CACNB4 explained

Voltage-dependent L-type calcium channel subunit beta-4 is a protein that in humans is encoded by the CACNB4 gene.^{[1] [2]}

Function

This gene encodes a member of the beta subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Various versions of each of these subunits exist, either expressed from similar genes or the result of alternative splicing. The protein described in this record plays an important role in calcium channel function by modulating G protein inhibition, increasing peak calcium current, controlling the alpha-1 subunit membrane targeting and shifting the voltage dependence of activation and inactivation. Alternate transcriptional splice variants of this gene, encoding different isoforms, have been characterized.^[2]

Clinical significance

Certain mutations in this gene have been associated with idiopathic generalized epilepsy (IGE) and juvenile myoclonic epilepsy (JME).^[2]

Interactions

CACNB4 has been shown to interact with Cav2.1.^{[3] [4]}

See also

• Voltage-dependent calcium channel

Further reading

• Volsen SG, Day NC, McCormack AL . The expression of voltage-dependent calcium channel beta subunits in human cerebellum. . Neuroscience . 80 . 1 . 161–74 . 1997 . 9252229 . 10.1016/S0306-4522(97)00115-2 . 27406120 . etal.
• Lory P, Ophoff RA, Nahmias J . Towards a unified nomenclature describing voltage-gated calcium channel genes. . Hum. Genet. . 100 . 2 . 149–50 . 1997 . 9254840 . 10.1007/s004390050481 . 21167466 .
• Taviaux S, Williams ME, Harpold MM . Assignment of human genes for beta 2 and beta 4 subunits of voltage-dependent Ca²⁺ channels to chromosomes 10p12 and 2q22-q23. . Hum. Genet. . 100 . 2 . 151–4 . 1997 . 9254841 . 10.1007/PL00008704 . 5689556 . etal.
• Walker D, Bichet D, Campbell KP, De Waard M . A beta 4 isoform-specific interaction site in the carboxyl-terminal region of the voltage-dependent Ca²⁺ channel alpha 1A subunit. . J. Biol. Chem. . 273 . 4 . 2361–7 . 1998 . 9442082 . 10.1074/jbc.273.4.2361 . free .
• Betz R, Leibiger B, Farnebo F . Mapping of the human Ca²⁺ channel beta 4 subunit to 2q22-23 and its expression in developing mouse. . Mamm. Genome . 9 . 4 . 310–1 . 1998 . 9530629 . 10.1007/s003359900755 . 43010915 . etal.
• Day NC, Volsen SG, McCormack AL . The expression of voltage-dependent calcium channel beta subunits in human hippocampus. . Brain Res. Mol. Brain Res. . 60 . 2 . 259–69 . 1998 . 9757060 . 10.1016/S0169-328X(98)00186-7 . etal.
• Walker D, Bichet D, Geib S . A new beta subtype-specific interaction in alpha1A subunit controls P/Q-type Ca²⁺ channel activation. . J. Biol. Chem. . 274 . 18 . 12383–90 . 1999 . 10212211 . 10.1074/jbc.274.18.12383 . etal. free .
• Escayg A, De Waard M, Lee DD . Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. . Am. J. Hum. Genet. . 66 . 5 . 1531–9 . 2000 . 10762541 . 10.1086/302909 . 1378014 . etal.
• Helton TD, Horne WA . Alternative splicing of the beta 4 subunit has alpha1 subunit subtype-specific effects on Ca²⁺ channel gating. . J. Neurosci. . 22 . 5 . 1573–82 . 2002 . 11880487 . 10.1523/JNEUROSCI.22-05-01573.2002 . 6758875 .
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . etal. 2002PNAS...9916899M . free .
• Finlin BS, Crump SM, Satin J, Andres DA . Regulation of voltage-gated calcium channel activity by the Rem and Rad GTPases. . Proc. Natl. Acad. Sci. U.S.A. . 100 . 24 . 14469–74 . 2004 . 14623965 . 10.1073/pnas.2437756100 . 283615 . 2003PNAS..10014469F . free .
• Chen YH, Li MH, Zhang Y . Structural basis of the alpha1-beta subunit interaction of voltage-gated Ca²⁺ channels. . Nature . 429 . 6992 . 675–80 . 2004 . 15170217 . 10.1038/nature02641 . etal. 2004Natur.429..675C . 4422712 .
• Suzuki Y, Yamashita R, Shirota M . Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions. . Genome Res. . 14 . 9 . 1711–8 . 2004 . 15342556 . 10.1101/gr.2435604 . 515316 . etal.
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Vendel AC, Rithner CD, Lyons BA, Horne WA . Solution structure of the N-terminal A domain of the human voltage-gated Ca²⁺channel beta4a subunit. . Protein Sci. . 15 . 2 . 378–83 . 2006 . 16385006 . 10.1110/ps.051894506 . 2242464 .
• Vendel AC, Terry MD, Striegel AR . Alternative splicing of the voltage-gated Ca²⁺ channel beta4 subunit creates a uniquely folded N-terminal protein binding domain with cell-specific expression in the cerebellar cortex. . J. Neurosci. . 26 . 10 . 2635–44 . 2006 . 16525042 . 10.1523/JNEUROSCI.0067-06.2006 . 6675161 . etal. free .
• von Brevern M, Ta N, Shankar A . Migrainous vertigo: mutation analysis of the candidate genes CACNA1A, ATP1A2, SCN1A, and CACNB4. . Headache . 46 . 7 . 1136–41 . 2006 . 16866717 . 10.1111/j.1526-4610.2006.00504.x . 40915635 . etal.
• Kobayashi T, Yamada Y, Fukao M . The GK domain of the voltage-dependent calcium channel beta subunit is essential for binding to the alpha subunit. . Biochem. Biophys. Res. Commun. . 360 . 3 . 679–83 . 2007 . 17618603 . 10.1016/j.bbrc.2007.06.112 . etal.

Notes and References

1. Escayg A, Jones JM, Kearney JA, Hitchcock PF, Meisler MH . Calcium channel beta 4 (CACNB4): human ortholog of the mouse epilepsy gene lethargic . Genomics . 50 . 1 . 14–22 . Apr 1999 . 9628818 . 10.1006/geno.1998.5311 .
2. Web site: Entrez Gene: CACNB4 calcium channel, voltage-dependent, beta 4 subunit.
3. 10.1074/jbc.273.4.2361 . Walker . D . Bichet D . Campbell K P . De Waard M . Jan 1998 . A beta 4 isoform-specific interaction site in the carboxyl-terminal region of the voltage-dependent Ca²⁺ channel alpha 1A subunit . J. Biol. Chem. . 273 . 4 . 2361–7 . United States. 0021-9258. 9442082 . free .
4. 10.1074/jbc.274.18.12383 . Walker . D . Bichet D . Geib S . Mori E . Cornet V . Snutch T P . Mori Y . De Waard M . Apr 1999 . A new beta subtype-specific interaction in alpha1A subunit controls P/Q-type Ca²⁺ channel activation . J. Biol. Chem. . 274 . 18 . 12383–90 . United States. 0021-9258. 10212211 . free .