From Wikipedia, the free encyclopedia
Mammalian protein found in Homo sapiens
Utrophin is a
protein that in humans is encoded by the UTRN
gene .
[5]
[6] The name is a short form for ubiquitous
dystrophin .
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.
[7] 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.
See also
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000152818 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000019820 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^ Nguyen TM, Le TT, Blake DJ, Davies KE, Morris GE (Dec 1992).
"Utrophin, the autosomal homologue of dystrophin, is widely-expressed and membrane-associated in cultured cell lines" . FEBS Lett . 313 (1): 19–22.
doi :
10.1016/0014-5793(92)81174-K .
PMID
1426262 .
S2CID
22121696 .
^
"Entrez Gene: UTRN utrophin" .
^
This article incorporates
text available under the
CC BY 4.0 license. Betts, J Gordon; Desaix, Peter; Johnson, Eddie; Johnson, Jody E; Korol, Oksana; Kruse, Dean; Poe, Brandon; Wise, James; Womble, Mark D; Young, Kelly A (May 14, 2023). Anatomy & Physiology . Houston: OpenStax CNX. 10.3 Muscle Fiber Contraction and Relaxation.
ISBN
978-1-947172-04-3 .
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" (PDF) . Cell. Mol. Life Sci . 63 (14): 1614–31.
doi :
10.1007/s00018-005-5461-0 .
PMID
16710609 .
S2CID
8580596 .
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.
Bibcode :
1992Natur.360..591T .
doi :
10.1038/360591a0 .
PMID
1461283 .
S2CID
4233655 .
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.
Bibcode :
1991PNAS...88.3243L .
doi :
10.1073/pnas.88.8.3243 .
PMC
51422 .
PMID
2014247 .
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 .
S2CID
23466676 .
Love DR, Hill DF, Dickson G, et al. (1989). "An autosomal transcript in skeletal muscle with homology to dystrophin". Nature . 339 (6219): 55–8.
Bibcode :
1989Natur.339...55L .
doi :
10.1038/339055a0 .
PMID
2541343 .
S2CID
4366298 .
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 .
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 .
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 .
S2CID
45699698 .
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 .
S2CID
115277 .
Nawrotzki R, Loh NY, Ruegg MA, et al. (1999).
"Characterisation of alpha-dystrobrevin in muscle" (PDF) . J. Cell Sci . 111 (17): 2595–605.
doi :
10.1242/jcs.111.17.2595 .
PMID
9701558 .
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 .
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 .
External links