Different families of proteins that linked because they perform recognizably similar classes of work, even if unrelated by protein homology, form a guild of protein families. In a typical bioinformatics grammar, a key feature may be the presence of a protein (or cluster of proteins) from a particular guild rather than from a particular protein family.

CRISPR-associated proteins form a guild (PMID:16292354).

Capsular biosynthesis enzymes in bacteria form a guild.

Bacteriocin maturation proteins or, more generally, ribosomally translated natural product maturation proteins, form a guild.

Type 2 toxin-antitoxin systems occur as a tandem pairing of a member of the guild of toxins with a member of the guild of antitoxins (see PMID:19493340).

In annotation-walking, mix-and-match association patterns involving guilds can lead to progressive discovery of additional guild member families.