Interferon gamma signaling (Homo sapiens)

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Interferon-gamma (IFN-gamma) belongs to the type II interferon family and is secreted by activated immune cells-primarily T and NK cells, but also B-cells and APC. INFG exerts its effect on cells by interacting with the specific IFN-gamma receptor (IFNGR). IFNGR consists of two chains, namely IFNGR1 (also known as the IFNGR alpha chain) and IFNGR2 (also known as the IFNGR beta chain). IFNGR1 is the ligand binding receptor and is required but not sufficient for signal transduction, whereas IFNGR2 do not bind IFNG independently but mainly plays a role in IFNG signaling and is generally the limiting factor in IFNG responsiveness. Both IFNGR chains lack intrinsic kinase/phosphatase activity and thus rely on other signaling proteins like Janus-activated kinase 1 (JAK1), JAK2 and Signal transducer and activator of transcription 1 (STAT-1) for signal transduction. IFNGR complex in its resting state is a preformed tetramer and upon IFNG association undergoes a conformational change. This conformational change induces the phosphorylation and activation of JAK1, JAK2, and STAT1 which in turn induces genes containing the gamma-interferon activation sequence (GAS) in the promoter. Source:Reactome.

Ontology Tags



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  48. Greenlund AC, Farrar MA, Viviano BL, Schreiber RD.; ''Ligand-induced IFN gamma receptor tyrosine phosphorylation couples the receptor to its signal transduction system (p91).''; PubMed
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  50. Gough DJ, Levy DE, Johnstone RW, Clarke CJ.; ''IFNgamma signaling-does it mean JAK-STAT?''; PubMed
  51. Thiel DJ, le Du MH, Walter RL, D'Arcy A, Chène C, Fountoulakis M, Garotta G, Winkler FK, Ealick SE.; ''Observation of an unexpected third receptor molecule in the crystal structure of human interferon-gamma receptor complex.''; PubMed


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81633view13:10, 21 August 2015ReactomeTeamVersion53
77096view08:39, 17 July 2014ReactomeTeamFixed remaining interactions
76802view12:18, 16 July 2014ReactomeTeamFixed remaining interactions
76125view10:19, 11 June 2014ReactomeTeamRe-fixing comment source
75837view11:40, 10 June 2014ReactomeTeamReactome 48 Update
75198view09:43, 9 May 2014AnweshaFixing comment source for displaying WikiPathways description
74845view10:07, 30 April 2014ReactomeTeamReactome46
44865view09:58, 6 October 2011MartijnVanIerselOntology Term : 'immune response pathway' added !
42056view21:53, 4 March 2011MaintBotAutomatic update
39862view05:53, 21 January 2011MaintBotNew pathway

External references

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NameTypeDatabase referenceComment
HLA class II


antigen, DQ
ProteinP01920 (Uniprot-TrEMBL)
Class I MHC heavy chain (MHC HC)R-HSA-983117 (Reactome)
IFNG ProteinP01579 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DRB1-8

beta chain
ProteinQ30134 (Uniprot-TrEMBL)
IFNGR1:JAK1:INFG2:JAK2ComplexR-HSA-873810 (Reactome)
SP100ProteinP23497 (Uniprot-TrEMBL)
IFNGR1 ProteinP15260 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DRB1-11

beta chain
ProteinP20039 (Uniprot-TrEMBL)
JAK1 ProteinP23458 (Uniprot-TrEMBL)
GAF bound to GAS promoter elementComplexR-HSA-1031710 (Reactome)
IFNGR2 ProteinP38484 (Uniprot-TrEMBL)
OAS proteinsR-HSA-1015696 (Reactome)
JAK2 ProteinO60674 (Uniprot-TrEMBL)
HLA class II


antigen, DQ
ProteinP01906 (Uniprot-TrEMBL)
IFNG:IFNGR1:JAK1:IFNGR2:JAK2ComplexR-HSA-873829 (Reactome)
HLA class II

histocompatibility antigen, DR beta 5

ProteinQ30154 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
HLA class II

histocompatibility antigen, DRB1-15

beta chain
ProteinP01911 (Uniprot-TrEMBL)
IFNG:IFNGR1:JAK1:IFNGR2:p-JAK2ComplexR-HSA-873811 (Reactome)
IFNG homodimerComplexR-HSA-873823 (Reactome)
p-Y1007-JAK2 ProteinO60674 (Uniprot-TrEMBL)
CIITAProteinP33076 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:16761 (ChEBI)
MT2AProteinP02795 (Uniprot-TrEMBL)
IFNG:IFNGR1:p-JAK1:IFNGR2:p-JAK2ComplexR-HSA-873820 (Reactome)
B2M(21-119)ProteinP61769 (Uniprot-TrEMBL)
p-Y-JAK1 ProteinP23458 (Uniprot-TrEMBL)
MHC class II alpha/beta dimerComplexR-HSA-2213189 (Reactome)
IFNG:p-IFNGR1:p-JAK1:IFNGR2:p-JAK2ComplexR-HSA-873814 (Reactome)
HLA class II

histocompatibility antigen, DR alpha

chain precursor
ProteinP01903 (Uniprot-TrEMBL)
p-Y440-IFNGR1 ProteinP15260 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DQB1*0602 beta chain

ProteinP01920 (Uniprot-TrEMBL)
STAT1-1ProteinP42224-1 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DRB1-1

beta chain
ProteinP04229 (Uniprot-TrEMBL)
STAT1 bound to p-IFNGR1ComplexR-HSA-873828 (Reactome)
HLA class II

histocompatibility antigen, DRB1-13

beta chain
ProteinQ5Y7A7 (Uniprot-TrEMBL)
STAT1-1 ProteinP42224-1 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DRB1-4

beta chain
ProteinP13760 (Uniprot-TrEMBL)
p-STAT1(Y701) bound to p-IFNGR1ComplexR-HSA-873817 (Reactome)
HLA class II

histocompatibility antigen, DRB3-1 beta chain

ProteinP79483 (Uniprot-TrEMBL)
p-Y701-STAT1-1 ProteinP42224-1 (Uniprot-TrEMBL)
GAS promoter region

in IFNG-regulated

R-NUL-1031708 (Reactome)
IFNG-activated factor (GAF)ComplexR-HSA-873827 (Reactome)
GBPR-HSA-1031695 (Reactome)
p-S727,Y701-STAT1-1 ProteinP42224-1 (Uniprot-TrEMBL)
FCGRAR-HSA-1031694 (Reactome)
IFNG-activated factor (GAF)ComplexR-HSA-873824 (Reactome)
PTAFRProteinP25105 (Uniprot-TrEMBL)
IFNG:IFNGR1:JAK1:IFNGR2:p-JAK2:SOCS-1/-3ComplexR-HSA-873821 (Reactome)
PMLProteinP29590 (Uniprot-TrEMBL)
SOCS1 ProteinO15524 (Uniprot-TrEMBL)
IFN-gamma upregulated CAMsR-HSA-1031690 (Reactome)
SOCS3 ProteinO14543 (Uniprot-TrEMBL)
IRF 1-9R-HSA-1015695 (Reactome)
SOCS-1 and SOCS-3R-HSA-877267 (Reactome)
IFI30ProteinP13284 (Uniprot-TrEMBL)
PTPN6ProteinP29350 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DP alpha

chain precursor
ProteinP20036 (Uniprot-TrEMBL)
PIAS1ProteinO75925 (Uniprot-TrEMBL)
HLA class II


antigen, DQ
ProteinP01909 (Uniprot-TrEMBL)
SUMO1ProteinP63165 (Uniprot-TrEMBL)
HLA class II


antigen, DP
ProteinP04440 (Uniprot-TrEMBL)
p-STAT1 dimer:PIAS:SUMO1ComplexR-HSA-877297 (Reactome)
HLA class II

histocompatibility antigen, DQ beta 2

ProteinP05538 (Uniprot-TrEMBL)
PIAS1 ProteinO75925 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DR beta 4

ProteinP13762 (Uniprot-TrEMBL)
SUMO1 ProteinP63165 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DR-1 beta

chain precursor
ProteinP01912 (Uniprot-TrEMBL)
p-STAT1 dimer bound to p-IFNGR1ComplexR-HSA-909556 (Reactome)
HLA class II

histocompatibility antigen, DRB1-10

beta chain
ProteinQ30167 (Uniprot-TrEMBL)
CaMKII and PKC-deltaR-HSA-909568 (Reactome)
HLA class II

histocompatibility antigen, DRB1-12

beta chain
ProteinQ95IE3 (Uniprot-TrEMBL)
PTPN1ProteinP18031 (Uniprot-TrEMBL)
HLA class II

histocompatibility antigen, DRB1-14

beta chain
ProteinQ9GIY3 (Uniprot-TrEMBL)
H2OMetaboliteCHEBI:15377 (ChEBI)
HLA class II

histocompatibility antigen, DRB1-16

beta chain
ProteinQ29974 (Uniprot-TrEMBL)
PiMetaboliteCHEBI:18367 (ChEBI)
HLA class II

histocompatibility antigen, DRB1-7

beta chain
ProteinP13761 (Uniprot-TrEMBL)
PTPs-SHP1/2/PTP1BR-HSA-997298 (Reactome)
HLA class II

histocompatibility antigen, DRB1-9 beta chain

ProteinQ9TQE0 (Uniprot-TrEMBL)
PTPN2-1ProteinP17706-2 (Uniprot-TrEMBL)
INFG induced TRIMsR-HSA-5624346 (Reactome)
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