Biology:MYPN
 Generic protein structure example |
Myopalladin is a protein that in humans is encoded by the MYPN gene. Myopalladin is a muscle protein responsible for tethering proteins at the Z-disc and for communicating between the sarcomere and the nucleus in cardiac and skeletal muscle[1][2][3]
Structure
Myopalladin is a 145.2 kDa protein composed of 1320 amino acids.[4][5] Myopalladin has five Ig-like repeats within the protein, and a proline-rich domain. Myopalladin binds the Src homology domain of nebulette and nebulin and tethers it to alpha-actinin via its C-terminal domain binding to the EF hand domains of alpha-actinin. The N-terminal region of myopalladin binds to the nuclear protein CARP, known to regulate gene expression in muscle.[1] It also has been shown to bind ANKRD23.[6]
Function
Myopalladin has dual subcellular localization, residing in both the nucleus and sarcomere/I-bands in muscle. Accordingly, myopalladin has functions in both sarcomere assembly and in control of gene expression.[1] Specifics of these functions were gleaned from studies involving MYPN mutants associated with various cardiomyopathies. The Q529X myopalladin mutant demonstrated incompetence in recruiting key binding partners such as desmin, alpha-actinin and CARP to the Z-disc during myofibrilogenesis. In contrast, the Y20C mutant resulted in decreased expression of binding partners.[7]
Clinical significance
Mutations in MYPN have been linked to dilated cardiomyopathy, hypertrophic cardiomyopathy and restrictive cardiomyopathy.[7][8]
References
- ↑ 1.0 1.1 1.2 "Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies". The Journal of Cell Biology 153 (2): 413–27. April 2001. doi:10.1083/jcb.153.2.413. PMID 11309420.
- ↑ "Interaction of nebulin SH3 domain with titin PEVK and myopalladin: implications for the signaling and assembly role of titin and nebulin". FEBS Letters 532 (3): 273–8. December 2002. doi:10.1016/S0014-5793(02)03655-4. PMID 12482578.
- ↑ "Entrez Gene: MYPN myopalladin". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=84665.
- ↑ Chung, Joon-Sub. "Protein Information - Myopalladin". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). NHLBI Proteomics Center at UCLA. http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=Q86TC9.
- ↑ "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–53. October 2013. doi:10.1161/CIRCRESAHA.113.301151. PMID 23965338.
- ↑ "The muscle ankyrin repeat proteins: CARP, ankrd2/Arpp and DARP as a family of titin filament-based stress response molecules". Journal of Molecular Biology 333 (5): 951–64. November 2003. doi:10.1016/j.jmb.2003.09.012. PMID 14583192.
- ↑ 7.0 7.1 "Molecular basis for clinical heterogeneity in inherited cardiomyopathies due to myopalladin mutations". Human Molecular Genetics 21 (9): 2039–53. May 2012. doi:10.1093/hmg/dds022. PMID 22286171.
- ↑ "Mutations in the Z-band protein myopalladin gene and idiopathic dilated cardiomyopathy". Cardiovascular Research 77 (1): 118–25. January 2008. doi:10.1093/cvr/cvm015. PMID 18006477.
Further reading
- "DNA cloning using in vitro site-specific recombination". Genome Research 10 (11): 1788–95. November 2000. doi:10.1101/gr.143000. PMID 11076863.
- "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. March 2001. doi:10.1101/gr.GR1547R. PMID 11230166.
- "The muscle ankyrin repeat proteins: CARP, ankrd2/Arpp and DARP as a family of titin filament-based stress response molecules". Journal of Molecular Biology 333 (5): 951–64. November 2003. doi:10.1016/j.jmb.2003.09.012. PMID 14583192.
- "From ORFeome to biology: a functional genomics pipeline". Genome Research 14 (10B): 2136–44. October 2004. doi:10.1101/gr.2576704. PMID 15489336.
- "The LIFEdb database in 2006". Nucleic Acids Research 34 (Database issue): D415–8. January 2006. doi:10.1093/nar/gkj139. PMID 16381901.
- "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nature Biotechnology 24 (10): 1285–92. October 2006. doi:10.1038/nbt1240. PMID 16964243.
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