CACNA2D1 Membrane Protein Introduction

Introduction of CACNA2D1

CACNA2D1, voltage-dependent calcium channel subunit alpha-2/delta-1, is a protein that in humans is encoded by the CACNA2D1 gene. CACNA2D1 is involved in the voltage-dependent calcium channel complex. This calcium channel mediates the calcium influx when membrane polarization happens. The calcium channel complex consists of four subunits in a 1:1:1:1 ratio including alpha-1, alpha-2/delta, beta, and gamma.

Basic Information of CACNA2D1
Protein Name	Voltage-dependent calcium channel subunit alpha-2/delta-1
Gene Name	CACNA2D1
Aliases	Voltage-gated calcium channel subunit alpha-2/delta-1, CACNL2A, CCHL2A, MHS3
Organism	Homo sapiens (Human)
UniProt ID	P54289
Transmembrane Times	1
Length (aa)	1103
Sequence	MAAGCLLALTLTLFQSLLIGPSSEEPFPSAVTIKSWVDKMQEDLVTLAKTASGVNQLVDIYEKYQDLYTVEPNNARQLVEIAARDIEKLLSNRSKALVRLALEAEKVQAAHQWREDFASNEVVYYNAKDDLDPEKNDSEPGSQRIKPVFIEDANFGRQISYQHAAVHIPTDIYEGSTIVLNELNWTSALDEVFKKNREEDPSLLWQVFGSATGLARYYPASPWVDNSRTPNKIDLYDVRRRPWYIQGAASPKDMLILVDVSGSVSGLTLKLIRTSVSEMLETLSDDDFVNVASFNSNAQDVSCFQHLVQANVRNKKVLKDAVNNITAKGITDYKKGFSFAFEQLLNYNVSRANCNKIIMLFTDGGEERAQEIFNKYNKDKKVRVFTFSVGQHNYDRGPIQWMACENKGYYYEIPSIGAIRINTQEYLDVLGRPMVLAGDKAKQVQWTNVYLDALELGLVITGTLPVFNITGQFENKTNLKNQLILGVMGVDVSLEDIKRLTPRFTLCPNGYYFAIDPNGYVLLHPNLQPKPIGVGIPTINLRKRRPNIQNPKSQEPVTLDFLDAELENDIKVEIRNKMIDGESGEKTFRTLVKSQDERYIDKGNRTYTWTPVNGTDYSLALVLPTYSFYYIKAKLEETITQARYSETLKPDNFEESGYTFIAPRDYCNDLKISDNNTEFLLNFNEFIDRKTPNNPSCNADLINRVLLDAGFTNELVQNYWSKQKNIKGVKARFVVTDGGITRVYPKEAGENWQENPETYEDSFYKRSLDNDNYVFTAPYFNKSGPGAYESGIMVSKAVEIYIQGKLLKPAVVGIKIDVNSWIENFTKTSIRDPCAGPVCDCKRNSDVMDCVILDDGGFLLMANHDDYTNQIGRFFGEIDPSLMRHLVNISVYAFNKSYDYQSVCEPGAAPKQGAGHRSAYVPSVADILQIGWWATAAAWSILQQFLLSLTFPRLLEAVEMEDDDFTASLSKQSCITEQTQYFFDNDSKSFSGVLDCGNCSRIFHGEKLMNTNLIFIMVESKGTCPCDTRLLIQAEQTSDGPNPCDMVKQPRYRKGPDVCFDNNVLEDYTDCGGVSGLNPSLWYIIGIQFLLLWLVSGSTHRLL

Function of CACNA2D1 Membrane Protein

CACNA2D1 is the alpha-2/delta subunit of voltage-dependent calcium channel complex which can regulate calcium current density and activation/inactivation kinetics of the calcium channel. It plays an important role in excitation-contraction coupling. This protein can be cleaved into alpha-2 and delta subunits, and alternate transcriptional splice variants of this gene have been observed. It has been reported that CACNA2D1 can regulate intraocular pressure and can be a therapeutic target. Also, it has been reported that this gene is associated with diabetes disease. In addition, it has been reported that this calcium channel is upregulated in the dorsal spinal cord, and can mediate spinal cord injury-induced neuropathic pain states.

Fig.1 The heteromultimeric voltage-sensitive Ca²⁺ channel, which comprises α1, α2δ, β and γ subunits. (Dooley, 2007)

Application ofCACNA2D1 Membrane Protein in Literature

Chintalapudi S.R., et al. Systems genetics identifies a role for Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility. Nat Commun. 2017, 8(1): 1755. PubMed ID: 29176626

This article indicates that CACNA2D1 can modulate intraocular pressure and can be a promising therapeutic target.
Mastrolia V., et al. Loss of α2δ-1 Calcium Channel Subunit Function Increases the Susceptibility for Diabetes. Diabetes. 2017, 66(4): 897-907. PubMed ID: 28115397

This article demonstrates that the loss of the calcium channel function of CACNA2D1 increases the susceptibility for developing diabetes in a sex-dependent manner.
Chen J., et al. The α2δ-1-NMDA Receptor Complex Is Critically Involved in Neuropathic Pain Development and Gabapentin Therapeutic Actions. Cell Rep. 2018, 22(9): 2307-2321. PubMed ID: 29490268

This study reveals that CACNA2D1 is an NMDAR-interacting protein that increases NMDAR synaptic delivery in neuropathic pain. Gabapentinoids reduce neuropathic pain by inhibiting forward trafficking of CACNA2D1-NMDAR complexes.
Spencer S., et al. α2δ-1 signaling in nucleus accumbens is necessary for cocaine-induced relapse. J Neurosci. 2014, 34(25): 8605-11. PubMed ID: 24948814

This article demonstrates that CACNA2D1 contributes specifically to cocaine-reinstated drug seeking, and identifies this protein as a target for the development of cocaine relapse medications. This article also informs ongoing discussion in the literature regarding the efficacy of gabapentin as a candidate addiction therapy.
Cassidy J.S., et al. Functional exofacially tagged N-type calcium channels elucidate the interaction with auxiliary α2δ-1 subunits. Proc Natl Acad Sci U S A. 2014,111(24): 8979-84. PubMed ID: 24889613

This article reveals Ca_V2.2 and CACNA2D1 are intimately associated with the plasma membrane and allow us to infer a region of interaction.

CACNA2D1 Preparation Options

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Reference

Dooley D J, et al. (2007). Ca²⁺ channel alpha2delta ligands: novel modulators of neurotransmission. Trends Pharmacol Sci. 28(2):75-82.

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