Biology:CACNB4

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Voltage-dependent L-type calcium channel subunit beta-4 is a protein that in humans is encoded by the CACNB4 gene.

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.

Clinical significance

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

Interactions

CACNB4 has been shown to interact with Cav2.1.

See also

• Voltage-dependent calcium channel

Further reading

• "The expression of voltage-dependent calcium channel beta subunits in human cerebellum.". Neuroscience 80 (1): 161–74. 1997. doi:10.1016/S0306-4522(97)00115-2. PMID 9252229. 
• "Towards a unified nomenclature describing voltage-gated calcium channel genes.". Hum. Genet. 100 (2): 149–50. 1997. doi:10.1007/s004390050481. PMID 9254840. 
• "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. doi:10.1007/PL00008704. PMID 9254841. 
• "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. doi:10.1074/jbc.273.4.2361. PMID 9442082. 
• "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. doi:10.1007/s003359900755. PMID 9530629. 
• "The expression of voltage-dependent calcium channel beta subunits in human hippocampus.". Brain Res. Mol. Brain Res. 60 (2): 259–69. 1998. doi:10.1016/S0169-328X(98)00186-7. PMID 9757060. 
• "A new beta subtype-specific interaction in alpha1A subunit controls P/Q-type Ca²⁺ channel activation.". J. Biol. Chem. 274 (18): 12383–90. 1999. doi:10.1074/jbc.274.18.12383. PMID 10212211. 
• "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. doi:10.1086/302909. PMID 10762541. 
• "Alternative splicing of the beta 4 subunit has alpha1 subunit subtype-specific effects on Ca²⁺ channel gating.". J. Neurosci. 22 (5): 1573–82. 2002. doi:10.1523/JNEUROSCI.22-05-01573.2002. PMID 11880487. 
• "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. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M. 
• "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. doi:10.1073/pnas.2437756100. PMID 14623965. Bibcode: 2003PNAS..10014469F. 
• "Structural basis of the alpha1-beta subunit interaction of voltage-gated Ca²⁺ channels.". Nature 429 (6992): 675–80. 2004. doi:10.1038/nature02641. PMID 15170217. Bibcode: 2004Natur.429..675C. 
• "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.". Genome Res. 14 (9): 1711–8. 2004. doi:10.1101/gr.2435604. PMID 15342556. 
• "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. 2004. doi:10.1101/gr.2596504. PMID 15489334. 
• "Solution structure of the N-terminal A domain of the human voltage-gated Ca²⁺channel beta4a subunit.". Protein Sci. 15 (2): 378–83. 2006. doi:10.1110/ps.051894506. PMID 16385006. 
• "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. doi:10.1523/JNEUROSCI.0067-06.2006. PMID 16525042. 
• "Migrainous vertigo: mutation analysis of the candidate genes CACNA1A, ATP1A2, SCN1A, and CACNB4.". Headache 46 (7): 1136–41. 2006. doi:10.1111/j.1526-4610.2006.00504.x. PMID 16866717. 
• "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. doi:10.1016/j.bbrc.2007.06.112. PMID 17618603. 

External links

• CACNB4+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
• Human CACNB4 genome location and CACNB4 gene details page in the UCSC Genome Browser.
• Overview of all the structural information available in the PDB for UniProt: O00305 (Voltage-dependent L-type calcium channel subunit beta-4) at the PDBe-KB.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.