IFNG

This gene encodes a soluble cytokine that is a member of the type II interferon class. The encoded protein is secreted by cells of both the innate and adaptive immune systems. The active protein is a homodimer that binds to the interferon gamma receptor which triggers a cellular response to viral and microbial infections. Mutations in this gene are associated with an increased susceptibility to viral, bacterial and parasitic infections and to several autoimmune diseases. [provided by RefSeq, Dec 2015]

Interferon Gamma

Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (PubMed:16914093, PubMed:8666937).

Primarily signals through the JAK-STAT pathway after interaction with its receptor IFNGR1 to affect gene regulation (PubMed:8349687).

Upon IFNG binding, IFNGR1 intracellular domain opens out to allow association of downstream signaling components JAK2, JAK1 and STAT1, leading to STAT1 activation, nuclear translocation and transcription of IFNG-regulated genes. Many of the induced genes are transcription factors such as IRF1 that are able to further drive regulation of a next wave of transcription (PubMed:16914093).

Plays a role in class I antigen presentation pathway by inducing a replacement of catalytic proteasome subunits with immunoproteasome subunits (PubMed:8666937).

In turn, increases the quantity, quality, and repertoire of peptides for class I MHC loading (PubMed:8163024).

Increases the efficiency of peptide generation also by inducing the expression of activator PA28 that associates with the proteasome and alters its proteolytic cleavage preference (PubMed:11112687).

Up-regulates as well MHC II complexes on the cell surface by promoting expression of several key molecules such as cathepsins B/CTSB, H/CTSH, and L/CTSL (PubMed:7729559).

Participates in the regulation of hematopoietic stem cells during development and under homeostatic conditions by affecting their development, quiescence, and differentiation (By similarity).

Adaptive immune response Source: GO_Central
Apoptotic process Source: MGI
Astrocyte activation Source: ARUK-UCL
Cell surface receptor signaling pathway Source: ProtInc
Defense response to virus Source: UniProtKB-KW
Extrinsic apoptotic signaling pathway Source: BHF-UCL
Humoral immune response Source: GO_Central
Interferon-gamma-mediated signaling pathway Source: CAFA
Macrophage activation involved in immune response Source: ARUK-UCL
Macrophage differentiation Source: ARUK-UCL
Microglial cell activation Source: ARUK-UCL
Negative regulation of amyloid-beta clearance Source: ARUK-UCL
Negative regulation of epithelial cell differentiation Source: BHF-UCL
Negative regulation of gene expression Source: UniProtKB
Negative regulation of interleukin-17 production Source: BHF-UCL
Negative regulation of smooth muscle cell proliferation Source: BHF-UCL
Negative regulation of tau-protein kinase activity Source: ARUK-UCL
Negative regulation of transcription, DNA-templated Source: CAFA
Negative regulation of transcription by RNA polymerase II Source: BHF-UCL
Neuroinflammatory response Source: ARUK-UCL
Positive regulation of amyloid-beta formation Source: ARUK-UCL
Positive regulation of autophagy Source: UniProtKB
Positive regulation of calcidiol 1-monooxygenase activity Source: BHF-UCL
Positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation involved in immune response Source: UniProtKB
Positive regulation of cell population proliferation Source: BHF-UCL
Positive regulation of cellular respiration Source: ARUK-UCL
Positive regulation of chemokine production Source: ARUK-UCL
Positive regulation of core promoter binding Source: CAFA
Positive regulation of cytokine production Source: ARUK-UCL
Positive regulation of epithelial cell migration Source: CACAO
Positive regulation of exosomal secretion Source: UniProtKB
Positive regulation of fructose 1,6-bisphosphate 1-phosphatase activity Source: BHF-UCL
Positive regulation of fructose 1,6-bisphosphate metabolic process Source: BHF-UCL
Positive regulation of gene expression Source: UniProtKB
Positive regulation of glycolytic process Source: ARUK-UCL
Positive regulation of inflammatory response Source: ARUK-UCL
Positive regulation of interleukin-12 production Source: UniProtKB
Positive regulation of interleukin-1 beta production Source: ARUK-UCL
Positive regulation of interleukin-23 production Source: BHF-UCL
Positive regulation of interleukin-6 production Source: ARUK-UCL
Positive regulation of iron ion import across plasma membrane Source: ARUK-UCL
Positive regulation of killing of cells of other organism Source: BHF-UCL
Positive regulation of membrane protein ectodomain proteolysis Source: BHF-UCL
Positive regulation of MHC class II biosynthetic process Source: ARUK-UCL
Positive regulation of neurogenesis Source: ARUK-UCL
Positive regulation of neuron death Source: ARUK-UCL
Positive regulation of nitric oxide biosynthetic process Source: BHF-UCL
Positive regulation of nitric-oxide synthase biosynthetic process Source: ARUK-UCL
Positive regulation of nitrogen compound metabolic process Source: ARUK-UCL
Positive regulation of NMDA glutamate receptor activity Source: ARUK-UCL
Positive regulation of osteoclast differentiation Source: BHF-UCL
Positive regulation of peptidyl-serine phosphorylation of STAT protein Source: MGI
Positive regulation of phagocytosis Source: ARUK-UCL
Positive regulation of protein-containing complex assembly Source: CAFA
Positive regulation of protein deacetylation Source: CAFA
Positive regulation of protein import into nucleus Source: CAFA
Positive regulation of protein localization to plasma membrane Source: UniProtKB
Positive regulation of protein phosphorylation Source: CAFA
Positive regulation of protein serine/threonine kinase activity Source: CAFA
Positive regulation of signaling receptor activity Source: ARUK-UCL
Positive regulation of smooth muscle cell apoptotic process Source: BHF-UCL
Positive regulation of tumor necrosis factor (ligand) superfamily member 11 production Source: BHF-UCL
Positive regulation of tumor necrosis factor production Source: ARUK-UCL
Positive regulation of tyrosine phosphorylation of STAT protein Source: BHF-UCL
Positive regulation of vitamin D biosynthetic process Source: BHF-UCL
Receptor signaling pathway via JAK-STAT Source: ARUK-UCL
Regulation of growth Source: UniProtKB-KW
Regulation of insulin secretion Source: BHF-UCL
Regulation of protein ADP-ribosylation Source: CAFA
Response to virus Source: MGI

Secreted

Aplastic anemia (AA):
A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements. It is characterized by peripheral pancytopenia and marrow hypoplasia.
Immunodeficiency 69 (IMD69):
A form of Mendelian susceptibility to mycobacterial disease, a rare condition caused by impairment of interferon-gamma mediated immunity. It is characterized by predisposition to illness caused by moderately virulent mycobacterial species, such as Bacillus Calmette-Guerin (BCG) vaccine, environmental non-tuberculous mycobacteria, and by the more virulent Mycobacterium tuberculosis. Other microorganisms rarely cause severe clinical disease in individuals with susceptibility to mycobacterial infections. Clinical outcome severity depends on the degree of impairment of interferon-gamma mediated immunity. IMD69 is an autosomal recessive disorder manifesting with fever, hepatosplenomegaly, leukocytosis, and thrombocytosis during the acute infection.

Proteolytic processing produces C-terminal heterogeneity, with proteins ending alternatively at Gly-150, Met-157 or Gly-161.