| 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.
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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.
Relaxin is encoded by two non-allelic genes in humans and great apes, and by
a single gene in all other species studied to date [5]. The expression of
human relaxin genes (H1 and H2) has been characterised in placenta, decidua,
prostate and ovary: H2 relaxin mRNA was detected in the ovary, term
placenta, decidua, and prostate gland; by contrast, H1 gene expression was
detected only in the prostate gland [5]. Synthesised in the corpora lutea of
ovaries during pregnancy, relaxin is released into the blood stream prior to
parturition [10]. With oestrogen, it acts to produce dilation of the birth
canal in many mammals, its major biological role being to remodel the
reproductive tract to facilitate the birth process [10].
RELAXIN is a 6-element fingerprint that provides a signature for the
relaxins. The fingerprint was derived from an initial alignment of 13
sequences: the motifs were drawn from conserved regions spanning virtually
the full alignment length, focusing on those sections that characterise the
relaxins 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 13 sequences was identified. Six
partial matches were also found, all of which are relaxins and placentins
that fail to make significant matches with one or more motifs.
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