Protein-coding gene in humans
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 .
[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:
ACTA1 ,
[19]
ACTG2 ,
[19]
BANF1 ,
[20]
[21]
BCLAF1 ,
[22]
CTNNB1 ,
[11]
[23]
GMCL1 ,
[21]
LMNA ,
[19]
[24]
[25]
[26]
PSME1 ,
[24]
SYNE1 ,
[27]
[28]
[29]
SYNE2 ,
[27]
[29]
[30]
TMEM43 ,
[31] and
YTHDC1 .
[24]
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000102119 –
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^
a
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^
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^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
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"Protein sequence of human EMD (Uniprot ID: P50402)" . Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) . Archived from
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^
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^ 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.
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^
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b Wheeler MA, Warley A, Roberts RG, Ehler E, Ellis JA (Mar 2010).
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^ Manilal S, Sewry CA, Pereboev A, Man N, Gobbi P, Hawkes S, Love DR, Morris GE (Feb 1999).
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^
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^ Wheeler MA, Warley A, Roberts RG, Ehler E, Ellis JA (March 2010).
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^
a
b Emery AE (Jun 2000). "Emery–Dreifuss muscular dystrophy - a 40 year retrospective". Neuromuscular Disorders . 10 (4–5): 228–32.
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^ Small K, Warren ST (Jan 1998).
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^ Li M, Craigie R (Jun 2006).
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^
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.
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^ Berk JM, Simon DN, Jenkins-Houk CR, Westerbeck JW, Grønning-Wang LM, Carlson CR, Wilson KL (Sep 2014).
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^
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.
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^ 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.
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^ 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).
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^
a
b
c Wilkinson FL, Holaska JM, Zhang Z, Sharma A, Manilal S, Holt I, Stamm S, Wilson KL, Morris GE (Jun 2003).
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^ 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.
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^ 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.
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^
a
b Zhang Q, Skepper JN, Yang F, Davies JD, Hegyi L, Roberts RG, Weissberg PL, Ellis JA, Shanahan CM (Dec 2001).
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^
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.
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^ Zhang Q, Ragnauth CD, Skepper JN, Worth NF, Warren DT, Roberts RG, Weissberg PL, Ellis JA, Shanahan CM (Feb 2005).
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^ 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.
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Further reading
Gant TM, Wilson KL (1998). "Nuclear assembly". Annu. Rev. Cell Dev. Biol . 13 : 669–95.
doi :
10.1146/annurev.cellbio.13.1.669 .
PMID
9442884 .
Helbling-Leclerc A, Bonne G, Schwartz K (2002).
"Emery–Dreifuss muscular dystrophy" . Eur. J. Hum. Genet . 10 (3): 157–61.
doi :
10.1038/sj.ejhg.5200744 .
PMID
11973618 .
Holaska JM, Wilson KL (2006).
"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.
doi :
10.1002/ar.a.20334 .
PMC
2559942 .
PMID
16761279 .
Bione S, Tamanini F, Maestrini E, Tribioli C, Poustka A, Torri G, Rivella S, Toniolo D (1994).
"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.
doi :
10.1073/pnas.90.23.10977 .
PMC
47904 .
PMID
8248200 .
Bione S, Small K, Aksmanovic VM, D'Urso M, Ciccodicola A, Merlini L, Morandi L, Kress W, Yates JR, Warren ST (1996). "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.
doi :
10.1093/hmg/4.10.1859 .
PMID
8595407 .
Yamada T, Kobayashi T (1996). "A novel emerin mutation in a Japanese patient with Emery–Dreifuss muscular dystrophy". Hum. Genet . 97 (5): 693–4.
doi :
10.1007/BF02281886 .
PMID
8655156 .
S2CID
32857705 .
Chen EY, Zollo M, Mazzarella R, Ciccodicola A, Chen CN, Zuo L, Heiner C, Burough F, Repetto M, Schlessinger D, D'Urso M (1997).
"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.
doi :
10.1093/hmg/5.5.659 .
PMID
8733135 .
Ellis JA, Craxton M, Yates JR, Kendrick-Jones J (1998). "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.
doi :
10.1242/jcs.111.6.781 .
PMID
9472006 .
Squarzoni S, Sabatelli P, Ognibene A, Toniolo D, Cartegni L, Cobianchi F, Petrini S, Merlini L, Maraldi NM (1998). "Immunocytochemical detection of emerin within the nuclear matrix". Neuromuscul. Disord . 8 (5): 338–44.
doi :
10.1016/S0960-8966(98)00031-5 .
PMID
9673989 .
S2CID
6113119 .
Ellis JA, Yates JR, Kendrick-Jones J, Brown CA (1999). "Changes at P183 of emerin weaken its protein-protein interactions resulting in X-linked Emery–Dreifuss muscular dystrophy". Hum. Genet . 104 (3): 262–8.
doi :
10.1007/s004390050946 .
PMID
10323252 .
S2CID
26202307 .
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 (2001). "Emerin presence in platelets". Acta Neuropathol . 100 (3): 291–8.
doi :
10.1007/s004019900169 .
PMID
10965799 .
S2CID
6097295 .
Martins SB, Eide T, Steen RL, Jahnsen T, Skålhegg BS, Collas P (2001).
"HA95 is a protein of the chromatin and nuclear matrix regulating nuclear envelope dynamics" . J. Cell Sci . 113 (21): 3703–13.
doi :
10.1242/jcs.113.21.3703 .
PMID
11034899 .
Hartley JL, Temple GF, Brasch MA (2001).
"DNA Cloning Using In Vitro Site-Specific Recombination" . Genome Res . 10 (11): 1788–95.
doi :
10.1101/gr.143000 .
PMC
310948 .
PMID
11076863 .
Laguri C, Gilquin B, Wolff N, Romi-Lebrun R, Courchay K, Callebaut I, Worman HJ, Zinn-Justin S (2001).
"Structural characterization of the LEM motif common to three human inner nuclear membrane proteins" . Structure . 9 (6): 503–11.
doi :
10.1016/S0969-2126(01)00611-6 .
PMID
11435115 .
PDB gallery
1jei : LEM DOMAIN OF HUMAN INNER NUCLEAR MEMBRANE PROTEIN EMERIN
2odc : LEM-domain of the nuclear envelope protein emerin
2odg : Complex of barrier-to-autointegration factor and LEM-domain of emerin
External links