Interferon alpha/beta signaling (Homo sapiens)

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18, 22, 28, 3713, 428, 28, 311912, 2827, 34, 40181, 5, 6, 9, 16...20, 2242, 45254, 16, 36, 433, 14, 233911, 29, 30, 372, 11, 20, 32, 33, 37...3918, 357, 1512mitochondrionendoplasmic reticulum lumenextracellular exosomenucleoplasmcytosolIRF7 IFNAR2-2 p-Y1054,Y1055-TYK2 class I MHC B27 BST2 gene IFITM3 gene IFNAR2-2 HLA class I histocompatibility antigen, A-31 alpha chain IFI27 gene BST2IFNAR1 IFNAR2-2 IFNAR2-2STAT2 STAT1-1 SOCS-1 and SOCS-3ABCE1 EGR1GBP2 gene IFI35 gene class I MHC B47 class I MHC B35 IFIT3 gene ABCE1:RNASEL dimerSTAT2 ISG15 gene HLA class I histocompatibility antigen, Cw-6 alpha chain precursor HLA class I histocompatibility antigen, alpha chain G precursor RSAD2 gene IRF5 p-Y701-STAT1-1 dimerclass I MHC B40 PiISGF3 bound to ISREpromotor elementsIFIT1class I MHC B18 HLA class I histocompatibility antigen, A-34 alpha chain class I MHC B59 RSAD2 gene p-Y701-STAT1-2 p-Y1054,Y1055-TYK2 STAT2 Pip-Y466,Y481-IFNAR1 HLA class I histocompatibility antigen, A-43 alpha chain HLA class I histocompatibility antigen, Cw-5 alpha chain precursor ABCE1HLA class I histocompatibility antigen, A-69 alpha chain p-TYK2:p-IFNAR1:SOCS-1/SOCS-3:IFNA/B:IFNAR2:p-JAK1:STAT2JAK1 HLA class I histocompatibility antigen, E alpha chain precursor p-Y-JAK1 IFI27ADPHLA class I histocompatibility antigen, A-32 alpha chain XAF1TYK2 p-Y701-STAT1-1 STAT2 PTPN6IFNAR2-2 ATPIRF6 IFNAR1 HLA class I histocompatibility antigen, Cw-7 alpha chain precursor IFNAR2-2 class I MHC B81 OAS1 HLA-B H2OIFNA HLA class I histocompatibility antigen, A-3 alpha chain precursor IFIT1 gene IFNA IFNA STAT2class I MHC B13 ATPIRF4 IRF 1-9 genes RNASELBST2 gene ADPclass I MHC B67 TYK2 IFNB1 p-Y701-STAT1-1 p-Y-JAK1 p-Y1054,Y1055-TYK2 p-Y-JAK1 p-Y701-STAT1-1 class I MHC B49 IP6K2class I MHC B45 USP18GBP2class I MHC B15 OASL STAT2 IFNB1 IFIT1 gene p-Y701-STAT1-2 HLA-H class I MHC B52 HLA class I histocompatibility antigen, Cw-14 alpha chain EGR1 gene OAS genes IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2IFNA HLA class I histocompatibility antigen, Cw-16 alpha chain p-Y701-STAT1-1 MX GTPases genes IFNA/B:IFNAR2:JAK1:STAT2STAT2 HLA class I histocompatibility antigen, Cw-15 alpha chain IFNAR2-2 class I MHC B58 STAT2 IFN alpha/beta(IFNA/B)ISGF3HLA class I histocompatibility antigen, alpha chain F precursor HLA class I histocompatibility antigen, A-26 alpha chain ISG20 gene IFNA GBP2 gene p-Y466,Y481-IFNAR1 HLA class I histocompatibility antigen, Cw-17 alpha chain IFNAR2:JAK1:STAT2IFIT2 gene STAT1IRF 1-9IFNAR2c:UBP43p-Y690-STAT2 TYK2 class I MHC B8 HLA class I histocompatibility antigen, Cw-4 alpha chain precursor IFIT3 gene class I MHC B38 IFI27 gene IFNB1 IRF3 IFNB1 HLA class I histocompatibility antigen, A-2 alpha chain class I MHC B53 p-Y690-STAT2 ISG15 gene IFIT2PTPN11 class I MHC B46 HLA class I histocompatibility antigen, A-29 alpha chain SAMHD1 gene IRF9 Piclass I MHC B39 p-Y701-STAT1-1 HLA class I histocompatibility antigen, Cw-2 alpha chain IFNAR2-2 HLA class I histocompatibility antigen, A-11 alpha chain STAT1-1SAMHD1 gene HLA class I histocompatibility antigen, Cw-3 alpha chain precursor PTPN11PSMB8 gene p-Y1054,Y1055-TYK2 IFNAR1 SOCS3 IP6K2 gene p-Y1054,Y1055-TYK2 IFITM1 gene HLA class I histocompatibility antigen, A-80 alpha chain JAK1 IRF1 IFI35USP18 p-Y701-STAT1-2 class I MHC B50 class I MHC B51 HLA class I histocompatibility antigen, A-36 alpha chain p-Y-JAK1 H2OOAS proteinsHLA class I histocompatibility antigen, Cw-18 alpha chain IFNA IFITM2SOCS1 class I MHC B55 HLA class I histocompatibility antigen, A-68 alpha chain HLA class I histocompatibility antigen, Cw-1 alpha chain p-Y701-STAT1 dimerISGF3RNASEL IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:p-STAT1IFITM2 gene HLA class I histocompatibility antigen, A-66 alpha chain p-Y-JAK1 HLA class I histocompatibility antigen, A-25 alpha chain IRF2 IFNA p-Y466,Y481-IFNAR1 STAT2 p-Y690-STAT2 class I MHC B37 PSMB8class I MHC B57 ADPp-Y466,Y481-IFNAR1 JAK1 p-Y-JAK1 PTPN1p-STAT2:p-STAT1STAT2 HLA class I histocompatibility antigen, A-23 alpha chain STAT1-2 IFI6IRF9 IFNB1 IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:TYK2STAT2 IFITM3IFNB1 OAS3 IRF 1-9 genes p-Y701-STAT1-2 ATPp-Y701-STAT1-2 EGR1 gene p-Y466,Y481-IFNAR1 IFNB1 class I MHC B41 ADAR gene MX2 IFNAR1:TYK2IRF9 p-Y690-STAT2 p-Y690-STAT2 class I MHC B7 HLA class I histocompatibility antigen, A-24 alpha chain p-Y701-STAT1-1 IFNA class I MHC B73 IRF9IP6K2 gene RSAD2STAT1-1 HLA class I histocompatibility antigen, A-1 alpha chain precursor class I MHC B56 IFIT2 gene IFNAR2-2 IFNA RNASEL gene HLA class I histocompatibility antigen, Cw-8 alpha chain IFNB1 class I MHC B44 p-Y1054,Y1055-TYK2 p-Y690-STAT2 p-Y701-STAT1-1 IFNAR1 ATPIFI6 gene Class I MHC heavychain (MHC HC)PTPN6,PTPN11IFNB1 STAT2 IRF9 MX GTPases genes IFNA ADPADAR gene Class I MHC heavy chain genes ADPIFIT3ADARIFNAR2-2 HLA class I histocompatibility antigen, A-74 alpha chain SOCS3 IFNA/B:IFNAR2:p-JAK1:STAT2:IFNAR1:p-TYK2IFITM3 gene class I MHC B42 Type I IFN-regulatedgenes with ISREpromoter elementsPSMB8 gene IRF8 IFNAR2-2 IFNA/B:IFNAR2:JAK1:STAT2:IFNAR1:TYK2XAF1 gene IFNB1 class I MHC B82 IFI35 gene p-Y466,Y481-IFNAR1 IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2:STAT1IFITM2 gene IFNAR2-2 class I MHC B14 HLA class I histocompatibility antigen, A-30 alpha chain XAF1 gene HLA class I histocompatibility antigen, Cw-12 alpha chain SOCS1 IFITM1IFNB1 RNASEL p-Y690-STAT2 Class I MHC heavy chain genes SAMHD1IFNA PTPN6 IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2STAT1-2 IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:STAT2MX1 ISG15p-Y1054,Y1055-TYK2 ISG20ISG20 gene ATPclass I MHC B78 H2OMx GTPasesRNASEL dimerOAS2 class I MHC B54 RNASEL gene OAS genes IFITM1 gene IFI6 gene p-Y-JAK1 IFNAR2-2 HLA class I histocompatibility antigen, A-33 alpha chain p-Y-JAK1 1010101010101010101010


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: 66
Reactome Author 
Reactome Author: Garapati, Phani Vijay

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Ontology Terms

 

Bibliography

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History

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CompareRevisionActionTimeUserComment
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)
ADAR gene ProteinENSG00000160710 (Ensembl)
ADARProteinP55265 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
BST2 gene ProteinENSG00000130303 (Ensembl)
BST2ProteinQ10589 (Uniprot-TrEMBL)
Class I MHC heavy chain (MHC HC)ComplexR-HSA-983117 (Reactome)
Class I MHC heavy chain genes R-HSA-9034148 (Reactome)
EGR1 gene ProteinENSG00000120738 (Ensembl)
EGR1ProteinP18146 (Uniprot-TrEMBL)
GBP2 gene ProteinENSG00000162645 (Ensembl)
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)
IFI27 gene ProteinENSG00000165949 (Ensembl)
IFI27ProteinP40305 (Uniprot-TrEMBL)
IFI35 gene ProteinENSG00000068079 (Ensembl)
IFI35ProteinP80217 (Uniprot-TrEMBL)
IFI6 gene ProteinENSG00000126709 (Ensembl)
IFI6ProteinP09912 (Uniprot-TrEMBL)
IFIT1 gene ProteinENSG00000185745 (Ensembl)
IFIT1ProteinP09914 (Uniprot-TrEMBL)
IFIT2 gene ProteinENSG00000119922 (Ensembl)
IFIT2ProteinP09913 (Uniprot-TrEMBL)
IFIT3 gene ProteinENSG00000119917 (Ensembl)
IFIT3ProteinO14879 (Uniprot-TrEMBL)
IFITM1 gene ProteinENSG00000185885 (Ensembl)
IFITM1ProteinP13164 (Uniprot-TrEMBL)
IFITM2 gene ProteinENSG00000185201 (Ensembl)
IFITM2ProteinQ01629 (Uniprot-TrEMBL)
IFITM3 gene ProteinENSG00000142089 (Ensembl)
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)
IP6K2 gene ProteinENSG00000068745 (Ensembl)
IP6K2ProteinQ9UHH9 (Uniprot-TrEMBL)
IRF 1-9 genes R-HSA-9034177 (Reactome)
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)
ISG15 gene ProteinENSG00000187608 (Ensembl)
ISG15ProteinP05161 (Uniprot-TrEMBL)
ISG20 gene ProteinENSG00000172183 (Ensembl)
ISG20ProteinQ96AZ6 (Uniprot-TrEMBL)
ISGF3 bound to ISRE promotor elementsComplexR-HSA-1015697 (Reactome)
ISGF3ComplexR-HSA-909698 (Reactome)
ISGF3ComplexR-HSA-913527 (Reactome)
JAK1 ProteinP23458 (Uniprot-TrEMBL)
MX GTPases genes R-HSA-9034165 (Reactome)
MX1 ProteinP20591 (Uniprot-TrEMBL)
MX2 ProteinP20592 (Uniprot-TrEMBL)
Mx GTPasesComplexR-HSA-1015693 (Reactome)
OAS genes R-HSA-9034139 (Reactome)
OAS proteinsComplexR-HSA-1015696 (Reactome)
OAS1 ProteinP00973 (Uniprot-TrEMBL)
OAS2 ProteinP29728 (Uniprot-TrEMBL)
OAS3 ProteinQ9Y6K5 (Uniprot-TrEMBL)
OASL ProteinQ15646 (Uniprot-TrEMBL)
PSMB8 gene ProteinENSG00000204264 (Ensembl)
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)
RNASEL gene ProteinENSG00000135828 (Ensembl)
RNASELProteinQ05823 (Uniprot-TrEMBL)
RSAD2 gene ProteinENSG00000134321 (Ensembl)
RSAD2ProteinQ8WXG1 (Uniprot-TrEMBL)
SAMHD1 gene ProteinENSG00000101347 (Ensembl)
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)
Type I IFN-regulated

genes with ISRE

promoter elements
ComplexR-HSA-9034125 (Reactome)
USP18 ProteinQ9UMW8 (Uniprot-TrEMBL)
USP18ProteinQ9UMW8 (Uniprot-TrEMBL)
XAF1 gene ProteinENSG00000132530 (Ensembl)
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-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 dimerComplexR-HSA-913526 (Reactome)
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-909726 (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-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-TYK2:p-STAT2mim-catalysisR-HSA-909718 (Reactome)
IFNA/B:IFNAR2:p-JAK1:STAT2:p-IFNAR1:p-TYK2:p-STAT2mim-catalysisR-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)
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)
Type I IFN-regulated

genes with ISRE

promoter elements
R-HSA-1015699 (Reactome)
Type I IFN-regulated

genes with ISRE

promoter elements
R-HSA-1015702 (Reactome)
USP18R-HSA-912685 (Reactome)
XAF1ArrowR-HSA-1015702 (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 dimerArrowR-HSA-913529 (Reactome)
p-Y701-STAT1-1 dimerArrowR-HSA-909718 (Reactome)
p-Y701-STAT1-1 dimerR-HSA-913529 (Reactome)
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