CLCKA_HUMAN
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 03-AUG-2022, entry version 190.
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; Q8N865: C7orf31; NbExp=3; IntAct=EBI-11980535, EBI-10174456;
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; 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; P51800; -.
DR PeptideAtlas; P51800; -.
DR PRIDE; P51800; -.
DR ProteomicsDB; 17361; -.
DR ProteomicsDB; 56399; -. [P51800-1]
DR ProteomicsDB; 64544; -.
DR Antibodypedia; 29061; 190 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 CTD; 1187; -.
DR DisGeNET; 1187; -.
DR GeneCards; CLCNKA; -.
DR HGNC; HGNC:2026; CLCNKA.
DR HPA; ENSG00000186510; Tissue enhanced (kidney, parathyroid gland).
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; YWRAFFS; -.
DR OrthoDB; 271925at2759; -.
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 1068 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 93 other tissues.
DR Genevisible; P51800; HS.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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:0034765; P:regulation of ion transmembrane transport; IEA:UniProtKB-KW.
DR GO; GO:0070293; P:renal absorption; TAS:UniProtKB.
DR GO; GO:0030321; P:transepithelial chloride transport; TAS:ProtInc.
DR Gene3D; 3.10.580.10; -; 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 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; SSF54631; 1.
DR SUPFAM; SSF81340; SSF81340; 1.
DR PROSITE; PS51371; CBS; 2.
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
