Full text data of CA1
CA1
[Confidence: high (present in two of the MS resources)]
Carbonic anhydrase 1; 4.2.1.1 (Carbonate dehydratase I; Carbonic anhydrase B; CAB; Carbonic anhydrase I; CA-I)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Carbonic anhydrase 1; 4.2.1.1 (Carbonate dehydratase I; Carbonic anhydrase B; CAB; Carbonic anhydrase I; CA-I)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00215983
IPI00215983 carbonic anhydrase I carbonic anhydrase I membrane n/a 1 n/a n/a n/a n/a n/a n/a 3 n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00215983 carbonic anhydrase I carbonic anhydrase I membrane n/a 1 n/a n/a n/a n/a n/a n/a 3 n/a n/a n/a n/a n/a n/a n/a n/a 1 n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P00915
ID CAH1_HUMAN Reviewed; 261 AA.
AC P00915;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 153.
DE RecName: Full=Carbonic anhydrase 1;
DE EC=4.2.1.1;
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;
GN Name=CA1;
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].
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
RT carbonic 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 2-261.
RX PubMed=4217196;
RA Giraud N., Marriq C., Laurent-Tabusse G.;
RT "Primary structure of human B erythrocyte carbonic anhydrase. 3.
RT Sequence 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;
RA Lin K.-T.D., Deutsch H.F.;
RT "Human carbonic anhydrases. XI. The complete primary structure of
RT carbonic anhydrase B.";
RL J. Biol. Chem. 248:1885-1893(1973).
RN [7]
RP SEQUENCE REVISION.
RX PubMed=4207120;
RA Lin K.-T.D., Deutsch H.F.;
RT "Human carbonic anhydrases. XII. The complete primary structure of the
RT C isozyme.";
RL J. Biol. Chem. 249:2329-2337(1974).
RN [8]
RP FUNCTION, 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
RT mimicking the physiological reaction?";
RL J. Biol. Inorg. Chem. 4:528-536(1999).
RN [9]
RP ENZYME 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,
RT VII, and XIV with l- and d-histidine and crystallographic analysis of
RT their adducts with isoform II: engineering proton-transfer processes
RT within the active site of an enzyme.";
RL Chemistry 12:7057-7066(2006).
RN [10]
RP ENZYME 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,
RT VII, and XIV with L- and D-phenylalanine and crystallographic analysis
RT of their adducts with isozyme II: stereospecific recognition within
RT the active site of an enzyme and its consequences for the drug
RT design.";
RL J. Med. Chem. 49:3019-3027(2006).
RN [11]
RP ENZYME REGULATION.
RX PubMed=17127057; DOI=10.1016/j.bmcl.2006.11.027;
RA Temperini C., Innocenti A., Scozzafava A., Mastrolorenzo A.,
RA Supuran C.T.;
RT "Carbonic anhydrase activators: L-Adrenaline plugs the active site
RT entrance of isozyme II, activating better isoforms I, IV, VA, VII, and
RT XIV.";
RL Bioorg. Med. Chem. Lett. 17:628-635(2007).
RN [12]
RP ENZYME 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 ENZYME 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 [14]
RP BIOPHYSICOCHEMICAL PROPERTIES, AND ENZYME 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 [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.,
RA Buerckstuemmer T., 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 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.,
RA Petef M., Strandberg B., Waara I., Adler L., Falkbring S.O.,
RA Goethe P.O., Nyman P.O.;
RT "Structure of human carbonic anhydrase B. I. Crystallization and heavy
RT atom modifications.";
RL J. Mol. Biol. 63:601-604(1972).
RN [17]
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.,
RA 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 [18]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC
RP 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 [19]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC
RP ION 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
RT revealed from the structures of iodide and gold cyanide inhibitor
RT complexes.";
RL Acta Crystallogr. D 50:731-738(1994).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC
RP ION 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
RT I complexed with bicarbonate.";
RL J. Mol. Biol. 241:226-232(1994).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC
RP ION 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
RT drug complexes of human carbonic anhydrase I enzyme.";
RL J. Mol. Biol. 243:298-309(1994).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC
RP ION, 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
RT anhydrase I, CA I Michigan 1: evidence for a second zinc binding site
RT involving arginine coordination.";
RL Biochemistry 41:6237-6244(2002).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC
RP ION 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
RT of an adduct of isoform I.";
RL Bioorg. Med. Chem. Lett. 16:5152-5156(2006).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC
RP ION AND INHIBITORS, AND ENZYME REGULATION.
RX PubMed=16506782; DOI=10.1021/ja057257n;
RA Jude K.M., Banerjee A.L., Haldar M.K., Manokaran S., Roy B.,
RA Mallik S., Srivastava D.K., Christianson D.W.;
RT "Ultrahigh resolution crystal structures of human carbonic anhydrases
RT I and II complexed with 'two-prong' inhibitors reveal the molecular
RT basis of high affinity.";
RL J. Am. Chem. Soc. 128:3011-3018(2006).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 6-260 IN COMPLEX WITH ZINC
RP ION AND THE ANTIVIRAL FOSCARNET, AND ENZYME 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 [26]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC
RP ION AND INHIBITORS, AND ENZYME 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 [27]
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.
RT Identification of the carbonic anhydrase-1 variant with CA1 Guam.";
RL Am. J. Hum. Genet. 33:105-111(1981).
RN [28]
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.,
RA Yu Y.-S.L., Tashian R.E.;
RT "Marked zinc activation of ester hydrolysis by a mutation, 67-His
RT (CAT) to Arg (CGT), in the active site of human carbonic anhydrase
RT I.";
RL Hum. Mutat. 4:294-296(1994).
CC -!- FUNCTION: Reversible hydration of carbon dioxide. Can hydrates
CC cyanamide to urea.
CC -!- CATALYTIC ACTIVITY: H(2)CO(3) = CO(2) + H(2)O.
CC -!- COFACTOR: Zinc.
CC -!- ENZYME REGULATION: Activated by histamine, imidazole, L-
CC adrenaline, L- and D-histidine, and L- and D-phenylalanine.
CC Inhibited by coumarins, sulfonamide derivatives such as
CC acetazolamide, benzenesulfonamide and derivatives (4-
CC carboxyethylbenzene-sulfonamide, 4-carboxyethylbenzene-sulfonamide
CC ethyl ester, 4-(acetyl-2-aminoethyl)benzene-sulfonamide, 4-
CC aminoethylbenzene-sulfonamide), and 'prong inhibitors' BR15, BR17,
CC BR22 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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.0 mM for CO(2);
CC KM=15 mM for 4-nitrophenyl acetate;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the alpha-carbonic anhydrase family.
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DR EMBL; X05014; CAA28663.1; -; mRNA.
DR EMBL; M33987; AAA51910.1; -; mRNA.
DR EMBL; BC027890; AAH27890.1; -; mRNA.
DR PIR; JQ0786; CRHU1.
DR RefSeq; NP_001122301.1; NM_001128829.2.
DR RefSeq; NP_001122302.1; NM_001128830.2.
DR RefSeq; NP_001122303.1; NM_001128831.2.
DR RefSeq; NP_001158302.1; NM_001164830.1.
DR RefSeq; NP_001729.1; NM_001738.3.
DR UniGene; Hs.23118; -.
DR PDB; 1AZM; X-ray; 2.00 A; A=2-260.
DR PDB; 1BZM; X-ray; 2.00 A; A=2-260.
DR PDB; 1CRM; X-ray; 2.00 A; A=2-260.
DR PDB; 1CZM; X-ray; 2.00 A; A=2-260.
DR PDB; 1HCB; X-ray; 1.60 A; A=2-260.
DR PDB; 1HUG; X-ray; 2.00 A; A=2-260.
DR PDB; 1HUH; X-ray; 2.20 A; A=2-260.
DR PDB; 1J9W; X-ray; 2.60 A; A/B=2-260.
DR PDB; 1JV0; X-ray; 2.00 A; A/B=2-260.
DR PDB; 2CAB; X-ray; 2.00 A; A=2-260.
DR PDB; 2FOY; X-ray; 1.55 A; A/B=2-260.
DR PDB; 2FW4; X-ray; 2.00 A; A/B=2-260.
DR PDB; 2IT4; X-ray; 2.00 A; A/B=6-260.
DR PDB; 2NMX; X-ray; 1.55 A; A/B=2-261.
DR PDB; 2NN1; X-ray; 1.65 A; A/B=2-260.
DR PDB; 2NN7; X-ray; 1.85 A; A/B=2-260.
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 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 ProteinModelPortal; P00915; -.
DR SMR; P00915; 4-261.
DR IntAct; P00915; 2.
DR STRING; 9606.ENSP00000256119; -.
DR BindingDB; P00915; -.
DR ChEMBL; CHEMBL2095180; -.
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; DB00606; Cyclothiazide.
DR DrugBank; DB01119; Diazoxide.
DR DrugBank; DB01144; Dichlorphenamide.
DR DrugBank; DB01031; Ethinamate.
DR DrugBank; DB00311; Ethoxzolamide.
DR DrugBank; DB00999; Hydrochlorothiazide.
DR DrugBank; DB00774; Hydroflumethiazide.
DR DrugBank; DB01202; Levetiracetam.
DR DrugBank; DB00703; Methazolamide.
DR DrugBank; DB00232; Methyclothiazide.
DR DrugBank; DB01325; Quinethazone.
DR DrugBank; DB01021; Trichlormethiazide.
DR DrugBank; DB00661; Verapamil.
DR DrugBank; DB00909; Zonisamide.
DR PhosphoSite; P00915; -.
DR DMDM; 115449; -.
DR DOSAC-COBS-2DPAGE; P00915; -.
DR REPRODUCTION-2DPAGE; IPI00215983; -.
DR REPRODUCTION-2DPAGE; P00915; -.
DR UCD-2DPAGE; P00915; -.
DR PaxDb; P00915; -.
DR PeptideAtlas; P00915; -.
DR PRIDE; P00915; -.
DR DNASU; 759; -.
DR Ensembl; ENST00000256119; ENSP00000256119; ENSG00000133742.
DR Ensembl; ENST00000431316; ENSP00000392338; ENSG00000133742.
DR Ensembl; ENST00000432364; ENSP00000401551; ENSG00000133742.
DR Ensembl; ENST00000523022; ENSP00000429798; ENSG00000133742.
DR Ensembl; ENST00000523953; ENSP00000430656; ENSG00000133742.
DR Ensembl; ENST00000542576; ENSP00000443517; ENSG00000133742.
DR GeneID; 759; -.
DR KEGG; hsa:759; -.
DR UCSC; uc003ydh.3; human.
DR CTD; 759; -.
DR GeneCards; GC08M086315; -.
DR HGNC; HGNC:1368; CA1.
DR HPA; CAB025790; -.
DR HPA; HPA006558; -.
DR MIM; 114800; gene.
DR neXtProt; NX_P00915; -.
DR PharmGKB; PA25984; -.
DR eggNOG; COG3338; -.
DR HOGENOM; HOG000112637; -.
DR HOVERGEN; HBG002837; -.
DR InParanoid; P00915; -.
DR KO; K01672; -.
DR OMA; ETKHDTS; -.
DR OrthoDB; EOG7WMCK7; -.
DR PhylomeDB; P00915; -.
DR BRENDA; 4.2.1.1; 2681.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P00915; -.
DR EvolutionaryTrace; P00915; -.
DR GeneWiki; CA1_(gene); -.
DR GenomeRNAi; 759; -.
DR NextBio; 3070; -.
DR PRO; PR:P00915; -.
DR ArrayExpress; P00915; -.
DR Bgee; P00915; -.
DR CleanEx; HS_CA1; -.
DR Genevestigator; P00915; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0004089; F:carbonate dehydratase activity; TAS:ProtInc.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0015701; P:bicarbonate transport; TAS:Reactome.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:InterPro.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR Gene3D; 3.10.200.10; -; 1.
DR InterPro; IPR001148; Carbonic_anhydrase_a.
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:SF30; PTHR18952:SF30; 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; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Lyase; Metal-binding; Polymorphism;
KW Reference proteome; Zinc.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 261 Carbonic anhydrase 1.
FT /FTId=PRO_0000077409.
FT REGION 200 201 Substrate binding (By similarity).
FT ACT_SITE 65 65 Proton acceptor (By similarity).
FT ACT_SITE 129 129 By similarity.
FT METAL 65 65 Zinc 2; variant Michigan-1.
FT METAL 68 68 Zinc 2; variant Michigan-1.
FT METAL 95 95 Zinc 1; catalytic.
FT METAL 97 97 Zinc 1; catalytic.
FT METAL 120 120 Zinc 1; catalytic.
FT METAL 201 201 Zinc 2; variant Michigan-1.
FT BINDING 200 200 Substrate.
FT MOD_RES 2 2 N-acetylalanine.
FT VARIANT 68 68 H -> R (in variant Michigan-1; confers
FT enhanced esterase activity and an
FT additional zinc binding site).
FT /FTId=VAR_001378.
FT VARIANT 143 143 A -> V (in dbSNP:rs7821248).
FT /FTId=VAR_048679.
FT VARIANT 254 254 G -> R (in Guam).
FT /FTId=VAR_001379.
FT CONFLICT 75 76 DN -> ND (in Ref. 4; AA sequence and 5;
FT AA sequence).
FT TURN 10 12
FT HELIX 14 19
FT HELIX 22 25
FT STRAND 26 28
FT STRAND 32 34
FT TURN 36 38
FT STRAND 48 51
FT HELIX 54 56
FT STRAND 57 62
FT STRAND 67 71
FT STRAND 74 82
FT STRAND 89 98
FT STRAND 100 104
FT STRAND 107 110
FT STRAND 116 125
FT TURN 126 128
FT HELIX 132 135
FT STRAND 141 153
FT HELIX 156 158
FT HELIX 159 164
FT HELIX 165 167
FT STRAND 174 176
FT HELIX 182 185
FT STRAND 192 197
FT STRAND 208 215
FT STRAND 217 219
FT HELIX 221 228
FT STRAND 230 233
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
//
ID CAH1_HUMAN Reviewed; 261 AA.
AC P00915;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 153.
DE RecName: Full=Carbonic anhydrase 1;
DE EC=4.2.1.1;
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;
GN Name=CA1;
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].
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
RT carbonic 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 2-261.
RX PubMed=4217196;
RA Giraud N., Marriq C., Laurent-Tabusse G.;
RT "Primary structure of human B erythrocyte carbonic anhydrase. 3.
RT Sequence 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;
RA Lin K.-T.D., Deutsch H.F.;
RT "Human carbonic anhydrases. XI. The complete primary structure of
RT carbonic anhydrase B.";
RL J. Biol. Chem. 248:1885-1893(1973).
RN [7]
RP SEQUENCE REVISION.
RX PubMed=4207120;
RA Lin K.-T.D., Deutsch H.F.;
RT "Human carbonic anhydrases. XII. The complete primary structure of the
RT C isozyme.";
RL J. Biol. Chem. 249:2329-2337(1974).
RN [8]
RP FUNCTION, 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
RT mimicking the physiological reaction?";
RL J. Biol. Inorg. Chem. 4:528-536(1999).
RN [9]
RP ENZYME 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,
RT VII, and XIV with l- and d-histidine and crystallographic analysis of
RT their adducts with isoform II: engineering proton-transfer processes
RT within the active site of an enzyme.";
RL Chemistry 12:7057-7066(2006).
RN [10]
RP ENZYME 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,
RT VII, and XIV with L- and D-phenylalanine and crystallographic analysis
RT of their adducts with isozyme II: stereospecific recognition within
RT the active site of an enzyme and its consequences for the drug
RT design.";
RL J. Med. Chem. 49:3019-3027(2006).
RN [11]
RP ENZYME REGULATION.
RX PubMed=17127057; DOI=10.1016/j.bmcl.2006.11.027;
RA Temperini C., Innocenti A., Scozzafava A., Mastrolorenzo A.,
RA Supuran C.T.;
RT "Carbonic anhydrase activators: L-Adrenaline plugs the active site
RT entrance of isozyme II, activating better isoforms I, IV, VA, VII, and
RT XIV.";
RL Bioorg. Med. Chem. Lett. 17:628-635(2007).
RN [12]
RP ENZYME 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 ENZYME 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 [14]
RP BIOPHYSICOCHEMICAL PROPERTIES, AND ENZYME 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 [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.,
RA Buerckstuemmer T., 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 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.,
RA Petef M., Strandberg B., Waara I., Adler L., Falkbring S.O.,
RA Goethe P.O., Nyman P.O.;
RT "Structure of human carbonic anhydrase B. I. Crystallization and heavy
RT atom modifications.";
RL J. Mol. Biol. 63:601-604(1972).
RN [17]
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.,
RA 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 [18]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC
RP 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 [19]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC
RP ION 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
RT revealed from the structures of iodide and gold cyanide inhibitor
RT complexes.";
RL Acta Crystallogr. D 50:731-738(1994).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC
RP ION 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
RT I complexed with bicarbonate.";
RL J. Mol. Biol. 241:226-232(1994).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC
RP ION 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
RT drug complexes of human carbonic anhydrase I enzyme.";
RL J. Mol. Biol. 243:298-309(1994).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC
RP ION, 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
RT anhydrase I, CA I Michigan 1: evidence for a second zinc binding site
RT involving arginine coordination.";
RL Biochemistry 41:6237-6244(2002).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC
RP ION 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
RT of an adduct of isoform I.";
RL Bioorg. Med. Chem. Lett. 16:5152-5156(2006).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC
RP ION AND INHIBITORS, AND ENZYME REGULATION.
RX PubMed=16506782; DOI=10.1021/ja057257n;
RA Jude K.M., Banerjee A.L., Haldar M.K., Manokaran S., Roy B.,
RA Mallik S., Srivastava D.K., Christianson D.W.;
RT "Ultrahigh resolution crystal structures of human carbonic anhydrases
RT I and II complexed with 'two-prong' inhibitors reveal the molecular
RT basis of high affinity.";
RL J. Am. Chem. Soc. 128:3011-3018(2006).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 6-260 IN COMPLEX WITH ZINC
RP ION AND THE ANTIVIRAL FOSCARNET, AND ENZYME 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 [26]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC
RP ION AND INHIBITORS, AND ENZYME 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 [27]
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.
RT Identification of the carbonic anhydrase-1 variant with CA1 Guam.";
RL Am. J. Hum. Genet. 33:105-111(1981).
RN [28]
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.,
RA Yu Y.-S.L., Tashian R.E.;
RT "Marked zinc activation of ester hydrolysis by a mutation, 67-His
RT (CAT) to Arg (CGT), in the active site of human carbonic anhydrase
RT I.";
RL Hum. Mutat. 4:294-296(1994).
CC -!- FUNCTION: Reversible hydration of carbon dioxide. Can hydrates
CC cyanamide to urea.
CC -!- CATALYTIC ACTIVITY: H(2)CO(3) = CO(2) + H(2)O.
CC -!- COFACTOR: Zinc.
CC -!- ENZYME REGULATION: Activated by histamine, imidazole, L-
CC adrenaline, L- and D-histidine, and L- and D-phenylalanine.
CC Inhibited by coumarins, sulfonamide derivatives such as
CC acetazolamide, benzenesulfonamide and derivatives (4-
CC carboxyethylbenzene-sulfonamide, 4-carboxyethylbenzene-sulfonamide
CC ethyl ester, 4-(acetyl-2-aminoethyl)benzene-sulfonamide, 4-
CC aminoethylbenzene-sulfonamide), and 'prong inhibitors' BR15, BR17,
CC BR22 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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.0 mM for CO(2);
CC KM=15 mM for 4-nitrophenyl acetate;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the alpha-carbonic anhydrase family.
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DR EMBL; X05014; CAA28663.1; -; mRNA.
DR EMBL; M33987; AAA51910.1; -; mRNA.
DR EMBL; BC027890; AAH27890.1; -; mRNA.
DR PIR; JQ0786; CRHU1.
DR RefSeq; NP_001122301.1; NM_001128829.2.
DR RefSeq; NP_001122302.1; NM_001128830.2.
DR RefSeq; NP_001122303.1; NM_001128831.2.
DR RefSeq; NP_001158302.1; NM_001164830.1.
DR RefSeq; NP_001729.1; NM_001738.3.
DR UniGene; Hs.23118; -.
DR PDB; 1AZM; X-ray; 2.00 A; A=2-260.
DR PDB; 1BZM; X-ray; 2.00 A; A=2-260.
DR PDB; 1CRM; X-ray; 2.00 A; A=2-260.
DR PDB; 1CZM; X-ray; 2.00 A; A=2-260.
DR PDB; 1HCB; X-ray; 1.60 A; A=2-260.
DR PDB; 1HUG; X-ray; 2.00 A; A=2-260.
DR PDB; 1HUH; X-ray; 2.20 A; A=2-260.
DR PDB; 1J9W; X-ray; 2.60 A; A/B=2-260.
DR PDB; 1JV0; X-ray; 2.00 A; A/B=2-260.
DR PDB; 2CAB; X-ray; 2.00 A; A=2-260.
DR PDB; 2FOY; X-ray; 1.55 A; A/B=2-260.
DR PDB; 2FW4; X-ray; 2.00 A; A/B=2-260.
DR PDB; 2IT4; X-ray; 2.00 A; A/B=6-260.
DR PDB; 2NMX; X-ray; 1.55 A; A/B=2-261.
DR PDB; 2NN1; X-ray; 1.65 A; A/B=2-260.
DR PDB; 2NN7; X-ray; 1.85 A; A/B=2-260.
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 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 ProteinModelPortal; P00915; -.
DR SMR; P00915; 4-261.
DR IntAct; P00915; 2.
DR STRING; 9606.ENSP00000256119; -.
DR BindingDB; P00915; -.
DR ChEMBL; CHEMBL2095180; -.
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; DB00606; Cyclothiazide.
DR DrugBank; DB01119; Diazoxide.
DR DrugBank; DB01144; Dichlorphenamide.
DR DrugBank; DB01031; Ethinamate.
DR DrugBank; DB00311; Ethoxzolamide.
DR DrugBank; DB00999; Hydrochlorothiazide.
DR DrugBank; DB00774; Hydroflumethiazide.
DR DrugBank; DB01202; Levetiracetam.
DR DrugBank; DB00703; Methazolamide.
DR DrugBank; DB00232; Methyclothiazide.
DR DrugBank; DB01325; Quinethazone.
DR DrugBank; DB01021; Trichlormethiazide.
DR DrugBank; DB00661; Verapamil.
DR DrugBank; DB00909; Zonisamide.
DR PhosphoSite; P00915; -.
DR DMDM; 115449; -.
DR DOSAC-COBS-2DPAGE; P00915; -.
DR REPRODUCTION-2DPAGE; IPI00215983; -.
DR REPRODUCTION-2DPAGE; P00915; -.
DR UCD-2DPAGE; P00915; -.
DR PaxDb; P00915; -.
DR PeptideAtlas; P00915; -.
DR PRIDE; P00915; -.
DR DNASU; 759; -.
DR Ensembl; ENST00000256119; ENSP00000256119; ENSG00000133742.
DR Ensembl; ENST00000431316; ENSP00000392338; ENSG00000133742.
DR Ensembl; ENST00000432364; ENSP00000401551; ENSG00000133742.
DR Ensembl; ENST00000523022; ENSP00000429798; ENSG00000133742.
DR Ensembl; ENST00000523953; ENSP00000430656; ENSG00000133742.
DR Ensembl; ENST00000542576; ENSP00000443517; ENSG00000133742.
DR GeneID; 759; -.
DR KEGG; hsa:759; -.
DR UCSC; uc003ydh.3; human.
DR CTD; 759; -.
DR GeneCards; GC08M086315; -.
DR HGNC; HGNC:1368; CA1.
DR HPA; CAB025790; -.
DR HPA; HPA006558; -.
DR MIM; 114800; gene.
DR neXtProt; NX_P00915; -.
DR PharmGKB; PA25984; -.
DR eggNOG; COG3338; -.
DR HOGENOM; HOG000112637; -.
DR HOVERGEN; HBG002837; -.
DR InParanoid; P00915; -.
DR KO; K01672; -.
DR OMA; ETKHDTS; -.
DR OrthoDB; EOG7WMCK7; -.
DR PhylomeDB; P00915; -.
DR BRENDA; 4.2.1.1; 2681.
DR Reactome; REACT_111217; Metabolism.
DR SABIO-RK; P00915; -.
DR EvolutionaryTrace; P00915; -.
DR GeneWiki; CA1_(gene); -.
DR GenomeRNAi; 759; -.
DR NextBio; 3070; -.
DR PRO; PR:P00915; -.
DR ArrayExpress; P00915; -.
DR Bgee; P00915; -.
DR CleanEx; HS_CA1; -.
DR Genevestigator; P00915; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0004089; F:carbonate dehydratase activity; TAS:ProtInc.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0015701; P:bicarbonate transport; TAS:Reactome.
DR GO; GO:0006730; P:one-carbon metabolic process; IEA:InterPro.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR Gene3D; 3.10.200.10; -; 1.
DR InterPro; IPR001148; Carbonic_anhydrase_a.
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:SF30; PTHR18952:SF30; 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; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Lyase; Metal-binding; Polymorphism;
KW Reference proteome; Zinc.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 261 Carbonic anhydrase 1.
FT /FTId=PRO_0000077409.
FT REGION 200 201 Substrate binding (By similarity).
FT ACT_SITE 65 65 Proton acceptor (By similarity).
FT ACT_SITE 129 129 By similarity.
FT METAL 65 65 Zinc 2; variant Michigan-1.
FT METAL 68 68 Zinc 2; variant Michigan-1.
FT METAL 95 95 Zinc 1; catalytic.
FT METAL 97 97 Zinc 1; catalytic.
FT METAL 120 120 Zinc 1; catalytic.
FT METAL 201 201 Zinc 2; variant Michigan-1.
FT BINDING 200 200 Substrate.
FT MOD_RES 2 2 N-acetylalanine.
FT VARIANT 68 68 H -> R (in variant Michigan-1; confers
FT enhanced esterase activity and an
FT additional zinc binding site).
FT /FTId=VAR_001378.
FT VARIANT 143 143 A -> V (in dbSNP:rs7821248).
FT /FTId=VAR_048679.
FT VARIANT 254 254 G -> R (in Guam).
FT /FTId=VAR_001379.
FT CONFLICT 75 76 DN -> ND (in Ref. 4; AA sequence and 5;
FT AA sequence).
FT TURN 10 12
FT HELIX 14 19
FT HELIX 22 25
FT STRAND 26 28
FT STRAND 32 34
FT TURN 36 38
FT STRAND 48 51
FT HELIX 54 56
FT STRAND 57 62
FT STRAND 67 71
FT STRAND 74 82
FT STRAND 89 98
FT STRAND 100 104
FT STRAND 107 110
FT STRAND 116 125
FT TURN 126 128
FT HELIX 132 135
FT STRAND 141 153
FT HELIX 156 158
FT HELIX 159 164
FT HELIX 165 167
FT STRAND 174 176
FT HELIX 182 185
FT STRAND 192 197
FT STRAND 208 215
FT STRAND 217 219
FT HELIX 221 228
FT STRAND 230 233
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
//
MIM
114800
*RECORD*
*FIELD* NO
114800
*FIELD* TI
*114800 CARBONIC ANHYDRASE I; CA1
;;CA I;;
CARBONIC ANHYDRASE A;;
CARBONIC ANHYDRASE B, FORMERLY
read more*FIELD* TX
DESCRIPTION
Carbonic anhydrases (CAs; carbonate dehydratase; carbonate hydrolyase;
EC 4.2.1.1) form a large family of genes encoding zinc metalloenzymes of
great physiologic importance. As catalysts of the reversible hydration
of carbon dioxide, these enzymes participate in a variety of biologic
processes, including respiration, calcification, acid-base balance, bone
resorption, and the formation of aqueous humor, cerebrospinal fluid,
saliva, and gastric acid (Dodgson et al., 1991). CAs are encoded by
members of 3 independent CA gene families, i.e., alpha-CA, beta-CA, and
gamma-CA (Hewett-Emmett and Tashian, 1996). Genes in the alpha-carbonic
anhydrase family encode either active carbonic anhydrase isozymes or
'acatalytic' (i.e., devoid of CO2 hydration activity) carbonic
anhydrase-related proteins. Alpha-carbonic anhydrases show extensive
diversity in tissue distribution and in their putative or established
biologic functions. Some of the alpha-CAs are expressed in almost all
tissues (e.g., CA II, 611492), whereas some show a more restricted
expression (e.g., CA VI (114780) in salivary glands). In cells, they may
reside in cytoplasm, in mitochondria, or in secretory granules, or
associate with membranes.
CLONING
Erythrocyte carbonic anhydrase has 2 isoenzymes with different amino
acid sequences and specific activities. B and C were the original
designations for these 2 major forms which later were called CA I (or A)
and CA II (or B; 611492), respectively. Tashian (1969) reviewed the
biochemical genetics of the 2 forms of red cell carbonic anhydrase,
which are under the control of separate autosomal loci.
Andersson et al. (1972) stated that CA I is the major form of the enzyme
in human red cells. They found that the protein consists of 260 amino
acids. Barlow et al. (1987) cloned human carbonic anhydrase I cDNA.
MAPPING
CA I and CA II are linked in the rodent genus Cavia (Carter, 1972),
closely linked in an Old World monkey, Macaca nemestrina (DeSimone et
al., 1973), and tightly linked in the mouse (Eicher et al., 1976).
Using a cDNA clone of the CA1 gene in the study of human-rodent hybrids,
Butterworth et al. (1985) and Edwards et al. (1986) assigned the CA1
gene to chromosome 8, which carries a cluster of CA genes.
By somatic cell genetic techniques and in situ hybridization, Davis et
al. (1986, 1987) mapped the CA1 and CA3 (114750) genes to 8q13-q22. By
pulsed field gel electrophoresis, Lowe et al. (1991) determined that the
order of the genes is CA2, CA3, CA1. CA2 and CA3 are separated by 20 kb
and are transcribed in the same direction, away from CA1. CA1 is
separated from CA3 by over 80 kb and is transcribed in the opposite
direction to CA2 and CA3. Lowe et al. (1991) concluded that the
arrangement of the genes is consistent with proposals that the
duplication event that gave rise to CA1 predated the duplication that
gave rise to CA2 and CA3. The order of the 3 genes differs from that
suggested for the mouse based on recombination frequency.
GENE STRUCTURE
Tashian (1992) reviewed the gene organization and evolutionary
relationships of the carbonic anhydrases. See also Hewett-Emmett and
Tashian (1996).
GENE FUNCTION
Gao et al. (2007) performed proteomic analysis on vitreous fluid samples
and found that the CA1 concentration from patients with diabetic
retinopathy (see 603933) was 15.3 and 8.2 times higher than that from
nondiabetic patients and diabetics with no diabetic retinopathy,
respectively. Intravitreous injection of CA1 in rats increased retinal
vessel leakage and caused intraretinal edema. CA1-induced alkalinization
of vitreous increased kallilkrein (see 147910) and its generation of
factor XIIa (see 610619); complement-1 inhibitor (C1NH; 606860),
neutralizing antibody to prekallikrein (KLKB1; 229000), and bradykinin
receptor (see 600337) antagonism decreased CA1-induced retinal edema.
Subdural infusion of CA1 in rats induced cerebral vascular permeability.
Gao et al. (2007) concluded that extracellular CA1 mediates hemorrhagic
retinal and cerebral vascular permeability through prekallikrein
activation.
MOLECULAR GENETICS
By starch gel electrophoresis, Tashian et al. (1963) detected a
genetically determined variant of erythrocyte carbonic anhydrase.
The amino acid change in several CA I mutants was determined by Carter
et al. (1972). Moore et al. (1973) demonstrated the autosomal dominant
inheritance of CA I and CA II variants.
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
- Carbonic Anhydrase I Deficiency
In a family on the Greek island of Icaria, Kendall and Tashian (1977)
found virtually complete absence of erythrocyte carbonic anhydrase I in
3 persons and reduced levels thought to represent the heterozygous state
in 2 others. No obvious hematologic or renal consequences were found in
any of them. Venta et al. (1987) reported preliminary observations
involving restriction analysis of DNA from white cells of CA I-deficient
members of this family, which showed that the deficiency is not caused
by a major deletion in at least 1 part of the gene. Wagner et al. (1991)
and Tashian (1992) reported that CA I-deficient members of this family
have a missense mutation in exon 7 of their CA1 gene (arg246-to-his;
114800.0002). Replacement of the highly conserved arg246 is the probable
cause of the CA I deficiency.
*FIELD* AV
.0001
CARBONIC ANHYDRASE I, GUAM
CA1, GLY253ARG
Carbonic anhydrase Guam has substitution of arginine for glycine
(Tashian and Carter, 1976). Omoto et al. (1981) established identity of
a CA-1 variant in Philippine Negritos, CA-1(3N), to CA-1(Guam); both
have substitution of arginine for glycine at amino acid 253.
.0002
CARBONIC ANHYDRASE I DEFICIENCY
CA1, ARG246HIS
In healthy members with almost complete absence of red cell CA I in the
Icaria family reported by Kendall and Tashian (1977), Wagner et al.
(1991) found an arg246-to-his missense mutation in the CA1 gene.
*FIELD* SA
Blake (1978); Blake and Kirk (1978); Carter (1972); Goriki et al.
(1979); Hopkinson et al. (1974); Kageoka et al. (1981); Lindskog et
al. (1971); Marriq et al. (1970); Omoto (1979); Shapira et al. (1974);
Tashian et al. (1971)
*FIELD* RF
1. Andersson, B.; Nyman, P. O.; Strid, L.: Amino acid sequence of
human erythrocyte carbonic anhydrase B. Biochem. Biophys. Res. Commun. 48:
670-677, 1972.
2. Barlow, J. H.; Lowe, N.; Edwards, Y. H.; Butterworth, P. H. W.
: Human carbonic anhydrase I cDNA. Nucleic Acids Res. 15: 2386 only,
1987.
3. Blake, N. M.: Genetic variants of carbonic anhydrase in the Asian-Pacific
area. Ann. Hum. Biol. 5: 557-568, 1978.
4. Blake, N. M.; Kirk, R. L.: Widespread distribution of variant
forms of carbonic anhydrase in Australian aboriginals. Med. J. Aust. 1:
183-185, 1978.
5. Butterworth, P.; Barlow, J.; Konialis, C.; Povey, S.; Edwards,
Y. H.: The assignment of human erythrocyte carbonic anhydrase CA1
to chromosome 8. (Abstract) Cytogenet. Cell Genet. 40: 597 only,
1985.
6. Carter, N. D.: Carbonic anhydrase isozymes in Cavia porcellus,
Cavia aperea and their hybrids. Comp. Biochem. Physiol. B 43: 743-747,
1972.
7. Carter, N. D.: Carbonic anhydrase II polymorphism in Africa. Hum.
Hered. 22: 539-541, 1972.
8. Carter, N. D.; Tashian, R. E.; Huntsman, R. G.; Sacker, L.: Characterization
of two new variants of red cell carbonic anhydrase in the British
population: Ca Ie Portsmouth and Ca Ie Hull. Am. J. Hum. Genet. 24:
330-338, 1972.
9. Davis, M. B.; West, L. F.; Barlow, J. H.; Butterworth, P. H. W.;
Lloyd, J. C.; Edwards, Y. H.: Regional localization of carbonic anhydrase
genes CA1 and CA3 on human chromosome 8. Somat. Cell Molec. Genet. 13:
173-178, 1987.
10. Davis, M. B.; West, L. F.; Butterworth, P.; Edwards, Y. H.: The
assignment of human carbonic anhydrases CA1 and CA3 to chromosome
8q13-22. (Abstract) 7th Int. Cong. Hum. Genet., Berlin 616 only,
1986.
11. DeSimone, J.; Linde, M.; Tashian, R. E.: Evidence for linkage
of carbonic anhydrase isozyme genes in the pig-tailed macaque, Macaca
nemestrina. Nature N.B. 242: 55-56, 1973.
12. Dodgson, S. J.; Tashian, R. E.; Gross, G.; Carter, N. D.: The
Carbonic Anhydrases: Cellular Physiology and Molecular Genetics. New
York: Plenum , 1991.
13. Edwards, Y. H.; Barlow, J. H.; Konialis, C. P.; Povey, S.; Butterworth,
P. H. W.: Assignment of the gene determining human carbonic anhydrase,
CAI, to chromosome 8. Ann. Hum. Genet. 50: 123-129, 1986.
14. Eicher, E. M.; Stern, R. H.; Womack, J. E.; Davisson, M. T.; Roderick,
T. H.; Reynolds, S. C.: Evolution of mammalian carbonic anhydrase
loci by tandem duplication: close linkage of Car-1 and Car-2 to the
centromere region of chromosome 3 of the mouse. Biochem. Genet. 14:
651-660, 1976.
15. Gao, B.-B.; Clermont, A.; Rook, S.; Fonda, S. J.; Srinivasan,
V. J.; Wojtkowski, M.; Fujimoto, J. G.; Avery, R. L.; Arrigg, P. G.;
Bursell, S.-E.; Aiello, L. P.; Feener, E. P.: Extracellular carbonic
anhydrase mediates hemorrhagic retinal and cerebral vascular permeability
through prekallikrein activation. Nature Med. 13: 181-188, 2007.
16. Goriki, K.; Tashian, R. E.; Stroup, S. K.; Yu, Y.-S. L.; Henriksson,
D. M.: Chemical characterization of a new Japanese variant of carbonic
anhydrase I, Ca 2 (Nagasaki 1) (76 arg-to-gln). Biochem. Genet. 17:
449-460, 1979.
17. Hewett-Emmett, D.; Tashian, R. E.: Functional diversity, conservation
and convergence in the evolution of the alpha-, beta-, and gamma-carbonic
anhydrase gene families. Molec. Phylogenet. Evol. 5: 50-77, 1996.
18. Hopkinson, D. A.; Coppock, J. S.; Muhlemann, M. F.; Edwards, Y.
H.: The detection and differentiation of the products of the human
carbonic anhydrase loci, Ca I and Ca II, using fluorogenic substrates. Ann.
Hum. Genet. 38: 155-162, 1974.
19. Kageoka, T.; Hewett-Emmett, D.; Stroup, S. K.; Yu, Y.-S. L.; Tashian,
R. E.: Amino acid substitution and chemical characterization of a
Japanese variant of carbonic anhydrase I: CA I Hiroshima-1 (86 asp-to-gly). Biochem.
Genet. 19: 535-549, 1981.
20. Kendall, A. G.; Tashian, R. E.: Erythrocyte carbonic anhydrase
I: inherited deficiency in humans. Science 197: 471-472, 1977.
21. Lindskog, S.; Henderson, L. E.; Kannan, K. K.; Liljas, A.; Nyman,
P. O.; Strandberg, B.: Carbonic anhydrase.In: Boyer, P. D.: The
Enzymes. New York: Academic Press (pub.) 5: 1971. Pp. 587-665.
22. Lowe, N.; Edwards, Y. H.; Edwards, M.; Butterworth, P. H. W.:
Physical mapping of the human carbonic anhydrase gene cluster on chromosome
8. Genomics 10: 882-888, 1991.
23. Marriq, C.; Gulian, J. M.; Laurent, G.: Cleavage by cyanogen
bromide of carbonic anhydrase from human erythrocyte B. Biochim.
Biophys. Acta 221: 662-664, 1970.
24. Moore, M. J.; Deutsch, H. F.; Ellis, F. R.: Human carbonic anhydrase.
IX. Inheritance of variant erythrocyte forms. Am. J. Hum. Genet. 25:
29-35, 1973.
25. Omoto, K.: Carbonic anhydrase-I polymorphism in a Philippine
aboriginal population. Am. J. Hum. Genet. 31: 747-750, 1979.
26. Omoto, K.; Ueda, S.; Goriki, K.; Takahashi, N.; Misawa, S.; Pagaran,
I. G.: Population genetic studies of the Philippine Negritos. III.
Identification of the carbonic anhydrase-1 variant with CA(1) Guam. Am.
J. Hum. Genet. 33: 105-111, 1981.
27. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
28. Shapira, E.; Ben-Yoseph, Y.; Eyal, G.; Russell, A.: Enzymatically
inactive red cell carbonic anhydrase B in a family with renal tubular
acidosis. J. Clin. Invest. 53: 59-63, 1974.
29. Tashian, R. E.: The esterases and carbonic anhydrases of human
erythrocytes.In: Yunis, J. J.: Biochemical Methods in Red Cell Genetics.
New York: Academic Press (pub.) 1969. Pp. 307-336.
30. Tashian, R. E.: Genetics of the mammalian carbonic anhydrases. Adv.
Genet. 30: 321-356, 1992.
31. Tashian, R. E.; Carter, N. D.: Biochemical genetics of carbonic
anhydrase. Adv. Hum. Genet. 7: 1-56, 1976.
32. Tashian, R. E.; Goodman, M.; Headings, V. E.; Desimone, J.; Ward,
R. H.: Genetic variation and evolution in the red cell carbonic anhydrase
isozymes of Macaque monkeys. Biochem. Genet. 5: 183-200, 1971.
33. Tashian, R. E.; Plato, C. C.; Shows, T. B.: Inherited variant
of erythrocyte carbonic anhydrase in Micronesians from Guam and Saipan. Science 140:
53-54, 1963.
34. Venta, P. J.; Montgomery, J. C.; Tashian, R. E.: Molecular genetics
of carbonic anhydrase isozymes. Isozymes: Curr. Top. Biol. Med. Res. 14:
59-72, 1987.
35. Wagner, L. E.; Venta, P. J.; Tashian, R. E.: A human carbonic
anhydrase I deficiency appears to be caused by a destabilizing amino
acid substitution (246arg-to-his). Isozyme Bull. 24: 35 only, 1991.
*FIELD* CN
Marla J. F. O'Neill - updated: 4/12/2007
*FIELD* CD
Victor A. McKusick: 6/16/1986
*FIELD* ED
carol: 12/01/2009
carol: 2/13/2009
carol: 11/20/2008
carol: 10/11/2007
wwang: 4/18/2007
terry: 4/12/2007
carol: 3/2/2000
carol: 2/29/2000
terry: 11/18/1998
carol: 11/9/1998
carol: 9/28/1998
alopez: 6/23/1997
mark: 5/18/1995
carol: 5/11/1994
mimadm: 4/18/1994
carol: 10/26/1993
carol: 10/21/1993
supermim: 3/20/1992
*RECORD*
*FIELD* NO
114800
*FIELD* TI
*114800 CARBONIC ANHYDRASE I; CA1
;;CA I;;
CARBONIC ANHYDRASE A;;
CARBONIC ANHYDRASE B, FORMERLY
read more*FIELD* TX
DESCRIPTION
Carbonic anhydrases (CAs; carbonate dehydratase; carbonate hydrolyase;
EC 4.2.1.1) form a large family of genes encoding zinc metalloenzymes of
great physiologic importance. As catalysts of the reversible hydration
of carbon dioxide, these enzymes participate in a variety of biologic
processes, including respiration, calcification, acid-base balance, bone
resorption, and the formation of aqueous humor, cerebrospinal fluid,
saliva, and gastric acid (Dodgson et al., 1991). CAs are encoded by
members of 3 independent CA gene families, i.e., alpha-CA, beta-CA, and
gamma-CA (Hewett-Emmett and Tashian, 1996). Genes in the alpha-carbonic
anhydrase family encode either active carbonic anhydrase isozymes or
'acatalytic' (i.e., devoid of CO2 hydration activity) carbonic
anhydrase-related proteins. Alpha-carbonic anhydrases show extensive
diversity in tissue distribution and in their putative or established
biologic functions. Some of the alpha-CAs are expressed in almost all
tissues (e.g., CA II, 611492), whereas some show a more restricted
expression (e.g., CA VI (114780) in salivary glands). In cells, they may
reside in cytoplasm, in mitochondria, or in secretory granules, or
associate with membranes.
CLONING
Erythrocyte carbonic anhydrase has 2 isoenzymes with different amino
acid sequences and specific activities. B and C were the original
designations for these 2 major forms which later were called CA I (or A)
and CA II (or B; 611492), respectively. Tashian (1969) reviewed the
biochemical genetics of the 2 forms of red cell carbonic anhydrase,
which are under the control of separate autosomal loci.
Andersson et al. (1972) stated that CA I is the major form of the enzyme
in human red cells. They found that the protein consists of 260 amino
acids. Barlow et al. (1987) cloned human carbonic anhydrase I cDNA.
MAPPING
CA I and CA II are linked in the rodent genus Cavia (Carter, 1972),
closely linked in an Old World monkey, Macaca nemestrina (DeSimone et
al., 1973), and tightly linked in the mouse (Eicher et al., 1976).
Using a cDNA clone of the CA1 gene in the study of human-rodent hybrids,
Butterworth et al. (1985) and Edwards et al. (1986) assigned the CA1
gene to chromosome 8, which carries a cluster of CA genes.
By somatic cell genetic techniques and in situ hybridization, Davis et
al. (1986, 1987) mapped the CA1 and CA3 (114750) genes to 8q13-q22. By
pulsed field gel electrophoresis, Lowe et al. (1991) determined that the
order of the genes is CA2, CA3, CA1. CA2 and CA3 are separated by 20 kb
and are transcribed in the same direction, away from CA1. CA1 is
separated from CA3 by over 80 kb and is transcribed in the opposite
direction to CA2 and CA3. Lowe et al. (1991) concluded that the
arrangement of the genes is consistent with proposals that the
duplication event that gave rise to CA1 predated the duplication that
gave rise to CA2 and CA3. The order of the 3 genes differs from that
suggested for the mouse based on recombination frequency.
GENE STRUCTURE
Tashian (1992) reviewed the gene organization and evolutionary
relationships of the carbonic anhydrases. See also Hewett-Emmett and
Tashian (1996).
GENE FUNCTION
Gao et al. (2007) performed proteomic analysis on vitreous fluid samples
and found that the CA1 concentration from patients with diabetic
retinopathy (see 603933) was 15.3 and 8.2 times higher than that from
nondiabetic patients and diabetics with no diabetic retinopathy,
respectively. Intravitreous injection of CA1 in rats increased retinal
vessel leakage and caused intraretinal edema. CA1-induced alkalinization
of vitreous increased kallilkrein (see 147910) and its generation of
factor XIIa (see 610619); complement-1 inhibitor (C1NH; 606860),
neutralizing antibody to prekallikrein (KLKB1; 229000), and bradykinin
receptor (see 600337) antagonism decreased CA1-induced retinal edema.
Subdural infusion of CA1 in rats induced cerebral vascular permeability.
Gao et al. (2007) concluded that extracellular CA1 mediates hemorrhagic
retinal and cerebral vascular permeability through prekallikrein
activation.
MOLECULAR GENETICS
By starch gel electrophoresis, Tashian et al. (1963) detected a
genetically determined variant of erythrocyte carbonic anhydrase.
The amino acid change in several CA I mutants was determined by Carter
et al. (1972). Moore et al. (1973) demonstrated the autosomal dominant
inheritance of CA I and CA II variants.
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
- Carbonic Anhydrase I Deficiency
In a family on the Greek island of Icaria, Kendall and Tashian (1977)
found virtually complete absence of erythrocyte carbonic anhydrase I in
3 persons and reduced levels thought to represent the heterozygous state
in 2 others. No obvious hematologic or renal consequences were found in
any of them. Venta et al. (1987) reported preliminary observations
involving restriction analysis of DNA from white cells of CA I-deficient
members of this family, which showed that the deficiency is not caused
by a major deletion in at least 1 part of the gene. Wagner et al. (1991)
and Tashian (1992) reported that CA I-deficient members of this family
have a missense mutation in exon 7 of their CA1 gene (arg246-to-his;
114800.0002). Replacement of the highly conserved arg246 is the probable
cause of the CA I deficiency.
*FIELD* AV
.0001
CARBONIC ANHYDRASE I, GUAM
CA1, GLY253ARG
Carbonic anhydrase Guam has substitution of arginine for glycine
(Tashian and Carter, 1976). Omoto et al. (1981) established identity of
a CA-1 variant in Philippine Negritos, CA-1(3N), to CA-1(Guam); both
have substitution of arginine for glycine at amino acid 253.
.0002
CARBONIC ANHYDRASE I DEFICIENCY
CA1, ARG246HIS
In healthy members with almost complete absence of red cell CA I in the
Icaria family reported by Kendall and Tashian (1977), Wagner et al.
(1991) found an arg246-to-his missense mutation in the CA1 gene.
*FIELD* SA
Blake (1978); Blake and Kirk (1978); Carter (1972); Goriki et al.
(1979); Hopkinson et al. (1974); Kageoka et al. (1981); Lindskog et
al. (1971); Marriq et al. (1970); Omoto (1979); Shapira et al. (1974);
Tashian et al. (1971)
*FIELD* RF
1. Andersson, B.; Nyman, P. O.; Strid, L.: Amino acid sequence of
human erythrocyte carbonic anhydrase B. Biochem. Biophys. Res. Commun. 48:
670-677, 1972.
2. Barlow, J. H.; Lowe, N.; Edwards, Y. H.; Butterworth, P. H. W.
: Human carbonic anhydrase I cDNA. Nucleic Acids Res. 15: 2386 only,
1987.
3. Blake, N. M.: Genetic variants of carbonic anhydrase in the Asian-Pacific
area. Ann. Hum. Biol. 5: 557-568, 1978.
4. Blake, N. M.; Kirk, R. L.: Widespread distribution of variant
forms of carbonic anhydrase in Australian aboriginals. Med. J. Aust. 1:
183-185, 1978.
5. Butterworth, P.; Barlow, J.; Konialis, C.; Povey, S.; Edwards,
Y. H.: The assignment of human erythrocyte carbonic anhydrase CA1
to chromosome 8. (Abstract) Cytogenet. Cell Genet. 40: 597 only,
1985.
6. Carter, N. D.: Carbonic anhydrase isozymes in Cavia porcellus,
Cavia aperea and their hybrids. Comp. Biochem. Physiol. B 43: 743-747,
1972.
7. Carter, N. D.: Carbonic anhydrase II polymorphism in Africa. Hum.
Hered. 22: 539-541, 1972.
8. Carter, N. D.; Tashian, R. E.; Huntsman, R. G.; Sacker, L.: Characterization
of two new variants of red cell carbonic anhydrase in the British
population: Ca Ie Portsmouth and Ca Ie Hull. Am. J. Hum. Genet. 24:
330-338, 1972.
9. Davis, M. B.; West, L. F.; Barlow, J. H.; Butterworth, P. H. W.;
Lloyd, J. C.; Edwards, Y. H.: Regional localization of carbonic anhydrase
genes CA1 and CA3 on human chromosome 8. Somat. Cell Molec. Genet. 13:
173-178, 1987.
10. Davis, M. B.; West, L. F.; Butterworth, P.; Edwards, Y. H.: The
assignment of human carbonic anhydrases CA1 and CA3 to chromosome
8q13-22. (Abstract) 7th Int. Cong. Hum. Genet., Berlin 616 only,
1986.
11. DeSimone, J.; Linde, M.; Tashian, R. E.: Evidence for linkage
of carbonic anhydrase isozyme genes in the pig-tailed macaque, Macaca
nemestrina. Nature N.B. 242: 55-56, 1973.
12. Dodgson, S. J.; Tashian, R. E.; Gross, G.; Carter, N. D.: The
Carbonic Anhydrases: Cellular Physiology and Molecular Genetics. New
York: Plenum , 1991.
13. Edwards, Y. H.; Barlow, J. H.; Konialis, C. P.; Povey, S.; Butterworth,
P. H. W.: Assignment of the gene determining human carbonic anhydrase,
CAI, to chromosome 8. Ann. Hum. Genet. 50: 123-129, 1986.
14. Eicher, E. M.; Stern, R. H.; Womack, J. E.; Davisson, M. T.; Roderick,
T. H.; Reynolds, S. C.: Evolution of mammalian carbonic anhydrase
loci by tandem duplication: close linkage of Car-1 and Car-2 to the
centromere region of chromosome 3 of the mouse. Biochem. Genet. 14:
651-660, 1976.
15. Gao, B.-B.; Clermont, A.; Rook, S.; Fonda, S. J.; Srinivasan,
V. J.; Wojtkowski, M.; Fujimoto, J. G.; Avery, R. L.; Arrigg, P. G.;
Bursell, S.-E.; Aiello, L. P.; Feener, E. P.: Extracellular carbonic
anhydrase mediates hemorrhagic retinal and cerebral vascular permeability
through prekallikrein activation. Nature Med. 13: 181-188, 2007.
16. Goriki, K.; Tashian, R. E.; Stroup, S. K.; Yu, Y.-S. L.; Henriksson,
D. M.: Chemical characterization of a new Japanese variant of carbonic
anhydrase I, Ca 2 (Nagasaki 1) (76 arg-to-gln). Biochem. Genet. 17:
449-460, 1979.
17. Hewett-Emmett, D.; Tashian, R. E.: Functional diversity, conservation
and convergence in the evolution of the alpha-, beta-, and gamma-carbonic
anhydrase gene families. Molec. Phylogenet. Evol. 5: 50-77, 1996.
18. Hopkinson, D. A.; Coppock, J. S.; Muhlemann, M. F.; Edwards, Y.
H.: The detection and differentiation of the products of the human
carbonic anhydrase loci, Ca I and Ca II, using fluorogenic substrates. Ann.
Hum. Genet. 38: 155-162, 1974.
19. Kageoka, T.; Hewett-Emmett, D.; Stroup, S. K.; Yu, Y.-S. L.; Tashian,
R. E.: Amino acid substitution and chemical characterization of a
Japanese variant of carbonic anhydrase I: CA I Hiroshima-1 (86 asp-to-gly). Biochem.
Genet. 19: 535-549, 1981.
20. Kendall, A. G.; Tashian, R. E.: Erythrocyte carbonic anhydrase
I: inherited deficiency in humans. Science 197: 471-472, 1977.
21. Lindskog, S.; Henderson, L. E.; Kannan, K. K.; Liljas, A.; Nyman,
P. O.; Strandberg, B.: Carbonic anhydrase.In: Boyer, P. D.: The
Enzymes. New York: Academic Press (pub.) 5: 1971. Pp. 587-665.
22. Lowe, N.; Edwards, Y. H.; Edwards, M.; Butterworth, P. H. W.:
Physical mapping of the human carbonic anhydrase gene cluster on chromosome
8. Genomics 10: 882-888, 1991.
23. Marriq, C.; Gulian, J. M.; Laurent, G.: Cleavage by cyanogen
bromide of carbonic anhydrase from human erythrocyte B. Biochim.
Biophys. Acta 221: 662-664, 1970.
24. Moore, M. J.; Deutsch, H. F.; Ellis, F. R.: Human carbonic anhydrase.
IX. Inheritance of variant erythrocyte forms. Am. J. Hum. Genet. 25:
29-35, 1973.
25. Omoto, K.: Carbonic anhydrase-I polymorphism in a Philippine
aboriginal population. Am. J. Hum. Genet. 31: 747-750, 1979.
26. Omoto, K.; Ueda, S.; Goriki, K.; Takahashi, N.; Misawa, S.; Pagaran,
I. G.: Population genetic studies of the Philippine Negritos. III.
Identification of the carbonic anhydrase-1 variant with CA(1) Guam. Am.
J. Hum. Genet. 33: 105-111, 1981.
27. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
28. Shapira, E.; Ben-Yoseph, Y.; Eyal, G.; Russell, A.: Enzymatically
inactive red cell carbonic anhydrase B in a family with renal tubular
acidosis. J. Clin. Invest. 53: 59-63, 1974.
29. Tashian, R. E.: The esterases and carbonic anhydrases of human
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*FIELD* CN
Marla J. F. O'Neill - updated: 4/12/2007
*FIELD* CD
Victor A. McKusick: 6/16/1986
*FIELD* ED
carol: 12/01/2009
carol: 2/13/2009
carol: 11/20/2008
carol: 10/11/2007
wwang: 4/18/2007
terry: 4/12/2007
carol: 3/2/2000
carol: 2/29/2000
terry: 11/18/1998
carol: 11/9/1998
carol: 9/28/1998
alopez: 6/23/1997
mark: 5/18/1995
carol: 5/11/1994
mimadm: 4/18/1994
carol: 10/26/1993
carol: 10/21/1993
supermim: 3/20/1992