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Database: UniProt
Entry: CAC1S_RABIT
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Original site: CAC1S_RABIT 
ID   CAC1S_RABIT             Reviewed;        1873 AA.
AC   P07293;
DT   01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1988, sequence version 1.
DT   25-OCT-2017, entry version 149.
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 alpha-1S subunit {ECO:0000303|PubMed:15201141, ECO:0000303|PubMed:1660150, ECO:0000303|PubMed:25667046};
DE            Short=DHPR {ECO:0000303|PubMed:10388749, ECO:0000303|PubMed:25667046};
DE   AltName: Full=Voltage-gated calcium channel subunit alpha Cav1.1;
GN   Name=CACNA1S; Synonyms=CACH1, CACNL1A3;
OS   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae;
OC   Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, TISSUE
RP   SPECIFICITY, DIHYDROPYRIDINE BINDING, SUBUNIT, AND SUBCELLULAR
RP   LOCATION.
RC   TISSUE=Skeletal muscle;
RX   PubMed=3037387; DOI=10.1038/328313a0;
RA   Tanabe T., Takeshima H., Mikami A., Flockerzi V., Takahashi H.,
RA   Kangawa K., Kojima M., Matsuo H., Hirose T., Numa S.;
RT   "Primary structure of the receptor for calcium channel blockers from
RT   skeletal muscle.";
RL   Nature 328:313-318(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Skeletal muscle;
RX   PubMed=2458626; DOI=10.1126/science.2458626;
RA   Ellis S.B., Williams M.E., Ways N.R., Brenner R., Sharp A.H.,
RA   Leung A.T., Campbell K.P., McKenna E., Koch W.J., Hui A., Schwartz A.,
RA   Harpold M.M.;
RT   "Sequence and expression of mRNAs encoding the alpha 1 and alpha 2
RT   subunits of a DHP-sensitive calcium channel.";
RL   Science 241:1661-1664(1988).
RN   [3]
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.,
RA   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   [4]
RP   PHENYLALKYLAMINE-BINDING REGION.
RX   PubMed=2174553; DOI=10.1073/pnas.87.23.9108;
RA   Striessnig J., Glossmann H., Catterall W.A.;
RT   "Identification of a phenylalkylamine binding region within the alpha
RT   1 subunit of skeletal muscle Ca2+ channels.";
RL   Proc. Natl. Acad. Sci. U.S.A. 87:9108-9112(1990).
RN   [5]
RP   DIHYDROPYRIDINE-BINDING REGION.
RX   PubMed=1656465; DOI=10.1073/pnas.88.20.9203;
RA   Nakayama H., Taki M., Striessnig J., Glossmann H., Catterall W.A.,
RA   Kanaoka Y.;
RT   "Identification of 1,4-dihydropyridine binding regions within the
RT   alpha 1 subunit of skeletal muscle Ca2+ channels by photoaffinity
RT   labeling with diazipine.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:9203-9207(1991).
RN   [6]
RP   DIHYDROPYRIDINE-BINDING REGION.
RX   PubMed=1660150; DOI=10.1073/pnas.88.23.10769;
RA   Striessnig J., Murphy B.J., Catterall W.A.;
RT   "Dihydropyridine receptor of L-type Ca2+ channels: identification of
RT   binding domains for [3H](+)-PN200-110 and [3H]azidopine within the
RT   alpha 1 subunit.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:10769-10773(1991).
RN   [7]
RP   PHOSPHORYLATION AT SER-687 AND SER-1617.
RX   PubMed=2844809;
RA   Roehrkasten A., Meyer H.E., Nastainczyk W., Sieber M., Hofmann F.;
RT   "CAMP-dependent protein kinase rapidly phosphorylates serine-687 of
RT   the skeletal muscle receptor for calcium channel blockers.";
RL   J. Biol. Chem. 263:15325-15329(1988).
RN   [8]
RP   PHOSPHORYLATION BY PKA.
RX   PubMed=2549550; DOI=10.1073/pnas.86.17.6816;
RA   Nunoki K., Florio V., Catterall W.A.;
RT   "Activation of purified calcium channels by stoichiometric protein
RT   phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 86:6816-6820(1989).
RN   [9]
RP   FUNCTION, AND SUBCELLULAR LOCATION.
RX   PubMed=9465115;
RA   Grabner M., Dirksen R.T., Beam K.G.;
RT   "Tagging with green fluorescent protein reveals a distinct subcellular
RT   distribution of L-type and non-L-type Ca2+ channels expressed in
RT   dysgenic myotubes.";
RL   Proc. Natl. Acad. Sci. U.S.A. 95:1903-1908(1998).
RN   [10]
RP   INTERACTION WITH RYR1, AND DOMAIN.
RX   PubMed=10388749; DOI=10.1016/S0006-3495(99)76881-5;
RA   Dulhunty A.F., Laver D.R., Gallant E.M., Casarotto M.G., Pace S.M.,
RA   Curtis S.;
RT   "Activation and inhibition of skeletal RyR channels by a part of the
RT   skeletal DHPR II-III loop: effects of DHPR Ser687 and FKBP12.";
RL   Biophys. J. 77:189-203(1999).
RN   [11]
RP   FUNCTION, MUTAGENESIS OF ARG-1086, SUBCELLULAR LOCATION, AND DOMAIN.
RX   PubMed=15201141; DOI=10.1152/ajpcell.00173.2004;
RA   Weiss R.G., O'Connell K.M., Flucher B.E., Allen P.D., Grabner M.,
RA   Dirksen R.T.;
RT   "Functional analysis of the R1086H malignant hyperthermia mutation in
RT   the DHPR reveals an unexpected influence of the III-IV loop on
RT   skeletal muscle EC coupling.";
RL   Am. J. Physiol. 287:C1094-C1102(2004).
RN   [12]
RP   STRUCTURE BY NMR OF 671-690, AND DOMAIN.
RX   PubMed=10766780; DOI=10.1074/jbc.275.16.11631;
RA   Casarotto M.G., Gibson F., Pace S.M., Curtis S.M., Mulcair M.,
RA   Dulhunty A.F.;
RT   "A structural requirement for activation of skeletal ryanodine
RT   receptors by peptides of the dihydropyridine receptor II-III loop.";
RL   J. Biol. Chem. 275:11631-11637(2000).
RN   [13]
RP   X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 34-415 IN COMPLEX WITH
RP   CACNB2, AND SUBUNIT.
RX   PubMed=15134636; DOI=10.1016/S0896-6273(04)00250-8;
RA   Opatowsky Y., Chen C.-C., Campbell K.P., Hirsch J.A.;
RT   "Structural analysis of the voltage-dependent calcium channel beta
RT   subunit functional core and its complex with the alpha1 interaction
RT   domain.";
RL   Neuron 42:387-399(2004).
RN   [14]
RP   STRUCTURE BY ELECTRON MICROSCOPY (15 ANGSTROMS), SUBUNIT, TISSUE
RP   SPECIFICITY, SUBCELLULAR LOCATION, AND TOPOLOGY.
RC   TISSUE=Skeletal muscle {ECO:0000303|PubMed:25667046};
RX   PubMed=25667046; DOI=10.1038/srep08370;
RA   Hu H., Wang Z., Wei R., Fan G., Wang Q., Zhang K., Yin C.C.;
RT   "The molecular architecture of dihydropyrindine receptor/L-type Ca2+
RT   channel complex.";
RL   Sci. Rep. 5:8370-8370(2015).
RN   [15] {ECO:0000244|PDB:3JBR}
RP   STRUCTURE BY ELECTRON MICROSCOPY (4.20 ANGSTROMS) IN COMPLEX WITH
RP   CACNG1; CACNB2 AND CACNA2D1, SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY,
RP   TISSUE SPECIFICITY, IDENTIFICATION BY MASS SPECTROMETRY, AND DOMAIN.
RC   TISSUE=Skeletal muscle {ECO:0000303|PubMed:26680202};
RX   PubMed=26680202; DOI=10.1126/science.aad2395;
RA   Wu J., Yan Z., Li Z., Yan C., Lu S., Dong M., Yan N.;
RT   "Structure of the voltage-gated calcium channel Cav1.1 complex.";
RL   Science 350:2395-2395(2015).
RN   [16] {ECO:0000244|PDB:5GJV, ECO:0000244|PDB:5GJW}
RP   STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) IN COMPLEX WITH
RP   CALCIUM; CACNB1; CACNG1 AND CACNA2D1, SUBUNIT, SUBCELLULAR LOCATION,
RP   TOPOLOGY, TISSUE SPECIFICITY, IDENTIFICATION BY MASS SPECTROMETRY,
RP   DOMAIN, DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-257.
RC   TISSUE=Skeletal muscle {ECO:0000303|PubMed:27580036};
RX   PubMed=27580036; DOI=10.1038/nature19321;
RA   Wu J., Yan Z., Li Z., Qian X., Lu S., Dong M., Zhou Q., Yan N.;
RT   "Structure of the voltage-gated calcium channel Cav1.1 at 3.6A
RT   resolution.";
RL   Nature 537:191-196(2016).
CC   -!- FUNCTION: Pore-forming, alpha-1S subunit of the voltage-gated
CC       calcium channel that gives rise to L-type calcium currents in
CC       skeletal muscle (PubMed:9465115, PubMed:15201141). Calcium
CC       channels containing the alpha-1S subunit play an important role in
CC       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       (PubMed:9465115 PubMed:15201141). Long-lasting (L-type) calcium
CC       channels belong to the 'high-voltage activated' (HVA) group.
CC       {ECO:0000269|PubMed:15201141, ECO:0000269|PubMed:9465115,
CC       ECO:0000305}.
CC   -!- ENZYME REGULATION: Channel activity is blocked by dihydropyridines
CC       (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-
CC       IIIA (omega-Aga-IIIA). It is however insensitive to omega-
CC       conotoxin-GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-
CC       IVA). {ECO:0000305|PubMed:1656465, ECO:0000305|PubMed:1660150,
CC       ECO:0000305|PubMed:2174553, ECO:0000305|PubMed:3037387}.
CC   -!- SUBUNIT: Component of a calcium channel complex consisting of a
CC       pore-forming alpha subunit (CACNA1S) and the ancillary subunits
CC       CACNB1 or CACNB2, CACNG1 and CACNA2D1 (PubMed:3037387,
CC       PubMed:15134636, PubMed:25667046, PubMed:26680202,
CC       PubMed:27580036). The channel complex contains alpha, beta, gamma
CC       and delta subunits in a 1:1:1:1 ratio, i.e. it contains either
CC       CACNB1 or CACNB2 (PubMed:15134636, PubMed:25667046,
CC       PubMed:26680202, PubMed:27580036). CACNA1S channel activity is
CC       modulated by the auxiliary subunits (CACNB1 or CACNB2, CACNG1 and
CC       CACNA2D1). Interacts with DYSF and JSRP1 (By similarity).
CC       Interacts with RYR1 (PubMed:10388749). Interacts with CALM (By
CC       similarity). {ECO:0000250|UniProtKB:Q02789,
CC       ECO:0000250|UniProtKB:Q13698, ECO:0000269|PubMed:10388749,
CC       ECO:0000269|PubMed:15134636, ECO:0000269|PubMed:25667046,
CC       ECO:0000269|PubMed:26680202, ECO:0000269|PubMed:27580036,
CC       ECO:0000269|PubMed:3037387}.
CC   -!- INTERACTION:
CC       P13806:CACNA2D1; NbExp=3; IntAct=EBI-8613624, EBI-9683767;
CC       P19517:CACNB1; NbExp=4; IntAct=EBI-8613624, EBI-978604;
CC       P19518:CACNG1; NbExp=3; IntAct=EBI-8613624, EBI-9683808;
CC       Q96RG2:PASK (xeno); NbExp=2; IntAct=EBI-8613624, EBI-1042651;
CC   -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma
CC       {ECO:0000269|PubMed:15201141, ECO:0000269|PubMed:25667046,
CC       ECO:0000269|PubMed:26680202, ECO:0000269|PubMed:27580036,
CC       ECO:0000269|PubMed:9465115, ECO:0000305|PubMed:3037387}; Multi-
CC       pass membrane protein {ECO:0000269|PubMed:25667046,
CC       ECO:0000269|PubMed:26680202, ECO:0000269|PubMed:27580036,
CC       ECO:0000305|PubMed:3037387}. Note=Detected on T-tubules
CC       (extensions of the sarcolemma). {ECO:0000269|PubMed:25667046}.
CC   -!- TISSUE SPECIFICITY: Detected in skeletal muscle T-tubules (at
CC       protein level). {ECO:0000269|PubMed:25667046,
CC       ECO:0000269|PubMed:26680202, ECO:0000269|PubMed:27580036,
CC       ECO:0000269|PubMed:3037387}.
CC   -!- DOMAIN: Each of the four internal repeats contains five
CC       hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one
CC       positively charged transmembrane segment (S4). S4 segments
CC       probably represent the voltage-sensor and are characterized by a
CC       series of positively charged amino acids at every third position.
CC       {ECO:0000269|PubMed:26680202, ECO:0000269|PubMed:27580036}.
CC   -!- DOMAIN: The loop between repeats II and III interacts with the
CC       ryanodine receptor, and is therefore important for calcium release
CC       from the endoplasmic reticulum necessary for muscle contraction.
CC       {ECO:0000305|PubMed:10388749, ECO:0000305|PubMed:10766780,
CC       ECO:0000305|PubMed:15201141}.
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
CC       form by post-translational proteolysis close to Phe-1690.
CC       {ECO:0000305|PubMed:3037387}.
CC   -!- PTM: Both the minor and major forms are phosphorylated in vitro by
CC       PKA. Phosphorylation by PKA activates the calcium channel.
CC       {ECO:0000269|PubMed:2549550, ECO:0000269|PubMed:2844809}.
CC   -!- SIMILARITY: Belongs to the calcium channel alpha-1 subunit (TC
CC       1.A.1.11) family. CACNA1S subfamily. {ECO:0000305}.
DR   EMBL; X05921; CAA29355.1; -; mRNA.
DR   EMBL; M23919; AAA31159.1; -; mRNA.
DR   PIR; A30063; A30063.
DR   RefSeq; NP_001095190.1; NM_001101720.1.
DR   UniGene; Ocu.1826; -.
DR   PDB; 1DU1; NMR; -; A=671-690.
DR   PDB; 1JZP; NMR; -; A=671-690.
DR   PDB; 1T3L; X-ray; 2.20 A; B=357-374.
DR   PDB; 3JBR; EM; 4.20 A; A=1-1395, A=1521-1873.
DR   PDB; 5GJV; EM; 3.60 A; A=1-1873.
DR   PDB; 5GJW; EM; 3.90 A; A=1-1873.
DR   PDBsum; 1DU1; -.
DR   PDBsum; 1JZP; -.
DR   PDBsum; 1T3L; -.
DR   PDBsum; 3JBR; -.
DR   PDBsum; 5GJV; -.
DR   PDBsum; 5GJW; -.
DR   DisProt; DP00228; -.
DR   ProteinModelPortal; P07293; -.
DR   SMR; P07293; -.
DR   DIP; DIP-61879N; -.
DR   IntAct; P07293; 4.
DR   MINT; MINT-8146707; -.
DR   ChEMBL; CHEMBL4169; -.
DR   TCDB; 1.A.1.11.2; the voltage-gated ion channel (vic) superfamily.
DR   iPTMnet; P07293; -.
DR   SwissPalm; P07293; -.
DR   PRIDE; P07293; -.
DR   GeneID; 100009585; -.
DR   KEGG; ocu:100009585; -.
DR   CTD; 779; -.
DR   HOGENOM; HOG000231529; -.
DR   HOVERGEN; HBG050763; -.
DR   InParanoid; P07293; -.
DR   KO; K04857; -.
DR   EvolutionaryTrace; P07293; -.
DR   PRO; PR:P07293; -.
DR   Proteomes; UP000001811; Unplaced.
DR   GO; GO:1990454; C:L-type voltage-gated calcium channel complex; IDA:UniProtKB.
DR   GO; GO:0030315; C:T-tubule; IDA:UniProtKB.
DR   GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR   GO; GO:0044325; F:ion channel binding; IPI:CAFA.
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:UniProtKB.
DR   GO; GO:0071313; P:cellular response to caffeine; IDA:UniProtKB.
DR   GO; GO:0060314; P:regulation of ryanodine-sensitive calcium-release channel activity; IMP:CAFA.
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   PANTHER; PTHR10037:SF190; PTHR10037:SF190; 1.
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; Calcium; Calcium channel; Calcium transport;
KW   Calmodulin-binding; Cell membrane; Complete proteome;
KW   Direct protein sequencing; Disulfide bond; Glycoprotein; Ion channel;
KW   Ion transport; Membrane; Metal-binding; Phosphoprotein; Polymorphism;
KW   Reference proteome; Repeat; Transmembrane; Transmembrane helix;
KW   Transport; Voltage-gated channel.
FT   CHAIN         1   1873       Voltage-dependent L-type calcium channel
FT                                subunit alpha-1S.
FT                                /FTId=PRO_0000053945.
FT   TOPO_DOM      1     51       Cytoplasmic.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM     52     70       Helical; Name=S1 of repeat I.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM     71     85       Extracellular.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM     86    106       Helical; Name=S2 of repeat I.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM    107    115       Cytoplasmic.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM    116    136       Helical; Name=S3 of repeat I.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM    137    160       Extracellular.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM    161    179       Helical; Name=S4 of repeat I.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM    180    196       Cytoplasmic.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM    197    218       Helical; Name=S5 of repeat I.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM    219    279       Extracellular.
FT                                {ECO:0000269|PubMed:27580036}.
FT   INTRAMEM    280    301       Pore-forming.
FT                                {ECO:0000269|PubMed:26680202,
FT                                ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM    302    309       Extracellular.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM    310    330       Helical; Name=S6 of repeat I.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM    331    432       Cytoplasmic.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM    433    451       Helical; Name=S1 of repeat II.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM    452    462       Extracellular.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM    463    483       Helical; Name=S2 of repeat II.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM    484    494       Cytoplasmic.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM    495    514       Helical; Name=S3 of repeat II.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM    515    523       Extracellular.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM    524    542       Helical; Name=S4 of repeat II.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM    543    561       Cytoplasmic.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM    562    581       Helical; Name=S5 of repeat II.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM    582    601       Extracellular.
FT                                {ECO:0000269|PubMed:27580036}.
FT   INTRAMEM    602    623       Pore-forming.
FT                                {ECO:0000269|PubMed:26680202,
FT                                ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM    624    633       Extracellular.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM    634    653       Helical; Name=S6 of repeat II.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM    654    799       Cytoplasmic.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM    800    818       Helical; Name=S1 of repeat III.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM    819    830       Extracellular.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM    831    850       Helical; Name=S2 of repeat III.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM    851    866       Cytoplasmic.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM    867    885       Helical; Name=S3 of repeat III.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM    886    892       Extracellular.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM    893    911       Helical; Name=S4 of repeat III.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM    912    930       Cytoplasmic.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM    931    950       Helical; Name=S5 of repeat III.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM    951   1000       Extracellular.
FT                                {ECO:0000269|PubMed:27580036}.
FT   INTRAMEM   1001   1021       Pore-forming.
FT                                {ECO:0000269|PubMed:26680202,
FT                                ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM   1022   1038       Extracellular.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM   1039   1060       Helical; Name=S6 of repeat III.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM   1061   1118       Cytoplasmic.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM   1119   1140       Helical; Name=S1 of repeat IV.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM   1141   1148       Extracellular.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM   1149   1170       Helical; Name=S2 of repeat IV.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM   1171   1180       Cytoplasmic.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM   1181   1200       Helical; Name=S3 of repeat IV.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM   1201   1231       Extracellular.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM   1232   1250       Helical; Name=S4 of repeat IV.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM   1251   1268       Cytoplasmic.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM   1269   1289       Helical; Name=S5 of repeat IV.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM   1290   1311       Extracellular.
FT                                {ECO:0000269|PubMed:27580036}.
FT   INTRAMEM   1312   1330       Pore-forming.
FT                                {ECO:0000269|PubMed:26680202,
FT                                ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM   1331   1356       Extracellular.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TRANSMEM   1357   1381       Helical; Name=S6 of repeat IV.
FT                                {ECO:0000269|PubMed:27580036}.
FT   TOPO_DOM   1382   1873       Cytoplasmic.
FT                                {ECO:0000269|PubMed:27580036}.
FT   REPEAT       38    337       I. {ECO:0000305}.
FT   REPEAT      418    664       II. {ECO:0000305}.
FT   REPEAT      786   1068       III. {ECO:0000305}.
FT   REPEAT     1105   1384       IV. {ECO:0000305}.
FT   CA_BIND    1410   1421       {ECO:0000250}.
FT   REGION      357    374       Binding to the beta subunit.
FT                                {ECO:0000269|PubMed:27580036}.
FT   REGION      988   1077       Dihydropyridine binding.
FT                                {ECO:0000269|PubMed:1656465,
FT                                ECO:0000269|PubMed:1660150}.
FT   REGION     1337   1403       Dihydropyridine binding.
FT                                {ECO:0000269|PubMed:1656465}.
FT   REGION     1349   1391       Phenylalkylamine binding.
FT                                {ECO:0000269|PubMed:2174553}.
FT   REGION     1522   1542       Interaction with calmodulin.
FT                                {ECO:0000250|UniProtKB:Q13698}.
FT   MOTIF       290    293       Selectivity filter of repeat I.
FT                                {ECO:0000305|PubMed:26680202,
FT                                ECO:0000305|PubMed:27580036}.
FT   MOTIF       612    615       Selectivity filter of repeat II.
FT                                {ECO:0000305|PubMed:26680202,
FT                                ECO:0000305|PubMed:27580036}.
FT   MOTIF      1012   1015       Selectivity filter of repeat III.
FT                                {ECO:0000305|PubMed:26680202,
FT                                ECO:0000305|PubMed:27580036}.
FT   MOTIF      1321   1324       Selectivity filter of repeat IV.
FT                                {ECO:0000305|PubMed:26680202,
FT                                ECO:0000305|PubMed:27580036}.
FT   COMPBIAS    562    568       Poly-Leu.
FT   METAL       292    292       Calcium. {ECO:0000244|PDB:5GJW,
FT                                ECO:0000269|PubMed:27580036}.
FT   METAL       614    614       Calcium. {ECO:0000244|PDB:5GJV,
FT                                ECO:0000269|PubMed:27580036}.
FT   METAL      1014   1014       Calcium. {ECO:0000244|PDB:5GJV,
FT                                ECO:0000269|PubMed:27580036}.
FT   SITE       1690   1691       Cleavage. {ECO:0000305}.
FT   MOD_RES     393    393       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q02789}.
FT   MOD_RES     397    397       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q02789}.
FT   MOD_RES     687    687       Phosphoserine; by PKA.
FT                                {ECO:0000269|PubMed:2844809}.
FT   MOD_RES    1392   1392       Phosphoserine; by PKA. {ECO:0000255}.
FT   MOD_RES    1575   1575       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q02485}.
FT   MOD_RES    1579   1579       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:Q02485}.
FT   MOD_RES    1617   1617       Phosphoserine; by PKA.
FT                                {ECO:0000269|PubMed:2844809}.
FT   CARBOHYD     79     79       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    257    257       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000244|PDB:5GJV}.
FT   DISULFID    226    254       {ECO:0000244|PDB:5GJV,
FT                                ECO:0000244|PDB:5GJW,
FT                                ECO:0000269|PubMed:27580036}.
FT   DISULFID    245    261       {ECO:0000244|PDB:5GJV,
FT                                ECO:0000244|PDB:5GJW,
FT                                ECO:0000269|PubMed:27580036}.
FT   DISULFID    957    968       {ECO:0000244|PDB:5GJV,
FT                                ECO:0000244|PDB:5GJW,
FT                                ECO:0000269|PubMed:27580036}.
FT   DISULFID   1338   1352       {ECO:0000244|PDB:5GJV,
FT                                ECO:0000244|PDB:5GJW,
FT                                ECO:0000269|PubMed:27580036}.
FT   VARIANT     165    165       R -> K.
FT   VARIANT     258    258       G -> D.
FT   VARIANT    1870   1870       P -> L.
FT   MUTAGEN    1086   1086       R->H: Shifts the threshold potential to
FT                                more negative values and lowers the
FT                                concentration threshold for channel
FT                                activation by caffeine.
FT                                {ECO:0000269|PubMed:15201141}.
FT   CONFLICT    694    694       T -> R (in Ref. 2; AAA31159).
FT                                {ECO:0000305}.
FT   CONFLICT   1808   1808       T -> M (in Ref. 2; AAA31159).
FT                                {ECO:0000305}.
FT   CONFLICT   1815   1815       A -> V (in Ref. 2; AAA31159).
FT                                {ECO:0000305}.
FT   CONFLICT   1835   1835       A -> E (in Ref. 2; AAA31159).
FT                                {ECO:0000305}.
FT   HELIX       359    372       {ECO:0000244|PDB:1T3L}.
FT   HELIX       672    677       {ECO:0000244|PDB:1DU1}.
FT   TURN        678    681       {ECO:0000244|PDB:1DU1}.
SQ   SEQUENCE   1873 AA;  212029 MW;  047B10D1946B0796 CRC64;
     MEPSSPQDEG LRKKQPKKPL PEVLPRPPRA LFCLTLQNPL RKACISIVEW KPFETIILLT
     IFANCVALAV YLPMPEDDNN SLNLGLEKLE YFFLTVFSIE AAMKIIAYGF LFHQDAYLRS
     GWNVLDFIIV FLGVFTAILE QVNVIQSNTA PMSSKGAGLD VKALRAFRVL RPLRLVSGVP
     SLQVVLNSIF KAMLPLFHIA LLVLFMVIIY AIIGLELFKG KMHKTCYYIG TDIVATVENE
     KPSPCARTGS GRPCTINGSE CRGGWPGPNH GITHFDNFGF SMLTVYQCIT MEGWTDVLYW
     VNDAIGNEWP WIYFVTLILL GSFFILNLVL GVLSGEFTKE REKAKSRGTF QKLREKQQLE
     EDLRGYMSWI TQGEVMDVED LREGKLSLEE GGSDTESLYE IEGLNKIIQF IRHWRQWNRV
     FRWKCHDLVK SRVFYWLVIL IVALNTLSIA SEHHNQPLWL THLQDIANRV LLSLFTIEML
     LKMYGLGLRQ YFMSIFNRFD CFVVCSGILE LLLVESGAMT PLGISVLRCI RLLRLFKITK
     YWTSLSNLVA SLLNSIRSIA SLLLLLFLFI IIFALLGMQL FGGRYDFEDT EVRRSNFDNF
     PQALISVFQV LTGEDWNSVM YNGIMAYGGP SYPGVLVCIY FIILFVCGNY ILLNVFLAIA
     VDNLAEAESL TSAQKAKAEE RKRRKMSRGL PDKTEEEKSV MAKKLEQKPK GEGIPTTAKL
     KVDEFESNVN EVKDPYPSAD FPGDDEEDEP EIPVSPRPRP LAELQLKEKA VPIPEASSFF
     IFSPTNKVRV LCHRIVNATW FTNFILLFIL LSSAALAAED PIRAESVRNQ ILGYFDIAFT
     SVFTVEIVLK MTTYGAFLHK GSFCRNYFNI LDLLVVAVSL ISMGLESSTI SVVKILRVLR
     VLRPLRAINR AKGLKHVVQC VFVAIRTIGN IVLVTTLLQF MFACIGVQLF KGKFFSCNDL
     SKMTEEECRG YYYVYKDGDP TQMELRPRQW IHNDFHFDNV LSAMMSLFTV STFEGWPQLL
     YRAIDSNEED MGPVYNNRVE MAIFFIIYII LIAFFMMNIF VGFVIVTFQE QGETEYKNCE
     LDKNQRQCVQ YALKARPLRC YIPKNPYQYQ VWYVVTSSYF EYLMFALIML NTICLGMQHY
     HQSEEMNHIS DILNVAFTII FTLEMILKLL AFKARGYFGD PWNVFDFLIV IGSIIDVILS
     EIDTFLASSG GLYCLGGGCG NVDPDESARI SSAFFRLFRV MRLIKLLSRA EGVRTLLWTF
     IKSFQALPYV ALLIVMLFFI YAVIGMQMFG KIALVDGTQI NRNNNFQTFP QAVLLLFRCA
     TGEAWQEILL ACSYGKLCDP ESDYAPGEEY TCGTNFAYYY FISFYMLCAF LIINLFVAVI
     MDNFDYLTRD WSILGPHHLD EFKAIWAEYD PEAKGRIKHL DVVTLLRRIQ PPLGFGKFCP
     HRVACKRLVG MNMPLNSDGT VTFNATLFAL VRTALKIKTE GNFEQANEEL RAIIKKIWKR
     TSMKLLDQVI PPIGDDEVTV GKFYATFLIQ EHFRKFMKRQ EEYYGYRPKK DTVQIQAGLR
     TIEEEAAPEI RRTISGDLTA EEELERAMVE AAMEERIFRR TGGLFGQVDT FLERTNSLPP
     VMANQRPLQF AEIEMEELES PVFLEDFPQD ARTNPLARAN TNNANANVAY GNSNHSNNQM
     FSSVHCEREF PGEAETPAAG RGALSHSHRA LGPHSKPCAG KLNGQLVQPG MPINQAPPAP
     CQQPSTDPPE RGQRRTSLTG SLQDEAPQRR SSEGSTPRRP APATALLIQE ALVRGGLDTL
     AADAGFVTAT SQALADACQM EPEEVEVAAT ELLKARESVQ GMASVPGSLS RRSSLGSLDQ
     VQGSQETLIP PRP
//
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