MYPN

myopalladin
Identifiers
Aliases	MYPN, CMD1DD, CMH22, MYOP, RCM4
External IDs	MGI: 1916052 HomoloGene: 23778 GeneCards: 84665
Gene ontology Molecular function • SH3 domain binding • cytoskeletal protein binding • actin binding • protein binding • muscle alpha-actinin binding Cellular component • cytoplasm • sarcomere • Z disc • I band • cell nucleus Biological process • sarcomere organization Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	84665	68802
Ensembl	ENSG00000138347	ENSMUSG00000020067
UniProt	Q86TC9	Q5DTJ9
RefSeq (mRNA)	XM_011540292 NM_001256267 NM_001256268 NM_032578 NR_045662 NR_045663 XM_006718043	NM_182992
RefSeq (protein)	NP_001243196.1 NP_115967.2	NP_892037.2
Location (UCSC)	Chr 10: 68.11 – 68.21 Mb	Chr 10: 63.12 – 63.2 Mb
PubMed search
Wikidata

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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.^[6] It also has been shown to bind ANKRD23.^[7]

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.^[6] 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.^[8]

Clinical significance

Mutations in MYPN have been linked to dilated cardiomyopathy, hypertrophic cardiomyopathy and restrictive cardiomyopathy.^[8][9]

References

1. Bang ML, Mudry RE, McElhinny AS, Trombitás K, Geach AJ, Yamasaki R, Sorimachi H, Granzier H, Gregorio CC, Labeit S (Apr 2001). "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. doi:10.1083/jcb.153.2.413. PMC 2169455. PMID 11309420.
2. Ma K, Wang K (Dec 2002). "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. doi:10.1016/S0014-5793(02)03655-4. PMID 12482578.
3. "Entrez Gene: MYPN myopalladin".
4. Chung, Joon-Sub. "Protein Information - Myopalladin". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). NHLBI Proteomics Center at UCLA. Retrieved 2015-04-29.
5. Zong, N. C.; Li, H; Li, H; Lam, M. P.; Jimenez, R. C.; Kim, C. S.; Deng, N; Kim, A. K.; Choi, J. H.; Zelaya, I; Liem, D; Meyer, D; Odeberg, J; Fang, C; Lu, H. J.; Xu, T; Weiss, J; Duan, H; Uhlen, M; Yates Jr, 3rd; Apweiler, R; Ge, J; Hermjakob, H; Ping, P (2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
6. Bang ML, Mudry RE, McElhinny AS, Trombitás K, Geach AJ, Yamasaki R, Sorimachi H, Granzier H, Gregorio CC, Labeit S (Apr 2001). "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): 413–428. doi:10.1083/jcb.153.2.413. PMC 2169455. PMID 11309420.
7. Miller MK, Bang ML, Witt CC, Labeit D, Trombitas C, Watanabe K, Granzier H, McElhinny AS, Gregorio CC, Labeit S (Nov 2003). "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. doi:10.1016/j.jmb.2003.09.012. PMID 14583192.
8. Purevjav E, Arimura T, Augustin S, Huby AC, Takagi K, Nunoda S, Kearney DL, Taylor MD, Terasaki F, Bos JM, Ommen SR, Shibata H, Takahashi M, Itoh-Satoh M, McKenna WJ, Murphy RT, Labeit S, Yamanaka Y, Machida N, Park JE, Alexander PM, Weintraub RG, Kitaura Y, Ackerman MJ, Kimura A, Towbin JA (May 2012). "Molecular basis for clinical heterogeneity in inherited cardiomyopathies due to myopalladin mutations". Human Molecular Genetics 21 (9): 2039–53. doi:10.1093/hmg/dds022. PMID 22286171.
9. Duboscq-Bidot L, Xu P, Charron P, Neyroud N, Dilanian G, Millaire A, Bors V, Komajda M, Villard E (Jan 2008). "Mutations in the Z-band protein myopalladin gene and idiopathic dilated cardiomyopathy". Cardiovascular Research 77 (1): 118–25. doi:10.1093/cvr/cvm015. PMID 18006477.

Further reading

• 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.
• Miller MK, Bang ML, Witt CC, Labeit D, Trombitas C, Watanabe K, Granzier H, McElhinny AS, Gregorio CC, Labeit S (Nov 2003). "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. doi:10.1016/j.jmb.2003.09.012. PMID 14583192.
• 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.
• Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (Oct 2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nature Biotechnology 24 (10): 1285–92. doi:10.1038/nbt1240. PMID 16964243.