****************************
* 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].
 - Insect prothoracicotropic hormone (PTTH) (bombyxin) [3].
 - Locust insulin-related peptide (LIRP) [4].
 - Molluscan insulin-related peptides 1 and 2 (MIP) [5].

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-x(3)-C-x(4)-[LIVMF]-x(3)-C
                    [The four C's are involved in disulfide bonds]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for a sponge insulin [6] which lacks the first cysteine of the A chain.
-Other sequence(s) detected in SWISS-PROT: NONE.
-Last update: June 1992 / Pattern and text revised.

[ 1] Blundell T.L., Humbel R.E.
     Nature 287:781-787(1980).
[ 2] Humbel R.E.
     Eur. J. Biochem. 190:445-462(1990).
[ 3] 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).
[ 4] Lagueux M., Lwoff L., Meister M., Goltzene F., Hoffmann J.A.
     Eur. J. Biochem. 187:249-254(1990).
[ 5] Smit A.B., Geraerts W.P.M., Meester I., van Heerikhuizen H., Joosse J.
     Eur. J. Biochem. 199:699-703(1991).
[ 6] Robitzki A., Schroder H.C., Ugarkovic D., Pfeifer K., Uhlenbruck G.,
     Muller W.E.G.
     EMBO J. 8:2905-2909(1989).