Taxonomic distribution of proteins containing DBC1 domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing DBC1 domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Analysis of DBC1 and its homologs suggests a potential mechanism for regulationof sirtuin domain deacetylases by NAD metabolites.

Anantharaman V, Aravind L
Cell Cycle. 2008; 7: 1467-72

Deleted in Breast Cancer-1 (DBC1) and its paralog CARP-1 are large multi-domainproteins, with a nuclear or perinuclear localization, and a role in promotingapoptosis upon processing by caspases. Recent studies on human DBC1 show that it is a specific inhibitor of the sirtuin-type deacetylase, Sirt1, whichdeacetylates histones and p53. Using sensitive sequence profile searches andHMM-HMM comparisons we show that the central conserved globular domain present inthe DBC1 and it homologs from diverse eukaryotes is a catalytically inactiveversion of the Nudix hydrolase (MutT) domain. Given that Nudix domains are known to bind nucleoside diphosphate sugars and NAD, we predict that this domain inDBC1 and its homologs binds NAD metabolites such as ADP-ribose. Hence, we proposethat DBC1 and its homologs are likely to regulate the activity of SIRT1 orrelated deacetylases by sensing the soluble products or substrates of theNAD-dependent deacetylation reaction. The complex domain architectures of themembers of the DBC1 family, which include fusions to the RNA-binding S1-likedomain, the DNA-binding SAP domain and EF-hand domains, suggest that they arelikely to function as integrators of distinct regulatory signals includingchromatin protein modification, soluble compounds in NAD metabolism, apoptoticstimuli and RNA recognition.