Abstract
Titin is an extremely large protein found in highest concentrations in heart and skeletal muscle. The single mammalian gene is expressed in multiple isoforms as a result of alternative splicing. Although titin isoform expression is controlled developmentally and in a tissue specific manner, the vast number of potential splicing pathways far exceeds those described in any other alternatively spliced gene. Over 1 million human splice pathways for a single individual can be potentially derived from the PEVK region alone. A new splicing pattern for the human cardiac N2BA isoform type has been found in which the PEVK region includes only the N2B type exons. The alterations in splicing and titin isoform expression in human heart disease provide impetus for future detailed study of the splicing mechanisms for this giant protein.
Highlights
Titin is the third most abundant protein in vertebrate striated muscle, with an average adult human containing ∼ 0.5 kg [1]
The C-terminal A-band segment of titin is attached to the thick filament via multiple binding sites for myosin and C-protein [6] and two Cterminal titin regions from adjacent half-sarcomeres overlap in the M-line region of the sarcomere [7]
The collapsed tandem Ig segments are straightened while their individual Ig domains remained folded
Summary
Titin is the third most abundant protein (after myosin and actin) in vertebrate striated muscle, with an average adult human containing ∼ 0.5 kg [1]. Titin’s several extensible elements establish titin as a critical, multifunctional sarcomeric component These extensible elements are composed of (1) Tandem Ig segments (consisting of serially linked immunoglobulin-like domains), (2) the PEVK region (so called for its high content of proline (P), glutamate (E), valine (V), and lysine (K) residues), and (3) the cardiacspecific N2B unique sequence (N2B-Us) (Figure 1). It was later found that the myocardium expresses two major classes of titin isoforms: a smaller N2B and a larger N2BA that contained both the N2B and N2A unique sequences [24, 25] (Figure 2). All these known titin isoforms contain PEVK and tandem Ig segments. A number of excellent reviews should be consulted for further details on the structure and function of titin [6, 19, 28,29,30,31,32,33]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
