SH2like

SH2like refers to a class of protein domains that closely resemble the Src homology 2 (SH2) domain in overall fold and presumed mechanism, but show sequence divergence and/or structural differences that alter ligand recognition. These domains are often annotated as SH2-like in genomic and protein databases when they retain a similar beta-sheet/alpha-helix core but do not preserve all canonical SH2 features, such as the exact phosphotyrosine-binding pocket.

Structurally, SH2like domains typically maintain a conserved core that facilitates protein–protein interactions, yet substitutions or insertions can modify binding specificity. Some SH2like domains retain partial affinity for phosphotyrosine-containing motifs, while others diverge to recognize alternative ligands, including non-phosphorylated sequences or different post-translational modifications. This variation can expand the signaling repertoire of the proteins they inhabit and may influence factors such as localization, interaction networks, and enzymatic regulation.

Occurrence and evolution of SH2like domains are observed across diverse eukaryotic lineages, including animals, plants, and fungi. They are often found within multi-domain proteins involved in signaling cascades, where SH2like modules can modulate interactions in response to cellular cues. The origins of SH2like domains may involve divergent evolution from classical SH2 domains or domain shuffling events that create new interaction interfaces.

Detection and study rely on sequence similarity searches, structural analyses, and domain profiling. Experimental approaches include binding assays with phosphotyrosine-containing ligands and structural determinations to map the binding pocket and assess specificity. SH2like domains illustrate how small changes in a conserved fold can diversify protein–protein interaction networks.