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Gene Review

IFNAR1  -  interferon (alpha, beta and omega) receptor 1

Homo sapiens

Synonyms: AVP, CRF2-1, Cytokine receptor class-II member 1, Cytokine receptor family 2 member 1, IFN-R-1, ...
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Disease relevance of IFNAR1


Psychiatry related information on IFNAR1

  • This finding suggests that in the double TG mouse model mDCs once infected facilitate systemic MV spreading and infection, which depend on mDC MV permissiveness determined by the level of type I IFN generated via IFNAR1 [6].

High impact information on IFNAR1

  • STAT3 as an adapter to couple phosphatidylinositol 3-kinase to the IFNAR1 chain of the type I interferon receptor [7].
  • Mechanisms underlying down-regulation of the type I interferon receptor consisting of IFNAR1 and IFNAR2 subunits remain largely unknown [8].
  • These findings characterize SCF(HOS) as an E3 ubiquitin ligase that is essential for ubiquitination, proteolysis and down-regulation of IFNAR1, and implicate HOS in the regulation of cellular responses to IFNalpha [8].
  • HOS expression and activities are required for IFNalpha-stimulated ubiquitination of IFNAR1, endocytosis of the type I interferon receptor, down-regulation of IFNAR1 levels, and IFNAR1 proteolysis via the lysosomal pathway [8].
  • The tyrosine kinase Tyk2 controls IFNAR1 cell surface expression [9].

Chemical compound and disease context of IFNAR1

  • The magnitude of pressor response to NA in the LSA was increased by i.v. pretreatment with the ganglion blocker pentolinium (10 mg/kg) and significantly reduced by i.v. pretreatment with the V(1)-vasopressin receptor antagonist dTyr (CH2)5(Me) AVP (50 mug/kg) [10].
  • We have previously demonstrated that both all-trans retinoic acid (ATRA) and interferon á (IFNá) can inhibit proliferation of human PNET cells and that ATRA can up-regulate IFNá receptor expression in vitro [11].
  • Involvement of anteroventral third ventricular AMPA/kainate receptors in both hyperosmotic and hypovolemic AVP secretion in conscious rats [12].
  • Felypressin and AVP induced a pressor effect, and bradycardia was inhibited by IV V1 antagonist [13].

Biological context of IFNAR1

  • One subunit, IFNAR1, has low affinity binding for interferon yet is required for signal transduction [14].
  • A trend detected with a single nucleotide polymorphism SNP 16469 (A/T) located at the third intron of the IFNAR1 gene, suggesting modest association with relapse-free status, will require confirmation in an independent data set [15].
  • IFNalpha promotes the phosphorylation of IFNAR1 on Ser535, followed by recruitment of the E3 ubiquitin ligase, beta-TrCP2 (beta-transducin repeats-containing protein 2), ubiquitination of IFNAR1 and proteolysis [16].
  • No alteration of the expression level of IFNAR-1 was observed with respect to the -408 genotypes or to interferon treatment response [2].
  • Although the amino acid sequences of various IFN-alpha/beta subtypes differ markedly, they are all considered to share a common three-dimensional structure and to bind the same heterodimeric receptor, composed of the IFNAR-1 and IFNAR-2 subunits [17].

Anatomical context of IFNAR1


Associations of IFNAR1 with chemical compounds


Physical interactions of IFNAR1


Enzymatic interactions of IFNAR1

  • Studies of mutant Tyk2 forms deleted at the N terminus indicated that the integrity of the N-terminal region is required to sustain IFNAR1 [27].

Co-localisations of IFNAR1


Regulatory relationships of IFNAR1

  • Both are IFN dependent and abrogated by a monoclonal antibody which blocks IFNAR action [22].
  • TYK2 activity promotes ligand-induced IFNAR1 proteolysis [16].
  • Further, IFN-beta treatment stimulated IFNAR-1-associated phosphoinositol kinase activity equally in either U1.wt or U1.KR930 cells [29].

Other interactions of IFNAR1

  • The ifnar1 component is well characterized and a putative ifnar2 cDNA has recently been identified [30].
  • In both model systems, titration of the Tyk2 kinase away from the Ifnar1 receptor chain accounts for the observed cross-interference [31].
  • NF-kappaB activation requires the IFN-dependent association of STAT3 with the IFNAR1 chain of the IFN receptor [32].
  • These experiments indicated that IFNAR1 forms a complex containing the MeV-accessory proteins C and V, RACK1, and STAT1 in MeV-infected cells but not in uninfected cells [33].
  • After IFN-beta treatment for 5 min, a tyrosine-phosphorylated protein of approximately 95 kDa (beta-PTyr) is found bound to IFNAR, but can be dissociated by denaturation [22].
  • The lack of IFNAR1 palmitoylation affects selectively the activation of Stat2, which results in a lack of efficient Stat1 activation and nuclear translocation and IFN-alpha-activated gene transcription [34].

Analytical, diagnostic and therapeutic context of IFNAR1


  1. A protein-arginine methyltransferase binds to the intracytoplasmic domain of the IFNAR1 chain in the type I interferon receptor. Abramovich, C., Yakobson, B., Chebath, J., Revel, M. EMBO J. (1997) [Pubmed]
  2. IFNAR1 and IFNAR2 polymorphisms confer susceptibility to multiple sclerosis but not to interferon-beta treatment response. Leyva, L., Fernández, O., Fedetz, M., Blanco, E., Fernández, V.E., Oliver, B., León, A., Pinto-Medel, M.J., Mayorga, C., Guerrero, M., Luque, G., Alcina, A., Matesanz, F. J. Neuroimmunol. (2005) [Pubmed]
  3. Interferon-alpha receptor-1 (IFNAR1) variants are associated with protection against cerebral malaria in the Gambia. Aucan, C., Walley, A.J., Hennig, B.J., Fitness, J., Frodsham, A., Zhang, L., Kwiatkowski, D., Hill, A.V. Genes Immun. (2003) [Pubmed]
  4. Promoter polymorphisms of the interferon-alpha receptor gene and development of Interferon-induced depressive symptoms in patients with chronic hepatitis C: preliminary findings. Yoshida, K., Alagbe, O., Wang, X., Woolwine, B., Thornbury, M., Raison, C.L., Miller, A.H. Neuropsychobiology (2005) [Pubmed]
  5. Intrahepatic mRNA Levels of Type I Interferon Receptor and Interferon-Stimulated Genes in Genotype 1b Chronic Hepatitis C. Association between IFNAR1 mRNA Level and Sustained Response to Interferon Therapy. Taniguchi, H., Iwasaki, Y., Takahashi, A., Shimomura, H., Moriya, A., Yu, P.C., Umeoka, F., Fujioka, S., Koide, N., Shiratori, Y. Intervirology (2007) [Pubmed]
  6. Wild-type measles virus infection in human CD46/CD150-transgenic mice: CD11c-positive dendritic cells establish systemic viral infection. Shingai, M., Inoue, N., Okuno, T., Okabe, M., Akazawa, T., Miyamoto, Y., Ayata, M., Honda, K., Kurita-Taniguchi, M., Matsumoto, M., Ogura, H., Taniguchi, T., Seya, T. J. Immunol. (2005) [Pubmed]
  7. STAT3 as an adapter to couple phosphatidylinositol 3-kinase to the IFNAR1 chain of the type I interferon receptor. Pfeffer, L.M., Mullersman, J.E., Pfeffer, S.R., Murti, A., Shi, W., Yang, C.H. Science (1997) [Pubmed]
  8. SCF(HOS) ubiquitin ligase mediates the ligand-induced down-regulation of the interferon-alpha receptor. Kumar, K.G., Tang, W., Ravindranath, A.K., Clark, W.A., Croze, E., Fuchs, S.Y. EMBO J. (2003) [Pubmed]
  9. The tyrosine kinase Tyk2 controls IFNAR1 cell surface expression. Ragimbeau, J., Dondi, E., Alcover, A., Eid, P., Uzé, G., Pellegrini, S. EMBO J. (2003) [Pubmed]
  10. Pressor effects of noradrenaline injected into the lateral septal area of unanesthetized rats. Scopinho, A.A., Resstel, L.B., Antunes-Rodrigues, J., Corr??a, F.M. Brain Res. (2006) [Pubmed]
  11. Effects of all-trans retinoic acid and interferon alpha in peripheral neuroectodermal tumor cell cultures and xenografts. Rosolen, A., Favaretto, G., Masarotto, G., Cavazzana, A., Zanesco, L., Frascella, E. Int. J. Oncol. (1998) [Pubmed]
  12. Involvement of anteroventral third ventricular AMPA/kainate receptors in both hyperosmotic and hypovolemic AVP secretion in conscious rats. Yamaguchi, K., Yamada, T. Brain Res. Bull. (2006) [Pubmed]
  13. Cardiovascular effects of felypressin. Cecanho, R., De Luca, L.A., Ranali, J. Anesthesia progress (2006) [Pubmed]
  14. A negative regulatory region in the intracellular domain of the human interferon-alpha receptor. Gibbs, V.C., Takahashi, M., Aguet, M., Chuntharapai, A. J. Biol. Chem. (1996) [Pubmed]
  15. Pharmacogenomic analysis of interferon receptor polymorphisms in multiple sclerosis. Sriram, U., Barcellos, L.F., Villoslada, P., Rio, J., Baranzini, S.E., Caillier, S., Stillman, A., Hauser, S.L., Montalban, X., Oksenberg, J.R. Genes Immun. (2003) [Pubmed]
  16. TYK2 activity promotes ligand-induced IFNAR1 proteolysis. Marijanovic, Z., Ragimbeau, J., Kumar, K.G., Fuchs, S.Y., Pellegrini, S. Biochem. J. (2006) [Pubmed]
  17. N-glycosylation of murine IFN-beta in a putative receptor-binding region. Sommereyns, C., Michiels, T. J. Interferon Cytokine Res. (2006) [Pubmed]
  18. Temporal expression of type I interferon receptor in the peri-implantation ovine extra-embryonic membranes: demonstration that human IFNalpha can bind to this receptor. Imakawa, K., Tamura, K., Lee, R.S., Ji, Y., Kogo, H., Sakai, S., Christenson, R.K. Endocr. J. (2002) [Pubmed]
  19. The antiviral action of interferon is potentiated by removal of the conserved IRTAM domain of the IFNAR1 chain of the interferon alpha/beta receptor: effects on JAK-STAT activation and receptor down-regulation. Basu, L., Yang, C.H., Murti, A., Garcia, J.V., Croze, E., Constantinescu, S.N., Mullersman, J.E., Pfeffer, L.M. Virology (1998) [Pubmed]
  20. Role of type I interferons during macrophage activation by lipopolysaccharide. Vadiveloo, P.K., Vairo, G., Hertzog, P., Kola, I., Hamilton, J.A. Cytokine (2000) [Pubmed]
  21. 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. Ito, K., Tanaka, H., Ito, T., Sultana, T.A., Kyo, T., Imanaka, F., Ohmoto, Y., Kimura, A. Eur. J. Haematol. (2004) [Pubmed]
  22. Differential tyrosine phosphorylation of the IFNAR chain of the type I interferon receptor and of an associated surface protein in response to IFN-alpha and IFN-beta. Abramovich, C., Shulman, L.M., Ratovitski, E., Harroch, S., Tovey, M., Eid, P., Revel, M. EMBO J. (1994) [Pubmed]
  23. Functional subdomains of STAT2 required for preassociation with the alpha interferon receptor and for signaling. Li, X., Leung, S., Kerr, I.M., Stark, G.R. Mol. Cell. Biol. (1997) [Pubmed]
  24. Specific contribution of Tyk2 JH regions to the binding and the expression of the interferon alpha/beta receptor component IFNAR1. Richter, M.F., Duménil, G., Uzé, G., Fellous, M., Pellegrini, S. J. Biol. Chem. (1998) [Pubmed]
  25. Direct association of STAT3 with the IFNAR-1 chain of the human type I interferon receptor. Yang, C.H., Shi, W., Basu, L., Murti, A., Constantinescu, S.N., Blatt, L., Croze, E., Mullersman, J.E., Pfeffer, L.M. J. Biol. Chem. (1996) [Pubmed]
  26. Inquiring into the differential action of interferons (IFNs): an IFN-alpha2 mutant with enhanced affinity to IFNAR1 is functionally similar to IFN-beta. Jaitin, D.A., Roisman, L.C., Jaks, E., Gavutis, M., Piehler, J., Van der Heyden, J., Uze, G., Schreiber, G. Mol. Cell. Biol. (2006) [Pubmed]
  27. The amino-terminal region of Tyk2 sustains the level of interferon alpha receptor 1, a component of the interferon alpha/beta receptor. Gauzzi, M.C., Barbieri, G., Richter, M.F., Uzé, G., Ling, L., Fellous, M., Pellegrini, S. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  28. Three distinct loci on human chromosome 21 contribute to interferon-alpha/beta responsiveness. Raz, R., Cheung, K., Ling, L., Levy, D.E. Somat. Cell Mol. Genet. (1995) [Pubmed]
  29. Catalytically active TYK2 is essential for interferon-beta-mediated phosphorylation of STAT3 and interferon-alpha receptor-1 (IFNAR-1) but not for activation of phosphoinositol 3-kinase. Rani, M.R., Leaman, D.W., Han, Y., Leung, S., Croze, E., Fish, E.N., Wolfman, A., Ransohoff, R.M. J. Biol. Chem. (1999) [Pubmed]
  30. Mutant U5A cells are complemented by an interferon-alpha beta receptor subunit generated by alternative processing of a new member of a cytokine receptor gene cluster. Lutfalla, G., Holland, S.J., Cinato, E., Monneron, D., Reboul, J., Rogers, N.C., Smith, J.M., Stark, G.R., Gardiner, K., Mogensen, K.E. EMBO J. (1995) [Pubmed]
  31. Down-modulation of type 1 interferon responses by receptor cross-competition for a shared Jak kinase. Dondi, E., Pattyn, E., Lutfalla, G., Van Ostade, X., Uzé, G., Pellegrini, S., Tavernier, J. J. Biol. Chem. (2001) [Pubmed]
  32. Interferon alpha /beta promotes cell survival by activating nuclear factor kappa B through phosphatidylinositol 3-kinase and Akt. Yang, C.H., Murti, A., Pfeffer, S.R., Kim, J.G., Donner, D.B., Pfeffer, L.M. J. Biol. Chem. (2001) [Pubmed]
  33. Measles virus suppresses interferon-alpha signaling pathway: suppression of Jak1 phosphorylation and association of viral accessory proteins, C and V, with interferon-alpha receptor complex. Yokota, S., Saito, H., Kubota, T., Yokosawa, N., Amano, K., Fujii, N. Virology (2003) [Pubmed]
  34. Palmitoylation of interferon-alpha (IFN-alpha) receptor subunit IFNAR1 is required for the activation of Stat1 and Stat2 by IFN-alpha. Claudinon, J., Gonnord, P., Beslard, E., Marchetti, M., Mitchell, K., Boularan, C., Johannes, L., Eid, P., Lamaze, C. J. Biol. Chem. (2009) [Pubmed]
  35. Potent inhibitory effects of type I interferons on human adrenocortical carcinoma cell growth. van Koetsveld, P.M., Vitale, G., de Herder, W.W., Feelders, R.A., van der Wansem, K., Waaijers, M., van Eijck, C.H., Speel, E.J., Croze, E., van der Lely, A.J., Lamberts, S.W., Hofland, L.J. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  36. The human type I interferon receptor. Identification of the interferon beta-specific receptor-associated phosphoprotein. Croze, E., Russell-Harde, D., Wagner, T.C., Pu, H., Pfeffer, L.M., Perez, H.D. J. Biol. Chem. (1996) [Pubmed]
  37. Characterization of a soluble ternary complex formed between human interferon-beta-1a and its receptor chains. Arduini, R.M., Strauch, K.L., Runkel, L.A., Carlson, M.M., Hronowski, X., Foley, S.F., Young, C.N., Cheng, W., Hochman, P.S., Baker, D.P. Protein Sci. (1999) [Pubmed]
  38. Sequence analysis of the porcine IFNAR1 and IFNGR2 genes. Leeb, T., Dolle, K., Haase, B. Cytogenet. Genome Res. (2006) [Pubmed]
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