Cavγ5

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

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Introduction

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

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Gene

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]).

Species	NCBI gene ID	Chromosome	Position
Human	27091	17	59634
Mouse	140723	11	40450
Rat	140726	10	42191

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Transcript

Species	NCBI accession	Length (nt)
Human	NM_145811.3	10576
Mouse	NM_001199301.1	3771
Rat	NM_080693.1	828

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Protein Isoforms

Species	Uniprot ID	Length (aa)
Human	Q9UF02	275
Mouse	Q8VHW4	275
Rat	Q8VHW8	275

Isoforms

Transcript

Length (nt)

Protein

Length (aa)

Variant

Isoform

Known

NM_001199301.1

3771

NP_001186230.1

275

transcript variant 1

NM_080644.3

3678

NP_542375.1

275

transcript variant 2

Predicted

XM_011248720.3

4262

XP_011247022.1

190

transcript variant X1

isoform X1

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Post-Translational Modifications

PTM

Position

Type

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Structure

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

Species	Area (Å²)	Reference
Human	3404.61	source
Mouse	2644.84	source
Rat	2384.13	source

Methodology for AlphaFold size prediction and disclaimer are available here

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Function

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

106

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).

478

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

1310

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

1311

Chu PJ et al. Calcium channel gamma subunits provide insights into the evolution of this gene family.
Gene, 2001 Dec 12 , 280 (37-48).

1312

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).

1313

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).

1328

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

1335

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).

1336

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).

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Credits

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/96/ , accessed on 2024 Dec 21

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