SYNPO2

Myopodin is_associated_with::protein, also called Synaptopodin-2 is a is_associated_with::protein that in humans is encoded by the SYNPO2 is_associated_with::gene. Myopodin is expressed in cardiac, is_associated_with::smooth muscle and is_associated_with::skeletal muscle, and localizes to Z-disc structures.

Structure
Myopodin is a 117.4 kDa protein composed of 1093 amino acids, although four alternatively-spliced isoforms have been described. Myopodin contains one PPXY motif, multiple PXXP motifs, and two potential is_associated_with::nuclear localization sequences (one N-terminal and one C-terminal). PPXY motifs have been shown to mediate interactions, and PXXP motifs represent potential sites of interaction for is_associated_with::SH3 domain-containing proteins. Myopodin contains a novel actin binding site (between amino acids 410 and 563) in the center of the protein.

Function
During is_associated_with::myotube differentiation, myopodin interacts with is_associated_with::stress fibers prior to co-localizing with alpha actinin-2 at Z-discs in mature striated muscle cells. Myopodin has been shown to shuttle between the nucleus and is_associated_with::cytoplasm in is_associated_with::myoblasts and myotubes in response to stress; its export from the nucleus is sensitive to lemtomycin B. The nuclear localization of myopodin is sensitive to Importin 13, which directly binds myopodin and facilitates its translocation. Importin binding and nuclear import of myopodin appears to be mediated by is_associated_with::serine/is_associated_with::threonine phosphorylation-dependent binding of myopodin to 14-3-3 beta Myopodin appears to regulate compartmentalized, intracellular signal transduction between the Z-disc and nucleus in is_associated_with::cardiac muscle cells, by forming a Z-disc signaling complex with alpha actinin-2, is_associated_with::calcineurin, is_associated_with::CaMKII, muscle-specific A-kinase anchoring protein, and myomegalin. Specifically, phosphorylation by is_associated_with::protein kinase A or is_associated_with::CaMKII, and dephosphorylation by is_associated_with::calcineurin facilitates the binding or release, respectively, of 14-3-3-beta, and the corresponding nuclear or is_associated_with::cytoplasmic localization, respectively, of myopodin.

Interactions
Myopodin interacts with actin, alpha actinin-2, Importin 13, is_associated_with::protein kinase A, is_associated_with::CaMKII, is_associated_with::calcineurin, and 14-3-3 beta.