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In genetics, a sequence motif is a nucleotide or amino-acid sequence pattern that is widespread and has, or is conjectured to have, a biological significance. For proteins, a sequence motif is distinguished from a structural motif, a motif formed by the three dimensional arrangement of amino acids, which may not be adjacent.
An example is the N-glycosylation site motif:
Additional recommended knowledge
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 acids 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 proteins 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.
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.
Consider the N-glycosylation site motif mentioned above:
This pattern may be written as
Motifs and consensus sequences
For example, the defining sequence for the IQ motif may be taken to be:
Usually, however, the first letter is
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:
Pattern description notations
Several notations for describing motifs are in use but most of them are variants of standard notations for regular expressions 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:
Thus the pattern
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, '
PROSITE allows the following pattern elements in addition to those described previously:
The signature of the C2H2-type zinc finger domain is:
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.
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:
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Sequence_motif". A list of authors is available in Wikipedia.|