SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3)

SH3 domain-binding glutamic acid-rich-like protein 3 (SH3BGRL3) is a cytoplasmic, thioredoxin superfamily protein lacking the canonical redox-active Cys motif of glutaredoxins, and is thus not redox-active itself[1][3][4]. It is encoded by the SH3BGRL3 gene on human chromosome 1p34.3-p35 and is highly conserved across species[2][6]. SH3BGRL3 structurally resembles glutaredoxins and is thought to modulate their activity and participate in cytoskeleton organization[1][4][5]. It is widely but variably expressed in human tissues and is implicated in energy metabolism, particularly ATP synthesis and oxidative phosphorylation pathways[2]. In cancer biology, SH3BGRL3 is frequently upregulated in tumors such as gastric, renal, urothelial, and glioblastoma, where its overexpression is associated with higher tumor invasiveness, poor prognosis, and altered immune infiltration, especially increased tumor-associated macrophages[2][3]. It physically and functionally interacts with epidermal growth factor receptor (EGFR/ErbB1) and possibly HER2/ErbB2 proteins, promoting pathways associated with cancer progression and epithelial-mesenchymal transition[2]. SH3BGRL3 may serve as a biomarker for outcome prediction, though there are currently no approved drugs specifically targeting this protein, nor well-documented safety concerns for such targeting[2][3][4][5].

Other names

SH3BP-1TIP-B1TNF inhibitory protein B1SH3 domain-binding protein 1epididymis secretory protein Li 297SH3BGRL3-like protein