Insulin‐like growth factor (IGF)‐II is considered to function as an important fetal growth factor, which is structurally and functionally related to IGF‐I and proinsulin. At least in vitro, IGF‐II actions are mediated through the IGF‐I receptor and to a lesser extent the insulin receptor. After birth, the function of IGF‐II is less clear although in adults the serum level of IGF‐II exceeds that of IGF‐I several fold. The IGF‐II gene is maternally imprinted, with exception of the liver and several parts of the brain, where it is expressed from both alleles. The regulation, organization, and translation of the IGF‐II gene is complex, with five different putative promotors leading to a range of noncoding and coding mRNAs. The 180‐amino acid pre‐pro‐IGF‐II translation product can be divided into five domains and include a N‐terminal signal peptide of 24 amino acid residues, the 67 amino acid long mature protein, and an 89 residues extension at the COOH terminus, designated as the E‐domain. After removal of the signal peptide, the processing of pro‐IGF‐II into mature IGF‐II requires various steps including glycosylation of the E‐domain followed by the action of endo‐proteases. Several of these processing intermediates can be found in the human circulation. There is increasing evidence that, besides IGF‐II, several incompletely processed precursor forms of the protein, and even a 34‐amino acid peptide (preptin) derived from the E‐domain of pro‐IGF‐II, exhibit distinct biological activities. This review will focus on the current insights regarding the specific roles of the latter proteins in cancer, glucose homeostasis, and bone physiology. To address this topic clearly in the right context, a concise overview of the biological and biochemical properties of IGF‐II and several relevant aspects of the IGF system will be provided.

中文翻译：

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胰岛素样生长因子-II 和含有部分胰岛素样生长因子-II E 域的生物活性蛋白。

胰岛素样生长因子 (IGF)-II 被认为是一种重要的胎儿生长因子，其在结构和功能上与 IGF-I 和胰岛素原有关。至少在体外，IGF-II 的作用是通过 IGF-I 受体介导的，在较小程度上通过胰岛素受体介导。出生后，IGF-II 的功能不太清楚，尽管在成人中，IGF-II 的血清水平超过 IGF-I 数倍。IGF-II 基因是母系印记的，除了肝脏和大脑的几个部分，它由两个等位基因表达。IGF-II 基因的调控、组织和翻译是复杂的，有五种不同的假定启动子导致一系列非编码和编码 mRNA。180 个氨基酸的 pre-pro-IGF-II 翻译产物可分为五个结构域，包括 24 个氨基酸残基的 N 端信号肽、67 个氨基酸长的成熟蛋白和在 COOH 处的 89 个残基延伸终端，指定为 E 域。去除信号肽后，将 pro-IGF-II 加工成成熟的 IGF-II 需要多个步骤，包括 E 结构域的糖基化，然后是内切蛋白酶的作用。这些加工中间体中有几种可以在人体循环中找到。越来越多的证据表明，除了 IGF-II 之外，该蛋白质的几种未完全加工的前体形式，甚至来自 pro-IGF-II 的 E 结构域的 34 个氨基酸的肽 (preptin) 都表现出不同的生物活性。本综述将重点关注后一种蛋白质在癌症、葡萄糖稳态和骨生理学中的具体作用的当前见解。为了在正确的上下文中清楚地讨论这个主题，将提供对 IGF-II 的生物学和生化特性以及 IGF 系统的几个相关方面的简要概述。