Carbonic anhydrase 9

Details

Name
Carbonic anhydrase 9
Synonyms
  • 4.2.1.1
  • CA-IX
  • CAIX
  • Carbonate dehydratase IX
  • Carbonic anhydrase IX
  • G250
  • Membrane antigen MN
  • MN
  • P54/58N
  • pMW1
  • RCC-associated antigen G250
  • Renal cell carcinoma-associated antigen G250
Gene Name
CA9
Organism
Humans
Amino acid sequence
>lcl|BSEQ0011744|Carbonic anhydrase 9
MAPLCPSPWLPLLIPAPAPGLTVQLLLSLLLLVPVHPQRLPRMQEDSPLGGGSSGEDDPL
GEEDLPSEEDSPREEDPPGEEDLPGEEDLPGEEDLPEVKPKSEEEGSLKLEDLPTVEAPG
DPQEPQNNAHRDKEGDDQSHWRYGGDPPWPRVSPACAGRFQSPVDIRPQLAAFCPALRPL
ELLGFQLPPLPELRLRNNGHSVQLTLPPGLEMALGPGREYRALQLHLHWGAAGRPGSEHT
VEGHRFPAEIHVVHLSTAFARVDEALGRPGGLAVLAAFLEEGPEENSAYEQLLSRLEEIA
EEGSETQVPGLDISALLPSDFSRYFQYEGSLTTPPCAQGVIWTVFNQTVMLSAKQLHTLS
DTLWGPGDSRLQLNFRATQPLNGRVIEASFPAGVDSSPRAAEPVQLNSCLAAGDILALVF
GLLFAVTSVAFLVQMRRQHRRGTKGGVSYRPAEVAETGA
Number of residues
459
Molecular Weight
49697.36
Theoretical pI
4.36
GO Classification
Functions
carbonate dehydratase activity / zinc ion binding
Processes
bicarbonate transport / cellular response to hypoxia / morphogenesis of an epithelium / one-carbon metabolic process / regulation of transcription from RNA polymerase II promoter in response to hypoxia / response to drug / response to testosterone / secretion / small molecule metabolic process
Components
basolateral plasma membrane / integral component of membrane / microvillus membrane / nucleolus / plasma membrane
General Function
Zinc ion binding
Specific Function
Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.
Pfam Domain Function
Transmembrane Regions
415-435
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0011745|Carbonic anhydrase 9 (CA9)
ATGGCTCCCCTGTGCCCCAGCCCCTGGCTCCCTCTGTTGATCCCGGCCCCTGCTCCAGGC
CTCACTGTGCAACTGCTGCTGTCACTGCTGCTTCTGGTGCCTGTCCATCCCCAGAGGTTG
CCCCGGATGCAGGAGGATTCCCCCTTGGGAGGAGGCTCTTCTGGGGAAGATGACCCACTG
GGCGAGGAGGATCTGCCCAGTGAAGAGGATTCACCCAGAGAGGAGGATCCACCCGGAGAG
GAGGATCTACCTGGAGAGGAGGATCTACCTGGAGAGGAGGATCTACCTGAAGTTAAGCCT
AAATCAGAAGAAGAGGGCTCCCTGAAGTTAGAGGATCTACCTACTGTTGAGGCTCCTGGA
GATCCTCAAGAACCCCAGAATAATGCCCACAGGGACAAAGAAGGGGATGACCAGAGTCAT
TGGCGCTATGGAGGCGACCCGCCCTGGCCCCGGGTGTCCCCAGCCTGCGCGGGCCGCTTC
CAGTCCCCGGTGGATATCCGCCCCCAGCTCGCCGCCTTCTGCCCGGCCCTGCGCCCCCTG
GAACTCCTGGGCTTCCAGCTCCCGCCGCTCCCAGAACTGCGCCTGCGCAACAATGGCCAC
AGTGTGCAACTGACCCTGCCTCCTGGGCTAGAGATGGCTCTGGGTCCCGGGCGGGAGTAC
CGGGCTCTGCAGCTGCATCTGCACTGGGGGGCTGCAGGTCGTCCGGGCTCGGAGCACACT
GTGGAAGGCCACCGTTTCCCTGCCGAGATCCACGTGGTTCACCTCAGCACCGCCTTTGCC
AGAGTTGACGAGGCCTTGGGGCGCCCGGGAGGCCTGGCCGTGTTGGCCGCCTTTCTGGAG
GAGGGCCCGGAAGAAAACAGTGCCTATGAGCAGTTGCTGTCTCGCTTGGAAGAAATCGCT
GAGGAAGGCTCAGAGACTCAGGTCCCAGGACTGGACATATCTGCACTCCTGCCCTCTGAC
TTCAGCCGCTACTTCCAATATGAGGGGTCTCTGACTACACCGCCCTGTGCCCAGGGTGTC
ATCTGGACTGTGTTTAACCAGACAGTGATGCTGAGTGCTAAGCAGCTCCACACCCTCTCT
GACACCCTGTGGGGACCTGGTGACTCTCGGCTACAGCTGAACTTCCGAGCGACGCAGCCT
TTGAATGGGCGAGTGATTGAGGCCTCCTTCCCTGCTGGAGTGGACAGCAGTCCTCGGGCT
GCTGAGCCAGTCCAGCTGAATTCCTGCCTGGCTGCTGGTGACATCCTAGCCCTGGTTTTT
GGCCTCCTTTTTGCTGTCACCAGCGTCGCGTTCCTTGTGCAGATGAGAAGGCAGCACAGA
AGGGGAACCAAAGGGGGTGTGAGCTACCGCCCAGCAGAGGTAGCCGAGACTGGAGCCTAG
Chromosome Location
9
Locus
9p13-p12
External Identifiers
ResourceLink
UniProtKB IDQ16790
UniProtKB Entry NameCAH9_HUMAN
GenBank Gene IDX66839
GenAtlas IDCA9
HGNC IDHGNC:1383
General References
  1. Pastorek J, Pastorekova S, Callebaut I, Mornon JP, Zelnik V, Opavsky R, Zat'ovicova M, Liao S, Portetelle D, Stanbridge EJ, et al.: Cloning and characterization of MN, a human tumor-associated protein with a domain homologous to carbonic anhydrase and a putative helix-loop-helix DNA binding segment. Oncogene. 1994 Oct;9(10):2877-88. [PubMed:8084592]
  2. Grabmaier K, Vissers JL, De Weijert MC, Oosterwijk-Wakka JC, Van Bokhoven A, Brakenhoff RH, Noessner E, Mulders PA, Merkx G, Figdor CG, Adema GJ, Oosterwijk E: Molecular cloning and immunogenicity of renal cell carcinoma-associated antigen G250. Int J Cancer. 2000 Mar 15;85(6):865-70. [PubMed:10709109]
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  5. Zhang Z, Henzel WJ: Signal peptide prediction based on analysis of experimentally verified cleavage sites. Protein Sci. 2004 Oct;13(10):2819-24. Epub 2004 Aug 31. [PubMed:15340161]
  6. Pastorekova S, Zavadova Z, Kostal M, Babusikova O, Zavada J: A novel quasi-viral agent, MaTu, is a two-component system. Virology. 1992 Apr;187(2):620-6. [PubMed:1312272]
  7. Zavada J, Zavadova Z, Pastorekova S, Ciampor F, Pastorek J, Zelnik V: Expression of MaTu-MN protein in human tumor cultures and in clinical specimens. Int J Cancer. 1993 May 8;54(2):268-74. [PubMed:8486430]
  8. Dorai T, Sawczuk IS, Pastorek J, Wiernik PH, Dutcher JP: The role of carbonic anhydrase IX overexpression in kidney cancer. Eur J Cancer. 2005 Dec;41(18):2935-47. [PubMed:16310354]
  9. Kohler K, Hillebrecht A, Schulze Wischeler J, Innocenti A, Heine A, Supuran CT, Klebe G: Saccharin inhibits carbonic anhydrases: possible explanation for its unpleasant metallic aftertaste. Angew Chem Int Ed Engl. 2007;46(40):7697-9. [PubMed:17705204]
  10. 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]
  11. Hilvo M, Baranauskiene L, Salzano AM, Scaloni A, Matulis D, Innocenti A, Scozzafava A, Monti SM, Di Fiore A, De Simone G, Lindfors M, Janis J, Valjakka J, Pastorekova S, Pastorek J, Kulomaa MS, Nordlund HR, Supuran CT, Parkkila S: Biochemical characterization of CA IX, one of the most active carbonic anhydrase isozymes. J Biol Chem. 2008 Oct 10;283(41):27799-809. doi: 10.1074/jbc.M800938200. Epub 2008 Aug 13. [PubMed:18703501]
  12. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648]
  13. 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]
  14. Maresca A, Temperini C, Vu H, Pham NB, Poulsen SA, Scozzafava A, Quinn RJ, Supuran CT: Non-zinc mediated inhibition of carbonic anhydrases: coumarins are a new class of suicide inhibitors. J Am Chem Soc. 2009 Mar 4;131(8):3057-62. doi: 10.1021/ja809683v. [PubMed:19206230]
  15. Kral V, Mader P, Collard R, Fabry M, Horejsi M, Rezacova P, Kozisek M, Zavada J, Sedlacek J, Rulisek L, Brynda J: Stabilization of antibody structure upon association to a human carbonic anhydrase IX epitope studied by X-ray crystallography, microcalorimetry, and molecular dynamics simulations. Proteins. 2008 May 15;71(3):1275-87. [PubMed:18041760]
  16. Alterio V, Hilvo M, Di Fiore A, Supuran CT, Pan P, Parkkila S, Scaloni A, Pastorek J, Pastorekova S, Pedone C, Scozzafava A, Monti SM, De Simone G: Crystal structure of the catalytic domain of the tumor-associated human carbonic anhydrase IX. Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16233-8. doi: 10.1073/pnas.0908301106. Epub 2009 Sep 14. [PubMed:19805286]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB05304GirentuximabinvestigationalunknownDetails
DB00562BenzthiazideapprovedunknowninhibitorDetails
DB00774Hydroflumethiazideapproved, investigationalunknowninhibitorDetails
DB00909Zonisamideapproved, investigationalunknowninhibitorDetails
DB08846Ellagic AcidinvestigationalunknowninhibitorDetails
DB09460Sodium carbonateapprovedunknowninhibitorDetails