PROSITE documentation PDOC00235Insulin 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.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Blundell T.L. Humbel R.E. |
| Title | Hormone families: pancreatic hormones and homologous growth factors. | |
| Source | Nature 287:781-787(1980). | |
| PubMed ID | 6107857 |
| 2 | Authors | Humbel R.E. |
| Title | Insulin-like growth factors I and II. | |
| Source | Eur. J. Biochem. 190:445-462(1990). | |
| PubMed ID | 2197088 |
| 3 | Authors | Adham I.M. Burkhardt E. Benahmed M. Engel W. |
| Title | Cloning of a cDNA for a novel insulin-like peptide of the testicular Leydig cells. | |
| Source | J. Biol. Chem. 268:26668-26672(1993). | |
| PubMed ID | 8253799 |
| 4 | Authors | Chassin D. Laurent A. Janneau J.-L. Berger R. Bellet D. |
| Title | Cloning of a new member of the insulin gene superfamily (INSL4) expressed in human placenta. | |
| Source | Genomics 29:465-470(1995). | |
| PubMed ID | 8666396 |
| 5 | Authors | Nagasawa H. Kataoka H. Isogai A. Tamura S. Suzuki A. Mizoguchi A. Fujiwara Y. Suzuki A. Takahashi S.Y. Ishizaki H. |
| Source | Proc. Natl. Acad. Sci. U.S.A. 83:5480-5483(1986). |
| 6 | Authors | Lagueux M. Lwoff L. Meister M. Goltzene F. Hoffmann J.A. |
| Title | cDNAs from neurosecretory cells of brains of Locusta migratoria (Insecta, Orthoptera) encoding a novel member of the superfamily of insulins. | |
| Source | Eur. J. Biochem. 187:249-254(1990). | |
| PubMed ID | 1688797 |
| 7 | Authors | Smit A.B. Geraerts W.P.M. Meester I. van Heerikhuizen H. Joosse J. |
| Title | Characterization of a cDNA clone encoding molluscan insulin-related peptide II of Lymnaea stagnalis. | |
| Source | Eur. J. Biochem. 199:699-703(1991). | |
| PubMed ID | 1868853 |
| 8 | Authors | Duret L. Guex N. Peitsch M.C. Bairoch A. |
| Title | New insulin-like proteins with atypical disulfide bond pattern characterized in Caenorhabditis elegans by comparative sequence analysis and homology modeling. | |
| Source | Genome Res. 8:348-353(1998). | |
| PubMed ID | 9548970 |
| 9 | Authors | Robitzki A. Schroder H.C. Ugarkovic D. Pfeifer K. Uhlenbruck G. Muller W.E.G. |
| Title | Demonstration of an endocrine signaling circuit for insulin in the sponge Geodia cydonium. | |
| Source | EMBO J. 8:2905-2909(1989). | |
| PubMed ID | 2531072 |
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