Carbonic anhydrase 4

Details

Name
Carbonic anhydrase 4
Synonyms
  • 4.2.1.1
  • CA-IV
  • Carbonate dehydratase IV
  • Carbonic anhydrase IV
Gene Name
CA4
UniProtKB Entry
P22748Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0001068|Carbonic anhydrase 4
MRMLLALLALSAARPSASAESHWCYEVQAESSNYPCLVPVKWGGNCQKDRQSPINIVTTK
AKVDKKLGRFFFSGYDKKQTWTVQNNGHSVMMLLENKASISGGGLPAPYQAKQLHLHWSD
LPYKGSEHSLDGEHFAMEMHIVHEKEKGTSRNVKEAQDPEDEIAVLAFLVEAGTQVNEGF
QPLVEALSNIPKPEMSTTMAESSLLDLLPKEEKLRHYFRYLGSLTTPTCDEKVVWTVFRE
PIQLHREQILAFSQKLYYDKEQTVSMKDNVRPLQQLGQRTVIKSGAPGRPLPWALPALLG
PMLACLLAGFLR
Number of residues
312
Molecular Weight
35032.075
Theoretical pI
7.94
GO Classification
Components
external side of plasma membrane
General Function
Catalyzes the reversible hydration of carbon dioxide into bicarbonate and protons and thus is essential to maintaining intracellular and extracellular pH (PubMed:15563508, PubMed:16686544, PubMed:16807956, PubMed:17127057, PubMed:17314045, PubMed:17652713, PubMed:17705204, PubMed:18618712, PubMed:19186056, PubMed:19206230, PubMed:7625839). May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis (PubMed:15563508). It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid (PubMed:15563508)
Specific Function
carbonate dehydratase activity
Pfam Domain Function
Signal Regions
1-18
Transmembrane Regions
Not Available
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0010374|Carbonic anhydrase 4 (CA4)
ATGCGGATGCTGCTGGCGCTCCTGGCCCTCTCCGCGGCGCGGCCATCGGCCAGTGCAGAG
TCACACTGGTGCTACGAGGTTCAAGCCGAGTCCTCCAACTACCCCTGCTTGGTGCCAGTC
AAGTGGGGTGGAAACTGCCAGAAGGACCGCCAGTCCCCCATCAACATCGTCACCACCAAG
GCAAAGGTGGACAAAAAACTGGGACGCTTCTTCTTCTCTGGCTACGATAAGAAGCAAACG
TGGACTGTCCAAAATAACGGGCACTCAGTGATGATGTTGCTGGAGAACAAGGCCAGCATT
TCTGGAGGAGGACTGCCTGCCCCATACCAGGCCAAACAGTTGCACCTGCACTGGTCCGAC
TTGCCATATAAGGGCTCGGAGCACAGCCTCGATGGGGAGCACTTTGCCATGGAGATGCAC
ATAGTACATGAGAAAGAGAAGGGGACATCGAGGAATGTGAAAGAGGCCCAGGACCCTGAA
GACGAAATTGCGGTGCTGGCCTTTCTGGTGGAGGCTGGAACCCAGGTGAACGAGGGCTTC
CAGCCACTGGTGGAGGCACTGTCTAATATCCCCAAACCTGAGATGAGCACTACGATGGCA
GAGAGCAGCCTGTTGGACCTGCTCCCCAAGGAGGAGAAACTGAGGCACTACTTCCGCTAC
CTGGGCTCACTCACCACACCGACCTGCGATGAGAAGGTCGTCTGGACTGTGTTCCGGGAG
CCCATTCAGCTTCACAGAGAACAGATCCTGGCATTCTCTCAGAAGCTGTACTACGACAAG
GAACAGACAGTGAGCATGAAGGACAATGTCAGGCCCCTGCAGCAGCTGGGGCAGCGCACG
GTGATAAAGTCCGGGGCCCCGGGTCGGCCGCTGCCCTGGGCCCTGCCTGCCCTGCTGGGC
CCCATGCTGGCCTGCCTGCTGGCCGGCTTCCTGCGATGA
Chromosome Location
17
Locus
17q23.1
External Identifiers
ResourceLink
UniProtKB IDP22748
UniProtKB Entry NameCAH4_HUMAN
GenBank Protein ID179791
GenBank Gene IDM83670
GeneCard IDCA4
GenAtlas IDCA4
HGNC IDHGNC:1375
PDB ID(s)1ZNC, 3F7B, 3F7U, 3FW3, 5IPZ, 5JN8, 5JN9, 5JNA, 5JNC, 5KU6
KEGG IDhsa:762
IUPHAR/Guide To Pharmacology ID2599
NCBI Gene ID762
General References
  1. 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. [Article]
  2. 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. [Article]
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  4. Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006 Apr 20;440(7087):1045-9. [Article]
  5. 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. [Article]
  6. 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. [Article]
  7. 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. [Article]
  8. 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. [Article]
  9. 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. [Article]
  10. 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. [Article]
  11. 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. [Article]
  12. 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. [Article]
  13. 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. [Article]
  14. 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. [Article]
  15. 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. [Article]
  16. 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. [Article]
  17. 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. [Article]
  18. Vernier W, Chong W, Rewolinski D, Greasley S, Pauly T, Shaw M, Dinh D, Ferre RA, Meador JW 3rd, Nukui S, Ornelas M, Paz RL, Reyner E: Thioether benzenesulfonamide inhibitors of carbonic anhydrases II and IV: structure-based drug design, synthesis, and biological evaluation. Bioorg Med Chem. 2010 May 1;18(9):3307-19. doi: 10.1016/j.bmc.2010.03.014. Epub 2010 Mar 11. [Article]
  19. 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. [Article]
  20. Alvarez BV, Vithana EN, Yang Z, Koh AH, Yeung K, Yong V, Shandro HJ, Chen Y, Kolatkar P, Palasingam P, Zhang K, Aung T, Casey JR: Identification and characterization of a novel mutation in the carbonic anhydrase IV gene that causes retinitis pigmentosa. Invest Ophthalmol Vis Sci. 2007 Aug;48(8):3459-68. [Article]
  21. Tian Y, Tang L, Cui J, Zhu X: Screening for the carbonic anhydrase IV gene mutations in Chinese retinitis pigmentosa patients. Curr Eye Res. 2010 May;35(5):440-4. doi: 10.3109/02713680903503512. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Carbonic anhydrase 4 (Humans)protein
primary
Carbonic anhydrase (Humans)protein
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
MethyclothiazidewithdrawnunknowntargetinhibitorDetails
TopiramateapprovedyestargetinhibitorDetails
BendroflumethiazideapprovedunknowntargetinhibitorDetails
BenzthiazideapprovedunknowntargetinhibitorDetails
Hydroflumethiazideapproved, investigational, withdrawnunknowntargetinhibitorDetails
Trichlormethiazideapproved, vet_approvedunknowntargetinhibitorDetails
DorzolamideapprovedyestargetinhibitorDetails
Zonisamideapproved, investigationalunknowntargetinhibitorDetails
Acetazolamideapproved, vet_approvedyestargetinhibitorDetails
EthoxzolamidewithdrawnyestargetinhibitorDetails
MethazolamideapprovedyestargetinhibitorDetails
Diclofenamideapproved, investigationalyestargetinhibitorDetails
BrinzolamideapprovedunknowntargetinhibitorDetails
Ellagic acidinvestigationalyestargetinhibitorDetails
Sodium carbonateapprovedunknowntargetinhibitorDetails
Ferulic acidexperimentalyestargetinhibitorDetails
5-[(phenylsulfonyl)amino]-1,3,4-thiadiazole-2-sulfonamideexperimentalyestargetinhibitorDetails
Sodium citrateapproved, investigationalyestargetinhibitorDetails
Phenylboronic acidexperimentalyestargetinhibitorDetails
Sodium phosphate, dibasicapprovedyestargetinhibitorDetails
4-(2-AMINOETHYL)BENZENESULFONAMIDEexperimentalyestargetinhibitorDetails
Hexamethylene diamineexperimentalyestargetinhibitorDetails
CadaverineexperimentalyestargetinhibitorDetails
p-Coumaric acidexperimentalyestargetinhibitorDetails
1,2-DihydroxybenzeneexperimentalyestargetinhibitorDetails
CoumarinexperimentalyestargetinhibitorDetails
Cianidanolapproved, withdrawnyestargetinhibitorDetails
Pyruvic acidapproved, investigational, nutraceuticalyestargetinhibitorDetails
Curcuminapproved, investigationalyestargetinhibitorDetails
Mafenideapproved, vet_approved, withdrawnyestargetinhibitorDetails
Salicylic acidapproved, investigational, vet_approvedyestargetinhibitorDetails
Spermineexperimental, nutraceuticalyestargetinhibitorDetails
Phenolapproved, experimentalyestargetinhibitorDetails
BenzthiazideapprovedyestargetinhibitorDetails
CyclothiazideapprovedyestargetinhibitorDetails