Interferon alpha/beta signaling (Homo sapiens)

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4, 9, 34, 4223, 421, 5-7, 13...4, 401, 3, 19, 4131, 342, 8, 9, 21, 25...12, 281016, 22, 3711, 35, 4223417, 2727, 29189, 20, 25, 361032IFNAR2:p-JAK1:STAT2[plasma membrane]IFN alpha/beta(IFNA/B)[extracellularregion]IFNA [extracellularregion]p-STAT2:p-STAT1:p-IFNAR1:p-TYK2[plasma membrane]IFN alpha/beta(IFNA/B)[extracellularregion]p-STAT2:p-IFNAR1:p-TYK2[plasma membrane]cytosolp-STAT1 [cytosol]IFN alpha/beta(IFNA/B)[extracellularregion]p-STAT2:p-STAT1[cytosol]endoplasmic reticulum lumenIFNA/B:IFNAR2:p-JAK1:STAT2[plasma membrane]IFN alpha/beta(IFNA/B)[extracellularregion]ISGF3 [cytosol]IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:STAT2[plasma membrane]IFNAR2c:UBP43[plasma membrane]p-STAT2:p-STAT1[cytosol]IFNA [extracellularregion]IFNA [extracellularregion]p-IFNAR1:p-TYK2[plasma membrane]p-STAT2:p-STAT1[nucleoplasm]IFNAR2:p-JAK1:STAT2[plasma membrane]IFNA [extracellularregion]IFN alpha/beta(IFNA/B)[extracellularregion]IFNA/B:IFNAR2:JAK1:STAT2:IFNAR1:TYK2[plasma membrane]IFNA [extracellularregion]p-STAT1 [cytosol]IFNA [extracellularregion]IFNA [extracellularregion]IFNAR2:JAK1:STAT2[plasma membrane]nucleoplasmIFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:STAT1[plasma membrane]p-STAT2:p-STAT1[nucleoplasm]p-STAT2:STAT1:p-IFNAR1:p-TYK2[plasma membrane]IFNA/B:IFNAR2:p-JAK1:STAT2[plasma membrane]IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:p-STAT1[plasma membrane]IFNAR2:p-JAK1:STAT2[plasma membrane]IFNAR1:TYK2 [plasmamembrane]IFNA [extracellularregion]IFN alpha/beta(IFNA/B)[extracellularregion]IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2[plasma membrane]IFNA/B:IFNAR2:JAK1:STAT2[plasma membrane]IFNAR2:p-JAK1:STAT2[plasma membrane]p-STAT1 homodimer[cytosol]STAT1 [cytosol]p-TYK2:p-IFNAR1:SOCS-1/SOCS-3:IFNA/B:IFNAR2:p-JAK1:STAT2[plasma membrane]p-STAT1[nucleoplasm]IFN alpha/beta(IFNA/B)[extracellularregion]IFNAR2:JAK1:STAT2[plasma membrane]ISGF3 bound to ISREpromotor elements[nucleoplasm]IFNAR1:TYK2 [plasmamembrane]IFNA/B:IFNAR2:p-JAK1:STAT2[plasma membrane]IFNAR1:TYK2 [plasmamembrane]IFNAR2:p-JAK1:STAT2[plasma membrane]IFN alpha/beta(IFNA/B)[extracellularregion]IFN alpha/beta(IFNA/B)[extracellularregion]IFNAR1:p-TYK2[plasma membrane]IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:TYK2[plasma membrane]STAT2:p-IFNAR1:p-TYK2[plasma membrane]mitochondrionp-STAT1 [cytosol]IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2[plasma membrane]IFNA [extracellularregion]IFN alpha/beta(IFNA/B)[extracellularregion]p-IFNAR1:p-TYK2:SOCS-1/SOCS-3[plasma membrane]IFNAR2:JAK1:STAT2[plasma membrane]ISGF3 [nucleoplasm]IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:p-TYK2[plasma membrane]p-STAT2:STAT1[cytosol]IFNAR2:p-JAK1:STAT2[plasma membrane]SOCS-1 and SOCS-3[cytosol]IFNAR2:p-JAK1:STAT2[plasma membrane]IFNAR2:p-JAK1:STAT2[plasma membrane]IFNA/B:IFNAR2:JAK1:STAT2[plasma membrane]IFNA/B:IFNAR2:p-JAK1:STAT2[plasma membrane]ISGF3 [nucleoplasm]p-STAT2:p-STAT1[cytosol]p-STAT1:p-STAT1[nucleoplasm]p-STAT1[nucleoplasm]IFNA [extracellularregion]IFNA14[extracellularregion]IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2IFNA14[extracellularregion]IFNA7 [extracellularregion]IRF9 [nucleoplasm]IFNA8 [extracellularregion]IFNA17[extracellularregion]p-Y-JAK1 [cytosol]p-STAT1 homodimerp-Y1054,Y1055-TYK2[cytosol]IFNA1 [extracellularregion]IFNB1 [extracellularregion]IFNA2 [extracellularregion]PiSTAT2 [cytosol]IFNA21[extracellularregion]IFNA2 [extracellularregion]IFNB1 [extracellularregion]p-STAT2:p-STAT1p-Y690-STAT2[nucleoplasm]IFNA8 [extracellularregion]IFNA14[extracellularregion]IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:STAT1IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:p-STAT1p-Y701-STAT1-1[nucleoplasm]p-Y690-STAT2[cytosol]IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:TYK2STAT1-1 [cytosol]GBP2IFNA17[extracellularregion]STAT2 [cytosol]IFNA2 [extracellularregion]STAT2 [cytosol]IFNA21[extracellularregion]H2OIRF9 [cytosol]IFNA4 [extracellularregion]IFNA21[extracellularregion]IFNAR2-2 [plasmamembrane]IFNA7 [extracellularregion]RNASELIFNA8 [extracellularregion]ATPEGR1IFNA10[extracellularregion]IFNAR1 [plasmamembrane]p-Y1054,Y1055-TYK2[cytosol]IFNAR2c:UBP43XAF1p-Y1054,Y1055-TYK2[cytosol]ADARIFNA21[extracellularregion]IFNA6 [extracellularregion]IRF 1-9IFNA10[extracellularregion]IFNA5 [extracellularregion]IFNA10[extracellularregion]STAT1-2 [cytosol]IFNA21[extracellularregion]IFNA7 [extracellularregion]IFNA7 [extracellularregion]p-Y-JAK1 [cytosol]IFNAR2-2 [plasmamembrane]IFNA16[extracellularregion]IFNAR2-2 [plasmamembrane]IFNA4 [extracellularregion]IFNA1 [extracellularregion]IFNA10[extracellularregion]IFNB1 [extracellularregion]TYK2 [cytosol]IFNA4 [extracellularregion]IFNA5 [extracellularregion]IFNA5 [extracellularregion]ATPUSP18 [cytosol]IFNA7 [extracellularregion]IFNAR2-2 [plasmamembrane]IFNA4 [extracellularregion]IFNA4 [extracellularregion]IFNAR1 [plasmamembrane]SOCS1 [cytosol]p-Y-JAK1 [cytosol]IFNA16[extracellularregion]IFNA14[extracellularregion]IFNB1 [extracellularregion]p-Y466,Y481-IFNAR1[plasma membrane]IFNA16[extracellularregion]IFN alpha/beta(IFNA/B)IFITM2IFNAR2-2 [plasmamembrane]IFNA10[extracellularregion]USP18IFNAR2-2 [plasmamembrane]p-Y701-STAT1-1[nucleoplasm]IFI6IFNA2 [extracellularregion]IFNAR2-2 [plasmamembrane]Class I MHC heavychain (MHC HC)p-Y-JAK1 [cytosol]STAT1-1IFNA8 [extracellularregion]IFNA4 [extracellularregion]IFNAR2-2 [plasmamembrane]IFNA1 [extracellularregion]STAT2 [cytosol]IFNA2 [extracellularregion]p-Y690-STAT2[cytosol]PTPN1ADPPip-Y466,Y481-IFNAR1[plasma membrane]IFNA1 [extracellularregion]p-Y-JAK1 [cytosol]ISRE promoterelements in type IIFN-regulated genesIFNA8 [extracellularregion]ADPIFITM3STAT1p-Y1054,Y1055-TYK2[cytosol]p-Y466,Y481-IFNAR1[plasma membrane]IFNAR2-2 [plasmamembrane]SHP-2/SHP-1IFNB1 [extracellularregion]p-Y1054,Y1055-TYK2[cytosol]p-Y690-STAT2[cytosol]STAT2 [cytosol]IFNA17[extracellularregion]IFNA1 [extracellularregion]ISG20IFNA14[extracellularregion]OAS proteinsSTAT2 [cytosol]IFNA4 [extracellularregion]IFNA21[extracellularregion]IFNA5 [extracellularregion]IFNA5 [extracellularregion]PTPN11p-Y466,Y481-IFNAR1[plasma membrane]STAT2 [cytosol]IRF9IFNA21[extracellularregion]p-Y701-STAT1-2[nucleoplasm]IFNA2 [extracellularregion]PTPN6p-Y-JAK1 [cytosol]IFNA21[extracellularregion]p-Y690-STAT2[nucleoplasm]STAT2 [cytosol]IFNA16[extracellularregion]IFNB1 [extracellularregion]IFNB1 [extracellularregion]IFNA7 [extracellularregion]IFNA5 [extracellularregion]ADPATPIFNA10[extracellularregion]STAT2 [cytosol]JAK1 [cytosol]Mx GTPasesIFNA7 [extracellularregion]IFNA2 [extracellularregion]STAT2IFNA2 [extracellularregion]PSMB8IFNA8 [extracellularregion]IFNAR2-2IFNA6 [extracellularregion]p-Y690-STAT2[cytosol]IFNA7 [extracellularregion]IFNA21[extracellularregion]IRF9 [nucleoplasm]JAK1 [cytosol]IFNA4 [extracellularregion]ISGF3IFIT3IFNA16[extracellularregion]IFNA16[extracellularregion]IFIT2p-Y466,Y481-IFNAR1[plasma membrane]IFNA5 [extracellularregion]p-Y1054,Y1055-TYK2[cytosol]IFNA6 [extracellularregion]ATPIFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2IFNA2 [extracellularregion]IFNA5 [extracellularregion]IFNA5 [extracellularregion]IFNA8 [extracellularregion]PiIFNA17[extracellularregion]IFNAR1 [plasmamembrane]IFI35IFNA14[extracellularregion]IFNA17[extracellularregion]IFNA16[extracellularregion]IFNA16[extracellularregion]p-Y701-STAT1-2[nucleoplasm]IFNA10[extracellularregion]IFNA16[extracellularregion]p-Y701-STAT1-1[cytosol]IFNA8 [extracellularregion]TYK2 [cytosol]IFNA17[extracellularregion]IFNA14[extracellularregion]ISGF3p-Y701-STAT1-1[cytosol]IFNA7 [extracellularregion]IFNAR2-2 [plasmamembrane]IFNA17[extracellularregion]p-Y466,Y481-IFNAR1[plasma membrane]p-Y690-STAT2[cytosol]p-Y-JAK1 [cytosol]IFNA17[extracellularregion]IFNA8 [extracellularregion]IFIT1IFNA5 [extracellularregion]IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:STAT2p-Y701-STAT1-2[cytosol]p-TYK2:p-IFNAR1:SOCS-1/SOCS-3:IFNA/B:IFNAR2:p-JAK1:STAT2IFNA10[extracellularregion]IFNA4 [extracellularregion]IFNA14[extracellularregion]IP6K2TYK2 [cytosol]IFNA1 [extracellularregion]IFNAR1 [plasmamembrane]ISG15IFNA1 [extracellularregion]IFNAR1:TYK2IFNA8 [extracellularregion]ATPIFNAR2-2 [plasmamembrane]IFNA17[extracellularregion]p-STAT1:p-STAT1IFNA10[extracellularregion]IFNB1 [extracellularregion]IFNA6 [extracellularregion]SOCS3 [cytosol]STAT2 [cytosol]H2Op-Y701-STAT1-2[cytosol]IFITM1IFNA1 [extracellularregion]p-Y701-STAT1-1[nucleoplasm]IFNA/B:IFNAR2:JAK1:STAT2IFNA1 [extracellularregion]p-Y701-STAT1-2[cytosol]IFNA6 [extracellularregion]JAK1 [cytosol]IFNA7 [extracellularregion]IFNA21[extracellularregion]SOCS-1 and SOCS-3IFNAR2-2 [plasmamembrane]IFNB1 [extracellularregion]H2OIFNA6 [extracellularregion]IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:p-TYK2IFNA14[extracellularregion]p-Y-JAK1 [cytosol]IFNA4 [extracellularregion]IFNA10[extracellularregion]IFNA6 [extracellularregion]ISGF3 bound to ISREpromotor elementsp-Y701-STAT1-1[cytosol]IFNA1 [extracellularregion]IFNA17[extracellularregion]IFNA14[extracellularregion]p-Y1054,Y1055-TYK2[cytosol]IFNA16[extracellularregion]IFNA/B:IFNAR2:JAK1:STAT2:IFNAR1:TYK2p-Y701-STAT1-1[cytosol]IFNA6 [extracellularregion]STAT2 [cytosol]IFI27IFNAR2:JAK1:STAT2IFNA6 [extracellularregion]IFNB1 [extracellularregion]IFNA2 [extracellularregion]ADPIFNA6 [extracellularregion]


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

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Bibliography

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History

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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 (MHC HC)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 (IFNA/B)ProteinREACT_26595 (Reactome)
IFNA/B:IFNAR2:JAK1:STAT2:IFNAR1:TYK2ComplexREACT_25725 (Reactome)
IFNA/B:IFNAR2:JAK1:STAT2ComplexREACT_26015 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:TYK2ComplexREACT_26140 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:p-TYK2ComplexREACT_26001 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:STAT2ComplexREACT_25990 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:STAT1ComplexREACT_26740 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:p-STAT1ComplexREACT_26770 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2ComplexREACT_26908 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2ComplexREACT_26083 (Reactome)
IFNA1 [extracellular region]ProteinP01562 (Uniprot-TrEMBL)
IFNA10

[extracellular

region]		ProteinP01566 (Uniprot-TrEMBL)
IFNA14

[extracellular

region]		ProteinP01570 (Uniprot-TrEMBL)
IFNA16

[extracellular

region]		ProteinP05015 (Uniprot-TrEMBL)
IFNA17

[extracellular

region]		ProteinP01571 (Uniprot-TrEMBL)
IFNA2 [extracellular region]ProteinP01563 (Uniprot-TrEMBL)
IFNA21

[extracellular

region]		ProteinP01568 (Uniprot-TrEMBL)
IFNA4 [extracellular region]ProteinP05014 (Uniprot-TrEMBL)
IFNA5 [extracellular region]ProteinP01569 (Uniprot-TrEMBL)
IFNA6 [extracellular region]ProteinP05013 (Uniprot-TrEMBL)
IFNA7 [extracellular region]ProteinP01567 (Uniprot-TrEMBL)
IFNA8 [extracellular region]ProteinP32881 (Uniprot-TrEMBL)
IFNAR1 [plasma membrane]ProteinP17181 (Uniprot-TrEMBL)
IFNAR1:TYK2ComplexREACT_25562 (Reactome)
IFNAR2-2 [plasma membrane]ProteinP48551-2 (Uniprot-TrEMBL)
IFNAR2-2ProteinP48551-2 (Uniprot-TrEMBL)
IFNAR2:JAK1:STAT2ComplexREACT_25438 (Reactome)
IFNAR2c:UBP43ComplexREACT_26598 (Reactome)
IFNB1 [extracellular region]ProteinP01574 (Uniprot-TrEMBL)
IP6K2ProteinQ9UHH9 (Uniprot-TrEMBL)
IRF 1-9ProteinREACT_26465 (Reactome)
IRF9 [cytosol]ProteinQ00978 (Uniprot-TrEMBL)
IRF9 [nucleoplasm]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 genes		REACT_26432 (Reactome)
JAK1 [cytosol]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 [cytosol]ProteinO15524 (Uniprot-TrEMBL)
SOCS3 [cytosol]ProteinO14543 (Uniprot-TrEMBL)
STAT1-1 [cytosol]ProteinP42224-1 (Uniprot-TrEMBL)
STAT1-1ProteinP42224-1 (Uniprot-TrEMBL)
STAT1-2 [cytosol]ProteinP42224-2 (Uniprot-TrEMBL)
STAT1ProteinREACT_17621 (Reactome)
STAT2 [cytosol]ProteinP52630 (Uniprot-TrEMBL)
STAT2ProteinP52630 (Uniprot-TrEMBL)
TYK2 [cytosol]ProteinP29597 (Uniprot-TrEMBL)
USP18 [cytosol]ProteinQ9UMW8 (Uniprot-TrEMBL)
USP18ProteinQ9UMW8 (Uniprot-TrEMBL)
XAF1ProteinQ6GPH4 (Uniprot-TrEMBL)
p-STAT1 homodimerComplexREACT_26275 (Reactome)
p-STAT1:p-STAT1ComplexREACT_26749 (Reactome)
p-STAT2:p-STAT1ComplexREACT_27063 (Reactome)
p-TYK2:p-IFNAR1:SOCS-1/SOCS-3:IFNA/B:IFNAR2:p-JAK1:STAT2ComplexREACT_26646 (Reactome)
p-Y-JAK1 [cytosol]ProteinP23458 (Uniprot-TrEMBL)
p-Y1054,Y1055-TYK2 [cytosol]ProteinP29597 (Uniprot-TrEMBL)
p-Y466,Y481-IFNAR1 [plasma membrane]ProteinP17181 (Uniprot-TrEMBL)
p-Y690-STAT2 [cytosol]ProteinP52630 (Uniprot-TrEMBL)
p-Y690-STAT2 [nucleoplasm]ProteinP52630 (Uniprot-TrEMBL)
p-Y701-STAT1-1 [cytosol]ProteinP42224-1 (Uniprot-TrEMBL)
p-Y701-STAT1-1 [nucleoplasm]ProteinP42224-1 (Uniprot-TrEMBL)
p-Y701-STAT1-2 [cytosol]ProteinP42224-2 (Uniprot-TrEMBL)
p-Y701-STAT1-2 [nucleoplasm]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 (MHC HC)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 (IFNA/B)REACT_25100 (Reactome)
IFNA/B:IFNAR2:JAK1:STAT2:IFNAR1:TYK2ArrowREACT_25206 (Reactome)
IFNA/B:IFNAR2:JAK1:STAT2:IFNAR1:TYK2ArrowREACT_25289 (Reactome)
IFNA/B:IFNAR2:JAK1:STAT2:IFNAR1:TYK2REACT_25065 (Reactome)
IFNA/B:IFNAR2:JAK1:STAT2:IFNAR1:TYK2REACT_25401 (Reactome)
IFNA/B:IFNAR2:JAK1:STAT2:IFNAR1:TYK2mim-catalysisREACT_25401 (Reactome)
IFNA/B:IFNAR2:JAK1:STAT2ArrowREACT_25100 (Reactome)
IFNA/B:IFNAR2:JAK1:STAT2REACT_25206 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:TYK2ArrowREACT_25329 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:TYK2REACT_25289 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:p-TYK2ArrowREACT_25401 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:p-TYK2REACT_25329 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:p-TYK2REACT_25383 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:p-TYK2mim-catalysisREACT_25383 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:STAT2ArrowREACT_25238 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:STAT2REACT_25291 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:STAT2mim-catalysisREACT_25291 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:STAT1ArrowREACT_24939 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:p-STAT1ArrowREACT_25017 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:p-STAT1REACT_24939 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:p-STAT1REACT_25021 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2ArrowREACT_25291 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2REACT_25017 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2mim-catalysisREACT_25017 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2mim-catalysisREACT_25105 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2ArrowREACT_25021 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2ArrowREACT_25383 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2REACT_25238 (Reactome)
IFNAR1:TYK2REACT_25206 (Reactome)
IFNAR2-2REACT_24958 (Reactome)
IFNAR2:JAK1:STAT2REACT_25100 (Reactome)
IFNAR2c:UBP43ArrowREACT_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_24942 (Reactome)
ISGF3 bound to ISRE promotor elementsArrowREACT_25192 (Reactome)
ISGF3ArrowREACT_25169 (Reactome)
ISGF3ArrowREACT_25284 (Reactome)
ISGF3REACT_24942 (Reactome)
ISGF3REACT_25169 (Reactome)
ISRE promoter

elements in type I

IFN-regulated genes		REACT_24942 (Reactome)
Mx GTPasesArrowREACT_25192 (Reactome)
OAS proteinsArrowREACT_25192 (Reactome)
PSMB8ArrowREACT_25192 (Reactome)
PTPN11mim-catalysisREACT_24939 (Reactome)
PTPN1mim-catalysisREACT_25329 (Reactome)
PTPN6mim-catalysisREACT_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-STAT1 homodimerREACT_25256 (Reactome)
p-STAT1:p-STAT1ArrowREACT_25256 (Reactome)
p-STAT2:p-STAT1ArrowREACT_25021 (Reactome)
p-STAT2:p-STAT1REACT_25284 (Reactome)
p-TYK2:p-IFNAR1:SOCS-1/SOCS-3:IFNA/B:IFNAR2:p-JAK1:STAT2ArrowREACT_25065 (Reactome)
Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1835"
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