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Identification
HMDB Protein ID HMDBP03137
Secondary Accession Numbers
  • 8686
  • HMDBP04947
Name Carbonic anhydrase 4
Synonyms
  1. CA-IV
  2. Carbonate dehydratase IV
  3. Carbonic anhydrase IV
Gene Name CA4
Protein Type Unknown
Biological Properties
General Function Involved in carbonate dehydratase activity
Specific Function Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid.
Pathways
  • Proximal tubule bicarbonate reclamation
Reactions
Hydrogen carbonate → CO(2) + Water details
Hydrogen carbonate → Carbon dioxide + Water details
GO Classification
Biological Process
small molecule metabolic process
response to drug
bicarbonate transport
organ development
response to steroid hormone stimulus
one-carbon metabolic process
Cellular Component
Golgi apparatus
perinuclear region of cytoplasm
endoplasmic reticulum-Golgi intermediate compartment
sarcoplasmic reticulum
trans-Golgi network
brush border membrane
anchored to external side of plasma membrane
apical plasma membrane
secretory granule membrane
transport vesicle membrane
rough endoplasmic reticulum
sarcolemma
Component
membrane
cell part
membrane part
plasma membrane
intrinsic to membrane
anchored to membrane
Function
ion binding
cation binding
metal ion binding
binding
catalytic activity
carbonate dehydratase activity
transition metal ion binding
zinc ion binding
lyase activity
carbon-oxygen lyase activity
hydro-lyase activity
Molecular Function
metal ion binding
zinc ion binding
carbonate dehydratase activity
Process
metabolic process
cellular metabolic process
one-carbon metabolic process
Cellular Location
  1. Cell membrane
  2. Lipid-anchor
  3. GPI-anchor
Gene Properties
Chromosome Location 17
Locus 17q23
SNPs CA4
Gene Sequence
>939 bp
ATGCGGATGCTGCTGGCGCTCCTGGCCCTCTCCGCGGCGCGGCCATCGGCCAGTGCAGAG
TCACACTGGTGCTACGAGGTTCAAGCCGAGTCCTCCAACTACCCCTGCTTGGTGCCAGTC
AAGTGGGGTGGAAACTGCCAGAAGGACCGCCAGTCCCCCATCAACATCGTCACCACCAAG
GCAAAGGTGGACAAAAAACTGGGACGCTTCTTCTTCTCTGGCTACGATAAGAAGCAAACG
TGGACTGTCCAAAATAACGGGCACTCAGTGATGATGTTGCTGGAGAACAAGGCCAGCATT
TCTGGAGGAGGACTGCCTGCCCCATACCAGGCCAAACAGTTGCACCTGCACTGGTCCGAC
TTGCCATATAAGGGCTCGGAGCACAGCCTCGATGGGGAGCACTTTGCCATGGAGATGCAC
ATAGTACATGAGAAAGAGAAGGGGACATCGAGGAATGTGAAAGAGGCCCAGGACCCTGAA
GACGAAATTGCGGTGCTGGCCTTTCTGGTGGAGGCTGGAACCCAGGTGAACGAGGGCTTC
CAGCCACTGGTGGAGGCACTGTCTAATATCCCCAAACCTGAGATGAGCACTACGATGGCA
GAGAGCAGCCTGTTGGACCTGCTCCCCAAGGAGGAGAAACTGAGGCACTACTTCCGCTAC
CTGGGCTCACTCACCACACCGACCTGCGATGAGAAGGTCGTCTGGACTGTGTTCCGGGAG
CCCATTCAGCTTCACAGAGAACAGATCCTGGCATTCTCTCAGAAGCTGTACTACGACAAG
GAACAGACAGTGAGCATGAAGGACAATGTCAGGCCCCTGCAGCAGCTGGGGCAGCGCACG
GTGATAAAGTCCGGGGCCCCGGGTCGGCCGCTGCCCTGGGCCCTGCCTGCCCTGCTGGGC
CCCATGCTGGCCTGCCTGCTGGCCGGCTTCCTGCGATGA
Protein Properties
Number of Residues 312
Molecular Weight 35032.075
Theoretical pI 7.821
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Carbonic anhydrase 4
MRMLLALLALSAARPSASAESHWCYEVQAESSNYPCLVPVKWGGNCQKDRQSPINIVTTK
AKVDKKLGRFFFSGYDKKQTWTVQNNGHSVMMLLENKASISGGGLPAPYQAKQLHLHWSD
LPYKGSEHSLDGEHFAMEMHIVHEKEKGTSRNVKEAQDPEDEIAVLAFLVEAGTQVNEGF
QPLVEALSNIPKPEMSTTMAESSLLDLLPKEEKLRHYFRYLGSLTTPTCDEKVVWTVFRE
PIQLHREQILAFSQKLYYDKEQTVSMKDNVRPLQQLGQRTVIKSGAPGRPLPWALPALLG
PMLACLLAGFLR
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P22748
UniProtKB/Swiss-Prot Entry Name CAH4_HUMAN
PDB IDs
GenBank Gene ID M83670
GeneCard ID CA4
GenAtlas ID CA4
HGNC ID HGNC:1375
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Temperini C, Scozzafava A, Vullo D, Supuran CT: Carbonic anhydrase activators. Activation of isozymes I, II, IV, VA, VII, and XIV with l- and d-histidine and crystallographic analysis of their adducts with isoform II: engineering proton-transfer processes within the active site of an enzyme. Chemistry. 2006 Sep 18;12(27):7057-66. [PubMed:16807956 ]
  3. Temperini C, Scozzafava A, Vullo D, Supuran CT: Carbonic anhydrase activators. Activation of isoforms I, II, IV, VA, VII, and XIV with L- and D-phenylalanine and crystallographic analysis of their adducts with isozyme II: stereospecific recognition within the active site of an enzyme and its consequences for the drug design. J Med Chem. 2006 May 18;49(10):3019-27. [PubMed:16686544 ]
  4. Temperini C, Innocenti A, Scozzafava A, Mastrolorenzo A, Supuran CT: Carbonic anhydrase activators: L-Adrenaline plugs the active site entrance of isozyme II, activating better isoforms I, IV, VA, VII, and XIV. Bioorg Med Chem Lett. 2007 Feb 1;17(3):628-35. Epub 2006 Nov 15. [PubMed:17127057 ]
  5. Crocetti L, Maresca A, Temperini C, Hall RA, Scozzafava A, Muhlschlegel FA, Supuran CT: A thiabendazole sulfonamide shows potent inhibitory activity against mammalian and nematode alpha-carbonic anhydrases. Bioorg Med Chem Lett. 2009 Mar 1;19(5):1371-5. doi: 10.1016/j.bmcl.2009.01.038. Epub 2009 Jan 19. [PubMed:19186056 ]
  6. Maresca A, Temperini C, Vu H, Pham NB, Poulsen SA, Scozzafava A, Quinn RJ, Supuran CT: Non-zinc mediated inhibition of carbonic anhydrases: coumarins are a new class of suicide inhibitors. J Am Chem Soc. 2009 Mar 4;131(8):3057-62. doi: 10.1021/ja809683v. [PubMed:19206230 ]
  7. Di Fiore A, Monti SM, Hilvo M, Parkkila S, Romano V, Scaloni A, Pedone C, Scozzafava A, Supuran CT, De Simone G: Crystal structure of human carbonic anhydrase XIII and its complex with the inhibitor acetazolamide. Proteins. 2009 Jan;74(1):164-75. doi: 10.1002/prot.22144. [PubMed:18618712 ]
  8. Temperini C, Innocenti A, Guerri A, Scozzafava A, Rusconi S, Supuran CT: Phosph(on)ate as a zinc-binding group in metalloenzyme inhibitors: X-ray crystal structure of the antiviral drug foscarnet complexed to human carbonic anhydrase I. Bioorg Med Chem Lett. 2007 Apr 15;17(8):2210-5. Epub 2007 Feb 8. [PubMed:17314045 ]
  9. Kohler K, Hillebrecht A, Schulze Wischeler J, Innocenti A, Heine A, Supuran CT, Klebe G: Saccharin inhibits carbonic anhydrases: possible explanation for its unpleasant metallic aftertaste. Angew Chem Int Ed Engl. 2007;46(40):7697-9. [PubMed:17705204 ]
  10. Yang Z, Alvarez BV, Chakarova C, Jiang L, Karan G, Frederick JM, Zhao Y, Sauve Y, Li X, Zrenner E, Wissinger B, Hollander AI, Katz B, Baehr W, Cremers FP, Casey JR, Bhattacharya SS, Zhang K: Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal photoreceptor degeneration. Hum Mol Genet. 2005 Jan 15;14(2):255-65. Epub 2004 Nov 24. [PubMed:15563508 ]
  11. Okuyama T, Sato S, Zhu XL, Waheed A, Sly WS: Human carbonic anhydrase IV: cDNA cloning, sequence comparison, and expression in COS cell membranes. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1315-9. [PubMed:1311094 ]
  12. Okuyama T, Batanian JR, Sly WS: Genomic organization and localization of gene for human carbonic anhydrase IV to chromosome 17q. Genomics. 1993 Jun;16(3):678-84. [PubMed:8325641 ]
  13. Zhu XL, Sly WS: Carbonic anhydrase IV from human lung. Purification, characterization, and comparison with membrane carbonic anhydrase from human kidney. J Biol Chem. 1990 May 25;265(15):8795-801. [PubMed:2111324 ]
  14. Waheed A, Okuyama T, Heyduk T, Sly WS: 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. 1996 Sep 15;333(2):432-8. [PubMed:8809084 ]
  15. Okuyama T, Waheed A, Kusumoto W, Zhu XL, Sly WS: Carbonic anhydrase IV: role of removal of C-terminal domain in glycosylphosphatidylinositol anchoring and realization of enzyme activity. Arch Biochem Biophys. 1995 Jul 10;320(2):315-22. [PubMed:7625839 ]
  16. Stams T, Nair SK, Okuyama T, Waheed A, Sly WS, Christianson DW: 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. 1996 Nov 26;93(24):13589-94. [PubMed:8942978 ]