Carbonic anhydrase 9

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CA9
Protein CA9 PDB 2HKF.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases CA9, CAIX, MN, carbonic anhydrase 9
External IDs MGI: 2447188 HomoloGene: 20325 GeneCards: CA9
RNA expression pattern
PBB GE CA9 205199 at fs.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001216

NM_139305

RefSeq (protein)

NP_001207

NP_647466

Location (UCSC) Chr 9: 35.67 – 35.68 Mb Chr 4: 43.51 – 43.51 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Carbonic anhydrase 9 (CA9/CAIX) is an enzyme that in humans is encoded by the CA9 gene.[3][4][5]

Function[edit]

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.[5]

Clinical significance[edit]

CAIX is a transmembrane protein and is a tumor-associated carbonic anhydrase isoenzyme. It is over-expressed in VHL mutated clear-cell renal cell carcinoma (ccRCC) and hypoxic solid tumors, but is low-expressed in normal kidney and most other normal tissues. It may be involved in cell proliferation and transformation. This gene is mapped to 9p13-p12.[5]

CAIX is a 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[6] although this association has been questioned.[7]

As a drug target[edit]

Girentuximab, an antibody to carbonic anhydrase IX, is an investigational agent in clinical trials for renal cell carcinoma.[8]

References[edit]

  1. ^ "Human PubMed Reference:". 
  2. ^ "Mouse PubMed Reference:". 
  3. ^ Opavský R, Pastoreková S, Zelník V, Gibadulinová A, Stanbridge EJ, Závada J, Kettmann R, Pastorek J (May 1996). "Human MN/CA9 gene, a novel member of the carbonic anhydrase family: structure and exon to protein domain relationships". Genomics. 33 (3): 480–7. PMID 8661007. doi:10.1006/geno.1996.0223. 
  4. ^ Nakagawa Y, Uemura H, Hirao Y, Yoshida K, Saga S, Yoshikawa K (Oct 1998). "Radiation hybrid mapping of the human MN/CA9 locus to chromosome band 9p12-p13". Genomics. 53 (1): 118–9. PMID 9787087. doi:10.1006/geno.1998.5483. 
  5. ^ a b c "Entrez Gene: CA9 carbonic anhydrase IX". 
  6. ^ Kirkpatrick JP, Rabbani ZN, Bentley RC, Hardee ME, Karol S, Meyer J, Oosterwijk E, Havrilesky L, Secord AA, Vujaskovic Z, Dewhirst MW, Jones EL (2008). "Elevated CAIX Expression is Associated with an Increased Risk of Distant Failure in Early-Stage Cervical Cancer". Biomarker Insights. 3: 45–55. PMC 2688355Freely accessible. PMID 19578493. 
  7. ^ Li J, Zhang G, Wang X, Li XF (2015). "Is carbonic anhydrase IX a validated target for molecular imaging of cancer and hypoxia?". Future Oncology (London, England). 11 (10): 1531–41. PMID 25963430. doi:10.2217/fon.15.11. 
  8. ^ Bedke J, Stenzl A (2013). "Immunotherapeutic strategies for the treatment of renal cell carcinoma: where are we now?". Expert Review of Anticancer Therapy. 13 (12): 1399–408. PMID 24215158. doi:10.1586/14737140.2013.856761. 

Further reading[edit]

  • Nishimori I, Onishi S (2001). "Carbonic anhydrase isozymes in the human pancreas". Digestive and Liver Disease. 33 (1): 68–74. PMID 11303978. doi:10.1016/s1590-8658(01)80138-9. 
  • Pastoreková S, Závadová Z, Kostál M, Babusíková O, Závada J (Apr 1992). "A novel quasi-viral agent, MaTu, is a two-component system". Virology. 187 (2): 620–6. PMID 1312272. doi:10.1016/0042-6822(92)90464-Z. 
  • Pastorek J, Pastoreková S, Callebaut I, Mornon JP, Zelník V, Opavský R, Zat'ovicová M, Liao S, Portetelle D, Stanbridge EJ (Oct 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, Ciampor F, Pastorek J, Zelník V (May 1993). "Expression of MaTu-MN protein in human tumor cultures and in clinical specimens". International Journal of Cancer. 54 (2): 268–74. PMID 8486430. doi:10.1002/ijc.2910540218. 
  • Pastoreková S, Parkkila S, Parkkila AK, Opavský R, Zelník V, Saarnio J, Pastorek J (Feb 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. PMID 9024293. doi:10.1053/gast.1997.v112.pm9024293. 
  • Saarnio J, Parkkila S, Parkkila AK, Waheed A, Casey MC, Zhou XY, Pastoreková S, Pastorek J, Karttunen T, Haukipuro K, Kairaluoma MI, Sly WS (Apr 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". The Journal of Histochemistry and Cytochemistry. 46 (4): 497–504. PMID 9524195. doi:10.1177/002215549804600409. 
  • Ivanov SV, Kuzmin I, Wei MH, Pack S, Geil L, Johnson BE, Stanbridge EJ, Lerman MI (Oct 1998). "Down-regulation of transmembrane carbonic anhydrases in renal cell carcinoma cell lines by wild-type von Hippel-Lindau transgenes". Proceedings of the National Academy of Sciences of the United States of America. 95 (21): 12596–601. PMC 22876Freely accessible. PMID 9770531. doi:10.1073/pnas.95.21.12596. 
  • 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 (Mar 2000). "Molecular cloning and immunogenicity of renal cell carcinoma-associated antigen G250". International Journal of Cancer. 85 (6): 865–70. PMID 10709109. doi:10.1002/(SICI)1097-0215(20000315)85:6<865::AID-IJC21>3.0.CO;2-Q. 
  • Kivelä AJ, Parkkila S, Saarnio J, Karttunen TJ, Kivelä J, Parkkila AK, Pastoreková S, Pastorek J, Waheed A, Sly WS, Rajaniemi H (Sep 2000). "Expression of transmembrane carbonic anhydrase isoenzymes IX and XII in normal human pancreas and pancreatic tumours". Histochemistry and Cell Biology. 114 (3): 197–204. PMID 11083462. doi:10.1007/s004180000181. 
  • Wingo T, Tu C, Laipis PJ, Silverman DN (Nov 2001). "The catalytic properties of human carbonic anhydrase IX". Biochemical and Biophysical Research Communications. 288 (3): 666–9. PMID 11676494. doi:10.1006/bbrc.2001.5824. 
  • Kivela AJ, Saarnio J, Karttunen TJ, Kivelä J, Parkkila AK, Pastorekova S, Pastorek J, Waheed A, Sly WS, Parkkila TS, Rajaniemi H (Oct 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". Digestive Diseases and Sciences. 46 (10): 2179–86. PMID 11680594. doi:10.1023/A:1011910931210. 
  • Koukourakis MI, Giatromanolaki A, Sivridis E, Simopoulos K, Pastorek J, Wykoff CC, Gatter KC, Harris AL (Nov 2001). "Hypoxia-regulated carbonic anhydrase-9 (CA9) relates to poor vascularization and resistance of squamous cell head and neck cancer to chemoradiotherapy". Clinical Cancer Research. 7 (11): 3399–403. PMID 11705854. 
  • Grabmaier K, de Weijert M, Uemura H, Schalken J, Oosterwijk E (Aug 2002). "Renal cell carcinoma-associated G250 methylation and expression: in vivo and in vitro studies". Urology. 60 (2): 357–62. PMID 12137853. doi:10.1016/S0090-4295(02)01711-9. 
  • Kaluz S, Kaluzová M, Chrastina A, Olive PL, Pastoreková S, Pastorek J, Lerman MI, Stanbridge EJ (Aug 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 Research. 62 (15): 4469–77. PMID 12154057. 
  • Swinson DE, Jones JL, Richardson D, Wykoff C, Turley H, Pastorek J, Taub N, Harris AL, O'Byrne KJ (Feb 2003). "Carbonic anhydrase IX expression, a novel surrogate marker of tumor hypoxia, is associated with a poor prognosis in non-small-cell lung cancer". Journal of Clinical Oncology. 21 (3): 473–82. PMID 12560438. doi:10.1200/JCO.2003.11.132. 
  • Bui MH, Seligson D, Han KR, Pantuck AJ, Dorey FJ, Huang Y, Horvath S, Leibovich BC, Chopra S, Liao SY, Stanbridge E, Lerman MI, Palotie A, Figlin RA, Belldegrun AS (Feb 2003). "Carbonic anhydrase IX is an independent predictor of survival in advanced renal clear cell carcinoma: implications for prognosis and therapy". Clinical Cancer Research. 9 (2): 802–11. PMID 12576453.