ID   S12A5_HUMAN             Reviewed;        1139 AA.
AC   Q9H2X9; A2RTX2; Q5VZ41; Q9H4Z0; Q9ULP4;
DT   13-DEC-2002, integrated into UniProtKB/Swiss-Prot.
DT   04-DEC-2007, sequence version 3.
DT   03-AUG-2022, entry version 174.
DE   RecName: Full=Solute carrier family 12 member 5;
DE   AltName: Full=Electroneutral potassium-chloride cotransporter 2;
DE   AltName: Full=K-Cl cotransporter 2;
DE            Short=hKCC2;
DE   AltName: Full=Neuronal K-Cl cotransporter;
GN   Name=SLC12A5; Synonyms=KCC2, KIAA1176;
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 2).
RC   TISSUE=Brain;
RX   PubMed=12106695; DOI=10.1016/s0169-328x(02)00190-0;
RA   Song L., Mercado A., Vazquez N., Xie Q., Desai R., George A.L. Jr.,
RA   Gamba G., Mount D.B.;
RT   "Molecular, functional, and genomic characterization of human KCC2, the
RT   neuronal K-Cl cotransporter.";
RL   Brain Res. Mol. Brain Res. 103:91-105(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=11780052; DOI=10.1038/414865a;
RA   Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA   Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA   Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA   Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA   Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA   Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA   Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA   Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA   Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA   Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA   Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA   Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA   Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA   Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA   Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA   Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA   Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA   Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA   Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA   Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA   Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA   Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 20.";
RL   Nature 414:865-871(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [LARGE SCALE MRNA] OF 1-175 (ISOFORM 1).
RX   PubMed=16344560; DOI=10.1101/gr.4039406;
RA   Kimura K., Wakamatsu A., Suzuki Y., Ota T., Nishikawa T., Yamashita R.,
RA   Yamamoto J., Sekine M., Tsuritani K., Wakaguri H., Ishii S., Sugiyama T.,
RA   Saito K., Isono Y., Irie R., Kushida N., Yoneyama T., Otsuka R., Kanda K.,
RA   Yokoi T., Kondo H., Wagatsuma M., Murakawa K., Ishida S., Ishibashi T.,
RA   Takahashi-Fujii A., Tanase T., Nagai K., Kikuchi H., Nakai K., Isogai T.,
RA   Sugano S.;
RT   "Diversification of transcriptional modulation: large-scale identification
RT   and characterization of putative alternative promoters of human genes.";
RL   Genome Res. 16:55-65(2006).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 9-1109 (ISOFORM 2), AND VARIANT
RP   LEU-1100.
RC   TISSUE=Brain;
RX   PubMed=10574461; DOI=10.1093/dnares/6.5.329;
RA   Hirosawa M., Nagase T., Ishikawa K., Kikuno R., Nomura N., Ohara O.;
RT   "Characterization of cDNA clones selected by the GeneMark analysis from
RT   size-fractionated cDNA libraries from human brain.";
RL   DNA Res. 6:329-336(1999).
RN   [6]
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   [7]
RP   FUNCTION, INVOLVEMENT IN EIG14, VARIANT EIG14 HIS-975, AND CHARACTERIZATION
RP   OF VARIANT EIG14 HIS-975.
RX   PubMed=24668262; DOI=10.1002/embr.201438749;
RA   Puskarjov M., Seja P., Heron S.E., Williams T.C., Ahmad F., Iona X.,
RA   Oliver K.L., Grinton B.E., Vutskits L., Scheffer I.E., Petrou S.,
RA   Blaesse P., Dibbens L.M., Berkovic S.F., Kaila K.;
RT   "A variant of KCC2 from patients with febrile seizures impairs neuronal
RT   Cl- extrusion and dendritic spine formation.";
RL   EMBO Rep. 15:723-729(2014).
RN   [8]
RP   INVOLVEMENT IN DEE34, VARIANTS DEE34 HIS-311; PRO-426 AND ASP-551, AND
RP   CHARACTERIZATION OF VARIANTS DEE34 HIS-311; PRO-426 AND ASP-551.
RX   PubMed=26333769; DOI=10.1038/ncomms9038;
RA   Stoedberg T., McTague A., Ruiz A.J., Hirata H., Zhen J., Long P.,
RA   Farabella I., Meyer E., Kawahara A., Vassallo G., Stivaros S.M.,
RA   Bjursell M.K., Stranneheim H., Tigerschioeld S., Persson B., Bangash I.,
RA   Das K., Hughes D., Lesko N., Lundeberg J., Scott R.C., Poduri A.,
RA   Scheffer I.E., Smith H., Gissen P., Schorge S., Reith M.E., Topf M.,
RA   Kullmann D.M., Harvey R.J., Wedell A., Kurian M.A.;
RT   "Mutations in SLC12A5 in epilepsy of infancy with migrating focal
RT   seizures.";
RL   Nat. Commun. 6:8038-8038(2015).
RN   [9]
RP   VARIANT [LARGE SCALE ANALYSIS] ASP-847.
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   [10]
RP   INVOLVEMENT IN EIG14, VARIANTS EIG14 HIS-975 AND CYS-1072, AND
RP   CHARACTERIZATION OF VARIANTS EIG14 HIS-975 AND CYS-1072.
RX   PubMed=24928908; DOI=10.15252/embr.201438840;
RA   Kahle K.T., Merner N.D., Friedel P., Silayeva L., Liang B., Khanna A.,
RA   Shang Y., Lachance-Touchette P., Bourassa C., Levert A., Dion P.A.,
RA   Walcott B., Spiegelman D., Dionne-Laporte A., Hodgkinson A., Awadalla P.,
RA   Nikbakht H., Majewski J., Cossette P., Deeb T.Z., Moss S.J., Medina I.,
RA   Rouleau G.A.;
RT   "Genetically encoded impairment of neuronal KCC2 cotransporter function in
RT   human idiopathic generalized epilepsy.";
RL   EMBO Rep. 15:766-774(2014).
RN   [11]
RP   VARIANT TRP-1071, AND VARIANTS EIG14 HIS-975 AND CYS-1072.
RX   PubMed=26528127; DOI=10.3389/fncel.2015.00386;
RA   Merner N.D., Chandler M.R., Bourassa C., Liang B., Khanna A.R., Dion P.,
RA   Rouleau G.A., Kahle K.T.;
RT   "Regulatory domain or CpG site variation in SLC12A5, encoding the chloride
RT   transporter KCC2, in human autism and schizophrenia.";
RL   Front. Cell. Neurosci. 9:386-386(2015).
CC   -!- FUNCTION: Mediates electroneutral potassium-chloride cotransport in
CC       mature neurons and is required for neuronal Cl(-) homeostasis. As major
CC       extruder of intracellular chloride, it establishes the low neuronal
CC       Cl(-) levels required for chloride influx after binding of GABA-A and
CC       glycine to their receptors, with subsequent hyperpolarization and
CC       neuronal inhibition (By similarity). Involved in the regulation of
CC       dendritic spine formation and maturation (PubMed:24668262).
CC       {ECO:0000250|UniProtKB:Q63633, ECO:0000269|PubMed:24668262}.
CC   -!- ACTIVITY REGULATION: Inhibited by WNK3. {ECO:0000269|PubMed:21613606}.
CC   -!- SUBUNIT: Homomultimer and heteromultimer with other K-Cl
CC       cotransporters. Interacts with AP2A1 (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=KCC2a;
CC         IsoId=Q9H2X9-1; Sequence=Displayed;
CC       Name=2; Synonyms=KCC2b;
CC         IsoId=Q9H2X9-2; Sequence=VSP_029909;
CC   -!- TISSUE SPECIFICITY: Brain specific. Detected in neuronal cells.
CC   -!- DISEASE: Developmental and epileptic encephalopathy 34 (DEE34)
CC       [MIM:616645]: A form of epileptic encephalopathy, a heterogeneous group
CC       of severe early-onset epilepsies characterized by refractory seizures,
CC       neurodevelopmental impairment, and poor prognosis. Development is
CC       normal prior to seizure onset, after which cognitive and motor delays
CC       become apparent. DEE34 is characterized by onset of refractory
CC       migrating focal seizures in infancy. Affected children show
CC       developmental regression and are severely impaired globally.
CC       {ECO:0000269|PubMed:26333769}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- DISEASE: Epilepsy, idiopathic generalized 14 (EIG14) [MIM:616685]: An
CC       autosomal dominant form of idiopathic generalized epilepsy, a disorder
CC       characterized by recurring generalized seizures in the absence of
CC       detectable brain lesions and/or metabolic abnormalities. Generalized
CC       seizures arise diffusely and simultaneously from both hemispheres of
CC       the brain. Seizure types include juvenile myoclonic seizures, absence
CC       seizures, and generalized tonic-clonic seizures.
CC       {ECO:0000269|PubMed:24668262, ECO:0000269|PubMed:24928908,
CC       ECO:0000269|PubMed:26528127}. Note=Disease susceptibility is associated
CC       with variants affecting the gene represented in this entry.
CC   -!- MISCELLANEOUS: Inhibited by furosemide and bumetanide.
CC   -!- SIMILARITY: Belongs to the SLC12A transporter family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AF208159; AAG43493.1; -; mRNA.
DR   EMBL; AL162458; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC132668; AAI32669.1; -; mRNA.
DR   EMBL; BC132670; AAI32671.1; -; mRNA.
DR   EMBL; AB033002; BAA86490.1; -; mRNA.
DR   EMBL; DA102113; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; DA328785; -; NOT_ANNOTATED_CDS; mRNA.
DR   CCDS; CCDS13391.1; -. [Q9H2X9-2]
DR   CCDS; CCDS46610.1; -. [Q9H2X9-1]
DR   RefSeq; NP_001128243.1; NM_001134771.1. [Q9H2X9-1]
DR   RefSeq; NP_065759.1; NM_020708.4. [Q9H2X9-2]
DR   PDB; 6M23; EM; 3.20 A; A/B=26-1139.
DR   PDB; 7D8Z; EM; 3.40 A; A/B=1-1139.
DR   PDBsum; 6M23; -.
DR   PDBsum; 7D8Z; -.
DR   AlphaFoldDB; Q9H2X9; -.
DR   SMR; Q9H2X9; -.
DR   BioGRID; 121538; 6.
DR   IntAct; Q9H2X9; 6.
DR   MINT; Q9H2X9; -.
DR   STRING; 9606.ENSP00000387694; -.
DR   BindingDB; Q9H2X9; -.
DR   ChEMBL; CHEMBL1615384; -.
DR   DrugBank; DB00887; Bumetanide.
DR   DrugBank; DB00761; Potassium chloride.
DR   GuidetoPHARMACOLOGY; 972; -.
DR   TCDB; 2.A.30.1.18; the cation-chloride cotransporter (ccc) family.
DR   GlyGen; Q9H2X9; 2 sites.
DR   iPTMnet; Q9H2X9; -.
DR   PhosphoSitePlus; Q9H2X9; -.
DR   SwissPalm; Q9H2X9; -.
DR   BioMuta; SLC12A5; -.
DR   DMDM; 161784306; -.
DR   EPD; Q9H2X9; -.
DR   jPOST; Q9H2X9; -.
DR   MassIVE; Q9H2X9; -.
DR   MaxQB; Q9H2X9; -.
DR   PaxDb; Q9H2X9; -.
DR   PeptideAtlas; Q9H2X9; -.
DR   PRIDE; Q9H2X9; -.
DR   ProteomicsDB; 80632; -. [Q9H2X9-1]
DR   ProteomicsDB; 80633; -. [Q9H2X9-2]
DR   ABCD; Q9H2X9; 1 sequenced antibody.
DR   Antibodypedia; 1580; 344 antibodies from 29 providers.
DR   DNASU; 57468; -.
DR   Ensembl; ENST00000243964.7; ENSP00000243964.4; ENSG00000124140.15. [Q9H2X9-2]
DR   Ensembl; ENST00000454036.6; ENSP00000387694.1; ENSG00000124140.15. [Q9H2X9-1]
DR   GeneID; 57468; -.
DR   KEGG; hsa:57468; -.
DR   MANE-Select; ENST00000243964.7; ENSP00000243964.4; NM_020708.5; NP_065759.1. [Q9H2X9-2]
DR   UCSC; uc002xrb.3; human. [Q9H2X9-1]
DR   CTD; 57468; -.
DR   DisGeNET; 57468; -.
DR   GeneCards; SLC12A5; -.
DR   GeneReviews; SLC12A5; -.
DR   HGNC; HGNC:13818; SLC12A5.
DR   HPA; ENSG00000124140; Tissue enhanced (brain, retina).
DR   MalaCards; SLC12A5; -.
DR   MIM; 606726; gene.
DR   MIM; 616645; phenotype.
DR   MIM; 616685; phenotype.
DR   neXtProt; NX_Q9H2X9; -.
DR   OpenTargets; ENSG00000124140; -.
DR   Orphanet; 293181; Malignant migrating focal seizures of infancy.
DR   PharmGKB; PA37814; -.
DR   VEuPathDB; HostDB:ENSG00000124140; -.
DR   eggNOG; KOG2082; Eukaryota.
DR   GeneTree; ENSGT00940000160827; -.
DR   HOGENOM; CLU_001883_1_2_1; -.
DR   InParanoid; Q9H2X9; -.
DR   OMA; RAGGHCS; -.
DR   OrthoDB; 1190626at2759; -.
DR   PhylomeDB; Q9H2X9; -.
DR   TreeFam; TF313657; -.
DR   PathwayCommons; Q9H2X9; -.
DR   Reactome; R-HSA-426117; Cation-coupled Chloride cotransporters.
DR   SignaLink; Q9H2X9; -.
DR   SIGNOR; Q9H2X9; -.
DR   BioGRID-ORCS; 57468; 21 hits in 1074 CRISPR screens.
DR   GeneWiki; Chloride_potassium_symporter_5; -.
DR   GenomeRNAi; 57468; -.
DR   Pharos; Q9H2X9; Tchem.
DR   PRO; PR:Q9H2X9; -.
DR   Proteomes; UP000005640; Chromosome 20.
DR   RNAct; Q9H2X9; protein.
DR   Bgee; ENSG00000124140; Expressed in right hemisphere of cerebellum and 130 other tissues.
DR   ExpressionAtlas; Q9H2X9; baseline and differential.
DR   Genevisible; Q9H2X9; HS.
DR   GO; GO:0071944; C:cell periphery; IDA:ARUK-UCL.
DR   GO; GO:0032590; C:dendrite membrane; IEA:Ensembl.
DR   GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR   GO; GO:0005887; C:integral component of plasma membrane; IEA:InterPro.
DR   GO; GO:0043005; C:neuron projection; IDA:ARUK-UCL.
DR   GO; GO:0043025; C:neuronal cell body; IDA:ARUK-UCL.
DR   GO; GO:0043204; C:perikaryon; IEA:Ensembl.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0045202; C:synapse; IEA:GOC.
DR   GO; GO:0008519; F:ammonium transmembrane transporter activity; IEA:Ensembl.
DR   GO; GO:0015108; F:chloride transmembrane transporter activity; IDA:UniProtKB.
DR   GO; GO:0015379; F:potassium:chloride symporter activity; IDA:UniProtKB.
DR   GO; GO:0019901; F:protein kinase binding; IPI:ParkinsonsUK-UCL.
DR   GO; GO:0006884; P:cell volume homeostasis; IBA:GO_Central.
DR   GO; GO:0030644; P:cellular chloride ion homeostasis; IDA:UniProtKB.
DR   GO; GO:0006873; P:cellular ion homeostasis; IDA:UniProtKB.
DR   GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR   GO; GO:0055064; P:chloride ion homeostasis; IBA:GO_Central.
DR   GO; GO:1902476; P:chloride transmembrane transport; IBA:GO_Central.
DR   GO; GO:0060996; P:dendritic spine development; IDA:UniProtKB.
DR   GO; GO:0006971; P:hypotonic response; IDA:UniProtKB.
DR   GO; GO:0051452; P:intracellular pH reduction; IEA:Ensembl.
DR   GO; GO:0006811; P:ion transport; IDA:UniProtKB.
DR   GO; GO:0007612; P:learning; IEA:Ensembl.
DR   GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR   GO; GO:0055075; P:potassium ion homeostasis; IBA:GO_Central.
DR   GO; GO:1990573; P:potassium ion import across plasma membrane; IBA:GO_Central.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR   GO; GO:0040040; P:thermosensory behavior; IEA:Ensembl.
DR   InterPro; IPR004841; AA-permease/SLC12A_dom.
DR   InterPro; IPR030358; KCC2.
DR   InterPro; IPR000076; KCL_cotranspt.
DR   InterPro; IPR018491; SLC12_C.
DR   InterPro; IPR004842; SLC12A_fam.
DR   PANTHER; PTHR11827; PTHR11827; 1.
DR   PANTHER; PTHR11827:SF54; PTHR11827:SF54; 1.
DR   Pfam; PF00324; AA_permease; 2.
DR   Pfam; PF03522; SLC12; 3.
DR   PRINTS; PR01081; KCLTRNSPORT.
DR   TIGRFAMs; TIGR00930; 2a30; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Chloride; Disease variant; Epilepsy;
KW   Glycoprotein; Ion transport; Membrane; Phosphoprotein; Potassium;
KW   Potassium transport; Reference proteome; Symport; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..1139
FT                   /note="Solute carrier family 12 member 5"
FT                   /id="PRO_0000178034"
FT   TOPO_DOM        1..133
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        134..154
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        156..176
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        177..194
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        195..215
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        217..237
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        238..254
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        255..275
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        278..298
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        299..418
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        419..439
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        459..479
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        480..496
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        497..517
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        570..590
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        591..630
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        631..651
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        848..868
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        869..1139
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REGION          1..63
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          92..116
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          942..1052
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        19..44
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        98..112
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        942..966
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        980..996
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1021..1040
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         57
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q63633"
FT   MOD_RES         1045
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q91V14"
FT   MOD_RES         1048
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q91V14"
FT   MOD_RES         1049
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q91V14"
FT   CARBOHYD        442
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        833
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1..40
FT                   /note="MSRRFTVTSLPPAGPARSPDPESRRHSVADPRHLPGEDVK -> MLNNLTDC
FT                   EDGDGGANP (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:10574461,
FT                   ECO:0000303|PubMed:12106695, ECO:0000303|PubMed:15489334"
FT                   /id="VSP_029909"
FT   VARIANT         311
FT                   /note="L -> H (in DEE34; results in reduced chloride
FT                   transport; decreased localization at the cell surface;
FT                   dbSNP:rs863225306)"
FT                   /evidence="ECO:0000269|PubMed:26333769"
FT                   /id="VAR_075078"
FT   VARIANT         407
FT                   /note="P -> A (in dbSNP:rs16985442)"
FT                   /id="VAR_027414"
FT   VARIANT         426
FT                   /note="L -> P (in DEE34; results in loss of chloride
FT                   transport; decreased localization at the cell surface;
FT                   dbSNP:rs863225304)"
FT                   /evidence="ECO:0000269|PubMed:26333769"
FT                   /id="VAR_075079"
FT   VARIANT         551
FT                   /note="G -> D (in DEE34; results in loss of chloride
FT                   transport; decreased localization at the cell surface;
FT                   dbSNP:rs863225305)"
FT                   /evidence="ECO:0000269|PubMed:26333769"
FT                   /id="VAR_075080"
FT   VARIANT         847
FT                   /note="G -> D (in a colorectal cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036557"
FT   VARIANT         975
FT                   /note="R -> H (in EIG14; rare variant associated with
FT                   disease susceptibility; results in reduced chloride
FT                   transport; decreased localization at the cell surface;
FT                   unable to induce cortical dendritic spines formation;
FT                   dbSNP:rs142740233)"
FT                   /evidence="ECO:0000269|PubMed:24668262,
FT                   ECO:0000269|PubMed:24928908, ECO:0000269|PubMed:26528127"
FT                   /id="VAR_075081"
FT   VARIANT         1071
FT                   /note="R -> W (in dbSNP:rs369042030)"
FT                   /evidence="ECO:0000269|PubMed:26528127"
FT                   /id="VAR_075082"
FT   VARIANT         1072
FT                   /note="R -> C (in EIG14; rare variant associated with
FT                   disease susceptibility; results in reduced chloride
FT                   transport; dbSNP:rs548424453)"
FT                   /evidence="ECO:0000269|PubMed:24928908,
FT                   ECO:0000269|PubMed:26528127"
FT                   /id="VAR_075083"
FT   VARIANT         1100
FT                   /note="P -> L (in dbSNP:rs17297532)"
FT                   /evidence="ECO:0000269|PubMed:10574461"
FT                   /id="VAR_024994"
FT   HELIX           82..88
FT                   /evidence="ECO:0007829|PDB:7D8Z"
FT   HELIX           99..102
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           103..105
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           122..125
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           127..133
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           137..141
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           143..149
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   TURN            152..154
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   TURN            156..162
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           163..177
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           188..191
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   TURN            192..194
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           198..201
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           203..228
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          241..243
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           245..270
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           272..277
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           279..299
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   TURN            300..302
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          308..314
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          326..328
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          332..334
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           341..344
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          348..352
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           356..359
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          364..369
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   TURN            371..373
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           378..380
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          395..397
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          412..414
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           423..430
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           431..433
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           437..441
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          442..446
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           450..463
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           466..476
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   TURN            477..479
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           482..485
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   TURN            489..495
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           500..502
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          503..505
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           508..520
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   TURN            521..524
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           525..538
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           543..549
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          555..558
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           559..567
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           569..571
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   TURN            572..574
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   TURN            577..579
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           581..605
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          614..616
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   TURN            618..620
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           621..634
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           638..644
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           646..663
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          664..666
FT                   /evidence="ECO:0007829|PDB:7D8Z"
FT   HELIX           667..681
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          685..687
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          688..691
FT                   /evidence="ECO:0007829|PDB:7D8Z"
FT   STRAND          698..700
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           713..722
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          729..736
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           738..741
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           743..756
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   TURN            757..760
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          763..772
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           773..782
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          793..796
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          803..806
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   TURN            808..810
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           812..823
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          827..832
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           834..836
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          850..852
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          854..856
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           859..868
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          871..876
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          880..885
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          887..889
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           894..903
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   TURN            904..906
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          910..915
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   TURN            923..927
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           931..940
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   TURN            946..948
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          949..951
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   TURN            953..957
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           1078..1087
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          1088..1091
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          1093..1096
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           1104..1106
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   TURN            1107..1110
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   HELIX           1111..1117
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   TURN            1118..1120
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   STRAND          1122..1128
FT                   /evidence="ECO:0007829|PDB:6M23"
FT   CONFLICT        Q9H2X9-2:2
FT                   /note="L -> P (in Ref. 1; AAG43493)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1139 AA;  126184 MW;  100C097AF1FD4B3E CRC64;
     MSRRFTVTSL PPAGPARSPD PESRRHSVAD PRHLPGEDVK GDGNPKESSP FINSTDTEKG
     KEYDGKNMAL FEEEMDTSPM VSSLLSGLAN YTNLPQGSRE HEEAENNEGG KKKPVQAPRM
     GTFMGVYLPC LQNIFGVILF LRLTWVVGIA GIMESFCMVF ICCSCTMLTA ISMSAIATNG
     VVPAGGSYYM ISRSLGPEFG GAVGLCFYLG TTFAGAMYIL GTIEILLAYL FPAMAIFKAE
     DASGEAAAML NNMRVYGTCV LTCMATVVFV GVKYVNKFAL VFLGCVILSI LAIYAGVIKS
     AFDPPNFPIC LLGNRTLSRH GFDVCAKLAW EGNETVTTRL WGLFCSSRFL NATCDEYFTR
     NNVTEIQGIP GAASGLIKEN LWSSYLTKGV IVERSGMTSV GLADGTPIDM DHPYVFSDMT
     SYFTLLVGIY FPSVTGIMAG SNRSGDLRDA QKSIPTGTIL AIATTSAVYI SSVVLFGACI
     EGVVLRDKFG EAVNGNLVVG TLAWPSPWVI VIGSFFSTCG AGLQSLTGAP RLLQAISRDG
     IVPFLQVFGH GKANGEPTWA LLLTACICEI GILIASLDEV APILSMFFLM CYMFVNLACA
     VQTLLRTPNW RPRFRYYHWT LSFLGMSLCL ALMFICSWYY ALVAMLIAGL IYKYIEYRGA
     EKEWGDGIRG LSLSAARYAL LRLEEGPPHT KNWRPQLLVL VRVDQDQNVV HPQLLSLTSQ
     LKAGKGLTIV GSVLEGTFLE NHPQAQRAEE SIRRLMEAEK VKGFCQVVIS SNLRDGVSHL
     IQSGGLGGLQ HNTVLVGWPR NWRQKEDHQT WRNFIELVRE TTAGHLALLV TKNVSMFPGN
     PERFSEGSID VWWIVHDGGM LMLLPFLLRH HKVWRKCKMR IFTVAQMDDN SIQMKKDLTT
     FLYHLRITAE VEVVEMHESD ISAYTYEKTL VMEQRSQILK QMHLTKNERE REIQSITDES
     RGSIRRKNPA NTRLRLNVPE ETAGDSEEKP EEEVQLIHDQ SAPSCPSSSP SPGEEPEGEG
     ETDPEKVHLT WTKDKSVAEK NKGPSPVSSE GIKDFFSMKP EWENLNQSNV RRMHTAVRLN
     EVIVKKSRDA KLVLLNMPGP PRNRNGDENY MEFLEVLTEH LDRVMLVRGG GREVITIYS
//