title: The human insulin superfamily of polypeptide hormones.
abstract: The identification in the 1950s of insulin, an essential carbohydrate regulatory hormone, as consisting of not one but two peptide chains linked by three disulfide bonds in a distinctive pattern was a milestone in peptide chemistry. When it was later found that relaxin also possessed a similar overall structure, the term 'insulin superfamily' was coined. Use of methods of conventional protein chemistry followed by recombinant DNA and more recently bioinformatics has led to the recognition that insulin is the precursor to a large protein superfamily that extends beyond the human. Insulin-like peptides are found not only in vertebrates such as mammals, birds, reptiles, amphibians but also in the invertebrates such as chordates, molluscs and insects. All superfamily members share the distinctive insulin structural motif. In the human, there exists ten members of the superfamily, each of which are expressed on the ribosome as a single-chain pre-prohormone that undergoes proteolytic processing to produce eight double-chain mature proteins and two single-chain forms. The six cysteine residues that form the three insulin disulfide cross-links - one intramolecular within the A-chain and two intermolecular between that A- and B-chains - are absolutely conserved across all members of the superfamily. They are responsible for imparting a similar overall tertiary structure. The human insulin superfamily members have each evolved to assume remarkably distinctive biological functions ranging from glucose homeostasis to neuroendocrine actions. That such diversity is contained within a modestly sized superfamily is testament to efficiency of the insulin structural motif as an evolutionary template.
authors.affiliation: Howard Florey Institute, University of Melbourne, Victoria 3010, Australia.
authors.forename: Fazel
authors.initials: F
authors.lastname: Shabanpoor
authors.forename: Frances
authors.initials: F
authors.lastname: Separovic
authors.forename: John D
authors.initials: JD
authors.lastname: Wade
mesh_terms: D000595:Amino Acid Sequence; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D005810:Multigene Family; D036361:Peptide Hormones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D011487:Protein Conformation
chemical_list: D036361:Peptide Hormones