CAC1C_MOUSE
ID CAC1C_MOUSE Reviewed; 2139 AA.
AC Q01815; Q04476; Q61242; Q99242;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 210.
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=MELC-CC;
DE AltName: Full=Mouse brain class C;
DE Short=MBC;
DE AltName: Full=Voltage-gated calcium channel subunit alpha Cav1.2;
GN Name=Cacna1c; Synonyms=Cach2, Cacn2, Cacnl1a1, Cchl1a1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=1385406; DOI=10.1016/s0021-9258(18)50008-9;
RA Ma W.-J., Holz R.W., Uhler M.D.;
RT "Expression of a cDNA for a neuronal calcium channel alpha1 subunit
RT enhances secretion from adrenal chromaffin cells.";
RL J. Biol. Chem. 267:22728-22732(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1162-1455 (ISOFORMS 1 AND 2).
RC STRAIN=ICR; TISSUE=Ovary;
RX PubMed=2173707; DOI=10.1016/s0021-9258(17)30522-7;
RA Perez-Reyes E., Wei X., Castellano A., Birnbaumer L.;
RT "Molecular diversity of L-type calcium channels. Evidence for alternative
RT splicing of the transcripts of three non-allelic genes.";
RL J. Biol. Chem. 265:20430-20436(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 762-1070.
RA Chaudhari N.;
RL Submitted (JAN-1993) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 265-2139 (ISOFORM 3).
RC STRAIN=DBA/2J; TISSUE=Erythroleukemia;
RX PubMed=7814415; DOI=10.1074/jbc.270.1.483;
RA Ma Y., Kobrinsky E., Marks A.R.;
RT "Cloning and expression of a novel truncated calcium channel from non-
RT excitable cells.";
RL J. Biol. Chem. 270:483-493(1995).
RN [5]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=10973973; DOI=10.1074/jbc.m006467200;
RA Seisenberger C., Specht V., Welling A., Platzer J., Pfeifer A.,
RA Kuehbandner S., Striessnig J., Klugbauer N., Feil R., Hofmann F.;
RT "Functional embryonic cardiomyocytes after disruption of the L-type alpha1C
RT (Cav1.2) calcium channel gene in the mouse.";
RL J. Biol. Chem. 275:39193-39199(2000).
RN [6]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=14609949; DOI=10.1093/emboj/cdg583;
RA Moosmang S., Schulla V., Welling A., Feil R., Feil S., Wegener J.W.,
RA Hofmann F., Klugbauer N.;
RT "Dominant role of smooth muscle L-type calcium channel Cav1.2 for blood
RT pressure regulation.";
RL EMBO J. 22:6027-6034(2003).
RN [7]
RP INTERACTION WITH CABP5, TISSUE SPECIFICITY, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=18586882; DOI=10.1167/iovs.08-2236;
RA Rieke F., Lee A., Haeseleer F.;
RT "Characterization of Ca2+-binding protein 5 knockout mouse retina.";
RL Invest. Ophthalmol. Vis. Sci. 49:5126-5135(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-469; THR-476; SER-808;
RP SER-815; SER-1670 AND SER-1691, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP INTERACTION WITH CIB1.
RX PubMed=20639889; DOI=10.1038/nm.2181;
RA Heineke J., Auger-Messier M., Correll R.N., Xu J., Benard M.J., Yuan W.,
RA Drexler H., Parise L.V., Molkentin J.D.;
RT "CIB1 is a regulator of pathological cardiac hypertrophy.";
RL Nat. Med. 16:872-879(2010).
RN [10]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP AND MUTAGENESIS OF 1794-HIS--PRO-1796 AND 1797-PRO--LEU-2139.
RX PubMed=21216955; DOI=10.1074/jbc.m110.175307;
RA Fu Y., Westenbroek R.E., Yu F.H., Clark J.P. III, Marshall M.R.,
RA Scheuer T., Catterall W.A.;
RT "Deletion of the distal C terminus of CaV1.2 channels leads to loss of
RT beta-adrenergic regulation and heart failure in vivo.";
RL J. Biol. Chem. 286:12617-12626(2011).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=22355118; DOI=10.1073/pnas.1120172109;
RA Swift F., Franzini-Armstrong C., Oeyehaug L., Enger U.H., Andersson K.B.,
RA Christensen G., Sejersted O.M., Louch W.E.;
RT "Extreme sarcoplasmic reticulum volume loss and compensatory T-tubule
RT remodeling after Serca2 knockout.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:3997-4001(2012).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-1670, AND
RP PHOSPHORYLATION AT SER-1670 AND SER-1897.
RX PubMed=25368181; DOI=10.1073/pnas.1419129111;
RA Fu Y., Westenbroek R.E., Scheuer T., Catterall W.A.;
RT "Basal and beta-adrenergic regulation of the cardiac calcium channel CaV1.2
RT requires phosphorylation of serine 1700.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:16598-16603(2014).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-1897 BY PKA, AND
RP MUTAGENESIS OF SER-1897.
RX PubMed=28119464; DOI=10.1126/scisignal.aaf9647;
RA Nystoriak M.A., Nieves-Cintron M., Patriarchi T., Buonarati O.R.,
RA Prada M.P., Morotti S., Grandi E., Fernandes J.D., Forbush K., Hofmann F.,
RA Sasse K.C., Scott J.D., Ward S.M., Hell J.W., Navedo M.F.;
RT "Ser1928 phosphorylation by PKA stimulates the L-type Ca2+ channel CaV1.2
RT and vasoconstriction during acute hyperglycemia and diabetes.";
RL Sci. Signal. 10:0-0(2017).
CC -!- FUNCTION: Pore-forming, alpha-1C subunit of the voltage-gated calcium
CC channel that gives rise to L-type calcium currents (PubMed:14609949,
CC PubMed:18586882, PubMed:21216955, PubMed:25368181, PubMed:28119464).
CC Mediates influx of calcium ions into the cytoplasm, and thereby
CC triggers calcium release from the sarcoplasm (By similarity). Plays an
CC important role in excitation-contraction coupling in the heart.
CC Required for normal heart development and normal regulation of heart
CC rhythm (PubMed:21216955). Required for normal contraction of smooth
CC muscle cells in blood vessels and in the intestine. Essential for
CC normal blood pressure regulation via its role in the contraction of
CC arterial smooth muscle cells (PubMed:14609949, PubMed:28119464). Long-
CC lasting (L-type) calcium channels belong to the 'high-voltage
CC activated' (HVA) group (Probable). {ECO:0000250|UniProtKB:P15381,
CC ECO:0000269|PubMed:14609949, ECO:0000269|PubMed:18586882,
CC ECO:0000269|PubMed:21216955, ECO:0000269|PubMed:25368181,
CC ECO:0000269|PubMed:28119464, ECO:0000305}.
CC -!- ACTIVITY REGULATION: Inhibited by dihydropyridines (DHP), such as
CC isradipine (PubMed:14609949, PubMed:21216955). Inhibited by nifedipine.
CC Channel activity is regulated by Ca(2+) and calmodulin. Binding of
CC STAC1, STAC2 or STAC3 to a region that overlaps with the calmodulin
CC binding site inhibits channel inactivation by Ca(2+) and calmodulin (By
CC similarity). Binding of calmodulin or CABP1 at the same regulatory
CC sites results in opposite effects on the channel function. Shear stress
CC and pressure increases calcium channel activity (By similarity).
CC {ECO:0000250|UniProtKB:P15381, ECO:0000250|UniProtKB:Q13936,
CC ECO:0000269|PubMed:14609949, ECO:0000269|PubMed:21216955}.
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. The channel complex contains alpha, beta, gamma and delta
CC subunits in a 1:1:1:1 ratio, i.e. it contains only one of each type of
CC subunit. CACNA1C channel activity is modulated by ancillary subunits,
CC such as CACNB1, CACNB2, CACNB3, CACNA2D1 and CACNA2D4 (By similarity).
CC Interacts with the gamma subunits CACNG4, CACNG6, CACNG7 and CACNG8 (By
CC similarity). Interacts with CACNB1 (By similarity). Interacts with
CC CACNB2. Identified in a complex with CACNA2D4 and CACNB3. Interacts
CC with CACNB3. Interacts with CACNA2D1. Interacts with CACNA2D4.
CC Interacts with CALM1. Interacts (via the N-terminus and the C-terminal
CC C and IQ motifs) with CABP1; this inhibits Ca(2+)-dependent channel
CC inactivation. The binding via the C motif is calcium independent
CC whereas the binding via IQ requires the presence of calcium and is
CC mutually exclusive with calmodulin binding (By similarity). The binding
CC to the cytoplasmic N-terminal domain is calcium independent but is
CC essential for the channel modulation (By similarity). Interacts (via C-
CC terminal CDB motif) with CABP5; in a calcium-dependent manner
CC (PubMed:18586882). Interacts with CIB1; the interaction increases upon
CC cardiomyocytes hypertrophy (PubMed:20639889). Interacts with STAC2 and
CC STAC3; this inhibits channel inactivation (By similarity).
CC {ECO:0000250|UniProtKB:P15381, ECO:0000250|UniProtKB:Q13936,
CC ECO:0000269|PubMed:18586882, ECO:0000269|PubMed:20639889}.
CC -!- INTERACTION:
CC Q01815; P51637: Cav3; NbExp=4; IntAct=EBI-644904, EBI-298576;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14609949,
CC ECO:0000269|PubMed:18586882, ECO:0000269|PubMed:21216955}; Multi-pass
CC membrane protein {ECO:0000305}. Cell membrane, sarcolemma
CC {ECO:0000269|PubMed:25368181, ECO:0000269|PubMed:28119464}; Multi-pass
CC membrane protein {ECO:0000305}. Perikaryon
CC {ECO:0000250|UniProtKB:P22002}. Postsynaptic density membrane
CC {ECO:0000250|UniProtKB:P22002}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:P22002}. Cell membrane, sarcolemma, T-tubule
CC {ECO:0000269|PubMed:22355118}. 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. Localized in T-tubules, as shown in SERCA2-
CC knockout cardiomyocytes (PubMed:22355118).
CC {ECO:0000250|UniProtKB:P15381, ECO:0000269|PubMed:22355118}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=CACH2A;
CC IsoId=Q01815-1; Sequence=Displayed;
CC Name=2; Synonyms=CACH2D;
CC IsoId=Q01815-2; Sequence=VSP_000900, VSP_000901;
CC Name=3; Synonyms=Truncated;
CC IsoId=Q01815-3; Sequence=VSP_000896, VSP_000897, VSP_000898,
CC VSP_000899, VSP_000901;
CC -!- TISSUE SPECIFICITY: Detected in embryonic heart (PubMed:10973973,
CC PubMed:21216955). Detected in retina in rod bipolar cells
CC (PubMed:18586882). Detected in tibialis artery (at protein level)
CC (PubMed:14609949). Detected in smooth muscle cells from tibialis artery
CC and in mesenteric artery (PubMed:14609949). High expression in heart,
CC followed by brain and spinal cord (PubMed:1385406).
CC {ECO:0000269|PubMed:10973973, ECO:0000269|PubMed:1385406,
CC ECO:0000269|PubMed:14609949, ECO:0000269|PubMed:18586882,
CC ECO:0000269|PubMed:21216955}.
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-1897 activates the channel
CC (PubMed:28119464). Elevated levels of blood glucose lead to increased
CC phosphorylation by PKA. {ECO:0000269|PubMed:28119464}.
CC -!- DISRUPTION PHENOTYPE: Mutant embryos appear normal and have normal
CC heartbeat at 12.5 dpc. All are dead by 14.5 dpc.
CC {ECO:0000269|PubMed:10973973}.
CC -!- SIMILARITY: Belongs to the calcium channel alpha-1 subunit (TC
CC 1.A.1.11) family. CACNA1C subfamily. {ECO:0000305}.
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DR EMBL; L01776; AAB59633.1; -; mRNA.
DR EMBL; M57973; AAA63291.1; -; mRNA.
DR EMBL; L06233; AAA37351.1; -; mRNA.
DR EMBL; U17869; AAA62612.1; -; mRNA.
DR CCDS; CCDS71821.1; -. [Q01815-3]
DR CCDS; CCDS80590.1; -. [Q01815-1]
DR PIR; A44467; A44467.
DR RefSeq; NP_001153005.1; NM_001159533.2. [Q01815-1]
DR AlphaFoldDB; Q01815; -.
DR BMRB; Q01815; -.
DR SMR; Q01815; -.
DR BioGRID; 198432; 16.
DR ComplexPortal; CPX-3194; Cardiac muscle VGCC complex.
DR CORUM; Q01815; -.
DR DIP; DIP-32232N; -.
DR IntAct; Q01815; 92.
DR MINT; Q01815; -.
DR STRING; 10090.ENSMUSP00000108413; -.
DR BindingDB; Q01815; -.
DR ChEMBL; CHEMBL2529; -.
DR DrugCentral; Q01815; -.
DR GuidetoPHARMACOLOGY; 529; -.
DR TCDB; 1.A.1.11.6; the voltage-gated ion channel (vic) superfamily.
DR GlyGen; Q01815; 4 sites.
DR iPTMnet; Q01815; -.
DR PhosphoSitePlus; Q01815; -.
DR SwissPalm; Q01815; -.
DR MaxQB; Q01815; -.
DR PeptideAtlas; Q01815; -.
DR PRIDE; Q01815; -.
DR ProteomicsDB; 273821; -. [Q01815-1]
DR ProteomicsDB; 273822; -. [Q01815-2]
DR ProteomicsDB; 273823; -. [Q01815-3]
DR ABCD; Q01815; 2 sequenced antibodies.
DR Antibodypedia; 22118; 521 antibodies from 40 providers.
DR DNASU; 12288; -.
DR Ensembl; ENSMUST00000075591; ENSMUSP00000075021; ENSMUSG00000051331. [Q01815-1]
DR Ensembl; ENSMUST00000078320; ENSMUSP00000077433; ENSMUSG00000051331. [Q01815-1]
DR Ensembl; ENSMUST00000112825; ENSMUSP00000108444; ENSMUSG00000051331. [Q01815-3]
DR GeneID; 12288; -.
DR KEGG; mmu:12288; -.
DR UCSC; uc009dls.3; mouse. [Q01815-3]
DR UCSC; uc012erl.2; mouse. [Q01815-1]
DR CTD; 775; -.
DR MGI; MGI:103013; Cacna1c.
DR VEuPathDB; HostDB:ENSMUSG00000051331; -.
DR eggNOG; KOG2301; Eukaryota.
DR GeneTree; ENSGT00940000156127; -.
DR InParanoid; Q01815; -.
DR OrthoDB; 172471at2759; -.
DR PhylomeDB; Q01815; -.
DR Reactome; R-MMU-422356; Regulation of insulin secretion.
DR Reactome; R-MMU-5576892; Phase 0 - rapid depolarisation.
DR Reactome; R-MMU-5576893; Phase 2 - plateau phase.
DR BioGRID-ORCS; 12288; 1 hit in 69 CRISPR screens.
DR ChiTaRS; Cacna1c; mouse.
DR PRO; PR:Q01815; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q01815; protein.
DR Bgee; ENSMUSG00000051331; Expressed in cardiac muscle of left ventricle and 173 other tissues.
DR ExpressionAtlas; Q01815; baseline and differential.
DR Genevisible; Q01815; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0002095; C:caveolar macromolecular signaling complex; IDA:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0043198; C:dendritic shaft; IDA:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; ISO:MGI.
DR GO; GO:0099056; C:integral component of presynaptic membrane; ISO:MGI.
DR GO; GO:1990454; C:L-type voltage-gated calcium channel complex; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0043025; C:neuronal cell body; IDA:MGI.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0014069; C:postsynaptic density; ISO:MGI.
DR GO; GO:0098839; C:postsynaptic density membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045211; C:postsynaptic membrane; ISS:SynGO.
DR GO; GO:0042734; C:presynaptic membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0042383; C:sarcolemma; ISO:MGI.
DR GO; GO:0030315; C:T-tubule; IDA:MGI.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; ISS:BHF-UCL.
DR GO; GO:0030018; C:Z disc; IDA:MGI.
DR GO; GO:0051393; F:alpha-actinin binding; ISS:BHF-UCL.
DR GO; GO:0005516; F:calmodulin binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
DR GO; GO:0008331; F:high voltage-gated calcium channel activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0051721; F:protein phosphatase 2A binding; ISO:MGI.
DR GO; GO:0031369; F:translation initiation factor binding; ISO:MGI.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IDA:MGI.
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; IDA:MGI.
DR GO; GO:1905030; F:voltage-gated ion channel activity involved in regulation of postsynaptic membrane potential; IMP:SynGO.
DR GO; GO:0007628; P:adult walking behavior; IGI:MGI.
DR GO; GO:0070509; P:calcium ion import; ISO:MGI.
DR GO; GO:0098703; P:calcium ion import across plasma membrane; IDA:MGI.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISO:MGI.
DR GO; GO:0061577; P:calcium ion transmembrane transport via high voltage-gated calcium channel; ISS:UniProtKB.
DR GO; GO:0006816; P:calcium ion transport; IDA:MGI.
DR GO; GO:0060402; P:calcium ion transport into cytosol; ISS:UniProtKB.
DR GO; GO:0017156; P:calcium-ion regulated exocytosis; IMP:MGI.
DR GO; GO:0043010; P:camera-type eye development; ISO:MGI.
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; IDA:MGI.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IMP:MGI.
DR GO; GO:0007268; P:chemical synaptic transmission; IMP:MGI.
DR GO; GO:0035115; P:embryonic forelimb morphogenesis; ISO:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IDA:MGI.
DR GO; GO:0042593; P:glucose homeostasis; IMP:MGI.
DR GO; GO:0030252; P:growth hormone secretion; IDA:MGI.
DR GO; GO:0007507; P:heart development; ISO:MGI.
DR GO; GO:0002520; P:immune system development; ISO:MGI.
DR GO; GO:0030073; P:insulin secretion; IMP:MGI.
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; IDA:UniProtKB.
DR GO; GO:1904879; P:positive regulation of calcium ion transmembrane transport via high voltage-gated calcium channel; ISO:MGI.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:MGI.
DR GO; GO:0008217; P:regulation of blood pressure; IMP:MGI.
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; IMP:MGI.
DR GO; GO:0019229; P:regulation of vasoconstriction; IMP:MGI.
DR GO; GO:0098911; P:regulation of ventricular cardiac muscle cell action potential; ISS:BHF-UCL.
DR GO; GO:0006939; P:smooth muscle contraction; IMP:MGI.
DR GO; GO:0060083; P:smooth muscle contraction involved in micturition; IMP:MGI.
DR GO; GO:0008542; P:visual learning; IMP:MGI.
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 Alternative splicing; Calcium; Calcium channel; Calcium transport;
KW Calmodulin-binding; Cell membrane; Cell projection; Disulfide bond;
KW Glycoprotein; Ion channel; Ion transport; Membrane; Metal-binding;
KW Phosphoprotein; Postsynaptic cell membrane; Reference proteome; Repeat;
KW Synapse; Transmembrane; Transmembrane helix; Transport;
KW Voltage-gated channel.
FT CHAIN 1..2139
FT /note="Voltage-dependent L-type calcium channel subunit
FT alpha-1C"
FT /id="PRO_0000053929"
FT TOPO_DOM 1..124
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 125..143
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 144..158
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 159..179
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 180..188
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 189..209
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 210..232
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 233..251
FT /note="Helical; Name=S4 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 252..268
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 269..290
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 291..350
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 351..372
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 373..380
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 381..401
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 402..524
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 525..543
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 544..554
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 555..575
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 576..586
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 587..606
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 607..615
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 616..634
FT /note="Helical; Name=S4 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 635..653
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 654..673
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 674..693
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 694..715
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 716..725
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 726..745
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 746..900
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 901..919
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 920..931
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 932..951
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 952..967
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 968..986
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 987..993
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 994..1012
FT /note="Helical; Name=S4 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1013..1031
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1032..1051
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1052..1101
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1102..1122
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1123..1139
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1140..1161
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1162..1219
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1220..1241
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1242..1249
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1250..1271
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1272..1281
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1282..1301
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1302..1324
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1325..1343
FT /note="Helical; Name=S4 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1344..1361
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1362..1382
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1383..1404
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1405..1423
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1424..1451
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1452..1476
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1477..2139
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REPEAT 111..408
FT /note="I"
FT REPEAT 510..756
FT /note="II"
FT REPEAT 887..1169
FT /note="III"
FT REPEAT 1206..1479
FT /note="IV"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 47..68
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:Q13936"
FT REGION 73..98
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 428..445
FT /note="AID/alpha-interaction domain; mediates interaction
FT with the beta subunit"
FT /evidence="ECO:0000250|UniProtKB:P22002"
FT REGION 449..481
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 764..861
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 829..876
FT /note="Interaction with STAC2"
FT /evidence="ECO:0000250|UniProtKB:Q13936"
FT REGION 1089..1178
FT /note="Dihydropyridine binding"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT REGION 1430..1498
FT /note="Dihydropyridine binding"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT REGION 1444..1486
FT /note="Phenylalkylamine binding"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT REGION 1611..1644
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:Q13936"
FT REGION 1611..1638
FT /note="Important for interaction with STAC1, STAC2 and
FT STAC3"
FT /evidence="ECO:0000250|UniProtKB:P15381"
FT REGION 1617..1637
FT /note="Calmodulin-binding IQ region"
FT /evidence="ECO:0000250|UniProtKB:Q13936"
FT REGION 1651..1670
FT /note="Important for localization in at the junctional
FT membrane"
FT /evidence="ECO:0000250|UniProtKB:P15381"
FT REGION 1732..1773
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1940..1966
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 361..364
FT /note="Selectivity filter of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT MOTIF 704..707
FT /note="Selectivity filter of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT MOTIF 1113..1116
FT /note="Selectivity filter of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT MOTIF 1414..1417
FT /note="Selectivity filter of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT COMPBIAS 764..809
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 826..842
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1947..1962
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 363
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT BINDING 706
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT BINDING 1115
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 476
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 808
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 815
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1670
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:25368181,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 1691
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1897
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:25368181,
FT ECO:0000269|PubMed:28119464"
FT CARBOHYD 153
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 328
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1388
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1439
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 298..326
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT DISULFID 316..332
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT DISULFID 1058..1069
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT DISULFID 1431..1447
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT VAR_SEQ 1..264
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:7814415"
FT /id="VSP_000896"
FT VAR_SEQ 372..391
FT /note="MQDAMGYELPWVYFVSLVIF -> VNDAVGRDWPWIYFVTLIII (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:7814415"
FT /id="VSP_000897"
FT VAR_SEQ 464
FT /note="M -> RGAPAGLHDQKKGKFAWFSHSTETHV (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:7814415"
FT /id="VSP_000898"
FT VAR_SEQ 932..951
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:7814415"
FT /id="VSP_000899"
FT VAR_SEQ 1277..1304
FT /note="GYFSDPWNVFDFLIVIGSIIDVILSETN -> HYFCDAWNTFDALIVVGSIV
FT DIAITEVH (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2173707"
FT /id="VSP_000900"
FT VAR_SEQ 1305..1315
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:2173707,
FT ECO:0000303|PubMed:7814415"
FT /id="VSP_000901"
FT MUTAGEN 1670
FT /note="S->A: Expected to abolish a phosphorylation site.
FT Decreased channel activity. No effect on phosphorylation at
FT S-1897. Causes heart hypertrophy and decreased exercise
FT tolerance in adult mice."
FT /evidence="ECO:0000269|PubMed:25368181"
FT MUTAGEN 1794..1796
FT /note="HGP->LSK: Strongly decreased channel activity due to
FT decreased expression at the cell membrane, leading to
FT hypertrophy of the right heart ventricle, heart failure and
FT perinatal death; when associated with 1797-P--L-2139 DEL."
FT /evidence="ECO:0000269|PubMed:21216955"
FT MUTAGEN 1797..2139
FT /note="Missing: Strongly decreased channel activity due to
FT decreased expression at the cell membrane, leading to
FT hypertrophy of the right heart ventricle, heart failure and
FT perinatal death; when associated with 1794-L--K-1796."
FT /evidence="ECO:0000269|PubMed:21216955"
FT MUTAGEN 1897
FT /note="S->A: Loss of phosphorylation site. Abolishes
FT increased vasoconstriction in response to elevated blood
FT glucose."
FT /evidence="ECO:0000269|PubMed:28119464"
FT CONFLICT 310
FT /note="E -> K (in Ref. 4; AAA62612)"
FT /evidence="ECO:0000305"
FT CONFLICT 477
FT /note="E -> D (in Ref. 4; AAA62612)"
FT /evidence="ECO:0000305"
FT CONFLICT 555
FT /note="V -> D (in Ref. 4; AAA62612)"
FT /evidence="ECO:0000305"
FT CONFLICT 811..812
FT /note="AD -> GS (in Ref. 4; AAA62612)"
FT /evidence="ECO:0000305"
FT CONFLICT 822
FT /note="N -> H (in Ref. 4; AAA62612)"
FT /evidence="ECO:0000305"
FT CONFLICT 825
FT /note="D -> A (in Ref. 4; AAA62612)"
FT /evidence="ECO:0000305"
FT CONFLICT 831
FT /note="N -> P (in Ref. 4; AAA62612)"
FT /evidence="ECO:0000305"
FT CONFLICT 837..841
FT /note="HSNPD -> TPTQT (in Ref. 3; AAA37351)"
FT /evidence="ECO:0000305"
FT CONFLICT 934..938
FT /note="GNADY -> FYFDI (in Ref. 3; AAA37351)"
FT /evidence="ECO:0000305"
FT CONFLICT 942
FT /note="S -> T (in Ref. 3; AAA37351)"
FT /evidence="ECO:0000305"
FT CONFLICT 946
FT /note="L -> I (in Ref. 3; AAA37351)"
FT /evidence="ECO:0000305"
FT CONFLICT 949
FT /note="I -> A (in Ref. 3; AAA37351)"
FT /evidence="ECO:0000305"
FT CONFLICT 977..978
FT /note="VS -> LC (in Ref. 4; AAA62612)"
FT /evidence="ECO:0000305"
FT CONFLICT 1065
FT /note="T -> A (in Ref. 4; AAA62612)"
FT /evidence="ECO:0000305"
FT CONFLICT 1507
FT /note="E -> K (in Ref. 4; AAA62612)"
FT /evidence="ECO:0000305"
FT CONFLICT 1525
FT /note="Q -> H (in Ref. 4; AAA62612)"
FT /evidence="ECO:0000305"
FT CONFLICT 1633
FT /note="K -> E (in Ref. 4; AAA62612)"
FT /evidence="ECO:0000305"
FT CONFLICT 1959
FT /note="G -> A (in Ref. 4; AAA62612)"
FT /evidence="ECO:0000305"
FT CONFLICT 1963..1964
FT /note="RP -> ST (in Ref. 4; AAA62612)"
FT /evidence="ECO:0000305"
FT CONFLICT 1970
FT /note="T -> H (in Ref. 4; AAA62612)"
FT /evidence="ECO:0000305"
FT CONFLICT 1974
FT /note="E -> K (in Ref. 4; AAA62612)"
FT /evidence="ECO:0000305"
FT CONFLICT 2086
FT /note="A -> R (in Ref. 4; AAA62612)"
FT /evidence="ECO:0000305"
FT CONFLICT 2097
FT /note="F -> L (in Ref. 4; AAA62612)"
FT /evidence="ECO:0000305"
FT CONFLICT 2110
FT /note="A -> V (in Ref. 4; AAA62612)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2139 AA; 240138 MW; B564C57A8644E165 CRC64;
MVNENTRMYV PEENHQGSNY GSPRPAHANM NANAAAGLAP EHIPTPGAAL SWQAAIDAAR
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 MSPLGISVLR CVRLLRIFKI TRYWNSLSNL VASLLNSVRS IASLLLLLFL
FIIIFSLLGM QLFGGKFNFD EMQTRRSTFD NFPQSLLTVF QILTGEDWNS VMYDGIMAYG
GPSFPGMLVC IYFIILFICG NYILLNVFLA IAVDNLADAE SLTSAQKEEE EEKERKKLAR
TASPEKKQEV MEKPAVEESK EEKIELKSIT ADGESPPTTK INMDDLQPSE NEDKSPHSNP
DTAGEEDEEE PEMPVGPRPR PLSELHLKEK AVPMPEASAF FIFSPNNRFR LQCHRIVNDT
IFTNLILFFI LLSSISLAAE DPVQHTSFRN HILGNADYVF TSIFTLEIIL KMTAYGAFLH
KGSFCRNYFN ILDLLVVSVS LISFGIQSSA INVVKILRVL RVLRPLRAIN RAKGLKHVVQ
CVFVAIRTIG NIVIVTTLLQ FMFACIGVQL FKGKLYTCSD SSKQTEAECK GNYITYKDGE
VDHPIIQPRS WENSKFDFDN VLAAMMALFT VSTFEGWPEL LYRSIDSHTE DKGPIYNYRV
EISIFFIIYI IIIAFFMMNI FVGFVIVTFQ EQGEQEYKNC ELDKNQRQCV EYALKARPLR
RYIPKNQHQY KVWYVVNSTY FEYLMFVLIL LNTICLAMQH YGQSCLFKIA MNILNMLFTG
LFTVEMILKL IAFKPKGYFS DPWNVFDFLI VIGSIIDVIL SETNPAEHTQ CSPSMSAEEN
SRISITFFRL FRVMRLVKLL SRGEGIRTLL WTFIKSFQAL PYVALLIVML FFIYAVIGMQ
VFGKIALNDT TEINRNNNFQ TFPQAVLLLF RCATGEAWQD IMLACMPGKK CAPESEPSNS
TEGETPCGSS FAVFYFISFY MLCAFLIINL FVAVIMDNFD YLTRDWSILG PHHLDEFKRI
WAEYDPEAKG RIKHLDVVTL LRRIQPPLGF GKLCPHRVAC KRLVSMNMPL NSDGTVMFNA
TLFALVRTAL RIKTEGNLEQ ANEELRAIIK KIWKRTSMKL LDQVVPPAGD DEVTVGKFYA
TFLIQEYFRK FKKRKEQGLV GKPSQRNALS LQAGLRTLHD IGPEIRRAIS GDLTAEEELD
KAMKEAVSAA SEDDIFRRAG GLFGNHVTYY QSDSRGNFPQ TFATQRPLHI NKTGNNQADT
ESPSHEKLVD STFTPSSYSS TGSNANINNA NNTALGRFPH PAGYSSTVST VEGHGPPLSP
AVRVQEAAWK LSSKRCHSRE SQGATVNQEI FPDETRSVRM SEEAEYCSEP SLLSTDMFSY
QEDEHRQLTC PEEDKREIQP SPKRSFLRSA SLGRRASFHL ECLKRQKDQG GDISQKTALP
LHLVHHQALA VAGLSPLLQR SHSPTTFPRP CPTPPVTPGS RGRPLRPIPT LRLEGAESSE
KLNSSFPSIH CSSWSEETTA CSGSSSMARR ARPVSLTVPS QAGAPGRQFH GSASSLVEAV
LISEGLGQFA QDPKFIEVTT QELADACDMT IEEMENAADN ILSGGAQQSP NGTLLPFVNC
RDPGQDRAVA PEDESCAYAL GRGRSEEALA DSRSYVSNL
