Eukaryotic-type carbonic anhydrase

No Pfam abstract.

InterPro entry IPR001148

Carbonic anhydrases (CA: ) are zinc metalloenzymes which catalyse the reversible hydration of carbon dioxide to bicarbonate PUBMED:18336305, PUBMED:10978542. CAs have essential roles in facilitating the transport of carbon dioxide and protons in the intracellular space, across biological membranes and in the layers of the extracellular space; they are also involved in many other processes, from respiration and photosynthesis in eukaryotes to cyanate degradation in prokaryotes. There are five known evolutionarily distinct CA families (alpha, beta, gamma, delta and epsilon) that have no significant sequence identity and have structurally distinct overall folds. Some CAs are membrane-bound, while others act in the cytosol; there are several related proteins that lack enzymatic activity. The active site of alpha-CAs is well described, consisting of a zinc ion coordinated through 3 histidine residues and a water molecule/hydroxide ion that acts as a potent nucleophile. The enzyme employs a two-step mechanism: in the first step, there is a nucleophilic attack of a zinc-bound hydroxide ion on carbon dioxide; in the second step, the active site is regenerated by the ionisation of the zinc-bound water molecule and the removal of a proton from the active site PUBMED:9336012. Beta- and gamma-CAs also employ a zinc hydroxide mechanism, although at least some beta-class enzymes do not have water directly coordinated to the metal ion.

• The alpha-CAs are found predominantly in animals but also in bacteria and green algae. There are at least 15 isoforms found in mammals, which can be subdivided into cytosolic CAs (CA-I, CA-II, CA-III, CA-VII and CA XIII), mitochondrial CAs (CA-VA and CA-VB), secreted CAs (CA-VI), membrane-associated (CA-IV, CA-IX, CA-XII and CA-XIV) and those without CA activity, the CA-related proteins (CA-RP VIII, X and XI).

• The beta-CAs are highly abundant in plants, diatoms, eubacteria and archaea PUBMED:16407248, PUBMED:12107142. The beta-CAs are far more diverse in sequence than other classes, and can be divided into different clades based on sequence identity, with the plant enzymes forming two clades representing dicotyledonous and monocotyledonous plants. Characterisation of these enzymes reveals sharp differences between the beta class, which forms dimers, tetramers, hexamers and octomers, and the alpha and gamma classes, which form strictly monomers and trimers.

• The gamma-CAs may be the most ancient form of carbonic anhydrases, having evolved long before the alpha class, to which it is more closely related than to the beta-class PUBMED:18289884, PUBMED:18336318. The reaction mechanism of the gamma-class is similar to that of the alpha-class, even though the overall folds are dissimilar and the active site residues differ.

• The delta-CAs are found in marine algae and dinoflagellates PUBMED:18467453.

• The epsilon-CAs are found in prokaryotes such as Thiobacillus neapolitanus (Halothiobacillus neapolitanus) in which it is a component of the carboxysome shell, where it could supply the active sites of RuBisCO in the carboxysome with the high concentrations of carbon dioxide necessary for optimal RuBisCO activity and efficient carbon fixation PUBMED:14729686.

This entry represents alpha class carbonic anhydrases.

More information about these proteins can be found at Protein of the Month: Carbonic Anhydrase PUBMED:.

External database links

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

There are various ways to view or download the sequence alignments that we store. You can use a sequence viewer to look at either the seed or full alignment for the family, or you can look at a plain text version of the sequence in a variety of different formats. More...

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The main seed and full alignments are generated using sequences from the UniProt sequence database. However, we also generate alignments using sequences from the NCBI sequence database and the "metaseq" metagenomics dataset.

You can view alignments from these two additional datasets using the form above, or you can download alignments of NCBI or metagenomics sequences, as gzip-compressed files.

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MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER2.

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

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HMM information

There is 1 interaction for this family. More...

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Carb_anhydrase domain has been found.