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After birth, the function of IGF\u2010II is less clear although in adults the serum level of IGF\u2010II exceeds that of IGF\u2010I several fold. The IGF\u2010II 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\u2010II gene is complex, with five different putative promotors leading to a range of noncoding and coding mRNAs. The 180\u2010amino acid pre\u2010pro\u2010IGF\u2010II translation product can be divided into five domains and include a N\u2010terminal 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\u2010domain. After removal of the signal peptide, the processing of pro\u2010IGF\u2010II into mature IGF\u2010II requires various steps including glycosylation of the E\u2010domain followed by the action of endo\u2010proteases. Several of these processing intermediates can be found in the human circulation. There is increasing evidence that, besides IGF\u2010II, several incompletely processed precursor forms of the protein, and even a 34\u2010amino acid peptide (preptin) derived from the E\u2010domain of pro\u2010IGF\u2010II, 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\u2010II and several relevant aspects of the IGF system will be provided.<\/jats:p>","DOI":"10.1002\/biof.1623","type":"journal-article","created":{"date-parts":[[2020,2,6]],"date-time":"2020-02-06T09:49:22Z","timestamp":1580982562000},"page":"563-578","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Insulin\u2010like growth factor\u2010II and bioactive proteins containing a part of the E\u2010domain of pro\u2010insulin\u2010like growth factor\u2010II"],"prefix":"10.1002","volume":"46","author":[{"given":"Jaap","family":"van Doorn","sequence":"first","affiliation":[{"name":"Department of Genetics, Section Metabolic Diagnostics University Medical Center Utrecht, Utrecht University  Utrecht The 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