[IFNG_HUMAN] In Caucasians, genetic variation in IFNG is associated with the risk of aplastic anemia (AA) [MIM:609135]. AA is a rare disease in which the reduction of the circulating blood cells results from damage to the stem cell pool in bone marrow. In most patients, the stem cell lesion is caused by an autoimmune attack. T-lymphocytes, activated by an endogenous or exogenous, and most often unknown antigenic stimulus, secrete cytokines, including IFN-gamma, which would in turn be able to suppress hematopoiesis.
Function
[IFNG_HUMAN] Produced by lymphocytes activated by specific antigens or mitogens. IFN-gamma, in addition to having antiviral activity, has important immunoregulatory functions. It is a potent activator of macrophages, it has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of the type I interferons.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Ectromelia virus (ECTV) encodes an IFN-gamma-binding protein (IFN-gammaBP(ECTV)) that disrupts IFN-gamma signaling and its ability to induce an antiviral state within cells. IFN-gammaBP(ECTV) is an important virulence factor that is highly conserved (>90%) in all orthopoxviruses, including variola virus, the causative agent of smallpox. The 2.2-A crystal structure of the IFN-gammaBP(ECTV)/IFN-gamma complex reveals IFN-gammaBP(ECTV) consists of an IFN-gammaR1 ligand-binding domain and a 57-aa helix-turn-helix (HTH) motif that is structurally related to the transcription factor TFIIA. The HTH motif forms a tetramerization domain that results in an IFN-gammaBP(ECTV)/IFN-gamma complex containing four IFN-gammaBP(ECTV) chains and two IFN-gamma dimers. The structure, combined with biochemical and cell-based assays, demonstrates that IFN-gammaBP(ECTV) tetramers are required for efficient IFN-gamma antagonism.
Structure and mechanism of IFN-gamma antagonism by an orthopoxvirus IFN-gamma-binding protein.,Nuara AA, Walter LJ, Logsdon NJ, Yoon SI, Jones BC, Schriewer JM, Buller RM, Walter MR Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):1861-6. Epub 2008 Feb 5. PMID:18252829[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑Nuara AA, Walter LJ, Logsdon NJ, Yoon SI, Jones BC, Schriewer JM, Buller RM, Walter MR. Structure and mechanism of IFN-gamma antagonism by an orthopoxvirus IFN-gamma-binding protein. Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):1861-6. Epub 2008 Feb 5. PMID:18252829
