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

Asilidin-1 family

Conotoxin A superfamily

Conotoxin M superfamily

Conotoxin O1 family

Conotoxin O1 superfamily

CRISP family

CRISP family, Venom allergen 5-like subfamily

Ectatomin family, Ectatomin-Et subfamily

Long (4 C-C) scorpion toxin superfamily, Sodium channel inhibitor family, Alpha subfamily

Long (4 C-C) scorpion toxin superfamily, Sodium channel inhibitor family, Beta subfamily

Neurotoxin (omega-lctx) family

Neurotoxin 01 (U2-agtx) family

Neurotoxin 02 (plectoxin) family

Neurotoxin 02 (plectoxin) family, 01 (Tx3) subfamily

Neurotoxin 02 (plectoxin) family, 02 (plectoxin) subfamily

Neurotoxin 02 (plectoxin) family, 03 (omega-agtx) subfamily

Neurotoxin 02 (plectoxin) family, 09 subfamily

Neurotoxin 04 (omega-agtx) family, 01 (type I omega-agtx) subfamily

Neurotoxin 04 (omega-agtx) family, 03 (type II/III omega-agtx) subfamily

Neurotoxin 08 (Shiva) family, 01 (omega toxin) subfamily

Neurotoxin 08 (Shiva) family, 02 (omega/kappa toxin) subfamily

Neurotoxin 09 (Tx3-6) family

Neurotoxin 10 (Hwtx-1) family

Neurotoxin 10 (Hwtx-1) family, 01 (AU5A) subfamily

Neurotoxin 10 (Hwtx-1) family, 02 (AU5B) subfamily

Neurotoxin 10 (Hwtx-1) family, 04 (CcoTx1) subfamily

Neurotoxin 10 (Hwtx-1) family, 07 (GrTx) subfamily

Neurotoxin 10 (Hwtx-1) family, 08 (Gtx1-15) subfamily

Neurotoxin 10 (Hwtx-1) family, 09 (HaTx) subfamily

Neurotoxin 10 (Hwtx-1) family, 17 (Hntx-9) subfamily

Neurotoxin 10 (Hwtx-1) family, 19 (HpTX2) subfamily

Neurotoxin 10 (Hwtx-1) family, 23 (HwTx-I) subfamily

Neurotoxin 10 (Hwtx-1) family, 28 (Jztx-11) subfamily

Neurotoxin 10 (Hwtx-1) family, 41 (Jztx-36) subfamily

Neurotoxin 10 (Hwtx-1) family, 53 (PNTx27C4) subfamily

Neurotoxin 10 (Hwtx-1) family, 54 (ProTx-1) subfamily

Neurotoxin 10 (Hwtx-1) family, 56 (SNX-482) subfamily

Neurotoxin 10 (Hwtx-1) family, 59 (Tltx) subfamily

Neurotoxin 12 (Hwtx-2) family, 03 (juruin) subfamily

Neurotoxin 12 (Hwtx-2) family, 06 (TXP1) subfamily

Neurotoxin 13 (insecticidal toxin ABC) family, 01 (Aps III) subfamily

Neurotoxin 14 (magi-1) family, 08 (Ltx-4) subfamily

Neurotoxin 15 family, 02 (omega-actx) subfamily

Neurotoxin 19 (CSTX) family

Neurotoxin 19 (CSTX) family, 04 (U1-Lctx) subfamily

Neurotoxin 28 (Litx) family

Neurotoxin 30 (phrixotoxin) family

Neurotoxin 36 family, 02 subfamily

Not in a family

O1 superfamily

O2 superfamily, Contryphan family

Poneritoxin-Ae1 family

Scoloptoxin-05 family

Scoloptoxin-10 family

Scoloptoxin-13 family

Scoloptoxin-15 family

Snake three-finger toxin family, Long-chain subfamily, Type II alpha-neurotoxin sub-subfamily

Snake three-finger toxin family, Short-chain subfamily, L-type calcium blocker sub-subfamily

Spiderine family, Spiderine subfamily

Venom Kunitz-type family

Venom Ptu1-like knottin family