SH3 domain-binding protein 2 (SH3BP2)

SH3 domain-binding protein 2 (SH3BP2) is a scaffold/adaptor protein encoded by the SH3BP2 gene on chromosome 4p16.3[5]. It participates in intracellular signaling, especially in immune system cells (B cells, T cells, natural killer cells, macrophages) and is critical for the formation and function of osteoclasts, which are bone-resorbing cells responsible for bone remodeling[2][3]. SH3BP2 lacks catalytic activity and instead modulates signaling by interacting with many other proteins, including Syk, Vav proteins, PLCγ1/2, 14-3-3 proteins, and Cbl, orchestrating phosphorylation cascades that influence immune cell activation and osteoclastogenesis[3]. Mutations in SH3BP2 cause cherubism, a pediatric bone disorder characterized by cystic lesions in the jaw, through a gain-of-function mechanism that increases osteoclast number and inflammatory signaling. SH3BP2 also forms part of a larger signalosome complex involved in both innate and adaptive immune pathways, and recent data indicate its expression is upregulated in certain kidney disorders (e.g., MCD, FSGS), linking it to immunopathogenesis in those diseases as well[4]. It has also been identified as a prognostic marker in several cancers, but no drugs directly target SH3BP2 in current clinical use[6][7].

Other names

3BP23BP-2CRBMCRPMRES4-23FLJ42079FLJ54978Abl-SH3 binding protein 2TNFAIP3 interacting protein 2