Interferon gamma signaling (Homo sapiens)

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1-428-3020, 25-2737, 3828, 30, 3141-442039, 4016-1932, 3334-366, 7, 10-158, 9, 44-4821, 2223-25lysosomal lumennucleoplasmcytosolendoplasmic reticulum lumenIFNG-activated factor (GAF)IFNG homodimerH2OATPSP100H2OPTPs-SHP1/2/PTP1BADPIFNG:IFNGR1:JAK1:IFNGR2:JAK2TC-PTPaADPGBPOAS proteinsGAF bound to GAS promoter elementATPp-STAT1(Y701) bound to p-IFNGR1ADPADPHLA IIPTP1BClass I MHC heavy chain (MHC HC)STAT1SUMO1IFNG:IFNGR1:p-JAK1:IFNGR2:p-JAK2ATPGAS promoter region in IFNG-regulated genesIFNG:IFNGR1:JAK1:IFNGR2:p-JAK2:SOCS-1/-3PMLPAF receptorATPIFN-gamma upregulated CAMsSHP1STAT1-alphaSTAT1 bound to p-IFNGR1IFNG:p-IFNGR1:p-JAK1:IFNGR2:p-JAK2IFNGR1:JAK1:INFG2:JAK2ATPIFNG:IFNGR1:JAK1:IFNGR2:p-JAK2SOCS-1 and SOCS-3FCGRGamma-interferon-inducible lysosomal thiol reductaseCaMKII and PKC-deltaPIAS1Metallothionein-2ADPOrthophosphateBeta-2-microglobulinp-STAT1 dimer bound to p-IFNGR1p-STAT1 dimer:PIAS:SUMO1MHC class II transactivatorIFNG-activated factor (GAF)OrthophosphateIRF 1-956, 78, 9


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.

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External references


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NameTypeDatabase referenceComment
ADP Metabolite16761 (ChEBI)
ATP Metabolite15422 (ChEBI)


ProteinP61769 (UniProt)
CaMKII and PKC-delta ProteinREACT_26704 (Reactome)
Class I MHC

heavy chain (MHC HC)

ProteinREACT_26784 (Reactome)
FCGR ProteinREACT_26475 (Reactome)
GAF bound to GAS

promoter element

ComplexREACT_25470 (Reactome)
GAS promoter region

in IFNG-regulated genes

UnknownREACT_26763 (Reactome)
GBP ProteinREACT_26189 (Reactome)

inducible lysosomal thiol reductase

ProteinP13284 (UniProt)
H2O Metabolite15377 (ChEBI)
HLA II ProteinREACT_13194 (Reactome)

upregulated CAMs

ProteinREACT_26072 (Reactome)
IFNG homodimer ComplexREACT_26955 (Reactome)

factor (GAF)

ComplexREACT_26144 (Reactome)

factor (GAF)

ComplexREACT_26637 (Reactome)


ComplexREACT_25865 (Reactome)


ComplexREACT_26738 (Reactome)

IFNGR2:p-JAK2: SOCS-1/-3

ComplexREACT_26775 (Reactome)


ComplexREACT_26286 (Reactome)


ComplexREACT_25650 (Reactome)


ComplexREACT_25803 (Reactome)
IRF 1-9 ProteinREACT_26465 (Reactome)
MHC class II


ProteinP33076 (UniProt)
Metallothionein-2 ProteinP02795 (UniProt)
OAS proteins ProteinREACT_26755 (Reactome)
Orthophosphate Metabolite18367 (ChEBI)
PAF receptor ProteinP25105 (UniProt)
PIAS1 ProteinO75925 (UniProt)
PML ProteinP29590 (UniProt)
PTP1B ProteinP18031 (UniProt)


ProteinREACT_26675 (Reactome)
SHP1 ProteinP29350 (UniProt)
SOCS-1 and


ProteinREACT_25587 (Reactome)
SP100 ProteinP23497 (UniProt)
STAT1 ProteinP42224-1 (UniProt)
STAT1 bound to p-


ComplexREACT_26587 (Reactome)
STAT1-alpha ProteinP42224-1 (UniProt)
SUMO1 ProteinP63165 (UniProt)
TC-PTPa ProteinP17706-2 (UniProt)
p-STAT1 dimer

bound to p-IFNGR1

ComplexREACT_25936 (Reactome)
p-STAT1 dimer:


ComplexREACT_25840 (Reactome)

bound to p-IFNGR1

ComplexREACT_26108 (Reactome)

Annotated Interactions

No annotated interactions

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