Functional annotation of proteins

Fig. 2. Functional annotation of protein B from sequence similarities to protein A. The correct annotation lies above the dotted line. Incorrect cases lie below the dotted line. Objects colored in red indicate errors in annotation. Similar shading of objects...

Comparison of protein active site structures for functional annotation of proteins and drug design. Proteins 65 124-135... 

Fleischmann, W., S. Moller, A. Gateau, and R. Apweiler. 1999. A novel method for automatic functional annotation of proteins. Bioinformatics 15 228-33. 

Fleming, R, Muller, A, MacCallum, R M., Sternberg, M. J. (2004). 3D-GENOMICS A database to compare structural and functional annotations of proteins between sequenced genomes. Nucleic... 

Natale, D.A., Vinayaka, C.R. and Wu, C.H., Large-scale, classification-driven, rule-based functional annotation of proteins. In Subramaniam, S. (Ed.), Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics. Proteomics Volume. 2005. 

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Barglow KT, Cravatt BF (2007) Activity-based protein profiling for the functional annotation of enzymes. Nat Methods 4 822-827... 

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. 

Kreienkamp HJ, Larusson HJ, Witte I, et al. Functional annotation of two orphan G-protein-coupled receptors, Drostarl and -2, from Drosophila mela-nogaster and their ligands by reverse pharmacology. J Biol Chem 2002 277 39937-39943. 

Knowledge of protein primary sequence, quantities, posttranslational modifications (PTMs), structures, protein-protein (P-P) interactions, cellular spatial relationships, and functions are seven important attributes (see Table 4.2) needed for comprehensive protein expression analysis. It is this multifold and complex nature of protein attributes that has spawned the development of so different many proteomic technologies. Some of these challenges in proteomic analysis include defining the identities and quantities of an entire proteome in a particular spatial location (i.e., serum, liver mitochondria, brain), the existence of multiple protein forms and complexes, the evolving structural and functional annotations of the human and rodent... 

Figure 1 Schematic illustration of the proteomics process comprising the utilization of both gel-base and liquid-phase separations interphased to mass spectrometry analysis followed by database search mining, annotation, and a final link to the functional role of proteins.

The conditio sine qua non for structure-based drug design is the identification and functional annotation of the relevant binding site(s) in a target protein. A number of methods, closely related to the characteristics of binding sites and the restraints imposed on the formation of functional structural units, are discussed in Section 4.2. The most commonly used methods can be classified into geometry-based methods for cavity detection, methods for identifying specific patterns, and evolutionary methods. 

Functional annotation of novel gene products used to be mainly based on sequence homologies to previously known proteins. For distant relatives, these homologies are often limited to a few short, but usually characteristic, sequence motifs. Tentative assigmnents of this kind can now be put on a solid basis by more sophisticated and powerful approaches, such as threading techifiques, which aim at verifying the compatibility of a given amino acid sequence with a 3D-fold. 

In this chapter, we describe steps for protein function annotation of a newly sequenced genome in detail and also discuss tools for each step. Each step... 

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)... 

Computational proteomics refers to the large-scale generation and analysis of 3D protein structural information. Accurate prediction of protein contact maps is the beginning and essential step for computational proteomics. The major resource for computational proteomics is the currently available information on protein and nucleic acid structures. The 3D-GENOM1CS (www.sbg.bio.ic.au.uk/3dgenomics/) and PDB (http // www.rcsb.org/pdb/), and other databases provide a broad range of structural and functional annotations for proteins from sequenced genomes and protein 3D structures, which make a solid foundation for computational proteomics. 

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