{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
{END}