Sequence of human insulin gene

Nature (Impact Factor: 41.46). 04/1980; 284(5751):26-32. DOI: 10.1038/284026a0
Source: PubMed


The human insulin gene contains two intervening sequences, one is within the region transcribed into the 5'-untranslated segment of the mRNA and the other interrupts the C-peptide encoding region. A comparison of the human with the rat insulin genes indicates potential regulatory regions in the DNA segment preceding the gene and suggests that the ancestral form of the insulin gene had two intervening sequences.

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Available from: Howard M Goodman, Jun 26, 2014
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    • "The signal peptide (the first 23–24 aa at the N-terminus) is removed during insertion into the endoplasmic reticulum, resulting in proinsulin (86 aa, ~9.5 kDa). Proinsulin consists of three domains: an amino-terminal B chain (30 aa, ~3.4 kDa), a carboxy-terminal A chain (21 aa, ~2.4 kDa) and a connecting C chain (34 aa, ~3.0 kDa)78. Within the endoplasmic reticulum, proinsulin is cut by neuroendocrine-cell-specific prohormone convertases (PC1 and PC2) to excise the C chain. "
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    • "This has been best achieved by basal-bolus therapy using multiple daily injections or continuous subcutaneous insulin infusion pumps. There have been many major breakthroughs since 1922, but none more important than the cloning and sequencing of the insulin gene in 1980,2 which brought about the introduction of unlimited supplies of bacterially expressed human insulin and the technology to modify the structure of the protein, such that there are now at least six rapid-acting or long-acting analogues. Combined with advances in glucose monitoring, these modified insulins have allowed patients to control their blood glucose levels within relatively narrow limits. "
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    • "The human insulin superfamily consists of ten members including a single insulin (Bell et al. 1980), IGF1 and IGF2 (Rinderknecht and Humbel 1978), relaxins (Bedarkar et al. 1977), relaxin-like growth factors (Bullesbach and Schwabe 1995) and an early placental insulin-like peptide (Chassin et al. 1995). We focus our discussion of neural modulation and behavior on the role of three genes: insulin, IGF1 and IGF2 (Bell et al. 1980; Harper et al. 1981; Owerbach et al. 1980). Similar to the rat and mouse insulin genes, the mammalian insulin gene encodes a preproinsulin peptide, which has an A-chain, B-chain, C-peptide and signal sequence (Murray-Rust et al. 1992). "
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