Interferon alpha/beta signaling (Homo sapiens)

From WikiPathways

Revision as of 16:19, 31 October 2018 by ReactomeTeam (Talk | contribs)
Jump to: navigation, search
26, 32, 34, 4234, 3711, 2510, 15, 475, 12, 1617, 26, 30, 4522, 2813, 328, 426, 20, 24, 293281, 4, 26, 36-38, 4522143, 6, 9, 18, 19, 21...25, 4433, 42, 4340nucleoplasmextracellular exosomemitochondrioncytosolendoplasmic reticulum lumenIRF8 HLA class I histocompatibility antigen, A-11 alpha chain HLA class I histocompatibility antigen, A-36 alpha chain STAT1-2 class I MHC B59 STAT2 IRF9 p-Y701-STAT1-1 p-Y1054,Y1055-TYK2 IFNA IRF9class I MHC B8 HLA-H IRF3 ISGF3IFNB1 ISGF3RNASEL dimerADPclass I MHC B53 STAT1-1 p-Y1054,Y1055-TYK2 ISRE promoter elements in type I IFN-regulated genes STAT2 BST2IRF1 HLA class I histocompatibility antigen, A-66 alpha chain RNASEL IRF6 IFNAR2-2 HLA class I histocompatibility antigen, A-31 alpha chain class I MHC B57 p-TYK2:p-IFNAR1:SOCS-1/SOCS-3:IFNA/B:IFNAR2:p-JAK1:STAT2RNASEL p-Y701-STAT1-1 ATPclass I MHC B15 p-Y1054,Y1055-TYK2 Piclass I MHC B47 IFNAR1:TYK2STAT2 USP18p-Y690-STAT2 p-Y690-STAT2 class I MHC B7 HLA class I histocompatibility antigen, E alpha chain precursor p-Y701-STAT1-2 HLA class I histocompatibility antigen, A-80 alpha chain class I MHC B49 IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:TYK2p-Y701-STAT1-1 IRF9 IFNA/B:IFNAR2:JAK1:STAT2:IFNAR1:TYK2p-Y701-STAT1-2 ABCE1MX2 SAMHD1HLA class I histocompatibility antigen, A-32 alpha chain class I MHC B81 HLA class I histocompatibility antigen, A-3 alpha chain precursor IRF5 HLA class I histocompatibility antigen, A-25 alpha chain PTPN6,PTPN11IFNAR2c:UBP43IFNA HLA class I histocompatibility antigen, Cw-17 alpha chain STAT2 RSAD2HLA class I histocompatibility antigen, Cw-6 alpha chain precursor IFNAR2-2 HLA class I histocompatibility antigen, A-23 alpha chain IFN alpha/beta(IFNA/B)IFNB1 HLA class I histocompatibility antigen, Cw-12 alpha chain IFNB1 IFNB1 HLA class I histocompatibility antigen, A-33 alpha chain p-Y690-STAT2 IFNA class I MHC B45 p-Y-JAK1 class I MHC B55 STAT2 class I MHC B46 class I MHC B58 ADPIFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:STAT2IFI27ABCE1 HLA class I histocompatibility antigen, A-30 alpha chain ISGF3 bound to ISREpromotor elementsSTAT1-2 IFNAR2-2IFNB1 p-Y-JAK1 class I MHC B42 HLA class I histocompatibility antigen, A-43 alpha chain HLA class I histocompatibility antigen, A-34 alpha chain class I MHC B56 IFNB1 class I MHC B51 STAT2H2OPiSTAT2 IFNA STAT2 IFI6IFNB1 IFIT3SOCS-1 and SOCS-3STAT2 HLA class I histocompatibility antigen, A-74 alpha chain Class I MHC heavychain (MHC HC)IFNAR1 HLA class I histocompatibility antigen, Cw-15 alpha chain IRF9 class I MHC B38 p-Y-JAK1 IFNA SOCS1 class I MHC B78 TYK2 p-Y-JAK1 IFNAR2:JAK1:STAT2p-Y690-STAT2 PTPN6p-Y1054,Y1055-TYK2 TYK2 STAT1-1 ADPclass I MHC B52 class I MHC B37 ATPHLA class I histocompatibility antigen, Cw-8 alpha chain OAS1 ISG15Mx GTPasesHLA class I histocompatibility antigen, Cw-16 alpha chain HLA class I histocompatibility antigen, A-24 alpha chain HLA class I histocompatibility antigen, Cw-1 alpha chain HLA class I histocompatibility antigen, A-69 alpha chain IFNAR1 OAS2 HLA-B HLA class I histocompatibility antigen, A-68 alpha chain p-Y701-STAT1-2 class I MHC B41 IFNA HLA class I histocompatibility antigen, Cw-14 alpha chain class I MHC B18 IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2class I MHC B50 IFNAR2-2 HLA class I histocompatibility antigen, Cw-7 alpha chain precursor HLA class I histocompatibility antigen, Cw-18 alpha chain MX1 IP6K2JAK1 IFNAR2-2 HLA class I histocompatibility antigen, alpha chain F precursor IFNAR2-2 class I MHC B14 class I MHC B67 IFIT2class I MHC B82 IFNAR1 class I MHC B73 HLA class I histocompatibility antigen, alpha chain G precursor p-Y466,Y481-IFNAR1 USP18 JAK1 p-Y701-STAT1-1 dimerH2OATPSTAT1PTPN1HLA class I histocompatibility antigen, A-29 alpha chain p-STAT2:p-STAT1ADARIFNAR2-2 EGR1STAT1-1IFNAR2-2 HLA class I histocompatibility antigen, Cw-3 alpha chain precursor IFITM1p-Y466,Y481-IFNAR1 p-Y466,Y481-IFNAR1 p-Y-JAK1 TYK2 class I MHC B54 class I MHC B35 IFNA class I MHC B39 p-Y701-STAT1-1 IFNAR2-2 p-Y701-STAT1-2 IFNA/B:IFNAR2:JAK1:STAT2p-Y466,Y481-IFNAR1 p-Y466,Y481-IFNAR1 p-Y-JAK1 IFNA ABCE1:RNASEL dimerISRE promoterelements in type IIFN-regulated genesIRF4 SOCS3 IFNB1 p-Y701-STAT1-1 IFNB1 ADPPTPN11HLA class I histocompatibility antigen, Cw-4 alpha chain precursor PiHLA class I histocompatibility antigen, A-2 alpha chain IFNA IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:p-STAT1STAT2 p-Y690-STAT2 IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:STAT1p-Y1054,Y1055-TYK2 ATPPTPN11 IFNB1 STAT2 OAS3 IFITM3STAT2 HLA class I histocompatibility antigen, Cw-2 alpha chain PTPN6 p-Y701-STAT1-1 JAK1 class I MHC B27 IFNA p-Y690-STAT2 IFNAR2-2 RNASELIRF9 IFNAR2-2 GBP2p-Y1054,Y1055-TYK2 OASL H2Oclass I MHC B44 p-STAT1:p-STAT1IRF2 IRF7 ATPp-Y-JAK1 IFNAR2-2 IFI35IFNA SOCS1 IFNAR2-2 SOCS3 HLA class I histocompatibility antigen, A-1 alpha chain precursor PSMB8IFNB1 p-Y701-STAT1-1 class I MHC B13 IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:p-TYK2HLA class I histocompatibility antigen, A-26 alpha chain ISG20p-Y701-STAT1-2 HLA class I histocompatibility antigen, Cw-5 alpha chain precursor p-Y690-STAT2 IFIT1IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2IRF 1-9IFITM2class I MHC B40 p-Y1054,Y1055-TYK2 XAF1p-Y466,Y481-IFNAR1 IFNAR1 p-Y-JAK1 OAS proteins77777777777


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. View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 909733
Reactome-version 
Reactome version: 63
Reactome Author 
Reactome Author: Garapati, Phani Vijay

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
ABCE1 ProteinP61221 (Uniprot-TrEMBL)
ABCE1:RNASEL dimerComplexR-HSA-5223322 (Reactome)
ABCE1ProteinP61221 (Uniprot-TrEMBL)
ADARProteinP55265 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
BST2ProteinQ10589 (Uniprot-TrEMBL)
Class I MHC heavy chain (MHC HC)ComplexR-HSA-983117 (Reactome)
EGR1ProteinP18146 (Uniprot-TrEMBL)
GBP2ProteinP32456 (Uniprot-TrEMBL)
H2OMetaboliteCHEBI:15377 (ChEBI)
HLA class I histocompatibility antigen, A-1 alpha chain precursor ProteinP30443 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, A-11 alpha chain ProteinP13746 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, A-2 alpha chain ProteinP01892 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, A-23 alpha chain ProteinP30447 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, A-24 alpha chain ProteinP05534 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, A-25 alpha chain ProteinP18462 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, A-26 alpha chain ProteinP30450 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, A-29 alpha chain ProteinP30512 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, A-3 alpha chain precursor ProteinP04439 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, A-30 alpha chain ProteinP16188 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, A-31 alpha chain ProteinP16189 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, A-32 alpha chain ProteinP10314 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, A-33 alpha chain ProteinP16190 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, A-34 alpha chain ProteinP30453 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, A-36 alpha chain ProteinP30455 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, A-43 alpha chain ProteinP30456 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, A-66 alpha chain ProteinP30457 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, A-68 alpha chain ProteinP01891 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, A-69 alpha chain ProteinP10316 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, A-74 alpha chain ProteinP30459 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, A-80 alpha chain ProteinQ09160 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, Cw-1 alpha chain ProteinP30499 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, Cw-12 alpha chain ProteinP30508 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, Cw-14 alpha chain ProteinP30510 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, Cw-15 alpha chain ProteinQ07000 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, Cw-16 alpha chain ProteinQ29960 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, Cw-17 alpha chain ProteinQ95604 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, Cw-18 alpha chain ProteinQ29865 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, Cw-2 alpha chain ProteinP30501 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, Cw-3 alpha chain precursor ProteinP04222 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, Cw-4 alpha chain precursor ProteinP30504 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, Cw-5 alpha chain precursor ProteinQ9TNN7 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, Cw-6 alpha chain precursor ProteinQ29963 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, Cw-7 alpha chain precursor ProteinP10321 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, Cw-8 alpha chain ProteinP30505 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, E alpha chain precursor ProteinP13747 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, alpha chain F precursor ProteinP30511 (Uniprot-TrEMBL)
HLA class I histocompatibility antigen, alpha chain G precursor ProteinP17693 (Uniprot-TrEMBL)
HLA-B ProteinP30486 (Uniprot-TrEMBL)
HLA-H ProteinP01893 (Uniprot-TrEMBL)
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 (IFNA/B)ComplexR-HSA-909690 (Reactome)
IFNA R-HSA-909688 (Reactome)
IFNA/B:IFNAR2:JAK1:STAT2:IFNAR1:TYK2ComplexR-HSA-909703 (Reactome)
IFNA/B:IFNAR2:JAK1:STAT2ComplexR-HSA-918195 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:TYK2ComplexR-HSA-997300 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:p-TYK2ComplexR-HSA-909705 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:STAT2ComplexR-HSA-909696 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:STAT1ComplexR-HSA-997304 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:p-STAT1ComplexR-HSA-909711 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2ComplexR-HSA-909697 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2ComplexR-HSA-909704 (Reactome)
IFNAR1 ProteinP17181 (Uniprot-TrEMBL)
IFNAR1:TYK2ComplexR-HSA-909708 (Reactome)
IFNAR2-2 ProteinP48551-2 (Uniprot-TrEMBL)
IFNAR2-2ProteinP48551-2 (Uniprot-TrEMBL)
IFNAR2:JAK1:STAT2ComplexR-HSA-918193 (Reactome)
IFNAR2c:UBP43ComplexR-HSA-912690 (Reactome)
IFNB1 ProteinP01574 (Uniprot-TrEMBL)
IP6K2ProteinQ9UHH9 (Uniprot-TrEMBL)
IRF 1-9ComplexR-HSA-1015695 (Reactome)
IRF1 ProteinP10914 (Uniprot-TrEMBL)
IRF2 ProteinP14316 (Uniprot-TrEMBL)
IRF3 ProteinQ14653 (Uniprot-TrEMBL)
IRF4 ProteinQ15306 (Uniprot-TrEMBL)
IRF5 ProteinQ13568 (Uniprot-TrEMBL)
IRF6 ProteinO14896 (Uniprot-TrEMBL)
IRF7 ProteinQ92985 (Uniprot-TrEMBL)
IRF8 ProteinQ02556 (Uniprot-TrEMBL)
IRF9 ProteinQ00978 (Uniprot-TrEMBL)
IRF9ProteinQ00978 (Uniprot-TrEMBL)
ISG15ProteinP05161 (Uniprot-TrEMBL)
ISG20ProteinQ96AZ6 (Uniprot-TrEMBL)
ISGF3 bound to ISRE promotor elementsComplexR-HSA-1015697 (Reactome)
ISGF3ComplexR-HSA-909698 (Reactome)
ISGF3ComplexR-HSA-913527 (Reactome)
ISRE promoter

elements in type I

IFN-regulated genes
R-ALL-1015692 (Reactome)
ISRE promoter elements in type I IFN-regulated genes R-ALL-1015692 (Reactome)
JAK1 ProteinP23458 (Uniprot-TrEMBL)
MX1 ProteinP20591 (Uniprot-TrEMBL)
MX2 ProteinP20592 (Uniprot-TrEMBL)
Mx GTPasesComplexR-HSA-1015693 (Reactome)
OAS proteinsComplexR-HSA-1015696 (Reactome)
OAS1 ProteinP00973 (Uniprot-TrEMBL)
OAS2 ProteinP29728 (Uniprot-TrEMBL)
OAS3 ProteinQ9Y6K5 (Uniprot-TrEMBL)
OASL ProteinQ15646 (Uniprot-TrEMBL)
PSMB8ProteinP28062 (Uniprot-TrEMBL)
PTPN11 ProteinQ06124 (Uniprot-TrEMBL)
PTPN11ProteinQ06124 (Uniprot-TrEMBL)
PTPN1ProteinP18031 (Uniprot-TrEMBL)
PTPN6 ProteinP29350 (Uniprot-TrEMBL)
PTPN6,PTPN11ComplexR-HSA-389744 (Reactome)
PTPN6ProteinP29350 (Uniprot-TrEMBL)
PiMetaboliteCHEBI:18367 (ChEBI)
RNASEL ProteinQ05823 (Uniprot-TrEMBL)
RNASEL dimerComplexR-HSA-5357403 (Reactome)
RNASELProteinQ05823 (Uniprot-TrEMBL)
RSAD2ProteinQ8WXG1 (Uniprot-TrEMBL)
SAMHD1ProteinQ9Y3Z3 (Uniprot-TrEMBL)
SOCS-1 and SOCS-3ComplexR-HSA-877267 (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)
STAT1ComplexR-HSA-380755 (Reactome)
STAT2 ProteinP52630 (Uniprot-TrEMBL)
STAT2ProteinP52630 (Uniprot-TrEMBL)
TYK2 ProteinP29597 (Uniprot-TrEMBL)
USP18 ProteinQ9UMW8 (Uniprot-TrEMBL)
USP18ProteinQ9UMW8 (Uniprot-TrEMBL)
XAF1ProteinQ6GPH4 (Uniprot-TrEMBL)
class I MHC B13 ProteinP30461 (Uniprot-TrEMBL)
class I MHC B14 ProteinP30462 (Uniprot-TrEMBL)
class I MHC B15 ProteinP30464 (Uniprot-TrEMBL)
class I MHC B18 ProteinP30466 (Uniprot-TrEMBL)
class I MHC B27 ProteinP03989 (Uniprot-TrEMBL)
class I MHC B35 ProteinP30685 (Uniprot-TrEMBL)
class I MHC B37 ProteinP18463 (Uniprot-TrEMBL)
class I MHC B38 ProteinQ95365 (Uniprot-TrEMBL)
class I MHC B39 ProteinP30475 (Uniprot-TrEMBL)
class I MHC B40 ProteinQ04826 (Uniprot-TrEMBL)
class I MHC B41 ProteinP30479 (Uniprot-TrEMBL)
class I MHC B42 ProteinP30480 (Uniprot-TrEMBL)
class I MHC B44 ProteinP30481 (Uniprot-TrEMBL)
class I MHC B45 ProteinP30483 (Uniprot-TrEMBL)
class I MHC B46 ProteinP30484 (Uniprot-TrEMBL)
class I MHC B47 ProteinP30485 (Uniprot-TrEMBL)
class I MHC B49 ProteinP30487 (Uniprot-TrEMBL)
class I MHC B50 ProteinP30488 (Uniprot-TrEMBL)
class I MHC B51 ProteinP18464 (Uniprot-TrEMBL)
class I MHC B52 ProteinP30490 (Uniprot-TrEMBL)
class I MHC B53 ProteinP30491 (Uniprot-TrEMBL)
class I MHC B54 ProteinP30492 (Uniprot-TrEMBL)
class I MHC B55 ProteinP30493 (Uniprot-TrEMBL)
class I MHC B56 ProteinP30495 (Uniprot-TrEMBL)
class I MHC B57 ProteinP18465 (Uniprot-TrEMBL)
class I MHC B58 ProteinP10319 (Uniprot-TrEMBL)
class I MHC B59 ProteinQ29940 (Uniprot-TrEMBL)
class I MHC B67 ProteinQ29836 (Uniprot-TrEMBL)
class I MHC B7 ProteinP01889 (Uniprot-TrEMBL)
class I MHC B73 ProteinQ31612 (Uniprot-TrEMBL)
class I MHC B78 ProteinP30498 (Uniprot-TrEMBL)
class I MHC B8 ProteinP30460 (Uniprot-TrEMBL)
class I MHC B81 ProteinQ31610 (Uniprot-TrEMBL)
class I MHC B82 ProteinQ29718 (Uniprot-TrEMBL)
p-STAT1:p-STAT1ComplexR-HSA-913526 (Reactome)
p-STAT2:p-STAT1ComplexR-HSA-909702 (Reactome)
p-TYK2:p-IFNAR1:SOCS-1/SOCS-3:IFNA/B:IFNAR2:p-JAK1:STAT2ComplexR-HSA-912681 (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-STAT1-1 dimerComplexR-HSA-913524 (Reactome)
p-Y701-STAT1-2 ProteinP42224-2 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ABCE1:RNASEL dimerArrowR-HSA-5223305 (Reactome)
ABCE1R-HSA-5223305 (Reactome)
ADARArrowR-HSA-1015702 (Reactome)
ADPArrowR-HSA-909718 (Reactome)
ADPArrowR-HSA-909729 (Reactome)
ADPArrowR-HSA-909730 (Reactome)
ADPArrowR-HSA-909732 (Reactome)
ATPR-HSA-909718 (Reactome)
ATPR-HSA-909726 (Reactome)
ATPR-HSA-909729 (Reactome)
ATPR-HSA-909730 (Reactome)
ATPR-HSA-909732 (Reactome)
BST2ArrowR-HSA-1015702 (Reactome)
Class I MHC heavy chain (MHC HC)ArrowR-HSA-1015702 (Reactome)
EGR1ArrowR-HSA-1015702 (Reactome)
GBP2ArrowR-HSA-1015702 (Reactome)
H2OR-HSA-997309 (Reactome)
H2OR-HSA-997311 (Reactome)
H2OR-HSA-997314 (Reactome)
IFI27ArrowR-HSA-1015702 (Reactome)
IFI35ArrowR-HSA-1015702 (Reactome)
IFI6ArrowR-HSA-1015702 (Reactome)
IFIT1ArrowR-HSA-1015702 (Reactome)
IFIT2ArrowR-HSA-1015702 (Reactome)
IFIT3ArrowR-HSA-1015702 (Reactome)
IFITM1ArrowR-HSA-1015702 (Reactome)
IFITM2ArrowR-HSA-1015702 (Reactome)
IFITM3ArrowR-HSA-1015702 (Reactome)
IFN alpha/beta (IFNA/B)R-HSA-909720 (Reactome)
IFNA/B:IFNAR2:JAK1:STAT2:IFNAR1:TYK2ArrowR-HSA-909724 (Reactome)
IFNA/B:IFNAR2:JAK1:STAT2:IFNAR1:TYK2ArrowR-HSA-997314 (Reactome)
IFNA/B:IFNAR2:JAK1:STAT2:IFNAR1:TYK2R-HSA-909729 (Reactome)
IFNA/B:IFNAR2:JAK1:STAT2:IFNAR1:TYK2R-HSA-912680 (Reactome)
IFNA/B:IFNAR2:JAK1:STAT2:IFNAR1:TYK2mim-catalysisR-HSA-909729 (Reactome)
IFNA/B:IFNAR2:JAK1:STAT2ArrowR-HSA-909720 (Reactome)
IFNA/B:IFNAR2:JAK1:STAT2R-HSA-909724 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:TYK2ArrowR-HSA-997311 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:TYK2R-HSA-997314 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:p-TYK2ArrowR-HSA-909729 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:p-TYK2R-HSA-909730 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:p-TYK2R-HSA-997311 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:p-TYK2mim-catalysisR-HSA-909730 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:STAT2ArrowR-HSA-909719 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:STAT2R-HSA-909732 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:STAT2mim-catalysisR-HSA-909732 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:STAT1ArrowR-HSA-997309 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:p-STAT1ArrowR-HSA-909726 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:p-STAT1R-HSA-909722 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:p-STAT1R-HSA-997309 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:p-STAT1mim-catalysisR-HSA-909718 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:p-STAT1mim-catalysisR-HSA-909726 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2ArrowR-HSA-909732 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2R-HSA-909726 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2ArrowR-HSA-909722 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2ArrowR-HSA-909730 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2R-HSA-909719 (Reactome)
IFNAR1:TYK2R-HSA-909724 (Reactome)
IFNAR2-2R-HSA-912685 (Reactome)
IFNAR2:JAK1:STAT2R-HSA-909720 (Reactome)
IFNAR2c:UBP43ArrowR-HSA-912685 (Reactome)
IP6K2ArrowR-HSA-1015702 (Reactome)
IRF 1-9ArrowR-HSA-1015702 (Reactome)
IRF9R-HSA-909725 (Reactome)
ISG15ArrowR-HSA-1015702 (Reactome)
ISG20ArrowR-HSA-1015702 (Reactome)
ISGF3 bound to ISRE promotor elementsArrowR-HSA-1015699 (Reactome)
ISGF3 bound to ISRE promotor elementsArrowR-HSA-1015702 (Reactome)
ISGF3ArrowR-HSA-909721 (Reactome)
ISGF3ArrowR-HSA-909725 (Reactome)
ISGF3R-HSA-1015699 (Reactome)
ISGF3R-HSA-909721 (Reactome)
ISRE promoter

elements in type I

IFN-regulated genes
R-HSA-1015699 (Reactome)
Mx GTPasesArrowR-HSA-1015702 (Reactome)
OAS proteinsArrowR-HSA-1015702 (Reactome)
PSMB8ArrowR-HSA-1015702 (Reactome)
PTPN11mim-catalysisR-HSA-997309 (Reactome)
PTPN1mim-catalysisR-HSA-997311 (Reactome)
PTPN6,PTPN11TBarR-HSA-909726 (Reactome)
PTPN6mim-catalysisR-HSA-997314 (Reactome)
PiArrowR-HSA-997309 (Reactome)
PiArrowR-HSA-997311 (Reactome)
PiArrowR-HSA-997314 (Reactome)
R-HSA-1015699 (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.
R-HSA-1015702 (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.
R-HSA-5223305 (Reactome) 2-5A-dependent ribonuclease (RNASEL) is an endoribonuclease that is activated in the interferon (IFN) antiviral response. Its anti-viral effects are probably a combination of induction of apoptosis, cleavage of viral mRNA and induction of other anti-viral genes. ATP-binding cassette sub-family E member 1 (ABCE1, aka RNase L inhibitor, RLI) directly interacts with RNASEL and inhibits its endoribonuclease activity, thus antagonising the anti-viral effect of the IFN-regulated 2-5A/RNase L pathway (Martinand et al. 1998, Martinand et al. 1999, Le Roy et al. 2001).
R-HSA-909718 (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).
R-HSA-909719 (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.
R-HSA-909720 (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.
R-HSA-909721 (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.
R-HSA-909722 (Reactome) The phosphorylated STAT2:STAT1 heterodimers thus formed disassociate from the IFNAR1 subunit and translocates to the nucleus.
R-HSA-909724 (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.
R-HSA-909725 (Reactome) The phosphorylated STAT2:STAT1 heterodimer associates with interferon-regulating factor 9 (IRF9) to form the interferon-stimulated gene factor 3 (ISGF3) complex.
R-HSA-909726 (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). These STATs recruited to the phosporylated IFNAR1 form two distinct transcriptional activator complexes, namely, IFN-alpha-activated factor (AAF) and IFN-stimulated gene factor 3 (ISGF3). AAF is a homodimer of STAT1, whereas ISGF3 is a heterotrimeric complex of STAT1, STAT2 and IRF9 (also known as p48 or ISGF3gamma) (Honda et al. 2005).
R-HSA-909729 (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.
R-HSA-909730 (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.
R-HSA-909732 (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.
R-HSA-912680 (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.
R-HSA-912685 (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.
R-HSA-913529 (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.
R-HSA-997309 (Reactome) SHP2 negatively regulates the IFN-induced JAK-STAT pathway by dephosphorylating STAT1 on Y701.
R-HSA-997311 (Reactome) TYK2 bears the substrate recognition motif for PTP1B, and on IFN stimulation PTP1B interacts with and dephosphorylates TYK2.
R-HSA-997314 (Reactome) SHP1 directly associates with and dephosphorylates JAK1/2.
RNASEL dimerR-HSA-5223305 (Reactome)
RNASELArrowR-HSA-1015702 (Reactome)
RSAD2ArrowR-HSA-1015702 (Reactome)
SAMHD1ArrowR-HSA-1015702 (Reactome)
SOCS-1 and SOCS-3R-HSA-912680 (Reactome)
STAT1-1R-HSA-909718 (Reactome)
STAT1R-HSA-909726 (Reactome)
STAT2R-HSA-909719 (Reactome)
USP18R-HSA-912685 (Reactome)
XAF1ArrowR-HSA-1015702 (Reactome)
p-STAT1:p-STAT1ArrowR-HSA-913529 (Reactome)
p-STAT2:p-STAT1ArrowR-HSA-909722 (Reactome)
p-STAT2:p-STAT1R-HSA-909725 (Reactome)
p-TYK2:p-IFNAR1:SOCS-1/SOCS-3:IFNA/B:IFNAR2:p-JAK1:STAT2ArrowR-HSA-912680 (Reactome)
p-TYK2:p-IFNAR1:SOCS-1/SOCS-3:IFNA/B:IFNAR2:p-JAK1:STAT2TBarR-HSA-909729 (Reactome)
p-Y701-STAT1-1 dimerArrowR-HSA-909718 (Reactome)
p-Y701-STAT1-1 dimerR-HSA-913529 (Reactome)
Personal tools