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 27-MAR-2024, entry version 210. DE RecName: Full=Carbonic anhydrase 12 {ECO:0000305}; DE EC=4.2.1.1 {ECO:0000269|PubMed:26911677}; 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 {ECO:0000312|HGNC:HGNC:1371}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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 chromosomal RT localization of a carbonic anhydrase gene that is overexpressed in some RT 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 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., 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 [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 project: RT 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., Heine A., RA 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-ray RT crystal structure of the antiviral drug foscarnet complexed to human RT 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 inhibitors RT 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., Scozzafava A., RA Quinn R.J., Supuran C.T.; RT "Non-zinc mediated inhibition of carbonic anhydrases: coumarins are a new RT 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 with RT the inhibitor acetazolamide."; RL Proteins 74:164-175(2009). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, RP VARIANT HYCHL GLN-121, AND CHARACTERIZATION OF VARIANTS HYCHL GLN-121 AND RP 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., Arcara K.M., RA Nguyen H., Luan S., Belchis D., Hertecant J., Zabner J., Sly W.S., RA Cutting G.R.; RT "Loss of carbonic anhydrase XII function in individuals with elevated sweat RT 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 ION RP 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., Sly W.S., RA Christianson D.W.; RT "Crystal structure of the dimeric extracellular domain of human carbonic RT anhydrase XII, a bitopic membrane protein overexpressed in certain cancer RT tumor cells."; RL Proc. Natl. Acad. Sci. U.S.A. 98:9545-9550(2001). RN [14] RP VARIANT HYCHL LYS-143, INVOLVEMENT IN HYCHL, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=21035102; DOI=10.1016/j.ajhg.2010.10.008; RA Feldshtein M., Elkrinawi S., Yerushalmi B., Marcus B., Vullo D., Romi H., RA 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 sweat RT associated with a mutation in the active site of carbonic 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; Xref=Rhea:RHEA:10748, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:17544; EC=4.2.1.1; CC Evidence={ECO:0000269|PubMed:26911677}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:11493685}; CC -!- ACTIVITY REGULATION: Inhibited by coumarins, saccharin, sulfonamide CC derivatives such as acetazolamide (AZA), benzenesulfonamide and CC derivatives (4-carboxyethylbenzene-sulfonamide, 4-carboxyethylbenzene- CC sulfonamide ethyl ester, 4-(acetyl-2-aminoethyl)benzene-sulfonamide, 4- CC aminoethylbenzene-sulfonamide) and Foscarnet (phosphonoformate CC trisodium salt). {ECO:0000269|PubMed:17314045, CC ECO:0000269|PubMed:17407288, ECO:0000269|PubMed:17705204, CC ECO:0000269|PubMed:18618712, ECO:0000269|PubMed:19186056, CC ECO:0000269|PubMed:19206230}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=12 mM for CO(2) {ECO:0000269|PubMed:18618712, CC ECO:0000269|PubMed:21035102}; CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11493685}. CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein. CC 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 levels in CC the renal cell cancers than in surrounding normal kidney tissue. CC Moderately expressed in pancreas, ovary and testis. Expressed in sweat CC glands and bronchiolar epithelium (PubMed:26911677). CC {ECO:0000269|PubMed:26911677}. CC -!- DISEASE: Hyperchlorhidrosis, isolated (HYCHL) [MIM:143860]: An CC autosomal recessive disorder characterized by excessive sweating and CC increased sweat chloride levels. Affected individuals suffer from CC episodes of hyponatremic dehydration and report increased amounts of CC visible salt precipitates in sweat. {ECO:0000269|PubMed:21035102, CC ECO:0000269|PubMed:21184099, ECO:0000269|PubMed:26911677}. Note=The CC disease is caused by variants affecting the gene represented in this CC 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 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 PDB; 6G5L; X-ray; 1.21 A; A/B/C/D=30-291. DR PDB; 6G7A; X-ray; 1.42 A; A/B/C/D=30-291. DR PDB; 6QN0; X-ray; 1.89 A; A/B/C/D=30-291. DR PDB; 6QNG; X-ray; 1.67 A; A/B/C/D=30-291. DR PDB; 6QNL; X-ray; 1.53 A; A/B/C/D=30-291. DR PDB; 6R6Y; X-ray; 1.38 A; A/B/C/D=30-291. DR PDB; 6R71; X-ray; 2.00 A; A/B=30-291. DR PDB; 6RPS; X-ray; 2.79 A; A/B=31-291. DR PDB; 6T5P; X-ray; 1.50 A; A/B/C/D=30-291. DR PDB; 6T5Q; X-ray; 1.80 A; A/B/C/D=30-291. DR PDB; 7PP9; X-ray; 2.34 A; A/B/C/D=30-291. DR PDB; 7PUU; X-ray; 1.51 A; A/B/C/D=30-291. DR PDB; 7PUV; X-ray; 1.40 A; A/B/C/D=30-291. DR PDB; 7PUW; X-ray; 1.42 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 PDBsum; 6G5L; -. DR PDBsum; 6G7A; -. DR PDBsum; 6QN0; -. DR PDBsum; 6QNG; -. DR PDBsum; 6QNL; -. DR PDBsum; 6R6Y; -. DR PDBsum; 6R71; -. DR PDBsum; 6RPS; -. DR PDBsum; 6T5P; -. DR PDBsum; 6T5Q; -. DR PDBsum; 7PP9; -. DR PDBsum; 7PUU; -. DR PDBsum; 7PUV; -. DR PDBsum; 7PUW; -. DR AlphaFoldDB; O43570; -. DR SMR; O43570; -. DR BioGRID; 107225; 24. DR IntAct; O43570; 15. DR MINT; O43570; -. DR STRING; 9606.ENSP00000178638; -. DR BindingDB; O43570; -. DR ChEMBL; CHEMBL3242; -. DR DrugBank; DB00819; Acetazolamide. DR DrugBank; DB00562; Benzthiazide. DR DrugBank; DB08846; Ellagic acid. DR DrugBank; DB00774; Hydroflumethiazide. DR DrugBank; DB00909; Zonisamide. DR DrugCentral; O43570; -. DR GuidetoPHARMACOLOGY; 2747; -. DR GlyConnect; 1064; 1 N-Linked glycan (1 site). DR GlyCosmos; O43570; 3 sites, 1 glycan. DR GlyGen; O43570; 3 sites, 1 N-linked glycan (1 site). DR iPTMnet; O43570; -. DR PhosphoSitePlus; O43570; -. DR SwissPalm; O43570; -. DR BioMuta; CA12; -. DR EPD; O43570; -. DR jPOST; O43570; -. DR MassIVE; O43570; -. DR MaxQB; O43570; -. DR PaxDb; 9606-ENSP00000178638; -. DR PeptideAtlas; O43570; -. DR ProteomicsDB; 49059; -. [O43570-1] DR ProteomicsDB; 49060; -. [O43570-2] DR ABCD; O43570; 1 sequenced antibody. DR Antibodypedia; 2237; 609 antibodies from 33 providers. DR DNASU; 771; -. DR Ensembl; ENST00000178638.8; ENSP00000178638.3; ENSG00000074410.14. [O43570-1] DR Ensembl; ENST00000344366.7; ENSP00000343088.3; ENSG00000074410.14. [O43570-2] DR GeneID; 771; -. DR KEGG; hsa:771; -. DR MANE-Select; ENST00000178638.8; ENSP00000178638.3; NM_001218.5; NP_001209.1. DR UCSC; uc002amc.4; human. [O43570-1] DR AGR; HGNC:1371; -. DR CTD; 771; -. DR DisGeNET; 771; -. DR GeneCards; CA12; -. DR HGNC; HGNC:1371; CA12. DR HPA; ENSG00000074410; Tissue enhanced (choroid plexus, kidney, skin). DR MalaCards; CA12; -. DR MIM; 143860; phenotype. DR MIM; 603263; gene. DR neXtProt; NX_O43570; -. DR OpenTargets; ENSG00000074410; -. DR Orphanet; 542657; Isolated hyperchlorhidrosis. DR PharmGKB; PA25987; -. DR VEuPathDB; HostDB:ENSG00000074410; -. DR eggNOG; KOG0382; Eukaryota. DR GeneTree; ENSGT00940000159282; -. DR HOGENOM; CLU_039326_1_2_1; -. DR InParanoid; O43570; -. DR OMA; KWSYIGP; -. DR OrthoDB; 49814at2759; -. DR PhylomeDB; O43570; -. DR TreeFam; TF316425; -. DR BRENDA; 4.2.1.1; 2681. DR PathwayCommons; O43570; -. DR Reactome; R-HSA-1475029; Reversible hydration of carbon dioxide. DR SignaLink; O43570; -. DR BioGRID-ORCS; 771; 15 hits in 1155 CRISPR screens. DR ChiTaRS; CA12; human. DR EvolutionaryTrace; O43570; -. DR GeneWiki; CA12; -. DR GenomeRNAi; 771; -. DR Pharos; O43570; Tclin. DR PRO; PR:O43570; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; O43570; Protein. DR Bgee; ENSG00000074410; Expressed in renal medulla and 183 other cell types or tissues. DR ExpressionAtlas; O43570; baseline and differential. DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl. DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0004089; F:carbonate dehydratase activity; IBA:GO_Central. DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc. DR GO; GO:0055064; P:chloride ion homeostasis; IMP:UniProtKB. DR GO; GO:0044849; P:estrous cycle; IEA:Ensembl. DR GO; GO:0006730; P:one-carbon metabolic process; IBA:GO_Central. DR CDD; cd03126; alpha_CA_XII_XIV; 1. DR Gene3D; 3.10.200.10; Alpha carbonic anhydrase; 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 PANTHER; PTHR18952; CARBONIC ANHYDRASE; 1. DR PANTHER; PTHR18952:SF19; CARBONIC ANHYDRASE 12; 1. DR Pfam; PF00194; Carb_anhydrase; 1. DR SMART; SM01057; Carb_anhydrase; 1. DR SUPFAM; SSF51069; Carbonic anhydrase; 1. DR PROSITE; PS00162; ALPHA_CA_1; 1. DR PROSITE; PS51144; ALPHA_CA_2; 1. DR Genevisible; O43570; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Disease variant; KW Disulfide bond; Glycoprotein; Lyase; Membrane; Metal-binding; KW Reference proteome; Signal; Transmembrane; Transmembrane helix; Zinc. FT SIGNAL 1..24 FT /evidence="ECO:0000255" FT CHAIN 25..354 FT /note="Carbonic anhydrase 12" FT /id="PRO_0000004248" FT TOPO_DOM 25..301 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 302..322 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 323..354 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 30..289 FT /note="Alpha-carbonic anhydrase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01134" FT ACT_SITE 94 FT /note="Proton donor/acceptor" FT /evidence="ECO:0000250|UniProtKB:P00918" FT BINDING 119 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:11493685" FT BINDING 121 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:11493685" FT BINDING 145 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:11493685" FT BINDING 226..227 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P00918" FT CARBOHYD 28 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 80 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 162 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 50..230 FT /evidence="ECO:0000269|PubMed:11493685" FT VAR_SEQ 292..302 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.3" FT /id="VSP_000772" FT VARIANT 121 FT /note="H -> Q (in HYCHL; severe decrease of activity in the FT presence of physiological NaCl concentrations; no effect on FT localization to cell membrane; dbSNP:rs775067652)" FT /evidence="ECO:0000269|PubMed:26911677" FT /id="VAR_081182" FT VARIANT 143 FT /note="E -> K (in HYCHL; severe decrease of activity in the FT presence of physiological NaCl concentrations; mutant FT enzyme is highly inhibited by acetazolamide and shows FT higher sensitivity to inhibition by anions compared to FT wild-type; the mutation affects the chloride-mediated FT negative feedback regulation of the enzyme leading to FT excessive chloride secretion in sweat; no effect on FT localization to cell membrane; dbSNP:rs267606694)" FT /evidence="ECO:0000269|PubMed:21035102, FT ECO:0000269|PubMed:21184099, ECO:0000269|PubMed:26911677" FT /id="VAR_065292" FT CONFLICT 305 FT /note="I -> T (in Ref. 4; BAG38121)" FT /evidence="ECO:0000305" FT HELIX 36..38 FT /evidence="ECO:0007829|PDB:5MSA" FT HELIX 40..45 FT /evidence="ECO:0007829|PDB:5MSA" FT HELIX 48..51 FT /evidence="ECO:0007829|PDB:5MSA" FT STRAND 52..54 FT /evidence="ECO:0007829|PDB:5MSA" FT HELIX 62..64 FT /evidence="ECO:0007829|PDB:5MSA" FT STRAND 65..67 FT /evidence="ECO:0007829|PDB:5MSA" FT STRAND 75..78 FT /evidence="ECO:0007829|PDB:5MSA" FT STRAND 85..91 FT /evidence="ECO:0007829|PDB:5MSA" FT STRAND 93..99 FT /evidence="ECO:0007829|PDB:5MSA" FT STRAND 105..111 FT /evidence="ECO:0007829|PDB:5MSA" FT STRAND 113..122 FT /evidence="ECO:0007829|PDB:5MSA" FT STRAND 132..135 FT /evidence="ECO:0007829|PDB:5MSA" FT STRAND 141..150 FT /evidence="ECO:0007829|PDB:5MSA" FT TURN 151..153 FT /evidence="ECO:0007829|PDB:5MSA" FT HELIX 157..160 FT /evidence="ECO:0007829|PDB:5MSA" FT STRAND 167..176 FT /evidence="ECO:0007829|PDB:5MSA" FT HELIX 181..187 FT /evidence="ECO:0007829|PDB:5MSA" FT HELIX 188..192 FT /evidence="ECO:0007829|PDB:5MSA" FT STRAND 199..203 FT /evidence="ECO:0007829|PDB:5MSA" FT HELIX 207..210 FT /evidence="ECO:0007829|PDB:5MSA" FT TURN 213..216 FT /evidence="ECO:0007829|PDB:4Q0L" FT STRAND 218..223 FT /evidence="ECO:0007829|PDB:5MSA" FT STRAND 234..241 FT /evidence="ECO:0007829|PDB:5MSA" FT STRAND 243..245 FT /evidence="ECO:0007829|PDB:5MSA" FT HELIX 247..255 FT /evidence="ECO:0007829|PDB:5MSA" FT STRAND 258..260 FT /evidence="ECO:0007829|PDB:5MSA" FT STRAND 285..288 FT /evidence="ECO:0007829|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 //