DBC1 and it homologs from diverse eukaryotes are a catalytically inactive version of the Nudix hydrolase (MutT) domain ((PUBMED:18418069)). DBC1 is predicted to bind NAD metabolites and regulate the activity of SIRT1 or related deacetylases by sensing the soluble products or substrates of the NAD-dependent deacetylation reaction ((PUBMED:18418069)).
This entry represents the central conserved globular domain present in DBC1 and homologues, and is a catalytically inactive version of the Nudix hydrolase (MutT) domain [ (PUBMED:18418069) ]. It may have a role in binding NAD metabolites, such as ADP-ribose.
Deleted in breast cancer 1 (DBC1), also known as cell division cycle and apoptosis regulator protein 2 (CCAR2), and its paralogous cell division cycle and apoptosis regulator protein 1 (CCAR1) are large multi-domain proteins, with a nuclear or perinuclear localisation, and a role in promoting apoptosis upon processing by caspases [ (PUBMED:18418069) ].
Family alignment:
There are 1043 DBC1 domains in 1041 proteins in SMART's nrdb database.
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Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing DBC1 domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with DBC1 domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing DBC1 domain in the selected taxonomic class.
Analysis of DBC1 and its homologs suggests a potential mechanism for regulationof sirtuin domain deacetylases by NAD metabolites.
Cell Cycle. 2008; 7: 1467-72
Display abstract
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.
Links (links to other resources describing this domain)
