Literature References | 1. BLUNDELL, T.L. AND HUMBEL, R.E.
Hormone families: pancreatic hormones and homologous growth factors.
NATURE 287 781-7 (1980).
2. BELL, G.I., PICTET, R.L., RUTTER, W.J., CORDELL, B., TISCHER, E. AND
GOODMAN, H.M.
Sequence of the human insulin gene.
NATURE 284 26-32 (1980).
3. BELL, G.I., SWAIN, W.F., PICTET, R.L., CORDELL, B., GOODMAN, H.M. AND
RUTTER, W.J.
Nucleotide sequence of a cDNA clone encoding human preproinsulin.
NATURE 282 525-527 (1979).
4. GARIBAY-TUPAS, J.L., CSISZAR, K., FOX, M., POVEY, S. AND
BRYANT-GREENWOOD, G.D.
Analysis of the 5'-upstream regions of the human relaxin H1 and H2 genes
and their chromosomal localization on chromosome 9p24.1 by radiation hybrid
and breakpoint mapping.
J.MOL.ENDOCRINOL. 23 355-365 (1999).
5. GUNNERSEN, J.M., FU, P., ROCHE, P.J. AND TREGEAR, G.W.
Expression of human relaxin genes: characterization of a novel
alternatively-spliced human relaxin mRNA species.
MOL.CELL.ENDOCRINOL. 118 85-94 (1996).
6. KONDO, H., INO, M., SUZUKI, A., ISHIZAKI, H. AND IWAMI, M.
Multiple gene copies for bombyxin, an insulin-related peptide of the
silkmoth Bombyx mori: structural signs for gene rearrangement and
duplication responsible for generation of multiple molecular forms of
bombyxin.
J.MOL.BIOL. 259 926-937 (1996).
7. COOKE, R.M., HARVEY, T.S. AND CAMPBELL, I.D.
Solution structure of human insulin-like growth factor 1: a nuclear magnetic
resonance and restrained molecular dynamics study.
BIOCHEMISTRY 30 5484-5491 (1991).
8. SATO, A., NISHIMURA, S., OHKUBO, T., KYOGOKU, Y., KOYAMA, S.,
KOBAYASHI, M., YASUDA, T. AND KOBAYASHI, Y.
1H-NMR assignment and secondary structure of human insulin-like growth
factor-I (IGF-I) in solution.
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9. BRANGE, J., DODSON, G.G., EDWARDS, D.J., HOLDEN, P.H. AND
WHITTINGHAM, J.L.
A model of insulin fibrils derived from the X-ray crystal structure of a
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Documentation | The insulin family of proteins groups together several evolutionarily
related active peptides [1]: these include insulin [2,3], relaxin [4,5],
insect prothoracicotropic hormone (bombyxin) [6], insulin-like growth
factors (IGF1 and IGF2) [7,8], mammalian Leydig cell-specific insulin-like
peptide (gene INSL3), early placenta insulin-like peptide (ELIP) (gene
INSL4), locust insulin-related peptide (LIRP), molluscan insulin-related
peptides (MIP), and Caenorhabditis elegans insulin-like peptides. The 3D
structures of a number of family members have been determined [7-9]. The
fold comprises two polypeptide chains (A and B) linked by two disulphide
bonds: all share a conserved arrangement of 4 cysteines in their A chain,
the first of which is linked by a disulphide bond to the third, while the
second and fourth are linked by interchain disulphide bonds to cysteines
in the B chain.
Insulin is found in many animals, and is involved in the regulation of
normal glucose homeostasis. It also has other specific physiological
effects, such as increasing the permeability of cells to monosaccharides,
amino acids and fatty acids, and accelerating glycolysis and glycogen
synthesis in the liver [2]. Insulin exerts its effects by interaction with
a cell-surface receptor, which may also result in the promotion of cell
growth [2].
Insulin is synthesised as a prepropeptide from which an endoplasmic
reticulum-targeting sequence is cleaved to yield proinsulin. The sequence
of prosinsulin contains 2 well-conserved regions (designated A and B),
separated by an intervening connecting region (C), which is variable
between species [3]. The connecting region is cleaved, liberating the
active protein, which contains the A and B chains, held together by 2
disulphide bonds [3].
INSULIN is a 3-element fingerprint that provides a signature for insulins.
The fingerprint was derived from an initial alignment of 28 sequences: the
motifs were drawn from conserved regions spanning virtually the full
alignment length, focusing on those sections that characterise insulins but
distinguish them from closely related members of the insulin family. Three
iterations on SPTR55_38f were required to reach convergence, at which point
a true set comprising 105 sequences was identified. Four partial matches
were also found, all of which are insulins that fail to make signficant
matches with motifs 2 or 3.
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