Myosin VIIA is protein that in humans is encoded by the MYO7Agene.[5] Myosin VIIA is a member of the unconventional myosin superfamily of proteins.[6] Myosins are actin binding molecular motors that use the enzymatic conversion of ATP - ADP + inorganic phosphate (Pi) to provide the energy for movement.
Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. Myosin VIIA is an unconventional myosin with the longest tail (1360 aa). The tail is expected to dimerize, resulting in a two-headed molecule. Unconventional myosins have diverse functions in eukaryotic cells and are primarily thought to be involved in the movement or linkage of intra-cellular membranes and organelles to the actin cytoskeleton via interactions mediated by their highly divergent tail domains.
Mutations in the MYO7A gene cause the Usher syndrome type 1B, a combined deafness/blindness disorder.[6] Affected individuals are typically profoundly deaf at birth and then undergo progressive retinal degeneration.[7]
Model organisms have been used in the study of MYO7A function. A spontaneous mutant mouse line, called Myo7ash1-6J[19] was generated. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[17][20] Twenty three tests were carried out on mutant mice and ten significant abnormalities were observed.[17] Male homozygousmutant mice displayed a decreased body weight, a decrease in body fat, improved glucose tolerance and abnormal pelvic girdle bone morphology. Homozygous mutant mice of both sex displayed various abnormalities in a modified SHIRPA test, including abnormal gait, tail dragging and an absence of pinna reflex, a decrease in grip strength, an increased thermal pain threshold, severe hearing impairment and a number of abnormal indirect calorimetry and clinical chemistry parameters.[17]
^Smith RJ, Berlin CI, Hejtmancik JF, Keats BJ, Kimberling WJ, Lewis RA, Möller CG, Pelias MZ, Tranebjaerg L (March 1994). "Clinical diagnosis of the Usher syndromes. Usher Syndrome Consortium". American Journal of Medical Genetics. 50 (1): 32–8. doi:10.1002/ajmg.1320500107. PMID8160750.
Wolfrum U (2003). "The Cellular Function of the Usher Gene Product Myosin VIIa is Specified by Its Ligands". Retinal Degenerations. Advances in Experimental Medicine and Biology. Vol. 533. pp. 133–42. CiteSeerX10.1.1.501.2021. doi:10.1007/978-1-4615-0067-4_17. ISBN 978-1-4613-4909-9. PMID15180257.
Kimberling WJ, Möller CG, Davenport S, Priluck IA, Beighton PH, Greenberg J, Reardon W, Weston MD, Kenyon JB, Grunkemeyer JA (December 1992). "Linkage of Usher syndrome type I gene (USH1B) to the long arm of chromosome 11". Genomics. 14 (4): 988–94. doi:10.1016/S0888-7543(05)80121-1. PMID1478677.
Guilford P, Ayadi H, Blanchard S, Chaib H, Le Paslier D, Weissenbach J, Drira M, Petit C (June 1994). "A human gene responsible for neurosensory, non-syndromic recessive deafness is a candidate homologue of the mouse sh-1 gene". Human Molecular Genetics. 3 (6): 989–93. doi:10.1093/hmg/3.6.989. PMID7951250.
Wagenaar M, ter Rahe B, van Aarem A, Huygen P, Admiraal R, Bleeker-Wagemakers E, Pinckers A, Kimberling W, Cremers C (November 1995). "Clinical findings in obligate carriers of type I Usher syndrome". American Journal of Medical Genetics. 59 (3): 375–9. doi:10.1002/ajmg.1320590319. hdl:2066/21703. PMID8599365. S2CID22357870.
Liu XZ, Walsh J, Mburu P, Kendrick-Jones J, Cope MJ, Steel KP, Brown SD (June 1997). "Mutations in the myosin VIIA gene cause non-syndromic recessive deafness". Nature Genetics. 16 (2): 188–90. doi:10.1038/ng0697-188. PMID9171832. S2CID13506848.
Weil D, Küssel P, Blanchard S, Lévy G, Levi-Acobas F, Drira M, Ayadi H, Petit C (June 1997). "The autosomal recessive isolated deafness, DFNB2, and the Usher 1B syndrome are allelic defects of the myosin-VIIA gene". Nature Genetics. 16 (2): 191–3. doi:10.1038/ng0697-191. PMID9171833. S2CID23555323.
Liu XZ, Walsh J, Tamagawa Y, Kitamura K, Nishizawa M, Steel KP, Brown SD (November 1997). "Autosomal dominant non-syndromic deafness caused by a mutation in the myosin VIIA gene". Nature Genetics. 17 (3): 268–9. doi:10.1038/ng1197-268. PMID9354784. S2CID20566524.
