Myopalladin

{{Short description|Protein-coding gene in the species Homo sapiens}}

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{{cite journal | vauthors = Bang ML, Mudry RE, McElhinny AS, Trombitás K, Geach AJ, Yamasaki R, Sorimachi H, Granzier H, Gregorio CC, Labeit S | title = Myopalladin, a novel 145-kilodalton sarcomeric protein with multiple roles in Z-disc and I-band protein assemblies | journal = The Journal of Cell Biology | volume = 153 | issue = 2 | pages = 413–27 | date = April 2001 | pmid = 11309420 | pmc = 2169455 | doi = 10.1083/jcb.153.2.413 }}{{cite journal | vauthors = Ma K, Wang K | title = Interaction of nebulin SH3 domain with titin PEVK and myopalladin: implications for the signaling and assembly role of titin and nebulin | journal = FEBS Letters | volume = 532 | issue = 3 | pages = 273–8 | date = December 2002 | pmid = 12482578 | doi = 10.1016/S0014-5793(02)03655-4 | s2cid = 18125444 | doi-access = free }}{{cite web | title = Entrez Gene: MYPN myopalladin| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=84665}}

Structure

Myopalladin is a 145.2 kDa protein composed of 1320 amino acids.{{Cite web |work=Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) |title=Protein Information - Myopalladin |url= http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=Q86TC9 |publisher=NHLBI Proteomics Center at UCLA |access-date = 2015-04-29|first = Joon-Sub|last = Chung}}{{cite journal | vauthors = Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = October 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }} 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. It also has been shown to bind ANKRD23.{{cite journal | vauthors = Miller MK, Bang ML, Witt CC, Labeit D, Trombitas C, Watanabe K, Granzier H, McElhinny AS, Gregorio CC, Labeit S | title = The muscle ankyrin repeat proteins: CARP, ankrd2/Arpp and DARP as a family of titin filament-based stress response molecules | journal = Journal of Molecular Biology | volume = 333 | issue = 5 | pages = 951–64 | date = November 2003 | pmid = 14583192 | doi = 10.1016/j.jmb.2003.09.012 }}

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. 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.{{cite journal | vauthors = 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 | title = Molecular basis for clinical heterogeneity in inherited cardiomyopathies due to myopalladin mutations | journal = Human Molecular Genetics | volume = 21 | issue = 9 | pages = 2039–53 | date = May 2012 | pmid = 22286171 | doi = 10.1093/hmg/dds022 | pmc=3315208}}

Clinical significance

Mutations in MYPN have been linked to nemaline myopathy, dilated cardiomyopathy, hypertrophic cardiomyopathy and restrictive cardiomyopathy.{{cite journal | vauthors = Duboscq-Bidot L, Xu P, Charron P, Neyroud N, Dilanian G, Millaire A, Bors V, Komajda M, Villard E | title = Mutations in the Z-band protein myopalladin gene and idiopathic dilated cardiomyopathy | journal = Cardiovascular Research | volume = 77 | issue = 1 | pages = 118–25 | date = January 2008 | pmid = 18006477 | doi = 10.1093/cvr/cvm015 | doi-access = free }}

{{cite journal | vauthors = Laitila, J, Wallgren, C | title = Recent advances in nemaline myopathy | journal = Neuromuscular Disorders | volume = 31 | issue = 10 | date = 2021 | pages = 955–967 | doi = 10.1016/j.nmd.2021.07.012 | pmid = 34561123 | doi-access = free | hdl = 10138/337407 | hdl-access = free }}

Myopalladin

Structure

Function

Clinical significance

References

Further reading