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.
有效結構
PDB	直系同源檢索：PDBe, RCSB
PDB查詢代碼列表
	1IPB, 1IPC, 1WKW, 2GPQ, 2V8W, 2V8X, 2V8Y, 2W97, 3AM7, 3TF2, 3U7X, 4AZA, 4DT6, 4DUM
標識
代號	EIF4E; AUTS19; CBP; EIF4E1; EIF4EL1; EIF4F
擴展標識	遺傳學：133440 鼠基因：95305 同源基因：123817 ChEMBL: 4848 GeneCards: EIF4E Gene
基因本體論描述
分子功能	· RNA cap binding; · translation initiation factor activity; · protein binding; · eukaryotic initiation factor 4G binding;
細胞成分	· cytoplasmic mRNA processing body; · cytosol; · mRNA cap binding complex; · cytoplasmic stress granule; · eukaryotic translation initiation factor 4F complex; · RNA-induced silencing complex;
生物過程	· 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表達模式
	更多表達數據
直系同源體
物種	人類
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查詢	[1]
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真核起始因子4E（英文：eukaryotic initiation factor 4E，簡稱「eIF4E」）是一種帽結合蛋白，可以特異性地識別mRNA的5'端的帽子結構，它在真核翻譯的起始過程中發揮重要作用。

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eIF4E可以與eIF4A和eIF4G共同組成eIF4F 複合物參與真核翻譯起始。因此，通過與mRNA的5'端的帽子結構結合，eIF4E就可以將eIF4A帶到mRNA的5'端，讓eIF4A發揮解旋酶活性來打開mRNA的5'端的二級結構。^[1]

異構體

在真核生物中，eIF4E有許多異構體；在不同物種間，其數量也有差異。不同的eIF4E異構體有不同的帽結合活性，這就可用於對不同mRNA進行選擇性翻譯。^[1]有一些細胞進程需要特異的eIF4E異構體的活性。例如，在果蠅中除去eIF4E-1和eIF4E-2會導致雌性無卵巢發育。還有一些eIF4E異構體具有許多不同的功能。例如，果蠅的eIF4E-6被發現無法與eIF4G結合，可能是作為翻譯阻遏蛋白；^[2]人體中的eIF4E-1被發現參與了對一系列特異mRNA的核mRNA轉運。^[3]

結構

eIF4E含有一個由8條反平行β鏈組成的彎曲的β摺疊片以及三個幾乎平行於β摺疊片頂部鏈的α螺旋。eIF4E識別帽子的工作就由7-甲基-鳥嘌呤和吲哚基團之間的堆積來完成。該堆積由兩個絕對保守的色氨酸殘基，依靠三個類Watson-Crick氫鍵和范德華力同第三個保守色氨酸聯繫起來。^[4]

磷酸化作用可以調控eIF4E的活性。例如哺乳動物eIF4E的209位的絲氨酸的磷酸化可增強eIF4E同加帽mRNA的結合併穩固eIF4E和eIF4G間的相互作用。^[5]^[6]但也有人認為該位點的磷酸化並不影響蛋白質的翻譯過程。^[7]

參考文獻

[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.

參見

[eIF4-1] [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] [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] [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] [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] [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] [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] [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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