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Protein

Carbonic anhydrase 12

Gene

CA12

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.

Catalytic activityi

H2CO3 = CO2 + H2O.

Cofactori

Zn2+1 Publication

Enzyme 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
    • one-carbon metabolic process Source: InterPro
    Complete GO annotation...

    Keywords - Molecular functioni

    Lyase

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    BioCyciZFISH:HS01139-MONOMER.
    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

    HGNCiHGNC:1371. CA12.

    Subcellular locationi

    Topology

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

    GO - Cellular componenti

    • integral component of membrane Source: ProtInc
    • plasma membrane Source: Reactome
    Complete GO annotation...

    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 rs267606694dbSNPEnsembl.1

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNETi771.
    MalaCardsiCA12.
    MIMi143860. phenotype.
    OpenTargetsiENSG00000074410.
    PharmGKBiPA25987.

    Chemistry databases

    ChEMBLiCHEMBL3242.
    DrugBankiDB00562. Benzthiazide.
    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...)Sequence analysis1
    Disulfide bondi50 ↔ 2301 Publication
    Glycosylationi80N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi162N-linked (GlcNAc...)Sequence analysis1

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    MaxQBiO43570.
    PaxDbiO43570.
    PeptideAtlasiO43570.
    PRIDEiO43570.

    PTM databases

    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.
    CleanExiHS_CA12.
    ExpressionAtlasiO43570. baseline and differential.
    GenevisibleiO43570. HS.

    Organism-specific databases

    HPAiCAB025181.
    CAB062549.
    CAB068179.
    HPA008773.

    Interactioni

    Subunit structurei

    Homodimer.1 Publication

    Protein-protein interaction databases

    BioGridi107225. 8 interactors.
    IntActiO43570. 10 interactors.
    MINTiMINT-1392387.
    STRINGi9606.ENSP00000178638.

    Chemistry databases

    BindingDBiO43570.

    Structurei

    Secondary structure

    1354
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi36 – 38Combined sources3
    Helixi40 – 42Combined sources3
    Turni43 – 46Combined sources4
    Helixi48 – 51Combined sources4
    Beta strandi52 – 54Combined sources3
    Helixi62 – 64Combined sources3
    Beta strandi65 – 67Combined sources3
    Beta strandi75 – 78Combined sources4
    Beta strandi85 – 91Combined sources7
    Beta strandi93 – 99Combined sources7
    Beta strandi105 – 111Combined sources7
    Beta strandi113 – 122Combined sources10
    Beta strandi132 – 135Combined sources4
    Beta strandi141 – 150Combined sources10
    Turni151 – 153Combined sources3
    Helixi157 – 160Combined sources4
    Beta strandi167 – 176Combined sources10
    Helixi181 – 187Combined sources7
    Helixi188 – 193Combined sources6
    Beta strandi199 – 203Combined sources5
    Helixi207 – 210Combined sources4
    Turni213 – 216Combined sources4
    Beta strandi218 – 223Combined sources6
    Beta strandi234 – 241Combined sources8
    Beta strandi243 – 245Combined sources3
    Helixi247 – 255Combined sources9
    Beta strandi258 – 260Combined sources3
    Beta strandi285 – 288Combined sources4

    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[»]
    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
    Contains 1 alpha-carbonic anhydrase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG0382. Eukaryota.
    COG3338. LUCA.
    GeneTreeiENSGT00760000118915.
    HOGENOMiHOG000112637.
    HOVERGENiHBG002837.
    InParanoidiO43570.
    KOiK01672.
    OMAiPPCYPTV.
    OrthoDBiEOG091G0XFM.
    PhylomeDBiO43570.
    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.
    IPR018430. Carbonic_anhydrase_CA12.
    [Graphical view]
    PANTHERiPTHR18952. PTHR18952. 1 hit.
    PTHR18952:SF19. PTHR18952:SF19. 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]

    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

    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

    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 rs267606694dbSNPEnsembl.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

    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[»]
    ProteinModelPortaliO43570.
    SMRiO43570.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi107225. 8 interactors.
    IntActiO43570. 10 interactors.
    MINTiMINT-1392387.
    STRINGi9606.ENSP00000178638.

    Chemistry databases

    BindingDBiO43570.
    ChEMBLiCHEMBL3242.
    DrugBankiDB00562. Benzthiazide.
    DB00999. Hydrochlorothiazide.
    DB00774. Hydroflumethiazide.
    DB00909. Zonisamide.
    GuidetoPHARMACOLOGYi2747.

    PTM databases

    iPTMnetiO43570.
    PhosphoSitePlusiO43570.

    Polymorphism and mutation databases

    BioMutaiCA12.

    Proteomic databases

    MaxQBiO43570.
    PaxDbiO43570.
    PeptideAtlasiO43570.
    PRIDEiO43570.

    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.
    GeneCardsiCA12.
    HGNCiHGNC:1371. CA12.
    HPAiCAB025181.
    CAB062549.
    CAB068179.
    HPA008773.
    MalaCardsiCA12.
    MIMi143860. phenotype.
    603263. gene.
    neXtProtiNX_O43570.
    OpenTargetsiENSG00000074410.
    PharmGKBiPA25987.
    GenAtlasiSearch...

    Phylogenomic databases

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

    Enzyme and pathway databases

    BioCyciZFISH:HS01139-MONOMER.
    BRENDAi4.2.1.1. 2681.
    ReactomeiR-HSA-1475029. Reversible hydration of carbon dioxide.

    Miscellaneous databases

    ChiTaRSiCA12. human.
    EvolutionaryTraceiO43570.
    GeneWikiiCA12.
    GenomeRNAii771.
    PROiO43570.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000074410.
    CleanExiHS_CA12.
    ExpressionAtlasiO43570. baseline and differential.
    GenevisibleiO43570. 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.
    IPR018430. Carbonic_anhydrase_CA12.
    [Graphical view]
    PANTHERiPTHR18952. PTHR18952. 1 hit.
    PTHR18952:SF19. PTHR18952:SF19. 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...

    Entry informationi

    Entry nameiCAH12_HUMAN
    AccessioniPrimary (citable) accession number: O43570
    Secondary accession number(s): B2RE24, Q53YE5, Q9BWG2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: June 1, 1998
    Last modified: November 2, 2016
    This is version 164 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 15
      Human chromosome 15: 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    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 one 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.