{PDOC60016}
{PS60016; OMEGA_ACTX_1}
{PS60017; OMEGA_ACTX_2}
{BEGIN}
************************************************
* Omega-atracotoxin (ACTX) families signatures *
************************************************

Omega-atracotoxins (ACTX)  form  a family of neurotoxins that block insect but
not vertebrate voltage-gated calcium channels. Omega-ACTXs are environmentally
benign, insect-specific   toxins   that  represent  excellent  leads  for  the
development of  new  pesticides.  Omega-ACTXs comprise a disulfide-rich region
that has  a  [C-C-CC-C-C]  arrangement  and  possess  a  Knottin scaffold (see
<PDOC60004>) [1,2,3,4,5].

The omega-ACTX  type  1  family  contains  36  to 37-residue toxins with three
highly conserved   but  structurally  disordered  N-terminal  residues,  which
precede the  first  cysteine  residue  (see <PDB:1AXH>) [1,2,3,5]. This family
includes:

 - Omega-ACTX Hv1a, Hv1b, Hv1c, Hv1d, Hv1e, Hv1f from Hadronyche versuta (Blue
   mountains funnel-web spider) (Atrax versutus),
 - Omega-ACTX Ar1a from Atrax robustus (Funnel-web spider),
 - Omega-missulenatoxin-Mb1a from Missulena bradleyi (Eastern mouse spider).

The omega-ACTX  type  2  family  contains  43  to  45-residue  toxins  with  a
disordered C-terminal lipophilic extension (see <PDB:1G9P>) [4,5]. This family
includes:

 - Omega-ACTX  Hv2a from Hadronyche versuta (Blue mountains funnel-web spider)
   (Atrax versutus),
 - Omega ACTX As2a, As2b from Atrax sp. Illawarra (Funnel-web spider),
 - Omega  ACTX  Hi2a,  Hi2b  from Hadronyche infensa (Fraser island funnel-web
   spider).

                                   +------------------+
                                   |                  |
                      ********     ######             |
                   xxxCxxxxxxCxxxxxCCxxxCxxxxxxxxxxxxxC
                      |      |      |   |
                      +------|------+   |
                             +----------+

'C': conserved cysteine involved in a disulfide bond.
'*': position of the pattern for type 1.
'#': position of the pattern for type 2.

We developed two signature patterns for omega-ACTXs, one for the type 1 family
and one for the type 2 family.

-Conserved pattern: C-[IT]-P-S-G-Q-P-C
                    [The 2 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.

-Conserved pattern: C-C-[GE]-[ML]-T-P-x-C
                    [The 3 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: June 2005 / First entry.

[ 1] Fletcher J.I., Smith R., O'Donoghue S.I., Nilges M., Connor M.,
     Howden M.E.H., Christie M.J., King G.F.
     "The structure of a novel insecticidal neurotoxin,
     omega-atracotoxin-HV1, from the venom of an Australian funnel web
     spider."
     Nat. Struct. Biol. 4:559-566(1997).
     PubMed=9228949
[ 2] Wang X., Smith R., Fletcher J.I., Wilson H., Wood C.J., Howden M.E.H.,
     King G.F.
     "Structure-function studies of omega-atracotoxin, a potent antagonist
     of insect voltage-gated calcium channels."
     Eur. J. Biochem. 264:488-494(1999).
     PubMed=10491095
[ 3] Tedford H.W., Gilles N., Menez A., Doering C.J., Zamponi G.W.,
     King G.F.
     "Scanning mutagenesis of omega-atracotoxin-Hv1a reveals a spatially
     restricted epitope that confers selective activity against insect
     calcium channels."
     J. Biol. Chem. 279:44133-44140(2004).
     PubMed=15308644; DOI=10.1074/jbc.M404006200
[ 4] Wang X., Connor M., Wilson D., Wilson H.I., Nicholson G.M.,
     Smith R., Shaw D., Mackay J.P., Alewood P.F., Christie M.J.,
     King G.F.
     "Discovery and structure of a potent and highly specific blocker of
     insect calcium channels."
     J. Biol. Chem. 276:40306-40312(2001).
     PubMed=11522785; DOI=10.1074/jbc.M105206200
[ 5] Corzo G., Escoubas P.
     "Pharmacologically active spider peptide toxins."
     Cell. Mol. Life Sci. 60:2409-2426(2003).
     PubMed=14625686; DOI=10.1007/s00018-003-3108-6
[E1] https://bioserv.cbs.cnrs.fr

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