Interferon-gamma
From Wikipedia, the free encyclopedia
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Interferon gamma
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| Identifiers | |
| Symbol(s) | IFNG |
| Entrez | 3458 |
| OMIM | 147570 |
| RefSeq | NM_000619 |
| UniProt | P01579 |
| PDB | 1HIG |
| Other data | |
| Locus | Chr. 12 q24.1 |
Interferon-gamma or IFN-γ is a dimerized soluble cytokine that is the only member of the type II class of interferons.[1] This interferon was originally called macrophage-activating factor.
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[edit] Structure of IFN-γ
The IFN-γ monomer consists of a core of six α-helices and an extended unfolded sequence in the C-terminal region.[2] This is shown in the structural models below. The α-helices in the core of the structure are numbred 1 to 6.
The biologically active dimer is formed by anti-parallel inter-locking of the two monomers as shown below. In the cartoon model, one monomer is shown in red, the other in blue.
In the dimerised protein shown in the box to the right, the C-termini extend out on opposite sides, from the main body of the structure. A region of amino acids near each C-terminal interacts directly an IFN-γ cell surface receptor.
[edit] Biological activity
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Interferon-gamma
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| Systematic (IUPAC) name | |
| ? | |
| Identifiers | |
| CAS number | 82115-62-6 |
| ATC code | L03AB03 |
| PubChem | ? |
| DrugBank | BTD00017 |
| Chemical data | |
| Formula | C761H1206N214O225S6 |
| Mol. weight | 17145.6 g/mol |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
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| Legal status | |
| Routes | ? |
In contrast to interferon-α and interferon-β which can be expressed by all cells, IFN-γ is secreted by T lymphocytes and NK cells only. Also known as immune interferon, IFN-γ is the only Type II interferon. It is serologically distinct from Type I interferons and it is acid-labile, while the type I variants are acid-stable.
IFN-γ has antiviral, immunoregulatory, and anti-tumour properties.[3] It alters transcription in up to 30 genes producing a variety of physiological and cellular responses. Activation by IFN-γ is achieved by its interaction with a heterodimeric receptor consisting of IFNGR1 & IFNGR2 (interferon gamma receptors). IFN-γ binding to the receptor activates the JAK-STAT pathway. In addition, IFN-γ activates APCs and promotes Th1 differentiation by upregulating the transcription factor T-bet.
IFN-γ is the hallmark cytokine of Th1 cells (Th2 cells produce IL-4). NK cells and CD8+ cytotoxic T cells also produce IFN-γ. IFN-γ suppresses osteoclast formation by rapidly degrading the RANK adaptor protein TRAF6 in the RANK-RANKL signaling pathway, which otherwise stimulates the production of NFκB.
[edit] Therapeutic uses
Interferons are used to treat infectious diseases, but can also precipitate autoimmunity (in up to 19% people treated with these cytokines).
[edit] References
- ^ Gray and Goeddel, Structure of the human immune interferon gene. Nature, 1982, 298, page 859 - 863
- ^ Ealick et al., Three-dimensional structure of recombinant human interferon-gamma. Science, 1991, Vol 252, 698-702
- ^ Schroder et al., Interferon-γ an overview of signals, mechanisms and functions. Journal of Leukocyte Biology. 2004, Volume 75, pages 163-189.
