{PDOC60026}
{PS60026; ERGTX}
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* Ergtoxin (ErgTx) family signature *
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The Ergtoxin  (ErgTx)  family  is a class of peptides from scorpion venom that
specifically block  ERG (ether-a-go-go-related gene) K+ channels of the nerve,
heart and endocrine cells [1 to 3].

Peptides of  the  ErgTx  family  have from 42 to 47 amino acid residues cross-
linked by  four  disulfide  bridges.  The  four  disulfide  bridges  have been
assigned as  C1-C4,  C2-C6,  C3-C7 and C5-C8 (see the schematic representation
below) [1].  ErgTxs consist of a triple-stranded beta-sheet and an alpha-helix
(see <PDB:1NE5>),  as  is  typical  of  K+ channel scorpion toxins. There is a
large hydrophobic  patch  on  the  surface of the toxin, surrounding a central
lysine residue located near the beta-hairpin loop between the second and third
strands of  the beta-sheet. It has been postulated that this hydrophobic patch
is likely to form part of the binding surface of the toxin [2]. Peptides of
the ErgTx family possess a Knottin scaffold (see <PDOC60004>) [E1].

                                        +------------+
                                        #            #
                        CxxxxCxxxxxCxxxCCxxxCxxxCxxxxC
                        |    |     |   |    |   |
                        |    |     +---|----|---+
                        |    +---------|----+
                        +--------------+

'C': conserved cysteine involved in a disulfide bond.
'#': positions of the cysteine, which are not involved in knottin scaffold.

Some proteins known to belong to the ErgTx family are listed below:

 - ErgTx1, ErgTx2 and ErgTx3 from Centruroides elegans (Bark scorpion).
 - ErgTx1,  ErgTx2,  ErgTx3  and  ErgTx4  from  Centruroides  exilicauda (Bark
   scorpion).
 - ErgTx1,   ErgTx2   and  ErgTx3  from  Centruroides  gracilis  (Slenderbrown
   scorpion) (Florida bark scorpion).
 - ErgTx1,  ErgTx2,  ErgTx3  and  ErgTx4  from  Centruroides limpidus limpidus
   (Mexican scorpion).
 - ErgTx1, ErgTx2, ErgTx3, ErgTx4, ErgTx5 and Gamma-KTx 4.12 from Centruroides
   sculpturatus (Bark scorpion).
 - ErgTx,  ErgTx2, ErgTx3, ErgTx4 and ErgTx5 from Centruroides noxius (Mexican
   scorpion).

We have developed a pattern that contains the eight conserved cysteines.

-Conserved pattern: C-x(5)-C-x-K-X(6)-C-x(2)-C-C-x(9)-C-x(4)-C-x-C
                    [The 8 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.

-Expert(s) to contact by email:
           Ramakumar S.; ramak@physics.iisc.ernet.in

-Last update: January 2006 / First entry.

[ 1] Scaloni A., Bottiglieri C., Ferrara L., Corona M., Gurrola G.B.,
     Batista C., Wanke E., Possani L.D.
     "Disulfide bridges of ergtoxin, a member of a new sub-family of
     peptide blockers of the ether-a-go-go-related K+ channel."
     FEBS. Lett. 479:156-157(2000).
     PubMed=11023354
[ 2] Torres A.M., Bansal P., Alewood P.F., Bursill J.A., Kuchel P.W.,
     Vandenberg J.I.
     "Solution structure of CnErg1 (Ergtoxin), a HERG specific scorpion
     toxin."
     FEBS. Lett. 539:138-142(2003).
     PubMed=12650941
[ 3] Corona M., Gurrola G.B., Merino E., Cassulini R.R., Valdez-Cruz N.A.,
     Garcia B., Ramirez-Dominguez M.E., Coronas F.I.V., Zamudio F.Z.,
     Wanke E., Possani L.D.
     "A large number of novel Ergtoxin-like genes and ERG K+-channels
     blocking peptides from scorpions of the genus Centruroides."
     FEBS. Lett. 532:121-126(2002).
     PubMed=12459475
[E1] https://bioserv.cbs.cnrs.fr

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