SH3 & PX domain-containing protein 2A (SH3 multiple domains protein 1, five SH3 domain-containing protein, adaptor protein TKS5, SH3PXD2A, FISH, KIAA0418, SH3MD1)
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Function
- required for
- podosome formation
- degradation of extracellular matrix
- binds PIP3 & PIP2
- interacts with ADAM12, ADAM15, ADAM19
- phosphorylation plays a regulatory role in the protein localization (see Structure: below)
- phosphorylated on Ser upon DNA damage, probably by ATM or ATR
Structure
- PX domain is required for podosome localization & for binding of PIP3 & PIP2
- 5th SH3 domain mediates binding with ADAM12, ADAM15 & ADAM19
- tyrosine phosphorylated by SRC
- intramolecular interaction of PX domain with the 3rd SH3 domain maintains protein in cytoplasm, phosphorylation disrupts this interaction, resulting in the redistribution of the protein from cytoplasm to the perimembrane region
- contains 1 PX domain (phox homology domain)
- contains 5 SH3 domains
Compartment
- cytoplasm, cell projection, podosome
- cytoplasmic in normal cells
- localizes to podosomes in SRC-transformed cells
Alternative splicing
named isoforms=2
Pathology
- mediates the neurotoxic effect of beta-amyloid peptide in association with ADAM12
- role in invasiveness of some cancer cells
- found in several cancer cell lines, including invasive breast carcinomas & melanomas