Utrophin

UTRN
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 1BHD, 1QAG,%%s1BHD, 1QAG
Identifiers
Aliases	UTRN , DMDL, DRP, DRP1, utrophin
External IDs	OMIM: 128240; MGI: 104631; HomoloGene: 21398; GeneCards: UTRN; OMA:UTRN - orthologs
Gene location (Human) Chr. Chromosome 6 (human) [1] Band 6q24.2 Start 144,285,335 bp [1] End 144,853,034 bp [1]
Gene location (Mouse) Chr. Chromosome 10 (mouse) [2] Band 10 A1|10 3.77 cM Start 12,257,932 bp [2] End 12,745,109 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon sural nerve tendon of biceps brachii trigeminal ganglion epithelium of colon monocyte visceral pleura pericardium parietal pleura epithelium of nasopharynx Top expressed in iris ciliary body Paneth cell ascending aorta aortic valve vestibular membrane of cochlear duct retinal pigment epithelium fossa right lung right lung lobe More reference expression data BioGPS More reference expression data
Gene ontology Molecular function vinculin binding zinc ion binding metal ion binding integrin binding actin filament binding protein binding actin binding protein kinase binding Cellular component cytoplasm postsynaptic membrane contractile ring membrane filopodium growth cone neuromuscular junction plasma membrane synapse dystrophin-associated glycoprotein complex nucleoplasm cell junction cortical actin cytoskeleton sarcolemma extracellular exosome cytoskeleton filopodium membrane protein-containing complex Biological process muscle contraction positive regulation of cell-matrix adhesion muscle organ development neuromuscular junction development regulation of sodium ion transmembrane transporter activity response to denervation involved in regulation of muscle adaptation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7402 22288 Ensembl ENSG00000152818 ENSMUSG00000019820 UniProt P46939 Q5T097 n/a RefSeq (mRNA) NM_007124 NM_001375323 NM_011682 RefSeq (protein) NP_009055 NP_001362252 n/a Location (UCSC) Chr 6: 144.29 – 144.85 Mb Chr 10: 12.26 – 12.75 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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 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. ^[7]

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

1. GRCh38: Ensembl release 89: ENSG00000152818 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000019820 – Ensembl, May 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. 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 Letters. 313 (1): 19–22. doi: 10.1016/0014-5793(92)81174-K . PMID   1426262. S2CID   22121696.
6. "Entrez Gene: UTRN utrophin".
7.  This article incorporates text available under the CC BY 4.0 license.Betts JG, Desaix P, Johnson E, Johnson JE, Korol O, Kruse D, et al. (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 (Jul 2006). "Role of dystrophin and utrophin for assembly and function of the dystrophin glycoprotein complex in non-muscle tissue" (PDF). Cellular and Molecular Life Sciences. 63 (14): 1614–1631. doi:10.1007/s00018-005-5461-0. PMC   11136313 . PMID   16710609. S2CID   8580596.
• Khurana TS, Watkins SC, Kunkel LM (Oct 1992). "The subcellular distribution of chromosome 6-encoded dystrophin-related protein in the brain". The Journal of Cell Biology. 119 (2): 357–366. doi:10.1083/jcb.119.2.357. PMC   2289652 . PMID   1400579.
• Tinsley JM, Blake DJ, Roche A, Fairbrother U, Riss J, Byth BC, et al. (Dec 1992). "Primary structure of dystrophin-related protein". Nature. 360 (6404): 591–593. Bibcode:1992Natur.360..591T. doi:10.1038/360591a0. PMID   1461283. S2CID   4233655.
• Love DR, Morris GE, Ellis JM, Fairbrother U, Marsden RF, Bloomfield JF, et al. (Apr 1991). "Tissue distribution of the dystrophin-related gene product and expression in the mdx and dy mouse". Proceedings of the National Academy of Sciences of the United States of America. 88 (8): 3243–3247. Bibcode:1991PNAS...88.3243L. doi: 10.1073/pnas.88.8.3243 . PMC   51422 . PMID   2014247.
• Buckle VJ, Guenet JL, Simon-Chazottes D, Love DR, Davies KE (Aug 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". Human Genetics. 85 (3): 324–326. doi:10.1007/BF00206755. PMID   2203673. S2CID   23466676.
• Love DR, Hill DF, Dickson G, Spurr NK, Byth BC, Marsden RF, et al. (May 1989). "An autosomal transcript in skeletal muscle with homology to dystrophin". Nature. 339 (6219): 55–58. Bibcode:1989Natur.339...55L. doi:10.1038/339055a0. PMID   2541343. S2CID   4366298.
• Belkin AM, Burridge K (Nov 1995). "Localization of utrophin and aciculin at sites of cell-matrix and cell-cell adhesion in cultured cells". Experimental Cell Research. 221 (1): 132–140. doi:10.1006/excr.1995.1360. PMID   7589238.
• Ahn AH, Kunkel LM (Feb 1995). "Syntrophin binds to an alternatively spliced exon of dystrophin". The Journal of Cell Biology. 128 (3): 363–371. doi:10.1083/jcb.128.3.363. PMC   2120343 . PMID   7844150.
• Belkin AM, Burridge K (Mar 1995). "Association of aciculin with dystrophin and utrophin". Journal of Biological Chemistry. 270 (11): 6328–6337. doi: 10.1074/jbc.270.11.6328 . PMID   7890770.
• Pearce M, Blake DJ, Tinsley JM, Byth BC, Campbell L, Monaco AP, et al. (Nov 1993). "The utrophin and dystrophin genes share similarities in genomic structure". Human Molecular Genetics. 2 (11): 1765–1772. doi:10.1093/hmg/2.11.1765. PMID   8281135.
• Ahn AH, Freener CA, Gussoni E, Yoshida M, Ozawa E, Kunkel LM (Feb 1996). "The three human syntrophin genes are expressed in diverse tissues, have distinct chromosomal locations, and each bind to dystrophin and its relatives". Journal of Biological Chemistry. 271 (5): 2724–2730. doi: 10.1074/jbc.271.5.2724 . PMID   8576247.
• Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi: 10.1101/gr.6.9.791 . PMID   8889548.
• Guo WX, Nichol M, Merlie JP (Dec 1996). "Cloning and expression of full length mouse utrophin: the differential association of utrophin and dystrophin with AChR clusters". FEBS Letters. 398 (2–3): 259–264. doi: 10.1016/S0014-5793(96)01216-1 . PMID   8977119. S2CID   45699698.
• Deconinck AE, Rafael JA, Skinner JA, Brown SC, Potter AC, Metzinger L, et al. (Aug 1997). "Utrophin-dystrophin-deficient mice as a model for Duchenne muscular dystrophy". Cell. 90 (4): 717–727. doi: 10.1016/S0092-8674(00)80532-2 . PMID   9288751. S2CID   115277.
• Nawrotzki R, Loh NY, Ruegg MA, Davies KE, Blake DJ (Sep 1998). "Characterisation of alpha-dystrobrevin in muscle" (PDF). Journal of Cell Science. 111 ( Pt 17) (17): 2595–2605. doi:10.1242/jcs.111.17.2595. PMID   9701558.
• Keep NH, Norwood FL, Moores CA, Winder SJ, Kendrick-Jones J (Jan 1999). "The 2.0 A structure of the second calponin homology domain from the actin-binding region of the dystrophin homologue utrophin". Journal of Molecular Biology. 285 (3): 1257–1264. doi:10.1006/jmbi.1998.2406. PMID   9887274.
• Wilson J, Putt W, Jimenez C, Edwards YH (Jul 1999). "Up71 and up140, two novel transcripts of utrophin that are homologues of short forms of dystrophin". Human Molecular Genetics. 8 (7): 1271–1278. doi: 10.1093/hmg/8.7.1271 . PMID   10369873.
• Blake DJ, Hawkes R, Benson MA, Beesley PW (Nov 1999). "Different dystrophin-like complexes are expressed in neurons and glia". The Journal of Cell Biology. 147 (3): 645–658. doi:10.1083/jcb.147.3.645. PMC   2151186 . PMID   10545507.
• Keep NH, Winder SJ, Moores CA, Walke S, Norwood FL, Kendrick-Jones J (Dec 1999). "Crystal structure of the actin-binding region of utrophin reveals a head-to-tail dimer". Structure. 7 (12). London, England: 1539–1546. doi: 10.1016/S0969-2126(00)88344-6 . PMID   10647184.

• Tan N, Lansman, JB (Aug 2014). "Utrophin regulates modal gating of mechanosensitive ion channels in dystrophic skeletal mus;e". The Journal of Physiology. 592 (15): 3303–3323. doi:10.1113/jphysiol.2014.274332. PMC   4146377 . PMID   24879867.

External links

• Utrophin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)