Emerin

Last updated
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: EMD
Orthologs
SpeciesHumanMouse
Entrez

2010

13726

Ensembl

ENSG00000102119

ENSMUSG00000001964

UniProt

P50402

O08579

RefSeq (mRNA)

NM_000117

NM_007927

RefSeq (protein)

NP_000108

NP_031953

Location (UCSC) Chr X: 154.38 – 154.38 Mb Chr X: 73.3 – 73.31 Mb
PubMed search [3] [4]
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 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.

Contents

It is named after Alan Emery. [5]

Structure

Emerin is a 29.0 kDa (34 kDa observed MW) protein composed of 254 amino acids. [6] 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. [7] In cardiac, skeletal, and smooth muscle, emerin localizes to the inner nuclear membrane; [8] [9] expression of emerin is highest in skeletal and cardiac muscle. [7] In cardiac muscle specifically, emerin also resides at adherens junctions within intercalated discs. [10] [11] [12]

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. [13] Emerin appears to be involved in mechanotransduction, as emerin-deficient mouse fibroblasts failed to transduce normal mechanosensitive gene expression responses to strain stimuli. [14] 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. [15]

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. [16] 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. [16] 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. [17]

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. [18]

Interactions

Emerin has been shown to interact with:

Related Research Articles

<span class="mw-page-title-main">Muscular dystrophy</span> Genetic disorder

Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily affected, the degree of weakness, how fast they worsen, and when symptoms begin. Some types are also associated with problems in other organs.

<span class="mw-page-title-main">Plectin</span> Mammalian protein found in Homo sapiens

Plectin is a giant protein found in nearly all mammalian cells which acts as a link between the three main components of the cytoskeleton: actin microfilaments, microtubules and intermediate filaments. In addition, plectin links the cytoskeleton to junctions found in the plasma membrane that structurally connect different cells. By holding these different networks together, plectin plays an important role in maintaining the mechanical integrity and viscoelastic properties of tissues.

<span class="mw-page-title-main">Dysferlin</span> Protein encoded by the DYSF gene in humans

Dysferlin also known as dystrophy-associated fer-1-like protein is a protein that in humans is encoded by the DYSF gene. Dysferlin is linked with plasma membrane repair., stabilization of calcium signaling and the development of the T-tubule system of the muscle A defect in the DYSF gene, located on chromosome 2p12-14, results in several types of muscular dystrophy; including Miyoshi myopathy (MM), Limb-girdle muscular dystrophy type 2B (LGMD2B) and Distal Myopathy (DM). A reduction or absence of dysferlin, termed dysferlinopathy, usually becomes apparent in the third or fourth decade of life and is characterised by weakness and wasting of various voluntary skeletal muscles. Pathogenic mutations leading to dysferlinopathy can occur throughout the DYSF gene.

<span class="mw-page-title-main">Desmoglein-2</span> Protein found in humans

Desmoglein-2 is a protein that in humans is encoded by the DSG2 gene. Desmoglein-2 is highly expressed in epithelial cells and cardiomyocytes. Desmoglein-2 is localized to desmosome structures at regions of cell-cell contact and functions to structurally adhere adjacent cells together. In cardiac muscle, these regions are specialized regions known as intercalated discs. Mutations in desmoglein-2 have been associated with arrhythmogenic right ventricular cardiomyopathy and familial dilated cardiomyopathy.

<span class="mw-page-title-main">Catenin beta-1</span> Mammalian protein found in Homo sapiens

Catenin beta-1, also known as β-catenin (beta-catenin), is a protein that in humans is encoded by the CTNNB1 gene.

<span class="mw-page-title-main">Emery–Dreifuss muscular dystrophy</span> Medical condition

Emery–Dreifuss muscular dystrophy (EDMD) is a type of muscular dystrophy, a group of heritable diseases that cause progressive impairment of muscles. EDMD affects muscles used for movement, causing atrophy, weakness and contractures. It almost always affects the heart, causing abnormal rhythms, heart failure, or sudden cardiac death. It is rare, affecting 0.39 per 100,000 people. It is named after Alan Eglin H. Emery and Fritz E. Dreifuss.

<span class="mw-page-title-main">Plakoglobin</span> Mammalian protein found in Homo sapiens

Plakoglobin, also known as junction plakoglobin or gamma-catenin, is a protein that in humans is encoded by the JUP gene. Plakoglobin is a member of the catenin protein family and homologous to β-catenin. Plakoglobin is a cytoplasmic component of desmosomes and adherens junctions structures located within intercalated discs of cardiac muscle that function to anchor sarcomeres and join adjacent cells in cardiac muscle. Mutations in plakoglobin are associated with arrhythmogenic right ventricular dysplasia.

<span class="mw-page-title-main">Laminopathy</span> Medical condition

Laminopathies are a group of rare genetic disorders caused by mutations in genes encoding proteins of the nuclear lamina. They are included in the more generic term nuclear envelopathies that was coined in 2000 for diseases associated with defects of the nuclear envelope. Since the first reports of laminopathies in the late 1990s, increased research efforts have started to uncover the vital role of nuclear envelope proteins in cell and tissue integrity in animals.

<span class="mw-page-title-main">Prelamin-A/C</span> Filament protein

Prelamin-A/C, or lamin A/C is a protein that in humans is encoded by the LMNA gene. Lamin A/C belongs to the lamin family of proteins.

<span class="mw-page-title-main">Sarcospan</span>

Sarcospan is a protein that in humans is encoded by the SSPN gene.

<span class="mw-page-title-main">Integrin alpha 7</span>

Alpha-7 integrin is a protein that in humans is encoded by the ITGA7 gene. Alpha-7 integrin is critical for modulating cell-matrix interactions. Alpha-7 integrin is highly expressed in cardiac muscle, skeletal muscle and smooth muscle cells, and localizes to Z-disc and costamere structures. Mutations in ITGA7 have been associated with congenital myopathies and noncompaction cardiomyopathy, and altered expression levels of alpha-7 integrin have been identified in various forms of muscular dystrophy.

<span class="mw-page-title-main">MYOT</span> Mammalian protein found in Homo sapiens

Myotilin is a protein that in humans is encoded by the MYOT gene. Myotilin also known as TTID is a muscle protein that is found within the Z-disc of sarcomeres.

<span class="mw-page-title-main">SGCG</span> Protein-coding gene in the species Homo sapiens

Gamma-sarcoglycan is a protein that in humans is encoded by the SGCG gene. The α to δ-sarcoglycans are expressed predominantly (β) or exclusively in striated muscle. A mutation in any of the sarcoglycan genes may lead to a secondary deficiency of the other sarcoglycan proteins, presumably due to destabilisation of the sarcoglycan complex. The disease-causing mutations in the α to δ genes cause disruptions within the dystrophin-associated protein (DAP) complex in the muscle cell membrane. The transmembrane components of the DAP complex link the cytoskeleton to the extracellular matrix in adult muscle fibres, and are essential for the preservation of the integrity of the muscle cell membrane.

<span class="mw-page-title-main">SYNE2</span> Protein-coding gene in the species Homo sapiens

Nesprin-2 is a protein that in humans is encoded by the SYNE2 gene. The human SYNE2 gene consists of 116 exons and encodes nesprin-2, a member of the nuclear envelope (NE) spectrin-repeat (nesprin) family. Nesprins are modular proteins with a central extended spectrin-repeat (SR) rod domain and a C-terminal Klarsicht/ANC-1/Syne homology (KASH) transmembrane domain, which acts as a NE-targeting motif. Nesprin-2 (Nesp2) binds to cytoplasmic F-actin, tethering the nucleus to the cytoskeleton and maintaining the structural integrity of the nucleus.

<span class="mw-page-title-main">BCLAF1</span> Protein-coding gene in the species Homo sapiens

Bcl-2-associated transcription factor 1 is a Bcl-2 family protein in humans that is encoded by the BCLAF1 gene.

<span class="mw-page-title-main">TMEM43</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 43 is a protein that in humans is encoded by the TMEM43 gene. TMEM43 may have an important role in maintaining nuclear envelope structure by organizing protein complexes at the inner nuclear membrane. Required for retaining emerin at the inner nuclear membrane. However, the localization of TMEM43 in myocardial tissue is controversial discussed. Franke et al. demonstrated that TMEM43 is localized at the intercalated disc but not at the nuclear envelope. In contrast Christensen et al. have shown that TMEM43 is mainly localized at the sarcolemma. Mutations in TMEM43 are associated with ARVD and EDMD7.

<span class="mw-page-title-main">TOR1AIP1</span> Protein-coding gene in the species Homo sapiens

Torsin-1A-interacting protein 1 is a protein that in humans is encoded by the TOR1AIP1 gene. More commonly known as lamina associated polypeptide 1 (LAP1), it is a type II integral membrane protein that resides in the inner nuclear membrane. The luminal domain of LAP1 interacts with Torsin A and is necessary for the ATPase activity of Torsin A. LAP1 plays a critical role in skeletal and heart muscle. Mutations in TOR1AIP1 have been linked to muscular dystrophy and cardiomyopathy. It's deletion from mouse hepatocytes leads to defected very-low density lipoprotein secretion and causes non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

<span class="mw-page-title-main">Catenin alpha-1</span> Protein-coding gene in the species Homo sapiens

αE-catenin, also known as Catenin alpha-1 is a protein that in humans is encoded by the CTNNA1 gene. αE-catenin is highly expressed in cardiac muscle and localizes to adherens junctions at intercalated disc structures where it functions to mediate the anchorage of actin filaments to the sarcolemma. αE-catenin also plays a role in tumor metastasis and skin cell function.

<span class="mw-page-title-main">Inner nuclear membrane protein</span> Protein embedded in inner membrane of nuclear envelope

Inner nuclear membrane proteins are membrane proteins that are embedded in or associated with the inner membrane of the nuclear envelope. There are about 60 INM proteins, most of which are poorly characterized with respect to structure and function. Among the few well-characterized INM proteins are lamin B receptor (LBR), lamina-associated polypeptide 1 (LAP1), lamina-associated polypeptide-2 (LAP2), emerin and MAN1.

<span class="mw-page-title-main">LMNA-related congenital muscular dystrophy</span> Medical condition

Lamin A/C congenital muscular dystrophy (CMD) is a disease that it is included in laminopathies. Laminopathies are caused, among other mutations, to mutations in LMNA, a gene that synthesizes lamins A and C.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000102119 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000001964 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Peter Harper, Lois Reynolds, Tilli Tansey, eds. (2010). Clinical Genetics in Britain: Origins and development. Wellcome Witnesses to Contemporary Medicine. History of Modern Biomedicine Research Group. pp. 118–119. ISBN   978-0-85484-127-1. Wikidata   Q29581774.
  6. ↑ "Protein sequence of human EMD (Uniprot ID: P50402)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Archived from the original on 4 March 2016. Retrieved 16 September 2015.
  7. 1 2 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. S2CID   7719215.
  8. ↑ 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. S2CID   11030787.
  9. ↑ 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.
  10. ↑ 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.
  11. 1 2 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. S2CID   27205170.
  12. ↑ 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.
  13. ↑ "Entrez Gene: EMD emerin (Emery–Dreifuss muscular dystrophy)".
  14. ↑ 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. PMC   2171355 . PMID   16115958.
  15. ↑ 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. 67 (5): 781–96. doi:10.1007/s00018-009-0219-8. PMID   19997769. S2CID   27205170.
  16. 1 2 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. S2CID   26523560.
  17. ↑ 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.
  18. ↑ Li M, Craigie R (Jun 2006). "Virology: HIV goes nuclear". Nature. 441 (7093): 581–2. Bibcode:2006Natur.441..581L. doi: 10.1038/441581a . PMID   16738646.
  19. 1 2 3 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.
  20. ↑ 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. PMC   4163644 . PMID   25052089.
  21. 1 2 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.
  22. ↑ 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. 271 (5): 1035–45. doi:10.1111/j.1432-1033.2004.04007.x. PMID   15009215.
  23. ↑ 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. PMC   1523183 . PMID   16858403.
  24. 1 2 3 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. 270 (11): 2459–66. doi: 10.1046/j.1432-1033.2003.03617.x . PMID   12755701.
  25. ↑ 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.
  26. ↑ 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.
  27. 1 2 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. doi:10.1242/jcs.114.24.4485. PMID   11792814.
  28. ↑ 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.
  29. 1 2 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.
  30. ↑ 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.
  31. ↑ 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.

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