Interferon, gamma
Interferon gamma, line representation
Available structures: 1eku, 1fg9, 1fyh, 1hig
Identifiers
Symbol(s)	IFNG; IFG; IFI
External IDs	OMIM: 147570 MGI: 107656 HomoloGene: 55526
RNA expression pattern
More reference expression data
Orthologs
	Human	Mouse
Entrez	3458	15978
Ensembl	ENSG00000111537	ENSMUSG00000055170
Uniprot	P01579	Q6TDH0
Refseq	NM_000619 (mRNA) NP_000610 (protein)	NM_008337 (mRNA) NP_032363 (protein)
Location	Chr 12: 66.83 - 66.84 Mb	Chr 10: 117.84 - 117.85 Mb
Pubmed search	[1]	[2]

Interferon-gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The Human Genome Organisation (HUGO is an organization involved in the Human Genome Project, a project about mapping the human genome The Mouse Genome Informatics (MGI website is run by The Jackson Laboratory. HomoloGene, a tool of the National Center for Biotechnology Information (NCBI is a system for automated detection of homologs (similarity attributable to descent The Entrez Global Query Cross-Database Search System is a powerful Federated search engine or Web portal that allows users to search many discrete Health sciences Ensembl is a joint scientific project between the European Bioinformatics Institute and the Wellcome Trust Sanger Institute, which was launched in 1999 in response to the imminent UniProt is the uni versal prot ein resource a central repository of Protein data created by combining Swiss-Prot, TrEMBL PubMed is a free search engine for accessing the MEDLINE database of citations and abstracts of biomedical research articles A dimer is a Chemical or Biological entity consisting of two subunits called Monomers which are held together by either Intramolecular forces Cytokines are a category of signalling Proteins and Glycoproteins that like Hormones and Neurotransmitters, are used extensively in cellular Interferons ( IFN s are natural Proteins produced by the cells of the Immune system of most Vertebrates in response to challenges by foreign agents ^[1] This interferon was originally called macrophage-activating factor. A macrophage activating factor (MAF is a Lymphokine that primes Macrophages to become cytotoxic to Tumors It also controls the expression of

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. A monomer (from Greek mono "one" and meros "part" is a small Molecule that may become chemically bonded to other ^[2][3] This is shown in the structural models below. The α-helices in the core of the structure are numbered 1 to 6.

Line and cartoon representation of a IFN-γ monomer

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.

Line and cartoon representation of a IFN-γ dimer

The structural models shown above (see protein data bank code 1FG9) are all shortened at their C-termini by 17 amino acids. The Protein Data Bank ( PDB) is a repository for 3-D structural data of Proteins and Nucleic acids These data typically obtained by X-ray crystallography Full length IFN-γ is 143 amino acids in length, the models are 126 amino acids in length. Affinity for the glycosaminoglycan heparan sulfate resides solely within the deleted sequence of 17 amino acids. Glycosaminoglycans (GAGs or mucopolysaccharides are long unbranched Polysaccharides consisting of a repeating Disaccharide unit Heparan sulfate (HS is a linear Polysaccharide found in all animal tissues ^[4]

Biological activity

In contrast to interferon-α and interferon-β which can be expressed by all cells, IFN-γ is secreted by Th1 cells, Tc cells, dendritic cells and NK cells. T helper cells (also known as effector T cells or Th cells) are a sub-group of Lymphocytes (a type of White blood cell or A cytotoxic T cell (also known as TC, CTL T-Killer cell cytolytic T cell CD8+ T-cells or killer T cell) belongs to a sub-group of T lymphocytes Dendritic cells (DCs are Immune cells and form part of the Mammalian Immune system. Natural killer cells (or NK cells) are a type of Cytotoxic Lymphocyte that constitute a major component of the Innate immune system. Also known as immune interferon, IFN-γ is the only Type II interferon. Interferons ( IFN s are natural Proteins produced by the cells of the Immune system of most Vertebrates in response to challenges by foreign agents It is serologically distinct from Type I interferons and it is acid-labile, while the type I variants are acid-stable. Serology is the scientific study of blood serum. In practice the term usually refers to the Diagnostic identification of antibodies in the serum

IFN-γ has antiviral, immunoregulatory, and anti-tumour properties. ^[5] It alters transcription in up to 30 genes producing a variety of physiological and cellular responses. Amongst the effects are:

• Increase antigen presentation of macrophages. Macrophages ( Greek: "big eaters" from makros "large" + phagein "eat" ( Mø) are cells within the tissues that
• Activate and increase lysosome activity in macrophages
• Suppress Th2 cell activity. Lysosomes are Organelles that contain Digestive enzymes (acid Hydrolases. T helper cells (also known as effector T cells or Th cells) are a sub-group of Lymphocytes (a type of White blood cell or
• Cause normal cells to express class II MHC molecules
• Promotes adhesion and binding required for leukocyte migration
• Promotes NK cell activity

Activation by IFN-γ is achieved by its interaction with a heterodimeric receptor consisting of IFNGR1 & IFNGR2 (interferon gamma receptors). MHC ( Major histocompatibility complex) Class II molecules are found only on a few specialized cell types including Macrophages Dendritic cells and Natural killer cells (or NK cells) are a type of Cytotoxic Lymphocyte that constitute a major component of the Innate immune system. IFN-γ binding to the receptor activates the JAK-STAT pathway. The JAK-STAT signaling pathway takes part in the regulation of cellular responses to Cytokines and Growth factors Employing Janus kinases (JAKs and In addition, IFN-γ activates APCs and promotes Th1 differentiation by upregulating the transcription factor T-bet. See also Antigen presentation An antigen-presenting cell ( APC) or accessory cell is a cell that displays foreign Antigen complexed T helper cells (also known as effector T cells or Th cells) are a sub-group of Lymphocytes (a type of White blood cell or In the field of Molecular biology, a transcription factor (sometimes called a sequence-specific DNA binding factor is a Protein that binds to specific sequences

IFN-γ is the hallmark cytokine of Th1 cells (Th2 cells produce IL-4). Cytokines are a category of signalling Proteins and Glycoproteins that like Hormones and Neurotransmitters, are used extensively in cellular T helper cells (also known as effector T cells or Th cells) are a sub-group of Lymphocytes (a type of White blood cell or T helper cells (also known as effector T cells or Th cells) are a sub-group of Lymphocytes (a type of White blood cell or NK cells and CD8+ cytotoxic T cells also produce IFN-γ. Natural killer cells (or NK cells) are a type of Cytotoxic Lymphocyte that constitute a major component of the Innate immune system. 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. An osteoclast (from the Greek words for "bone" and "broken" is a type of Bone cell that removes Bone tissue by removing its Mineralized matrix RANK (Receptor Activator of Nuclear Factor κ B, also known as TRANCE Receptor is a type I membrane protein which is expressed on the surface of Osteoclasts and is involved TRAF6 is a TRAF human protein RANK (Receptor Activator of Nuclear Factor κ B, also known as TRANCE Receptor is a type I membrane protein which is expressed on the surface of Osteoclasts and is involved RANKL ( Receptor Activator for Nuclear Factor κ B Ligand) also known as TNF-related activation-induced cytokine (TRANCE osteoprotegerin ligand (OPGL and ODF (osteoclast NF-κB ( nuclear factor-kappa B) is a protein complex that is a Transcription factor.

Therapeutic uses

Interferons are used to treat infectious diseases and cancer. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity Excretion is the process of eliminating waste products of Metabolism and other non-useful materials The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction In Pharmacology and Toxicology, a route Interferons ( IFN s are natural Proteins produced by the cells of the Immune system of most Vertebrates in response to challenges by foreign agents

Scientists at the University of California at Berkeley have recently discovered that Diindolylmethane (DIM), a naturally occurring compound found in Brassica vegetables, upon oral consumption, is a direct and potent activator of Interferon-Gamma production and sensitivity within the body leading the way for the study of this compound as an anti-viral, anti-bacterial and anti-cancer therapeutic. Brassica ( Brás-si-ca) is a genus of plants in the mustard family ( Brassicaceae) As this is a dietary compound found in edible vegetables, this has caused a lot of excitement in the immunology field. This compound has also been shown to synergize with Interferon-Gamma in the expression and potentiation of the MHC-I Complex, leading to its study as a possible adjuvant to Interferon-gamma therapeutic models.

References

1. ^ Gray, P. W. and Goeddel, D. V. (1982). "Structure of the human immune interferon gene". Nature 298: 859–863. doi:10.1038/298859a0. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document.  
2. ^ Ealick, S. E. , Cook, W. J. et al. (1991). "Three-dimensional structure of recombinant human interferon-gamma". Science 252: 698–702. doi:10.1126/science.1902591. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document.  
3. ^ Thiel, D. J. et al. (2000). "Observation of an unexpected third receptor molecule in the crystal structure of human interferon-γ receptor complex". Structure 8 (9): 927–936. doi:10.1016/S0969-2126(00)00184-2. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document.  
4. ^ Vanhaverbeke, C. Simorre, J-P. et al. (2004). "NMR characterization of the interaction between the C-terminal domain of interferon-γ and heparin-derived oligosaccharides" 384: 93–99. PMID 15270718.  
5. ^ Schroder et al. (2004). "Interferon-γ an overview of signals, mechanisms and functions". Journal of Leukocyte Biology 75: 163–189. doi:10.1189/jlb.0603252. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document.  

Further reading