Carbonic anhydrase 4

Details

Name
Carbonic anhydrase 4
Synonyms
  • 4.2.1.1
  • CA-IV
  • Carbonate dehydratase IV
  • Carbonic anhydrase IV
Gene Name
CA4
Organism
Humans
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
Functions
carbonate dehydratase activity / zinc ion binding
Processes
bicarbonate transport / one-carbon metabolic process / organ development / response to drug / response to steroid hormone / small molecule metabolic process
Components
anchored component of external side of plasma membrane / apical plasma membrane / brush border membrane / cell surface / endoplasmic reticulum-Golgi intermediate compartment / extracellular exosome / Golgi apparatus / membrane / perinuclear region of cytoplasm / plasma membrane / rough endoplasmic reticulum / sarcolemma / sarcoplasmic reticulum / secretory granule membrane / trans-Golgi network / transport vesicle membrane
General Function
Zinc ion binding
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.
Pfam Domain Function
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
External Identifiers
ResourceLink
UniProtKB IDP22748
UniProtKB Entry NameCAH4_HUMAN
GenBank Protein ID179791
GenBank Gene IDM83670
GenAtlas IDCA4
HGNC IDHGNC:1375
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. [PubMed:1311094]
  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. [PubMed:8325641]
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  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. [PubMed:2111324]
  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. [PubMed:8809084]
  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. [PubMed:7625839]
  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. [PubMed:16807956]
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  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. [PubMed:17314045]
  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. [PubMed:19186056]
  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. [PubMed:19206230]
  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. [PubMed:18618712]
  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. [PubMed:8942978]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00232MethyclothiazideapprovedunknowninhibitorDetails
DB00273TopiramateapprovedyesinhibitorDetails
DB00436BendroflumethiazideapprovedunknowninhibitorDetails
DB00562BenzthiazideapprovedunknowninhibitorDetails
DB00606CyclothiazideapprovedunknowninhibitorDetails
DB00774Hydroflumethiazideapproved, investigationalunknowninhibitorDetails
DB01021Trichlormethiazideapproved, vet_approvedunknowninhibitorDetails
DB00869DorzolamideapprovedunknowninhibitorDetails
DB00909Zonisamideapproved, investigationalunknowninhibitorDetails
DB00819Acetazolamideapproved, vet_approvedyesinhibitorDetails
DB00311EthoxzolamidewithdrawnyesinhibitorDetails
DB00703MethazolamideapprovedyesinhibitorDetails
DB01144Diclofenamideapproved, investigationalyesinhibitorDetails
DB01194BrinzolamideapprovedunknowninhibitorDetails
DB08846Ellagic acidinvestigationalunknowninhibitorDetails
DB09460Sodium carbonateapprovedunknowninhibitorDetails