Functions of myosin light chain-2 (MYL2) in cardiac muscle and disease

Gene. 2015 Sep 10;569(1):14-20. doi: 10.1016/j.gene.2015.06.027. Epub 2015 Jun 12.


Myosin light chain-2 (MYL2, also called MLC-2) is an ~19kDa sarcomeric protein that belongs to the EF-hand calcium binding protein superfamily and exists as three major isoforms encoded by three distinct genes in mammalian striated muscle. Each of the three different MLC-2 genes (MLC-2f; fast twitch skeletal isoform, MLC-2v; cardiac ventricular and slow twitch skeletal isoform, MLC-2a; cardiac atrial isoform) has a distinct developmental expression pattern in mammals. Genetic loss-of-function studies in mice demonstrated an essential role for cardiac isoforms of MLC-2, MLC-2v and MLC-2a, in cardiac contractile function during early embryogenesis. In the adult heart, MLC-2v function is regulated by phosphorylation, which displays a specific 1`expression pattern (high in epicardium and low in endocardium) across the heart. These data along with new data from computational models, genetic mouse models, and human studies have revealed a direct role for MLC-2v phosphorylation in cross-bridge cycling kinetics, calcium-dependent cardiac muscle contraction, cardiac torsion, cardiac function and various cardiac diseases. This review focuses on the regulatory functions of MLC-2 in the embryonic and adult heart, with an emphasis on phosphorylation-driven actions of MLC-2v in adult cardiac muscle, which provide new insights into mechanisms regulating myosin cycling kinetics and human cardiac diseases.

Keywords: Cardiac disease; Cardiac function; Cardiac muscle; Cardiac torsion; Contraction; Heart; Myosin light chain kinase; Myosin light chain-2 (MYL2/MLC-2); Phosphorylation; Sarcomere; Ventricular myosin light chain-2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cardiac Myosins / genetics*
  • Cardiac Myosins / metabolism
  • Heart / physiopathology*
  • Heart Ventricles / metabolism
  • Heart Ventricles / physiopathology*
  • Humans
  • Mice
  • Muscular Diseases / genetics*
  • Muscular Diseases / physiopathology
  • Myocardium / pathology
  • Myosin Light Chains / genetics*
  • Myosin Light Chains / metabolism
  • Protein Isoforms


  • Myosin Light Chains
  • Protein Isoforms
  • myosin light chain 2
  • Cardiac Myosins