MYO7A

MYO7A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3PVL
Identifiers
Aliases	MYO7A , DFNA11, DFNB2, MYOVIIA, MYU7A, NSRD2, USH1B, myosin VIIA
External IDs	OMIM: 276903 MGI: 104510 HomoloGene: 219 GeneCards: MYO7A
Gene location (Human) Chr. Chromosome 11 (human) [1] Band 11q13.5 Start 77,128,246 bp [1] End 77,215,241 bp [1]
Gene location (Mouse) Chr. Chromosome 7 (mouse) [2] Band 7 E1|7 53.57 cM Start 97,700,267 bp [2] End 97,768,731 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Left adrenal gland right lobe of liver anterior pituitary spleen frontal pole retinal pigment epithelium placenta sural nerve subcutaneous adipose tissue body of pancreas Top expressed in fourth ventricle adrenal gland yolk sac retinal pigment epithelium iris testicle utricle ciliary body seminiferous tubule jejunum More reference expression data BioGPS n/a
Gene ontology Molecular function nucleotide binding spectrin binding protein homodimerization activity protein domain specific binding ADP binding calmodulin binding microfilament motor activity protein binding actin binding cytoskeletal motor activity ATP binding microtubule motor activity microtubule binding actin filament binding protein-containing complex binding protein N-terminus binding Cellular component cytosol photoreceptor inner segment melanosome photoreceptor outer segment stereocilium photoreceptor connecting cilium microvillus lysosomal membrane cell cortex apical plasma membrane myosin VII complex upper tip-link density cytoskeleton myosin complex synapse cytoplasm stereocilium base Biological process sensory perception inner ear receptor cell stereocilium organization pigment granule localization sensory perception of light stimulus post-embryonic animal organ morphogenesis sensory perception of sound mechanoreceptor differentiation pigment granule transport auditory receptor cell stereocilium organization phagolysosome assembly inner ear auditory receptor cell differentiation cell projection organization equilibrioception inner ear morphogenesis eye photoreceptor cell development phagocytosis inner ear development inner ear receptor cell differentiation intracellular protein transport lysosome organization visual perception actin filament-based movement microtubule-based movement Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4647 17921 Ensembl ENSG00000137474 ENSMUSG00000030761 UniProt Q13402 P97479 RefSeq (mRNA) NM_000260 NM_001127179 NM_001127180 NM_001369365 NM_001256081 NM_001256082 NM_001256083 NM_008663 RefSeq (protein) NP_000251 NP_001120652 NP_001356294 NP_001243010 NP_001243011 NP_001243012 NP_032689 Location (UCSC) Chr 11: 77.13 – 77.22 Mb Chr 7: 97.7 – 97.77 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Myosin VIIA is protein that in humans is encoded by the MYO7A gene. ^[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.

MYO7A is expressed in a number of mammalian tissues, including testis, kidney, lung, inner ear, retina and the ciliated epithelium of the nasal mucosa.

Clinical significance

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

Myo7a mutant mouse phenotype

Characteristic	Phenotype
Homozygote viability	Normal
Fertility	Normal
Body weight	Abnormal [8]
Anxiety	Normal
Neurological assessment	Abnormal [9]
Grip strength	Abnormal [10]
Hot plate	Abnormal [11]
Dysmorphology	Normal
Indirect calorimetry	Abnormal [12]
Glucose tolerance test	Abnormal [13]
Auditory brainstem response	Abnormal
DEXA	Abnormal [14]
Radiography	Abnormal [15]
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Abnormal [16]
Plasma immunoglobulins	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Tail epidermis wholemount	Normal
Skin Histopathology	Normal
All tests and analysis from [17] [18]

Model organisms have been used in the study of MYO7A function. A spontaneous mutant mouse line, called Myo7a^{sh1-6J [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 homozygous mutant 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]

References

1. GRCh38: Ensembl release 89: ENSG00000137474 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000030761 - 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. Hasson T, Skowron JF, Gilbert DJ, Avraham KB, Perry WL, Bement WM, Anderson BL, Sherr EH, Chen ZY, Greene LA, Ward DC, Corey DP, Mooseker MS, Copeland NG, Jenkins NA (September 1996). "Mapping of unconventional myosins in mouse and human". Genomics. 36 (3): 431–9. doi: 10.1006/geno.1996.0488 . PMID   8884266.
6. Weil 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. PMID   7870171. S2CID   4324416.
7. 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. PMID   8160750.
8. "Body weight data for Myo7a". Wellcome Trust Sanger Institute.
9. "Neurological assessment data for Myo7a". Wellcome Trust Sanger Institute.
10. "Grip strength data for Myo7a". Wellcome Trust Sanger Institute.
11. "Hot plate data for Myo7a". Wellcome Trust Sanger Institute.
12. "Indirect calorimetry data for Myo7a". Wellcome Trust Sanger Institute.
13. "Glucose tolerance test data for Myo7a". Wellcome Trust Sanger Institute.
14. "DEXA data for Myo7a". Wellcome Trust Sanger Institute.
15. "Radiography data for Myo7a". Wellcome Trust Sanger Institute.
16. "Clinical chemistry data for Myo7a". Wellcome Trust Sanger Institute.
17. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID   85911512.
18. Mouse Resources Portal, Wellcome Trust Sanger Institute.
19. "Mouse Genome Informatics".
20. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC   3218837 . PMID   21722353.

External links

• GeneReviews/NCBI/NIH/UW entry on Usher Syndrome Type I
• Overview of all the structural information available in the PDB for UniProt : Q13402 (Human Unconventional myosin-VIIa) at the PDBe-KB .
• Overview of all the structural information available in the PDB for UniProt : P97479 (Mouse Unconventional myosin-VIIa) at the PDBe-KB .

Further reading

• Wolfrum U (2004). "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. CiteSeerX   10.1.1.501.2021 . doi:10.1007/978-1-4615-0067-4_17. ISBN   978-1-4613-4909-9. PMID   15180257.
• el-Amraoui A, Sahly I, Picaud S, Sahel J, Abitbol M, Petit C (August 1996). "Human Usher 1B/mouse shaker-1: the retinal phenotype discrepancy explained by the presence/absence of myosin VIIA in the photoreceptor cells". Human Molecular Genetics. 5 (8): 1171–8. doi: 10.1093/hmg/5.8.1171 . PMID   8842737.
• Adato A, Weil D, Kalinski H, Pel-Or Y, Ayadi H, Petit C, Korostishevsky M, Bonne-Tamir B (October 1997). "Mutation profile of all 49 exons of the human myosin VIIA gene, and haplotype analysis, in Usher 1B families from diverse origins". American Journal of Human Genetics. 61 (4): 813–21. doi:10.1086/514899. PMC   1716000 . PMID   9382091.
• Liu XZ, Hope C, Walsh J, Newton V, Ke XM, Liang CY, Xu LR, Zhou JM, Trump D, Steel KP, Bundey S, Brown SD (September 1998). "Mutations in the myosin VIIA gene cause a wide phenotypic spectrum, including atypical Usher syndrome". American Journal of Human Genetics. 63 (3): 909–12. doi:10.1086/302026. PMC   1377414 . PMID   9718356.
• 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. PMID   1478677.
• Hasson T, Heintzelman MB, Santos-Sacchi J, Corey DP, Mooseker MS (October 1995). "Expression in cochlea and retina of myosin VIIa, the gene product defective in Usher syndrome type 1B". Proceedings of the National Academy of Sciences of the United States of America. 92 (21): 9815–9. Bibcode:1995PNAS...92.9815H. doi: 10.1073/pnas.92.21.9815 . PMC   40893 . PMID   7568224.
• 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. PMID   7951250.
• Bement WM, Hasson T, Wirth JA, Cheney RE, Mooseker MS (July 1994). "Identification and overlapping expression of multiple unconventional myosin genes in vertebrate cell types". Proceedings of the National Academy of Sciences of the United States of America. 91 (14): 6549–53. Bibcode:1994PNAS...91.6549B. doi: 10.1073/pnas.91.14.6549 . PMC   44240 . PMID   8022818.
• 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 . PMID   8599365. S2CID   22357870.
• Weil D, Levy G, Sahly I, Levi-Acobas F, Blanchard S, El-Amraoui A, Crozet F, Philippe H, Abitbol M, Petit C (April 1996). "Human myosin VIIA responsible for the Usher 1B syndrome: a predicted membrane-associated motor protein expressed in developing sensory epithelia". Proceedings of the National Academy of Sciences of the United States of America. 93 (8): 3232–7. Bibcode:1996PNAS...93.3232W. doi: 10.1073/pnas.93.8.3232 . PMC   39588 . PMID   8622919.
• Tamagawa Y, Kitamura K, Ishida T, Ishikawa K, Tanaka H, Tsuji S, Nishizawa M (June 1996). "A gene for a dominant form of non-syndromic sensorineural deafness (DFNA11) maps within the region containing the DFNB2 recessive deafness gene". Human Molecular Genetics. 5 (6): 849–52. doi: 10.1093/hmg/5.6.849 . PMID   8776602.
• Chen ZY, Hasson T, Kelley PM, Schwender BJ, Schwartz MF, Ramakrishnan M, Kimberling WJ, Mooseker MS, Corey DP (September 1996). "Molecular cloning and domain structure of human myosin-VIIa, the gene product defective in Usher syndrome 1B". Genomics. 36 (3): 440–8. doi: 10.1006/geno.1996.0489 . PMID   8884267.
• Weston MD, Kelley PM, Overbeck LD, Wagenaar M, Orten DJ, Hasson T, Chen ZY, Corey D, Mooseker M, Sumegi J, Cremers C, Moller C, Jacobson SG, Gorin MB, Kimberling WJ (November 1996). "Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients". American Journal of Human Genetics. 59 (5): 1074–83. PMC   1914835 . PMID   8900236.
• Lévy G, Levi-Acobas F, Blanchard S, Gerber S, Larget-Piet D, Chenal V, Liu XZ, Newton V, Steel KP, Brown SD, Munnich A, Kaplan J, Petit C, Weil D (January 1997). "Myosin VIIA gene: heterogeneity of the mutations responsible for Usher syndrome type IB". Human Molecular Genetics. 6 (1): 111–6. doi: 10.1093/hmg/6.1.111 . PMID   9002678.
• Kelley PM, Weston MD, Chen ZY, Orten DJ, Hasson T, Overbeck LD, Pinnt J, Talmadge CB, Ing P, Mooseker MS, Corey D, Sumegi J, Kimberling WJ (February 1997). "The genomic structure of the gene defective in Usher syndrome type Ib (MYO7A)". Genomics. 40 (1): 73–9. doi:10.1006/geno.1996.4545. PMID   9070921. S2CID   19026117.
• 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. PMID   9171832. S2CID   13506848.
• 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. PMID   9171833. S2CID   23555323.
• 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. PMID   9354784. S2CID   20566524.