Carbonic anhydrase 9

Carbonic anhydrase IX
Rendering based on PDB 2HKF.
Available structures PDB 2HKF, 3IAI
Identifiers
Symbols	CA9; CAIX; MN
External IDs	OMIM: 603179 MGI: 2447188 HomoloGene: 20325 GeneCards: CA9 Gene
EC number	4.2.1.1
Gene Ontology Molecular function • carbonate dehydratase activity • zinc ion binding • lyase activity • metal ion binding Cellular component • nucleus • nucleolus • plasma membrane • integral to membrane • microvillus membrane • cell projection Biological process • morphogenesis of an epithelium • one-carbon metabolic process • secretion Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	768	230099
Ensembl	ENSG00000107159	ENSMUSG00000028463
UniProt	Q16790	Q8VHB5
RefSeq (mRNA)	NM_001216.2	NM_139305.2
RefSeq (protein)	NP_001207.2	NP_647466.2
Location (UCSC)	Chr 9: 35.67 – 35.68 Mb	Chr 4: 43.52 – 43.53 Mb
PubMed search	[1]	[2]

Carbonic anhydrase 9 is an enzyme that in humans is encoded by the CA9 gene.

Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. They show extensive diversity in tissue distribution and in their subcellular localization. CA IX is a transmembrane protein and the only tumor-associated carbonic anhydrase isoenzyme known. It is expressed in all clear-cell renal cell carcinoma, but is not detected in normal kidney or most other normal tissues. It may be involved in cell proliferation and transformation. This gene was mapped to 17q21.2 by fluorescence in situ hybridization, however, radiation hybrid mapping localized it to 9p13-p12.

CAIX is considered to be one of the best cellular biomarkers of hypoxia. Furthermore, recent studies examining the association between CAIX levels and various clinicopathological outcomes suggest that CAIX expression may also be a valuable prognostic indicator for overall survival. Antibodies against CAIX serve as excellent excellent biomarkers of hypoxic regions in many solid tumors.

Further reading

• Nishimori I, Onishi S (2001). "Carbonic anhydrase isozymes in the human pancreas.". Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 33 (1): 68–74. PMID 11303978. 
• Pastoreková S, Závadová Z, Kostál M, et al. (1992). "A novel quasi-viral agent, MaTu, is a two-component system.". Virology 187 (2): 620–6. doi:10.1016/0042-6822(92)90464-Z. PMID 1312272. 
• Pastorek J, Pastoreková S, Callebaut I, et al. (1994). "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 9 (10): 2877–88. PMID 8084592. 
• Závada J, Závadová Z, Pastoreková S, et al. (1993). "Expression of MaTu-MN protein in human tumor cultures and in clinical specimens.". Int. J. Cancer 54 (2): 268–74. doi:10.1002/ijc.2910540218. PMID 8486430. 
• Pastoreková S, Parkkila S, Parkkila AK, et al. (1997). "Carbonic anhydrase IX, MN/CA IX: analysis of stomach complementary DNA sequence and expression in human and rat alimentary tracts.". Gastroenterology 112 (2): 398–408. doi:10.1053/gast.1997.v112.pm9024293. PMID 9024293. 
• Saarnio J, Parkkila S, Parkkila AK, et al. (1998). "Immunohistochemistry of carbonic anhydrase isozyme IX (MN/CA IX) in human gut reveals polarized expression in the epithelial cells with the highest proliferative capacity.". J. Histochem. Cytochem. 46 (4): 497–504. PMID 9524195. 
• Ivanov SV, Kuzmin I, Wei MH, et al. (1998). "Down-regulation of transmembrane carbonic anhydrases in renal cell carcinoma cell lines by wild-type von Hippel-Lindau transgenes.". Proc. Natl. Acad. Sci. U.S.A. 95 (21): 12596–601. doi:10.1073/pnas.95.21.12596. PMC 22876. PMID 9770531. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=22876. 
• Grabmaier K, Vissers JL, De Weijert MC, et al. (2000). "Molecular cloning and immunogenicity of renal cell carcinoma-associated antigen G250.". Int. J. Cancer 85 (6): 865–70. doi:10.1002/(SICI)1097-0215(20000315)85:6<865::AID-IJC21>3.0.CO;2-Q. PMID 10709109. 
• Kivelä AJ, Parkkila S, Saarnio J, et al. (2001). "Expression of transmembrane carbonic anhydrase isoenzymes IX and XII in normal human pancreas and pancreatic tumours.". Histochem. Cell Biol. 114 (3): 197–204. PMID 11083462. 
• Wingo T, Tu C, Laipis PJ, Silverman DN (2001). "The catalytic properties of human carbonic anhydrase IX.". Biochem. Biophys. Res. Commun. 288 (3): 666–9. doi:10.1006/bbrc.2001.5824. PMID 11676494. 
• Kivela AJ, Saarnio J, Karttunen TJ, et al. (2001). "Differential expression of cytoplasmic carbonic anhydrases, CA I and II, and membrane-associated isozymes, CA IX and XII, in normal mucosa of large intestine and in colorectal tumors.". Dig. Dis. Sci. 46 (10): 2179–86. doi:10.1023/A:1011910931210. PMID 11680594. 
• Koukourakis MI, Giatromanolaki A, Sivridis E, et al. (2002). "Hypoxia-regulated carbonic anhydrase-9 (CA9) relates to poor vascularization and resistance of squamous cell head and neck cancer to chemoradiotherapy.". Clin. Cancer Res. 7 (11): 3399–403. PMID 11705854. 
• Grabmaier K, de Weijert M, Uemura H, et al. (2002). "Renal cell carcinoma-associated G250 methylation and expression: in vivo and in vitro studies.". Urology 60 (2): 357–62. doi:10.1016/S0090-4295(02)01711-9. PMID 12137853. 
• Kaluz S, Kaluzová M, Chrastina A, et al. (2002). "Lowered oxygen tension induces expression of the hypoxia marker MN/carbonic anhydrase IX in the absence of hypoxia-inducible factor 1 alpha stabilization: a role for phosphatidylinositol 3'-kinase.". Cancer Res. 62 (15): 4469–77. PMID 12154057. 
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Swinson DE, Jones JL, Richardson D, et al. (2003). "Carbonic anhydrase IX expression, a novel surrogate marker of tumor hypoxia, is associated with a poor prognosis in non-small-cell lung cancer.". J. Clin. Oncol. 21 (3): 473–82. doi:10.1200/JCO.2003.11.132. PMID 12560438. 
• Bui MH, Seligson D, Han KR, et al. (2003). "Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy.". Clin. Cancer Res. 9 (2): 802–11. PMID 12576453.