ShK proteins are named after a toxin from the sea anemone Stichodactyla helianthus that blocks a voltage-gated potassium channel (Kv) (Tudor et al., 1998). In helminths, this motif had previously been discovered in the Maizels Lab by David Gems in the intestinal nematode Toxocara canis (Gems et al., 1995; Gems et al. 1996). The domain was characterised as a 6-Cysteine 36-amino acid module that was found in non-identical repeats fused to the phosphatidylethanolamine-binding protein module in the secreted TES-26 (Gems et al., 1995), and to multiple secreted TES-120 mucins (Gems et al., 1996). The original name of NC6 (Nematode Cys-6) was for a short time replaced by SXC (SiX Cysteine).The original name “NC6” was for a short time replaced by “SXC” but now conventionally referred to as ShK.
An ShK from the filarial nematode Brugia malayi has been trialled as a novel anti-inflammatory agent that blocks the Kv channel in T cells (Chhabra et al., 2014)
A prominent ShK from the enteropathogenic nematode Steinernema carpocapsae, is Sc-ShK-1 which when injected into Drosophila fruitflies, compromises their immunity to bacterial pathogens (Lima et al., 2022).
Chhabra, S., Chang, S.C., Nguyen, H.M., Huq, R., Tanner, M.R., Londono, L.M., Estrada, R., Dhawan, V., Chauhan, S., Upadhyay, S.K., Gindin, M., Hotez, P.J., Valenzuela, J.G., Mohanty, B., Swarbrick, J.D., Wulff, H., Iadonato, S.P., Gutman, G.A., Beeton, C., Pennington, M.W., Norton, R.S. and Chandy, K.G. (2014). Kv1.3 channel-blocking immunomodulatory peptides from parasitic worms: implications for autoimmune diseases. FASEB J 28(9): 3952-3964. http://www.ncbi.nlm.nih.gov/pubmed/24891519
Gems, D.H., Ferguson, C.J., Robertson, B.D., Nieves, R., Page, A.P., Blaxter, M.L. and Maizels, R.M. (1995). An abundant, trans-spliced mRNA from Toxocara canis infective larvae encodes a 26 kDa protein with homology to phosphatidylethanolamine binding proteins. Journal of Biological Chemistry 270: 18517-18522.
Gems, D.H. and Maizels, R.M. (1996). An abundantly expressed mucin-like protein from Toxocara canis infective larvae: the precursor of the larval surface coat glycoproteins. Proceedings of the National Academy of Sciences USA 93: 1665-1670.
Lima, A.K., Dhillon, H. and Dillman, A.R. (2022). ShK-domain-containing protein from a parasitic nematode modulates Drosophila melanogaster immunity. Pathogens 11(10). PMC9610955 10.3390/pathogens11101094. https://www.ncbi.nlm.nih.gov/pubmed/36297151
Tudor, J.E., Pennington, M.W. and Norton, R.S. (1998). Ionisation behaviour and solution properties of the potassium-channel blocker ShK toxin. Eur J Biochem 251(1-2): 133-141.