8.B.40.  The Conotoxin (Con-ikot-ikot/Conopressin/Conophysin/Conokunitzin/ConoCAP) (CCCCC) Family

  The precursor proteins of this family mostly consist of large conotoxins of ~ 125 aas with an N-terminal TMS. They have been named as noted in the title of the paper by Robinson and Norton 2014. Conus snail polypeptides cause excitotoxicity by blocking desensitization of AMPA receptors (Walker et al. 2009). 9.3 KDa components of the injected venom of Conus purpurascens define a new five-disulfide conotoxin framework (Möller and Marí 2011). There are many conotoxins (Sudewi et al. 2019; Zamora-Bustillos et al. 2021).

This family belongs to the Conotoxin Superfamily.



Möller, C. and F. Marí. (2011). 9.3 KDa components of the injected venom of Conus purpurascens define a new five-disulfide conotoxin framework. Biopolymers 96: 158-165.

Moreno, E., C. Tovar-Palacio, P. de los Heros, B. Guzmán, N.A. Bobadilla, N. Vázquez, D. Riccardi, E. Poch, and G. Gamba. (2004). A single nucleotide polymorphism alters the activity of the renal Na+:Cl- cotransporter and reveals a role for transmembrane segment 4 in chloride and thiazide affinity. J. Biol. Chem. 279: 16553-16560.

Peng, C., G. Yao, B.M. Gao, C.X. Fan, C. Bian, J. Wang, Y. Cao, B. Wen, Y. Zhu, Z. Ruan, X. Zhao, X. You, J. Bai, J. Li, Z. Lin, S. Zou, X. Zhang, Y. Qiu, J. Chen, S.L. Coon, J. Yang, J.S. Chen, and Q. Shi. (2016). High-throughput identification of novel conotoxins from the Chinese tubular cone snail (Conus betulinus) by multi-transcriptome sequencing. Gigascience 5: 17.

Robinson, S.D. and R.S. Norton. (2014). Conotoxin gene superfamilies. Mar Drugs 12: 6058-6101.

Sudewi, A.A.R., N.M. Susilawathi, B.K. Mahardika, A.N. Mahendra, M. Pharmawati, M.A. Phuong, and G.N. Mahardika. (2019). Selecting Potential Neuron.al Drug Leads from Conotoxins of Various Venomous Marine Cone Snails in Bali, Indonesia. ACS Omega 4: 19483-19490.

Walker, C.S., S. Jensen, M. Ellison, J.A. Matta, W.Y. Lee, J.S. Imperial, N. Duclos, P.J. Brockie, D.M. Madsen, J.T. Isaac, B. Olivera, and A.V. Maricq. (2009). A novel Conus snail polypeptide causes excitotoxicity by blocking desensitization of AMPA receptors. Curr. Biol. 19: 900-908.

Zamora-Bustillos, R., M.A. Martínez-Núñez, M.B. Aguilar, R.C. Collí-Dula, and D.A. Brito-Domínguez. (2021). Identification of Novel Conotoxin Precursors from the Cone Snail by High-Throughput RNA Sequencing. Mar Drugs 19:.


TC#NameOrganismal TypeExample

Con-ikot-ikot conotoxin of 123 aas and 1 N-terminal TMS. It exists as a dimer and inhibits AMPA receptor desensitization (Walker et al. 2009) and possibly ionotropic glutamate receptors (Robinson and Norton 2014).

Con-ikot-ikot of Conus striatus (Striated cone)


Conotoxin of 108 aas and 1 N-terminal TMS (Peng et al. 2016).

Conotoxin of Conus betulinus


Conotoxin of 117 aa

Conotoxin of Conus praecellens


TC#NameOrganismal TypeExample