Cavγ4
Description: calcium channel, voltage-dependent, gamma subunit 4 Gene: cacng4 Alias: cacng4
The protein encoded by CACNG4 (also known as MGC11138; MGC24983) is a type I transmembrane AMPA receptor regulatory protein (TARP), also known as gamma4 (c4) subunit. 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 II TARP and another calcium channel gamma subunit.
http://www.ncbi.nlm.nih.gov/gene/27092
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].
The four c subunits identified as regulators of AMPA receptor function (c2, c3, c4, and c8; the TARPs) are widely expressed in the brain and share highly conserved sequences that are quite distinct from c1 and c6 (Arikkath [1324], Black [478]).
Transcript
Species | NCBI accession | Length (nt) | |
---|---|---|---|
Human | NM_014405.4 | 3583 | |
Mouse | NM_019431.4 | 3649 | |
Rat | NM_080692.1 | 984 |
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 cytoplasmic C-terminal regions of the TARPs (to which cacng4 = gamma4 = c4 belongs) contain a number of regulatory sites including a PDZ-binding motif. This PDZ-binding motif (TTPV) is critical for targeting AMPA receptors to the synapse. Chen [1310]
Cavγ4 predicted AlphaFold size
Methodology for AlphaFold size prediction and disclaimer are available here
The four c subunits identified as regulators of AMPA receptor function (c2, c3, c4, and c8; the TARPs) are widely expressed in the brain and share highly conserved sequences that are quite distinct from c1 and c6 (Arikkath [1324], Black [478]).
γ 4 mRNA was highly expressed in caudate putamen, olfactory bulb, habenulae and less so in cerebellum and thalamus. γ 2 and γ 4 expression in cerebellum came predominantly from Purkinje cells. (Black [478])
γ 4 was expressed broadly in brain with very strong expression in fetal brain and some increased expression in caudate nucleus, putamen, and thalamus. There was substantial expression in prostate and lung and less expression in testes, stomach, pancreas, small intestine, placenta, and uterus. Because γ 4 was highly expressed in fetal brain, it is hypothesized to have a potential role during development. This hypothesis is supported by Kious et al. (2002) [1334] who found γ 4 expression in the chick cranial neural plate and in the cranial and dorsal root ganglia. Timing of expression correlates precisely with the onset of neuronal differentiation. γ 4 expression is also observed in the myotome and a subpopulation of differentiating myoblasts in the limb bud. In the distal cranial ganglia, γ 4 expression was detected in cells destined to become neurons and neural crest cells. The authors hypothesize that γ 4’s subtle effects on VGCC calcium transients effects neuronal differentiation. (Black [478])
The most distinct features of the TARPs are the terminal PDZ-binding motifs overlapped with PKA phosphorylation sites. The terminal TTPV motif is known to interact with PSD-95 in the postsynaptic density and the binding is regulated by the PKA motif immediately preceding the PDZ-binding motif (Chetkovich [1325], Choi [1326]). In addition to the critical PDZ-binding motif, the C-terminal regions of the four c subunits known as the TARPs (c2, c3, c4, c8) also contain regulatory sites that control AMPA receptor targeting. (Chen [1310])
References
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).
Arikkath J
et al.
Auxiliary subunits: essential components of the voltage-gated calcium channel complex.
Curr. Opin. Neurobiol.,
2003
Jun
, 13 (298-307).
Chetkovich DM
et al.
Phosphorylation of the postsynaptic density-95 (PSD-95)/discs large/zona occludens-1 binding site of stargazin regulates binding to PSD-95 and synaptic targeting of AMPA receptors.
J. Neurosci.,
2002
Jul
15
, 22 (5791-6).
Choi J
et al.
Phosphorylation of stargazin by protein kinase A regulates its interaction with PSD-95.
J. Biol. Chem.,
2002
Apr
5
, 277 (12359-63).
Kious BM
et al.
Identification and characterization of a calcium channel gamma subunit expressed in differentiating neurons and myoblasts.
Dev. Biol.,
2002
Mar
15
, 243 (249-59).
Credits
To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/95/ , accessed on 2024 Dec 02