Endogenous

CACNA1S CACH1 CACN1 CACNL1A3

Voltage-dependent L-type calcium channel subunit alpha-1S (Calcium channel, L type, alpha-1 polypeptide, isoform 3, skeletal muscle) (Voltage-gated calcium channel subunit alpha Cav1.1)

calcium voltage-gated channel subunit alpha1 S(CACNA1S) Homo sapiens This gene encodes one of the five subunits of the slowly inactivating L-type voltage-dependent calcium channel in skeletal muscle cells. Mutations in this gene have been associated with hypokalemic periodic paralysis, thyrotoxic periodic paralysis and malignant hyperthermia susceptibility. [provided by RefSeq, Jul 2008],

Disease:Defects in CACNA1S are a cause of periodic paralysis hypokalemic (HOKPP) [MIM:170400]; also designated HYPOPP. HOKPP is an autosomal dominant disorder manifested by episodic flaccid generalized muscle weakness associated with falls of serum potassium levels.,Disease:Defects in CACNA1S are the cause of malignant hyperthermia susceptibility 5 (MHS5) [MIM:601887]; an autosomal dominant disorder that is potentially lethal in susceptible individuals on exposure to commonly used inhalational anesthetics and depolarizing muscle relaxants.,Domain:Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position.,Domain:The loop between repeats II and III interacts with the ryanodine receptor, and is therefore important for calcium release from the endoplasmic reticulum necessary for muscle contraction.,Function:Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1S gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle.,PTM:Phosphorylation by PKA activates the calcium channel.,similarity:Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family.,subunit:Multisubunit complex consisting of alpha-1, alpha-2, beta and delta subunits in a 1:1:1:1 ratio. The channel activity is directed by the pore-forming and voltage-sensitive alpha-1 subunit. In many cases, this subunit is sufficient to generate voltage-sensitive calcium channel activity. The auxiliary subunits beta and alpha-2/delta linked by a disulfide bridge regulate the channel activity. An additional gamma subunit is present only in skeletal muscle L-type channel. Interacts with DYSF and JSRP1.,tissue specificity:Skeletal muscle specific.,

Cell membrane, sarcolemma, T-tubule ; Multi-pass membrane protein .

>>MAPK signaling pathway ;
>>Calcium signaling pathway ;
>>cGMP-PKG signaling pathway ;
>>cAMP signaling pathway ;
>>Cardiac muscle contraction ;
>>Adrenergic signaling in cardiomyocytes ;
>>Vascular smooth muscle contraction ;
>>Retrograde endocannabinoid signaling ;
>>Cholinergic synapse ;
>>Serotonergic synapse ;
>>GABAergic synapse ;
>>Insulin secretion ;
>>GnRH signaling pathway ;
>>Oxytocin signaling pathway ;
>>Renin secretion ;
>>Aldosterone synthesis and secretion ;
>>Cortisol synthesis and secretion ;
>>GnRH secretion ;
>>Cushing syndrome ;
>>Growth hormone synthesis, secretion and action ;
>>Alzheimer disease ;
>>Prion disease ;
>>Pathways of neurodegeneration - multiple diseases ;
>>Chemical carcinogenesis - receptor activation ;
>>Hypertrophic cardiomyopathy ;
>>Arrhythmogenic right ventricular cardiomyopathy ;
>>Dilated cardiomyopathy