γ-干扰素

現有可用的蛋白結構：
Pfam	結構（旧版） / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum（英语：PDBsum）	結構概要

IFN-γ
IFN-γ
	Crystal structure of a biologically active single chain mutant of human interferon gamma
鑑定
標誌	?
Pfam	PF00714（旧版）
Pfam宗系	CL0053（旧版）
InterPro（英语：InterPro）	IPR002069
SCOP（英语：Structural Classification of Proteins）	1rfb / SUPFAM
Pfam
現有可用的蛋白結構：
Pfam	結構（旧版） / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum（英语：PDBsum）	結構概要

干扰素-γ
干扰素-γ
	γ-干擾素晶體結構線狀表示
有效结构
PDB	直系同源检索：PDBe, RCSB
PDB查询代码列表
	1EKU, 1FG9, 1FYH, 1HIG, 3BES
标识
代号	IFNG; IFG; IFI
扩展标识	遗传学：147570 鼠基因：107656 同源基因：55526 GeneCards: IFNG Gene
基因本体论描述
分子功能	· cytokine activity; · interferon-gamma receptor binding;
细胞成分	· extracellular region; · extracellular space; · external side of plasma membrane;
生物过程	· protein import into nucleus, translocation; · negative regulation of transcription from RNA polymerase II promoter; · neutrophil apoptotic process; · regulation of the force of heart contraction; · positive regulation of mesenchymal cell proliferation; · adaptive immune response; · CD8-positive, alpha-beta T cell differentiation involved in immune response; · negative regulation of mesenchymal to epithelial transition involved in metanephros morphogenesis; · apoptotic process; · cellular component movement; · humoral immune response; · cell cycle arrest; · cell surface receptor signaling pathway; · response to virus; · cytokine-mediated signaling pathway; · antigen processing and presentation; · neutrophil chemotaxis; · endoplasmic reticulum unfolded protein response; · negative regulation of myelination; · positive regulation of synaptic transmission, cholinergic; · negative regulation of interleukin-17 production; · positive regulation of interleukin-12 production; · positive regulation of interleukin-23 production; · positive regulation of tumor necrosis factor production; · positive regulation of peptidyl-serine phosphorylation of STAT protein; · positive regulation of smooth muscle cell apoptotic process; · positive regulation of T cell proliferation; · response to drug; · positive regulation of tyrosine phosphorylation of Stat1 protein; · defense response to bacterium; · defense response to protozoan; · negative regulation of growth of symbiont in host; · positive regulation of chemokine biosynthetic process; · positive regulation of interleukin-12 biosynthetic process; · positive regulation of MHC class II biosynthetic process; · positive regulation of interleukin-6 biosynthetic process; · positive regulation of nitric oxide biosynthetic process; · positive regulation of neuron differentiation; · positive regulation of osteoclast differentiation; · positive regulation of cell adhesion; · positive regulation of transcription from RNA polymerase II promoter; · positive regulation of isotype switching to IgG isotypes; · negative regulation of smooth muscle cell proliferation; · positive regulation of interleukin-1 beta secretion; · regulation of insulin secretion; · positive regulation of membrane protein ectodomain proteolysis; · defense response to virus; · positive regulation of killing of cells of other organism; · interferon-gamma-mediated signaling pathway; · regulation of interferon-gamma-mediated signaling pathway; · positive regulation of fructose 1,6-bisphosphate 1-phosphatase activity; · positive regulation of fructose 1,6-bisphosphate metabolic process; · positive regulation of vitamin D biosynthetic process; · positive regulation of calcidiol 1-monooxygenase activity; · cellular response to lipopolysaccharide; · cellular response to interleukin-18; · negative regulation of metanephric nephron tubule epithelial cell differentiation; · positive regulation of tumor necrosis factor (ligand) superfamily member 11 production;
	Sources: Amigo / QuickGO
RNA表达模式
	更多表达数据
直系同源体
物种	人类
Entrez	3458
Ensembl	ENSG00000111537
UniProt	P01579
mRNA序列	NM_000619
蛋白序列	NP_000610
基因位置	Chr 12:; 68.55 – 68.55 Mb
PubMed查询	[1]
	查; 论; 编;

干扰素-γ（Interferon gamma、Interferon-γ、IFNG、IFNγ）是水溶性二聚体的细胞因子^[2]。是II型干扰素的唯一成员^[3]曾被称为巨噬细胞活化因子。

Γ-干扰素
臨床資料
商品名（英语：Drug nomenclature）	Actimmune
AHFS/Drugs.com	Monograph
MedlinePlus	a601152
ATC碼	L03AB03 (WHO)
识别信息
IUPAC命名法 Human interferon gamma-1b
CAS号	82115-62-6 ^Y 98059-61-1
DrugBank	DB00033^N
ChemSpider	NA^Y
ChEMBL	ChEMBL1201564^N
化学信息
化学式	C₇₆₁H₁₂₀₆N₂₁₄O₂₂₅S₆
摩尔质量	17145.6 g/mol

结构

干扰素-γ的单体是由六个α螺旋组成一个核心^[4]和在C端区延伸展开的片断序列。

生物活性的二聚体是由两个反平行相互锁定的单体形成。

生物活性

所有的细胞都可以产生干扰素-α（英语：Interferon alfa）和干扰素-β，而干扰素-γ只由自然杀伤细胞（NK细胞）和活化的T细胞产生。I型干扰素对酸稳定，而干扰素-γ则遇酸变性。

干扰素-γ具有抗病毒、免疫调节及抗肿瘤特性^[5]。干扰素-γ可以与干扰素伽玛受体（英语：Interferon-gamma receptor）(IFNGR)结合，进而调节JAK-STAT通路。干扰素-γ激活抗原提呈细胞，通过上调转录因子T-bet而促进I型辅助T细胞(Th1细胞)的分化。

干扰素-γ是I型辅助T细胞(Th1细胞)的标志性的细胞因子。II型辅助T细胞(Th2细胞)释放白细胞介素-4（IL-4）和白细胞介素-13（IL-13）。自然杀伤细胞和CD8⁺T细胞也产生干扰素-γ。干扰素-γ通过迅速降解RANK-RANKL信号通路的TRAF6而抑制破骨细胞形成。

治疗用途

干扰素可以用来治疗传染病，但也能促成自體免疫。在接受干扰素伽玛治疗的病人中，多达19%的病人会有自體免疫.

干擾素IFNγ用於豬生殖與呼吸道綜合症PRRSV的治療上，有試驗發現干擾素IFNγ能活化先天免疫細胞，進而達到抑制病毒數量的效果。^[6]

A型流感的治療上，也有小鼠試驗表現出當缺失干擾素後，流感感染小鼠死亡率大幅提升且體內病毒數量維持高濃度水平；相較之下，體內有干擾素存在的小鼠，流感病毒數量隨著干擾素的生成而逐漸下降。^[7]

参考文献

^ PDB 1FG9; Thiel DJ, le Du MH, Walter RL, D'Arcy A, Chène C, Fountoulakis M, Garotta G, Winkler FK, Ealick SE. Observation of an unexpected third receptor molecule in the crystal structure of human interferon-gamma receptor complex. Structure. September 2000, 8 (9): 927–36. PMID 10986460. doi:10.1016/S0969-2126(00)00184-2.
^ Gray PW, Goeddel DV. Structure of the human immune interferon gene. Nature. 1982 Aug 26;298(5877):859-63.
^ Gray PW, Goeddel DV. Structure of the human immune interferon gene. Nature. August 1982, 298 (5877): 859–63. PMID 6180322. doi:10.1038/298859a0.
^ Ealick SE, et al., Three-dimensional structure of recombinant human interferon-gamma. Science. 1991 May 3;252(5006):698-702.
^ Schroder K, Hertzog PJ, Ravasi T, Hume DA. Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol. 2004 Feb;75(2):163-89.
^ Bautista, E. M.; Molitor, T. W. IFNγ inhibits porcine reproductive and respiratory syndrome virus replication in macrophages. Archives of Virology. 1999-06, 144 (6): 1191–1200. ISSN 0304-8608. doi:10.1007/s007050050578.
^ Hoshino, Akinori; Takenaka, Hiroshi; Mizukoshi, Osamu; Imanishi, Jiro; Kishida, Tsunataro; Tovey, Michael G. Effect of anti-interferon serum of influenza virus infection in mice. Antiviral Research. 1983-03, 3 (1): 59–65. ISSN 0166-3542. doi:10.1016/0166-3542(83)90015-3.

延伸閱讀

Hall, Stephen K. A commotion in the blood: life, death, and the immune system. New York: Henry Holt. 1997. ISBN 0-8050-5841-9.
Ikeda H, Old LJ, Schreiber RD. The roles of IFN gamma in protection against tumor development and cancer immunoediting.. Cytokine Growth Factor Rev. 2002, 13 (2): 95–109. PMID 11900986. doi:10.1016/S1359-6101(01)00038-7.
Chesler DA, Reiss CS. The role of IFN-gamma in immune responses to viral infections of the central nervous system.. Cytokine Growth Factor Rev. 2003, 13 (6): 441–54. PMID 12401479. doi:10.1016/S1359-6101(02)00044-8.
Dessein A, Kouriba B, Eboumbou C, Dessein H, Argiro L, Marquet S, Elwali NE, Rodrigues V, Li Y, Doumbo O, Chevillard C. Interleukin-13 in the skin and interferon-gamma in the liver are key players in immune protection in human schistosomiasis.. Immunol. Rev. 2005, 201: 180–90. PMID 15361241. doi:10.1111/j.0105-2896.2004.00195.x.
Joseph AM, Kumar M, Mitra D. Nef: "necessary and enforcing factor" in HIV infection.. Curr. HIV Res. 2005, 3 (1): 87–94. PMID 15638726. doi:10.2174/1570162052773013.
Copeland KF. Modulation of HIV-1 transcription by cytokines and chemokines.. Mini reviews in medicinal chemistry. 2006, 5 (12): 1093–101. PMID 16375755. doi:10.2174/138955705774933383.
Chiba H, Kojima T, Osanai M, Sawada N. The significance of interferon-gamma-triggered internalization of tight-junction proteins in inflammatory bowel disease.. Sci. STKE. 2006, 2006 (316): pe1. PMID 16391178. doi:10.1126/stke.3162006pe1.
Tellides G, Pober JS. Interferon-gamma axis in graft arteriosclerosis.. Circ. Res. 2007, 100 (5): 622–32. PMID 17363708. doi:10.1161/01.RES.0000258861.72279.29.

参看

外部链接

MeSH|Interferon+Type+II （页面存档备份，存于互联网档案馆）

[PDB_1FG9-1] PDB 1FG9; Thiel DJ, le Du MH, Walter RL, D'Arcy A, Chène C, Fountoulakis M, Garotta G, Winkler FK, Ealick SE. Observation of an unexpected third receptor molecule in the crystal structure of human interferon-gamma receptor complex. Structure. September 2000, 8 (9): 927–36. PMID 10986460. doi:10.1016/S0969-2126(00)00184-2.

[2] Gray PW, Goeddel DV. Structure of the human immune interferon gene. Nature. 1982 Aug 26;298(5877):859-63.

[pmid6180322-3] Gray PW, Goeddel DV. Structure of the human immune interferon gene. Nature. August 1982, 298 (5877): 859–63. PMID 6180322. doi:10.1038/298859a0.

[4] Ealick SE, et al., Three-dimensional structure of recombinant human interferon-gamma. Science. 1991 May 3;252(5006):698-702.

[5] Schroder K, Hertzog PJ, Ravasi T, Hume DA. Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol. 2004 Feb;75(2):163-89.

[6] Bautista, E. M.; Molitor, T. W. IFNγ inhibits porcine reproductive and respiratory syndrome virus replication in macrophages. Archives of Virology. 1999-06, 144 (6): 1191–1200. ISSN 0304-8608. doi:10.1007/s007050050578.

[7] Hoshino, Akinori; Takenaka, Hiroshi; Mizukoshi, Osamu; Imanishi, Jiro; Kishida, Tsunataro; Tovey, Michael G. Effect of anti-interferon serum of influenza virus infection in mice. Antiviral Research. 1983-03, 3 (1): 59–65. ISSN 0166-3542. doi:10.1016/0166-3542(83)90015-3.

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