SH3 and PX domain-containing protein 2B (SH3PXD2B)

SH3 and PX domain-containing protein 2B (SH3PXD2B), also known as TKS4, is an adaptor protein characterized by one PX domain and four SH3 (Src homology 3) domains[1][2][3][4][5]. It is crucial for the formation and function of podosomes and invadopodia—specialized, actin-rich membrane structures that mediate cell adhesion, cell migration, and extracellular matrix (ECM) degradation[1][2][3][4][5]. SH3PXD2B serves as a scaffold, recruiting proteins such as matrix metalloproteinases (MMPs), ADAM metalloproteases, and components of the NADPH oxidase (NOX) complex to the membrane, facilitating processes like ECM remodeling and regulated ROS production[1][4]. SH3PXD2B is required for normal embryonic development in tissues such as bone, heart, and eye. Mutations in this protein cause severe multisystem congenital syndromes, including Frank-ter Haar syndrome (FTHS) and Borrone dermato-cardio-skeletal syndrome (BDCS), both characterized by skeletal, craniofacial, cardiovascular, and ocular abnormalities[1][2]. While not a classical drug target such as a receptor, enzyme, or transporter, its role in cell invasion and ECM remodeling suggests potential relevance to cancer metastasis[4].

Other names

FAD49KIAA1295TKS4FLJ20831Adapter protein HOFIFactor for adipocyte differentiation 49Tyrosine kinase substrate with four SH3 domainsFTHSHOFITSK4