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Description

SH3 and PX domain-containing protein 2A (UniProt: Q5TCZ1, also known as Adapter protein TKS5, Five SH3 domain-containing protein, SH3 multiple domains protein 1, Tyrosine kinase substrate with five SH3 domains) is encoded by the SH3PXD2A (also known as FISH, KIAA0418, SH3MD1, TKS5) gene (Gene ID: 9644) in human. Adapter protein TKS5 is a scaffolding protein that is required for podosome formation, degradation of the extracellular matrix, and for invasion in some cancer cells. Three isoforms of TKS5 have been described that are produced by alternative splicing. TKS5 is a cytoplasmic protein in normal cells, but it localizes to podosomes in SRC-transformed cells. It is found in several cancer cell lines, particularly invasive breast carcinomas and melanomas. TKS5 contains one PX (phx homology) domain and five SH3 domains. The PX domain is required for podosome localization because of its ability to bind phosphoinosiltols, such as PtdIns3P and PtdIns(3,4)P2 and to lesser extent PtdIns5P and PtdIns(3,5)P2. Its binding with ADAM12, ADAM15 and ADAM19 is mediated by the fifth SH3 domain. The intramolecular interaction of the PX domain with the third SH3 domain maintains the protein in the cytoplasm and phosphorylation disrupts this interaction, resulting in the redistribution of the protein from cytoplasm to the perimembrane region.