| Structural highlights
Disease
[EMD_HUMAN] Defects in EMD are the cause of Emery-Dreifuss muscular dystrophy type 1 (EDMD1) [MIM:310300]. A degenerative myopathy characterized by weakness and atrophy of muscle without involvement of the nervous system, early contractures of the elbows Achilles tendons and spine, and cardiomyopathy associated with cardiac conduction defects.[1] [2] [3] [4]
Function
[EMD_HUMAN] Stabilizes and promotes the formation of a nuclear actin cortical network. Stimulates actin polymerization in vitro by binding and stabilizing the pointed end of growing filaments. Inhibits beta-catenin activity by preventing its accumulation in the nucleus. Acts by influencing the nuclear accumulation of beta-catenin through a CRM1-dependent export pathway. Links centrosomes to the nuclear envelope via a microtubule association. EMD and BAF are cooperative cofactors of HIV-1 infection. Association of EMD with the viral DNA requires the presence of BAF and viral integrase. The association of viral DNA with chromatin requires the presence of BAF and EMD. Required for proper localization of non-farnesylated prelamin-A/C.[5] [6] [7] [8] [9]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Like Duchenne and Becker muscular dystrophies, Emery-Dreifuss muscular dystrophy (EDMD) is characterized by myopathic and cardiomyopathic abnormalities. EDMD has the particularity of being linked to mutations in nuclear proteins. The X-linked form of EDMD is caused by mutations in the emerin gene, whereas autosomal dominant EDMD is caused by mutations in the lamin A/C gene. Emerin colocalizes with lamin A/C in interphase cells, and binds in vitro to lamin A/C. Recent work suggests that lamin A/C might serve as a receptor for emerin. We have undertaken a structural analysis of emerin, and in particular of its N-terminal domain, which is comprised in the emerin segment critical for binding to lamin A/C. We show that region 2-54 of emerin adopts the LEM fold. This fold was originally described in the two N-terminal domains of another inner nuclear membrane protein called lamina-associated protein 2 (LAP2). The existence of a conserved solvent-exposed surface on the LEM domains of LAP2 and emerin is discussed, as well as the nature of a possible common target.
Structural analysis of emerin, an inner nuclear membrane protein mutated in X-linked Emery-Dreifuss muscular dystrophy.,Wolff N, Gilquin B, Courchay K, Callebaut I, Worman HJ, Zinn-Justin S FEBS Lett. 2001 Jul 20;501(2-3):171-6. PMID:11470279[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Holaska JM, Kowalski AK, Wilson KL. Emerin caps the pointed end of actin filaments: evidence for an actin cortical network at the nuclear inner membrane. PLoS Biol. 2004 Sep;2(9):E231. Epub 2004 Aug 24. PMID:15328537 doi:10.1371/journal.pbio.0020231
- ↑ Haraguchi T, Holaska JM, Yamane M, Koujin T, Hashiguchi N, Mori C, Wilson KL, Hiraoka Y. Emerin binding to Btf, a death-promoting transcriptional repressor, is disrupted by a missense mutation that causes Emery-Dreifuss muscular dystrophy. Eur J Biochem. 2004 Mar;271(5):1035-45. PMID:15009215
- ↑ Ellis JA, Yates JR, Kendrick-Jones J, Brown CA. Changes at P183 of emerin weaken its protein-protein interactions resulting in X-linked Emery-Dreifuss muscular dystrophy. Hum Genet. 1999 Mar;104(3):262-8. PMID:10323252
- ↑ Holt I, Clements L, Manilal S, Morris GE. How does a g993t mutation in the emerin gene cause Emery-Dreifuss muscular dystrophy? Biochem Biophys Res Commun. 2001 Oct 12;287(5):1129-33. PMID:11587540 doi:10.1006/bbrc.2001.5708
- ↑ Holaska JM, Kowalski AK, Wilson KL. Emerin caps the pointed end of actin filaments: evidence for an actin cortical network at the nuclear inner membrane. PLoS Biol. 2004 Sep;2(9):E231. Epub 2004 Aug 24. PMID:15328537 doi:10.1371/journal.pbio.0020231
- ↑ Markiewicz E, Tilgner K, Barker N, van de Wetering M, Clevers H, Dorobek M, Hausmanowa-Petrusewicz I, Ramaekers FC, Broers JL, Blankesteijn WM, Salpingidou G, Wilson RG, Ellis JA, Hutchison CJ. The inner nuclear membrane protein emerin regulates beta-catenin activity by restricting its accumulation in the nucleus. EMBO J. 2006 Jul 26;25(14):3275-85. Epub 2006 Jul 20. PMID:16858403 doi:10.1038/sj.emboj.7601230
- ↑ Jacque JM, Stevenson M. The inner-nuclear-envelope protein emerin regulates HIV-1 infectivity. Nature. 2006 Jun 1;441(7093):641-5. Epub 2006 May 7. PMID:16680152 doi:10.1038/nature04682
- ↑ Salpingidou G, Smertenko A, Hausmanowa-Petrucewicz I, Hussey PJ, Hutchison CJ. A novel role for the nuclear membrane protein emerin in association of the centrosome to the outer nuclear membrane. J Cell Biol. 2007 Sep 10;178(6):897-904. Epub 2007 Sep 4. PMID:17785515 doi:10.1083/jcb.200702026
- ↑ Capanni C, Del Coco R, Mattioli E, Camozzi D, Columbaro M, Schena E, Merlini L, Squarzoni S, Maraldi NM, Lattanzi G. Emerin-prelamin A interplay in human fibroblasts. Biol Cell. 2009 Sep;101(9):541-54. doi: 10.1042/BC20080175. PMID:19323649 doi:10.1042/BC20080175
- ↑ Wolff N, Gilquin B, Courchay K, Callebaut I, Worman HJ, Zinn-Justin S. Structural analysis of emerin, an inner nuclear membrane protein mutated in X-linked Emery-Dreifuss muscular dystrophy. FEBS Lett. 2001 Jul 20;501(2-3):171-6. PMID:11470279
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