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Protein

Carbonic anhydrase 2

Gene

CA2

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

Functioni

Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate exchange activity of SLC26A6.By similarity3 Publications

Miscellaneous

Target of drugs used in treatments against glaucoma disorder and breast cancer.

Catalytic activityi

H2CO3 = CO2 + H2O.

Cofactori

Zn2+22 Publications, Co2+1 PublicationNote: Zinc. Can also use cobalt(II) with lower efficiency, but not copper(II), nickel(II) and manganese(II).1 Publication

Enzyme regulationi

Activated by X-ray, histamine, L-adrenaline, L- and D-phenylalanine, L- and D-histidine, L-His-OMe and beta-Ala-His (carnosine). Competitively inhibited by saccharin, thioxolone, coumarins, 667-coumate, celecoxib (Celebrex), valdecoxib (Bextra), SC-125, SC-560, diclofenac, acetate, azide, bromide, sulfonamide derivatives such as acetazolamide (AZA), methazolamide (MZA), ethoxzolamide (EZA), dichlorophenamide (DCP), brinzolamide, dansylamide, thiabendazole-5-sulfonamide, trifluoromethane sulfonamide and N-hydroxysulfamide, fructose-based sugar sulfamate RWJ-37497, and Foscarnet (phosphonoformate trisodium salt). Repressed strongly by hydrogen sulfide(HS) and weakly by nitrate (NO3). Esterase activity weakly reduced by cyanamide. N-hydroxyurea interfers with zinc binding and inhibit activity.27 Publications

Absorptioni

Abs(max)=550 nm10 PublicationsAt pH 7.0. Shows a second maximum at 618 nm.

Kineticsi

  1. KM=10 mM for CO210 Publications
  2. KM=82 mM for H2CO310 Publications
  3. KM=3 mM for 4-nitrophenyl acetate10 Publications

    pH dependencei

    Optimum pH is 6-8.10 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei62Activator3 Publications1
    Active sitei64Proton acceptor3 Publications1
    Active sitei673 Publications1
    Binding sitei67Activator3 Publications1
    Binding sitei92Activator3 Publications1
    Metal bindingi94Zinc; catalytic23 Publications1
    Metal bindingi96Zinc; catalytic22 Publications1
    Metal bindingi119Zinc; catalytic22 Publications1
    Active sitei1273 Publications1

    GO - Molecular functioni

    • arylesterase activity Source: CACAO
    • carbonate dehydratase activity Source: CACAO
    • zinc ion binding Source: UniProtKB

    GO - Biological processi

    Keywordsi

    Molecular functionLyase
    LigandMetal-binding, Zinc

    Enzyme and pathway databases

    BRENDAi4.2.1.1 2681
    ReactomeiR-HSA-1237044 Erythrocytes take up carbon dioxide and release oxygen
    R-HSA-1247673 Erythrocytes take up oxygen and release carbon dioxide
    R-HSA-1475029 Reversible hydration of carbon dioxide
    SABIO-RKiP00918

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Carbonic anhydrase 2 (EC:4.2.1.1)
    Alternative name(s):
    Carbonate dehydratase II
    Carbonic anhydrase C
    Short name:
    CAC
    Carbonic anhydrase II
    Short name:
    CA-II
    Gene namesi
    Name:CA2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 8

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000104267.9
    HGNCiHGNC:1373 CA2
    MIMi611492 gene
    neXtProtiNX_P00918

    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

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Osteopetrosis, autosomal recessive 3 (OPTB3)5 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with mental retardation.
    See also OMIM:259730
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_00138192Q → P in OPTB3; in Czechoslovakia. 2 Publications1
    Natural variantiVAR_02100994H → Y in OPTB3; partial loss of activity. 1 Publication1
    Natural variantiVAR_001382107H → Y in OPTB3; frequent mutation. 4 PublicationsCorresponds to variant dbSNP:rs118203933EnsemblClinVar.1
    Natural variantiVAR_021010144G → R in OPTB3; complete loss of activity. 1 Publication1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi5W → A: Impaired activity, not rescued by 4-methylimidazole (4-MI); when associated with W-64. 1 Publication1
    Mutagenesisi7Y → F: Enhanced activity. 2 Publications1
    Mutagenesisi7Y → H: Reduced proton transfer rate. 2 Publications1
    Mutagenesisi62N → A: Reduced activity. 3 Publications1
    Mutagenesisi62N → D: Strongly reduced activity. 3 Publications1
    Mutagenesisi62N → H: Reduced proton transfer; when associated with A-64. 3 Publications1
    Mutagenesisi62N → L: Reduced activity. 3 Publications1
    Mutagenesisi62N → T: Reduced activity. 3 Publications1
    Mutagenesisi62N → V: Reduced activity. 3 Publications1
    Mutagenesisi64H → A: Reduced CO(2) hydrase activity, rescued by 4-methylimidazole (4-MI). Reduced proton transfer; when associated with H-62. Enhanced proton transfer; when associated with H-67. Enhanced proton transfer capacity; when associated with H-99. 4 Publications1
    Mutagenesisi64H → G: Impaired activity, not rescued by 4-methylimidazole (4-MI). 4 Publications1
    Mutagenesisi64H → W: Impaired activity, rescued by 4-methylimidazole (4-MI). Impaired activity, not rescued by 4-methylimidazole (4-MI); when associated with A-5. 4 Publications1
    Mutagenesisi65A → F: Reduced activity. 1 Publication1
    Mutagenesisi65A → H, L or S: Normal activity. 1 Publication1
    Mutagenesisi67N → H: Enhanced proton transfer; when associated with A-64. 3 Publications1
    Mutagenesisi67N → L: Reduced activity. 3 Publications1
    Mutagenesisi67N → Q: Normal activity. 3 Publications1
    Mutagenesisi94H → C, D, E, N or Q: Strongly reduced CO(2) hydrase and p-nitrophenyl acetate esterase activities, impaired stability of zinc binding. 2 Publications1
    Mutagenesisi106E → A or Q: Strongly reduced CO(2) hydrase activity. 2 Publications1
    Mutagenesisi106E → D: Normal CO(2) hydrase activity. 2 Publications1
    Mutagenesisi117E → Q: Strongly reduced activity and sulfonamide affinity. 1 Publication1
    Mutagenesisi119H → D, N or Q: Reduced activity. 1 Publication1
    Mutagenesisi119H → E: Strongly reduced activity. 1 Publication1
    Mutagenesisi121V → A, G, I, L or S: Reduced CO(2) hydrase and p-nitrophenyl acetate esterase activities. 1 Publication1
    Mutagenesisi121V → K or R: Strongly reduced CO(2) hydrase and p-nitrophenyl acetate esterase activities. 1 Publication1
    Mutagenesisi142V → F or Y: Strongly impaired activity. 1 Publication1
    Mutagenesisi142V → G: Weakly impaired activity. 1 Publication1
    Mutagenesisi142V → H: Impaired activity. 1 Publication1
    Mutagenesisi197L → A: Reduced CO(2) hydrase activity. 1 Publication1
    Mutagenesisi197L → E, H or R: Strongly reduced CO(2) hydrase activity. 1 Publication1
    Mutagenesisi197L → F: Normal activity. 1 Publication1
    Mutagenesisi198T → A, C, H or P: Strongly reduced activity. 5 Publications1
    Mutagenesisi198T → D or E: Strongly reduced activity, but enhanced zinc affinity. 5 Publications1
    Mutagenesisi198T → S or V: Reduced activity. 5 Publications1
    Mutagenesisi199T → H: Higher affinity for bicarbonate. Enhanced proton transfer capacity; when associated with A-64. 3 Publications1
    Mutagenesisi199T → S: Enhanced p-nitrophenyl acetate esterase activity, but normal CO(2) hydrase activity. 3 Publications1
    Mutagenesisi201P → A: Normal CO(2) hydrase activity, but impaired stability. 1 Publication1

    Keywords - Diseasei

    Disease mutation, Osteopetrosis

    Organism-specific databases

    DisGeNETi760
    MalaCardsiCA2
    MIMi259730 phenotype
    OpenTargetsiENSG00000104267
    Orphaneti2785 Osteopetrosis with renal tubular acidosis
    PharmGKBiPA25989

    Chemistry databases

    ChEMBLiCHEMBL205
    DrugBankiDB03333 (4-sulfamoyl-phenyl)-thiocarbamic acid O-(2-thiophen-3-yl-ethyl) ester
    DB02479 (R)-N-(3-Indol-1-Yl-2-Methyl-Propyl)-4-Sulfamoyl-Benzamide
    DB03950 (S)-N-(3-Indol-1-Yl-2-Methyl-Propyl)-4-Sulfamoyl-Benzamide
    DB08659 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide
    DB08046 2-chloro-5-[(1S)-1-hydroxy-3-oxo-2H-isoindol-1-yl]benzenesulfonamide
    DB08156 3-[4-(AMINOSULFONYL)PHENYL]PROPANOIC ACID
    DB04203 3-Mercuri-4-Aminobenzenesulfonamide
    DB04394 3-Nitro-4-(2-Oxo-Pyrrolidin-1-Yl)-Benzenesulfonamide
    DB08782 4-(2-AMINOETHYL)BENZENESULFONAMIDE
    DB02429 4-(Aminosulfonyl)-N-[(4-Fluorophenyl)Methyl]-Benzamide
    DB01671 4-(Hydroxymercury)Benzoic Acid
    DB08202 4-({[(4-METHYLPIPERAZIN-1-YL)AMINO]CARBONOTHIOYL}AMINO)BENZENESULFONAMIDE
    DB01784 4-Flourobenzenesulfonamide
    DB03385 4-Methylimidazole
    DB03697 4-Sulfonamide-[1-(4-Aminobutane)]Benzamide
    DB04002 4-Sulfonamide-[4-(Thiomethylaminobutane)]Benzamide
    DB00819 Acetazolamide
    DB03877 AL4623
    DB04089 AL5300
    DB01964 AL5424
    DB03526 AL5927
    DB04371 AL6528
    DB02220 Al7089a
    DB03221 AL7099A
    DB02602 AL7182
    DB02535 Aminodi(Ethyloxy)Ethylaminocarbonylbenzenesulfonamide
    DB00436 Bendroflumethiazide
    DB00562 Benzthiazide
    DB01194 Brinzolamide
    DB00880 Chlorothiazide
    DB02679 Cyanamide
    DB00606 Cyclothiazide
    DB02866 Dansylamide
    DB01119 Diazoxide
    DB01144 Diclofenamide
    DB00869 Dorzolamide
    DB08846 Ellagic Acid
    DB01031 Ethinamate
    DB00311 Ethoxzolamide
    DB08157 ETHYL 3-[4-(AMINOSULFONYL)PHENYL]PROPANOATE
    DB01942 Formic Acid
    DB00695 Furosemide
    DB00999 Hydrochlorothiazide
    DB00774 Hydroflumethiazide
    DB08165 indane-5-sulfonamide
    DB03975 Mercuribenzoic Acid
    DB00703 Methazolamide
    DB00232 Methyclothiazide
    DB02069 N-(2-Flouro-Benzyl)-4-Sulfamoyl-Benzamide
    DB08301 N-({[4-(AMINOSULFONYL)PHENYL]AMINO}CARBONYL)-4-METHYLBENZENESULFONAMIDE
    DB03596 N-[2-(1h-Indol-5-Yl)-Butyl]-4-Sulfamoyl-Benzamide
    DB07476 N-[4-(AMINOSULFONYL)PHENYL]-2-MERCAPTOBENZAMIDE
    DB01748 N-Benzyl-4-Sulfamoyl-Benzamide
    DB08155 N-{2-[4-(AMINOSULFONYL)PHENYL]ETHYL}ACETAMIDE
    DB07710 PHENYLALANYLAMINODI(ETHYLOXY)ETHYL BENZENESULFONAMIDEAMINOCARBONYLBENZENESULFONAMIDE
    DB01325 Quinethazone
    DB09460 Sodium carbonate
    DB08329 SULTHIAME
    DB00273 Topiramate
    DB01021 Trichlormethiazide
    DB03904 Urea
    DB00909 Zonisamide

    Polymorphism and mutation databases

    BioMutaiCA2

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemoved2 Publications
    ChainiPRO_00000774182 – 260Carbonic anhydrase 2Add BLAST259

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei2N-acetylserine2 Publications1
    Modified residuei2PhosphoserineBy similarity1
    Modified residuei165PhosphoserineCombined sources1
    Modified residuei172PhosphoserineCombined sources1

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    EPDiP00918
    PaxDbiP00918
    PeptideAtlasiP00918
    PRIDEiP00918
    ProteomicsDBi12616
    51292

    2D gel databases

    OGPiP00918
    REPRODUCTION-2DPAGEiIPI00218414
    P00918
    UCD-2DPAGEiP00918

    PTM databases

    iPTMnetiP00918
    PhosphoSitePlusiP00918

    Expressioni

    Gene expression databases

    BgeeiENSG00000104267
    CleanExiHS_CA2
    ExpressionAtlasiP00918 baseline and differential
    GenevisibleiP00918 HS

    Organism-specific databases

    HPAiCAB010102
    HPA001550

    Interactioni

    Subunit structurei

    Interacts with SLC4A4. Interaction with SLC4A7 regulates SLC4A7 transporter activity. Interacts with SLC26A6 isoform 4 (via C-terminus cytoplasmic domain).90 Publications

    Protein-protein interaction databases

    BioGridi107215, 14 interactors
    IntActiP00918, 6 interactors
    MINTiP00918
    STRINGi9606.ENSP00000285379

    Chemistry databases

    BindingDBiP00918

    Structurei

    Secondary structure

    1260
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi6 – 8Combined sources3
    Turni9 – 11Combined sources3
    Turni13 – 15Combined sources3
    Helixi16 – 18Combined sources3
    Helixi21 – 24Combined sources4
    Beta strandi25 – 27Combined sources3
    Beta strandi31 – 33Combined sources3
    Turni35 – 37Combined sources3
    Beta strandi38 – 40Combined sources3
    Beta strandi42 – 44Combined sources3
    Beta strandi45 – 50Combined sources6
    Beta strandi56 – 61Combined sources6
    Beta strandi63 – 70Combined sources8
    Beta strandi73 – 75Combined sources3
    Beta strandi77 – 82Combined sources6
    Turni83 – 85Combined sources3
    Beta strandi88 – 97Combined sources10
    Beta strandi106 – 109Combined sources4
    Beta strandi115 – 124Combined sources10
    Helixi125 – 127Combined sources3
    Helixi130 – 133Combined sources4
    Beta strandi139 – 151Combined sources13
    Helixi154 – 156Combined sources3
    Helixi157 – 162Combined sources6
    Helixi163 – 165Combined sources3
    Beta strandi172 – 174Combined sources3
    Helixi180 – 183Combined sources4
    Beta strandi190 – 195Combined sources6
    Beta strandi206 – 213Combined sources8
    Beta strandi215 – 217Combined sources3
    Helixi219 – 225Combined sources7
    Turni226 – 228Combined sources3
    Beta strandi229 – 231Combined sources3
    Beta strandi233 – 235Combined sources3
    Beta strandi247 – 249Combined sources3
    Beta strandi251 – 253Combined sources3
    Beta strandi256 – 258Combined sources3

    3D structure databases

    ProteinModelPortaliP00918
    SMRiP00918
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP00918

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini3 – 259Alpha-carbonic anhydrasePROSITE-ProRule annotationAdd BLAST257

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni198 – 199Substrate binding2 Publications2

    Sequence similaritiesi

    Belongs to the alpha-carbonic anhydrase family.Curated

    Phylogenomic databases

    eggNOGiKOG0382 Eukaryota
    COG3338 LUCA
    GeneTreeiENSGT00760000118915
    HOGENOMiHOG000112637
    HOVERGENiHBG002837
    InParanoidiP00918
    KOiK18245
    OMAiHTVDKKK
    OrthoDBiEOG091G0XFM
    PhylomeDBiP00918
    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
    PANTHERiPTHR18952 PTHR18952, 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

    Sequencei

    Sequence statusi: Complete.

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

    P00918-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSHHWGYGKH NGPEHWHKDF PIAKGERQSP VDIDTHTAKY DPSLKPLSVS
    60 70 80 90 100
    YDQATSLRIL NNGHAFNVEF DDSQDKAVLK GGPLDGTYRL IQFHFHWGSL
    110 120 130 140 150
    DGQGSEHTVD KKKYAAELHL VHWNTKYGDF GKAVQQPDGL AVLGIFLKVG
    160 170 180 190 200
    SAKPGLQKVV DVLDSIKTKG KSADFTNFDP RGLLPESLDY WTYPGSLTTP
    210 220 230 240 250
    PLLECVTWIV LKEPISVSSE QVLKFRKLNF NGEGEPEELM VDNWRPAQPL
    260
    KNRQIKASFK
    Length:260
    Mass (Da):29,246
    Last modified:January 23, 2007 - v2
    Checksum:i2EC2BB7548F10558
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti179 – 180DP → AA in AAH11949 (PubMed:15489334).Curated2

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_00138018K → E in Jogjakarta. 1 PublicationCorresponds to variant dbSNP:rs118203931EnsemblClinVar.1
    Natural variantiVAR_00138192Q → P in OPTB3; in Czechoslovakia. 2 Publications1
    Natural variantiVAR_02100994H → Y in OPTB3; partial loss of activity. 1 Publication1
    Natural variantiVAR_001382107H → Y in OPTB3; frequent mutation. 4 PublicationsCorresponds to variant dbSNP:rs118203933EnsemblClinVar.1
    Natural variantiVAR_021010144G → R in OPTB3; complete loss of activity. 1 Publication1
    Natural variantiVAR_001383236P → H in Melbourne. 1 PublicationCorresponds to variant dbSNP:rs118203932EnsemblClinVar.1
    Natural variantiVAR_001384252N → D. Corresponds to variant dbSNP:rs2228063EnsemblClinVar.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M77181
    , M77176, M77177, M77178, M77179, M77180 Genomic DNA Translation: AAA51909.1
    Y00339 mRNA Translation: CAA68426.1
    X03251 Genomic DNA Translation: CAA27012.1
    J03037 mRNA Translation: AAA51908.1
    CR536526 mRNA Translation: CAG38763.1
    CR541875 mRNA Translation: CAG46673.1
    AK312978 mRNA Translation: BAG35815.1
    CH471068 Genomic DNA Translation: EAW87136.1
    BC011949 mRNA Translation: AAH11949.1
    M36532 mRNA Translation: AAA51911.1
    CCDSiCCDS6239.1
    PIRiA27175 CRHU2
    RefSeqiNP_000058.1, NM_000067.2
    UniGeneiHs.155097

    Genome annotation databases

    EnsembliENST00000285379; ENSP00000285379; ENSG00000104267
    GeneIDi760
    KEGGihsa:760

    Keywords - Coding sequence diversityi

    Polymorphism

    Similar proteinsi