The transglutaminase 2 interactome in <scp>HUVECs</scp> suggests its participation in an <scp>RNA</scp> ‐binding protein network

Transglutaminase 2 (TG2) exhibits various protein-modifying catalytic and protein-protein interaction properties and is highly expressed in endothelial cells. To provide insight into its endothelial functions, the TG2 interactome was identified in HUVECs using biotinylated recombinant TG2 and affinity chromatography. Subsequently, endogenous TG2-silenced and a triple Flag-tagged transgenic TG2-expressing HUVEC line was created, allowing isolation of intracellularly assembled TG2-interacting proteins. Conformation-dependency of TG2's interactome was also determined. RNA-binding proteins associated with TG2 were the most enriched gene ontology terms in all experiments, with a 42% overlap between the TG2 interactome and known RNA-binding proteins in HUVECs. Consistent with TG2's recently described RNA-binding ability, our findings reveal its potential role in post-transcriptional regulation at a central hub within the RNA-binding protein network.