Myosin VIIA isprotein that in humans is encoded by theMYO7Agene.[5] Myosin VIIA is a member of the unconventionalmyosin superfamily of proteins.[6] Myosins areactin 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, anactin-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 ineukaryotic cells and are primarily thought to be involved in the movement or linkage of intra-cellular membranes andorganelles to the actin cytoskeleton via interactions mediated by their highly divergent tail domains.
Mutations in theMYO7A gene cause theUsher 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, calledMyo7ash1-6J[19] was generated. Male and female animals underwent a standardizedphenotypic screen to determine the effects of deletion.[17][20] Twenty three tests were carried out onmutant mice and ten significant abnormalities were observed.[17] Malehomozygousmutant mice displayed a decreased body weight, a decrease in body fat, improvedglucose tolerance and abnormalpelvic girdle bone morphology. Homozygous mutant mice of both sex displayed various abnormalities in a modifiedSHIRPA test, including abnormal gait, tail dragging and an absence ofpinna reflex, a decrease ingrip strength, an increased thermalpain threshold, severehearing impairment and a number of abnormalindirect calorimetry andclinical chemistry parameters.[17]
^abWeil D, Blanchard S, Kaplan J, Guilford P, Gibson F, Walsh J, Mburu P, Varela A, Levilliers J, Weston MD (March 1995). "Defective myosin VIIA gene responsible for Usher syndrome type 1B".Nature.374 (6517):60–1.Bibcode:1995Natur.374...60W.doi:10.1038/374060a0.PMID7870171.S2CID4324416.
^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.
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.
