Utrophin

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Utrophin
other names

Dystrophin-related protein 1

Existing structural data : 1BHD , 1QAG

Properties of human protein
Mass / length primary structure 395 kDa, 3433 AS
Identifier
Gene names UTRN DMDL, DRP1
External IDs
Orthologue
human House mouse
Entrez 7402 22288
Ensemble ENSG00000152818 ENSMUSG00000019820
UniProt P46939 E9Q6R7
Refseq (mRNA) NM_007124 NM_011682
Refseq (protein) NP_009055 NP_035812
Gene locus Chr 6: 144.29 - 144.85 Mb Chr 10: 12.38 - 12.86 Mb
PubMed search 7402 22288

Utrophin is a protein which inter alia in mice , humans and other primates occurs and in nerve fibers, neuromuscular junctions , the skeletal muscles , the vascular muscles and fetal and regenerating muscles expressed is. It probably plays a role in anchoring the cytoskeleton to the plasma membrane . It is an autosomal homologue to dystrophin . The name is derived from ubiquitous dystrophin (Eng. "Ubiquitous dystrophin").

In humans for utrophin is coding UTRN - gene on chromosome 6 locus q24.2. It is assumed that the UTRN gene and the DMD gene, which codes for dystrophin, arose from a gene duplication in prehistoric times.

structure

Utrophin has a molar mass of 395 kDa and consists of 3433 amino acids . As a homologue to dystrophin, its amino acid sequence is approximately 80% identical to it. In addition, there are other basic similarities between the two proteins. This includes an actin- binding N -terminus , a coiled-coil wound three times , and a C -terminus , which consists of protein-protein interaction domains that can interact with dystroglycan regions.

Clinical reference

There is a certain clinical relationship between utrophin and Duchenne muscular dystrophy : in mdx mice, which show muscle wasting and therefore serve as an animal model for Duchenne muscular dystrophy, the expression of utrophin is upregulated. Such an overexpression of utrophin improves the muscle function of mdx mice, it serves as a kind of substitute for the dystrophin, which is only inadequate in Duchenne muscular dystrophy. This would also explain why Duchenne muscular dystrophy breaks out at the earliest when the high perinatal expression of utrophin in the adult muscles drops to lower values. Such an upregulation of utrophin could also try to treat the Duchenne muscular dystrophy and the Becker muscular dystrophy , so that here too utrophin serves as a substitute for the missing dystrophin. Summit Therapeutics already offers such a therapy, which attempts to increase the expression of utrophin by taking oral medication.

Conversely, however, no disease is known that is caused by a genetic malfunction of utrophin. Mice with a UTRN - gene knockout show only weak neuromuscular defects, so it is believed that other molecules are much more important for the differentiation of the postsynaptic membrane.

There is also evidence that UTRN acts as a tumor suppressor gene .

Individual evidence

  1. ↑ a b T. M. Nguyen, TT Le u. a .: Utrophin, the autosomal homologue of dystrophin, is widely-expressed and membrane-associated in cultured cell lines. In: FEBS letters. Volume 313, Number 1, November 1992, pp. 19-22, PMID 1426262 .
  2. ↑ UniProt P46939
  3. ↑ a b Utrophin . In: Lexikon der Naturwissenschaft , Spektrum Akademischer Verlag, Heidelberg 2000.
  4. ^ DR Love, DF Hill et al. a .: An autosomal transcript in skeletal muscle with homology to dystrophin. In: Nature. Volume 339, Number 6219, May 1989, pp. 55-58, doi : 10.1038 / 339055a0 , PMID 2541343 .
  5. ↑ a b c d e Utrophin.  In: Online Mendelian Inheritance in Man . (English)
  6. ↑ M. Pearce, DJ Blake et al. a .: The utrophin and dystrophin genes share similarities in genomic structure. In: Human Molecular Genetics . Volume 2, Number 11, November 1993, pp. 1765-1772, PMID 8281135 .
  7. ↑ JM Tinsley, DJ Blake et al. a .: Primary structure of dystrophin-related protein. In: Nature. Volume 360, Number 6404, December 1992, pp. 591-593, doi : 10.1038 / 360591a0 , PMID 1461283 .
  8. ↑ [1]
  9. ↑ D. Baban, KE Davies: Microarray analysis of mdx mice expressing high levels of utrophin: therapeutic implications for dystrophin deficiency. In: Neuromuscular disorders. Volume 18, number 3, March 2008, pp. 239-247, doi : 10.1016 / j.nmd.2007.11.011 , PMID 18343112 .
  10. ↑ M. Kramer: Determination of the protein expression of MMP-1, MMP-2, TIMP-1 and TIMP-2 by means of immunohistochemistry and Western blot in Duchenne muscular dystrophy. Dissertation, Medical Faculty Charité, 2012, p. 18.
  11. ↑ RC Hirst, KJ McCullagh and KE Davies: Utrophin upregulation in Duchenne muscular dystrophy . In: Acta Myologica . 24, No. 3, December 2005, pp. 209-216. PMID 16629055 .
  12. ↑ Duchenne Muscular Dystroophy . Summit Therapeutics , 2014, accessed August 21, 2015.
  13. ^ D. Hilton-Jones, MV Squier: Dystrophin-associated protein complex: clinical implications. In: The Lancet. Volume 341, Number 8844, February 1993, pp. 528-529, PMID 8094778 .
  14. ↑ Y. Li, J. Huang et al. a .: UTRN on chromosome 6q24 is mutated in multiple tumors. In: Oncogene. Volume 26, Number 42, September 2007, pp. 6220-6228, doi : 10.1038 / sj.onc.1210432 , PMID 17384672 .