Channelpedia

Cavβ2

Description: calcium channel, voltage-dependent, beta 2 subunit
Gene: cacnb2
Alias: cacnb2, CACNLB2, CAVB2, Cavbeta2

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Introduction

CACNB2 (also known as MYSB; CAVB2; CACNLB2; FLJ23743) encodes a subunit of a voltage-dependent calcium channel protein which is a member of the voltage-gated calcium channel superfamily. The gene product was originally identified as an antigen target in Lambert-Eaton myasthenic syndrome which is an autoimmune disorder. Mutations in this gene are associated with Brugada symdrome. Alternatively spliced variants have been identified for this gene.

http://www.ncbi.nlm.nih.gov/gene/783


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Gene

Five distinct b2 subunits, varying only in the proximal amino terminus, have been cloned from different species including rat (Perez-Reyes et al., 1992 [1267]), rabbit (Hullin et al., 1992 [1275]), human (Rosenfeld et al., 1993 [1276]), and mouse (Massa et al., 1995 [1277]). Until (2003), however, no more than three of the b2 forms have been identified in any one species (Qin et al., 1998 [1274]), rendering it ambiguous whether they represent bona fide splice variants of the b2 gene. (From Takahashi [235])

Species NCBI gene ID Chromosome Position
Human 783 10 403133
Mouse 12296 2 384950
Rat 116600 17 345370

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Transcript

Species NCBI accession Length (nt)
Human NM_000724.4 6199
Mouse NM_023116.4 3945
Rat NM_001398773.1 4710

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Protein Isoforms

Species Uniprot ID Length (aa)
Human Q08289 660
Mouse Q8CC27 655
Rat Q8VGC3 655

Isoforms

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

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Post-Translational Modifications

PTM
Position
Type

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Structure

Cavβ2 predicted AlphaFold size

Species Area (Å2) Reference
Human 8163.38 source
Mouse 8505.92 source
Rat 10952.86 source

Methodology for AlphaFold size prediction and disclaimer are available here


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Expression and Distribution

cacnb2 is the dominant b subunit expressed in heart (Perez-Reyes et al., 1992 [1267]; Pichler et al., 1997 [1269]; Haase et al., 2000 [1270]) and retina (Ball et al., 2002 [1271]), but is also an important component of HVA Ca21 channels expressed in brain (Ludwig et al., 1997 [474]; Pichler et al., 1997 [1269]), smooth muscle (Reimer et al., 2000 [1272]), and pancreas (Iwashima et al., 2001 [1273]). (List from Takahashi [235])


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Function

Auxiliary b subunits are potent determinants of Ca2+ channel behavior. Qualitatively, all four b-subunit isoforms act similarly to markedly increase surface membrane expression of co-expressed alpha1-subunits (Chien et al., 1995 [1261]; Brice et al., 1997 [1262]; Gao et al., 1999 [1263]; Yamaguchi et al., 2000 [1264]), dramatically enhance Ca2+ current amplitude over that obtained with alpha1 alone (Singer et al., 1991 [1265]; Jones et al., 1998 [1266]), and produce hyperpolarizing shifts in the voltage-dependence of channel activation (Singer et al., 1991 [1265]; Perez-Reyes et al., 1992 [1267]; De Waard et al., 1994 [1268]).

Sequence analysis of the human genome permitted cloning of five Ca2+-channel b2 splice variants (b2a–b2e) that differed only in their proximal amino-termini. The functional consequences of such b2-subunit diversity were explored in recombinant L-type channels reconstituted in HEK 293 cells. b2a and b2e targeted autonomously to the plasma membrane, whereas b2b–b2d localized to the cytosol when expressed in HEK 293 cells. The pattern of modulation of L-type channel voltage-dependent inactivation gating correlated with the subcellular localization of the component b2 variant—membrane- bound b2a and b2e subunits conferred slow(er) channel inactivation kinetics and displayed a smaller fraction of channels recovering from inactivation with fast kinetics, compared to b2b–b2d channels. (Takahashi [235])


References

Singer D et al. The roles of the subunits in the function of the calcium channel.
Science, 1991 Sep 27 , 253 (1553-7).

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

Perez-Reyes E et al. Cloning and expression of a cardiac/brain beta subunit of the L-type calcium channel.
J. Biol. Chem., 1992 Jan 25 , 267 (1792-7).

De Waard M et al. Subunit regulation of the neuronal alpha 1A Ca2+ channel expressed in Xenopus oocytes.
J. Physiol. (Lond.), 1995 Jun 15 , 485 ( Pt 3) (619-34).

Pichler M et al. Beta subunit heterogeneity in neuronal L-type Ca2+ channels.
J. Biol. Chem., 1997 May 23 , 272 (13877-82).

Ball SL et al. Role of the beta(2) subunit of voltage-dependent calcium channels in the retinal outer plexiform layer.
Invest. Ophthalmol. Vis. Sci., 2002 May , 43 (1595-603).

Reimer D et al. beta subunit heterogeneity of L-type Ca(2+) channels in smooth muscle tissues.
FEBS Lett., 2000 Feb 4 , 467 (65-9).

Qin N et al. Unique regulatory properties of the type 2a Ca2+ channel beta subunit caused by palmitoylation.
Proc. Natl. Acad. Sci. U.S.A., 1998 Apr 14 , 95 (4690-5).

Rosenfeld MR et al. Cloning and characterization of a Lambert-Eaton myasthenic syndrome antigen.
Ann. Neurol., 1993 Jan , 33 (113-20).


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