View source for Emerin

{{Infobox_gene}}

'''Emerin''' is a protein that in humans is encoded by the ''EMD'' gene, also known as the ''STA'' gene. Emerin, together with [[LEMD3|MAN1]], is a LEM domain-containing [[Transmembrane protein|integral]] [[protein]] of the [[Inner nuclear membrane proteins|inner]] [[Cell nucleus|nuclear]] membrane in vertebrates. Emerin is highly expressed in [[cardiac muscle|cardiac]] and [[skeletal muscle]]. In [[cardiac muscle]], emerin localizes to [[adherens junction]]s within [[intercalated disc]]s where it appears to function in mechanotransduction of cellular strain and in [[CTNNB1|beta-catenin]] signaling. Mutations in emerin cause [[X-linked recessive inheritance|X-linked recessive]] [[Emery–Dreifuss muscular dystrophy]], cardiac conduction abnormalities and [[dilated cardiomyopathy]].

It is named after [[Alan Emery]].<ref name="HoMBRG">{{cite Q|Q29581774|pages=118-119}}</ref>

== Structure ==

Emerin is a 29.0 kDa (34 kDa observed MW) [[protein]] composed of 254 [[amino acid]]s.<ref>{{cite web|title=Protein sequence of human EMD (Uniprot ID: P50402)|url=http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P50402|website=Cardiac Organellar Protein Atlas Knowledgebase (COPaKB)|accessdate=16 September 2015}}</ref> Emerin is a [[serine]]-rich [[protein]] with an [[N-terminus|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.<ref name="ReferenceA">{{cite journal | vauthors = Bione S, Maestrini E, Rivella S, Mancini M, Regis S, Romeo G, Toniolo D | title = Identification of a novel X-linked gene responsible for Emery–Dreifuss muscular dystrophy | journal = Nature Genetics | volume = 8 | issue = 4 | pages = 323–7 | date = Dec 1994 | pmid = 7894480 | doi = 10.1038/ng1294-323 }}</ref> In [[cardiac muscle|cardiac]], [[skeletal muscle|skeletal]], and [[smooth muscle]], emerin localizes to the inner [[nuclear membrane]];<ref>{{cite journal | vauthors = Nagano A, Koga R, Ogawa M, Kurano Y, Kawada J, Okada R, Hayashi YK, Tsukahara T, Arahata K | title = Emerin deficiency at the nuclear membrane in patients with Emery–Dreifuss muscular dystrophy | journal = Nature Genetics | volume = 12 | issue = 3 | pages = 254–9 | date = Mar 1996 | pmid = 8589715 | doi = 10.1038/ng0396-254 }}</ref><ref>{{cite journal | vauthors = Manilal S, Nguyen TM, Sewry CA, Morris GE | title = The Emery–Dreifuss muscular dystrophy protein, emerin, is a nuclear membrane protein | journal = Human Molecular Genetics | volume = 5 | issue = 6 | pages = 801–8 | date = Jun 1996 | pmid = 8776595 | doi=10.1093/hmg/5.6.801}}</ref> expression of emerin is highest in [[skeletal muscle|skeletal]] and [[cardiac muscle]].<ref name="ReferenceA"/> In [[cardiac muscle]] specifically, emerin also resides at [[adherens junction]]s within [[intercalated disc]]s.<ref>{{cite journal | vauthors = 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 | title = Heart-specific localization of emerin: new insights into Emery–Dreifuss muscular dystrophy | journal = Human Molecular Genetics | volume = 6 | issue = 13 | pages = 2257–64 | date = Dec 1997 | pmid = 9361031 | doi=10.1093/hmg/6.13.2257}}</ref><ref name="Wheeler_2010"/><ref>{{cite journal | vauthors = Manilal S, Sewry CA, Pereboev A, Man N, Gobbi P, Hawkes S, Love DR, Morris GE | title = Distribution of emerin and lamins in the heart and implications for Emery–Dreifuss muscular dystrophy | journal = Human Molecular Genetics | volume = 8 | issue = 2 | pages = 353–9 | date = Feb 1999 | pmid = 9949197 | doi=10.1093/hmg/8.2.353}}</ref>

== 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]].<ref name="entrez">{{cite web | title = Entrez Gene: EMD emerin (Emery–Dreifuss muscular dystrophy)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2010| accessdate = }}</ref> Emerin appears to be involved in mechanotransduction, as emerin-deficient mouse [[fibroblasts]] failed to transduce normal mechanosensitive gene expression responses to strain stimuli.<ref>{{cite journal|last1=Lammerding|first1=J|last2=Hsiao|first2=J|last3=Schulze|first3=PC|last4=Kozlov|first4=S|last5=Stewart|first5=CL|last6=Lee|first6=RT|title=Abnormal nuclear shape and impaired mechanotransduction in emerin-deficient cells.|journal=The Journal of Cell Biology|date=29 August 2005|volume=170|issue=5|pages=781–91|pmid=16115958|doi=10.1083/jcb.200502148|pmc=2171355}}</ref> In [[cardiac muscle]], emerin is also found complexed to [[CTNNB1|beta-catenin]] at [[adherens junction]]s of [[intercalated disc]]s, and [[cardiomyocyte]]s from hearts lacking emerin showed [[CTNNB1|beta-catenin]] redistribution as well as perturbed [[intercalated disc]] architecture and myocyte shape. This interaction appears to be regulated by [[GSK3B|glycogen synthase kinase 3 beta]].<ref>{{cite journal|last1=Wheeler|first1=MA|last2=Warley|first2=A|last3=Roberts|first3=RG|last4=Ehler|first4=E|last5=Ellis|first5=JA|title=Identification of an emerin-beta-catenin complex in the heart important for intercalated disc architecture and beta-catenin localisation.|journal=Cellular and molecular life sciences : CMLS|date=March 2010|volume=67|issue=5|pages=781–96|pmid=19997769|doi=10.1007/s00018-009-0219-8}}</ref>

== Clinical significance ==

Mutations in emerin cause [[X-linked recessive inheritance|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]], [[First-degree atrioventricular block|PR prolongation]] to complete [[heart block]].<ref name="ReferenceB">{{cite journal | vauthors = Emery AE | title = Emery–Dreifuss muscular dystrophy - a 40 year retrospective | journal = Neuromuscular Disorders | volume = 10 | issue = 4–5 | pages = 228–32 | date = Jun 2000 | pmid = 10838246 | doi=10.1016/s0960-8966(00)00105-x}}</ref> In these patients, immunostaining of emerin is lost in various tissues, including muscle, skin [[fibroblast]]s, and [[leukocyte]]s, however diagnostic protocols involve mutational analysis rather than protein staining.<ref name="ReferenceB"/> 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.<ref>{{cite journal | vauthors = Small K, Warren ST | title = Emerin deletions occurring on both Xq28 inversion backgrounds | journal = Human Molecular Genetics | volume = 7 | issue = 1 | pages = 135–9 | date = Jan 1998 | pmid = 9384614 | doi=10.1093/hmg/7.1.135}}</ref>

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.<ref>{{cite journal | vauthors = Li M, Craigie R | title = Virology: HIV goes nuclear | journal = Nature | volume = 441 | issue = 7093 | pages = 581–2 | date = Jun 2006 | pmid = 16738646 | doi = 10.1038/441581a }}</ref>

== Interactions ==

Emerin has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[ACTA1]],<ref name = pmid12670476>{{cite journal | vauthors = Lattanzi G, Cenni V, Marmiroli S, Capanni C, Mattioli E, Merlini L, Squarzoni S, Maraldi NM | title = Association of emerin with nuclear and cytoplasmic actin is regulated in differentiating myoblasts | journal = Biochemical and Biophysical Research Communications | volume = 303 | issue = 3 | pages = 764–70 | date = Apr 2003 | pmid = 12670476 | doi = 10.1016/s0006-291x(03)00415-7 }}</ref>
* [[ACTG2]],<ref name="pmid12670476"/> 
* [[BANF1]],<ref>{{cite journal | vauthors = Berk JM, Simon DN, Jenkins-Houk CR, Westerbeck JW, Grønning-Wang LM, Carlson CR, Wilson KL | title = The molecular basis of emerin-emerin and emerin-BAF interactions | journal = Journal of Cell Science | volume = 127 | issue = Pt 18 | pages = 3956–69 | date = Sep 2014 | pmid = 25052089 | doi = 10.1242/jcs.148247 | pmc=4163644}}</ref><ref name = "Holaska_2003">{{cite journal | vauthors = Holaska JM, Lee KK, Kowalski AK, Wilson KL | title = Transcriptional repressor germ cell-less (GCL) and barrier to autointegration factor (BAF) compete for binding to emerin in vitro | journal = The Journal of Biological Chemistry | volume = 278 | issue = 9 | pages = 6969–75 | date = Feb 2003 | pmid = 12493765 | doi = 10.1074/jbc.M208811200 }}</ref>
* [[BCLAF1]],<ref>{{cite journal | vauthors = Haraguchi T, Holaska JM, Yamane M, Koujin T, Hashiguchi N, Mori C, Wilson KL, Hiraoka Y | title = Emerin binding to Btf, a death-promoting transcriptional repressor, is disrupted by a missense mutation that causes Emery–Dreifuss muscular dystrophy | journal = European Journal of Biochemistry / FEBS | volume = 271 | issue = 5 | pages = 1035–45 | date = Mar 2004 | pmid = 15009215 | doi=10.1111/j.1432-1033.2004.04007.x}}</ref>
* [[CTNNB1]],<ref name = "Wheeler_2010">{{cite journal | vauthors = Wheeler MA, Warley A, Roberts RG, Ehler E, Ellis JA | title = Identification of an emerin-beta-catenin complex in the heart important for intercalated disc architecture and beta-catenin localisation | journal = Cellular and Molecular Life Sciences | volume = 67 | issue = 5 | pages = 781–96 | date = Mar 2010 | pmid = 19997769 | doi = 10.1007/s00018-009-0219-8 }}</ref><ref>{{cite journal | vauthors = 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 | title = The inner nuclear membrane protein emerin regulates beta-catenin activity by restricting its accumulation in the nucleus | journal = The EMBO Journal | volume = 25 | issue = 14 | pages = 3275–85 | date = Jul 2006 | pmid = 16858403 | doi = 10.1038/sj.emboj.7601230 | pmc=1523183}}</ref>
* [[GMCL1]],<ref name = "Holaska_2003"/>
* [[LMNA]],<ref name = pmid12670476/><ref name = pmid12755701/><ref name = pmid11173535>{{cite journal | vauthors = Sakaki M, Koike H, Takahashi N, Sasagawa N, Tomioka S, Arahata K, Ishiura S | title = Interaction between emerin and nuclear lamins | journal = Journal of Biochemistry | volume = 129 | issue = 2 | pages = 321–7 | date = Feb 2001 | pmid = 11173535 | doi = 10.1093/oxfordjournals.jbchem.a002860 }}</ref><ref name = pmid10673356>{{cite journal | vauthors = Clements L, Manilal S, Love DR, Morris GE | title = Direct interaction between emerin and lamin A | journal = Biochemical and Biophysical Research Communications | volume = 267 | issue = 3 | pages = 709–14 | date = Jan 2000 | pmid = 10673356 | doi = 10.1006/bbrc.1999.2023 }}</ref>
* [[PSME1]],<ref name = pmid12755701/>
* [[SYNE1]],<ref name = "Zhang_2001">{{cite journal | vauthors = Zhang Q, Skepper JN, Yang F, Davies JD, Hegyi L, Roberts RG, Weissberg PL, Ellis JA, Shanahan CM | title = Nesprins: a novel family of spectrin-repeat-containing proteins that localize to the nuclear membrane in multiple tissues | journal = Journal of Cell Science | volume = 114 | issue = Pt 24 | pages = 4485–98 | date = Dec 2001 | pmid = 11792814 }}</ref><ref>{{cite journal | vauthors = Mislow JM, Holaska JM, Kim MS, Lee KK, Segura-Totten M, Wilson KL, McNally EM | title = Nesprin-1alpha self-associates and binds directly to emerin and lamin A in vitro | journal = FEBS Letters | volume = 525 | issue = 1–3 | pages = 135–40 | date = Aug 2002 | pmid = 12163176 | doi=10.1016/s0014-5793(02)03105-8}}</ref><ref name = "Wheeler_2007">{{cite journal | vauthors = Wheeler MA, Davies JD, Zhang Q, Emerson LJ, Hunt J, Shanahan CM, Ellis JA | title = 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 | journal = Experimental Cell Research | volume = 313 | issue = 13 | pages = 2845–57 | date = Aug 2007 | pmid = 17462627 | doi = 10.1016/j.yexcr.2007.03.025 }}</ref>
* [[SYNE2]],<ref name = "Zhang_2001"/><ref name = "Wheeler_2007"/><ref>{{cite journal | vauthors = Zhang Q, Ragnauth CD, Skepper JN, Worth NF, Warren DT, Roberts RG, Weissberg PL, Ellis JA, Shanahan CM | title = 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 = Journal of Cell Science | volume = 118 | issue = Pt 4 | pages = 673–87 | date = Feb 2005 | pmid = 15671068 | doi = 10.1242/jcs.01642 }}</ref>
* [[TMEM43]],<ref>{{cite journal | vauthors = Bengtsson L, Otto H | title = LUMA interacts with emerin and influences its distribution at the inner nuclear membrane | journal = Journal of Cell Science | volume = 121 | issue = Pt 4 | pages = 536–48 | date = Feb 2008 | pmid = 18230648 | doi = 10.1242/jcs.019281 }}</ref> and
* [[YTHDC1]].<ref name = pmid12755701>{{cite journal | vauthors = Wilkinson FL, Holaska JM, Zhang Z, Sharma A, Manilal S, Holt I, Stamm S, Wilson KL, Morris GE | title = Emerin interacts in vitro with the splicing-associated factor, YT521-B | journal = European Journal of Biochemistry / FEBS | volume = 270 | issue = 11 | pages = 2459–66 | date = Jun 2003 | pmid = 12755701 | doi = 10.1046/j.1432-1033.2003.03617.x }}</ref>
{{Div col end}}

== References ==
{{Reflist|33em}}

== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Gant TM, Wilson KL | title = Nuclear assembly. | journal = Annu. Rev. Cell Dev. Biol. | volume = 13 | issue =  | pages = 669–95 | year = 1998 | pmid = 9442884 | doi = 10.1146/annurev.cellbio.13.1.669 }}
* {{cite journal | vauthors = Helbling-Leclerc A, Bonne G, Schwartz K | title = Emery–Dreifuss muscular dystrophy. | journal = Eur. J. Hum. Genet. | volume = 10 | issue = 3 | pages = 157–61 | year = 2002 | pmid = 11973618 | doi = 10.1038/sj.ejhg.5200744 }}
* {{cite journal | vauthors = Holaska JM, Wilson KL | title = Multiple roles for emerin: implications for Emery–Dreifuss muscular dystrophy | journal = The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology | volume = 288 | issue = 7 | pages = 676–80 | year = 2006 | pmid = 16761279 | pmc = 2559942 | doi = 10.1002/ar.a.20334 }}
* {{cite journal | vauthors = Bione S, Tamanini F, Maestrini E, Tribioli C, Poustka A, Torri G, Rivella S, Toniolo D | title = Transcriptional organization of a 450-kb region of the human X chromosome in Xq28 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 90 | issue = 23 | pages = 10977–81 | year = 1994 | pmid = 8248200 | pmc = 47904 | doi = 10.1073/pnas.90.23.10977 }}
* {{cite journal | vauthors = Bione S, Small K, Aksmanovic VM, D'Urso M, Ciccodicola A, Merlini L, Morandi L, Kress W, Yates JR, Warren ST | title = Identification of new mutations in the Emery–Dreifuss muscular dystrophy gene and evidence for genetic heterogeneity of the disease | journal = Hum. Mol. Genet. | volume = 4 | issue = 10 | pages = 1859–63 | year = 1996 | pmid = 8595407 | doi = 10.1093/hmg/4.10.1859 }}
* {{cite journal | vauthors = Yamada T, Kobayashi T | title = A novel emerin mutation in a Japanese patient with Emery–Dreifuss muscular dystrophy | journal = Hum. Genet. | volume = 97 | issue = 5 | pages = 693–4 | year = 1996 | pmid = 8655156 | doi = 10.1007/BF02281886 }}
* {{cite journal | vauthors = Chen EY, Zollo M, Mazzarella R, Ciccodicola A, Chen CN, Zuo L, Heiner C, Burough F, Repetto M, Schlessinger D, D'Urso M | title = 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 | journal = Hum. Mol. Genet. | volume = 5 | issue = 5 | pages = 659–68 | year = 1997 | pmid = 8733135 | doi = 10.1093/hmg/5.5.659 }}
* {{cite journal | vauthors = Ellis JA, Craxton M, Yates JR, Kendrick-Jones J | title = Aberrant intracellular targeting and cell cycle-dependent phosphorylation of emerin contribute to the Emery–Dreifuss muscular dystrophy phenotype | journal = J. Cell Sci. | volume = 111 | issue = 6 | pages = 781–92 | year = 1998 | pmid = 9472006 | doi =  }}
* {{cite journal | vauthors = Squarzoni S, Sabatelli P, Ognibene A, Toniolo D, Cartegni L, Cobianchi F, Petrini S, Merlini L, Maraldi NM | title = Immunocytochemical detection of emerin within the nuclear matrix | journal = Neuromuscul. Disord. | volume = 8 | issue = 5 | pages = 338–44 | year = 1998 | pmid = 9673989 | doi = 10.1016/S0960-8966(98)00031-5 }}
* {{cite journal | vauthors = Ellis JA, Yates JR, Kendrick-Jones J, Brown CA | title = Changes at P183 of emerin weaken its protein-protein interactions resulting in X-linked Emery–Dreifuss muscular dystrophy | journal = Hum. Genet. | volume = 104 | issue = 3 | pages = 262–8 | year = 1999 | pmid = 10323252 | doi = 10.1007/s004390050946 }}
* {{cite journal | vauthors = Squarzoni S, Sabatelli P, Capanni C, Petrini S, Ognibene A, Toniolo D, Cobianchi F, Zauli G, Bassini A, Baracca A, Guarnieri C, Merlini L, Maraldi NM | title = Emerin presence in platelets | journal = Acta Neuropathol. | volume = 100 | issue = 3 | pages = 291–8 | year = 2001 | pmid = 10965799 | doi = 10.1007/s004019900169 }}
* {{cite journal | vauthors = Martins SB, Eide T, Steen RL, Jahnsen T, Skålhegg BS, Collas P | title = HA95 is a protein of the chromatin and nuclear matrix regulating nuclear envelope dynamics | journal = J. Cell Sci. | volume = 113 | issue = 21 | pages = 3703–13 | year = 2001 | pmid = 11034899 | doi =  }}
* {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA Cloning Using In Vitro Site-Specific Recombination | journal = Genome Res. | volume = 10 | issue = 11 | pages = 1788–95 | year = 2001 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
* {{cite journal | vauthors = Laguri C, Gilquin B, Wolff N, Romi-Lebrun R, Courchay K, Callebaut I, Worman HJ, Zinn-Justin S | title = Structural characterization of the LEM motif common to three human inner nuclear membrane proteins | journal = Structure | volume = 9 | issue = 6 | pages = 503–11 | year = 2001 | pmid = 11435115 | doi = 10.1016/S0969-2126(01)00611-6 }}
{{refend}}
{{PDB Gallery|geneid=2010}}

== External links ==
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=edmd  GeneReviews/NCBI/NIH/UW entry on Emery–Dreifuss muscular dystrophy]
* {{MeshName|EMD+protein,+human}}

[[Category:Molecular biology]]