Interferon alpha/beta signaling (Homo sapiens)

From WikiPathways

Revision as of 10:17, 11 June 2014 by ReactomeTeam (Talk | contribs)
Jump to: navigation, search
6, 11, 22, 313, 8, 2211, 141, 4, 7, 12, 23...627, 3722, 2413, 25282, 5, 189, 10, 14, 16, 21...6, 3424322817, 36, 41, 4320, 3715, 16, 19, 3126p-STAT2p-STAT1 p-STAT2p-STAT1 p-STAT1 p-STAT2p-IFNAR1p-TYK2 p-STAT1 p-STAT1 homodimer IFNA/BIFNAR2p-JAK1STAT2p-IFNAR1p-TYK2p-STAT2STAT1 IFNA/BIFNAR2p-JAK1STAT2IFNAR1p-TYK2 IFNAR2p-JAK1STAT2 IFNA/BIFNAR2p-JAK1STAT2 p-STAT1 IFN alpha/beta IFNA/BIFNAR2JAK1STAT2IFNAR1TYK2 IFNA IFN alpha/beta p-STAT2STAT1 IFN alpha/beta IFN alpha/beta SOCS-1 and SOCS-3 IFNAR2p-JAK1STAT2 ISGF3 IFNA IFNAR2JAK1STAT2 IFNA IFNA IFNAR1p-TYK2 IFNA/BIFNAR2JAK1STAT2 p-STAT1 IFNA/BIFNAR2p-JAK1STAT2p-IFNAR1p-TYK2p-STAT2 IFNA/BIFNAR2p-JAK1STAT2 IFNAR2p-JAK1STAT2 IFN alpha/beta IFNA IFNAR2p-JAK1STAT2 IFNA/BIFNAR2p-JAK1STAT2p-IFNAR1p-TYK2 p-STAT2STAT1p-IFNAR1p-TYK2 IFN alpha/beta IFNA/BIFNAR2JAK1STAT2 ISGF3 IFNA/BIFNAR2p-JAK1STAT2IFNAR1TYK2 p-STAT2p-STAT1 IFNAR1TYK2 p-STAT2p-STAT1p-IFNAR1p-TYK2 p-STAT1p-STAT1 IFNAR2p-JAK1STAT2 IFNA/BIFNAR2p-JAK1STAT2 STAT2p-IFNAR1p-TYK2 IFNAR2p-JAK1STAT2 ISGF3 IFNA/BIFNAR2p-JAK1STAT2p-IFNAR1p-TYK2STAT2 p-IFNAR1p-TYK2SOCS-1/SOCS-3 STAT1 IFNAR2cUBP43 endoplasmic reticulum lumenIFNAR2JAK1STAT2 IFNAR1TYK2 ISGF3 bound to ISRE promotor elements IFN alpha/beta IFN alpha/beta IFNAR1TYK2 mitochondrionp-STAT1 nucleoplasmIFNA cytosolp-TYK2p-IFNAR1SOCS-1/SOCS-3IFNA/BIFNAR2p-JAK1STAT2 p-STAT2p-STAT1 IFNAR2p-JAK1STAT2 IFNA p-IFNAR1p-TYK2 IFNA IFNA/BIFNAR2p-JAK1STAT2p-IFNAR1p-TYK2p-STAT2p-STAT1 IFNA p-STAT2p-STAT1 IFNA IFNAR2JAK1STAT2 IFNAR2p-JAK1STAT2 IFNA/BIFNAR2p-JAK1STAT2 IFN alpha/beta IFN alpha/beta IFNA2 IFNA10 IFNA4 IFNB1 p-Y466,Y481-IFNAR1 IFNAR2-2 IFNA/BIFNAR2p-JAK1STAT2IFNAR1TYK2IFNA2 TYK2 p-Y-JAK1 SOCS3 IFNA14 IFNA14 IFIT3IFNA1 STAT1-2 IFNA1 p-Y701-STAT1-1 IFNA4 IFNA4 IFNA16 ATPIFNA21 IFNA21 ISRE promoter elements in type I IFN-regulated genesp-Y690-STAT2 p-Y-JAK1 IRF 1-9IFNA/BIFNAR2p-JAK1STAT2p-IFNAR1p-TYK2p-STAT2STAT1IFI6IFNA5 STAT2 IFNA6 STAT2 IFNA21 PTPN6IFNA6 IFNA6 IFNA7 ATPIFNAR1TYK2p-Y1054,Y1055-TYK2 p-Y1054,Y1055-TYK2 IFNA10 IFNA17 IFNA14 STAT1-1IFNAR1 IFNAR2-2 IFNA5 IFNA8 IFNAR2-2 IFNA16 p-Y1054,Y1055-TYK2 p-Y701-STAT1-2 IP6K2ISG20IFNA7 IFNAR2-2 STAT1JAK1 p-Y690-STAT2 ATPMx GTPasesp-Y701-STAT1-1 IFNA10 STAT2 IFNA16 JAK1 IFNA14 IFNB1 IFNA7 SHP-2/SHP-1TYK2 p-Y701-STAT1-1 ATPIFNA4 IFNA6 p-Y1054,Y1055-TYK2 IFNAR2-2 IFNA/BIFNAR2p-JAK1STAT2p-IFNAR1p-TYK2STAT2IFNA16 IRF9IFNB1 RNASELIFNA2 IFNA16 IFNA5 IFNAR2-2 SOCS-1 and SOCS-3p-Y-JAK1 IFNAR2-2 IFNA6 EGR1IFNA4 PTPN1XAF1SOCS1 IFNAR2-2 IFNA7 IFIT1IFNA14 TYK2 IFITM1IFNA17 p-Y690-STAT2 H2OIFNA17 IFNAR2-2IFNA/BIFNAR2p-JAK1STAT2p-IFNAR1p-TYK2p-STAT2IFI35p-Y-JAK1 IFNA1 p-STAT2p-STAT1IFITM2STAT2 p-TYK2p-IFNAR1SOCS-1/SOCS-3IFNA/BIFNAR2p-JAK1STAT2IFNA14 p-Y-JAK1 IFNA16 p-Y701-STAT1-2 ADPIFNA6 IFNA17 IFNA17 IFNA14 IFNA6 IFNB1 IFNA6 IFNA5 GBP2OAS proteinsp-STAT1 homodimerp-Y-JAK1 IFNA4 IFNA8 IFNA/BIFNAR2JAK1STAT2STAT2 IFNA7 Pip-Y-JAK1 IFNA6 p-Y1054,Y1055-TYK2 IFN alpha/beta ATPIFNA21 ADPIRF9 IFNA4 IFI27IFNA8 IFNA1 p-Y466,Y481-IFNAR1 IFNA17 IFNA8 IFNA/BIFNAR2p-JAK1STAT2p-IFNAR1p-TYK2IFNA10 IFNA1 IFNA1 STAT2 IFNA5 IFNA10 p-Y690-STAT2 IFNAR2-2 p-Y466,Y481-IFNAR1 H2OIFNA17 IFNA7 STAT2 IFNA5 ADPIFNA/BIFNAR2p-JAK1STAT2IFNAR1p-TYK2IFNA8 IFNA7 IFNA5 IFNA2 IFNA21 p-Y701-STAT1-1 IFNA16 IFNA8 IFNAR2-2 IFNA14 IFNA5 ISGF3IFNA8 STAT2 IFITM3IFNA21 IFNA10 IFNA17 IFNA4 IFNA5 IFNA4 Class I MHC heavy chain IFNA21 ISGF3JAK1 IFNA8 p-Y690-STAT2 p-Y466,Y481-IFNAR1 IFNA4 H2OIFNAR2-2 IFNA2 IFNA2 IFNAR2JAK1STAT2ADPIFNA21 IFNB1 p-Y701-STAT1-1 IFNA14 IFNA10 IRF9 STAT2 ADARIFNA7 IFNA14 IFNB1 p-Y701-STAT1-1 IFNAR2-2 p-Y701-STAT1-2 p-Y701-STAT1-2 p-Y701-STAT1-1 IFNA1 IFNA2 p-Y1054,Y1055-TYK2 IFNA16 IFNAR1 IFNA8 IFNA/BIFNAR2p-JAK1STAT2p-IFNAR1p-TYK2p-STAT2p-STAT1IFNA5 IRF9 IFNAR2cUBP43IFNA16 p-Y690-STAT2 p-Y466,Y481-IFNAR1 STAT2 ISG15PTPN11IFNA21 IFNA1 USP18 IFNA10 ISGF3 bound to ISRE promotor elementsIFNB1 IFNB1 p-Y1054,Y1055-TYK2 IFNB1 IFNA10 PiIFNAR1 p-Y466,Y481-IFNAR1 STAT1-1 IFNA6 IFNA1 IFNA21 IFNA17 IFNA7 IFNA7 IFNAR1 IFNA2 IFIT2STAT2 PSMB8USP18IFNA16 IFNA17 IFNA2 p-Y690-STAT2 PiIFNA10 p-STAT1p-STAT1IFNB1 STAT2IFNA/BIFNAR2JAK1STAT2IFNAR1TYK2p-Y701-STAT1-2 p-Y-JAK1 IFNA2 IFNA1 IFNA8


Description

Type I interferons (IFNs) are composed of various genes including IFN alpha (IFNA), beta (IFNB), omega, epsilon, and kappa. In humans the IFNA genes are composed of more than 13 subfamily genes, whereas there is only one IFNB gene. The large family of IFNA/B proteins all bind to a single receptor which is composed of two distinct chains: IFNAR1 and IFNAR2. The IFNA/B stimulation of the IFNA receptor complex leads to the formation of two transcriptional activator complexes: IFNA-activated-factor (AAF), which is a homodimer of STAT1 and IFN-stimulated gene factor 3 (ISGF3), which comprises STAT1, STAT2 and a member of the IRF family, IRF9/P48. AAF mediates activation of the IRF-1 gene by binding to GAS (IFNG-activated site), whereas ISGF3 activates several IFN-inducible genes including IRF3 and IRF7. Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=909733

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Marié I, Svab J, Robert N, Galabru J, Hovanessian AG.; ''Differential expression and distinct structure of 69- and 100-kDa forms of 2-5A synthetase in human cells treated with interferon.''; PubMed Europe PMC Scholia
  2. Colamonici O, Yan H, Domanski P, Handa R, Smalley D, Mullersman J, Witte M, Krishnan K, Krolewski J.; ''Direct binding to and tyrosine phosphorylation of the alpha subunit of the type I interferon receptor by p135tyk2 tyrosine kinase.''; PubMed Europe PMC Scholia
  3. Leaman DW, Chawla-Sarkar M, Vyas K, Reheman M, Tamai K, Toji S, Borden EC.; ''Identification of X-linked inhibitor of apoptosis-associated factor-1 as an interferon-stimulated gene that augments TRAIL Apo2L-induced apoptosis.''; PubMed Europe PMC Scholia
  4. Yan H, Krishnan K, Greenlund AC, Gupta S, Lim JT, Schreiber RD, Schindler CW, Krolewski JJ.; ''Phosphorylated interferon-alpha receptor 1 subunit (IFNaR1) acts as a docking site for the latent form of the 113 kDa STAT2 protein.''; PubMed Europe PMC Scholia
  5. Rani MR, Leaman DW, Han Y, Leung S, Croze E, Fish EN, Wolfman A, Ransohoff RM.; ''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.''; PubMed Europe PMC Scholia
  6. Andersson I, Bladh L, Mousavi-Jazi M, Magnusson KE, Lundkvist A, Haller O, Mirazimi A.; ''Human MxA protein inhibits the replication of Crimean-Congo hemorrhagic fever virus.''; PubMed Europe PMC Scholia
  7. Li X, Leung S, Qureshi S, Darnell JE, Stark GR.; ''Formation of STAT1-STAT2 heterodimers and their role in the activation of IRF-1 gene transcription by interferon-alpha.''; PubMed Europe PMC Scholia
  8. Clark JD, Flanagan ME, Telliez JB.; ''Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases.''; PubMed Europe PMC Scholia
  9. Geiger TR, Martin JM.; ''The Epstein-Barr virus-encoded LMP-1 oncoprotein negatively affects Tyk2 phosphorylation and interferon signaling in human B cells.''; PubMed Europe PMC Scholia
  10. Stebbing J, Phelan A, Griffin I, Tucker C, Oechsle O, Smith D, Richardson P.; ''COVID-19: combining antiviral and anti-inflammatory treatments.''; PubMed Europe PMC Scholia
  11. Chuntharapai A, Gibbs V, Lu J, Ow A, Marsters S, Ashkenazi A, De Vos A, Jin Kim K.; ''Determination of residues involved in ligand binding and signal transmission in the human IFN-alpha receptor 2.''; PubMed Europe PMC Scholia
  12. Martinand C, Montavon C, Salehzada T, Silhol M, Lebleu B, Bisbal C.; ''RNase L inhibitor is induced during human immunodeficiency virus type 1 infection and down regulates the 2-5A/RNase L pathway in human T cells.''; PubMed Europe PMC Scholia
  13. Hanan EJ, van Abbema A, Barrett K, Blair WS, Blaney J, Chang C, Eigenbrot C, Flynn S, Gibbons P, Hurley CA, Kenny JR, Kulagowski J, Lee L, Magnuson SR, Morris C, Murray J, Pastor RM, Rawson T, Siu M, Ultsch M, Zhou A, Sampath D, Lyssikatos JP.; ''Discovery of potent and selective pyrazolopyrimidine janus kinase 2 inhibitors.''; PubMed Europe PMC Scholia
  14. Improta T, Schindler C, Horvath CM, Kerr IM, Stark GR, Darnell JE.; ''Transcription factor ISGF-3 formation requires phosphorylated Stat91 protein, but Stat113 protein is phosphorylated independently of Stat91 protein.''; PubMed Europe PMC Scholia
  15. Der SD, Yang YL, Weissmann C, Williams BR.; ''A double-stranded RNA-activated protein kinase-dependent pathway mediating stress-induced apoptosis.''; PubMed Europe PMC Scholia
  16. Le Roy F, Bisbal C, Silhol M, Martinand C, Lebleu B, Salehzada T.; ''The 2-5A/RNase L/RNase L inhibitor (RLI) [correction of (RNI)] pathway regulates mitochondrial mRNAs stability in interferon alpha-treated H9 cells.''; PubMed Europe PMC Scholia
  17. Cajean-Feroldi C, Nosal F, Nardeux PC, Gallet X, Guymarho J, Baychelier F, Sempé P, Tovey MG, Escary JL, Eid P.; ''Identification of residues of the IFNAR1 chain of the type I human interferon receptor critical for ligand binding and biological activity.''; PubMed Europe PMC Scholia
  18. Kohli A, Zhang X, Yang J, Russell RS, Donnelly RP, Sheikh F, Sherman A, Young H, Imamichi T, Lempicki RA, Masur H, Kottilil S.; ''Distinct and overlapping genomic profiles and antiviral effects of Interferon-λ and -α on HCV-infected and noninfected hepatoma cells.''; PubMed Europe PMC Scholia
  19. Zhao C, Denison C, Huibregtse JM, Gygi S, Krug RM.; ''Human ISG15 conjugation targets both IFN-induced and constitutively expressed proteins functioning in diverse cellular pathways.''; PubMed Europe PMC Scholia
  20. Malakhova OA, Kim KI, Luo JK, Zou W, Kumar KG, Fuchs SY, Shuai K, Zhang DE.; ''UBP43 is a novel regulator of interferon signaling independent of its ISG15 isopeptidase activity.''; PubMed Europe PMC Scholia
  21. Roisman LC, Jaitin DA, Baker DP, Schreiber G.; ''Mutational analysis of the IFNAR1 binding site on IFNalpha2 reveals the architecture of a weak ligand-receptor binding-site.''; PubMed Europe PMC Scholia
  22. Der SD, Zhou A, Williams BR, Silverman RH.; ''Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays.''; PubMed Europe PMC Scholia
  23. Nyman TA, Tölö H, Parkkinen J, Kalkkinen N.; ''Identification of nine interferon-alpha subtypes produced by Sendai virus-induced human peripheral blood leucocytes.''; PubMed Europe PMC Scholia
  24. Mowen K, David M.; ''Regulation of STAT1 nuclear export by Jak1.''; PubMed Europe PMC Scholia
  25. Qureshi SA, Salditt-Georgieff M, Darnell JE.; ''Tyrosine-phosphorylated Stat1 and Stat2 plus a 48-kDa protein all contact DNA in forming interferon-stimulated-gene factor 3.''; PubMed Europe PMC Scholia
  26. Chill JH, Quadt SR, Levy R, Schreiber G, Anglister J.; ''The human type I interferon receptor: NMR structure reveals the molecular basis of ligand binding.''; PubMed Europe PMC Scholia
  27. de Veer MJ, Holko M, Frevel M, Walker E, Der S, Paranjape JM, Silverman RH, Williams BR.; ''Functional classification of interferon-stimulated genes identified using microarrays.''; PubMed Europe PMC Scholia
  28. Morrison BH, Bauer JA, Kalvakolanu DV, Lindner DJ.; ''Inositol hexakisphosphate kinase 2 mediates growth suppressive and apoptotic effects of interferon-beta in ovarian carcinoma cells.''; PubMed Europe PMC Scholia
  29. Uzé G, Schreiber G, Piehler J, Pellegrini S.; ''The receptor of the type I interferon family.''; PubMed Europe PMC Scholia
  30. Wesoly J, Szweykowska-Kulinska Z, Bluyssen HA.; ''STAT activation and differential complex formation dictate selectivity of interferon responses.''; PubMed Europe PMC Scholia
  31. David M.; ''Transcription factors in interferon signaling.''; PubMed Europe PMC Scholia
  32. Chawla-Sarkar M, Lindner DJ, Liu YF, Williams BR, Sen GC, Silverman RH, Borden EC.; ''Apoptosis and interferons: role of interferon-stimulated genes as mediators of apoptosis.''; PubMed Europe PMC Scholia
  33. Sadler AJ, Williams BR.; ''Interferon-inducible antiviral effectors.''; PubMed Europe PMC Scholia
  34. Richardson P, Griffin I, Tucker C, Smith D, Oechsle O, Phelan A, Rawling M, Savory E, Stebbing J.; ''Baricitinib as potential treatment for 2019-nCoV acute respiratory disease.''; PubMed Europe PMC Scholia
  35. Müller M, Briscoe J, Laxton C, Guschin D, Ziemiecki A, Silvennoinen O, Harpur AG, Barbieri G, Witthuhn BA, Schindler C.; ''The protein tyrosine kinase JAK1 complements defects in interferon-alpha/beta and -gamma signal transduction.''; PubMed Europe PMC Scholia
  36. Domanski P, Fish E, Nadeau OW, Witte M, Platanias LC, Yan H, Krolewski J, Pitha P, Colamonici OR.; ''A region of the beta subunit of the interferon alpha receptor different from box 1 interacts with Jak1 and is sufficient to activate the Jak-Stat pathway and induce an antiviral state.''; PubMed Europe PMC Scholia
  37. Martinez-Moczygemba M, Gutch MJ, French DL, Reich NC.; ''Distinct STAT structure promotes interaction of STAT2 with the p48 subunit of the interferon-alpha-stimulated transcription factor ISGF3.''; PubMed Europe PMC Scholia
  38. Fridman JS, Scherle PA, Collins R, Burn TC, Li Y, Li J, Covington MB, Thomas B, Collier P, Favata MF, Wen X, Shi J, McGee R, Haley PJ, Shepard S, Rodgers JD, Yeleswaram S, Hollis G, Newton RC, Metcalf B, Friedman SM, Vaddi K.; ''Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050.''; PubMed Europe PMC Scholia
  39. Wreschner DH, McCauley JW, Skehel JJ, Kerr IM.; ''Interferon action--sequence specificity of the ppp(A2'p)nA-dependent ribonuclease.''; PubMed Europe PMC Scholia
  40. Myers MP, Andersen JN, Cheng A, Tremblay ML, Horvath CM, Parisien JP, Salmeen A, Barford D, Tonks NK.; ''TYK2 and JAK2 are substrates of protein-tyrosine phosphatase 1B.''; PubMed Europe PMC Scholia
  41. You M, Yu DH, Feng GS.; ''Shp-2 tyrosine phosphatase functions as a negative regulator of the interferon-stimulated Jak/STAT pathway.''; PubMed Europe PMC Scholia
  42. Martinand C, Salehzada T, Silhol M, Lebleu B, Bisbal C.; ''RNase L inhibitor (RLI) antisense constructions block partially the down regulation of the 2-5A/RNase L pathway in encephalomyocarditis-virus-(EMCV)-infected cells.''; PubMed Europe PMC Scholia
  43. Gavutis M, Lata S, Lamken P, Müller P, Piehler J.; ''Lateral ligand-receptor interactions on membranes probed by simultaneous fluorescence-interference detection.''; PubMed Europe PMC Scholia
  44. Shuai K, Horvath CM, Huang LH, Qureshi SA, Cowburn D, Darnell JE.; ''Interferon activation of the transcription factor Stat91 involves dimerization through SH2-phosphotyrosyl peptide interactions.''; PubMed Europe PMC Scholia
  45. Leaman DW, Chawla-Sarkar M, Jacobs B, Vyas K, Sun Y, Ozdemir A, Yi T, Williams BR, Borden EC.; ''Novel growth and death related interferon-stimulated genes (ISGs) in melanoma: greater potency of IFN-beta compared with IFN-alpha2.''; PubMed Europe PMC Scholia
  46. Pervolaraki K, Rastgou Talemi S, Albrecht D, Bormann F, Bamford C, Mendoza JL, Garcia KC, McLauchlan J, Höfer T, Stanifer ML, Boulant S.; ''Differential induction of interferon stimulated genes between type I and type III interferons is independent of interferon receptor abundance.''; PubMed Europe PMC Scholia
  47. Quintás-Cardama A, Vaddi K, Liu P, Manshouri T, Li J, Scherle PA, Caulder E, Wen X, Li Y, Waeltz P, Rupar M, Burn T, Lo Y, Kelley J, Covington M, Shepard S, Rodgers JD, Haley P, Kantarjian H, Fridman JS, Verstovsek S.; ''Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms.''; PubMed Europe PMC Scholia
  48. Cao XM, Guy GR, Sukhatme VP, Tan YH.; ''Regulation of the Egr-1 gene by tumor necrosis factor and interferons in primary human fibroblasts.''; PubMed Europe PMC Scholia
  49. Xu D, Qu CK.; ''Protein tyrosine phosphatases in the JAK/STAT pathway.''; PubMed Europe PMC Scholia
  50. Li X, Leung S, Kerr IM, Stark GR.; ''Functional subdomains of STAT2 required for preassociation with the alpha interferon receptor and for signaling.''; PubMed Europe PMC Scholia
  51. Friedman RL, Manly SP, McMahon M, Kerr IM, Stark GR.; ''Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells.''; PubMed Europe PMC Scholia
  52. Gauzzi MC, Velazquez L, McKendry R, Mogensen KE, Fellous M, Pellegrini S.; ''Interferon-alpha-dependent activation of Tyk2 requires phosphorylation of positive regulatory tyrosines by another kinase.''; PubMed Europe PMC Scholia
  53. Justesen J, Hartmann R, Kjeldgaard NO.; ''Gene structure and function of the 2'-5'-oligoadenylate synthetase family.''; PubMed Europe PMC Scholia
  54. Lamken P, Lata S, Gavutis M, Piehler J.; ''Ligand-induced assembling of the type I interferon receptor on supported lipid bilayers.''; PubMed Europe PMC Scholia
  55. Jiao H, Berrada K, Yang W, Tabrizi M, Platanias LC, Yi T.; ''Direct association with and dephosphorylation of Jak2 kinase by the SH2-domain-containing protein tyrosine phosphatase SHP-1.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
114797view16:29, 25 January 2021ReactomeTeamReactome version 75
113240view11:30, 2 November 2020ReactomeTeamReactome version 74
112460view15:41, 9 October 2020ReactomeTeamReactome version 73
101367view11:25, 1 November 2018ReactomeTeamreactome version 66
100905view21:00, 31 October 2018ReactomeTeamreactome version 65
100446view19:35, 31 October 2018ReactomeTeamreactome version 64
99995view16:19, 31 October 2018ReactomeTeamreactome version 63
99549view14:53, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99182view12:42, 31 October 2018ReactomeTeamreactome version 62
93744view13:33, 16 August 2017ReactomeTeamreactome version 61
93258view11:18, 9 August 2017ReactomeTeamreactome version 61
86337view09:15, 11 July 2016ReactomeTeamreactome version 56
83224view10:25, 18 November 2015ReactomeTeamVersion54
81620view13:09, 21 August 2015ReactomeTeamVersion53
77078view08:37, 17 July 2014ReactomeTeamFixed remaining interactions
76783view12:14, 16 July 2014ReactomeTeamFixed remaining interactions
76106view10:17, 11 June 2014ReactomeTeamRe-fixing comment source
75818view11:37, 10 June 2014ReactomeTeamReactome 48 Update
75168view14:11, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74815view08:54, 30 April 2014ReactomeTeamReactome46
44864view09:57, 6 October 2011MartijnVanIerselOntology Term : 'immune response pathway' added !
42055view21:53, 4 March 2011MaintBotAutomatic update
39861view05:53, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ADARProteinP55265 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Class I MHC heavy chain ProteinREACT_26784 (Reactome)
EGR1ProteinP18146 (Uniprot-TrEMBL)
GBP2ProteinP32456 (Uniprot-TrEMBL)
H2OMetaboliteCHEBI:15377 (ChEBI)
IFI27ProteinP40305 (Uniprot-TrEMBL)
IFI35ProteinP80217 (Uniprot-TrEMBL)
IFI6ProteinP09912 (Uniprot-TrEMBL)
IFIT1ProteinP09914 (Uniprot-TrEMBL)
IFIT2ProteinP09913 (Uniprot-TrEMBL)
IFIT3ProteinO14879 (Uniprot-TrEMBL)
IFITM1ProteinP13164 (Uniprot-TrEMBL)
IFITM2ProteinQ01629 (Uniprot-TrEMBL)
IFITM3ProteinQ01628 (Uniprot-TrEMBL)
IFN alpha/beta ProteinREACT_26595 (Reactome)
IFNA/B

IFNAR2 JAK1 STAT2 IFNAR1

TYK2		ComplexREACT_25725 (Reactome)
IFNA/B

IFNAR2 JAK1

STAT2		ComplexREACT_26015 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 IFNAR1

TYK2		ComplexREACT_26140 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 IFNAR1

p-TYK2		ComplexREACT_26001 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 p-IFNAR1 p-TYK2

STAT2		ComplexREACT_25990 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 p-IFNAR1 p-TYK2 p-STAT2

STAT1		ComplexREACT_26740 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 p-IFNAR1 p-TYK2 p-STAT2

p-STAT1		ComplexREACT_26770 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 p-IFNAR1 p-TYK2

p-STAT2		ComplexREACT_26908 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 p-IFNAR1

p-TYK2		ComplexREACT_26083 (Reactome)
IFNA1 ProteinP01562 (Uniprot-TrEMBL)
IFNA10 ProteinP01566 (Uniprot-TrEMBL)
IFNA14 ProteinP01570 (Uniprot-TrEMBL)
IFNA16 ProteinP05015 (Uniprot-TrEMBL)
IFNA17 ProteinP01571 (Uniprot-TrEMBL)
IFNA2 ProteinP01563 (Uniprot-TrEMBL)
IFNA21 ProteinP01568 (Uniprot-TrEMBL)
IFNA4 ProteinP05014 (Uniprot-TrEMBL)
IFNA5 ProteinP01569 (Uniprot-TrEMBL)
IFNA6 ProteinP05013 (Uniprot-TrEMBL)
IFNA7 ProteinP01567 (Uniprot-TrEMBL)
IFNA8 ProteinP32881 (Uniprot-TrEMBL)
IFNAR1 TYK2ComplexREACT_25562 (Reactome)
IFNAR1 ProteinP17181 (Uniprot-TrEMBL)
IFNAR2

JAK1

STAT2		ComplexREACT_25438 (Reactome)
IFNAR2-2 ProteinP48551-2 (Uniprot-TrEMBL)
IFNAR2-2ProteinP48551-2 (Uniprot-TrEMBL)
IFNAR2c UBP43ComplexREACT_26598 (Reactome)
IFNB1 ProteinP01574 (Uniprot-TrEMBL)
IP6K2ProteinQ9UHH9 (Uniprot-TrEMBL)
IRF 1-9ProteinREACT_26465 (Reactome)
IRF9 ProteinQ00978 (Uniprot-TrEMBL)
IRF9ProteinQ00978 (Uniprot-TrEMBL)
ISG15ProteinP05161 (Uniprot-TrEMBL)
ISG20ProteinQ96AZ6 (Uniprot-TrEMBL)
ISGF3 bound to ISRE promotor elementsComplexREACT_25455 (Reactome)
ISGF3ComplexREACT_25406 (Reactome)
ISGF3ComplexREACT_25831 (Reactome)
ISRE promoter elements in type I IFN-regulated genesREACT_26432 (Reactome)
JAK1 ProteinP23458 (Uniprot-TrEMBL)
Mx GTPasesProteinREACT_25553 (Reactome)
OAS proteinsProteinREACT_26755 (Reactome)
PSMB8ProteinP28062 (Uniprot-TrEMBL)
PTPN11ProteinQ06124 (Uniprot-TrEMBL)
PTPN1ProteinP18031 (Uniprot-TrEMBL)
PTPN6ProteinP29350 (Uniprot-TrEMBL)
PiMetaboliteCHEBI:18367 (ChEBI)
RNASELProteinQ05823 (Uniprot-TrEMBL)
SHP-2/SHP-1ProteinREACT_20250 (Reactome)
SOCS-1 and SOCS-3ProteinREACT_25587 (Reactome)
SOCS1 ProteinO15524 (Uniprot-TrEMBL)
SOCS3 ProteinO14543 (Uniprot-TrEMBL)
STAT1-1 ProteinP42224-1 (Uniprot-TrEMBL)
STAT1-1ProteinP42224-1 (Uniprot-TrEMBL)
STAT1-2 ProteinP42224-2 (Uniprot-TrEMBL)
STAT1ProteinREACT_17621 (Reactome)
STAT2 ProteinP52630 (Uniprot-TrEMBL)
STAT2ProteinP52630 (Uniprot-TrEMBL)
TYK2 ProteinP29597 (Uniprot-TrEMBL)
USP18 ProteinQ9UMW8 (Uniprot-TrEMBL)
USP18ProteinQ9UMW8 (Uniprot-TrEMBL)
XAF1ProteinQ6GPH4 (Uniprot-TrEMBL)
p-STAT1 p-STAT1ComplexREACT_26749 (Reactome)
p-STAT1 homodimerComplexREACT_26275 (Reactome)
p-STAT2 p-STAT1ComplexREACT_27063 (Reactome)
p-TYK2

p-IFNAR1 SOCS-1/SOCS-3 IFNA/B IFNAR2 p-JAK1

STAT2		ComplexREACT_26646 (Reactome)
p-Y-JAK1 ProteinP23458 (Uniprot-TrEMBL)
p-Y1054,Y1055-TYK2 ProteinP29597 (Uniprot-TrEMBL)
p-Y466,Y481-IFNAR1 ProteinP17181 (Uniprot-TrEMBL)
p-Y690-STAT2 ProteinP52630 (Uniprot-TrEMBL)
p-Y701-STAT1-1 ProteinP42224-1 (Uniprot-TrEMBL)
p-Y701-STAT1-2 ProteinP42224-2 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ADARArrowREACT_25192 (Reactome)
ADPArrowREACT_25105 (Reactome)
ADPArrowREACT_25291 (Reactome)
ADPArrowREACT_25383 (Reactome)
ADPArrowREACT_25401 (Reactome)
ATPREACT_25017 (Reactome)
ATPREACT_25105 (Reactome)
ATPREACT_25291 (Reactome)
ATPREACT_25383 (Reactome)
ATPREACT_25401 (Reactome)
Class I MHC heavy chain ArrowREACT_25192 (Reactome)
EGR1ArrowREACT_25192 (Reactome)
GBP2ArrowREACT_25192 (Reactome)
H2OREACT_24939 (Reactome)
H2OREACT_25289 (Reactome)
H2OREACT_25329 (Reactome)
IFI27ArrowREACT_25192 (Reactome)
IFI35ArrowREACT_25192 (Reactome)
IFI6ArrowREACT_25192 (Reactome)
IFIT1ArrowREACT_25192 (Reactome)
IFIT2ArrowREACT_25192 (Reactome)
IFIT3ArrowREACT_25192 (Reactome)
IFITM1ArrowREACT_25192 (Reactome)
IFITM2ArrowREACT_25192 (Reactome)
IFITM3ArrowREACT_25192 (Reactome)
IFN alpha/beta REACT_25100 (Reactome)
IFNA/B

IFNAR2 JAK1 STAT2 IFNAR1

TYK2		ArrowREACT_25289 (Reactome)
IFNA/B

IFNAR2 JAK1 STAT2 IFNAR1

TYK2		REACT_25065 (Reactome)
IFNA/B

IFNAR2 JAK1 STAT2 IFNAR1

TYK2		REACT_25401 (Reactome)
IFNA/B

IFNAR2 JAK1

STAT2		REACT_25206 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 IFNAR1

TYK2		ArrowREACT_25329 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 IFNAR1

TYK2		REACT_25289 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 IFNAR1

p-TYK2		ArrowREACT_25401 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 IFNAR1

p-TYK2		REACT_25329 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 IFNAR1

p-TYK2		REACT_25383 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 p-IFNAR1 p-TYK2

STAT2		REACT_25291 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 p-IFNAR1 p-TYK2 p-STAT2

STAT1		ArrowREACT_24939 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 p-IFNAR1 p-TYK2 p-STAT2

p-STAT1		REACT_24939 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 p-IFNAR1 p-TYK2

p-STAT2		ArrowREACT_25291 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 p-IFNAR1 p-TYK2

p-STAT2		REACT_25017 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 p-IFNAR1 p-TYK2

p-STAT2		REACT_25105 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 p-IFNAR1

p-TYK2		ArrowREACT_25021 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 p-IFNAR1

p-TYK2		ArrowREACT_25383 (Reactome)
IFNA/B

IFNAR2 p-JAK1 STAT2 p-IFNAR1

p-TYK2		REACT_25238 (Reactome)
IFNAR1 TYK2REACT_25206 (Reactome)
IFNAR2

JAK1

STAT2		REACT_25100 (Reactome)
IFNAR2-2REACT_24958 (Reactome)
IP6K2ArrowREACT_25192 (Reactome)
IRF 1-9ArrowREACT_25192 (Reactome)
IRF9REACT_25284 (Reactome)
ISG15ArrowREACT_25192 (Reactome)
ISG20ArrowREACT_25192 (Reactome)
ISGF3 bound to ISRE promotor elementsArrowREACT_25192 (Reactome)
ISGF3REACT_24942 (Reactome)
ISRE promoter elements in type I IFN-regulated genesREACT_24942 (Reactome)
Mx GTPasesArrowREACT_25192 (Reactome)
OAS proteinsArrowREACT_25192 (Reactome)
PSMB8ArrowREACT_25192 (Reactome)
PTPN11REACT_24939 (Reactome)
PTPN1REACT_25329 (Reactome)
PTPN6REACT_25289 (Reactome)
PiArrowREACT_24939 (Reactome)
PiArrowREACT_25289 (Reactome)
PiArrowREACT_25329 (Reactome)
REACT_24939 (Reactome) SHP2 negatively regulates the IFN-induced JAK-STAT pathway by dephosphorylating STAT1 on Y701.
REACT_24942 (Reactome) Effects of IFNs result from induction of a subset of genes, called IFN stimulated genes (ISGs). These ISGs are mainly implicated in anti-viral, anti-angiogenic, immunomodulatory, cell cycle inhibitory effects and apoptotic functions. All IFNA/B-stimulated genes have a conserved region of about 15bp in their promoter called the Interferon Stimulation Response Element (ISRE). The transcription factor ISGF3 binds to this ISRE and induce the transcription of these genes by IFN.
REACT_24958 (Reactome) UBP43, a type I IFN-inducible cysteine protease acts as a negative regulator of type I IFN signaling. UBP43 binds directly to IFNAR2 and blocks JAK-receptor interaction leading to inhibition of downstream phosphorylation and other signaling events.
REACT_25017 (Reactome) Phosphotyrosine on STAT2 acts as docking site for STAT1 molecules. STAT1 binds to phosphorylated STAT2 and this is followed by STAT1 phosphorylation on tyrosine residue 701 (Y701) and is followed by p-STAT2:p-STAT1 heterodimer formation and nuclear translocation.
REACT_25021 (Reactome) The phosphorylated STAT2:STAT1 heterodimers thus formed disassociate from the IFNAR1 subunit and translocates to the nucleus.
REACT_25065 (Reactome) SOCS1/3 are the major negative regulators of IFNA/B signaling. They inhibit JAKs catalytic activity directly through their kinase inhibitory region (KIR) and turn off downstream IFNA/B signaling. SOCS1 may also prevent IFN signaling by targeting the signaling machinery to ubiquitin-proteasomal degradation pathway.
REACT_25100 (Reactome) The ligand IFNalpha/beta (IFNA/B), interacts independently with the two interferon receptor subunits. Based on detailed binding studies with the extracellular domains of the receptor subunits tethered onto solid-supported membranes, a two-step binding mechanism was experimentally confirmed, where the ligand binds first to one of the receptor subunits and then recruits the second subunit (Gavutis et al. 2005). The efficiency of recruitment of the IFNA receptor subunits by the IFN ligand depends on the absolute and relative concentration of the receptor subunits.
IFNAR2 chain constitutively associates with JAK1 kinase in its cytoplasmic domain. In addition IFNAR2 also binds STAT2 in a constitutive manner and this interaction is biochemically different from the interaction of STAT2 with phosphorylated IFNAR1. Although this interaction facilitates the recruitment of STAT2 to the receptors, the biological significance of this constitutive STAT2 interaction to IFNAR2 remains unclear (Nguyen et al, 2002). IFNAR2 not only associates with STAT2, but also with STAT1 and this binding of STAT1 to IFNAR2 depends on the presence of STAT2 but not vice versa.
IFNA/B may first bind to the high-affinity subunit IFNAR2 and subsequently recruit IFNAR1 in a transient fashion (Lamken et al. 2004). Different type I IFNs interact differently with the two IFNA receptor (IFNAR) subunits, IFNB generates a more stable signaling complex than IFNA subtypes. The interaction between IFNalpha2 (IFNA2) and IFNAR2 has an affinity in the nM range, whereas the affinity of the interaction with INFB is about tenfold tighter.
REACT_25105 (Reactome) Under certain conditions type I IFNs, IFNA/B are able to activate genes through a second STAT-based signaling cascade enabling the formation of p-STAT1:p-STAT1 homodimers called IFNA-activated-factor (AAF).
REACT_25169 (Reactome) The resultant ISGF3 trimeric complex then migrates to the nucleus and binds to interferon-stimulated response elements (ISREs). IRF9 is the DNA binding part of this ISGF3 complex. These ISREs are present in the promoters of a subset of ISGs (interferon stimulated genes), such as promyelocytic leukemia (PML), ISG15 ubiquitin-like modifier (ISG15), interferon-induced protein with tetratricopeptide repeats 2 (ISG54) and interferon alpha-inducible protein 6 (IFI6) to elicit an antiviral response.
REACT_25192 (Reactome) Around 300 IFN-induced genes have been identified from different oligonucleotide microarray studies in melanoma (WM9) and fibrosarcoma (HT1080) cell lines as well as from human dendritic cells treated with IFN. Only the proteins which are well studied and their function characterized are represented here.
REACT_25206 (Reactome) The extracellular domain of IFNAR1 is atypical, consisting of a tandem array of four FNIII domains and the first three N-terminal FNIII domains are involved in ligand recognition. IFNAR1 is recruited to the binary complex (IFNA/B:IFNAR2) on the membrane to form the ternary complex (IFNAR2:IFNA/B:IFNAR1). TYK2 kinase is pre-associated with IFNAR1 and JAK1 with IFNAR2. The binding of IFNA/B to IFNA receptors brings these JAK kinase together, allowing cross-phosphorylation and kinase activation.
REACT_25238 (Reactome) Phosphorylated tyrosine residue 466 on IFNAR1 acts as a docking site for STAT2. Latent STAT2 is recruited to this phosphotyrosine residue via its SH2 domain.
REACT_25256 (Reactome) IFNA-activated-factor (AAF) translocates to nucleus and then promotes the expression of a distinct set of gamma activated sequence (GAS)-driven genes like IRF1. IRF1, in turn, induces the transcription of ISG15, ISG54 and IFI6 genes. This second pathway of STAT1 homodimer formation is primarily activated by IFNG and is likely to account for some of the functional overlap between type I and type II IFNs.
REACT_25284 (Reactome) The phosphorylated STAT2:STAT1 heterodimer associates with interferon-regulating factor 9 (IRF9) to form the interferon-stimulated gene factor 3 (ISGF3) complex.
REACT_25289 (Reactome) SHP1 directly associates with and dephosphorylates JAK1/2.
REACT_25291 (Reactome) STAT2 recruited to the IFNAR1 subunit then becomes tyrosine phosphorylated on residue 690 by TYK2 kinase. This phosphotyrosine provides a docking site for recruitment of STAT1 to IFNAR1, which is then tyrosine phosphorylated and activated.
REACT_25329 (Reactome) TYK2 bears the substrate recognition motif for PTP1B, and on IFN stimulation PTP1B interacts with and dephosphorylates TYK2.
REACT_25383 (Reactome) TYK2 functions as part of a receptor complex to trigger intracellular signaling in response to IFNA/B. TYK2 bound to IFNAR1 subunit is activated in response to IFNA/B treatment and this in turn phosphorylates two tyrosine residues Y466 and Y481 in the juxta-membrane region of IFNAR1.
REACT_25401 (Reactome) The two chains IFNAR1 and IFNAR2 are pre-associated with the JAK kinases TYK2 and JAK1, respectively. Receptor heterodimerization brings these JAK kinases into close proximity and they are activated by reciprocal trans-phosphorylation. Tyr-1054 and Tyr-1055 within the activation loop of TYK2 sub-domain VII are critical for TYK2 activation. For JAK1 two tyrosine residues with in the KEYY motif (Tyr 1034 and Tyr 1035) of the kinase domain are thought to be transphosphorylated.
RNASELArrowREACT_25192 (Reactome)
SHP-2/SHP-1TBarREACT_25017 (Reactome)
SOCS-1 and SOCS-3REACT_25065 (Reactome)
STAT1-1REACT_25105 (Reactome)
STAT1REACT_25017 (Reactome)
STAT2REACT_25238 (Reactome)
USP18REACT_24958 (Reactome)
XAF1ArrowREACT_25192 (Reactome)
p-STAT1 homodimerArrowREACT_25105 (Reactome)
p-STAT2 p-STAT1ArrowREACT_25021 (Reactome)
p-STAT2 p-STAT1REACT_25284 (Reactome)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1835"
Personal tools