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Protein MYOT PDB 2KDG.png
Rendering based on PDB 2KDG.
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM604103 MGI1889800 HomoloGene4942 GeneCards: MYOT Gene
RNA expression pattern
PBB GE MYOT 219728 at tn.png
More reference expression data
Species Human Mouse
Entrez 9499 58916
Ensembl ENSG00000120729 ENSMUSG00000024471
UniProt Q9UBF9 Q9JIF9
RefSeq (mRNA) NM_001135940 NM_001033621
RefSeq (protein) NP_001129412 NP_001028793
Location (UCSC) Chr 5:
137.2 – 137.22 Mb
Chr 18:
44.33 – 44.36 Mb
PubMed search [1] [2]

Myotilin is a protein that in humans is encoded by the MYOT gene.[1][2][3]

Striated muscle sarcomeres are highly organized structures composed of actin (thin) and myosin (thick) filaments that slide past each other during contraction. The integrity of sarcomeres is controlled by a set of structural proteins, among which are titin (TTN; MIM 188840), a giant molecule that contains several immunoglobulin (Ig)-like domains and associates with thin and thick filaments, and alpha-actinin (ACTN1; MIM 102575), an actin cross-linking protein. Mutations in several sarcomeric and sarcolemmal proteins have been shown to result in muscular dystrophy and cardiomyopathy.[supplied by OMIM][3]
Myotilin (myofibrillar titin-like protein) also known as TTID (TiTin Immunoglobulin Domain) is a skeletal muscle protein that is found within the Z-disc of sarcomeres. It is mutated in various forms of muscular dystrophy:

- Limb-Girdle Muscular Dystrophy type 1A (LGMD1A)
- Myofibrillar Myopathy (MFM)
- Spheroid Body Myopathy
- Distal Myopathy

Myotilin was originally identified as a novel alpha-actinin binding partner with two Ig-like domains, that localised to the Z-disc.[4] The C2-type Ig-like domains reside at the C-terminal half, and are most homologous to Ig domains 2-3 of palladin and Ig domains 4-5 of myopalladin and more distantly related to Z-disc Ig domains 7 and 8 of titin. By contrast, the N-terminal part of myotilin is unique, consisting of a serine-rich region with no homology to known proteins. Several disease-associated mutations involve serine residues within the serine-rich domain. Myotilin expression in human tissues is mainly restricted to striated muscles and nerves. In muscles, myotilin is predominantly found within the Z-discs. Myotilin forms homodimers and binds alpha-actinin, actin,[5] Filamin C,[6] FATZ-1[7] and ZASP.[8] Myotilin induces the formation of actin bundles in vitro and in non-muscle cells. A ternary complex myotilin/actin/alpha-actinin can be observed in vitro and actin bundles formed in this conditions appear more tightly packed than those induced by alpha-actinin alone. It was demonstrated that myotilin stabilises F-actin by slowing down the disassembly rate. Ectopic overexpression of truncated myotilin causes the disruption of nascent myofibrils and the co-accumulation of myotilin and titin in amorphous cytoplasmic precipitates. In mature sarcomeres, wild-type myotilin co-localises with alpha-actinin and Z-disc titin, showing the striated pattern typical of sarcomeric proteins. Targeted disruption of myotilin gene in mice does not cause significant alteration in muscle function.[9] On the other hand, transgenic mice with mutated myotilin develop muscle dystrophy.[10]


  1. ^ Godley LA, Lai F, Liu J, Zhao N, Le Beau MM (Nov 1999). "TTID: A novel gene at 5q31 encoding a protein with titin-like features". Genomics 60 (2): 226–33. doi:10.1006/geno.1999.5912. PMID 10486214. 
  2. ^ Salmikangas P, Mykkanen OM, Gronholm M, Heiska L, Kere J, Carpen O (Aug 1999). "Myotilin, a novel sarcomeric protein with two Ig-like domains, is encoded by a candidate gene for limb-girdle muscular dystrophy". Hum Mol Genet 8 (7): 1329–36. doi:10.1093/hmg/8.7.1329. PMID 10369880. 
  3. ^ a b "Entrez Gene: MYOT myotilin". 
  4. ^ Salmikangas, P., et al., Myotilin, a novel sarcomeric protein with two Ig-like domains, is encoded by a candidate gene for limb-girdle muscular dystrophy. Hum Mol Genet, 1999. 8(7): p. 1329-36
  5. ^ Salmikangas, P., et al., Myotilin, the limb-girdle muscular dystrophy 1A (LGMD1A) protein, cross-links actin filaments and controls sarcomere assembly. Hum Mol Genet, 2003. 12(2): p. 189-203
  6. ^ van der Ven, P.F., et al., Indications for a novel muscular dystrophy pathway. gamma-filamin, the muscle-specific filamin isoform, interacts with myotilin. J Cell Biol, 2000. 151(2): p. 235-48
  7. ^ Gontier, Y., et al., The Z-disc proteins myotilin and FATZ-1 interact with each other and are connected to the sarcolemma via muscle-specific filamins. J Cell Sci, 2005. 118(Pt 16): p. 3739-49.
  8. ^ von Nandelstadh, P., et al., A class III PDZ binding motif in myotilin and FATZ families binds Enigma family proteins – a common link for Zdisc myopathies. Mol Cell Biol, 2009.
  9. ^ Moza M, et al. Targeted deletion of the muscular dystrophy gene myotilin does not perturb muscle structure or function in mice. Mol Cell Biol. 2007, 27(1):244-252
  10. ^ Garvey, S.M., et al., Transgenic mice expressing the myotilin T57I mutation unite the pathology associated with LGMD1A and MFM. Hum Mol Genet, 2006. 15(15): p. 2348-62

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