Conus ~ VenomZone

Cone snails are marine gastropod mollusks that are found in reef environments throughout the world. They prey upon other marine organisms such as annelids and polychaetes (vermivorous), mollusks (molluscivorous) or fish (piscivorous). To capture and immobilize their prey, they developed in their venom a variety of toxins (or conotoxins also called conopeptides) that inhibit a range of membrane bound receptors and ion channels. Even cone snails only feed of marine animals their toxins are also active against mammalian channels/receptors, making them valuable tools in medical research.

Each cone snail venom may contain up to 200 peptides (Olivera, 2006, Terlau and Olivera, 2004) and given that there are over 500 cone snail species (Olivera et al., 2012), the library of bioactive peptides is huge (about 10,000).

These bioactive peptides have been grouped structurally into superfamilies on the basis of similarities in precursor signal peptide sequences and the cysteine patterns of conotoxin mature peptide regions (cysteine frameworks), and in pharmacological families based on the specificity to molecular targets.

Conus textile (Image from Wikipedia / licensed under Creative Commons).

The table below shows the classification of conotoxins based on the pharmacological family.

Pharmacological family	UniProtKB entries	Activity (impairs function of)
Alpha-conotoxin		Nicotinic acetylcholine receptor (nAChR)
Chi-conotoxin		Neuronal noradrenaline transporter
Delta-conotoxin		Voltage-gated Na channel (agonist, delay inactivation)
Epsilon-conotoxin		Presynaptic Ca channel or G protein-coupled presynaptic receptor
Gamma-conotoxin		Neuronal pacemaker cation current (inward cation current)
Iota-conotoxin		Voltage-gated Na channel (agonist, no delayed inactivation)
Kappa-conotoxin		Voltage-gated K channel (blocker)
Mu-conotoxin		Voltage-gated Na channel (antagonist, blocker)
MuO-conotoxin		Voltage-gated Na channel (antagonist, voltage-gating modifier)
Omega-conotoxin		Voltage-gated Ca channel (blocker)
Rho-conotoxin		Alpha1-adrenoceptor (GPCR)
Sigma-conotoxin		Serotonin-gated ion channel (GPCR)
Conantokin		N-Methyl D-aspartate (NMDA) receptor

The table below shows the classification of conotoxins based on the cysteine framework.

Cysteine framework	number of cysteines	Cysteine pattern
I	4	CC-C-C
		α3/2 (CCxxxCxxC)
		α3/5 (CCxxxCxxxxxC)
		α4/2 (CCxxxxCxxC)
		α4/3 (CCxxxxCxxxC)
		α4/4 (CCxxxxCxxxxC)
		α4/5 (CCxxxxCxxxxxC)
		α4/6 (CCxxxxCxxxxxxC)
		α4/7 (CCxxxxCxxxxxxxC)
		α4/8 (CCxxxxCxxxxxxxxC)
		α5/5 (CCxxxxCxxxxxxxxC)
		α5/8 (CCxxxxxCxxxxxxxxC)
		α9/4 (CCxxxxxxxxxCxxxxC)
II	6	CCC-C-C-C
III	6	CC-C-C-CC
IV	6	CC-C-C-C-C
V	4	CC-CC
VI/VII	6	C-C-CC-C-C
VIII	10	C-C-C-C-C-C-C-C-C-C
IX	6	C-C-C-C-C-C
X	4	CC-CX[hydroxyPro]C
XI	8	C-C-CC-CC-C-C
XII	8	C-C-C-C-CC-C-C
XIII	8	C-C-C-CC-C-C-C
XIV	4	C-C-C-C
XV	8	C-C-CC-C-C-C-C
XVI	4	C-C-CC
XVII	8	C-C-CC-C-CC-C
XVIII	6	C-C-CC-CC
XIX	10	C-C-C-CCC-C-C-C-C
XX	10	C-CC-C-CC-C-C-C-C
XXI	10	CC-C-C-C-CC-C-C-C
XXII	8	C-C-C-C-C-C-C-C
XXIII	6	C-C-C-CC-C
XXIV	4	C-CC-C
XXV	6	C-C-C-C-CC
XXVI	8	C-C-C-C-CC-CC
XXVII	8	C-C-C-CCC-C-C
XXVIII	10	C-C-C-CC-C-C-C-C-C
XXIX	8	CCC-C-CC-C-C
XXX	6	C-C-CCC-C-C-C-CC
XXXII	6	C-CC-C-C-C
special cases
conantokin, contulakin, conorfamide, conomap, conophan, conolysin	0	no cysteine
conantokin, contulakin, conopressin, contryphan	2	C-C
conkunitzin	4	C-C-C-C
homodimer	5	C-C-C-C-C
	6	C-C-C-CC-C
	7	C-C-C-CC-C-C
	8	CCC-C-CC-C-C
	8	C-C-CCC-C-C-C
	8	C-C-C-C-C-C-CC
	9	C-C-C-C-C-C-C-C-C
	10	C-C-CC-CC-C-C-C-C
	13	CC-CC-C-C-C-CC-C-C-C-C

The table below shows the classification of conotoxins based on similarities in precursor signal peptide sequences.

Protein family or Superfamily in UniProtKB	UniProtKB entries
Conotoxin A superfamily
Conotoxin B superfamily
Conotoxin C superfamily
Conotoxin D superfamily
Conotoxin E superfamily
Conotoxin F superfamily
Conotoxin G superfamily
Conotoxin G2 superfamily
Conotoxin H superfamily
Conotoxin J superfamily
Conotoxin I1 superfamily
Conotoxin I2 superfamily
Conotoxin I3 superfamily
Conotoxin K superfamily
Conotoxin L superfamily
Conotoxin M superfamily
Conotoxin N superfamily
Conotoxin O1 superfamily
Conotoxin O2 superfamily
Conotoxin O3 superfamily
Conotoxin P superfamily
Conotoxin R superfamily
Conotoxin S superfamily
Conotoxin T superfamily
Conotoxin U superfamily
Conotoxin V superfamily
Conotoxin Y superfamily
Conotoxin NSf-1 superfamily


CRISP family
FARP (FMRFamide related peptide) family
NPY family
Venom Kunitz-type family
Phospholipase A2 family
Vasopressin/oxytocin family
Porin family

SUPERFAMILY:	Conoidea
Family:	Conidae
Genus:	Conus
Species:	californicus
Species:	consors
Species:	litteratus
Species:	ventricosus
Species:	textile

Conus

Venom protein entries in UniProtKB/Swiss-Prot

Conus abbreviatus (Abbreviated cone) (Miliariconus abbreviatus)

Conus achatinus (Little frog cone)

Conus adamsonii (Cone snail)

Conus amadis (Amadis cone)

Conus ammiralis (Admiral cone)

Conus anabathrum floridanus (Florida cone) (Conus floridanus floridensis)

Conus anemone (Anemone cone)

Conus araneosus (Cobweb cone)

Conus archon (Magistrate cone)

Conus arenatus (Sand-dusted cone)

Conus asiaticus (Cone snail)

Conus ateralbus (Cone snail)

Conus aulicus (Princely cone)

Conus aurisiacus (Aurisiacus cone)

Conus australis (Austral cone) (Asprella australis)

Conus bandanus (Banded marble cone)

Conus bayani (Bayan's cone) (Stellaconus bayani)

Conus betulinus (Beech cone)

Conus brunneus (Wood's brown cone)

Conus bullatus (Bubble cone)

Conus buxeus loroisii (Cone snail) (Conus loroisii)

Conus cancellatus (Cancellate cone) (Conus austini)

Conus capitaneus (Captain cone)

Conus caracteristicus (Characteristic cone)

Conus catus (Cat cone)

Conus consors (Singed cone)

Conus coronatus (Crowned cone)

Conus distans (Distant cone)

Conus ebraeus (Hebrew cone)

Conus eburneus (Ivory cone)

Conus emaciatus (False virgin cone)

Conus episcopatus (Bishop's cone)

Conus ermineus (Agate cone) (Chelyconus ermineus)

Conus ferrugineus (Cone snail)

Conus figulinus (Fig cone)

Conus flavidus (Yellow Pacific cone)

Conus floridulus (Cone snail) (Lividoconus floridulus)

Conus frigidus (Frigid cone)

Conus fulmen (Thunderbolt cone) (Chelyconus fulmen)

Conus generalis (General cone)

Conus geographus (Geography cone) (Nubecula geographus)

Conus gladiator (Gladiator cone)

Conus gloriamaris (Glory-of-the-Sea cone)

Conus grahami (Cone snail) (Africonus grahami)

Conus imperialis (Imperial cone)

Conus inscriptus (Engraved cone)

Conus kinoshitai (Kinoshita's cone)

Conus kintoki (Cone snail) (Virgiconus kintoki)

Conus lenavati (Cone snail)

Conus leopardus (Leopard cone)

Conus limpusi (Cone snail)

Conus litteratus (Lettered cone)

Conus lividus (Livid cone)

Conus lynceus (Lynceus cone)

Conus magnificus (Magnificent cone) (Darioconus magnificus)

Conus magus (Magical cone)

Conus maioensis (Sea snail) (Africonus maioensis)

Conus marmoreus (Marble cone)

Conus miles (Soldier cone) (Mile cone)

Conus miliaris (Thousand-spot cone)

Conus milneedwardsi (Glory of India cone snail)

Conus monachus (Cone snail)

Conus moncuri (Sea snail)

Conus monile (Necklace cone)

Conus mus (Mouse cone)

Conus mustelinus (Weasel cone)

Conus natalis (Natal textile cone)

Conus neocostatus (Cone snail) (Asprella neocostatus)

Conus nigropunctatus (Black-spot cone)

Conus obscurus (Obscure cone) (Conus halitropus)

Conus ochroleucus (Perfect cone) (Graphiconus ochroleucus)

Conus omaria (Omaria cone)

Conus parius (Cone snail)

Conus pennaceus (Feathered cone) (Conus episcopus)

Conus pergrandis (Grand cone)

Conus pictus (Cone snail)

Conus planorbis (Planorbis cone)

Conus princeps (Prince cone)