BgK, a 37-residue peptide toxin from the sea anemone Bunodosoma granulifera,
and ShK, a 35-residue peptide toxin from the sea anemone Stichodactyla
helianthus, are potent inhibitors of K(+) channels. There is a large
superfamily of proteins that contains domains (referred to as ShKT domains)
ressembling these two toxins. Many of these proteins are metallopeptidases,
whereas others are prolyl-4-hydroxylases, tyrosinases (see <PDOC00398>),
peroxidases (see <PDOC00394>), oxidoreductases, or proteins containing
epidermal growth factor-like domains (see <PDOC00021>), thrombospondin-type
repeats (see <PDOC50092>), or trypsin-like serine protease domains (see
<PDOC00124>) [1]. The ShKT domain has also been called NC6 (nematode six-cysteine) domain [2], SXC (six-cysteine) domain [2,3,4,5] and ICR (ion channel
regulator) [1,6]. The ShKT domain is short (36 to 42 amino acids), with six
conserved cysteines and a number of other conserved residues. The fold adopted
by the ShKT domain contains two nearly perpendicular stretches of helices,
with no additional canonical secondary structures (see <PDB:1BGK>) [7]. The
globular architecture of the ShKT domain is stabilized by three disulfides,
one of them linking the two helices. In venomous creatures, the ShKT domain
may have been modified to give rise to potent ion channel blockers, whereas
the incorporation of this domain into plant oxidoreductases and prolyl
hydroxylases and into worm astacin-like metalloproteases and trypsin-like
serines protaeses produced enzymes with potential channel-modulatory activity.
Some proteins known to contain a ShKT domain are listed below:
Carribean sea anemone ShK, a potassium channel toxin [1].
Toxocara canis family of secreted mucins Tc-MUC-1 to -5, which are
implicated in immune evasion. They combine two evolutionarily distinct
modules, the mucin and ShkT domains [2,3].
Some Caenorhabditis elegans astacin-like proteins (nematode astacins, NAS),
metalloproteases [5].
Vertebrate cysteine-rich secretory proteins (Crisp) (see <PDOC00772>) [6].
Mammalian microfibrillar-associated protein 2 (MFAP2 or MAGP1), a matrix
protein.
Plant prolyl 4-hydroxylase.
The profile we developed covers the entire ShKT domain.
Loukas A. Hintz M. Linder D. Mullin N.P. Parkinson J. Tetteh K.K.A. Maizels R.M.
Title
A family of secreted mucins from the parasitic nematode Toxocara canis bears diverse mucin domains but shares similar flanking six-cysteine repeat motifs.
Dauplais M. Lecoq A. Song J. Cotton J. Jamin N. Gilquin B. Roumestand C. Vita C. de Medeiros C.L.C. Rowan E.G. Harvey A.L. Menez A.
Title
On the convergent evolution of animal toxins. Conservation of a diad of functional residues in potassium channel-blocking toxins with unrelated structures.
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