γ-干扰素

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

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

干扰素-γ
	γ-干擾素晶體結構線狀表示[1]
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

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**
系统（IUPAC）命名名称
Human interferon gamma-1b
临床数据
商品名	Actimmune
Drugs.com	Monograph
MedlinePlus	a601152
识别
CAS注册号	82115-62-6 98059-61-1
ATC代码	L03AB03
DrugBank	DB00033^N
ChemSpider	NA
ChEMBL	CHEMBL1201564^N
化学
化学式	C₇₆₁H₁₂₀₆N₂₁₄O₂₂₅S₆
摩尔质量	17145.6 g/mol

结构

干扰素伽玛蛋白的单体是由六个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和干扰素-β，而干扰素伽玛只由活化T细胞和自然杀伤细胞（NK细胞）产生。在血清学上，I型干扰素是酸稳定，而干扰素伽玛则遇酸变性。

干扰素伽玛具有抗病毒、免疫调节及抗肿瘤特性[5]。可以与结合到干扰素伽玛受体(IFNGR)，干扰素伽玛受体由两个亚基组成。干扰素伽玛结合激活其受体调节JAK-STAT通路。干扰素伽玛激活抗原提呈细胞，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。

干扰素伽玛是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细胞也产生干扰素伽玛。干扰素伽玛通过迅速降解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. . 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. . 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. . 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. . 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. . New York: Henry Holt. 1997. ISBN 0-8050-5841-9.
Ikeda H, Old LJ, Schreiber RD. . Cytokine Growth Factor Rev. 2002, 13 (2): 95–109. PMID 11900986. doi:10.1016/S1359-6101(01)00038-7.
Chesler DA, Reiss CS. . 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. . Immunol. Rev. 2005, 201: 180–90. PMID 15361241. doi:10.1111/j.0105-2896.2004.00195.x.
Joseph AM, Kumar M, Mitra D. . Curr. HIV Res. 2005, 3 (1): 87–94. PMID 15638726. doi:10.2174/1570162052773013.
Copeland KF. . Mini reviews in medicinal chemistry. 2006, 5 (12): 1093–101. PMID 16375755. doi:10.2174/138955705774933383.
Chiba H, Kojima T, Osanai M, Sawada N. . Sci. STKE. 2006, 2006 (316): pe1. PMID 16391178. doi:10.1126/stke.3162006pe1.
Tellides G, Pober JS. . 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

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.

[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. . 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. . 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. . 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. . Antiviral Research. 1983-03, 3 (1): 59–65. ISSN 0166-3542. doi:10.1016/0166-3542(83)90015-3.