PROSITE documentation PDOC51670
ShKT domain profile


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].
  • Sea anemone BgK, a potassium channel toxin [7].
  • 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.

Last update:

April 2013 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

SHKT, PS51670; ShKT domain profile  (MATRIX)


1AuthorsRangaraju S. Khoo K.K. Feng Z.-P. Crossley G. Nugent D. Khaytin I. Chi V. Pham C. Calabresi P. Pennington M.W. Norton R.S. Chandy K.G.
TitlePotassium channel modulation by a toxin domain in matrix metalloprotease 23.
SourceJ. Biol. Chem. 285:9124-9136(2010).
PubMed ID19965868

2AuthorsLoukas A. Hintz M. Linder D. Mullin N.P. Parkinson J. Tetteh K.K.A. Maizels R.M.
TitleA family of secreted mucins from the parasitic nematode Toxocara canis bears diverse mucin domains but shares similar flanking six-cysteine repeat motifs.
SourceJ. Biol. Chem. 275:39600-39607(2000).
PubMed ID10950959

3AuthorsDoedens A. Loukas A. Maizels R.M.
TitleA cDNA encoding Tc-MUC-5, a mucin from Toxocara canis larvae identified by expression screening.
SourceActa Trop. 79:211-217(2001).
PubMed ID11412804

4AuthorsBlaxter M.
TitleCaenorhabditis elegans is a nematode.
SourceScience 282:2041-2046(1998).
PubMed ID9851921

5AuthorsMoehrlen F. Hutter H. Zwilling R.
TitleThe astacin protein family in Caenorhabditis elegans.
SourceEur. J. Biochem. 270:4909-4920(2003).
PubMed ID14653817

6AuthorsGibbs G.M. Scanlon M.J. Swarbrick J. Curtis S. Gallant E. Dulhunty A.F. O'Bryan M.K.
TitleThe cysteine-rich secretory protein domain of Tpx-1 is related to ion channel toxins and regulates ryanodine receptor Ca2+ signaling.
SourceJ. Biol. Chem. 281:4156-4163(2006).
PubMed ID16339766

7AuthorsDauplais 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.
TitleOn the convergent evolution of animal toxins. Conservation of a diad of functional residues in potassium channel-blocking toxins with unrelated structures.
SourceJ. Biol. Chem. 272:4302-4309(1997).
PubMed ID9020148

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