Crystallographic structure of IL-2 (center alpha helices) complexed with the common gamma chain (IL2RG; 10 O'Clock to 1 O'Clock), IL2RA (4 O'Clock), and IL2RB (7 O'Clock to 9 O'Clock). Each protein is individually rainbow colored (N-terminus = blue, C-terminus = red).
This protein is located on the surface of immature blood-forming cells in bone marrow. One end of the protein resides outside of the cell where it binds to cytokines and the other end of the protein resides in the interior of the cell where it transmits signals to the cell's nucleus. The common gamma chain partners with other proteins to direct blood-forming cells to form lymphocytes (a type of white blood cell). The receptor also directs the growth and maturation of lymphocyte subtypes: T cells, B cells, and natural killer cells. These cells kill viruses, make antibodies, and help regulate the entire immune system.
Cytokine receptor common subunit gamma also known as interleukin-2 receptor subunit gamma or IL-2RG is a protein that in humans is encoded by the IL2RGgene. The human IL2RG gene is located on the long (q) arm of the X chromosome at position 13.1, from base pair 70,110,279 to base pair 70,114,423.
IL-7 receptor and signaling, common γ chain (blue) and IL-7 receptor-α (green)
Lymphocytes expressing the common gamma chain can form functional receptors for these cytokine proteins, which transmit signals from one cell to another and direct programs of cellular differentiation.
X-linked severe combined immunodeficiency is caused by mutations in the IL2RG gene. More than 200 different mutations in the IL2RG gene have been identified in people with X-linked severe combined immunodeficiency (SCID). Most of these mutations involve changes in one or a few nucleotides (DNA building blocks) in the gene. These changes lead to the production of a nonfunctional version of the common gamma chain protein or no production of protein. Without the common gamma chain, important chemical signals are not relayed to the nucleus and lymphocytes cannot develop normally. A lack of functional mature lymphocytes disrupts the immune system's ability to protect the body from infection. Sufferers have no functional immunity and can die within months after birth without successful bone marrow transplantation or alternatively, isolation from exposure to pathogens. Without important developmental signals from IL-7 and IL-15, T-cell and NK cell populations respectively fail to develop.
Experiments in animal models have shown X-SCID to occur similarly in dogs, but not in mice.
Alterations in the immune response are involved in pathogenesis of many neuropsychiatric disorders including schizophrenia. Distinct gene variants of a number of pro-inﬂammatory and chemotactic cytokines together with their receptors associate with this disorder. IL2RG represents an important signaling component of many interleukin receptors and so far, no data on the functional state of this receptor in schizophrenia have been reported. Over-expression of the IL2RG gene may be implicated in altered immune response in schizophrenia and contribute to the pathogenesis of this disorder.
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