voltage-dependent Ca+2 channel alpha-1S (voltage-dependent Ca+2 channel-alpha 1 isoform 3 skeletal muscle, L type, CACNA1S, CACNL1A3, CACH1, CACN1,)

Function: - pore-forming & voltage-sensitive alpha-1 subunit of voltage-sensitive Ca⁺² channel - alpha-1S gives rise to L-type Ca⁺² currents a) L-type Ca⁺² channels (long-lasting) belong to the 'high-voltage activated' (HVA) group b) blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, & by omega-agatoxin-IIIA (omega-Aga-IIIA) c) insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) & omega-agatoxin-IVA (omega-Aga-IVA) - role in excitation-contraction coupling in skeletal muscle - interacts with DYSF & JSRP1 - phosphorylation by PKA activates the Ca⁺² channel Structure: - each of the 4 internal repeats contains 5 hydrophobic transmembrane segments (S1, S2, S3, S5, S6) & one positively charged transmembrane segment (S4) - S4 segments probably represent the voltage-sensor & are characterized by a series of positively charged amino acids at every third position - the loop between repeats II & III interacts with the ryanodine receptor, & is therefore important for Ca⁺² release from the endoplasmic reticulum in muscle contraction - belongs to the Ca⁺² channel alpha-1 subunit (TC 1.A.1.11) family - an additional gamma subunit is present only in skeletal muscle L-type channel Compartment: membrane Expression: skeletal muscle specific Pathology: - mutations in CACNA1S associated with a) hypokalemic periodic paralysis b) susceptibility to malignant hyperthermia 5 Laboratory: - CACNA1S gene mutation

Related

CACNA1S gene mutation familial periodic paralysis (hyperkalemic, normokalemic, hypokalemic, HYPP, NKPP, HYPOPP) malignant hyperthermia/hyperthermia of anesthesia voltage-dependent Ca+2 channel

Properties

SIZE: MW = 212 kD entity length = 1873 aa COMPARTMENT: cellular membrane MOTIF: cytoplasmic domain {1-51} transmembrane domain {52-70} exoplasmic loop {71-88} MOTIF: N-glycosylation site {N79} transmembrane domain {89-108} cytoplasmic loop {109-120} transmembrane domain {121-139} exoplasmic loop {140-160} transmembrane domain {161-179} cytoplasmic loop {180-198} transmembrane domain {199-218} exoplasmic loop {219-309} MOTIF: N-glycosylation site {N257} transmembrane domain {310-334} cytoplasmic loop {335-432} MOTIF: BINDING TO BETA SUBUNIT {357-374} transmembrane domain {433-451} exoplasmic loop {452-466} transmembrane domain {467-486} cytoplasmic loop {487-494} transmembrane domain {495-513} exoplasmic loop {514-523} transmembrane domain {524-542} cytoplasmic loop {543-561} transmembrane domain {562-581} MOTIF: leucine residue {562-568} (7) exoplasmic loop {582-636} transmembrane domain {637-661} cytoplasmic loop {662-799} MOTIF: Ser phosphorylation site {S687} FOR-PHOSPHORYLATION-BY: protein kinase A transmembrane domain {800-818} exoplasmic loop {819-834} transmembrane domain {835-854} cytoplasmic loop {855-866} transmembrane domain {867-885} exoplasmic loop {886-892} transmembrane domain {893-911} cytoplasmic loop {912-930} transmembrane domain {931-950} exoplasmic loop {951-1040} transmembrane domain {1041-1065} cytoplasmic loop {1066-1118} transmembrane domain {1119-1137} exoplasmic loop {1138-1152} MOTIF: N-glycosylation site {N1141} transmembrane domain {1153-1172} cytoplasmic loop {1173-1180} transmembrane domain {1181-1199} exoplasmic loop {1200-1231} transmembrane domain {1232-1250} cytoplasmic loop {1251-1269} transmembrane domain {1270-1289} exoplasmic loop {1290-1356} transmembrane domain {1357-1381} cytoplasmic domain {1382-1873} MOTIF: Ser phosphorylation site {S1392} FOR-PHOSPHORYLATION-BY: protein kinase A

Database Correlations

OMIM correlations MORBIDMAP 114208 UniProt Q13698 PFAM correlations Entrez Gene 779