Novex-3, the tiny titin of muscle

Dalma Kellermayer, John E. Smith, Henk Granzier

Research output: Research - peer-reviewReview article

Abstract

The giant multi-functional striated muscle protein titin is the third most abundant muscle protein after myosin and actin. Titin plays a pivotal role in myocardial passive stiffness, structural integrity and stress-initiated signaling pathways. The complete sequence of the human titin gene contains three isoform-specific mutually exclusive exons [termed novel exons (novex)] coding for the I-band sequence, named novex-1 (exon 45), novex-2 (exon 46) and novex-3 (exon 48). Transcripts containing either the novex-1 or novex-2 exons code for the novex-1 and novex-2 titin isoforms. The novex-3 transcript contains a stop codon and polyA tail signal, resulting in an unusually small (∼700 kDa) isoform, referred to as novex-3 titin. This ‘tiny titin’ isoform extends from the Z-disc (N-terminus) to novex-3 (C-terminus) and is expressed in all striated muscles. Biochemical analysis of novex-3 titin in cardiomyocytes shows that obscurin, a vertebrate muscle protein, binds to novex-3 titin. The novex-3/obscurin complex localizes to the Z-disc region and may regulate calcium, and SH3- and GTPase-associated myofibrillar signaling pathways. Therefore, novex-3 titin could be involved in stress-initiated sarcomeric restructuring.

LanguageEnglish (US)
Pages201-206
Number of pages6
JournalBiophysical Reviews
Volume9
Issue number3
DOIs
StatePublished - Jun 1 2017

Fingerprint

Connectin
Exons
Muscles
Protein Isoforms
Muscle Proteins
Striated Muscle
Terminator Codon
GTP Phosphohydrolases
Myosins
Cardiac Myocytes
Vertebrates
Tail
Actins
Calcium
Genes

Keywords

  • Novex-3 titin
  • Obscurin
  • Titin
  • TTN sequence

ASJC Scopus subject areas

  • Structural Biology
  • Biophysics
  • Molecular Biology

Cite this

Kellermayer, D., Smith, J. E., & Granzier, H. (2017). Novex-3, the tiny titin of muscle. Biophysical Reviews, 9(3), 201-206. DOI: 10.1007/s12551-017-0261-y

Novex-3, the tiny titin of muscle. / Kellermayer, Dalma; Smith, John E.; Granzier, Henk.

In: Biophysical Reviews, Vol. 9, No. 3, 01.06.2017, p. 201-206.

Research output: Research - peer-reviewReview article

Kellermayer, D, Smith, JE & Granzier, H 2017, 'Novex-3, the tiny titin of muscle' Biophysical Reviews, vol 9, no. 3, pp. 201-206. DOI: 10.1007/s12551-017-0261-y
Kellermayer D, Smith JE, Granzier H. Novex-3, the tiny titin of muscle. Biophysical Reviews. 2017 Jun 1;9(3):201-206. Available from, DOI: 10.1007/s12551-017-0261-y
Kellermayer, Dalma ; Smith, John E. ; Granzier, Henk. / Novex-3, the tiny titin of muscle. In: Biophysical Reviews. 2017 ; Vol. 9, No. 3. pp. 201-206
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