Cavγ1
Description: calcium channel, voltage-dependent, gamma subunit 1 Gene: cacng1 Alias: cacng1, cacnlg
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]).
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]).
Transcript
| Species | NCBI accession | Length (nt) | |
|---|---|---|---|
| Human | NM_000727.4 | 1302 | |
| Mouse | NM_007582.2 | 1225 | |
| Rat | NM_019255.1 | 822 |
Protein Isoforms
Isoforms
Post-Translational Modifications
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
Methodology for AlphaFold size prediction and disclaimer are available here
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]).
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
Chen RS
et al.
Calcium channel gamma subunits: a functionally diverse protein family.
Cell Biochem. Biophys.,
2007
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Chu PJ
et al.
Calcium channel gamma subunits provide insights into the evolution of this gene family.
Gene,
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Burgess DL
et al.
A cluster of three novel Ca2+ channel gamma subunit genes on chromosome 19q13.4: evolution and expression profile of the gamma subunit gene family.
Genomics,
2001
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1
, 71 (339-50).
Burgess DL
et al.
Identification of three novel Ca(2+) channel gamma subunit genes reveals molecular diversification by tandem and chromosome duplication.
Genome Res.,
1999
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, 9 (1204-13).
Iles DE
et al.
Localization of the gamma-subunit of the skeletal muscle L-type voltage-dependent calcium channel gene (CACNLG) to human chromosome band 17q24 by in situ hybridization and identification of a polymorphic repetitive DNA sequence at the gene locus.
Cytogenet. Cell Genet.,
1993
, 64 (227-30).
Eberst R
et al.
Identification and functional characterization of a calcium channel gamma subunit.
Pflugers Arch.,
1997
Mar
, 433 (633-7).
Freise D
et al.
Absence of the gamma subunit of the skeletal muscle dihydropyridine receptor increases L-type Ca2+ currents and alters channel inactivation properties.
J. Biol. Chem.,
2000
May
12
, 275 (14476-81).
Held B
et al.
Skeletal muscle L-type Ca(2+) current modulation in gamma1-deficient and wildtype murine myotubes by the gamma1 subunit and cAMP.
J. Physiol. (Lond.),
2002
Mar
1
, 539 (459-68).
Osten P
et al.
Learning from stargazin: the mouse, the phenotype and the unexpected.
Curr. Opin. Neurobiol.,
2006
Jun
, 16 (275-80).
Qiao X
et al.
Nonchannel functions of the calcium channel gamma subunit: insight from research on the stargazer mutant.
J. Bioenerg. Biomembr.,
2003
Dec
, 35 (661-70).
Fukaya M
et al.
Spatial diversity in gene expression for VDCCgamma subunit family in developing and adult mouse brains.
Neurosci. Res.,
2005
Dec
, 53 (376-83).
Jay SD
et al.
Primary structure of the gamma subunit of the DHP-sensitive calcium channel from skeletal muscle.
Science,
1990
Apr
27
, 248 (490-2).
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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