Carbonic anhydrase 4

UniProt P22748 Organism Homo sapiens Gene CA4 EC 4.2.1.1

Also known as: CA4

Function

Catalyzes the reversible hydration of carbon dioxide into bicarbonate and protons and thus is essential to maintaining intracellular and extracellular pH. 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.

Classification

Family (Pfam): PF00194 Carb_anhydrase
InterPro: CA4/CA15, CA_dom, CA_dom_sf, Carbonic_anhydrase_a-class, Carbonic_anhydrase_a-class_CS
Functional cluster: Secreted Growth Factors & Cytokines

Experimental structures · PDB · 10

1ZNC X-ray 2.80A
3F7B X-ray 2.05A
3F7U X-ray 2.00A
3FW3 X-ray 1.72A
5IPZ X-ray 2.10A
5JN8 X-ray 1.85A
5JN9 X-ray 2.10A
5JNA X-ray 2.00A
5JNC X-ray 2.00A
5KU6 X-ray 1.80A

A predicted model is available from AlphaFold.

Gene Ontology · 17

Disease associations

retinitis pigmentosa 17 MONDO:0010945

Drugs targeting this protein · 7

ACETAZOLAMIDE SODIUM inhibitor
DICHLORPHENAMIDE inhibitor
ETHOXZOLAMIDE inhibitor
METHAZOLAMIDE inhibitor
ACETAZOLAMIDE inhibitor
TOPIRAMATE inhibitor
SULTHIAME inhibitor

Neighborhood · nearest proteins

Nearest neighbours of Carbonic anhydrase 4: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Carbonic anhydrase 4 0.97
Carbonic anhydrase 4 0.96
Carbonic anhydrase 4 0.93
Carbonic anhydrase 4 0.93
Carbonic anhydrase 15 0.90
Carbonic anhydrase 12 0.86
Carbonic anhydrase 12 0.84
Carbonic anhydrase 12 0.83
Carbonic anhydrase 9 0.82
Carbonic anhydrase 9 0.77
Carbonic anhydrase-related protein 11 0.77
Carbonic anhydrase-related protein 11 0.77

Co-cited proteins · studied together in the literature

Carbonic anhydrase 14 8 shared papers
Carbonic anhydrase 7 7 shared papers
Carbonic anhydrase 5A, mitochondrial 7 shared papers
Electrogenic sodium bicarbonate cotransporter 1 1 shared papers
Carbonic anhydrase 1 7 shared papers
Carbonic anhydrase 2 8 shared papers
Carbonic anhydrase 12 5 shared papers
Carbonic anhydrase 5B, mitochondrial 4 shared papers
Carbonic anhydrase 6 4 shared papers
Carbonic anhydrase 9 4 shared papers
Carbonic anhydrase 3 3 shared papers
Carbonic anhydrase 13 3 shared papers

Literature · 21 cited papers

Screening for the carbonic anhydrase IV gene mutations in Chinese retinitis pigmentosa patients. Curr. Eye Res. · 2010
Thioether benzenesulfonamide inhibitors of carbonic anhydrases II and IV: structure-based drug design, synthesis, and biological evaluation. Bioorg. Med. Chem. · 2010
Non-zinc mediated inhibition of carbonic anhydrases: coumarins are a new class of suicide inhibitors. J. Am. Chem. Soc. · 2009
A thiabendazole sulfonamide shows potent inhibitory activity against mammalian and nematode alpha-carbonic anhydrases. Bioorg. Med. Chem. Lett. · 2009
Crystal structure of human carbonic anhydrase XIII and its complex with the inhibitor acetazolamide. Proteins · 2009
Saccharin inhibits carbonic anhydrases: possible explanation for its unpleasant metallic aftertaste. Angew. Chem. Int. Ed. Engl. · 2007
Identification and characterization of a novel mutation in the carbonic anhydrase IV gene that causes retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. · 2007
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
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
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
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
DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature · 2006
… and 9 more in the literature graph

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