CAC1S_MOUSE
ID CAC1S_MOUSE Reviewed; 1852 AA.
AC Q02789; E9Q7B5; E9QPX8; F8VQE0; Q3UPG8; Q99240;
DT 01-FEB-2005, integrated into UniProtKB/Swiss-Prot.
DT 29-SEP-2021, sequence version 3.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Voltage-dependent L-type calcium channel subunit alpha-1S;
DE AltName: Full=Calcium channel, L type, alpha-1 polypeptide, isoform 3, skeletal muscle;
DE AltName: Full=Dihydropyridine receptor {ECO:0000303|PubMed:16550931, ECO:0000303|PubMed:28351836};
DE Short=DHPR {ECO:0000305};
DE AltName: Full=Voltage-gated calcium channel subunit alpha Cav1.1;
GN Name=Cacna1s; Synonyms=Cach1, Cach1b, Cacn1, Cacnl1a3;
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] (ISOFORM 2), AND DISEASE.
RC STRAIN=129/ReJ; TISSUE=Fetal skeletal muscle;
RX PubMed=1281468; DOI=10.1016/s0021-9258(18)35650-3;
RA Chaudhari N.;
RT "A single nucleotide deletion in the skeletal muscle-specific calcium
RT channel transcript of muscular dysgenesis (mdg) mice.";
RL J. Biol. Chem. 267:25636-25639(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 22-1852 (ISOFORM 3).
RC STRAIN=C57BL/6J;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1061-1360 (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 [5]
RP INTERACTION WITH JSRP1.
RX PubMed=12871958; DOI=10.1074/jbc.m305016200;
RA Anderson A.A., Treves S., Biral D., Betto R., Sandona D., Ronjat M.,
RA Zorzato F.;
RT "The novel skeletal muscle sarcoplasmic reticulum JP-45 protein. Molecular
RT cloning, tissue distribution, developmental expression, and interaction
RT with alpha 1.1 subunit of the voltage-gated calcium channel.";
RL J. Biol. Chem. 278:39987-39992(2003).
RN [6]
RP INTERACTION WITH DYSF.
RX PubMed=16550931;
RA Ampong B.N., Imamura M., Matsumiya T., Yoshida M., Takeda S.;
RT "Intracellular localization of dysferlin and its association with the
RT dihydropyridine receptor.";
RL Acta Myol. 24:134-144(2005).
RN [7]
RP INTERACTION WITH JSRP1.
RX PubMed=16638807; DOI=10.1242/jcs.02935;
RA Anderson A.A., Altafaj X., Zheng Z., Wang Z.-M., Delbono O., Ronjat M.,
RA Treves S., Zorzato F.;
RT "The junctional SR protein JP-45 affects the functional expression of the
RT voltage-dependent Ca2+ channel Cav1.1.";
RL J. Cell Sci. 119:2145-2155(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-393 AND SER-397, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, 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 STAC; STAC2 AND STAC3.
RX PubMed=29467163; DOI=10.1085/jgp.201711917;
RA Polster A., Nelson B.R., Papadopoulos S., Olson E.N., Beam K.G.;
RT "STAC proteins associate with the critical domain for excitation-
RT contraction coupling in the II-III loop of CaV1.1.";
RL J. Gen. Physiol. 150:613-624(2018).
RN [10] {ECO:0007744|PDB:4ZW2}
RP X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) OF 357-374 IN COMPLEX WITH CACNB1,
RP AND SUBUNIT.
RX PubMed=28351836; DOI=10.1074/jbc.m116.763896;
RA Norris N.C., Joseph S., Aditya S., Karunasekara Y., Board P.G.,
RA Dulhunty A.F., Oakley A.J., Casarotto M.G.;
RT "Structural and biophysical analyses of the skeletal dihydropyridine
RT receptor beta subunit beta1a reveal critical roles of domain interactions
RT for stability.";
RL J. Biol. Chem. 292:8401-8411(2017).
CC -!- FUNCTION: Pore-forming, alpha-1S subunit of the voltage-gated calcium
CC channel that gives rise to L-type calcium currents in skeletal muscle.
CC Calcium channels containing the alpha-1S subunit play an important role
CC in excitation-contraction coupling in skeletal muscle via their
CC interaction with RYR1, which triggers Ca(2+) release from the
CC sarcplasmic reticulum and ultimately results in muscle contraction.
CC Long-lasting (L-type) calcium channels belong to the 'high-voltage
CC activated' (HVA) group. {ECO:0000250|UniProtKB:P07293}.
CC -!- ACTIVITY REGULATION: Channel activity is blocked by dihydropyridines
CC (DHP), phenylalkylamines, and by benzothiazepines.
CC {ECO:0000250|UniProtKB:P07293}.
CC -!- SUBUNIT: Component of a calcium channel complex consisting of a pore-
CC forming alpha subunit (CACNA1S) and the ancillary subunits CACNB1 or
CC CACNB2, CACNG1 and CACNA2D1 (PubMed:28351836). The channel complex
CC contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e.
CC it contains either CACNB1 or CACNB2 (By similarity). CACNA1S channel
CC activity is modulated by the auxiliary subunits (CACNB1 or CACNB2,
CC CACNG1 and CACNA2D1). Interacts with DYSF and JSRP1 (PubMed:12871958,
CC PubMed:16550931, PubMed:16638807). Interacts with RYR1 (By similarity).
CC Interacts with STAC, STAC2 and STAC3 (via their SH3 domains)
CC (PubMed:29467163). Interacts with CALM (By similarity).
CC {ECO:0000250|UniProtKB:P07293, ECO:0000250|UniProtKB:Q13698,
CC ECO:0000269|PubMed:12871958, ECO:0000269|PubMed:16550931,
CC ECO:0000269|PubMed:16638807, ECO:0000269|PubMed:28351836,
CC ECO:0000269|PubMed:29467163}.
CC -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma, T-tubule
CC {ECO:0000250|UniProtKB:P07293}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P07293}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q02789-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q02789-2; Sequence=VSP_050420;
CC Name=3;
CC IsoId=Q02789-3; Sequence=VSP_050420, VSP_061231;
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. {ECO:0000250|UniProtKB:P07293}.
CC -!- DOMAIN: The loop between repeats II and III interacts with the
CC ryanodine receptor, and is therefore important for calcium release from
CC the endoplasmic reticulum necessary for muscle contraction.
CC {ECO:0000250|UniProtKB:P07293}.
CC -!- PTM: The alpha-1S subunit is found in two isoforms in the skeletal
CC muscle: a minor form of 212 kDa containing the complete amino acid
CC sequence, and a major form of 190 kDa derived from the full-length form
CC by post-translational proteolysis close to Phe-1690.
CC {ECO:0000250|UniProtKB:P07293}.
CC -!- PTM: Phosphorylated. Phosphorylation by PKA activates the calcium
CC channel. Both the minor and major forms are phosphorylated in vitro by
CC PKA. Phosphorylation at Ser-1575 is involved in beta-adrenergic-
CC mediated regulation of the channel. {ECO:0000250|UniProtKB:P07293}.
CC -!- DISEASE: Note=Defects in Cacna1s are the cause of muscular dysgenesis
CC (MDG), a lethal autosomal recessive disorder in which there is total
CC lack of excitation-contraction coupling in homozygotes, and which
CC results in complete skeletal muscle paralysis. A single nucleotide
CC deletion yields a protein with an altered and truncated C-terminus.
CC {ECO:0000269|PubMed:1281468}.
CC -!- SIMILARITY: Belongs to the calcium channel alpha-1 subunit (TC
CC 1.A.1.11) family. CACNA1S subfamily. {ECO:0000305}.
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DR EMBL; L06234; AAB59700.1; ALT_TERM; mRNA.
DR EMBL; AK143541; BAE25427.1; -; mRNA.
DR EMBL; GL456086; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M57968; AAA03684.1; -; mRNA.
DR EMBL; M57976; AAA63290.1; -; mRNA.
DR CCDS; CCDS35724.1; -. [Q02789-1]
DR CCDS; CCDS48380.1; -. [Q02789-3]
DR PIR; A45099; A45099.
DR RefSeq; NP_001074492.1; NM_001081023.1. [Q02789-1]
DR RefSeq; NP_055008.2; NM_014193.2. [Q02789-3]
DR PDB; 4ZW2; X-ray; 1.86 A; B=357-374.
DR PDBsum; 4ZW2; -.
DR AlphaFoldDB; Q02789; -.
DR SMR; Q02789; -.
DR ComplexPortal; CPX-3191; Skeletal muscle VGCC complex.
DR STRING; 10090.ENSMUSP00000107699; -.
DR BindingDB; Q02789; -.
DR ChEMBL; CHEMBL3988632; -.
DR GlyGen; Q02789; 3 sites.
DR iPTMnet; Q02789; -.
DR PhosphoSitePlus; Q02789; -.
DR MaxQB; Q02789; -.
DR PaxDb; Q02789; -.
DR PRIDE; Q02789; -.
DR ProteomicsDB; 273824; -. [Q02789-1]
DR ProteomicsDB; 273825; -. [Q02789-2]
DR ProteomicsDB; 349659; -.
DR ProteomicsDB; 359911; -.
DR ProteomicsDB; 361179; -.
DR Antibodypedia; 4015; 179 antibodies from 32 providers.
DR DNASU; 12292; -.
DR Ensembl; ENSMUST00000112064; ENSMUSP00000107695; ENSMUSG00000026407. [Q02789-1]
DR Ensembl; ENSMUST00000112068; ENSMUSP00000107699; ENSMUSG00000026407. [Q02789-3]
DR GeneID; 12292; -.
DR KEGG; mmu:12292; -.
DR CTD; 779; -.
DR MGI; MGI:88294; Cacna1s.
DR VEuPathDB; HostDB:ENSMUSG00000026407; -.
DR eggNOG; KOG2301; Eukaryota.
DR GeneTree; ENSGT00940000158289; -.
DR HOGENOM; CLU_000540_0_1_1; -.
DR InParanoid; Q02789; -.
DR OMA; SSIHYER; -.
DR OrthoDB; 172471at2759; -.
DR PhylomeDB; Q02789; -.
DR TreeFam; TF312805; -.
DR BioGRID-ORCS; 12292; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Cacna1s; mouse.
DR PRO; PR:Q02789; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q02789; protein.
DR Bgee; ENSMUSG00000026407; Expressed in hindlimb stylopod muscle and 98 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0044327; C:dendritic spine head; ISO:MGI.
DR GO; GO:0031674; C:I band; ISO:MGI.
DR GO; GO:1990454; C:L-type voltage-gated calcium channel complex; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0042383; C:sarcolemma; ISO:MGI.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IDA:MGI.
DR GO; GO:0030315; C:T-tubule; IDA:MGI.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; ISO:MGI.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0008331; F:high voltage-gated calcium channel activity; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IDA:MGI.
DR GO; GO:0098703; P:calcium ion import across plasma membrane; IBA:GO_Central.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IC:ComplexPortal.
DR GO; GO:0006816; P:calcium ion transport; IDA:MGI.
DR GO; GO:0071313; P:cellular response to caffeine; ISS:UniProtKB.
DR GO; GO:0007029; P:endoplasmic reticulum organization; IMP:MGI.
DR GO; GO:0002074; P:extraocular skeletal muscle development; IMP:MGI.
DR GO; GO:0055001; P:muscle cell development; IMP:MGI.
DR GO; GO:0006936; P:muscle contraction; IDA:MGI.
DR GO; GO:0007520; P:myoblast fusion; IMP:MGI.
DR GO; GO:0007528; P:neuromuscular junction development; IMP:MGI.
DR GO; GO:0045933; P:positive regulation of muscle contraction; IC:ComplexPortal.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0043501; P:skeletal muscle adaptation; IMP:MGI.
DR GO; GO:0048741; P:skeletal muscle fiber development; IDA:MGI.
DR GO; GO:0007519; P:skeletal muscle tissue development; IMP:MGI.
DR GO; GO:0001501; P:skeletal system development; IMP:MGI.
DR GO; GO:0006941; P:striated muscle contraction; 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; IPR005450; VDCC_L_a1ssu.
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; 1.
DR Pfam; PF16905; GPHH; 1.
DR Pfam; PF00520; Ion_trans; 4.
DR PRINTS; PR00167; CACHANNEL.
DR PRINTS; PR01630; LVDCCALPHA1.
DR PRINTS; PR01634; LVDCCALPHA1S.
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; Disulfide bond;
KW Glycoprotein; Ion channel; Ion transport; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..1852
FT /note="Voltage-dependent L-type calcium channel subunit
FT alpha-1S"
FT /id="PRO_0000053944"
FT TOPO_DOM 1..51
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 52..70
FT /note="Helical; Name=S1 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 71..85
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 86..106
FT /note="Helical; Name=S2 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 107..115
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 116..136
FT /note="Helical; Name=S3 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 137..160
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 161..179
FT /note="Helical; Name=S4 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 180..196
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 197..218
FT /note="Helical; Name=S5 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 219..279
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 280..301
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 302..309
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 310..330
FT /note="Helical; Name=S6 of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 331..432
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 433..451
FT /note="Helical; Name=S1 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 452..462
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 463..483
FT /note="Helical; Name=S2 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 484..494
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 495..514
FT /note="Helical; Name=S3 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 515..523
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 524..542
FT /note="Helical; Name=S4 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 543..561
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 562..581
FT /note="Helical; Name=S5 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 582..601
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 602..623
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 624..633
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 634..653
FT /note="Helical; Name=S6 of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 654..799
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 800..818
FT /note="Helical; Name=S1 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 819..830
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 831..850
FT /note="Helical; Name=S2 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 851..866
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 867..885
FT /note="Helical; Name=S3 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 886..892
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 893..911
FT /note="Helical; Name=S4 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 912..930
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 931..950
FT /note="Helical; Name=S5 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 951..1000
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1001..1021
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1022..1038
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1039..1060
FT /note="Helical; Name=S6 of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1061..1118
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1119..1140
FT /note="Helical; Name=S1 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1141..1148
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1149..1170
FT /note="Helical; Name=S2 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1171..1180
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1181..1200
FT /note="Helical; Name=S3 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1201..1231
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1232..1250
FT /note="Helical; Name=S4 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1251..1268
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1269..1289
FT /note="Helical; Name=S5 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1290..1311
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 1312..1330
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1331..1356
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 1357..1381
FT /note="Helical; Name=S6 of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT TOPO_DOM 1382..1852
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REPEAT 38..337
FT /note="I"
FT /evidence="ECO:0000305"
FT REPEAT 418..664
FT /note="II"
FT /evidence="ECO:0000305"
FT REPEAT 768..1068
FT /note="III"
FT /evidence="ECO:0000305"
FT REPEAT 1105..1384
FT /note="IV"
FT /evidence="ECO:0000305"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 357..374
FT /note="Binding to the beta subunit"
FT /evidence="ECO:0000269|PubMed:28351836"
FT REGION 675..712
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 731..757
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 988..1077
FT /note="Dihydropyridine binding"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT REGION 1337..1403
FT /note="Dihydropyridine binding"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT REGION 1349..1392
FT /note="Phenylalkylamine binding"
FT /evidence="ECO:0000250"
FT REGION 1349..1391
FT /note="Phenylalkylamine binding"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT REGION 1522..1542
FT /note="Interaction with calmodulin"
FT /evidence="ECO:0000250|UniProtKB:Q13698"
FT REGION 1702..1721
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1727..1762
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 290..293
FT /note="Selectivity filter of repeat I"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT MOTIF 612..615
FT /note="Selectivity filter of repeat II"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT MOTIF 1012..1015
FT /note="Selectivity filter of repeat III"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT MOTIF 1321..1324
FT /note="Selectivity filter of repeat IV"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT COMPBIAS 1..20
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 675..710
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 292
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT BINDING 614
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT BINDING 1014
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT MOD_RES 393
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 397
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 687
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT MOD_RES 1575
FT /note="Phosphoserine; by PKA and CAMK2"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT MOD_RES 1579
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q02485"
FT MOD_RES 1617
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 257
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1141
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 226..254
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT DISULFID 245..261
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT DISULFID 957..968
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT DISULFID 1338..1352
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT VAR_SEQ 1204..1222
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:1281468,
FT ECO:0000303|PubMed:16141072, ECO:0000303|PubMed:2173707"
FT /id="VSP_050420"
FT VAR_SEQ 1743..1747
FT /note="VTGAK -> LSQ (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_061231"
FT CONFLICT 1176
FT /note="G -> A (in Ref. 1; AAB59700)"
FT /evidence="ECO:0000305"
FT HELIX 358..372
FT /evidence="ECO:0007829|PDB:4ZW2"
SQ SEQUENCE 1852 AA; 210320 MW; 139AF2C98415AC88 CRC64;
MEPPSPQDEG LRKKQPKKPV PEILPRPPRA LFCLTLQNPL RKACISIVEW KPFETIILLT
IFANCVALAV YLPMPEDDNN TLNLGLEKLE YFFLIVFSIE AAMKIIAYGF LFHQDAYLRS
GWNVLDFIIV FLGVFTVILE QVNIIQTNTA PMSSKGAGLD VKALRAFRVL RPLRLVSGVP
SLQVVLNSIF KAMLPLFHIA LLVLFMVIIY AIIGLELFKG KMHKTCYFIG TDIVATVENE
KPSPCARTGS GRPCTINGSE CRGGWPGPNH GITHFDNFGF SMLTVYQCIS MEGWTDVLYW
VNDAIGNEWP WIYFVTLILL GSFFILNLVL GVLSGEFTKE REKAKSRGTF QKLREKQQLE
EDLRGYMSWI TQGEVMDVDD LREGKLSLDE GGSDTESLYE IEGLNKIIQF IRHWRQWNRV
FRWKCHDLVK SKVFYWLVIL IVALNTLSIA SEHHNQPLWL THLQDVANRV LLTLFTIEML
MKMYGLGLRQ YFMSIFNRFD CFVVCSGILE ILLVESGAMS PLGISVLRCI RLLRLFKITK
YWTSLSNLVA SLLNSIRSIA SLLLLLFLFI IIFALLGMQL FGGRYDFEDT EVRRSNFDNF
PQALISVFQV LTGEDWNSVM YNGIMAYGGP TYPGVLVCIY FIILFVCGNY ILLNVFLAIA
VDNLAEAESL TSAQKAKAEE RKRRKMSKGL PDKSEEERAT VTKKLEQKSK GEGIPTTAKL
KIDEFESNVN EVKDPYPSAD FPGDDEEDEP EIPVSPRPRP LAELQLKEKA VPIPEASSFF
IFSPTNKIRV LCHRIVNATW FTNFILLFIL LSSAALAAED PIRADSMRNQ ILEYFDYVFT
AVFTVEIVLK MTTYGAFLHK GSFCRNYFNI LDLLVVAVSL ISMGLESSAI SVVKILRVLR
VLRPLRAINR AKGLKHVVQC VFVAIRTIGN IVLVTTLLQF MFACIGVQLF KGKFYSCNDL
SKMTEEECRG YYYIYKDGDP TQIELRPRQW IHNDFHFDNV LSAMMSLFTV STFEGWPQLL
YKAIDSNEED TGPVYNNRVE MAIFFIIYII LIAFFMMNIF VGFVIVTFQE QGETEYKNCE
LDKNQRQCVQ YALKARPLRC YIPKNPYQYQ VWYVVTSSYF EYLMFALIML NTICLGMQHY
NQSEQMNHIS DILNVAFTII FTLEMVLKLI AFKPRGYFGD PWNVFDFLIV IGSIIDVILS
EIDTFLASSG GLYCLGGGCG NVDPDESARI SSAFFRLFRV MRLVKLLNRA EGVRTLLWTF
IKSFQALPYV ALLIVMLFFI YAVIGMQMFG KIAMVDGTQI NRNNNFQTFP QAVLLLFRCA
TGEAWQEILL ACSYGKLCDP ESDYAPGEEH TCGTNFAYYY FISFYMLCAF LIINLFVAVI
MDNFDYLTRD WSILGPHHLD EFKAIWAEYD PEAKGRIKHL DVVTLLRRIQ PPLGFGKFCP
HRVACKRLVG MNMPLNSDGT VTFNATLFAL VRTALKIKTE GNFEQANEEL RAIIKKIWKR
TSMKLLDQVI PPIGDDEVTV GKFYATFLIQ EHFRKFMKRQ EEYYGYRPKK DTVQIQAGLR
TIEEEAAPEI HRAISGDLTA EEELERAMVE AAMEEGIFRR TGGLFGQVDN FLERTNSLPP
VMANQRPLQF AEIEMEELES PVFLEDFPQN PGTHPLARAN TNNANANVAY GNSSHRNNPV
FSSICYEREF LGEADMPVTR EGPLSQPCRA SGPHSRSHVD KLKRPMTQRG MPEGQVPPSP
CQVTGAKAEH PVQKEGKGPT SRFLETPNSR NFEEHVPRNS AHRCTAPATA MLIQEALVRG
GLDSLAADAN FVMATGQALA DACQMEPEEV EVAATELLKQ ESPEGGAVPW EP
