{PDOC00243}
{PS00270; ENDOTHELIN}
{BEGIN}
*******************************
* Endothelin family signature *
*******************************

Endothelins (ET's) are a family  of  potent mammalian vasoconstrictor peptides
[1,2,3]. Sarafotoxins (SRTX) and bibrotoxin (BTX) are  cardiotoxins  from  the
venom of snakes of the Atractaspis family, structurally and functionally [4,5]
similar to  endothelin.  The  peptides  currently  known  to  belonging to the
ET/SRTX family are:

 - Endothelin 1 (ET-1).
 - Endothelin 2 (ET-2) which  is  also known in mouse as Vasoactive Intestinal
   Contractor (VIC).
 - Endothelin 3 (ET-3).
 - Sarafotoxins SRTX-A, -B, -C and -D from Atractaspis engaddensis.
 - Bibrotoxin (BTX) from Atractaspis bibroni.

As shown in the  following schematic  representation, these peptides which are
21 residues long contain two intramolecular disulfide bonds.

                        +-------------+
                        |             |
                        CxCxxxxxxxCxxxCxxxxxx
                          |       |
                          +-------+

'C': conserved cysteine involved in a disulfide bond.

As a  signature  pattern  for  this  family  of  proteins,  we  have taken the
conserved residues in the disulfide loops region.

-Consensus pattern: C-x-C-x(4)-D-x(2)-C-x(2)-[FY]-C
                    [The 4 C's are involved in disulfide bonds]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Note: In addition to endothelin, the precursors of ETs contain an endothelin-
 like domain which is also detected by this pattern.
-Note: The precursor of sarafotoxins is  a  large  protein  that  contains  12
 copies of various isoforms of the toxin [6].

-Last update: May 2004 / Text revised.

[ 1] Yanagisawa M., Masaki T.
     "Molecular biology and biochemistry of the endothelins."
     Trends Pharmacol. Sci. 10:374-378(1989).
     PubMed=2690429
[ 2] Simonson M.S., Dunn M.J.
     "Cellular signaling by peptides of the endothelin gene family."
     FASEB J. 4:2989-3000(1990).
     PubMed=2168326
[ 3] Rubanyi G.M., Parker Botelho L.H.
     "Endothelins."
     FASEB J. 5:2713-2720(1991).
     PubMed=1916094
[ 4] Kloog Y., Sokolovsky M.
     "Similarities in mode and sites of action of sarafotoxins and
     endothelins."
     Trends Pharmacol. Sci. 10:212-214(1989).
     PubMed=2549664
[ 5] Sokolovsky M.
     "Endothelins and sarafotoxins: physiological regulation, receptor
     subtypes and transmembrane signaling."
     Trends Biochem. Sci. 16:261-264(1991).
     PubMed=1656557
[ 6] Ducancel F., Matre V., Dupont C., Lajeunesse E., Wollberg Z.,
     Bdolah A., Kochva E., Boulain J.C.C., Menez A.
     "Cloning and sequence analysis of cDNAs encoding precursors of
     sarafotoxins. Evidence for an unusual 'rosary-type' organization."
     J. Biol. Chem. 268:3052-3055(1993).
     PubMed=8428983

--------------------------------------------------------------------------------
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}