SYNPO2

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.

SYNPO2
Identifiers
Aliases	SYNPO2, synaptopodin 2, SYISL
External IDs	MGI: 2153070 HomoloGene: 15400 GeneCards: SYNPO2
Gene location (Human) Chr. Chromosome 4 (human) Band 4q26 Start 118,850,688 bp End 119,061,247 bp
Gene location (Mouse) Chr. Chromosome 3 (mouse) Band 3|3 G1 Start 122,870,168 bp End 123,029,798 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in saphenous vein seminal vesicula nipple urethra body of tongue superficial temporal artery pericardium gastric mucosa vena cava pylorus 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 disc 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
Wikidata
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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.

Interactions

Myopodin interacts with:

• 14-3-3 beta,
• Actin, alpha, cardiac muscle 1,
• Actinin, alpha 2,
• Calcineurin,
• CaMKII,
• Importin 13, and
• Protein kinase A.

Further reading

• Houlgatte R, Mariage-Samson R, Duprat S, Tessier A, Bentolila S, Lamy B, Auffray C (Oct 1995). "The Genexpress Index: a resource for gene discovery and the genic map of the human genome". Genome Research. 5 (3): 272–304. doi:10.1101/gr.5.3.272. PMID 8593614.
• Hartley JL, Temple GF, Brasch MA (Nov 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
• Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A (Mar 2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
• Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (Sep 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
• Van Impe K, De Corte V, Eichinger L, Bruyneel E, Mareel M, Vandekerckhove J, Gettemans J (May 2003). "The Nucleo-cytoplasmic actin-binding protein CapG lacks a nuclear export sequence present in structurally related proteins". The Journal of Biological Chemistry. 278 (20): 17945–52. doi:10.1074/jbc.M209946200. PMID 12637565.
• Sanchez-Carbayo M, Schwarz K, Charytonowicz E, Cordon-Cardo C, Mundel P (Aug 2003). "Tumor suppressor role for myopodin in bladder cancer: loss of nuclear expression of myopodin is cell-cycle dependent and predicts clinical outcome". Oncogene. 22 (34): 5298–305. doi:10.1038/sj.onc.1206616. PMID 12917631.
• Jing L, Liu L, Yu YP, Dhir R, Acquafondada M, Landsittel D, Cieply K, Wells A, Luo JH (May 2004). "Expression of myopodin induces suppression of tumor growth and metastasis". The American Journal of Pathology. 164 (5): 1799–806. doi:10.1016/S0002-9440(10)63738-8. PMC 1615646. PMID 15111326.
• Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A (Oct 2004). "From ORFeome to biology: a functional genomics pipeline". Genome Research. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
• Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S (Jan 2006). "The LIFEdb database in 2006". Nucleic Acids Research. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.