Cavγ7
Description: calcium channel, voltage-dependent, gamma subunit 7 Gene: cacng7 Alias: cacng7
The protein encoded by CACNG7 is a type II transmembrane AMPA receptor regulatory protein (TARP). TARPs regulate both trafficking and channel gating of the AMPA receptors. 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, a type I TARP and a calcium channel gamma subunit. http://www.ncbi.nlm.nih.gov/gene/59284
Phylogenetic analysis suggests that all c subunits evolved from a single ancestral gene through tandem repeat and chromosome duplication (Burgesse [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) (Burgesse [1312], Chu [1311]). See also the phylogenetic tree, fig.2 in Black [478].
c5 and c7 are encoded by five exons in contrast to all other c subunits, which are encoded by four exons (Moss [1336], Chu [1311]). A protein originally identified as mouse c5 (Klugbauer [1328]) is currently named transmembrane protein 37 (Tmem37, NCBI database). Although Tmem37 is also a tetraspanin protein with the GLW motif characteristic of the pfam0082 protein family, its gene consists of only two exons, indicating a divergence from other c subunit genes during evolution. Based on phylogenetic evidence, Chu et al. proposed that Tmem37 should not be considered a member of the calcium channel c family (Chu [1311]). This conclusion is further supported by the observation that Tmem37 does not share the chromosomal linkage to c4 and c1 in human (Burgess [1313]), mouse and rat (Chu [1311]) that is seen for c5 (Table 2 in Chen [1310]).
Transcript
| Species | NCBI accession | Length (nt) | |
|---|---|---|---|
| Human | NM_031896.5 | 2754 | |
| Mouse | NM_133189.5 | 2342 | |
| Rat | NM_080695.1 | 828 |
Protein Isoforms
Isoforms
Post-Translational Modifications
The eight calcium channel c 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 c5 and c7 subunits are highly expressed in brain tissue and lack a C-terminal PDZ-binding motif in comparison to other gamma subunits (Chu [1311], Moss [1336]).
c5, c7: c5, and c7 are palmitoylated at both the N- and C- termini. Additionally, their C-terminal tails contain tyrosine phosphorylation sites. Chen [1310]
Cavγ7 predicted AlphaFold size
Methodology for AlphaFold size prediction and disclaimer are available here
c7 subunit dramatically reduced current density produced by the Cav2.2 subunit in Xenopus oocytes and COS-7 cells (Moss [1336]). However, when expressed in sympathetic neurons c7 failed to affect pre-existing HVA Ca2+ channels. Therefore, confirmation of the physiological influence of c7 on calcium current remains elusive. (Chen [1310])
γ7, which is homologous to γ5, regulates stability of certain mRNAs (Ferron [1342]) and, along with γ2 and γ8, controls trafficking and gating of AMPA receptors (Tomita [1343], Kato [1344]). It thus may be involved in ischemic cardiomyopathy (Gronich [1341]).
References
Chen RS
et al.
Calcium channel gamma subunits: a functionally diverse protein family.
Cell Biochem. Biophys.,
2007
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Chu PJ
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Calcium channel gamma subunits provide insights into the evolution of this gene family.
Gene,
2001
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12
, 280 (37-48).
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
Feb
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
Dec
, 9 (1204-13).
Klugbauer N
et al.
A family of gamma-like calcium channel subunits.
FEBS Lett.,
2000
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24
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Moss FJ
et al.
The novel product of a five-exon stargazin-related gene abolishes Ca(V)2.2 calcium channel expression.
EMBO J.,
2002
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2
, 21 (1514-23).
Gronich N
et al.
Molecular remodeling of ion channels, exchangers and pumps in atrial and ventricular myocytes in ischemic cardiomyopathy.
,
2010
Mar
18
, 4 ().
Ferron L
et al.
The stargazin-related protein gamma 7 interacts with the mRNA-binding protein heterogeneous nuclear ribonucleoprotein A2 and regulates the stability of specific mRNAs, including CaV2.2.
J. Neurosci.,
2008
Oct
15
, 28 (10604-17).
Tomita S
et al.
Functional studies and distribution define a family of transmembrane AMPA receptor regulatory proteins.
J. Cell Biol.,
2003
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26
, 161 (805-16).
Kato AS
et al.
New transmembrane AMPA receptor regulatory protein isoform, gamma-7, differentially regulates AMPA receptors.
J. Neurosci.,
2007
May
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, 27 (4969-77).
Credits
To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/98/ , accessed on 2024 Nov 21