Interferon gamma

Function

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).

Involvement in disease

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.

None

Disease susceptibility may be associated with variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

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

Sequence similarities

Belongs to the type II (or gamma) interferon family.

Tissue specificity

Released primarily from activated T lymphocytes.

Cellular localization

• Secreted

Alternative names

• Interferon gamma
• IFN-gamma
• Immune interferon
• IFNG

Database links

• entrezGene:3458
• omim:147570
• swissprot:P01579

Target type

Proteins

Primary research area

Immunology & Infectious Disease

Other research areas

• Immuno-oncology
• Neuroscience

Molecular weight

19348Da