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CACNA2D2 Membrane Protein Introduction

Introduction of CACNA2D2

CACNA2D2 is also named as voltage-dependent calcium channel subunit alpha-2/delta-2 which is a protein that in humans is encoded by the CACNA2D2 gene. In addition, it’s a protein which plays a key functional role in the voltage-dependent calcium channel complex. This calcium channel is identified as a calcium influx mediator once membrane polarization happens. The calcium channel complex is formed by alpha-1, alpha-2/delta, beta, and gamma subunits which are composed with a 1:1:1:1 ratio.

Basic Information of CACNA2D2
Protein Name Voltage-dependent calcium channel subunit alpha-2/delta-2
Gene Name CACNA2D2
Aliases Voltage-gated calcium channel subunit alpha-2/delta-2, KIAA0558
Organism Homo sapiens (Human)
UniProt ID Q9NY47
Transmembrane Times 1
Length (aa) 1150
Sequence MAVPARTCGASRPGPARTARPWPGCGPHPGPGTRRPTSGPPRPLWLLLPLLPLLAAPGASAYSFPQQHTMQHWARRLEQEVDGVMRIFGGVQQLREIYKDNRNLFEVQENEPQKLVEKVAGDIESLLDRKVQALKRLADAAENFQKAHRWQDNIKEEDIVYYDAKADAELDDPESEDVERGSKASTLRLDFIEDPNFKNKVNYSYAAVQIPTDIYKGSTVILNELNWTEALENVFMENRRQDPTLLWQVFGSATGVTRYYPATPWRAPKKIDLYDVRRRPWYIQGASSPKDMVIIVDVSGSVSGLTLKLMKTSVCEMLDTLSDDDYVNVASFNEKAQPVSCFTHLVQANVRNKKVFKEAVQGMVAKGTTGYKAGFEYAFDQLQNSNITRANCNKMIMMFTDGGEDRVQDVFEKYNWPNRTVRVFTFSVGQHNYDVTPLQWMACANKGYYFEIPSIGAIRINTQEYLDVLGRPMVLAGKEAKQVQWTNVYEDALGLGLVVTGTLPVFNLTQDGPGEKKNQLILGVMGIDVALNDIKRLTPNYTLGANGYVFAIDLNGYVLLHPNLKPQTTNFREPVTLDFLDAELEDENKEEIRRSMIDGNKGHKQIRTLVKSLDERYIDEVTRNYTWVPIRSTNYSLGLVLPPYSTFYLQANLSDQILQVKLPISKLKDFEFLLPSSFESEGHVFIAPREYCKDLNASDNNTEFLKNFIELMEKVTPDSKQCNNFLLHNLILDTGITQQLVERVWRDQDLNTYSLLAVFAATDGGITRVFPNKAAEDWTENPEPFNASFYRRSLDNHGYVFKPPHQDALLRPLELENDTVGILVSTAVELSLGRRTLRPAVVGVKLDLEAWAEKFKVLASNRTHQDQPQKCGPNSHCEMDCEVNNEDLLCVLIDDGGFLVLSNQNHQWDQVGRFFSEVDANLMLALYNNSFYTRKESYDYQAACAPQPPGNLGAAPRGVFVPTVADFLNLAWWTSAAAWSLFQQLLYGLIYHSWFQADPAEAEGSPETRESSCVMKQTQYYFGSVNASYNAIIDCGNCSRLFHAQRLTNTNLLFVVAEKPLCSQCEAGRLLQKETHSDGPEQCELVQRPRYRRGPHICFDYNATEDTSDCGRGASFPPSLGVLVSLQLLLLLGLPPRPQPQVLVHASRRL

Function of CACNA2D2 Membrane Protein

CACNA2D2 is the alpha-2/delta subunit of voltage-dependent calcium channel complex which can modulate calcium current density, as well as activation or inactivation kinetics of the calcium channel. It plays a critical functional role as a regulatory subunit for N-type (CACNA1B), P/Q-type calcium channel (CACNA1A), as well as L-type (CACNA1C OR CACNA1D) and possibly T-type (CACNA1G). Overexpression of CACNA2D2 can induce apoptosis. It has been reported that CACNA2D2 is important for normal hearing, and it can suppress axon regeneration in the adult CNS. In addition, CACNA2D2 can promote tumorigenesis by stimulating cell proliferation and angiogenesis and is associated with spontaneous Purkinje cell activity.

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

Application of CACNA2D2 Membrane Protein in Literature

  1. Fell B., et al. α2δ2 Controls the Function and Trans-Synaptic Coupling of Cav1.3 Channels in Mouse Inner Hair Cells and Is Essential for Normal Hearing. J Neurosci. 2016, 36(43): 11024-11036. PubMed ID: 27798183

    This article indicates that except for controlling the expression and gating properties of Cav1.3 channel, the extracellularly localized α2δ2 subunit plays a new role in mediating trans-synaptic alignment of presynaptic Ca2+ channels and postsynaptic AMPA receptors.

  2. Tedeschi A., et al. The Calcium Channel Subunit Alpha2delta2 Suppresses Axon Regeneration in the Adult CNS. Neuron. 2016, 92(2): 419-434. PubMed ID: 27720483

    This article demonstrates that targeting alpha2delta2 may be a novel treatment strategy to promote structural plasticity and regeneration following CNS trauma.

  3. Warnier M., et al. CACNA2D2 promotes tumorigenesis by stimulating cell proliferation and angiogenesis. Oncogene. 2015, 34(42): 5383-94. PubMed ID: 25619833

    This study reveals that action of α2δ2 on tumor development occurs not only through a stimulation of proliferation, but also through a stimulation of angiogenesis, via an increased secretion of vascular endothelial growth factor in cells overexpressing α2δ2.

  4. Davies A., et al. The alpha2delta subunits of voltage-gated calcium channels form GPI-anchored proteins, a posttranslational modification essential for function. Proc Natl Acad Sci U S A. 2010,107(4): 1654-9. PubMed ID: 20080692

    This article reveals the calcium channel function and other roles in synaptogenesis of alpha2delta subunits including α2δ1, α2δ2 and α2δ3.

  5. Donato R., et al. The ducky(2J) mutation in Cacna2d2 results in reduced spontaneous Purkinje cell activity and altered gene expression. J Neurosci. 2006, 26(48): 12576-86. PubMed ID: 17135419

    This article shows that ducky(2J) mutation in Cacna2d2 exhibits a significant reduction in spontaneous Purkinje cell activity and changes the gene expression level.

CACNA2D2 Preparation Options

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Reference

  1. 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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