Channelpedia

Cavγ1

Description: calcium channel, voltage-dependent, gamma subunit 1
Gene: cacng1
Alias: cacng1, cacnlg

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Introduction

Voltage-dependent calcium channels are composed of five subunits. The protein encoded by CACNG1 (also known as CACNLG) represents one of these subunits, gamma, and is one of two known gamma subunit proteins. This particular gamma subunit is part of skeletal muscle 1,4-dihydropyridine-sensitive calcium channels and is an integral membrane protein that plays a role in excitation-contraction coupling. This gene is part of a functionally diverse eight-member protein subfamily of the PMP-22/EMP/MP20 family and is located in a cluster with two family members that function as transmembrane AMPA receptor regulatory proteins (TARPs).

http://www.ncbi.nlm.nih.gov/gene/786

The founding member of the gamma subunit family, c1 (cacng1), was first isolated as a subunit of the high-voltage activated (HVA) calcium channel in skeletal muscle (Jay [1321]).


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Gene

Phylogenetic analysis suggests that all c subunits evolved from a single ancestral gene through tandem repeat and chromosome duplication (Burgess [1312], Chu [1311]). Based on sequence homology and chromosomal linkage the c subunits can be divided into three clusters: (c1, c6), (c5, c7), and (c2, c3, c4, c8) (Burgess [1312], Chu [1311]).

Species NCBI gene ID Chromosome Position
Human 786 17 12243
Mouse 12299 11 13258
Rat 29658 10 12688

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Transcript

Species NCBI accession Length (nt)
Human NM_000727.4 1302
Mouse NM_007582.2 1225
Rat NM_019255.1 822

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Protein Isoforms

Species Uniprot ID Length (aa)
Human Q06432 222
Mouse O70578 223
Rat P97707 223

Isoforms

Transcript
Length (nt)
Protein
Length (aa)
Variant
Isoform

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Post-Translational Modifications

PTM
Position
Type

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Structure

VDCCs are heteromeric proteins composed of a pore-forming a1 subunit and, potentially, as many as three auxiliary subunits: a2d, b, and c (=gamma) (Ertel [1224]).

The eight calcium channel gamma subunits share a predicted structure that includes four transmembrane domains with intracellular N- and C- termini (Fig. 1 in Chen [1310]). They are members of a large protein superfamily (pfam00822, a subset of the tetraspanin supergroup) that also includes claudins, proteins that are important components of tight junctions in epithelia. The c subunits share with the claudins a conserved GLW motif of unknown significance in the first extracellular loop. (Chen [1310])

The c1 and c6 subunits are distinguished from the other c subunits by their very short C-terminal cytoplasmic regions that lack functional motifs. (Chen [1310])

Cavγ1 predicted AlphaFold size

Species Area (Å2) Reference
Human 2041.30 source
Mouse 2289.87 source
Rat 2286.73 source

Methodology for AlphaFold size prediction and disclaimer are available here


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Expression and Distribution

c1 and c6 are predominantly expressed in striated muscle. While the c1 subunit seems to be exclusively expressed in skeletal muscle, the c6 subunit is expressed in both skeletal and cardiac muscles, and to a lesser extent in brain (Burgess [1313], Chu [1310], Fukaya [1320]).


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Function

Our current understanding of the cellular processes influenced by the gamma (c) subunits suggests a more diverse and complex range of regulatory functions than found with the other calcium channel auxiliary subunits. The gamma subunits interact not just with calcium channels but with other proteins as well. Principle cellular targets of several members of the calcium channel c subunit family may not be calcium channels at all. The first c subunit described, c1 (=cacng1), was isolated biochemically as a component of a calcium channel expressed in skeletal muscle and has been shown to alter calcium current properties in both native myocytes and in cell lines (Eberst [1315], Freise [1316], Held [1317]). Historically, as additional members of this protein family were identified by sequence homology to c1, it was assumed that their functional roles were also homologous. It now seems clear that this assignment of common function may not have been appropriate. Four of the eight gamma subunits (c2, c3, c4, c8) are known to act as transmembrane AMPA receptor regulatory proteins (TARPs). Their major cellular function seems to be the regulation of trafficking and gating of AMPA receptors (Osten [1318], X [1319]). Thus the assumption that all c subunit proteins act primarily as regulators of calcium channel function is likely to be incorrect.

The founding member of the c subunit family, c1 (cacng1), was first isolated as a subunit of the high-voltage activated (HVA) calcium channel in skeletal muscle (Jay [1321]). When co- expressed with the a1 subunit Cav1.2 in heterologous systems, c1 alters HVA calcium current kinetics and the voltage-dependency of inactivation (Eberst [1315]), although a negative report demonstrating no effects of this subunit on calcium current has also been published (Chen [1310]). The function of c1 has been studied in native skeletal muscle using the c1-null mouse (Arikkath [1322], Freise [1316], Held [1317]) .


References

Ertel EA et al. Nomenclature of voltage-gated calcium channels.
Neuron, 2000 Mar , 25 (533-5).

Chen RS et al. Calcium channel gamma subunits: a functionally diverse protein family.
Cell Biochem. Biophys., 2007 , 47 (178-86).

Eberst R et al. Identification and functional characterization of a calcium channel gamma subunit.
Pflugers Arch., 1997 Mar , 433 (633-7).

Osten P et al. Learning from stargazin: the mouse, the phenotype and the unexpected.
Curr. Opin. Neurobiol., 2006 Jun , 16 (275-80).

Arikkath J et al. Gamma 1 subunit interactions within the skeletal muscle L-type voltage-gated calcium channels.
J. Biol. Chem., 2003 Jan 10 , 278 (1212-9).


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Credits

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/92/ , accessed on 2024 Dec 12



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