utrophin

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/18 08:14:21」(JST)

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Utrophin
PDB rendering based on 1bhd.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1BHD, 1QAG
Identifiers
Symbols	UTRN ; DMDL; DRP; DRP1
External IDs	OMIM: 128240 MGI: 104631 HomoloGene: 21398 GeneCards: UTRN Gene
Gene ontology Molecular function • actin binding • integrin binding • calcium ion binding • protein binding • zinc ion binding • vinculin binding • protein kinase binding Cellular component • nucleus • nucleolus • cytoplasm • cytoskeleton • plasma membrane • dystrophin-associated glycoprotein complex • membrane • cell junction • filopodium • filopodium membrane • neuromuscular junction • protein complex • postsynaptic membrane • extracellular vesicular exosome • contractile ring Biological process • positive regulation of cell-matrix adhesion • muscle contraction • muscle organ development • regulation of sodium ion transmembrane transporter activity Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7402	22288
Ensembl	ENSG00000152818	ENSMUSG00000019820
UniProt	P46939	E9Q6R7
RefSeq (mRNA)	NM_007124	NM_011682
RefSeq (protein)	NP_009055	NP_035812
Location (UCSC)	Chr 6: 144.61 – 145.17 Mb	Chr 10: 12.38 – 12.86 Mb
PubMed search	[1]	[2]

Utrophin is a protein that in humans is encoded by the UTRN gene.

The protein encoded by this gene is a component of the cytoskeleton. Utrophin was found during research into Duchenne's muscular dystrophy. The name is a contraction for ubiquitous dystrophin. The 900 kb gene for utrophin is found on the long arm of human chromosome 6. Utrophin was discovered due to its homology with dystrophin. It was found by screening a peptide containing the C-terminal domain of dystrophin against cDNA libraries. The homology varies over its full length from less than 30% in regions of the central rod structural domain, to 85% (identity 73%) for the actin binding domain.

The tertiary structure of utrophin contains a C-terminus that consists of protein–protein interaction motifs that interact with dystroglycan, a central rod region consisting of a triple coiled-coil repeat, and an actin-binding N-terminus.

In normal muscle cells, utrophin is located at the neuromuscular synapse and myotendinous junctions. It is necessary for normal membrane maintenance, and for the clustering of the acetylcholine receptor. In adult humans, utrophin RNA is found ubiquitously, as the name implies, being abundant in the brain, kidney, liver, lung, muscle, spleen and stomach. In the human fetus during muscle differentiation, utrophin is found at the sarcolemma. It disappears when the fetus begins to express dystrophin.

Utrophin expression is dramatically increased in patients with Duchenne's muscular dystrophy (and female carriers), both in those muscle fibers lacking dystrophin and in rare, revertant fibers that express dystrophin.

No reports have yet associated mutation in the utrophin gene with disease, but it does not seem to play a critical role in development, since mice without utrophin develop normally.

References

Further reading

• Haenggi T, Fritschy JM (2006). "Role of dystrophin and utrophin for assembly and function of the dystrophin glycoprotein complex in non-muscle tissue.". Cell. Mol. Life Sci. 63 (14): 1614–31. doi:10.1007/s00018-005-5461-0. PMID 16710609. 
• Khurana TS, Watkins SC, Kunkel LM (1992). "The subcellular distribution of chromosome 6-encoded dystrophin-related protein in the brain.". J. Cell Biol. 119 (2): 357–66. doi:10.1083/jcb.119.2.357. PMC 2289652. PMID 1400579. 
• Tinsley JM, Blake DJ, Roche A et al. (1993). "Primary structure of dystrophin-related protein.". Nature 360 (6404): 591–3. doi:10.1038/360591a0. PMID 1461283.  CS1 maint: Explicit use of et al. (link)
• Love DR, Morris GE, Ellis JM et al. (1991). "Tissue distribution of the dystrophin-related gene product and expression in the mdx and dy mouse.". Proc. Natl. Acad. Sci. U.S.A. 88 (8): 3243–7. doi:10.1073/pnas.88.8.3243. PMC 51422. PMID 2014247.  CS1 maint: Explicit use of et al. (link)
• Buckle VJ, Guenet JL, Simon-Chazottes D et al. (1990). "Localisation of a dystrophin-related autosomal gene to 6q24 in man, and to mouse chromosome 10 in the region of the dystrophia muscularis (dy) locus.". Hum. Genet. 85 (3): 324–6. doi:10.1007/BF00206755. PMID 2203673.  CS1 maint: Explicit use of et al. (link)
• Love DR, Hill DF, Dickson G et al. (1989). "An autosomal transcript in skeletal muscle with homology to dystrophin.". Nature 339 (6219): 55–8. doi:10.1038/339055a0. PMID 2541343.  CS1 maint: Explicit use of et al. (link)
• Belkin AM, Burridge K (1995). "Localization of utrophin and aciculin at sites of cell-matrix and cell-cell adhesion in cultured cells.". Exp. Cell Res. 221 (1): 132–40. doi:10.1006/excr.1995.1360. PMID 7589238. 
• Ahn AH, Kunkel LM (1995). "Syntrophin binds to an alternatively spliced exon of dystrophin.". J. Cell Biol. 128 (3): 363–71. doi:10.1083/jcb.128.3.363. PMC 2120343. PMID 7844150. 
• Belkin AM, Burridge K (1995). "Association of aciculin with dystrophin and utrophin.". J. Biol. Chem. 270 (11): 6328–37. doi:10.1074/jbc.270.11.6328. PMID 7890770. 
• Pearce M, Blake DJ, Tinsley JM et al. (1994). "The utrophin and dystrophin genes share similarities in genomic structure.". Hum. Mol. Genet. 2 (11): 1765–72. doi:10.1093/hmg/2.11.1765. PMID 8281135.  CS1 maint: Explicit use of et al. (link)
• Ahn AH, Freener CA, Gussoni E et al. (1996). "The three human syntrophin genes are expressed in diverse tissues, have distinct chromosomal locations, and each bind to dystrophin and its relatives.". J. Biol. Chem. 271 (5): 2724–30. doi:10.1074/jbc.271.5.2724. PMID 8576247.  CS1 maint: Explicit use of et al. (link)
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery.". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548. 
• Guo WX, Nichol M, Merlie JP (1997). "Cloning and expression of full length mouse utrophin: the differential association of utrophin and dystrophin with AChR clusters.". FEBS Lett. 398 (2–3): 259–64. doi:10.1016/S0014-5793(96)01216-1. PMID 8977119. 
• Deconinck AE, Rafael JA, Skinner JA et al. (1997). "Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy". Cell 90 (4): 717–27. doi:10.1016/S0092-8674(00)80532-2. PMID 9288751.  CS1 maint: Explicit use of et al. (link)
• Nawrotzki R, Loh NY, Ruegg MA et al. (1999). "Characterisation of alpha-dystrobrevin in muscle". J. Cell. Sci. 111 (17): 2595–605. PMID 9701558.  CS1 maint: Explicit use of et al. (link)
• Keep NH, Norwood FL, Moores CA et al. (1999). "The 2.0 A structure of the second calponin homology domain from the actin-binding region of the dystrophin homologue utrophin". J. Mol. Biol. 285 (3): 1257–64. doi:10.1006/jmbi.1998.2406. PMID 9887274.  CS1 maint: Explicit use of et al. (link)
• Wilson J, Putt W, Jimenez C, Edwards YH (1999). "Up71 and up140, two novel transcripts of utrophin that are homologues of short forms of dystrophin". Hum. Mol. Genet. 8 (7): 1271–8. doi:10.1093/hmg/8.7.1271. PMID 10369873. 
• Blake DJ, Hawkes R, Benson MA, Beesley PW (1999). "Different dystrophin-like complexes are expressed in neurons and glia". J. Cell Biol. 147 (3): 645–58. doi:10.1083/jcb.147.3.645. PMC 2151186. PMID 10545507. 
• Keep NH, Winder SJ, Moores CA et al. (2000). "Crystal structure of the actin-binding region of utrophin reveals a head-to-tail dimer". Structure 7 (12): 1539–46. doi:10.1016/S0969-2126(00)88344-6. PMID 10647184.  CS1 maint: Explicit use of et al. (link)

• Tan N, Lansman, JB (2014). "Utrophin regulates modal gating of mechanosensitive ion channels in dystrophic skeletal mus;e.". J. Physiol. 1:592 (15): 3303–23. doi:10.1113/jphysiol.2014.274332. 

See also

• dystrophin

External links

• Utrophin at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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• 1. デュシェンヌ型およびベッカー型筋ジストロフィーの臨床的特徴および診断 clinical features and diagnosis of duchenne and becker muscular dystrophy

English Journal

• Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis.

• Chen HC1, Chin YF1, Lundy DJ1, Liang CT2, Chi YH3, Kuo P4, Hsieh PCH5,6.
• Scientific reports.Sci Rep.2017 Aug 7;7(1):7372. doi: 10.1038/s41598-017-05993-8.
• PMID 28785010

• Skeletal muscle secretome in Duchenne muscular dystrophy: a pivotal anti-inflammatory role of adiponectin.

• Lecompte S1, Abou-Samra M1, Boursereau R1, Noel L1, Brichard SM2.
• Cellular and molecular life sciences : CMLS.Cell Mol Life Sci.2017 Jul;74(13):2487-2501. doi: 10.1007/s00018-017-2465-5. Epub 2017 Feb 10.
• PMID 28188344

• Androgen receptor agonists increase lean mass, improve cardiopulmonary functions and extend survival in preclinical models of Duchenne muscular dystrophy.

• Ponnusamy S1, Sullivan RD2, You D3, Zafar N4, He Yang C4, Thiyagarajan T1, Johnson DL5, Barrett ML1, Koehler NJ1, Star M1, Stephenson EJ3,6, Bridges D3,6, Cormier SA3, Pfeffer LM4, Narayanan R1,7.
• Human molecular genetics.Hum Mol Genet.2017 Jul 1;26(13):2526-2540. doi: 10.1093/hmg/ddx150.
• PMID 28453658

Japanese Journal

• 臨床試験に向けた筋ジストロフィーの評価法の確立と患者登録システムの構築

• 川井 充
• 臨床神経学 49(11), 863-866, 2009-11-01
• 1987年のデュシェンヌ型筋ジストロフィーの原因タンパクの発見から20年あまりがたち，ようやくエクソンスキッピング，ストップコドンの読み飛ばし，ユートロフィンの過剰発現など原因に近いところを標的とする治療法が実現しようとしている．日本でも治療法開発の最終段階として臨床試験がが計画されている．この領域では臨床試験の経験が乏しいため，適切な治療効果測定法が確立していない．筋ジストロフィーでは有効な治療 …
• NAID 10026290994

• Functional role of downstream utrophin enhancer for utrophin expression in the skeletal muscle

• 谷端 淳
• 人間科学研究 21(2), 110-111, 2008-09-25
• NAID 120002909752

• Transduction of full-length dystrophin to multiple skeletal muscles improves motor performance and life span in utrophin/dystrophin double knockout mice

• Kawano Ryoko,Ishizaki Masatoshi,Maeda Yasushi,Uchida Yuji,Kimura En,Uchino Makoto,カワノ リョウコ,イシザキ マサトシ,マエダ ヤスシ,ウチダ ユウジ,キムラ エン,ウチノ マコト,河野 亮子,石崎 雅俊,前田 寧,内田 友二,木村 円,内野 誠
• Molecular Therapy 16(5), 825-831, 2008-05
• … We injected it into multiple proximal muscles of 7-day-old utrophin/dystrophin double knockout mice (dko mice) (which typically show symptoms quite similar to human DMD) because the proximal muscles are affected in DMD patients. …
• NAID 120002468583

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