All known eukaryotic and prokaryotic cytoplasm contain reductases which participate in reducing disulfide bonds. Thus, proteins are oxidized to form disulfide bonds only in certain extra-cytoplasmic compartments such as the periplasmic space in gram negative prokaryotes or endoplasmic reticulum in eukaryotes. Exceptions to this may occur in certain thermophilic archaea such as Crenarchaea and few thermophilic bacteria (e.g. Aquifex and Thermotoga). There are websites such as Phobius or SignalP that can be used to predict whether a protein is in the oxidizing periplasm or endoplasmic reticulum. One can get an idea of the importance of cysteines in a protein of interest by analyzing how conserved the cysteine residues are in close homologs.
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