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P00915 (CAH1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Carbonic anhydrase 1

EC=4.2.1.1
Alternative name(s):
Carbonate dehydratase I
Carbonic anhydrase B
Short name=CAB
Carbonic anhydrase I
Short name=CA-I
Gene names
Name:CA1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length261 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea. Ref.8

Catalytic activity

H2CO3 = CO2 + H2O.

Cofactor

Zinc.

Enzyme regulation

Activated by histamine, imidazole, L-adrenaline, L- and D-histidine, and L- and D-phenylalanine. Inhibited by coumarins, sulfonamide derivatives such as acetazolamide, benzenesulfonamide and derivatives (4-carboxyethylbenzene-sulfonamide, 4-carboxyethylbenzene-sulfonamide ethyl ester, 4-(acetyl-2-aminoethyl)benzene-sulfonamide, 4-aminoethylbenzene-sulfonamide), and 'prong inhibitors' BR15, BR17, BR22 and BR30. Activated by a short exposition to Foscarnet (phosphonoformate trisodium salt), but inhibited by a long one. Esterase activity weakly reduced by cyanamide. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.24 Ref.25 Ref.26

Subcellular location

Cytoplasm.

Sequence similarities

Belongs to the alpha-carbonic anhydrase family.

Biophysicochemical properties

Kinetic parameters:

KM=4.0 mM for CO2 Ref.8 Ref.14

KM=15 mM for 4-nitrophenyl acetate

Ontologies

Keywords
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   LigandMetal-binding
Zinc
   Molecular functionLyase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processbicarbonate transport

Traceable author statement. Source: Reactome

one-carbon metabolic process

Inferred from electronic annotation. Source: InterPro

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

   Molecular_functioncarbonate dehydratase activity

Traceable author statement Ref.2. Source: ProtInc

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.4
Chain2 – 261260Carbonic anhydrase 1
PRO_0000077409

Regions

Region200 – 2012Substrate binding By similarity

Sites

Active site651Proton acceptor By similarity
Active site1291 By similarity
Metal binding651Zinc 2; variant Michigan-1
Metal binding681Zinc 2; variant Michigan-1
Metal binding951Zinc 1; catalytic Ref.17
Metal binding971Zinc 1; catalytic Ref.17
Metal binding1201Zinc 1; catalytic Ref.17
Metal binding2011Zinc 2; variant Michigan-1
Binding site2001Substrate

Amino acid modifications

Modified residue21N-acetylalanine Ref.7

Natural variations

Natural variant681H → R in variant Michigan-1; confers enhanced esterase activity and an additional zinc binding site. Ref.22 Ref.28
VAR_001378
Natural variant1431A → V.
Corresponds to variant rs7821248 [ dbSNP | Ensembl ].
VAR_048679
Natural variant2541G → R in Guam. Ref.27
VAR_001379

Experimental info

Sequence conflict75 – 762DN → ND AA sequence Ref.4
Sequence conflict75 – 762DN → ND AA sequence Ref.5

Secondary structure

.................................................... 261
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P00915 [UniParc].

Last modified January 23, 2007. Version 2.
Checksum: 4959E5FA25E374F8

FASTA26128,870
        10         20         30         40         50         60 
MASPDWGYDD KNGPEQWSKL YPIANGNNQS PVDIKTSETK HDTSLKPISV SYNPATAKEI 

        70         80         90        100        110        120 
INVGHSFHVN FEDNDNRSVL KGGPFSDSYR LFQFHFHWGS TNEHGSEHTV DGVKYSAELH 

       130        140        150        160        170        180 
VAHWNSAKYS SLAEAASKAD GLAVIGVLMK VGEANPKLQK VLDALQAIKT KGKRAPFTNF 

       190        200        210        220        230        240 
DPSTLLPSSL DFWTYPGSLT HPPLYESVTW IICKESISVS SEQLAQFRSL LSNVEGDNAV 

       250        260 
PMQHNNRPTQ PLKGRTVRAS F 

« Hide

References

« Hide 'large scale' references
[1]"Human carbonic anhydrase I cDNA."
Barlow J.H., Lowe N., Edwards Y.H., Butterworth P.H.W.
Nucleic Acids Res. 15:2386-2386(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Structure and methylation patterns of the gene encoding human carbonic anhydrase I."
Lowe N., Brady H.J.M., Barlow J.H., Sowden J.C., Edwards M., Butterworth P.H.W.
Gene 93:277-283(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"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].
Tissue: Pancreas and Spleen.
[4]"Primary structure of human B erythrocyte carbonic anhydrase. 3. Sequence of CNBr fragment I and III (residues 149-260)."
Giraud N., Marriq C., Laurent-Tabusse G.
Biochimie 56:1031-1043(1974) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-261.
[5]"Amino acid sequence of human erythrocyte carbonic anhydrase B."
Andersson B., Nyman P.O., Strid L.
Biochem. Biophys. Res. Commun. 48:670-677(1972) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 20-261.
[6]"Human carbonic anhydrases. XI. The complete primary structure of carbonic anhydrase B."
Lin K.-T.D., Deutsch H.F.
J. Biol. Chem. 248:1885-1893(1973) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 12-261.
[7]"Human carbonic anhydrases. XII. The complete primary structure of the C isozyme."
Lin K.-T.D., Deutsch H.F.
J. Biol. Chem. 249:2329-2337(1974) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[8]"Carbonic anhydrase catalyzes cyanamide hydration to urea: is it mimicking the physiological reaction?"
Briganti F., Mangani S., Scozzafava A., Vernaglione G., Supuran C.T.
J. Biol. Inorg. Chem. 4:528-536(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
[9]"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.
[10]"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.
[11]"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.
[12]"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.
[13]"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.
[14]"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.
[15]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"Structure of human carbonic anhydrase B. I. Crystallization and heavy atom modifications."
Kannan K.K., Fridborg K., Bergsten P.C., Liljas A., Loevgren S., Petef M., Strandberg B., Waara I., Adler L., Falkbring S.O., Goethe P.O., Nyman P.O.
J. Mol. Biol. 63:601-604(1972) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260.
[17]"Crystal structure of human erythrocyte carbonic anhydrase B. Three-dimensional structure at a nominal 2.2-A resolution."
Kannan K.K., Notstrand B., Fridborg K., Loevgren S., Ohlsson A., Petef M.
Proc. Natl. Acad. Sci. U.S.A. 72:51-55(1975) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[18]"Structure, refinement, and function of carbonic anhydrase isozymes: refinement of human carbonic anhydrase I."
Kannan K.K., Ramanadham M., Jones T.A.
Ann. N. Y. Acad. Sci. 429:49-60(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC ION.
[19]"Differences in anionic inhibition of human carbonic anhydrase I revealed from the structures of iodide and gold cyanide inhibitor complexes."
Kumar V., Kannan K.K., Sathyamurthi P.
Acta Crystallogr. D 50:731-738(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC ION AND INHIBITORS.
[20]"Enzyme-substrate interactions. Structure of human carbonic anhydrase I complexed with bicarbonate."
Kumar V., Kannan K.K.
J. Mol. Biol. 241:226-232(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC ION AND BICARBONATE.
[21]"Drug-protein interactions. Refined structures of three sulfonamide drug complexes of human carbonic anhydrase I enzyme."
Chakravarty S., Kannan K.K.
J. Mol. Biol. 243:298-309(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC ION AND INHIBITORS.
[22]"Crystal structure of a zinc-activated variant of human carbonic anhydrase I, CA I Michigan 1: evidence for a second zinc binding site involving arginine coordination."
Ferraroni M., Tilli S., Briganti F., Chegwidden W.R., Supuran C.T., Wiebauer K.E., Tashian R.E., Scozzafava A.
Biochemistry 41:6237-6244(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC ION, VARIANT MICHIGAN-1 ARG-68.
[23]"Carbonic anhydrase activators: the first X-ray crystallographic study of an adduct of isoform I."
Temperini C., Scozzafava A., Supuran C.T.
Bioorg. Med. Chem. Lett. 16:5152-5156(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC ION AND ACTIVATORS, ACTIVATION BY IMIDAZOLE AND HISTIDINE.
[24]"Ultrahigh resolution crystal structures of human carbonic anhydrases I and II complexed with 'two-prong' inhibitors reveal the molecular basis of high affinity."
Jude K.M., Banerjee A.L., Haldar M.K., Manokaran S., Roy B., Mallik S., Srivastava D.K., Christianson D.W.
J. Am. Chem. Soc. 128:3011-3018(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC ION AND INHIBITORS, ENZYME REGULATION.
[25]"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: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 6-260 IN COMPLEX WITH ZINC ION AND THE ANTIVIRAL FOSCARNET, ENZYME REGULATION.
[26]"Structural analysis of charge discrimination in the binding of inhibitors to human carbonic anhydrases I and II."
Srivastava D.K., Jude K.M., Banerjee A.L., Haldar M., Manokaran S., Kooren J., Mallik S., Christianson D.W.
J. Am. Chem. Soc. 129:5528-5537(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 2-260 IN COMPLEX WITH ZINC ION AND INHIBITORS, ENZYME REGULATION.
[27]"Population genetic studies of the Philippine Negritos. III. Identification of the carbonic anhydrase-1 variant with CA1 Guam."
Omoto K., Ueda S., Goriki K., Takahashi N., Misawa S., Pagaran I.G.
Am. J. Hum. Genet. 33:105-111(1981) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GUAM ARG-254.
[28]"Marked zinc activation of ester hydrolysis by a mutation, 67-His (CAT) to Arg (CGT), in the active site of human carbonic anhydrase I."
Chegwidden W.R., Wagner L.E., Venta P.J., Bergenhem N.C.H., Yu Y.-S.L., Tashian R.E.
Hum. Mutat. 4:294-296(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MICHIGAN-1 ARG-68.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X05014 mRNA. Translation: CAA28663.1.
M33987 mRNA. Translation: AAA51910.1.
BC027890 mRNA. Translation: AAH27890.1.
PIRCRHU1. JQ0786.
RefSeqNP_001122301.1. NM_001128829.2.
NP_001122302.1. NM_001128830.2.
NP_001122303.1. NM_001128831.2.
NP_001158302.1. NM_001164830.1.
NP_001729.1. NM_001738.3.
UniGeneHs.23118.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1AZMX-ray2.00A2-260[»]
1BZMX-ray2.00A2-260[»]
1CRMX-ray2.00A2-260[»]
1CZMX-ray2.00A2-260[»]
1HCBX-ray1.60A2-260[»]
1HUGX-ray2.00A2-260[»]
1HUHX-ray2.20A2-260[»]
1J9WX-ray2.60A/B2-260[»]
1JV0X-ray2.00A/B2-260[»]
2CABX-ray2.00A2-260[»]
2FOYX-ray1.55A/B2-260[»]
2FW4X-ray2.00A/B2-260[»]
2IT4X-ray2.00A/B6-260[»]
2NMXX-ray1.55A/B2-261[»]
2NN1X-ray1.65A/B2-260[»]
2NN7X-ray1.85A/B2-260[»]
3LXEX-ray1.90A/B2-261[»]
3W6HX-ray2.96A/B2-261[»]
3W6IX-ray2.69A/E2-261[»]
ProteinModelPortalP00915.
SMRP00915. Positions 4-261.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107214. 2 interactions.
IntActP00915. 2 interactions.
STRING9606.ENSP00000256119.

Chemistry

BindingDBP00915.
ChEMBLCHEMBL2095180.
DrugBankDB00819. Acetazolamide.
DB00381. Amlodipine.
DB00436. Bendroflumethiazide.
DB00562. Benzthiazide.
DB01194. Brinzolamide.
DB00880. Chlorothiazide.
DB00606. Cyclothiazide.
DB01119. Diazoxide.
DB01144. Dichlorphenamide.
DB01031. Ethinamate.
DB00311. Ethoxzolamide.
DB00999. Hydrochlorothiazide.
DB00774. Hydroflumethiazide.
DB01202. Levetiracetam.
DB00703. Methazolamide.
DB00232. Methyclothiazide.
DB01325. Quinethazone.
DB01021. Trichlormethiazide.
DB00661. Verapamil.
DB00909. Zonisamide.
GuidetoPHARMACOLOGY2597.

PTM databases

PhosphoSiteP00915.

Polymorphism databases

DMDM115449.

2D gel databases

DOSAC-COBS-2DPAGEP00915.
REPRODUCTION-2DPAGEIPI00215983.
P00915.
UCD-2DPAGEP00915.

Proteomic databases

PaxDbP00915.
PeptideAtlasP00915.
PRIDEP00915.

Protocols and materials databases

DNASU759.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000256119; ENSP00000256119; ENSG00000133742.
ENST00000431316; ENSP00000392338; ENSG00000133742.
ENST00000432364; ENSP00000401551; ENSG00000133742.
ENST00000523022; ENSP00000429798; ENSG00000133742.
ENST00000523953; ENSP00000430656; ENSG00000133742.
ENST00000542576; ENSP00000443517; ENSG00000133742.
GeneID759.
KEGGhsa:759.
UCSCuc003ydh.3. human.

Organism-specific databases

CTD759.
GeneCardsGC08M086315.
HGNCHGNC:1368. CA1.
HPACAB025790.
HPA006558.
MIM114800. gene.
neXtProtNX_P00915.
PharmGKBPA25984.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3338.
HOGENOMHOG000112637.
HOVERGENHBG002837.
InParanoidP00915.
KOK01672.
OMAETKHDTS.
OrthoDBEOG7WMCK7.
PhylomeDBP00915.
TreeFamTF316425.

Enzyme and pathway databases

BRENDA4.2.1.1. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKP00915.

Gene expression databases

ArrayExpressP00915.
BgeeP00915.
CleanExHS_CA1.
GenevestigatorP00915.

Family and domain databases

Gene3D3.10.200.10. 1 hit.
InterProIPR001148. Carbonic_anhydrase_a.
IPR023561. Carbonic_anhydrase_a-class.
IPR018338. Carbonic_anhydrase_a-class_CS.
IPR018442. Carbonic_anhydrase_CA1.
[Graphical view]
PANTHERPTHR18952. PTHR18952. 1 hit.
PTHR18952:SF30. PTHR18952:SF30. 1 hit.
PfamPF00194. Carb_anhydrase. 1 hit.
[Graphical view]
SMARTSM01057. Carb_anhydrase. 1 hit.
[Graphical view]
SUPFAMSSF51069. SSF51069. 1 hit.
PROSITEPS00162. ALPHA_CA_1. 1 hit.
PS51144. ALPHA_CA_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP00915.
GeneWikiCA1_(gene).
GenomeRNAi759.
NextBio3070.
PROP00915.
SOURCESearch...

Entry information

Entry nameCAH1_HUMAN
AccessionPrimary (citable) accession number: P00915
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 155 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM