Emerin

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EMD
Protein EMD PDB 1jei.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases EMD, EDMD, LEMD5, STA, emerin
External IDs OMIM: 300384 MGI: 108117 HomoloGene: 91 GeneCards: 2010
RNA expression pattern
PBB GE EMD 209477 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000117

NM_007927

RefSeq (protein)

NP_000108.1

NP_031953.1

Location (UCSC) Chr X: 154.38 – 154.38 Mb Chr X: 74.25 – 74.26 Mb
PubMed search [1] [2]
Wikidata
View/Edit Human View/Edit Mouse

Emerin is a protein that in humans is encoded by the EMD gene, also known as the STA gene. Emerin, together with MAN1, 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.

Structure[edit]

Emerin is a 29.0 kDa (34 kDa observed MW) protein composed of 254 amino acids.[1] 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.[2] In cardiac, skeletal, and smooth muscle, emerin localizes to the inner nuclear membrane;[3][4] expression of emerin is highest in skeletal and cardiac muscle.[2] In cardiac muscle specifically, emerin also resides at adherens junctions within intercalated discs.[5][6][7]

Function[edit]

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.[8] Emerin appears to be involved in mechanotransduction, as emerin-deficient mouse fibroblasts failed to transduce normal mechanosensitive gene expression responses to strain stimuli.[9] 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.[10]

Clinical significance[edit]

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 .[11] 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.[11] 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.[12]

Moreover, recent research have found that the absence of functional emerin may decrease the infectivity of HIV-1. Thus, it is speculated that patients suffering from Emery-Dreifuss muscular dystrophy may have immunity to or show an irregular infection pattern to HIV-1.[13]

Interactions[edit]

Emerin has been shown to interact with:

References[edit]

  1. ^ "Protein sequence of human EMD (Uniprot ID: P50402)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Retrieved 16 September 2015. 
  2. ^ a b Bione S, Maestrini E, Rivella S, Mancini M, Regis S, Romeo G, Toniolo D (Dec 1994). "Identification of a novel X-linked gene responsible for Emery-Dreifuss muscular dystrophy". Nature Genetics 8 (4): 323–7. doi:10.1038/ng1294-323. PMID 7894480. 
  3. ^ Nagano A, Koga R, Ogawa M, Kurano Y, Kawada J, Okada R, Hayashi YK, Tsukahara T, Arahata K (Mar 1996). "Emerin deficiency at the nuclear membrane in patients with Emery-Dreifuss muscular dystrophy". Nature Genetics 12 (3): 254–9. doi:10.1038/ng0396-254. PMID 8589715. 
  4. ^ Manilal S, Nguyen TM, Sewry CA, Morris GE (Jun 1996). "The Emery-Dreifuss muscular dystrophy protein, emerin, is a nuclear membrane protein". Human Molecular Genetics 5 (6): 801–8. doi:10.1093/hmg/5.6.801. PMID 8776595. 
  5. ^ Cartegni L, di Barletta MR, Barresi R, Squarzoni S, Sabatelli P, Maraldi N, Mora M, Di Blasi C, Cornelio F, Merlini L, Villa A, Cobianchi F, Toniolo D (Dec 1997). "Heart-specific localization of emerin: new insights into Emery-Dreifuss muscular dystrophy". Human Molecular Genetics 6 (13): 2257–64. doi:10.1093/hmg/6.13.2257. PMID 9361031. 
  6. ^ a b Wheeler MA, Warley A, Roberts RG, Ehler E, Ellis JA (Mar 2010). "Identification of an emerin-beta-catenin complex in the heart important for intercalated disc architecture and beta-catenin localisation". Cellular and Molecular Life Sciences 67 (5): 781–96. doi:10.1007/s00018-009-0219-8. PMID 19997769. 
  7. ^ Manilal S, Sewry CA, Pereboev A, Man N, Gobbi P, Hawkes S, Love DR, Morris GE (Feb 1999). "Distribution of emerin and lamins in the heart and implications for Emery-Dreifuss muscular dystrophy". Human Molecular Genetics 8 (2): 353–9. doi:10.1093/hmg/8.2.353. PMID 9949197. 
  8. ^ "Entrez Gene: EMD emerin (Emery-Dreifuss muscular dystrophy)". 
  9. ^ Lammerding, J; Hsiao, J; Schulze, PC; Kozlov, S; Stewart, CL; Lee, RT (29 August 2005). "Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells.". The Journal of Cell Biology 170 (5): 781–91. doi:10.1083/jcb.200502148. PMID 16115958. 
  10. ^ Wheeler, MA; Warley, A; Roberts, RG; Ehler, E; Ellis, JA (March 2010). "Identification of an emerin-beta-catenin complex in the heart important for intercalated disc architecture and beta-catenin localisation.". Cellular and molecular life sciences : CMLS 67 (5): 781–96. doi:10.1007/s00018-009-0219-8. PMID 19997769. 
  11. ^ a b Emery AE (Jun 2000). "Emery-Dreifuss muscular dystrophy - a 40 year retrospective". Neuromuscular Disorders 10 (4-5): 228–32. doi:10.1016/s0960-8966(00)00105-x. PMID 10838246. 
  12. ^ Small K, Warren ST (Jan 1998). "Emerin deletions occurring on both Xq28 inversion backgrounds". Human Molecular Genetics 7 (1): 135–9. doi:10.1093/hmg/7.1.135. PMID 9384614. 
  13. ^ Li M, Craigie R (Jun 2006). "Virology: HIV goes nuclear". Nature 441 (7093): 581–2. doi:10.1038/441581a. PMID 16738646. 
  14. ^ a b c Lattanzi G, Cenni V, Marmiroli S, Capanni C, Mattioli E, Merlini L, Squarzoni S, Maraldi NM (Apr 2003). "Association of emerin with nuclear and cytoplasmic actin is regulated in differentiating myoblasts". Biochemical and Biophysical Research Communications 303 (3): 764–70. doi:10.1016/s0006-291x(03)00415-7. PMID 12670476. 
  15. ^ Berk JM, Simon DN, Jenkins-Houk CR, Westerbeck JW, Grønning-Wang LM, Carlson CR, Wilson KL (Sep 2014). "The molecular basis of emerin-emerin and emerin-BAF interactions". Journal of Cell Science 127 (Pt 18): 3956–69. doi:10.1242/jcs.148247. PMID 25052089. 
  16. ^ a b Holaska JM, Lee KK, Kowalski AK, Wilson KL (Feb 2003). "Transcriptional repressor germ cell-less (GCL) and barrier to autointegration factor (BAF) compete for binding to emerin in vitro". The Journal of Biological Chemistry 278 (9): 6969–75. doi:10.1074/jbc.M208811200. PMID 12493765. 
  17. ^ Haraguchi T, Holaska JM, Yamane M, Koujin T, Hashiguchi N, Mori C, Wilson KL, Hiraoka Y (Mar 2004). "Emerin binding to Btf, a death-promoting transcriptional repressor, is disrupted by a missense mutation that causes Emery-Dreifuss muscular dystrophy". European Journal of Biochemistry / FEBS 271 (5): 1035–45. doi:10.1111/j.1432-1033.2004.04007.x. PMID 15009215. 
  18. ^ 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 (Jul 2006). "The inner nuclear membrane protein emerin regulates beta-catenin activity by restricting its accumulation in the nucleus". The EMBO Journal 25 (14): 3275–85. doi:10.1038/sj.emboj.7601230. PMID 16858403. 
  19. ^ a b c Wilkinson FL, Holaska JM, Zhang Z, Sharma A, Manilal S, Holt I, Stamm S, Wilson KL, Morris GE (Jun 2003). "Emerin interacts in vitro with the splicing-associated factor, YT521-B". European Journal of Biochemistry / FEBS 270 (11): 2459–66. doi:10.1046/j.1432-1033.2003.03617.x. PMID 12755701. 
  20. ^ Sakaki M, Koike H, Takahashi N, Sasagawa N, Tomioka S, Arahata K, Ishiura S (Feb 2001). "Interaction between emerin and nuclear lamins". Journal of Biochemistry 129 (2): 321–7. doi:10.1093/oxfordjournals.jbchem.a002860. PMID 11173535. 
  21. ^ Clements L, Manilal S, Love DR, Morris GE (Jan 2000). "Direct interaction between emerin and lamin A". Biochemical and Biophysical Research Communications 267 (3): 709–14. doi:10.1006/bbrc.1999.2023. PMID 10673356. 
  22. ^ a b Zhang Q, Skepper JN, Yang F, Davies JD, Hegyi L, Roberts RG, Weissberg PL, Ellis JA, Shanahan CM (Dec 2001). "Nesprins: a novel family of spectrin-repeat-containing proteins that localize to the nuclear membrane in multiple tissues". Journal of Cell Science 114 (Pt 24): 4485–98. PMID 11792814. 
  23. ^ Mislow JM, Holaska JM, Kim MS, Lee KK, Segura-Totten M, Wilson KL, McNally EM (Aug 2002). "Nesprin-1alpha self-associates and binds directly to emerin and lamin A in vitro". FEBS Letters 525 (1-3): 135–40. doi:10.1016/s0014-5793(02)03105-8. PMID 12163176. 
  24. ^ a b Wheeler MA, Davies JD, Zhang Q, Emerson LJ, Hunt J, Shanahan CM, Ellis JA (Aug 2007). "Distinct functional domains in nesprin-1alpha and nesprin-2beta bind directly to emerin and both interactions are disrupted in X-linked Emery-Dreifuss muscular dystrophy". Experimental Cell Research 313 (13): 2845–57. doi:10.1016/j.yexcr.2007.03.025. PMID 17462627. 
  25. ^ Zhang Q, Ragnauth CD, Skepper JN, Worth NF, Warren DT, Roberts RG, Weissberg PL, Ellis JA, Shanahan CM (Feb 2005). "Nesprin-2 is a multi-isomeric protein that binds lamin and emerin at the nuclear envelope and forms a subcellular network in skeletal muscle". Journal of Cell Science 118 (Pt 4): 673–87. doi:10.1242/jcs.01642. PMID 15671068. 
  26. ^ Bengtsson L, Otto H (Feb 2008). "LUMA interacts with emerin and influences its distribution at the inner nuclear membrane". Journal of Cell Science 121 (Pt 4): 536–48. doi:10.1242/jcs.019281. PMID 18230648. 

Further reading[edit]

External links[edit]