Emerin

S Wikipedije, slobodne enciklopedije
EMD
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

1JEI, 2ODC, 2ODG

Identifikatori
AliasiEMD
Vanjski ID-jeviOMIM: 300384 MGI: 108117 HomoloGene: 91 GeneCards: EMD
Lokacija gena (čovjek)
Hromosom X
Hrom.Hromosom X[1]
Hromosom X
Genomska lokacija za EMD
Genomska lokacija za EMD
BendXq28Početak154,379,273 bp[1]
Kraj154,381,574 bp[1]
Lokacija gena (miš)
Hromosom X (miš)
Hrom.Hromosom X (miš)[2]
Hromosom X (miš)
Genomska lokacija za EMD
Genomska lokacija za EMD
BendX A7.3|X 37.92 cMPočetak73,298,293 bp[2]
Kraj73,305,154 bp[2]
Obrazac RNK ekspresije
Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija• GO:0001948, GO:0016582 vezivanje za proteine
• beta-tubulin binding
• actin binding
• cadherin binding
Ćelijska komponenta• integral component of membrane
• Jedarna membrana
• membrana
• nuclear inner membrane
• Endoplazmatski retikulum
• Mikrotubula
• nuclear outer membrane
• jedro
• nukleoplazma
• citoplazma
• nuclear envelope
• spindle pole centrosome
• cortical endoplasmic reticulum
• Diobeno vreteno
Biološki proces• Mišićna kontrakcija
• regulation of canonical Wnt signaling pathway
• cellular response to growth factor stimulus
• muscle organ development
• positive regulation of protein export from nucleus
• mitotic nuclear membrane disassembly
• skeletal muscle cell differentiation
• mitotic nuclear membrane reassembly
• negative regulation of fibroblast proliferation
• negative regulation of canonical Wnt signaling pathway
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez

2010

13726

Ensembl

ENSG00000102119

ENSMUSG00000001964

UniProt

P50402

O08579

RefSeq (mRNK)

NM_000117

NM_007927

RefSeq (bjelančevina)

NP_000108

NP_031953

Lokacija (UCSC)Chr X: 154.38 – 154.38 MbChr X: 73.3 – 73.31 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Emerin je protein koji kod ljudi kodiran genom EMD, poznatim i kao gen STA. Emerin, zajedno sa LEMD3, sadrži integralni protein membrane koji sadrži unutrašnja jedarna membrana kod kičmenjaka. Emerin je visoko izražen u srčanom i skeletnim mišićima. U srčanom mišiću, emerin se lokalizuje na adherens spojeve unutar gmeđukaliranog diska, dje izgleda da funkcionira u mehanotransdukciji ćelijskog soja i u signalizaciji beta-katenina. Mutacije emerina uzrokuju X-vezano recesivnu Emery-Dreifussovu mišićnu distrofiju, abnormalnosti srčanog provođenja i dilatiranu kardiomiopatiju.

Ime je dobio po Alanu Emeryiju.

Struktura[uredi | uredi izvor]

Emerin je protein od 29,0 kDa (u MW 34 kDa), sastavljen od 254 aminokiseline.[5] Emerin je serinom bogat protein sa N-krajem sa 20-aminokiselinskom hidrofobnom regijom koja je okružena nabijenim ostacima. Hidrofobna regija može biti važna za učvršćivanje proteina na membrani, s napunjenim završnim citosolnim repovima.[6] U srčanom, skeletnom i glatkom mišiću, emerin se lokalizuje u unutrašnju jedrovu membranu;[7][8] ekspresija emerina je najviša u skeletnim i srčanom mišiću.[6] Konkretno, u srčanom mišiću, emerin se također nlazi na adherens spojevima unutar interkaliranih diskova.[9][10][11]

Funkcija[uredi | uredi izvor]

Emerin je protein serinom bogate jedrove membrane i član porodice proteina povezane sa jedarnom laminom. Posreduje sidrenje membrane na citoskelet. Emery – Dreifussova mišićna distrofija nasljeđuje se kao X-vezana degenerativna miopatija koja je posljedica mutacije u genu EMD (također klinički poznat kao STA ).[12] Čini se da je emerin uključen u mehanotransdukciju, jer mišji fibroblast i s nedostatkom emerina nisu uspjeli transducirati normalne reakcije ekspresije mehanosenzitivnih gena na podražaje soja.[13] U srčanom mišiću, emerin se također nalazi u kompleksu sa beta-kateninom na adherens spoj evima interkaliranog diska. Kardiomiociti srca kojima nedostaje emerin pokazali su preraspodjelu beta-katenina, kao i poremećenu arhitekturu i oblik miocita interkaliranog diska . Ova interakcija regulirana je putem glikogen-sintaza kinaze 3 beta.[14]

Klinički značaj[uredi | uredi izvor]

Mutacije emerina uzrokuju X-vezano recesivno Emery – Dreifussove mišićne distrofije, koje karakteriziraju rane kontrakture u Ahilovim tetivama, laktovima i postcerviksnim mišićima. Javlja se mišićna slabost. koja je proksimalna u gornjim udovima i distalna u donjim udovima; zajedno sa srčanim defektima provodljivosti koji se kreću od sinusne bradikardije, produženja zupca PR do završetka srčanim blokom.[15] Kod ovih pacijenata imunobojenje emerina gubi se u različitim tkivima, uključujući mišiće, kožne fibroblaste i leukocita, ali dijagnostički protokoli uključuju mutacijsku analizu, a ne bojenje proteina.[15] U gotovo svim slučajevima, mutacije rezultiraju potpunom delecijom ili neotkrivljivim nivoima emerinskog proteina. Otprilike 20% slučajeva ima X hromosome sa inverzijom unutar Xq28 regiona.[16]

Šta više, nedavna istraživanja otkrila su da odsustvo funkcionalnog emerina može smanjiti infektivnost HIV-1. Stoga se nagađa da pacijenti koji pate od Emery-Dreifussove mišićne distrofije mogu imati imunost ili pokazati nepravilan obrazac infekcije sa HIV-1.[17]

Interakcije[uredi | uredi izvor]

Pokazano je da emerin ima interakcije sa:

Reference[uredi | uredi izvor]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000102119 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000001964 - Ensembl, maj 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. ^ "Protein sequence of human EMD (Uniprot ID: P50402)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Arhivirano s originala, 4. 3. 2016. Pristupljeno 16. 9. 2015.
  6. ^ 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.
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
  12. ^ "Entrez Gene: EMD emerin (Emery–Dreifuss muscular dystrophy)".
  13. ^ Lammerding, J; Hsiao, J; Schulze, PC; Kozlov, S; Stewart, CL; Lee, RT (29. 8. 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.
  14. ^ Wheeler, MA; Warley, A; Roberts, RG; Ehler, E; Ellis, JA (mart 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.
  15. ^ 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.
  16. ^ 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.
  17. ^ 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.
  18. ^ 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.
  19. ^ 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.
  20. ^ 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.
  21. ^ 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.
  22. ^ 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.
  23. ^ 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.
  24. ^ 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.
  25. ^ 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.
  26. ^ 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.
  27. ^ 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.
  28. ^ 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.
  29. ^ 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.
  30. ^ 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.

Dopunska literatura[uredi | uredi izvor]

Vanjski linkovi[uredi | uredi izvor]

Preuzeto iz "https://bs.wikipedia.org/w/index.php?title=Emerin&oldid=3496886"