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 IV is a glycosylphosphatidyl-inositol-anchored membrane isozyme expressed on the luminal surfaces of pulmonary (and certain other) capillaries and of proximal renal tubules. Its exact function is not known, however, it may have a role in inherited renal abnormalities of bicarbonate transport.[6]
CA IV has been identified in pulmonary epithelium of many mammalian species and may be uniquely adaptive for gas exchange necessary for the high metabolic requirements of mammals. A majority of the CO2 produced by metabolism is transported as bicarbonate (HCO− 3). At the tissue capillary, CO2 diffuses from tissue to plasma. Other forms of carbonic anhydrase enzyme are not present in the plasma, restricting the equilibrium reaction of CO2+H2O = H 2CO 3 = H+ HCO− 3. CO2 in the plasma diffuses into the Red Blood Cell. CA is present within the Red Blood Cell, facilitating the conversion of CO2 to HCO− 3. HCO− 3 so produced is transferred by the HCO− 3/Cl- "shuttle" from the interior of the Red Blood Cell to the plasma. HCO− 3 does not diffuse across cell membranes and, in the absence of CA, stays as HCO− 3 and concentrates in plasma. Up to 80% of metabolically produced CO2 is transported in plasma in the form of HCO− 3. Blood moves from the tissue capillary to the pulmonary capillary where CO2 is exchanged at the lung. In the pulmonary capillary, bicarbonate can not simply diffuse either into the Red Blood Cell or the alveoli. It is traditionally thought that HCO− 3 is returned to the interior of the Red Blood Cell by a reversal of the HCO− 3/Cl- shuttle, where, in the presence of CA, it is returned to a CO2 form to diffuse from the interior of the Red Blood Cell, to the plasma and then into the alveoli. Membrane bound CA (CA IV) on the luminal side of the pulmonary membrane would have direct contact with plasma HCO− 3 and would enzymatically convert HCO− 3 to CO2 in the area immediately proximal to the exchange membrane, greatly increasing the concentration gradient for exchange. In this way, plasma HCO− 3 can be converted to CO2 within the plasma compartment and exchanged with the alveoli without the requirement of returning the HCO− 3 to the interior of the Red Blood Cell.
^ abcGRCh38: Ensembl release 89: ENSG00000167434 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000000805 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Okuyama T, Batanian JR, Sly WS (Aug 1993). "Genomic organization and localization of gene for human carbonic anhydrase IV to chromosome 17q". Genomics. 16 (3): 678–84. doi:10.1006/geno.1993.1247. PMID 8325641.
^Sterling D, Alvarez BV, Casey JR (Jul 2002). "The extracellular component of a transport metabolon. Extracellular loop 4 of the human AE1 Cl-/HCO3- exchanger binds carbonic anhydrase IV". J. Biol. Chem. 277 (28): 25239–46. doi:10.1074/jbc.M202562200. PMID 11994299.
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Further readingedit
Okuyama T, Sato S, Zhu XL, Waheed A, Sly WS (1992). "Human carbonic anhydrase IV: cDNA cloning, sequence comparison, and expression in COS cell membranes". Proc. Natl. Acad. Sci. U.S.A. 89 (4): 1315–9. Bibcode:1992PNAS...89.1315O. doi:10.1073/pnas.89.4.1315. PMC48440. PMID 1311094.
Hageman GS, Zhu XL, Waheed A, Sly WS (1991). "Localization of carbonic anhydrase IV in a specific capillary bed of the human eye". Proc. Natl. Acad. Sci. U.S.A. 88 (7): 2716–20. Bibcode:1991PNAS...88.2716H. doi:10.1073/pnas.88.7.2716. PMC51309. PMID 1901414.
Zhu XL, Sly WS (1990). "Carbonic anhydrase IV from human lung. Purification, characterization, and comparison with membrane carbonic anhydrase from human kidney". J. Biol. Chem. 265 (15): 8795–801. doi:10.1016/S0021-9258(19)38958-6. PMID 2111324.
Carter ND, Fryer A, Grant AG, Hume R, Strange RG, Wistrand PJ (1990). "Membrane specific carbonic anhydrase (CAIV) expression in human tissues". Biochim. Biophys. Acta. 1026 (1): 113–6. doi:10.1016/0005-2736(90)90340-T. PMID 2116168.
Whitney PL, Briggle TV (1982). "Membrane-associated carbonic anhydrase purified from bovine lung". J. Biol. Chem. 257 (20): 12056–9. doi:10.1016/S0021-9258(18)33676-7. PMID 6811592.
Bardien S, Ebenezer N, Greenberg J, Inglehearn CF, Bartmann L, Goliath R, Beighton P, Ramesar R, Bhattacharya SS (1995). "An eighth locus for autosomal dominant retinitis pigmentosa is linked to chromosome 17q". Hum. Mol. Genet. 4 (8): 1459–62. doi:10.1093/hmg/4.8.1459. PMID 7581389.
Okuyama T, Waheed A, Kusumoto W, Zhu XL, Sly WS (1995). "Carbonic anhydrase IV: role of removal of C-terminal domain in glycosylphosphatidylinositol anchoring and realization of enzyme activity". Arch. Biochem. Biophys. 320 (2): 315–22. doi:10.1016/0003-9861(95)90015-2. PMID 7625839.
Mahieu I, Benjamin A, Stephens R, Walters D, Carter N (1995). "Characterization of membrane bound carbonic anhydrase IV (CA IV) located on the external surface of lung pulmonary endothelial cells". Biochem. Soc. Trans. 23 (2): 320S. doi:10.1042/bst023320s. PMID 7672351.
Sender S, Gros G, Waheed A, Hageman GS, Sly WS (1994). "Immunohistochemical localization of carbonic anhydrase IV in capillaries of rat and human skeletal muscle". J. Histochem. Cytochem. 42 (9): 1229–36. doi:10.1177/42.9.8064130. PMID 8064130.
Fleming RE, Parkkila S, Parkkila AK, Rajaniemi H, Waheed A, Sly WS (1996). "Carbonic anhydrase IV expression in rat and human gastrointestinal tract regional, cellular, and subcellular localization". J. Clin. Invest. 96 (6): 2907–13. doi:10.1172/JCI118362. PMC186002. PMID 8675662.
Waheed A, Okuyama T, Heyduk T, Sly WS (1996). "Carbonic anhydrase IV: purification of a secretory form of the recombinant human enzyme and identification of the positions and importance of its disulfide bonds". Arch. Biochem. Biophys. 333 (2): 432–8. doi:10.1006/abbi.1996.0412. PMID 8809084.
Parkkila S, Parkkila AK, Juvonen T, Waheed A, Sly WS, Saarnio J, Kaunisto K, Kellokumpu S, Rajaniemi H (1996). "Membrane-bound carbonic anhydrase IV is expressed in the luminal plasma membrane of the human gallbladder epithelium". Hepatology. 24 (5): 1104–8. doi:10.1002/hep.510240521. PMID 8903383. S2CID 11461543.
Stams T, Nair SK, Okuyama T, Waheed A, Sly WS, Christianson DW (1997). "Crystal structure of the secretory form of membrane-associated human carbonic anhydrase IV at 2.8-A resolution". Proc. Natl. Acad. Sci. U.S.A. 93 (24): 13589–94. doi:10.1073/pnas.93.24.13589. PMC19359. PMID 8942978.
Bardien S, Ramesar R, Bhattacharya S, Greenberg J (1997). "Retinitis pigmentosa locus on 17q (RP17): fine localization to 17q22 and exclusion of the PDEG and TIMP2 genes". Hum. Genet. 101 (1): 13–7. doi:10.1007/s004390050577. PMID 9385361. S2CID 26680917.
Sender S, Decker B, Fenske CD, Sly WS, Carter ND, Gros G (1998). "Localization of carbonic anhydrase IV in rat and human heart muscle". J. Histochem. Cytochem. 46 (7): 855–61. doi:10.1177/002215549804600709. PMID 9632745.
Wistrand PJ, Carter ND, Conroy CW, Mahieu I (1999). "Carbonic anhydrase IV activity is localized on the exterior surface of human erythrocytes". Acta Physiol. Scand. 165 (2): 211–8. doi:10.1046/j.1365-201x.1999.00478.x. PMID 10090333.
Fujikawa-Adachi K, Nishimori I, Sakamoto S, Morita M, Onishi S, Yonezawa S, Hollingsworth MA (1999). "Identification of carbonic anhydrase IV and VI mRNA expression in human pancreas and salivary glands". Pancreas. 18 (4): 329–35. doi:10.1097/00006676-199905000-00001. PMID 10231836.
Sterling D, Alvarez BV, Casey JR (2002). "The extracellular component of a transport metabolon. Extracellular loop 4 of the human AE1 Cl-/HCO3- exchanger binds carbonic anhydrase IV". J. Biol. Chem. 277 (28): 25239–46. doi:10.1074/jbc.M202562200. PMID 11994299.
External linksedit
GeneReviews/NCBI/NIH/UW entry on Retinitis Pigmentosa Overview
Overview of all the structural information available in the PDB for UniProt: P22748 (Carbonic anhydrase 4) at the PDBe-KB.
This article on a gene on human chromosome 17 is a stub. You can help Wikipedia by expanding it.
carbonic, anhydrase, enzyme, that, humans, encoded, gene, ca4available, structurespdbortholog, search, pdbe, rcsblist, codes1znc, 3f7b, 3f7u, 3fw3identifiersaliasesca4, caiv, car4, rp17, carbonic, anhydrase, 4external, idsomim, 114760, 1096574, homologene, 201. Carbonic anhydrase 4 is an enzyme that in humans is encoded by the CA4 gene 5 6 CA4Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes1ZNC 3F7B 3F7U 3FW3IdentifiersAliasesCA4 CAIV Car4 RP17 carbonic anhydrase 4External IDsOMIM 114760 MGI 1096574 HomoloGene 20183 GeneCards CA4Gene location Human Chr Chromosome 17 human 1 Band17q23 1Start60 149 942 bp 1 End60 170 899 bp 1 Gene location Mouse Chr Chromosome 11 mouse 2 Band11 11 CStart84 848 612 bp 2 End84 856 870 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inrectumcerebellar hemisphereright lungleft lobe of thyroid glandupper lobe of left lungcerebellar vermisright lobe of thyroid glandsubcutaneous adipose tissuekidneyleft ventricleTop expressed inleft colonyolk sacright lung lobeproximal tubulecerebellar vermislateral geniculate nucleuskidneyprimitive streakmedial geniculate nucleusjejunumMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionzinc ion binding metal ion binding protein binding lyase activity carbonate dehydratase activity carbonic anhydraseCellular componentrough endoplasmic reticulum Golgi apparatus membrane secretory granule membrane anchored component of plasma membrane plasma membrane transport vesicle membrane cell surface brush border membrane trans Golgi network basolateral plasma membrane apical plasma membrane anchored component of external side of plasma membrane perinuclear region of cytoplasm anchored component of membrane extracellular exosome endoplasmic reticulum Golgi intermediate compartmentBiological processone carbon metabolic process bicarbonate transport metabolismSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez76212351EnsemblENSG00000167434ENSMUSG00000000805UniProtP22748Q64444RefSeq mRNA NM 000717NM 007607RefSeq protein NP 000708NP 031633Location UCSC Chr 17 60 15 60 17 MbChr 11 84 85 84 86 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Interactions 3 References 4 Further reading 5 External linksFunction editCarbonic 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 IV is a glycosylphosphatidyl inositol anchored membrane isozyme expressed on the luminal surfaces of pulmonary and certain other capillaries and of proximal renal tubules Its exact function is not known however it may have a role in inherited renal abnormalities of bicarbonate transport 6 CA IV has been identified in pulmonary epithelium of many mammalian species and may be uniquely adaptive for gas exchange necessary for the high metabolic requirements of mammals A majority of the CO2 produced by metabolism is transported as bicarbonate HCO 3 At the tissue capillary CO2 diffuses from tissue to plasma Other forms of carbonic anhydrase enzyme are not present in the plasma restricting the equilibrium reaction of CO2 H2O H2 CO3 H HCO 3 CO2 in the plasma diffuses into the Red Blood Cell CA is present within the Red Blood Cell facilitating the conversion of CO2 to HCO 3 HCO 3 so produced is transferred by the HCO 3 Cl shuttle from the interior of the Red Blood Cell to the plasma HCO 3 does not diffuse across cell membranes and in the absence of CA stays as HCO 3 and concentrates in plasma Up to 80 of metabolically produced CO2 is transported in plasma in the form of HCO 3 Blood moves from the tissue capillary to the pulmonary capillary where CO2 is exchanged at the lung In the pulmonary capillary bicarbonate can not simply diffuse either into the Red Blood Cell or the alveoli It is traditionally thought that HCO 3 is returned to the interior of the Red Blood Cell by a reversal of the HCO 3 Cl shuttle where in the presence of CA it is returned to a CO2 form to diffuse from the interior of the Red Blood Cell to the plasma and then into the alveoli Membrane bound CA CA IV on the luminal side of the pulmonary membrane would have direct contact with plasma HCO 3 and would enzymatically convert HCO 3 to CO2 in the area immediately proximal to the exchange membrane greatly increasing the concentration gradient for exchange In this way plasma HCO 3 can be converted to CO2 within the plasma compartment and exchanged with the alveoli without the requirement of returning the HCO 3 to the interior of the Red Blood Cell Interactions editCA4 has been shown to interact with Band 3 7 References edit a b c GRCh38 Ensembl release 89 ENSG00000167434 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000000805 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Okuyama T Batanian JR Sly WS Aug 1993 Genomic organization and localization of gene for human carbonic anhydrase IV to chromosome 17q Genomics 16 3 678 84 doi 10 1006 geno 1993 1247 PMID 8325641 a b Entrez Gene CA4 carbonic anhydrase IV Sterling D Alvarez BV Casey JR Jul 2002 The extracellular component of a transport metabolon Extracellular loop 4 of the human AE1 Cl HCO3 exchanger binds carbonic anhydrase IV J Biol Chem 277 28 25239 46 doi 10 1074 jbc M202562200 PMID 11994299 Send toFurther reading editOkuyama T Sato S Zhu XL Waheed A Sly WS 1992 Human carbonic anhydrase IV cDNA cloning sequence comparison and expression in COS cell membranes Proc Natl Acad Sci U S A 89 4 1315 9 Bibcode 1992PNAS 89 1315O doi 10 1073 pnas 89 4 1315 PMC 48440 PMID 1311094 Hageman GS Zhu XL Waheed A Sly WS 1991 Localization of carbonic anhydrase IV in a specific capillary bed of the human eye Proc Natl Acad Sci U S A 88 7 2716 20 Bibcode 1991PNAS 88 2716H doi 10 1073 pnas 88 7 2716 PMC 51309 PMID 1901414 Zhu XL Sly WS 1990 Carbonic anhydrase IV from human lung Purification characterization and comparison with membrane carbonic anhydrase from human kidney J Biol Chem 265 15 8795 801 doi 10 1016 S0021 9258 19 38958 6 PMID 2111324 Carter ND Fryer A Grant AG Hume R Strange RG Wistrand PJ 1990 Membrane specific carbonic anhydrase CAIV expression in human tissues Biochim Biophys Acta 1026 1 113 6 doi 10 1016 0005 2736 90 90340 T PMID 2116168 Whitney PL Briggle TV 1982 Membrane associated carbonic anhydrase purified from bovine lung J Biol Chem 257 20 12056 9 doi 10 1016 S0021 9258 18 33676 7 PMID 6811592 Bardien S Ebenezer N Greenberg J Inglehearn CF Bartmann L Goliath R Beighton P Ramesar R Bhattacharya SS 1995 An eighth locus for autosomal dominant retinitis pigmentosa is linked to chromosome 17q Hum Mol Genet 4 8 1459 62 doi 10 1093 hmg 4 8 1459 PMID 7581389 Okuyama T Waheed A Kusumoto W Zhu XL Sly WS 1995 Carbonic anhydrase IV role of removal of C terminal domain in glycosylphosphatidylinositol anchoring and realization of enzyme activity Arch Biochem Biophys 320 2 315 22 doi 10 1016 0003 9861 95 90015 2 PMID 7625839 Mahieu I Benjamin A Stephens R Walters D Carter N 1995 Characterization of membrane bound carbonic anhydrase IV CA IV located on the external surface of lung pulmonary endothelial cells Biochem Soc Trans 23 2 320S doi 10 1042 bst023320s PMID 7672351 Sender S Gros G Waheed A Hageman GS Sly WS 1994 Immunohistochemical localization of carbonic anhydrase IV in capillaries of rat and human skeletal muscle J Histochem Cytochem 42 9 1229 36 doi 10 1177 42 9 8064130 PMID 8064130 Fleming RE Parkkila S Parkkila AK Rajaniemi H Waheed A Sly WS 1996 Carbonic anhydrase IV expression in rat and human gastrointestinal tract regional cellular and subcellular localization J Clin Invest 96 6 2907 13 doi 10 1172 JCI118362 PMC 186002 PMID 8675662 Waheed A Okuyama T Heyduk T Sly WS 1996 Carbonic anhydrase IV purification of a secretory form of the recombinant human enzyme and identification of the positions and importance of its disulfide bonds Arch Biochem Biophys 333 2 432 8 doi 10 1006 abbi 1996 0412 PMID 8809084 Parkkila S Parkkila AK Juvonen T Waheed A Sly WS Saarnio J Kaunisto K Kellokumpu S Rajaniemi H 1996 Membrane bound carbonic anhydrase IV is expressed in the luminal plasma membrane of the human gallbladder epithelium Hepatology 24 5 1104 8 doi 10 1002 hep 510240521 PMID 8903383 S2CID 11461543 Stams T Nair SK Okuyama T Waheed A Sly WS Christianson DW 1997 Crystal structure of the secretory form of membrane associated human carbonic anhydrase IV at 2 8 A resolution Proc Natl Acad Sci U S A 93 24 13589 94 doi 10 1073 pnas 93 24 13589 PMC 19359 PMID 8942978 Bardien S Ramesar R Bhattacharya S Greenberg J 1997 Retinitis pigmentosa locus on 17q RP17 fine localization to 17q22 and exclusion of the PDEG and TIMP2 genes Hum Genet 101 1 13 7 doi 10 1007 s004390050577 PMID 9385361 S2CID 26680917 Sender S Decker B Fenske CD Sly WS Carter ND Gros G 1998 Localization of carbonic anhydrase IV in rat and human heart muscle J Histochem Cytochem 46 7 855 61 doi 10 1177 002215549804600709 PMID 9632745 Wistrand PJ Carter ND Conroy CW Mahieu I 1999 Carbonic anhydrase IV activity is localized on the exterior surface of human erythrocytes Acta Physiol Scand 165 2 211 8 doi 10 1046 j 1365 201x 1999 00478 x PMID 10090333 Fujikawa Adachi K Nishimori I Sakamoto S Morita M Onishi S Yonezawa S Hollingsworth MA 1999 Identification of carbonic anhydrase IV and VI mRNA expression in human pancreas and salivary glands Pancreas 18 4 329 35 doi 10 1097 00006676 199905000 00001 PMID 10231836 Sterling D Alvarez BV Casey JR 2002 The extracellular component of a transport metabolon Extracellular loop 4 of the human AE1 Cl HCO3 exchanger binds carbonic anhydrase IV J Biol Chem 277 28 25239 46 doi 10 1074 jbc M202562200 PMID 11994299 External links editGeneReviews NCBI NIH UW entry on Retinitis Pigmentosa Overview Overview of all the structural information available in the PDB for UniProt P22748 Carbonic anhydrase 4 at the PDBe KB nbsp This article on a gene on human chromosome 17 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title Carbonic anhydrase 4 amp oldid 1182101073, wikipedia, wiki, book, books, library,
