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Protein

Carbonic anhydrase 5A, mitochondrial

Gene

CA5A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Reversible hydration of carbon dioxide. Low activity.

Catalytic activityi

H2CO3 = CO2 + H2O.

Cofactori

Zn2+By similarity

Enzyme regulationi

Activated by histamine, L-adrenaline, L- and D-histidine, and L- and D-phenylalanine. Inhibited by coumarins, sulfonamide derivatives such as acetazolamide and Foscarnet (phosphonoformate trisodium salt).7 Publications

Kineticsi

  1. KM=10.0 mM for CO21 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi130 – 1301Zinc; catalyticBy similarity
    Metal bindingi132 – 1321Zinc; catalyticBy similarity
    Metal bindingi155 – 1551Zinc; catalyticBy similarity
    Active sitei164 – 1641By similarity
    Active sitei167 – 1671Curated

    GO - Molecular functioni

    • carbonate dehydratase activity Source: ProtInc
    • zinc ion binding Source: InterPro

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Lyase

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    BRENDAi4.2.1.1. 2681.
    ReactomeiREACT_121123. Reversible hydration of carbon dioxide.
    SABIO-RKP35218.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Carbonic anhydrase 5A, mitochondrial (EC:4.2.1.1)
    Alternative name(s):
    Carbonate dehydratase VA
    Carbonic anhydrase VA
    Short name:
    CA-VA
    Gene namesi
    Name:CA5A
    Synonyms:CA5
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 16

    Organism-specific databases

    HGNCiHGNC:1377. CA5A.

    Subcellular locationi

    GO - Cellular componenti

    • mitochondrial matrix Source: Reactome
    • mitochondrion Source: ProtInc
    Complete GO annotation...

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Involvement in diseasei

    Hyperammonemia due to carbonic anhydrase VA deficiency (CA5AD)1 Publication

    The disease is caused by mutations affecting the gene represented in this entry.

    Disease descriptionAn autosomal recessive inborn error of metabolism, clinically characterized by infantile hyperammonemic encephalopathy. Metabolic abnormalities include hypoglycemia, hyperlactatemia, metabolic acidosis and respiratory alkalosis.

    See also OMIM:615751
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti233 – 2331S → P in CA5AD; reduced enzymatic activity. 1 Publication
    VAR_071188

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi615751. phenotype.
    Orphaneti401948. Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency.
    PharmGKBiPA25992.

    Chemistry

    DrugBankiDB01194. Brinzolamide.
    DB00909. Zonisamide.

    Polymorphism and mutation databases

    BioMutaiCA5A.
    DMDMi461680.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 3838MitochondrionAdd
    BLAST
    Chaini39 – 305267Carbonic anhydrase 5A, mitochondrialPRO_0000004234Add
    BLAST

    Proteomic databases

    MaxQBiP35218.
    PaxDbiP35218.
    PRIDEiP35218.

    PTM databases

    PhosphoSiteiP35218.

    Expressioni

    Gene expression databases

    BgeeiP35218.
    CleanExiHS_CA5A.
    GenevisibleiP35218. HS.

    Interactioni

    Protein-protein interaction databases

    BioGridi107218. 1 interaction.
    STRINGi9606.ENSP00000309649.

    Structurei

    3D structure databases

    ProteinModelPortaliP35218.
    SMRiP35218. Positions 61-296.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni235 – 2362Substrate bindingBy similarity

    Sequence similaritiesi

    Belongs to the alpha-carbonic anhydrase family.Curated

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG3338.
    GeneTreeiENSGT00760000118915.
    HOGENOMiHOG000112637.
    HOVERGENiHBG002837.
    InParanoidiP35218.
    KOiK01672.
    OMAiCLLPACR.
    OrthoDBiEOG7WMCK7.
    PhylomeDBiP35218.
    TreeFamiTF316425.

    Family and domain databases

    Gene3Di3.10.200.10. 1 hit.
    InterProiIPR001148. Carbonic_anhydrase_a.
    IPR023561. Carbonic_anhydrase_a-class.
    IPR018338. Carbonic_anhydrase_a-class_CS.
    [Graphical view]
    PANTHERiPTHR18952. PTHR18952. 1 hit.
    PfamiPF00194. Carb_anhydrase. 1 hit.
    [Graphical view]
    SMARTiSM01057. Carb_anhydrase. 1 hit.
    [Graphical view]
    SUPFAMiSSF51069. SSF51069. 1 hit.
    PROSITEiPS00162. ALPHA_CA_1. 1 hit.
    PS51144. ALPHA_CA_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P35218-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MLGRNTWKTS AFSFLVEQMW APLWSRSMRP GRWCSQRSCA WQTSNNTLHP
    60 70 80 90 100
    LWTVPVSVPG GTRQSPINIQ WRDSVYDPQL KPLRVSYEAA SCLYIWNTGY
    110 120 130 140 150
    LFQVEFDDAT EASGISGGPL ENHYRLKQFH FHWGAVNEGG SEHTVDGHAY
    160 170 180 190 200
    PAELHLVHWN SVKYQNYKEA VVGENGLAVI GVFLKLGAHH QTLQRLVDIL
    210 220 230 240 250
    PEIKHKDARA AMRPFDPSTL LPTCWDYWTY AGSLTTPPLT ESVTWIIQKE
    260 270 280 290 300
    PVEVAPSQLS AFRTLLFSAL GEEEKMMVNN YRPLQPLMNR KVWASFQATN

    EGTRS
    Length:305
    Mass (Da):34,750
    Last modified:February 1, 1994 - v1
    Checksum:iC4E998D269AB1FE5
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti233 – 2331S → P in CA5AD; reduced enzymatic activity. 1 Publication
    VAR_071188

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    L19297 mRNA. Translation: AAA02890.1.
    U25134 Genomic DNA. Translation: AAC99806.1.
    S80181
    , S80175, S80176, S80177, S80178, S80240, S80180 Genomic DNA. Translation: AAB47048.1.
    CH471114 Genomic DNA. Translation: EAW95372.1.
    BC137405 mRNA. Translation: AAI37406.1.
    BC137411 mRNA. Translation: AAI37412.1.
    CCDSiCCDS10965.1.
    PIRiA47745. CRHU5.
    RefSeqiNP_001730.1. NM_001739.1.
    UniGeneiHs.177446.

    Genome annotation databases

    EnsembliENST00000309893; ENSP00000309649; ENSG00000174990.
    GeneIDi763.
    KEGGihsa:763.
    UCSCiuc002fkn.1. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    L19297 mRNA. Translation: AAA02890.1.
    U25134 Genomic DNA. Translation: AAC99806.1.
    S80181
    , S80175, S80176, S80177, S80178, S80240, S80180 Genomic DNA. Translation: AAB47048.1.
    CH471114 Genomic DNA. Translation: EAW95372.1.
    BC137405 mRNA. Translation: AAI37406.1.
    BC137411 mRNA. Translation: AAI37412.1.
    CCDSiCCDS10965.1.
    PIRiA47745. CRHU5.
    RefSeqiNP_001730.1. NM_001739.1.
    UniGeneiHs.177446.

    3D structure databases

    ProteinModelPortaliP35218.
    SMRiP35218. Positions 61-296.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi107218. 1 interaction.
    STRINGi9606.ENSP00000309649.

    Chemistry

    BindingDBiP35218.
    ChEMBLiCHEMBL2111457.
    DrugBankiDB01194. Brinzolamide.
    DB00909. Zonisamide.

    PTM databases

    PhosphoSiteiP35218.

    Polymorphism and mutation databases

    BioMutaiCA5A.
    DMDMi461680.

    Proteomic databases

    MaxQBiP35218.
    PaxDbiP35218.
    PRIDEiP35218.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000309893; ENSP00000309649; ENSG00000174990.
    GeneIDi763.
    KEGGihsa:763.
    UCSCiuc002fkn.1. human.

    Organism-specific databases

    CTDi763.
    GeneCardsiGC16M087921.
    HGNCiHGNC:1377. CA5A.
    MIMi114761. gene.
    615751. phenotype.
    neXtProtiNX_P35218.
    Orphaneti401948. Hyperammonemic encephalopathy due to carbonic anhydrase VA deficiency.
    PharmGKBiPA25992.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG3338.
    GeneTreeiENSGT00760000118915.
    HOGENOMiHOG000112637.
    HOVERGENiHBG002837.
    InParanoidiP35218.
    KOiK01672.
    OMAiCLLPACR.
    OrthoDBiEOG7WMCK7.
    PhylomeDBiP35218.
    TreeFamiTF316425.

    Enzyme and pathway databases

    BRENDAi4.2.1.1. 2681.
    ReactomeiREACT_121123. Reversible hydration of carbon dioxide.
    SABIO-RKP35218.

    Miscellaneous databases

    GenomeRNAii763.
    NextBioi3086.
    PROiP35218.
    SOURCEiSearch...

    Gene expression databases

    BgeeiP35218.
    CleanExiHS_CA5A.
    GenevisibleiP35218. HS.

    Family and domain databases

    Gene3Di3.10.200.10. 1 hit.
    InterProiIPR001148. Carbonic_anhydrase_a.
    IPR023561. Carbonic_anhydrase_a-class.
    IPR018338. Carbonic_anhydrase_a-class_CS.
    [Graphical view]
    PANTHERiPTHR18952. PTHR18952. 1 hit.
    PfamiPF00194. Carb_anhydrase. 1 hit.
    [Graphical view]
    SMARTiSM01057. Carb_anhydrase. 1 hit.
    [Graphical view]
    SUPFAMiSSF51069. SSF51069. 1 hit.
    PROSITEiPS00162. ALPHA_CA_1. 1 hit.
    PS51144. ALPHA_CA_2. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Human mitochondrial carbonic anhydrase: cDNA cloning, expression, subcellular localization, and mapping to chromosome 16."
      Nagao Y., Platero J.S., Waheed A., Sly W.S.
      Proc. Natl. Acad. Sci. U.S.A. 90:7623-7627(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
      Tissue: Liver.
    2. "Genomic organization of the human gene (CA5) and pseudogene for mitochondrial carbonic anhydrase V and their localization to chromosomes 16q and 16p."
      Nagao Y., Batanian J.R., Clemente M.F., Sly W.S.
      Genomics 28:477-484(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Tissue: Umbilical cord.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    5. "Carbonic anhydrase activators. Activation of isozymes I, II, IV, VA, VII, and XIV with l- and d-histidine and crystallographic analysis of their adducts with isoform II: engineering proton-transfer processes within the active site of an enzyme."
      Temperini C., Scozzafava A., Vullo D., Supuran C.T.
      Chemistry 12:7057-7066(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION.
    6. "Carbonic anhydrase activators. Activation of isoforms I, II, IV, VA, VII, and XIV with L- and D-phenylalanine and crystallographic analysis of their adducts with isozyme II: stereospecific recognition within the active site of an enzyme and its consequences for the drug design."
      Temperini C., Scozzafava A., Vullo D., Supuran C.T.
      J. Med. Chem. 49:3019-3027(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION.
    7. "Carbonic anhydrase activators: L-Adrenaline plugs the active site entrance of isozyme II, activating better isoforms I, IV, VA, VII, and XIV."
      Temperini C., Innocenti A., Scozzafava A., Mastrolorenzo A., Supuran C.T.
      Bioorg. Med. Chem. Lett. 17:628-635(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION.
    8. "Phosph(on)ate as a zinc-binding group in metalloenzyme inhibitors: X-ray crystal structure of the antiviral drug foscarnet complexed to human carbonic anhydrase I."
      Temperini C., Innocenti A., Guerri A., Scozzafava A., Rusconi S., Supuran C.T.
      Bioorg. Med. Chem. Lett. 17:2210-2215(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION.
    9. "A thiabendazole sulfonamide shows potent inhibitory activity against mammalian and nematode alpha-carbonic anhydrases."
      Crocetti L., Maresca A., Temperini C., Hall R.A., Scozzafava A., Muehlschlegel F.A., Supuran C.T.
      Bioorg. Med. Chem. Lett. 19:1371-1375(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION.
    10. "Non-zinc mediated inhibition of carbonic anhydrases: coumarins are a new class of suicide inhibitors."
      Maresca A., Temperini C., Vu H., Pham N.B., Poulsen S.-A., Scozzafava A., Quinn R.J., Supuran C.T.
      J. Am. Chem. Soc. 131:3057-3062(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME REGULATION.
    11. "Crystal structure of human carbonic anhydrase XIII and its complex with the inhibitor acetazolamide."
      Di Fiore A., Monti S.M., Hilvo M., Parkkila S., Romano V., Scaloni A., Pedone C., Scozzafava A., Supuran C.T., De Simone G.
      Proteins 74:164-175(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
    12. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
      Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
      J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    13. Cited for: VARIANT CA5AD PRO-233, CHARACTERIZATION OF VARIANT CA5AD PRO-233.

    Entry informationi

    Entry nameiCAH5A_HUMAN
    AccessioniPrimary (citable) accession number: P35218
    Secondary accession number(s): B2RPF2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1994
    Last sequence update: February 1, 1994
    Last modified: June 24, 2015
    This is version 134 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 16
      Human chromosome 16: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.