UniProt functional annotation for P22002



	UniProt functional annotation for P22002

UniProt code: P22002.

Organism: Rattus norvegicus (Rat).

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

Function: Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents (Probable) (PubMed:15140941, PubMed:15170217). Mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm (By similarity). Plays an important role in excitation- contraction coupling in the heart (By similarity). Required for normal heart development and normal regulation of heart rhythm (By similarity). Required for normal contraction of smooth muscle cells in blood vessels and in the intestine. Essential for normal blood pressure regulation via its role in the contraction of arterial smooth muscle cells (By similarity). Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group (By similarity). {ECO:0000250|UniProtKB:P15381, ECO:0000250|UniProtKB:Q01815, ECO:0000250|UniProtKB:Q13936, ECO:0000269|PubMed:15140941, ECO:0000269|PubMed:15170217, ECO:0000305|PubMed:1648941}.

Activity regulation: Inhibited by dihydropyridines (DHP), such as isradipine (By similarity). Inhibited by nifedipine (By similarity). Channel activity is regulated by Ca(2+) and calmodulin (PubMed:15140941). Binding of STAC1, STAC2 or STAC3 to a region that overlaps with the calmodulin binding site inhibits channel inactivation by Ca(2+) and calmodulin (By similarity). Binding of calmodulin or CABP1 at the same regulatory sites results in opposite effects on the channel function (PubMed:15140941). Shear stress and pressure increases calcium channel activity (By similarity). {ECO:0000250|UniProtKB:P15381, ECO:0000250|UniProtKB:Q13936, ECO:0000269|PubMed:15140941}.

Subunit: Component of a calcium channel complex consisting of a pore- forming alpha subunit (CACNA1C) and ancillary beta, gamma and delta subunits (PubMed:15170217). The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e. it contains only one of each type of subunit. CACNA1C channel activity is modulated by ancillary subunits, such as CACNB1, CACNB2, CACNB3, CACNA2D1 and CACNA2D4 (By similarity). Interacts with the gamma subunits CACNG4, CACNG6, CACNG7 and CACNG8 (By similarity). Interacts with CACNB1 (By similarity). Interacts with CACNB2. Identified in a complex with CACNA2D4 and CACNB3 (By similarity). Interacts with CACNB3 (PubMed:24751537, PubMed:15170217). Interacts with CACNA2D1. Interacts with CACNA2D4. Interacts with CALM1. Interacts (via the N-terminus and the C-terminal C and IQ motifs) with CABP1; this inhibits Ca(2+)- dependent channel inactivation (PubMed:15140941). The binding via the C motif is calcium independent whereas the binding via IQ requires the presence of calcium and is mutually exclusive with calmodulin binding (PubMed:15140941). The binding to the cytoplasmic N-terminal domain is calcium independent but is essential for the channel modulation. Interacts (via C-terminal CDB motif) with CABP5; in a calcium-dependent manner. Interacts with CIB1; the interaction increases upon cardiomyocytes hypertrophy (By similarity). Interacts with STAC2 and STAC3; this inhibits channel inactivation (By similarity). {ECO:0000250|UniProtKB:P15381, ECO:0000250|UniProtKB:Q01815, ECO:0000250|UniProtKB:Q13936, ECO:0000269|PubMed:15140941, ECO:0000269|PubMed:15170217, ECO:0000269|PubMed:24751537}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:15140941, ECO:0000269|PubMed:15170217, ECO:0000305|PubMed:1648941}; Multi-pass membrane protein {ECO:0000305}. Cell membrane, sarcolemma {ECO:0000250|UniProtKB:P15381}; Multi-pass membrane protein {ECO:0000305}. Perikaryon {ECO:0000269|PubMed:15140941}. Cell junction, synapse, postsynaptic density membrane {ECO:0000269|PubMed:15140941}. Cell projection, dendrite {ECO:0000269|PubMed:15140941}. Cell membrane, sarcolemma, T-tubule {ECO:0000250|UniProtKB:Q01815}. Note=Colocalizes with ryanodine receptors in distinct clusters at the junctional membrane, where the sarcolemma and the sarcoplasmic reticulum are in close contact. The interaction between RRAD and CACNB2 promotes the expression of CACNA1C at the cell membrane. {ECO:0000250|UniProtKB:P15381}.

Tissue specificity: Detected in hippocampus and brain cortex, on neuronal cell bodies and dendrites, and in post-synaptic density in brain (at protein level) (PubMed:15140941). Isoforms 4 and 5 are expressed throughout the central nervous system, with highest levels in the olfactory bulb and cerebellum. Also expressed in heart, pituitary, adrenal gland, liver, kidney, and in a much lesser extent in testes and spleen. {ECO:0000269|PubMed:15140941}.

Developmental stage: Expressed from embryonic day 16 until the adult stage.

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: Binding of intracellular calcium through the EF-hand motif inhibits the opening of the channel. {ECO:0000250|UniProtKB:P15381}.

Ptm: Phosphorylation by PKA at Ser-1927 activates the channel (By similarity). Elevated levels of blood glucose lead to increased phosphorylation by PKA (By similarity). Is also phosphorylated in vitro by CaM-kinase II, PKC and CGPK (PubMed:8396138). {ECO:0000250|UniProtKB:Q01815, ECO:0000269|PubMed:8396138}.

Similarity: Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1C subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Rattus norvegicus (Rat).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.



Function:		Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents (Probable) (PubMed:15140941, PubMed:15170217). Mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm (By similarity). Plays an important role in excitation- contraction coupling in the heart (By similarity). Required for normal heart development and normal regulation of heart rhythm (By similarity). Required for normal contraction of smooth muscle cells in blood vessels and in the intestine. Essential for normal blood pressure regulation via its role in the contraction of arterial smooth muscle cells (By similarity). Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group (By similarity). {ECO:0000250\|UniProtKB:P15381, ECO:0000250\|UniProtKB:Q01815, ECO:0000250\|UniProtKB:Q13936, ECO:0000269\|PubMed:15140941, ECO:0000269\|PubMed:15170217, ECO:0000305\|PubMed:1648941}.


Activity regulation:		Inhibited by dihydropyridines (DHP), such as isradipine (By similarity). Inhibited by nifedipine (By similarity). Channel activity is regulated by Ca(2+) and calmodulin (PubMed:15140941). Binding of STAC1, STAC2 or STAC3 to a region that overlaps with the calmodulin binding site inhibits channel inactivation by Ca(2+) and calmodulin (By similarity). Binding of calmodulin or CABP1 at the same regulatory sites results in opposite effects on the channel function (PubMed:15140941). Shear stress and pressure increases calcium channel activity (By similarity). {ECO:0000250\|UniProtKB:P15381, ECO:0000250\|UniProtKB:Q13936, ECO:0000269\|PubMed:15140941}.
Subunit:		Component of a calcium channel complex consisting of a pore- forming alpha subunit (CACNA1C) and ancillary beta, gamma and delta subunits (PubMed:15170217). The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e. it contains only one of each type of subunit. CACNA1C channel activity is modulated by ancillary subunits, such as CACNB1, CACNB2, CACNB3, CACNA2D1 and CACNA2D4 (By similarity). Interacts with the gamma subunits CACNG4, CACNG6, CACNG7 and CACNG8 (By similarity). Interacts with CACNB1 (By similarity). Interacts with CACNB2. Identified in a complex with CACNA2D4 and CACNB3 (By similarity). Interacts with CACNB3 (PubMed:24751537, PubMed:15170217). Interacts with CACNA2D1. Interacts with CACNA2D4. Interacts with CALM1. Interacts (via the N-terminus and the C-terminal C and IQ motifs) with CABP1; this inhibits Ca(2+)- dependent channel inactivation (PubMed:15140941). The binding via the C motif is calcium independent whereas the binding via IQ requires the presence of calcium and is mutually exclusive with calmodulin binding (PubMed:15140941). The binding to the cytoplasmic N-terminal domain is calcium independent but is essential for the channel modulation. Interacts (via C-terminal CDB motif) with CABP5; in a calcium-dependent manner. Interacts with CIB1; the interaction increases upon cardiomyocytes hypertrophy (By similarity). Interacts with STAC2 and STAC3; this inhibits channel inactivation (By similarity). {ECO:0000250\|UniProtKB:P15381, ECO:0000250\|UniProtKB:Q01815, ECO:0000250\|UniProtKB:Q13936, ECO:0000269\|PubMed:15140941, ECO:0000269\|PubMed:15170217, ECO:0000269\|PubMed:24751537}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:15140941, ECO:0000269\|PubMed:15170217, ECO:0000305\|PubMed:1648941}; Multi-pass membrane protein {ECO:0000305}. Cell membrane, sarcolemma {ECO:0000250\|UniProtKB:P15381}; Multi-pass membrane protein {ECO:0000305}. Perikaryon {ECO:0000269\|PubMed:15140941}. Cell junction, synapse, postsynaptic density membrane {ECO:0000269\|PubMed:15140941}. Cell projection, dendrite {ECO:0000269\|PubMed:15140941}. Cell membrane, sarcolemma, T-tubule {ECO:0000250\|UniProtKB:Q01815}. Note=Colocalizes with ryanodine receptors in distinct clusters at the junctional membrane, where the sarcolemma and the sarcoplasmic reticulum are in close contact. The interaction between RRAD and CACNB2 promotes the expression of CACNA1C at the cell membrane. {ECO:0000250\|UniProtKB:P15381}.
Tissue specificity:		Detected in hippocampus and brain cortex, on neuronal cell bodies and dendrites, and in post-synaptic density in brain (at protein level) (PubMed:15140941). Isoforms 4 and 5 are expressed throughout the central nervous system, with highest levels in the olfactory bulb and cerebellum. Also expressed in heart, pituitary, adrenal gland, liver, kidney, and in a much lesser extent in testes and spleen. {ECO:0000269\|PubMed:15140941}.
Developmental stage:		Expressed from embryonic day 16 until the adult stage.
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:		Binding of intracellular calcium through the EF-hand motif inhibits the opening of the channel. {ECO:0000250\|UniProtKB:P15381}.
Ptm:		Phosphorylation by PKA at Ser-1927 activates the channel (By similarity). Elevated levels of blood glucose lead to increased phosphorylation by PKA (By similarity). Is also phosphorylated in vitro by CaM-kinase II, PKC and CGPK (PubMed:8396138). {ECO:0000250\|UniProtKB:Q01815, ECO:0000269\|PubMed:8396138}.
Similarity:		Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1C subfamily. {ECO:0000305}.