The IGF-II gene encodes a single transcript which results in a 156 amino acid protein, including an 89 amino acid E-domain. Pro-IGF-II is converted to mature IGF-II by sequential cleavage at amino acids 104, 87 and 67. Pro-IGF-II contains sites of O-linked glycosylation. Differential glycosylation and cleavage within the E-domain can therefore result in multiple pro-IGF-II isoforms. The pro-IGF-II proteins make up 10-20% of circulating IGF-II. Pro-IGF-II proteins are secreted by some tumour cell lines and levels are elevated in non-islet cell tumour hypoglycaemia.