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A protein motif is a recognizable recurring pattern in a protein's sequence or three-dimensional arrangement. A protein sequence motif describes characteristic residues and allowed variation; a protein structural motif describes a recurring spatial combination of structural elements. A motif can be part of a protein domain, without by itself being an independently folding domain or specifying the whole protein's function.

Sequence-pattern notation makes a useful distinction explicit. PROSITE uses defined residues, alternatives and wildcard positions to describe signatures found in protein sequences.^[ref] For an original illustration, take the invented four-position pattern A-x-G-x, with each x allowed any of 20 standard amino acids. It matches $20^2=400$ different residue strings. Finding a match therefore does not uniquely identify a sequence, much less prove a particular biochemical activity. This teaching pattern is not asserted to be a real biological signature.

The EF hand supplies a structural example: two alpha helices flank a loop associated with calcium ion binding in canonical members. Recognizing the arrangement, measuring binding and determining its physiological role are different kinds of evidence.^[ref]

Motifs are useful because local arrangements can recur in proteins with different overall architectures. A sequence signature can guide comparison or experimentation; a structure can test whether the relevant residues approach one another in space. Neither the word “motif” nor a pattern hit alone supplies an affinity measurement or a complete functional annotation.

A protein sequence motif is a characteristic pattern of amino acid residues in a protein sequence. A pattern can specify fixed residues, alternatives and variable-length or wildcard positions. It is a statement about residue order; it need not specify a complete protein structural motif or independently establish biochemical function. PROSITE documents such signatures together with their interpretation and matching syntax.^[ref]

For an original example, use the invented four-residue pattern D-x(2)-[ST]: an initial D, any two residues, then S or T. With 20 possible standard amino acids, it admitsstrings out of $20^4=160000$ possible four-residue strings. Under an explicitly stipulated uniform independent-residue model, a given window therefore matches with probability $1/200$. This is not an empirical background model for real proteins, and the pattern is not asserted to be a real biological signature.

A sequence of length 103 has 100 length-four windows. Under that model the expected value of the number of matches is $100/200=0.5$. Overlapping windows need not be independent for this expectation: summing their indicator expectations is sufficient. Thus finding a short pattern can occur without a demonstrated functional relationship.

A useful annotation combines the pattern with the rest of the sequence, structural context and experimental evidence. In a calcium-binding family, for example, an EF hand depends on the spatial arrangement and chemistry of coordinating groups, not merely on a count of pattern matches.^[ref]