Channelpedia

Cavβ3

Description: calcium channel, voltage-dependent, beta 3 subunit
Gene: cacnb3
Alias: cacnb3

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Introduction

Voltage dependent calcium channels (VDCC) auxiliary beta (Cavb1–4) and alpha2delta (Cava2d1–4) subunits associate with the alpha1 functional subunits (for review see Walker and De Waard, 1998 [1279]) and affect the biophysical properties of the alpha1 subunits as observed for the auxiliary subunits of voltage-dependent sodium and potassium channels (for review see Isom et al., 1994 [1247]; Trimmer, 1998 [1280]).


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Gene

CACNB3 (also known as CAB3; CACNLB3; FLJ58949) encodes beta 3 subunit of voltage dependent calcium channels.

http://www.ncbi.nlm.nih.gov/gene/784

Species NCBI gene ID Chromosome Position
Human 784 12 14461
Mouse 12297 15 16100
Rat 25297 7 12275

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Transcript

Species NCBI accession Length (nt)
Human NM_000725.4 2931
Mouse NM_007581.3 2822
Rat NM_012828.3 2521

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Protein Isoforms

Species Uniprot ID Length (aa)
Human P54284 484
Mouse P54285 484
Rat P54287 484

Isoforms

Transcript
Length (nt)
Protein
Length (aa)
Variant
Isoform

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Post-Translational Modifications

PTM
Position
Type

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Structure

High-voltage–activated calcium channels are comprised of a pore-forming alpha1 subunit, auxiliary beta and alpha2delta subunits, and, in some cases, an auxiliary gamma subunit (for review see Catterall, 2000 [477]).

The b subunit has been shown to interact with alpha1 subunit interaction domain (AID) in the cytoplasmic I-II linker of alpha1 subunit (Pragnell et al., 1994 [1290]; Witcher et al., 1995 [1291]), and all four beta subunits interacted with AID of Cav2.2-alpha-1 in vitro with high affinity (Kd of 5nM; Scott et al., 1996 [1292]).

Cavβ3 predicted AlphaFold size

Species Area (Å2) Reference
Human 4902.29 source
Mouse 6701.49 source
Rat 6120.49 source

Methodology for AlphaFold size prediction and disclaimer are available here


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Function

It has been shown that b auxiliary subunits increase current amplitude in voltage-dependent calcium channels (Mori et al., 1991; Neely et al., 1993 [1241]; Wakamori et al., 1993 [1286]; Jones et al., 1998 [1266]; Klugbauer et al., 1999 [1289]). However, Yasuda et al. [92] found a novel inhibitory effect of b3 subunit on macroscopic Ba2+ currents through recombinant N- and R-type calcium channels expressed in Xenopus oocytes.

Coexpression of beta subunits enhanced the level of channel expression in the plasma membrane (Williams et al., 1992 [1281]; Brust et al., 1993 [1282]) by chaperoning the translocation of alpha1 subunits (Chien et al., 1995 [1261]; Yamaguchi et al., 1998 [238]; Gao et al., 1999 [1283]; Gerster et al., 1999 [1284]) from ER where beta subunits antagonize the binding between alpha1 and an ER retention protein (Bichet et al., 2000 [1285]). In addition, beta subunits also increased channel open probability without affecting single-channel conductance (Neely et al., 1993 [1221]; Wakamori et al., 1993 [1286], 1999 [1287]; Jones et al., 1998 [1266]; Gerster et al., 1999 [1284]; Hohaus et al., 2000 [1288]). A hyperpolarizing shift of I-V relationships by beta subunits (Neely et al., 1993 [1241]; Yamaguchi et al., 1998 [238]) also partially contributes to an increase in macroscopic current amplitude.


References

477

Catterall WA Structure and regulation of voltage-gated Ca2+ channels.
Annu. Rev. Cell Dev. Biol., 2000 , 16 (521-55).

Isom LL et al. Auxiliary subunits of voltage-gated ion channels.
Neuron, 1994 Jun , 12 (1183-94).

Jones LP et al. Mechanism of auxiliary subunit modulation of neuronal alpha1E calcium channels.
J. Gen. Physiol., 1998 Aug , 112 (125-43).

Walker D et al. Subunit interaction sites in voltage-dependent Ca2+ channels: role in channel function.
Trends Neurosci., 1998 Apr , 21 (148-54).

Trimmer JS Regulation of ion channel expression by cytoplasmic subunits.
Curr. Opin. Neurobiol., 1998 Jun , 8 (370-4).

Klugbauer N et al. Molecular diversity of the calcium channel alpha2delta subunit.
J. Neurosci., 1999 Jan 15 , 19 (684-91).

Witcher DR et al. Association of native Ca2+ channel beta subunits with the alpha 1 subunit interaction domain.
J. Biol. Chem., 1995 Jul 28 , 270 (18088-93).

Scott VE et al. Beta subunit heterogeneity in N-type Ca2+ channels.
J. Biol. Chem., 1996 Feb 9 , 271 (3207-12).


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Credits

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