Description: calcium channel, voltage-dependent, beta 4 subunit
Gene: Cacnb4     Synonyms: cacnb4, CAB4, CACNLB4, EA5, EIG9, EJM, EJM4, EJM6



CACNB4 (also known as EA5; EJM; CAB4; EIG9; EJM4; EJM6; CACNLB) encodes a member of the beta subunit family of voltage-dependent calcium channel complex proteins. 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 encoded by this locus 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. Certain mutations in this gene have been associated with idiopathic generalized epilepsy (IGE) and juvenile myoclonic epilepsy (JME). Multiple transcript variants encoding different isoforms have been found for this gene.



Alternative splicing of different full-length b subunit isoforms not only generates variable coding sequences for N-terminal, HOOK, and C-terminal domains but also generates shorter variants with truncated Src homology 3 and/or GK domains. These variants result from splicing-induced frameshifts and subsequent early stop codons (Foell [1308], Hibino [1309]).

RGD ID Chromosome Position Species
68385 3 33934478-34072070 Rat
68559 2 52283840-52532101 Mouse
68558 2 152689285-152955593 Human

Cacnb4 : calcium channel, voltage-dependent, beta 4 subunit



Acc No Sequence Length Source
NM_001105733 n/A n/A NCBI
NM_001037099 n/A n/A NCBI
NM_146123 n/A n/A NCBI
NM_001005746 n/A n/A NCBI
NM_001005747 n/A n/A NCBI
NM_001145798 n/A n/A NCBI
NM_000726 n/A n/A NCBI



Accession Name Definition Evidence
GO:0005891 voltage-gated calcium channel complex A protein complex that forms a transmembrane channel through which calcium ions may pass in response to changes in membrane potential. IEA
GO:0045202 synapse The junction between a nerve fiber of one neuron and another neuron or muscle fiber or glial cell; the site of interneuronal communication. As the nerve fiber approaches the synapse it enlarges into a specialized structure, the presynaptic nerve ending, which contains mitochondria and synaptic vesicles. At the tip of the nerve ending is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane. In response to the arrival of nerve impulses, the presynaptic nerve ending secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane. IEA
GO:0005886 plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. IEA





Edit - History


Voltage-gated Ca2+ channels are multisubunit proteins composed of a pore-forming alpha1 subunit, a two-part alpha2delta/gamma integral membrane subunit, and a soluble cytosolic beta subunit (Dolphin [251]). The auxiliary beta subunit functions both as a chaperone in trafficking the channel complex to the plasma membrane and as a major regulator of channel gating (opening and closing). These functions are thought to occur mainly through a specific interaction between the beta subunit and the alpha1 interaction domain of the intracellular loop between alpha1 repeat motifs I and II (de Waard [1301]).

Sequence comparisons led to the initial discovery that Ca2+ channel b subunits are membrane- associated guanylate kinase proteins consisting of core Src homology 3 and guanylate kinase (GK)2 domains connected by a large variable loop (HOOK) (Hanlon [1304]). The core is flanked by highly variable N- and C-terminal domains. High resolution x-ray crystallographic studies further confirmed the structure of the b subunit core domains and determined that the interaction between the b and alpha1 subunits occurs via GK domain binding with high affinity to the alpha1 interaction domain of alpha1 (Chen [1254], Opatowsky [1305], Petegem [1306], Petegem 2008 [1307]).



Edit - History


An alternatively spliced, truncated b4 subunit (b4c) was identified in the human brain and shown to be highly expressed in nuclei of vestibular and deep cerebellar neurons. (Xu [1293])

Edit - History


Zebrafish embryos lacking b4 subunits failed to initiate epiboly and the underlying mechanism for this phenomenon maybe related to the high levels of b4 expression in yolk syncytial nuclei (Ebert [1302]). Other studies have shown that b subunit functions in the nucleus may be cell type- and splice variant-specific (Subramanyam [1303]).

b4c subunit belongs to the PXVXL protein family with epigenetic responsibilities. These proteins have multiple nuclear functions, including transcription regulation (TIF1a) and nucleosome assembly (CAF1). (Xu [1293])






Day NC et al. The expression of voltage-dependent calcium channel beta subunits in human hippocampus.
Brain Res. Mol. Brain Res., 1998 Oct 1 , 60 (259-69).


Dolphin AC Calcium channel diversity: multiple roles of calcium channel subunits.
Curr. Opin. Neurobiol., 2009 Jun , 19 (237-44).

De Waard M et al. Ca2+ channel regulation by a conserved beta subunit domain.
Neuron, 1994 Aug , 13 (495-503).

Ebert AM et al. Ca2+ channel-independent requirement for MAGUK family CACNB4 genes in initiation of zebrafish epiboly.
Proc. Natl. Acad. Sci. U.S.A., 2008 Jan 8 , 105 (198-203).



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