CorpusHuman Anatomy
MuscularMolecule

Titin

Titinum

Also known as: connectin

The largest known protein (≈3–4 MDa). Each molecule spans half a sarcomere from the Z disc to the M line, acting as a molecular spring and a template for the thick filament.

Sarcomere & Sliding Filaments

Overview

Mass≈3–4 MDa (≈27,000–35,000 amino acids)
SpanZ disc → M line (>1 µm)

Each titin molecule runs more than 1 µm, from the Z disc (N-terminus) to the M line (C-terminus). In the I band, its extensible segments (tandem immunoglobulin domains, the PEVK region and, in the heart, the N2B segment) act as a molecular spring. They create the passive tension of stretched muscle and help return the sarcomere to resting length after contraction. In the A band, titin binds tightly to the thick filament and serves as a ruler that keeps myosin centred and of the correct length. The M-line end of titin has a kinase domain that senses mechanical load and signals trophic pathways.

Different titin isoforms, produced by alternative splicing, change how stiff the muscle is. Cardiac N2B titin is stiffer than the longer N2BA isoform, which influences diastolic filling.

Parts & subdivisions

  1. Z-disc region
    Binds α-actinin and telethonin and anchors titin.
  2. I-band spring
    Ig domains + PEVK segment. It extends when the muscle is stretched and generates passive force.
  3. A-band region
    Bound to the thick filament, acting as a length template.
  4. M-line region
    Overlaps with titin from the opposite half-sarcomere and contains the titin kinase.

Function

  • Generates passive elastic tension and restores resting length
  • Centres the thick filament in the sarcomere
  • Acts as a template for sarcomere assembly and a mechanosensor

Clinical significance

Titin-related disease

Truncating TTN variants are the commonest genetic cause of dilated cardiomyopathy (≈20–25% of familial cases). TTN mutations also cause tibial muscular dystrophy and some congenital myopathies.

Compiled from standard anatomy and physiology references — see the Muscular System sources. For education only; not medical advice.