Possible catecholamine-binding domain present in a variety of eukaryotic proteins.
SMART accession number:
SM00664
Description:
A predominantly beta-sheet domain present as a regulatory N-terminal domain in dopamine beta-hydroxylase, mono-oxygenase X and SDR2. Its function remains unknown at present (Ponting, Human Molecular Genetics, in press).
The DOMON domain is an 110-125 residue long domain which has been identified in the physiologically important enzyme dopamine beta-monooxygenase and in several other secreted and transmembrane proteins from both plants and animals. It has been named after DOpamine beta-MOnooxygenase N-terminal domain. The DOMON domain can be found in one to four copies and in association with other domains, such as the Cu-ascorbate dependent monooxygenase domain, the epidermal growth factor domain, the trypsin inhibitor-like domain (TIL), the SEA domain and the Reelin domain [ (PUBMED:11551777) ]. The DOMON domain may be involved in heme and sugar recognition [ (PUBMED:17878204) ].
The sequence conservation is predominantly centred around patches of hydrophobic residues. The secondary structure prediction of the DOMON domain points to an all-beta-strand fold with seven or eight core strands supported by a buried core of conserved hydrophobic residues. There is a chraracteristic motif with two small positions (Gly or Ser) corresponding to a conserved turn immediately C-terminal to strand three. It has been proposed that the DOMON domain might form a beta-sandwich structure, with the strands distributed into two beta sheets as is seen in many extracellular adhesion domains such as the immunoglobulin, fibronectin type III, cadherin and PKD domains [ (PUBMED:11551777) ].
Family alignment:
There are 6897 DoH domains in 5840 proteins in SMART's nrdb database.
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Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing DoH domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with DoH domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing DoH domain in the selected taxonomic class.
Cellular role (predicted cellular role)
Binding / catalysis: unknown
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
Complete assignment of disulfide bonds in bovine dopaminebeta-hydroxylase.
Biochemistry. 1994; 33: 11563-75
Display abstract
Peptide mapping, chemical sequencing, microbore HPLC/electrosprayionization mass spectrometry (LC/ESI/MS), and matrix-assisted laserdesorption mass spectrometry (MALDI/MS) were used to identify the sites ofintra- and intermolecular disulfide linkages in bovine dopaminebeta-hydroxylase. The enzyme contains 14 cysteines and seven disulfidesper monomer. Edman sequencing of tryptic and peptic peptides determinedlinkages at positions Cys140-Cys582, Cys218-Cys269, Cys255-Cys281,Cys452-Cys474, Cys514-Cys514, and Cys516-Cys516, where cysteines atpositions 514 and 516 on one monomer disulfide pair with their homologs ona second monomer. These linkages were confirmed by LC/ESI/MS and MALDI/MS.Further analysis by LC/ESI/MS and MALDI/MS identified linkages atpositions Cys376-Cys489 and Cys380-Cys551. Cysteines 140 and 582 form adisulfide linkage that folds the C-terminus back in proximity to theN-terminus. The remaining intramolecular disulfides occur along twoseparate internal regions of the protein. The density of histidineresidues in these two regions suggests binding sites for two Cu2+ atomsper monomer. In addition, previously identified amino acids that reactwith mechanism-based inactivators occur in these two regions. We proposethat these five internal disulfide bonds define two Cu2+ binding domainsthat make up the active site of a dopamine beta-hydroxylase monomer.Considering previous data on the location of glycosylation sites,mechanism-based inactivation sites, and the disulfide linkages presentedhere, the data suggest an overall topology were the N- and C-termini arein close proximity and are solvent exposed and where the Cu2+ bindingsites are buried in two interior domains stabilized by five disulfidebonds.
Metabolism (metabolic pathways involving proteins which contain this domain)
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This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with DoH domain which could be assigned to a KEGG orthologous group, and not all proteins containing DoH domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.
