CDART: protein homology by domain architecture

Abstract

The Conserved Domain Architecture Retrieval Tool (CDART) performs similarity searches of the NCBI Entrez Protein Database based on domain architecture, defined as the sequential order of conserved domains in proteins. The algorithm finds protein similarities across significant evolutionary distances using sensitive protein domain profiles rather than by direct sequence similarity. Proteins similar to a query protein are grouped and scored by architecture. Relying on domain profiles allows CDART to be fast, and, because it relies on annotated functional domains, informative. Domain profiles are derived from several collections of domain definitions that include functional annotation. Searches can be further refined by taxonomy and by selecting domains of interest. CDART is available at http://www.ncbi.nlm.nih.gov/Structure/lexington/lexington.cgi.

Figure 1

The growth over time of the number of proteins known versus the growth in the number of unique domains. The left axis and red line are the cumulative sum of proteins in the NCBI Entrez Protein Database discovered in that year and in all previous years. The right axis and blue line are the total number of unique domains from the Conserved Domain Database that can be found in the cumulative set of proteins for each year, found by running RPS-BLAST on the set of proteins. Note that the zero slope in recent years may be caused by the need to accumulate multiple sequences to create a domain profile. However, this does not explain the inflection point in the curve beginning in 1990.

Figure 2

CDART results page for the tumor suppressor protein BRCA1 (accession NP_009225). Domains found in BRCA1 are shown in beads-on-a-string style at the top of the page and include zinc fingers and BRCT protein–protein interaction domains. Similar domain architectures are listed below using the same style. If an architecture contains more than one protein, it is preceded by a graphical icon, and clicking on the icon gives the full list of proteins with that architecture. At the bottom of the page are controls to subset the list of architectures by taxonomy and by domain.

Figure 3

The top left window allows users to select taxonomic groups of interest to subset CDART results. The lower right window is the results page for the search using BRCA1 subset by taxonomy to include only bacterial sequences. Note the large family of DNA ligases that contain the BRCT domain.