We and others had previously reported the DOMON (also called DoH) domain in several extracellular proteins from animals and plants, such as Dopamine beta- monooxygenase and SDR2. However, very little was known of its function in these contexts. Using sensitive sequence and structure comparison methods, we show that the DOMON domains are small molecule binding domains of the immunoglobulin fold that bind heme or sugars through a common mode. The presence of the heme-binding DOMON domain in several extracellular animals proteins suggest that they may be involved in yet unidentified redox reactions potentially related to protein hydroxylation or oxidative cross-linking. Interestingly, the classical vertebrate Dopamine beta-monooxygenase and the arthropod and nematode tyramine-beta-hydroxylase lack the heme coordinating motifs, although closely related proteins such as MOXD1 appear to retain heme binding. We also report the first prokaryotic members of this superfamily that include the gamma subunit of Ethyl benzene dehydrogenase (the cytochrome domain) and CbsA/cytochrome b558/556, and provide a detailed evolutionary history.
The uncharacterized DM13 domain also appears to be of prokaryotic origin and contains a highly conserved cysteine residue that could potentially be involved in redox reactions.
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