David I. Hurwitz

CDD: a Conserved Domain Database for the functional annotation of proteins

NCBI’s Conserved Domain Database (CDD) is a resource for the annotation of protein sequences with the location of conserved domain footprints, and functional sites inferred from these footprints. CDD includes manually curated domain models that make use of protein 3D structure to refine domain models 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. As CDD also imports domain family models from a variety of external sources, it is a partially redundant collection. To simplify protein annotation, redundant models and models describing homologous families are clustered into superfamilies. By default, domain footprints are annotated with the corresponding superfamily designation, on top of which specific annotation may indicate high-confidence assignment of family membership. Pre-computed domain annotation is available for proteins in the Entrez/Protein dataset, and a novel interface, Batch CD-Search, allows the computation and download of annotation for large sets of protein queries. CDD can be accessed via http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml.

CDD: NCBI's conserved domain database

NCBIs CDD, the Conserved Domain Database, enters its 15th year as a public resource for the annotation of proteins with the location of conserved domain footprints. Going forward, we strive to improve the coverage and consistency of domain annotation provided by CDD. We maintain a live search system as well as an archive of pre-computed domain annotation for sequences tracked in NCBIs Entrez protein database, which can be retrieved for single sequences or in bulk. We also maintain import procedures so that CDD contains domain models and domain definitions provided by several collections available in the public domain, as well as those produced by an in-house curation effort. The curation effort aims at increasing coverage and providing finer-grained classifications of common protein domains, for which a wealth of functional and structural data has become available. CDD curation generates alignment models of representative sequence fragments, which are in agreement with domain boundaries as observed in protein 3D structure, and which model the structurally conserved cores of domain families as well as annotate conserved features. CDD can be accessed at http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml.

CDD: a Conserved Domain Database for protein classification

The Conserved Domain Database (CDD) is the protein classification component of NCBIs Entrez query and retrieval system. CDD is linked to other Entrez databases such as Proteins, Taxonomy and PubMed®, and can be accessed at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=cdd. CD-Search, which is available at http://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi, is a fast, interactive tool to identify conserved domains in new protein sequences. CD-Search results for protein sequences in Entrez are pre-computed to provide links between proteins and domain models, and computational annotation visible upon request. Protein–protein queries submitted to NCBIs BLAST search service at http://www.ncbi.nlm.nih.gov/BLAST are scanned for the presence of conserved domains by default. While CDD started out as essentially a mirror of publicly available domain alignment collections, such as SMART, Pfam and COG, we have continued an effort to update, and in some cases replace these models with domain hierarchies curated at the NCBI. Here, we report on the progress of the curation effort and associated improvements in the functionality of the CDD information retrieval system.

CDD: specific functional annotation with the Conserved Domain Database.

NCBIs Conserved Domain Database (CDD) is a collection of multiple sequence alignments and derived database search models, which represent protein domains conserved in molecular evolution. The collection can be accessed at http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml, and is also part of NCBIs Entrez query and retrieval system, cross-linked 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 NCBIs Entrez system, and CDDs collection of models can be queried with novel protein sequences via the CD-Search service at http://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi. Starting with the latest version of CDD, v2.14, information from redundant and homologous domain models is summarized at a superfamily level, and domain annotation on proteins is flagged as either ‘specific’ (identifying molecular function with high confidence) or as ‘non-specific’ (identifying superfamily membership only).

CDD: a conserved domain database for interactive domain family analysis

The conserved domain database (CDD) is part of NCBIs Entrez database system and serves as a primary resource for the annotation of conserved domain footprints on protein sequences in Entrez. Entrezs global query interface can be accessed at and will search CDD and many other databases. Domain annotation for proteins in Entrez has been pre-computed and is readily available in the form of ‘Conserved Domain’ links. Novel protein sequences can be scanned against CDD using the CD-Search service; this service searches databases of CDD-derived profile models with protein sequence queries using BLAST heuristics, at . Protein query sequences submitted to NCBIs protein BLAST search service are scanned for conserved domain signatures by default. The CDD collection contains models imported from Pfam, SMART and COG, as well as domain models curated at NCBI. NCBI curated models are organized into hierarchies of domains related by common descent. Here we report on the status of the curation effort and present a novel helper application, CDTree, which enables users of the CDD resource to examine curated hierarchies. More importantly, CDD and CDTree used in concert, serve as a powerful tool in protein classification, as they allow users to analyze protein sequences in the context of domain family hierarchies.

CDD: conserved domains and protein three-dimensional structure

CDD, the Conserved Domain Database, is part of NCBI’s Entrez query and retrieval system and is also accessible via http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml. CDD provides annotation of protein sequences with the location of conserved domain footprints and functional sites inferred from these footprints. Pre-computed annotation is available via Entrez, and interactive search services accept single protein or nucleotide queries, as well as batch submissions of protein query sequences, utilizing RPS-BLAST to rapidly identify putative matches. CDD incorporates several protein domain and full-length protein model collections, and maintains an active curation effort that aims at providing fine grained classifications for major and well-characterized protein domain families, as supported by available protein three-dimensional (3D) structure and the published literature. To this date, the majority of protein 3D structures are represented by models tracked by CDD, and CDD curators are characterizing novel families that emerge from protein structure determination efforts.

CDD/SPARCLE: functional classification of proteins via subfamily domain architectures

NCBIs Conserved Domain Database (CDD) aims at annotating biomolecular sequences with the location of evolutionarily conserved protein domain footprints, and functional sites inferred from such footprints. An archive of pre-computed domain annotation is maintained for proteins tracked by NCBIs Entrez database, and live search services are offered as well. CDD curation staff supplements a comprehensive collection of protein domain and protein family models, which have been imported from external providers, with representations of selected domain families that are curated in-house and organized into hierarchical classifications of functionally distinct families and sub-families. CDD also supports comparative analyses of protein families via conserved domain architectures, and a recent curation effort focuses on providing functional characterizations of distinct subfamily architectures using SPARCLE: Subfamily Protein Architecture Labeling Engine. CDD can be accessed at https://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml.

MMDB: Entrez's 3D-structure database

Three-dimensional structures are now known within many protein families and it is quite likely, in searching a sequence database, that one will encounter a homolog with known structure. The goal of Entrezs 3D-structure database is to make this information, and the functional annotation it can provide, easily accessible to molecular biologists. To this end Entrezs search engine provides three powerful features. (i) Sequence and structure neighbors; one may select all sequences similar to one of interest, for example, and link to any known 3D structures. (ii) Links between databases; one may search by term matching in MEDLINE, for example, and link to 3D structures reported in these articles. (iii) Sequence and structure visualization; identifying a homolog with known structure, one may view molecular-graphic and alignment displays, to infer approximate 3D structure. In this article we focus on two features of Entrezs Molecular Modeling Database (MMDB) not described previously: links from individual biopolymer chains within 3D structures to a systematic taxonomy of organisms represented in molecular databases, and links from individual chains (and compact 3D domains within them) to structure neighbors, other chains (and 3D domains) with similar 3D structure. MMDB may be accessed at http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure.