Dystrophin

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Dystrophin

PDB rendering based on 1dxx.
Identifiers
Symbols DMD; BMD; CMD3B; DXS142; DXS164; DXS206; DXS230; DXS239; DXS268; DXS269; DXS270; DXS272
External IDs OMIM300377 MGI94909 HomoloGene20856 GeneCards: DMD Gene
RNA expression pattern
PBB GE DMD 203881 s at tn.png
PBB GE DMD 208086 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1756 13405
Ensembl ENSG00000198947 ENSMUSG00000045103
UniProt P11532 Q3TWL4
RefSeq (mRNA) NM_000109.3 NM_007868.5
RefSeq (protein) NP_000100.2 NP_031894.1
Location (UCSC) Chr X:
31.13 – 33.36 Mb
Chr X:
80.19 – 82.45 Mb
PubMed search [1] [2]

Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the costamere or the dystrophin-associated protein complex. Many muscle proteins, such as α-dystrobrevin, syncoilin, synemin, sarcoglycan, dystroglycan, and sarcospan, colocalize with dystrophin at the costamere.

The Dystrophin gene is the longest human gene known on DNA level, covering 2.4 megabases (0.08% of the human genome) at locus Xp21. However, it does not encode the longest protein known in humans, which is titin. The primary transcript measures about 2,400 kilobases and takes 16 hours to transcribe [citation needed - this number is not consistent with RNA Pol II transcription speed given in paper ""In vivo dynamics of RNA polymerase II transcription""]; the mature mRNA measures 14.0 kilobases.[1] The 79 exons[2] code for a protein of over 3500 amino acid residues.[3]

Contents

[edit] Pathology

Dystrophin deficiency has been definitively established as one of the root causes of the general class of myopathies collectively referred to as muscular dystrophy. The large cytosolic protein was first identified in 1987 by Louis M. Kunkel,[4] after the 1986 discovery of the mutated gene that causes Duchenne muscular dystrophy (DMD) .[5]

Normal skeletal muscle tissue contains only small amounts of dystrophin (about 0.002% of total muscle protein), but its absence (or abnormal expression) leads to the development of a severe and currently incurable constellation of symptoms most readily characterized by several aberrant intracellular signaling pathways that ultimately yield pronounced myofiber necrosis as well as progressive muscle weakness and fatigability. Most DMD patients become wheelchair-dependent early in life, and the gradual development of cardiac hypertrophy—a result of severe myocardial fibrosis—typically results in premature death in the first two or three decades of life. Mutations in the dystrophin gene that lead to the production of less defective, but still only partially functional dystrophin protein, result in a display of a much milder dystrophic phenotype in affected patients, resulting in the disease known as Becker's muscular dystrophy (BMD). In some cases the patient's phenotype is such that experts may decide differently on whether a patient should be diagnosed with DMD or BMD. The theory currently most commonly used to predict whether a mutation will result in a DMD or BMD phenotype, is the reading frame rule.[6]

Though its role in airway smooth muscle is not well established, recent research indicates that dystrophin along with other subunits of dystrophin glycoprotein complex is associated with phenotype maturation.[7]

[edit] Interactions

Dystrophin has been shown to interact with SNTB1,[8] Syntrophin, alpha 1[9][10][11] and DTNA.[12]

[edit] References

  1. ^ NCBI Sequence Viewer v2.0
  2. ^ Strachan T and Read AP, 1999. Human molecular genetics, BIOS Scientific, New York, USA
  3. ^ NCBI Sequence Viewer v2.0
  4. ^ Hoffman E, Brown R, Kunkel L (1987). "Dystrophin: the protein product of the Duchenne muscular dystrophy locus". Cell 51 (6): 919–28. doi:10.1016/0092-8674(87)90579-4. PMID 3319190. 
  5. ^ Monaco A, Neve R, Colletti-Feener C et al. (1986). "Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene". Nature 323 (6089): 646–50. doi:10.1038/323646a0. PMID 3773991. 
  6. ^ Aartsma-Rus A, et al. (2006). "Entries in the Leiden Duchenne muscular dystrophy mutation database: an overview of mutation types and paradoxical cases that confirm the reading-frame rule". Muscle Nerve 34 (2): 135–44. doi:10.1002/mus.20586. PMID 16770791. 
  7. ^ Sharma P, Tran T, Stelmack GL, et al. (2008). "Expression of the dystrophin-glycoprotein complex is a marker for human airway smooth muscle phenotype maturation". Am. J. Physiol. Lung Cell Mol. Physiol. 294 (1): L57–68. doi:10.1152/ajplung.00378.2007. PMID 17993586. 
  8. ^ Ahn, A H; Kunkel L M (Feb. 1995). "Syntrophin binds to an alternatively spliced exon of dystrophin". J. Cell Biol. (UNITED STATES) 128 (3): 363–71. doi:10.1083/jcb.128.3.363. ISSN 0021-9525. PMC 2120343. PMID 7844150. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2120343. 
  9. ^ Ahn, A H; Freener C A, Gussoni E, Yoshida M, Ozawa E, Kunkel L M (Feb. 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. (UNITED STATES) 271 (5): 2724–30. doi:10.1074/jbc.271.5.2724. ISSN 0021-9258. PMID 8576247. 
  10. ^ Yang, B; Jung D, Rafael J A, Chamberlain J S, Campbell K P (Mar. 1995). "Identification of alpha-syntrophin binding to syntrophin triplet, dystrophin, nNOS NOS1 ,and utrophin". J. Biol. Chem. (UNITED STATES) 270 (10): 4975–8. doi:10.1074/jbc.270.10.4975. ISSN 0021-9258. PMID 7890602. 
  11. ^ Gee, S H; Madhavan R, Levinson S R, Caldwell J H, Sealock R, Froehner S C (Jan. 1998). "Interaction of muscle and brain sodium channels with multiple members of the syntrophin family of dystrophin-associated proteins". J. Neurosci. (UNITED STATES) 18 (1): 128–37. ISSN 0270-6474. PMID 9412493. 
  12. ^ Sadoulet-Puccio, H M; Rajala M, Kunkel L M (Nov. 1997). "Dystrobrevin and dystrophin: an interaction through coiled-coil motifs". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 94 (23): 12413–8. doi:10.1073/pnas.94.23.12413. ISSN 0027-8424. PMC 24974. PMID 9356463. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=24974. 

[edit] Further reading

[edit] External links

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