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Gene Review

MYO5B  -  myosin VB

Homo sapiens

Synonyms: KIAA1119, Unconventional myosin-Vb
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Disease relevance of MYO5B


Psychiatry related information on MYO5B

  • From these and other data, we conclude that the essential role(s) of myosin I in A. nidulans is probably structural, requiring little, if any, actin-activated MgATPase or motor activity, which have long been considered the defining characteristics of the myosin family [6].
  • Cardiac myosin binding protein C gene is specifically expressed in heart during murine and human development [7].
  • After exercise, the recovery of phosphocreatine-an index of oxidative metabolic capacity of the muscle-was slower in the beta myosin heavy chain group (mean half time 0.65 (0.08) minutes) than in the troponin T group (0.60 (0.17) minutes) or controls (0.48 (0.14) minutes) [8].
  • In hyperthyroidism, the cross-bridge movement significantly preceded tension development, suggesting that hyperthyroid myosin (V1) has a longer latency period between the shift to the vicinity of the thin filament and force development [9].
  • Newly-reported structural information about certain proximities between points on bound nucleotide and points on the heavy chain of myosin S-1 are incorporated into a previously-reported [Botts, J. Thomason, J.F. & Morales, M.F. Proc. Nat. Acad. Sci. USA, 86, 2204-2208 (1989)] structure of S-1 [10].

High impact information on MYO5B

  • Kinetics shows that the binding of myosin to actin is a two-step process which affects ATP and ADP affinity [11].
  • Molecular genetics of myosin [12].
  • Structural and biochemical studies suggest that the position of tropomyosin (Tm) and troponin (Tn) on the thin filament determines the interaction of myosin with the binding sites on actin [13].
  • 3) The initial rate of force development depends mostly on the extent of Ca(2+) activation of the thin filament and myosin kinetic properties but depends little on the initial force level [13].
  • Second, the technology to measure picoNewton forces and nanometer distances has provided direct determinations of the force and step length generated by a single myosin molecule interacting with a single actin filament [14].

Chemical compound and disease context of MYO5B

  • DESIGN AND METHODS: Serum myosin heavy-chain fragments, TnT, and TnI were studied up to 12 days after diagnosis in relationship to the serum creatine kinase level in 20 patients with rhabdomyolysis [15].
  • METHODS AND RESULTS: Syngeneic splenocytes, coupled with cardiac myosin by use of ethylene carbodiimide, were administered intravenously before disease induction, and the effects of this peripheral tolerization on myosin-induced myocarditis were assessed [16].
  • Compounds interfering with actin function, including phalloidin, the catalytic subunit of Clostridium botulinum C2 toxin, and N-ethylmaleimide-treated myosin S1 fragments were microinjected into the axon [17].
  • The presence of ventricular myosin light chains in the atria of children with congenital heart disease was demonstrated by two-dimensional polyacrylamide gel electrophoresis, peptide mapping, and Western blot analysis [18].
  • All Lewis rats immunized with the rod exhibited severe myocarditis, and the immunization of the cyanogen bromide-cleaved peptide equivalent to human beta-cardiac myosin heavy chain RDCB9 (residues 1070 to 1165) induced moderate myocarditis [19].

Biological context of MYO5B

  • We propose that polarization of hepatocytes (i.e., canalicular biogenesis) requires recruitment of rab11a and myosin Vb to intracellular membranes that contain apical ABC transporters and transcytotic markers, permitting their targeting to the plasma membrane [20].
  • Myosin-binding protein C (MyBP-C) binds to myosin with two binding sites, one close to the N terminus and the other at the C terminus [21].
  • Yeast two-hybrid screening of a rabbit parietal cell cDNA library with dominant active Rab11a (Rab11aS20V) identified myosin Vb as an interacting protein for Rab11a, a marker for plasma membrane recycling systems [22].
  • The determination of the MYO6 genomic structure will enable screening of individuals with non-syndromic deafness, Usher's syndrome, or retinopathies associated with human chromosome 6q for mutations in this unconventional myosin [23].
  • Transfection of DsRed2-myosin Vb tail in MDCK cell lines stably transfected with wild-type or dominant active forms of Rab11a or Rab25 demonstrated that the distribution of Rab25S21V is only partially altered by expression of the myosin Vb tail [24].

Anatomical context of MYO5B

  • Additionally, S2 possesses a conserved charge distribution with three prominent rings of negative potential within S2-Delta, the first of which may provide a binding interface for the "blocked head" of smooth muscle myosin in the OFF state [25].
  • The observation that many disease-associated mutations affect the second negatively charged ring further suggests that charge interactions play an important role in regulation of cardiac muscle activity through myosin-binding protein C [25].
  • In this model, polarization is initiated upon delivery of rab11a-myosin Vb-containing membranes to the surface, which causes plasma membrane at the site of delivery to differentiate into apical domain (bile canaliculus) [20].
  • Myosin diversity in the human epithelial cell line Caco-2BBe, the porcine epithelial cell line LLC-PK1 (CL-4), human peripheral blood leukocytes, and human liver was analyzed [26].
  • Myosin VII (M7) plays a role in adhesion in both Dictyostelium and mammalian cells where it is a component of a complex of proteins that serve to link membrane receptors to the underlying actin cytoskeleton [27].

Associations of MYO5B with chemical compounds

  • As with Rab11a in MDCK cells, the myosin Vb immunoreactivity was dispersed with nocodazole treatment and relocated to the apical corners of cells with taxol treatment [22].
  • To do so, the cells were treated with ML-7, a myosin II light chain kinase inhibitor, or Y-27632, an inhibitor of Rho-kinase (ROCK), both of which block actomyosin contraction [28].
  • The gelation induced by warming (to 25 degrees C) the 100,000 g supernatant fraction (extract) of HeLa cells lysed in a buffer containing sucrose, ATP, DTE, EGTA, imidazole, and Triton X-100 was studied in the presence of myosin and heavy meromyosin (HMM) [29].
  • Myosin light chain kinase functions downstream of Ras/ERK to promote migration of urokinase-type plasminogen activator-stimulated cells in an integrin-selective manner [30].
  • Using nondenaturing polyacrylamide gel electrophoresis, we have identified two distinct myosin isoenzymes in human atrial tissue that correspond to the V1 and V3 isomyosins found in rat ventricular tissue [31].

Physical interactions of MYO5B


Other interactions of MYO5B


Analytical, diagnostic and therapeutic context of MYO5B

  • PCR amplification yielded 8-11 putative myosins (depending on the cDNA source) representing six distinct myosin classes [26].
  • Immunofluorescence studies indicated a colocalization of endogenous Rab11-FIP2 with green fluorescent protein-myosin Vb tail overexpressed in Madin-Darby canine kidney (MDCK) cells [32].
  • Co-immunoprecipitation experiments reveal that Dictyostelium M7 (DdM7) interacts with talinA, an actin-binding protein with a known role in cell-substrate adhesion [27].
  • Using NMR spectroscopy and isothermal titration calorimetry we demonstrate that cC2 alone binds to a fragment of myosin, S2Delta, with low affinity (k(D) = 1.1 mm) but exhibits a highly specific binding site [21].
  • In summary, our results provide evidence that myosin II-mediated actin contraction and the activity of Rho GTPases are necessary for the proper organization of a laminin-5 matrix and localization of hemidesmosome protein arrays in epithelial cells [28].


  1. From flies' eyes to our ears: mutations in a human class III myosin cause progressive nonsyndromic hearing loss DFNB30. Walsh, T., Walsh, V., Vreugde, S., Hertzano, R., Shahin, H., Haika, S., Lee, M.K., Kanaan, M., King, M.C., Avraham, K.B. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  2. Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus. Zhu, L., Vranckx, R., Van Kien, P.K., Lalande, A., Boisset, N., Mathieu, F., Wegman, M., Glancy, L., Gasc, J.M., Brunotte, F., Bruneval, P., Wolf, J.E., Michel, J.B., Jeunemaitre, X. Nat. Genet. (2006) [Pubmed]
  3. Induction of autoimmune myocarditis in interleukin-2-deficient mice. Grässl, G., Pummerer, C.L., Horak, I., Neu, N. Circulation (1997) [Pubmed]
  4. Identification of alpha- and beta-cardiac myosin heavy chain isoforms as major autoantigens in dilated cardiomyopathy. Caforio, A.L., Grazzini, M., Mann, J.M., Keeling, P.J., Bottazzo, G.F., McKenna, W.J., Schiaffino, S. Circulation (1992) [Pubmed]
  5. Myotonic dystrophy kinase-related Cdc42-binding kinase acts as a Cdc42 effector in promoting cytoskeletal reorganization. Leung, T., Chen, X.Q., Tan, I., Manser, E., Lim, L. Mol. Cell. Biol. (1998) [Pubmed]
  6. Myosin I mutants with only 1% of wild-type actin-activated MgATPase activity retain essential in vivo function(s). Liu, X., Osherov, N., Yamashita, R., Brzeska, H., Korn, E.D., May, G.S. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  7. Cardiac myosin binding protein C gene is specifically expressed in heart during murine and human development. Fougerousse, F., Delezoide, A.L., Fiszman, M.Y., Schwartz, K., Beckmann, J.S., Carrier, L. Circ. Res. (1998) [Pubmed]
  8. Abnormal skeletal muscle bioenergetics in familial hypertrophic cardiomyopathy. Thompson, C.H., Kemp, G.J., Taylor, D.J., Conway, M., Rajagopalan, B., O'Donoghue, A., Styles, P., McKenna, W.J., Radda, G.K. Heart (1997) [Pubmed]
  9. Cross-bridge and calcium behavior in ferret papillary muscle in different thyroid states. Yagi, N., Saeki, Y., Ishikawa, T., Kurihara, S. Jpn. J. Physiol. (2001) [Pubmed]
  10. The region in myosin S-1 that may be involved in energy transduction. Morales, M.F., Ue, K., Bivin, D.B. Adv. Exp. Med. Biol. (1993) [Pubmed]
  11. Structural mechanism of muscle contraction. Geeves, M.A., Holmes, K.C. Annu. Rev. Biochem. (1999) [Pubmed]
  12. Molecular genetics of myosin. Emerson, C.P., Bernstein, S.I. Annu. Rev. Biochem. (1987) [Pubmed]
  13. Regulation of contraction in striated muscle. Gordon, A.M., Homsher, E., Regnier, M. Physiol. Rev. (2000) [Pubmed]
  14. Actomyosin interaction in striated muscle. Cooke, R. Physiol. Rev. (1997) [Pubmed]
  15. Myosin heavy-chain fragments and cardiac troponins in the serum in rhabdomyolysis. Diagnostic specificity of new biochemical markers. Löfberg, M., Tähtelä, R., Härkönen, M., Somer, H. Arch. Neurol. (1995) [Pubmed]
  16. Prevention of autoimmune myocarditis through the induction of antigen-specific peripheral immune tolerance. Godsel, L.M., Wang, K., Schodin, B.A., Leon, J.S., Miller, S.D., Engman, D.M. Circulation (2001) [Pubmed]
  17. Impaired recycling of synaptic vesicles after acute perturbation of the presynaptic actin cytoskeleton. Shupliakov, O., Bloom, O., Gustafsson, J.S., Kjaerulff, O., Low, P., Tomilin, N., Pieribone, V.A., Greengard, P., Brodin, L. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  18. Expression of ventricular myosin subunits in the atria of children with congenital heart malformations. Shi, Q.W., Danilczyk, U., Wang, J.X., See, Y.P., Williams, W.G., Trusler, G.A., Beaulieu, R., Rose, V., Jackowski, G. Circ. Res. (1991) [Pubmed]
  19. Localization of porcine cardiac myosin epitopes that induce experimental autoimmune myocarditis. Inomata, T., Hanawa, H., Miyanishi, T., Yajima, E., Nakayama, S., Maita, T., Kodama, M., Izumi, T., Shibata, A., Abo, T. Circ. Res. (1995) [Pubmed]
  20. Rab11a and myosin Vb are required for bile canalicular formation in WIF-B9 cells. Wakabayashi, Y., Dutt, P., Lippincott-Schwartz, J., Arias, I.M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  21. Dissecting the N-terminal Myosin Binding Site of Human Cardiac Myosin-binding Protein C: STRUCTURE AND MYOSIN BINDING OF DOMAIN C2. Ababou, A., Gautel, M., Pfuhl, M. J. Biol. Chem. (2007) [Pubmed]
  22. Myosin vb is associated with plasma membrane recycling systems. Lapierre, L.A., Kumar, R., Hales, C.M., Navarre, J., Bhartur, S.G., Burnette, J.O., Provance, D.W., Mercer, J.A., Bähler, M., Goldenring, J.R. Mol. Biol. Cell (2001) [Pubmed]
  23. Genomic structure of the human unconventional myosin VI gene. Ahituv, N., Sobe, T., Robertson, N.G., Morton, C.C., Taggart, R.T., Avraham, K.B. Gene (2000) [Pubmed]
  24. Interactions of myosin vb with rab11 family members and cargoes traversing the plasma membrane recycling system. Lapierre, L.A., Goldenring, J.R. Meth. Enzymol. (2005) [Pubmed]
  25. Crystal structures of human cardiac beta-myosin II S2-{Delta} provide insight into the functional role of the S2 subfragment. Blankenfeldt, W., Thom??, N.H., Wray, J.S., Gautel, M., Schlichting, I. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  26. Identification and overlapping expression of multiple unconventional myosin genes in vertebrate cell types. Bement, W.M., Hasson, T., Wirth, J.A., Cheney, R.E., Mooseker, M.S. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  27. Identification of a myosin VII-talin complex. Tuxworth, R.I., Stephens, S., Ryan, Z.C., Titus, M.A. J. Biol. Chem. (2005) [Pubmed]
  28. Myosin-mediated cytoskeleton contraction and Rho GTPases regulate laminin-5 matrix assembly. DeHart, G.W., Jones, J.C. Cell Motil. Cytoskeleton (2004) [Pubmed]
  29. Effects of myosin and heavy meromyosin on actin-related gelation of HeLa cell extracts. Weihing, R.R. J. Cell Biol. (1977) [Pubmed]
  30. Myosin light chain kinase functions downstream of Ras/ERK to promote migration of urokinase-type plasminogen activator-stimulated cells in an integrin-selective manner. Nguyen, D.H., Catling, A.D., Webb, D.J., Sankovic, M., Walker, L.A., Somlyo, A.V., Weber, M.J., Gonias, S.L. J. Cell Biol. (1999) [Pubmed]
  31. Myosin isoenzyme distribution in overloaded human atrial tissue. Buttrick, P.M., Malhotra, A., Brodman, R., McDermott, L., Lam, L. Circulation (1986) [Pubmed]
  32. Rab11 family interacting protein 2 associates with Myosin Vb and regulates plasma membrane recycling. Hales, C.M., Vaerman, J.P., Goldenring, J.R. J. Biol. Chem. (2002) [Pubmed]
  33. Myosin VI is an actin-based motor that moves backwards. Wells, A.L., Lin, A.W., Chen, L.Q., Safer, D., Cain, S.M., Hasson, T., Carragher, B.O., Milligan, R.A., Sweeney, H.L. Nature (1999) [Pubmed]
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