CAC1C_RABIT
ID CAC1C_RABIT Reviewed; 2171 AA.
AC P15381; Q03716; Q28676; Q99243;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1990, sequence version 1.
DT 03-AUG-2022, entry version 166.
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=Smooth muscle calcium channel blocker receptor;
DE Short=CACB-receptor;
DE AltName: Full=Voltage-gated calcium channel subunit alpha Cav1.2;
GN Name=CACNA1C; Synonyms=CACH2, CACN2, CACNL1A1, CCHL1A1;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND ACTIVITY
RP REGULATION.
RC TISSUE=Heart;
RX PubMed=2474130; DOI=10.1038/340230a0;
RA Mikami A., Imoto K., Tanabe T., Ni Idomme T., Mori Y., Takeshima H.,
RA Narumiya S., Numa S.;
RT "Primary structure and functional expression of the cardiac
RT dihydropyridine-sensitive calcium channel.";
RL Nature 340:230-233(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Heart, and Lung;
RX PubMed=2169433; DOI=10.1016/0014-5793(90)81205-3;
RA Biel M., Ruth P., Bosse E., Hullin R., Stuehmer W., Flockerzi V.,
RA Hoffmann F.;
RT "Primary structure and functional expression of a high voltage activated
RT calcium channel from rabbit lung.";
RL FEBS Lett. 269:409-412(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-98 (ISOFORM 5).
RC TISSUE=Heart muscle;
RX PubMed=1652442; DOI=10.1111/j.1432-1033.1991.tb21051.x;
RA Biel M., Hullin R., Freundner S., Singer D., Dascal N., Flockerzi V.,
RA Hofmann F.;
RT "Tissue-specific expression of high-voltage-activated dihydropyridine-
RT sensitive L-type calcium channels.";
RL Eur. J. Biochem. 200:81-88(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1192-1485 (ISOFORM 2).
RC TISSUE=Heart;
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 [5]
RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS, CALCIUM-BINDING, AND SITE.
RX PubMed=8232554; DOI=10.1038/366158a0;
RA Yang J., Ellinor P.T., Sather W.A., Zhang J.-F., Tsien R.W.;
RT "Molecular determinants of Ca2+ selectivity and ion permeation in L-type
RT Ca2+ channels.";
RL Nature 366:158-161(1993).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF CYS-168.
RX PubMed=9502794; DOI=10.1523/jneurosci.18-07-02335.1998;
RA Ren D., Xu H., Eberl D.F., Chopra M., Hall L.M.;
RT "A mutation affecting dihydropyridine-sensitive current levels and
RT activation kinetics in Drosophila muscle and mammalian heart calcium
RT channels.";
RL J. Neurosci. 18:2335-2341(1998).
RN [7]
RP PHOSPHORYLATION BY PKA.
RX PubMed=1325377; DOI=10.1016/0014-5793(92)80804-p;
RA Yoshida A., Takahashi M., Nishimura S., Takeshima H., Kokubun S.;
RT "Cyclic AMP-dependent phosphorylation and regulation of the cardiac
RT dihydropyridine-sensitive Ca channel.";
RL FEBS Lett. 309:343-349(1992).
RN [8]
RP BETA-SUBUNIT BINDING DOMAIN, AND INTERACTION WITH CACNB1.
RX PubMed=7509046; DOI=10.1038/368067a0;
RA Pragnell M., de Waard M., Mori Y., Tanabe T., Snutch T.P., Campbell K.P.;
RT "Calcium channel beta-subunit binds to a conserved motif in the I-II
RT cytoplasmic linker of the alpha 1-subunit.";
RL Nature 368:67-70(1994).
RN [9]
RP EF-HAND MOTIF AND CALCIUM INACTIVATION, AND ACTIVITY REGULATION.
RX PubMed=7491499; DOI=10.1126/science.270.5241.1502;
RA de Leon M., Wang Y., Jones L., Perez-Reyes E., Wei X., Soong T.W.,
RA Snutch T.P., Yue D.T.;
RT "Essential Ca(2+)-binding motif for Ca(2+)-sensitive inactivation of L-type
RT Ca2+ channels.";
RL Science 270:1502-1505(1995).
RN [10]
RP PHOSPHORYLATION AT SER-1928 BY PKA.
RX PubMed=8756695; DOI=10.1021/bi953023c;
RA De Jongh K.S., Murphy B.J., Colvin A.A., Hell J.W., Takahashi M.,
RA Catterall W.A.;
RT "Specific phosphorylation of a site in the full-length form of the alpha 1
RT subunit of the cardiac L-type calcium channel by adenosine 3',5'-cyclic
RT monophosphate-dependent protein kinase.";
RL Biochemistry 35:10392-10402(1996).
RN [11]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, SUBUNIT, AND
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 [12]
RP INTERACTION WITH CACNB1, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15615847; DOI=10.1152/ajpheart.00348.2004;
RA Cohen R.M., Foell J.D., Balijepalli R.C., Shah V., Hell J.W., Kamp T.J.;
RT "Unique modulation of L-type Ca2+ channels by short auxiliary beta1d
RT subunit present in cardiac muscle.";
RL Am. J. Physiol. 288:H2363-H2374(2005).
RN [13]
RP SUBCELLULAR LOCATION, INTERACTION WITH CACNB2, AND FUNCTION.
RX PubMed=17525370; DOI=10.1161/circresaha.106.146399;
RA Yada H., Murata M., Shimoda K., Yuasa S., Kawaguchi H., Ieda M., Adachi T.,
RA Murata M., Ogawa S., Fukuda K.;
RT "Dominant negative suppression of Rad leads to QT prolongation and causes
RT ventricular arrhythmias via modulation of L-type Ca2+ channels in the
RT heart.";
RL Circ. Res. 101:69-77(2007).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND INTERACTION WITH CACNB1;
RP CACNB2; CACNA2D1; CACNG4; CACNG6; CACNG7 AND CACNG8.
RX PubMed=21127204; DOI=10.1096/fj.10-172353;
RA Yang L., Katchman A., Morrow J.P., Doshi D., Marx S.O.;
RT "Cardiac L-type calcium channel (Cav1.2) associates with gamma subunits.";
RL FASEB J. 25:928-936(2011).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 1681-LEU--GLY-1684;
RP 1685-LEU--LEU-1688 AND 1697-ARG--SER-1700.
RX PubMed=22928916; DOI=10.1042/bj20120773;
RA Nakada T., Flucher B.E., Kashihara T., Sheng X., Shibazaki T.,
RA Horiuchi-Hirose M., Gomi S., Hirose M., Yamada M.;
RT "The proximal C-terminus of alpha(1C) subunits is necessary for junctional
RT membrane targeting of cardiac L-type calcium channels.";
RL Biochem. J. 448:221-231(2012).
RN [16]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP GLU-393; GLU-736; LEU-775; THR-1066; GLU-1145 AND GLU-1446.
RX PubMed=23145875; DOI=10.1021/bi301124a;
RA Gez L.S., Hagalili Y., Shainberg A., Atlas D.;
RT "Voltage-driven Ca(2+) binding at the L-type Ca(2+) channel triggers
RT cardiac excitation-contraction coupling prior to Ca(2+) influx.";
RL Biochemistry 51:9658-9666(2012).
RN [17]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH STAC2 AND STAC3.
RX PubMed=25548159; DOI=10.1073/pnas.1423113112;
RA Polster A., Perni S., Bichraoui H., Beam K.G.;
RT "Stac adaptor proteins regulate trafficking and function of muscle and
RT neuronal L-type Ca2+ channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 112:602-606(2015).
RN [18]
RP FUNCTION, ACTIVITY REGULATION, INTERACTION WITH STAC1; STAC2 AND STAC3,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF PHE-1648; ILE-1654; PHE-1658 AND
RP ARG-1659.
RX PubMed=29363593; DOI=10.1073/pnas.1715997115;
RA Campiglio M., Coste de Bagneaux P., Ortner N.J., Tuluc P., Van Petegem F.,
RA Flucher B.E.;
RT "STAC proteins associate to the IQ domain of CaV1.2 and inhibit calcium-
RT dependent inactivation.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:1376-1381(2018).
RN [19] {ECO:0007744|PDB:4DEY}
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 435-539 IN COMPLEX WITH CACNB2,
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF GLY-449.
RX PubMed=22649239; DOI=10.1523/jneurosci.5727-11.2012;
RA Almagor L., Chomsky-Hecht O., Ben-Mocha A., Hendin-Barak D., Dascal N.,
RA Hirsch J.A.;
RT "The role of a voltage-dependent Ca2+ channel intracellular linker: a
RT structure-function analysis.";
RL J. Neurosci. 32:7602-7613(2012).
CC -!- FUNCTION: Pore-forming, alpha-1C subunit of the voltage-gated calcium
CC channel that gives rise to L-type calcium currents (PubMed:2474130,
CC PubMed:2169433, PubMed:8232554, PubMed:9502794, PubMed:9278523,
CC PubMed:15615847, PubMed:17525370, PubMed:21127204, PubMed:22928916,
CC PubMed:23145875, PubMed:29363593, PubMed:22649239). Mediates influx of
CC calcium ions into the cytoplasm, and thereby triggers calcium release
CC from the sarcoplasm (PubMed:23145875). Plays an important role in
CC excitation-contraction coupling in the heart (PubMed:17525370,
CC PubMed:22928916, PubMed:23145875). Required for normal heart
CC development and normal regulation of heart rhythm (By similarity).
CC Required for normal contraction of smooth muscle cells in blood vessels
CC and in the intestine. Essential for normal blood pressure regulation
CC via its role in the contraction of arterial smooth muscle cells (By
CC similarity). Long-lasting (L-type) calcium channels belong to the
CC 'high-voltage activated' (HVA) group (Probable).
CC {ECO:0000250|UniProtKB:Q01815, ECO:0000250|UniProtKB:Q13936,
CC ECO:0000269|PubMed:15615847, ECO:0000269|PubMed:17525370,
CC ECO:0000269|PubMed:21127204, ECO:0000269|PubMed:2169433,
CC ECO:0000269|PubMed:22649239, ECO:0000269|PubMed:22928916,
CC ECO:0000269|PubMed:23145875, ECO:0000269|PubMed:2474130,
CC ECO:0000269|PubMed:29363593, ECO:0000269|PubMed:8232554,
CC ECO:0000269|PubMed:9278523, ECO:0000269|PubMed:9502794, ECO:0000305}.
CC -!- ACTIVITY REGULATION: Inhibited by dihydropyridines (DHP), such as
CC isradipine (PubMed:2474130, PubMed:9278523). Inhibited by nifedipine
CC (PubMed:23145875). Channel activity is regulated by Ca(2+) and
CC calmodulin (PubMed:7491499, PubMed:29363593). Binding of STAC1, STAC2
CC or STAC3 to a region that overlaps with the calmodulin binding site
CC inhibits channel inactivation by Ca(2+) and calmodulin
CC (PubMed:29363593). Binding of calmodulin or CABP1 at the same
CC regulatory sites results in opposite effects on the channel function
CC (By similarity). Shear stress and pressure increases calcium channel
CC activity (By similarity). {ECO:0000250|UniProtKB:Q13936,
CC ECO:0000269|PubMed:23145875, ECO:0000269|PubMed:2474130,
CC ECO:0000269|PubMed:29363593, ECO:0000269|PubMed:7491499,
CC ECO:0000269|PubMed:9278523}.
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:17525370, PubMed:21127204). The channel complex
CC contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e.
CC it contains only one of each type of subunit (Probable). CACNA1C
CC channel activity is modulated by ancillary subunits, such as CACNB1,
CC CACNB2, CACNB3, CACNA2D1 and CACNA2D4 (PubMed:9278523, PubMed:15615847,
CC PubMed:17525370, PubMed:21127204). Interacts with CACNB1
CC (PubMed:7509046, PubMed:15615847, PubMed:21127204). Interacts with
CC CACNB2 (PubMed:17525370, PubMed:21127204, PubMed:22649239). Identified
CC in a complex with CACNA2D4 and CACNB3. Interacts with CACNB3 (By
CC similarity). Interacts with CACNA2D1 (PubMed:9278523, PubMed:21127204).
CC Interacts with the gamma subunits CACNG4, CACNG6, CACNG7 and CACNG8
CC (PubMed:21127204). Interacts with CACNA2D4 (By similarity). Interacts
CC with CALM1 (PubMed:29363593). Interacts (via the N-terminus and the C-
CC terminal C and IQ motifs) with CABP1; this inhibits Ca(2+)-dependent
CC channel inactivation. The binding via the C motif is calcium
CC independent whereas the binding via IQ requires the presence of calcium
CC and is mutually exclusive with calmodulin binding (By similarity). The
CC binding to the cytoplasmic N-terminal domain is calcium independent but
CC is essential for the channel modulation. Interacts (via C-terminal CDB
CC motif) with CABP5; in a calcium-dependent manner. Interacts with CIB1;
CC the interaction increases upon cardiomyocytes hypertrophy (By
CC similarity). Interacts with STAC1, STAC2 and STAC3; this inhibits
CC channel inactivation, probably by hindering CALM1 binding
CC (PubMed:25548159, PubMed:29363593). {ECO:0000250|UniProtKB:Q01815,
CC ECO:0000250|UniProtKB:Q13936, ECO:0000269|PubMed:15615847,
CC ECO:0000269|PubMed:17525370, ECO:0000269|PubMed:21127204,
CC ECO:0000269|PubMed:22649239, ECO:0000269|PubMed:25548159,
CC ECO:0000269|PubMed:29363593, ECO:0000269|PubMed:7509046,
CC ECO:0000269|PubMed:9278523, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15615847,
CC ECO:0000269|PubMed:17525370, ECO:0000269|PubMed:21127204,
CC ECO:0000269|PubMed:2169433, ECO:0000269|PubMed:22649239,
CC ECO:0000269|PubMed:2474130, ECO:0000269|PubMed:25548159,
CC ECO:0000269|PubMed:8232554, ECO:0000269|PubMed:9278523,
CC ECO:0000269|PubMed:9502794}; Multi-pass membrane protein {ECO:0000305}.
CC Cell membrane, sarcolemma {ECO:0000269|PubMed:22928916,
CC ECO:0000269|PubMed:23145875, ECO:0000269|PubMed:29363593}; 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: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
CC (PubMed:22928916, PubMed:29363593). The interaction between RRAD and
CC CACNB2 promotes the expression of CACNA1C at the cell membrane
CC (PubMed:17525370). {ECO:0000269|PubMed:17525370,
CC ECO:0000269|PubMed:22928916, ECO:0000269|PubMed:29363593}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=CACH2A;
CC IsoId=P15381-1; Sequence=Displayed;
CC Name=2; Synonyms=CACH2C;
CC IsoId=P15381-2; Sequence=VSP_000906;
CC Name=3; Synonyms=CACH2D;
CC IsoId=P15381-3; Sequence=VSP_000907;
CC Name=4; Synonyms=Lung;
CC IsoId=P15381-4; Sequence=VSP_000902, VSP_000904, VSP_000905,
CC VSP_000906;
CC Name=5; Synonyms=C141;
CC IsoId=P15381-5; Sequence=VSP_000902, VSP_000903;
CC -!- TISSUE SPECIFICITY: Expression in cardiac muscle. In lung, expressed in
CC airway and vascular smooth muscle cells.
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:0000269|PubMed:7491499}.
CC -!- PTM: Phosphorylation by PKA at Ser-1928 activates the channel
CC (PubMed:1325377). Elevated levels of blood glucose lead to increased
CC phosphorylation by PKA (By similarity). {ECO:0000250|UniProtKB:Q01815,
CC ECO:0000269|PubMed:1325377}.
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; X15539; CAA33546.1; -; mRNA.
DR EMBL; X55763; CAA39289.1; -; mRNA.
DR EMBL; X60782; CAA43196.1; -; mRNA.
DR EMBL; M57974; AAA31182.1; -; mRNA.
DR PIR; S05054; S05054.
DR PIR; S11339; S11339.
DR RefSeq; NP_001129994.1; NM_001136522.1. [P15381-1]
DR PDB; 4DEY; X-ray; 1.95 A; B=435-539.
DR PDB; 6CTB; NMR; -; B=1644-1668.
DR PDBsum; 4DEY; -.
DR PDBsum; 6CTB; -.
DR AlphaFoldDB; P15381; -.
DR BMRB; P15381; -.
DR SMR; P15381; -.
DR DIP; DIP-61286N; -.
DR IntAct; P15381; 3.
DR STRING; 9986.ENSOCUP00000009984; -.
DR BindingDB; P15381; -.
DR ChEMBL; CHEMBL2830; -.
DR DrugCentral; P15381; -.
DR iPTMnet; P15381; -.
DR PRIDE; P15381; -.
DR ABCD; P15381; 2 sequenced antibodies.
DR GeneID; 100101555; -.
DR KEGG; ocu:100101555; -.
DR CTD; 775; -.
DR eggNOG; KOG2301; Eukaryota.
DR InParanoid; P15381; -.
DR OrthoDB; 172471at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:1990454; C:L-type voltage-gated calcium channel complex; IDA:UniProtKB.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB.
DR GO; GO:0098839; C:postsynaptic density membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042383; C:sarcolemma; IDA:UniProtKB.
DR GO; GO:0030315; C:T-tubule; IDA:UniProtKB.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; ISS:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0008331; F:high voltage-gated calcium channel activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IDA:UniProtKB.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:0061577; P:calcium ion transmembrane transport via high voltage-gated calcium channel; IDA:BHF-UCL.
DR GO; GO:0060402; P:calcium ion transport into cytosol; IDA:UniProtKB.
DR GO; GO:0061337; P:cardiac conduction; ISS:UniProtKB.
DR GO; GO:0045762; P:positive regulation of adenylate cyclase activity; ISS:UniProtKB.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISS:UniProtKB.
DR GO; GO:0010881; P:regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion; IMP:UniProtKB.
DR GO; GO:0098903; P:regulation of membrane repolarization during action potential; IDA:BHF-UCL.
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..2171
FT /note="Voltage-dependent L-type calcium channel subunit
FT alpha-1C"
FT /id="PRO_0000053930"
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..1042
FT /note="Helical; Name=S4 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1043..1061
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1062..1081
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1082..1131
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1132..1152
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1153..1169
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1170..1191
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1192..1249
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1250..1271
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1272..1279
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1280..1301
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1302..1311
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1312..1331
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1332..1354
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1355..1373
FT /note="Helical; Name=S4 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1374..1391
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1392..1412
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1413..1434
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1435..1453
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1454..1481
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1482..1506
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1507..2171
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REPEAT 141..438
FT /note="I"
FT REPEAT 540..786
FT /note="II"
FT REPEAT 917..1199
FT /note="III"
FT REPEAT 1236..1509
FT /note="IV"
FT REGION 77..98
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250|UniProtKB:Q13936"
FT REGION 103..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:0000250|UniProtKB:P22002"
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 1119..1208
FT /note="Dihydropyridine binding"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT REGION 1460..1528
FT /note="Dihydropyridine binding"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT REGION 1474..1516
FT /note="Phenylalkylamine binding"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT REGION 1641..1668
FT /note="Important for interaction with STAC1, STAC2 and
FT STAC3"
FT /evidence="ECO:0000269|PubMed:29363593"
FT REGION 1647..1667
FT /note="Calmodulin-binding IQ region"
FT /evidence="ECO:0000250|UniProtKB:Q13936"
FT REGION 1681..1700
FT /note="Important for localization in at the junctional
FT membrane"
FT /evidence="ECO:0000269|PubMed:22928916"
FT REGION 1760..1797
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1971..2014
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2026..2060
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2114..2155
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 1143..1146
FT /note="Selectivity filter of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT MOTIF 1444..1447
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 1979..1996
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 1145
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT SITE 393
FT /note="Calcium ion selectivity and permeability"
FT /evidence="ECO:0000269|PubMed:8232554"
FT SITE 736
FT /note="Calcium ion selectivity and permeability"
FT /evidence="ECO:0000269|PubMed:8232554"
FT SITE 1145
FT /note="Calcium ion selectivity and permeability"
FT /evidence="ECO:0000269|PubMed:8232554"
FT SITE 1446
FT /note="Calcium ion selectivity and permeability"
FT /evidence="ECO:0000269|PubMed:8232554"
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:0000250|UniProtKB:Q01815"
FT MOD_RES 1700
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01815"
FT MOD_RES 1721
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01815"
FT MOD_RES 1928
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:8756695"
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 1418
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1469
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 1088..1099
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT DISULFID 1461..1477
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT VAR_SEQ 1..46
FT /note="MLRALVQPATPAYQPLPSHLSAETESTCKGTVVHEAQLNHFYISPG -> MV
FT NENTRMYIPEENHQ (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:1652442"
FT /id="VSP_000902"
FT VAR_SEQ 66..79
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:1652442"
FT /id="VSP_000903"
FT VAR_SEQ 402..421
FT /note="MQDAMGYELPWVYFVSLVIF -> VNDAVGRDWPWIYFVTLIII (in
FT isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_000904"
FT VAR_SEQ 494
FT /note="M -> RGTPAGLHAQKKGKFAWFSHSTETHV (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_000905"
FT VAR_SEQ 1307..1334
FT /note="GYFSDPWNVFDFLIVIGSIIDVILSETN -> HYFCDAWNTFDALIVVGSIV
FT DIAITEVH (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:2173707"
FT /id="VSP_000906"
FT VAR_SEQ 1335..1345
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_000907"
FT MUTAGEN 168
FT /note="C->G: Small reduction of current amplitude."
FT /evidence="ECO:0000269|PubMed:9502794"
FT MUTAGEN 168
FT /note="C->K,W: No current."
FT /evidence="ECO:0000269|PubMed:9502794"
FT MUTAGEN 168
FT /note="C->S: No effect."
FT /evidence="ECO:0000269|PubMed:9502794"
FT MUTAGEN 168
FT /note="C->Y: Slower channel activation and reduction of
FT current amplitude."
FT /evidence="ECO:0000269|PubMed:9502794"
FT MUTAGEN 393
FT /note="E->A: Loss of channel activity and ability to
FT trigger cardiomyocyte contraction; when associated with A-
FT 736; A-1145 and A-1446."
FT /evidence="ECO:0000269|PubMed:23145875"
FT MUTAGEN 393
FT /note="E->K: Drastic reduction of barium permeability.
FT Reduction of calcium block of lithium currents."
FT /evidence="ECO:0000269|PubMed:8232554"
FT MUTAGEN 393
FT /note="E->Q: Attenuates calcium block of inward barium,
FT lithium, or cadmium currents."
FT /evidence="ECO:0000269|PubMed:8232554"
FT MUTAGEN 449
FT /note="G->R: Decreased rate of channel inactivation."
FT /evidence="ECO:0000269|PubMed:22649239"
FT MUTAGEN 736
FT /note="E->A: Loss of channel activity and ability to
FT trigger cardiomyocyte contraction; when associated with A-
FT 393; A-1145 and A-1446."
FT /evidence="ECO:0000269|PubMed:23145875"
FT MUTAGEN 736
FT /note="E->K: Drastic reduction of barium permeability.
FT Reduction of calcium block of lithium currents."
FT /evidence="ECO:0000269|PubMed:8232554"
FT MUTAGEN 736
FT /note="E->Q: Attenuates calcium block of inward barium,
FT lithium, or cadmium currents."
FT /evidence="ECO:0000269|PubMed:8232554"
FT MUTAGEN 775
FT /note="L->P: Loss of nifedipine-sensitivity and channel
FT activity; when associated with Y-1066."
FT /evidence="ECO:0000269|PubMed:23145875"
FT MUTAGEN 1066
FT /note="T->Y: Loss of nifedipine-sensitivity and channel
FT activity; when associated with P-775."
FT /evidence="ECO:0000269|PubMed:23145875"
FT MUTAGEN 1145
FT /note="E->A: Loss of channel activity and ability to
FT trigger cardiomyocyte contraction; when associated with A-
FT 393; A-736 and A-1446."
FT /evidence="ECO:0000269|PubMed:23145875"
FT MUTAGEN 1145
FT /note="E->K: Drastic reduction of barium permeability.
FT Reduction of calcium block of lithium currents."
FT /evidence="ECO:0000269|PubMed:8232554"
FT MUTAGEN 1145
FT /note="E->Q: Attenuates calcium block of inward barium,
FT lithium, or cadmium currents."
FT /evidence="ECO:0000269|PubMed:8232554"
FT MUTAGEN 1446
FT /note="E->A: Loss of channel activity and ability to
FT trigger cardiomyocyte contraction; when associated with A-
FT 393; A-736 and A-1145."
FT /evidence="ECO:0000269|PubMed:23145875"
FT MUTAGEN 1446
FT /note="E->K: Moderate reduction of barium permeability.
FT Reduction of calcium block of lithium currents."
FT /evidence="ECO:0000269|PubMed:8232554"
FT MUTAGEN 1446
FT /note="E->Q: Attenuates calcium block of inward barium,
FT lithium, or cadmium currents."
FT /evidence="ECO:0000269|PubMed:8232554"
FT MUTAGEN 1648
FT /note="F->A: Mildly decreased interaction with STAC3."
FT /evidence="ECO:0000269|PubMed:29363593"
FT MUTAGEN 1654
FT /note="I->A: Strongly decreased interaction with STAC3."
FT /evidence="ECO:0000269|PubMed:29363593"
FT MUTAGEN 1658
FT /note="F->A: Decreased interaction with STAC3."
FT /evidence="ECO:0000269|PubMed:29363593"
FT MUTAGEN 1659
FT /note="R->A: Mildly decreased interaction with STAC3."
FT /evidence="ECO:0000269|PubMed:29363593"
FT MUTAGEN 1681..1684
FT /note="LQAG->AAAA: Strongly reduced channel clustering at
FT the junctional membrane."
FT /evidence="ECO:0000269|PubMed:22928916"
FT MUTAGEN 1685..1688
FT /note="LRTL->AAAA: Strongly reduced channel clustering at
FT the junctional membrane."
FT /evidence="ECO:0000269|PubMed:22928916"
FT MUTAGEN 1697..1700
FT /note="RAIS->AAAA: Strongly reduced channel clustering at
FT the junctional membrane."
FT /evidence="ECO:0000269|PubMed:22928916"
FT CONFLICT 1346
FT /note="N -> S (in Ref. 4; AAA31182)"
FT /evidence="ECO:0000305"
FT CONFLICT 1468
FT /note="H -> S (in Ref. 4; AAA31182)"
FT /evidence="ECO:0000305"
FT HELIX 451..475
FT /evidence="ECO:0007829|PDB:4DEY"
FT HELIX 1647..1664
FT /evidence="ECO:0007829|PDB:6CTB"
FT TURN 1665..1667
FT /evidence="ECO:0007829|PDB:6CTB"
SQ SEQUENCE 2171 AA; 242784 MW; B64F08F09D71C65D CRC64;
MLRALVQPAT PAYQPLPSHL SAETESTCKG TVVHEAQLNH FYISPGGSNY GSPRPAHANM
NANAAAGLAP EHIPTPGAAL SWQAAIDAAR QAKLMGSAGN ATISTVSSTQ RKRQQYGKPK
KQGSTTATRP PRALLCLTLK NPIRRACISI VEWKPFEIII LLTIFANCVA LAIYIPFPED
DSNATNSNLE RVEYLFLIIF TVEAFLKVIA YGLLFHPNAY LRNGWNLLDF IIVVVGLFSA
ILEQATKADG ANALGGKGAG FDVKALRAFR VLRPLRLVSG VPSLQVVLNS IIKAMVPLLH
IALLVLFVII IYAIIGLELF MGKMHKTCYN QEGVADVPAE DDPSPCALET GHGRQCQNGT
VCKPGWDGPK HGITNFDNFA FAMLTVFQCI TMEGWTDVLY WMQDAMGYEL PWVYFVSLVI
FGSFFVLNLV LGVLSGEFSK EREKAKARGD FQKLREKQQL EEDLKGYLDW ITQAEDIDPE
NEDEGMDEEK PRNMSMPTSE TESVNTENVA GGDIEGENCG ARLAHRISKS KFSRYWRRWN
RFCRRKCRAA VKSNVFYWLV IFLVFLNTLT IASEHYNQPH WLTEVQDTAN KALLALFTAE
MLLKMYSLGL QAYFVSLFNR FDCFIVCGGI LETILVETKV MSPLGISVLR CVRLLRIFKI
TRYWNSLSNL VASLLNSVRS IASLLLLLFL FIIIFSLLGM QLFGGKFNFD EMQTRRSTFD
NFPQSLLTVF QILTGEDWNS VMYDGIMAYG GPSFPGMLVC IYFIILFICG NYILLNVFLA
IAVDNLADAE SLTSAQKEEE EEKERKKLAR TASPEKKQEV VGKPALEEAK EEKIELKSIT
ADGESPPTTK INMDDLQPNE SEDKSPYPNP ETTGEEDEEE PEMPVGPRPR PLSELHLKEK
AVPMPEASAF FIFSPNNRFR LQCHRIVNDT IFTNLILFFI LLSSISLAAE DPVQHTSFRN
HILFYFDIVF TTIFTIEIAL 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 CSPSMNAEEN SRISITFFRL FRVMRLVKLL SRGEGIRTLL
WTFIKSFQAL PYVALLIVML FFIYAVIGMQ VFGKIALNDT TEINRNNNFQ TFPQAVLLLF
RCATGEAWQD IMLACMPGKK CAPESEPHNS 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 GLFGNHVSYY
QSDSRSAFPQ TFTTQRPLHI SKAGNNQGDT ESPSHEKLVD STFTPSSYSS TGSNANINNA
NNTALGRLPR PAGYPSTVST VEGHGSPLSP AVRAQEAAWK LSSKRCHSQE SQIAMACQEG
ASQDDNYDVR IGEDAECCSE PSLLSTEMLS YQDDENRQLA PPEEEKRDIR LSPKKGFLRS
ASLGRRASFH LECLKRQKNQ GGDISQKTVL PLHLVHHQAL AVAGLSPLLQ RSHSPTSLPR
PCATPPATPG SRGWPPQPIP TLRLEGADSS EKLNSSFPSI HCGSWSGENS PCRGDSSAAR
RARPVSLTVP SQAGAQGRQF HGSASSLVEA VLISEGLGQF AQDPKFIEVT TQELADACDL
TIEEMENAAD DILSGGARQS PNGTLLPFVN RRDPGRDRAG QNEQDASGAC APGCGQSEEA
LADRRAGVSS L
