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 27-MAR-2024, entry version 202. 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; GN Synonyms=NKCC1 {ECO:0000303|PubMed:33597714, GN ECO:0000303|PubMed:7629105}; 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, TRANSPORT ACTIVITY, RP ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, RP 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 PHOSPHORYLATION AT THR-212 AND THR-217. RX PubMed=12145305; DOI=10.1074/jbc.m206294200; RA Flemmer A.W., Gimenez I., Dowd B.F., Darman R.B., Forbush B.; RT "Activation of the Na-K-Cl cotransporter NKCC1 detected with a phospho- RT specific antibody."; RL J. Biol. Chem. 277:37551-37558(2002). RN [4] RP PHOSPHORYLATION AT THR-203; THR-207 AND THR-212, FUNCTION, ACTIVITY RP REGULATION, AND DOMAIN. RX PubMed=16669787; DOI=10.1042/bj20060220; RA Vitari A.C., Thastrup J., Rafiqi F.H., Deak M., Morrice N.A., RA Karlsson H.K., Alessi D.R.; RT "Functional interactions of the SPAK/OSR1 kinases with their upstream RT activator WNK1 and downstream substrate NKCC1."; RL Biochem. J. 397:223-231(2006). RN [5] RP ACTIVITY REGULATION. RX PubMed=16832045; DOI=10.1073/pnas.0604607103; RA Anselmo A.N., Earnest S., Chen W., Juang Y.C., Kim S.C., Zhao Y., RA Cobb M.H.; RT "WNK1 and OSR1 regulate the Na+, K+, 2Cl- cotransporter in HeLa cells."; RL Proc. Natl. Acad. Sci. U.S.A. 103:10883-10888(2006). RN [6] 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 [7] 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 [8] 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 [9] 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 [10] 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 [11] {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 [12] {ECO:0007744|PDB:7D10} RP STRUCTURE BY ELECTRON MICROSCOPY (3.52 ANGSTROMS), FUNCTION, SUBUNIT, AND RP MUTAGENESIS OF ARG-307; ARG-358; GLU-389; THR-486; PHE-487; PHE-488; RP SER-489; VAL-490; PHE-491; ALA-492; ILE-493; PHE-494; PHE-495; ALA-497; RP ALA-498; THR-499; GLY-500; ILE-501; LEU-502; ALA-503; GLY-504; ALA-505; RP ASN-506; ILE-507; ASP-510; SER-613; SER-614; LYS-624; ASP-632; GLU-670 AND RP LEU-671. RX PubMed=33597714; DOI=10.1038/s42003-021-01750-w; RA Zhang S., Zhou J., Zhang Y., Liu T., Friedel P., Zhuo W., Somasekharan S., RA Roy K., Zhang L., Liu Y., Meng X., Deng H., Zeng W., Li G., Forbush B., RA Yang M.; RT "The structural basis of function and regulation of neuronal cotransporters RT NKCC1 and KCC2."; RL Commun. Biol. 4:226-226(2021). RN [13] 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 [14] 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 [15] 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 [16] 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:32081947, PubMed:33597714, PubMed:32294086, CC PubMed:7629105, PubMed:16669787). Plays a vital role in the regulation CC of ionic balance and cell volume (PubMed:32081947, PubMed:32294086, CC PubMed:7629105, PubMed:16669787). {ECO:0000269|PubMed:16669787, CC ECO:0000269|PubMed:32081947, ECO:0000269|PubMed:32294086, CC ECO:0000269|PubMed:33597714, ECO:0000269|PubMed:7629105}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2 chloride(out) + K(+)(out) + Na(+)(out) = 2 chloride(in) + CC K(+)(in) + Na(+)(in); Xref=Rhea:RHEA:72395, ChEBI:CHEBI:17996, CC ChEBI:CHEBI:29101, ChEBI:CHEBI:29103; CC Evidence={ECO:0000269|PubMed:7629105}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:72396; CC Evidence={ECO:0000305|PubMed:7629105}; CC -!- ACTIVITY REGULATION: Activated following phosphorylation by OXSR1/OSR1 CC and STK39/SPAK downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4) CC (PubMed:16669787, PubMed:16832045, PubMed:21613606). Inhibited by CC bumetanide (PubMed:7629105, PubMed:32081947). CC {ECO:0000269|PubMed:16669787, ECO:0000269|PubMed:16832045, CC ECO:0000269|PubMed:21613606, ECO:0000269|PubMed:32081947, CC ECO:0000269|PubMed:7629105}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=19.6 mM for Na(+) {ECO:0000269|PubMed:7629105}; CC KM=2.68 mM for K(+) {ECO:0000269|PubMed:7629105}; CC KM=26.5 mM for Cl(-) {ECO:0000269|PubMed:7629105}; CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:32081947, CC ECO:0000269|PubMed:33597714}. CC -!- INTERACTION: CC P55011; P15311: EZR; NbExp=3; IntAct=EBI-2801449, EBI-1056902; CC P55011; O95747: OXSR1; NbExp=2; 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:0000305|PubMed:32081947, CC ECO:0000305|PubMed:33597714}. 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 -!- DOMAIN: The RFXV motifs mediate binding with OXSR1/OSR1 and STK39/SPAK. CC {ECO:0000269|PubMed:16669787}. CC -!- PTM: Phosphorylated at Thr-203, Thr-207 and Thr-212 by OXSR1/OSR1 and CC STK39/SPAK downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4), CC promoting its activity. {ECO:0000269|PubMed:16669787}. 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}. 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; 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 PDB; 7MXO; EM; 3.47 A; A/B=284-1206. DR PDB; 7N3N; EM; 3.33 A; A/B=1-1212. DR PDB; 7S1X; EM; 2.90 A; A/B=2-1212. DR PDB; 7S1Y; EM; 3.60 A; A/B=2-1212. DR PDB; 7S1Z; EM; 3.30 A; A/B=2-1212. DR PDB; 7SFL; EM; 3.87 A; A/B=286-1210. DR PDB; 7SMP; EM; 3.28 A; A/B=283-1211. DR PDB; 7ZGO; EM; 2.55 A; A/B=2-1212. DR PDBsum; 6PZT; -. DR PDBsum; 7D10; -. DR PDBsum; 7MXO; -. DR PDBsum; 7N3N; -. DR PDBsum; 7S1X; -. DR PDBsum; 7S1Y; -. DR PDBsum; 7S1Z; -. DR PDBsum; 7SFL; -. DR PDBsum; 7SMP; -. DR PDBsum; 7ZGO; -. DR AlphaFoldDB; P55011; -. DR EMDB; EMD-14709; -. DR EMDB; EMD-20537; -. DR EMDB; EMD-24074; -. DR EMDB; EMD-24141; -. DR EMDB; EMD-24807; -. DR EMDB; EMD-24812; -. DR EMDB; EMD-24813; -. DR EMDB; EMD-25092; -. DR EMDB; EMD-25204; -. DR EMDB; EMD-29096; -. DR EMDB; EMD-29097; -. DR EMDB; EMD-29098; -. DR EMDB; EMD-29099; -. DR EMDB; EMD-29100; -. DR EMDB; EMD-30542; -. DR EMDB; EMD-33641; -. DR EMDB; EMD-33803; -. DR EMDB; EMD-33804; -. DR EMDB; EMD-40759; -. DR SMR; P55011; -. DR BioGRID; 112447; 238. DR DIP; DIP-43979N; -. DR IntAct; P55011; 45. 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 GlyCosmos; P55011; 1 site, 3 glycans. DR GlyGen; P55011; 4 sites, 3 N-linked glycans (1 site), 1 O-linked glycan (1 site). DR iPTMnet; P55011; -. DR PhosphoSitePlus; P55011; -. DR SwissPalm; P55011; -. DR BioMuta; SLC12A2; -. DR DMDM; 1709292; -. DR EPD; P55011; -. DR jPOST; P55011; -. DR MassIVE; P55011; -. DR MaxQB; P55011; -. DR PaxDb; 9606-ENSP00000262461; -. DR PeptideAtlas; P55011; -. DR ProteomicsDB; 56757; -. [P55011-1] DR ProteomicsDB; 56758; -. [P55011-3] DR Pumba; P55011; -. DR Antibodypedia; 14071; 423 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 AGR; HGNC:10911; -. 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; 633024; SLC12A2-related autosomal dominant infantile-developmental delay-intellectual disability-sensorineural deafness syndrome. DR Orphanet; 633021; SLC12A2-related autosomal recessive neonatal-developmental delay-intellectual disability-feeding difficulty-sensorineural deafness syndrome. 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 OrthoDB; 5490251at2759; -. 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; 19 hits in 1170 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 192 other cell types or tissues. DR ExpressionAtlas; P55011; baseline and differential. 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; TAS:UniProt. 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:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:1903561; C:extracellular vesicle; HDA:UniProtKB. 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:chloride:monoatomic cation symporter activity; IDA: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:0019901; F:protein kinase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0051087; F:protein-folding chaperone binding; IPI:ARUK-UCL. DR GO; GO:0008511; F:sodium:potassium:chloride symporter activity; IDA:UniProtKB. DR GO; GO:0072488; P:ammonium transmembrane transport; IDA:UniProtKB. DR GO; GO:0006884; P:cell volume 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: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:0030644; P:intracellular chloride ion homeostasis; ISS:ARUK-UCL. DR GO; GO:0030007; P:intracellular potassium ion homeostasis; ISS:ARUK-UCL. DR GO; GO:0006883; P:intracellular sodium ion homeostasis; ISS:ARUK-UCL. DR GO; GO:0035633; P:maintenance of blood-brain barrier; ISS:ARUK-UCL. DR GO; GO:0006811; P:monoatomic ion transport; TAS:Reactome. 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 Gene3D; 1.20.1740.10; Amino acid/polyamine transporter I; 1. 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 NCBIfam; TIGR00930; 2a30; 1. DR PANTHER; PTHR11827:SF58; SOLUTE CARRIER FAMILY 12 MEMBER 2; 1. DR PANTHER; PTHR11827; SOLUTE CARRIER FAMILY 12, CATION COTRANSPORTERS; 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 Genevisible; P55011; HS. 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:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" 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|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TRANSMEM 322..343 FT /note="Helical" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TOPO_DOM 344..361 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TRANSMEM 362..397 FT /note="Helical" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TOPO_DOM 398..406 FT /note="Extracellular" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TRANSMEM 407..424 FT /note="Helical" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TOPO_DOM 425..429 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TRANSMEM 430..454 FT /note="Helical" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TOPO_DOM 455..486 FT /note="Extracellular" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TRANSMEM 487..507 FT /note="Discontinuously helical" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" 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|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TRANSMEM 515..542 FT /note="Helical" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TOPO_DOM 543..599 FT /note="Extracellular" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TRANSMEM 600..632 FT /note="Helical" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TOPO_DOM 633..653 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TRANSMEM 654..668 FT /note="Helical" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TOPO_DOM 669..670 FT /note="Extracellular" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TRANSMEM 671..697 FT /note="Helical" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TOPO_DOM 698..711 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TRANSMEM 712..730 FT /note="Helical" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TOPO_DOM 731 FT /note="Extracellular" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TRANSMEM 732..751 FT /note="Helical" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" FT TOPO_DOM 752..1212 FT /note="Cytoplasmic" FT /evidence="ECO:0000305|PubMed:32081947, FT ECO:0000305|PubMed:33597714" 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 MOTIF 80..83 FT /note="RFXV motif 1" FT /evidence="ECO:0000269|PubMed:16669787" FT MOTIF 138..141 FT /note="RFXV motif 2" FT /evidence="ECO:0000269|PubMed:16669787" 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 203 FT /note="Phosphothreonine; by OXSR1 and STK39" FT /evidence="ECO:0000269|PubMed:16669787" FT MOD_RES 207 FT /note="Phosphothreonine; by OXSR1 and STK39" FT /evidence="ECO:0000269|PubMed:16669787" FT MOD_RES 212 FT /note="Phosphothreonine; by OXSR1 and STK39" FT /evidence="ECO:0000269|PubMed:12145305, FT ECO:0000269|PubMed:16669787" FT MOD_RES 217 FT /note="Phosphothreonine" FT /evidence="ECO:0000269|PubMed:12145305, FT 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; dbSNP:rs1761279419)" 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; dbSNP:rs1763563407)" 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 MUTAGEN 307 FT /note="R->E: Abolished cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 358 FT /note="R->K: Strongly reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 389 FT /note="E->Q,R: Strongly reduced cation-chloride FT cotransporter activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 486 FT /note="T->C: Strongly reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 487 FT /note="F->C: Does not affect cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 488 FT /note="F->C: Slighly reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 489 FT /note="S->C: Slighly reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 490 FT /note="V->C: Strongly reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 491 FT /note="F->C: Reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 492 FT /note="A->C: Reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 493 FT /note="I->C: Reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 494 FT /note="F->C: Reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 495 FT /note="F->C: Reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 497 FT /note="A->C: Strongly reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 498 FT /note="A->C: Strongly reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 499 FT /note="T->C: Strongly reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 500 FT /note="G->C: Strongly reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 501 FT /note="I->C: Strongly reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 502 FT /note="L->C: Strongly reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 503 FT /note="A->C: Reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 504 FT /note="G->C: Strongly reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 505 FT /note="A->C: Strongly reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 506 FT /note="N->C: Strongly reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 507 FT /note="I->C: Strongly reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 510 FT /note="D->A,C,Q,K: Strongly reduced cation-chloride FT cotransporter activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 510 FT /note="D->N: Does not affect cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 613 FT /note="S->C,A,D,T: Abolished cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 614 FT /note="S->C,A,D,T: Abolished cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 624 FT /note="K->A,C,D: Nearly abolished cation-chloride FT cotransporter activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 632 FT /note="D->A,E: Strongly reduced cation-chloride FT cotransporter activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 670 FT /note="E->A,C: Slightly reduced cation-chloride FT cotransporter activity." FT /evidence="ECO:0000269|PubMed:33597714" FT MUTAGEN 671 FT /note="L->A,C: Reduced cation-chloride cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:33597714" FT HELIX 224..227 FT /evidence="ECO:0007829|PDB:7S1X" FT HELIX 243..247 FT /evidence="ECO:0007829|PDB:7S1X" FT HELIX 287..290 FT /evidence="ECO:0007829|PDB:7ZGO" FT HELIX 292..299 FT /evidence="ECO:0007829|PDB:7ZGO" FT STRAND 300..302 FT /evidence="ECO:0007829|PDB:7ZGO" FT HELIX 303..306 FT /evidence="ECO:0007829|PDB:7ZGO" FT HELIX 308..314 FT /evidence="ECO:0007829|PDB:7ZGO" FT HELIX 317..342 FT /evidence="ECO:0007829|PDB:7ZGO" FT STRAND 344..346 FT /evidence="ECO:0007829|PDB:7S1X" FT HELIX 352..359 FT /evidence="ECO:0007829|PDB:7ZGO" FT HELIX 362..397 FT /evidence="ECO:0007829|PDB:7ZGO" FT HELIX 405..426 FT /evidence="ECO:0007829|PDB:7ZGO" FT STRAND 428..430 FT /evidence="ECO:0007829|PDB:7MXO" FT HELIX 431..453 FT /evidence="ECO:0007829|PDB:7ZGO" FT TURN 458..460 FT /evidence="ECO:0007829|PDB:7ZGO" FT HELIX 461..463 FT /evidence="ECO:0007829|PDB:7ZGO" FT HELIX 470..476 FT /evidence="ECO:0007829|PDB:7ZGO" FT STRAND 482..484 FT /evidence="ECO:0007829|PDB:7N3N" FT HELIX 487..498 FT /evidence="ECO:0007829|PDB:7ZGO" FT HELIX 503..506 FT /evidence="ECO:0007829|PDB:7ZGO" FT HELIX 507..510 FT /evidence="ECO:0007829|PDB:7ZGO" FT STRAND 511..513 FT /evidence="ECO:0007829|PDB:7ZGO" FT HELIX 514..543 FT /evidence="ECO:0007829|PDB:7ZGO" FT STRAND 546..548 FT /evidence="ECO:0007829|PDB:7S1X" FT HELIX 552..554 FT /evidence="ECO:0007829|PDB:7SMP" FT TURN 556..558 FT /evidence="ECO:0007829|PDB:7MXO" FT HELIX 566..569 FT /evidence="ECO:0007829|PDB:7ZGO" FT HELIX 575..579 FT /evidence="ECO:0007829|PDB:7ZGO" FT STRAND 583..585 FT /evidence="ECO:0007829|PDB:7ZGO" FT TURN 586..588 FT /evidence="ECO:0007829|PDB:7ZGO" FT HELIX 592..596 FT /evidence="ECO:0007829|PDB:7ZGO" FT STRAND 597..599 FT /evidence="ECO:0007829|PDB:7ZGO" FT HELIX 600..631 FT /evidence="ECO:0007829|PDB:7ZGO" FT HELIX 636..642 FT /evidence="ECO:0007829|PDB:7ZGO" FT TURN 646..649 FT /evidence="ECO:0007829|PDB:7ZGO" FT HELIX 652..667 FT /evidence="ECO:0007829|PDB:7ZGO" FT HELIX 671..699 FT /evidence="ECO:0007829|PDB:7ZGO" FT HELIX 713..730 FT /evidence="ECO:0007829|PDB:7ZGO" FT HELIX 732..750 FT /evidence="ECO:0007829|PDB:7ZGO" FT STRAND 755..757 FT /evidence="ECO:0007829|PDB:7N3N" FT HELIX 761..778 FT /evidence="ECO:0007829|PDB:7S1X" FT HELIX 784..786 FT /evidence="ECO:0007829|PDB:7S1X" FT STRAND 791..793 FT /evidence="ECO:0007829|PDB:7S1X" FT TURN 798..800 FT /evidence="ECO:0007829|PDB:7S1X" FT HELIX 802..810 FT /evidence="ECO:0007829|PDB:7S1X" FT TURN 811..814 FT /evidence="ECO:0007829|PDB:7S1X" FT STRAND 818..824 FT /evidence="ECO:0007829|PDB:7S1X" FT HELIX 828..848 FT /evidence="ECO:0007829|PDB:7S1X" FT STRAND 854..859 FT /evidence="ECO:0007829|PDB:7S1X" FT HELIX 863..873 FT /evidence="ECO:0007829|PDB:7S1X" FT STRAND 883..887 FT /evidence="ECO:0007829|PDB:7S1X" FT TURN 890..894 FT /evidence="ECO:0007829|PDB:7S1X" FT HELIX 897..912 FT /evidence="ECO:0007829|PDB:7S1X" FT STRAND 916..921 FT /evidence="ECO:0007829|PDB:7S1X" FT STRAND 1019..1022 FT /evidence="ECO:0007829|PDB:7MXO" FT STRAND 1025..1027 FT /evidence="ECO:0007829|PDB:7S1X" FT HELIX 1035..1045 FT /evidence="ECO:0007829|PDB:7S1X" FT TURN 1047..1049 FT /evidence="ECO:0007829|PDB:7S1X" FT STRAND 1050..1053 FT /evidence="ECO:0007829|PDB:7S1X" FT STRAND 1056..1059 FT /evidence="ECO:0007829|PDB:7S1X" FT HELIX 1065..1078 FT /evidence="ECO:0007829|PDB:7S1X" FT STRAND 1086..1089 FT /evidence="ECO:0007829|PDB:7S1X" FT STRAND 1092..1094 FT /evidence="ECO:0007829|PDB:7SMP" FT HELIX 1098..1108 FT /evidence="ECO:0007829|PDB:7S1X" FT HELIX 1109..1111 FT /evidence="ECO:0007829|PDB:7S1X" FT TURN 1113..1116 FT /evidence="ECO:0007829|PDB:7S1X" FT HELIX 1121..1127 FT /evidence="ECO:0007829|PDB:7S1X" FT STRAND 1133..1135 FT /evidence="ECO:0007829|PDB:7SMP" FT HELIX 1137..1139 FT /evidence="ECO:0007829|PDB:7S1X" FT HELIX 1142..1159 FT /evidence="ECO:0007829|PDB:7S1X" FT HELIX 1160..1162 FT /evidence="ECO:0007829|PDB:7S1X" FT STRAND 1166..1169 FT /evidence="ECO:0007829|PDB:7S1X" FT TURN 1175..1177 FT /evidence="ECO:0007829|PDB:7S1X" FT HELIX 1180..1191 FT /evidence="ECO:0007829|PDB:7S1X" FT STRAND 1192..1195 FT /evidence="ECO:0007829|PDB:7S1X" FT STRAND 1197..1201 FT /evidence="ECO:0007829|PDB:7S1X" 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 //