UniProt functional annotation for Q02789



	UniProt functional annotation for Q02789

UniProt code: Q02789.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Pore-forming, alpha-1S subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle via their interaction with RYR1, which triggers Ca(2+) release from the sarcplasmic reticulum and ultimately results in muscle contraction. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. {ECO:0000250|UniProtKB:P07293}.

Activity regulation: Channel activity is blocked by dihydropyridines (DHP), phenylalkylamines, and by benzothiazepines. {ECO:0000250|UniProtKB:P07293}.

Subunit: Component of a calcium channel complex consisting of a pore- forming alpha subunit (CACNA1S) and the ancillary subunits CACNB1 or CACNB2, CACNG1 and CACNA2D1 (PubMed:28351836). The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e. it contains either CACNB1 or CACNB2 (By similarity). CACNA1S channel activity is modulated by the auxiliary subunits (CACNB1 or CACNB2, CACNG1 and CACNA2D1). Interacts with DYSF and JSRP1 (PubMed:12871958, PubMed:16550931, PubMed:16638807). Interacts with RYR1 (By similarity). Interacts with STAC, STAC2 and STAC3 (via their SH3 domains) (PubMed:29467163). Interacts with CALM (By similarity). {ECO:0000250|UniProtKB:P07293, ECO:0000250|UniProtKB:Q13698, ECO:0000269|PubMed:12871958, ECO:0000269|PubMed:16550931, ECO:0000269|PubMed:16638807, ECO:0000269|PubMed:28351836, ECO:0000269|PubMed:29467163}.

Subcellular location: Cell membrane, sarcolemma, T-tubule {ECO:0000250|UniProtKB:P07293}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P07293}.

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. {ECO:0000250|UniProtKB:P07293}.

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. {ECO:0000250|UniProtKB:P07293}.

Ptm: The alpha-1S subunit is found in two isoforms in the skeletal muscle: a minor form of 212 kDa containing the complete amino acid sequence, and a major form of 190 kDa derived from the full-length form by post-translational proteolysis close to Phe-1690. {ECO:0000250|UniProtKB:P07293}.

Ptm: Phosphorylated. Phosphorylation by PKA activates the calcium channel. Both the minor and major forms are phosphorylated in vitro by PKA. Phosphorylation at Ser-1575 is involved in beta-adrenergic- mediated regulation of the channel. {ECO:0000250|UniProtKB:P07293}.

Disease: Note=Defects in Cacna1s are the cause of muscular dysgenesis (MDG), a lethal autosomal recessive disorder in which there is total lack of excitation-contraction coupling in homozygotes, and which results in complete skeletal muscle paralysis. A single nucleotide deletion yields a protein with an altered and truncated C-terminus. {ECO:0000269|PubMed:1281468}.

Similarity: Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1S subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Pore-forming, alpha-1S subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle via their interaction with RYR1, which triggers Ca(2+) release from the sarcplasmic reticulum and ultimately results in muscle contraction. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. {ECO:0000250\|UniProtKB:P07293}.


Activity regulation:		Channel activity is blocked by dihydropyridines (DHP), phenylalkylamines, and by benzothiazepines. {ECO:0000250\|UniProtKB:P07293}.
Subunit:		Component of a calcium channel complex consisting of a pore- forming alpha subunit (CACNA1S) and the ancillary subunits CACNB1 or CACNB2, CACNG1 and CACNA2D1 (PubMed:28351836). The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e. it contains either CACNB1 or CACNB2 (By similarity). CACNA1S channel activity is modulated by the auxiliary subunits (CACNB1 or CACNB2, CACNG1 and CACNA2D1). Interacts with DYSF and JSRP1 (PubMed:12871958, PubMed:16550931, PubMed:16638807). Interacts with RYR1 (By similarity). Interacts with STAC, STAC2 and STAC3 (via their SH3 domains) (PubMed:29467163). Interacts with CALM (By similarity). {ECO:0000250\|UniProtKB:P07293, ECO:0000250\|UniProtKB:Q13698, ECO:0000269\|PubMed:12871958, ECO:0000269\|PubMed:16550931, ECO:0000269\|PubMed:16638807, ECO:0000269\|PubMed:28351836, ECO:0000269\|PubMed:29467163}.
Subcellular location:		Cell membrane, sarcolemma, T-tubule {ECO:0000250\|UniProtKB:P07293}; Multi-pass membrane protein {ECO:0000250\|UniProtKB:P07293}.
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. {ECO:0000250\|UniProtKB:P07293}.
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. {ECO:0000250\|UniProtKB:P07293}.
Ptm:		The alpha-1S subunit is found in two isoforms in the skeletal muscle: a minor form of 212 kDa containing the complete amino acid sequence, and a major form of 190 kDa derived from the full-length form by post-translational proteolysis close to Phe-1690. {ECO:0000250\|UniProtKB:P07293}.
Ptm:		Phosphorylated. Phosphorylation by PKA activates the calcium channel. Both the minor and major forms are phosphorylated in vitro by PKA. Phosphorylation at Ser-1575 is involved in beta-adrenergic- mediated regulation of the channel. {ECO:0000250\|UniProtKB:P07293}.
Disease:		Note=Defects in Cacna1s are the cause of muscular dysgenesis (MDG), a lethal autosomal recessive disorder in which there is total lack of excitation-contraction coupling in homozygotes, and which results in complete skeletal muscle paralysis. A single nucleotide deletion yields a protein with an altered and truncated C-terminus. {ECO:0000269\|PubMed:1281468}.
Similarity:		Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1S subfamily. {ECO:0000305}.