Myoferlin

Myoferlin is a protein that in humans is encoded by the MYOF gene.^[5][6][7][8]

MYOF
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2DMH, 2K2O
Identifiers
Aliases	MYOF, FER1L3, myoferlin, HAE7
External IDs	OMIM: 604603; MGI: 1919192; HomoloGene: 40882; GeneCards: MYOF; OMA:MYOF - orthologs
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10q23.33 Start 93,306,429 bp[1] End 93,482,334 bp[1]
Gene location (Mouse) Chr. Chromosome 19 (mouse)[2] Band 19|19 C2 Start 37,887,484 bp[2] End 38,032,025 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of hip gingival epithelium nasal epithelium skin of thigh stromal cell of endometrium mucosa of paranasal sinus epithelium of nasopharynx urethra palpebral conjunctiva decidua Top expressed in transitional epithelium of urinary bladder stroma of bone marrow decidua saccule endothelial cell of lymphatic vessel belly cord uterus right lung lobe yolk sac calvaria More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding phospholipid binding Cellular component caveola integral component of membrane plasma membrane nuclear membrane extracellular exosome nuclear envelope cytoplasmic vesicle membrane cytoplasmic vesicle intracellular membrane-bounded organelle nucleus membrane Biological process cellular response to heat plasma membrane repair muscle contraction blood circulation regulation of vascular endothelial growth factor receptor signaling pathway myoblast fusion glycerol metabolic process T-tubule organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 26509 226101 Ensembl ENSG00000138119 ENSMUSG00000048612 UniProt Q9NZM1 Q69ZN7 RefSeq (mRNA) NM_013451 NM_133337 NM_001099634 NM_001302140 NM_177035 RefSeq (protein) NP_038479 NP_579899 NP_001093104 NP_001289069 Location (UCSC) Chr 10: 93.31 – 93.48 Mb Chr 19: 37.89 – 38.03 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.^[8]

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.^[9]

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.^[10]

References

1. GRCh38: Ensembl release 89: ENSG00000138119 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000048612 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Davis DB, Delmonte AJ, Ly CT, McNally EM (January 2000). "Myoferlin, a candidate gene and potential modifier of muscular dystrophy". Human Molecular Genetics. 9 (2): 217–226. doi:10.1093/hmg/9.2.217. PMID 10607832.
6. Britton S, Freeman T, Vafiadaki E, Keers S, Harrison R, Bushby K, et al. (September 2000). "The third human FER-1-like protein is highly similar to dysferlin". Genomics. 68 (3): 313–321. doi:10.1006/geno.2000.6290. PMID 10995573.
7. Bernatchez PN, Acevedo L, Fernandez-Hernando C, Murata T, Chalouni C, Kim J, et al. (October 2007). "Myoferlin regulates vascular endothelial growth factor receptor-2 stability and function". The Journal of Biological Chemistry. 282 (42): 30745–30753. doi:10.1074/jbc.M704798200. PMID 17702744.
8. "Entrez Gene: FER1L3 fer-1-like 3, myoferlin (C. elegans)".
9. Harsini FM, Chebrolu S, Fuson KL, White MA, Rice AM, Sutton RB (July 2018). "FerA is a Membrane-Associating Four-Helix Bundle Domain in the Ferlin Family of Membrane-Fusion Proteins". Scientific Reports. 8 (1): 10949. Bibcode:2018NatSR...810949H. doi:10.1038/s41598-018-29184-1. PMC 6053371. PMID 30026467.
10. Blomme A, Costanza B, de Tullio P, Thiry M, Van Simaeys G, Boutry S, et al. (April 2017). "Myoferlin regulates cellular lipid metabolism and promotes metastases in triple-negative breast cancer". Oncogene. 36 (15): 2116–2130. doi:10.1038/onc.2016.369. PMID 27775075. S2CID 26225163.

Further reading

• Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (June 2002). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Research. 9 (3): 99–106. doi:10.1093/dnares/9.3.99. PMID 12168954.
• Nagase T, Ishikawa K, Kikuno R, Hirosawa M, Nomura N, Ohara O (October 1999). "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. doi:10.1093/dnares/6.5.337. PMID 10574462.
• Andersen JS, Lyon CE, Fox AH, Leung AK, Lam YW, Steen H, et al. (January 2002). "Directed proteomic analysis of the human nucleolus". Current Biology. 12 (1): 1–11. Bibcode:2002CBio...12....1A. doi:10.1016/S0960-9822(01)00650-9. PMID 11790298. S2CID 14132033.
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, et al. (August 2004). "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. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, et al. (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–648. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.