NameCarbonic 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 NameCA9
OrganismHuman
Amino acid sequence
>lcl|BSEQ0011744|Carbonic anhydrase 9
MAPLCPSPWLPLLIPAPAPGLTVQLLLSLLLLVPVHPQRLPRMQEDSPLGGGSSGEDDPL
GEEDLPSEEDSPREEDPPGEEDLPGEEDLPGEEDLPEVKPKSEEEGSLKLEDLPTVEAPG
DPQEPQNNAHRDKEGDDQSHWRYGGDPPWPRVSPACAGRFQSPVDIRPQLAAFCPALRPL
ELLGFQLPPLPELRLRNNGHSVQLTLPPGLEMALGPGREYRALQLHLHWGAAGRPGSEHT
VEGHRFPAEIHVVHLSTAFARVDEALGRPGGLAVLAAFLEEGPEENSAYEQLLSRLEEIA
EEGSETQVPGLDISALLPSDFSRYFQYEGSLTTPPCAQGVIWTVFNQTVMLSAKQLHTLS
DTLWGPGDSRLQLNFRATQPLNGRVIEASFPAGVDSSPRAAEPVQLNSCLAAGDILALVF
GLLFAVTSVAFLVQMRRQHRRGTKGGVSYRPAEVAETGA
Number of residues459
Molecular Weight49697.36
Theoretical pI4.36
GO Classification
Functions
  • zinc ion binding
  • carbonate dehydratase activity
Processes
  • cellular response to hypoxia
  • bicarbonate transport
  • one-carbon metabolic process
  • response to testosterone
  • regulation of transcription from RNA polymerase II promoter in response to hypoxia
  • morphogenesis of an epithelium
  • secretion
  • response to drug
  • small molecule metabolic process
Components
  • nucleolus
  • basolateral plasma membrane
  • microvillus membrane
  • plasma membrane
  • integral component of membrane
General FunctionZinc ion binding
Specific FunctionReversible 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 Regions415-435
GenBank Protein IDNot Available
UniProtKB IDQ16790
UniProtKB Entry NameCAH9_HUMAN
Cellular LocationNucleus
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
GenBank Gene IDX66839
GeneCard IDNot Available
GenAtlas IDCA9
HGNC IDHGNC:1383
Chromosome Location9
Locus9p13-p12
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. 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. 10709109
  3. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. 15164053
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 19805286