Cavγ5
Description: calcium channel, voltage-dependent, gamma subunit 5 Gene: cacng5 Alias: cacng5
The protein encoded by CACNG5 (also known as MGC126656; MGC126682) 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. This gene is a susceptibility locus for schizophrenia and bipolar disorder.
http://www.ncbi.nlm.nih.gov/gene/27091
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_145811.3 | 10576 | |
Mouse | NM_001199301.1 | 3771 | |
Rat | NM_080693.1 | 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]
Cavγ5 predicted AlphaFold size
Methodology for AlphaFold size prediction and disclaimer are available here
Earlier studies on mouse c5 used a protein that is currently identified as Tmem37 (Table 2 in Chen [1310]). Tmem37 did subtly accelerate calcium current activation and inactivation in heterologous expression system (Klugbauer [1328], Lacinova [106]).
References
Lacinova L
et al.
Modulation of gating currents of the Ca(v)3.1 calcium channel by alpha 2 delta 2 and gamma 5 subunits.
Arch. Biochem. Biophys.,
2004
May
15
, 425 (207-13).
Black JL
The voltage-gated calcium channel gamma subunits: a review of the literature.
J. Bioenerg. Biomembr.,
2003
Dec
, 35 (649-60).
Chen RS
et al.
Calcium channel gamma subunits: a functionally diverse protein family.
Cell Biochem. Biophys.,
2007
, 47 (178-86).
Chu PJ
et al.
Calcium channel gamma subunits provide insights into the evolution of this gene family.
Gene,
2001
Dec
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
Mar
24
, 470 (189-97).
Curtis D
et al.
Case-case genome-wide association analysis shows markers differentially associated with schizophrenia and bipolar disorder and implicates calcium channel genes.
Psychiatr. Genet.,
2011
Feb
, 21 (1-4).
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
Apr
2
, 21 (1514-23).
Credits
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