Conserved Domains and Protein Classification

Conserved Domain Database (CDD)

CDD is a protein annotation resource that consists of a collection of well-annotated multiple sequence alignment models for ancient domains and full-length proteins. These are available as position-specific score matrices (PSSMs) for fast identification of conserved domains in protein sequences via RPS-BLAST. CDD content includes NCBI-curated domains, which use 3D-structure information to explicitly define domain boundaries and provide insights into sequence/structure/function relationships, as well as domain models imported from a number of external source databases (Pfam, SMART, COG, PRK, TIGRFAMs).
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Batch CD-Search

CD-Search is NCBI's interface to searching the Conserved Domain Database with protein or nucleotide query sequences. It uses RPS-BLAST, a variant of PSI-BLAST, to quickly scan a set of pre-calculated position-specific scoring matrices (PSSMs) with a protein query. The results of CD-Search are presented as an annotation of protein domains on the user query sequence (illustrated example), and can be visualized as domain multiple sequence alignments with embedded user queries. High confidence associations between a query sequence and conserved domains are shown as specific hits. The CD-Search Help provides additional details, including information about running CD-Search locally.
Batch CD-Search serves as both a web application and a script interface for a conserved domain search on multiple protein sequences, accepting up to 4,000 proteins in a single job. It enables you to view a graphical display of the concise or full search result for any individual protein from your input list, or to download the results for the complete set of proteins. The Batch CD-Search Help provides additional details.
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Protein Classification

The Subfamily Protein Architecture Labeling Engine (SPARCLE) is a resource for the functional characterization and labeling of protein sequences that have been grouped by their characteristic domain architecture. To use SPARCLE, you can either: (1) enter a query protein sequence into CD-Search, which will display a "Protein Classification" on the results page if the query protein has a hit to a curated domain architecture in the SPARCLE database (example, using NP_387887 as the query sequence), or (2) search the SPARCLE database by keyword to retrieve domain architectures that contain the term(s) of interest in their descriptions (example, searching for the words "chloride" and "channel" in the domain architecture record, and limiting the results to curated architectures). With either approach, the corresponding SPARCLE record(s) will display the name and functional label of the architecture, supporting evidence, and links to other proteins with the same architecture.
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Domain Architectures

Conserved Domain Architecture Retrieval Tool (CDART) performs similarity searches of the Entrez Protein database based on domain architecture, defined as the sequential order of conserved domains in protein queries. CDART finds protein similarities across significant evolutionary distances using sensitive domain profiles rather than direct sequence similarity. Proteins similar to the query are grouped and scored by architecture. You can search CDART directly with a query protein sequence, or, if a sequence of interest is already in the Entrez Protein database, simply retrieve the record, open its "Links" menu, and select "Domain Relatives" to see the precalculated CDART results (illustrated example). Relying on domain profiles allows CDART to be fast and, because it relies on annotated functional domains, informative.
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CDTree is a helper application for your web browser that allows you to interactively view and examine conserved domain hierarchies curated at NCBI. CDTree works with Cn3D as its alignment viewer/editor, it is used in the CDD curation process and is a both classification and research tool for functional annotation and the study of protein and protein domain families.
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How to use the conserved domain resources: examples back to top

Identify the putative function of a protein sequence


Identify a protein's classification based on domain architecture


Identify the amino acids in a protein sequence that are putatively involved in functions such as binding or catalysis, as mapped from conserved domain annotations to the query sequence


View a query protein sequence embedded within the multiple sequence alignment of a domain model


Interactively view the 3D structure of a conserved domain


Find other proteins with similar domain architecture


Interactively view the phylogenetic sequence tree for a conserved domain model of interest with or without a query sequence embedded


What is a conserved domain?

Thumbnail image for 3D structure of type-1 insulin-like growth-factor receptor (IGF-1R), viewed in the free Cn3D structure viewing program and colored by domain.  Click on image to jump to a larger, annotated version in the CDD help document.

3-D structures and
conserved core motifs:

Thumbnail image for example of 3-dimensional structure: Cl- binding residues in Voltage-Gated Chloride Channel, cd00400.  Click on image to jump to a larger, annotated version in the CDD help document.

Conserved features
(binding and catalytic sites)

Thumbnail image for examples of Conserved Features (Sites) in Voltage-Gated Chloride Channel, cd00400, including Cl- selectivity filter, pore-gating glutamate residue, Cl- binding residues, and dimer interface..  Click on image to jump to a larger, annotated version in the CDD help document.

Protein classification
based on domain architecture

Thumbnail image of a SPARCLE summary page, showing proteins classified under th DNA gyrase subunit B architecture. Click on image for more information.

Proteins with
Similar Domain Architectures

Thumbnail image showing the domain relatives for protein sequence NP_081086, mouse DNA mismatch repair protein Mlh1. Domain relatives are protein sequences that contain one or more of the conserved domains found in the query sequence, as identified by the Conserved Domain Architecture Retrieval Tool (CDART).  Click on the image for an example of how to find domain relatives for a query protein.

Domain family hierarchies

Thumbnail image of domain hierarchy showing divergence in a protein family based on phylogenetic relationships of protein sequences and functional properties.  Click on image to jump to a larger, annotated version in the CDD help document.
Revised 27 November 2018