Interferon alpha/beta signaling (Homo sapiens)

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3, 9, 14, 384, 7, 12, 17, 18, 20...21, 2824, 30, 342713413, 416, 1619, 33, 37, 3923, 3810, 1614, 2913442, 8, 9, 151, 3, 58, 9, 11, 22, 29...38extracellular exosomecytosolnucleoplasmendoplasmic reticulum lumenmitochondrionSTAT2 p-Y1054,Y1055-TYK2 p-Y1054,Y1055-TYK2 IFNA/B:IFNAR2:JAK1:STAT2:IFNAR1:TYK2XAF1PTPN6 IRF8 p-Y-JAK1 RNASELIFNB1 p-Y466,Y481-IFNAR1 HLA class I histocompatibility antigen, Cw-15 alpha chain IRF9 class I MHC B54 p-Y701-STAT1-2 IFNB1 USP18 OAS3 IRF9 HLA class I histocompatibility antigen, A-33 alpha chain OAS2 IFNAR2-2 class I MHC B57 PTPN1IFIT1HLA class I histocompatibility antigen, A-11 alpha chain class I MHC B13 HLA class I histocompatibility antigen, A-23 alpha chain HLA class I histocompatibility antigen, A-68 alpha chain p-Y-JAK1 STAT2 ADPclass I MHC B47 class I MHC B38 HLA class I histocompatibility antigen, alpha chain F precursor MX1 IFNAR1:TYK2ATPIFNB1 p-STAT1 homodimerRSAD2H2OSTAT1p-Y690-STAT2 IFNAR1 STAT1-1 HLA class I histocompatibility antigen, Cw-4 alpha chain precursor BST2p-Y701-STAT1-1 HLA class I histocompatibility antigen, A-80 alpha chain JAK1 SOCS1 IFNA/B:IFNAR2:JAK1:STAT2STAT2 PiHLA class I histocompatibility antigen, A-24 alpha chain class I MHC B8 class I MHC B42 p-Y1054,Y1055-TYK2 IFNAR2-2 IFNA class I MHC B7 STAT2 class I MHC B81 H2Oclass I MHC B15 TYK2 p-Y1054,Y1055-TYK2 IP6K2p-Y1054,Y1055-TYK2 SOCS-1 and SOCS-3IFNAR1 HLA class I histocompatibility antigen, Cw-5 alpha chain precursor p-Y1054,Y1055-TYK2 p-STAT2:p-STAT1class I MHC B39 IFNAR2-2JAK1 HLA class I histocompatibility antigen, A-2 alpha chain p-Y-JAK1 class I MHC B27 PTPN6class I MHC B45 HLA class I histocompatibility antigen, Cw-8 alpha chain USP18IFN alpha/beta(IFNA/B)SAMHD1IFNAR2-2 IRF5 HLA class I histocompatibility antigen, Cw-3 alpha chain precursor class I MHC B46 HLA class I histocompatibility antigen, A-32 alpha chain STAT2 HLA class I histocompatibility antigen, Cw-6 alpha chain precursor HLA class I histocompatibility antigen, Cw-18 alpha chain IFITM2IFNAR1 p-Y690-STAT2 HLA class I histocompatibility antigen, Cw-16 alpha chain JAK1 IFNAR2:JAK1:STAT2class I MHC B78 ISRE promoter elements in type I IFN-regulated genes class I MHC B52 HLA class I histocompatibility antigen, alpha chain G precursor IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:p-STAT1IRF4 p-Y701-STAT1-1 HLA class I histocompatibility antigen, A-29 alpha chain IFNB1 p-Y701-STAT1-2 TYK2 HLA class I histocompatibility antigen, Cw-2 alpha chain p-TYK2:p-IFNAR1:SOCS-1/SOCS-3:IFNA/B:IFNAR2:p-JAK1:STAT2ISGF3 bound to ISREpromotor elementsp-Y690-STAT2 p-Y690-STAT2 STAT1-2 IFNB1 p-Y690-STAT2 p-Y690-STAT2 IFNA HLA class I histocompatibility antigen, A-43 alpha chain class I MHC B18 IFI35IFNAR2-2 ADPclass I MHC B40 class I MHC B82 HLA class I histocompatibility antigen, A-26 alpha chain STAT1-2 IFNA Mx GTPasesp-Y701-STAT1-2 IFIT3p-Y701-STAT1-1 class I MHC B55 class I MHC B49 p-Y701-STAT1-1 ISG15IFNB1 p-Y701-STAT1-2 IFNAR2-2 p-Y690-STAT2 HLA class I histocompatibility antigen, Cw-12 alpha chain IRF9 ATPSTAT2p-Y466,Y481-IFNAR1 p-Y-JAK1 IFNAR2-2 HLA class I histocompatibility antigen, A-66 alpha chain IFNA p-Y701-STAT1-2 IRF9IFNA p-Y701-STAT1-1 HLA class I histocompatibility antigen, Cw-7 alpha chain precursor OAS proteinsGBP2PTPN6,PTPN11IFNAR2-2 HLA class I histocompatibility antigen, A-34 alpha chain IFNAR2-2 IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2MX2 EGR1IFNB1 IFNAR2-2 HLA class I histocompatibility antigen, A-69 alpha chain IFNA IFITM3Class I MHC heavychain (MHC HC)p-Y466,Y481-IFNAR1 STAT1-1 ATPSTAT2 IFNA p-Y466,Y481-IFNAR1 HLA class I histocompatibility antigen, A-25 alpha chain IFNAR2c:UBP43IFNA IFNA p-Y-JAK1 p-Y466,Y481-IFNAR1 STAT2 HLA class I histocompatibility antigen, A-31 alpha chain IFNB1 H2OIFIT2p-Y466,Y481-IFNAR1 class I MHC B51 ISGF3IRF6 ADARIFITM1OAS1 IFNAR2-2 IFNAR2-2 HLA class I histocompatibility antigen, A-1 alpha chain precursor Pip-Y701-STAT1-1 class I MHC B73 HLA class I histocompatibility antigen, Cw-14 alpha chain ATPIFNAR1 ISGF3ISRE promoterelements in type IIFN-regulated genesIRF3 class I MHC B59 IFNAR2-2 class I MHC B67 ATPIFNA class I MHC B50 ADPIRF9 STAT2 class I MHC B44 STAT2 OASL IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:STAT1IRF1 SOCS1 p-STAT1:p-STAT1p-Y-JAK1 HLA class I histocompatibility antigen, A-3 alpha chain precursor HLA class I histocompatibility antigen, Cw-17 alpha chain class I MHC B56 ISG20HLA class I histocompatibility antigen, A-36 alpha chain class I MHC B14 IRF2 STAT2 class I MHC B58 IFI27STAT1-1ADPSOCS3 IFI6HLA class I histocompatibility antigen, E alpha chain precursor IFNB1 Piclass I MHC B53 class I MHC B41 IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:STAT2SOCS3 PSMB8IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2IFNB1 HLA class I histocompatibility antigen, Cw-1 alpha chain HLA class I histocompatibility antigen, A-30 alpha chain IRF 1-9p-Y1054,Y1055-TYK2 class I MHC B35 p-Y701-STAT1-1 IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:TYK2IRF7 IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:p-TYK2PTPN11IFNB1 STAT2 HLA class I histocompatibility antigen, A-74 alpha chain IFNA p-Y-JAK1 PTPN11 class I MHC B37 p-Y-JAK1 TYK2 2626262626262626262626


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.

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Bibliography

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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)
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)
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-NUL-1015692 (Reactome)
ISRE promoter elements in type I IFN-regulated genes R-NUL-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)
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 homodimerComplexR-HSA-913524 (Reactome)
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-STAT1-2 ProteinP42224-2 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
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-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.
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 homodimerArrowR-HSA-909718 (Reactome)
p-STAT1 homodimerR-HSA-913529 (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)
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