Identification of muscle specific ring finger proteins as potential regulators of the titin kinase domain

Thomas Centner, Junko Yano, Eiichi Kimura, Abigail S. McElhinny, Katarina Pelin, Christian C. Witt, Marie Louise Bang, Karoly Trombitas, Henk Granzier, Carol C. Gregorio, Hiroyuki Sorimachi, Siegfried Labeit

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335 Scopus citations


The giant myofibrillar protein titin contains within its C-terminal region a serine-threonine kinase of unknown function. We have identified a novel muscle specific RING finger protein, referred to as MURF-1, that binds in vitro to the titin repeats A168/A169 adjacent to the titin kinase domain. In myofibrils, MURF-1 is present within the periphery of the M-line lattice in close proximity to titin's catalytic kinase domain, within the Z-line lattice, and also in soluble form within the cytoplasm. Yeast two-hybrid screens with MURF-1 as a bait identified two other highly homologous MURF proteins, MURF-2 and MURF-3. MURF-1,2,3 proteins are encoded by distinct genes, share highly conserved N-terminal RING domains and in vitro form dimers/heterodimers by shared coiled-coil motifs. Of the MURF family, only MURF-1 interacts with titin repeats A168/A169, whereas MURF-3 has been reported to affect microtubule stability. Association of MURF-1 with M-line titin may potentially modulate titin's kinase activity similar to other known kinase-associated proteins, whereas differential expression and heterodimerization of MURF1, 2 and 3 may link together titin kinase and microtubule-dependent signal pathways in striated muscles.

Original languageEnglish
Pages (from-to)717-726
Number of pages10
JournalJournal of Molecular Biology
Issue number4
StatePublished - 2 Mar 2001
Externally publishedYes


  • M and Z-lines
  • Ring finger proteins
  • Striated muscle
  • Titin kinase domain


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