ID S12A3_HUMAN Reviewed; 1021 AA. AC P55017; A8MSJ2; C9JNN9; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 30-NOV-2010, sequence version 3. DT 27-MAR-2024, entry version 210. DE RecName: Full=Solute carrier family 12 member 3; DE AltName: Full=Na-Cl cotransporter {ECO:0000303|PubMed:22009145}; DE Short=NCC {ECO:0000303|PubMed:22009145}; DE AltName: Full=Na-Cl symporter; DE AltName: Full=Thiazide-sensitive sodium-chloride cotransporter; GN Name=SLC12A3 {ECO:0000303|PubMed:8812482, GN ECO:0000312|HGNC:HGNC:10912}; GN Synonyms=NCC {ECO:0000303|PubMed:22009145}, TSC; 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), VARIANTS GTLMNS TRP-209; GLY-264; RP LEU-349; ARG-421; ASN-486; CYS-496; SER-561 DEL; VAL-588; VAL-630; HIS-655; RP LEU-655; ARG-741; PRO-850 AND GLN-955, VARIANT THR-728, FUNCTION, AND RP ACTIVITY REGULATION. RX PubMed=8528245; DOI=10.1038/ng0196-24; RA Simon D.B., Nelson-Williams C., Bia M.J., Ellison D., Karet F.E., RA Molina A.M., Vaara I., Iwata F., Cushner H.M., Koolen M., Gainza F.J., RA Gitelman H.J., Lifton R.P.; RT "Gitelman's variant of Bartter's syndrome, inherited hypokalaemic RT alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl RT cotransporter."; RL Nat. Genet. 12:24-30(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLY-264, AND TISSUE RP SPECIFICITY. RC TISSUE=Kidney; RX PubMed=8812482; DOI=10.1006/geno.1996.0388; RA Mastroianni N., de Fusco M., Zollo M., Arrigo G., Zuffardi O., RA Bettinelli A., Ballabio A., Casari G.; RT "Molecular cloning, expression pattern, and chromosomal localization of the RT human Na-Cl thiazide-sensitive cotransporter (SLC12A3)."; RL Genomics 35:486-493(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT GLY-264. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [5] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=21613606; DOI=10.1152/ajpcell.00070.2011; RA Cruz-Rangel S., Melo Z., Vazquez N., Meade P., Bobadilla N.A., RA Pasantes-Morales H., Gamba G., Mercado A.; RT "Similar Effects of all WNK3 Variants upon SLC12 Cotransporters."; RL Am. J. Physiol. 301:C601-C608(2011). RN [6] RP FUNCTION, ACTIVITY REGULATION, PHOSPHORYLATION AT THR-46; THR-55; THR-60 RP AND SER-91, AND MUTAGENESIS OF ARG-19; THR-46; THR-55; THR-60 AND SER-91. RX PubMed=18270262; DOI=10.1242/jcs.025312; RA Richardson C., Rafiqi F.H., Karlsson H.K., Moleleki N., Vandewalle A., RA Campbell D.G., Morrice N.A., Alessi D.R.; RT "Activation of the thiazide-sensitive Na+-Cl- cotransporter by the WNK- RT regulated kinases SPAK and OSR1."; RL J. Cell Sci. 121:675-684(2008). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-91, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [8] RP TISSUE SPECIFICITY, AND CHARACTERIZATION OF VARIANTS GTLMNS ASP-121; RP SER-439; CYS-475 AND ARG-1021. RX PubMed=26099046; DOI=10.1038/nm.3890; RA Wang J., Sun C., Gerdes N., Liu C., Liao M., Liu J., Shi M.A., He A., RA Zhou Y., Sukhova G.K., Chen H., Cheng X.W., Kuzuya M., Murohara T., RA Zhang J., Cheng X., Jiang M., Shull G.E., Rogers S., Yang C.L., Ke Q., RA Jelen S., Bindels R., Ellison D.H., Jarolim P., Libby P., Shi G.P.; RT "Interleukin 18 function in atherosclerosis is mediated by the interleukin RT 18 receptor and the Na-Cl co-transporter."; RL Nat. Med. 21:820-826(2015). RN [9] RP TISSUE SPECIFICITY. RX PubMed=29993276; DOI=10.1152/ajprenal.00539.2017; RA Frische S., Chambrey R., Trepiccione F., Zamani R., Marcussen N., RA Alexander R.T., Skjoedt K., Svenningsen P., Dimke H.; RT "H+-ATPase B1 subunit localizes to thick ascending limb and distal RT convoluted tubule of rodent and human kidney."; RL Am. J. Physiol. 315:F429-F444(2018). RN [10] RP INTERACTION WITH KLHL3, AND UBIQUITINATION. RX PubMed=22406640; DOI=10.1038/ng.2218; RA Louis-Dit-Picard H., Barc J., Trujillano D., Miserey-Lenkei S., RA Bouatia-Naji N., Pylypenko O., Beaurain G., Bonnefond A., Sand O., RA Simian C., Vidal-Petiot E., Soukaseum C., Mandet C., Broux F., Chabre O., RA Delahousse M., Esnault V., Fiquet B., Houillier P., Bagnis C.I., Koenig J., RA Konrad M., Landais P., Mourani C., Niaudet P., Probst V., Thauvin C., RA Unwin R.J., Soroka S.D., Ehret G., Ossowski S., Caulfield M., Bruneval P., RA Estivill X., Froguel P., Hadchouel J., Schott J.J., Jeunemaitre X.; RT "KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion RT transport in the distal nephron."; RL Nat. Genet. 44:456-460(2012). RN [11] {ECO:0007744|PDB:7Y6I, ECO:0007744|PDB:7YG0, ECO:0007744|PDB:7YG1} RP STRUCTURE BY ELECTRON MICROSCOPY (2.85 ANGSTROMS) IN COMPLEX WITH CHLORIDE RP AND SODIUM, FUNCTION, TRANSPORTER ACTIVITY, SUBUNIT, GLYCOSYLATION AT RP ASN-406 AND ASN-426, AND MUTAGENESIS OF ASN-149; PHE-223; ASN-227; HIS-234; RP TYR-386; SER-467; SER-468 AND TYR-540. RX PubMed=36351028; DOI=10.1126/sciadv.add7176; RA Nan J., Yuan Y., Yang X., Shan Z., Liu H., Wei F., Zhang W., Zhang Y.; RT "Cryo-EM structure of the human sodium-chloride cotransporter NCC."; RL Sci. Adv. 8:eadd7176-eadd7176(2022). RN [12] {ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT} RP STRUCTURE BY ELECTRON MICROSCOPY (2.81 ANGSTROMS) OF 132-1021 IN COMPLEX RP WITH CHLORIDE; SODIUM; POLYTHIAZIDE AND ATP, FUNCTION, TRANSPORTER RP ACTIVITY, ACTIVITY REGULATION, DISULFIDE BONDS, DOMAIN, AND MUTAGENESIS OF RP ASP-62; TYR-70; ARG-83; LEU-86; ASN-149; ARG-158; PHE-223; GLU-240; RP SER-467; SER-468; ASN-526; TYR-540; PHE-765; ASP-838; PHE-886 AND ARG-1009. RX PubMed=36792826; DOI=10.1038/s41586-023-05718-0; RA Fan M., Zhang J., Lee C.L., Zhang J., Feng L.; RT "Structure and thiazide inhibition mechanism of the human Na-Cl RT cotransporter."; RL Nature 614:788-793(2023). RN [13] RP VARIANTS GTLMNS ASN-62; ASP-186; TRP-209; LEU-349; SER-439; GLU-478; RP ASN-486; CYS-496; PRO-542; VAL-588 AND ARG-731. RX PubMed=8900229; RA Mastroianni N., Bettinelli A., Bianchetti M., Colussi G., De Fusco M., RA Sereni F., Ballabio A., Casari G.; RT "Novel molecular variants of the Na-Cl cotransporter gene are responsible RT for Gitelman syndrome."; RL Am. J. Hum. Genet. 59:1019-1026(1996). RN [14] RP VARIANT GTLMNS PRO-623. RX PubMed=8954067; DOI=10.1210/jcem.81.12.8954067; RA Takeuchi K., Kure S., Kato T., Taniyama Y., Takahashi N., Ikeda Y., Abe T., RA Narisawa K., Muramatsu Y., Abe K.; RT "Association of a mutation in thiazide-sensitive Na-Cl cotransporter with RT familial Gitelman's syndrome."; RL J. Clin. Endocrinol. Metab. 81:4496-4499(1996). RN [15] RP VARIANTS GTLMNS TRP-209; PRO-215; THR-226; HIS-261; HIS-560; SER-613; RP HIS-642; ARG-649; CYS-655; ARG-738; ARG-741; PRO-850 AND CYS-852, AND RP VARIANTS GLN-904 AND CYS-919. RX PubMed=9734597; DOI=10.1046/j.1523-1755.1998.00070.x; RA Lemmink H.H., Knoers N.V.A.M., Karolyi L., van Dijk H., Niaudet P., RA Antignac C., Guay-Woodford L.M., Goodyer P.R., Carel J.-C., Hermes A., RA Seyberth H.W., Monnens L.A.H., van den Heuvel L.P.W.J.; RT "Novel mutations in the thiazide-sensitive NaCl cotransporter gene in RT patients with Gitelman syndrome with predominant localization to the C- RT terminal domain."; RL Kidney Int. 54:720-730(1998). RN [16] RP VARIANTS GTLMNS PRO-304; SER-439; ARG-731 AND ARG-741, AND VARIANT GLN-904. RX PubMed=10988270; DOI=10.1161/01.hyp.36.3.389; RA Melander O., Orho-Melander M., Bengtsson K., Lindblad U., Rastam L., RA Groop L., Hulthen U.L.; RT "Genetic variants of thiazide-sensitive NaCl-cotransporter in Gitelman's RT syndrome and primary hypertension."; RL Hypertension 36:389-394(2000). RN [17] RP VARIANTS GTLMNS LYS-180; GLU-569; MET-578; CYS-642 AND HIS-849. RX PubMed=10616841; DOI=10.1681/asn.v11165; RA Monkawa T., Kurihara I., Kobayashi K., Hayashi M., Saruta T.; RT "Novel mutations in thiazide-sensitive Na-Cl cotransporter gene of patients RT with Gitelman's syndrome."; RL J. Am. Soc. Nephrol. 11:65-70(2000). RN [18] RP VARIANTS GTLMNS PHE-154; LEU-178; GLN-209; ARG-284; VAL-313; TRP-321; RP TRP-334; CYS-399; LEU-555; LEU-615; GLY-642; LEU-643 AND VAL-729. RX PubMed=11168953; DOI=10.1046/j.1523-1755.2001.059002710.x; RA Cruz D.N., Shaer A.J., Bia M.J., Lifton R.P., Simon D.B.; RT "Gitelman's syndrome revisited: an evaluation of symptoms and health- RT related quality of life."; RL Kidney Int. 59:710-717(2001). RN [19] RP VARIANT GTLMNS LEU-643, AND VARIANT GLY-264. RX PubMed=11940055; DOI=10.1046/j.1365-2265.2002.01223.x; RA Pantanetti P., Arnaldi G., Balercia G., Mantero F., Giacchetti G.; RT "Severe hypomagnesaemia-induced hypocalcaemia in a patient with Gitelman's RT syndrome."; RL Clin. Endocrinol. (Oxf.) 56:413-418(2002). RN [20] RP VARIANT GTLMNS PRO-623. RX PubMed=12008755; DOI=10.1507/endocrj.49.91; RA Tajima T., Kobayashi Y., Abe S., Takahashi M., Konno M., Nakae J., RA Okuhara K., Satoh K., Ishikawa T., Imai T., Fujieda K.; RT "Two novel mutations of thiazide-sensitive Na-Cl cotrans porter (TSC) gene RT in two sporadic Japanese patients with Gitelman syndrome."; RL Endocr. J. 49:91-96(2002). RN [21] RP VARIANTS GTLMNS GLN-158; MET-163; ARG-172; TRP-209; VAL-316; VAL-374; RP GLU-463; THR-464; LEU-615; TRP-615; GLY-642; HIS-642; MET-677; CYS-852; RP SER-852; GLY-958 AND TYR-985, AND VARIANT GLN-904. RX PubMed=12112667; DOI=10.1002/humu.9045; RA Syren M.-L., Tedeschi S., Cesareo L., Bellantuono R., Colussi G., RA Procaccio M., Ali A., Domenici R., Malberti F., Sprocati M., Sacco M., RA Miglietti N., Edefonti A., Sereni F., Casari G., Coviello D.A., RA Bettinelli A.; RT "Identification of fifteen novel mutations in the SLC12A3 gene encoding the RT Na-Cl Co-transporter in Italian patients with Gitelman syndrome."; RL Hum. Mutat. 20:78-78(2002). RN [22] RP VARIANTS GTLMNS MET-60; VAL-569; CYS-642 AND HIS-849. RX PubMed=15069170; DOI=10.1093/ndt/gfh239; RA Maki N., Komatsuda A., Wakui H., Ohtani H., Kigawa A., Aiba N., Hamai K., RA Motegi M., Yamaguchi A., Imai H., Sawada K.; RT "Four novel mutations in the thiazide-sensitive Na-Cl co-transporter gene RT in Japanese patients with Gitelman's syndrome."; RL Nephrol. Dial. Transplant. 19:1761-1766(2004). RN [23] RP VARIANTS GTLMNS TYR-90; TYR-283 AND HIS-871. RX PubMed=15687331; DOI=10.1210/jc.2004-1905; RA Lin S.-H., Shiang J.-C., Huang C.-C., Yang S.-S., Hsu Y.-J., Cheng C.-J.; RT "Phenotype and genotype analysis in Chinese patients with Gitelman's RT syndrome."; RL J. Clin. Endocrinol. Metab. 90:2500-2507(2005). RN [24] RP VARIANT GTLMNS ILE-672. RX PubMed=16429844; DOI=10.5414/cnp65057; RA Terui K., Shoji M., Yamashiki J., Hirai Y., Ishiguro A., Tsutaya S., RA Kageyama K., Yasujima M., Suda T.; RT "A novel mutation of the thiazide-sensitive sodium chloride cotransporter RT gene in a Japanese family with Gitelman syndrome."; RL Clin. Nephrol. 65:57-60(2006). RN [25] RP VARIANTS GTLMNS LYS-68; ASN-69; HIS-145; MET-153; ASP-230; ALA-342; LEU-677 RP AND SER-867. RX PubMed=17654016; DOI=10.1080/10425170701400456; RA Fava C., Montagnana M., Rosberg L., Burri P., Joensson A., Wanby P., RA Wahrenberg H., Hulthen U.L., Aurell M., Guidi G.C., Melander O.; RT "Novel mutations in the SLC12A3 gene causing Gitelman's syndrome in RT Swedes."; RL DNA Seq. 18:395-399(2007). RN [26] RP VARIANTS GTLMNS HIS-849 AND HIS-852. RX PubMed=17873326; DOI=10.1007/s12020-007-0024-9; RA Aoi N., Nakayama T., Tahira Y., Haketa A., Yabuki M., Sekiyama T., RA Nakane C., Mano H., Kawachi H., Sato N., Soma M., Matsumoto K.; RT "Two novel genotypes of the thiazide-sensitive Na-Cl cotransporter RT (SLC12A3) gene in patients with Gitelman's syndrome."; RL Endocrine 31:149-153(2007). RN [27] RP VARIANTS GLY-264; THR-728; GLN-904 AND CYS-919, AND CHARACTERIZATION OF RP VARIANT CYS-919. RX PubMed=17885550; DOI=10.1097/hjh.0b013e3282a9be1b; RA Keszei A.P., Tisler A., Backx P.H., Andrulis I.L., Bull S.B., Logan A.G.; RT "Molecular variants of the thiazide-sensitive Na+-Cl- cotransporter in RT hypertensive families."; RL J. Hypertens. 25:2074-2081(2007). RN [28] RP VARIANTS GTLMNS MET-60; HIS-62; GLN-83; TRP-83; ASP-121; CYS-135; CYS-145; RP MET-150; MET-153; PRO-157; LEU-158; MET-163; VAL-166; ARG-172; LEU-178; RP THR-192; ILE-194; GLN-209; ARG-235; ASN-259; PRO-272; MET-304; PRO-304; RP VAL-313; TRP-321; TRP-334; GLU-374; MET-382; ILE-392; CYS-399; RP 433-GLN--CYS-436 DELINS LEU; SER-439; SER-442; ARG-463; THR-464; CYS-475; RP HIS-489; CYS-507; THR-523; SER-534; LEU-536; GLY-546; LEU-555; ARG-560; RP ASN-566 DEL; LEU-615; CYS-642; CYS-642; GLY-642; HIS-642; LEU-643; MET-647; RP HIS-655; LYS-ALA-PHE-TYR-SER-ASP-VAL-ILE-713 INS; VAL-729; ARG-735; RP ARG-741; LEU-751; THR-824; ASN-839; PHE-849; PRO-850; CYS-852; CYS-862; RP THR-872; GLN-887; TRP-934; TRP-935; GLN-955; GLY-958; ARG-980; TYR-985; RP GLN-1009 AND ARG-1021, CHARACTERIZATION OF VARIANT GTLMNS ASP-121; ILE-392; RP SER-442; CYS-475; HIS-489; LEU-751 AND ARG-1021, FUNCTION, AND SUBCELLULAR RP LOCATION. RX PubMed=22009145; DOI=10.1038/ejhg.2011.189; RA Glaudemans B., Yntema H.G., San-Cristobal P., Schoots J., Pfundt R., RA Kamsteeg E.J., Bindels R.J., Knoers N.V., Hoenderop J.G., Hoefsloot L.H.; RT "Novel NCC mutants and functional analysis in a new cohort of patients with RT Gitelman syndrome."; RL Eur. J. Hum. Genet. 20:263-270(2012). RN [29] RP INVOLVEMENT IN GTLMNS. RX PubMed=33772578; DOI=10.1093/qjmed/hcab066; RA Wang T., Chen Y., Yin X., Qiu H.; RT "Novel heterozygous mutation of SLC12A3 gene in Gitelman syndrome."; RL QJM 114:513-515(2021). RN [30] RP VARIANT GTLMNS CYS-852. RX PubMed=33462018; DOI=10.1136/bcr-2020-238097; RA Verissimo R., Leite de Sousa L., Carvalho T.J., Fidalgo P.; RT "Novel SLC12A3 mutation in Gitelman syndrome."; RL BMJ Case Rep. 14:0-0(2021). RN [31] RP VARIANTS GTLMNS MET-60 AND ASN-486, AND VARIANT GLY-264. RX PubMed=34079339; DOI=10.2147/ijgm.s308246; RA Zhong M., Zhai Z., Zhou X., Sun J., Chen H., Lu W.; RT "Three Novel Homozygous Mutations of the SLC12A3 Gene in a Gitelman RT Syndrome Patient."; RL Int. J. Gen. Med. 14:1999-2002(2021). RN [32] RP VARIANTS GTLMNS LYS-359; ASN-486; PHE-537; ASN-839 AND ARG-1010. RX PubMed=34657521; DOI=10.1080/00365513.2021.1989715; RA Wang F., Guo M., Li J., Ma S.; RT "Novel mutations of the SLC12A3 gene in patients with Gitelman syndrome."; RL Scand. J. Clin. Lab. Invest. 81:629-633(2021). RN [33] RP VARIANTS GTLMNS GLN-158 AND SER-212, CHARACTERIZATION OF VARIANTS GTLMNS RP GLN-158 AND SER-212, AND SUBCELLULAR LOCATION. RX PubMed=36370249; DOI=10.1007/s11684-022-0963-9; RA Li Z., Wu H., Wei S., Liu M., Shi Y., Li M., Wang N., Fang L., Xiang B., RA Gao L., Xu C., Zhao J.; RT "R158Q and G212S, novel pathogenic compound heterozygous variants in RT SLC12A3 of Gitelman syndrome."; RL Front. Med. 16:932-945(2022). RN [34] RP INVOLVEMENT IN GTLMNS. RX PubMed=36460433; DOI=10.1016/j.nefroe.2022.06.002; RA Correia A.L., Marques M.G., Alves R.; RT "Gitelman syndrome - A new mutation in the SLC12A3 gene."; RL Nefrologia 42:490-492(2022). RN [35] RP VARIANT GTLMNS LYS-304. RX PubMed=35693921; DOI=10.1177/2050313x221102294; RA De Silva N., Pathmanathan S., Sumanatilleke M., Dematapitiya C., RA Dissanayake P., Wijenayake U., Subasinghe V., Dissanayake V.; RT "A novel mutation of SLC12A3 gene causing Gitelman syndrome."; RL SAGE Open Med. Case Rep. 10:2050313X221102294-2050313X221102294(2022). CC -!- FUNCTION: Electroneutral sodium and chloride ion cotransporter, which CC acts as a key mediator of sodium and chloride reabsorption in kidney CC distal convoluted tubules (PubMed:21613606, PubMed:18270262, CC PubMed:22009145, PubMed:36351028, PubMed:36792826). Also acts as a CC receptor for the pro-inflammatory cytokine IL18, thereby contributing CC to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2 CC (By similarity). May act either independently of IL18R1, or in a CC complex with IL18R1 (By similarity). {ECO:0000250|UniProtKB:P59158, CC ECO:0000269|PubMed:18270262, ECO:0000269|PubMed:21613606, CC ECO:0000269|PubMed:22009145, ECO:0000269|PubMed:36351028, CC ECO:0000269|PubMed:36792826}. CC -!- CATALYTIC ACTIVITY: CC Reaction=chloride(out) + Na(+)(out) = chloride(in) + Na(+)(in); CC Xref=Rhea:RHEA:73887, ChEBI:CHEBI:17996, ChEBI:CHEBI:29101; CC Evidence={ECO:0000269|PubMed:36351028, ECO:0000269|PubMed:36792826}; CC -!- ACTIVITY REGULATION: Phosphorylation by OXSR1/OSR1 and STK39/SPAK in CC kidney distal convoluted tubules downstream of WNK4 promotes its CC activity (PubMed:18270262). Also activated by OXSR1/OSR1 and STK39/SPAK CC downstream of WNK3 (PubMed:21613606). Target of thiazide diuretics used CC in the treatment of high blood pressure (PubMed:8528245, CC PubMed:36792826). Thiazide drugs, such as polythiazide, specifically CC inhibit SLC12A3/NCC transporter activity by competing with chloride for CC binding and by locking SLC12A3/NCC in an outward-facing conformation CC (PubMed:36792826). {ECO:0000269|PubMed:18270262, CC ECO:0000269|PubMed:21613606, ECO:0000269|PubMed:36792826, CC ECO:0000269|PubMed:8528245}. CC -!- SUBUNIT: Homodimer (PubMed:36351028, PubMed:36792826). Interacts with CC KLHL3 (PubMed:22406640). Interacts with IL18R1; this interaction is CC increased by IL18 treatment (By similarity). CC {ECO:0000250|UniProtKB:P59158, ECO:0000269|PubMed:22406640, CC ECO:0000269|PubMed:36351028, ECO:0000269|PubMed:36792826}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:22009145, CC ECO:0000269|PubMed:36370249}; Multi-pass membrane protein CC {ECO:0000269|PubMed:36351028, ECO:0000269|PubMed:36792826}. Apical cell CC membrane {ECO:0000250|UniProtKB:P59158}; Multi-pass membrane protein CC {ECO:0000269|PubMed:36351028, ECO:0000269|PubMed:36792826}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P55017-1; Sequence=Displayed; CC Name=2; CC IsoId=P55017-2; Sequence=VSP_036318; CC Name=3; CC IsoId=P55017-3; Sequence=VSP_040100, VSP_036318; CC -!- TISSUE SPECIFICITY: Predominantly expressed in the kidney (at protein CC level) (PubMed:29993276, PubMed:8812482). Localizes to the distal CC convoluted tubules (at protein level)(PubMed:29993276). Not detected in CC normal aorta, but abundantly expressed in fatty streaks and advanced CC atherosclerotic lesions (at protein level) (PubMed:26099046). CC {ECO:0000269|PubMed:26099046, ECO:0000269|PubMed:29993276, CC ECO:0000269|PubMed:8812482}. CC -!- DOMAIN: Interaction between the cytoplasmic N-terminal and C-terminal CC domains (NTD and CTD, respectively) is essential for SLC12A3/NCC CC transporter activity (PubMed:36792826). Phosphorylation by OXSR1/OSR1 CC and STK39/SPAK may activate SLC12A3/NCC by facilitating this CC interaction (PubMed:36792826). {ECO:0000269|PubMed:36792826}. CC -!- PTM: Ubiquitinated; ubiquitination is essential for regulation of CC endocytosis. The BCR(KLHL3) complex was initially identified as a CC candidate ubiquitin ligase for SLC12A3 (PubMed:22406640). However, it CC was later shown that it is not the case. {ECO:0000269|PubMed:22406640}. CC -!- PTM: Phosphorylated at Thr-46, Thr-55, Thr-60 and Ser-91 by OXSR1/OSR1 CC and STK39/SPAK downstream of WNK4, promoting its activity CC (PubMed:18270262). Phosphorylated in response to IL18 (By similarity). CC {ECO:0000250|UniProtKB:P59158, ECO:0000269|PubMed:18270262}. CC -!- DISEASE: Gitelman syndrome (GTLMNS) [MIM:263800]: An autosomal CC recessive disorder characterized by hypokalemic alkalosis in CC combination with hypomagnesemia, low urinary calcium, and increased CC renin activity associated with normal blood pressure. Patients are CC often asymptomatic or present transient periods of muscular weakness CC and tetany, usually accompanied by abdominal pain, vomiting and fever. CC The phenotype is highly heterogeneous in terms of age at onset and CC severity. Cardinal features such as hypocalciuria and hypomagnesemia CC might also change during the life cycle of a given patient. It has CC overlapping features with Bartter syndrome. CC {ECO:0000269|PubMed:10616841, ECO:0000269|PubMed:10988270, CC ECO:0000269|PubMed:11168953, ECO:0000269|PubMed:11940055, CC ECO:0000269|PubMed:12008755, ECO:0000269|PubMed:12112667, CC ECO:0000269|PubMed:15069170, ECO:0000269|PubMed:15687331, CC ECO:0000269|PubMed:16429844, ECO:0000269|PubMed:17654016, CC ECO:0000269|PubMed:17873326, ECO:0000269|PubMed:22009145, CC ECO:0000269|PubMed:26099046, ECO:0000269|PubMed:33462018, CC ECO:0000269|PubMed:33772578, ECO:0000269|PubMed:34079339, CC ECO:0000269|PubMed:34657521, ECO:0000269|PubMed:35693921, CC ECO:0000269|PubMed:36370249, ECO:0000269|PubMed:36460433, CC ECO:0000269|PubMed:8528245, ECO:0000269|PubMed:8900229, CC ECO:0000269|PubMed:8954067, ECO:0000269|PubMed:9734597}. Note=The CC disease is caused by variants affecting the gene represented in this CC 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; U44128; AAC50355.1; -; mRNA. DR EMBL; X91220; CAA62613.1; -; mRNA. DR EMBL; AK315298; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AC012181; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS10770.1; -. [P55017-2] DR CCDS; CCDS45491.1; -. [P55017-3] DR CCDS; CCDS58464.1; -. [P55017-1] DR PIR; G01202; G01202. DR PIR; PC4180; PC4180. DR RefSeq; NP_000330.2; NM_000339.2. [P55017-2] DR RefSeq; NP_001119579.1; NM_001126107.1. [P55017-3] DR RefSeq; NP_001119580.1; NM_001126108.1. [P55017-1] DR PDB; 7Y6I; EM; 2.85 A; A/B=1-1021. DR PDB; 7YG0; EM; 3.75 A; A/B=1-1021. DR PDB; 7YG1; EM; 3.77 A; A/B=1-1021. DR PDB; 8FHN; EM; 3.00 A; A/B/C=132-263, A/B/C=265-1021. DR PDB; 8FHO; EM; 2.95 A; A/B/C=132-263, A/B/C=265-1021. DR PDB; 8FHP; EM; 3.04 A; A/B=132-263, A/B=265-1021. DR PDB; 8FHQ; EM; 2.81 A; A/B=132-263, A/B=265-1021. DR PDB; 8FHR; EM; 2.90 A; A/B=132-263, A/B=265-1021. DR PDB; 8FHT; EM; 3.02 A; A/B=1-1021. DR PDBsum; 7Y6I; -. DR PDBsum; 7YG0; -. DR PDBsum; 7YG1; -. DR PDBsum; 8FHN; -. DR PDBsum; 8FHO; -. DR PDBsum; 8FHP; -. DR PDBsum; 8FHQ; -. DR PDBsum; 8FHR; -. DR PDBsum; 8FHT; -. DR AlphaFoldDB; P55017; -. DR EMDB; EMD-29103; -. DR SMR; P55017; -. DR BioGRID; 112448; 20. DR ELM; P55017; -. DR IntAct; P55017; 1. DR STRING; 9606.ENSP00000402152; -. DR ChEMBL; CHEMBL1876; -. DR DrugBank; DB00436; Bendroflumethiazide. DR DrugBank; DB00562; Benzthiazide. DR DrugBank; DB00880; Chlorothiazide. DR DrugBank; DB00999; Hydrochlorothiazide. DR DrugBank; DB00808; Indapamide. DR DrugBank; DB00524; Metolazone. DR DrugBank; DB01324; Polythiazide. DR DrugBank; DB01325; Quinethazone. DR DrugBank; DB01021; Trichlormethiazide. DR DrugCentral; P55017; -. DR TCDB; 2.A.30.1.12; the cation-chloride cotransporter (ccc) family. DR GlyCosmos; P55017; 2 sites, No reported glycans. DR GlyGen; P55017; 2 sites. DR iPTMnet; P55017; -. DR PhosphoSitePlus; P55017; -. DR BioMuta; SLC12A3; -. DR DMDM; 313104194; -. DR jPOST; P55017; -. DR MassIVE; P55017; -. DR PaxDb; 9606-ENSP00000402152; -. DR PeptideAtlas; P55017; -. DR ProteomicsDB; 56759; -. [P55017-1] DR ProteomicsDB; 56760; -. [P55017-2] DR ProteomicsDB; 56761; -. [P55017-3] DR Antibodypedia; 28680; 278 antibodies from 22 providers. DR DNASU; 6559; -. DR Ensembl; ENST00000438926.6; ENSP00000402152.2; ENSG00000070915.10. [P55017-2] DR Ensembl; ENST00000563236.6; ENSP00000456149.2; ENSG00000070915.10. [P55017-1] DR Ensembl; ENST00000566786.5; ENSP00000457552.1; ENSG00000070915.10. [P55017-3] DR GeneID; 6559; -. DR KEGG; hsa:6559; -. DR MANE-Select; ENST00000563236.6; ENSP00000456149.2; NM_001126108.2; NP_001119580.2. DR UCSC; uc002ekd.4; human. [P55017-1] DR AGR; HGNC:10912; -. DR CTD; 6559; -. DR DisGeNET; 6559; -. DR GeneCards; SLC12A3; -. DR HGNC; HGNC:10912; SLC12A3. DR HPA; ENSG00000070915; Tissue enriched (kidney). DR MalaCards; SLC12A3; -. DR MIM; 263800; phenotype. DR MIM; 600968; gene. DR neXtProt; NX_P55017; -. DR OpenTargets; ENSG00000070915; -. DR Orphanet; 358; Gitelman syndrome. DR PharmGKB; PA321; -. DR VEuPathDB; HostDB:ENSG00000070915; -. DR eggNOG; KOG2083; Eukaryota. DR GeneTree; ENSGT00940000155044; -. DR InParanoid; P55017; -. DR OMA; PWMITEQ; -. DR OrthoDB; 5490251at2759; -. DR PhylomeDB; P55017; -. DR TreeFam; TF313191; -. DR PathwayCommons; P55017; -. DR Reactome; R-HSA-426117; Cation-coupled Chloride cotransporters. DR Reactome; R-HSA-5619087; Defective SLC12A3 causes Gitelman syndrome (GS). DR SignaLink; P55017; -. DR SIGNOR; P55017; -. DR BioGRID-ORCS; 6559; 10 hits in 1161 CRISPR screens. DR ChiTaRS; SLC12A3; human. DR GeneWiki; Sodium-chloride_symporter; -. DR GenomeRNAi; 6559; -. DR Pharos; P55017; Tclin. DR PRO; PR:P55017; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; P55017; Protein. DR Bgee; ENSG00000070915; Expressed in adult mammalian kidney and 62 other cell types or tissues. DR ExpressionAtlas; P55017; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IDA:MGI. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0015378; F:sodium:chloride symporter activity; IDA:UniProtKB. DR GO; GO:0008511; F:sodium:potassium:chloride symporter activity; IBA:GO_Central. DR GO; GO:0006884; P:cell volume homeostasis; IBA:GO_Central. DR GO; GO:0071241; P:cellular response to inorganic substance; IEA:Ensembl. 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:0006811; P:monoatomic ion transport; TAS:Reactome. 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:0070294; P:renal sodium ion absorption; IDA:UniProt. DR GO; GO:1904044; P:response to aldosterone; IEA:Ensembl. DR GO; GO:0002021; P:response to dietary excess; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; IEA:Ensembl. DR GO; GO:0055078; P:sodium ion homeostasis; IBA:GO_Central. DR GO; GO:0035725; P:sodium ion transmembrane transport; ISS:BHF-UCL. DR GO; GO:0006814; P:sodium ion transport; ISS:UniProtKB. 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; IPR018491; SLC12_C. DR InterPro; IPR002948; SLC12A3. DR InterPro; IPR004842; SLC12A_fam. DR NCBIfam; TIGR00930; 2a30; 1. DR PANTHER; PTHR11827:SF9; SOLUTE CARRIER FAMILY 12 MEMBER 3; 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; 2. DR PRINTS; PR01230; NACLTRNSPORT. DR Genevisible; P55017; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane; Chloride; KW Disease variant; Disulfide bond; Glycoprotein; Ion transport; Membrane; KW Nucleotide-binding; Phosphoprotein; Reference proteome; Sodium; KW Sodium transport; Symport; Transmembrane; Transmembrane helix; Transport; KW Ubl conjugation. FT CHAIN 1..1021 FT /note="Solute carrier family 12 member 3" FT /id="PRO_0000178026" FT TOPO_DOM 1..137 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TRANSMEM 138..166 FT /note="Discontinuously helical" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TOPO_DOM 167 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TRANSMEM 168..193 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TOPO_DOM 194..212 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TRANSMEM 213..249 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TOPO_DOM 250..257 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TRANSMEM 258..277 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TOPO_DOM 278 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TRANSMEM 279..305 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TOPO_DOM 306..339 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TRANSMEM 340..360 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TOPO_DOM 361..366 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TRANSMEM 367..396 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TOPO_DOM 397..453 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TRANSMEM 454..485 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TOPO_DOM 486..505 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TRANSMEM 506..523 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TOPO_DOM 524..525 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TRANSMEM 526..554 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TOPO_DOM 555..565 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TRANSMEM 566..584 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TOPO_DOM 585 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TRANSMEM 586..606 FT /note="Helical" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT TOPO_DOM 607..1021 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT BINDING 148 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHO, ECO:0007744|PDB:8FHP, FT ECO:0007744|PDB:8FHQ, ECO:0007744|PDB:8FHR, FT ECO:0007744|PDB:8FHT" FT BINDING 149 FT /ligand="polythiazide" FT /ligand_id="ChEBI:CHEBI:8327" FT /evidence="ECO:0000269|PubMed:36792826, FT ECO:0007744|PDB:8FHO, ECO:0007744|PDB:8FHP, FT ECO:0007744|PDB:8FHQ, ECO:0007744|PDB:8FHR" FT BINDING 151 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHO, ECO:0007744|PDB:8FHP, FT ECO:0007744|PDB:8FHQ, ECO:0007744|PDB:8FHR, FT ECO:0007744|PDB:8FHT" FT BINDING 227 FT /ligand="polythiazide" FT /ligand_id="ChEBI:CHEBI:8327" FT /evidence="ECO:0000269|PubMed:36792826, FT ECO:0007744|PDB:8FHO, ECO:0007744|PDB:8FHP, FT ECO:0007744|PDB:8FHQ" FT BINDING 234 FT /ligand="polythiazide" FT /ligand_id="ChEBI:CHEBI:8327" FT /evidence="ECO:0000269|PubMed:36792826, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR" FT BINDING 352 FT /ligand="polythiazide" FT /ligand_id="ChEBI:CHEBI:8327" FT /evidence="ECO:0000269|PubMed:36792826, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHP, FT ECO:0007744|PDB:8FHR" FT BINDING 353 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /evidence="ECO:0000305|PubMed:36351028, FT ECO:0000305|PubMed:36792826" FT BINDING 354 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /evidence="ECO:0000305|PubMed:36351028, FT ECO:0000305|PubMed:36792826" FT BINDING 355 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /evidence="ECO:0000305|PubMed:36351028, FT ECO:0000305|PubMed:36792826" FT BINDING 359 FT /ligand="polythiazide" FT /ligand_id="ChEBI:CHEBI:8327" FT /evidence="ECO:0000269|PubMed:36792826, FT ECO:0007744|PDB:8FHN" FT BINDING 464 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHO, ECO:0007744|PDB:8FHP, FT ECO:0007744|PDB:8FHQ, ECO:0007744|PDB:8FHR, FT ECO:0007744|PDB:8FHT" FT BINDING 467 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHO, ECO:0007744|PDB:8FHP, FT ECO:0007744|PDB:8FHQ, ECO:0007744|PDB:8FHR, FT ECO:0007744|PDB:8FHT" FT BINDING 468 FT /ligand="Na(+)" FT /ligand_id="ChEBI:CHEBI:29101" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHO, ECO:0007744|PDB:8FHP, FT ECO:0007744|PDB:8FHQ, ECO:0007744|PDB:8FHR, FT ECO:0007744|PDB:8FHT" FT BINDING 540 FT /ligand="chloride" FT /ligand_id="ChEBI:CHEBI:17996" FT /evidence="ECO:0000305|PubMed:36351028, FT ECO:0000305|PubMed:36792826" FT BINDING 648 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:36792826, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO" FT BINDING 655 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:36792826, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO" FT BINDING 677 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:36792826, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO" FT BINDING 741 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:36792826, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO" FT BINDING 780 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:36792826, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO" FT BINDING 781 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:36792826, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO" FT MOD_RES 43 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P59158" FT MOD_RES 46 FT /note="Phosphothreonine; by OXSR1 and STK39" FT /evidence="ECO:0000269|PubMed:18270262" FT MOD_RES 49 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P59158" FT MOD_RES 50 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P59158" FT MOD_RES 55 FT /note="Phosphothreonine; by OXSR1 and STK39" FT /evidence="ECO:0000269|PubMed:18270262" FT MOD_RES 60 FT /note="Phosphothreonine; by OXSR1 and STK39" FT /evidence="ECO:0000269|PubMed:18270262" FT MOD_RES 73 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P59158" FT MOD_RES 91 FT /note="Phosphoserine; by OXSR1 and STK39" FT /evidence="ECO:0000305|PubMed:18270262, FT ECO:0007744|PubMed:23186163" FT MOD_RES 124 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P59158" FT MOD_RES 126 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P59158" FT CARBOHYD 406 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0007744|PDB:7Y6I" FT CARBOHYD 426 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0007744|PDB:7Y6I" FT DISULFID 416..421 FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT DISULFID 430..436 FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826, ECO:0007744|PDB:7Y6I, FT ECO:0007744|PDB:8FHN, ECO:0007744|PDB:8FHO, FT ECO:0007744|PDB:8FHP, ECO:0007744|PDB:8FHQ, FT ECO:0007744|PDB:8FHR, ECO:0007744|PDB:8FHT" FT VAR_SEQ 95 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_040100" FT VAR_SEQ 807 FT /note="V -> GARPSVSGAL (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:8528245" FT /id="VSP_036318" FT VARIANT 60 FT /note="T -> M (in GTLMNS; dbSNP:rs371443644)" FT /evidence="ECO:0000269|PubMed:15069170, FT ECO:0000269|PubMed:22009145, ECO:0000269|PubMed:34079339" FT /id="VAR_039475" FT VARIANT 62 FT /note="D -> H (in GTLMNS; dbSNP:rs757490496)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075931" FT VARIANT 62 FT /note="D -> N (in GTLMNS)" FT /evidence="ECO:0000269|PubMed:8900229" FT /id="VAR_039476" FT VARIANT 68 FT /note="E -> K (in GTLMNS; dbSNP:rs763210286)" FT /evidence="ECO:0000269|PubMed:17654016" FT /id="VAR_039477" FT VARIANT 69 FT /note="H -> N (in GTLMNS; dbSNP:rs780502516)" FT /evidence="ECO:0000269|PubMed:17654016" FT /id="VAR_039478" FT VARIANT 83 FT /note="R -> Q (in GTLMNS; dbSNP:rs768527231)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075932" FT VARIANT 83 FT /note="R -> W (in GTLMNS; dbSNP:rs201255508)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075933" FT VARIANT 90 FT /note="H -> Y (in GTLMNS; dbSNP:rs1596883431)" FT /evidence="ECO:0000269|PubMed:15687331" FT /id="VAR_039479" FT VARIANT 121 FT /note="E -> D (in GTLMNS; 27% residual Na(+) uptake FT activity; increased MAPK1/3 (ERK1/2) phosphorylation in FT response to IL18; no effect on localization at the plasma FT membrane; dbSNP:rs146632606)" FT /evidence="ECO:0000269|PubMed:22009145, FT ECO:0000269|PubMed:26099046" FT /id="VAR_075934" FT VARIANT 135 FT /note="R -> C (in GTLMNS; dbSNP:rs749742102)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075935" FT VARIANT 145 FT /note="R -> C (in GTLMNS; dbSNP:rs148945966)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075936" FT VARIANT 145 FT /note="R -> H (in GTLMNS; dbSNP:rs374324018)" FT /evidence="ECO:0000269|PubMed:17654016" FT /id="VAR_039480" FT VARIANT 150 FT /note="I -> M (in GTLMNS; dbSNP:rs143714318)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075937" FT VARIANT 153 FT /note="V -> M (in GTLMNS; dbSNP:rs779074538)" FT /evidence="ECO:0000269|PubMed:17654016, FT ECO:0000269|PubMed:22009145" FT /id="VAR_039481" FT VARIANT 154 FT /note="I -> F (in GTLMNS; dbSNP:rs748547209)" FT /evidence="ECO:0000269|PubMed:11168953" FT /id="VAR_039482" FT VARIANT 157 FT /note="L -> P (in GTLMNS; dbSNP:rs775047246)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075938" FT VARIANT 158 FT /note="R -> L (in GTLMNS)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075939" FT VARIANT 158 FT /note="R -> Q (in GTLMNS; impaired protein structure; FT dbSNP:rs1274973729)" FT /evidence="ECO:0000269|PubMed:12112667, FT ECO:0000269|PubMed:36370249" FT /id="VAR_039483" FT VARIANT 163 FT /note="T -> M (in GTLMNS; dbSNP:rs267607050)" FT /evidence="ECO:0000269|PubMed:12112667, FT ECO:0000269|PubMed:22009145" FT /id="VAR_039484" FT VARIANT 166 FT /note="A -> V (in GTLMNS; dbSNP:rs779683214)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075940" FT VARIANT 172 FT /note="W -> R (in GTLMNS; dbSNP:rs757792232)" FT /evidence="ECO:0000269|PubMed:12112667, FT ECO:0000269|PubMed:22009145" FT /id="VAR_039485" FT VARIANT 178 FT /note="S -> L (in GTLMNS; dbSNP:rs772589653)" FT /evidence="ECO:0000269|PubMed:11168953, FT ECO:0000269|PubMed:22009145" FT /id="VAR_039486" FT VARIANT 180 FT /note="T -> K (in GTLMNS; dbSNP:rs146158333)" FT /evidence="ECO:0000269|PubMed:10616841" FT /id="VAR_039487" FT VARIANT 186 FT /note="G -> D (in GTLMNS; dbSNP:rs759426055)" FT /evidence="ECO:0000269|PubMed:8900229" FT /id="VAR_039488" FT VARIANT 192 FT /note="I -> T (in GTLMNS; associated with deletion of FT N-566; dbSNP:rs1231715433)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075941" FT VARIANT 194 FT /note="T -> I (in GTLMNS)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075942" FT VARIANT 209 FT /note="R -> Q (in GTLMNS; dbSNP:rs758035631)" FT /evidence="ECO:0000269|PubMed:11168953, FT ECO:0000269|PubMed:22009145" FT /id="VAR_039489" FT VARIANT 209 FT /note="R -> W (in GTLMNS; dbSNP:rs28936388)" FT /evidence="ECO:0000269|PubMed:12112667, FT ECO:0000269|PubMed:8528245, ECO:0000269|PubMed:8900229, FT ECO:0000269|PubMed:9734597" FT /id="VAR_007113" FT VARIANT 212 FT /note="G -> S (in GTLMNS; impaired protein structure)" FT /evidence="ECO:0000269|PubMed:36370249" FT /id="VAR_088220" FT VARIANT 215 FT /note="L -> P (in GTLMNS; dbSNP:rs780594361)" FT /evidence="ECO:0000269|PubMed:9734597" FT /id="VAR_039490" FT VARIANT 226 FT /note="A -> T (in GTLMNS; dbSNP:rs774753202)" FT /evidence="ECO:0000269|PubMed:9734597" FT /id="VAR_039491" FT VARIANT 230 FT /note="G -> D (in GTLMNS; dbSNP:rs375990084)" FT /evidence="ECO:0000269|PubMed:17654016" FT /id="VAR_039492" FT VARIANT 235 FT /note="T -> R (in GTLMNS)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075943" FT VARIANT 259 FT /note="D -> N (in GTLMNS; dbSNP:rs780461639)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075944" FT VARIANT 261 FT /note="R -> H (in GTLMNS; dbSNP:rs914588619)" FT /evidence="ECO:0000269|PubMed:9734597" FT /id="VAR_039493" FT VARIANT 264 FT /note="A -> G (in dbSNP:rs1529927)" FT /evidence="ECO:0000269|PubMed:11940055, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:17885550, FT ECO:0000269|PubMed:34079339, ECO:0000269|PubMed:8528245, FT ECO:0000269|PubMed:8812482" FT /id="VAR_039494" FT VARIANT 272 FT /note="L -> P (in GTLMNS; dbSNP:rs568513106)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075945" FT VARIANT 283 FT /note="S -> Y (in GTLMNS; dbSNP:rs1380031877)" FT /evidence="ECO:0000269|PubMed:15687331" FT /id="VAR_039495" FT VARIANT 284 FT /note="K -> R (in GTLMNS)" FT /evidence="ECO:0000269|PubMed:11168953" FT /id="VAR_039496" FT VARIANT 304 FT /note="T -> K (in GTLMNS)" FT /evidence="ECO:0000269|PubMed:35693921" FT /id="VAR_088221" FT VARIANT 304 FT /note="T -> M (in GTLMNS; dbSNP:rs755069436)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075946" FT VARIANT 304 FT /note="T -> P (in GTLMNS; dbSNP:rs753840283)" FT /evidence="ECO:0000269|PubMed:10988270, FT ECO:0000269|PubMed:22009145" FT /id="VAR_039497" FT VARIANT 313 FT /note="A -> V (in GTLMNS; dbSNP:rs140551719)" FT /evidence="ECO:0000269|PubMed:11168953, FT ECO:0000269|PubMed:22009145" FT /id="VAR_039498" FT VARIANT 316 FT /note="G -> V (in GTLMNS; dbSNP:rs748920885)" FT /evidence="ECO:0000269|PubMed:12112667" FT /id="VAR_039499" FT VARIANT 321 FT /note="R -> W (in GTLMNS; dbSNP:rs150046661)" FT /evidence="ECO:0000269|PubMed:11168953, FT ECO:0000269|PubMed:22009145" FT /id="VAR_039500" FT VARIANT 334 FT /note="R -> W (in GTLMNS; dbSNP:rs770702194)" FT /evidence="ECO:0000269|PubMed:11168953, FT ECO:0000269|PubMed:22009145" FT /id="VAR_039501" FT VARIANT 342 FT /note="G -> A (in GTLMNS)" FT /evidence="ECO:0000269|PubMed:17654016" FT /id="VAR_039502" FT VARIANT 349 FT /note="P -> L (in GTLMNS; dbSNP:rs121909383)" FT /evidence="ECO:0000269|PubMed:8528245, FT ECO:0000269|PubMed:8900229" FT /id="VAR_007114" FT VARIANT 359 FT /note="N -> K (in GTLMNS; uncertain significance)" FT /evidence="ECO:0000269|PubMed:34657521" FT /id="VAR_088222" FT VARIANT 374 FT /note="G -> E (in GTLMNS; dbSNP:rs773669504)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075947" FT VARIANT 374 FT /note="G -> V (in GTLMNS; dbSNP:rs773669504)" FT /evidence="ECO:0000269|PubMed:12112667" FT /id="VAR_039503" FT VARIANT 382 FT /note="T -> M (in GTLMNS; dbSNP:rs187885782)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075948" FT VARIANT 392 FT /note="T -> I (in GTLMNS; complete loss Na(+) uptake FT activity; partial loss of localization at the plasma FT membrane; dbSNP:rs748575829)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075949" FT VARIANT 399 FT /note="R -> C (in GTLMNS; dbSNP:rs775931992)" FT /evidence="ECO:0000269|PubMed:11168953, FT ECO:0000269|PubMed:22009145" FT /id="VAR_039504" FT VARIANT 421 FT /note="C -> R (in GTLMNS; dbSNP:rs28936387)" FT /evidence="ECO:0000269|PubMed:8528245" FT /id="VAR_007115" FT VARIANT 433..436 FT /note="QHSC -> L (in GTLMNS)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075950" FT VARIANT 439 FT /note="G -> S (in GTLMNS; does not affect MAPK1/3 (ERK1/2) FT phosphorylation in response to IL18; dbSNP:rs759377924)" FT /evidence="ECO:0000269|PubMed:10988270, FT ECO:0000269|PubMed:22009145, ECO:0000269|PubMed:26099046, FT ECO:0000269|PubMed:8900229" FT /id="VAR_039505" FT VARIANT 442 FT /note="N -> S (in GTLMNS; 68% residual Na(+) uptake FT activity; partial loss of localization at the plasma FT membrane)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075951" FT VARIANT 463 FT /note="G -> E (in GTLMNS; dbSNP:rs1375515522)" FT /evidence="ECO:0000269|PubMed:12112667" FT /id="VAR_039506" FT VARIANT 463 FT /note="G -> R (in GTLMNS; dbSNP:rs374163823)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075952" FT VARIANT 464 FT /note="A -> T (in GTLMNS; dbSNP:rs201945662)" FT /evidence="ECO:0000269|PubMed:12112667, FT ECO:0000269|PubMed:22009145" FT /id="VAR_039507" FT VARIANT 475 FT /note="S -> C (in GTLMNS; 40% residual Na(+) uptake FT activity; increased MAPK1/3 (ERK1/2) phosphorylation in FT response to IL18; no effect on localization at the plasma FT membrane; dbSNP:rs373017321)" FT /evidence="ECO:0000269|PubMed:22009145, FT ECO:0000269|PubMed:26099046" FT /id="VAR_075953" FT VARIANT 478 FT /note="K -> E (in GTLMNS; dbSNP:rs1355705043)" FT /evidence="ECO:0000269|PubMed:8900229" FT /id="VAR_039508" FT VARIANT 486 FT /note="D -> N (in GTLMNS; dbSNP:rs753523115)" FT /evidence="ECO:0000269|PubMed:34079339, FT ECO:0000269|PubMed:34657521, ECO:0000269|PubMed:8528245, FT ECO:0000269|PubMed:8900229" FT /id="VAR_007116" FT VARIANT 489 FT /note="Y -> H (in GTLMNS; 48% residual Na(+) uptake FT activity; no effect on localization at the plasma FT membrane)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075954" FT VARIANT 496 FT /note="G -> C (in GTLMNS; dbSNP:rs777612082)" FT /evidence="ECO:0000269|PubMed:8528245, FT ECO:0000269|PubMed:8900229" FT /id="VAR_007117" FT VARIANT 507 FT /note="R -> C (in GTLMNS; dbSNP:rs369510226)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075955" FT VARIANT 523 FT /note="A -> T (in GTLMNS; dbSNP:rs781137708)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075956" FT VARIANT 534 FT /note="N -> S (in GTLMNS; dbSNP:rs780433336)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075957" FT VARIANT 536 FT /note="F -> L (in GTLMNS; dbSNP:rs748650798)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075958" FT VARIANT 537 FT /note="L -> F (in GTLMNS; uncertain significance)" FT /evidence="ECO:0000269|PubMed:34657521" FT /id="VAR_088223" FT VARIANT 542 FT /note="L -> P (in GTLMNS; dbSNP:rs574357286)" FT /evidence="ECO:0000269|PubMed:8900229" FT /id="VAR_039509" FT VARIANT 546 FT /note="S -> G (in GTLMNS; dbSNP:rs1451284628)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075959" FT VARIANT 555 FT /note="S -> L (in GTLMNS; dbSNP:rs148038173)" FT /evidence="ECO:0000269|PubMed:11168953, FT ECO:0000269|PubMed:22009145" FT /id="VAR_039510" FT VARIANT 560 FT /note="P -> H (in GTLMNS; dbSNP:rs1402444800)" FT /evidence="ECO:0000269|PubMed:9734597" FT /id="VAR_039511" FT VARIANT 560 FT /note="P -> R (in GTLMNS; dbSNP:rs1402444800)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075960" FT VARIANT 561 FT /note="Missing (in GTLMNS)" FT /evidence="ECO:0000269|PubMed:8528245" FT /id="VAR_007118" FT VARIANT 566 FT /note="Missing (in GTLMNS; associated with T-192)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075961" FT VARIANT 569 FT /note="A -> E (in GTLMNS; dbSNP:rs79351185)" FT /evidence="ECO:0000269|PubMed:10616841" FT /id="VAR_039512" FT VARIANT 569 FT /note="A -> V (in GTLMNS; dbSNP:rs79351185)" FT /evidence="ECO:0000269|PubMed:15069170" FT /id="VAR_039513" FT VARIANT 578 FT /note="V -> M (in GTLMNS; dbSNP:rs139329616)" FT /evidence="ECO:0000269|PubMed:10616841" FT /id="VAR_039514" FT VARIANT 588 FT /note="A -> V (in GTLMNS; dbSNP:rs121909382)" FT /evidence="ECO:0000269|PubMed:8528245, FT ECO:0000269|PubMed:8900229" FT /id="VAR_007119" FT VARIANT 613 FT /note="G -> S (in GTLMNS; dbSNP:rs1222807128)" FT /evidence="ECO:0000269|PubMed:9734597" FT /id="VAR_039515" FT VARIANT 615 FT /note="S -> L (in GTLMNS; dbSNP:rs779160677)" FT /evidence="ECO:0000269|PubMed:11168953, FT ECO:0000269|PubMed:12112667, ECO:0000269|PubMed:22009145" FT /id="VAR_039516" FT VARIANT 615 FT /note="S -> W (in GTLMNS; dbSNP:rs779160677)" FT /evidence="ECO:0000269|PubMed:12112667" FT /id="VAR_039517" FT VARIANT 623 FT /note="L -> P (in GTLMNS; dbSNP:rs121909385)" FT /evidence="ECO:0000269|PubMed:12008755, FT ECO:0000269|PubMed:8954067" FT /id="VAR_039518" FT VARIANT 630 FT /note="G -> V (in GTLMNS; dbSNP:rs121909384)" FT /evidence="ECO:0000269|PubMed:8528245" FT /id="VAR_007120" FT VARIANT 642 FT /note="R -> C (in GTLMNS; dbSNP:rs200697179)" FT /evidence="ECO:0000269|PubMed:10616841, FT ECO:0000269|PubMed:15069170, ECO:0000269|PubMed:22009145" FT /id="VAR_039519" FT VARIANT 642 FT /note="R -> G (in GTLMNS; dbSNP:rs200697179)" FT /evidence="ECO:0000269|PubMed:11168953, FT ECO:0000269|PubMed:12112667, ECO:0000269|PubMed:22009145" FT /id="VAR_039520" FT VARIANT 642 FT /note="R -> H (in GTLMNS; dbSNP:rs147901432)" FT /evidence="ECO:0000269|PubMed:12112667, FT ECO:0000269|PubMed:22009145, ECO:0000269|PubMed:9734597" FT /id="VAR_039521" FT VARIANT 643 FT /note="P -> L (in GTLMNS; dbSNP:rs140012781)" FT /evidence="ECO:0000269|PubMed:11168953, FT ECO:0000269|PubMed:11940055, ECO:0000269|PubMed:22009145" FT /id="VAR_039522" FT VARIANT 647 FT /note="V -> M (in GTLMNS)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075962" FT VARIANT 649 FT /note="T -> R (in GTLMNS)" FT /evidence="ECO:0000269|PubMed:9734597" FT /id="VAR_039523" FT VARIANT 655 FT /note="R -> C (in GTLMNS; dbSNP:rs747249619)" FT /evidence="ECO:0000269|PubMed:9734597" FT /id="VAR_039524" FT VARIANT 655 FT /note="R -> H (in GTLMNS; dbSNP:rs121909380)" FT /evidence="ECO:0000269|PubMed:22009145, FT ECO:0000269|PubMed:8528245" FT /id="VAR_007121" FT VARIANT 655 FT /note="R -> L (in GTLMNS; dbSNP:rs121909380)" FT /evidence="ECO:0000269|PubMed:8528245" FT /id="VAR_007122" FT VARIANT 672 FT /note="M -> I (in GTLMNS)" FT /evidence="ECO:0000269|PubMed:16429844" FT /id="VAR_039525" FT VARIANT 677 FT /note="V -> L (in GTLMNS)" FT /evidence="ECO:0000269|PubMed:17654016" FT /id="VAR_039526" FT VARIANT 677 FT /note="V -> M (in GTLMNS; dbSNP:rs771326058)" FT /evidence="ECO:0000269|PubMed:12112667" FT /id="VAR_039527" FT VARIANT 713 FT /note="I -> IKAFYSDVI (in GTLMNS)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075963" FT VARIANT 728 FT /note="A -> T (in dbSNP:rs36049418)" FT /evidence="ECO:0000269|PubMed:17885550, FT ECO:0000269|PubMed:8528245" FT /id="VAR_007123" FT VARIANT 729 FT /note="G -> V (in GTLMNS; dbSNP:rs373901523)" FT /evidence="ECO:0000269|PubMed:11168953, FT ECO:0000269|PubMed:22009145" FT /id="VAR_039528" FT VARIANT 731 FT /note="G -> R (in GTLMNS; dbSNP:rs752101663)" FT /evidence="ECO:0000269|PubMed:10988270, FT ECO:0000269|PubMed:8900229" FT /id="VAR_039529" FT VARIANT 735 FT /note="P -> R (in GTLMNS; dbSNP:rs757761069)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075964" FT VARIANT 738 FT /note="L -> R (in GTLMNS)" FT /evidence="ECO:0000269|PubMed:9734597" FT /id="VAR_039530" FT VARIANT 741 FT /note="G -> R (in GTLMNS; dbSNP:rs138977195)" FT /evidence="ECO:0000269|PubMed:10988270, FT ECO:0000269|PubMed:22009145, ECO:0000269|PubMed:8528245, FT ECO:0000269|PubMed:9734597" FT /id="VAR_007124" FT VARIANT 751 FT /note="P -> L (in GTLMNS; 54% residual Na(+) uptake FT activity; no effect on localization at the plasma membrane; FT dbSNP:rs368068353)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075965" FT VARIANT 824 FT /note="S -> T (in GTLMNS; dbSNP:rs146845953)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075966" FT VARIANT 839 FT /note="D -> N (in GTLMNS; dbSNP:rs1298687889)" FT /evidence="ECO:0000269|PubMed:22009145, FT ECO:0000269|PubMed:34657521" FT /id="VAR_075967" FT VARIANT 849 FT /note="L -> F (in GTLMNS)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075968" FT VARIANT 849 FT /note="L -> H (in GTLMNS; dbSNP:rs185927948)" FT /evidence="ECO:0000269|PubMed:10616841, FT ECO:0000269|PubMed:15069170, ECO:0000269|PubMed:17873326" FT /id="VAR_039531" FT VARIANT 850 FT /note="L -> P (in GTLMNS; dbSNP:rs121909379)" FT /evidence="ECO:0000269|PubMed:22009145, FT ECO:0000269|PubMed:8528245, ECO:0000269|PubMed:9734597" FT /id="VAR_007125" FT VARIANT 852 FT /note="R -> C (in GTLMNS; dbSNP:rs373899077)" FT /evidence="ECO:0000269|PubMed:12112667, FT ECO:0000269|PubMed:22009145, ECO:0000269|PubMed:33462018, FT ECO:0000269|PubMed:9734597" FT /id="VAR_039532" FT VARIANT 852 FT /note="R -> H (in GTLMNS; dbSNP:rs751929135)" FT /evidence="ECO:0000269|PubMed:17873326" FT /id="VAR_039533" FT VARIANT 852 FT /note="R -> S (in GTLMNS)" FT /evidence="ECO:0000269|PubMed:12112667" FT /id="VAR_039534" FT VARIANT 854 FT /note="R -> K (in dbSNP:rs8060046)" FT /id="VAR_060106" FT VARIANT 862 FT /note="R -> C (in GTLMNS; dbSNP:rs754505583)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075969" FT VARIANT 867 FT /note="G -> S (in GTLMNS; dbSNP:rs370301695)" FT /evidence="ECO:0000269|PubMed:17654016" FT /id="VAR_039535" FT VARIANT 871 FT /note="R -> H (in GTLMNS)" FT /evidence="ECO:0000269|PubMed:15687331" FT /id="VAR_039536" FT VARIANT 872 FT /note="M -> T (in GTLMNS; dbSNP:rs752124879)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075970" FT VARIANT 887 FT /note="R -> Q (in GTLMNS; dbSNP:rs369360334)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075971" FT VARIANT 904 FT /note="R -> Q (in dbSNP:rs11643718)" FT /evidence="ECO:0000269|PubMed:10988270, FT ECO:0000269|PubMed:12112667, ECO:0000269|PubMed:17885550, FT ECO:0000269|PubMed:9734597" FT /id="VAR_039537" FT VARIANT 919 FT /note="R -> C (increases sodium transport; FT dbSNP:rs12708965)" FT /evidence="ECO:0000269|PubMed:17885550, FT ECO:0000269|PubMed:9734597" FT /id="VAR_039538" FT VARIANT 934 FT /note="R -> W (in GTLMNS; dbSNP:rs201721269)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075972" FT VARIANT 935 FT /note="R -> W (in GTLMNS; uncertain significance; FT dbSNP:rs56125220)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075973" FT VARIANT 955 FT /note="R -> Q (in GTLMNS; dbSNP:rs202114767)" FT /evidence="ECO:0000269|PubMed:22009145, FT ECO:0000269|PubMed:8528245" FT /id="VAR_007126" FT VARIANT 958 FT /note="R -> G (in GTLMNS; dbSNP:rs773428143)" FT /evidence="ECO:0000269|PubMed:12112667, FT ECO:0000269|PubMed:22009145" FT /id="VAR_039539" FT VARIANT 980 FT /note="G -> R (in GTLMNS; dbSNP:rs34803727)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075974" FT VARIANT 985 FT /note="C -> Y (in GTLMNS; dbSNP:rs199849117)" FT /evidence="ECO:0000269|PubMed:12112667, FT ECO:0000269|PubMed:22009145" FT /id="VAR_039540" FT VARIANT 1009 FT /note="R -> Q (in GTLMNS; dbSNP:rs370175770)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075975" FT VARIANT 1010 FT /note="G -> R (in GTLMNS; uncertain significance)" FT /evidence="ECO:0000269|PubMed:34657521" FT /id="VAR_088224" FT VARIANT 1021 FT /note="Q -> R (in GTLMNS; 58% residual Na(+) uptake FT activity; decreased MAPK1/3 (ERK1/2) phosphorylation in FT response to IL18; partial loss of localization at the FT plasma membrane; dbSNP:rs762026283)" FT /evidence="ECO:0000269|PubMed:22009145" FT /id="VAR_075976" FT MUTAGEN 19 FT /note="R->A: Abolished interaction with OXSR1/OSR1 and FT STK39/SPAK, preventing phosphorylation and activation." FT /evidence="ECO:0000269|PubMed:18270262" FT MUTAGEN 46 FT /note="T->A: Decreased phosphorylation by OXSR1/OSR1 and FT STK39/SPAK." FT /evidence="ECO:0000269|PubMed:18270262" FT MUTAGEN 55 FT /note="T->A: Decreased phosphorylation by OXSR1/OSR1 and FT STK39/SPAK." FT /evidence="ECO:0000269|PubMed:18270262" FT MUTAGEN 60 FT /note="T->A: Decreased phosphorylation by OXSR1/OSR1 and FT STK39/SPAK." FT /evidence="ECO:0000269|PubMed:18270262" FT MUTAGEN 62 FT /note="D->A: Abolished sodium and chloride ion FT cotransporter activity." FT /evidence="ECO:0000269|PubMed:36792826" FT MUTAGEN 70 FT /note="Y->A: Abolished sodium and chloride ion FT cotransporter activity." FT /evidence="ECO:0000269|PubMed:36792826" FT MUTAGEN 83 FT /note="R->A: Abolished sodium and chloride ion FT cotransporter activity." FT /evidence="ECO:0000269|PubMed:36792826" FT MUTAGEN 86 FT /note="L->A: Abolished sodium and chloride ion FT cotransporter activity." FT /evidence="ECO:0000269|PubMed:36792826" FT MUTAGEN 91 FT /note="S->A: Decreased phosphorylation by OXSR1/OSR1 and FT STK39/SPAK." FT /evidence="ECO:0000269|PubMed:18270262" FT MUTAGEN 149 FT /note="N->A: Reduced sensitivity to thiazide diuretics. FT Reduced sodium and chloride ion cotransporter activity." FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826" FT MUTAGEN 158 FT /note="R->A: Strongly reduced sodium and chloride ion FT cotransporter activity." FT /evidence="ECO:0000269|PubMed:36792826" FT MUTAGEN 223 FT /note="F->A: Reduced sensitivity to thiazide diuretics." FT /evidence="ECO:0000269|PubMed:36792826" FT MUTAGEN 227 FT /note="N->A: Strongly reduced sodium and chloride ion FT cotransporter activity." FT /evidence="ECO:0000269|PubMed:36351028" FT MUTAGEN 234 FT /note="H->A,Y: Strongly reduced sodium and chloride ion FT cotransporter activity." FT /evidence="ECO:0000269|PubMed:36351028" FT MUTAGEN 240 FT /note="E->A: Strongly reduced sodium and chloride ion FT cotransporter activity." FT /evidence="ECO:0000269|PubMed:36792826" FT MUTAGEN 386 FT /note="Y->A: Strongly reduced sodium and chloride ion FT cotransporter activity." FT /evidence="ECO:0000269|PubMed:36351028" FT MUTAGEN 467 FT /note="S->A: Abolished sodium and chloride ion FT cotransporter activity." FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826" FT MUTAGEN 468 FT /note="S->A: Abolished sodium and chloride ion FT cotransporter activity." FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826" FT MUTAGEN 526 FT /note="N->A: Strongly reduced sodium and chloride ion FT cotransporter activity." FT /evidence="ECO:0000269|PubMed:36792826" FT MUTAGEN 540 FT /note="Y->A: Abolished sodium and chloride ion FT cotransporter activity." FT /evidence="ECO:0000269|PubMed:36351028, FT ECO:0000269|PubMed:36792826" FT MUTAGEN 765 FT /note="F->A: Reduced sodium and chloride ion cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:36792826" FT MUTAGEN 838 FT /note="D->A: Abolished sodium and chloride ion FT cotransporter activity." FT /evidence="ECO:0000269|PubMed:36792826" FT MUTAGEN 886 FT /note="F->A: Reduced sodium and chloride ion cotransporter FT activity." FT /evidence="ECO:0000269|PubMed:36792826" FT MUTAGEN 1009 FT /note="R->A: Abolished sodium and chloride ion FT cotransporter activity." FT /evidence="ECO:0000269|PubMed:36792826" FT CONFLICT 459..460 FT /note="AG -> VV (in Ref. 2; CAA62613)" FT /evidence="ECO:0000305" FT CONFLICT 539 FT /note="S -> P (in Ref. 3; AK315298)" FT /evidence="ECO:0000305" FT CONFLICT 766 FT /note="D -> E (in Ref. 1; AAC50355)" FT /evidence="ECO:0000305" FT CONFLICT 778 FT /note="Missing (in Ref. 3; AK315298)" FT /evidence="ECO:0000305" FT TURN 68..70 FT /evidence="ECO:0007829|PDB:8FHO" FT HELIX 86..90 FT /evidence="ECO:0007829|PDB:8FHO" FT HELIX 138..141 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 143..150 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 154..157 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 159..165 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 167..193 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 202..204 FT /evidence="ECO:0007829|PDB:8FHR" FT HELIX 205..211 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 213..249 FT /evidence="ECO:0007829|PDB:8FHQ" FT STRAND 253..255 FT /evidence="ECO:0007829|PDB:8FHO" FT HELIX 258..263 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 265..276 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 280..303 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 310..314 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 322..327 FT /evidence="ECO:0007829|PDB:8FHQ" FT STRAND 335..337 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 340..347 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 348..350 FT /evidence="ECO:0007829|PDB:8FHQ" FT TURN 354..360 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 361..363 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 367..393 FT /evidence="ECO:0007829|PDB:8FHQ" FT TURN 394..396 FT /evidence="ECO:0007829|PDB:8FHQ" FT STRAND 411..413 FT /evidence="ECO:0007829|PDB:8FHT" FT HELIX 419..423 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 428..433 FT /evidence="ECO:0007829|PDB:8FHQ" FT TURN 440..442 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 446..450 FT /evidence="ECO:0007829|PDB:8FHQ" FT STRAND 451..453 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 455..483 FT /evidence="ECO:0007829|PDB:8FHQ" FT STRAND 489..491 FT /evidence="ECO:0007829|PDB:8FHO" FT HELIX 493..495 FT /evidence="ECO:0007829|PDB:8FHQ" FT TURN 501..503 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 506..522 FT /evidence="ECO:0007829|PDB:8FHQ" FT TURN 526..528 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 529..552 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 567..584 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 586..604 FT /evidence="ECO:0007829|PDB:8FHQ" FT HELIX 615..630 FT /evidence="ECO:0007829|PDB:8FHO" FT HELIX 631..633 FT /evidence="ECO:0007829|PDB:8FHO" FT STRAND 645..648 FT /evidence="ECO:0007829|PDB:8FHO" FT HELIX 652..654 FT /evidence="ECO:0007829|PDB:8FHO" FT HELIX 656..665 FT /evidence="ECO:0007829|PDB:8FHO" FT TURN 666..669 FT /evidence="ECO:0007829|PDB:8FHO" FT STRAND 672..675 FT /evidence="ECO:0007829|PDB:8FHO" FT STRAND 677..681 FT /evidence="ECO:0007829|PDB:8FHO" FT HELIX 688..702 FT /evidence="ECO:0007829|PDB:8FHO" FT STRAND 712..716 FT /evidence="ECO:0007829|PDB:8FHO" FT HELIX 717..727 FT /evidence="ECO:0007829|PDB:8FHO" FT STRAND 737..740 FT /evidence="ECO:0007829|PDB:8FHO" FT TURN 744..748 FT /evidence="ECO:0007829|PDB:8FHO" FT HELIX 751..766 FT /evidence="ECO:0007829|PDB:8FHO" FT STRAND 770..775 FT /evidence="ECO:0007829|PDB:8FHO" FT HELIX 821..823 FT /evidence="ECO:0007829|PDB:8FHO" FT STRAND 830..835 FT /evidence="ECO:0007829|PDB:8FHO" FT HELIX 842..851 FT /evidence="ECO:0007829|PDB:8FHO" FT HELIX 854..856 FT /evidence="ECO:0007829|PDB:8FHO" FT STRAND 860..865 FT /evidence="ECO:0007829|PDB:8FHO" FT HELIX 869..871 FT /evidence="ECO:0007829|PDB:8FHN" FT HELIX 872..879 FT /evidence="ECO:0007829|PDB:8FHO" FT HELIX 881..884 FT /evidence="ECO:0007829|PDB:8FHO" FT TURN 885..887 FT /evidence="ECO:0007829|PDB:8FHO" FT STRAND 899..901 FT /evidence="ECO:0007829|PDB:8FHO" FT HELIX 905..915 FT /evidence="ECO:0007829|PDB:8FHO" FT HELIX 916..918 FT /evidence="ECO:0007829|PDB:8FHO" FT HELIX 927..934 FT /evidence="ECO:0007829|PDB:8FHO" FT STRAND 938..940 FT /evidence="ECO:0007829|PDB:8FHN" FT HELIX 943..947 FT /evidence="ECO:0007829|PDB:8FHO" FT HELIX 950..966 FT /evidence="ECO:0007829|PDB:8FHO" FT TURN 967..969 FT /evidence="ECO:0007829|PDB:8FHO" FT STRAND 971..976 FT /evidence="ECO:0007829|PDB:8FHO" FT TURN 982..984 FT /evidence="ECO:0007829|PDB:8FHO" FT HELIX 987..996 FT /evidence="ECO:0007829|PDB:8FHO" FT STRAND 998..1000 FT /evidence="ECO:0007829|PDB:8FHO" FT STRAND 1005..1009 FT /evidence="ECO:0007829|PDB:8FHO" SQ SEQUENCE 1021 AA; 113139 MW; 629C5A42F3234B71 CRC64; MAELPTTETP GDATLCSGRF TISTLLSSDE PSPPAAYDSS HPSHLTHSST FCMRTFGYNT IDVVPTYEHY ANSTQPGEPR KVRPTLADLH SFLKQEGRHL HALAFDSRPS HEMTDGLVEG EAGTSSEKNP EEPVRFGWVK GVMIRCMLNI WGVILYLRLP WITAQAGIVL TWIIILLSVT VTSITGLSIS AISTNGKVKS GGTYFLISRS LGPELGGSIG LIFAFANAVG VAMHTVGFAE TVRDLLQEYG APIVDPINDI RIIAVVSVTV LLAISLAGME WESKAQVLFF LVIMVSFANY LVGTLIPPSE DKASKGFFSY RADIFVQNLV PDWRGPDGTF FGMFSIFFPS ATGILAGANI SGDLKDPAIA IPKGTLMAIF WTTISYLAIS ATIGSCVVRD ASGVLNDTVT PGWGACEGLA CSYGWNFTEC TQQHSCHYGL INYYQTMSMV SGFAPLITAG IFGATLSSAL ACLVSAAKVF QCLCEDQLYP LIGFFGKGYG KNKEPVRGYL LAYAIAVAFI IIAELNTIAP IISNFFLCSY ALINFSCFHA SITNSPGWRP SFQYYNKWAA LFGAIISVVI MFLLTWWAAL IAIGVVLFLL LYVIYKKPEV NWGSSVQAGS YNLALSYSVG LNEVEDHIKN YRPQCLVLTG PPNFRPALVD FVGTFTRNLS LMICGHVLIG PHKQRMPELQ LIANGHTKWL NKRKIKAFYS DVIAEDLRRG VQILMQAAGL GRMKPNILVV GFKKNWQSAH PATVEDYIGI LHDAFDFNYG VCVMRMREGL NVSKMMQAHI NPVFDPAEDG KEASARVDPK ALVKEEQATT IFQSEQGKKT IDIYWLFDDG GLTLLIPYLL GRKRRWSKCK IRVFVGGQIN RMDQERKAII SLLSKFRLGF HEVHILPDIN QNPRAEHTKR FEDMIAPFRL NDGFKDEATV NEMRRDCPWK ISDEEITKNR VKSLRQVRLN EIVLDYSRDA ALIVITLPIG RKGKCPSSLY MAWLETLSQD LRPPVILIRG NQENVLTFYC Q //