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We are deeply saddened by the passing of Amos Bairoch (1957–2025), the creator of PROSITE. We wish to dedicate our latest paper, published shortly before his death, to him. He will always be a source of inspiration to us.
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Amos Bairoch

PROSITE documentation PDOC00235
Insulin family signature


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PURL: https://purl.expasy.org/prosite/documentation/PDOC00235

Description

The insulin family of proteins [1] groups a number of active peptides which are evolutionary related. This family currently consists of:

  • Insulin.
  • Relaxin.
  • Insulin-like growth factors I and II (IGFs or somatomedins) [2].
  • Mammalian Leydig cell-specific insulin-like peptide (Ley-I-L) (gene INSL3) [3].
  • Mammalian early placenta insulin-likepeptide (ELIP) (gene INSL4) [4].
  • Insulin-like peptide 5 (gene INSL5).
  • Insect prothoracicotropic hormone (PTTH) (bombyxin) [5].
  • Locust insulin-related peptide (LIRP) [6].
  • Molluscan insulin-related peptides 1 to 5 (MIP) [7].
  • Caenorhabditis elegans insulin-like peptides [8].

Structurally, all these peptides consist of two polypeptide chains (A and B) linked by two disulfide bonds.

        B chain         xxxxxxCxxxxxxxxxxxxCxxxxxxxxx
                              |            |
        A chain         xxxxxCCxxxCxxxxxxxxCx
                             ***************
                             |    |
                             +----+
'C': conserved cysteine involved in a disulfide bond.
'*': position of the pattern.

As shown in the schematic representation above, they all share a conserved arrangement of four cysteines in their A chain. The first of these cysteines is linked by a disulfide bond to the third one and the second and fourth cysteines are linked by interchain disulfide bonds to cysteines in the B chain. As a pattern for this family of proteins, we have used the region which includes the four conserved cysteines in the A chain.

Last update:

December 2004 / Pattern and text revised.

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Technical section

PROSITE method (with tools and information) covered by this documentation:

INSULIN, PS00262; Insulin family signature  (PATTERN)


References

1AuthorsBlundell T.L. Humbel R.E.
TitleHormone families: pancreatic hormones and homologous growth factors.
SourceNature 287:781-787(1980).
PubMed ID6107857

2AuthorsHumbel R.E.
TitleInsulin-like growth factors I and II.
SourceEur. J. Biochem. 190:445-462(1990).
PubMed ID2197088

3AuthorsAdham I.M. Burkhardt E. Benahmed M. Engel W.
TitleCloning of a cDNA for a novel insulin-like peptide of the testicular Leydig cells.
SourceJ. Biol. Chem. 268:26668-26672(1993).
PubMed ID8253799

4AuthorsChassin D. Laurent A. Janneau J.-L. Berger R. Bellet D.
TitleCloning of a new member of the insulin gene superfamily (INSL4) expressed in human placenta.
SourceGenomics 29:465-470(1995).
PubMed ID8666396

5AuthorsNagasawa H. Kataoka H. Isogai A. Tamura S. Suzuki A. Mizoguchi A. Fujiwara Y. Suzuki A. Takahashi S.Y. Ishizaki H.
SourceProc. Natl. Acad. Sci. U.S.A. 83:5480-5483(1986).

6AuthorsLagueux M. Lwoff L. Meister M. Goltzene F. Hoffmann J.A.
TitlecDNAs from neurosecretory cells of brains of Locusta migratoria (Insecta, Orthoptera) encoding a novel member of the superfamily of insulins.
SourceEur. J. Biochem. 187:249-254(1990).
PubMed ID1688797

7AuthorsSmit A.B. Geraerts W.P.M. Meester I. van Heerikhuizen H. Joosse J.
TitleCharacterization of a cDNA clone encoding molluscan insulin-related peptide II of Lymnaea stagnalis.
SourceEur. J. Biochem. 199:699-703(1991).
PubMed ID1868853

8AuthorsDuret L. Guex N. Peitsch M.C. Bairoch A.
TitleNew insulin-like proteins with atypical disulfide bond pattern characterized in Caenorhabditis elegans by comparative sequence analysis and homology modeling.
SourceGenome Res. 8:348-353(1998).
PubMed ID9548970

9AuthorsRobitzki A. Schroder H.C. Ugarkovic D. Pfeifer K. Uhlenbruck G. Muller W.E.G.
TitleDemonstration of an endocrine signaling circuit for insulin in the sponge Geodia cydonium.
SourceEMBO J. 8:2905-2909(1989).
PubMed ID2531072



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