SAM (sterile alpha motif) domain of Ship2 subfamily is a protein-protein interaction domain. Ship2 proteins are lipid phosphatases (Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2) containing an N-terminal SH2 domain, a central phosphatase domain and a C-terminal SAM domain. Ship2 is involved in a number of PI3K signaling pathways. For example, it plays a role in regulation of the actin cytoskeleton remodeling, in insulin signaling pathways, and in EphA2 receptor endocytosis. SAM domain of Ship2 can interact with SAM domain of other proteins in these pathways, thus participating in signal transduction. In particular, SAM of Ship2 is known to form heterodimers with SAM domain of Eph-A2 receptor tyrosine kinase during receptor endocytosis as well as with SAM domain of PI3K effector protein Arap3 in the actin cytoskeleton signaling network. Since Ship2 plays a role in negatively regulating insulin signaling, it has been suggested that inhibition of its expression or function may contribute in treating type 2 diabetes and obesity-induced insulin resistance.
Feature 1:heterodimer interface ML [polypeptide binding site]
Evidence:
Comment:Highlighted residues are important for SAM_Ship2/SAM_EPHA2 and SAM_Ship2/SAM_Arap3 heterodimer formation via interactions with the mid-loop (ML) surface of SAM_Ship2 (based on chemical shift perturbation, isothermal titration calorimetry, mutagenesis and molecular modeling analysis).
Jiyao W et al.(2023). "The conserved domain database in 2023.",