Myoferlin Explained

Myoferlin is a protein that in humans is encoded by the MYOF gene.^{[1] [2] [3] [4]}

Mutations in dysferlin, a protein associated with the plasma membrane, can cause muscle weakness that affects both proximal and distal muscles. The protein encoded by this gene is a type II membrane protein that is structurally similar to dysferlin. It is a member of the ferlin family and associates with both plasma and nuclear membranes.

Two transcript variants encoding different isoforms have been found for this gene. Other possible variants have been detected, but their full-length natures have not been determined.^[5]

Structure and function

Myoferlin contains C2 domains that play a role in calcium-mediated membrane fusion events, suggesting that it may be involved in membrane regeneration and repair. Myoferlin also contains a FerA domain. FerA domains have been shown to interact with the membrane, suggesting that FerA domain in myoferlin may contribute to myoferlin's membrane interaction mechanism.^[6]

Clinical significance

Myoferlin is overexpressed in several types of cancers, especially pancreas and triple-negative breast cancer. Overexpression of myoferlin is associated with proliferation, migration and invasion of cancer cells and silencing myoferlin's gene in triple-negative breast cancer can significantly reduce tumor growth and metastatic progression.^[7]

Further reading

• Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T . Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones . DNA Research . 9 . 3 . 99–106 . June 2002 . 12168954 . 10.1093/dnares/9.3.99 . free .
• Nagase T, Ishikawa K, Kikuno R, Hirosawa M, Nomura N, Ohara O . Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro . DNA Research . 6 . 5 . 337–345 . October 1999 . 10574462 . 10.1093/dnares/6.5.337 . free .
• Andersen JS, Lyon CE, Fox AH, Leung AK, Lam YW, Steen H, Mann M, Lamond AI . Directed proteomic analysis of the human nucleolus . Current Biology . 12 . 1 . 1–11 . January 2002 . 11790298 . 10.1016/S0960-9822(01)00650-9 . 14132033 . free . 2002CBio...12....1A .
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP . Large-scale characterization of HeLa cell nuclear phosphoproteins . Proceedings of the National Academy of Sciences of the United States of America . 101 . 33 . 12130–12135 . August 2004 . 15302935 . 514446 . 10.1073/pnas.0404720101 . free . 2004PNAS..10112130B .
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M . Global, in vivo, and site-specific phosphorylation dynamics in signaling networks . Cell . 127 . 3 . 635–648 . November 2006 . 17081983 . 10.1016/j.cell.2006.09.026 . 7827573 . free .

Notes and References

1. Davis DB, Delmonte AJ, Ly CT, McNally EM . Myoferlin, a candidate gene and potential modifier of muscular dystrophy . Human Molecular Genetics . 9 . 2 . 217–226 . January 2000 . 10607832 . 10.1093/hmg/9.2.217 .
2. Britton S, Freeman T, Vafiadaki E, Keers S, Harrison R, Bushby K, Bashir R . The third human FER-1-like protein is highly similar to dysferlin . Genomics . 68 . 3 . 313–321 . September 2000 . 10995573 . 10.1006/geno.2000.6290 .
3. Bernatchez PN, Acevedo L, Fernandez-Hernando C, Murata T, Chalouni C, Kim J, Erdjument-Bromage H, Shah V, Gratton JP, McNally EM, Tempst P, Sessa WC . Myoferlin regulates vascular endothelial growth factor receptor-2 stability and function . The Journal of Biological Chemistry . 282 . 42 . 30745–30753 . October 2007 . 17702744 . 10.1074/jbc.M704798200 . free .
4. Web site: Entrez Gene: FER1L3 fer-1-like 3, myoferlin (C. elegans).
5. Web site: Entrez Gene: FER1L3 fer-1-like 3, myoferlin (C. elegans).
6. Harsini FM, Chebrolu S, Fuson KL, White MA, Rice AM, Sutton RB . FerA is a Membrane-Associating Four-Helix Bundle Domain in the Ferlin Family of Membrane-Fusion Proteins . Scientific Reports . 8 . 1 . 10949 . July 2018 . 30026467 . 6053371 . 10.1038/s41598-018-29184-1 . 2018NatSR...810949H .
7. Blomme A, Costanza B, de Tullio P, Thiry M, Van Simaeys G, Boutry S, Doumont G, Di Valentin E, Hirano T, Yokobori T, Gofflot S, Peulen O, Bellahcène A, Sherer F, Le Goff C, Cavalier E, Mouithys-Mickalad A, Jouret F, Cusumano PG, Lifrange E, Muller RN, Goldman S, Delvenne P, De Pauw E, Nishiyama M, Castronovo V, Turtoi A . Myoferlin regulates cellular lipid metabolism and promotes metastases in triple-negative breast cancer . Oncogene . 36 . 15 . 2116–2130 . April 2017 . 27775075 . 10.1038/onc.2016.369 . 26225163 . free .