S12A2_HUMAN
ID S12A2_HUMAN Reviewed; 1212 AA.
AC P55011; Q8N713; Q8WWH7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Solute carrier family 12 member 2;
DE AltName: Full=Basolateral Na-K-Cl symporter;
DE AltName: Full=Bumetanide-sensitive sodium-(potassium)-chloride cotransporter 2;
GN Name=SLC12A2; Synonyms=NKCC1;
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), FUNCTION, ACTIVITY REGULATION,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Colon;
RX PubMed=7629105; DOI=10.1074/jbc.270.30.17977;
RA Payne J.A., Xu J.-C., Haas M., Lytle Y.C., Ward D., Forbush B. III;
RT "Primary structure, functional expression, and chromosomal localization of
RT the bumetanide-sensitive Na-K-Cl cotransporter in human colon.";
RL J. Biol. Chem. 270:17977-17985(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 740-1066 (ISOFORM 2).
RC TISSUE=Eye;
RX PubMed=11700976; DOI=10.1006/abio.2001.5398;
RA Vibat C.R., Holland M.J., Kang J.J., Putney L.K., O'Donnell M.E.;
RT "Quantitation of Na(+)-K(+)-2Cl(-) cotransport splice variants in human
RT tissues using kinetic polymerase chain reaction.";
RL Anal. Biochem. 298:218-230(2001).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77 AND SER-79, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [5]
RP ACTIVITY REGULATION.
RX PubMed=21613606; DOI=10.1152/ajpcell.00070.2011;
RA Cruz-Rangel S., Melo Z., Vazquez N., Meade P., Bobadilla N.A.,
RA Pasantes-Morales H., Gamba G., Mercado A.;
RT "Similar Effects of all WNK3 Variants upon SLC12 Cotransporters.";
RL Am. J. Physiol. 301:C601-C608(2011).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77; THR-217; SER-940 AND
RP SER-994, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [8] {ECO:0007744|PDB:6PZT}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.46 ANGSTROMS), FUNCTION, ACTIVITY
RP REGULATION, SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY, AND MUTAGENESIS OF
RP ARG-294.
RX PubMed=32081947; DOI=10.1038/s41467-020-14790-3;
RA Yang X., Wang Q., Cao E.;
RT "Structure of the human cation-chloride cotransporter NKCC1 determined by
RT single-particle electron cryo-microscopy.";
RL Nat. Commun. 11:1016-1016(2020).
RN [9]
RP INVOLVEMENT IN KILQS.
RX PubMed=30740830; DOI=10.1002/humu.23722;
RG Undiagnosed Diseases Network;
RA Macnamara E.F., Koehler A.E., D'Souza P., Estwick T., Lee P., Vezina G.,
RA Fauni H., Braddock S.R., Torti E., Holt J.M., Sharma P., Malicdan M.C.V.,
RA Tifft C.J.;
RT "Kilquist syndrome: A novel syndromic hearing loss disorder caused by
RT homozygous deletion of SLC12A2.";
RL Hum. Mutat. 40:532-538(2019).
RN [10]
RP INVOLVEMENT IN DFNA78, INVOLVEMENT IN DELMNES, VARIANTS DELMNES VAL-327;
RP ILE-376; LEU-379; GLN-410; 892-TRP--SER-1212 DEL AND LYS-980, AND VARIANT
RP DFNA78 LYS-979.
RX PubMed=32658972; DOI=10.1093/brain/awaa176;
RA McNeill A., Iovino E., Mansard L., Vache C., Baux D., Bedoukian E., Cox H.,
RA Dean J., Goudie D., Kumar A., Newbury-Ecob R., Fallerini C., Renieri A.,
RA Lopergolo D., Mari F., Blanchet C., Willems M., Roux A.F., Pippucci T.,
RA Delpire E.;
RT "SLC12A2 variants cause a neurodevelopmental disorder or cochleovestibular
RT defect.";
RL Brain 143:2380-2387(2020).
RN [11]
RP INVOLVEMENT IN KILQS.
RX PubMed=32754646; DOI=10.1212/nxg.0000000000000478;
RA Stoedberg T., Magnusson M., Lesko N., Wredenberg A., Martin Munoz D.,
RA Stranneheim H., Wedell A.;
RT "SLC12A2 mutations cause NKCC1 deficiency with encephalopathy and impaired
RT secretory epithelia.";
RL Neurol. Genet. 6:e478-e478(2020).
RN [12]
RP INVOLVEMENT IN DFNA78, FUNCTION, VARIANTS DFNA78 LYS-979; TYR-981 AND
RP THR-988, AND CHARACTERIZATION OF VARIANTS DFNA78 TYR-981 AND THR-988.
RX PubMed=32294086; DOI=10.1371/journal.pgen.1008643;
RA Mutai H., Wasano K., Momozawa Y., Kamatani Y., Miya F., Masuda S.,
RA Morimoto N., Nara K., Takahashi S., Tsunoda T., Homma K., Kubo M.,
RA Matsunaga T.;
RT "Variants encoding a restricted carboxy-terminal domain of SLC12A2 cause
RT hereditary hearing loss in humans.";
RL PLoS Genet. 16:e1008643-e1008643(2020).
CC -!- FUNCTION: Cation-chloride cotransporter which mediates the
CC electroneutral transport of chloride, potassium and/or sodium ions
CC across the membrane (PubMed:32294086). Plays a vital role in the
CC regulation of ionic balance and cell volume.
CC {ECO:0000269|PubMed:32081947, ECO:0000269|PubMed:32294086,
CC ECO:0000269|PubMed:7629105}.
CC -!- ACTIVITY REGULATION: Inhibited by bumetanide (PubMed:7629105,
CC PubMed:32081947). Activated by WNK3 (PubMed:21613606).
CC {ECO:0000269|PubMed:21613606, ECO:0000269|PubMed:32081947,
CC ECO:0000269|PubMed:7629105}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:32081947}.
CC -!- INTERACTION:
CC P55011; P15311: EZR; NbExp=3; IntAct=EBI-2801449, EBI-1056902;
CC P55011; O95747: OXSR1; NbExp=3; IntAct=EBI-2801449, EBI-620853;
CC -!- SUBCELLULAR LOCATION: Basolateral cell membrane
CC {ECO:0000305|PubMed:32081947, ECO:0000305|PubMed:7629105}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P55011-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P55011-3; Sequence=VSP_006105;
CC -!- TISSUE SPECIFICITY: Expressed in many tissues.
CC {ECO:0000269|PubMed:7629105}.
CC -!- DISEASE: Deafness, autosomal dominant, 78 (DFNA78) [MIM:619081]: A form
CC of non-syndromic deafness characterized by congenital, profound
CC bilateral sensorineural hearing loss affecting all frequencies. Some
CC patients may have mild motor delay early in life due to vestibular
CC dysfunction. Sensorineural hearing loss results from damage to the
CC neural receptors of the inner ear, the nerve pathways to the brain, or
CC the area of the brain that receives sound information.
CC {ECO:0000269|PubMed:32294086, ECO:0000269|PubMed:32658972}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Delpire-McNeill syndrome (DELMNES) [MIM:619083]: An autosomal
CC dominant neurodevelopmental disorder characterized by global
CC developmental delay, hypotonia with delayed or absent walking,
CC bilateral sensorineural deafness, poor or absent speech, and mild to
CC severe intellectual disability. Additional variable features may
CC include spasticity or minor involvement of other organ systems, such as
CC hip dislocation or ventricular septal defect.
CC {ECO:0000269|PubMed:32658972}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Kilquist syndrome (KILQS) [MIM:619080]: An autosomal
CC recessive, multisystem disorder characterized by severe global
CC developmental delay, sensorineural hearing loss, poor overall growth,
CC mild facial dysmorphism, gastrointestinal anomalies such as
CC gastroesophageal reflux or midgut malrotation, and a striking lack of
CC tear fluid, saliva, and sweat. {ECO:0000269|PubMed:30740830,
CC ECO:0000269|PubMed:32754646}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the SLC12A transporter family. {ECO:0000305}.
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DR EMBL; U30246; AAC50561.1; -; mRNA.
DR EMBL; AF439152; AAL32454.1; -; mRNA.
DR CCDS; CCDS4144.1; -. [P55011-1]
DR CCDS; CCDS58965.1; -. [P55011-3]
DR PIR; A57187; A57187.
DR RefSeq; NP_001037.1; NM_001046.2. [P55011-1]
DR PDB; 6PZT; EM; 3.46 A; A/B=1-1212.
DR PDB; 7D10; EM; 3.52 A; A/B=1-1212.
DR PDBsum; 6PZT; -.
DR PDBsum; 7D10; -.
DR AlphaFoldDB; P55011; -.
DR SMR; P55011; -.
DR BioGRID; 112447; 220.
DR DIP; DIP-43979N; -.
DR IntAct; P55011; 39.
DR MINT; P55011; -.
DR STRING; 9606.ENSP00000262461; -.
DR BindingDB; P55011; -.
DR ChEMBL; CHEMBL1615383; -.
DR DrugBank; DB00887; Bumetanide.
DR DrugBank; DB11098; Potassium bicarbonate.
DR DrugBank; DB00761; Potassium chloride.
DR DrugBank; DB01325; Quinethazone.
DR DrugBank; DB00214; Torasemide.
DR DrugCentral; P55011; -.
DR GuidetoPHARMACOLOGY; 969; -.
DR TCDB; 2.A.30.1.4; the cation-chloride cotransporter (ccc) family.
DR GlyConnect; 1761; 3 N-Linked glycans (1 site).
DR GlyGen; P55011; 4 sites, 3 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; P55011; -.
DR PhosphoSitePlus; P55011; -.
DR BioMuta; SLC12A2; -.
DR DMDM; 1709292; -.
DR EPD; P55011; -.
DR jPOST; P55011; -.
DR MassIVE; P55011; -.
DR MaxQB; P55011; -.
DR PaxDb; P55011; -.
DR PeptideAtlas; P55011; -.
DR PRIDE; P55011; -.
DR ProteomicsDB; 56757; -. [P55011-1]
DR ProteomicsDB; 56758; -. [P55011-3]
DR Antibodypedia; 14071; 374 antibodies from 40 providers.
DR DNASU; 6558; -.
DR Ensembl; ENST00000262461.7; ENSP00000262461.2; ENSG00000064651.14. [P55011-1]
DR Ensembl; ENST00000343225.4; ENSP00000340878.4; ENSG00000064651.14. [P55011-3]
DR GeneID; 6558; -.
DR KEGG; hsa:6558; -.
DR MANE-Select; ENST00000262461.7; ENSP00000262461.2; NM_001046.3; NP_001037.1.
DR UCSC; uc010jdg.4; human. [P55011-1]
DR CTD; 6558; -.
DR DisGeNET; 6558; -.
DR GeneCards; SLC12A2; -.
DR HGNC; HGNC:10911; SLC12A2.
DR HPA; ENSG00000064651; Tissue enhanced (salivary).
DR MalaCards; SLC12A2; -.
DR MIM; 600840; gene.
DR MIM; 619080; phenotype.
DR MIM; 619081; phenotype.
DR MIM; 619083; phenotype.
DR neXtProt; NX_P55011; -.
DR OpenTargets; ENSG00000064651; -.
DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability.
DR Orphanet; 528084; Non-specific syndromic intellectual disability.
DR PharmGKB; PA35806; -.
DR VEuPathDB; HostDB:ENSG00000064651; -.
DR eggNOG; KOG2083; Eukaryota.
DR GeneTree; ENSGT00940000155742; -.
DR HOGENOM; CLU_001883_0_0_1; -.
DR InParanoid; P55011; -.
DR OMA; DTISFEM; -.
DR PhylomeDB; P55011; -.
DR TreeFam; TF313191; -.
DR PathwayCommons; P55011; -.
DR Reactome; R-HSA-426117; Cation-coupled Chloride cotransporters.
DR SignaLink; P55011; -.
DR SIGNOR; P55011; -.
DR BioGRID-ORCS; 6558; 15 hits in 1082 CRISPR screens.
DR ChiTaRS; SLC12A2; human.
DR GenomeRNAi; 6558; -.
DR Pharos; P55011; Tclin.
DR PRO; PR:P55011; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P55011; protein.
DR Bgee; ENSG00000064651; Expressed in palpebral conjunctiva and 191 other tissues.
DR ExpressionAtlas; P55011; baseline and differential.
DR Genevisible; P55011; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0009925; C:basal plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044297; C:cell body; ISS:ARUK-UCL.
DR GO; GO:0044298; C:cell body membrane; TAS:ARUK-UCL.
DR GO; GO:0071944; C:cell periphery; IDA:ARUK-UCL.
DR GO; GO:0042995; C:cell projection; ISS:ARUK-UCL.
DR GO; GO:0031253; C:cell projection membrane; TAS:ARUK-UCL.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:ARUK-UCL.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:1903561; C:extracellular vesicle; HDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0016328; C:lateral plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0043005; C:neuron projection; IDA:ARUK-UCL.
DR GO; GO:0043025; C:neuronal cell body; IDA:ARUK-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0008519; F:ammonium transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0015377; F:cation:chloride symporter activity; IDA:ARUK-UCL.
DR GO; GO:0051087; F:chaperone binding; IPI:ARUK-UCL.
DR GO; GO:0051879; F:Hsp90 protein binding; IPI:ARUK-UCL.
DR GO; GO:0046873; F:metal ion transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:0015079; F:potassium ion transmembrane transporter activity; ISS:ARUK-UCL.
DR GO; GO:0015379; F:potassium:chloride symporter activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0008511; F:sodium:potassium:chloride symporter activity; IBA:GO_Central.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0072488; P:ammonium transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006884; P:cell volume homeostasis; ISS:ARUK-UCL.
DR GO; GO:0030644; P:cellular chloride ion homeostasis; ISS:ARUK-UCL.
DR GO; GO:0030007; P:cellular potassium ion homeostasis; ISS:ARUK-UCL.
DR GO; GO:1990869; P:cellular response to chemokine; IMP:BHF-UCL.
DR GO; GO:0035865; P:cellular response to potassium ion; ISS:ARUK-UCL.
DR GO; GO:0006883; P:cellular sodium ion homeostasis; ISS:ARUK-UCL.
DR GO; GO:0055064; P:chloride ion homeostasis; IBA:GO_Central.
DR GO; GO:1902476; P:chloride transmembrane transport; ISS:ARUK-UCL.
DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; ISS:ARUK-UCL.
DR GO; GO:0006972; P:hyperosmotic response; IEA:Ensembl.
DR GO; GO:0098658; P:inorganic anion import across plasma membrane; ISS:ARUK-UCL.
DR GO; GO:0098659; P:inorganic cation import across plasma membrane; IDA:ARUK-UCL.
DR GO; GO:0006811; P:ion transport; TAS:Reactome.
DR GO; GO:0035633; P:maintenance of blood-brain barrier; ISS:ARUK-UCL.
DR GO; GO:0061044; P:negative regulation of vascular wound healing; ISS:ARUK-UCL.
DR GO; GO:1904450; P:positive regulation of aspartate secretion; ISS:ARUK-UCL.
DR GO; GO:0045795; P:positive regulation of cell volume; IEA:Ensembl.
DR GO; GO:0055075; P:potassium ion homeostasis; IBA:GO_Central.
DR GO; GO:1990573; P:potassium ion import across plasma membrane; ISS:ARUK-UCL.
DR GO; GO:1904464; P:regulation of matrix metallopeptidase secretion; ISS:ARUK-UCL.
DR GO; GO:0150003; P:regulation of spontaneous synaptic transmission; ISS:ARUK-UCL.
DR GO; GO:0055078; P:sodium ion homeostasis; IBA:GO_Central.
DR GO; GO:0098719; P:sodium ion import across plasma membrane; ISS:ARUK-UCL.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0010818; P:T cell chemotaxis; IMP:BHF-UCL.
DR GO; GO:0070634; P:transepithelial ammonium transport; IDA:UniProtKB.
DR GO; GO:0030321; P:transepithelial chloride transport; IDA:UniProtKB.
DR GO; GO:0150104; P:transport across blood-brain barrier; NAS:ARUK-UCL.
DR InterPro; IPR004841; AA-permease/SLC12A_dom.
DR InterPro; IPR013612; AA_permease_N.
DR InterPro; IPR002444; NKCC1.
DR InterPro; IPR018491; SLC12_C.
DR InterPro; IPR002443; SLC12A1/SLC12A2.
DR InterPro; IPR004842; SLC12A_fam.
DR PANTHER; PTHR11827; PTHR11827; 1.
DR PANTHER; PTHR11827:SF58; PTHR11827:SF58; 1.
DR Pfam; PF00324; AA_permease; 1.
DR Pfam; PF08403; AA_permease_N; 1.
DR Pfam; PF03522; SLC12; 1.
DR PRINTS; PR01207; NAKCLTRNSPRT.
DR PRINTS; PR01208; NAKCLTRSPRT1.
DR TIGRFAMs; TIGR00930; 2a30; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell membrane; Chloride;
KW Deafness; Disease variant; Disulfide bond; Intellectual disability;
KW Ion transport; Membrane; Non-syndromic deafness; Phosphoprotein; Potassium;
KW Potassium transport; Reference proteome; Sodium; Sodium transport; Symport;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1212
FT /note="Solute carrier family 12 member 2"
FT /id="PRO_0000178023"
FT TOPO_DOM 1..286
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 287..313
FT /note="Discontinuously helical"
FT /evidence="ECO:0000255"
FT INTRAMEM 287..299
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:32081947"
FT INTRAMEM 300..307
FT /evidence="ECO:0000305|PubMed:32081947"
FT INTRAMEM 308..313
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:32081947"
FT TOPO_DOM 314..321
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 322..343
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 344..361
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 362..397
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 398..406
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 407..424
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 425..429
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 430..454
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 455..486
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 487..507
FT /note="Discontinuously helical"
FT /evidence="ECO:0000255"
FT INTRAMEM 487..498
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:32081947"
FT INTRAMEM 499..500
FT /evidence="ECO:0000305|PubMed:32081947"
FT INTRAMEM 501..507
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:32081947"
FT TOPO_DOM 508..514
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 515..542
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 543..599
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 600..632
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 633..653
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 654..668
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 669..670
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 671..697
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 698..711
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 712..730
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 731
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 732..751
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 752..1212
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 36..81
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 112..138
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 150..193
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 962..989
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 170..187
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 962..988
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22223895"
FT MOD_RES 77
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 79
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 212
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P55014"
FT MOD_RES 217
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 230
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P55016"
FT MOD_RES 242
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55016"
FT MOD_RES 266
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P55012"
FT MOD_RES 940
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 944
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P55012"
FT MOD_RES 994
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT DISULFID 563..568
FT /evidence="ECO:0000269|PubMed:32081947,
FT ECO:0007744|PDB:6PZT"
FT DISULFID 577..582
FT /evidence="ECO:0000269|PubMed:32081947,
FT ECO:0007744|PDB:6PZT"
FT VAR_SEQ 976..991
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11700976"
FT /id="VSP_006105"
FT VARIANT 327
FT /note="A -> V (in DELMNES)"
FT /evidence="ECO:0000269|PubMed:32658972"
FT /id="VAR_085083"
FT VARIANT 376
FT /note="N -> I (in DELMNES)"
FT /evidence="ECO:0000269|PubMed:32658972"
FT /id="VAR_085084"
FT VARIANT 379
FT /note="A -> L (in DELMNES; requires 2 nucleotide
FT substitutions)"
FT /evidence="ECO:0000269|PubMed:32658972"
FT /id="VAR_085085"
FT VARIANT 410
FT /note="R -> Q (in DELMNES; dbSNP:rs537215758)"
FT /evidence="ECO:0000269|PubMed:32658972"
FT /id="VAR_085086"
FT VARIANT 892..1212
FT /note="Missing (in DELMNES)"
FT /evidence="ECO:0000269|PubMed:32658972"
FT /id="VAR_085087"
FT VARIANT 979
FT /note="E -> K (in DFNA78; dbSNP:rs1581138934)"
FT /evidence="ECO:0000269|PubMed:32294086,
FT ECO:0000269|PubMed:32658972"
FT /id="VAR_085088"
FT VARIANT 980
FT /note="E -> K (in DELMNES)"
FT /evidence="ECO:0000269|PubMed:32658972"
FT /id="VAR_085089"
FT VARIANT 981
FT /note="D -> Y (in DFNA78; reduced chloride transmembrane
FT transport; dbSNP:rs1581138944)"
FT /evidence="ECO:0000269|PubMed:32294086"
FT /id="VAR_085090"
FT VARIANT 988
FT /note="P -> T (in DFNA78; reduced chloride transmembrane
FT transport; dbSNP:rs1581138965)"
FT /evidence="ECO:0000269|PubMed:32294086"
FT /id="VAR_085091"
FT MUTAGEN 294
FT /note="R->A: Severely impairs transporter activity."
FT /evidence="ECO:0000269|PubMed:32081947"
FT HELIX 290..299
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 302..314
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 317..341
FT /evidence="ECO:0007829|PDB:6PZT"
FT TURN 342..344
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 352..359
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 362..397
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 405..424
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 431..453
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 458..460
FT /evidence="ECO:0007829|PDB:6PZT"
FT STRAND 463..465
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 470..474
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 487..494
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 495..498
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 501..505
FT /evidence="ECO:0007829|PDB:6PZT"
FT TURN 506..508
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 515..517
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 518..541
FT /evidence="ECO:0007829|PDB:6PZT"
FT STRAND 552..556
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 566..570
FT /evidence="ECO:0007829|PDB:6PZT"
FT STRAND 578..580
FT /evidence="ECO:0007829|PDB:6PZT"
FT STRAND 583..588
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 592..596
FT /evidence="ECO:0007829|PDB:6PZT"
FT STRAND 597..599
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 600..631
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 636..638
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 642..644
FT /evidence="ECO:0007829|PDB:6PZT"
FT STRAND 646..649
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 653..667
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 671..697
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 713..729
FT /evidence="ECO:0007829|PDB:6PZT"
FT HELIX 732..751
FT /evidence="ECO:0007829|PDB:6PZT"
SQ SEQUENCE 1212 AA; 131447 MW; A6BF174ACCDA2EC1 CRC64;
MEPRPTAPSS GAPGLAGVGE TPSAAALAAA RVELPGTAVP SVPEDAAPAS RDGGGVRDEG
PAAAGDGLGR PLGPTPSQSR FQVDLVSENA GRAAAAAAAA AAAAAAAGAG AGAKQTPADG
EASGESEPAK GSEEAKGRFR VNFVDPAASS SAEDSLSDAA GVGVDGPNVS FQNGGDTVLS
EGSSLHSGGG GGSGHHQHYY YDTHTNTYYL RTFGHNTMDA VPRIDHYRHT AAQLGEKLLR
PSLAELHDEL EKEPFEDGFA NGEESTPTRD AVVTYTAESK GVVKFGWIKG VLVRCMLNIW
GVMLFIRLSW IVGQAGIGLS VLVIMMATVV TTITGLSTSA IATNGFVRGG GAYYLISRSL
GPEFGGAIGL IFAFANAVAV AMYVVGFAET VVELLKEHSI LMIDEINDIR IIGAITVVIL
LGISVAGMEW EAKAQIVLLV ILLLAIGDFV IGTFIPLESK KPKGFFGYKS EIFNENFGPD
FREEETFFSV FAIFFPAATG ILAGANISGD LADPQSAIPK GTLLAILITT LVYVGIAVSV
GSCVVRDATG NVNDTIVTEL TNCTSAACKL NFDFSSCESS PCSYGLMNNF QVMSMVSGFT
PLISAGIFSA TLSSALASLV SAPKIFQALC KDNIYPAFQM FAKGYGKNNE PLRGYILTFL
IALGFILIAE LNVIAPIISN FFLASYALIN FSVFHASLAK SPGWRPAFKY YNMWISLLGA
ILCCIVMFVI NWWAALLTYV IVLGLYIYVT YKKPDVNWGS STQALTYLNA LQHSIRLSGV
EDHVKNFRPQ CLVMTGAPNS RPALLHLVHD FTKNVGLMIC GHVHMGPRRQ AMKEMSIDQA
KYQRWLIKNK MKAFYAPVHA DDLREGAQYL MQAAGLGRMK PNTLVLGFKK DWLQADMRDV
DMYINLFHDA FDIQYGVVVI RLKEGLDISH LQGQEELLSS QEKSPGTKDV VVSVEYSKKS
DLDTSKPLSE KPITHKVEEE DGKTATQPLL KKESKGPIVP LNVADQKLLE ASTQFQKKQG
KNTIDVWWLF DDGGLTLLIP YLLTTKKKWK DCKIRVFIGG KINRIDHDRR AMATLLSKFR
IDFSDIMVLG DINTKPKKEN IIAFEEIIEP YRLHEDDKEQ DIADKMKEDE PWRITDNELE
LYKTKTYRQI RLNELLKEHS STANIIVMSL PVARKGAVSS ALYMAWLEAL SKDLPPILLV
RGNHQSVLTF YS
