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Dystrophin (DMD)

Function: - may play a role in anchoring the cytoskeleton to the plasma membrane - interacts with the syntrophins SNTA1, SNTB1, SNTB2, SNTG1 & SNTG2 - interacts with KRT19 - interacts with SYNM - part of dystrophin associated protein complex (DPC) which includes: - dystroglycan complex: alpha & beta dystroglycans - sarcoglycan complex: alpha, beta, gamma & delta sarcoglycan - sarcospan - syntrophin - alpha-dystrobrevin - nNOS - SAPK3 - SAST (syntrophin associated serine/threonine kinase) - skeletal muscle voltage gated sodium channels - intermediate filament proteins - syncoilin - desmuslin - synemin - aquaporin 4 - dystroglycan ligands include: - laminins - agrin - perlecan - neurexin - nidogen - biglycan - in non-muscle tissue, alpha-neurexin & erbB4 are also associated with components of the DPC Structure: - contains 2 CH (calponin-homology) domains - contains 22 spectrin repeats - contains 1 WW domain - contains 1 ZZ-type Zn+2 finger Compartment: - cell membrane, sarcolemma - peripheral membrane protein; cytoplasmic side - cytoplasm, cytoskeleton Alternative splicing: named isoforms=5; Additional isoforms seem to exist Expression: - expressed in muscle fibers accumulating in the costameres of myoplasm at the sarcolemma - expressed in brain, muscle, kidney, lung & testis - isoform 5 is expressed in heart, brain, liver, testis & hepatoma cells - most tissues contain transcripts of multiple isoforms - only isoform 5 is detected in heart & liver Pathology: - mutations associated with a) Duchenne muscular dystrophy b) Becker muscular dystrophy c) X-linked dilated cardiomyopathy type 3B Note: - the DMD gene is the largest known gene in humans; - it is 2.4 million base-pairs in size - comprises 79 exons - takes > 16 hours to be transcribed & cotranscriptionally spliced

Related

Becker muscular dystrophy Duchenne muscular dystrophy (pseudohypertrophic) dystrophin, DMD or BMD gene

General

contractile protein cytoskeletal protein phosphoprotein zinc finger protein

Properties

SIZE: entity length = 3685 aa MW = 427 kD COMPARTMENT: cytoplasm MOTIF: actin-binding site SITE: 1-240 FOR-BINDING-OF: F-actin MOTIF: calponin homology domain NAME: calponin homology domain SITE: 15-119 calponin homology domain NAME: calponin homology domain SITE: 134-237 spectrin repeat {339-447} spectrin repeat {448-556} spectrin repeat {559-667} spectrin repeat {719-828} spectrin repeat {830-934} spectrin repeat {943-1045} spectrin repeat {1048-1154} spectrin repeat {1157-1263} spectrin repeat {1266-1367} SYNM interaction {1415-1913} MOTIF: spectrin repeat {1468-1568} spectrin repeat {1571-1676} Thr phosphorylation site {T1590} spectrin repeat {1679-1780} spectrin repeat {1877-1979} spectrin repeat {2011-2101} spectrin repeat {2104-2208} spectrin repeat {2211-2318} spectrin repeat {2475-2577} spectrin repeat {2580-2686} spectrin repeat {2689-2802} spectrin repeat {2805-2907} spectrin repeat {2909-2931} spectrin repeat {2934-3040} WW domain (W/rsp5/WWP domain) {3055-3088} SYNM interaction {3058-3408} MOTIF: Zn finger ZZ-type NAME: Zn finger ZZ-type SITE: 3307-3354 EFFECTOR-BOUND: Zn+2 Binds to SNTB1 {3466-3518} MOTIF: Ser phosphorylation site {S3483} Ser phosphorylation site {S3613} Ser phosphorylation site {S3617} Ser phosphorylation site {S3623} Ser phosphorylation site {S3624} Thr phosphorylation site {T3652} Ser phosphorylation site {S3666} MISC-INFO: cysteine-rich region SPECTRIN-LIKE-REPEATS

Database Correlations

OMIM correlations UniProt P11532 Entrez Gene 1756

References

  1. Bar S et al A novel product of the Duchenne muscular dystrophy gene which greatly differs from the known isoforms in its structure and tissue distribution. Biochem J 272:557 1990 PMID: 2176467
  2. Entrez Gene :accession 1756
  3. Blake DJ & Martin-Rendon E Intermediate filaments and the function of the dystrophin-protein complex. Trends Cardiovasc Med 12(5):224-8, 2002 PMID: 12161077
  4. Michele DE & Campbell KP Dystrophin-glycoprotein complex: post-translational processing and dystroglycan function. J Biol Chem 278(18):15457-60, 2003 PMID: 12556455
  5. Tidball J, 9th Annual UCLA Research Conference on Aging, June 17, 2004 (conference speaker)
  6. UniProt :accession P11532
  7. DMD; Note: Dystrophin mutation Database http://www.dmd.nl/database.html
  8. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=DMD
  9. SHMPD; The Singapore human mutation and polymorphism database http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=DMD
  10. Wikipedia; Dystrophin entry http://en.wikipedia.org/wiki/Dystrophin