SYNPO2

Myopodin protein, also called Synaptopodin-2 is a protein that in humans is encoded by the SYNPO2 gene.^[5][6][7] Myopodin is expressed in cardiac, smooth muscle and skeletal muscle, and localizes to Z-disc structures.

SYNPO2
Identifiers
Aliases	SYNPO2, synaptopodin 2, SYISL
External IDs	MGI: 2153070; HomoloGene: 15400; GeneCards: SYNPO2; OMA:SYNPO2 - orthologs
Gene location (Human) Chr. Chromosome 4 (human)[1] Band 4q26 Start 118,850,688 bp[1] End 119,061,247 bp[1]
Gene location (Mouse) Chr. Chromosome 3 (mouse)[2] Band 3|3 G1 Start 122,870,168 bp[2] End 123,029,798 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in saphenous vein tail of epididymis seminal vesicula Skeletal muscle tissue of rectus abdominis Skeletal muscle tissue of biceps brachii nipple urethra body of tongue superficial temporal artery pericardium Top expressed in triceps brachii muscle ankle temporal muscle soleus muscle digastric muscle sternocleidomastoid muscle gastrocnemius muscle thoracic diaphragm extraocular muscle intercostal muscle More reference expression data BioGPS n/a
Gene ontology Molecular function 14-3-3 protein binding protein binding muscle alpha-actinin binding actin binding filamin binding alpha-actinin binding protein-macromolecule adaptor activity Cellular component cytoplasm nucleus cytosol intracellular membrane-bounded organelle stress fiber vesicle tethering complex cytoskeleton focal adhesion cell junction actin cytoskeleton Z discdkac Biological process autophagosome assembly positive regulation of cell migration positive regulation of actin filament bundle assembly regulation of Rho-dependent protein serine/threonine kinase activity chaperone-mediated autophagy Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 171024 118449 Ensembl ENSG00000172403 ENSMUSG00000050315 UniProt Q9UMS6 Q91YE8 RefSeq (mRNA) NM_001128933 NM_001128934 NM_001286754 NM_001286755 NM_133477 NM_001389263 NM_001389264 NM_080451 NM_001388502 NM_001389265 NM_001389266 RefSeq (protein) NP_001122405 NP_001122406 NP_001273683 NP_001273684 NP_597734 NP_536699 NP_001375431 NP_001376194 NP_001376195 Location (UCSC) Chr 4: 118.85 – 119.06 Mb Chr 3: 122.87 – 123.03 Mb PubMed search [3] [4]
Wikidata
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Structure

Myopodin is a 117.4 kDa protein composed of 1093 amino acids,^[8] although four alternatively-spliced isoforms have been described.^[9] Myopodin contains one PPXY motif, multiple PXXP motifs, and two potential nuclear localization sequences (one N-terminal and one C-terminal).^[5] 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.^[5]

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.^[5] 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.^[5] The nuclear localization of myopodin is sensitive to Importin 13, which directly binds myopodin and facilitates its translocation.^[6] Importin binding and nuclear import of myopodin appears to be mediated by serine/threonine phosphorylation-dependent binding of myopodin to 14-3-3 beta^[10] 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.^[11] 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.^[11]

Interactions

Myopodin interacts with:

• 14-3-3 beta,^[11]
• Actin, alpha, cardiac muscle 1,^[5]
• Actinin, alpha 2,^[5]
• Calcineurin,^[11]
• CaMKII,^[11]
• Importin 13,^[6] and
• Protein kinase A.^[11]