Hmdb loader
Identification
HMDB Protein ID HMDBP02058
Secondary Accession Numbers
  • 7537
  • HMDBP04946
Name Carbonic anhydrase 2
Synonyms
  1. CA-II
  2. CAC
  3. Carbonate dehydratase II
  4. Carbonic anhydrase C
  5. Carbonic anhydrase II
Gene Name CA2
Protein Type Unknown
Biological Properties
General Function Involved in carbonate dehydratase activity
Specific Function 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.
Pathways
  • Bile secretion
  • Collecting duct acid secretion
  • Gastric acid secretion
  • Pancreatic secretion
  • Proximal tubule bicarbonate reclamation
Reactions
Hydrogen carbonate → CO(2) + Water details
Hydrogen carbonate → Carbon dioxide + Water details
GO Classification
Biological Process
small molecule metabolic process
response to zinc ion
response to stress
response to pH
bicarbonate transport
carbon dioxide transport
morphogenesis of an epithelium
odontogenesis of dentin-containing tooth
positive regulation of bone resorption
positive regulation of cellular pH reduction
positive regulation of osteoclast differentiation
secretion
kidney development
one-carbon metabolic process
response to estrogen stimulus
Cellular Component
cytosol
apical part of cell
basolateral plasma membrane
extracellular space
microvillus
axon
Function
ion binding
cation binding
metal ion binding
binding
catalytic activity
carbonate dehydratase activity
transition metal ion binding
zinc ion binding
lyase activity
carbon-oxygen lyase activity
hydro-lyase activity
Molecular Function
metal ion binding
zinc ion binding
carbonate dehydratase activity
Process
metabolic process
cellular metabolic process
one-carbon metabolic process
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location 8
Locus 8q22
SNPs CA2
Gene Sequence
>783 bp
ATGTCCCATCACTGGGGGTACGGCAAACACAACGGACCTGAGCACTGGCATAAGGACTTC
CCCATTGCCAAGGGAGAGCGCCAGTCCCCTGTTGACATCGACACTCATACAGCCAAGTAT
GACCCTTCCCTGAAGCCCCTGTCTGTTTCCTATGATCAAGCAACTTCCCTGAGGATCCTC
AACAATGGTCATGCTTTCAACGTGGAGTTTGATGACTCTCAGGACAAAGCAGTGCTCAAG
GGAGGACCCCTGGATGGCACTTACAGATTGATTCAGTTTCACTTTCACTGGGGTTCACTT
GATGGACAAGGTTCAGAGCATACTGTGGATAAAAAGAAATATGCTGCAGAACTTCACTTG
GTTCACTGGAACACCAAATATGGGGATTTTGGGAAAGCTGTGCAGCAACCTGATGGACTG
GCCGTTCTAGGTATTTTTTTGAAGGTTGGCAGCGCTAAACCGGGCCTTCAGAAAGTTGTT
GATGTGCTGGATTCCATTAAAACAAAGGGCAAGAGTGCTGACTTCACTAACTTCGATCCT
CGTGGCCTCCTTCCTGAATCCCTGGATTACTGGACCTACCCAGGCTCACTGACCACCCCT
CCTCTTCTGGAATGTGTGACCTGGATTGTGCTCAAGGAACCCATCAGCGTCAGCAGCGAG
CAGGTGTTGAAATTCCGTAAACTTAACTTCAATGGGGAGGGTGAACCCGAAGAACTGATG
GTGGACAACTGGCGCCCAGCTCAGCCACTGAAGAACAGGCAAATCAAAGCTTCCTTCAAA
TAA
Protein Properties
Number of Residues 260
Molecular Weight 29245.895
Theoretical pI 7.405
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Carbonic anhydrase 2
MSHHWGYGKHNGPEHWHKDFPIAKGERQSPVDIDTHTAKYDPSLKPLSVSYDQATSLRIL
NNGHAFNVEFDDSQDKAVLKGGPLDGTYRLIQFHFHWGSLDGQGSEHTVDKKKYAAELHL
VHWNTKYGDFGKAVQQPDGLAVLGIFLKVGSAKPGLQKVVDVLDSIKTKGKSADFTNFDP
RGLLPESLDYWTYPGSLTTPPLLECVTWIVLKEPISVSSEQVLKFRKLNFNGEGEPEELM
VDNWRPAQPLKNRQIKASFK
GenBank ID Protein 29587
UniProtKB/Swiss-Prot ID P00918
UniProtKB/Swiss-Prot Entry Name CAH2_HUMAN
PDB IDs
GenBank Gene ID Y00339
GeneCard ID CA2
GenAtlas ID CA2
HGNC ID HGNC:1373
References
General References
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  8. Crocetti L, Maresca A, Temperini C, Hall RA, Scozzafava A, Muhlschlegel FA, Supuran CT: A thiabendazole sulfonamide shows potent inhibitory activity against mammalian and nematode alpha-carbonic anhydrases. Bioorg Med Chem Lett. 2009 Mar 1;19(5):1371-5. doi: 10.1016/j.bmcl.2009.01.038. Epub 2009 Jan 19. [PubMed:19186056 ]
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  12. Temperini C, Innocenti A, Guerri A, Scozzafava A, Rusconi S, Supuran CT: 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. Bioorg Med Chem Lett. 2007 Apr 15;17(8):2210-5. Epub 2007 Feb 8. [PubMed:17314045 ]
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  22. Eriksson AE, Jones TA, Liljas A: Refined structure of human carbonic anhydrase II at 2.0 A resolution. Proteins. 1988;4(4):274-82. [PubMed:3151019 ]
  23. Eriksson AE, Kylsten PM, Jones TA, Liljas A: Crystallographic studies of inhibitor binding sites in human carbonic anhydrase II: a pentacoordinated binding of the SCN- ion to the zinc at high pH. Proteins. 1988;4(4):283-93. [PubMed:3151020 ]
  24. Krebs JF, Fierke CA, Alexander RS, Christianson DW: Conformational mobility of His-64 in the Thr-200----Ser mutant of human carbonic anhydrase II. Biochemistry. 1991 Sep 24;30(38):9153-60. [PubMed:1909891 ]
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  26. Nair SK, Calderone TL, Christianson DW, Fierke CA: Altering the mouth of a hydrophobic pocket. Structure and kinetics of human carbonic anhydrase II mutants at residue Val-121. J Biol Chem. 1991 Sep 15;266(26):17320-5. [PubMed:1910042 ]
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  33. Tweedy NB, Nair SK, Paterno SA, Fierke CA, Christianson DW: Structure and energetics of a non-proline cis-peptidyl linkage in a proline-202-->alanine carbonic anhydrase II variant. Biochemistry. 1993 Oct 19;32(41):10944-9. [PubMed:8218160 ]
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  38. Xue Y, Liljas A, Jonsson BH, Lindskog S: Structural analysis of the zinc hydroxide-Thr-199-Glu-106 hydrogen-bond network in human carbonic anhydrase II. Proteins. 1993 Sep;17(1):93-106. [PubMed:7901850 ]
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  45. Boriack PA, Christianson DW, Kingery-Wood J, Whitesides GM: Secondary interactions significantly removed from the sulfonamide binding pocket of carbonic anhydrase II influence inhibitor binding constants. J Med Chem. 1995 Jun 23;38(13):2286-91. [PubMed:7608893 ]
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  47. Huang CC, Lesburg CA, Kiefer LL, Fierke CA, Christianson DW: Reversal of the hydrogen bond to zinc ligand histidine-119 dramatically diminishes catalysis and enhances metal equilibration kinetics in carbonic anhydrase II. Biochemistry. 1996 Mar 19;35(11):3439-46. [PubMed:8639494 ]
  48. Scolnick LR, Christianson DW: X-ray crystallographic studies of alanine-65 variants of carbonic anhydrase II reveal the structural basis of compromised proton transfer in catalysis. Biochemistry. 1996 Dec 24;35(51):16429-34. [PubMed:8987974 ]
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  62. Gruneberg S, Stubbs MT, Klebe G: Successful virtual screening for novel inhibitors of human carbonic anhydrase: strategy and experimental confirmation. J Med Chem. 2002 Aug 15;45(17):3588-602. [PubMed:12166932 ]
  63. Grzybowski BA, Ishchenko AV, Kim CY, Topalov G, Chapman R, Christianson DW, Whitesides GM, Shakhnovich EI: Combinatorial computational method gives new picomolar ligands for a known enzyme. Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1270-3. Epub 2002 Jan 29. [PubMed:11818565 ]
  64. Duda D, Govindasamy L, Agbandje-McKenna M, Tu C, Silverman DN, McKenna R: The refined atomic structure of carbonic anhydrase II at 1.05 A resolution: implications of chemical rescue of proton transfer. Acta Crystallogr D Biol Crystallogr. 2003 Jan;59(Pt 1):93-104. Epub 2002 Dec 19. [PubMed:12499545 ]
  65. Weber A, Casini A, Heine A, Kuhn D, Supuran CT, Scozzafava A, Klebe G: Unexpected nanomolar inhibition of carbonic anhydrase by COX-2-selective celecoxib: new pharmacological opportunities due to related binding site recognition. J Med Chem. 2004 Jan 29;47(3):550-7. [PubMed:14736236 ]
  66. Lloyd MD, Pederick RL, Natesh R, Woo LW, Purohit A, Reed MJ, Acharya KR, Potter BV: Crystal structure of human carbonic anhydrase II at 1.95 A resolution in complex with 667-coumate, a novel anti-cancer agent. Biochem J. 2005 Feb 1;385(Pt 3):715-20. [PubMed:15453828 ]
  67. Fisher Z, Hernandez Prada JA, Tu C, Duda D, Yoshioka C, An H, Govindasamy L, Silverman DN, McKenna R: Structural and kinetic characterization of active-site histidine as a proton shuttle in catalysis by human carbonic anhydrase II. Biochemistry. 2005 Feb 1;44(4):1097-105. [PubMed:15667203 ]
  68. Lloyd MD, Thiyagarajan N, Ho YT, Woo LW, Sutcliffe OB, Purohit A, Reed MJ, Acharya KR, Potter BV: First crystal structures of human carbonic anhydrase II in complex with dual aromatase-steroid sulfatase inhibitors. Biochemistry. 2005 May 10;44(18):6858-66. [PubMed:15865431 ]
  69. Temperini C, Scozzafava A, Puccetti L, Supuran CT: Carbonic anhydrase activators: X-ray crystal structure of the adduct of human isozyme II with L-histidine as a platform for the design of stronger activators. Bioorg Med Chem Lett. 2005 Dec 1;15(23):5136-41. Epub 2005 Oct 7. [PubMed:16214338 ]
  70. Menchise V, De Simone G, Alterio V, Di Fiore A, Pedone C, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: stacking with Phe131 determines active site binding region of inhibitors as exemplified by the X-ray crystal structure of a membrane-impermeant antitumor sulfonamide complexed with isozyme II. J Med Chem. 2005 Sep 8;48(18):5721-7. [PubMed:16134940 ]
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