Fig. 2.

ADAM18 interactome. One of four hypothetical proteins (ADAM18, CAC2PBS, vimentin variant III, FAM81B) was further analyzed using bioinformatics tools including BLAST and functional domain search. ADAM18 interactome was established using PPI map software STRING 11.0 (http://string-db.org/) by adding a seed (ADAM18) in the query and applied 50/50 first and second shell interactions. The ADAM18 interactome shows a functional, indirect association and direct physical interactions. ADAM18 interactions in DR are derived from eight sources, including neighborhood, gene fusion, co-occurrence, high-throughput interaction experiments, and published knowledge (PubMed). ADAM18-UBE3A interaction shows a potential ubiquitin signaling by ubiquitin ligase E3A. Our ADAM18 interactome implies that phosphorylation signaling through ADAM18 may go through ADAM18-TGFA-EGFR-RHOA for one direction, as well as ADAM18-ESR1-PI3K-RAC1-CDC42-RAC2 pathway for the other direction