Protein annotation, domain families

Prosite is perhaps the best known of the domain databases (Hofmann et al., 1999). The Prosite database is a good source of high quality annotation for protein domain families. Prosite documentation includes a section on the functional meaning of a match to the entry and a list of example members of the family. Prosite documentation also includes literature references and cross links to other databases such as the PDB collection of protein structures (Bernstein et al., 1977). For each Prosite document, there is a Prosite pattern, profile, or both to detect the domain family. The profiles are the most sensitive detection method in Prosite. The Prosite profiles provide Zscores for matches allowing statistical evaluation of the match to a new protein. Profiles are now available for many of the common protein domains. Prosite profiles use the generalized profile software (Bucher et al., 1996). 

The SBASE database is a collection of annotated protein sequence segments (Murvai et al., 1999). SBASE avoids using consensus methods such as profile-HMMs and uses pairwise methods to detect domains. The database includes more than 130,000 annotated sequence segments that have been clustered into groups on the basis of BLAST similarities. SBASE currently contains 1038 domain families. 

A variety of domain or motif families occur only as extensions to other domains. The Bruton s tyrosine kinase motif (BTK), for example, is found only at the C terminus of PH domains. Similarly, a C-terminal extension (the S TK X domain) to some subfamilies of serine/threonine kinases (S TK) is not found in isolation. Cases where only the extension, and not the preceding domain, is found are strong evidence that the proteins are wrongly assembled from genomic sequence or else represent partial cDNA sequences (Fig. 9, see Color insert). Indeed, all five proteins annotated in SMART as containing a S TK X domain with no catalytic domain are noted to be fragments in their corresponding sequence database entries. 

Many databases provide information on functional annotation of the genomes of organisms. One such high-quality standard database is Pfam (19). Pfam is fundamentally a protein domain family database derived based on sequence similarity. Pfam provides details on the functional properties of protein domains of known function. Out of 1,590, 1,495, and 1,536 proteins encoded in the genomes of 26695, J99, and HPAG1 strains of H. pylori, respectively, 1,113, 1,130, and 1,143 proteins have at least 1 protein domain associated (defined by Pfam) with the amino acid sequence. Therefore, for these domains of H. pylori proteins, preliminary indication of their functions is available. 

SMART (Simple Modular Architecture Research Tool) [12-14] is a Web-based resource used for the annotation of protein domains and the analysis of domain architectures, with particular emphasis on mobile eukaryotic domains. Extensive annotation for each domain family is available, providing information relating to function, subcellular localization, phyletic distribution and tertiary structure. The January 2002 release has added more than 200 hand-curated domain models. This brings the total to over 600 domain families that are widely represented among nuclear, signalling and extracellular proteins. Annotation now includes links to the Online Mendelian Inheritance in Man (OMIM) database in cases where a human disease is associated with one or more mutations in a particular domain, (http //smart, embl-heidelberg. de/help/smart about. shtml)... 

The protein sequence database is also a text-numeric database with bibliographic links. It is the largest public domain protein sequence database. The current PIR-PSD release 75.04 (March, 2003) contains more than 280 000 entries of partial or complete protein sequences with information on functionalities of the protein, taxonomy (description of the biological source of the protein), sequence properties, experimental analyses, and bibliographic references. Queries can be started as a text-based search or a sequence similarity search. PIR-PSD contains annotated protein sequences with a superfamily/family classification. 

Whenever a TrEMBL entry is recognized by these procedures as a true member of a certain protein family, annotation about the potential function, active sites, cofactors, binding sites, domains, and subcellular locations is added to the entry. The main source of the annotation is compiled by extracting the annotation that is common to all SWISS-... 

To discover protein functional or structural sequence motifs, you could select proteins belonging to a given protein family based on sequence similarity, structure, annotation, or other means (23,37,38). You might further refine the selection to only include proteins from organisms with a particular feature, such as the ability to live in extreme environments (39). Another protein motif discovery application uses information from protein-protein interaction experiments. You can assemble a set of proteins that bind to a common host protein, to discover sequence motifs for the interacting domains. 

Labes M, Puhler A, Simon R (1990) A new family of RSFlOlO-derived expression and lac-fusion broad-host-range vectors for gram-negative bacteria. Gene 89(l) 37-46 Marchler-Bauer A, Lu S, Anderson JB, Chitsaz F, Derbyshire MK, DeWeese-Scott C, Bryant SH (2011) CDD a conserved domain database for the functional annotation of proteins. Nucleic Acids Res 39(Database issue) D225-229... 

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