myosin heavy chains
Myosin heavy chains (MYHs) are ubiquitous actin-based motor proteins that convert the chemical energy derived from hydrolysis of ATP into mechanical force that drives diverse motile processes, including cytokinesis, vesicular transport, and cellular locomotion, in eukaryotic cells.
In mammals at least 10 different myosin heavy chain (MHC) isoforms have been described from striated, smooth, and nonmuscle cells. These isoforms show expression that is spatially and temporally regulated during development. The hexameric myosin molecule consists of 2 heavy chains (200 kD each) and 2 pairs of light chains (16 to 20 kD each). The heavy chain can be divided into 2 domains, the globular amino terminal head responsible for binding to the myosin light chain and to actin as well as for ATP hydrolysis, and the alpha-helical carboxy terminal rod responsible for the ability of myosin to form filaments.
The MYHCs have been divided into 9 to 11 classes. The structural gene for the beta heavy chain of myosin is expressed predominantly in fetal life and is switched on in older animals under conditions of thyroid hormone depletion/replacement and in response to some physical stresses. Embryonic MYH3 (MIM.160720) and perinatal MYHCs predominate early during skeletal muscle development, persist in certain specialized muscles, such as extraocular and masseter, and are reexpressed in regenerating muscles.
Class II, or ’conventional,’ MYHCs include the extensively studied group of sarcomeric MYHCs that self associate to form filaments and function enzymatically to promote contraction in striated (cardiac and skeletal) muscles.
Structure
Muscle myosin is a heterohexamer consisting of 2 myosin heavy chains and 2 associated nonidentical pairs of myosin light chains. The 7 MYHC isoforms that predominate in mammalian skeletal muscles include 2 developmental isoforms, MYHC-embryonic (MYH3)(MIM.160720) and MYHC-perinatal (MYH8)(MIM.160741); 3 adult skeletal muscle isoforms, MYHC-IIa (MYH2) (MIM.160740), MYHC-IIb (MYH4) (MIM.160742), MYHC-IIx/d (MYH1); and MYHC-beta/slow (MYH7) (MIM.160760), which is also expressed in cardiac muscle. MYHC-extraocular (MYH13) (MIM.603487) is expressed primarily in extrinsic eye muscles.
Members
| MYH1 | MYH2 | MYH3 | MYH4 | MYH5 | MYH6 | MYH7 | MYH8 | MYH9 | MYH10 |
| MYH11 | MYH12 | MYH13 | MYH14 | MYH15 |
Pathology
| Gene | mutations in | OMIM |
| MYH2 | inclusion body myopathy-3 (IBM3) | MIM.605637 |
| MYH6 | familial hypertrophic cardiomyopathy | MIM.192600 |
| MYH7 | familial hypertrophic cardiomyopathy | MIM.192600 |
| MYH9 | May-Hegglin anomaly | MIM.155100 |
| MYH9 | Sebastian syndrome | MIM.605249 |
| MYH9 | Fechtner syndrome | MIM.153640 |
| MYH9 | autosomal dominant deafness (DFNA17) | MIM.603622 |
| MYH9 | Alport-like syndrome with macrothrombocytopenia (Epstein syndrome) | MIM.153650 |
| MYH11 | CBFB/MYH11 fusion protein in acute myeloid leukemia | |
| MYH12 | Griscelli disease (MYO5A) | MIM.214450 |
| MYH14 | autosomal dominant hearing impairment (DFNA4) |