Gene Symbol: Car4
Description: carbonic anhydrase 4
Alias: AW456718, Ca4, carbonic anhydrase 4, CA-IV, carbonate dehydratase IV, carbonic anhydrase IV
Species: mouse
Products:     Car4

Top Publications

  1. Scheibe R, Mundhenk K, Becker T, Hallerdei J, Waheed A, Shah G, et al. Carbonic anhydrases IV and IX: subcellular localization and functional role in mouse skeletal muscle. Am J Physiol Cell Physiol. 2008;294:C402-12 pubmed
    ..b>CA IV has been found to be located on the plasma membrane as well as on the sarcoplasmic reticulum (SR) membrane...
  2. Wandernoth P, Raubuch M, Mannowetz N, Becker H, Deitmer J, Sly W, et al. Role of carbonic anhydrase IV in the bicarbonate-mediated activation of murine and human sperm. PLoS ONE. 2010;5:e15061 pubmed publisher
    ..We here show that murine sperm possess extracellular CA IV that is transferred to the sperm surface as the sperm pass through the epididymis...
  3. Ogilvie J, Ohlemiller K, Shah G, Ulmasov B, Becker T, Waheed A, et al. Carbonic anhydrase XIV deficiency produces a functional defect in the retinal light response. Proc Natl Acad Sci U S A. 2007;104:8514-9 pubmed
    ..b>CA IV and CA XIV are membrane-bound isozymes expressed in the eye...
  4. Chandrashekar J, Yarmolinsky D, von Buchholtz L, Oka Y, Sly W, Ryba N, et al. The taste of carbonation. Science. 2009;326:443-5 pubmed publisher
    ..we demonstrated that the sour-sensing cells act as the taste sensors for carbonation, and showed that carbonic anhydrase 4, a glycosylphosphatidylinositol-anchored enzyme, functions as the principal CO2 taste sensor...
  5. Scheibe R, Gros G, Parkkila S, Waheed A, Grubb J, Shah G, et al. Expression of membrane-bound carbonic anhydrases IV, IX, and XIV in the mouse heart. J Histochem Cytochem. 2006;54:1379-91 pubmed
    Expression of membrane-bound carbonic anhydrases (CAs) of CA IV, CA IX, CA XII, and CA XIV has been investigated in the mouse heart...
  6. Ekstedt E, Holm L, Ridderstråle Y. Carbonic anhydrase in mouse testis and epididymis; transfer of isozyme IV to spermatozoa during passage. J Mol Histol. 2004;35:167-73 pubmed
    ..Spermatozoa, when studied in both the scanning electron and light microscope, were found to pickup membrane-bound CA IV during their passage through the epididymal duct...
  7. Hilvo M, Tolvanen M, Clark A, Shen B, Shah G, Waheed A, et al. Characterization of CA XV, a new GPI-anchored form of carbonic anhydrase. Biochem J. 2005;392:83-92 pubmed
    ..Phylogenetic analysis showed that mouse CA XV is related to CA IV. Therefore both of these enzymes were expressed in COS-7 cells and studied in parallel experiments...
  8. Shah G, Ulmasov B, Waheed A, Becker T, Makani S, Svichar N, et al. Carbonic anhydrase IV and XIV knockout mice: roles of the respective carbonic anhydrases in buffering the extracellular space in brain. Proc Natl Acad Sci U S A. 2005;102:16771-6 pubmed
    ..of these two isozymes in this and other physiological functions attributed to extracellular CAs, we produced CA IV and CA XIV knockout (KO) mice by targeted mutagenesis and the doubly deficient CA IV/XIV KO mice by intercrossing ..
  9. Kreple C, Lu Y, Taugher R, Schwager Gutman A, Du J, Stump M, et al. Acid-sensing ion channels contribute to synaptic transmission and inhibit cocaine-evoked plasticity. Nat Neurosci. 2014;17:1083-91 pubmed publisher
    ..Together, these data suggest that ASIC1A inhibits the plasticity underlying addiction-related behavior and raise the possibility of developing therapies for drug addiction by targeting ASIC-dependent neurotransmission. ..

More Information


  1. Vujovic M, Dudazy Gralla S, Hård J, Solsjö P, Warner A, Vennström B, et al. Thyroid hormone drives the expression of mouse carbonic anhydrase Car4 in kidney, lung and brain. Mol Cell Endocrinol. 2015;416:19-26 pubmed publisher
    ..with a mutation in thyroid hormone receptor α1 (TRα1), we here demonstrate that the expression of carbonic anhydrase 4 in lung and brain of the adult animal depends on intact TRα1 signaling...
  2. Narumiya H, Hidaka K, Shirai M, Terami H, Aburatani H, Morisaki T. Endocardiogenesis in embryoid bodies: novel markers identified by gene expression profiling. Biochem Biophys Res Commun. 2007;357:896-902 pubmed
    ..Further, they indicate that these new marker genes are useful to study the origin and induction of endocardial cells, and identify other endocardial markers. ..
  3. Pan P, Rodriguez A, Parkkila S. A systematic quantification of carbonic anhydrase transcripts in the mouse digestive system. BMC Mol Biol. 2007;8:22 pubmed
    ..Car3, Car12, Car13, and Car14 were detected in seven out of eight tissues and Car2 and Car4 were expressed in six tissues...
  4. Whittington D, Grubb J, Waheed A, Shah G, Sly W, Christianson D. Expression, assay, and structure of the extracellular domain of murine carbonic anhydrase XIV: implications for selective inhibition of membrane-associated isozymes. J Biol Chem. 2004;279:7223-8 pubmed
    ..The amino acid sequence identity of human CA XIV relative to the other membrane-associated isozymes (CA IV, CA IX, and CA XII) is 34-46%...
  5. Wen T, Mingler M, Wahl B, Khorki M, Pabst O, Zimmermann N, et al. Carbonic anhydrase IV is expressed on IL-5-activated murine eosinophils. J Immunol. 2014;192:5481-9 pubmed publisher
    ..b>Carbonic anhydrase IV (Car4) was a top dysregulated gene with 36-fold induction in allergen-elicited pulmonary eosinophils, ..
  6. Wandernoth P, Mannowetz N, Szczyrba J, Grannemann L, Wolf A, Becker H, et al. Normal Fertility Requires the Expression of Carbonic Anhydrases II and IV in Sperm. J Biol Chem. 2015;290:29202-16 pubmed publisher
    ..These results suggest that CAII and CAIV are required for optimal fertilization. ..
  7. Tamai S, Waheed A, Cody L, Sly W. Gly-63-->Gln substitution adjacent to His-64 in rodent carbonic anhydrase IVs largely explains their reduced activity. Proc Natl Acad Sci U S A. 1996;93:13647-52 pubmed
    ..CA IVs purified from bovine and rabbit lungs are high-activity enzymes, like human CA IV, while CA IV from mouse and rat lungs had only 10-20% as much catalytic activity...
  8. Reibring C, El Shahawy M, Hallberg K, Kannius Janson M, Nilsson J, Parkkila S, et al. Expression patterns and subcellular localization of carbonic anhydrases are developmentally regulated during tooth formation. PLoS ONE. 2014;9:e96007 pubmed publisher
    ..Our study provides important information for future single or multiple gene targeting strategies aiming at deciphering the function of CAs during odontogenesis. ..
  9. Pan P, Waheed A, Sly W, Parkkila S. Carbonic anhydrases in the mouse harderian gland. J Mol Histol. 2010;41:411-7 pubmed publisher
    ..Nine CA mRNAs were detectable in the gland. Car5b and Car13 showed the highest signals. Car4, Car6, and Car12 showed moderate expression levels, whereas Car2, Car3, Car7, and Car15 mRNAs were barely within ..
  10. Kim W, Matsui T, Yamao M, Ishibashi M, Tamada K, Takumi T, et al. The period of the somite segmentation clock is sensitive to Notch activity. Mol Biol Cell. 2011;22:3541-9 pubmed publisher
    ..Therefore we propose that the period of the somite segmentation clock is sensitive to Notch activity and that Nrarp plays essential roles in the morphology of vertebrae and ribs. ..
  11. Alvarez B, Loiselle F, Supuran C, Schwartz G, Casey J. Direct extracellular interaction between carbonic anhydrase IV and the human NBC1 sodium/bicarbonate co-transporter. Biochemistry. 2003;42:12321-9 pubmed publisher
    ..Electrogenic NBC1 catalyzes HCO(3)(-) fluxes in mammalian kidney, pancreas, and heart cells. Carbonic anhydrase IV (CAIV), which is also present in these tissues, is glycosylphosphatidyl inositol-anchored to the outer ..
  12. Stams T, Chen Y, Boriack Sjodin P, Hurt J, Liao J, May J, et al. Structures of murine carbonic anhydrase IV and human carbonic anhydrase II complexed with brinzolamide: molecular basis of isozyme-drug discrimination. Protein Sci. 1998;7:556-63 pubmed
    b>Carbonic anhydrase IV (CAIV) is a membrane-associated enzyme anchored to plasma membrane surfaces by a phosphatidylinositol glycan linkage. We have determined the 2...
  13. Brion L, Cammer W, Satlin L, Suarez C, Zavilowitz B, Schuster V. Expression of carbonic anhydrase IV in carbonic anhydrase II-deficient mice. Am J Physiol. 1997;273:F234-45 pubmed
    ..This study was designed to assess CA IV expression in a model of CMA in the mouse, i.e., congenital deficiency in CA II [CA(II)D]...
  14. Brion L, Suarez C, Zhang H, Cammer W. Up-regulation of carbonic anhydrase isozyme IV in CNS myelin of mice genetically deficient in carbonic anhydrase II. J Neurochem. 1994;63:360-6 pubmed
    ..CA(II)D resulted in a much lower total CA specific activity in all tissues examined but in higher CA IV specific activities in soluble and membrane-associated fractions and pure myelin...
  15. Tamai S, Cody L, Sly W. Molecular cloning of the mouse gene coding for carbonic anhydrase IV. Biochem Genet. 1996;34:31-43 pubmed
    b>Carbonic anhydrase IV (CA IV) is expressed on apical surfaces of renal tubular epithelium and endothelium of specialized capillary beds. It plays a key role in bicarbonate reabsorption in kidney and in CO2 transport in other tissues...
  16. Wu L, Sagong B, Choi J, Kim U, Bok J. A systematic survey of carbonic anhydrase mRNA expression during mammalian inner ear development. Dev Dyn. 2013;242:269-80 pubmed publisher
    ..The temporal and spatial expression patterns of each CA isozyme suggest unique and differential roles in inner ear development and function. ..
  17. Nishiguchi Y, Ohmoto M, Koki J, Enomoto T, Kominami R, Matsumoto I, et al. Bcl11b/Ctip2 is required for development of lingual papillae in mice. Dev Biol. 2016;416:98-110 pubmed publisher
    ..These results indicate that Bcl11b regulates the differentiation of keratinocytes in the tongue and identify Bcl11b as an essential factor for the lingual papilla morphogenesis. ..
  18. Wang X, Ouyang H, Yamamoto Y, Kumar P, Wei T, Dagher R, et al. Residual embryonic cells as precursors of a Barrett's-like metaplasia. Cell. 2011;145:1023-35 pubmed publisher
    ..Our findings suggest that certain precancerous lesions, such as Barrett's, initiate not from genetic alterations but from competitive interactions between cell lineages driven by opportunity...
  19. Hallerdei J, Scheibe R, Parkkila S, Waheed A, Sly W, Gros G, et al. T tubules and surface membranes provide equally effective pathways of carbonic anhydrase-facilitated lactic acid transport in skeletal muscle. PLoS ONE. 2010;5:e15137 pubmed publisher
    ..The data suggest that about half the CA-dependent muscular lactate flux occurs across the surface membrane, while the other half occurs across the membranes of the T tubuli. ..
  20. Giacomotto J, Pertl C, Borrel C, Walter M, Bulst S, Johnsen B, et al. Evaluation of the therapeutic potential of carbonic anhydrase inhibitors in two animal models of dystrophin deficient muscular dystrophy. Hum Mol Genet. 2009;18:4089-101 pubmed publisher
    ..These studies further demonstrated that a C. elegans-based screen coupled with a mouse model validation strategy can lead to the identification of potential pharmacological agents for rare diseases. ..
  21. Borenshtein D, Schlieper K, Rickman B, Chapman J, Schweinfest C, Fox J, et al. Decreased expression of colonic Slc26a3 and carbonic anhydrase iv as a cause of fatal infectious diarrhea in mice. Infect Immun. 2009;77:3639-50 pubmed publisher
    ..and FVB/N was associated with significant fluid loss in feces, a remarkable downregulation of Slc26a3 and carbonic anhydrase IV (CAIV) message and protein expression, retention of chloride in stool, and hypochloremia, suggesting ..
  22. Svichar N, Waheed A, Sly W, Hennings J, Hübner C, Chesler M. Carbonic anhydrases CA4 and CA14 both enhance AE3-mediated Cl--HCO3- exchange in hippocampal neurons. J Neurosci. 2009;29:3252-8 pubmed publisher
    Carbonic anhydrase (CA) activity in the brain extracellular space is attributable mainly to isoforms CA4 and CA14...
  23. Hurt J, Tu C, Laipis P, Silverman D. Catalytic properties of murine carbonic anhydrase IV. J Biol Chem. 1997;272:13512-8 pubmed
    A cDNA encoding the murine carbonic anhydrase IV (mCA IV) gene, modified to resemble a form of mature human carbonic anhydrase IV (Okuyama, T., Waheed, A., Kusumoto, W., Zhu, X. L., and Sly, W. S. (1995) Arch. Biochem. Biophys...
  24. Schneider H, Alt M, Klier M, Spiess A, Andes F, Waheed A, et al. GPI-anchored carbonic anhydrase IV displays both intra- and extracellular activity in cRNA-injected oocytes and in mouse neurons. Proc Natl Acad Sci U S A. 2013;110:1494-9 pubmed publisher
    ..b>CA IV expression in oocytes was confirmed by immunocytochemistry, and CA IV activity measured by mass spectrometry...
  25. Hurt J, Tu C, Laipis P. Isolation and expression of murine carbonic anhydrase IV. Protein Expr Purif. 1998;12:7-16 pubmed
    A 1193-bp cDNA containing the complete murine carbonic anhydrase IV coding sequence was isolated from a Balb/c kidney cDNA library...