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Kellermayer D, Smith JE, Granzier H. Novex-3, the tiny titin of muscle. Biophys Rev. 2017;9(3):201-206doi: 10.1007/s12551-017-0261-y.
Kellermayer, D., Smith, J. E., & Granzier, H. (2017). Novex-3, the tiny titin of muscle. Biophysical reviews, 9(3), 201-206. https://doi.org/10.1007/s12551-017-0261-y
Kellermayer, Dalma, et al. "Novex-3, the tiny titin of muscle." Biophysical reviews vol. 9,3 (2017): 201-206. doi: https://doi.org/10.1007/s12551-017-0261-y
Kellermayer D, Smith JE, Granzier H. Novex-3, the tiny titin of muscle. Biophys Rev. 2017 Jun;9(3):201-206. doi: 10.1007/s12551-017-0261-y. Epub 2017 Apr 07. PMID: 28510117; PMCID: PMC5498326.
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Biophys Rev. 2017 Jun;9(3):201-206. doi: 10.1007/s12551-017-0261-y. Epub 2017 Apr 07.

Novex-3, the tiny titin of muscle.

Biophysical reviews

Dalma Kellermayer, John E Smith, Henk Granzier

Affiliations

  1. Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, 85721, USA.
  2. Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, 85721, USA.
  3. Department of Cellular and Molecular Medicine, University of Arizona, Tucson, AZ, 85721, USA. [email protected].
  4. Sarver Molecular Cardiovascular Research Program, University of Arizona, Tucson, AZ, 85721, USA. [email protected].

PMID: 28510117 PMCID: PMC5498326 DOI: 10.1007/s12551-017-0261-y

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.

Keywords: Novex-3 titin; Obscurin; TTN sequence; Titin

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