真核起始因子4E

真核起始因子4E
真核起始因子4E
	PDB rendering based on 1ej1.
有效结构
PDB	直系同源检索：PDBe, RCSB
PDB查询代码列表
	1IPB, 1IPC, 1WKW, 2GPQ, 2V8W, 2V8X, 2V8Y, 2W97, 3AM7, 3TF2, 3U7X, 4AZA, 4DT6, 4DUM
标识
代号	EIF4E; AUTS19; CBP; EIF4E1; EIF4EL1; EIF4F
扩展标识	遗传学：133440 鼠基因：95305 同源基因：123817 ChEMBL: 4848 GeneCards: EIF4E Gene
基因本体论描述
分子功能	· RNA cap binding; · translation initiation factor activity; · protein binding; · eukaryotic initiation factor 4G binding;
细胞成分	· cytoplasmic mRNA processing body; · cytosol; · mRNA cap binding complex; · cytoplasmic stress granule; · eukaryotic translation initiation factor 4F complex; · RNA-induced silencing complex;
生物过程	· G1/S transition of mitotic cell cycle; · nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay; · nuclear-transcribed mRNA poly(A) tail shortening; · mRNA export from nucleus; · translation; · translational initiation; · regulation of translation; · insulin receptor signaling pathway; · gene expression; · RNA metabolic process; · mRNA metabolic process; · virus-host interaction; · cytokine-mediated signaling pathway; · lung development; · cellular protein metabolic process; · positive regulation of mitotic cell cycle;
	Sources: Amigo / QuickGO
RNA表达模式
	更多表达数据
直系同源体
物种	人类
Entrez	1977
Ensembl	ENSG00000151247
UniProt	P06730
mRNA序列	NM_001130678
蛋白序列	NP_001124150
基因位置	Chr 4:; 99.79 – 99.85 Mb
PubMed查询	[1]
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真核起始因子4E（英文：eukaryotic initiation factor 4E，简称“eIF4E”）是一种帽结合蛋白，可以特异性地识别mRNA的5'端的帽子结构，它在真核翻译的起始过程中发挥重要作用。

eIF4E可以与eIF4A和eIF4G共同组成eIF4F 复合物参与真核翻译起始。因此，通过与mRNA的5'端的帽子结构结合，eIF4E就可以将eIF4A带到mRNA的5'端，让eIF4A发挥解旋酶活性来打开mRNA的5'端的二级结构。^[1]

异构体

在真核生物中，eIF4E有许多异构体；在不同物种间，其数量也有差异。不同的eIF4E异构体有不同的帽结合活性，这就可用于对不同mRNA进行选择性翻译。^[1]有一些细胞进程需要特异的eIF4E异构体的活性。例如，在果蝇中除去eIF4E-1和eIF4E-2会导致雌性无卵巢发育。还有一些eIF4E异构体具有许多不同的功能。例如，果蝇的eIF4E-6被发现无法与eIF4G结合，可能是作为翻译阻遏蛋白；^[2]人体中的eIF4E-1被发现参与了对一系列特异mRNA的核mRNA转运。^[3]

结构

eIF4E含有一个由8条反平行β链组成的弯曲的β折叠片以及三个几乎平行于β折叠片顶部链的α螺旋。eIF4E识别帽子的工作就由7-甲基-鸟嘌呤和吲哚基团之间的堆积来完成。该堆积由两个绝对保守的色氨酸残基，依靠三个类Watson-Crick氢键和范德华力同第三个保守色氨酸联系起来。^[4]

磷酸化作用可以调控eIF4E的活性。例如哺乳动物eIF4E的209位的丝氨酸的磷酸化可增强eIF4E同加帽mRNA的结合并稳固eIF4E和eIF4G间的相互作用。^[5]^[6]但也有人认为该位点的磷酸化并不影响蛋白质的翻译过程。^[7]

参考文献

^ ^1.0 ^1.1 （英文）Hernández G, Vazquez-Pianzola P. Functional diversity of the eukaryotic translation initiation factors belonging to eIF4 families. Mech Dev. 2005, 122: 865–76. PMID 15922571.
^ （英文）Hernández G, Altmann M, Sierra JM, Urlaub H, Diez del Corral R, Schwartz P, Rivera-Pomar R. Functional analysis of seven genes encoding eight translation initiation factor 4E (eIF4E) isoforms in Drosophila. Mech Dev. 2005, 122: 529–43. PMID 15804566.
^ （英文）Strudwick S, Borden KL. The emerging roles of translation factor eIF4E in the nucleus. Differentiation. 2002, 70: 10–22. PMID 11963652.
^ （英文）Marcotrigiano J, Gingras AC, Sonenberg N, Burley SK. Cocrystal structure of the messenger RNA 5' cap-binding protein (eIF4E) bound to 7-methyl-GDP. Cell. 1997, 89: 951–61. PMID 9200613.
^ （英文）Waskiewicz AJ, Johnson JC, Penn B, Mahalingam M, Kimball SR, Cooper JA. Phosphorylation of the cap-binding protein eukaryotic translation initiation factor 4E by protein kinase Mnk1 in vivo. Mol Cell Biol. 1999, 19: 1871–80. PMID 10022874.
^ （英文）Pyronnet S, Imataka H, Gingras AC, Fukunaga R, Hunter T, Sonenberg N. Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E. EMBO J. 1999, 18: 270–9. PMID 9878069.
^ （英文）McKendrick L, Morley SJ, Pain VM, Jagus R, Joshi B. Phosphorylation of eukaryotic initiation factor 4E (eIF4E) at Ser209 is not required for protein synthesis in vitro and in vivo. Eur J Biochem. 2001, 268: 5375–85. PMID 11606200.

参见

[eIF4-1] 1.0 ^1.1 （英文）Hernández G, Vazquez-Pianzola P. Functional diversity of the eukaryotic translation initiation factors belonging to eIF4 families. Mech Dev. 2005, 122: 865–76. PMID 15922571.

[2] （英文）Hernández G, Altmann M, Sierra JM, Urlaub H, Diez del Corral R, Schwartz P, Rivera-Pomar R. Functional analysis of seven genes encoding eight translation initiation factor 4E (eIF4E) isoforms in Drosophila. Mech Dev. 2005, 122: 529–43. PMID 15804566.

[3] （英文）Strudwick S, Borden KL. The emerging roles of translation factor eIF4E in the nucleus. Differentiation. 2002, 70: 10–22. PMID 11963652.

[4] （英文）Marcotrigiano J, Gingras AC, Sonenberg N, Burley SK. Cocrystal structure of the messenger RNA 5' cap-binding protein (eIF4E) bound to 7-methyl-GDP. Cell. 1997, 89: 951–61. PMID 9200613.

[5] （英文）Waskiewicz AJ, Johnson JC, Penn B, Mahalingam M, Kimball SR, Cooper JA. Phosphorylation of the cap-binding protein eukaryotic translation initiation factor 4E by protein kinase Mnk1 in vivo. Mol Cell Biol. 1999, 19: 1871–80. PMID 10022874.

[6] （英文）Pyronnet S, Imataka H, Gingras AC, Fukunaga R, Hunter T, Sonenberg N. Human eukaryotic translation initiation factor 4G (eIF4G) recruits mnk1 to phosphorylate eIF4E. EMBO J. 1999, 18: 270–9. PMID 9878069.

[7] （英文）McKendrick L, Morley SJ, Pain VM, Jagus R, Joshi B. Phosphorylation of eukaryotic initiation factor 4E (eIF4E) at Ser209 is not required for protein synthesis in vitro and in vivo. Eur J Biochem. 2001, 268: 5375–85. PMID 11606200.

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