Voltage-dependent calcium channel, gamma-1 subunit (IPR005421)
Short name: VDCC_g1su
Overlapping homologous superfamilies
Ca2+ ions are unique in that they not only carry charge but they are also the most widely used of diffusible second messengers. Voltage-dependent Ca2+ channels (VDCC) are a family of molecules that allow cells to couple electrical activity to intracellular Ca2+ signalling. The opening and closing of these channels by depolarizing stimuli, such as action potentials, allows Ca2+ ions to enter neurons down a steep electrochemical gradient, producing transient intracellular Ca2+ signals. Many of the processes that occur in neurons, including transmitter release, gene transcription and metabolism are controlled by Ca2+ influx occurring simultaneously at different cellular locales. The pore is formed by the alpha-1 subunit which incorporates the conduction pore, the voltage sensor and gating apparatus, and the known sites of channel regulation by second messengers, drugs, and toxins [PMID: 14657414]. The activity of this pore is modulated by four tightly-coupled subunits: an intracellular beta subunit; a transmembrane gamma subunit; and a disulphide-linked complex of alpha-2 and delta subunits, which are proteolytically cleaved from the same gene product. Properties of the protein including gating voltage-dependence, G protein modulation and kinase susceptibility can be influenced by these subunits.
Voltage-gated calcium channels are classified as T, L, N, P, Q and R, and are distinguished by their sensitivity to pharmacological blocks, single-channel conductance kinetics, and voltage-dependence. On the basis of their voltage activation properties, the voltage-gated calcium classes can be further divided into two broad groups: the low (T-type) and high (L, N, P, Q and R-type) threshold-activated channels.
The voltage-dependent calcium channel gamma (VDCCG) subunit family consists of at least 8 members, which share a number of common structural features [PMID: 11170751]. Each member is predicted to possess 4 transmembrane domains, with intracellular N- and C-termini. The first extracellular loop contains a highly conserved N-glycosylation site and a pair of conserved cysteine residues. The C-terminal 7 residues of VDCCG-2, -3, -4 and -8 are also conserved and contain a consensus site for phosphorylation by cAMP and cGMP-dependent protein kinases, and a target site for binding by PDZ domain proteins [PMID: 11170751].
The VDCCG-1 subunit is a 25kDa protein expressed exclusively in skeletal muscle cells, where it functions as a dihydropyridine-sensitive, L-type calcium channel subunit [PMID: 2158672]. The modulatory properties of VDCCG-1 subunits have been investigated using heterologous expression systems. Coexpression of VDCCG-1 subunits with L-type or P/Q-type channels induces moderate changes in activation and inactivation properties, and modification of the peak current amplitude of these channels [PMID: 1718988, PMID: 1716787].
- PR01601 (VDCCGAMMA1)