voltage-dependent Ca+2 channel alpha-1A (voltage-dependent Ca+2 channel-alpha 1 isoform 4, L type, CACNA1A, CACNL1A4, CACH4, CACN3)

Function: - pore-forming & voltage-sensitive alpha-1 subunit of voltage-sensitive Ca⁺² channel - alpha-1A gives rise to P &/or Q-type Ca⁺² currents; P/Q-type Ca⁺² channels a) belong to the 'high-voltage activated' (HVA) group b) blocked by the funnel toxin (Ftx) & by the omega-agatoxin-IVA (omega-Aga-IVA) n) insensitive to dihydropyridines (DHP), & omega-conotoxin-GVIA (omega-CTx-GVIA) Structure: - each of the 4 internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) & one positively charged transmembrane segment (S4) - S4 segments probably represent the voltage-sensor; they are characterized by a series of positively charged amino acids at every third position - belongs to the Ca⁺² channel alpha-1 subunit (TC 1.A.1.11) family Compartment: membrane Alternative splicing: named isoforms=7; Additional isoforms seem to exist Expression: - brain specific - mainly found in cerebellum, cerebral cortex, thalamus & hypothalamus - no expression in heart, kidney, liver or muscle - Purkinje cells contain predominantly P-type VSCC; the Q-type is a prominent Ca⁺² current in cerebellar granule cells Polymorphism: - the poly-Gln region of CACNA1A is polymorphic: 6-17 repeats in the normal population; expanded to ~21-30 repeats in spinocerebellar ataxia type-6; repeat expansion also reported in episodic ataxia type 2 Pathology: - mutations associated with: a) familial hemiplegic migraine 1 b) spinocerebellar ataxia type-6 c) episodic ataxia type 2 Laboratory: - CACNA1A gene CAG repeats in blood/tissue

Related

CACNA1A gene; CALNL1A4 gene; SCA6 gene spinocerebellar ataxia type 6 (SCA-6) voltage-dependent Ca+2 channel

Properties

SIZE: MW = 282 kD entity length = 2505 aa COMPARTMENT: cellular membrane MOTIF: cytoplasmic domain {1-98} MOTIF: glycine residue {13-18} (6) transmembrane domain {99-117} exoplasmic loop {118-135} transmembrane domain {136-155} cytoplasmic loop {156-167} transmembrane domain {168-185} exoplasmic loop {186-190} transmembrane domain {191-209} cytoplasmic loop {210-228} transmembrane domain {229-248} exoplasmic loop {249-335} MOTIF: N-glycosylation site {N283} transmembrane domain {336-360} cytoplasmic loop {361-487} MOTIF: binding to beta subunit {383-400} transmembrane domain {488-506} exoplasmic loop {507-521} transmembrane domain {522-541} cytoplasmic loop {542-549} transmembrane domain {550-568} exoplasmic loop {569-578} transmembrane domain {579-597} cytoplasmic loop {598-616} transmembrane domain {617-636} exoplasmic loop {637-689} transmembrane domain {690-714} cytoplasmic loop {715-1242} MOTIF: glutamate residue {727-732} (6) arginine residue {1002-1007} (6) glutamate residue {1204-1207} (4) transmembrane domain {1243-1261} exoplasmic loop {1262-1277} transmembrane domain {1278-1297} cytoplasmic loop {1298-1309} transmembrane domain {1310-1328} exoplasmic loop {1329-1339} transmembrane domain {1340-1358} cytoplasmic loop {1359-1377} transmembrane domain {1378-1397} exoplasmic loop {1398-1484} transmembrane domain {1485-1509} cytoplasmic loop {1510-1564} transmembrane domain {1565-1593} exoplasmic loop {1594-1598} transmembrane domain {1599-1618} cytoplasmic loop {1619-1626} transmembrane domain {1627-1645} exoplasmic loop {1646-1652} transmembrane domain {1653-1671} cytoplasmic loop {1672-1690} transmembrane domain {1691-1710} exoplasmic loop {1711-1782} transmembrane domain {1783-1807} cytoplasmic domain {1808-2505} MOTIF: Ser phosphorylation site {S1822} Ca+2-binding site SITE: 1840-1851 Ser phosphorylation site {S2030} Tyr phosphorylation site {Y2076} histidine-rich region {2211-2220} MOTIF: histidine residue (SEVERAL) proline-rich region SITE: 2221-2224 MOTIF: proline residue (SEVERAL) Ser phosphorylation site {S2269} glutamine-rich region {2314-2324} MOTIF: glutamine residue (SEVERAL) Ser phosphorylation site {S2378}

Database Correlations

OMIM correlations MORBIDMAP 601011 UniProt O00555 PFAM correlations Entrez Gene 773 Kegg hsa:773