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   27-MAR-2024, entry version 193.
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}.
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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; 10090-ENSMUSP00000060457; -.
DR   PeptideAtlas; P23589; -.
DR   ProteomicsDB; 265325; -.
DR   Antibodypedia; 55888; 162 antibodies from 24 providers.
DR   DNASU; 12352; -.
DR   Ensembl; ENSMUST00000057653.8; ENSMUSP00000060457.8; ENSMUSG00000025317.8.
DR   GeneID; 12352; -.
DR   KEGG; mmu:12352; -.
DR   UCSC; uc009nsf.2; mouse.
DR   AGR; MGI:101946; -.
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; SIYDPQL; -.
DR   OrthoDB; 49814at2759; -.
DR   PhylomeDB; P23589; -.
DR   TreeFam; TF316425; -.
DR   Reactome; R-MMU-1475029; Reversible hydration of carbon dioxide.
DR   BioGRID-ORCS; 12352; 1 hit in 77 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 30 other cell types or tissues.
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: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   CDD; cd03118; alpha_CA_V; 1.
DR   Gene3D; 3.10.200.10; Alpha carbonic anhydrase; 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; CARBONIC ANHYDRASE; 1.
DR   PANTHER; PTHR18952:SF89; CARBONIC ANHYDRASE 5A, MITOCHONDRIAL-RELATED; 1.
DR   Pfam; PF00194; Carb_anhydrase; 1.
DR   SMART; SM01057; Carb_anhydrase; 1.
DR   SUPFAM; SSF51069; Carbonic anhydrase; 1.
DR   PROSITE; PS00162; ALPHA_CA_1; 1.
DR   PROSITE; PS51144; ALPHA_CA_2; 1.
DR   Genevisible; P23589; MM.
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
FT                   C-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
//