Voltage-gated calcium channel impairing toxin ~ VenomZone

Channel Voltage-gated calcium channels (Cav) are the key signal transducers of electrical signaling, converting depolarization of the cell membrane to an influx of calcium ions that initiates contraction, secretion, neurotransmission and other intracellular regulatory events. Skeletal muscle calcium channels first identified by drug labeling, purification, and functional reconstitution have a principal α1 subunit of 212-250 kDa.

The α1 subunit is associated with auxiliary α2, β, γ and δ subunits. The calcium channel α1 subunit is sufficient to form a voltage-gated calcium-selective pore by itself. Ten functional calcium channel α1 subunits are known in vertebrates, and they fall into three subfamilies that differ in function and regulation. The Cav1 subfamily (Cav1.1-Cav1.4) conducts L-type calcium currents that initiate contraction, endocrine secretion, and synaptic transmission at the specialized ribbon synapses involved in sensory input in the eye and ear. L-type calcium currents also are important regulators of gene expression and other intracellular processes. They are blocked by the classical calcium channel antagonists, including dihydropyridines, benzothiazepines, and phenylalkylamines. The Cav2 subfamily of calcium channels (Cav2.1-Cav2.3) conduct N-, P/Q- and R-type calcium currents that initiate fast synaptic transmission at synapses in the central and peripheral nervous systems and are blocked specifically by peptide neurotoxins from spider and cone snail venoms. The Cav3 subfamily of calcium channels (Cav3.1-Cav3.3) conduct T-type calcium currents that are important for repetitive action potential firing of neurons in the brain and in the pacemaker cells of the sino-atrial node in the heart. The protein-protein interactions as well as the functional and regulatory properties of different subfamilies of these ion channels are adapted to their distinct roles in electrical signaling and cellular signal transduction.

Cav1 and Cav2 channels have four distinct auxiliary subunits (Cavα2, Cavβ, Cavγ, and Cavδ), whereas Cav3 channels have none. Each subunits of Cav1 and Cav2 channels comprise a small protein family. The Cavα2 and Cavδ subunits are encoded by the same gene, whose translation product is proteolytically cleaved and disulfide linked to yield the mature extracellular α2 subunit glycoprotein of 140 kDa and transmembrane disulfide-linked δ subunit glycoprotein of 27 kDa. Four Cavα2δ genes are known. The four Cavβ subunits are all intracellular proteins with a common pattern of α helical and unstructured segments. They have important regulatory effects on cell surface expression and they also modulate the gating of calcium channels, causing enhanced activation upon depolarization and altered rate and voltage dependence of inactivation. Recent structural modeling and X-ray crystallography studies have revealed that these subunits contain conserved, interacting SH3 and guanylate kinase domains like the MAGUK family of scaffolding proteins, and therefore may interact with other intracellular proteins. Eight Cavγ subunit genes encode glycoproteins with four transmembrane segments. Although the Cavγ1 subunit is associated specifically with skeletal muscle Cav1.1 channels, other Cavγ subunits interact with other calcium channels, glutamate receptors and possibly with other membrane signaling proteins. Thus, the γ subunits discovered as components of calcium channels apparently have a more widespread role in assembly and cell surface expression of other membrane signaling proteins. Cav3 channels do not have auxiliary subunits.

Toxin

	Cav channels	Toxins from different taxa that target Cav channels. Click on to retrieve channels and toxins of interest.
	Human	Snake	Scorpion	Cone snail	Spider	Cnidarian	Insect	Other	All
Cav1.1/CACNA1S (L-type)		-	-	-	-	-	-	-	-
Cav1.2/CACNA1C (L-type)		-	-	-		-	-	-
Cav1.3/CACNA1D (L-type)		-	-	-	-	-	-	-	-
Cav1.4/CACNA1F (L-type)		-	-	-	-	-	-	-	-
Cav1 All (L-type)			-	-		-		-
Cav2.1/CACNA1A (P/Q-type)		-	-			-	-	-
Cav2.2/CACNA1B (N-type)		-	-			-		-
Cav2.3/CACNA1E (R-type)		-	-	-		-	-	-
Cav2 All		-	-			-		-
Cav3.1/CACNA1G (T-type)		-		-			-	-
Cav3.2/CACNA1H (T-type)		-		-	-		-	-
Cav3.3/CACNA1I (T-type)		-		-	-		-	-
Cav3 All (T-type)		-		-		-	-	-
Cav All						-		-

Voltage-gated calcium channel impairing toxin (Cav channel inhibitor)

Venom protein entries in UniProtKB/Swiss-Prot

Acanthoscurria paulensis (Brazilian giant black tarantula spider)

Agelena orientalis (Funnel-web spider)

Agelenopsis aperta (North American funnel-web spider) (Agelenopsis gertschi)

Allagelena opulenta (Funnel weaving spider) (Agelena opulenta)

Alopecosa marikovskyi (Wolf spider) (Lycosa kazakhstanicus)

Ancylometes sp. (South American fishing spider)

Anochetus emarginatus (Ant) (Stenomyrmex emarginatus)

Aphonopelma sp. (American tarantula)

Apomastus schlingeri (Trap-door spider) (Aptostichus schlingeri)

Atrax robustus (Sydney funnel-web spider)

Atrax sp. (strain Illawarra) (Funnel-web spider)

Avicularia sp. (Arboreal tarantula)

Brachypelma albiceps (Mexican golden redrump tarantula) (Brachypelma ruhnaui)

Bumba pulcherrimaklaasi (Tarantula spider) (Euathlus pulcherrimaklaasi)

Californiconus californicus (California cone) (Conus californicus)

Centruroides baergi (Scorpion) (Centruroides nigrovariatus baergi)

Ceratogyrus darlingi (Rear horned baboon tarantula)

Ceratogyrus marshalli (Straighthorned baboon tarantula) (Ceratogyrus cornuatus)

Conasprella delessertii (Sozon's cone) (Conus delessertii)

Conus achatinus (Little frog cone)

Conus amadis (Amadis cone)

Conus ammiralis (Admiral cone)

Conus arenatus (Sand-dusted cone)

Conus bullatus (Bubble cone)

Conus buxeus loroisii (Cone snail) (Conus loroisii)

Conus capitaneus (Captain cone)

Conus catus (Cat cone)

Conus consors (Singed cone)

Conus eburneus (Ivory cone)

Conus fulmen (Thunderbolt cone) (Chelyconus fulmen)

Conus geographus (Geography cone) (Nubecula geographus)

Conus imperialis (Imperial cone)

Conus litteratus (Lettered cone)

Conus magus (Magical cone)

Conus marmoreus (Marble cone)

Conus moncuri (Sea snail)

Conus mucronatus (Pointed cone) (Phasmoconus mucronatus)

Conus pennaceus (Feathered cone) (Conus episcopus)

Conus planorbis (Planorbis cone)

Conus pulicarius (Flea-bitten cone)

Conus quercinus (Oak cone)

Conus radiatus (Rayed cone)

Conus regularis (Regular cone)

Conus striatus (Striated cone)

Conus textile (Cloth-of-gold cone)

Conus tulipa (Fish-hunting cone snail) (Tulip cone)

Conus ventricosus (Mediterranean cone)

Coremiocnemis tropix (Australian tarantula spider)

Ctenus ornatus (Brazilian spider) (Oligoctenus ornatus)

Cupiennius salei (American wandering spider)

Cyriopagopus hainanus (Chinese bird spider) (Haplopelma hainanum)

Cyriopagopus schmidti (Chinese bird spider) (Haplopelma schmidti)

Davus fasciatus (Costa Rican tiger rump) (Cyclosternum fasciatus)

Dendroaspis angusticeps (Eastern green mamba) (Naja angusticeps)

Dendroaspis jamesoni kaimosae (Eastern Jameson's mamba)

Dendroaspis polylepis polylepis (Black mamba)

Ectatomma tuberculatum (Selva ant)

Gloydius blomhoffii (Mamushi) (Agkistrodon halys blomhoffi)

Glycera tridactyla (Glycerine worm) (Glycera convoluta)

Grammostola porteri (Tarantula spider) (Lasiodora porteri)

Grammostola rosea (Chilean rose tarantula) (Grammostola spatulata)

Hadronyche formidabilis (Northern tree funnel-web spider) (Atrax formidabilis)

Hadronyche infensa (Fraser island funnel-web spider) (Atrax infensus)

Hadronyche modesta (Victorian funnel-web spider)

Hadronyche venenata (Tasmanian funnel-web spider) (Atrax venenatus)

Hadronyche versuta (Blue mountains funnel-web spider) (Atrax versutus)

Heloderma horridum horridum (Mexican beaded lizard)

Heteropoda venatoria (Brown huntsman spider) (Aranea venatoria)

Hydrophis hardwickii (Hardwick's spine-bellied seasnake) (Lapemis hardwickii)

Hysterocrates gigas (Cameroon red baboon tarantula)

Kukulcania hibernalis (Southern house spider) (Filistata hibernalis)

Laticauda semifasciata (Black-banded sea krait) (Pseudolaticauda semifasciata)

Loxosceles intermedia (Brown spider)

Lycosa praegrandis (Wolf spider)

Machimus arthriticus (Breck robberfly) (Asilus arthriticus)

Missulena bradleyi (Eastern mouse spider)

Monocentropus balfouri (Socotra Island blue baboon tarantula)

Naja naja (Indian cobra)