SH3 And PX Domain Containing Protein 2B (SH3PXD2B)

SH3PXD2B encodes an adapter protein that is characterized by a PX domain and four Src homology 3 domains. The encoded protein is required for podosome formation and is involved in cell adhesion and migration of numerous cell types. Mutations in this gene are the cause of Frank-ter Haar syndrome. the isolated PX domain of TKS4 bound phosphatidylinositol 3,4-bisphosphate and PtdIns3P. It also bound more weakly to phosphatidic acid. Knockdown or knockout of Tks4 in mouse fibroblasts resulted in cells unable to form pseudopods and with an inhibited ability to degrade a gelatin film, which was due to reduced pseudopod recruitment of membrane type-1 matrix metalloproteinase. These functions were rescued by reintroduction of wildtype Tks4, but not by Tks4 with mutations at the putative tyrosine phosphorylation sites.