CAH12_HUMAN
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 03-AUG-2022, entry version 201.
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=12.0 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}.
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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; 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; 7PUU; -.
DR PDBsum; 7PUV; -.
DR PDBsum; 7PUW; -.
DR AlphaFoldDB; O43570; -.
DR SMR; O43570; -.
DR BioGRID; 107225; 22.
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 GlyGen; O43570; 3 sites, 1 N-linked glycan (1 site).
DR iPTMnet; O43570; -.
DR PhosphoSitePlus; O43570; -.
DR BioMuta; CA12; -.
DR EPD; O43570; -.
DR jPOST; O43570; -.
DR MassIVE; O43570; -.
DR MaxQB; O43570; -.
DR PaxDb; O43570; -.
DR PeptideAtlas; O43570; -.
DR PRIDE; O43570; -.
DR ProteomicsDB; 49059; -. [O43570-1]
DR ProteomicsDB; 49060; -. [O43570-2]
DR ABCD; O43570; 1 sequenced antibody.
DR Antibodypedia; 2237; 539 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 CTD; 771; -.
DR DisGeNET; 771; -.
DR GeneCards; CA12; -.
DR HGNC; HGNC:1371; CA12.
DR HPA; ENSG00000074410; Tissue enhanced (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; SKWSYIG; -.
DR OrthoDB; 1377476at2759; -.
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; 14 hits in 1073 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 181 other tissues.
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; IBA:GO_Central.
DR GO; GO:0004089; F:carbonate dehydratase activity; IBA:GO_Central.
DR GO; GO:0016836; F:hydro-lyase 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:0006730; P:one-carbon metabolic process; IBA:GO_Central.
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; 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
