MYH7

MYH7 is a gene encoding a myosin heavy chain beta (MHC-β) isoform (slow twitch) expressed primarily in the heart, but also in skeletal muscles (type I fibers).[5] This isoform is distinct from the fast isoform of cardiac myosin heavy chain, MYH6, referred to as MHC-α. MHC-β is the major protein comprising the thick filament in cardiac muscle and plays a major role in cardiac muscle contraction.

MYH7
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3DTP, 4DB1, 4P7H, 4XA1, 4XA3, 4XA4, 4XA6, 4PA0, 5CHX, 5CJ0, 5CJ4, 5CJ1, 2FXO, 2FXM
Identifiers
Aliases	MYH7, CMD1S, CMH1, MPD1, MYHCB, SPMD, SPMM, myosin, heavy chain 7, cardiac muscle, beta, myosin heavy chain 7
External IDs	OMIM: 160760 MGI: 2155600 HomoloGene: 68044 GeneCards: MYH7
Gene location (Human) Chr. Chromosome 14 (human)[1] Band 14q11.2 Start 23,412,740 bp[1] End 23,435,660 bp[1]
Gene location (Mouse) Chr. Chromosome 14 (mouse)[2] Band 14 C3|14 28.01 cM Start 54,970,684 bp[2] End 54,994,626 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • nucleotide binding • actin-dependent ATPase activity • calmodulin binding • GO:0001948 protein binding • actin binding • cellular motor activity • ATP binding • ATPase activity • microfilament motor activity • actin filament binding • microtubule motor activity • microtubule binding Cellular component • cytoplasm • stress fiber • Z disc • myosin filament • myosin complex • muscle myosin complex • myofibril • sarcomere Biological process • cardiac muscle contraction • adult heart development • transition between fast and slow fiber • regulation of the force of heart contraction • skeletal muscle contraction • regulation of slow-twitch skeletal muscle fiber contraction • regulation of heart rate • ventricular cardiac muscle tissue morphogenesis • ATP metabolic process • muscle filament sliding • striated muscle contraction • regulation of the force of skeletal muscle contraction • muscle contraction • cardiac muscle hypertrophy in response to stress • microtubule-based movement Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4625	140781
Ensembl	ENSG00000092054	ENSMUSG00000053093
UniProt	P12883	Q91Z83
RefSeq (mRNA)	NM_000257	NM_080728 NM_001361607
RefSeq (protein)	NP_000248	NP_542766 NP_001348536
Location (UCSC)	Chr 14: 23.41 – 23.44 Mb	Chr 14: 54.97 – 54.99 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Structure

MHC-β is a 223 kDa protein composed of 1935 amino acids.[6][7] MHC-β is a hexameric, asymmetric motor forming the bulk of the thick filament in cardiac muscle. MHC-β is composed of N-terminal globular heads (20 nm) that project laterally, and alpha helical tails (130 nm) that dimerize and multimerize into a coiled-coil motif to form the light meromyosin (LMM), thick filament rod. The 9 nm alpha-helical neck region of each MHC-β head non-covalently binds two light chains, essential light chain (MYL3) and regulatory light chain (MYL2).[8] Approximately 300 myosin molecules constitute one thick filament.[9] There are two isoforms of cardiac MHC, α and β, which display 93% homology. MHC-α and MHC-β display significantly different enzymatic properties, with α having 150-300% the contractile velocity and 60-70% actin attachment time as that of β.[10][11] MHC-β is predominately expressed in the human ventricle, while MHC-α is predominantly expressed in human atria.

Function

It is the enzymatic activity of the ATPase in the myosin head that cyclically hydrolyzes ATP, fueling the myosin power stroke. This process converts chemical to mechanical energy, and propels shortening of the sarcomeres in order to generate intraventricular pressure and power. An accepted mechanism for this process is that ADP-bound myosin attaches to actin while thrusting tropomyosin inwards,[12] then the S1-S2 myosin lever arm rotates ~70° about the converter domain and drives actin filaments towards the M-line.[13]

Clinical significance

Several mutations in MYH7 have been associated with inherited cardiomyopathies. Lowrance et al. were the first to identify the causative mutation Arg403Gln for hypertrophic cardiomyopathy (HCM) in the MYH7 gene.[14] Studies have since identified several more MYH7 mutations, that are estimated to be causal in approximately 40% of HCM cases. This condition is an autosomal-dominant disease, in which a single copy of the variant gene causes enlargement of the left ventricle of the heart. Disease onset usually occurs later in life, perhaps triggered by changes in thyroid hormone function and/or physical stress.

Another condition associated to mutations in this gene is paraspinal and proximal muscle atrophy.[15]

References

1. GRCh38: Ensembl release 89: ENSG00000092054 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000053093 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Quiat D, Voelker KA, Pei J, Grishin NV, Grange RW, Bassel-Duby R, Olson EN (Jun 2011). "Concerted regulation of myofiber-specific gene expression and muscle performance by the transcriptional repressor Sox6". Proceedings of the National Academy of Sciences of the United States of America. 108 (25): 10196–201. doi:10.1073/pnas.1107413108. PMC 3121857. PMID 21633012.
6. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB)". heartproteome.org. Retrieved 2015-10-14.
7. Zong, N. C.; Li, H; Li, H; Lam, M. P.; Jimenez, R. C.; Kim, C. S.; Deng, N; Kim, A. K.; Choi, J. H.; Zelaya, I; Liem, D; Meyer, D; Odeberg, J; Fang, C; Lu, H. J.; Xu, T; Weiss, J; Duan, H; Uhlen, M; Yates Jr, 3rd; Apweiler, R; Ge, J; Hermjakob, H; Ping, P (2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
8. Palmer BM (Sep 2005). "Thick filament proteins and performance in human heart failure". Heart Failure Reviews. 10 (3): 187–97. doi:10.1007/s10741-005-5249-1. PMID 16416042.
9. Harris SP, Lyons RG, Bezold KL (Mar 2011). "In the thick of it: HCM-causing mutations in myosin binding proteins of the thick filament". Circulation Research. 108 (6): 751–764. doi:10.1161/CIRCRESAHA.110.231670. PMC 3076008. PMID 21415409.
10. Palmer BM (Sep 2005). "Thick filament proteins and performance in human heart failure". Heart Failure Reviews. 10 (3): 187–97. doi:10.1007/s10741-005-5249-1. PMID 16416042.
11. Alpert NR, Brosseau C, Federico A, Krenz M, Robbins J, Warshaw DM (Oct 2002). "Molecular mechanics of mouse cardiac myosin isoforms". American Journal of Physiology. Heart and Circulatory Physiology. 283 (4): H1446-54. doi:10.1152/ajpheart.00274.2002. PMID 12234796.
12. McKillop DF, Geeves MA (Aug 1993). "Regulation of the interaction between actin and myosin subfragment 1: evidence for three states of the thin filament". Biophysical Journal. 65 (2): 693–701. doi:10.1016/S0006-3495(93)81110-X. PMC 1225772. PMID 8218897.
13. Tyska MJ, Warshaw DM (Jan 2002). "The myosin power stroke". Cell Motility and the Cytoskeleton. 51 (1): 1–15. doi:10.1002/cm.10014. PMID 11810692.
14. Geisterfer-Lowrance, A. A.; Kass, S; Tanigawa, G; Vosberg, H. P.; McKenna, W; Seidman, C. E.; Seidman, J. G. (1990). "A molecular basis for familial hypertrophic cardiomyopathy: A beta cardiac myosin heavy chain gene missense mutation". Cell. 62 (5): 999–1006. doi:10.1016/0092-8674(90)90274-i. PMID 1975517.
15. Park JM, Kim YJ, Yoo JH, Hong YB, Park JH, Koo H, Chung KW, Choi BO (Jul 2013). "A novel MYH7 mutation with prominent paraspinal and proximal muscle involvement". Neuromuscular Disorders. 23 (7): 580–6. doi:10.1016/j.nmd.2013.04.003. PMID 23707328.

Further reading

• Jaaskelainen P, Miettinen R, Karkkainen P, Toivonen L, Laakso M, Kuusisto J (2004). "Genetics of hypertrophic cardiomyopathy in eastern Finland: few founder mutations with benign or intermediary phenotypes". Annals of Medicine. 36 (1): 23–32. doi:10.1080/07853890310017161. PMID 15000344.
• Kamisago M, Schmitt JP, McNamara D, Seidman C, Seidman JG (2007). "Sarcomere protein gene mutations and inherited heart disease: a beta-cardiac myosin heavy chain mutation causing endocardial fibroelastosis and heart failure". Novartis Foundation Symposium. 274: 176–89, discussion 189–95, 272–6. doi:10.1002/0470029331.ch11. PMID 17019812.

External links

• Mass spectrometry characterization of MYH7 at COPaKB [1]
• GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview
• GeneReviews/NCBI/NIH/UW entry on Laing Distal Myopathy
• MYH7+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)

1. Zong, N. C.; Li, H; Li, H; Lam, M. P.; Jimenez, R. C.; Kim, C. S.; Deng, N; Kim, A. K.; Choi, J. H.; Zelaya, I; Liem, D; Meyer, D; Odeberg, J; Fang, C; Lu, H. J.; Xu, T; Weiss, J; Duan, H; Uhlen, M; Yates Jr, 3rd; Apweiler, R; Ge, J; Hermjakob, H; Ping, P (2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.