2ys1

Structural highlights

Disease

DYN2_HUMAN Defects in DNM2 are a cause of centronuclear myopathy type 1 (CNM1) [MIM:160150. A congenital muscle disorder characterized by progressive muscular weakness and wasting involving mainly limb girdle, trunk, and neck muscles. It may also affect distal muscles. Weakness may be present during childhood or adolescence or may not become evident until the third decade of life. Ptosis is a frequent clinical feature. The most prominent histopathologic features include high frequency of centrally located nuclei in muscle fibers not secondary to regeneration, radial arrangement of sarcoplasmic strands around the central nuclei, and predominance and hypotrophy of type 1 fibers.^{[1] [2] [3] [4] [5] [6] [7] [8] [9]} Defects in DNM2 are the cause of Charcot-Marie-Tooth disease dominant intermediate type B (CMTDIB) [MIM:606482. Charcot-Marie-Tooth disease (CMT) is a clinically and genetically heterogeneous disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. CMTDIB is a form of Charcot-Marie-Tooth disease characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.^{[10] [11]} Defects in DNM2 are the cause of Charcot-Marie-Tooth disease type 2M (CMT2M) [MIM:606482. An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal regeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Nerve conduction velocities are normal or slightly reduced.

Function

DYN2_HUMAN Microtubule-associated force-producing protein involved in producing microtubule bundles and able to bind and hydrolyze GTP. Most probably involved in vesicular trafficking processes, in particular endocytosis. Involved in cytokinesis.^[12]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ Bitoun M, Maugenre S, Jeannet PY, Lacene E, Ferrer X, Laforet P, Martin JJ, Laporte J, Lochmuller H, Beggs AH, Fardeau M, Eymard B, Romero NB, Guicheney P. Mutations in dynamin 2 cause dominant centronuclear myopathy. Nat Genet. 2005 Nov;37(11):1207-9. Epub 2005 Oct 16. PMID:16227997 doi:ng1657
2. ↑ Bitoun M, Bevilacqua JA, Prudhon B, Maugenre S, Taratuto AL, Monges S, Lubieniecki F, Cances C, Uro-Coste E, Mayer M, Fardeau M, Romero NB, Guicheney P. Dynamin 2 mutations cause sporadic centronuclear myopathy with neonatal onset. Ann Neurol. 2007 Dec;62(6):666-70. PMID:17932957 doi:10.1002/ana.21235
3. ↑ Echaniz-Laguna A, Nicot AS, Carre S, Franques J, Tranchant C, Dondaine N, Biancalana V, Mandel JL, Laporte J. Subtle central and peripheral nervous system abnormalities in a family with centronuclear myopathy and a novel dynamin 2 gene mutation. Neuromuscul Disord. 2007 Dec;17(11-12):955-9. Epub 2007 Sep 6. PMID:17825552 doi:10.1016/j.nmd.2007.06.467
4. ↑ Bitoun M, Durieux AC, Prudhon B, Bevilacqua JA, Herledan A, Sakanyan V, Urtizberea A, Cartier L, Romero NB, Guicheney P. Dynamin 2 mutations associated with human diseases impair clathrin-mediated receptor endocytosis. Hum Mutat. 2009 Oct;30(10):1419-27. doi: 10.1002/humu.21086. PMID:19623537 doi:10.1002/humu.21086
5. ↑ Bitoun M, Bevilacqua JA, Eymard B, Prudhon B, Fardeau M, Guicheney P, Romero NB. A new centronuclear myopathy phenotype due to a novel dynamin 2 mutation. Neurology. 2009 Jan 6;72(1):93-5. doi: 10.1212/01.wnl.0000338624.25852.12. PMID:19122038 doi:10.1212/01.wnl.0000338624.25852.12
6. ↑ Jungbluth H, Cullup T, Lillis S, Zhou H, Abbs S, Sewry C, Muntoni F. Centronuclear myopathy with cataracts due to a novel dynamin 2 (DNM2) mutation. Neuromuscul Disord. 2010 Jan;20(1):49-52. doi: 10.1016/j.nmd.2009.10.005. Epub, 2009 Nov 22. PMID:19932620 doi:10.1016/j.nmd.2009.10.005
7. ↑ Melberg A, Kretz C, Kalimo H, Wallgren-Pettersson C, Toussaint A, Bohm J, Stalberg E, Laporte J. Adult course in dynamin 2 dominant centronuclear myopathy with neonatal onset. Neuromuscul Disord. 2010 Jan;20(1):53-6. doi: 10.1016/j.nmd.2009.10.006. Epub, 2009 Nov 22. PMID:19932619 doi:10.1016/j.nmd.2009.10.006
8. ↑ Susman RD, Quijano-Roy S, Yang N, Webster R, Clarke NF, Dowling J, Kennerson M, Nicholson G, Biancalana V, Ilkovski B, Flanigan KM, Arbuckle S, Malladi C, Robinson P, Vucic S, Mayer M, Romero NB, Urtizberea JA, Garcia-Bragado F, Guicheney P, Bitoun M, Carlier RY, North KN. Expanding the clinical, pathological and MRI phenotype of DNM2-related centronuclear myopathy. Neuromuscul Disord. 2010 Apr;20(4):229-37. doi: 10.1016/j.nmd.2010.02.016. Epub, 2010 Mar 12. PMID:20227276 doi:10.1016/j.nmd.2010.02.016
9. ↑ Bohm J, Biancalana V, Dechene ET, Bitoun M, Pierson CR, Schaefer E, Karasoy H, Dempsey MA, Klein F, Dondaine N, Kretz C, Haumesser N, Poirson C, Toussaint A, Greenleaf RS, Barger MA, Mahoney LJ, Kang PB, Zanoteli E, Vissing J, Witting N, Echaniz-Laguna A, Wallgren-Pettersson C, Dowling J, Merlini L, Oldfors A, Bomme Ousager L, Melki J, Krause A, Jern C, Oliveira AS, Petit F, Jacquette A, Chaussenot A, Mowat D, Leheup B, Cristofano M, Poza Aldea JJ, Michel F, Furby A, Llona JE, Van Coster R, Bertini E, Urtizberea JA, Drouin-Garraud V, Beroud C, Prudhon B, Bedford M, Mathews K, Erby LA, Smith SA, Roggenbuck J, Crowe CA, Brennan Spitale A, Johal SC, Amato AA, Demmer LA, Jonas J, Darras BT, Bird TD, Laurino M, Welt SI, Trotter C, Guicheney P, Das S, Mandel JL, Beggs AH, Laporte J. Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy. Hum Mutat. 2012 Jun;33(6):949-59. doi: 10.1002/humu.22067. Epub 2012 Apr 4. PMID:22396310 doi:10.1002/humu.22067
10. ↑ Bitoun M, Durieux AC, Prudhon B, Bevilacqua JA, Herledan A, Sakanyan V, Urtizberea A, Cartier L, Romero NB, Guicheney P. Dynamin 2 mutations associated with human diseases impair clathrin-mediated receptor endocytosis. Hum Mutat. 2009 Oct;30(10):1419-27. doi: 10.1002/humu.21086. PMID:19623537 doi:10.1002/humu.21086
11. ↑ Zuchner S, Noureddine M, Kennerson M, Verhoeven K, Claeys K, De Jonghe P, Merory J, Oliveira SA, Speer MC, Stenger JE, Walizada G, Zhu D, Pericak-Vance MA, Nicholson G, Timmerman V, Vance JM. Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease. Nat Genet. 2005 Mar;37(3):289-94. Epub 2005 Jan 30. PMID:15731758 doi:ng1514
12. ↑ Thompson HM, Skop AR, Euteneuer U, Meyer BJ, McNiven MA. The large GTPase dynamin associates with the spindle midzone and is required for cytokinesis. Curr Biol. 2002 Dec 23;12(24):2111-7. PMID:12498685