Utrophin

{{Short description|Mammalian protein found in Homo sapiens}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox gene}}

'''Utrophin''' is a protein that in humans is encoded by the ''UTRN'' gene.<ref name="Nguyen_1992">{{cite journal | vauthors = Nguyen TM, Le TT, Blake DJ, Davies KE, Morris GE | title = Utrophin, the autosomal homologue of dystrophin, is widely-expressed and membrane-associated in cultured cell lines | journal = FEBS Letters | volume = 313 | issue = 1 | pages = 19–22 | date = Dec 1992 | pmid = 1426262 | doi = 10.1016/0014-5793(92)81174-K | bibcode = 1992FEBSL.313...19T | s2cid = 22121696 | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: UTRN utrophin | url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=7402 }}</ref> The name is a short form for ''ubiquitous dystrophin''. The 900 kb gene for utrophin is found on the long arm of human chromosome 6.

== Discovery ==

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 of utrophin to dystrophin 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.

== Tissue distribution ==

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.

== Structure ==

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.

== Function ==

The protein encoded by this gene is a component of the cytoskeleton. Utrophin was found during research into Duchenne's muscular dystrophy, where boosting its production was found to prevent cellular damage from occurring.<ref name="Openstax Anatomy & Physiology attribution">{{CC-notice|cc=by4|url=https://openstax.org/books/anatomy-and-physiology/pages/10-3-muscle-fiber-contraction-and-relaxation}} {{cite book | vauthors = Betts JG, Desaix P, Johnson E, Johnson JE, Korol O, Kruse D, Poe B, Wise J, Womble MD, Young KA | title = Anatomy & Physiology | location = Houston | date = May 14, 2023 | publisher = OpenStax CNX | isbn = 978-1-947172-04-3 | at = 10.3 Muscle Fiber Contraction and Relaxation }}</ref>

== Clinical significance ==

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.

==See also== * dystrophin

==References== {{reflist}}

==Further reading== {{refbegin | 2}} *{{cite journal | vauthors = Haenggi T, Fritschy JM | title = Role of dystrophin and utrophin for assembly and function of the dystrophin glycoprotein complex in non-muscle tissue. | journal = Cellular and Molecular Life Sciences | volume = 63 | issue = 14 | pages = 1614–1631 | date = Jul 2006 | pmid = 16710609 | pmc = 11136313 | doi = 10.1007/s00018-005-5461-0 | s2cid = 8580596 | url = http://doc.rero.ch/record/311337/files/18_2005_Article_5461.pdf }} *{{cite journal | vauthors = Khurana TS, Watkins SC, Kunkel LM | title = The subcellular distribution of chromosome 6-encoded dystrophin-related protein in the brain. | journal = The Journal of Cell Biology | volume = 119 | issue = 2 | pages = 357–366 | date = Oct 1992 | pmid = 1400579 | pmc = 2289652 | doi = 10.1083/jcb.119.2.357 }} *{{cite journal | vauthors = Tinsley JM, Blake DJ, Roche A, Fairbrother U, Riss J, Byth BC, Knight AE, Kendrick-Jones J, Suthers GK, Love DR, et A | title = Primary structure of dystrophin-related protein. | journal = Nature | volume = 360 | issue = 6404 | pages = 591–593 | date = Dec 1992 | pmid = 1461283 | doi = 10.1038/360591a0 | bibcode = 1992Natur.360..591T | s2cid = 4233655 }} *{{cite journal | vauthors = Love DR, Morris GE, Ellis JM, Fairbrother U, Marsden RF, Bloomfield JF, Edwards YH, Slater CP, Parry DJ, Davies KE | title = Tissue distribution of the dystrophin-related gene product and expression in the mdx and dy mouse. | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 8 | pages = 3243–3247 | date = Apr 1991 | pmid = 2014247 | pmc = 51422 | doi = 10.1073/pnas.88.8.3243 | bibcode = 1991PNAS...88.3243L | doi-access = free }} *{{cite journal | vauthors = Buckle VJ, Guenet JL, Simon-Chazottes D, Love DR, Davies KE | title = 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. | journal = Human Genetics | volume = 85 | issue = 3 | pages = 324–326 | date = Aug 1990 | pmid = 2203673 | doi = 10.1007/BF00206755 | s2cid = 23466676 }} *{{cite journal | vauthors = Love DR, Hill DF, Dickson G, Spurr NK, Byth BC, Marsden RF, Walsh FS, Edwards YH, Davies KE | title = An autosomal transcript in skeletal muscle with homology to dystrophin. | journal = Nature | volume = 339 | issue = 6219 | pages = 55–58 | date = May 1989 | pmid = 2541343 | doi = 10.1038/339055a0 | bibcode = 1989Natur.339...55L | s2cid = 4366298 }} *{{cite journal | vauthors = Belkin AM, Burridge K | title = Localization of utrophin and aciculin at sites of cell-matrix and cell-cell adhesion in cultured cells. | journal = Experimental Cell Research | volume = 221 | issue = 1 | pages = 132–140 | date = Nov 1995 | pmid = 7589238 | doi = 10.1006/excr.1995.1360 }} *{{cite journal | vauthors = Ahn AH, Kunkel LM | title = Syntrophin binds to an alternatively spliced exon of dystrophin. | journal = The Journal of Cell Biology | volume = 128 | issue = 3 | pages = 363–371 | date = Feb 1995 | pmid = 7844150 | pmc = 2120343 | doi = 10.1083/jcb.128.3.363 }} *{{cite journal | vauthors = Belkin AM, Burridge K | title = Association of aciculin with dystrophin and utrophin. | journal = Journal of Biological Chemistry | volume = 270 | issue = 11 | pages = 6328–6337 | date = Mar 1995 | pmid = 7890770 | doi = 10.1074/jbc.270.11.6328 | doi-access = free }} *{{cite journal | vauthors = Pearce M, Blake DJ, Tinsley JM, Byth BC, Campbell L, Monaco AP, Davies KE | title = The utrophin and dystrophin genes share similarities in genomic structure. | journal = Human Molecular Genetics | volume = 2 | issue = 11 | pages = 1765–1772 | date = Nov 1993 | pmid = 8281135 | doi = 10.1093/hmg/2.11.1765 }} *{{cite journal | vauthors = Ahn AH, Freener CA, Gussoni E, Yoshida M, Ozawa E, Kunkel LM | title = The three human syntrophin genes are expressed in diverse tissues, have distinct chromosomal locations, and each bind to dystrophin and its relatives. | journal = Journal of Biological Chemistry | volume = 271 | issue = 5 | pages = 2724–2730 | date = Feb 1996 | pmid = 8576247 | doi = 10.1074/jbc.271.5.2724 | doi-access = free }} *{{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery. | journal = Genome Research | volume = 6 | issue = 9 | pages = 791–806 | date = Sep 1996 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 | doi-access = free }} *{{cite journal | vauthors = Guo WX, Nichol M, Merlie JP | title = Cloning and expression of full length mouse utrophin: the differential association of utrophin and dystrophin with AChR clusters. | journal = FEBS Letters | volume = 398 | issue = 2–3 | pages = 259–264 | date = Dec 1996 | pmid = 8977119 | doi = 10.1016/S0014-5793(96)01216-1 | bibcode = 1996FEBSL.398..259A | s2cid = 45699698 | doi-access = free }} *{{cite journal | vauthors = Deconinck AE, Rafael JA, Skinner JA, Brown SC, Potter AC, Metzinger L, Watt DJ, Dickson JG, Tinsley JM, Davies KE | title = Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy | journal = Cell | volume = 90 | issue = 4 | pages = 717–727 | date = Aug 1997 | pmid = 9288751 | doi = 10.1016/S0092-8674(00)80532-2 | s2cid = 115277 | doi-access = free }} *{{cite journal | vauthors = Nawrotzki R, Loh NY, Ruegg MA, Davies KE, Blake DJ | title = Characterisation of alpha-dystrobrevin in muscle | journal = Journal of Cell Science | volume = 111 ( Pt 17) | issue = 17 | pages = 2595–2605 | date = Sep 1998 | pmid = 9701558 | doi = 10.1242/jcs.111.17.2595 | url = http://edoc.unibas.ch/2773/1/2595.full.pdf }} *{{cite journal | vauthors = Keep NH, Norwood FL, Moores CA, Winder SJ, Kendrick-Jones J | title = The 2.0 A structure of the second calponin homology domain from the actin-binding region of the dystrophin homologue utrophin | journal = Journal of Molecular Biology | volume = 285 | issue = 3 | pages = 1257–1264 | date = Jan 1999 | pmid = 9887274 | doi = 10.1006/jmbi.1998.2406 }} *{{cite journal | vauthors = Wilson J, Putt W, Jimenez C, Edwards YH | title = Up71 and up140, two novel transcripts of utrophin that are homologues of short forms of dystrophin | journal = Human Molecular Genetics | volume = 8 | issue = 7 | pages = 1271–1278 | date = Jul 1999 | pmid = 10369873 | doi = 10.1093/hmg/8.7.1271 | doi-access = free }} *{{cite journal | vauthors = Blake DJ, Hawkes R, Benson MA, Beesley PW | title = Different dystrophin-like complexes are expressed in neurons and glia | journal = The Journal of Cell Biology | volume = 147 | issue = 3 | pages = 645–658 | date = Nov 1999 | pmid = 10545507 | pmc = 2151186 | doi = 10.1083/jcb.147.3.645 }} *{{cite journal | vauthors = Keep NH, Winder SJ, Moores CA, Walke S, Norwood FL, Kendrick-Jones J | title = Crystal structure of the actin-binding region of utrophin reveals a head-to-tail dimer | journal = Structure | location = London, England | volume = 7 | issue = 12 | pages = 1539–1546 | date = Dec 1999 | pmid = 10647184 | doi = 10.1016/S0969-2126(00)88344-6 | doi-access = free }} {{refend}} {{PDB Gallery|geneid=7402}} *{{cite journal | vauthors = Tan N, Lansman, JB | title = Utrophin regulates modal gating of mechanosensitive ion channels in dystrophic skeletal mus;e. | journal = The Journal of Physiology | volume = 592 | issue = 15 | pages = 3303–3323 | date = Aug 2014 | pmid = 24879867 | pmc = 4146377 | doi = 10.1113/jphysiol.2014.274332 }}

==External links== * {{MeshName|Utrophin}}

Category:Cytoskeleton Category:Muscular dystrophy Category:Cell adhesion proteins Category:Muscle protectors Category:Muscle stabilizers