SH3PXD2A (TKS5, FISH) was discovered as an adaptor protein and Src substrate (Lock et al. 1998). It is essential for invadopodia and podosome formation in many different cell types. It is not required for precursor initiation but is needed for precursor stabilization (Sharma et al. 2013). It contains a phox homology (PX) domain that binds the membrane phosphoinositides PI3P and PI(3,4)P2 (Abram et al. 2003) In Src-transformed NIH 3T3 cells, TKS5 and PI(3,4)P2 localize to podosomes via a GRB2-dependent mechanism (Oikawa et al. 2008).

TKS5 directly binds to the ADAM family proteases 12, 15, and 19 (Abram et al. 2003), N-WASP, dynamin-2, and Grb2 (Oikawa et al. 2008) and NCK1 and 2 (Styli et al. 2009). In vivo, decreased Tks5 expression correlates with reductions in tumor growth, metastasis, and angiogenesis (Blouw et al. 2008).