The Conserved Domain Database (CDD) is a database of well-annotated multiple sequence alignment

Multiple sequence alignment

A multiple sequence alignment is a sequence alignment of three or more biological sequences, generally protein, DNA, or RNA. In many cases, the input set of query sequences are assumed to have an evolutionary relationship by which they share a lineage and are descended from a common ancestor...

 models and derived database search models, for ancient domains

Protein domain

A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...

and full-length proteins.

Philosophy

Domains can be thought of as distinct functional and/or structural units of a protein. These two classifications coincide rather often, as a matter of fact, and what is found as an independently folding unit of a polypeptide chain also carries specific function. Domains are often identified as recurring (sequence or structure) units, which may exist in various contexts. In molecular evolution such domains may have been utilized as building blocks, and may have been recombined in different arrangements to modulate protein function. CDD defines conserved domains as recurring units in molecular evolution, the extents of which can be determined by sequence and structure analysis.

The goal of the NCBI conserved domain curation project is to provide database users with insights into how patterns of residue conservation and divergence in a family relate to functional properties, and to provide useful links to more detailed information that may help to understand those sequence/structure/function relationships. To do this, CDD Curators include the following types of information in order to supplement and enrich the traditional multiple sequence alignments that form the foundation of domain models: 3-dimensional structures and conserved core motifs, conserved features/sites, phylogenetic organization, links to electronic literature resources.

Content

CDD content includes NCBI manually curated domain models and domain models imported from a number of external source databases (Pfam, SMART, COG, PRK, TIGRFAM). What is unique about NCBI-curated domains is that they use 3D-structure information to explicitly define domain boundaries, align blocks, amend alignment details, and provide insights into sequence/structure/function relationships. Manually curated models are organized hierarchically if they describe domain families that are clearly related by common descent. To provide a non-redundant view of the data, CDD clusters similar domain models from various sources into superfamilies.

Searching the database

The collection is also part of NCBI’s Entrez query and retrieval system, crosslinked to numerous other resources. CDD provides annotation of domain footprints and conserved functional sites on protein sequences. Precalculated domain annotation can be retrieved for protein sequences tracked in NCBI’s Entrez system, and CDD’s collection of models can be queried with novel protein sequences via * , or at* , that allows the computation and download of annotation for large sets of protein queries.