SH3 domain-containing GRB2-like endophilin B2 (SH3GLB2)

SH3 domain-containing GRB2-like endophilin B2 (SH3GLB2) is an intracellular protein with roles in membrane organization, cytoskeletal architecture, and mitochondrial quality control. It contains a Src homology 3 (SH3) domain, allowing for direct and indirect protein-protein interactions—such as with plectin 1 and vimentin—to organize perinuclear intermediate filament networks. SH3GLB2 aggregates and translocates to damaged mitochondria during mitophagy, acting in concert with homolog endophilin B1 for selective mitochondrial degradation. Additionally, SH3GLB2 positively modulates endocytic trafficking processes, including endosome maturation, receptor (e.g., EGFR) degradation, and autophagic flux; it is also implicated in postsynaptic receptor internalization and, potentially, viral entry. As a tumor-associated antigen, SH3GLB2 is overexpressed in metastatic prostate cancer, capable of priming T cells and thus of interest for cancer immunotherapy.

Other names

Endophilin-B2KIAA1848PP578PP6569PP9455RRIG1Retinoid receptor-induced gene 1SH3 domain-containing GRB2-like protein B2SH3GLB2

Immunotherapeutic approaches would rely on targeting immunogenic epitopes presented by SH3GLB2 in tumor cells to prime T cell responses. No approved drugs or direct pharmacological inhibitors are described.