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MYL3
Identifiers
Aliases	MYL3, CMH8, MLC1SB, MLC1V, VLC1, MLC-lV/sb, VLCl, myosin light chain 3
External IDs	OMIM: 160790; MGI: 97268; HomoloGene: 20099; GeneCards: MYL3; OMA:MYL3 - orthologs
Gene location (Human) Chr. Chromosome 3 (human) Band 3p21.31 Start 46,835,111 bp End 46,882,172 bp
Gene location (Mouse) Chr. Chromosome 9 (mouse) Band 9 F2|9 60.69 cM Start 110,570,929 bp End 110,598,866 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in apex of heart right ventricle muscle of thigh myocardium of left ventricle triceps brachii muscle Skeletal muscle tissue of biceps brachii thoracic diaphragm vastus lateralis muscle Skeletal muscle tissue of rectus abdominis glutes Top expressed in interventricular septum myocardium of ventricle cardiac muscles atrioventricular valve soleus muscle cardiac muscle tissue of left ventricle endocardial cushion right ventricle plantaris muscle esophagus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function calcium ion binding structural constituent of muscle cytoskeletal motor activity actin monomer binding myosin II heavy chain binding Cellular component cytosol muscle myosin complex sarcomere A band I band myosin complex Biological process ventricular cardiac muscle tissue morphogenesis regulation of striated muscle contraction skeletal muscle tissue development positive regulation of ATP-dependent activity cardiac muscle contraction regulation of the force of heart contraction muscle filament sliding Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4634 17897 Ensembl ENSG00000160808 ENSMUSG00000059741 UniProt P08590 P09542 RefSeq (mRNA) NM_000258 NM_010859 NM_001364484 RefSeq (protein) NP_000249 NP_000249.1 NP_034989 NP_001351413 Location (UCSC) Chr 3: 46.84 – 46.88 Mb Chr 9: 110.57 – 110.6 Mb PubMed search
Wikidata
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Myosin essential light chain (ELC), ventricular/cardiac isoform is a protein that in humans is encoded by the MYL3 gene. 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

Cardiac, ventricular ELC is 21.9 kDa and composed of 195 amino acids (See human MYL3 sequences features here Archived 2015-09-24 at the Wayback Machine). 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, 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. The N-terminal region of cardiac ELC is functionally 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

Studies have provided evidence for ELC as modulator of myosin crossbridge 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, and further studies demonstrated that this region of ELC modulates the affinity of myosin for actin.

Clinical significance

Mutations in MYL3 have been identified as a cause of familial hypertrophic cardiomyopathy, and associated with a mid-left ventricular chamber type hypertrophy. Five mutations in MYL3 have been identified to date: M149V, R154H, E56G, A57G and E143K. 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.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000160808 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000059741 – 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. Shi Q, Li RK, Mickle DA, Jackowski G (November 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.
6. Cohen-Haguenauer O, Barton PJ, Van Cong N, Cohen A, Masset M, Buckingham M, Frézal J (February 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. S2CID 6703175.
7. "Entrez Gene: MYL3 myosin, light chain 3, alkali; ventricular, skeletal, slow".
8. Rayment I, Rypniewski WR, Schmidt-Bäse K, Smith R, Tomchick DR, Benning MM, Winkelmann DA, Wesenberg G, Holden HM (July 1993). "Three-dimensional structure of myosin subfragment-1: a molecular motor". Science. 261 (5117): 50–8. Bibcode:1993Sci...261...50R. doi:10.1126/science.8316857. PMID 8316857.
9. Collins JH (February 1991). "Myosin light chains and troponin C: structural and evolutionary relationships revealed by amino acid sequence comparisons". Journal of Muscle Research and Cell Motility. 12 (1): 3–25. doi:10.1007/bf01781170. PMID 2050809. S2CID 27878606.
10. Rarick HM, Opgenorth TJ, von Geldern TW, Wu-Wong JR, Solaro RJ (October 1996). "An essential myosin light chain peptide induces supramaximal stimulation of cardiac myofibrillar ATPase activity". The Journal of Biological Chemistry. 271 (43): 27039–43. doi:10.1074/jbc.271.43.27039. PMID 8900193.
11. Stepkowski D, Efimova N, Paczyņska A, Moczarska A, Nieznańska H, Kakol I (June 1997). "The possible role of myosin A1 light chain in the weakening of actin-myosin interaction". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 1340 (1): 105–14. doi:10.1016/s0167-4838(97)00031-9. PMID 9217020.
12. ^ Harris SP, Lyons RG, Bezold KL (March 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.
13. Poetter K, Jiang H, Hassanzadeh S, Master SR, Chang A, Dalakas MC, Rayment I, Sellers JR, Fananapazir L, Epstein ND (May 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. S2CID 742106.
14. Richard P, Charron P, Carrier L, Ledeuil C, Cheav T, Pichereau C, Benaiche A, Isnard R, Dubourg O, Burban M, Gueffet JP, Millaire A, Desnos M, Schwartz K, Hainque B, Komajda M (May 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.
15. Lee W, Hwang TH, Kimura A, Park SW, Satoh M, Nishi H, Harada H, Toyama J, Park JE (February 2001). "Different expressivity of a ventricular essential myosin light chain gene Ala57Gly mutation in familial hypertrophic cardiomyopathy". American Heart Journal. 141 (2): 184–9. doi:10.1067/mhj.2001.112487. PMID 11174330. S2CID 23534623.
16. Olson TM, Karst ML, Whitby FG, Driscoll DJ (May 2002). "Myosin light chain mutation causes autosomal recessive cardiomyopathy with mid-cavitary hypertrophy and restrictive physiology". Circulation. 105 (20): 2337–40. doi:10.1161/01.cir.0000018444.47798.94. PMID 12021217.

Further reading

• Schaub MC, Hefti MA, Zuellig RA, Morano I (February 1998). "Modulation of contractility in human cardiac hypertrophy by myosin essential light chain isoforms". Cardiovascular Research. 37 (2): 381–404. doi:10.1016/S0008-6363(97)00258-7. PMID 9614495.
• Stragier P, Kunkel B, Kroos L, Losick R (January 1989). "Chromosomal rearrangement generating a composite gene for a developmental transcription factor". Science. 243 (4890): 507–12. Bibcode:1989Sci...243..507S. doi:10.1126/science.2536191. PMID 2536191.
• Fodor WL, Darras B, Seharaseyon J, Falkenthal S, Francke U, Vanin EF (February 1989). "Human ventricular/slow twitch myosin alkali light chain gene characterization, sequence, and chromosomal location". The Journal of Biological Chemistry. 264 (4): 2143–9. doi:10.1016/S0021-9258(18)94153-0. PMID 2789520.
• Hoffmann E, Shi QW, Floroff M, Mickle DA, Wu TW, Olley PM, Jackowski G (March 1988). "Molecular cloning and complete nucleotide sequence of a human ventricular myosin light chain 1". Nucleic Acids Research. 16 (5): 2353. doi:10.1093/nar/16.5.2353. PMC 338240. PMID 3357795.
• Kurabayashi M, Komuro I, Tsuchimochi H, Takaku F, Yazaki Y (September 1988). "Molecular cloning and characterization of human atrial and ventricular myosin alkali light chain cDNA clones". The Journal of Biological Chemistry. 263 (27): 13930–6. doi:10.1016/S0021-9258(18)68333-4. PMID 3417683.
• Henry GD, Trayer IP, Brewer S, Levine BA (April 1985). "The widespread distribution of alpha-N-trimethylalanine as the N-terminal amino acid of light chains from vertebrate striated muscle myosins". European Journal of Biochemistry. 148 (1): 75–82. doi:10.1111/j.1432-1033.1985.tb08809.x. PMID 3979397.
• Kovalyov LI, Shishkin SS, Efimochkin AS, Kovalyova MA, Ershova ES, Egorov TA, Musalyamov AK (July 1995). "The major protein expression profile and two-dimensional protein database of human heart". Electrophoresis. 16 (7): 1160–9. doi:10.1002/elps.11501601192. PMID 7498159. S2CID 32209361.
• Poetter K, Jiang H, Hassanzadeh S, Master SR, Chang A, Dalakas MC, Rayment I, Sellers JR, Fananapazir L, Epstein ND (May 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. S2CID 742106.
• Takeuchi K, Senba S, Furukawa K, Eto M, Morita F (February 1999). "Localization of 17-kDa myosin light chain isoforms in cultured aortic smooth muscle cells". Journal of Biochemistry. 125 (2): 334–42. doi:10.1093/oxfordjournals.jbchem.a022291. PMID 9990131.
• Andersen PS, Havndrup O, Bundgaard H, Moolman-Smook JC, Larsen LA, Mogensen J, Brink PA, Børglum AD, Corfield VA, Kjeldsen K, Vuust J, Christiansen M (December 2001). "Myosin light chain mutations in familial hypertrophic cardiomyopathy: phenotypic presentation and frequency in Danish and South African populations". Journal of Medical Genetics. 38 (12): 43e–43. doi:10.1136/jmg.38.12.e43. PMC 1734772. PMID 11748309.
• Olson TM, Karst ML, Whitby FG, Driscoll DJ (May 2002). "Myosin light chain mutation causes autosomal recessive cardiomyopathy with mid-cavitary hypertrophy and restrictive physiology". Circulation. 105 (20): 2337–40. doi:10.1161/01.CIR.0000018444.47798.94. PMID 12021217.
• Moretti A, Weig HJ, Ott T, Seyfarth M, Holthoff HP, Grewe D, Gillitzer A, Bott-Flügel L, Schömig A, Ungerer M, Laugwitz KL (September 2002). "Essential myosin light chain as a target for caspase-3 in failing myocardium". Proceedings of the National Academy of Sciences of the United States of America. 99 (18): 11860–5. Bibcode:2002PNAS...9911860M. doi:10.1073/pnas.182373099. PMC 129359. PMID 12186978.
• Richard P, Charron P, Carrier L, Ledeuil C, Cheav T, Pichereau C, Benaiche A, Isnard R, Dubourg O, Burban M, Gueffet JP, Millaire A, Desnos M, Schwartz K, Hainque B, Komajda M (May 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.
• Xie B, Huang R, Huang L, Zhou G, Gong Z (October 2003). "The functional domains of human ventricular myosin light chain 1". Biophysical Chemistry. 106 (1): 57–66. doi:10.1016/S0301-4622(03)00172-8. PMID 14516912.
• Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S (September 2004). "Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions". Genome Research. 14 (9): 1711–8. doi:10.1101/gr.2435604. PMC 515316. PMID 15342556.

External links

• Mass spectrometry characterization of MYL3 at COPaKB Archived 2015-09-24 at the Wayback Machine
• GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview

• Genes on human chromosome 3