CAC1C_RAT
ID CAC1C_RAT Reviewed; 2169 AA.
AC P22002; P27733; P27734; Q62816; Q63271; Q64178;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1991, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Voltage-dependent L-type calcium channel subunit alpha-1C;
DE AltName: Full=Calcium channel, L type, alpha-1 polypeptide, isoform 1, cardiac muscle;
DE AltName: Full=Rat brain class C {ECO:0000303|PubMed:1648941};
DE Short=RBC {ECO:0000303|PubMed:1648941};
DE AltName: Full=Voltage-gated calcium channel subunit alpha Cav1.2;
GN Name=Cacna1c; Synonyms=Cach2, Cacn2, Cacnl1a1, Cchl1a1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Aorta;
RX PubMed=2170396; DOI=10.1016/s0021-9258(18)38232-2;
RA Koch W.J., Ellinor P.T., Schwartz A.;
RT "cDNA cloning of a dihydropyridine-sensitive calcium channel from rat
RT aorta. Evidence for the existence of alternatively spliced forms.";
RL J. Biol. Chem. 265:17786-17791(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 5), FUNCTION, AND SUBCELLULAR
RP LOCATION.
RC TISSUE=Brain;
RX PubMed=1648941; DOI=10.1016/0896-6273(91)90073-9;
RA Snutch T.P., Tomlinson W.J., Leonard J.P., Gilbert M.M.;
RT "Distinct calcium channels are generated by alternative splicing and are
RT differentially expressed in the mammalian CNS.";
RL Neuron 7:45-57(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1168-1413 (ISOFORM 1).
RX PubMed=1692134; DOI=10.1073/pnas.87.9.3391;
RA Snutch T.P., Leonard J.P., Gilbert M.M., Lester H.A., Davidson N.;
RT "Rat brain expresses a heterogeneous family of calcium channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:3391-3395(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1269-1415 (ISOFORMS 1; 2 AND 3).
RX PubMed=1311102; DOI=10.1073/pnas.89.4.1497;
RA Diebold R.J., Koch W.J., Ellinor P.T., Wang J.-J., Muthuchamy M.,
RA Wieczorek D.F., Schwartz A.;
RT "Mutually exclusive exon splicing of the cardiac calcium channel a1 subunit
RT generates developmentally regulated isoforms in the rat heart.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:1497-1501(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1269-1387.
RC TISSUE=Myometrium;
RX PubMed=7485440; DOI=10.1152/ajpcell.1995.269.4.c1008;
RA Tezuka N., Ali M., Chwalisz K., Garfield R.E.;
RT "Changes in transcripts encoding calcium channel subunits of rat myometrium
RT during pregnancy.";
RL Am. J. Physiol. 269:C1008-C1017(1995).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1202-1495 (ISOFORM 3).
RC TISSUE=Osteosarcoma;
RX PubMed=7479909; DOI=10.1073/pnas.92.24.10914;
RA Barry E.L.R., Gesek F.A., Froehner S.C., Friedman P.A.;
RT "Multiple calcium channel transcripts in rat osteosarcoma cells: selective
RT activation of alpha 1D isoform by parathyroid hormone.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:10914-10918(1995).
RN [7]
RP PHOSPHORYLATION.
RX PubMed=8396138; DOI=10.1016/s0021-9258(19)36536-6;
RA Hell J.W., Yokoyama C.T., Wong S.T., Warner C., Snutch T.P.,
RA Catterall W.A.;
RT "Differential phosphorylation of two size forms of the neuronal class C L-
RT type calcium channel alpha 1 subunit.";
RL J. Biol. Chem. 268:19451-19457(1993).
RN [8]
RP INTERACTION WITH CACNA2D1.
RX PubMed=9278523; DOI=10.1523/jneurosci.17-18-06884.1997;
RA Felix R., Gurnett C.A., De Waard M., Campbell K.P.;
RT "Dissection of functional domains of the voltage-dependent Ca2+ channel
RT alpha2delta subunit.";
RL J. Neurosci. 17:6884-6891(1997).
RN [9]
RP INTERACTION WITH CABP1, FUNCTION, ACTIVITY REGULATION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15140941; DOI=10.1523/jneurosci.5523-03.2004;
RA Zhou H., Kim S.-A., Kirk E.A., Tippens A.L., Sun H., Haeseleer F., Lee A.;
RT "Ca2+-binding protein-1 facilitates and forms a postsynaptic complex with
RT Cav1.2 (L-type) Ca2+ channels.";
RL J. Neurosci. 24:4698-4708(2004).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-845; SER-1699 AND SER-1720,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [11]
RP INTERACTION WITH CACNB3.
RX PubMed=24751537; DOI=10.1083/jcb.201304101;
RA Beguin P., Nagashima K., Mahalakshmi R.N., Vigot R., Matsunaga A., Miki T.,
RA Ng M.Y., Ng Y.J., Lim C.H., Tay H.S., Hwang L.A., Firsov D., Tang B.L.,
RA Inagaki N., Mori Y., Seino S., Launey T., Hunziker W.;
RT "BARP suppresses voltage-gated calcium channel activity and Ca2+-evoked
RT exocytosis.";
RL J. Cell Biol. 205:233-249(2014).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 452-476 IN COMPLEX WITH CACNB3,
RP FUNCTION, AND REGION.
RX PubMed=15170217; DOI=10.1038/nature02641;
RA Chen Y.H., Li M.H., Zhang Y., He L.L., Yamada Y., Fitzmaurice A., Shen Y.,
RA Zhang H., Tong L., Yang J.;
RT "Structural basis of the alpha1-beta subunit interaction of voltage-gated
RT Ca2+ channels.";
RL Nature 429:675-680(2004).
CC -!- FUNCTION: Pore-forming, alpha-1C subunit of the voltage-gated calcium
CC channel that gives rise to L-type calcium currents (Probable)
CC (PubMed:15140941, PubMed:15170217). Mediates influx of calcium ions
CC into the cytoplasm, and thereby triggers calcium release from the
CC sarcoplasm (By similarity). Plays an important role in excitation-
CC contraction coupling in the heart (By similarity). Required for normal
CC heart development and normal regulation of heart rhythm (By
CC similarity). Required for normal contraction of smooth muscle cells in
CC blood vessels and in the intestine. Essential for normal blood pressure
CC regulation via its role in the contraction of arterial smooth muscle
CC cells (By similarity). Long-lasting (L-type) calcium channels belong to
CC the 'high-voltage activated' (HVA) group (By similarity).
CC {ECO:0000250|UniProtKB:P15381, ECO:0000250|UniProtKB:Q01815,
CC ECO:0000250|UniProtKB:Q13936, ECO:0000269|PubMed:15140941,
CC ECO:0000269|PubMed:15170217, ECO:0000305|PubMed:1648941}.
CC -!- ACTIVITY REGULATION: Inhibited by dihydropyridines (DHP), such as
CC isradipine (By similarity). Inhibited by nifedipine (By similarity).
CC Channel activity is regulated by Ca(2+) and calmodulin
CC (PubMed:15140941). Binding of STAC1, STAC2 or STAC3 to a region that
CC overlaps with the calmodulin binding site inhibits channel inactivation
CC by Ca(2+) and calmodulin (By similarity). Binding of calmodulin or
CC CABP1 at the same regulatory sites results in opposite effects on the
CC channel function (PubMed:15140941). Shear stress and pressure increases
CC calcium channel activity (By similarity).
CC {ECO:0000250|UniProtKB:P15381, ECO:0000250|UniProtKB:Q13936,
CC ECO:0000269|PubMed:15140941}.
CC -!- SUBUNIT: Component of a calcium channel complex consisting of a pore-
CC forming alpha subunit (CACNA1C) and ancillary beta, gamma and delta
CC subunits (PubMed:15170217). The channel complex contains alpha, beta,
CC gamma and delta subunits in a 1:1:1:1 ratio, i.e. it contains only one
CC of each type of subunit. CACNA1C channel activity is modulated by
CC ancillary subunits, such as CACNB1, CACNB2, CACNB3, CACNA2D1 and
CC CACNA2D4 (By similarity). Interacts with the gamma subunits CACNG4,
CC CACNG6, CACNG7 and CACNG8 (By similarity). Interacts with CACNB1 (By
CC similarity). Interacts with CACNB2. Identified in a complex with
CC CACNA2D4 and CACNB3 (By similarity). Interacts with CACNB3
CC (PubMed:24751537, PubMed:15170217). Interacts with CACNA2D1. Interacts
CC with CACNA2D4. Interacts with CALM1. Interacts (via the N-terminus and
CC the C-terminal C and IQ motifs) with CABP1; this inhibits Ca(2+)-
CC dependent channel inactivation (PubMed:15140941). The binding via the C
CC motif is calcium independent whereas the binding via IQ requires the
CC presence of calcium and is mutually exclusive with calmodulin binding
CC (PubMed:15140941). The binding to the cytoplasmic N-terminal domain is
CC calcium independent but is essential for the channel modulation.
CC Interacts (via C-terminal CDB motif) with CABP5; in a calcium-dependent
CC manner. Interacts with CIB1; the interaction increases upon
CC cardiomyocytes hypertrophy (By similarity). Interacts with STAC2 and
CC STAC3; this inhibits channel inactivation (By similarity).
CC {ECO:0000250|UniProtKB:P15381, ECO:0000250|UniProtKB:Q01815,
CC ECO:0000250|UniProtKB:Q13936, ECO:0000269|PubMed:15140941,
CC ECO:0000269|PubMed:15170217, ECO:0000269|PubMed:24751537}.
CC -!- INTERACTION:
CC P22002; P63329: Ppp3ca; NbExp=5; IntAct=EBI-1185084, EBI-7022944;
CC P22002; Q9WUD9: Src; NbExp=4; IntAct=EBI-1185084, EBI-7784541;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15140941,
CC ECO:0000269|PubMed:15170217, ECO:0000305|PubMed:1648941}; Multi-pass
CC membrane protein {ECO:0000305}. Cell membrane, sarcolemma
CC {ECO:0000250|UniProtKB:P15381}; Multi-pass membrane protein
CC {ECO:0000305}. Perikaryon {ECO:0000269|PubMed:15140941}. Postsynaptic
CC density membrane {ECO:0000269|PubMed:15140941}. Cell projection,
CC dendrite {ECO:0000269|PubMed:15140941}. Cell membrane, sarcolemma, T-
CC tubule {ECO:0000250|UniProtKB:Q01815}. Note=Colocalizes with ryanodine
CC receptors in distinct clusters at the junctional membrane, where the
CC sarcolemma and the sarcoplasmic reticulum are in close contact. The
CC interaction between RRAD and CACNB2 promotes the expression of CACNA1C
CC at the cell membrane. {ECO:0000250|UniProtKB:P15381}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Comment=Additional isoforms seem to exist.;
CC Name=2; Synonyms=S3B;
CC IsoId=P22002-1; Sequence=Displayed;
CC Name=1; Synonyms=S3A;
CC IsoId=P22002-2; Sequence=VSP_000911;
CC Name=3; Synonyms=D1, ROB2;
CC IsoId=P22002-3; Sequence=VSP_000912;
CC Name=4; Synonyms=rbC-I;
CC IsoId=P22002-4; Sequence=VSP_000908, VSP_000910, VSP_000911;
CC Name=5; Synonyms=rbC-II;
CC IsoId=P22002-5; Sequence=VSP_000908, VSP_000909, VSP_000910;
CC -!- TISSUE SPECIFICITY: Detected in hippocampus and brain cortex, on
CC neuronal cell bodies and dendrites, and in post-synaptic density in
CC brain (at protein level) (PubMed:15140941). Isoforms 4 and 5 are
CC expressed throughout the central nervous system, with highest levels in
CC the olfactory bulb and cerebellum. Also expressed in heart, pituitary,
CC adrenal gland, liver, kidney, and in a much lesser extent in testes and
CC spleen. {ECO:0000269|PubMed:15140941}.
CC -!- DEVELOPMENTAL STAGE: Expressed from embryonic day 16 until the adult
CC stage.
CC -!- DOMAIN: Each of the four internal repeats contains five hydrophobic
CC transmembrane segments (S1, S2, S3, S5, S6) and one positively charged
CC transmembrane segment (S4). S4 segments probably represent the voltage-
CC sensor and are characterized by a series of positively charged amino
CC acids at every third position.
CC -!- DOMAIN: Binding of intracellular calcium through the EF-hand motif
CC inhibits the opening of the channel. {ECO:0000250|UniProtKB:P15381}.
CC -!- PTM: Phosphorylation by PKA at Ser-1927 activates the channel (By
CC similarity). Elevated levels of blood glucose lead to increased
CC phosphorylation by PKA (By similarity). Is also phosphorylated in vitro
CC by CaM-kinase II, PKC and CGPK (PubMed:8396138).
CC {ECO:0000250|UniProtKB:Q01815, ECO:0000269|PubMed:8396138}.
CC -!- SIMILARITY: Belongs to the calcium channel alpha-1 subunit (TC
CC 1.A.1.11) family. CACNA1C subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M59786; AAA85463.1; -; mRNA.
DR EMBL; M67515; AAA18905.1; -; mRNA.
DR EMBL; M67516; AAA42016.1; -; mRNA.
DR EMBL; M91242; AAA41460.1; -; Genomic_DNA.
DR EMBL; M91240; AAA41460.1; JOINED; Genomic_DNA.
DR EMBL; M89924; AAA41460.1; JOINED; Genomic_DNA.
DR EMBL; M91241; AAA41460.1; JOINED; Genomic_DNA.
DR EMBL; S80558; AAB35528.1; -; mRNA.
DR EMBL; U31815; AAA89157.1; -; mRNA.
DR RefSeq; NP_036649.2; NM_012517.2.
DR PDB; 1VYT; X-ray; 2.60 A; E/F=452-476.
DR PDBsum; 1VYT; -.
DR AlphaFoldDB; P22002; -.
DR SMR; P22002; -.
DR BioGRID; 246425; 4.
DR CORUM; P22002; -.
DR IntAct; P22002; 4.
DR MINT; P22002; -.
DR STRING; 10116.ENSRNOP00000009268; -.
DR BindingDB; P22002; -.
DR ChEMBL; CHEMBL3762; -.
DR DrugCentral; P22002; -.
DR GuidetoPHARMACOLOGY; 529; -.
DR GlyGen; P22002; 4 sites.
DR iPTMnet; P22002; -.
DR PhosphoSitePlus; P22002; -.
DR PaxDb; P22002; -.
DR PRIDE; P22002; -.
DR ABCD; P22002; 2 sequenced antibodies.
DR GeneID; 24239; -.
DR KEGG; rno:24239; -.
DR UCSC; RGD:2245; rat. [P22002-1]
DR CTD; 775; -.
DR RGD; 2245; Cacna1c.
DR eggNOG; KOG2301; Eukaryota.
DR InParanoid; P22002; -.
DR OrthoDB; 172471at2759; -.
DR PhylomeDB; P22002; -.
DR Reactome; R-RNO-422356; Regulation of insulin secretion.
DR Reactome; R-RNO-5576892; Phase 0 - rapid depolarisation.
DR Reactome; R-RNO-5576893; Phase 2 - plateau phase.
DR EvolutionaryTrace; P22002; -.
DR PRO; PR:P22002; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0002095; C:caveolar macromolecular signaling complex; ISO:RGD.
DR GO; GO:0009986; C:cell surface; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0030425; C:dendrite; IDA:UniProtKB.
DR GO; GO:0043198; C:dendritic shaft; ISO:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0016021; C:integral component of membrane; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IDA:SynGO.
DR GO; GO:0099056; C:integral component of presynaptic membrane; IDA:SynGO.
DR GO; GO:1990454; C:L-type voltage-gated calcium channel complex; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0014069; C:postsynaptic density; IDA:UniProtKB.
DR GO; GO:0098839; C:postsynaptic density membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045211; C:postsynaptic membrane; IDA:SynGO.
DR GO; GO:0042734; C:presynaptic membrane; IDA:SynGO.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0042383; C:sarcolemma; IDA:RGD.
DR GO; GO:0030315; C:T-tubule; IDA:RGD.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; IDA:RGD.
DR GO; GO:0030018; C:Z disc; IDA:BHF-UCL.
DR GO; GO:0051393; F:alpha-actinin binding; ISS:BHF-UCL.
DR GO; GO:0005516; F:calmodulin binding; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0008331; F:high voltage-gated calcium channel activity; IDA:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR GO; GO:0051721; F:protein phosphatase 2A binding; IPI:RGD.
DR GO; GO:0031369; F:translation initiation factor binding; IPI:RGD.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:BHF-UCL.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IDA:RGD.
DR GO; GO:0086056; F:voltage-gated calcium channel activity involved in AV node cell action potential; ISS:BHF-UCL.
DR GO; GO:0086007; F:voltage-gated calcium channel activity involved in cardiac muscle cell action potential; ISS:BHF-UCL.
DR GO; GO:1905030; F:voltage-gated ion channel activity involved in regulation of postsynaptic membrane potential; ISO:RGD.
DR GO; GO:0007628; P:adult walking behavior; ISO:RGD.
DR GO; GO:0070509; P:calcium ion import; IMP:RGD.
DR GO; GO:0098703; P:calcium ion import across plasma membrane; ISO:RGD.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISO:RGD.
DR GO; GO:0061577; P:calcium ion transmembrane transport via high voltage-gated calcium channel; IDA:UniProtKB.
DR GO; GO:0006816; P:calcium ion transport; IMP:RGD.
DR GO; GO:0060402; P:calcium ion transport into cytosol; ISS:UniProtKB.
DR GO; GO:0017156; P:calcium-ion regulated exocytosis; ISO:RGD.
DR GO; GO:0043010; P:camera-type eye development; ISO:RGD.
DR GO; GO:0061337; P:cardiac conduction; ISS:UniProtKB.
DR GO; GO:0086002; P:cardiac muscle cell action potential involved in contraction; ISS:BHF-UCL.
DR GO; GO:0086065; P:cell communication involved in cardiac conduction; ISO:RGD.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:RGD.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IEP:RGD.
DR GO; GO:0007268; P:chemical synaptic transmission; ISO:RGD.
DR GO; GO:0035115; P:embryonic forelimb morphogenesis; ISO:RGD.
DR GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
DR GO; GO:0030252; P:growth hormone secretion; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0002520; P:immune system development; ISO:RGD.
DR GO; GO:0030073; P:insulin secretion; ISO:RGD.
DR GO; GO:0098912; P:membrane depolarization during atrial cardiac muscle cell action potential; ISS:BHF-UCL.
DR GO; GO:0086045; P:membrane depolarization during AV node cell action potential; ISS:BHF-UCL.
DR GO; GO:0086012; P:membrane depolarization during cardiac muscle cell action potential; ISS:BHF-UCL.
DR GO; GO:0045762; P:positive regulation of adenylate cyclase activity; ISS:UniProtKB.
DR GO; GO:1904879; P:positive regulation of calcium ion transmembrane transport via high voltage-gated calcium channel; IMP:RGD.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:RGD.
DR GO; GO:0008217; P:regulation of blood pressure; ISO:RGD.
DR GO; GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; ISS:UniProtKB.
DR GO; GO:0086091; P:regulation of heart rate by cardiac conduction; ISS:BHF-UCL.
DR GO; GO:0046620; P:regulation of organ growth; ISO:RGD.
DR GO; GO:0019229; P:regulation of vasoconstriction; ISO:RGD.
DR GO; GO:0098911; P:regulation of ventricular cardiac muscle cell action potential; ISS:BHF-UCL.
DR GO; GO:0006939; P:smooth muscle contraction; ISO:RGD.
DR GO; GO:0060083; P:smooth muscle contraction involved in micturition; ISO:RGD.
DR GO; GO:0008542; P:visual learning; ISO:RGD.
DR Gene3D; 1.20.120.350; -; 4.
DR InterPro; IPR031688; CAC1F_C.
DR InterPro; IPR031649; GPHH_dom.
DR InterPro; IPR005821; Ion_trans_dom.
DR InterPro; IPR014873; VDCC_a1su_IQ.
DR InterPro; IPR005451; VDCC_L_a1csu.
DR InterPro; IPR005446; VDCC_L_a1su.
DR InterPro; IPR002077; VDCCAlpha1.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR Pfam; PF08763; Ca_chan_IQ; 1.
DR Pfam; PF16885; CAC1F_C; 2.
DR Pfam; PF16905; GPHH; 1.
DR Pfam; PF00520; Ion_trans; 4.
DR PRINTS; PR00167; CACHANNEL.
DR PRINTS; PR01630; LVDCCALPHA1.
DR PRINTS; PR01635; LVDCCALPHA1C.
DR SMART; SM01062; Ca_chan_IQ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Calcium channel;
KW Calcium transport; Calmodulin-binding; Cell membrane; Cell projection;
KW Disulfide bond; Glycoprotein; Ion channel; Ion transport; Membrane;
KW Metal-binding; Phosphoprotein; Postsynaptic cell membrane;
KW Reference proteome; Repeat; Synapse; Transmembrane; Transmembrane helix;
KW Transport; Voltage-gated channel.
FT CHAIN 1..2169
FT /note="Voltage-dependent L-type calcium channel subunit
FT alpha-1C"
FT /id="PRO_0000053931"
FT TOPO_DOM 1..154
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 155..173
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 174..188
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 189..209
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 210..218
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 219..239
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 240..262
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 263..281
FT /note="Helical; Name=S4 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 282..298
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 299..320
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 321..380
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 381..402
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 403..410
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 411..431
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 432..554
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 555..573
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 574..584
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 585..605
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 606..616
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 617..636
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 637..645
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 646..664
FT /note="Helical; Name=S4 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 665..683
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 684..703
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 704..723
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 724..745
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 746..755
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 756..775
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 776..930
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 931..949
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 950..961
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 962..981
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 982..997
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 998..1016
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1017..1023
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1024..1041
FT /note="Helical; Name=S4 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1042..1060
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1061..1080
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1081..1130
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1131..1151
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1152..1168
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1169..1190
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1191..1248
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1249..1270
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1271..1278
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1279..1300
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1301..1310
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1311..1330
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1331..1353
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1354..1372
FT /note="Helical; Name=S4 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1373..1390
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1391..1411
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1412..1433
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1434..1452
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1453..1480
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1481..1505
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1506..2169
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REPEAT 141..438
FT /note="I"
FT REPEAT 540..786
FT /note="II"
FT REPEAT 917..1198
FT /note="III"
FT REPEAT 1235..1508
FT /note="IV"
FT REGION 77..98
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:Q13936"
FT REGION 104..128
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 458..475
FT /note="AID/alpha-interaction domain; mediates interaction
FT with the beta subunit"
FT /evidence="ECO:0000269|PubMed:15170217"
FT REGION 479..511
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 794..891
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 859..906
FT /note="Interaction with STAC2"
FT /evidence="ECO:0000250|UniProtKB:Q13936"
FT REGION 1118..1207
FT /note="Dihydropyridine binding"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT REGION 1459..1527
FT /note="Dihydropyridine binding"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT REGION 1473..1515
FT /note="Phenylalkylamine binding"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT REGION 1640..1673
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:Q13936"
FT REGION 1640..1667
FT /note="Important for interaction with STAC1, STAC2 and
FT STAC3"
FT /evidence="ECO:0000250|UniProtKB:P15381"
FT REGION 1646..1666
FT /note="Calmodulin-binding IQ region"
FT /evidence="ECO:0000250|UniProtKB:Q13936"
FT REGION 1680..1699
FT /note="Important for localization in at the junctional
FT membrane"
FT /evidence="ECO:0000250|UniProtKB:P15381"
FT REGION 1761..1793
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1970..1998
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 391..394
FT /note="Selectivity filter of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT MOTIF 734..737
FT /note="Selectivity filter of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT MOTIF 1142..1145
FT /note="Selectivity filter of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT MOTIF 1443..1446
FT /note="Selectivity filter of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT COMPBIAS 794..839
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 856..872
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1977..1992
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 393
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT BINDING 736
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT BINDING 1144
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT MOD_RES 499
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01815"
FT MOD_RES 506
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q01815"
FT MOD_RES 838
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01815"
FT MOD_RES 845
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1699
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1720
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1927
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:Q01815"
FT CARBOHYD 183
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 358
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1417
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1468
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 328..356
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT DISULFID 346..362
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT DISULFID 1460..1476
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT VAR_SEQ 1..46
FT /note="MIRAFAQPSTPPYQPLSSCLSEDTERKFKGKVVHEAQLNCFYISPG -> MV
FT NENTRMYVPEENHQ (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:1648941"
FT /id="VSP_000908"
FT VAR_SEQ 810
FT /note="R -> RPAR (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:1648941"
FT /id="VSP_000909"
FT VAR_SEQ 964..979
FT /note="FYFDIVFTTIFTIEIA -> GNADYVFTSIFTLEII (in isoform 4
FT and isoform 5)"
FT /evidence="ECO:0000303|PubMed:1648941"
FT /id="VSP_000910"
FT VAR_SEQ 1306..1333
FT /note="HYFCDAWNTFDALIVVGSIVDIAITEVH -> GYFSDPSNVFDFLIVIGSII
FT AVILSETN (in isoform 1 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:1648941,
FT ECO:0000303|PubMed:1692134"
FT /id="VSP_000911"
FT VAR_SEQ 1334..1344
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:7479909"
FT /id="VSP_000912"
FT CONFLICT 83
FT /note="L -> Q (in Ref. 2; AAA18905/AAA42016)"
FT /evidence="ECO:0000305"
FT CONFLICT 87
FT /note="D -> G (in Ref. 2; AAA18905)"
FT /evidence="ECO:0000305"
FT CONFLICT 520
FT /note="G -> R (in Ref. 2; AAA18905)"
FT /evidence="ECO:0000305"
FT CONFLICT 648..649
FT /note="CW -> VL (in Ref. 2; AAA18905/AAA42016)"
FT /evidence="ECO:0000305"
FT CONFLICT 678
FT /note="L -> V (in Ref. 2; AAA18905/AAA42016)"
FT /evidence="ECO:0000305"
FT CONFLICT 769..770
FT /note="SP -> CG (in Ref. 2; AAA18905/AAA42016)"
FT /evidence="ECO:0000305"
FT CONFLICT 777
FT /note="L -> V (in Ref. 2; AAA18905/AAA42016)"
FT /evidence="ECO:0000305"
FT CONFLICT 871
FT /note="D -> N (in Ref. 2; AAA18905)"
FT /evidence="ECO:0000305"
FT CONFLICT 1037
FT /note="R -> RA (in Ref. 2; AAA18905/AAA42016)"
FT /evidence="ECO:0000305"
FT CONFLICT 1098
FT /note="S -> C (in Ref. 2; AAA18905/AAA42016)"
FT /evidence="ECO:0000305"
FT CONFLICT 1107
FT /note="T -> D (in Ref. 2; AAA18905/AAA42016)"
FT /evidence="ECO:0000305"
FT CONFLICT 1229
FT /note="P -> R (in Ref. 2; AAA18905/AAA42016, 3; no
FT nucleotide entry and 6; AAA89157)"
FT /evidence="ECO:0000305"
FT CONFLICT 1306
FT /note="H -> D (in Ref. 5; AAB35528)"
FT /evidence="ECO:0000305"
FT CONFLICT 1306
FT /note="H -> G (in Ref. 2; AAA42016 and 6; AAA89157)"
FT /evidence="ECO:0000305"
FT CONFLICT 1329
FT /note="I -> L (in Ref. 5; AAB35528)"
FT /evidence="ECO:0000305"
FT CONFLICT 1471
FT /note="E -> K (in Ref. 2; AAA18905)"
FT /evidence="ECO:0000305"
FT CONFLICT 1911
FT /note="C -> S (in Ref. 2; AAA18905/AAA42016)"
FT /evidence="ECO:0000305"
FT CONFLICT 2084
FT /note="K -> N (in Ref. 2; AAA18905)"
FT /evidence="ECO:0000305"
FT CONFLICT 2154
FT /note="R -> Q (in Ref. 2; AAA42016)"
FT /evidence="ECO:0000305"
FT HELIX 454..474
FT /evidence="ECO:0007829|PDB:1VYT"
SQ SEQUENCE 2169 AA; 243482 MW; D3ADBD20E4763B69 CRC64;
MIRAFAQPST PPYQPLSSCL SEDTERKFKG KVVHEAQLNC FYISPGGSNY GSPRPAHANM
NANAAAGLAP EHIPTPGAAL SWLAAIDAAR QAKLMGSAGN ATISTVSSTQ RKRQQYGKPK
KQGGTTATRP PRALLCLTLK NPIRRACISI VEWKPFEIII LLTIFANCVA LAIYIPFPED
DSNATNSNLE RVEYLFLIIF TVEAFLKVIA YGLLFHPNAY LRNGWNLLDF IIVVVGLFSA
ILEQATKADG ANALGGKGAG FDVKALRAFR VLRPLRLVSG VPSLQVVLNS IIKAMVPLLH
IALLVLFVII IYAIIGLELF MGKMHKTCYN QEGIIDVPAE EDPSPCALET GHGRQCQNGT
VCKPGWDGPK HGITNFDNFA FAMLTVFQCI TMEGWTDVLY WMQDAMGYEL PWVYFVSLVI
FGSFFVLNLV LGVLSGEFSK EREKAKARGD FQKLREKQQL EEDLKGYLDW ITQAEDIDPE
NEDEGMDEDK PRNMSMPTSE TESVNTENVA GGDIEGENCG ARLAHRISKS KFSRYWRRWN
RFCRRKCRAA VKSNVFYWLV IFLVFLNTLT IASEHYNQPH WLTEVQDTAN KALLALFTAE
MLLKMYSLGL QAYFVSLFNR FDCFIVCGGI LETILVETKI MSPLGISCWR CVRLLRIFKI
TRYWNSLSNL VASLLNSLRS IASLLLLLFL FIIIFSLLGM QLFGGKFNFD EMQTRRSTFD
NFPQSLLTVF QILTGEDWNS VMYDGIMAYG GPSFPGMLVC IYFIILFISP NYILLNLFLA
IAVDNLADAE SLTSAQKEEE EEKERKKLAR TASPEKKQEV MEKPAVEESK EEKIELKSIT
ADGESPPTTK INMDDLQPSE NEDKSPHSNP DTAGEEDEEE PEMPVGPRPR PLSELHLKEK
AVPMPEASAF FIFSPNNRFR LQCHRIVNDT IFTNLILFFI LLSSISLAAE DPVQHTSFRN
HILFYFDIVF TTIFTIEIAL KMTAYGAFLH KGSFCRNYFN ILDLLVVSVS LISFGIQSSA
INVVKILRVL RVLRPLRINR AKGLKHVVQC VFVAIRTIGN IVIVTTLLQF MFACIGVQLF
KGKLYTCSDS SKQTEAESKG NYITYKTGEV DHPIIQPRSW ENSKFDFDNV LAAMMALFTV
STFEGWPELL YRSIDSHTED KGPIYNYRVE ISIFFIIYII IIAFFMMNIF VGFVIVTFQE
QGEQEYKNCE LDKNQRQCVE YALKARPLPR YIPKNQHQYK VWYVVNSTYF EYLMFVLILL
NTICLAMQHY GQSCLFKIAM NILNMLFTGL FTVEMILKLI AFKPKHYFCD AWNTFDALIV
VGSIVDIAIT EVHPAEHTQC SPSMSAEENS RISITFFRLF RVMRLVKLLS RGEGIRTLLW
TFIKSFQALP YVALLIVMLF FIYAVIGMQV FGKIALNDTT EINRNNNFQT FPQAVLLLFR
CATGEAWQDI MLACMPGKKC APESEPSNST EGETPCGSSF AVFYFISFYM LCAFLIINLF
VAVIMDNFDY LTRDWSILGP HHLDEFKRIW AEYDPEAKGR IKHLDVVTLL RRIQPPLGFG
KLCPHRVACK RLVSMNMPLN SDGTVMFNAT LFALVRTALR IKTEGNLEQA NEELRAIIKK
IWKRTSMKLL DQVVPPAGDD EVTVGKFYAT FLIQEYFRKF KKRKEQGLVG KPSQRNALSL
QAGLRTLHDI GPEIRRAISG DLTAEEELDK AMKEAVSAAS EDDIFRRAGG LFGNHVSYYQ
SDSRSNFPQT FATQRPLHIN KTGNNQADTE SPSHEKLVDS TFTPSSYSST GSNANINNAN
NTALGRFPHP AGYSSTVSTV EGHGPPLSPA VRVQEAAWKL SSKRCHSRES QGATVSQDMF
PDETRSSVRL SEEVEYCSEP SLLSTDILSY QDDENRQLTC LEEDKREIQP CPKRSFLRSA
SLGRRASFHL ECLKRQKDQG GDISQKTALP LHLVHHQALA VAGLSPLLQR SHSPSTFPRP
RPTPPVTPGS RGRPLQPIPT LRLEGAESSE KLNSSFPSIH CSSWSEETTA CSGGSSMARR
ARPVSLTVPS QAGAPGRQFH GSASSLVEAV LISEGLGQFA QDPKFIEVTT QELADACDMT
IEEMENAADN ILSGGAQQSP NGTLLPFVNC RDPGQDRAVV PEDESCVYAL GRGRSEEALP
DSRSYVSNL
