Biology:Emerin

Short description: Protein-coding gene in humans

Generic protein structure example

Emerin is a protein that in humans is encoded by the EMD gene, also known as the STA gene. Emerin, together with LEMD3, is a LEM domain-containing integral protein of the inner nuclear membrane in vertebrates. Emerin is highly expressed in cardiac and skeletal muscle. In cardiac muscle, emerin localizes to adherens junctions within intercalated discs where it appears to function in mechanotransduction of cellular strain and in beta-catenin signaling. Mutations in emerin cause X-linked recessive Emery–Dreifuss muscular dystrophy, cardiac conduction abnormalities and dilated cardiomyopathy.

It is named after Alan Emery.

Structure

Emerin is a 29.0 kDa (34 kDa observed MW) protein composed of 254 amino acids. Emerin is a serine-rich protein with an N-terminal 20-amino acid hydrophobic region that is flanked by charged residues; the hydrophobic region may be important for anchoring the protein to the membrane, with the charged terminal tails being cytosolic. In cardiac, skeletal, and smooth muscle, emerin localizes to the inner nuclear membrane; expression of emerin is highest in skeletal and cardiac muscle. In cardiac muscle specifically, emerin also resides at adherens junctions within intercalated discs.

Function

Emerin is a serine-rich nuclear membrane protein and a member of the nuclear lamina-associated protein family. It mediates membrane anchorage to the cytoskeleton. Emery–Dreifuss muscular dystrophy is an X-linked inherited degenerative myopathy resulting from mutation in the EMD (also known clinically as STA) gene. Emerin appears to be involved in mechanotransduction, as emerin-deficient mouse fibroblasts failed to transduce normal mechanosensitive gene expression responses to strain stimuli. In cardiac muscle, emerin is also found complexed to beta-catenin at adherens junctions of intercalated discs, and cardiomyocytes from hearts lacking emerin showed beta-catenin redistribution as well as perturbed intercalated disc architecture and myocyte shape. This interaction appears to be regulated by glycogen synthase kinase 3 beta.

Clinical significance

Mutations in emerin cause X-linked recessive Emery–Dreifuss muscular dystrophy, which is characterized by early contractures in the Achilles tendons, elbows and post-cervical muscles; muscle weakness proximal in the upper limbs and distal in lower limbs; along with cardiac conduction defects that range from sinus bradycardia, PR prolongation to complete heart block. In these patients, immunostaining of emerin is lost in various tissues, including muscle, skin fibroblasts, and leukocytes, however diagnostic protocols involve mutational analysis rather than protein staining. In nearly all cases, mutations result in a complete deletion, or undetectable levels, of emerin protein. Approximately 20% of cases have X chromosomes with an inversion within the Xq28 region.

Moreover, recent research have found that the absence of functional emerin may decrease the infectivity of HIV-1. Thus, it is speculated that patients with Emery–Dreifuss muscular dystrophy may have immunity to or show an irregular infection pattern to HIV-1.

Interactions

Emerin has been shown to interact with:

• ACTA1,
• ACTG2,
• BANF1,
• BCLAF1,
• CTNNB1,
• GMCL1,
• LMNA,
• PSME1,
• SYNE1,
• SYNE2,
• TMEM43, and
• YTHDC1.

Further reading

• "Nuclear assembly.". Annu. Rev. Cell Dev. Biol. 13: 669–95. 1998. doi:10.1146/annurev.cellbio.13.1.669. PMID 9442884. 
• "Emery–Dreifuss muscular dystrophy.". Eur. J. Hum. Genet. 10 (3): 157–61. 2002. doi:10.1038/sj.ejhg.5200744. PMID 11973618. 
• "Multiple roles for emerin: implications for Emery–Dreifuss muscular dystrophy". The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology 288 (7): 676–80. 2006. doi:10.1002/ar.a.20334. PMID 16761279. 
• "Transcriptional organization of a 450-kb region of the human X chromosome in Xq28". Proc. Natl. Acad. Sci. U.S.A. 90 (23): 10977–81. 1994. doi:10.1073/pnas.90.23.10977. PMID 8248200. 
• "Identification of new mutations in the Emery–Dreifuss muscular dystrophy gene and evidence for genetic heterogeneity of the disease". Hum. Mol. Genet. 4 (10): 1859–63. 1996. doi:10.1093/hmg/4.10.1859. PMID 8595407. 
• "A novel emerin mutation in a Japanese patient with Emery–Dreifuss muscular dystrophy". Hum. Genet. 97 (5): 693–4. 1996. doi:10.1007/BF02281886. PMID 8655156. 
• "Long-range sequence analysis in Xq28: thirteen known and six candidate genes in 219.4 kb of high GC DNA between the RCP/GCP and G6PD loci". Hum. Mol. Genet. 5 (5): 659–68. 1997. doi:10.1093/hmg/5.5.659. PMID 8733135. 
• "Aberrant intracellular targeting and cell cycle-dependent phosphorylation of emerin contribute to the Emery–Dreifuss muscular dystrophy phenotype". J. Cell Sci. 111 (6): 781–92. 1998. doi:10.1242/jcs.111.6.781. PMID 9472006. 
• "Immunocytochemical detection of emerin within the nuclear matrix". Neuromuscul. Disord. 8 (5): 338–44. 1998. doi:10.1016/S0960-8966(98)00031-5. PMID 9673989. 
• "Changes at P183 of emerin weaken its protein-protein interactions resulting in X-linked Emery–Dreifuss muscular dystrophy". Hum. Genet. 104 (3): 262–8. 1999. doi:10.1007/s004390050946. PMID 10323252. 
• "Emerin presence in platelets". Acta Neuropathol. 100 (3): 291–8. 2001. doi:10.1007/s004019900169. PMID 10965799. 
• "HA95 is a protein of the chromatin and nuclear matrix regulating nuclear envelope dynamics". J. Cell Sci. 113 (21): 3703–13. 2001. doi:10.1242/jcs.113.21.3703. PMID 11034899. 
• "DNA Cloning Using In Vitro Site-Specific Recombination". Genome Res. 10 (11): 1788–95. 2001. doi:10.1101/gr.143000. PMID 11076863. 
• "Structural characterization of the LEM motif common to three human inner nuclear membrane proteins". Structure 9 (6): 503–11. 2001. doi:10.1016/S0969-2126(01)00611-6. PMID 11435115. 

External links

• GeneReviews/NCBI/NIH/UW entry on Emery–Dreifuss muscular dystrophy
• EMD+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)