S12A5_HUMAN
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}.
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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
