PROSITE database searches

PROSITE is a database of biologically significant sites and patterns (amino acid residues) formulated from a known family of proteins as the characteristic familial identifiers or signatures that can be used to detected such family from the query sequences of proteins. If the PROSITE database (prosite.dat downloaded from http //expasy.hcuge.ch/sprot/prosite.html) is installed in the usrstuff directory, selecting Search for PROSITE tool from the Edit menu returns a list of ProSite for... 

It can be difficult if not impossible to find the domain structure of a protein of interest from the primary literature. The sequence may contain many common domains, but these are usually not apparent from searches of literature. Articles defining new domains may include the protein, but only in an alignment figure, which are not searchable. Perhaps, with the advent of online access to articles, the full text including figures may become searchable. Fortunately there have been several attempts to make this hidden information available in away that can be easily searched. These resources, called domain family databases, are exemplified by Prosite, Pfam, Prints, and SMART. These databases gather information from the literature about common domains and make it searchable in a variety of ways. They usually allow a researcher to look at the domain organization of proteins in the sequence database that have been precalculated and also provide a way to search new sequences... 

The BLOCKS database contains blocks for each family (Henikoff and Henikoff, 1991 Henikoff et al., 1999). Blocks are ungapped multiple sequence alignments that are exacdy equivalent to the motifs found in the PRINTS database. The families in BLOCKS are currently derived from Prosite and PRINTS families. The bulk of BLOCKS entries are constructed from Prosite, using the lists of true positive members they provide. Motifs are automatically derived from the members of the Prosite family. Note that BLOCKS does not use the Prosite patterns to construct its motifs. BLOCKS provides functionality to search motifs against motifs this feature is not provided by other databases. 

When a novel homology domain has been discovered, it is possible to store the corresponding domain descriptor (profile or HMM) in a number of dedicated domain databases, which can be used to analyze newly identified sequences for their domain content [9, 10]. Several competing domain- and motif-databases exist, including PROSITE, PFAM, SMART, and Superfam, which contain descriptors for most, if not all, of the known domains involved in the ubiquitin system [11-14]. Recently, a new meta-database named INTERPRO has been established, which tries to combine the descriptors of several domain databases under a single user interface [15]. Pointers to the very useful search engines of the domain databases are provided in Table 12.1. 

The ENZYME nomenclature database (Figure 7.3) of ExPASy (Expert Protein Analysis System) at http //www.expasy.ch/enzyme/ can be searched by entering EC number or enzyme names. The query returns information on EC number, enzyme name, catalytic activity, cofactors (if any) and pointers to Swiss-Prot sequence, ProSite, and human disease(s) of the enzyme deficiency. 

The ProtSite search can be conducted at ScanProsite tool (selecting Scan a sequence for the occurrence of PROSITE patterns) of ExPASy Proteomic tools (http //www.expasy.ch/tools/scnpsite.html), or PPSearch of EBI (http //www2.ebi.ac. uk/ppsearch/) or ProfileScan server (http //www.isrec.isb-sib.ch/software/PFSCAN form.html). On the search form, paste the query sequence, select options (e.g., display in PPSearch and databases in ProfileScan) and click the Run/Start the Scan button. The search results are returned (after clicking SEView applet button in ProfileScan) with different outputs as shown in Figure 12.16. 

In addition to conventional sequence motifs (Prosite, BLOCKS, PRINTS, etc.), the compilation of structural motifs indicative of specific functions from known structures has been proposed [268]. This should improve even the results obtained with multiple (one-dimensional sequence) patterns exploited in the BLOCKS and PRINTS databases. Recently, the use of models to define approximate structural motifs (sometimes called fuzzy functional forms, FFFs [269]) has been put forward to construct a library of such motifs enhancing the range of applicability of motif searches at the price of reduced sensitivity and specificity. Such approaches are supported by the fact that, often, active sites of proteins necessary for specific functions are much more conserved than the overall protein structure (e.g. bacterial and eukaryotic serine proteases), such that an inexact model could have a partly accurately conserved part responsible for function. As the structural genomics projects produce a more and more comprehensive picture of the structure space with representatives for all major protein folds and with the improved homology search methods linking the related sequences and structures to such representatives, comprehensive libraries of highly discriminative structural motifs are envisionable. 

As computer science and molecular biology merge in the new field of bioinformatics, the use of pattern expression syntax like regular expressions has been introduced to the life scientists. They see it in databases like PROSITE. They also see it in the Internet search engines like Google. 

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