Description: calcium channel, voltage-dependent, gamma subunit 5
Gene: Cacng5     Synonyms: cacng5

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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.

Experimental data

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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]).

RGD ID Chromosome Position Species
628805 10 97300594-97309023 Rat
734379 11 107735919-107772676 Mouse
734378 17 64873451-64881357 Human

Cacng5 : calcium channel, voltage-dependent, gamma subunit 5



Acc No Sequence Length Source
NM_080693 n/A n/A NCBI
NM_080644 n/A n/A NCBI
NM_001199301 n/A n/A NCBI
NM_145811 n/A n/A NCBI
NM_014404 n/A n/A NCBI







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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]





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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]).






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


Black JL. et al. The voltage-gated calcium channel gamma subunits: a review of the literature.
J. Bioenerg. Biomembr., 2003 Dec , 35 (649-60).

Hofmann F. et al. A family of gamma-like calcium channel subunits.
FEBS Lett., 2000 Mar 24 , 470 (189-97).


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).