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An example is the ''N''-glycosylation site motif: : ''Asn, followed by anything but Pro, followed by either Ser or Thr, followed by anything but Pro'' where the three-letter abbreviations are the conventional designations for Amino Acid s (see Genetic Code ). OVERVIEW When a sequence motif appears in the Exon of a Gene , it may Encode the " Structural Motif " of a Protein ; that is a stereotypical element of the Overall Structure of the protein. Nevertheless, motifs need not be associated with a distinctive Secondary Structure . " Noncoding " sequences are not Translated into proteins, and Nucleic Acid s with such motifs need not deviate from the typical shape (e.g. the "B-form" DNA Double Helix ). Outside of gene exons, there exist Regulatory Sequence motifs and motifs within the " Junk ," such as Satellite DNA . Some of these are believed to affect the shape of nucleic acids (see for example RNA Self-splicing ), but this is only sometimes the case. For example, many DNA Binding Protein s that have affinities for specific motifs only bind DNA in its double-helical form. They are able to recognize motifs through contact with the double helix's major or minor groove. Short coding motifs, which appear to lack secondary structure, include those that Label proteins for delivery to particular parts of a Cell , or mark them for Phosphorylation . Within a sequence or Database of sequences, researchers search and find motifs using computer-based techniques of Sequence Analysis , such as BLAST . Such techniques belong to the discipline of Bioinformatics . See also Consensus Sequence . MOTIF BIOINFORMATICS Consider the ''N''-glycosylation site motif mentioned above: : ''Asn, followed by anything but Pro, followed by either Ser or Thr, followed by anything but Pro'' This pattern may be written as N{P} where means either X or Y.The notation {Link without Title} does not give any indication of the probability of X or Y occurring in the pattern. Sometimes patterns are defined in terms of a probabilistic model such as a Hidden Markov Model .Motifs and consensus sequences The notation {Link without Title} means X or Y or Z, but does not indicate the likelihood of any particular match. For this reason, two or more patterns are often associated with a single motif: the defining pattern, and various typical patterns.For example, the defining sequence for the IQ motif may be taken to be: : {Link without Title} Qxxx {Link without Title} Gxxx {Link without Title} xx {Link without Title} where x signifies any amino acid, and the square brackets indicate an alternative (see below for further details about notation).Usually, however, the first letter is I, and both {Link without Title} choices resolve to R. Since the last choice is so wide, the pattern IQxxxRGxxxR is sometimes equated with the IQ motif itself, but a more accurate description would be a ''consensus sequence for the IQ motif''.De novo computational discovery of motifs There are software programs which, given multiple input sequences, attempt to identify one or more candidate motifs. One example is MEME , which generates statistical information for each candidate. Other algorithms include: CisModule, AlignAce, PhyloGibbs, Weeder. Discovery through evolutionary conservation Motifs have been discovered by studying similar genes in different species. For example, by aligning the amino acid sequences specified by the GCM (''glial cells missing'') gene in man, mouse and ''D. melanogaster'', Akiyama and others discovered a pattern which they called the GCM motif. It spans about 150 amino acid residues, and begins as follows:
The authors were able to show that the motif has DNA binding activity. A motif discovery algorithm that considers phylogenetic conservation is PhyloGibbs .12}} Pattern description notations Several notations for describing motifs are in use but most of them are variants of standard notations for Regular Expression s and use these conventions:
The fundamental idea behind all these notations is the matching principle, which assigns a meaning to a sequence of elements of the pattern notation: : ''a sequence of elements of the pattern notation matches a sequence of amino acids if and only if the latter sequence can be partitioned into subsequences in such a way that each pattern element matches the corresponding subsequence in turn.'' Thus the pattern [CDE F matches the six amino acid sequences corresponding to ACF, ADF, AEF, BCF, BDF, and BEF.Different pattern description notations have other ways of forming pattern elements. One of these notations is the PROSITE notation, described in the following subsection. PROSITE pattern notation The PROSITE notation uses the IUPAC one-letter codes and conforms to the above description with the exception that a concatenation symbol, ' -', is used between pattern elements, but it is often dropped between letters of the pattern alphabet.PROSITE allows the following pattern elements in addition to those described previously:
Some examples:
The signature of the C2H2-type '' Zinc Finger '' domain is:
Matrices A matrix of numbers containing scores for each residue or nucleotide at each position of a fixed-length motif. There are two types of weight matrices.
An example of a PFM from the TRANSFAC database for the transcription factor AP-1: The first column specifies the position, the second column contains the number of occurrences of A at that position, the third column contains the number of occurrences of C at that position, the fourth column contains the number of occurrences of G at that position, the fifth column contains the number of occurrences of T at that position, and the last column contains IUPAC notation for that position. Note that each the sums of occurrences for A, C, G, and T for each row should be equal because the PFM is derived from aggregating several consensus sequences. Another scheme This example comes from the paper by Matsuda and colleagues cited below. The '' E. Coli '' lactose Operon repressor LacI ( PDB id 1lccA) and ''E. coli'' catabolite gene activator (PDB id 3gapA) both have a ''helix-turn-helix'' motif, but their amino acid sequences do not show much similarity, as shown in the table below. Matsuda and colleagues devised a code called the ''3D chain code'' for representing a protein structure as a string of letters. This encoding scheme reveals the similarity between the proteins much more clearly than the amino acid sequence: SEE ALSO REFERENCES Further reading
EXTERNAL LINKS Motif-finding methods
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