CACNA2D3

CACNA2D3
Identifiers
Aliases	CACNA2D3 , HSA272268, calcium voltage-gated channel auxiliary subunit alpha2delta 3
External IDs	OMIM: 606399 MGI: 1338890 HomoloGene: 74929 GeneCards: CACNA2D3
Gene location (Human)
Chr.	Chromosome 3 (human)
End	55,074,557 bp
Gene location (Mouse)
Chr.	Chromosome 14 (mouse)
End	29,443,821 bp
RNA expression pattern
	Top expressed in
	middle temporal gyrus; ; Brodmann area 23; ; endothelial cell; ; nucleus accumbens; ; superior frontal gyrus; ; dorsolateral prefrontal cortex; ; prefrontal cortex; ; Brodmann area 9; ; postcentral gyrus; ; sperm;
	Top expressed in
	olfactory tubercle; ; nucleus accumbens; ; medial dorsal nucleus; ; globus pallidus; ; facial motor nucleus; ; subiculum; ; prefrontal cortex; ; superior frontal gyrus; ; anterior horn of spinal cord; ; primary motor cortex;
	More reference expression data
	n/a
Gene ontology
Molecular function	metal ion binding ; voltage-gated ion channel activity ; calcium channel activity ; voltage-gated calcium channel activity ;
Cellular component	integral component of membrane ; plasma membrane ; membrane ; voltage-gated calcium channel complex ;
Biological process	regulation of ion transmembrane transport ; ion transport ; calcium ion transport ; calcium ion transmembrane transport ; cardiac conduction ;
	Sources:Amigo / QuickGO
Orthologs
	55799
	12294
	ENSG00000157445
	ENSMUSG00000021991
	Q8IZS8
	Q9Z1L5
	NM_018398
	NM_009785
	NP_060868
	NP_033915
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated March 04, 2023

Calcium channel, voltage-dependent, alpha 2/delta subunit 3 is a protein that in humans is encoded by the CACNA2D3 gene on chromosome 3 (locus 3p21.1). ^[5]

Function

This gene encodes a member of the alpha-2/delta 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. Research on a highly similar protein in rabbit suggests the protein described in this record is cleaved into alpha-2 and delta subunits. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized.

Clinical significance

Number of studies reported an association between methylation of the CACNA2D3 gene and cancer.

Breast cancer

Methylation-dependent transcriptional silencing of CACNA2D3 gene may contribute to the metastatic phenotype of breast cancer. Analysis of methylation in the CACNA2D3 CpG island may have potential as a biomarker for risk of development of metastatic disease.^[6]

Gastric cancer

The loss of CACNA2D3 gene expression through aberrant promoter hypermethylation may contribute to gastric carcinogenesis, and CACNA2D3 gene methylation is a useful prognostic marker for patients with advanced gastric cancer.^[7] Physical exercise was correlated with a lower methylation frequency of CACNA2D3.^[8]

Related Research Articles

Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (e.g., muscle, glial cells, neurons, etc.) with a permeability to the calcium ion Ca²⁺. These channels are slightly permeable to sodium ions, so they are also called Ca²⁺-Na⁺ channels, but their permeability to calcium is about 1000-fold greater than to sodium under normal physiological conditions.

Calcium channel, voltage-dependent, L type, alpha 1C subunit is a protein that in humans is encoded by the CACNA1C gene. Ca_v1.2 is a subunit of L-type voltage-dependent calcium channel.

The R-type calcium channel is a type of voltage-dependent calcium channel. Like the others of this class, the α₁ subunit forms the pore through which calcium enters the cell and determines most of the channel's properties. This α₁ subunit is also known as the calcium channel, voltage-dependent, R type, alpha 1E subunit (CACNA1E) or Cav_2.3 which in humans is encoded by the CACNA1E gene. They are strongly expressed in cortex, hippocampus, striatum, amygdala and interpeduncular nucleus.

The L-type calcium channel is part of the high-voltage activated family of voltage-dependent calcium channel. "L" stands for long-lasting referring to the length of activation. This channel has four isoforms: Cav1.1, Cav1.2, Cav1.3, and Cav1.4.

Ca_v2.1, also called the P/Q voltage-dependent calcium channel, is a calcium channel found mainly in the brain. Specifically, it is found on the presynaptic terminals of neurons in the brain and cerebellum. Ca_v2.1 plays an important role in controlling the release of neurotransmitters between neurons. It is composed of multiple subunits, including alpha-1, beta, alpha-2/delta, and gamma subunits. The alpha-1 subunit is the pore-forming subunit, meaning that the calcium ions flow through it. Different kinds of calcium channels have different isoforms (versions) of the alpha-1 subunit. Ca_v2.1 has the alpha-1A subunit, which is encoded by the CACNA1A gene. Mutations in CACNA1A have been associated with various neurologic disorders, including familial hemiplegic migraine, episodic ataxia type 2, and spinocerebellar ataxia type 6.

Ca_v1.4 also known as the calcium channel, voltage-dependent, L type, alpha 1F subunit (CACNA1F), is a human gene.

Ca_v1.1 also known as the calcium channel, voltage-dependent, L type, alpha 1S subunit, (CACNA1S), is a protein which in humans is encoded by the CACNA1S gene. It is also known as CACNL1A3 and the dihydropyridine receptor.

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

Voltage-dependent L-type calcium channel subunit beta-1 is a protein that in humans is encoded by the CACNB1 gene.

Calcium channel, voltage-dependent, L type, alpha 1D subunit is a protein that in humans is encoded by the CACNA1D gene. Ca_v1.3 channels belong to the Ca_v1 family, which form L-type calcium currents and are sensitive to selective inhibition by dihydropyridines (DHP).

Voltage-dependent L-type calcium channel subunit beta-3 is a protein that in humans is encoded by the CACNB3 gene.

Voltage-dependent calcium channel subunit alpha-2/delta-1 is a protein that in humans is encoded by the CACNA2D1 gene.

Calcium channel, voltage-dependent, T type, alpha 1H subunit, also known as CACNA1H, is a protein which in humans is encoded by the CACNA1H gene.

Voltage-dependent calcium channel gamma-4 subunit is a protein that in humans is encoded by the CACNG4 gene.

Voltage-dependent calcium channel subunit alpha2delta-2 is a protein that in humans is encoded by the CACNA2D2 gene.

Calcium channel, voltage-dependent, T type, alpha 1I subunit, also known as CACNA1I or Ca_v3.3 is a protein which in humans is encoded by the CACNA1I gene.

The voltage-dependent N-type calcium channel subunit alpha-1B is a protein that in humans is encoded by the CACNA1B gene. The α1B protein, together with β and α2δ subunits forms N-type calcium channel PMID 26386135. It is a R-type calcium channel.

Calcium channel, voltage-dependent, T type, alpha 1G subunit, also known as CACNA1G or Ca_v3.1 is a protein which in humans is encoded by the CACNA1G gene. It is one of the primary targets in the pharmacology of absence seizure.

In molecular biology, miR-137 is a short non-coding RNA molecule that functions to regulate the expression levels of other genes by various mechanisms. miR-137 is located on human chromosome 1p22 and has been implicated to act as a tumor suppressor in several cancer types including colorectal cancer, squamous cell carcinoma and melanoma via cell cycle control.

Calcium channel, voltage-dependent, alpha 2/delta subunit 4 is a protein that in humans is encoded by the CACNA2D4 gene.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000157445 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000021991 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Entrez Gene: Calcium channel, voltage-dependent, alpha 2/delta subunit 3".
↑ Palmieri C, Rudraraju B, Monteverde M, Lattanzio L, Gojis O, Brizio R, Garrone O, Merlano M, Syed N, Lo Nigro C, Crook T (2012). "Methylation of the calcium channel regulatory subunit α2δ-3 (CACNA2D3) predicts site-specific relapse in oestrogen receptor-positive primary breast carcinomas". Br. J. Cancer. 107 (2): 375–81. doi:10.1038/bjc.2012.231. PMC 3394973 . PMID 22644305.
↑ Wanajo A, Sasaki A, Nagasaki H, Shimada S, Otsubo T, Owaki S, Shimizu Y, Eishi Y, Kojima K, Nakajima Y, Kawano T, Yuasa Y, Akiyama Y (2008). "Methylation of the calcium channel-related gene, CACNA2D3, is frequent and a poor prognostic factor in gastric cancer". Gastroenterology. 135 (2): 580–90. doi:10.1053/j.gastro.2008.05.041. PMID 18588891.
↑ Yuasa Y, Nagasaki H, Akiyama Y, Hashimoto Y, Takizawa T, Kojima K, Kawano T, Sugihara K, Imai K, Nakachi K (2009). "DNA methylation status is inversely correlated with green tea intake and physical activity in gastric cancer patients". Int. J. Cancer. 124 (11): 2677–82. doi:10.1002/ijc.24231. PMID 19170207. S2CID 46627170.

External links

Human CACNA2D3 genome location and CACNA2D3 gene details page in the UCSC Genome Browser .

Palmieri C, Rudraraju B, Monteverde M, Lattanzio L, Gojis O, Brizio R, Garrone O, Merlano M, Syed N, Lo Nigro C, Crook T (2012). "Methylation of the calcium channel regulatory subunit α2δ-3 (CACNA2D3) predicts site-specific relapse in oestrogen receptor-positive primary breast carcinomas". British Journal of Cancer. 107 (2): 375–81. doi:10.1038/bjc.2012.231. PMC 3394973 . PMID 22644305.
Leone PE, González MB, Elosua C, Gómez-Moreta JA, Lumbreras E, Robledo C, Santos-Briz A, Valero JM, de la Guardia RD, Gutiérrez NC, Hernández JM, García JL (2012). "Integration of global spectral karyotyping, CGH arrays, and expression arrays reveals important genes in the pathogenesis of glioblastoma multiforme". Annals of Surgical Oncology. 19 (7): 2367–79. doi:10.1245/s10434-011-2202-5. PMID 22395973. S2CID 1687472.
Abo-Dalo B, Kim HG, Roes M, Stefanova M, Higgins A, Shen Y, Mundlos S, Quade BJ, Gusella JF, Kutsche K (2007). "Extensive molecular genetic analysis of the 3p14.3 region in patients with Zimmermann-Laband syndrome". American Journal of Medical Genetics Part A. 143A (22): 2668–74. doi:10.1002/ajmg.a.32034. PMID 17937436. S2CID 22798244.
Wang KS, Liu XF, Aragam N (2010). "A genome-wide meta-analysis identifies novel loci associated with schizophrenia and bipolar disorder". Schizophrenia Research. 124 (1–3): 192–9. doi:10.1016/j.schres.2010.09.002. PMID 20889312. S2CID 21402201.
Ovsyannikova IG, Kennedy RB, O'Byrne M, Jacobson RM, Pankratz VS, Poland GA (2012). "Genome-wide association study of antibody response to smallpox vaccine". Vaccine. 30 (28): 4182–9. doi:10.1016/j.vaccine.2012.04.055. PMC 3367131 . PMID 22542470.
Hanke S, Bugert P, Chudek J, Kovacs G (2001). "Cloning a calcium channel alpha2delta-3 subunit gene from a putative tumor suppressor gene region at chromosome 3p21.1 in conventional renal cell carcinoma". Gene. 264 (1): 69–75. doi:10.1016/s0378-1119(00)00600-4. PMID 11245980.
Neely GG, Hess A, Costigan M, Keene AC, Goulas S, Langeslag M, Griffin RS, Belfer I, Dai F, Smith SB, Diatchenko L, Gupta V, Xia CP, Amann S, Kreitz S, Heindl-Erdmann C, Wolz S, Ly CV, Arora S, Sarangi R, Dan D, Novatchkova M, Rosenzweig M, Gibson DG, Truong D, Schramek D, Zoranovic T, Cronin SJ, Angjeli B, Brune K, Dietzl G, Maixner W, Meixner A, Thomas W, Pospisilik JA, Alenius M, Kress M, Subramaniam S, Garrity PA, Bellen HJ, Woolf CJ, Penninger JM (2010). "A genome-wide Drosophila screen for heat nociception identifies α2δ3 as an evolutionarily conserved pain gene". Cell. 143 (4): 628–38. doi:10.1016/j.cell.2010.09.047. PMC 3040441 . PMID 21074052.
Qin N, Yagel S, Momplaisir ML, Codd EE, D'Andrea MR (2002). "Molecular cloning and characterization of the human voltage-gated calcium channel alpha(2)delta-4 subunit". Molecular Pharmacology. 62 (3): 485–96. doi:10.1124/mol.62.3.485. PMID 12181424.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000157445 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000021991 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] "Entrez Gene: Calcium channel, voltage-dependent, alpha 2/delta subunit 3".

[pmid22644305-6] Palmieri C, Rudraraju B, Monteverde M, Lattanzio L, Gojis O, Brizio R, Garrone O, Merlano M, Syed N, Lo Nigro C, Crook T (2012). "Methylation of the calcium channel regulatory subunit α2δ-3 (CACNA2D3) predicts site-specific relapse in oestrogen receptor-positive primary breast carcinomas". Br. J. Cancer. 107 (2): 375–81. doi:10.1038/bjc.2012.231. PMC 3394973 . PMID 22644305.

[pmid18588891-7] Wanajo A, Sasaki A, Nagasaki H, Shimada S, Otsubo T, Owaki S, Shimizu Y, Eishi Y, Kojima K, Nakajima Y, Kawano T, Yuasa Y, Akiyama Y (2008). "Methylation of the calcium channel-related gene, CACNA2D3, is frequent and a poor prognostic factor in gastric cancer". Gastroenterology. 135 (2): 580–90. doi:10.1053/j.gastro.2008.05.041. PMID 18588891.

[pmid19170207-8] Yuasa Y, Nagasaki H, Akiyama Y, Hashimoto Y, Takizawa T, Kojima K, Kawano T, Sugihara K, Imai K, Nakachi K (2009). "DNA methylation status is inversely correlated with green tea intake and physical activity in gastric cancer patients". Int. J. Cancer. 124 (11): 2677–82. doi:10.1002/ijc.24231. PMID 19170207. S2CID 46627170.

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