Motifs PROSITE database

The PROSITE database" " of protein sequence motifs is a standard. The motifs are represented by patterns and profiles. Patterns are denoted using the single letter amino acid alphabet, with each position separated by a hyphen, e.g., A-D-E. X is used if any residue is allowed. If several residues are allowed at a given position, they are grouped in square brackets (e.g., [AC]-D-E). Disallowed residues are grouped in curly brackets A-D- FGH. A repeat is indicated by its length after the... 

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. 

The PROSITE database, maintained by the Swiss Institute of Bioinformatics (SIB), was the first database that tried to catalog functional motifs and domains of proteins1621. Nowadays, PROSITE consists of two major parts storing different types of descriptors the pattern library and the profile library1631. 

The majority of prosite documentation refers to motifs rather than profiles. The motifs are less sensitive than profiles and do not provide statistical scores. The motifs correspond to active sites and other important functional sites in proteins. The motifs are expressed as regular expressions that can be used to detect matching proteins in the database. An example of a motif from Prosite would be the /V-glycosylation motif,... 

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. 

Pattern and motif analysis Motif Scan PROSITE Pfam http //myhits.isb-sib.ch/cgi-bin/motif scan http //us.expasy.org/prosite/ http //www.sanger.ac.uk/Software/Pfam/ Einding motifs in a sequence. Protein fanulies and domains. Protein fanulies database of hidden Markov models (HMMs). 

Motif umi domain databases. PROSITE (http //www.expasy. org/cgi-bin/nicesite) and PFAM (http //www.sanger.ac.uk/ cgi-bin/Pfam/getacc). 

Sigrist, C. J., Cerutti, L., Hulo, N., Gattiker, A., Falquet, L., Pagni, M., Bairoch, A., and Bucher, P. (2002). PROSITE A documented database using patterns and profiles as motif descriptors. Brief Bioinform. 3, 265—274. 

The sequence motifs identified in this way may be different from the motifs/ fingerprints listed in the Prosite [31], Blocks [75], and especially PRINTS [33, 76] databases, which use single or multiple conserved regions as consensus signatures to describe families or subfamilies and which are used as automated diagnostic tools for inserting new members into the framework of the already classified members. 

There are other approaches to family databases that rely more extensively on sequence similarity to define classes of genes or proteins. For example, PROSITE (49) is a resource that uses regular expressions to define patterns of residues that represent biologically significant sequence motifs. Recent versions have incorporated profiles, weight matrices that express the characteristics of a gene... 

As well as these general motif databases, there are some more specialized sequence analysis tools for identifying particular structural or functional features. One well-studied example is that of coiled coils. The program COILS " allows one to compare a sequence against profiles derived from known parallel two-stranded coiled coils, to assess the likelihood that the query sequence is indeed a coiled coil. More involved analyses based on pairwise interactions have been developed, such as PAIRCOIL. Several families of coiled coils are actually well recognized by their PROSITE motifs. However, the leucine zipper PROSITE motif, L-X(6)-L-X(6)-L-X(6)-L, is poorly discriminating, and for this specific family of coiled coils, the program TRESPASSER provides a more refined identification... 

There are also several protein family databases. Prosite [14] and Blocks [22] provide motifs or patterns for protein families, so that new proteins can be examined to see if they fit into a particular protein family. PFAM [13] and... 

Protein motifs can represent, among other things, the active sites of enzymes. They can also identify protein regions involved in determining protein structure and stability. The PROSITE, BLOCKS, and PRINTS databases (3-5) contain hundreds of protein motifs corresponding to enzyme active sites, binding sites, and protein family signatures. Motifs can also be used to identify features that confer particular chemical characteristics (such as thermal stability) on proteins (6). Protein sequence motifs can also be used to classify proteins into families (5). 

The importance of motif discovery is born out by the growth in motif databases such as TRANSFAC, JASPAR, SCPD, DBTBS, RegulonDB (7-10) for DNA motifs and PROSITE, BLOCKS, and PRINTS (3-5) for protein motifs. However, far more motifs remain to be discovered. For example, TFBS motifs are known for only about 500 vertebrate TFs, but it is estimated that there are about 2000 TFs in mammalian genomes alone (7,11). 

An integrated database based on SwissProt, TrEMBL, Pfam, PRINTS and PROSitE, and thus includes data on proteins, protein families, and do-mains/motifs, providing useful information for predicting protein struc-tme and function for sequenced genomes. 

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