-spot residues T46/I47/M48, and antiviral potency scales with this binding affinity, making IFNAR2 engagement rate-limiting for signaling (PMID:10339405, PMID:10556041); productive responsiveness additionally requires the partner subunit IFNAR1, with which it forms an allosterically coupled ternary complex on the ligand (PMID:9322767, PMID:20047337). Signaling is driven by the IFNAR2 intracellular domain, which associates with JAK1 and constitutively binds STAT2 in a phosphorylation-independent manner; tyrosine phosphorylation of the IFNAR2 ICD (Y335/Y510 in mouse) drives dissociation of phosphorylated STATs to sustain signaling flux, and IFNAR2 dimerization is itself sufficient to activate STAT1/2 via JAK1 and TYK2 (PMID:15717316, PMID:34813358, PMID:36118237). The IFNAR2 ICD is also released by presenilin-dependent regulated intramembrane proteolysis and translocates to the nucleus as a ternary complex with STAT2 and IRF9, where it modulates ISRE-linked transcription (PMID:15286706, PMID:18456457). Soluble IFNAR2 isoforms generated by alternative RNA processing act as agonists at low concentrations and competitive antagonists at high concentrations, and can stabilize circulating IFN-beta (PMID:11154225, PMID:14980076, PMID:11939908). Human loss-of-function and trafficking-defective IFNAR2 variants abolish IFN-I responses and confer heightened viral vulnerability (PMID:26424569, PMID:35442417). Independent of its cytokine-receptor role, IFNAR2 serves as an HCV entry factor via direct binding of its D2 domain to viral-envelope apolipoprotein E (PMID:31972076).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1997 High

    Established that the functional murine type I IFN receptor requires two distinct subunits rather than one, defining IFNAR2 as one of two obligatory chains.

    Evidence cDNA co-expression of muIFNaR1 and muIFNaR2 with an IFN-responsive luciferase reporter in human cells, with single-subunit negative controls

    PMID:9322767

    Open questions at the time
    • Did not resolve which subunit binds ligand with high affinity
    • No structural or biophysical characterization of the interaction
  2. 1999 High

    Defined IFNAR2 as the high-affinity ligand-binding subunit and mapped the binding interface, showing IFNAR2 engagement is rate-limiting for IFN signaling.

    Evidence Multiple orthogonal biophysics (gel filtration, cross-linking, SPR, RIfS) and alanine-scanning mutagenesis with antiviral potency assays on recombinant ifnar2-EC and IFNalpha2

    PMID:10339405 PMID:10556041

    Open questions at the time
    • Did not define how IFNAR1 contributes to the ternary complex geometry
    • Did not connect binding to intracellular signaling output
  3. 1999 High

    Showed the IFNAR2 intracellular/transmembrane domain alone can initiate ISG transcription upon dimerization but is insufficient for durable antiviral protection, partitioning early signaling from sustained effector output.

    Evidence EpoR-IFNaR chimeric receptors in 2fTGH and TYK2-deficient cells with promoter reporters, antiviral effector time courses, and viral challenge

    PMID:10574956

    Open questions at the time
    • Did not identify the ICD residues required for signaling
    • Mechanism of IFNAR1 requirement for sustained effector expression unresolved
  4. 2001 High

    Demonstrated that a soluble IFNAR2 isoform can transmit signal through IFNAR1 alone and acts as a concentration-dependent agonist/antagonist, revealing IFNAR2 can function without its own cytoplasmic domain.

    Evidence Serum fractionation, competitive reporter assays, and antiproliferative/complex-formation assays using Ifnar-2-/- primary thymocytes

    PMID:11154225

    Open questions at the time
    • Physiological concentrations governing agonist vs antagonist switch not defined in humans
    • Relationship to membrane isoform regulation unclear
  5. 2002 Medium

    Characterized the gene architecture and promoter regulation generating transmembrane and soluble IFNAR2 isoforms, explaining how isoform balance is controlled and is itself IFN-inducible.

    Evidence Genomic cloning, promoter-luciferase deletion analysis across cell lines, and RT-PCR isoform profiling of murine Ifnar-2

    PMID:11939908

    Open questions at the time
    • Human promoter regulation not directly addressed
    • Trans-acting factors controlling the negative regulatory region not identified
  6. 2004 High

    Identified regulated intramembrane proteolysis of IFNAR2 that releases a nuclear-targeting ICD with transcription-modulating activity, uncovering a non-canonical nuclear arm of IFNAR2 function.

    Evidence Membrane-fraction immunoblotting, chimeric receptors, GFP-ICD imaging, and Gal4 reporter assays with presenilin and HDAC dependency in stimulated cells

    PMID:15286706

    Open questions at the time
    • In vivo physiological significance of the released ICD not established
    • Cleavage protease(s) downstream of presenilin not fully defined
  7. 2004 Medium

    Reported IFNAR2 interactions extending beyond canonical signaling, linking it to stress-activated pathways and to pharmacologic stabilization of IFN-beta.

    Evidence Yeast two-hybrid, co-IP, and co-localization for ovine IFNAR2-Sin1; in vivo pharmacokinetics and xenograft efficacy for soluble IFNAR2-IFN-beta complexes

    PMID:14980076 PMID:15345682

    Open questions at the time
    • Sin1 interaction not independently replicated and functional consequence unclear
    • Human relevance of the Sin1 link unaddressed
  8. 2005 High

    Mechanistically defined the nuclear ICD activity as STAT2-dependent, showing constitutive phosphorylation-independent STAT2 binding via its transactivation domain plus a JAK1 requirement.

    Evidence Gal4-ICD reporter assays in STAT2-deficient cells complemented with WT vs TAD-mutant STAT2, JAK1 inhibition, and STAT2-binding-site mutagenesis

    PMID:15717316

    Open questions at the time
    • Target gene set modulated by the ICD-STAT2 axis not defined
    • Quantitative contribution relative to canonical ISGF3 signaling unknown
  9. 2007 High

    Showed that ligand identity controls IFNAR2 receptor fate, with IFNalpha2 driving recycling and IFNbeta driving degradation, providing a trafficking basis for differential signaling outcomes.

    Evidence Quantitative flow-cytometry surface decay, internalization/recycling assays, and JAK/STAT kinetics across cell lines with variable IFNAR1

    PMID:17627610

    Open questions at the time
    • Sorting machinery directing recycling vs degradation not identified
    • Link between trafficking fate and downstream gene programs not fully mapped
  10. 2008 Medium

    Resolved the nuclear transport mechanism of the ICD by showing it forms an ICD-STAT2-IRF9 ternary complex where STAT2 bridges and IRF9's NLS drives nuclear entry.

    Evidence Co-IP, GFP-ICD nuclear localization, and complementation in STAT2/IRF9-deficient cells with co-localization imaging

    PMID:18456457

    Open questions at the time
    • Single-lab finding without reciprocal in vivo validation
    • Transcriptional targets of the nuclear ternary complex not enumerated
  11. 2010 High

    Provided structural evidence for allosteric coupling between IFNAR1 and IFNAR2 binding sites on the shared ligand, explaining how the two subunits cooperate in ternary complex assembly.

    Evidence TROSY-HSQC NMR chemical-shift perturbation mapping of the 89 kDa IFNalpha2/IFNAR2-EC/IFNAR1-EC complex

    PMID:20047337

    Open questions at the time
    • Does not connect allosteric changes to specific signaling output differences
    • Conformational dynamics in full-length membrane receptors not addressed
  12. 2015 High

    Established IFNAR2 as essential and non-redundant for human antiviral immunity through a causative loss-of-function mutation rescuable by wild-type cDNA.

    Evidence Patient resequencing, IFN signaling and viral-control assays in patient cells, and complementation with WT IFNAR2

    PMID:26424569

    Open questions at the time
    • Full clinical spectrum of IFNAR2 deficiency not delineated here
    • Tissue-specific consequences beyond antiviral control not addressed
  13. 2014 Medium

    Linked IFNAR2 signaling to a defined cell-fate program, showing the IFNalpha/IFNAR2 axis drives cell-cycle arrest and apoptosis in hepatocellular carcinoma cells.

    Evidence Fucci live-cell imaging, IFNAR2 loss-of-function, and apoptosis/cell-cycle assays in HuH7 cells

    PMID:25012666

    Open questions at the time
    • Single cell line; generality across tissues unknown
    • Downstream effectors coupling IFNAR2 to apoptosis not defined
  14. 2020 High

    Revealed a cytokine-receptor-independent role of IFNAR2 as an HCV entry factor binding viral apolipoprotein E through its D2 domain.

    Evidence IFNAR2 knockdown, direct D2-apoE binding assays, antibody blocking, multi-genotype infection assays, and humanized mouse validation

    PMID:31972076

    Open questions at the time
    • Structural basis of D2-apoE binding not resolved
    • Relationship between entry-factor role and signaling role not integrated
  15. 2020 Medium

    Connected IFNAR2 deficiency to impaired innate effector function, showing disrupted NK cell degranulation and IFNgamma regulation.

    Evidence Ex vivo NK functional assays on patient PBMC with STAT1 phosphorylation and ISG induction readouts

    PMID:33193576

    Open questions at the time
    • Single case report with limited replication
    • Cell-intrinsic vs systemic contributions to NK phenotype not separated
  16. 2021 High

    Defined the IFNAR2 ICD as the principal driver of JAK-STAT initiation, with its tyrosines promoting phosphorylated-STAT dissociation to maintain signaling flux while IFNAR1 tyrosines are dispensable.

    Evidence Systematic ICD truncation/tyrosine mutagenesis in IFNAR1/IFNAR2 double-knockout cells with STAT phosphorylation, gene activation, and antiviral assays

    PMID:34813358

    Open questions at the time
    • Identity of phosphatases or release machinery acting on STATs not defined
    • Quantitative kinetics of STAT cycling not measured
  17. 2022 High

    Showed IFNAR2 homodimerization is sufficient to activate STAT1/2 via JAK1/TYK2 and pinpointed Y335/Y510 as the unique signaling tyrosines, while a human trafficking-defective variant confirmed surface expression is required for function.

    Evidence Nanobody-based synthetic receptor chimeras with separation-of-function mutagenesis; patient p.Ser53Pro analysis with surface-expression, glycosylation, IFN-response and complementation assays; CRISPR knockout in THP1 monocytes

    PMID:35442417 PMID:36118237 PMID:36346319

    Open questions at the time
    • Whether IFNAR2 homodimers form physiologically without IFNAR1 unknown
    • Tonic-like residual ISG program of partial-function alleles incompletely characterized
  18. 2025 Medium

    Demonstrated that a viral protein subverts IFNAR2 by driving its autophagic degradation to blunt JAK-STAT signaling, identifying IFNAR2 as a target of immune evasion.

    Evidence Ectopic expression and co-IP of ASFV pB125R with IFNAR2, JAK-STAT reporter assays, autophagy inhibition, and ISGF3 nuclear translocation assays in HEK293T/PK-15 cells

    PMID:40270033

    Open questions at the time
    • Single-lab finding without independent replication
    • Degradation machinery and physiological relevance during infection not fully established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the canonical surface signaling role, the proteolytically released nuclear ICD arm, and the IFNAR2 trafficking and HCV-entry functions are integrated and balanced within a single cell remains unresolved.
  • No unified model linking surface signaling, RIP-released nuclear ICD, and entry-factor roles
  • Physiological triggers and quantitative contribution of regulated proteolysis in vivo unknown
  • Structural basis of full-length ternary signaling complex not solved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0060090 molecular adaptor activity 3 GO:0048018 receptor ligand activity 2 GO:0001618 virus receptor activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005634 nucleus 2
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 3 R-HSA-1643685 Disease 2 R-HSA-5357801 Programmed Cell Death 1
Partners
APOLIPOPROTEIN EIFNAR1IRF9JAK1SIN1STAT2
Complex memberships
ICD-STAT2-IRF9 ternary complexType I interferon receptor (IFNAR1/IFNAR2 heterodimer)

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 The extracellular domain of IFNAR2 (ifnar2-EC) binds IFNalpha2 with 1:1 stoichiometry and ~10 nM affinity, as established by gel filtration, chemical cross-linking, BIAcore, reflectometric interference spectroscopy, and fluorescence de-quenching. The association rate has a significant electrostatic component (salt-dependent), and binding affinity decreases with decreasing pH (pKa ~6.7), indicating protonation of a titratable residue at the binding interface. Gel filtration, chemical cross-linking, surface plasmon resonance (BIAcore), reflectometric interference spectroscopy, fluorescence de-quenching, recombinant protein reconstitution Journal of molecular biology High 10339405
1999 Mutational analysis defined the functional binding epitope on IFNalpha2 (hot-spots L30 and R33 on the AB loop) and on ifnar2-EC (hot-spots T46, I47, M48, plus ~10 additional residues). Although IFNalpha2 and IFNbeta compete for the same epitope on ifnar2, mutagenesis revealed distinct centers of binding, suggesting different angular orientations that may differentially couple to cytoplasmic signaling. Antiviral potency correlated proportionally with ifnar2 binding affinity, implicating ifnar2 binding as rate-limiting for IFN signaling. Alanine-scanning mutagenesis, label-free surface plasmon resonance kinetics and thermodynamics, antiviral potency assays Journal of molecular biology High 10556041
1997 The murine type I IFN receptor requires two subunits: muIFNaR1 and muIFNaR2 (49% identical to human IFNAR2). Co-expression of both subunits with an IFN-responsive luciferase reporter in human cells conferred responsiveness to murine IFN-beta; neither subunit alone was sufficient. cDNA library screening, co-expression of receptor subunits with luciferase reporter, functional reconstitution in human cells Gene High 9322767
2001 A soluble isoform of murine Ifnar-2 (muIfnar-2a) is present in serum and biological fluids. At low concentrations it acts as an agonist: it forms a complex with IFN-alpha/beta and cell-surface muIfnar-1, and this complex transmits an antiproliferative signal through the Ifnar-1 chain alone (tested on Ifnar-2-/- primary thymocytes), demonstrating that signal transduction can occur through Ifnar-1 in the absence of the Ifnar-2 cytoplasmic domain. At high concentrations the soluble receptor competitively inhibits IFN activity. Western blot of serum fractions, competitive inhibition reporter assay (L929 cells), antiproliferative and antiviral assays with primary cells, cell-surface complex formation assay using Ifnar-2-/- thymocytes Blood High 11154225
1999 Dimerization of IFNaR2-2 intracellular/transmembrane domain alone (via EpoR extracellular domain chimera) is sufficient to induce IFN-responsive gene transcription (6-16 promoter) upon ligand stimulation, but is insufficient for full antiviral protection. IFNaR1 is required for sustained mRNA and protein levels of antiviral effectors (PKR, OAS, MxA) at later time points. Chimeric receptor constructs (EpoR extracellular/IFNaR intracellular domains), transfection into 2fTGH and TYK2-deficient cells, promoter reporter assay, gene expression time course, Western blot, viral challenge assay The Journal of biological chemistry High 10574956
2004 IFNAR2 (IFNaR2) undergoes regulated proteolytic cleavage in response to PMA, IFN-alpha, EGF, and PKC-delta overexpression, generating a transmembrane stub and releasing the intracellular domain (ICD) in a presenilin-dependent, multi-step process resembling Notch/APP regulated intramembrane proteolysis. The released ICD localizes to the nucleus (GFP fusion) and, when fused to Gal4 DBD, represses transcription of ISRE-linked reporters in a histone deacetylase-dependent manner. Immunoblotting of membrane fractions, chimeric receptor constructs, pharmacological stimulation, fluorescence microscopy (GFP-ICD), Gal4 reporter transcription assay, HDAC inhibitor treatment Oncogene High 15286706
2005 The IFNaR2 intracellular domain (ICD) modulates transcription through the C-terminal transactivation domain of STAT2. STAT2 binds constitutively to the ICD in a tyrosine-phosphorylation-independent manner. Complementation of STAT2-deficient cells with wild-type STAT2 (but not a TAD-deleted mutant) restored ICD-mediated transcriptional effects. JAK1 kinase activity is also required for ICD-mediated transcription. Mutation of the STAT2 binding site on the ICD reduced its transcriptional activity. Gal4 DBD-ICD reporter assay in STAT2-deficient cells, complementation with WT vs. TAD-mutant STAT2, JAK1 inhibition, site-directed mutagenesis of STAT2 binding site Journal of cellular physiology High 15717316
2007 IFNalpha2 and IFNbeta stimulate comparable immediate JAK/STAT activation, but differ in IFNAR2 trafficking: after IFNalpha2 binding, IFNAR2 is internalized and recycled back to the cell surface, whereas after IFNbeta binding it is routed to degradation. This differential routing is governed by the stability and intracellular lifetime of the ternary ligand-receptor complex. Quantitative measurement of surface receptor decay by flow cytometry, internalization/recycling assays, JAK/STAT phosphorylation kinetics across multiple cell lines with variable IFNAR1 levels The Biochemical journal High 17627610
2008 The IFNaR2 ICD, STAT2, and IRF9 form a ternary complex. STAT2 acts as an adaptor bridging the ICD to IRF9. The bipartite nuclear localization signal within IRF9 is the primary determinant driving nuclear transit of the ICD-containing complex (visualized with GFP-ICD). Both STAT2 and IRF9 are required for nuclear transit of the IFNaR2 ICD. Co-immunoprecipitation, GFP-ICD nuclear localization assay, genetic complementation in STAT2/IRF9-deficient cells, co-localization imaging Cellular signalling Medium 18456457
2010 NMR mapping of IFNalpha2 bound to the binary IFNalpha2/IFNAR2-EC complex revealed that IFNAR1-EC binding affects a patch on the same face as the IFNAR2 binding site (in addition to two patches on the opposing face), demonstrating allosteric communication between the IFNAR1 and IFNAR2 binding sites on IFNalpha2. 1H-15N TROSY-HSQC NMR spectroscopy at 800 MHz on the 89 kDa ternary complex; chemical shift perturbation mapping Biochemistry High 20047337
2021 IFNAR2 ICD has a major role in initiating JAK-STAT signaling: successive truncations of the IFNAR2 ICD proportionally decreased constitutive STAT binding, STAT phosphorylation, and target gene activation. Tyrosine residues in the IFNAR1 ICD were not required for signaling, but simultaneous mutation of all IFNAR2 ICD tyrosines reduced STAT phosphorylation and antiviral activity without abolishing constitutive STAT2 binding, suggesting that IFNAR2 ICD tyrosine phosphorylation drives dissociation of phosphorylated STATs to maintain high signaling flux. JAK1 is associated with IFNAR2 and TYK2 with IFNAR1. Receptor ICD truncation/mutation analysis in IFNAR1/IFNAR2 double-knockout cells reconstituted with defined receptor mutants; STAT phosphorylation assays, gene activation assays, antiviral protection assays Science signaling High 34813358
2022 Using synthetic receptor chimeras (nanobody-based extracellular domains fused to native IFNAR transmembrane/intracellular domains), IFNAR2 homodimers were sufficient to induce STAT1/2 signaling via JAK1 and TYK2, whereas IFNAR1 homodimers were not. Mutagenesis identified Y510 and Y335 in murine IFNAR2 as the unique phosphorylation sites required for STAT1/2 activation; other tyrosines in IFNAR1 and IFNAR2 were not involved. Synthetic receptor chimeras (nanobody-based), STAT1/2 phosphorylation assays, transcriptome analysis, viral replication inhibition assay, intracellular deletion variants and point mutations Frontiers in microbiology High 36118237
2015 A homozygous loss-of-function mutation in IFNAR2 rendered patient cells unresponsive to IFN-alpha/beta. Reconstitution of patient cells with wild-type IFNAR2 restored IFN-alpha/beta responsiveness and control of IFN-attenuated viruses, establishing IFNAR2 as essential and non-redundant for IFN-I signaling in human antiviral immunity. Targeted resequencing, functional assays on patient-derived cells (IFN signaling, viral control), complementation with wild-type IFNAR2 cDNA Science translational medicine High 26424569
2022 A missense variant p.Ser53Pro in IFNAR2 prevents cell-surface expression of IFNAR2 protein; small amounts persist intracellularly in an aberrantly glycosylated state. Cells exclusively expressing p.Ser53Pro lacked responses to recombinant IFN-I and showed heightened viral vulnerability in vitro—a phenotype rescued by wild-type IFNAR2 complementation. Patient genetic analysis, cell surface expression assays, glycosylation analysis, IFN-I response assays (ISG induction, STAT phosphorylation), viral challenge in vitro, wild-type IFNAR2 complementation The Journal of experimental medicine High 35442417
2020 In IFNAR2-deficient patient NK cells stimulated with IFNalpha, the expected increase in degranulation was impaired and the expected inhibition of IFNgamma production was absent, demonstrating that IFNAR2-dependent IFN-I signaling is required for normal NK cell effector function modulation. Ex vivo NK cell functional assays (degranulation, IFNgamma production) on patient PBMC; STAT1 phosphorylation and ISG induction assays Frontiers in genetics Medium 33193576
2004 Soluble IFNAR2 (sIFNAR-2) forms a specific complex with IFN-beta, extending its serum half-life from minutes to hours in mice when co-administered intravenously, and enhances its antitumor efficacy 9–27-fold in xenograft models. The enhancement depends on slow release of IFN-beta from the complex in vivo. In vitro antiviral enhancement assay, in vivo mouse pharmacokinetic studies (IV administration), xenograft SCID mouse survival assay Journal of interferon & cytokine research Medium 14980076
2004 IFNAR2 interacts with stress-activated protein kinase-interacting protein 1 (Sin1) via the C-terminal 185 amino acids of ovine IFNAR2. The interaction is constitutive (yeast two-hybrid and co-immunoprecipitation). When co-expressed, ovSin1 and ovIFNAR2 co-localize at the plasma membrane and perinuclear structures, suggesting Sin1 links IFN-I signaling to stress-activated pathways. Yeast two-hybrid screen of ovine endometrial cDNA library, co-immunoprecipitation, co-localization by immunofluorescence microscopy Endocrinology Medium 15345682
2014 IFN-alpha induces cell cycle arrest in G0/G1 phases leading to apoptosis through an IFNAR2-dependent signaling pathway in HuH7 hepatocellular carcinoma cells. Time-lapse imaging with a Fucci fluorescent cell cycle indicator showed that the IFN-alpha/IFNAR2 axis sensitizes cells to apoptosis in the S/G2/M phases in preparation for death in G0/G1. Fucci-based live-cell time-lapse imaging, IFNAR2 loss-of-function, biochemical apoptosis assays, cell cycle analysis The Journal of biological chemistry Medium 25012666
2020 IFNAR2 was identified as a novel HCV entry factor. IFNAR2 binds HCV virions through a direct interaction of its D2 domain with the C-terminal end of apolipoprotein E (apoE) on the viral envelope. Silencing IFNAR2 reduced HCV proliferation. An anti-IFNAR2 D2 domain antibody attenuated the IFNAR2-apoE interaction and impaired HCV infection. Recombinant IFNAR2 protein inhibited multiple HCV genotypes in vitro and in humanized mice. Chemical probes, IFNAR2 knockdown, direct binding assay (IFNAR2 D2 domain with apoE), antibody blocking, in vitro infection assays across HCV genotypes, humanized transgenic mouse model ACS chemical biology High 31972076
2025 The African swine fever virus protein B125R binds to IFNAR2 and promotes its autophagic degradation, thereby impairing JAK-STAT signal transduction at an early stage, reducing nuclear translocation of the ISGF3 complex and decreasing ISG production. Ectopic expression in HEK293T and PK-15 cells, co-immunoprecipitation (pB125R–IFNAR2 interaction), IFN-beta-triggered JAK-STAT reporter assays, autophagy inhibition experiments, ISGF3 nuclear translocation assay Veterinary research Medium 40270033
2022 Human IFN-I signaling in THP1 monocytic cells absolutely requires IFNAR2, as shown by complete loss of ISG induction upon CRISPR/Cas9 knockout. A 7-bp deletion IFNAR2 mutant retains partial responsiveness to IFNbeta by upregulating a subset of tonic-like ISGs; this residual signaling still depends on IFNAR2 protein expression (via exon skipping producing a truncated but functional protein). CRISPR/Cas9 knockout, IFN-beta stimulation, ISG expression profiling, RT-qPCR, Western blot, CRISPR-induced exon-skipping analysis Journal of interferon & cytokine research Medium 36346319
2002 The murine Ifnar-2 gene spans ~33 kb, consists of 9 exons and 8 introns, and generates one transmembrane (Ifnar-2c) and two soluble (Ifnar-2a/2a') isoforms by alternative RNA processing. Promoter analysis defined three regulatory regions: a proximal region conferring high basal expression, a distal region conferring IFN-inducible expression, and a negative regulatory region between them. The two transcript isoforms (2a and 2c) are independently regulated in some cell types. Genomic cloning, promoter-luciferase reporter assays, IFN treatment of multiple cell lines, RT-PCR isoform analysis The Biochemical journal Medium 11939908

Source papers

Stage 0 corpus · 53 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Human IFNAR2 deficiency: Lessons for antiviral immunity. Science translational medicine 196 26424569
1999 Biophysical analysis of the interaction of human ifnar2 expressed in E. coli with IFNalpha2. Journal of molecular biology 109 10339405
2001 The soluble murine type I interferon receptor Ifnar-2 is present in serum, is independently regulated, and has both agonistic and antagonistic properties. Blood 87 11154225
1999 Mutational and structural analysis of the binding interface between type I interferons and their receptor Ifnar2. Journal of molecular biology 84 10556041
2022 Life-threatening viral disease in a novel form of autosomal recessive IFNAR2 deficiency in the Arctic. The Journal of experimental medicine 78 35442417
2021 IFNAR1 and IFNAR2 play distinct roles in initiating type I interferon-induced JAK-STAT signaling and activating STATs. Science signaling 69 34813358
2002 Expression of interferon receptor subunits, IFNAR1 and IFNAR2, in the ovine uterus. Biology of reproduction 69 12193393
2007 Comparable potency of IFNalpha2 and IFNbeta on immediate JAK/STAT activation but differential down-regulation of IFNAR2. The Biochemical journal 68 17627610
2005 IFNAR1 and IFNAR2 polymorphisms confer susceptibility to multiple sclerosis but not to interferon-beta treatment response. Journal of neuroimmunology 68 15885318
2004 Regulated proteolysis of the IFNaR2 subunit of the interferon-alpha receptor. Oncogene 44 15286706
1997 Mammalian type I interferon receptors consists of two subunits: IFNaR1 and IFNaR2. Gene 44 9322767
2005 Structural, kinetic, and thermodynamic analysis of the binding of the 40 kDa PEG-interferon-alpha2a and its individual positional isomers to the extracellular domain of the receptor IFNAR2. Bioconjugate chemistry 41 15898717
2018 IFNAR2 Is Required for Anti-influenza Immunity and Alters Susceptibility to Post-influenza Bacterial Superinfections. Frontiers in immunology 40 30473701
2021 Loss-of-function mutations in IFNAR2 in COVID-19 severe infection susceptibility. Journal of global antimicrobial resistance 36 34273592
2014 Interferon-α acts on the S/G2/M phases to induce apoptosis in the G1 phase of an IFNAR2-expressing hepatocellular carcinoma cell line. The Journal of biological chemistry 35 25012666
2009 Association study of IFNAR2 and IL10RB genes with the susceptibility and interferon response in HBV infection. Journal of viral hepatitis 33 19714778
2022 IFNAR2 relevance in the clinical outcome of individuals with severe COVID-19. Frontiers in immunology 32 35967349
1998 Expression of interferon receptor genes (IFNAR1 and IFNAR2 mRNA) in the liver may predict outcome after interferon therapy in patients with chronic genotype 2a or 2b hepatitis C virus infection. Journal of clinical gastroenterology 32 9563926
2004 Formation of human IFN-beta complex with the soluble type I interferon receptor IFNAR-2 leads to enhanced IFN stability, pharmacokinetics, and antitumor activity in xenografted SCID mice. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 31 14980076
2020 IFNAR2 Deficiency Causing Dysregulation of NK Cell Functions and Presenting With Hemophagocytic Lymphohistiocytosis. Frontiers in genetics 28 33193576
1999 Dimerization of the interferon type I receptor IFNaR2-2 is sufficient for induction of interferon effector genes but not for full antiviral activity. The Journal of biological chemistry 27 10574956
2017 Role of Functional IFNL4, IFNLR1, IFNA, IFNAR2 Polymorphisms in Hepatitis B virus-related liver disease in Han Chinese population. Journal of viral hepatitis 20 29080269
2006 Binding Characteristics of IFN-alpha Subvariants to IFNAR2-EC and Influence of the 6-Histidine Tag. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 19 17238829
2004 Initial expression of interferon alpha receptor 2 (IFNAR2) on CD34-positive cells and its down-regulation correlate with clinical response to interferon therapy in chronic myelogenous leukemia. European journal of haematology 19 15287917
2002 Multiple regions within the promoter of the murine Ifnar-2 gene confer basal and inducible expression. The Biochemical journal 19 11939908
2010 NMR mapping of the IFNAR1-EC binding site on IFNalpha2 reveals allosteric changes in the IFNAR2-EC binding site. Biochemistry 17 20047337
2004 Optimizing the binding affinity of a carrier protein: a case study on the interaction between soluble ifnar2 and interferon beta. The Journal of biological chemistry 17 14960565
2005 Intracellular domain of the IFNaR2 interferon receptor subunit mediates transcription via Stat2. Journal of cellular physiology 16 15717316
2023 Association of IFNAR2 rs2236757 and OAS3 rs10735079 Polymorphisms with Susceptibility to COVID-19 Infection and Severity in Palestine. Interdisciplinary perspectives on infectious diseases 14 37745867
2016 Characterization of interferon α and β receptor IFNAR1 and IFNAR2 expression and regulation in the uterine endometrium during the estrous cycle and pregnancy in pigs. Theriogenology 12 27769575
2004 Interaction of stress-activated protein kinase-interacting protein-1 with the interferon receptor subunit IFNAR2 in uterine endometrium. Endocrinology 12 15345682
2021 Deleterious single nucleotide polymorphisms (SNPs) of human IFNAR2 gene facilitate COVID-19 severity in patients: a comprehensive in silico approach. Journal of biomolecular structure & dynamics 11 34355676
2013 Association of IFNAR2 and IL10RB genes in chronic hepatitis B virus infection. Tissue antigens 9 23745570
2008 Nuclear transit of the intracellular domain of the interferon receptor subunit IFNaR2 requires Stat2 and Irf9. Cellular signalling 9 18456457
2004 A flow cytometric method for determination of the interferon receptor IFNAR2 subunit in peripheral blood leukocyte subsets. Journal of pharmacological and toxicological methods 9 15233969
2022 Synthetic mimetics assigned a major role to IFNAR2 in type I interferon signaling. Frontiers in microbiology 8 36118237
2022 Type I interferon receptor (IFNAR2) deficiency reveals Zika virus cytopathicity in human macrophages and microglia. Frontiers in immunology 8 36439115
2020 Antiviral, Immunomodulatory and Antiproliferative Activities of Recombinant Soluble IFNAR2 without IFN-ß Mediation. Journal of clinical medicine 7 32244308
2023 Participation of Single-Nucleotide Variants in IFNAR1 and IFNAR2 in the Immune Response against SARS-CoV-2 Infection: A Systematic Review. Pathogens (Basel, Switzerland) 6 38003785
2020 Identification of Interferon Receptor IFNAR2 As a Novel HCV Entry Factor by Using Chemical Probes. ACS chemical biology 6 31972076
2017 Expression of IFNAR1 and IFNAR2 in cattle placenta during early pregnancy. Reproduction in domestic animals = Zuchthygiene 6 29194800
2007 The combination of IFN-alpha2 and IFN-alpha8 exhibits synergistic antiproliferative activity on renal cell carcinoma (RCC) cell lines through increased binding affinity for IFNAR-2. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 6 17572016
2022 Specific activation of embryonic IFNAR1 and endometrial IFNAR2 induced by embryonic IFNτ directs normal uterine fate for bovine early implantation. Journal of reproductive immunology 5 35907379
2022 Knockdown of IFNAR2 reduces the inflammatory response in mouse model of type 1 diabetes. Biochemical and biophysical research communications 4 35728283
2024 Study on the correlation between DPP9 rs2109069 and IFNAR2 rs2236757 polymorphisms with COVID-19 mortality. Nucleosides, nucleotides & nucleic acids 3 38660988
2024 Severe Adverse Reaction to Measles Vaccine Due to Homozygous Mutation in the IFNAR2 Gene: A Case Report and Literature Review. Journal of clinical immunology 3 39436454
2022 Human IFNAR2 Mutant Generated by CRISPR/Cas9-Induced Exon Skipping Upregulates a Subset of Tonic-Like Interferon-Stimulated Genes Upon IFNβ Stimulation. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 3 36346319
2025 The African swine fever virus B125R protein antagonizes JAK-STAT signalling by promoting the degradation of IFNAR2. Veterinary research 2 40270033
2025 Genetic Predictors of Paxlovid Treatment Response: The Role of IFNAR2, OAS1, OAS3, and ACE2 in COVID-19 Clinical Course. Journal of personalized medicine 2 40278335
2012 Expression of IFNAR2 mRNA in peripheral blood mononuclear cells of patients with HCV infection. Acta gastro-enterologica Belgica 1 22870788
2026 IFNAR2 p.F8S Variant Associates with Severe COVID-19 and Adaptive Immune Cell Activation Modulation. International journal of molecular sciences 0 41596638
2026 Establishment of an IFNAR2 Knockout Pig Model for Severe Dengue-Like Pathology. Journal of medical virology 0 42171447
2026 Pregnancy in Type I Interferon Receptor (IFNAR2) Knockout Sheep Challenges the Accepted Paradigm for Pregnancy Recognition in Ruminants. Biology of reproduction 0 42261664

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