CAH5A_MOUSE
ID CAH5A_MOUSE Reviewed; 299 AA.
AC P23589;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Carbonic anhydrase 5A, mitochondrial {ECO:0000305|PubMed:7937950};
DE EC=4.2.1.1 {ECO:0000269|PubMed:7937950};
DE AltName: Full=Carbonate dehydratase VA;
DE Short=CA Y {ECO:0000303|PubMed:7937950};
DE AltName: Full=Carbonic anhydrase VA;
DE Short=CA-VA;
DE Flags: Precursor;
GN Name=Ca5a {ECO:0000312|MGI:MGI:101946}; Synonyms=Ca5, Car5, Car5a;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BIO-HTT; TISSUE=Liver;
RX PubMed=2109313; DOI=10.1093/nar/18.6.1646;
RA Amor-Gueret M., Levi-Strauss M.;
RT "Nucleotide and derived amino-acid sequence of a cDNA encoding a new mouse
RT carbonic anhydrase.";
RL Nucleic Acids Res. 18:1646-1646(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 30-41, TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, AND FUNCTION.
RC TISSUE=Liver;
RX PubMed=7937950; DOI=10.1073/pnas.91.22.10330;
RA Nagao Y., Srinivasan M., Platero J.S., Svendrowski M., Waheed A., Sly W.S.;
RT "Mitochondrial carbonic anhydrase (isozyme V) in mouse and rat: cDNA
RT cloning, expression, subcellular localization, processing, and tissue
RT distribution.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:10330-10334(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF PHE-95; LYS-121 AND
RP TYR-161.
RX PubMed=9882455; DOI=10.1006/abbi.1998.0984;
RA Earnhardt J.N., Wright S.K., Qian M., Tu C., Laipis P.J., Viola R.E.,
RA Silverman D.N.;
RT "Introduction of histidine analogs leads to enhanced proton transfer in
RT carbonic anhydrase V.";
RL Arch. Biochem. Biophys. 361:264-270(1999).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-66, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 55-299 IN COMPLEX WITH INHIBITORS
RP AND ZINC ION, AND MUTAGENESIS OF TYR-94.
RX PubMed=7479916; DOI=10.1073/pnas.92.24.10949;
RA Boriack-Sjodin P.A., Heck R.W., Laipis P.J., Silverman D.N.,
RA Christianson D.W.;
RT "Structure determination of murine mitochondrial carbonic anhydrase V at
RT 2.45-A resolution: implications for catalytic proton transfer and inhibitor
RT design.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:10949-10953(1995).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 52-299 IN COMPLEX WITH ZINC ION,
RP AND MUTAGENESIS OF TYR-94; PHE-95 AND TYR-161.
RX PubMed=8794740; DOI=10.1021/bi9608018;
RA Heck R.W., Boriack-Sjodin P.A., Qian M., Tu C., Christianson D.W.,
RA Laipis P.J., Silverman D.N.;
RT "Structure-based design of an intramolecular proton transfer site in murine
RT carbonic anhydrase V.";
RL Biochemistry 35:11605-11611(1996).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.88 ANGSTROMS) OF 55-299 IN COMPLEX WITH INHIBITORS
RP AND ZINC ION, AND MUTAGENESIS OF PHE-95 AND TYR-161.
RX PubMed=11851394; DOI=10.1021/bi015808q;
RA Jude K.M., Wright S.K., Tu C., Silverman D.N., Viola R.E.,
RA Christianson D.W.;
RT "Crystal structure of F65A/Y131C-methylimidazole carbonic anhydrase V
RT reveals architectural features of an engineered proton shuttle.";
RL Biochemistry 41:2485-2491(2002).
CC -!- FUNCTION: Mitochondrial carbonic anhydrase that catalyzes the
CC reversible conversion of carbon dioxide to bicarbonate/HCO3
CC (PubMed:7937950). Mitochondria are impermeable to HCO3, and thus this
CC intramitochondrial carbonic anhydrase is pivotal in providing HCO3 for
CC multiple mitochondrial enzymes that catalyze the formation of essential
CC metabolites of intermediary metabolism in the urea and Krebs cycles (By
CC similarity). {ECO:0000250|UniProtKB:P35218,
CC ECO:0000269|PubMed:7937950}.
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:7937950};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10749;
CC Evidence={ECO:0000305|PubMed:7937950};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:10750;
CC Evidence={ECO:0000305|PubMed:7937950};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:11851394, ECO:0000269|PubMed:7479916,
CC ECO:0000269|PubMed:8794740};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7-8. {ECO:0000269|PubMed:9882455};
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:7937950}.
CC -!- TISSUE SPECIFICITY: Liver. {ECO:0000269|PubMed:7937950}.
CC -!- SIMILARITY: Belongs to the alpha-carbonic anhydrase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X51971; CAA36233.1; -; mRNA.
DR EMBL; BC030174; AAH30174.1; -; mRNA.
DR CCDS; CCDS22731.1; -.
DR PIR; S12579; S12579.
DR RefSeq; NP_031634.2; NM_007608.2.
DR PDB; 1DMX; X-ray; 2.45 A; A/B=53-299.
DR PDB; 1DMY; X-ray; 2.45 A; A/B=53-299.
DR PDB; 1KEQ; X-ray; 1.88 A; A/B=53-299.
DR PDB; 1URT; X-ray; 2.80 A; A=52-299.
DR PDBsum; 1DMX; -.
DR PDBsum; 1DMY; -.
DR PDBsum; 1KEQ; -.
DR PDBsum; 1URT; -.
DR AlphaFoldDB; P23589; -.
DR SMR; P23589; -.
DR STRING; 10090.ENSMUSP00000060457; -.
DR BindingDB; P23589; -.
DR iPTMnet; P23589; -.
DR PhosphoSitePlus; P23589; -.
DR jPOST; P23589; -.
DR MaxQB; P23589; -.
DR PaxDb; P23589; -.
DR PeptideAtlas; P23589; -.
DR PRIDE; P23589; -.
DR ProteomicsDB; 265325; -.
DR Antibodypedia; 55888; 148 antibodies from 24 providers.
DR DNASU; 12352; -.
DR Ensembl; ENSMUST00000057653; ENSMUSP00000060457; ENSMUSG00000025317.
DR GeneID; 12352; -.
DR KEGG; mmu:12352; -.
DR UCSC; uc009nsf.2; mouse.
DR CTD; 12352; -.
DR MGI; MGI:101946; Car5a.
DR VEuPathDB; HostDB:ENSMUSG00000025317; -.
DR eggNOG; KOG0382; Eukaryota.
DR GeneTree; ENSGT00940000162066; -.
DR HOGENOM; CLU_039326_2_1_1; -.
DR InParanoid; P23589; -.
DR OMA; NAWKTSA; -.
DR OrthoDB; 1377476at2759; -.
DR PhylomeDB; P23589; -.
DR TreeFam; TF316425; -.
DR Reactome; R-MMU-1475029; Reversible hydration of carbon dioxide.
DR BioGRID-ORCS; 12352; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Car5a; mouse.
DR EvolutionaryTrace; P23589; -.
DR PRO; PR:P23589; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; P23589; protein.
DR Bgee; ENSMUSG00000025317; Expressed in left lobe of liver and 27 other tissues.
DR Genevisible; P23589; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0004089; F:carbonate dehydratase activity; IDA:MGI.
DR GO; GO:0016836; F:hydro-lyase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006094; P:gluconeogenesis; TAS:MGI.
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 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; Direct protein sequencing; Lyase; Metal-binding;
KW Mitochondrion; Reference proteome; Transit peptide; Zinc.
FT TRANSIT 1..29
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:7937950"
FT CHAIN 30..299
FT /note="Carbonic anhydrase 5A, mitochondrial"
FT /id="PRO_0000004235"
FT DOMAIN 30..290
FT /note="Alpha-carbonic anhydrase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01134"
FT BINDING 124
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:11851394,
FT ECO:0000269|PubMed:7479916, ECO:0000269|PubMed:8794740"
FT BINDING 126
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:11851394,
FT ECO:0000269|PubMed:7479916, ECO:0000269|PubMed:8794740"
FT BINDING 149
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:11851394,
FT ECO:0000269|PubMed:7479916, ECO:0000269|PubMed:8794740"
FT MOD_RES 66
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT VARIANT 151..153
FT /note="VHW -> FM (in strain: BIO-HTT)"
FT MUTAGEN 94
FT /note="Y->A: No effect on carbonate dehydratase activity."
FT /evidence="ECO:0000269|PubMed:7479916,
FT ECO:0000269|PubMed:8794740"
FT MUTAGEN 94
FT /note="Y->H: No effect on carbonate dehydratase activity.
FT Enhanced proton transfer due to removal of the steric
FT hindrance of F-95; when associated with A-95."
FT /evidence="ECO:0000269|PubMed:7479916,
FT ECO:0000269|PubMed:8794740"
FT MUTAGEN 95
FT /note="F->A: No effect on carbonate dehydratase activity.
FT Enhanced proton transfer; when associated with H-94 or C-
FT 161."
FT /evidence="ECO:0000269|PubMed:11851394,
FT ECO:0000269|PubMed:8794740, ECO:0000269|PubMed:9882455"
FT MUTAGEN 121
FT /note="K->C: No effect on carbonate dehydratase activity."
FT /evidence="ECO:0000269|PubMed:9882455"
FT MUTAGEN 161
FT /note="Y->A: No effect on carbonate dehydratase activity."
FT /evidence="ECO:0000269|PubMed:11851394,
FT ECO:0000269|PubMed:8794740, ECO:0000269|PubMed:9882455"
FT MUTAGEN 161
FT /note="Y->C: No effect on carbonate dehydratase activity.
FT Enhanced proton transfer; when associated with A-95."
FT /evidence="ECO:0000269|PubMed:11851394,
FT ECO:0000269|PubMed:8794740, ECO:0000269|PubMed:9882455"
FT MUTAGEN 161
FT /note="Y->H: No effect on carbonate dehydratase activity."
FT /evidence="ECO:0000269|PubMed:11851394,
FT ECO:0000269|PubMed:8794740, ECO:0000269|PubMed:9882455"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:1KEQ"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:1KEQ"
FT STRAND 75..80
FT /evidence="ECO:0007829|PDB:1KEQ"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:1KEQ"
FT STRAND 86..91
FT /evidence="ECO:0007829|PDB:1KEQ"
FT STRAND 93..100
FT /evidence="ECO:0007829|PDB:1KEQ"
FT STRAND 104..112
FT /evidence="ECO:0007829|PDB:1KEQ"
FT STRAND 118..127
FT /evidence="ECO:0007829|PDB:1KEQ"
FT STRAND 136..139
FT /evidence="ECO:0007829|PDB:1KEQ"
FT STRAND 145..154
FT /evidence="ECO:0007829|PDB:1KEQ"
FT TURN 155..157
FT /evidence="ECO:0007829|PDB:1KEQ"
FT HELIX 161..164
FT /evidence="ECO:0007829|PDB:1KEQ"
FT STRAND 171..182
FT /evidence="ECO:0007829|PDB:1KEQ"
FT HELIX 185..191
FT /evidence="ECO:0007829|PDB:1KEQ"
FT HELIX 192..196
FT /evidence="ECO:0007829|PDB:1KEQ"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:1KEQ"
FT HELIX 211..214
FT /evidence="ECO:0007829|PDB:1KEQ"
FT STRAND 221..226
FT /evidence="ECO:0007829|PDB:1KEQ"
FT STRAND 237..244
FT /evidence="ECO:0007829|PDB:1KEQ"
FT STRAND 246..248
FT /evidence="ECO:0007829|PDB:1KEQ"
FT HELIX 250..256
FT /evidence="ECO:0007829|PDB:1KEQ"
FT STRAND 260..262
FT /evidence="ECO:0007829|PDB:1KEQ"
FT STRAND 264..266
FT /evidence="ECO:0007829|PDB:1DMX"
FT STRAND 286..290
FT /evidence="ECO:0007829|PDB:1KEQ"
SQ SEQUENCE 299 AA; 34072 MW; 2698CABA00686151 CRC64;
MLRRDPRKPL AILRHVGLLC ATGPQRWRFQ HSCAEEHSNC ARHPLWTGPV SSAEGTRQSP
INIQWKDSVY DPQLAPLRVS YDAASCRYLW NTGYFFQVEF DDSCEDSGIS GGPLGNHYRL
KQFHFHWGAT DEWGSEHAVD GHTYPAELHL VHWNSTKYEN YKKASVGENG LAVIGVFLKL
GAHHQALQKL VDVLPEVRHK DTQVAMGPFD PSCLLPACRD YWTYPGSLTT PPLAESVTWI
VQKTPVEVSP SQLSTFRTLL FSGRGEEEDV MVNNYRPLQP LRDRKLRSSF RLDRTKMRS
