SH3 domain-binding glutamic acid-rich-like protein 2 (SH3BGRL2)

SH3 domain-binding glutamic acid-rich-like protein 2 is a protein of the SH3BGR family, sharing homology with small thioredoxin-like proteins and defined by a conserved proline-rich domain that facilitates interactions with SH3, WW, and EVH1 domain-containing proteins[1][2]. SH3BGRL2 is localized in the nucleus and perinuclear region, modulates cell differentiation, tissue development, and cytoskeletal protein expression. It is transcriptionally activated by TGF-β1 via the TGF-β receptor/Smad pathway in cancer cells, and has dual roles in cancer: it suppresses cell proliferation and tumor growth, while paradoxically enhancing cell migration, invasiveness, and metastasis in certain contexts (notably breast cancer)[1][3]. SH3BGRL2 acts as a tumor suppressor in clear cell renal cell carcinoma by inhibiting epithelial-mesenchymal transition and regulating the Hippo signaling pathway, which governs cell proliferation, adhesion, and migration[2]. Its expression is downregulated in several cancer types. Interacting proteins include SPTAN1, SPTBN1, myosin-1C, and flightless-1 (FLII), with mechanistic effects on cell structure and motility[1][3]. The biological function of SH3BGRL2 in non-cancer contexts, such as erythroid differentiation or diabetes, remains largely unexplored. Key scientific points: - SH3BGRL2 is a cytosolic/nuclear protein and not a receptor, enzyme, transporter, or transcription factor in typical classification[2][3]. - Its disease relevance is mostly in cancer biology, with a dual role as both suppressor of growth and promoter of metastasis. - No targeted therapeutics or approved interacting drugs currently exist for SH3BGRL2. If further detail is required for drug screening or therapeutic applications, experimental validation will be necessary due to the current lack of pharmacological agents or safety data for direct SH3BGRL2 targeting[1][2][3].

Other names

SH3BGRL2FASH3Fovea-associated SH3 domain-binding proteinSH3 domain binding glutamic acid-rich protein like 2

Not established for drugs; as an endogenous protein, it acts via repression of cytoskeletal gene expression (SPTAN1/SPTBN1), modulates cell adhesion and migration (through Hippo pathway, TGF-β pathway), and impacts EMT and cell proliferation