ID CAH12_HUMAN Reviewed; 354 AA. AC O43570; B2RE24; Q53YE5; Q9BWG2; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-1998, sequence version 1. DT 13-FEB-2019, entry version 181. DE RecName: Full=Carbonic anhydrase 12; DE EC=4.2.1.1; DE AltName: Full=Carbonate dehydratase XII; DE AltName: Full=Carbonic anhydrase XII; DE Short=CA-XII; DE AltName: Full=Tumor antigen HOM-RCC-3.1.3; DE Flags: Precursor; GN Name=CA12; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND CHARACTERIZATION. RC TISSUE=Renal cell carcinoma; RX PubMed=9636197; DOI=10.1073/pnas.95.13.7608; RA Tuereci O., Sahin U., Vollmar E., Siemer S., Goettert E., Seitz G., RA Parkkila A.-K., Shah G.N., Grubb J.H., Pfreundschuh M., Sly W.S.; RT "Human carbonic anhydrase XII: cDNA cloning, expression, and RT chromosomal localization of a carbonic anhydrase gene that is RT overexpressed in some renal cell cancers."; RL Proc. Natl. Acad. Sci. U.S.A. 95:7608-7613(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Lung; RX PubMed=9770531; DOI=10.1073/pnas.95.21.12596; RA Ivanov S.V., Kuzmin I., Wei M.-H., Pack S., Geil L., Johnson B.E., RA Stanbridge E.J., Lerman M.I.; RT "Down-regulation of transmembrane carbonic anhydrases in renal cell RT carcinoma cell lines by wild-type von Hippel-Lindau transgenes."; RL Proc. Natl. Acad. Sci. U.S.A. 95:12596-12601(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Trachea; 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., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA 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., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Eye, and Kidney; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP ACTIVITY REGULATION. RX PubMed=17705204; DOI=10.1002/anie.200701189; RA Koehler K., Hillebrecht A., Schulze Wischeler J., Innocenti A., RA Heine A., Supuran C.T., Klebe G.; RT "Saccharin inhibits carbonic anhydrases: possible explanation for its RT unpleasant metallic aftertaste."; RL Angew. Chem. Int. Ed. Engl. 46:7697-7699(2007). RN [7] RP ACTIVITY REGULATION. RX PubMed=17314045; DOI=10.1016/j.bmcl.2007.01.113; RA Temperini C., Innocenti A., Guerri A., Scozzafava A., Rusconi S., RA Supuran C.T.; RT "Phosph(on)ate as a zinc-binding group in metalloenzyme inhibitors: X- RT ray crystal structure of the antiviral drug foscarnet complexed to RT human carbonic anhydrase I."; RL Bioorg. Med. Chem. Lett. 17:2210-2215(2007). RN [8] RP ACTIVITY REGULATION. RX PubMed=17407288; DOI=10.1021/ja068359w; RA Srivastava D.K., Jude K.M., Banerjee A.L., Haldar M., Manokaran S., RA Kooren J., Mallik S., Christianson D.W.; RT "Structural analysis of charge discrimination in the binding of RT inhibitors to human carbonic anhydrases I and II."; RL J. Am. Chem. Soc. 129:5528-5537(2007). RN [9] RP ACTIVITY REGULATION. RX PubMed=19186056; DOI=10.1016/j.bmcl.2009.01.038; RA Crocetti L., Maresca A., Temperini C., Hall R.A., Scozzafava A., RA Muehlschlegel F.A., Supuran C.T.; RT "A thiabendazole sulfonamide shows potent inhibitory activity against RT mammalian and nematode alpha-carbonic anhydrases."; RL Bioorg. Med. Chem. Lett. 19:1371-1375(2009). RN [10] RP ACTIVITY REGULATION. RX PubMed=19206230; DOI=10.1021/ja809683v; RA Maresca A., Temperini C., Vu H., Pham N.B., Poulsen S.-A., RA Scozzafava A., Quinn R.J., Supuran C.T.; RT "Non-zinc mediated inhibition of carbonic anhydrases: coumarins are a RT new class of suicide inhibitors."; RL J. Am. Chem. Soc. 131:3057-3062(2009). RN [11] RP BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION. RX PubMed=18618712; DOI=10.1002/prot.22144; RA Di Fiore A., Monti S.M., Hilvo M., Parkkila S., Romano V., Scaloni A., RA Pedone C., Scozzafava A., Supuran C.T., De Simone G.; RT "Crystal structure of human carbonic anhydrase XIII and its complex RT with the inhibitor acetazolamide."; RL Proteins 74:164-175(2009). RN [12] RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, VARIANT HYCHL GLN-121, RP FUNCTION, AND CHARACTERIZATION OF VARIANTS HYCHL GLN-121 AND LYS-143. RX PubMed=26911677; DOI=10.1093/hmg/ddw065; RA Lee M., Vecchio-Pagan B., Sharma N., Waheed A., Li X., Raraigh K.S., RA Robbins S., Han S.T., Franca A.L., Pellicore M.J., Evans T.A., RA Arcara K.M., Nguyen H., Luan S., Belchis D., Hertecant J., Zabner J., RA Sly W.S., Cutting G.R.; RT "Loss of carbonic anhydrase XII function in individuals with elevated RT sweat chloride concentration and pulmonary airway disease."; RL Hum. Mol. Genet. 25:1923-1933(2016). RN [13] RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 30-291 IN COMPLEX WITH ZINC RP ION AND THE INHIBITOR ACETAZOLAMIDE, DISULFIDE BOND, AND SUBUNIT. RX PubMed=11493685; DOI=10.1073/pnas.161301298; RA Whittington D.A., Waheed A., Ulmasov B., Shah G.N., Grubb J.H., RA Sly W.S., Christianson D.W.; RT "Crystal structure of the dimeric extracellular domain of human RT carbonic anhydrase XII, a bitopic membrane protein overexpressed in RT certain cancer tumor cells."; RL Proc. Natl. Acad. Sci. U.S.A. 98:9545-9550(2001). RN [14] RP VARIANT HYCHL LYS-143, AND INVOLVEMENT IN HYCHL. RX PubMed=21035102; DOI=10.1016/j.ajhg.2010.10.008; RA Feldshtein M., Elkrinawi S., Yerushalmi B., Marcus B., Vullo D., RA Romi H., Ofir R., Landau D., Sivan S., Supuran C.T., Birk O.S.; RT "Hyperchlorhidrosis caused by homozygous mutation in CA12, encoding RT carbonic anhydrase XII."; RL Am. J. Hum. Genet. 87:713-720(2010). RN [15] RP VARIANT HYCHL LYS-143. RX PubMed=21184099; DOI=10.1007/s00439-010-0930-4; RA Muhammad E., Leventhal N., Parvari G., Hanukoglu A., Hanukoglu I., RA Chalifa-Caspi V., Feinstein Y., Weinbrand J., Jacoby H., Manor E., RA Nagar T., Beck J.C., Sheffield V.C., Hershkovitz E., Parvari R.; RT "Autosomal recessive hyponatremia due to isolated salt wasting in RT sweat associated with a mutation in the active site of carbonic RT cnhydrase 12."; RL Hum. Genet. 129:397-405(2011). CC -!- FUNCTION: Reversible hydration of carbon dioxide. CC {ECO:0000269|PubMed:26911677}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + hydrogencarbonate = CO2 + H2O; CC Xref=Rhea:RHEA:10748, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16526, ChEBI:CHEBI:17544; EC=4.2.1.1; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:11493685}; CC -!- ACTIVITY REGULATION: Inhibited by coumarins, saccharin, CC sulfonamide derivatives such as acetazolamide (AZA), CC benzenesulfonamide and derivatives (4-carboxyethylbenzene- CC sulfonamide, 4-carboxyethylbenzene-sulfonamide ethyl ester, 4- CC (acetyl-2-aminoethyl)benzene-sulfonamide, 4-aminoethylbenzene- CC sulfonamide) and Foscarnet (phosphonoformate trisodium salt). CC {ECO:0000269|PubMed:17314045, ECO:0000269|PubMed:17407288, CC ECO:0000269|PubMed:17705204, ECO:0000269|PubMed:18618712, CC ECO:0000269|PubMed:19186056, ECO:0000269|PubMed:19206230}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=12.0 mM for CO(2) {ECO:0000269|PubMed:18618712}; CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11493685}. CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane CC protein. Cell membrane {ECO:0000269|PubMed:26911677}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O43570-1; Sequence=Displayed; CC Name=2; CC IsoId=O43570-2; Sequence=VSP_000772; CC -!- TISSUE SPECIFICITY: Highly expressed in colon, kidney, prostate, CC intestine and activated lymphocytes. Expressed at much higher CC levels in the renal cell cancers than in surrounding normal kidney CC tissue. Moderately expressed in pancreas, ovary and testis. CC Expressed in sweat glands and bronchiolar epithelium CC (PubMed:26911677). {ECO:0000269|PubMed:26911677}. CC -!- DISEASE: Hyperchlorhidrosis, isolated (HYCHL) [MIM:143860]: An CC autosomal recessive disorder characterized by excessive sweating CC and increased sweat chloride levels. Affected individuals suffer CC from episodes of hyponatremic dehydration and report increased CC amounts of visible salt precipitates in sweat. CC {ECO:0000269|PubMed:21035102, ECO:0000269|PubMed:21184099, CC ECO:0000269|PubMed:26911677}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the alpha-carbonic anhydrase family. CC {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; AF051882; AAC39789.1; -; mRNA. DR EMBL; AF037335; AAC63952.1; -; mRNA. DR EMBL; BT006656; AAP35302.1; -; mRNA. DR EMBL; AK315769; BAG38121.1; -; mRNA. DR EMBL; BC000278; AAH00278.1; -; mRNA. DR EMBL; BC011691; AAH11691.1; -; mRNA. DR EMBL; BC023981; AAH23981.1; -; mRNA. DR CCDS; CCDS10185.1; -. [O43570-1] DR CCDS; CCDS10186.1; -. [O43570-2] DR RefSeq; NP_001209.1; NM_001218.4. [O43570-1] DR RefSeq; NP_996808.1; NM_206925.2. [O43570-2] DR UniGene; Hs.210995; -. DR UniGene; Hs.603780; -. DR PDB; 1JCZ; X-ray; 1.55 A; A/B=30-291. DR PDB; 1JD0; X-ray; 1.50 A; A/B=30-291. DR PDB; 4HT2; X-ray; 1.45 A; A/B/C/D=30-291. DR PDB; 4KP5; X-ray; 1.45 A; A/B/C/D=30-291. DR PDB; 4KP8; X-ray; 1.80 A; A/B/C/D=30-291. DR PDB; 4Q0L; X-ray; 2.00 A; A/B/C/D=30-291. DR PDB; 4QJ0; X-ray; 1.55 A; A/B/C/D=30-291. DR PDB; 4QJO; X-ray; 1.80 A; A/B/C/D=30-291. DR PDB; 4QJW; X-ray; 1.55 A; A/B/C/D=30-291. DR PDB; 4WW8; X-ray; 1.42 A; A/B/C/D=30-291. DR PDB; 5LL5; X-ray; 1.42 A; A/B/C/D=30-291. DR PDB; 5LL9; X-ray; 1.45 A; A/B/C/D=30-291. DR PDB; 5LLO; X-ray; 1.60 A; A/B/C/D=30-291. DR PDB; 5LLP; X-ray; 1.48 A; A/B/C/D=30-291. DR PDB; 5MSA; X-ray; 1.20 A; A/B/C/D=30-291. DR PDB; 5MSB; X-ray; 1.30 A; A/B/C/D=30-291. DR PDBsum; 1JCZ; -. DR PDBsum; 1JD0; -. DR PDBsum; 4HT2; -. DR PDBsum; 4KP5; -. DR PDBsum; 4KP8; -. DR PDBsum; 4Q0L; -. DR PDBsum; 4QJ0; -. DR PDBsum; 4QJO; -. DR PDBsum; 4QJW; -. DR PDBsum; 4WW8; -. DR PDBsum; 5LL5; -. DR PDBsum; 5LL9; -. DR PDBsum; 5LLO; -. DR PDBsum; 5LLP; -. DR PDBsum; 5MSA; -. DR PDBsum; 5MSB; -. DR ProteinModelPortal; O43570; -. DR SMR; O43570; -. DR BioGrid; 107225; 9. DR IntAct; O43570; 10. DR MINT; O43570; -. DR STRING; 9606.ENSP00000178638; -. DR BindingDB; O43570; -. DR ChEMBL; CHEMBL3242; -. DR DrugBank; DB00562; Benzthiazide. DR DrugBank; DB08846; Ellagic Acid. DR DrugBank; DB00999; Hydrochlorothiazide. DR DrugBank; DB00774; Hydroflumethiazide. DR DrugBank; DB00909; Zonisamide. DR GuidetoPHARMACOLOGY; 2747; -. DR GlyConnect; 1064; -. DR iPTMnet; O43570; -. DR PhosphoSitePlus; O43570; -. DR BioMuta; CA12; -. DR EPD; O43570; -. DR jPOST; O43570; -. DR MaxQB; O43570; -. DR PaxDb; O43570; -. DR PeptideAtlas; O43570; -. DR PRIDE; O43570; -. DR ProteomicsDB; 49059; -. DR ProteomicsDB; 49060; -. [O43570-2] DR DNASU; 771; -. DR Ensembl; ENST00000178638; ENSP00000178638; ENSG00000074410. [O43570-1] DR Ensembl; ENST00000344366; ENSP00000343088; ENSG00000074410. [O43570-2] DR GeneID; 771; -. DR KEGG; hsa:771; -. DR UCSC; uc002amc.4; human. [O43570-1] DR CTD; 771; -. DR DisGeNET; 771; -. DR EuPathDB; HostDB:ENSG00000074410.13; -. DR GeneCards; CA12; -. DR HGNC; HGNC:1371; CA12. DR HPA; CAB025181; -. DR HPA; CAB062549; -. DR HPA; CAB068179; -. DR HPA; HPA008773; -. DR HPA; HPA073203; -. DR MalaCards; CA12; -. DR MIM; 143860; phenotype. DR MIM; 603263; gene. DR neXtProt; NX_O43570; -. DR OpenTargets; ENSG00000074410; -. DR PharmGKB; PA25987; -. DR eggNOG; KOG0382; Eukaryota. DR eggNOG; COG3338; LUCA. DR GeneTree; ENSGT00940000159282; -. DR HOGENOM; HOG000112637; -. DR HOVERGEN; HBG002837; -. DR InParanoid; O43570; -. DR KO; K01672; -. DR OMA; HTVGGKH; -. DR OrthoDB; 692851at2759; -. DR PhylomeDB; O43570; -. DR TreeFam; TF316425; -. DR BRENDA; 4.2.1.1; 2681. DR Reactome; R-HSA-1475029; Reversible hydration of carbon dioxide. DR ChiTaRS; CA12; human. DR EvolutionaryTrace; O43570; -. DR GeneWiki; CA12; -. DR GenomeRNAi; 771; -. DR PRO; PR:O43570; -. DR Proteomes; UP000005640; Chromosome 15. DR Bgee; ENSG00000074410; Expressed in 204 organ(s), highest expression level in cortex of kidney. DR ExpressionAtlas; O43570; baseline and differential. DR Genevisible; O43570; HS. DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0004089; F:carbonate dehydratase activity; TAS:Reactome. DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc. DR GO; GO:0015701; P:bicarbonate transport; TAS:Reactome. DR GO; GO:0055064; P:chloride ion homeostasis; IMP:UniProtKB. DR Gene3D; 3.10.200.10; -; 1. DR InterPro; IPR001148; CA_dom. DR InterPro; IPR036398; CA_dom_sf. DR InterPro; IPR023561; Carbonic_anhydrase_a-class. DR InterPro; IPR018338; Carbonic_anhydrase_a-class_CS. DR InterPro; IPR018430; Carbonic_anhydrase_CA12. DR PANTHER; PTHR18952; PTHR18952; 1. DR PANTHER; PTHR18952:SF19; PTHR18952:SF19; 1. DR Pfam; PF00194; Carb_anhydrase; 1. DR SMART; SM01057; Carb_anhydrase; 1. DR SUPFAM; SSF51069; SSF51069; 1. DR PROSITE; PS00162; ALPHA_CA_1; 1. DR PROSITE; PS51144; ALPHA_CA_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Complete proteome; KW Disease mutation; Disulfide bond; Glycoprotein; Lyase; Membrane; KW Metal-binding; Reference proteome; Signal; Transmembrane; KW Transmembrane helix; Zinc. FT SIGNAL 1 24 {ECO:0000255}. FT CHAIN 25 354 Carbonic anhydrase 12. FT /FTId=PRO_0000004248. FT TOPO_DOM 25 301 Extracellular. {ECO:0000255}. FT TRANSMEM 302 322 Helical. {ECO:0000255}. FT TOPO_DOM 323 354 Cytoplasmic. {ECO:0000255}. FT DOMAIN 30 289 Alpha-carbonic anhydrase. FT {ECO:0000255|PROSITE-ProRule:PRU01134}. FT REGION 226 227 Substrate binding. FT {ECO:0000250|UniProtKB:P00918}. FT ACT_SITE 94 94 Proton acceptor. FT {ECO:0000250|UniProtKB:P00918}. FT ACT_SITE 154 154 {ECO:0000250|UniProtKB:P00918}. FT METAL 119 119 Zinc; catalytic. FT {ECO:0000269|PubMed:11493685}. FT METAL 121 121 Zinc; catalytic. FT {ECO:0000269|PubMed:11493685}. FT METAL 145 145 Zinc; catalytic. FT {ECO:0000269|PubMed:11493685}. FT CARBOHYD 28 28 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 80 80 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 162 162 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 50 230 {ECO:0000269|PubMed:11493685}. FT VAR_SEQ 292 302 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|Ref.3}. FT /FTId=VSP_000772. FT VARIANT 121 121 H -> Q (in HYCHL; severe decrease of FT activity in the presence of physiological FT NaCl concentrations; no effect on FT localization to cell membrane; FT dbSNP:rs775067652). FT {ECO:0000269|PubMed:26911677}. FT /FTId=VAR_081182. FT VARIANT 143 143 E -> K (in HYCHL; severe decrease of FT activity in the presence of physiological FT NaCl concentrations; mutant enzyme is FT highly inhibited by acetazolamide and FT shows higher sensitivity to inhibition by FT anions compared to wild-type; the FT mutation affects the chloride-mediated FT negative feedback regulation of the FT enzyme leading to excessive chloride FT secretion in sweat; no effect on FT localization to cell membrane; FT dbSNP:rs267606694). FT {ECO:0000269|PubMed:21035102, FT ECO:0000269|PubMed:21184099, FT ECO:0000269|PubMed:26911677}. FT /FTId=VAR_065292. FT CONFLICT 305 305 I -> T (in Ref. 4; BAG38121). FT {ECO:0000305}. FT HELIX 36 38 {ECO:0000244|PDB:5MSA}. FT HELIX 40 45 {ECO:0000244|PDB:5MSA}. FT HELIX 48 51 {ECO:0000244|PDB:5MSA}. FT STRAND 52 54 {ECO:0000244|PDB:5MSA}. FT HELIX 62 64 {ECO:0000244|PDB:5MSA}. FT STRAND 65 67 {ECO:0000244|PDB:5MSA}. FT STRAND 75 78 {ECO:0000244|PDB:5MSA}. FT STRAND 85 91 {ECO:0000244|PDB:5MSA}. FT STRAND 93 99 {ECO:0000244|PDB:5MSA}. FT STRAND 105 111 {ECO:0000244|PDB:5MSA}. FT STRAND 113 122 {ECO:0000244|PDB:5MSA}. FT STRAND 132 135 {ECO:0000244|PDB:5MSA}. FT STRAND 141 150 {ECO:0000244|PDB:5MSA}. FT TURN 151 153 {ECO:0000244|PDB:5MSA}. FT HELIX 157 160 {ECO:0000244|PDB:5MSA}. FT STRAND 167 176 {ECO:0000244|PDB:5MSA}. FT HELIX 181 187 {ECO:0000244|PDB:5MSA}. FT HELIX 188 192 {ECO:0000244|PDB:5MSA}. FT STRAND 199 203 {ECO:0000244|PDB:5MSA}. FT HELIX 207 210 {ECO:0000244|PDB:5MSA}. FT TURN 213 216 {ECO:0000244|PDB:4Q0L}. FT STRAND 218 223 {ECO:0000244|PDB:5MSA}. FT STRAND 234 241 {ECO:0000244|PDB:5MSA}. FT STRAND 243 245 {ECO:0000244|PDB:5MSA}. FT HELIX 247 255 {ECO:0000244|PDB:5MSA}. FT STRAND 258 260 {ECO:0000244|PDB:5MSA}. FT STRAND 285 288 {ECO:0000244|PDB:5MSA}. SQ SEQUENCE 354 AA; 39451 MW; 9016216BF2CA6C0C CRC64; MPRRSLHAAA VLLLVILKEQ PSSPAPVNGS KWTYFGPDGE NSWSKKYPSC GGLLQSPIDL HSDILQYDAS LTPLEFQGYN LSANKQFLLT NNGHSVKLNL PSDMHIQGLQ SRYSATQLHL HWGNPNDPHG SEHTVSGQHF AAELHIVHYN SDLYPDASTA SNKSEGLAVL AVLIEMGSFN PSYDKIFSHL QHVKYKGQEA FVPGFNIEEL LPERTAEYYR YRGSLTTPPC NPTVLWTVFR NPVQISQEQL LALETALYCT HMDDPSPREM INNFRQVQKF DERLVYTSFS QVQVCTAAGL SLGIILSLAL AGILGICIVV VVSIWLFRRK SIKKGDNKGV IYKPATKMET EAHA //