1.C.112 The Cubozoan Protein Toxin (CPT) Family Class Cubozoa includes several species of box jellyfish that are harmful to humans and other animals. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. Accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). Novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as alpha-pore-forming toxins. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components were reviewed by Brinkman and Burnell 2009 with emphasis on cubozoan cytolysins and other box jellyfish toxins.
References:
Andreosso, A., P.S. Bansal, M.J. Smout, D. Wilson, J.E. Seymour, and N.L. Daly. (2018). Structural Characterisation of Predicted Helical Regions in the CfTX-1 Toxin. Mar Drugs 16:.
Brinkman DL., Konstantakopoulos N., McInerney BV., Mulvenna J., Seymour JE., Isbister GK. and Hodgson WC. (2014). Chironex fleckeri (box jellyfish) venom proteins: expansion of a cnidarian toxin family that elicits variable cytolytic and cardiovascular effects. J Biol Chem. 289(8):4798-812.
Brinkman, D. and J. Burnell. (2007). Identification, cloning and sequencing of two major venom proteins from the box jellyfish, Chironex fleckeri. Toxicon 50: 850-860.
Brinkman, D.L. and J.N. Burnell. (2009). Biochemical and molecular characterisation of cubozoan protein toxins. Toxicon 54: 1162-1173.
Law, Y.H. (2018). Stopping the sting. Science 362: 631-635.
Nagai, H., K. Takuwa, M. Nakao, B. Sakamoto, G.L. Crow, and T. Nakajima. (2000). Isolation and characterization of a novel protein toxin from the Hawaiian box jellyfish (sea wasp) Carybdea alata. Biochem. Biophys. Res. Commun. 275: 589-594.
Nagai, H., K. Takuwa, M. Nakao, E. Ito, M. Miyake, M. Noda, and T. Nakajima. (2000). Novel proteinaceous toxins from the box jellyfish (sea wasp) Carybdea rastoni. Biochem. Biophys. Res. Commun. 275: 582-588.
Tibballs, J., A.A. Yanagihara, H.C. Turner, and K. Winkel. (2011). Immunological and toxinological responses to jellyfish stings. Inflamm Allergy Drug Targets 10: 438-446.
Examples:
TC#	Name	Organismal Type	Example
1.C.112.1.1	Cubozoan toxin, CaTX-A of 463 aas. This toxin has potent hemolytic activity, is lethal to crayfish. causes cutaneous inflammation in humans, and may act as a pore-forming toxin, disrupting normal transmembrane ion concentration gradients in susceptible cells (Nagai et al. 2000; Brinkman and Burnell 2009).	Animals (Jellyfish)	CaTX-A of Carybdea alata

1.C.112.1.2	*Toxin A of 454 aas; causes cardiiovascular and cytotoxic effects (Brinkman et al.* 2014).**		Toxin A of Chironex fleckeri

1.C.112.1.3	Toxin TX1 of 486 aas and 2 - 4 N-terminal α-helical TMSs, possibly with up to 15 C-terminal transmembrane β-strands (Law 2018).	Animals	Toxin TX1 of Aurelia aurita

1.C.112.1.4	C. fleckeri toxin-1 (CfTX-1) of 456 aas, one of the two most abundant proteins found in the nematocysts of the box jellyfish Chironex fleckeri. One or more of the 5 possible α-helical TMSs may be involved in pore-formation. May be similar to pore-forming insecticidal delta-endotoxins Cry1Aa, Cry3Bb and Cry3A (Brinkman and Burnell 2007). The transmembrane region(s) in CfTX-1 have been predicted on the basis of the behavior of peptides corresponding in sequence to two regions (Andreosso et al. 2018).		*CfTX-1 of Chironex fleckeri* (Box jellyfish)**

1.C.112.1.5	*Toxin B precursor, TX-B, of 461 aas and 2 - 4 N-terminal TMSs and up to 15 C-termnal β-strands (Tibballs et al.* 2011) .**		*TXB of Chironex fleckeri* (Box jellyfish)**

1.C.112.1.6	Toxin CaTx-A of 446 aas.		CaTx-A of Exaiptasia pallida

1.C.112.1.7	Uncharacterized toxin of 420 aas.		UP of Crassostrea gigas (Pacific oyster) (Crassostrea angulata)

1.C.112.1.8	Uncharacterized protein of 292 aas and 2 - 4 TMSs.		UP of Stylophora pistillata

1.C.112.1.9	CrTx-A cytotoxin of 450 aas with 4 probable TMSs, one at the N-terminus, two at about residue110, and a fourth at about residue 230. It has potent hemolytic activity and is lethal to mice and crayfish (Nagai et al. 2000). It causes cutaneous inflammation in humans and may act as a pore-forming toxin, disrupting normal transmembrane ion concentration gradients in susceptible cells.		CrTx-A of Carybdea rastonii (Box jellyfish)

Examples:
TC#	Name	Organismal Type	Example