PROSITE documentation PDOC00235
Insulin family signature


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.


Technical section

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

INSULIN, PS00262; Insulin family signature  (PATTERN)


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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