CAN_CANAL
ID CAN_CANAL Reviewed; 281 AA.
AC Q5AJ71; A0A1D8PJ71;
DT 11-DEC-2013, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Carbonic anhydrase;
DE EC=4.2.1.1;
DE AltName: Full=Carbonate dehydratase;
DE AltName: Full=Non-classical export protein 103;
GN Name=NCE103; OrderedLocusNames=CAALFM_C301300CA;
GN ORFNames=CaO19.1721, CaO19.9289;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [4]
RP FUNCTION.
RX PubMed=16303561; DOI=10.1016/j.cub.2005.10.040;
RA Klengel T., Liang W.J., Chaloupka J., Ruoff C., Schroppel K., Naglik J.R.,
RA Eckert S.E., Mogensen E.G., Haynes K., Tuite M.F., Levin L.R., Buck J.,
RA Muhlschlegel F.A.;
RT "Fungal adenylyl cyclase integrates CO2 sensing with cAMP signaling and
RT virulence.";
RL Curr. Biol. 15:2021-2026(2005).
RN [5]
RP INDUCTION.
RX PubMed=16151249; DOI=10.1128/ec.4.9.1562-1573.2005;
RA Murillo L.A., Newport G., Lan C.Y., Habelitz S., Dungan J., Agabian N.M.;
RT "Genome-wide transcription profiling of the early phase of biofilm
RT formation by Candida albicans.";
RL Eukaryot. Cell 4:1562-1573(2005).
RN [6]
RP CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=18723348; DOI=10.1016/j.bmcl.2008.07.122;
RA Innocenti A., Muhlschlegel F.A., Hall R.A., Steegborn C., Scozzafava A.,
RA Supuran C.T.;
RT "Carbonic anhydrase inhibitors: inhibition of the beta-class enzymes from
RT the fungal pathogens Candida albicans and Cryptococcus neoformans with
RT simple anions.";
RL Bioorg. Med. Chem. Lett. 18:5066-5070(2008).
RN [7]
RP INDUCTION.
RX PubMed=18653474; DOI=10.1091/mbc.e07-09-0946;
RA Ramsdale M., Selway L., Stead D., Walker J., Yin Z., Nicholls S.M.,
RA Crowe J., Sheils E.M., Brown A.J.;
RT "MNL1 regulates weak acid-induced stress responses of the fungal pathogen
RT Candida albicans.";
RL Mol. Biol. Cell 19:4393-4403(2008).
RN [8]
RP CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=19297172; DOI=10.1016/j.bmc.2009.02.058;
RA Innocenti A., Hall R.A., Schlicker C., Muhlschlegel F.A., Supuran C.T.;
RT "Carbonic anhydrase inhibitors. Inhibition of the beta-class enzymes from
RT the fungal pathogens Candida albicans and Cryptococcus neoformans with
RT aliphatic and aromatic carboxylates.";
RL Bioorg. Med. Chem. 17:2654-2657(2009).
RN [9]
RP CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=19450983; DOI=10.1016/j.bmc.2009.05.002;
RA Innocenti A., Hall R.A., Schlicker C., Scozzafava A., Steegborn C.,
RA Muhlschlegel F.A., Supuran C.T.;
RT "Carbonic anhydrase inhibitors. Inhibition and homology modeling studies of
RT the fungal beta-carbonic anhydrase from Candida albicans with
RT sulfonamides.";
RL Bioorg. Med. Chem. 17:4503-4509(2009).
RN [10]
RP CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=19375309; DOI=10.1016/j.bmcl.2009.03.147;
RA Innocenti A., Winum J.Y., Hall R.A., Muhlschlegel F.A., Scozzafava A.,
RA Supuran C.T.;
RT "Carbonic anhydrase inhibitors. Inhibition of the fungal beta-carbonic
RT anhydrases from Candida albicans and Cryptococcus neoformans with boronic
RT acids.";
RL Bioorg. Med. Chem. Lett. 19:2642-2645(2009).
RN [11]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=20061162; DOI=10.1016/j.bmc.2009.12.058;
RA Innocenti A., Hall R.A., Scozzafava A., Muhlschlegel F.A., Supuran C.T.;
RT "Carbonic anhydrase activators: activation of the beta-carbonic anhydrases
RT from the pathogenic fungi Candida albicans and Cryptococcus neoformans with
RT amines and amino acids.";
RL Bioorg. Med. Chem. 18:1034-1037(2010).
RN [12]
RP CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=20299219; DOI=10.1016/j.bmcl.2010.02.103;
RA Guzel O., Maresca A., Hall R.A., Scozzafava A., Mastrolorenzo A.,
RA Muhlschlegel F.A., Supuran C.T.;
RT "Carbonic anhydrase inhibitors. The beta-carbonic anhydrases from the
RT fungal pathogens Cryptococcus neoformans and Candida albicans are strongly
RT inhibited by substituted-phenyl-1H-indole-5-sulfonamides.";
RL Bioorg. Med. Chem. Lett. 20:2508-2511(2010).
RN [13]
RP INDUCTION.
RX PubMed=21592964; DOI=10.1074/jbc.m111.233569;
RA Singh R.P., Prasad H.K., Sinha I., Agarwal N., Natarajan K.;
RT "Cap2-HAP complex is a critical transcriptional regulator that has dual but
RT contrasting roles in regulation of iron homeostasis in Candida albicans.";
RL J. Biol. Chem. 286:25154-25170(2011).
RN [14]
RP CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=21332115; DOI=10.1021/jm1013242;
RA Davis R.A., Hofmann A., Osman A., Hall R.A., Muhlschlegel F.A., Vullo D.,
RA Innocenti A., Supuran C.T., Poulsen S.A.;
RT "Natural product-based phenols as novel probes for mycobacterial and fungal
RT carbonic anhydrases.";
RL J. Med. Chem. 54:1682-1692(2011).
RN [15]
RP CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=22209456; DOI=10.1016/j.bmcl.2011.12.033;
RA Monti S.M., Maresca A., Viparelli F., Carta F., De Simone G.,
RA Muhlschlegel F.A., Scozzafava A., Supuran C.T.;
RT "Dithiocarbamates are strong inhibitors of the beta-class fungal carbonic
RT anhydrases from Cryptococcus neoformans, Candida albicans and Candida
RT glabrata.";
RL Bioorg. Med. Chem. Lett. 22:859-862(2012).
RN [16]
RP INDUCTION, AND FUNCTION.
RX PubMed=22253597; DOI=10.1371/journal.ppat.1002485;
RA Cottier F., Raymond M., Kurzai O., Bolstad M., Leewattanapasuk W.,
RA Jimenez-Lopez C., Lorenz M.C., Sanglard D., Vachova L., Pavelka N.,
RA Palkova Z., Muhlschlegel F.A.;
RT "The bZIP transcription factor Rca1p is a central regulator of a novel
RT CO(2) sensing pathway in yeast.";
RL PLoS Pathog. 8:E1002485-E1002485(2012).
CC -!- FUNCTION: Catalyzes the reversible hydration of CO(2) to H(2)CO(3). The
CC main role may be to provide inorganic carbon for the bicarbonate-
CC dependent carboxylation reactions catalyzed by pyruvate carboxylase,
CC acetyl-CoA carboxylase and carbamoyl-phosphate synthetase. Involved in
CC protection against oxidative damage. Acts as a CO(2) chemosensor and
CC induces CO(2)-mediated filamentation. Essential for pathological growth
CC in niches where sufficient CO(2) is not supplied by the host. Necessary
CC for white-to-opaque switching at low CO(2) concentrations.
CC {ECO:0000269|PubMed:16303561, ECO:0000269|PubMed:22253597}.
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:18723348,
CC ECO:0000269|PubMed:19297172, ECO:0000269|PubMed:19375309,
CC ECO:0000269|PubMed:19450983, ECO:0000269|PubMed:20061162,
CC ECO:0000269|PubMed:20299219, ECO:0000269|PubMed:21332115,
CC ECO:0000269|PubMed:22209456};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Amines and amino acids act as activators of
CC catalytic activity, whereas natural product-based phenols,
CC dithiocarbamates, aliphatic and aromatic carboxylates, boronic acids,
CC and sulfonamides act as inhibitors of enzymatic activity. Also
CC inhibited by anions such as cyanide and carbonate, and to a lesser
CC extent by sulfate, phenylboronic, and phenyl arsonic acid.
CC {ECO:0000269|PubMed:18723348, ECO:0000269|PubMed:19297172,
CC ECO:0000269|PubMed:19375309, ECO:0000269|PubMed:19450983,
CC ECO:0000269|PubMed:20061162, ECO:0000269|PubMed:20299219,
CC ECO:0000269|PubMed:21332115, ECO:0000269|PubMed:22209456}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8.2 mM for CO(2) {ECO:0000269|PubMed:20061162};
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Mitochondrion intermembrane
CC space.
CC -!- INDUCTION: Strongly expressed when cells are grown in ambient air but
CC non-detectable when cultured in air enriched with CO(2). Up-regulated
CC by MNL1, HAP43, RCA1, and during early stages of biofilm development.
CC {ECO:0000269|PubMed:16151249, ECO:0000269|PubMed:18653474,
CC ECO:0000269|PubMed:21592964, ECO:0000269|PubMed:22253597}.
CC -!- SIMILARITY: Belongs to the beta-class carbonic anhydrase family.
CC {ECO:0000305}.
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DR EMBL; CP017625; AOW28173.1; -; Genomic_DNA.
DR RefSeq; XP_721792.1; XM_716699.1.
DR PDB; 6GWU; X-ray; 2.20 A; A/B/C/D=56-263.
DR PDBsum; 6GWU; -.
DR AlphaFoldDB; Q5AJ71; -.
DR SMR; Q5AJ71; -.
DR BioGRID; 1219715; 1.
DR STRING; 237561.Q5AJ71; -.
DR BindingDB; Q5AJ71; -.
DR ChEMBL; CHEMBL5337; -.
DR DrugCentral; Q5AJ71; -.
DR PRIDE; Q5AJ71; -.
DR GeneID; 3636621; -.
DR KEGG; cal:CAALFM_C301300CA; -.
DR CGD; CAL0000198627; NCE103.
DR VEuPathDB; FungiDB:C3_01300C_A; -.
DR eggNOG; KOG1578; Eukaryota.
DR HOGENOM; CLU_053879_3_1_1; -.
DR InParanoid; Q5AJ71; -.
DR OrthoDB; 1136193at2759; -.
DR SABIO-RK; Q5AJ71; -.
DR PRO; PR:Q5AJ71; -.
DR Proteomes; UP000000559; Chromosome 3.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005758; C:mitochondrial intermembrane space; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0004089; F:carbonate dehydratase activity; IDA:CGD.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0015976; P:carbon utilization; IEA:InterPro.
DR GO; GO:0071244; P:cellular response to carbon dioxide; IBA:GO_Central.
DR GO; GO:0034599; P:cellular response to oxidative stress; IBA:GO_Central.
DR GO; GO:0036166; P:phenotypic switching; IMP:CGD.
DR GO; GO:1900239; P:regulation of phenotypic switching; IMP:CGD.
DR Gene3D; 3.40.1050.10; -; 1.
DR InterPro; IPR001765; Carbonic_anhydrase.
DR InterPro; IPR015892; Carbonic_anhydrase_CS.
DR InterPro; IPR036874; Carbonic_anhydrase_sf.
DR PANTHER; PTHR11002; PTHR11002; 1.
DR Pfam; PF00484; Pro_CA; 1.
DR SMART; SM00947; Pro_CA; 1.
DR SUPFAM; SSF53056; SSF53056; 1.
DR PROSITE; PS00705; PROK_CO2_ANHYDRASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Lyase; Metal-binding; Mitochondrion; Nucleus;
KW Reference proteome; Virulence; Zinc.
FT CHAIN 1..281
FT /note="Carbonic anhydrase"
FT /id="PRO_0000424600"
FT BINDING 106
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 161
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 164
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:6GWU"
FT HELIX 67..85
FT /evidence="ECO:0007829|PDB:6GWU"
FT HELIX 88..95
FT /evidence="ECO:0007829|PDB:6GWU"
FT STRAND 100..106
FT /evidence="ECO:0007829|PDB:6GWU"
FT HELIX 113..116
FT /evidence="ECO:0007829|PDB:6GWU"
FT STRAND 122..128
FT /evidence="ECO:0007829|PDB:6GWU"
FT HELIX 129..131
FT /evidence="ECO:0007829|PDB:6GWU"
FT HELIX 138..149
FT /evidence="ECO:0007829|PDB:6GWU"
FT STRAND 154..161
FT /evidence="ECO:0007829|PDB:6GWU"
FT HELIX 165..171
FT /evidence="ECO:0007829|PDB:6GWU"
FT HELIX 180..183
FT /evidence="ECO:0007829|PDB:6GWU"
FT HELIX 185..192
FT /evidence="ECO:0007829|PDB:6GWU"
FT HELIX 195..199
FT /evidence="ECO:0007829|PDB:6GWU"
FT TURN 200..203
FT /evidence="ECO:0007829|PDB:6GWU"
FT HELIX 205..225
FT /evidence="ECO:0007829|PDB:6GWU"
FT HELIX 228..235
FT /evidence="ECO:0007829|PDB:6GWU"
FT STRAND 240..246
FT /evidence="ECO:0007829|PDB:6GWU"
FT TURN 248..250
FT /evidence="ECO:0007829|PDB:6GWU"
FT STRAND 253..256
FT /evidence="ECO:0007829|PDB:6GWU"
SQ SEQUENCE 281 AA; 31591 MW; 81828A5F8E120DFB CRC64;
MGRENILKYQ LEHDHESDLV TEKDQSLLLD NNNNLNGMNN TIKTHPVRVS SGNHNNFPFT
LSSESTLQDF LNNNKFFVDS IKHNHGNQIF DLNGQGQSPH TLWIGCSDSR AGDQCLATLP
GEIFVHRNIA NIVNANDISS QGVIQFAIDV LKVKKIIVCG HTDCGGIWAS LSKKKIGGVL
DLWLNPVRHI RAANLKLLEE YNQDPKLKAK KLAELNVISS VTALKRHPSA SVALKKNEIE
VWGMLYDVAT GYLSQVEIPQ DEFEDLFHVH DEHDEEEYNP H
