Extended Data Fig. 8: Sequence-similarity network of sequences related to SN243 (red), starting with a list of significant hits from a MGnify search.
From: Functional metagenomic screening identifies an unexpected β-glucuronidase

Shown in purple and yellow are the only other known GH3 enzymes with β-glucuronidase activity (no edge with SN243) and the 427 nodes directly connected to SN243 with an E-value < e-40, respectively. The closest MGnify hit (MGYP000481601007) aligned with an E-value of 1.1e-229 to SN243 (corresponding to a 55% identity and 87% query coverage). Homology analysis of MGYP000481601007 with characterized sequences (UniProt/SwissProt) returns β-glucosidase/β-xylosidase hits with much lower homology to the query (E-value of the closest hit: 3e-28; Q46684.1). The discovery and functional characterization of SN243 (and closely related sequences in its perimeter) add a bridgehead in sequence space that can help with the annotation of related sequences. Even though sequence similarity does not strictly predict functional similarity, the characterization of SN243 illuminates the functional potential in this sequence neighborhood.