{PDOC00235} {PS00262; INSULIN} {BEGIN} **************************** * 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. -Consensus pattern: C-C-{P}-{P}-x-C-[STDNEKPI]-x(3)-[LIVMFS]-x(3)-C [The 4 C's are involved in disulfide bonds] -Sequences known to belong to this class detected by the pattern: ALL, except for what was thought to be a sponge insulin [9], but which originates from an unidentified rodent and which contains sequencing errors and lacks the first cysteine of the A chain. -Other sequence(s) detected in Swiss-Prot: 1. -Last update: December 2004 / Pattern and text revised. [ 1] Blundell T.L., Humbel R.E. "Hormone families: pancreatic hormones and homologous growth factors." Nature 287:781-787(1980). PubMed=6107857 [ 2] Humbel R.E. "Insulin-like growth factors I and II." Eur. J. Biochem. 190:445-462(1990). PubMed=2197088 [ 3] Adham I.M., Burkhardt E., Benahmed M., Engel W. "Cloning of a cDNA for a novel insulin-like peptide of the testicular Leydig cells." J. Biol. Chem. 268:26668-26672(1993). PubMed=8253799 [ 4] Chassin D., Laurent A., Janneau J.-L., Berger R., Bellet D. "Cloning of a new member of the insulin gene superfamily (INSL4) expressed in human placenta." Genomics 29:465-470(1995). PubMed=8666396 [ 5] Nagasawa H., Kataoka H., Isogai A., Tamura S., Suzuki A., Mizoguchi A., Fujiwara Y., Suzuki A., Takahashi S.Y., Ishizaki H. Proc. Natl. Acad. Sci. U.S.A. 83:5480-5483(1986). [ 6] Lagueux M., Lwoff L., Meister M., Goltzene F., Hoffmann J.A. "cDNAs from neurosecretory cells of brains of Locusta migratoria (Insecta, Orthoptera) encoding a novel member of the superfamily of insulins." Eur. J. Biochem. 187:249-254(1990). PubMed=1688797 [ 7] Smit A.B., Geraerts W.P.M., Meester I., van Heerikhuizen H., Joosse J. "Characterization of a cDNA clone encoding molluscan insulin-related peptide II of Lymnaea stagnalis." Eur. J. Biochem. 199:699-703(1991). PubMed=1868853 [ 8] Duret L., Guex N., Peitsch M.C., Bairoch A. "New insulin-like proteins with atypical disulfide bond pattern characterized in Caenorhabditis elegans by comparative sequence analysis and homology modeling." Genome Res. 8:348-353(1998). PubMed=9548970 [ 9] Robitzki A., Schroder H.C., Ugarkovic D., Pfeifer K., Uhlenbruck G., Muller W.E.G. "Demonstration of an endocrine signaling circuit for insulin in the sponge Geodia cydonium." EMBO J. 8:2905-2909(1989). PubMed=2531072 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}