CAH7_HUMAN
ID CAH7_HUMAN Reviewed; 264 AA.
AC P43166; Q541F0; Q86YU0;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Carbonic anhydrase 7;
DE EC=4.2.1.1;
DE AltName: Full=Carbonate dehydratase VII;
DE AltName: Full=Carbonic anhydrase VII;
DE Short=CA-VII;
GN Name=CA7;
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 [GENOMIC DNA] (ISOFORM 1).
RX PubMed=1783392; DOI=10.1016/0888-7543(91)90006-z;
RA Montgomery J.C., Venta P.J., Eddy R.L., Fukushima Y.S., Shows T.B.,
RA Tashian R.E.;
RT "Characterization of the human gene for a newly discovered carbonic
RT anhydrase, CA VII, and its localization to chromosome 16.";
RL Genomics 11:835-848(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RA Chen Y., Huang C.-H.;
RT "Molecular identification of carbonic anhydrases (CA) and CA-related (CAR)
RT genes.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10493829; DOI=10.1006/geno.1999.5927;
RA Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J.,
RA Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X.,
RA Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C.,
RA Adams M.D.;
RT "Genome duplications and other features in 12 Mb of DNA sequence from human
RT chromosome 16p and 16q.";
RL Genomics 60:295-308(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon, Kidney, and Stomach;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP ACTIVITY REGULATION.
RX PubMed=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 [7]
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 [8]
RP ACTIVITY REGULATION.
RX PubMed=17705204; DOI=10.1002/anie.200701189;
RA Koehler K., Hillebrecht A., Schulze Wischeler J., Innocenti A., Heine A.,
RA Supuran C.T., Klebe G.;
RT "Saccharin inhibits carbonic anhydrases: possible explanation for its
RT unpleasant metallic aftertaste.";
RL Angew. Chem. Int. Ed. Engl. 46:7697-7699(2007).
RN [9]
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 [10]
RP ACTIVITY REGULATION.
RX PubMed=17314045; DOI=10.1016/j.bmcl.2007.01.113;
RA Temperini C., Innocenti A., Guerri A., Scozzafava A., Rusconi S.,
RA Supuran C.T.;
RT "Phosph(on)ate as a zinc-binding group in metalloenzyme inhibitors: X-ray
RT crystal structure of the antiviral drug foscarnet complexed to human
RT carbonic anhydrase I.";
RL Bioorg. Med. Chem. Lett. 17:2210-2215(2007).
RN [11]
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 [12]
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 [13]
RP X-RAY CRYSTALLOGRAPHY (2.32 ANGSTROMS) OF 5-262 IN COMPLEX WITH ZINC IONS.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human carbonic anhydrase VII [isoform 1], CA7.";
RL Submitted (JUN-2010) to the PDB data bank.
CC -!- FUNCTION: Reversible hydration of carbon dioxide.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hydrogencarbonate = CO2 + H2O; Xref=Rhea:RHEA:10748,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:17544; EC=4.2.1.1;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|Ref.13};
CC -!- ACTIVITY REGULATION: Activated by histamine, L-adrenaline, L- and D-
CC histidine, and L- and D-phenylalanine. Inhibited by coumarins,
CC sulfonamide derivatives such as acetazolamide (AZA), by saccharin and
CC Foscarnet (phosphonoformate trisodium salt).
CC {ECO:0000269|PubMed:16686544, ECO:0000269|PubMed:16807956,
CC ECO:0000269|PubMed:17127057, ECO:0000269|PubMed:17314045,
CC ECO:0000269|PubMed:17705204, ECO:0000269|PubMed:19186056,
CC ECO:0000269|PubMed:19206230}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P43166-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P43166-2; Sequence=VSP_044254;
CC -!- SIMILARITY: Belongs to the alpha-carbonic anhydrase family.
CC {ECO:0000305}.
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DR EMBL; M76423; AAA51923.1; -; Genomic_DNA.
DR EMBL; M76420; AAA51923.1; JOINED; Genomic_DNA.
DR EMBL; M76421; AAA51923.1; JOINED; Genomic_DNA.
DR EMBL; M76422; AAA51923.1; JOINED; Genomic_DNA.
DR EMBL; AY075019; AAL78167.1; -; mRNA.
DR EMBL; AY075020; AAL78168.1; -; mRNA.
DR EMBL; AC004638; AAC23785.1; -; Genomic_DNA.
DR EMBL; AC044802; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471092; EAW83047.1; -; Genomic_DNA.
DR EMBL; BC033865; AAH33865.1; -; mRNA.
DR CCDS; CCDS10821.1; -. [P43166-1]
DR CCDS; CCDS42173.1; -. [P43166-2]
DR PIR; A55272; CRHU7.
DR RefSeq; NP_001014435.1; NM_001014435.1. [P43166-2]
DR RefSeq; NP_005173.1; NM_005182.2. [P43166-1]
DR RefSeq; XP_005256193.1; XM_005256136.3.
DR RefSeq; XP_011521614.1; XM_011523312.1. [P43166-2]
DR PDB; 3MDZ; X-ray; 2.32 A; A=5-262.
DR PDB; 3ML5; X-ray; 2.05 A; A=1-264.
DR PDB; 6G4T; X-ray; 1.91 A; A=1-264.
DR PDB; 6H36; X-ray; 1.85 A; A=1-264.
DR PDB; 6H37; X-ray; 1.90 A; A=1-264.
DR PDB; 6H38; X-ray; 1.70 A; A=1-264.
DR PDB; 6SDT; X-ray; 1.94 A; A=1-264.
DR PDB; 6ZR9; X-ray; 2.05 A; A=1-264.
DR PDB; 7NC4; X-ray; 1.60 A; A=1-264.
DR PDB; 7P1A; X-ray; 1.58 A; A=1-264.
DR PDBsum; 3MDZ; -.
DR PDBsum; 3ML5; -.
DR PDBsum; 6G4T; -.
DR PDBsum; 6H36; -.
DR PDBsum; 6H37; -.
DR PDBsum; 6H38; -.
DR PDBsum; 6SDT; -.
DR PDBsum; 6ZR9; -.
DR PDBsum; 7NC4; -.
DR PDBsum; 7P1A; -.
DR AlphaFoldDB; P43166; -.
DR SMR; P43166; -.
DR STRING; 9606.ENSP00000345659; -.
DR BindingDB; P43166; -.
DR ChEMBL; CHEMBL2326; -.
DR DrugBank; DB00819; Acetazolamide.
DR DrugBank; DB00562; Benzthiazide.
DR DrugBank; DB00606; Cyclothiazide.
DR DrugBank; DB01144; Diclofenamide.
DR DrugBank; DB08846; Ellagic acid.
DR DrugBank; DB00311; Ethoxzolamide.
DR DrugBank; DB00774; Hydroflumethiazide.
DR DrugBank; DB00703; Methazolamide.
DR DrugBank; DB00909; Zonisamide.
DR DrugCentral; P43166; -.
DR GuidetoPHARMACOLOGY; 2749; -.
DR iPTMnet; P43166; -.
DR PhosphoSitePlus; P43166; -.
DR BioMuta; CA7; -.
DR DMDM; 1168744; -.
DR MassIVE; P43166; -.
DR PaxDb; P43166; -.
DR PeptideAtlas; P43166; -.
DR PRIDE; P43166; -.
DR ProteomicsDB; 55595; -. [P43166-1]
DR ProteomicsDB; 70472; -.
DR Antibodypedia; 29327; 135 antibodies from 27 providers.
DR DNASU; 766; -.
DR Ensembl; ENST00000338437.7; ENSP00000345659.2; ENSG00000168748.14. [P43166-1]
DR Ensembl; ENST00000394069.3; ENSP00000377632.3; ENSG00000168748.14. [P43166-2]
DR GeneID; 766; -.
DR KEGG; hsa:766; -.
DR MANE-Select; ENST00000338437.7; ENSP00000345659.2; NM_005182.3; NP_005173.1.
DR UCSC; uc002eqi.4; human. [P43166-1]
DR CTD; 766; -.
DR DisGeNET; 766; -.
DR GeneCards; CA7; -.
DR HGNC; HGNC:1381; CA7.
DR HPA; ENSG00000168748; Tissue enriched (intestine).
DR MIM; 114770; gene.
DR neXtProt; NX_P43166; -.
DR OpenTargets; ENSG00000168748; -.
DR PharmGKB; PA25996; -.
DR VEuPathDB; HostDB:ENSG00000168748; -.
DR eggNOG; KOG0382; Eukaryota.
DR GeneTree; ENSGT00940000159757; -.
DR HOGENOM; CLU_039326_2_1_1; -.
DR InParanoid; P43166; -.
DR OMA; RMRMENN; -.
DR OrthoDB; 1377476at2759; -.
DR PhylomeDB; P43166; -.
DR TreeFam; TF316425; -.
DR BRENDA; 4.2.1.1; 2681.
DR PathwayCommons; P43166; -.
DR Reactome; R-HSA-1475029; Reversible hydration of carbon dioxide.
DR SABIO-RK; P43166; -.
DR BioGRID-ORCS; 766; 20 hits in 1069 CRISPR screens.
DR ChiTaRS; CA7; human.
DR GeneWiki; Carbonic_anhydrase_7; -.
DR GenomeRNAi; 766; -.
DR Pharos; P43166; Tclin.
DR PRO; PR:P43166; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P43166; protein.
DR Bgee; ENSG00000168748; Expressed in mucosa of transverse colon and 72 other tissues.
DR ExpressionAtlas; P43166; baseline and differential.
DR Genevisible; P43166; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0004089; F:carbonate dehydratase activity; TAS:ProtInc.
DR GO; GO:0016836; F:hydro-lyase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0070050; P:neuron cellular homeostasis; IEA:Ensembl.
DR GO; GO:0006730; P:one-carbon metabolic process; IBA:GO_Central.
DR GO; GO:0032849; P:positive regulation of cellular pH reduction; IEA:Ensembl.
DR GO; GO:0032230; P:positive regulation of synaptic transmission, GABAergic; IEA:Ensembl.
DR GO; GO:2001225; P:regulation of chloride transport; IEA:Ensembl.
DR GO; GO:0051453; P:regulation of intracellular pH; IBA:GO_Central.
DR CDD; cd03149; alpha_CA_VII; 1.
DR Gene3D; 3.10.200.10; -; 1.
DR InterPro; IPR041890; Alpha_CA_VII.
DR InterPro; IPR001148; CA_dom.
DR InterPro; IPR036398; CA_dom_sf.
DR InterPro; IPR023561; Carbonic_anhydrase_a-class.
DR InterPro; IPR018338; Carbonic_anhydrase_a-class_CS.
DR PANTHER; PTHR18952; PTHR18952; 1.
DR Pfam; PF00194; Carb_anhydrase; 1.
DR SMART; SM01057; Carb_anhydrase; 1.
DR SUPFAM; SSF51069; SSF51069; 1.
DR PROSITE; PS00162; ALPHA_CA_1; 1.
DR PROSITE; PS51144; ALPHA_CA_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Lyase; Metal-binding;
KW Reference proteome; Zinc.
FT CHAIN 1..264
FT /note="Carbonic anhydrase 7"
FT /id="PRO_0000077431"
FT DOMAIN 5..262
FT /note="Alpha-carbonic anhydrase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01134"
FT ACT_SITE 66
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:P00918"
FT BINDING 96
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|Ref.13"
FT BINDING 98
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|Ref.13"
FT BINDING 121
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|Ref.13"
FT BINDING 201..202
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00918"
FT VAR_SEQ 1..56
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_044254"
FT TURN 11..13
FT /evidence="ECO:0007829|PDB:7P1A"
FT HELIX 15..20
FT /evidence="ECO:0007829|PDB:7P1A"
FT HELIX 23..26
FT /evidence="ECO:0007829|PDB:7P1A"
FT STRAND 27..29
FT /evidence="ECO:0007829|PDB:7P1A"
FT HELIX 37..39
FT /evidence="ECO:0007829|PDB:7P1A"
FT STRAND 40..42
FT /evidence="ECO:0007829|PDB:7P1A"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:7P1A"
FT STRAND 58..63
FT /evidence="ECO:0007829|PDB:7P1A"
FT STRAND 68..72
FT /evidence="ECO:0007829|PDB:7P1A"
FT STRAND 75..83
FT /evidence="ECO:0007829|PDB:7P1A"
FT STRAND 90..99
FT /evidence="ECO:0007829|PDB:7P1A"
FT STRAND 108..111
FT /evidence="ECO:0007829|PDB:7P1A"
FT STRAND 117..125
FT /evidence="ECO:0007829|PDB:7P1A"
FT TURN 127..129
FT /evidence="ECO:0007829|PDB:7P1A"
FT HELIX 133..136
FT /evidence="ECO:0007829|PDB:7P1A"
FT STRAND 142..154
FT /evidence="ECO:0007829|PDB:7P1A"
FT HELIX 159..165
FT /evidence="ECO:0007829|PDB:7P1A"
FT HELIX 167..169
FT /evidence="ECO:0007829|PDB:7P1A"
FT STRAND 175..177
FT /evidence="ECO:0007829|PDB:7P1A"
FT HELIX 183..186
FT /evidence="ECO:0007829|PDB:7P1A"
FT STRAND 193..198
FT /evidence="ECO:0007829|PDB:7P1A"
FT STRAND 209..216
FT /evidence="ECO:0007829|PDB:7P1A"
FT STRAND 218..220
FT /evidence="ECO:0007829|PDB:7P1A"
FT HELIX 222..228
FT /evidence="ECO:0007829|PDB:7P1A"
FT STRAND 232..234
FT /evidence="ECO:0007829|PDB:7P1A"
FT STRAND 236..238
FT /evidence="ECO:0007829|PDB:7P1A"
FT STRAND 259..262
FT /evidence="ECO:0007829|PDB:7P1A"
SQ SEQUENCE 264 AA; 29658 MW; 7AD559FC6E07EF96 CRC64;
MTGHHGWGYG QDDGPSHWHK LYPIAQGDRQ SPINIISSQA VYSPSLQPLE LSYEACMSLS
ITNNGHSVQV DFNDSDDRTV VTGGPLEGPY RLKQFHFHWG KKHDVGSEHT VDGKSFPSEL
HLVHWNAKKY STFGEAASAP DGLAVVGVFL ETGDEHPSMN RLTDALYMVR FKGTKAQFSC
FNPKCLLPAS RHYWTYPGSL TTPPLSESVT WIVLREPICI SERQMGKFRS LLFTSEDDER
IHMVNNFRPP QPLKGRVVKA SFRA
