1lw3

Structural highlights

Disease

[MTMR2_HUMAN] Defects in MTMR2 are the cause of Charcot-Marie-Tooth disease type 4B1 (CMT4B1) [MIM:601382]. CMT4B1 is a recessive, severe form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathy and primary peripheral axonal neuropathy. Demyelinating CMT neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. By convention, autosomal recessive forms of demyelinating Charcot-Marie-Tooth disease are designated CMT4.^{[1] [2]}

Function

[MTMR2_HUMAN] Phosphatase that acts on lipids with a phosphoinositol headgroup. Has phosphatase activity towards phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate.^{[3] [4]}

Evolutionary Conservation

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

References

1. ↑ Bolino A, Muglia M, Conforti FL, LeGuern E, Salih MA, Georgiou DM, Christodoulou K, Hausmanowa-Petrusewicz I, Mandich P, Schenone A, Gambardella A, Bono F, Quattrone A, Devoto M, Monaco AP. Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2. Nat Genet. 2000 May;25(1):17-9. PMID:10802647 doi:10.1038/75542
2. ↑ Nelis E, Erdem S, Tan E, Lofgren A, Ceuterick C, De Jonghe P, Van Broeckhoven C, Timmerman V, Topaloglu H. A novel homozygous missense mutation in the myotubularin-related protein 2 gene associated with recessive Charcot-Marie-Tooth disease with irregularly folded myelin sheaths. Neuromuscul Disord. 2002 Nov;12(9):869-73. PMID:12398840
3. ↑ Kim SA, Vacratsis PO, Firestein R, Cleary ML, Dixon JE. Regulation of myotubularin-related (MTMR)2 phosphatidylinositol phosphatase by MTMR5, a catalytically inactive phosphatase. Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4492-7. Epub 2003 Mar 31. PMID:12668758 doi:10.1073/pnas.0431052100
4. ↑ Franklin NE, Taylor GS, Vacratsis PO. Endosomal targeting of the phosphoinositide 3-phosphatase MTMR2 is regulated by an N-terminal phosphorylation site. J Biol Chem. 2011 May 6;286(18):15841-53. doi: 10.1074/jbc.M110.209122. Epub 2011, Mar 3. PMID:21372139 doi:10.1074/jbc.M110.209122
5. ↑ Begley MJ, Taylor GS, Kim SA, Veine DM, Dixon JE, Stuckey JA. Crystal structure of a phosphoinositide phosphatase, MTMR2: insights into myotubular myopathy and Charcot-Marie-Tooth syndrome. Mol Cell. 2003 Dec;12(6):1391-402. PMID:14690594