{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P00918","secondaryAccessions":["B2R7G8","Q6FI12","Q96ET9"],"uniProtkbId":"CAH2_HUMAN","entryAudit":{"firstPublicDate":"1986-07-21","lastAnnotationUpdateDate":"2026-06-10","lastSequenceUpdateDate":"2007-01-23","entryVersion":278,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Carbonic anhydrase 2"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12171926"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15300855"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1909891"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1910042"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7761440"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7901850"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9398308"}],"value":"4.2.1.1"}]},"alternativeNames":[{"fullName":{"value":"Carbonate dehydratase II"}},{"fullName":{"value":"Carbonic anhydrase C"},"shortNames":[{"value":"CAC"}]},{"fullName":{"value":"Carbonic anhydrase II"},"shortNames":[{"value":"CA-II"}]},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Cyanamide hydratase CA2"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10550681"}],"value":"4.2.1.69"}]}]},"genes":[{"geneName":{"value":"CA2"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10550681"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11015219"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11327835"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11802772"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11831900"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12056894"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12171926"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1336460"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14736236"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15300855"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15453828"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15667203"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15865431"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15990874"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16106378"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16214338"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16290146"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16686544"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16759856"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16807956"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17127057"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17251017"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17314045"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17330962"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17346964"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17540563"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17588751"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17705204"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18024029"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18162396"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18266323"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18374572"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18481843"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18618712"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18640037"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18942852"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1909891"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1910042"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19170619"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19186056"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19206230"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19520834"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19778001"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7761440"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7901850"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8218160"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8262987"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8399159"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8451242"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8485129"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8639494"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9265618"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9398308"}],"value":"Catalyzes the reversible hydration of carbon dioxide (PubMed:11327835, PubMed:11802772, PubMed:11831900, PubMed:12056894, PubMed:12171926, PubMed:1336460, PubMed:14736236, PubMed:15300855, PubMed:15453828, PubMed:15667203, PubMed:15865431, PubMed:16106378, PubMed:16214338, PubMed:16290146, PubMed:16686544, PubMed:16759856, PubMed:16807956, PubMed:17127057, PubMed:17251017, PubMed:17314045, PubMed:17330962, PubMed:17346964, PubMed:17540563, PubMed:17588751, PubMed:17705204, PubMed:18024029, PubMed:18162396, PubMed:18266323, PubMed:18374572, PubMed:18481843, PubMed:18618712, PubMed:18640037, PubMed:18942852, PubMed:1909891, PubMed:1910042, PubMed:19170619, PubMed:19186056, PubMed:19206230, PubMed:19520834, PubMed:19778001, PubMed:7761440, PubMed:7901850, PubMed:8218160, PubMed:8262987, PubMed:8399159, PubMed:8451242, PubMed:8485129, PubMed:8639494, PubMed:9265618, PubMed:9398308). Can also hydrate cyanamide to urea (PubMed:10550681, PubMed:11015219). Stimulates the chloride-bicarbonate exchange activity of SLC26A6 (PubMed:15990874). Essential for bone resorption and osteoclast differentiation (PubMed:15300855). Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"hydrogencarbonate + H(+) = CO2 + H2O","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:10748"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:16526"},{"database":"ChEBI","id":"CHEBI:17544"}],"ecNumber":"4.2.1.1","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11327835"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11802772"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11831900"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12056894"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12171926"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1336460"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14736236"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15300855"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15453828"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15667203"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15865431"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16106378"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16214338"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16290146"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16686544"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16759856"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16807956"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17127057"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17251017"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17314045"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17330962"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17346964"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17540563"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17588751"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17705204"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18024029"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18162396"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18266323"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18374572"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18481843"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18618712"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18640037"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18942852"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1909891"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1910042"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19170619"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19186056"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19206230"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19520834"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19778001"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7761440"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7901850"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8218160"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8262987"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8399159"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8451242"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8485129"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8639494"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9265618"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9398308"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"urea = cyanamide + H2O","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:23056"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:16199"},{"database":"ChEBI","id":"CHEBI:16698"}],"ecNumber":"4.2.1.69","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10550681"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11015219"}]}},{"commentType":"COFACTOR","cofactors":[{"name":"Zn(2+)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11076507"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12499545"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1336460"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1433293"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1909891"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19583303"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"3151019"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"3151020"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7761440"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7803386"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7901850"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8218160"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8262987"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8331673"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8399159"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8431430"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8451242"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8482389"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8639494"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8987974"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9398308"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9865942"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:29105"}},{"name":"Co(2+)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19583303"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:48828"}}],"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19583303"}],"value":"Zinc. Can also use cobalt(II) with lower efficiency, but not copper(II), nickel(II) and manganese(II)."}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11802772"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1336460"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14736236"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16214338"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16290146"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16686544"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16759856"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16807956"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17127057"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17314045"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17540563"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17588751"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17705204"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18024029"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18162396"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18266323"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18374572"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18481843"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18618712"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18640037"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1910042"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19170619"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19186056"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19206230"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19520834"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19778001"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9265618"}],"value":"Activated by X-ray, histamine, L-adrenaline, L- and D-phenylalanine, L- and D-histidine, L-His-OMe and beta-Ala-His (carnosine). Competitively inhibited by saccharin, thioxolone, coumarins, 667-coumate, celecoxib (Celebrex), valdecoxib (Bextra), SC-125, SC-560, diclofenac, acetate, azide, bromide, sulfonamide derivatives such as acetazolamide (AZA), methazolamide (MZA), ethoxzolamide (EZA), dichlorophenamide (DCP), brinzolamide, dansylamide, thiabendazole-5-sulfonamide, trifluoromethane sulfonamide and N-hydroxysulfamide, fructose-based sugar sulfamate RWJ-37497, and Foscarnet (phosphonoformate trisodium salt). Repressed strongly by hydrogen sulfide(HS) and weakly by nitrate (NO(3)). Esterase activity weakly reduced by cyanamide. N-hydroxyurea interferes with zinc binding and inhibit activity"}],"commentType":"ACTIVITY REGULATION"},{"commentType":"BIOPHYSICOCHEMICAL PROPERTIES","kineticParameters":{"michaelisConstants":[{"constant":9.3,"unit":"mM","substrate":"CO(2)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18618712"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7761440"}]},{"constant":11.0,"unit":"mM","substrate":"CO(2)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1909891"}]},{"constant":8.2,"unit":"mM","substrate":"CO(2)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9398308"}]},{"constant":82.0,"unit":"mM","substrate":"H(2)CO(3)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8262987"}]},{"constant":2.9,"unit":"mM","substrate":"4-nitrophenyl acetate","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10550681"}]}]},"phDependence":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15667203"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17330962"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18942852"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8262987"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9398308"}],"value":"Optimum pH is 6-8."}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14567693"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14736710"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15218065"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15990874"}],"value":"Interacts with SLC4A4 (PubMed:14567693, PubMed:15218065). Interaction with SLC4A7 regulates SLC4A7 transporter activity (PubMed:14736710). Interacts with SLC26A6 isoform 4 (via C-terminus cytoplasmic domain) (PubMed:15990874)"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15990874"}],"value":"Colocalized with SLC26A6 at the surface of the cell membrane in order to form a bicarbonate transport metabolon. Displaced from the cytosolic surface of the cell membrane by PKC in phorbol myristate acetate (PMA)-induced cells"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15990874"}],"value":"Cytoplasm","id":"SL-0086"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15990874"}],"value":"Cell membrane","id":"SL-0039"}}]},{"commentType":"DISEASE","disease":{"diseaseId":"Osteopetrosis, autosomal recessive 3","diseaseAccession":"DI-01252","acronym":"OPTB3","description":"A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with intellectual disability.","diseaseCrossReference":{"database":"MIM","id":"259730"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15300855"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1542674"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1928091"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8834238"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9143915"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17251017"}],"value":"Target of drugs used in treatments against glaucoma disorder and breast cancer"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the alpha-carbonic anhydrase family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Initiator methionine","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":1,"modifier":"EXACT"}},"description":"Removed","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"4207120"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"823150"}]},{"type":"Chain","location":{"start":{"value":2,"modifier":"EXACT"},"end":{"value":260,"modifier":"EXACT"}},"description":"Carbonic anhydrase 2","featureId":"PRO_0000077418"},{"type":"Domain","location":{"start":{"value":3,"modifier":"EXACT"},"end":{"value":259,"modifier":"EXACT"}},"description":"Alpha-carbonic anhydrase","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU01134"}]},{"type":"Active site","location":{"start":{"value":64,"modifier":"EXACT"},"end":{"value":64,"modifier":"EXACT"}},"description":"Proton donor/acceptor","evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"15667203"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"17330962"}]},{"type":"Binding 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