CAC1S_HUMAN
ID CAC1S_HUMAN Reviewed; 1873 AA.
AC Q13698; A4IF51; B1ALM2; Q12896; Q13934;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2008, sequence version 4.
DT 03-AUG-2022, entry version 218.
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=Voltage-gated calcium channel subunit alpha Cav1.1;
GN Name=CACNA1S;
GN Synonyms=CACH1, CACN1, CACNL1A3 {ECO:0000303|PubMed:7713519,
GN ECO:0000303|PubMed:8838325};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS HIS-458 AND ASP-1840.
RC TISSUE=Skeletal muscle;
RX PubMed=7713519; DOI=10.1006/geno.1994.1677;
RA Hogan K., Powers P.A., Gregg R.G.;
RT "Cloning of the human skeletal muscle alpha 1 subunit of the
RT dihydropyridine-sensitive L-type calcium channel (CACNL1A3).";
RL Genomics 24:608-609(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ASP-1840.
RX PubMed=8838325; DOI=10.1006/geno.1996.0066;
RA Hogan K., Gregg R.G., Powers P.A.;
RT "The structure of the gene encoding the human skeletal muscle alpha 1
RT subunit of the dihydropyridine-sensitive L-type calcium channel
RT (CACNL1A3).";
RL Genomics 31:392-394(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-1800.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 788-830; 1019-1085 AND 1293-1318.
RX PubMed=7916735; DOI=10.1006/geno.1993.1017;
RA Gregg R.G., Couch F., Hogan K., Powers P.A.;
RT "Assignment of the human gene for the alpha-1 subunit of the skeletal
RT muscle DHP-sensitive calcium channel (CACNL1A3) to chromosome 1q31-q32.";
RL Genomics 15:107-112(1993).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1200-1300, AND VARIANTS HOKPP1 GLY-1239 AND
RP HIS-1239.
RX PubMed=8004673; DOI=10.1016/0092-8674(94)90135-x;
RA Ptacek L.J., Tawil R., Griggs R.C., Engel A.G., Layzer R.B., Kwiecinski H.,
RA McManis P.G., Santiago L., Moore M., Fouad G., Bradley P., Leppert M.F.;
RT "Dihydropyridine receptor mutations cause hypokalemic periodic paralysis.";
RL Cell 77:863-868(1994).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1223-1413.
RA Soldatov N.M.;
RT "Human skeletal muscle L-type Ca2+ channel alpha 1S subunit gene shows
RT splicing patterns similar to alpha 1C and alpha 1D genes in the region
RT involved in hereditary disorders.";
RL Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP INVOLVEMENT IN SUSCEPTIBILITY TO TTPP1.
RX PubMed=15001631; DOI=10.1210/jc.2003-030924;
RA Kung A.W., Lau K.S., Fong G.C., Chan V.;
RT "Association of novel single nucleotide polymorphisms in the calcium
RT channel alpha 1 subunit gene (Ca(v)1.1) and thyrotoxic periodic
RT paralysis.";
RL J. Clin. Endocrinol. Metab. 89:1340-1345(2004).
RN [9] {ECO:0007744|PDB:2VAY}
RP X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 1522-1542 IN COMPLEX WITH CALM.
RX PubMed=19473981; DOI=10.1074/jbc.m109.013326;
RA Halling D.B., Georgiou D.K., Black D.J., Yang G., Fallon J.L.,
RA Quiocho F.A., Pedersen S.E., Hamilton S.L.;
RT "Determinants in CaV1 channels that regulate the Ca2+ sensitivity of bound
RT calmodulin.";
RL J. Biol. Chem. 284:20041-20051(2009).
RN [10] {ECO:0007744|PDB:6B27}
RP X-RAY CRYSTALLOGRAPHY (1.73 ANGSTROMS) OF 747-760 IN COMPLEX WITH STAC2,
RP AND INTERACTION WITH STAC; STAC2 AND STAC3.
RX PubMed=29078335; DOI=10.1073/pnas.1708852114;
RA Wong King Yuen S.M., Campiglio M., Tung C.C., Flucher B.E., Van Petegem F.;
RT "Structural insights into binding of STAC proteins to voltage-gated calcium
RT channels.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E9520-E9528(2017).
RN [11]
RP VARIANT HOKPP1 HIS-528.
RX PubMed=7987325; DOI=10.1093/hmg/3.8.1415;
RA Jurkatt-Rott K., Lehmann-Horn F., Elbaz A., Heine R., Gregg R.G., Hogan K.,
RA Powers P.A., Lapie P., Vale-Santos J.E., Weissenbach J., Fontaine B.;
RT "A calcium channel mutation causing hypokalemic periodic paralysis.";
RL Hum. Mol. Genet. 3:1415-1419(1994).
RN [12]
RP SEQUENCE REVISION, VARIANT MHS5 HIS-1086, AND VARIANTS HIS-458 AND
RP CYS-1539.
RX PubMed=9199552; DOI=10.1086/515454;
RA Monnier N., Procaccio V., Stieglitz P., Lunardi J.;
RT "Malignant-hyperthermia susceptibility is associated with a mutation of the
RT alpha-1-subunit of the human dihydropyridine-sensitive L-type voltage-
RT dependent calcium-channel receptor in skeletal muscle.";
RL Am. J. Hum. Genet. 60:1316-1325(1997).
RN [13]
RP VARIANTS HOKPP1 HIS-528; HIS-1239 AND GLY-1239.
RX PubMed=18162704; DOI=10.3346/jkms.2007.22.6.946;
RA Kim J.-B., Kim M.-H., Lee S.J., Kim D.-J., Lee B.C.;
RT "The genotype and clinical phenotype of Korean patients with familial
RT hypokalemic periodic paralysis.";
RL J. Korean Med. Sci. 22:946-951(2007).
RN [14]
RP VARIANT HOKPP1 HIS-1239.
RX PubMed=17418573; DOI=10.1016/j.nmd.2007.01.020;
RA Houinato D., Laleye A., Adjien C., Adjagba M., Sternberg D., Hilbert P.,
RA Vallat J.M., Darboux R.B., Funalot B., Avode D.G.;
RT "Hypokalaemic periodic paralysis due to the CACNA1S R1239H mutation in a
RT large African family.";
RL Neuromuscul. Disord. 17:419-422(2007).
RN [15]
RP VARIANTS HOKPP1 GLY-528; HIS-528; SER-900; GLY-1239 AND HIS-1239.
RX PubMed=19118277; DOI=10.1212/01.wnl.0000342387.65477.46;
RA Matthews E., Labrum R., Sweeney M.G., Sud R., Haworth A., Chinnery P.F.,
RA Meola G., Schorge S., Kullmann D.M., Davis M.B., Hanna M.G.;
RT "Voltage sensor charge loss accounts for most cases of hypokalemic periodic
RT paralysis.";
RL Neurology 72:1544-1547(2009).
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. The channel complex contains alpha, beta,
CC gamma and delta subunits in a 1:1:1:1 ratio, i.e. it contains either
CC CACNB1 or CACNB2 (By similarity). CACNA1S channel activity is modulated
CC by the auxiliary subunits (CACNB1 or CACNB2, CACNG1 and CACNA2D1).
CC Interacts with DYSF and JSRP1 (By similarity). Interacts with RYR1 (By
CC similarity). Interacts with STAC, STAC2 and STAC3 (via their SH3
CC domains) (PubMed:29078335). Interacts with CALM (PubMed:19473981).
CC {ECO:0000250|UniProtKB:P07293, ECO:0000250|UniProtKB:Q02789,
CC ECO:0000269|PubMed:19473981, ECO:0000269|PubMed:29078335}.
CC -!- INTERACTION:
CC Q13698; Q9BWC9: CCDC106; NbExp=3; IntAct=EBI-5329490, EBI-711501;
CC Q13698; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-5329490, EBI-3867333;
CC Q13698; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-5329490, EBI-16439278;
CC Q13698; Q86UT5: PDZD3; NbExp=3; IntAct=EBI-5329490, EBI-8744528;
CC Q13698; Q04864-2: REL; NbExp=3; IntAct=EBI-5329490, EBI-10829018;
CC Q13698; Q9H2K2: TNKS2; NbExp=2; IntAct=EBI-5329490, EBI-4398527;
CC -!- SUBCELLULAR LOCATION: Cell membrane, sarcolemma, T-tubule
CC {ECO:0000250|UniProtKB:P07293}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P07293}.
CC -!- TISSUE SPECIFICITY: Skeletal muscle specific.
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: Periodic paralysis hypokalemic 1 (HOKPP1) [MIM:170400]: An
CC autosomal dominant disorder manifested by episodic flaccid generalized
CC muscle weakness associated with falls of serum potassium levels.
CC {ECO:0000269|PubMed:17418573, ECO:0000269|PubMed:18162704,
CC ECO:0000269|PubMed:19118277, ECO:0000269|PubMed:7987325,
CC ECO:0000269|PubMed:8004673}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Malignant hyperthermia 5 (MHS5) [MIM:601887]: Autosomal
CC dominant disorder that is potentially lethal in susceptible individuals
CC on exposure to commonly used inhalational anesthetics and depolarizing
CC muscle relaxants. {ECO:0000269|PubMed:9199552}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- DISEASE: Thyrotoxic periodic paralysis 1 (TTPP1) [MIM:188580]: A
CC sporadic muscular disorder characterized by episodic weakness and
CC hypokalemia during a thyrotoxic state. It is clinically similar to
CC hereditary hypokalemic periodic paralysis, except for the fact that
CC hyperthyroidism is an absolute requirement for disease manifestation.
CC The disease presents with recurrent episodes of acute muscular weakness
CC of the four extremities that vary in severity from paresis to complete
CC paralysis. Attacks are triggered by ingestion of a high carbohydrate
CC load or strenuous physical activity followed by a period of rest.
CC Thyrotoxic periodic paralysis can occur in association with any cause
CC of hyperthyroidism, but is most commonly associated with Graves
CC disease. {ECO:0000269|PubMed:15001631}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
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; L33798; AAA51902.1; -; mRNA.
DR EMBL; U30707; AAB37235.1; -; Genomic_DNA.
DR EMBL; U30666; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30667; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30668; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30669; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30670; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30671; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30672; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30673; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30674; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30675; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30676; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30677; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30678; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30679; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30680; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30681; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30682; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30683; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30684; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30685; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30686; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30687; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30688; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30689; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30690; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30691; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30692; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30693; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30694; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30695; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30696; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30697; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30698; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30699; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30700; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30701; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30702; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30703; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30704; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30705; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; U30706; AAB37235.1; JOINED; Genomic_DNA.
DR EMBL; AL358473; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL139159; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC133671; AAI33672.1; -; mRNA.
DR EMBL; M87486; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M87487; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; M87488; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U09784; AAA20531.1; -; mRNA.
DR EMBL; Z50091; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z50092; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z50093; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS1407.1; -.
DR PIR; A55645; A55645.
DR PIR; I38611; I38611.
DR RefSeq; NP_000060.2; NM_000069.2.
DR PDB; 2VAY; X-ray; 1.94 A; B=1522-1542.
DR PDB; 6B27; X-ray; 1.73 A; G/H/I/J/K/L=747-760.
DR PDBsum; 2VAY; -.
DR PDBsum; 6B27; -.
DR AlphaFoldDB; Q13698; -.
DR SMR; Q13698; -.
DR BioGRID; 107233; 9.
DR ComplexPortal; CPX-3192; Skeletal muscle VGCC complex.
DR IntAct; Q13698; 12.
DR MINT; Q13698; -.
DR STRING; 9606.ENSP00000355192; -.
DR BindingDB; Q13698; -.
DR ChEMBL; CHEMBL3805; -.
DR DrugBank; DB01118; Amiodarone.
DR DrugBank; DB09229; Aranidipine.
DR DrugBank; DB09231; Benidipine.
DR DrugBank; DB13746; Bioallethrin.
DR DrugBank; DB11148; Butamben.
DR DrugBank; DB11093; Calcium citrate.
DR DrugBank; DB11348; Calcium Phosphate.
DR DrugBank; DB14481; Calcium phosphate dihydrate.
DR DrugBank; DB09232; Cilnidipine.
DR DrugBank; DB00568; Cinnarizine.
DR DrugBank; DB04920; Clevidipine.
DR DrugBank; DB04855; Dronedarone.
DR DrugBank; DB06751; Drotaverine.
DR DrugBank; DB00228; Enflurane.
DR DrugBank; DB00153; Ergocalciferol.
DR DrugBank; DB00898; Ethanol.
DR DrugBank; DB01023; Felodipine.
DR DrugBank; DB13961; Fish oil.
DR DrugBank; DB00270; Isradipine.
DR DrugBank; DB09236; Lacidipine.
DR DrugBank; DB00825; Levomenthol.
DR DrugBank; DB00653; Magnesium sulfate.
DR DrugBank; DB09238; Manidipine.
DR DrugBank; DB01388; Mibefradil.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01115; Nifedipine.
DR DrugBank; DB06712; Nilvadipine.
DR DrugBank; DB00393; Nimodipine.
DR DrugBank; DB00401; Nisoldipine.
DR DrugBank; DB01054; Nitrendipine.
DR DrugBank; DB00252; Phenytoin.
DR DrugBank; DB09090; Pinaverium.
DR DrugBank; DB00243; Ranolazine.
DR DrugBank; DB00421; Spironolactone.
DR DrugBank; DB00273; Topiramate.
DR DrugBank; DB09089; Trimebutine.
DR DrugCentral; Q13698; -.
DR GuidetoPHARMACOLOGY; 528; -.
DR TCDB; 1.A.1.11.32; the voltage-gated ion channel (vic) superfamily.
DR GlyGen; Q13698; 3 sites.
DR iPTMnet; Q13698; -.
DR PhosphoSitePlus; Q13698; -.
DR BioMuta; CACNA1S; -.
DR DMDM; 209572767; -.
DR jPOST; Q13698; -.
DR MassIVE; Q13698; -.
DR PaxDb; Q13698; -.
DR PeptideAtlas; Q13698; -.
DR PRIDE; Q13698; -.
DR Antibodypedia; 4015; 179 antibodies from 32 providers.
DR DNASU; 779; -.
DR Ensembl; ENST00000362061.4; ENSP00000355192.3; ENSG00000081248.12.
DR GeneID; 779; -.
DR KEGG; hsa:779; -.
DR MANE-Select; ENST00000362061.4; ENSP00000355192.3; NM_000069.3; NP_000060.2.
DR UCSC; uc001gvv.4; human.
DR CTD; 779; -.
DR DisGeNET; 779; -.
DR GeneCards; CACNA1S; -.
DR GeneReviews; CACNA1S; -.
DR HGNC; HGNC:1397; CACNA1S.
DR HPA; ENSG00000081248; Group enriched (skeletal muscle, tongue).
DR MalaCards; CACNA1S; -.
DR MIM; 114208; gene.
DR MIM; 170400; phenotype.
DR MIM; 188580; phenotype.
DR MIM; 601887; phenotype.
DR neXtProt; NX_Q13698; -.
DR OpenTargets; ENSG00000081248; -.
DR Orphanet; 681; Hypokalemic periodic paralysis.
DR Orphanet; 423; Malignant hyperthermia of anesthesia.
DR Orphanet; 397755; Periodic paralysis with transient compartment-like syndrome.
DR Orphanet; 79102; Thyrotoxic periodic paralysis.
DR PharmGKB; PA85; -.
DR VEuPathDB; HostDB:ENSG00000081248; -.
DR eggNOG; KOG2301; Eukaryota.
DR GeneTree; ENSGT00940000158289; -.
DR InParanoid; Q13698; -.
DR OMA; SSIHYER; -.
DR OrthoDB; 172471at2759; -.
DR PhylomeDB; Q13698; -.
DR TreeFam; TF312805; -.
DR PathwayCommons; Q13698; -.
DR Reactome; R-HSA-419037; NCAM1 interactions.
DR SignaLink; Q13698; -.
DR SIGNOR; Q13698; -.
DR BioGRID-ORCS; 779; 23 hits in 1073 CRISPR screens.
DR ChiTaRS; CACNA1S; human.
DR EvolutionaryTrace; Q13698; -.
DR GeneWiki; Cav1.1; -.
DR GenomeRNAi; 779; -.
DR Pharos; Q13698; Tclin.
DR PRO; PR:Q13698; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q13698; protein.
DR Bgee; ENSG00000081248; Expressed in gluteal muscle and 85 other tissues.
DR ExpressionAtlas; Q13698; baseline and differential.
DR Genevisible; Q13698; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031674; C:I band; IDA:UniProtKB.
DR GO; GO:1990454; C:L-type voltage-gated calcium channel complex; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0030315; C:T-tubule; IDA:UniProtKB.
DR GO; GO:0005891; C:voltage-gated calcium channel complex; IDA: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: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:UniProtKB.
DR GO; GO:0071313; P:cellular response to caffeine; ISS:UniProtKB.
DR GO; GO:0007029; P:endoplasmic reticulum organization; IEA:Ensembl.
DR GO; GO:0002074; P:extraocular skeletal muscle development; IEA:Ensembl.
DR GO; GO:0006936; P:muscle contraction; IMP:UniProtKB.
DR GO; GO:0007520; P:myoblast fusion; IEA:Ensembl.
DR GO; GO:0007528; P:neuromuscular junction development; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0048741; P:skeletal muscle fiber development; IEA:Ensembl.
DR GO; GO:0001501; P:skeletal system development; IEA:Ensembl.
DR GO; GO:0006941; P:striated muscle contraction; IEA:Ensembl.
DR DisProt; DP01103; -.
DR Gene3D; 1.20.120.350; -; 4.
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; 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; Disease variant; 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..1873
FT /note="Voltage-dependent L-type calcium channel subunit
FT alpha-1S"
FT /id="PRO_0000053943"
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..1873
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 786..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:0000250|UniProtKB:Q02789"
FT REGION 675..717
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 747..760
FT /note="Interaction with STAC, STAC2 and STAC3 (via SH3
FT domains)"
FT /evidence="ECO:0000269|PubMed:29078335"
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..1391
FT /note="Phenylalkylamine binding"
FT /evidence="ECO:0000250|UniProtKB:P07293"
FT REGION 1522..1542
FT /note="Interaction with calmodulin"
FT /evidence="ECO:0000269|PubMed:19473981"
FT REGION 1731..1780
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 COMPBIAS 1748..1772
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:0000250|UniProtKB:Q02789"
FT MOD_RES 397
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02789"
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 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 VARIANT 69
FT /note="A -> G (in dbSNP:rs12406479)"
FT /id="VAR_046970"
FT VARIANT 458
FT /note="L -> H (in dbSNP:rs12742169)"
FT /evidence="ECO:0000269|PubMed:7713519,
FT ECO:0000269|PubMed:9199552"
FT /id="VAR_001498"
FT VARIANT 528
FT /note="R -> G (in HOKPP1; dbSNP:rs80338778)"
FT /evidence="ECO:0000269|PubMed:19118277"
FT /id="VAR_054953"
FT VARIANT 528
FT /note="R -> H (in HOKPP1; dbSNP:rs80338777)"
FT /evidence="ECO:0000269|PubMed:18162704,
FT ECO:0000269|PubMed:19118277, ECO:0000269|PubMed:7987325"
FT /id="VAR_001499"
FT VARIANT 900
FT /note="R -> S (in HOKPP1)"
FT /evidence="ECO:0000269|PubMed:19118277"
FT /id="VAR_054954"
FT VARIANT 1086
FT /note="R -> H (in MHS5; dbSNP:rs1800559)"
FT /evidence="ECO:0000269|PubMed:9199552"
FT /id="VAR_001500"
FT VARIANT 1239
FT /note="R -> G (in HOKPP1; dbSNP:rs28930069)"
FT /evidence="ECO:0000269|PubMed:18162704,
FT ECO:0000269|PubMed:19118277, ECO:0000269|PubMed:8004673"
FT /id="VAR_001501"
FT VARIANT 1239
FT /note="R -> H (in HOKPP1; dbSNP:rs28930068)"
FT /evidence="ECO:0000269|PubMed:17418573,
FT ECO:0000269|PubMed:18162704, ECO:0000269|PubMed:19118277,
FT ECO:0000269|PubMed:8004673"
FT /id="VAR_001502"
FT VARIANT 1539
FT /note="R -> C (in dbSNP:rs3850625)"
FT /evidence="ECO:0000269|PubMed:9199552"
FT /id="VAR_001503"
FT VARIANT 1658
FT /note="R -> H (in dbSNP:rs13374149)"
FT /id="VAR_046971"
FT VARIANT 1800
FT /note="L -> S (in dbSNP:rs12139527)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_046972"
FT VARIANT 1840
FT /note="E -> D (in dbSNP:rs1042379)"
FT /evidence="ECO:0000269|PubMed:7713519,
FT ECO:0000269|PubMed:8838325"
FT /id="VAR_046973"
FT CONFLICT 26
FT /note="R -> S (in Ref. 2; AAB37235)"
FT /evidence="ECO:0000305"
FT CONFLICT 265
FT /note="W -> C (in Ref. 1; AAA51902 and 2; AAB37235)"
FT /evidence="ECO:0000305"
FT CONFLICT 574
FT /note="A -> R (in Ref. 1; AAA51902 and 2; AAB37235)"
FT /evidence="ECO:0000305"
FT CONFLICT 627..628
FT /note="YG -> SS (in Ref. 1; AAA51902)"
FT /evidence="ECO:0000305"
FT CONFLICT 628
FT /note="G -> R (in Ref. 2; AAB37235)"
FT /evidence="ECO:0000305"
FT CONFLICT 916..919
FT /note="Missing (in Ref. 2; AAB37235)"
FT /evidence="ECO:0000305"
FT CONFLICT 918..919
FT /note="VQ -> AR (in Ref. 1; AAA51902)"
FT /evidence="ECO:0000305"
FT CONFLICT 1180
FT /note="D -> N (in Ref. 1; AAA51902 and 2; AAB37235)"
FT /evidence="ECO:0000305"
FT CONFLICT 1294..1295
FT /note="LV -> FE (in Ref. 6; AAA20531)"
FT /evidence="ECO:0000305"
FT CONFLICT 1318
FT /note="R -> RHA (in Ref. 2; AAB37235)"
FT /evidence="ECO:0000305"
FT CONFLICT 1472
FT /note="R -> G (in Ref. 2; AAB37235)"
FT /evidence="ECO:0000305"
FT CONFLICT 1510
FT /note="I -> M (in Ref. 2; AAB37235)"
FT /evidence="ECO:0000305"
FT CONFLICT 1532
FT /note="H -> D (in Ref. 2; AAB37235)"
FT /evidence="ECO:0000305"
FT CONFLICT 1671
FT /note="G -> A (in Ref. 1; AAA51902 and 2; AAB37235)"
FT /evidence="ECO:0000305"
FT CONFLICT 1710
FT /note="V -> S (in Ref. 1; AAA51902)"
FT /evidence="ECO:0000305"
FT CONFLICT 1815
FT /note="A -> G (in Ref. 1; AAA51902 and 2; AAB37235)"
FT /evidence="ECO:0000305"
FT HELIX 1523..1536
FT /evidence="ECO:0007829|PDB:2VAY"
FT HELIX 1538..1541
FT /evidence="ECO:0007829|PDB:2VAY"
SQ SEQUENCE 1873 AA; 212350 MW; 7B7446727E578913 CRC64;
MEPSSPQDEG LRKKQPKKPV PEILPRPPRA LFCLTLENPL RKACISIVEW KPFETIILLT
IFANCVALAV YLPMPEDDNN SLNLGLEKLE YFFLIVFSIE AAMKIIAYGF LFHQDAYLRS
GWNVLDFTIV FLGVFTVILE QVNVIQSHTA PMSSKGAGLD VKALRAFRVL RPLRLVSGVP
SLQVVLNSIF KAMLPLFHIA LLVLFMVIIY AIIGLELFKG KMHKTCYFIG TDIVATVENE
EPSPCARTGS GRRCTINGSE CRGGWPGPNH GITHFDNFGF SMLTVYQCIT MEGWTDVLYW
VNDAIGNEWP WIYFVTLILL GSFFILNLVL GVLSGEFTKE REKAKSRGTF QKLREKQQLD
EDLRGYMSWI TQGEVMDVED FREGKLSLDE GGSDTESLYE IAGLNKIIQF IRHWRQWNRI
FRWKCHDIVK SKVFYWLVIL IVALNTLSIA SEHHNQPLWL TRLQDIANRV LLSLFTTEML
MKMYGLGLRQ YFMSIFNRFD CFVVCSGILE ILLVESGAMT PLGISVLRCI RLLRIFKITK
YWTSLSNLVA SLLNSIRSIA SLLLLLFLFI VIFALLGMQL FGGRYDFEDT EVRRSNFDNF
PQALISVFQV LTGEDWTSMM YNGIMAYGGP SYPGMLVCIY FIILFVCGNY ILLNVFLAIA
VDNLAEAESL TSAQKAKAEE KKRRKMSKGL PDKSEEEKST MAKKLEQKPK GEGIPTTAKL
KIDEFESNVN EVKDPYPSAD FPGDDEEDEP EIPLSPRPRP LAELQLKEKA VPIPEASSFF
IFSPTNKIRV LCHRIVNATW FTNFILLFIL LSSAALAAED PIRADSMRNQ ILKHFDIGFT
SVFTVEIVLK MTTYGAFLHK GSFCRNYFNM LDLLVVAVSL ISMGLESSAI SVVKILRVLR
VLRPLRAINR AKGLKHVVQC MFVAISTIGN IVLVTTLLQF MFACIGVQLF KGKFFRCTDL
SKMTEEECRG YYYVYKDGDP MQIELRHREW VHSDFHFDNV LSAMMSLFTV STFEGWPQLL
YKAIDSNAED VGPIYNNRVE MAIFFIIYII LIAFFMMNIF VGFVIVTFQE QGETEYKNCE
LDKNQRQCVQ YALKARPLRC YIPKNPYQYQ VWYIVTSSYF EYLMFALIML NTICLGMQHY
NQSEQMNHIS DILNVAFTII FTLEMILKLM AFKARGYFGD PWNVFDFLIV IGSIIDVILS
EIDTFLASSG GLYCLGGGCG NVDPDESARI SSAFFRLFRV MRLIKLLSRA EGVRTLLWTF
IKSFQALPYV ALLIVMLFFI YAVIGMQMFG KIALVDGTQI NRNNNFQTFP QAVLLLFRCA
TGEAWQEILL ACSYGKLCDP ESDYAPGEEY TCGTNFAYYY FISFYMLCAF LVINLFVAVI
MDNFDYLTRD WSILGPHHLD EFKAIWAEYD PEAKGRIKHL DVVTLLRRIQ PPLGFGKFCP
HRVACKRLVG MNMPLNSDGT VTFNATLFAL VRTALKIKTE GNFEQANEEL RAIIKKIWKR
TSMKLLDQVI PPIGDDEVTV GKFYATFLIQ EHFRKFMKRQ EEYYGYRPKK DIVQIQAGLR
TIEEEAAPEI CRTVSGDLAA EEELERAMVE AAMEEGIFRR TGGLFGQVDN FLERTNSLPP
VMANQRPLQF AEIEMEEMES PVFLEDFPQD PRTNPLARAN TNNANANVAY GNSNHSNSHV
FSSVHYEREF PEETETPATR GRALGQPCRV LGPHSKPCVE MLKGLLTQRA MPRGQAPPAP
CQCPRVESSM PEDRKSSTPG SLHEETPHSR STRENTSRCS APATALLIQK ALVRGGLGTL
AADANFIMAT GQALADACQM EPEEVEIMAT ELLKGREAPE GMASSLGCLN LGSSLGSLDQ
HQGSQETLIP PRL
