SYNPO2

Description

The SYNPO2 (synaptopodin 2) is a protein-coding gene located on chromosome 4.

Myopodin protein, also called Synaptopodin-2 is a protein that in humans is encoded by the SYNPO2 gene. Myopodin is expressed in cardiac, smooth muscle and 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 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 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 myotube differentiation, myopodin interacts 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 cytoplasm in 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 serine/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 cardiac muscle cells, by forming a Z-disc signaling complex with alpha actinin-2, calcineurin, CaMKII, muscle-specific A-kinase anchoring protein, and myomegalin. Specifically, phosphorylation by protein kinase A or CaMKII, and dephosphorylation by calcineurin facilitates the binding or release, respectively, of 14-3-3-beta, and the corresponding nuclear or cytoplasmic localization, respectively, of myopodin.

SYNPO2, also known as Myopodin, has actin-binding and actin-bundling activity. It can induce the formation of F-actin networks in a manner that is specific to its isoforms. It is thought to be an adapter protein that connects nascent myofibers to the sarcolemma through ZYX, which may contribute to the early formation and stabilization of Z lines. SYNPO2 is involved in autophagosome formation and may play a role in chaperone-assisted selective autophagy (CASA) that helps maintain Z lines in striated muscle under mechanical stress. It may link the CASA chaperone machinery to a membrane-tethering and fusion complex that provides autophagosome membranes. SYNPO2 is involved in regulating cell migration and may act as a tumor suppressor. Its interactions with other proteins include ACTN2, AKAP6, PPP3CA, CAMK2A, YWHAB, KPNA2, IPO13, ZYX, FLNC, ILK, BAG3, HSPA8, HSPB8, and VPS18.

SYNPO2 is also known as SYISL.

Associated Diseases

WES Whole Exome Sequencing