CAH1_HUMAN
ID CAH1_HUMAN Reviewed; 261 AA.
AC P00915;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=Carbonic anhydrase 1;
DE EC=4.2.1.1 {ECO:0000269|PubMed:10550681};
DE AltName: Full=Carbonate dehydratase I;
DE AltName: Full=Carbonic anhydrase B;
DE Short=CAB;
DE AltName: Full=Carbonic anhydrase I;
DE Short=CA-I;
DE AltName: Full=Cyanamide hydratase CA1 {ECO:0000305};
DE EC=4.2.1.69 {ECO:0000269|PubMed:10550681};
GN Name=CA1;
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].
RX PubMed=3104879; DOI=10.1093/nar/15.5.2386;
RA Barlow J.H., Lowe N., Edwards Y.H., Butterworth P.H.W.;
RT "Human carbonic anhydrase I cDNA.";
RL Nucleic Acids Res. 15:2386-2386(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2121614; DOI=10.1016/0378-1119(90)90236-k;
RA Lowe N., Brady H.J.M., Barlow J.H., Sowden J.C., Edwards M.,
RA Butterworth P.H.W.;
RT "Structure and methylation patterns of the gene encoding human carbonic
RT anhydrase I.";
RL Gene 93:277-283(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas, and Spleen;
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 [4]
RP PROTEIN SEQUENCE OF 2-261, CLEAVAGE OF INITIATOR METHIONINE, AND
RP ACETYLATION AT ALA-2.
RX PubMed=4217196; DOI=10.1016/s0300-9084(74)80093-3;
RA Giraud N., Marriq C., Laurent-Tabusse G.;
RT "Primary structure of human B erythrocyte carbonic anhydrase. 3. Sequence
RT of CNBr fragment I and III (residues 149-260).";
RL Biochimie 56:1031-1043(1974).
RN [5]
RP PROTEIN SEQUENCE OF 20-261.
RX PubMed=4625868; DOI=10.1016/0006-291x(72)90400-7;
RA Andersson B., Nyman P.O., Strid L.;
RT "Amino acid sequence of human erythrocyte carbonic anhydrase B.";
RL Biochem. Biophys. Res. Commun. 48:670-677(1972).
RN [6]
RP PROTEIN SEQUENCE OF 12-261.
RX PubMed=4632246; DOI=10.1016/s0021-9258(19)44161-6;
RA Lin K.-T.D., Deutsch H.F.;
RT "Human carbonic anhydrases. XI. The complete primary structure of carbonic
RT anhydrase B.";
RL J. Biol. Chem. 248:1885-1893(1973).
RN [7]
RP SEQUENCE REVISION.
RX PubMed=4207120; DOI=10.1016/s0021-9258(19)42734-8;
RA Lin K.-T.D., Deutsch H.F.;
RT "Human carbonic anhydrases. XII. The complete primary structure of the C
RT isozyme.";
RL J. Biol. Chem. 249:2329-2337(1974).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=10550681; DOI=10.1007/s007750050375;
RA Briganti F., Mangani S., Scozzafava A., Vernaglione G., Supuran C.T.;
RT "Carbonic anhydrase catalyzes cyanamide hydration to urea: is it mimicking
RT the physiological reaction?";
RL J. Biol. Inorg. Chem. 4:528-536(1999).
RN [9]
RP ACTIVITY REGULATION.
RX PubMed=16807956; DOI=10.1002/chem.200600159;
RA Temperini C., Scozzafava A., Vullo D., Supuran C.T.;
RT "Carbonic anhydrase activators. Activation of isozymes I, II, IV, VA, VII,
RT and XIV with l- and d-histidine and crystallographic analysis of their
RT adducts with isoform II: engineering proton-transfer processes within the
RT active site of an enzyme.";
RL Chemistry 12:7057-7066(2006).
RN [10]
RP ACTIVITY REGULATION.
RX PubMed=16686544; DOI=10.1021/jm0603320;
RA Temperini C., Scozzafava A., Vullo D., Supuran C.T.;
RT "Carbonic anhydrase activators. Activation of isoforms I, II, IV, VA, VII,
RT and XIV with L- and D-phenylalanine and crystallographic analysis of their
RT adducts with isozyme II: stereospecific recognition within the active site
RT of an enzyme and its consequences for the drug design.";
RL J. Med. Chem. 49:3019-3027(2006).
RN [11]
RP ACTIVITY REGULATION.
RX PubMed=17127057; DOI=10.1016/j.bmcl.2006.11.027;
RA Temperini C., Innocenti A., Scozzafava A., Mastrolorenzo A., Supuran C.T.;
RT "Carbonic anhydrase activators: L-Adrenaline plugs the active site entrance
RT of isozyme II, activating better isoforms I, IV, VA, VII, and XIV.";
RL Bioorg. Med. Chem. Lett. 17:628-635(2007).
RN [12]
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 [13]
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 [14]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY
RP 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 [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260.
RX PubMed=4622589; DOI=10.1016/0022-2836(72)90452-4;
RA Kannan K.K., Fridborg K., Bergsten P.C., Liljas A., Loevgren S., Petef M.,
RA Strandberg B., Waara I., Adler L., Falkbring S.O., Goethe P.O., Nyman P.O.;
RT "Structure of human carbonic anhydrase B. I. Crystallization and heavy atom
RT modifications.";
RL J. Mol. Biol. 63:601-604(1972).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RX PubMed=804171; DOI=10.1073/pnas.72.1.51;
RA Kannan K.K., Notstrand B., Fridborg K., Loevgren S., Ohlsson A., Petef M.;
RT "Crystal structure of human erythrocyte carbonic anhydrase B. Three-
RT dimensional structure at a nominal 2.2-A resolution.";
RL Proc. Natl. Acad. Sci. U.S.A. 72:51-55(1975).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC ION.
RX PubMed=6430186; DOI=10.1111/j.1749-6632.1984.tb12314.x;
RA Kannan K.K., Ramanadham M., Jones T.A.;
RT "Structure, refinement, and function of carbonic anhydrase isozymes:
RT refinement of human carbonic anhydrase I.";
RL Ann. N. Y. Acad. Sci. 429:49-60(1984).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC ION
RP AND INHIBITORS.
RX PubMed=15299369; DOI=10.1107/s0907444994001873;
RA Kumar V., Kannan K.K., Sathyamurthi P.;
RT "Differences in anionic inhibition of human carbonic anhydrase I revealed
RT from the structures of iodide and gold cyanide inhibitor complexes.";
RL Acta Crystallogr. D 50:731-738(1994).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC ION
RP AND BICARBONATE.
RX PubMed=8057362; DOI=10.1006/jmbi.1994.1491;
RA Kumar V., Kannan K.K.;
RT "Enzyme-substrate interactions. Structure of human carbonic anhydrase I
RT complexed with bicarbonate.";
RL J. Mol. Biol. 241:226-232(1994).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC ION
RP AND INHIBITORS.
RX PubMed=7932756; DOI=10.1006/jmbi.1994.1655;
RA Chakravarty S., Kannan K.K.;
RT "Drug-protein interactions. Refined structures of three sulfonamide drug
RT complexes of human carbonic anhydrase I enzyme.";
RL J. Mol. Biol. 243:298-309(1994).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC ION,
RP AND VARIANT MICHIGAN-1 ARG-68.
RX PubMed=12009884; DOI=10.1021/bi0120446;
RA Ferraroni M., Tilli S., Briganti F., Chegwidden W.R., Supuran C.T.,
RA Wiebauer K.E., Tashian R.E., Scozzafava A.;
RT "Crystal structure of a zinc-activated variant of human carbonic anhydrase
RT I, CA I Michigan 1: evidence for a second zinc binding site involving
RT arginine coordination.";
RL Biochemistry 41:6237-6244(2002).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC ION
RP AND ACTIVATORS, AND ACTIVATION BY IMIDAZOLE AND HISTIDINE.
RX PubMed=16870440; DOI=10.1016/j.bmcl.2006.07.021;
RA Temperini C., Scozzafava A., Supuran C.T.;
RT "Carbonic anhydrase activators: the first X-ray crystallographic study of
RT an adduct of isoform I.";
RL Bioorg. Med. Chem. Lett. 16:5152-5156(2006).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC ION
RP AND INHIBITORS, AND ACTIVITY REGULATION.
RX PubMed=16506782; DOI=10.1021/ja057257n;
RA Jude K.M., Banerjee A.L., Haldar M.K., Manokaran S., Roy B., Mallik S.,
RA Srivastava D.K., Christianson D.W.;
RT "Ultrahigh resolution crystal structures of human carbonic anhydrases I and
RT II complexed with 'two-prong' inhibitors reveal the molecular basis of high
RT affinity.";
RL J. Am. Chem. Soc. 128:3011-3018(2006).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 6-260 IN COMPLEX WITH ZINC ION
RP AND THE ANTIVIRAL FOSCARNET, AND 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 [27]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC ION
RP AND INHIBITORS, AND 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 [28]
RP VARIANT GUAM ARG-254.
RX PubMed=6781336;
RA Omoto K., Ueda S., Goriki K., Takahashi N., Misawa S., Pagaran I.G.;
RT "Population genetic studies of the Philippine Negritos. III. Identification
RT of the carbonic anhydrase-1 variant with CA1 Guam.";
RL Am. J. Hum. Genet. 33:105-111(1981).
RN [29]
RP VARIANT MICHIGAN-1 ARG-68.
RX PubMed=7866410; DOI=10.1002/humu.1380040411;
RA Chegwidden W.R., Wagner L.E., Venta P.J., Bergenhem N.C.H., Yu Y.-S.L.,
RA Tashian R.E.;
RT "Marked zinc activation of ester hydrolysis by a mutation, 67-His (CAT) to
RT Arg (CGT), in the active site of human carbonic anhydrase I.";
RL Hum. Mutat. 4:294-296(1994).
CC -!- FUNCTION: Catalyzes the reversible hydration of carbon dioxide
CC (PubMed:10550681, PubMed:18618712). Can hydrate cyanamide to urea
CC (PubMed:10550681). {ECO:0000269|PubMed:10550681,
CC ECO:0000269|PubMed:18618712}.
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; Evidence={ECO:0000269|PubMed:10550681,
CC ECO:0000269|PubMed:18618712};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=urea = cyanamide + H2O; Xref=Rhea:RHEA:23056,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:16199, ChEBI:CHEBI:16698; EC=4.2.1.69;
CC Evidence={ECO:0000269|PubMed:10550681};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:12009884, ECO:0000269|PubMed:15299369,
CC ECO:0000269|PubMed:16506782, ECO:0000269|PubMed:16870440,
CC ECO:0000269|PubMed:17314045, ECO:0000269|PubMed:17407288,
CC ECO:0000269|PubMed:6430186, ECO:0000269|PubMed:7932756,
CC ECO:0000269|PubMed:804171, ECO:0000269|PubMed:8057362};
CC -!- ACTIVITY REGULATION: Activated by histamine, imidazole, L-adrenaline,
CC L- and D-histidine, and L- and D-phenylalanine. Inhibited by coumarins,
CC sulfonamide derivatives such as acetazolamide, benzenesulfonamide and
CC derivatives (4-carboxyethylbenzene-sulfonamide, 4-carboxyethylbenzene-
CC sulfonamide ethyl ester, 4-(acetyl-2-aminoethyl)benzene-sulfonamide, 4-
CC aminoethylbenzene-sulfonamide), and 'prong inhibitors' BR15, BR17, BR22
CC and BR30. Activated by a short exposition to Foscarnet
CC (phosphonoformate trisodium salt), but inhibited by a long one.
CC Esterase activity weakly reduced by cyanamide.
CC {ECO:0000269|PubMed:16506782, ECO:0000269|PubMed:16686544,
CC ECO:0000269|PubMed:16807956, ECO:0000269|PubMed:17127057,
CC ECO:0000269|PubMed:17314045, ECO:0000269|PubMed:17407288,
CC ECO:0000269|PubMed:18618712, ECO:0000269|PubMed:19186056,
CC ECO:0000269|PubMed:19206230}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.0 mM for CO(2) {ECO:0000269|PubMed:10550681,
CC ECO:0000269|PubMed:18618712};
CC KM=15 mM for 4-nitrophenyl acetate {ECO:0000269|PubMed:10550681,
CC ECO:0000269|PubMed:18618712};
CC -!- INTERACTION:
CC P00915; Q12800: TFCP2; NbExp=6; IntAct=EBI-3912102, EBI-717422;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:B0BNN3}.
CC -!- SIMILARITY: Belongs to the alpha-carbonic anhydrase family.
CC {ECO:0000305}.
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DR EMBL; X05014; CAA28663.1; -; mRNA.
DR EMBL; M33987; AAA51910.1; -; mRNA.
DR EMBL; BC027890; AAH27890.1; -; mRNA.
DR CCDS; CCDS6237.1; -.
DR PIR; JQ0786; CRHU1.
DR RefSeq; NP_001122301.1; NM_001128829.3.
DR RefSeq; NP_001122302.1; NM_001128830.3.
DR RefSeq; NP_001122303.1; NM_001128831.3.
DR RefSeq; NP_001158302.1; NM_001164830.1.
DR RefSeq; NP_001729.1; NM_001738.4.
DR PDB; 1AZM; X-ray; 2.00 A; A=2-261.
DR PDB; 1BZM; X-ray; 2.00 A; A=2-261.
DR PDB; 1CRM; X-ray; 2.00 A; A=2-261.
DR PDB; 1CZM; X-ray; 2.00 A; A=2-261.
DR PDB; 1HCB; X-ray; 1.60 A; A=2-261.
DR PDB; 1HUG; X-ray; 2.00 A; A=2-261.
DR PDB; 1HUH; X-ray; 2.20 A; A=2-261.
DR PDB; 1J9W; X-ray; 2.60 A; A/B=2-261.
DR PDB; 1JV0; X-ray; 2.00 A; A/B=2-261.
DR PDB; 2CAB; X-ray; 2.00 A; A=2-261.
DR PDB; 2FOY; X-ray; 1.55 A; A/B=2-261.
DR PDB; 2FW4; X-ray; 2.00 A; A/B=2-261.
DR PDB; 2IT4; X-ray; 2.00 A; A/B=6-261.
DR PDB; 2NMX; X-ray; 1.55 A; A/B=2-261.
DR PDB; 2NN1; X-ray; 1.65 A; A/B=2-261.
DR PDB; 2NN7; X-ray; 1.85 A; A/B=2-261.
DR PDB; 3LXE; X-ray; 1.90 A; A/B=2-261.
DR PDB; 3W6H; X-ray; 2.96 A; A/B=2-261.
DR PDB; 3W6I; X-ray; 2.69 A; A/E=2-261.
DR PDB; 4WR7; X-ray; 1.50 A; A/B=3-261.
DR PDB; 4WUP; X-ray; 1.75 A; A/B=3-261.
DR PDB; 4WUQ; X-ray; 1.75 A; A/B=3-261.
DR PDB; 5E2M; X-ray; 1.41 A; A/B=3-261.
DR PDB; 5GMM; X-ray; 2.00 A; A/B=1-261.
DR PDB; 6EVR; X-ray; 1.50 A; A/B=1-261.
DR PDB; 6EX1; X-ray; 1.60 A; A/B=1-261.
DR PDB; 6F3B; X-ray; 1.40 A; A/B=1-261.
DR PDB; 6FAF; X-ray; 1.99 A; A/B=1-261.
DR PDB; 6FAG; X-ray; 1.79 A; A/B=1-261.
DR PDB; 6G3V; X-ray; 1.69 A; A/B=1-261.
DR PDB; 6HWZ; X-ray; 1.64 A; A/B=1-261.
DR PDB; 6I0J; X-ray; 1.35 A; A/B=1-261.
DR PDB; 6I0L; X-ray; 1.40 A; A/B=1-261.
DR PDB; 6SWM; X-ray; 2.77 A; A/B=1-261.
DR PDB; 6XZE; X-ray; 1.54 A; A/B=1-261.
DR PDB; 6XZO; X-ray; 1.44 A; A/B=1-261.
DR PDB; 6XZS; X-ray; 1.53 A; A/B=1-261.
DR PDB; 6XZX; X-ray; 1.55 A; A/B=1-261.
DR PDB; 6XZY; X-ray; 1.66 A; A/B=1-261.
DR PDB; 6Y00; X-ray; 1.37 A; A/B=1-261.
DR PDB; 7Q0D; X-ray; 1.24 A; A/B=1-261.
DR PDBsum; 1AZM; -.
DR PDBsum; 1BZM; -.
DR PDBsum; 1CRM; -.
DR PDBsum; 1CZM; -.
DR PDBsum; 1HCB; -.
DR PDBsum; 1HUG; -.
DR PDBsum; 1HUH; -.
DR PDBsum; 1J9W; -.
DR PDBsum; 1JV0; -.
DR PDBsum; 2CAB; -.
DR PDBsum; 2FOY; -.
DR PDBsum; 2FW4; -.
DR PDBsum; 2IT4; -.
DR PDBsum; 2NMX; -.
DR PDBsum; 2NN1; -.
DR PDBsum; 2NN7; -.
DR PDBsum; 3LXE; -.
DR PDBsum; 3W6H; -.
DR PDBsum; 3W6I; -.
DR PDBsum; 4WR7; -.
DR PDBsum; 4WUP; -.
DR PDBsum; 4WUQ; -.
DR PDBsum; 5E2M; -.
DR PDBsum; 5GMM; -.
DR PDBsum; 6EVR; -.
DR PDBsum; 6EX1; -.
DR PDBsum; 6F3B; -.
DR PDBsum; 6FAF; -.
DR PDBsum; 6FAG; -.
DR PDBsum; 6G3V; -.
DR PDBsum; 6HWZ; -.
DR PDBsum; 6I0J; -.
DR PDBsum; 6I0L; -.
DR PDBsum; 6SWM; -.
DR PDBsum; 6XZE; -.
DR PDBsum; 6XZO; -.
DR PDBsum; 6XZS; -.
DR PDBsum; 6XZX; -.
DR PDBsum; 6XZY; -.
DR PDBsum; 6Y00; -.
DR PDBsum; 7Q0D; -.
DR AlphaFoldDB; P00915; -.
DR BMRB; P00915; -.
DR PCDDB; P00915; -.
DR SMR; P00915; -.
DR BioGRID; 107214; 9.
DR IntAct; P00915; 5.
DR MINT; P00915; -.
DR STRING; 9606.ENSP00000430656; -.
DR BindingDB; P00915; -.
DR ChEMBL; CHEMBL261; -.
DR DrugBank; DB08156; 3-[4-(AMINOSULFONYL)PHENYL]PROPANOIC ACID.
DR DrugBank; DB00819; Acetazolamide.
DR DrugBank; DB00381; Amlodipine.
DR DrugBank; DB00436; Bendroflumethiazide.
DR DrugBank; DB00562; Benzthiazide.
DR DrugBank; DB01194; Brinzolamide.
DR DrugBank; DB00880; Chlorothiazide.
DR DrugBank; DB00310; Chlorthalidone.
DR DrugBank; DB00606; Cyclothiazide.
DR DrugBank; DB01119; Diazoxide.
DR DrugBank; DB01144; Diclofenamide.
DR DrugBank; DB00869; Dorzolamide.
DR DrugBank; DB08846; Ellagic acid.
DR DrugBank; DB01031; Ethinamate.
DR DrugBank; DB00311; Ethoxzolamide.
DR DrugBank; DB08157; ETHYL 3-[4-(AMINOSULFONYL)PHENYL]PROPANOATE.
DR DrugBank; DB00774; Hydroflumethiazide.
DR DrugBank; DB00703; Methazolamide.
DR DrugBank; DB00423; Methocarbamol.
DR DrugBank; DB00232; Methyclothiazide.
DR DrugBank; DB08155; N-{2-[4-(AMINOSULFONYL)PHENYL]ETHYL}ACETAMIDE.
DR DrugBank; DB01325; Quinethazone.
DR DrugBank; DB09460; Sodium carbonate.
DR DrugBank; DB09472; Sodium sulfate.
DR DrugBank; DB00273; Topiramate.
DR DrugBank; DB01021; Trichlormethiazide.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB00909; Zonisamide.
DR DrugCentral; P00915; -.
DR GuidetoPHARMACOLOGY; 2597; -.
DR GlyConnect; 2846; 1 O-Linked glycan (2 sites).
DR GlyGen; P00915; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P00915; -.
DR PhosphoSitePlus; P00915; -.
DR BioMuta; CA1; -.
DR DMDM; 115449; -.
DR DOSAC-COBS-2DPAGE; P00915; -.
DR REPRODUCTION-2DPAGE; IPI00215983; -.
DR REPRODUCTION-2DPAGE; P00915; -.
DR UCD-2DPAGE; P00915; -.
DR CPTAC; CPTAC-1302; -.
DR CPTAC; non-CPTAC-1091; -.
DR jPOST; P00915; -.
DR MassIVE; P00915; -.
DR PaxDb; P00915; -.
DR PeptideAtlas; P00915; -.
DR PRIDE; P00915; -.
DR ProteomicsDB; 51291; -.
DR TopDownProteomics; P00915; -.
DR Antibodypedia; 1380; 663 antibodies from 41 providers.
DR DNASU; 759; -.
DR Ensembl; ENST00000431316.3; ENSP00000392338.1; ENSG00000133742.14.
DR Ensembl; ENST00000523022.6; ENSP00000429798.1; ENSG00000133742.14.
DR Ensembl; ENST00000523953.5; ENSP00000430656.1; ENSG00000133742.14.
DR Ensembl; ENST00000542576.5; ENSP00000443517.1; ENSG00000133742.14.
DR GeneID; 759; -.
DR KEGG; hsa:759; -.
DR MANE-Select; ENST00000523022.6; ENSP00000429798.1; NM_001128831.4; NP_001122303.1.
DR CTD; 759; -.
DR DisGeNET; 759; -.
DR GeneCards; CA1; -.
DR HGNC; HGNC:1368; CA1.
DR HPA; ENSG00000133742; Group enriched (bone marrow, intestine).
DR MIM; 114800; gene.
DR neXtProt; NX_P00915; -.
DR OpenTargets; ENSG00000133742; -.
DR PharmGKB; PA25984; -.
DR VEuPathDB; HostDB:ENSG00000133742; -.
DR eggNOG; KOG0382; Eukaryota.
DR GeneTree; ENSGT00940000161270; -.
DR InParanoid; P00915; -.
DR OMA; DYGSEHT; -.
DR OrthoDB; 1377476at2759; -.
DR PhylomeDB; P00915; -.
DR TreeFam; TF316425; -.
DR BioCyc; MetaCyc:HS05785-MON; -.
DR BRENDA; 4.2.1.1; 2681.
DR PathwayCommons; P00915; -.
DR Reactome; R-HSA-1237044; Erythrocytes take up carbon dioxide and release oxygen.
DR Reactome; R-HSA-1247673; Erythrocytes take up oxygen and release carbon dioxide.
DR Reactome; R-HSA-1475029; Reversible hydration of carbon dioxide.
DR Reactome; R-HSA-8950505; Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation.
DR SABIO-RK; P00915; -.
DR SignaLink; P00915; -.
DR BioGRID-ORCS; 759; 11 hits in 1076 CRISPR screens.
DR ChiTaRS; CA1; human.
DR EvolutionaryTrace; P00915; -.
DR GeneWiki; CA1_(gene); -.
DR GenomeRNAi; 759; -.
DR Pharos; P00915; Tclin.
DR PRO; PR:P00915; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P00915; protein.
DR Bgee; ENSG00000133742; Expressed in mucosa of transverse colon and 120 other tissues.
DR ExpressionAtlas; P00915; baseline and differential.
DR Genevisible; P00915; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0004064; F:arylesterase activity; IMP:CACAO.
DR GO; GO:0004089; F:carbonate dehydratase activity; IMP:CACAO.
DR GO; GO:0018820; F:cyanamide hydratase activity; IEA:RHEA.
DR GO; GO:0016836; F:hydro-lyase activity; IDA:CACAO.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
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; IPR018442; Carbonic_anhydrase_CA1.
DR PANTHER; PTHR18952; PTHR18952; 1.
DR PANTHER; PTHR18952:SF82; PTHR18952:SF82; 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; Acetylation; Cytoplasm; Direct protein sequencing; Lyase;
KW Metal-binding; Reference proteome; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:4217196"
FT CHAIN 2..261
FT /note="Carbonic anhydrase 1"
FT /id="PRO_0000077409"
FT DOMAIN 4..261
FT /note="Alpha-carbonic anhydrase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01134"
FT REGION 1..31
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 241..261
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 65
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P00918"
FT BINDING 65
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /note="in variant Michigan-1"
FT /evidence="ECO:0000269|PubMed:12009884"
FT BINDING 68
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /note="in variant Michigan-1"
FT /evidence="ECO:0000269|PubMed:12009884"
FT BINDING 95
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:12009884,
FT ECO:0000269|PubMed:15299369, ECO:0000269|PubMed:16506782,
FT ECO:0000269|PubMed:16870440, ECO:0000269|PubMed:17314045,
FT ECO:0000269|PubMed:17407288, ECO:0000269|PubMed:6430186,
FT ECO:0000269|PubMed:7932756, ECO:0000269|PubMed:804171,
FT ECO:0000269|PubMed:8057362"
FT BINDING 97
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:12009884,
FT ECO:0000269|PubMed:15299369, ECO:0000269|PubMed:16506782,
FT ECO:0000269|PubMed:16870440, ECO:0000269|PubMed:17314045,
FT ECO:0000269|PubMed:17407288, ECO:0000269|PubMed:6430186,
FT ECO:0000269|PubMed:7932756, ECO:0000269|PubMed:804171,
FT ECO:0000269|PubMed:8057362"
FT BINDING 120
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:12009884,
FT ECO:0000269|PubMed:15299369, ECO:0000269|PubMed:16506782,
FT ECO:0000269|PubMed:16870440, ECO:0000269|PubMed:17314045,
FT ECO:0000269|PubMed:17407288, ECO:0000269|PubMed:6430186,
FT ECO:0000269|PubMed:7932756, ECO:0000269|PubMed:804171,
FT ECO:0000269|PubMed:8057362"
FT BINDING 200..201
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00918"
FT BINDING 200
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:8057362"
FT BINDING 201
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /note="in variant Michigan-1"
FT /evidence="ECO:0000269|PubMed:12009884"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|PubMed:4207120,
FT ECO:0000269|PubMed:4217196"
FT VARIANT 68
FT /note="H -> R (in variant Michigan-1; confers enhanced
FT esterase activity and an additional zinc binding site;
FT dbSNP:rs990757234)"
FT /evidence="ECO:0000269|PubMed:12009884,
FT ECO:0000269|PubMed:7866410"
FT /id="VAR_001378"
FT VARIANT 143
FT /note="A -> V (in dbSNP:rs7821248)"
FT /id="VAR_048679"
FT VARIANT 254
FT /note="G -> R (in Guam; dbSNP:rs121909577)"
FT /evidence="ECO:0000269|PubMed:6781336"
FT /id="VAR_001379"
FT CONFLICT 75..76
FT /note="DN -> ND (in Ref. 4; AA sequence and 5; AA
FT sequence)"
FT /evidence="ECO:0000305"
FT TURN 10..12
FT /evidence="ECO:0007829|PDB:7Q0D"
FT TURN 14..16
FT /evidence="ECO:0007829|PDB:7Q0D"
FT HELIX 17..19
FT /evidence="ECO:0007829|PDB:7Q0D"
FT HELIX 22..25
FT /evidence="ECO:0007829|PDB:7Q0D"
FT STRAND 26..28
FT /evidence="ECO:0007829|PDB:7Q0D"
FT STRAND 32..34
FT /evidence="ECO:0007829|PDB:1J9W"
FT HELIX 36..38
FT /evidence="ECO:0007829|PDB:7Q0D"
FT STRAND 48..51
FT /evidence="ECO:0007829|PDB:7Q0D"
FT HELIX 54..56
FT /evidence="ECO:0007829|PDB:7Q0D"
FT STRAND 57..62
FT /evidence="ECO:0007829|PDB:7Q0D"
FT STRAND 64..71
FT /evidence="ECO:0007829|PDB:7Q0D"
FT STRAND 74..82
FT /evidence="ECO:0007829|PDB:7Q0D"
FT STRAND 89..98
FT /evidence="ECO:0007829|PDB:7Q0D"
FT STRAND 100..104
FT /evidence="ECO:0007829|PDB:1HCB"
FT STRAND 107..110
FT /evidence="ECO:0007829|PDB:7Q0D"
FT STRAND 116..124
FT /evidence="ECO:0007829|PDB:7Q0D"
FT TURN 126..128
FT /evidence="ECO:0007829|PDB:7Q0D"
FT HELIX 132..135
FT /evidence="ECO:0007829|PDB:7Q0D"
FT STRAND 141..153
FT /evidence="ECO:0007829|PDB:7Q0D"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:7Q0D"
FT HELIX 159..164
FT /evidence="ECO:0007829|PDB:7Q0D"
FT HELIX 165..167
FT /evidence="ECO:0007829|PDB:7Q0D"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:7Q0D"
FT HELIX 182..185
FT /evidence="ECO:0007829|PDB:7Q0D"
FT STRAND 192..197
FT /evidence="ECO:0007829|PDB:7Q0D"
FT STRAND 208..215
FT /evidence="ECO:0007829|PDB:7Q0D"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:7Q0D"
FT HELIX 221..228
FT /evidence="ECO:0007829|PDB:7Q0D"
FT STRAND 230..233
FT /evidence="ECO:0007829|PDB:7Q0D"
SQ SEQUENCE 261 AA; 28870 MW; 4959E5FA25E374F8 CRC64;
MASPDWGYDD KNGPEQWSKL YPIANGNNQS PVDIKTSETK HDTSLKPISV SYNPATAKEI
INVGHSFHVN FEDNDNRSVL KGGPFSDSYR LFQFHFHWGS TNEHGSEHTV DGVKYSAELH
VAHWNSAKYS SLAEAASKAD GLAVIGVLMK VGEANPKLQK VLDALQAIKT KGKRAPFTNF
DPSTLLPSSL DFWTYPGSLT HPPLYESVTW IICKESISVS SEQLAQFRSL LSNVEGDNAV
PMQHNNRPTQ PLKGRTVRAS F
