Cavβ2
Description: calcium channel, voltage-dependent, beta 2 subunit Gene: cacnb2 Alias: cacnb2, CACNLB2, CAVB2, Cavbeta2
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
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])
Transcript
| Species | NCBI accession | Length (nt) | |
|---|---|---|---|
| Human | NM_000724.4 | 6199 | |
| Mouse | NM_023116.4 | 3945 | |
| Rat | NM_001398773.1 | 4710 |
Protein Isoforms
Isoforms
Post-Translational Modifications
Structure
Cavβ2 predicted AlphaFold size
Methodology for AlphaFold size prediction and disclaimer are available here
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])
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
Takahashi SX
et al.
Distinctive modulatory effects of five human auxiliary beta2 subunit splice variants on L-type calcium channel gating.
Biophys. J.,
2003
May
, 84 (3007-21).
Sokolov S
et al.
Inactivation determinant in the I-II loop of the Ca2+ channel alpha1-subunit and beta-subunit interaction affect sensitivity for the phenylalkylamine (-)gallopamil.
J. Physiol. (Lond.),
1999
Sep
1
, 519 Pt 2 (315-22).
Ludwig A
et al.
Regional expression and cellular localization of the alpha1 and beta subunit of high voltage-activated calcium channels in rat brain.
J. Neurosci.,
1997
Feb
15
, 17 (1339-49).
Chien AJ
et al.
Roles of a membrane-localized beta subunit in the formation and targeting of functional L-type Ca2+ channels.
J. Biol. Chem.,
1995
Dec
15
, 270 (30036-44).
Brice NL
et al.
Importance of the different beta subunits in the membrane expression of the alpha1A and alpha2 calcium channel subunits: studies using a depolarization-sensitive alpha1A antibody.
Eur. J. Neurosci.,
1997
Apr
, 9 (749-59).
Gao T
et al.
Complexes of the alpha1C and beta subunits generate the necessary signal for membrane targeting of class C L-type calcium channels.
J. Biol. Chem.,
1999
Jan
22
, 274 (2137-44).
Yamaguchi H
et al.
Cloning of the beta(2a) subunit of the voltage-dependent calcium channel from human heart: cooperative effect of alpha(2)/delta and beta(2a) on the membrane expression of the alpha(1C) subunit.
Biochem. Biophys. Res. Commun.,
2000
Jan
7
, 267 (156-63).
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).
Haase H
et al.
Expression of Ca(2+) channel subunits during cardiac ontogeny in mice and rats: identification of fetal alpha(1C) and beta subunit isoforms.
J. Cell. Biochem.,
2000
Jan
, 76 (695-703).
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).
Iwashima Y
et al.
Downregulation of the voltage-dependent calcium channel (VDCC) beta-subunit mRNAs in pancreatic islets of type 2 diabetic rats.
Biochem. Biophys. Res. Commun.,
2001
Jan
26
, 280 (923-32).
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).
Hullin R
et al.
Calcium channel beta subunit heterogeneity: functional expression of cloned cDNA from heart, aorta and brain.
EMBO J.,
1992
Mar
, 11 (885-90).
Rosenfeld MR
et al.
Cloning and characterization of a Lambert-Eaton myasthenic syndrome antigen.
Ann. Neurol.,
1993
Jan
, 33 (113-20).
Massa E
et al.
Comparison of fura-2 imaging and electrophysiological analysis of murine calcium channel alpha 1 subunits coexpressed with novel beta 2 subunit isoforms.
Mol. Pharmacol.,
1995
Apr
, 47 (707-16).
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