ID   CLCKA_HUMAN             Reviewed;         687 AA.
AC   P51800; B4DPD3; E7EPH6; Q5T5P8; Q5T5Q4; Q7Z6D1; Q86VT1;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   24-JAN-2024, entry version 198.
DE   RecName: Full=Chloride channel protein ClC-Ka;
DE            Short=Chloride channel Ka;
DE   AltName: Full=ClC-K1;
GN   Name=CLCNKA;
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] (ISOFORM 1).
RC   TISSUE=Kidney;
RX   PubMed=8041726; DOI=10.1073/pnas.91.15.6943;
RA   Kieferle S., Fong P., Bens M., Vandewalle A., Jentsch T.;
RT   "Two highly homologous members of the ClC chloride channel family in both
RT   rat and human kidney.";
RL   Proc. Natl. Acad. Sci. U.S.A. 91:6943-6947(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT THR-447.
RC   TISSUE=Kidney;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANTS GLY-83;
RP   GLN-357 AND THR-447.
RC   TISSUE=Kidney;
RA   Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA   Tanaka A., Yokoyama S.;
RL   Submitted (JUL-2006) to the EMBL/GenBank/DDBJ databases.
RN   [4]
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   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANTS
RP   ILE-67 AND PHE-315.
RC   TISSUE=Colon;
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   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 153-203.
RA   Schutte B.C., Malik M.I., Fingert J., Barna T.J., Stone E., Lamb F.S.;
RT   "Refined chromosomal localization of six human CLCN chloride ion channel
RT   genes.";
RL   Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   TISSUE SPECIFICITY.
RX   PubMed=11734858; DOI=10.1038/35107099;
RA   Estevez R., Boettger T., Stein V., Birkenhaeger R., Otto E.,
RA   Hildebrandt F., Jentsch T.J.;
RT   "Barttin is a Cl- channel beta-subunit crucial for renal Cl-reabsorption
RT   and inner ear K+ secretion.";
RL   Nature 414:558-561(2001).
RN   [8]
RP   INVOLVEMENT IN BARTS4B.
RX   PubMed=18310267; DOI=10.1136/jmg.2007.052944;
RA   Nozu K., Inagaki T., Fu X.J., Nozu Y., Kaito H., Kanda K., Sekine T.,
RA   Igarashi T., Nakanishi K., Yoshikawa N., Iijima K., Matsuo M.;
RT   "Molecular analysis of digenic inheritance in Bartter syndrome with
RT   sensorineural deafness.";
RL   J. Med. Genet. 45:182-186(2008).
RN   [9]
RP   ACTIVITY REGULATION, CALCIUM-BINDING SITES, AND MUTAGENESIS OF GLU-259;
RP   GLU-261; ASP-278 AND GLU-281.
RX   PubMed=23148261; DOI=10.1085/jgp.201210878;
RA   Gradogna A., Fenollar-Ferrer C., Forrest L.R., Pusch M.;
RT   "Dissecting a regulatory calcium-binding site of CLC-K kidney chloride
RT   channels.";
RL   J. Gen. Physiol. 140:681-696(2012).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 533-687, AND SUBUNIT.
RX   PubMed=17562318; DOI=10.1016/j.str.2007.04.013;
RA   Markovic S., Dutzler R.;
RT   "The structure of the cytoplasmic domain of the chloride channel ClC-Ka
RT   reveals a conserved interaction interface.";
RL   Structure 15:715-725(2007).
RN   [11]
RP   VARIANT BARTS4B CYS-80.
RX   PubMed=15044642; DOI=10.1056/nejmoa032843;
RA   Schlingmann K.P., Konrad M., Jeck N., Waldegger P., Reinalter S.C.,
RA   Holder M., Seyberth H.W., Waldegger S.;
RT   "Salt wasting and deafness resulting from mutations in two chloride
RT   channels.";
RL   N. Engl. J. Med. 350:1314-1319(2004).
CC   -!- FUNCTION: Voltage-gated chloride channel. Chloride channels have
CC       several functions including the regulation of cell volume; membrane
CC       potential stabilization, signal transduction and transepithelial
CC       transport. May be important in urinary concentrating mechanisms.
CC   -!- ACTIVITY REGULATION: Activated by extracellular calcium and inhibited
CC       by extracellular protons. {ECO:0000305|PubMed:23148261}.
CC   -!- SUBUNIT: Homodimer (PubMed:17562318). Interacts with BSND. Forms
CC       heteromers with BSND in the thin ascending limb of Henle (By
CC       similarity). {ECO:0000250|UniProtKB:Q9WUB7,
CC       ECO:0000269|PubMed:17562318}.
CC   -!- INTERACTION:
CC       P51800; P51800: CLCNKA; NbExp=2; IntAct=EBI-12538872, EBI-12538872;
CC       P51800-3; Q9H2G9: BLZF1; NbExp=3; IntAct=EBI-11980535, EBI-2548012;
CC       P51800-3; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-11980535, EBI-3867333;
CC       P51800-3; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-11980535, EBI-747204;
CC       P51800-3; Q86T90: KIAA1328; NbExp=3; IntAct=EBI-11980535, EBI-3437878;
CC       P51800-3; Q9BS75: KLHL20; NbExp=3; IntAct=EBI-11980535, EBI-10693436;
CC       P51800-3; Q5T749: KPRP; NbExp=3; IntAct=EBI-11980535, EBI-10981970;
CC       P51800-3; Q15323: KRT31; NbExp=3; IntAct=EBI-11980535, EBI-948001;
CC       P51800-3; O76011: KRT34; NbExp=3; IntAct=EBI-11980535, EBI-1047093;
CC       P51800-3; O76014: KRT37; NbExp=3; IntAct=EBI-11980535, EBI-1045716;
CC       P51800-3; Q6A163: KRT39; NbExp=3; IntAct=EBI-11980535, EBI-11958242;
CC       P51800-3; Q3LI59: KRTAP21-2; NbExp=3; IntAct=EBI-11980535, EBI-18395721;
CC       P51800-3; Q9BQ66: KRTAP4-12; NbExp=3; IntAct=EBI-11980535, EBI-739863;
CC       P51800-3; Q9UBR4-2: LHX3; NbExp=3; IntAct=EBI-11980535, EBI-12039345;
CC       P51800-3; Q8WWY6: MBD3L1; NbExp=3; IntAct=EBI-11980535, EBI-12516603;
CC       P51800-3; P17568: NDUFB7; NbExp=3; IntAct=EBI-11980535, EBI-1246238;
CC       P51800-3; Q9BYU1: PBX4; NbExp=3; IntAct=EBI-11980535, EBI-10302990;
CC       P51800-3; O94991: SLITRK5; NbExp=3; IntAct=EBI-11980535, EBI-17240818;
CC       P51800-3; Q8N865: SPMIP4; NbExp=3; IntAct=EBI-11980535, EBI-10174456;
CC       P51800-3; Q99081-3: TCF12; NbExp=3; IntAct=EBI-11980535, EBI-11952764;
CC       P51800-3; P15884-3: TCF4; NbExp=3; IntAct=EBI-11980535, EBI-13636688;
CC       P51800-3; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-11980535, EBI-11139477;
CC       P51800-3; Q12933: TRAF2; NbExp=3; IntAct=EBI-11980535, EBI-355744;
CC       P51800-3; Q96RU7: TRIB3; NbExp=3; IntAct=EBI-11980535, EBI-492476;
CC       P51800-3; Q8NB15: ZNF511; NbExp=3; IntAct=EBI-11980535, EBI-10269136;
CC   -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P51800-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P51800-2; Sequence=VSP_044700;
CC       Name=3;
CC         IsoId=P51800-3; Sequence=VSP_045795;
CC   -!- TISSUE SPECIFICITY: Expressed predominantly in the kidney. All nephron
CC       segments expressing BSND also express CLCNK proteins.
CC       {ECO:0000269|PubMed:11734858}.
CC   -!- DISEASE: Bartter syndrome 4B, neonatal, with sensorineural deafness
CC       (BARTS4B) [MIM:613090]: A digenic form of Bartter syndrome, an
CC       autosomal recessive disorder characterized by impaired salt
CC       reabsorption in the thick ascending loop of Henle with pronounced salt
CC       wasting, hypokalemic metabolic alkalosis, and varying degrees of
CC       hypercalciuria. BARTS4B is associated with sensorineural deafness.
CC       {ECO:0000269|PubMed:15044642, ECO:0000269|PubMed:18310267}. Note=The
CC       disease is caused by variants affecting distinct genetic loci,
CC       including the gene represented in this entry. Loss-of-function of both
CC       CLCNKA and CLCNKB results in the disease phenotype (PubMed:18310267).
CC       {ECO:0000269|PubMed:18310267}.
CC   -!- SIMILARITY: Belongs to the chloride channel (TC 2.A.49) family. CLCNKA
CC       subfamily. {ECO:0000305}.
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DR   EMBL; Z30643; CAA83120.1; -; mRNA.
DR   EMBL; AK298285; BAG60545.1; -; mRNA.
DR   EMBL; AK225550; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AL355994; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC048282; AAH48282.1; -; mRNA.
DR   EMBL; BC053869; AAH53869.1; -; mRNA.
DR   EMBL; U93878; AAB65148.1; -; Genomic_DNA.
DR   CCDS; CCDS167.1; -. [P51800-1]
DR   CCDS; CCDS41269.1; -. [P51800-3]
DR   CCDS; CCDS57973.1; -. [P51800-2]
DR   PIR; C57713; C57713.
DR   RefSeq; NP_001036169.1; NM_001042704.1. [P51800-3]
DR   RefSeq; NP_001244068.1; NM_001257139.1. [P51800-2]
DR   RefSeq; NP_004061.3; NM_004070.3. [P51800-1]
DR   PDB; 2PFI; X-ray; 1.60 A; A/B=533-687.
DR   PDBsum; 2PFI; -.
DR   AlphaFoldDB; P51800; -.
DR   SMR; P51800; -.
DR   BioGRID; 107601; 23.
DR   DIP; DIP-29432N; -.
DR   IntAct; P51800; 24.
DR   STRING; 9606.ENSP00000332771; -.
DR   DrugBank; DB04552; Niflumic acid.
DR   DrugBank; DB09295; Talniflumate.
DR   DrugCentral; P51800; -.
DR   GuidetoPHARMACOLOGY; 700; -.
DR   iPTMnet; P51800; -.
DR   PhosphoSitePlus; P51800; -.
DR   BioMuta; CLCNKA; -.
DR   DMDM; 1705857; -.
DR   EPD; P51800; -.
DR   jPOST; P51800; -.
DR   MassIVE; P51800; -.
DR   PaxDb; 9606-ENSP00000332771; -.
DR   PeptideAtlas; P51800; -.
DR   ProteomicsDB; 17361; -.
DR   ProteomicsDB; 56399; -. [P51800-1]
DR   ProteomicsDB; 64544; -.
DR   Antibodypedia; 29061; 207 antibodies from 26 providers.
DR   DNASU; 1187; -.
DR   Ensembl; ENST00000331433.5; ENSP00000332771.4; ENSG00000186510.12. [P51800-1]
DR   Ensembl; ENST00000375692.5; ENSP00000364844.1; ENSG00000186510.12. [P51800-3]
DR   Ensembl; ENST00000439316.6; ENSP00000414445.2; ENSG00000186510.12. [P51800-2]
DR   GeneID; 1187; -.
DR   KEGG; hsa:1187; -.
DR   MANE-Select; ENST00000331433.5; ENSP00000332771.4; NM_004070.4; NP_004061.3.
DR   UCSC; uc001axu.4; human. [P51800-1]
DR   AGR; HGNC:2026; -.
DR   CTD; 1187; -.
DR   DisGeNET; 1187; -.
DR   GeneCards; CLCNKA; -.
DR   HGNC; HGNC:2026; CLCNKA.
DR   HPA; ENSG00000186510; Tissue enriched (kidney).
DR   MalaCards; CLCNKA; -.
DR   MIM; 602024; gene.
DR   MIM; 613090; phenotype.
DR   neXtProt; NX_P51800; -.
DR   OpenTargets; ENSG00000186510; -.
DR   Orphanet; 89938; Bartter syndrome type 4.
DR   PharmGKB; PA26553; -.
DR   VEuPathDB; HostDB:ENSG00000186510; -.
DR   eggNOG; KOG0476; Eukaryota.
DR   GeneTree; ENSGT00940000158748; -.
DR   HOGENOM; CLU_006904_4_0_1; -.
DR   InParanoid; P51800; -.
DR   OMA; VCGMEWY; -.
DR   OrthoDB; 1194at2759; -.
DR   PhylomeDB; P51800; -.
DR   TreeFam; TF300522; -.
DR   PathwayCommons; P51800; -.
DR   Reactome; R-HSA-2672351; Stimuli-sensing channels.
DR   SignaLink; P51800; -.
DR   BioGRID-ORCS; 1187; 39 hits in 1148 CRISPR screens.
DR   EvolutionaryTrace; P51800; -.
DR   GeneWiki; CLCNKA; -.
DR   GenomeRNAi; 1187; -.
DR   Pharos; P51800; Tchem.
DR   PRO; PR:P51800; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; P51800; Protein.
DR   Bgee; ENSG00000186510; Expressed in metanephros cortex and 95 other cell types or tissues.
DR   GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0005247; F:voltage-gated chloride channel activity; IBA:GO_Central.
DR   GO; GO:0006821; P:chloride transport; IBA:GO_Central.
DR   GO; GO:0070293; P:renal absorption; TAS:UniProtKB.
DR   GO; GO:0030321; P:transepithelial chloride transport; TAS:ProtInc.
DR   CDD; cd04591; CBS_pair_voltage-gated_CLC_euk_bac; 1.
DR   CDD; cd03683; ClC_1_like; 1.
DR   Gene3D; 3.10.580.10; CBS-domain; 1.
DR   Gene3D; 1.10.3080.10; Clc chloride channel; 1.
DR   InterPro; IPR000644; CBS_dom.
DR   InterPro; IPR046342; CBS_dom_sf.
DR   InterPro; IPR014743; Cl-channel_core.
DR   InterPro; IPR001807; Cl-channel_volt-gated.
DR   InterPro; IPR002250; Cl_channel-K.
DR   PANTHER; PTHR45720; CHLORIDE CHANNEL PROTEIN 2; 1.
DR   PANTHER; PTHR45720:SF16; CHLORIDE CHANNEL PROTEIN CLC-KA; 1.
DR   Pfam; PF00571; CBS; 1.
DR   Pfam; PF00654; Voltage_CLC; 1.
DR   PRINTS; PR00762; CLCHANNEL.
DR   PRINTS; PR01119; CLCHANNELKDY.
DR   SMART; SM00116; CBS; 1.
DR   SUPFAM; SSF54631; CBS-domain pair; 1.
DR   SUPFAM; SSF81340; Clc chloride channel; 1.
DR   PROSITE; PS51371; CBS; 2.
DR   Genevisible; P51800; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Bartter syndrome; Calcium; CBS domain;
KW   Chloride; Chloride channel; Deafness; Disease variant; Ion channel;
KW   Ion transport; Membrane; Metal-binding; Reference proteome; Repeat;
KW   Transmembrane; Transmembrane helix; Transport; Voltage-gated channel.
FT   CHAIN           1..687
FT                   /note="Chloride channel protein ClC-Ka"
FT                   /id="PRO_0000094455"
FT   TRANSMEM        52..72
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        161..181
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        202..222
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        236..256
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        282..302
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        329..349
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        396..416
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        417..437
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        452..472
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        486..506
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        507..687
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          551..609
FT                   /note="CBS 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT   DOMAIN          626..684
FT                   /note="CBS 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00703"
FT   BINDING         259
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000305|PubMed:23148261"
FT   BINDING         261
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000305|PubMed:23148261"
FT   BINDING         278
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000305|PubMed:23148261"
FT   BINDING         281
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /evidence="ECO:0000305|PubMed:23148261"
FT   VAR_SEQ         77..119
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_044700"
FT   VAR_SEQ         615
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3"
FT                   /id="VSP_045795"
FT   VARIANT         8
FT                   /note="R -> H (in dbSNP:rs9442189)"
FT                   /id="VAR_048695"
FT   VARIANT         45
FT                   /note="R -> H (in dbSNP:rs35932996)"
FT                   /id="VAR_033768"
FT   VARIANT         67
FT                   /note="M -> I (in dbSNP:rs17855678)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_030784"
FT   VARIANT         80
FT                   /note="W -> C (in BARTS4B; a patient also carrying a
FT                   mutation in CLCNKB; dbSNP:rs121909137)"
FT                   /evidence="ECO:0000269|PubMed:15044642"
FT                   /id="VAR_063074"
FT   VARIANT         83
FT                   /note="R -> G (in dbSNP:rs10927887)"
FT                   /evidence="ECO:0000269|Ref.3"
FT                   /id="VAR_019787"
FT   VARIANT         315
FT                   /note="Y -> F (in dbSNP:rs12126269)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_019788"
FT   VARIANT         357
FT                   /note="H -> Q (in dbSNP:rs79751787)"
FT                   /evidence="ECO:0000269|Ref.3"
FT                   /id="VAR_068971"
FT   VARIANT         447
FT                   /note="A -> T (in dbSNP:rs1805152)"
FT                   /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.3"
FT                   /id="VAR_014465"
FT   VARIANT         534
FT                   /note="R -> W (in dbSNP:rs12140223)"
FT                   /id="VAR_059209"
FT   VARIANT         683
FT                   /note="P -> L (in dbSNP:rs12746751)"
FT                   /id="VAR_061095"
FT   MUTAGEN         259
FT                   /note="E->N: Calcium insensitive."
FT                   /evidence="ECO:0000269|PubMed:23148261"
FT   MUTAGEN         261
FT                   /note="E->Q: Calcium insensitive."
FT                   /evidence="ECO:0000269|PubMed:23148261"
FT   MUTAGEN         278
FT                   /note="D->N: Calcium insensitive."
FT                   /evidence="ECO:0000269|PubMed:23148261"
FT   MUTAGEN         281
FT                   /note="E->D: Calcium insensitive."
FT                   /evidence="ECO:0000269|PubMed:23148261"
FT   CONFLICT        28
FT                   /note="I -> V (in Ref. 2; BAG60545)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        451
FT                   /note="G -> D (in Ref. 2; BAG60545)"
FT                   /evidence="ECO:0000305"
FT   HELIX           547..550
FT                   /evidence="ECO:0007829|PDB:2PFI"
FT   HELIX           564..572
FT                   /evidence="ECO:0007829|PDB:2PFI"
FT   STRAND          577..583
FT                   /evidence="ECO:0007829|PDB:2PFI"
FT   TURN            585..587
FT                   /evidence="ECO:0007829|PDB:2PFI"
FT   STRAND          589..595
FT                   /evidence="ECO:0007829|PDB:2PFI"
FT   HELIX           596..604
FT                   /evidence="ECO:0007829|PDB:2PFI"
FT   HELIX           618..623
FT                   /evidence="ECO:0007829|PDB:2PFI"
FT   HELIX           641..650
FT                   /evidence="ECO:0007829|PDB:2PFI"
FT   STRAND          654..660
FT                   /evidence="ECO:0007829|PDB:2PFI"
FT   STRAND          663..669
FT                   /evidence="ECO:0007829|PDB:2PFI"
FT   HELIX           670..681
FT                   /evidence="ECO:0007829|PDB:2PFI"
SQ   SEQUENCE   687 AA;  75285 MW;  E97C6928470A4460 CRC64;
     MEELVGLREG FSGDPVTLQE LWGPCPHIRR AIQGGLEWLK QKVFRLGEDW YFLMTLGVLM
     ALVSYAMNFA IGCVVRAHQW LYREIGDSHL LRYLSWTVYP VALVSFSSGF SQSITPSSGG
     SGIPELKTML AGVILEDYLD IKNFGAKVVG LSCTLATGST LFLGKVGPFV HLSVMIAAYL
     GRVRTTTIGE PENKSKQNEM LVAAAAVGVA TVFAAPFSGV LFSIEVMSSH FSVRDYWRGF
     FAATCGAFIF RLLAVFNSEQ ETITSLYKTS FRVDVPFDLP EIFFFVALGG ICGVLSCAYL
     FCQRTFLSFI KTNRYSSKLL ATSKPVYSAL ATLLLASITY PPGVGHFLAS RLSMKQHLDS
     LFDNHSWALM TQNSSPPWPE ELDPQHLWWE WYHPRFTIFG TLAFFLVMKF WMLILATTIP
     MPAGYFMPIF ILGAAIGRLL GEALAVAFPE GIVTGGVTNP IMPGGYALAG AAAFSGAVTH
     TISTALLAFE LTGQIVHALP VLMAVLAANA IAQSCQPSFY DGTIIVKKLP YLPRILGRNI
     GSHHVRVEHF MNHSITTLAK DTPLEEVVKV VTSTDVTEYP LVESTESQIL VGIVQRAQLV
     QALQAEPPSR APGHQQCLQD ILARGCPTEP VTLTLFSETT LHQAQNLFKL LNLQSLFVTS
     RGRAVGCVSW VEMKKAISNL TNPPAPK
//