Genomic sequence motifs

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. 

Figure 2.3 Metagenomic cloning experiments. Isolation of genomic DNA directly from environments (soil, plants, mixed environments or thermal-vent worms are the examples Illustrated here) can recover DNA fragments which could encode for enzymes. The DNA fragments can be ligated to plasmids or DNA linkers, and then subjected to functional screening (expression cloning) and/or sequence analysis. Amplification by PCR can sometimes be used to yield libraries enriched with clones containing selected sequence motifs relating to families of enzymes...

Iron-sulfur proteins are a group of enzymes and other electron carriers that contain clusters of iron and sulfide linked directly to amino-acyl side chains, usually cysteines. They are widely distributed in nature. Soon after their discovery. Hall et al. (1971) proposed that they could be used to follow the course of evolution. Studies of genome sequences have revealed that iron-sulfur cluster binding motifs are among the most commonly recognized sequences. 

Interpretation of results of these studies is still difficult. Results of two-hybrid methods become more useful if they can be coordinated with other approaches. For example, computational methods can predict interactions from genome sequences alone. 11/0 More than 45,000 interactions have been predicted among yeast proteins. Reliable identification of such motifs as DNA-binding domains and Ca2+- binding domains can complement two-hybrid analysis.11 The yeast genome is predicted to contain 162 coiled-coil sequences and at least 213 unique interactions between them.0 Examination of sequences of protein families in the Protein Data Bank (PDB) led to prediction of 8151 interactions of 664 types between protein families in yeast.P... 

Chemokines possess definitive sequence motifs and are small and highly expressed in many tissues. In contrast, chemokine receptors are comparatively large and are expressed at relatively low levels in a tissue/cell type-restricted manner. These differential features favor EST cloning as a way to find new chemokines and homology hybridization cloning, particularly starting from genomic DNA libraries, as a way to identify novel chemokine receptors. 

Nevill-Manning, C. G Wu, T. D. Brutlag, D. L. (1998). Highly specific protein sequence motifs for genome analysis. Proc Natl Acad Sci USA 95,5865-71. 

Short tandem repeat (STR) or microsatellite loci consist of DNA sequence motifs that have core repeats of two to seven base pairs. Examples include the dinucleotide 5 CACACACA 3 and the tetranucleotide 5 TTTATTTATTTA 3". Thousands of STRs are scattered throughout the genome. Because they are flanked by unique sequences, each can be specifically amplified with the polymerase chain reaction (PGR) for analysis. In populations of individuals, multiple alleles may be present based on differences in the number of repeated motifs at the locus. STRs have many characteristics that make them ideal for identity testing (1) They can be analyzed in fluorescent automated systems (2) alleles can be assigned in a definitive manner following analysis (3) STR loci are almost always transmitted in families in a Mendelian fashion (4) the loci may have 10 or more alleles, often with... 

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. 

Johansson, O., Alkema, W Wasserman, W. W and Lagergren, J. (2003) Identification of functional clusters of transcription factor binding motifs in genome sequences the MSCAN algorithm. Bioinformatics 19, 169-176. 

GFScan [45] is a tool for associating genomic DNA sequences with gene families. The family-specific sequence motifs used for matching query sequences are derived from protein motifs in PROSITE and the genomic structureof known members of the family. 

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