ID   CLCN1_HUMAN             Reviewed;         988 AA.
AC   P35523; A4D2H5; Q2M202;
DT   01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT   02-NOV-2010, sequence version 3.
DT   02-SEP-2026, entry version 224.
DE   RecName: Full=Chloride channel protein 1;
DE            Short=ClC-1 {ECO:0000303|PubMed:8112288};
DE   AltName: Full=Chloride channel protein, skeletal muscle;
GN   Name=CLCN1 {ECO:0000303|PubMed:8533761, ECO:0000312|HGNC:HGNC:2019};
GN   Synonyms=CLC1;
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 [GENOMIC DNA / MRNA], VARIANT MCAD LEU-480, VARIANT
RP   GLN-300, CHARACTERIZATION OF VARIANTS MCAD GLU-230 AND LEU-480,
RP   CHARACTERIZATION OF VARIANT GLN-300, FUNCTION, TRANSPORTER ACTIVITY,
RP   SUBUNIT, AND SUBCELLULAR LOCATION.
RX   PubMed=8112288; DOI=10.1002/j.1460-2075.1994.tb06315.x;
RA   Steinmeyer K., Lorenz C., Pusch M., Koch M.C., Jentsch T.J.;
RT   "Multimeric structure of ClC-1 chloride channel revealed by mutations in
RT   dominant myotonia congenita (Thomsen).";
RL   EMBO J. 13:737-743(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12690205; DOI=10.1126/science.1083423;
RA   Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA   Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA   Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA   Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA   Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA   Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA   Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA   Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA   Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA   Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA   Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA   Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA   Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA   Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA   Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA   Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA   Adams M.D., Tsui L.-C.;
RT   "Human chromosome 7: DNA sequence and biology.";
RL   Science 300:767-772(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT TRP-118.
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   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 171-988, AND VARIANT MCAR CYS-413.
RX   PubMed=1379744; DOI=10.1126/science.1379744;
RA   Koch M.C., Steinmeyer K., Lorenz C., Ricker K., Wolf F., Otto M., Zoll B.,
RA   Lehmann-Horn F., Grzeschik K.-H., Jentsch T.J.;
RT   "The skeletal muscle chloride channel in dominant and recessive human
RT   myotonia.";
RL   Science 257:797-800(1992).
RN   [5]
RP   PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANT MCAD GLU-230.
RX   PubMed=7981750; DOI=10.1038/ng0493-305;
RA   George A.L. Jr., Crackower M.A., Abdalla J.A., Hudson A.J., Ebers G.C.;
RT   "Molecular basis of Thomsen's disease (autosomal dominant myotonia
RT   congenita).";
RL   Nat. Genet. 3:305-310(1993).
RN   [6]
RP   FUNCTION, AND TRANSPORTER ACTIVITY.
RX   PubMed=8130334; DOI=10.1016/s0006-3495(94)80753-2;
RA   Pusch M., Steinmeyer K., Jentsch T.J.;
RT   "Low single channel conductance of the major skeletal muscle chloride
RT   channel, ClC-1.";
RL   Biophys. J. 66:149-152(1994).
RN   [7]
RP   FUNCTION, TRANSPORTER ACTIVITY, SUBCELLULAR LOCATION, AND CHARACTERIZATION
RP   OF VARIANT MCAD GLU-230.
RX   PubMed=9122265; DOI=10.1073/pnas.94.6.2729;
RA   Fahlke C., Beck C.L., George A.L. Jr.;
RT   "A mutation in autosomal dominant myotonia congenita affects pore
RT   properties of the muscle chloride channel.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:2729-2734(1997).
RN   [8]
RP   FUNCTION, AND TRANSPORTER ACTIVITY.
RX   PubMed=9565403; DOI=10.1085/jgp.111.5.653;
RA   Rychkov G.Y., Pusch M., Roberts M.L., Jentsch T.J., Bretag A.H.;
RT   "Permeation and block of the skeletal muscle chloride channel, ClC-1, by
RT   foreign anions.";
RL   J. Gen. Physiol. 111:653-665(1998).
RN   [9]
RP   FUNCTION, ACTIVITY REGULATION, CHARACTERIZATION OF VARIANT MCAD MET-290,
RP   AND CHARACTERIZATION OF VARIANT MCAD/MCAR ASN-556.
RX   PubMed=10051520; DOI=10.1085/jgp.113.3.457;
RA   Saviane C., Conti F., Pusch M.;
RT   "The muscle chloride channel ClC-1 has a double-barreled appearance that is
RT   differentially affected in dominant and recessive myotonia.";
RL   J. Gen. Physiol. 113:457-468(1999).
RN   [10]
RP   FUNCTION, AND CHARACTERIZATION OF VARIANT MCAD MET-290.
RX   PubMed=10962018; DOI=10.1085/jgp.116.3.433;
RA   Accardi A., Pusch M.;
RT   "Fast and slow gating relaxations in the muscle chloride channel CLC-1.";
RL   J. Gen. Physiol. 116:433-444(2000).
RN   [11]
RP   FUNCTION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT MYOTONIA
RP   LEVIOR ARG-552.
RX   PubMed=12456816; DOI=10.1113/jphysiol.2002.027037;
RA   Ryan A., Ruedel R., Kuchenbecker M., Fahlke C.;
RT   "A novel alteration of muscle chloride channel gating in myotonia levior.";
RL   J. Physiol. (Lond.) 545:345-354(2002).
RN   [12]
RP   FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF THR-636; PRO-638;
RP   SER-651; HIS-847; LEU-848 AND ALA-849.
RX   PubMed=16027167; DOI=10.1074/jbc.m502890200;
RA   Bennetts B., Rychkov G.Y., Ng H.L., Morton C.J., Stapleton D., Parker M.W.,
RA   Cromer B.A.;
RT   "Cytoplasmic ATP-sensing domains regulate gating of skeletal muscle ClC-1
RT   chloride channels.";
RL   J. Biol. Chem. 280:32452-32458(2005).
RN   [13]
RP   REVIEW, AND TOPOLOGY.
RX   PubMed=37892996; DOI=10.3390/biomedicines11102622;
RA   Brenes O., Pusch M., Morales F.;
RT   "ClC-1 Chloride Channel: Inputs on the Structure-Function Relationship of
RT   Myotonia Congenita-Causing Mutations.";
RL   Biomedicines 11:0-0(2023).
RN   [14]
RP   STRUCTURE BY ELECTRON MICROSCOPY (3.36 ANGSTROMS), SUBUNIT, TOPOLOGY,
RP   FUNCTION, AND SITE.
RX   PubMed=29809153; DOI=10.7554/elife.36629;
RA   Park E., MacKinnon R.;
RT   "Structure of the CLC-1 chloride channel from Homo sapiens.";
RL   Elife 7:0-0(2018).
RN   [15]
RP   STRUCTURE BY ELECTRON MICROSCOPY (3.63 ANGSTROMS), SUBUNIT, TOPOLOGY,
RP   FUNCTION, TRANSPORTER ACTIVITY, AND ACTIVITY REGULATION.
RX   PubMed=31022181; DOI=10.1371/journal.pbio.3000218;
RA   Wang K., Preisler S.S., Zhang L., Cui Y., Missel J.W., Gronberg C.,
RA   Gotfryd K., Lindahl E., Andersson M., Calloe K., Egea P.F., Klaerke D.A.,
RA   Pusch M., Pedersen P.A., Zhou Z.H., Gourdon P.;
RT   "Structure of the human ClC-1 chloride channel.";
RL   PLoS Biol. 17:e3000218-e3000218(2019).
RN   [16]
RP   VARIANTS MCAR ILE-327; CYS-413 AND SER-496, CHARACTERIZATION OF VARIANTS
RP   MCAR ILE-327 AND SER-496, AND FUNCTION.
RX   PubMed=7951242; DOI=10.1093/hmg/3.6.941;
RA   Lorenz C., Meyer-Kleine C., Steinmeyer K., Koch M.C., Jentsch T.J.;
RT   "Genomic organization of the human muscle chloride channel ClC-1 and
RT   analysis of novel mutations leading to Becker-type myotonia.";
RL   Hum. Mol. Genet. 3:941-946(1994).
RN   [17]
RP   VARIANT MCAR GLY-136.
RX   PubMed=7981681; DOI=10.1093/hmg/3.7.1123;
RA   Heine R., George A.L. Jr., Pika U., Deymeer F., Ruedel R., Lehmann-Horn F.;
RT   "Proof of a non-functional muscle chloride channel in recessive myotonia
RT   congenita (Becker) by detection of a 4 base pair deletion.";
RL   Hum. Mol. Genet. 3:1123-1128(1994).
RN   [18]
RP   VARIANTS MCAR LEU-167 AND GLN-338, AND VARIANT GLN-300.
RX   PubMed=7874130;
RA   George A.L. Jr., Sloan-Brown K., Fenichel G.M., Mitchell G.A., Spiegel R.,
RA   Pascuzzi R.M.;
RT   "Nonsense and missense mutations of the muscle chloride channel gene in
RT   patients with myotonia congenita.";
RL   Hum. Mol. Genet. 3:2071-2072(1994).
RN   [19]
RP   VARIANTS MCAR CYS-105; GLY-136; GLY-165; LEU-167; LYS-291; THR-329;
RP   CYS-413; ARG-482 AND VAL-485, AND VARIANT MCAD GLN-317.
RX   PubMed=8533761;
RA   Meyer-Kleine C., Steinmeyer K., Ricker K., Jentsch T.J., Koch M.C.;
RT   "Spectrum of mutations in the major human skeletal muscle chloride channel
RT   gene (CLCN1) leading to myotonia.";
RL   Am. J. Hum. Genet. 57:1325-1334(1995).
RN   [20]
RP   VARIANT MCAD MET-290, VARIANT MYOTONIA LEVIOR ARG-552, AND VARIANT TRP-118.
RX   PubMed=7581380; DOI=10.1093/hmg/4.8.1397;
RA   Lehmann-Horn F., Mailaender V., Heine R., George A.L. Jr.;
RT   "Myotonia levior is a chloride channel disorder.";
RL   Hum. Mol. Genet. 4:1397-1402(1995).
RN   [21]
RP   VARIANT MCAD MET-290, VARIANT MCAR LYS-291, CHARACTERIZATION OF VARIANTS
RP   MCAD MET-290; GLN-317 AND LEU-480, CHARACTERIZATION OF VARIANT MCAR
RP   LYS-291, CHARACTERIZATION OF VARIANT MYOTONIA LEVIOR ARG-552, AND
RP   MUTAGENESIS OF ILE-290 AND GLU-291.
RX   PubMed=8845168; DOI=10.1016/0896-6273(95)90023-3;
RA   Pusch M., Steinmeyer K., Koch M.C., Jentsch T.J.;
RT   "Mutations in dominant human myotonia congenita drastically alter the
RT   voltage dependence of the CIC-1 chloride channel.";
RL   Neuron 15:1455-1463(1995).
RN   [22]
RP   VARIANTS MCAR CYS-150; ARG-200; CYS-261 AND VAL-415.
RX   PubMed=8571958;
RA   Mailaender V., Heine R., Deymeer F., Lehmann-Horn F.;
RT   "Novel muscle chloride channel mutations and their effects on heterozygous
RT   carriers.";
RL   Am. J. Hum. Genet. 58:317-324(1996).
RN   [23]
RP   VARIANTS MCAD/MCAR LEU-236; GLU-285; ALA-286; SER-307; VAL-485 AND ASN-556,
RP   CHARACTERIZATION OF VARIANTS MCAD/MCAR LEU-236; GLU-285; ALA-286; SER-307
RP   AND ASN-556, AND FUNCTION.
RX   PubMed=9736777; DOI=10.1093/hmg/7.11.1753;
RA   Kubisch C., Schmidt-Rose T., Fontaine B., Bretag A.H., Jentsch T.J.;
RT   "ClC-1 chloride channel mutations in myotonia congenita: variable
RT   penetrance of mutations shifting the voltage dependence.";
RL   Hum. Mol. Genet. 7:1753-1760(1998).
RN   [24]
RP   VARIANTS MCAR ILE-563 AND LEU-708.
RX   PubMed=10215406;
RX   DOI=10.1002/(sici)1098-1004(1998)11:4<331::aid-humu12>3.0.co;2-3;
RA   Sangiuolo F., Botta A., Mesoraca A., Servidei S., Merlini L., Fratta G.,
RA   Novelli G., Dallapiccola B.;
RT   "Identification of five new mutations and three novel polymorphisms in the
RT   muscle chloride channel gene (CLCN1) in 20 Italian patients with dominant
RT   and recessive myotonia congenita.";
RL   Hum. Mutat. 11:331-331(1998).
RN   [25]
RP   VARIANTS MCAD/MCAR VAL-161; THR-313 AND ASN-556.
RX   PubMed=9566422; DOI=10.1212/wnl.50.4.1176;
RA   Plassart-Schiess E., Gervais A., Eymard B., Lagueny A., Pouget J.,
RA   Warter J.-M., Fardeau M., Jentsch T.J., Fontaine B.;
RT   "Novel muscle chloride channel (CLCN1) mutations in myotonia congenita with
RT   various modes of inheritance including incomplete dominance and
RT   penetrance.";
RL   Neurology 50:1176-1179(1998).
RN   [26]
RP   VARIANT MCAR ARG-499, CHARACTERIZATION OF VARIANT MCAR ARG-499, AND
RP   MUTAGENESIS OF ARG-496; GLY-499 AND GLU-500.
RX   PubMed=10644771; DOI=10.1074/jbc.275.4.2999;
RA   Zhang J., Sanguinetti M.C., Kwiecinski H., Ptacek L.J.;
RT   "Mechanism of inverted activation of ClC-1 channels caused by a novel
RT   myotonia congenita mutation.";
RL   J. Biol. Chem. 275:2999-3005(2000).
RN   [27]
RP   VARIANT MCAR LEU-932.
RX   PubMed=11113225; DOI=10.1212/wnl.55.11.1697;
RA   Nagamitsu S., Matsuura T., Khajavi M., Armstrong R., Gooch C., Harati Y.,
RA   Ashizawa T.;
RT   "A 'dystrophic' variant of autosomal recessive myotonia congenita caused by
RT   novel mutations in the CLCN1 gene.";
RL   Neurology 55:1697-1703(2000).
RN   [28]
RP   VARIANTS MCAD VAL-128; LYS-193; SER-307 AND LEU-480, VARIANT MCAR GLU-285,
RP   AND VARIANTS THR-437 AND ASN-614.
RX   PubMed=12661046; DOI=10.1002/mus.10347;
RA   Colding-Joergensen E., DunOe M., Schwartz M., Vissing J.;
RT   "Decrement of compound muscle action potential is related to mutation type
RT   in myotonia congenita.";
RL   Muscle Nerve 27:449-455(2003).
RN   [29]
RP   VARIANT [LARGE SCALE ANALYSIS] LYS-548.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
RN   [30]
RP   VARIANT MCAR SER-190.
RX   PubMed=19697366; DOI=10.1002/mus.21525;
RA   Shalata A., Furman H., Adir V., Adir N., Hujeirat Y., Shalev S.A.,
RA   Borochowitz Z.U.;
RT   "Myotonia congenita in a large consanguineous Arab family: insight into the
RT   clinical spectrum of carriers and double heterozygotes of a novel mutation
RT   in the chloride channel CLCN1 gene.";
RL   Muscle Nerve 41:464-469(2010).
RN   [31]
RP   VARIANTS MCAR ARG-164; ARG-197; ILE-533; LEU-536; SER-845 AND GLU-947,
RP   CHARACTERIZATION OF VARIANTS MCAR ARG-164; SER-190; ARG-197 AND SER-845,
RP   AND FUNCTION.
RX   PubMed=22521272; DOI=10.1016/j.jns.2012.03.024;
RA   Ulzi G., Lecchi M., Sansone V., Redaelli E., Corti E., Saccomanno D.,
RA   Pagliarani S., Corti S., Magri F., Raimondi M., D'Angelo G., Modoni A.,
RA   Bresolin N., Meola G., Wanke E., Comi G.P., Lucchiari S.;
RT   "Myotonia congenita: novel mutations in CLCN1 gene and functional
RT   characterizations in Italian patients.";
RL   J. Neurol. Sci. 318:65-71(2012).
RN   [32]
RP   VARIANTS MCAR LEU-167; ARG-277; TYR-277 AND THR-527, CHARACTERIZATION OF
RP   VARIANTS MCAR ARG-277 AND TYR-277, FUNCTION, AND TRANSPORTER ACTIVITY.
RX   PubMed=22641783; DOI=10.1113/jphysiol.2012.232785;
RA   Weinberger S., Wojciechowski D., Sternberg D., Lehmann-Horn F.,
RA   Jurkat-Rott K., Becher T., Begemann B., Fahlke C., Fischer M.;
RT   "Disease-causing mutations C277R and C277Y modify gating of human ClC-1
RT   chloride channels in myotonia congenita.";
RL   J. Physiol. (Lond.) 590:3449-3464(2012).
RN   [33]
RP   VARIANTS MCAD PRO-198 AND LEU-484, CHARACTERIZATION OF VARIANTS MCAD
RP   PRO-198 AND LEU-484, VARIANTS MCAR PRO-628 AND GLY-640, AND
RP   CHARACTERIZATION OF VARIANTS MCAR PRO-628 AND GLY-640.
RX   PubMed=26096614; DOI=10.1113/jp270358;
RA   Imbrici P., Maggi L., Mangiatordi G.F., Dinardo M.M., Altamura C.,
RA   Brugnoni R., Alberga D., Pinter G.L., Ricci G., Siciliano G., Micheli R.,
RA   Annicchiarico G., Lattanzi G., Nicolotti O., Morandi L., Bernasconi P.,
RA   Desaphy J.F., Mantegazza R., Camerino D.C.;
RT   "ClC-1 mutations in myotonia congenita patients: insights into molecular
RT   gating mechanisms and genotype-phenotype correlation.";
RL   J. Physiol. (Lond.) 593:4181-4199(2015).
RN   [34]
RP   VARIANTS MCAR ALA-82; SER-190; VAL-270 AND TRP-453, CHARACTERIZATION OF
RP   VARIANTS MCAR ALA-82; SER-190; VAL-270 AND TRP-453, AND FUNCTION.
RX   PubMed=26007199; DOI=10.1007/s12017-015-8356-8;
RA   Portaro S., Altamura C., Licata N., Camerino G.M., Imbrici P., Musumeci O.,
RA   Rodolico C., Conte Camerino D., Toscano A., Desaphy J.F.;
RT   "Clinical, molecular, and functional characterization of CLCN1 mutations in
RT   three families with recessive myotonia congenita.";
RL   NeuroMolecular Med. 17:285-296(2015).
RN   [35]
RP   VARIANTS MCAR ARG-43; LEU-70; ASP-137; HIS-160; SER-496 AND GLU-855,
RP   CHARACTERIZATION OF VARIANTS MCAR ARG-43; LEU-70; ASP-137 AND HIS-160,
RP   FUNCTION, SUBCELLULAR LOCATION, AND SUBUNIT.
RX   PubMed=26502825; DOI=10.1038/srep15382;
RA   Ronstedt K., Sternberg D., Detro-Dassen S., Gramkow T., Begemann B.,
RA   Becher T., Kilian P., Grieschat M., Machtens J.P., Schmalzing G.,
RA   Fischer M., Fahlke C.;
RT   "Impaired surface membrane insertion of homo- and heterodimeric human
RT   muscle chloride channels carrying amino-terminal myotonia-causing
RT   mutations.";
RL   Sci. Rep. 5:15382-15382(2015).
RN   [36]
RP   VARIANTS MCAR CYS-105; LEU-167 AND PRO-412, VARIANT ARG-154,
RP   CHARACTERIZATION OF VARIANTS MCAR CYS-105; LEU-167 AND PRO-412,
RP   CHARACTERIZATION OF VARIANT ARG-154, AND FUNCTION.
RX   PubMed=26510092; DOI=10.1002/humu.22916;
RA   Vindas-Smith R., Fiore M., Vasquez M., Cuenca P., Del Valle G.,
RA   Lagostena L., Gaitan-Penas H., Estevez R., Pusch M., Morales F.;
RT   "Identification and functional characterization of CLCN1 mutations found in
RT   nondystrophic myotonia patients.";
RL   Hum. Mutat. 37:74-83(2016).
RN   [37]
RP   VARIANT MCAD LYS-950.
RX   PubMed=27653901; DOI=10.1016/j.jns.2016.08.030;
RA   Kato H., Kokunai Y., Dalle C., Kubota T., Madokoro Y., Yuasa H., Uchida Y.,
RA   Ikeda T., Mochizuki H., Nicole S., Fontaine B., Takahashi M.P., Mitake S.;
RT   "A case of non-dystrophic myotonia with concomitant mutations in the SCN4A
RT   and CLCN1 genes.";
RL   J. Neurol. Sci. 369:254-258(2016).
RN   [38]
RP   VARIANT MCAD HIS-480, AND CHARACTERIZATION OF VARIANT MCAD HIS-480.
RX   PubMed=27666773; DOI=10.1016/j.nmd.2016.08.016;
RA   Mori Y., Yamashita S., Kato M., Masuda T., Takamatsu K., Kumamoto T.,
RA   Sasaki R., Ando Y.;
RT   "Thomsen disease with ptosis and abnormal MR findings.";
RL   Neuromuscul. Disord. 26:805-808(2016).
CC   -!- FUNCTION: Voltage-gated chloride channel involved in skeletal muscle
CC       excitability. Generates most of the plasma membrane chloride
CC       conductance in skeletal muscle fibers, stabilizes the resting membrane
CC       potential and contributes to the repolarization phase during action
CC       potential firing (PubMed:12456816, PubMed:16027167, PubMed:22521272,
CC       PubMed:22641783, PubMed:26007199, PubMed:26502825, PubMed:26510092,
CC       PubMed:7951242, PubMed:8112288, PubMed:8130334, PubMed:9122265,
CC       PubMed:9565403, PubMed:9736777). Forms a homodimeric channel where each
CC       subunit has its own ion conduction pathway. Conducts double-barreled
CC       currents controlled by two types of gates, two fast glutamate gates
CC       that control each subunit independently and a slow common gate that
CC       opens and shuts off both subunits simultaneously. Has a significant
CC       open probability at muscle resting potential and is further activated
CC       upon membrane depolarization (PubMed:10051520, PubMed:10962018,
CC       PubMed:29809153, PubMed:31022181). Permeable to small monovalent anions
CC       with ion selectivity for chloride > thiocyanate > bromide > nitrate >
CC       iodide (PubMed:9122265, PubMed:9565403). {ECO:0000269|PubMed:10051520,
CC       ECO:0000269|PubMed:10962018, ECO:0000269|PubMed:12456816,
CC       ECO:0000269|PubMed:16027167, ECO:0000269|PubMed:22521272,
CC       ECO:0000269|PubMed:22641783, ECO:0000269|PubMed:26007199,
CC       ECO:0000269|PubMed:26502825, ECO:0000269|PubMed:26510092,
CC       ECO:0000269|PubMed:29809153, ECO:0000269|PubMed:31022181,
CC       ECO:0000269|PubMed:7951242, ECO:0000269|PubMed:8112288,
CC       ECO:0000269|PubMed:8130334, ECO:0000269|PubMed:9122265,
CC       ECO:0000269|PubMed:9565403, ECO:0000269|PubMed:9736777}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=chloride(in) = chloride(out); Xref=Rhea:RHEA:29823,
CC         ChEBI:CHEBI:17996; Evidence={ECO:0000269|PubMed:22641783,
CC         ECO:0000269|PubMed:31022181, ECO:0000269|PubMed:8112288,
CC         ECO:0000269|PubMed:8130334, ECO:0000269|PubMed:9122265,
CC         ECO:0000269|PubMed:9565403};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=thiocyanate(in) = thiocyanate(out); Xref=Rhea:RHEA:75347,
CC         ChEBI:CHEBI:18022; Evidence={ECO:0000269|PubMed:9122265,
CC         ECO:0000269|PubMed:9565403};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=bromide(in) = bromide(out); Xref=Rhea:RHEA:75383,
CC         ChEBI:CHEBI:15858; Evidence={ECO:0000269|PubMed:22641783,
CC         ECO:0000269|PubMed:9122265, ECO:0000269|PubMed:9565403,
CC         ECO:0000305|PubMed:8112288};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=nitrate(in) = nitrate(out); Xref=Rhea:RHEA:34923,
CC         ChEBI:CHEBI:17632; Evidence={ECO:0000269|PubMed:22641783,
CC         ECO:0000269|PubMed:9122265, ECO:0000269|PubMed:9565403};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=iodide(out) = iodide(in); Xref=Rhea:RHEA:66324,
CC         ChEBI:CHEBI:16382; Evidence={ECO:0000269|PubMed:22641783,
CC         ECO:0000269|PubMed:9122265, ECO:0000269|PubMed:9565403,
CC         ECO:0000305|PubMed:8112288};
CC   -!- ACTIVITY REGULATION: Modulated by membrane voltage with depolarization
CC       favouring channel opening and hyperpolarization favouring channel
CC       closure. Inhibited by acidic pH and ATP binding due to a shift of
CC       voltage dependence of common gating to more positive voltages.
CC       Inhibited by 9-anthracene-carboxylic. {ECO:0000269|PubMed:10051520,
CC       ECO:0000269|PubMed:16027167, ECO:0000269|PubMed:31022181}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:26502825,
CC       ECO:0000269|PubMed:29809153, ECO:0000269|PubMed:31022181,
CC       ECO:0000305|PubMed:8112288}.
CC   -!- INTERACTION:
CC       P35523; Q92624: APPBP2; NbExp=6; IntAct=EBI-10206780, EBI-743771;
CC       P35523; Q9UHD4: CIDEB; NbExp=3; IntAct=EBI-10206780, EBI-7062247;
CC       P35523; Q8IZU0: FAM9B; NbExp=3; IntAct=EBI-10206780, EBI-10175124;
CC       P35523; Q9NQX1-2: PRDM5; NbExp=3; IntAct=EBI-10206780, EBI-12859340;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12456816,
CC       ECO:0000269|PubMed:26502825, ECO:0000269|PubMed:8112288,
CC       ECO:0000269|PubMed:9122265}; Multi-pass membrane protein {ECO:0000255}.
CC       Cell membrane, sarcolemma {ECO:0000250|UniProtKB:Q64347}; Multi-pass
CC       membrane protein {ECO:0000255}. Cell membrane, sarcolemma, T-tubule
CC       {ECO:0000250|UniProtKB:Q64347}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- TISSUE SPECIFICITY: Predominantly expressed in skeletal muscles.
CC   -!- DISEASE: Myotonia congenita, autosomal dominant (MCAD) [MIM:160800]: A
CC       non-dystrophic skeletal muscle disorder characterized by muscle
CC       stiffness and an inability of the muscle to relax after voluntary
CC       contraction. Most patients have symptom onset in the legs, which later
CC       progresses to the arms, neck, and facial muscles. Many patients show
CC       marked hypertrophy of the lower limb muscles. The autosomal dominant
CC       form (Thomsen disease) is less common and less severe than the
CC       autosomal recessive one (Becker disease). A milder form of autosomal
CC       dominant myotonia is characterized by isolated myotonia without muscle
CC       weakness, hypotrophy, or hypertrophy (myotonia levior).
CC       {ECO:0000269|PubMed:10051520, ECO:0000269|PubMed:10962018,
CC       ECO:0000269|PubMed:12661046, ECO:0000269|PubMed:26096614,
CC       ECO:0000269|PubMed:27653901, ECO:0000269|PubMed:27666773,
CC       ECO:0000269|PubMed:7581380, ECO:0000269|PubMed:7981750,
CC       ECO:0000269|PubMed:8112288, ECO:0000269|PubMed:8533761,
CC       ECO:0000269|PubMed:8845168, ECO:0000269|PubMed:9122265,
CC       ECO:0000269|PubMed:9566422, ECO:0000269|PubMed:9736777}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- DISEASE: Myotonia congenita, autosomal recessive (MCAR) [MIM:255700]: A
CC       non-dystrophic skeletal muscle disorder characterized by muscle
CC       stiffness and an inability of the muscle to relax after voluntary
CC       contraction. Most patients have symptom onset in the legs, which later
CC       progresses to the arms, neck, and facial muscles. Many patients show
CC       marked hypertrophy of the lower limb muscles. The autosomal recessive
CC       form (Becker disease) is more severe than the autosomal dominant one
CC       (Thomsen disease). {ECO:0000269|PubMed:10051520,
CC       ECO:0000269|PubMed:10215406, ECO:0000269|PubMed:10644771,
CC       ECO:0000269|PubMed:11113225, ECO:0000269|PubMed:12661046,
CC       ECO:0000269|PubMed:1379744, ECO:0000269|PubMed:19697366,
CC       ECO:0000269|PubMed:22521272, ECO:0000269|PubMed:22641783,
CC       ECO:0000269|PubMed:26007199, ECO:0000269|PubMed:26096614,
CC       ECO:0000269|PubMed:26502825, ECO:0000269|PubMed:26510092,
CC       ECO:0000269|PubMed:7874130, ECO:0000269|PubMed:7951242,
CC       ECO:0000269|PubMed:7981681, ECO:0000269|PubMed:8533761,
CC       ECO:0000269|PubMed:8571958, ECO:0000269|PubMed:8845168,
CC       ECO:0000269|PubMed:9566422, ECO:0000269|PubMed:9736777}. Note=The
CC       disease is caused by variants affecting the gene represented in this
CC       entry.
CC   -!- MISCELLANEOUS: Each monomer is composed of 18 alpha helices arranged in
CC       an internal pseudo-symmetry with an inverted membrane orientation. Most
CC       helices do not traverse the membrane completely.
CC       {ECO:0000305|PubMed:29809153, ECO:0000305|PubMed:31022181,
CC       ECO:0000305|PubMed:37892996}.
CC   -!- SIMILARITY: Belongs to the chloride channel (TC 2.A.49) family. ClC-
CC       1/CLCN1 subfamily. {ECO:0000305}.
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DR   EMBL; Z25587; CAA80996.1; -; Genomic_DNA.
DR   EMBL; Z25884; CAA81103.1; -; mRNA.
DR   EMBL; CH236959; EAL23786.1; -; Genomic_DNA.
DR   EMBL; BC112156; AAI12157.1; -; mRNA.
DR   EMBL; BC113495; AAI13496.1; -; mRNA.
DR   EMBL; M97820; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; L08261; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; L08262; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; L08263; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; L08264; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; L08265; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; Z25753; CAB56792.1; -; Genomic_DNA.
DR   EMBL; Z25754; CAB56792.1; JOINED; Genomic_DNA.
DR   EMBL; Z25755; CAB56792.1; JOINED; Genomic_DNA.
DR   EMBL; Z25756; CAB56792.1; JOINED; Genomic_DNA.
DR   EMBL; Z25757; CAB56792.1; JOINED; Genomic_DNA.
DR   EMBL; Z25758; CAB56792.1; JOINED; Genomic_DNA.
DR   EMBL; Z25759; CAB56792.1; JOINED; Genomic_DNA.
DR   EMBL; Z25760; CAB56792.1; JOINED; Genomic_DNA.
DR   EMBL; Z25761; CAB56792.1; JOINED; Genomic_DNA.
DR   EMBL; Z25762; CAB56792.1; JOINED; Genomic_DNA.
DR   EMBL; Z25763; CAB56792.1; JOINED; Genomic_DNA.
DR   EMBL; Z25764; CAB56792.1; JOINED; Genomic_DNA.
DR   EMBL; Z25765; CAB56792.1; JOINED; Genomic_DNA.
DR   EMBL; Z25766; CAB56792.1; JOINED; Genomic_DNA.
DR   EMBL; Z25767; CAB56792.1; JOINED; Genomic_DNA.
DR   EMBL; Z25752; CAB56792.1; JOINED; Genomic_DNA.
DR   EMBL; Z25768; CAB56814.1; -; Genomic_DNA.
DR   EMBL; Z25872; CAB56814.1; JOINED; Genomic_DNA.
DR   CCDS; CCDS5881.1; -.
DR   PIR; S37078; S37078.
DR   RefSeq; NP_000074.3; NM_000083.3.
DR   PDB; 6COY; EM; 3.36 A; A/B=1-988.
DR   PDB; 6COZ; EM; 3.36 A; A/B=1-988.
DR   PDB; 6QV6; EM; 3.63 A; A/B=1-988.
DR   PDB; 6QVB; EM; 4.34 A; A/B=1-988.
DR   PDB; 6QVC; EM; 4.00 A; A/B=1-988.
DR   PDB; 6QVD; EM; 4.34 A; A/B=1-988.
DR   PDB; 6QVU; EM; 4.20 A; A/B=1-988.
DR   PDB; 8WXI; EM; 2.57 A; A/B=1-988.
DR   PDB; 8WXJ; EM; 2.68 A; A/B=1-988.
DR   AlphaFoldDB; P35523; -.
DR   EMDB; EMD-37908; -.
DR   EMDB; EMD-37909; -.
DR   EMDB; EMD-4645; -.
DR   EMDB; EMD-4646; -.
DR   EMDB; EMD-4647; -.
DR   EMDB; EMD-4649; -.
DR   EMDB; EMD-4657; -.
DR   EMDB; EMD-7544; -.
DR   EMDB; EMD-7545; -.
DR   SMR; P35523; -.
DR   BioGRID; 107594; 13.
DR   FunCoup; P35523; 130.
DR   IntAct; P35523; 6.
DR   MINT; P35523; -.
DR   STRING; 9606.ENSP00000339867; -.
DR   BindingDB; P35523; -.
DR   GuidetoPHARMACOLOGY; 698; -.
DR   TCDB; 2.A.49.2.1; the chloride carrier/channel (clc) family.
DR   iPTMnet; P35523; -.
DR   PhosphoSitePlus; P35523; -.
DR   BioMuta; CLCN1; -.
DR   DMDM; 311033468; -.
DR   jPOST; P35523; -.
DR   MassIVE; P35523; -.
DR   PaxDb; 9606-ENSP00000339867; -.
DR   PeptideAtlas; P35523; -.
DR   ProteomicsDB; 55076; -.
DR   Antibodypedia; 32627; 152 antibodies from 24 providers.
DR   DNASU; 1180; -.
DR   Ensembl; ENST00000343257.7; ENSP00000339867.2; ENSG00000188037.15.
DR   GeneID; 1180; -.
DR   KEGG; hsa:1180; -.
DR   MANE-Select; ENST00000343257.7; ENSP00000339867.2; NM_000083.3; NP_000074.3.
DR   UCSC; uc003wcr.2; human.
DR   AGR; HGNC:2019; -.
DR   ClinPGx; PA26546; -.
DR   CTD; 1180; -.
DR   DisGeNET; 1180; -.
DR   GeneCards; CLCN1; -.
DR   GeneReviews; CLCN1; -.
DR   HGNC; HGNC:2019; CLCN1.
DR   HPA; ENSG00000188037; Tissue enriched (skeletal).
DR   MalaCards; CLCN1; -.
DR   MIM; 118425; gene.
DR   MIM; 160800; phenotype.
DR   MIM; 255700; phenotype.
DR   OpenTargets; ENSG00000188037; -.
DR   Orphanet; 614; Thomsen and Becker disease.
DR   VEuPathDB; HostDB:ENSG00000188037; -.
DR   eggNOG; KOG0476; Eukaryota.
DR   GeneTree; ENSGT00940000157383; -.
DR   HOGENOM; CLU_006904_0_1_1; -.
DR   InParanoid; P35523; -.
DR   OMA; KHIGDPE; -.
DR   OrthoDB; 4564at2759; -.
DR   PAN-GO; P35523; 3 GO annotations based on evolutionary models.
DR   PhylomeDB; P35523; -.
DR   PathwayCommons; P35523; -.
DR   Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR   SignaLink; P35523; -.
DR   Agora; ENSG00000188037; -.
DR   BioGRID-ORCS; 1180; 13 hits in 1139 CRISPR screens.
DR   ChiTaRS; CLCN1; human.
DR   GeneWiki; CLCN1; -.
DR   GenomeRNAi; 1180; -.
DR   Pharos; P35523; Tbio.
DR   PRO; PR:P35523; -.
DR   Proteomes; UP000005640; Chromosome 7.
DR   RNAct; P35523; protein.
DR   Bgee; ENSG00000188037; Expressed in hindlimb stylopod muscle and 94 other cell types or tissues.
DR   ExpressionAtlas; P35523; baseline and differential.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0030315; C:T-tubule; IEA:UniProtKB-SubCell.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0005247; F:voltage-gated chloride channel activity; IMP:UniProtKB.
DR   GO; GO:1902476; P:chloride transmembrane transport; IMP:UniProtKB.
DR   GO; GO:0006821; P:chloride transport; IBA:GO_Central.
DR   GO; GO:0006936; P:muscle contraction; IMP:UniProtKB.
DR   CDD; cd03683; ClC_1_like; 1.
DR   FunFam; 1.10.3080.10:FF:000003; Chloride channel 2; 1.
DR   FunFam; 3.10.580.10:FF:000027; Chloride channel protein; 1.
DR   FunFam; 3.10.580.10:FF:000030; Chloride channel protein; 1.
DR   Gene3D; 3.10.580.10; CBS-domain; 2.
DR   Gene3D; 1.10.3080.10; Clc chloride channel; 1.
DR   InterPro; IPR046342; CBS_dom_sf.
DR   InterPro; IPR014743; Cl-channel_core.
DR   InterPro; IPR002243; Cl_channel-1.
DR   InterPro; IPR050970; Cl_channel_volt-gated.
DR   InterPro; IPR001807; ClC.
DR   PANTHER; PTHR45720:SF4; CHLORIDE CHANNEL PROTEIN 1; 1.
DR   PANTHER; PTHR45720; CHLORIDE CHANNEL PROTEIN 2; 1.
DR   Pfam; PF00654; Voltage_CLC; 1.
DR   PRINTS; PR00762; CLCHANNEL.
DR   PRINTS; PR01112; CLCHANNEL1.
DR   SUPFAM; SSF54631; CBS-domain pair; 1.
DR   SUPFAM; SSF81340; Clc chloride channel; 1.
DR   PROSITE; PS51371; CBS; 2.
DR   PDBsum; 6COY; -.
DR   PDBsum; 6COZ; -.
DR   PDBsum; 6QV6; -.
DR   PDBsum; 6QVB; -.
DR   PDBsum; 6QVC; -.
DR   PDBsum; 6QVD; -.
DR   PDBsum; 6QVU; -.
DR   PDBsum; 8WXI; -.
DR   PDBsum; 8WXJ; -.
PE   1: Evidence at protein level;
KW   3D-structure; CBS domain; Cell membrane; Chloride; Chloride channel;
KW   Disease variant; Ion channel; Ion transport; Membrane; Phosphoprotein;
KW   Proteomics identification; Reference proteome; Repeat; Transmembrane;
KW   Transmembrane helix; Transport; Voltage-gated channel.
FT   CHAIN           1..988
FT                   /note="Chloride channel protein 1"
FT                   /id="PRO_0000094429"
FT   TOPO_DOM        1..118
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        119..150
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   TOPO_DOM        151..158
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        159..179
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   TOPO_DOM        180..183
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   INTRAMEM        184..189
FT                   /note="Note=Loop between two helices"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   INTRAMEM        190..195
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   TOPO_DOM        196..208
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   INTRAMEM        209..224
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   INTRAMEM        225..230
FT                   /note="Note=Loop between two helices"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   INTRAMEM        231..246
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   TOPO_DOM        247..268
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   INTRAMEM        269..280
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   INTRAMEM        281..290
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   TOPO_DOM        291..301
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        302..321
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   TOPO_DOM        322..347
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        348..376
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   TOPO_DOM        377..390
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        391..408
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   TOPO_DOM        409..414
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   INTRAMEM        415..418
FT                   /note="Note=Loop between two helices"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   INTRAMEM        419..426
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   TOPO_DOM        427..457
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   INTRAMEM        458..475
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   INTRAMEM        476..482
FT                   /note="Note=Loop between two helices"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   INTRAMEM        483..498
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   TOPO_DOM        499..521
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   INTRAMEM        522..538
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   INTRAMEM        539..540
FT                   /note="Note=Loop between two helices"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   INTRAMEM        541..554
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   TOPO_DOM        555..557
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   INTRAMEM        558..571
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   INTRAMEM        572..575
FT                   /note="Note=Loop between two helices"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   INTRAMEM        576..578
FT                   /note="Helical"
FT                   /evidence="ECO:0000305|PubMed:29809153,
FT                   ECO:0000305|PubMed:31022181, ECO:0000305|PubMed:37892996,
FT                   ECO:0007744|PDB:6COY, ECO:0007744|PDB:6QV6"
FT   TOPO_DOM        579..988
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   DOMAIN          609..668
FT                   /note="CBS 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT   DOMAIN          821..876
FT                   /note="CBS 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT   REGION          65..92
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          713..764
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          880..988
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           188..192
FT                   /note="Selectivity filter part_1"
FT                   /evidence="ECO:0000250"
FT   MOTIF           230..234
FT                   /note="Selectivity filter part_2"
FT                   /evidence="ECO:0000250"
FT   MOTIF           482..486
FT                   /note="Selectivity filter part_3"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        65..75
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        887..906
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        929..941
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        950..967
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        979..988
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         189
FT                   /ligand="chloride"
FT                   /ligand_id="ChEBI:CHEBI:17996"
FT                   /evidence="ECO:0000250|UniProtKB:P37019"
FT   BINDING         484
FT                   /ligand="chloride"
FT                   /ligand_id="ChEBI:CHEBI:17996"
FT                   /evidence="ECO:0000250|UniProtKB:P37019"
FT   BINDING         578
FT                   /ligand="chloride"
FT                   /ligand_id="ChEBI:CHEBI:17996"
FT                   /evidence="ECO:0000250|UniProtKB:P37019"
FT   SITE            232
FT                   /note="Protopore gate"
FT                   /evidence="ECO:0000305|PubMed:29809153"
FT   MOD_RES         886
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q64347"
FT   VARIANT         43
FT                   /note="Q -> R (in MCAR; decreased chloride transport;
FT                   decreased localization to the plasma membrane; dominant
FT                   negative effect on chloride transport and localization to
FT                   the plasma membrane; no significant effect on chloride
FT                   channel activity; no effect on homodimerization;
FT                   dbSNP:rs868831424)"
FT                   /evidence="ECO:0000269|PubMed:26502825"
FT                   /id="VAR_075588"
FT   VARIANT         70
FT                   /note="S -> L (in MCAR; uncertain significance; no effect
FT                   on chloride transport; dbSNP:rs769312894)"
FT                   /evidence="ECO:0000269|PubMed:26502825"
FT                   /id="VAR_075589"
FT   VARIANT         82
FT                   /note="T -> A (in MCAR; uncertain significance; no effect
FT                   on chloride transport; dbSNP:rs772100356)"
FT                   /evidence="ECO:0000269|PubMed:26007199"
FT                   /id="VAR_075590"
FT   VARIANT         105
FT                   /note="R -> C (in MCAR; no effect on chloride transport;
FT                   dbSNP:rs201509501)"
FT                   /evidence="ECO:0000269|PubMed:26510092,
FT                   ECO:0000269|PubMed:8533761"
FT                   /id="VAR_001582"
FT   VARIANT         118
FT                   /note="G -> W (in dbSNP:rs10282312)"
FT                   /evidence="ECO:0000269|PubMed:15489334,
FT                   ECO:0000269|PubMed:7581380"
FT                   /id="VAR_001583"
FT   VARIANT         128
FT                   /note="M -> V (in MCAD; dbSNP:rs80356699)"
FT                   /evidence="ECO:0000269|PubMed:12661046"
FT                   /id="VAR_075591"
FT   VARIANT         136
FT                   /note="D -> G (in MCAR)"
FT                   /evidence="ECO:0000269|PubMed:7981681,
FT                   ECO:0000269|PubMed:8533761"
FT                   /id="VAR_001584"
FT   VARIANT         137
FT                   /note="Y -> D (in MCAR; reduced chloride transport;
FT                   decreased localization to the plasma membrane; no
FT                   significant effect on chloride channel activity;
FT                   dbSNP:rs748639603)"
FT                   /evidence="ECO:0000269|PubMed:26502825"
FT                   /id="VAR_075592"
FT   VARIANT         150
FT                   /note="Y -> C (in MCAR)"
FT                   /evidence="ECO:0000269|PubMed:8571958"
FT                   /id="VAR_001585"
FT   VARIANT         154
FT                   /note="Q -> R (no effect on chloride transport;
FT                   dbSNP:rs111482384)"
FT                   /evidence="ECO:0000269|PubMed:26510092"
FT                   /id="VAR_075593"
FT   VARIANT         160
FT                   /note="Q -> H (in MCAR; reduced chloride transport;
FT                   decreased localization to the plasma membrane; no
FT                   significant effect on chloride channel activity;
FT                   dbSNP:rs771532474)"
FT                   /evidence="ECO:0000269|PubMed:26502825"
FT                   /id="VAR_075594"
FT   VARIANT         161
FT                   /note="F -> V (in MCAD and MCAR)"
FT                   /evidence="ECO:0000269|PubMed:9566422"
FT                   /id="VAR_001586"
FT   VARIANT         164
FT                   /note="W -> R (in MCAR; altered chloride channel activity;
FT                   dbSNP:rs1802429044)"
FT                   /evidence="ECO:0000269|PubMed:22521272"
FT                   /id="VAR_075595"
FT   VARIANT         165
FT                   /note="V -> G (in MCAR; dbSNP:rs1586485438)"
FT                   /evidence="ECO:0000269|PubMed:8533761"
FT                   /id="VAR_001587"
FT   VARIANT         167
FT                   /note="F -> L (in MCAR; no effect on chloride transport;
FT                   dbSNP:rs149729531)"
FT                   /evidence="ECO:0000269|PubMed:22641783,
FT                   ECO:0000269|PubMed:26510092, ECO:0000269|PubMed:7874130,
FT                   ECO:0000269|PubMed:8533761"
FT                   /id="VAR_001588"
FT   VARIANT         190
FT                   /note="G -> S (in MCAR; loss of chloride channel activity;
FT                   dbSNP:rs797045032)"
FT                   /evidence="ECO:0000269|PubMed:19697366,
FT                   ECO:0000269|PubMed:22521272, ECO:0000269|PubMed:26007199"
FT                   /id="VAR_075596"
FT   VARIANT         193
FT                   /note="E -> K (in MCAD; dbSNP:rs80356686)"
FT                   /evidence="ECO:0000269|PubMed:12661046"
FT                   /id="VAR_075597"
FT   VARIANT         197
FT                   /note="I -> R (in MCAR; changed chloride channel activity)"
FT                   /evidence="ECO:0000269|PubMed:22521272"
FT                   /id="VAR_075598"
FT   VARIANT         198
FT                   /note="L -> P (in MCAD; reduced chloride transport; changed
FT                   calcium channel activity; changed gating of the channel;
FT                   dbSNP:rs1347382107)"
FT                   /evidence="ECO:0000269|PubMed:26096614"
FT                   /id="VAR_075599"
FT   VARIANT         200
FT                   /note="G -> R (in MCAD and MCAR; dbSNP:rs1563074523)"
FT                   /evidence="ECO:0000269|PubMed:8571958"
FT                   /id="VAR_001589"
FT   VARIANT         230
FT                   /note="G -> E (in MCAD and MCAR; changed ion selectivity;
FT                   loss of chloride transport; mild dominant effect;
FT                   dbSNP:rs80356700)"
FT                   /evidence="ECO:0000269|PubMed:7981750,
FT                   ECO:0000269|PubMed:8112288, ECO:0000269|PubMed:9122265"
FT                   /id="VAR_001590"
FT   VARIANT         236
FT                   /note="V -> L (in MCAR; loss of chloride transport; changed
FT                   calcium channel activity; changed gating of the channel;
FT                   dbSNP:rs776173406)"
FT                   /evidence="ECO:0000269|PubMed:9736777"
FT                   /id="VAR_001591"
FT   VARIANT         261
FT                   /note="Y -> C (in MCAR; dbSNP:rs200621976)"
FT                   /evidence="ECO:0000269|PubMed:8571958"
FT                   /id="VAR_001592"
FT   VARIANT         270
FT                   /note="G -> V (in MCAR; decreased chloride channel
FT                   activity)"
FT                   /evidence="ECO:0000269|PubMed:26007199"
FT                   /id="VAR_075600"
FT   VARIANT         277
FT                   /note="C -> R (in MCAR; reduced chloride transport; reduced
FT                   open probabilities of both protopore and common gating of
FT                   the channel; leads to a positive shift of the voltage
FT                   dependence of channel conductance; no effect on protein
FT                   abundance; dbSNP:rs757109632)"
FT                   /evidence="ECO:0000269|PubMed:22641783"
FT                   /id="VAR_075601"
FT   VARIANT         277
FT                   /note="C -> Y (in MCAR; reduced chloride transport; reduced
FT                   open probabilities of both protopore and common gating of
FT                   the channel; leads to a positive shift of the voltage
FT                   dependence of channel conductance; changed ion selectivity;
FT                   no effect on protein abundance; dbSNP:rs1802528255)"
FT                   /evidence="ECO:0000269|PubMed:22641783"
FT                   /id="VAR_075602"
FT   VARIANT         285
FT                   /note="G -> E (in MCAR; loss of chloride channel activity;
FT                   dbSNP:rs150885084)"
FT                   /evidence="ECO:0000269|PubMed:12661046,
FT                   ECO:0000269|PubMed:9736777"
FT                   /id="VAR_001593"
FT   VARIANT         286
FT                   /note="V -> A (in MCAD; reduced chloride transport; changed
FT                   calcium channel activity; changed gating of the channel;
FT                   dominant negative effect; dbSNP:rs80356689)"
FT                   /evidence="ECO:0000269|PubMed:9736777"
FT                   /id="VAR_001594"
FT   VARIANT         290
FT                   /note="I -> M (in MCAD; reduced chloride transport; changed
FT                   chloride channel activity; changed gating of the channel;
FT                   leads to a positive shift of the voltage dependence of
FT                   channel conductance; decreased open probabilities of fast
FT                   and slow gates; dominant negative effect;
FT                   dbSNP:rs80356690)"
FT                   /evidence="ECO:0000269|PubMed:10051520,
FT                   ECO:0000269|PubMed:10962018, ECO:0000269|PubMed:7581380,
FT                   ECO:0000269|PubMed:8845168"
FT                   /id="VAR_001595"
FT   VARIANT         291
FT                   /note="E -> K (in MCAR; loss of calcium channel activity;
FT                   no dominant negative effect; dbSNP:rs121912805)"
FT                   /evidence="ECO:0000269|PubMed:8533761,
FT                   ECO:0000269|PubMed:8845168"
FT                   /id="VAR_001596"
FT   VARIANT         300
FT                   /note="R -> Q (no effect on chloride transport;
FT                   dbSNP:rs118066140)"
FT                   /evidence="ECO:0000269|PubMed:7874130,
FT                   ECO:0000269|PubMed:8112288"
FT                   /id="VAR_001597"
FT   VARIANT         307
FT                   /note="F -> S (in MCAD; reduced chloride transport; changed
FT                   chloride channel activity; changed gating of the channel;
FT                   dominant negative effect; dbSNP:rs80356701)"
FT                   /evidence="ECO:0000269|PubMed:12661046,
FT                   ECO:0000269|PubMed:9736777"
FT                   /id="VAR_001598"
FT   VARIANT         313
FT                   /note="A -> T (in MCAD and MCAR; dbSNP:rs80356692)"
FT                   /evidence="ECO:0000269|PubMed:9566422"
FT                   /id="VAR_001599"
FT   VARIANT         317
FT                   /note="R -> Q (in MCAD; reduced chloride transport; changed
FT                   chloride channel activity; changed gating of the channel;
FT                   dbSNP:rs80356702)"
FT                   /evidence="ECO:0000269|PubMed:8533761,
FT                   ECO:0000269|PubMed:8845168"
FT                   /id="VAR_001600"
FT   VARIANT         327
FT                   /note="V -> I (in MCAR; due to a nucleotide substitution
FT                   that can affect splicing or results in missense variant
FT                   I-327; the missense variant does not affect chloride
FT                   channel activity when expressed in Xenopus oocytes;
FT                   dbSNP:rs774396430)"
FT                   /evidence="ECO:0000269|PubMed:7951242"
FT                   /id="VAR_001601"
FT   VARIANT         329
FT                   /note="I -> T (in MCAR)"
FT                   /evidence="ECO:0000269|PubMed:8533761"
FT                   /id="VAR_001602"
FT   VARIANT         338
FT                   /note="R -> Q (in MCAD and MCAR; dbSNP:rs80356703)"
FT                   /evidence="ECO:0000269|PubMed:7874130"
FT                   /id="VAR_001603"
FT   VARIANT         412
FT                   /note="Q -> P (in MCAR; loss of chloride transport;
FT                   decreased localization to the plasma membrane; loss of
FT                   homodimerization; might be degraded; dbSNP:rs1279658001)"
FT                   /evidence="ECO:0000269|PubMed:26510092"
FT                   /id="VAR_075603"
FT   VARIANT         413
FT                   /note="F -> C (in MCAR; dbSNP:rs121912799)"
FT                   /evidence="ECO:0000269|PubMed:1379744,
FT                   ECO:0000269|PubMed:7951242, ECO:0000269|PubMed:8533761"
FT                   /id="VAR_001604"
FT   VARIANT         415
FT                   /note="A -> V (in MCAR; dbSNP:rs2116854732)"
FT                   /evidence="ECO:0000269|PubMed:8571958"
FT                   /id="VAR_001605"
FT   VARIANT         437
FT                   /note="A -> T (in dbSNP:rs41276054)"
FT                   /evidence="ECO:0000269|PubMed:12661046"
FT                   /id="VAR_001606"
FT   VARIANT         453
FT                   /note="R -> W (in MCAR; uncertain significance; no effect
FT                   on chloride channel activity; dbSNP:rs376026619)"
FT                   /evidence="ECO:0000269|PubMed:26007199"
FT                   /id="VAR_075604"
FT   VARIANT         480
FT                   /note="P -> H (in MCAD; decreased protein abundance;
FT                   dbSNP:rs80356694)"
FT                   /evidence="ECO:0000269|PubMed:27666773"
FT                   /id="VAR_077244"
FT   VARIANT         480
FT                   /note="P -> L (in MCAD; loss of chloride transport; changed
FT                   chloride channel activity; changed gating of the channel;
FT                   dominant effect; dbSNP:rs80356694)"
FT                   /evidence="ECO:0000269|PubMed:12661046,
FT                   ECO:0000269|PubMed:8112288, ECO:0000269|PubMed:8845168"
FT                   /id="VAR_001607"
FT   VARIANT         482
FT                   /note="G -> R (in MCAR; dbSNP:rs746125212)"
FT                   /evidence="ECO:0000269|PubMed:8533761"
FT                   /id="VAR_001608"
FT   VARIANT         484
FT                   /note="F -> L (in MCAD; reduced chloride transport; changed
FT                   calcium channel activity; changed channel gating; no
FT                   dominant negative effect; dbSNP:rs1312002847)"
FT                   /evidence="ECO:0000269|PubMed:26096614"
FT                   /id="VAR_075605"
FT   VARIANT         485
FT                   /note="M -> V (in MCAR; dbSNP:rs146457619)"
FT                   /evidence="ECO:0000269|PubMed:8533761,
FT                   ECO:0000269|PubMed:9736777"
FT                   /id="VAR_001609"
FT   VARIANT         496
FT                   /note="R -> S (in MCAR; loss of chloride channel activity;
FT                   recessive; dbSNP:rs121912801)"
FT                   /evidence="ECO:0000269|PubMed:26502825,
FT                   ECO:0000269|PubMed:7951242"
FT                   /id="VAR_001610"
FT   VARIANT         499
FT                   /note="G -> R (in MCAR; reduced chloride transport; changed
FT                   calcium channel activity; changed channel gating;
FT                   dbSNP:rs121912807)"
FT                   /evidence="ECO:0000269|PubMed:10644771"
FT                   /id="VAR_075606"
FT   VARIANT         527
FT                   /note="I -> T (in MCAR; uncertain significance;
FT                   dbSNP:rs1319653705)"
FT                   /evidence="ECO:0000269|PubMed:22641783"
FT                   /id="VAR_075607"
FT   VARIANT         533
FT                   /note="T -> I (in MCAR; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:22521272"
FT                   /id="VAR_075608"
FT   VARIANT         536
FT                   /note="V -> L (in MCAR; uncertain significance;
FT                   dbSNP:rs777685454)"
FT                   /evidence="ECO:0000269|PubMed:22521272"
FT                   /id="VAR_075609"
FT   VARIANT         548
FT                   /note="E -> K (in a breast cancer sample; somatic mutation;
FT                   dbSNP:rs546411827)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036300"
FT   VARIANT         552
FT                   /note="Q -> R (in MCAD and MCAR; also found in myotonia
FT                   levior; reduced chloride transport; changed calcium channel
FT                   activity; changed channel gating; weak dominant negative
FT                   effect; dbSNP:rs80356696)"
FT                   /evidence="ECO:0000269|PubMed:12456816,
FT                   ECO:0000269|PubMed:7581380, ECO:0000269|PubMed:8845168"
FT                   /id="VAR_001611"
FT   VARIANT         556
FT                   /note="I -> N (in MCAD and MCAR; mild form; reduced
FT                   chloride transport; changed chloride channel activity;
FT                   changed gating of the channel; leads to a positive shift of
FT                   the voltage dependence of channel conductance; partial
FT                   dominant negative effect; dbSNP:rs80356697)"
FT                   /evidence="ECO:0000269|PubMed:10051520,
FT                   ECO:0000269|PubMed:9566422, ECO:0000269|PubMed:9736777"
FT                   /id="VAR_001612"
FT   VARIANT         563
FT                   /note="V -> I (in MCAR)"
FT                   /evidence="ECO:0000269|PubMed:10215406"
FT                   /id="VAR_001613"
FT   VARIANT         614
FT                   /note="K -> N (in dbSNP:rs140205115)"
FT                   /evidence="ECO:0000269|PubMed:12661046"
FT                   /id="VAR_075610"
FT   VARIANT         628
FT                   /note="L -> P (in MCAR; uncertain significance; no effect
FT                   on calcium channel activity)"
FT                   /evidence="ECO:0000269|PubMed:26096614"
FT                   /id="VAR_075611"
FT   VARIANT         640
FT                   /note="V -> G (in MCAR; reduced calcium channel activity;
FT                   dbSNP:rs1803111906)"
FT                   /evidence="ECO:0000269|PubMed:26096614"
FT                   /id="VAR_075612"
FT   VARIANT         708
FT                   /note="F -> L (in MCAR)"
FT                   /evidence="ECO:0000269|PubMed:10215406"
FT                   /id="VAR_001614"
FT   VARIANT         727
FT                   /note="P -> L (in dbSNP:rs13438232)"
FT                   /id="VAR_047779"
FT   VARIANT         845
FT                   /note="G -> S (in MCAR; uncertain significance; no effect
FT                   on chloride channel activity; dbSNP:rs755433272)"
FT                   /evidence="ECO:0000269|PubMed:22521272"
FT                   /id="VAR_075613"
FT   VARIANT         855
FT                   /note="G -> E (in MCAR; uncertain significance;
FT                   dbSNP:rs1554439879)"
FT                   /evidence="ECO:0000269|PubMed:26502825"
FT                   /id="VAR_075614"
FT   VARIANT         932
FT                   /note="P -> L (in MCAR; uncertain significance;
FT                   dbSNP:rs80356706)"
FT                   /evidence="ECO:0000269|PubMed:11113225"
FT                   /id="VAR_075615"
FT   VARIANT         947
FT                   /note="V -> E (in MCAR; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:22521272"
FT                   /id="VAR_075616"
FT   VARIANT         950
FT                   /note="E -> K (in MCAD; uncertain significance;
FT                   dbSNP:rs201506176)"
FT                   /evidence="ECO:0000269|PubMed:27653901"
FT                   /id="VAR_079520"
FT   MUTAGEN         290
FT                   /note="I->C,E,F,G,K,L,Q,T,V,Y: Changed chloride channel
FT                   activity; changed gating of the channel."
FT                   /evidence="ECO:0000269|PubMed:8845168"
FT   MUTAGEN         291
FT                   /note="E->D: No effect on calcium channel activity."
FT                   /evidence="ECO:0000269|PubMed:8845168"
FT   MUTAGEN         291
FT                   /note="E->L: Loss of calcium channel activity."
FT                   /evidence="ECO:0000269|PubMed:8845168"
FT   MUTAGEN         496
FT                   /note="R->K: Changed gating of the channel."
FT                   /evidence="ECO:0000269|PubMed:10644771"
FT   MUTAGEN         499
FT                   /note="G->K,E: Changed gating of the channel."
FT                   /evidence="ECO:0000269|PubMed:10644771"
FT   MUTAGEN         499
FT                   /note="G->Q: No effect on gating of the channel."
FT                   /evidence="ECO:0000269|PubMed:10644771"
FT   MUTAGEN         500
FT                   /note="E->Q: No effect on channel function."
FT                   /evidence="ECO:0000269|PubMed:10644771"
FT   MUTAGEN         636
FT                   /note="T->A: Reduces the effect of adenosine nucleotides on
FT                   common gate."
FT                   /evidence="ECO:0000269|PubMed:16027167"
FT   MUTAGEN         638
FT                   /note="P->A: Reduces the effect of adenosine nucleotides on
FT                   common gate."
FT                   /evidence="ECO:0000269|PubMed:16027167"
FT   MUTAGEN         651
FT                   /note="S->A: Has normal sensitivity to adenosine
FT                   nucleotides."
FT                   /evidence="ECO:0000269|PubMed:16027167"
FT   MUTAGEN         847
FT                   /note="H->A: Reduces the effect of adenosine nucleotides on
FT                   common gate."
FT                   /evidence="ECO:0000269|PubMed:16027167"
FT   MUTAGEN         848
FT                   /note="L->A: Abrogates the effect of adenosine nucleotides
FT                   on common gate."
FT                   /evidence="ECO:0000269|PubMed:16027167"
FT   MUTAGEN         849
FT                   /note="A->V: Has normal sensitivity to adenosine
FT                   nucleotides."
FT                   /evidence="ECO:0000269|PubMed:16027167"
FT   CONFLICT        697
FT                   /note="L -> P (in Ref. 1; CAA80996/CAA81103)"
FT                   /evidence="ECO:0000305"
FT   HELIX           116..152
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   HELIX           157..181
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   HELIX           184..186
FT                   /evidence="ECO:0007829|PDB:6COY"
FT   HELIX           191..198
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   TURN            204..207
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   HELIX           209..223
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   TURN            224..226
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   TURN            232..234
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   HELIX           235..247
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   HELIX           248..252
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   HELIX           263..279
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   HELIX           282..292
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   STRAND          295..298
FT                   /evidence="ECO:0007829|PDB:8WXJ"
FT   HELIX           299..322
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   STRAND          327..333
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   STRAND          339..341
FT                   /evidence="ECO:0007829|PDB:6COY"
FT   TURN            345..347
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   HELIX           348..378
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   HELIX           380..388
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   HELIX           392..404
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   TURN            407..415
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   HELIX           420..427
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   TURN            433..437
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   STRAND          441..443
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   HELIX           444..447
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   STRAND          448..450
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   STRAND          452..454
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   HELIX           456..474
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   STRAND          475..480
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   HELIX           484..505
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   STRAND          510..514
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   STRAND          515..517
FT                   /evidence="ECO:0007829|PDB:6COY"
FT   HELIX           521..537
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   HELIX           542..550
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   HELIX           556..571
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   HELIX           577..584
FT                   /evidence="ECO:0007829|PDB:8WXI"
FT   HELIX           605..608
FT                   /evidence="ECO:0007829|PDB:6COZ"
FT   STRAND          609..611
FT                   /evidence="ECO:0007829|PDB:6COZ"
FT   HELIX           622..631
FT                   /evidence="ECO:0007829|PDB:6COZ"
FT   STRAND          635..641
FT                   /evidence="ECO:0007829|PDB:6COZ"
FT   TURN            643..646
FT                   /evidence="ECO:0007829|PDB:6COZ"
FT   STRAND          647..653
FT                   /evidence="ECO:0007829|PDB:6COZ"
FT   HELIX           654..665
FT                   /evidence="ECO:0007829|PDB:6COZ"
FT   HELIX           799..810
FT                   /evidence="ECO:0007829|PDB:6COZ"
FT   HELIX           834..843
FT                   /evidence="ECO:0007829|PDB:6COZ"
FT   STRAND          851..853
FT                   /evidence="ECO:0007829|PDB:6COZ"
FT   STRAND          856..860
FT                   /evidence="ECO:0007829|PDB:6COZ"
FT   HELIX           863..875
FT                   /evidence="ECO:0007829|PDB:6COZ"
SQ   SEQUENCE   988 AA;  108626 MW;  CA838BCD2AF3CA68 CRC64;
     MEQSRSQQRG GEQSWWGSDP QYQYMPFEHC TSYGLPSENG GLQHRLRKDA GPRHNVHPTQ
     IYGHHKEQFS DREQDIGMPK KTGSSSTVDS KDEDHYSKCQ DCIHRLGQVV RRKLGEDGIF
     LVLLGLLMAL VSWSMDYVSA KSLQAYKWSY AQMQPSLPLQ FLVWVTFPLV LILFSALFCH
     LISPQAVGSG IPEMKTILRG VVLKEYLTMK AFVAKVVALT AGLGSGIPVG KEGPFVHIAS
     ICAAVLSKFM SVFCGVYEQP YYYSDILTVG CAVGVGCCFG TPLGGVLFSI EVTSTYFAVR
     NYWRGFFAAT FSAFVFRVLA VWNKDAVTIT ALFRTNFRMD FPFDLKELPA FAAIGICCGL
     LGAVFVYLHR QVMLGVRKHK ALSQFLAKHR LLYPGIVTFV IASFTFPPGM GQFMAGELMP
     REAISTLFDN NTWVKHAGDP ESLGQSAVWI HPRVNVVIII FLFFVMKFWM SIVATTMPIP
     CGGFMPVFVL GAAFGRLVGE IMAMLFPDGI LFDDIIYKIL PGGYAVIGAA ALTGAVSHTV
     STAVICFELT GQIAHILPMM VAVILANMVA QSLQPSLYDS IIQVKKLPYL PDLGWNQLSK
     YTIFVEDIMV RDVKFVSASY TYGELRTLLQ TTTVKTLPLV DSKDSMILLG SVERSELQAL
     LQRHLCPERR LRAAQEMARK LSELPYDGKA RLAGEGLPGA PPGRPESFAF VDEDEDEDLS
     GKSELPPSLA LHPSTTAPLS PEEPNGPLPG HKQQPEAPEP AGQRPSIFQS LLHCLLGRAR
     PTKKKTTQDS TDLVDNMSPE EIEAWEQEQL SQPVCFDSCC IDQSPFQLVE QTTLHKTHTL
     FSLLGLHLAY VTSMGKLRGV LALEELQKAI EGHTKSGVQL RPPLASFRNT TSTRKSTGAP
     PSSAENWNLP EDRPGATGTG DVIAASPETP VPSPSPEPPL SLAPGKVEGE LEELELVESP
     GLEEELADIL QGPSLRSTDE EDEDELIL
//