Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Carbonic anhydrase 12

Gene

CA12

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

Functioni

Reversible hydration of carbon dioxide.

Catalytic activityi

H2CO3 = CO2 + H2O.

Cofactori

Zn2+1 Publication

Activity regulationi

Inhibited by coumarins, saccharin, sulfonamide derivatives such as acetazolamide (AZA), benzenesulfonamide and derivatives (4-carboxyethylbenzene-sulfonamide, 4-carboxyethylbenzene-sulfonamide ethyl ester, 4-(acetyl-2-aminoethyl)benzene-sulfonamide, 4-aminoethylbenzene-sulfonamide) and Foscarnet (phosphonoformate trisodium salt).6 Publications

Kineticsi

  1. KM=12.0 mM for CO21 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei94Proton acceptorBy similarity1
    Metal bindingi119Zinc; catalytic1 Publication1
    Metal bindingi121Zinc; catalytic1 Publication1
    Metal bindingi145Zinc; catalytic1 Publication1
    Active sitei154By similarity1

    GO - Molecular functioni

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

    GO - Biological processi

    • bicarbonate transport Source: Reactome
    • chloride ion homeostasis Source: UniProtKB

    Keywordsi

    Molecular functionLyase
    LigandMetal-binding, Zinc

    Enzyme and pathway databases

    BRENDAi4.2.1.1 2681
    ReactomeiR-HSA-1475029 Reversible hydration of carbon dioxide

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Carbonic anhydrase 12 (EC:4.2.1.1)
    Alternative name(s):
    Carbonate dehydratase XII
    Carbonic anhydrase XII
    Short name:
    CA-XII
    Tumor antigen HOM-RCC-3.1.3
    Gene namesi
    Name:CA12
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 15

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000074410.13
    HGNCiHGNC:1371 CA12
    MIMi603263 gene
    neXtProtiNX_O43570

    Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini25 – 301ExtracellularSequence analysisAdd BLAST277
    Transmembranei302 – 322HelicalSequence analysisAdd BLAST21
    Topological domaini323 – 354CytoplasmicSequence analysisAdd BLAST32

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Hyperchlorhidrosis, isolated (HCHLH)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA disorder characterized by excessive sweating and increased sweat chloride levels. Affected individuals suffer from episodes of hyponatremic dehydration and report increased amounts of visible salt precipitates in sweat.
    See also OMIM:143860
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_065292143E → K in HCHLH; mild reduction of activity; mutant enzyme is highly inhibited by acetazolamide and shows higher sensitivity to inhibition by anions compared to wild-type; the mutation affects the chloride-mediated negative feedback regulation of the enzyme leading to excessive chloride secretion in sweat. 1 PublicationCorresponds to variant dbSNP:rs267606694EnsemblClinVar.1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi771
    MalaCardsiCA12
    MIMi143860 phenotype
    OpenTargetsiENSG00000074410
    PharmGKBiPA25987

    Chemistry databases

    ChEMBLiCHEMBL3242
    DrugBankiDB00562 Benzthiazide
    DB08846 Ellagic Acid
    DB00999 Hydrochlorothiazide
    DB00774 Hydroflumethiazide
    DB00909 Zonisamide
    GuidetoPHARMACOLOGYi2747

    Polymorphism and mutation databases

    BioMutaiCA12

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 24Sequence analysisAdd BLAST24
    ChainiPRO_000000424825 – 354Carbonic anhydrase 12Add BLAST330

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Glycosylationi28N-linked (GlcNAc...) asparagineSequence analysis1
    Disulfide bondi50 ↔ 2301 Publication
    Glycosylationi80N-linked (GlcNAc...) asparagineSequence analysis1
    Glycosylationi162N-linked (GlcNAc...) asparagineSequence analysis1

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    EPDiO43570
    MaxQBiO43570
    PaxDbiO43570
    PeptideAtlasiO43570
    PRIDEiO43570
    ProteomicsDBi49059
    49060 [O43570-2]

    PTM databases

    GlyConnecti1064
    iPTMnetiO43570
    PhosphoSitePlusiO43570

    Expressioni

    Tissue specificityi

    Highly expressed in colon, kidney, prostate, intestine and activated lymphocytes. Expressed at much higher levels in the renal cell cancers than in surrounding normal kidney tissue. Moderately expressed in pancreas, ovary and testis.

    Gene expression databases

    BgeeiENSG00000074410 Expressed in 204 organ(s), highest expression level in cortex of kidney
    CleanExiHS_CA12
    ExpressionAtlasiO43570 baseline and differential
    GenevisibleiO43570 HS

    Organism-specific databases

    HPAiCAB025181
    CAB062549
    CAB068179
    HPA008773
    HPA073203

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    Protein-protein interaction databases

    BioGridi107225, 8 interactors
    IntActiO43570, 10 interactors
    MINTiO43570
    STRINGi9606.ENSP00000178638

    Chemistry databases

    BindingDBiO43570

    Structurei

    Secondary structure

    1354
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    ProteinModelPortaliO43570
    SMRiO43570
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO43570

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini30 – 289Alpha-carbonic anhydrasePROSITE-ProRule annotationAdd BLAST260

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni226 – 227Substrate bindingBy similarity2

    Sequence similaritiesi

    Belongs to the alpha-carbonic anhydrase family.Curated

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG0382 Eukaryota
    COG3338 LUCA
    GeneTreeiENSGT00760000118915
    HOGENOMiHOG000112637
    HOVERGENiHBG002837
    InParanoidiO43570
    KOiK01672
    OMAiHTVGGKH
    OrthoDBiEOG091G0XFM
    PhylomeDBiO43570
    TreeFamiTF316425

    Family and domain databases

    Gene3Di3.10.200.10, 1 hit
    InterProiView protein in InterPro
    IPR001148 CA_dom
    IPR036398 CA_dom_sf
    IPR023561 Carbonic_anhydrase_a-class
    IPR018338 Carbonic_anhydrase_a-class_CS
    IPR018430 Carbonic_anhydrase_CA12
    PANTHERiPTHR18952 PTHR18952, 1 hit
    PTHR18952:SF19 PTHR18952:SF19, 1 hit
    PfamiView protein in Pfam
    PF00194 Carb_anhydrase, 1 hit
    SMARTiView protein in SMART
    SM01057 Carb_anhydrase, 1 hit
    SUPFAMiSSF51069 SSF51069, 1 hit
    PROSITEiView protein in PROSITE
    PS00162 ALPHA_CA_1, 1 hit
    PS51144 ALPHA_CA_2, 1 hit

    Sequences (2+)i

    Sequence statusi: Complete.

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

    This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

    This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

    Isoform 1 (identifier: O43570-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide
            10         20         30         40         50
    MPRRSLHAAA VLLLVILKEQ PSSPAPVNGS KWTYFGPDGE NSWSKKYPSC
    60 70 80 90 100
    GGLLQSPIDL HSDILQYDAS LTPLEFQGYN LSANKQFLLT NNGHSVKLNL
    110 120 130 140 150
    PSDMHIQGLQ SRYSATQLHL HWGNPNDPHG SEHTVSGQHF AAELHIVHYN
    160 170 180 190 200
    SDLYPDASTA SNKSEGLAVL AVLIEMGSFN PSYDKIFSHL QHVKYKGQEA
    210 220 230 240 250
    FVPGFNIEEL LPERTAEYYR YRGSLTTPPC NPTVLWTVFR NPVQISQEQL
    260 270 280 290 300
    LALETALYCT HMDDPSPREM INNFRQVQKF DERLVYTSFS QVQVCTAAGL
    310 320 330 340 350
    SLGIILSLAL AGILGICIVV VVSIWLFRRK SIKKGDNKGV IYKPATKMET

    EAHA
    Length:354
    Mass (Da):39,451
    Last modified:June 1, 1998 - v1
    Checksum:i9016216BF2CA6C0C
    GO
    Isoform 2 (identifier: O43570-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         292-302: Missing.

    Show »
    Length:343
    Mass (Da):38,408
    Checksum:i87FD35255B137D18
    GO

    Computationally mapped potential isoform sequencesi

    There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    Gene namesLengthAnnotation
    B3KUB4B3KUB4_HUMAN
    Carbonic anhydrase 12
    CA12 hCG_2003428
    283Annotation score:

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti305I → T in BAG38121 (PubMed:14702039).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_065292143E → K in HCHLH; mild reduction of activity; mutant enzyme is highly inhibited by acetazolamide and shows higher sensitivity to inhibition by anions compared to wild-type; the mutation affects the chloride-mediated negative feedback regulation of the enzyme leading to excessive chloride secretion in sweat. 1 PublicationCorresponds to variant dbSNP:rs267606694EnsemblClinVar.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_000772292 – 302Missing in isoform 2. 2 PublicationsAdd BLAST11

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF051882 mRNA Translation: AAC39789.1
    AF037335 mRNA Translation: AAC63952.1
    BT006656 mRNA Translation: AAP35302.1
    AK315769 mRNA Translation: BAG38121.1
    BC000278 mRNA Translation: AAH00278.1
    BC011691 mRNA Translation: AAH11691.1
    BC023981 mRNA Translation: AAH23981.1
    CCDSiCCDS10185.1 [O43570-1]
    CCDS10186.1 [O43570-2]
    RefSeqiNP_001209.1, NM_001218.4 [O43570-1]
    NP_996808.1, NM_206925.2 [O43570-2]
    UniGeneiHs.210995
    Hs.603780

    Genome annotation databases

    EnsembliENST00000178638; ENSP00000178638; ENSG00000074410 [O43570-1]
    ENST00000344366; ENSP00000343088; ENSG00000074410 [O43570-2]
    GeneIDi771
    KEGGihsa:771
    UCSCiuc002amc.4 human [O43570-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Similar proteinsi

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF051882 mRNA Translation: AAC39789.1
    AF037335 mRNA Translation: AAC63952.1
    BT006656 mRNA Translation: AAP35302.1
    AK315769 mRNA Translation: BAG38121.1
    BC000278 mRNA Translation: AAH00278.1
    BC011691 mRNA Translation: AAH11691.1
    BC023981 mRNA Translation: AAH23981.1
    CCDSiCCDS10185.1 [O43570-1]
    CCDS10186.1 [O43570-2]
    RefSeqiNP_001209.1, NM_001218.4 [O43570-1]
    NP_996808.1, NM_206925.2 [O43570-2]
    UniGeneiHs.210995
    Hs.603780

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1JCZX-ray1.55A/B30-291[»]
    1JD0X-ray1.50A/B30-291[»]
    4HT2X-ray1.45A/B/C/D30-291[»]
    4KP5X-ray1.45A/B/C/D30-291[»]
    4KP8X-ray1.80A/B/C/D30-291[»]
    4Q0LX-ray2.00A/B/C/D30-291[»]
    4QJ0X-ray1.55A/B/C/D30-291[»]
    4QJOX-ray1.80A/B/C/D30-291[»]
    4QJWX-ray1.55A/B/C/D30-291[»]
    4WW8X-ray1.42A/B/C/D30-291[»]
    5LL5X-ray1.42A/B/C/D30-291[»]
    5LL9X-ray1.45A/B/C/D30-291[»]
    5LLOX-ray1.60A/B/C/D30-291[»]
    5LLPX-ray1.48A/B/C/D30-291[»]
    5MSAX-ray1.20A/B/C/D30-291[»]
    5MSBX-ray1.30A/B/C/D30-291[»]
    ProteinModelPortaliO43570
    SMRiO43570
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi107225, 8 interactors
    IntActiO43570, 10 interactors
    MINTiO43570
    STRINGi9606.ENSP00000178638

    Chemistry databases

    BindingDBiO43570
    ChEMBLiCHEMBL3242
    DrugBankiDB00562 Benzthiazide
    DB08846 Ellagic Acid
    DB00999 Hydrochlorothiazide
    DB00774 Hydroflumethiazide
    DB00909 Zonisamide
    GuidetoPHARMACOLOGYi2747

    PTM databases

    GlyConnecti1064
    iPTMnetiO43570
    PhosphoSitePlusiO43570

    Polymorphism and mutation databases

    BioMutaiCA12

    Proteomic databases

    EPDiO43570
    MaxQBiO43570
    PaxDbiO43570
    PeptideAtlasiO43570
    PRIDEiO43570
    ProteomicsDBi49059
    49060 [O43570-2]

    Protocols and materials databases

    DNASUi771
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000178638; ENSP00000178638; ENSG00000074410 [O43570-1]
    ENST00000344366; ENSP00000343088; ENSG00000074410 [O43570-2]
    GeneIDi771
    KEGGihsa:771
    UCSCiuc002amc.4 human [O43570-1]

    Organism-specific databases

    CTDi771
    DisGeNETi771
    EuPathDBiHostDB:ENSG00000074410.13
    GeneCardsiCA12
    HGNCiHGNC:1371 CA12
    HPAiCAB025181
    CAB062549
    CAB068179
    HPA008773
    HPA073203
    MalaCardsiCA12
    MIMi143860 phenotype
    603263 gene
    neXtProtiNX_O43570
    OpenTargetsiENSG00000074410
    PharmGKBiPA25987
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG0382 Eukaryota
    COG3338 LUCA
    GeneTreeiENSGT00760000118915
    HOGENOMiHOG000112637
    HOVERGENiHBG002837
    InParanoidiO43570
    KOiK01672
    OMAiHTVGGKH
    OrthoDBiEOG091G0XFM
    PhylomeDBiO43570
    TreeFamiTF316425

    Enzyme and pathway databases

    BRENDAi4.2.1.1 2681
    ReactomeiR-HSA-1475029 Reversible hydration of carbon dioxide

    Miscellaneous databases

    ChiTaRSiCA12 human
    EvolutionaryTraceiO43570
    GeneWikiiCA12
    GenomeRNAii771
    PROiPR:O43570
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000074410 Expressed in 204 organ(s), highest expression level in cortex of kidney
    CleanExiHS_CA12
    ExpressionAtlasiO43570 baseline and differential
    GenevisibleiO43570 HS

    Family and domain databases

    Gene3Di3.10.200.10, 1 hit
    InterProiView protein in InterPro
    IPR001148 CA_dom
    IPR036398 CA_dom_sf
    IPR023561 Carbonic_anhydrase_a-class
    IPR018338 Carbonic_anhydrase_a-class_CS
    IPR018430 Carbonic_anhydrase_CA12
    PANTHERiPTHR18952 PTHR18952, 1 hit
    PTHR18952:SF19 PTHR18952:SF19, 1 hit
    PfamiView protein in Pfam
    PF00194 Carb_anhydrase, 1 hit
    SMARTiView protein in SMART
    SM01057 Carb_anhydrase, 1 hit
    SUPFAMiSSF51069 SSF51069, 1 hit
    PROSITEiView protein in PROSITE
    PS00162 ALPHA_CA_1, 1 hit
    PS51144 ALPHA_CA_2, 1 hit
    ProtoNetiSearch...

    Entry informationi

    Entry nameiCAH12_HUMAN
    AccessioniPrimary (citable) accession number: O43570
    Secondary accession number(s): B2RE24, Q53YE5, Q9BWG2
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: June 1, 1998
    Last modified: November 7, 2018
    This is version 178 of the entry and version 1 of the sequence. See 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families
    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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human chromosome 15
      Human chromosome 15: entries, gene names and cross-references to MIM
    UniProt is an ELIXIR core data resource
    Main funding by: National Institutes of Health

    We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

    Do not show this banner again