MYL3

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Myosin, light chain 3, alkali; ventricular, skeletal, slow
Identifiers
Symbols MYL3 ; CMH8; MLC1SB; MLC1V; VLC1
External IDs OMIM160790 MGI97268 HomoloGene20099 GeneCards: MYL3 Gene
RNA expression pattern
PBB GE MYL3 205589 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4634 17897
Ensembl ENSG00000160808 ENSMUSG00000059741
UniProt P08590 P09542
RefSeq (mRNA) NM_000258 NM_010859
RefSeq (protein) NP_000249 NP_034989
Location (UCSC) Chr 3:
46.86 – 46.88 Mb
Chr 9:
110.74 – 110.77 Mb
PubMed search [1] [2]

Myosin essential light chain (ELC), ventricular/cardiac isoform is a protein that in humans is encoded by the MYL3 gene.[1][2][3] This cardiac ventricular/slow skeletal ELC isoform is distinct from that expressed in fast skeletal muscle (MYL1) and cardiac atrial muscle (MYL4). Ventricular ELC is part of the myosin molecule and is important in modulating cardiac muscle contraction.

Structure[edit]

Cardiac, ventricular ELC is 21.9 kDa and composed of 195 amino acids (See human MYL3 sequences features here). Cardiac ELC and the second light chain, regulatory light chain (RLC, MYL2), are non-covalently bound to IQXXXRGXXXR motifs in the 9 nm S1-S2 lever arm of the myosin head,[4] both alpha (MYH6) and beta (MYH7) isoforms. Both light chains are members of the EF-hand superfamily of proteins, which possess helix-loop-helix motifs in two globular domains connected by an alpha-helical linker. Though EF hand motifs are specialized to bind divalent ions such as calcium, cardiac ELC does not bind calcium at physiological levels.[5] The N-terminal region of cardiac ELC is functionlly unique in that it is positively charged, being rich in Lysine residues (amino acids 4-14), with subsequent unique structure governed by Proline-Alanine repeats (amino acids 15-36).

Function[edit]

Studies have provided evidence for ELC as modulator of myosin crossbrige kinetics. Treating cardiac myofibrils with the Lysine-rich N-terminal peptide (amino acids 5-14) evoked a supramaximal increase in cardiac myofibrillar MgATPase activity at submaximal calcium concentrations,[6] and further studies demonstrated that this region of ELC modulates the affinity of myosin for actin.[7]

Clinical significance[edit]

Mutations in MYL3 have been identified as a cause of familial hypertrophic cardiomyopathy, and associated with a mid-left ventricular chamber type hypertrophy.[8] Five mutations in MYL3 have been identified to date: M149V, R154H, E56G, A57G and E143K.[9][10][11][12] All of these cluster around two of the four EF-hand domains, suggesting that proper conformation in these regions is necessary for normal cardiac function.[8]

References[edit]

  1. ^ Shi Q, Li RK, Mickle DA, Jackowski G (Nov 1992). "Analysis of the upstream regulatory region of human ventricular myosin light chain 1 gene". Journal of Molecular and Cellular Cardiology 24 (11): 1221–9. doi:10.1016/0022-2828(92)93089-3. PMID 1479618. 
  2. ^ Cohen-Haguenauer O, Barton PJ, Van Cong N, Cohen A, Masset M, Buckingham M, Frézal J (Feb 1989). "Chromosomal assignment of two myosin alkali light-chain genes encoding the ventricular/slow skeletal muscle isoform and the atrial/fetal muscle isoform (MYL3, MYL4)". Human Genetics 81 (3): 278–82. doi:10.1007/bf00279004. PMID 2784124. 
  3. ^ "Entrez Gene: MYL3 myosin, light chain 3, alkali; ventricular, skeletal, slow". 
  4. ^ Rayment I, Rypniewski WR, Schmidt-Bäse K, Smith R, Tomchick DR, Benning MM, Winkelmann DA, Wesenberg G, Holden HM (1993). "Three-dimensional structure of myosin subfragment-1: a molecular motor". Science 261 (5117): 50–8. doi:10.1126/science.8316857. PMID 8316857. 
  5. ^ Collins JH (1991). "Myosin light chains and troponin C: structural and evolutionary relationships revealed by amino acid sequence comparisons". J. Muscle Res. Cell. Motil. 12 (1): 3–25. doi:10.1007/bf01781170. PMID 2050809. 
  6. ^ Rarick HM, Opgenorth TJ, von Geldern TW, Wu-Wong JR, Solaro RJ (1996). "An essential myosin light chain peptide induces supramaximal stimulation of cardiac myofibrillar ATPase activity". J. Biol. Chem. 271 (43): 27039–43. PMID 8900193. 
  7. ^ Stepkowski D, Efimova N, Paczyņska A, Moczarska A, Nieznańska H, Kakol I (1997). "The possible role of myosin A1 light chain in the weakening of actin-myosin interaction". Biochim. Biophys. Acta 1340 (1): 105–14. doi:10.1016/s0167-4838(97)00031-9. PMID 9217020. 
  8. ^ a b Harris, S. P.; Lyons, R. G.; Bezold, K. L. (2011). "In the thick of it: HCM-causing mutations in myosin binding proteins of the thick filament". Circulation Research 108 (6): 751–64. doi:10.1161/CIRCRESAHA.110.231670. PMC 3076008. PMID 21415409. 
  9. ^ Poetter, K; Jiang, H; Hassanzadeh, S; Master, S. R.; Chang, A; Dalakas, M. C.; Rayment, I; Sellers, J. R.; Fananapazir, L; Epstein, N. D. (1996). "Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle". Nature Genetics 13 (1): 63–9. doi:10.1038/ng0596-63. PMID 8673105. 
  10. ^ Richard, P; Charron, P; Carrier, L; Ledeuil, C; Cheav, T; Pichereau, C; Benaiche, A; Isnard, R; Dubourg, O; Burban, M; Gueffet, J. P.; Millaire, A; Desnos, M; Schwartz, K; Hainque, B; Komajda, M; Eurogene Heart Failure, Project (2003). "Hypertrophic cardiomyopathy: Distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy". Circulation 107 (17): 2227–32. doi:10.1161/01.CIR.0000066323.15244.54. PMID 12707239. 
  11. ^ Lee, W; Hwang, T. H.; Kimura, A; Park, S. W.; Satoh, M; Nishi, H; Harada, H; Toyama, J; Park, J. E. (2001). "Different expressivity of a ventricular essential myosin light chain gene Ala57Gly mutation in familial hypertrophic cardiomyopathy". American heart journal 141 (2): 184–9. PMID 11174330. 
  12. ^ Olson, T. M.; Karst, M. L.; Whitby, F. G.; Driscoll, D. J. (2002). "Myosin light chain mutation causes autosomal recessive cardiomyopathy with mid-cavitary hypertrophy and restrictive physiology". Circulation 105 (20): 2337–40. PMID 12021217. 

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