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voltage-dependent Ca+2 channel alpha-2/delta-1 (L type, dihydropyridine-sensitive, CACNA2D1, CACNL2A, CCHL2A)

Function: - alpha-2/delta subunit of voltage-dependent Ca+2 channel - regulates Ca+2 current density & activation/inactivation kinetics of the Ca+2 channel - dimer formed of alpha-2-1 & delta-1 chains, disulfide- linked - voltage-dependent Ca+2 channels are multisubunit complexes, consisting of alpha-1 (CACNA1), alpha-2 (CACNA2D), beta (CACNB) & delta (CACNA2D) subunits in a 1:1:1:1 ratio - may be proteolytically processed into subunits alpha-2-1 & delta-1 (putative) - role in excitation-contraction coupling (putative) - binds gabapentin Structure: - MIDAS-like motif in the VWFA domain binds divalent metal cations & is required to promote trafficking of alpha-1 (CACNA1) subunit to the plasma membrane by an integrin-like switch (putative) - belongs to the Ca+2 channel subunit alpha-2/delta family - contains 1 cache domain - contains 1 VWFA domain Compartment: membrane Expression: - central nervous system, skeletal muscle & aorta tissues

Related

gabapentin (Neurontin, Gralise) pregabalin (Lyrica,'son of gabapentin')

General

glycoprotein voltage-dependent Ca+2 channel alpha-2/delta

Properties

SIZE: MW = 123 kD entity length = 1091 aa COMPARTMENT: cellular membrane MOTIF: signal sequence {1-24} N-glycosylation site {N92} N-glycosylation site {N136} N-glycosylation site {N184} VWFA domain {253-430} MOTIF: MIDAS-like {259-263} N-glycosylation site {N324} N-glycosylation site {N348} Cache {446-537} N-glycosylation site {N594} N-glycosylation site {N663} N-glycosylation site {N876} transmembrane domain {1062-1082}

Database Correlations

OMIM 114204 UniProt P54289 PFAM correlations

References

  1. Williams ME et al Structure and functional expression of an omega-conotoxin- sensitive human N-type calcium channel. Science. 1992 Jul 17;257(5068):389-95. PMID: 1321501
  2. Witcher DR, De Waard M, Sakamoto J, Franzini-Armstrong C, Pragnell M, Kahl SD, Campbell KP. Subunit identification and reconstitution of the N-type Ca2+ channel complex purified from brain. Science. 1993 Jul 23;261(5120):486-9. PMID: 8392754
  3. Campbell KP et al The biochemistry and molecular biology of the dihydropyridine-sensitive calcium channel. TINS 11:425 1988 PMID: 2469159
  4. Monthly Prescribing Reference http://www.PrescribingReference.com