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Gene Review

CA5B  -  carbonic anhydrase VB, mitochondrial

Homo sapiens

Synonyms: CA-VB, Carbonate dehydratase VB, Carbonic anhydrase 5B, mitochondrial, Carbonic anhydrase VB
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Disease relevance of CA5B

  • OBJECTIVES: We reviewed our institution's experience with isolated (congenital) third-degree atrioventricular block (CAVB) to identify pre- and post-natal predictors of mortality and the requirement for pacemakers in infancy and childhood [1].
  • Increased mortality risk was associated with a fetal diagnosis of CAVB (13/15 deaths; p < 0.05), fetal hydrops (6/6 cases; p < 0.0001), endocardial fibroelastosis (5/5 cases; p < 0.0001) and delivery at < or = 32 weeks (4/6 cases; p < 0.05) [1].
  • Hypertrophy had only developed completely at 5 weeks CAVB [2].
  • CAVBP/DEP alternating chemotherapy for the treatment of intermediate and high grade non Hodgkin's lymphoma: final results of a pilot study [3].
  • Fifty four patients with squamous cell lung cancer, treated with Cyclophosphamide (750 mg/m2), Adriamycin (50 mg/m2), Vincristine (1.5 mg/m2) and Bleomycin (30 mg) (CAVB) in a 2 day scheduled regime, showed an overall median survival time (MST) of 32 weeks (28 weeks for non-responders and 46.5 weeks for responders--a non-significant difference) [4].

High impact information on CA5B

  • Analysis of phylogenetic relationships between these and other available human and mouse CA isozyme sequences revealed that mammalian CA VB evolved much more slowly than CA VA, accepting amino acid substitutions at least 4.5 times more slowly since each evolved from its respective human-mouse ancestral gene around 90 million years ago [5].
  • Both the differences in tissue distribution and the much greater evolutionary constraints on CA VB sequences suggest that CA VB and CA VA have evolved to assume different physiological roles [5].
  • Several lines of evidence suggest that the cDNA clone presented herein encodes a novel human mitochondrial CA isozyme, designated CA VB [6].
  • 1. Northern blot analysis in normal human tissues demonstrated expression of a 1.3-kilobase transcript in heart and skeletal muscle, and reverse transcription-polymerase chain reaction analysis showed expression of CA VB in pancreas, kidney, salivary glands, and spinal cord but not in liver [6].
  • Human mitochondrial carbonic anhydrase VB. cDNA cloning, mRNA expression, subcellular localization, and mapping to chromosome x [6].

Chemical compound and disease context of CA5B

  • The addition of Cis-platinum (50 mg/m2) to the unscheduled CAVB regime (CAVBP) in a further 22 patients did not result in an improvement either in survival or response, but added to the toxicity [4].

Anatomical context of CA5B

  • BACKGROUND: Because of the relative rarity of the disease, there is a paucity of data concerning the outcome of fetuses and children with isolated CAVB [1].
  • Eighteen patients (14 men and 4 women, aged 70 +/- 6.5 years) implanted with a dual chamber, dual sensor pacemaker for CAVB with normal sinus node chronotropic function were studied [7].

Associations of CA5B with chemical compounds

  • Similar to CA VA, CA VB is a "low activity" enzyme with a sensitivity to acetazolamide [6].
  • Three compounds showed better activity against hCA VB over hCA II, among which were sulpiride and ethoxzolamide, which were 2 times more effective inhibitors of the mitochondrial over the cytosolic isozyme. hCA VB is a druggable target and some of its inhibitors may lead to the development of novel antiobesity therapies [8].
  • METHODS AND RESULTS: Dogs in sinus rhythm, 2 and 5 weeks CAVB were compared to dogs chronically treated with Irbesartan (30 mg/kg BID) [2].
  • The aim of this study was to compare DDD and dual sensor VVIR (activity and QT) pacing modes in complete AV block (CAVB) [7].
  • CAVB biopsies had significantly longer APDs, a larger dispersion of repolarization and showed more EADs in the presence of ibutilide than SR biopsies [9].

Analytical, diagnostic and therapeutic context of CA5B


  1. Outcome of children with fetal, neonatal or childhood diagnosis of isolated congenital atrioventricular block. A single institution's experience of 30 years. Jaeggi, E.T., Hamilton, R.M., Silverman, E.D., Zamora, S.A., Hornberger, L.K. J. Am. Coll. Cardiol. (2002) [Pubmed]
  2. Asynchronous development of electrical remodeling and cardiac hypertrophy in the complete AV block dog. Schoenmakers, M., Ramakers, C., van Opstal, J.M., Leunissen, J.D., Londoño, C., Vos, M.A. Cardiovasc. Res. (2003) [Pubmed]
  3. CAVBP/DEP alternating chemotherapy for the treatment of intermediate and high grade non Hodgkin's lymphoma: final results of a pilot study. Palmieri, G., Caponigro, F., Iaffaioli, R.V., Contegiacomo, A., Montesarchio, V., Lauria, R., Calderopoli, R., Pagliarulo, C., Gridelli, C., Bianco, A.R. Hematological oncology. (1990) [Pubmed]
  4. Scheduled and unscheduled combination chemotherapy in the treatment of squamous cell lung cancer (cyclophosphamide, adriamycin, vincristine and bleomycin, with and without cis-platinum). Jones, D.H., Bleehen, N.M., Grant, R.M., Plowman, P.N., Roberts, J.T., Sikora, K., Watson, J.V., Wiltshire, C.R. Anticancer Res. (1983) [Pubmed]
  5. Mitochondrial carbonic anhydrase CA VB: differences in tissue distribution and pattern of evolution from those of CA VA suggest distinct physiological roles. Shah, G.N., Hewett-Emmett, D., Grubb, J.H., Migas, M.C., Fleming, R.E., Waheed, A., Sly, W.S. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  6. Human mitochondrial carbonic anhydrase VB. cDNA cloning, mRNA expression, subcellular localization, and mapping to chromosome x. Fujikawa-Adachi, K., Nishimori, I., Taguchi, T., Onishi, S. J. Biol. Chem. (1999) [Pubmed]
  7. A randomized, single-blind crossover comparison of the effects of chronic DDD and dual sensor VVIR pacing mode on quality-of-life and cardiopulmonary performance in complete heart block. Deharo, J.C., Badier, M., Thirion, X., Ritter, P., Provenier, F., Graux, P., Guillot, C., Mugica, J., Jordaens, L., Djiane, P. Pacing and clinical electrophysiology : PACE. (1996) [Pubmed]
  8. Carbonic anhydrase inhibitors. The mitochondrial isozyme VB as a new target for sulfonamide and sulfamate inhibitors. Nishimori, I., Vullo, D., Innocenti, A., Scozzafava, A., Mastrolorenzo, A., Supuran, C.T. J. Med. Chem. (2005) [Pubmed]
  9. Electrophysiological and proarrhythmic parameters in transmural canine left-ventricular needle biopsies. Verduyn, S.C., Jungschleger, J.G., Stengl, M., Spätjens, R.L., Beekman, J.D., Vos, M.A. Pflugers Arch. (2004) [Pubmed]
  10. Cause of atrioventricular block in patients after heart transplantation. Cui, G., Kobashigawa, J., Margarian, A., Sen, L. Transplantation (2003) [Pubmed]
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