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{{Infobox_gene}}
{{PBB_Controls
'''Myosin essential light chain''' (ELC), ventricular/cardiac isoform is a [[protein]] that in humans is encoded by the ''MYL3'' [[gene]].<ref name="pmid1479618">{{cite journal | vauthors = Shi Q, Li RK, Mickle DA, Jackowski G | title = Analysis of the upstream regulatory region of human ventricular myosin light chain 1 gene | journal = Journal of Molecular and Cellular Cardiology | volume = 24 | issue = 11 | pages = 1221–9 | date = November 1992 | pmid = 1479618 | pmc =  | doi = 10.1016/0022-2828(92)93089-3 }}</ref><ref name="pmid2784124">{{cite journal | vauthors = Cohen-Haguenauer O, Barton PJ, Van Cong N, Cohen A, Masset M, Buckingham M, Frézal J | title = Chromosomal assignment of two myosin alkali light-chain genes encoding the ventricular/slow skeletal muscle isoform and the atrial/fetal muscle isoform (MYL3, MYL4) | journal = Human Genetics | volume = 81 | issue = 3 | pages = 278–82 | date = February 1989 | pmid = 2784124 | pmc = | doi = 10.1007/bf00279004 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: MYL3 myosin, light chain 3, alkali; ventricular, skeletal, slow| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4634| accessdate = }}</ref> 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 [[MYH7|myosin]] molecule and is important in modulating cardiac [[muscle contraction]].
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| update_protein_box = yes
| update_summary = yes
| update_citations = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
==Structure==
{{GNF_Protein_box
Cardiac, ventricular ELC is 21.9 kDa and composed of 195 amino acids ([http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P08590 See human MYL3 sequences features here]). Cardiac ELC and the second light chain, [[MYL2|regulatory light chain]] (RLC, [[MYL2]]), are non-covalently bound to IQXXXRGXXXR motifs in the 9&nbsp;nm S1-S2 lever arm of the myosin head,<ref name="pmid8316857">{{cite journal | vauthors = Rayment I, Rypniewski WR, Schmidt-Bäse K, Smith R, Tomchick DR, Benning MM, Winkelmann DA, Wesenberg G, Holden HM | title = Three-dimensional structure of myosin subfragment-1: a molecular motor | journal = Science | volume = 261 | issue = 5117 | pages = 50–8 | date = July 1993 | pmid = 8316857 | doi = 10.1126/science.8316857 }}</ref> 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.<ref name="pmid2050809">{{cite journal | vauthors = Collins JH | title = Myosin light chains and troponin C: structural and evolutionary relationships revealed by amino acid sequence comparisons | journal = Journal of Muscle Research and Cell Motility | volume = 12 | issue = 1 | pages = 3–25 | date = February 1991 | pmid = 2050809 | doi = 10.1007/bf01781170 }}</ref> 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).
| image =
| image_source =
| PDB =
| Name = Myosin, light chain 3, alkali; ventricular, skeletal, slow
| HGNCid = 7584
| Symbol = MYL3
| AltSymbols =; CMH8; MLC1V; VLC1
| OMIM = 160790
| ECnumber = 
| Homologene = 20099
| MGIid = 97268
| GeneAtlas_image1 = PBB_GE_MYL3_205589_at_tn.png
| Function = {{GNF_GO|id=GO:0003774 |text = motor activity}} {{GNF_GO|id=GO:0005509 |text = calcium ion binding}} {{GNF_GO|id=GO:0008307 |text = structural constituent of muscle}}
| Component = {{GNF_GO|id=GO:0005859 |text = muscle myosin complex}} {{GNF_GO|id=GO:0016459 |text = myosin complex}}
| Process = {{GNF_GO|id=GO:0006936 |text = muscle contraction}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 4634
    | Hs_Ensembl = ENSG00000160808
    | Hs_RefseqProtein = NP_000249
    | Hs_RefseqmRNA = NM_000258
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 3
    | Hs_GenLoc_start = 46874371
    | Hs_GenLoc_end = 46879938
    | Hs_Uniprot = P08590
    | Mm_EntrezGene = 17897
    | Mm_Ensembl = ENSMUSG00000059741
    | Mm_RefseqmRNA = XM_979450
    | Mm_RefseqProtein = XP_984544
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 9
    | Mm_GenLoc_start = 110608494
    | Mm_GenLoc_end = 110614613
    | Mm_Uniprot = Q61935
  }}
}}
'''Myosin, light chain 3, alkali; ventricular, skeletal, slow''', also known as '''MYL3''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: MYL3 myosin, light chain 3, alkali; ventricular, skeletal, slow| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4634| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{PBB_Summary
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,<ref name="pmid8900193">{{cite journal | vauthors = Rarick HM, Opgenorth TJ, von Geldern TW, Wu-Wong JR, Solaro RJ | title = An essential myosin light chain peptide induces supramaximal stimulation of cardiac myofibrillar ATPase activity | journal = The Journal of Biological Chemistry | volume = 271 | issue = 43 | pages = 27039–43 | date = October 1996 | pmid = 8900193 | doi =  }}</ref> and further studies demonstrated that this region of ELC modulates the affinity of [[myosin]] for [[actin]].<ref name="pmid9217020">{{cite journal | vauthors = Stepkowski D, Efimova N, Paczyņska A, Moczarska A, Nieznańska H, Kakol I | title = The possible role of myosin A1 light chain in the weakening of actin-myosin interaction | journal = Biochimica et Biophysica Acta | volume = 1340 | issue = 1 | pages = 105–14 | date = June 1997 | pmid = 9217020 | doi = 10.1016/s0167-4838(97)00031-9 }}</ref>
| section_title =  
| summary_text = MYL3 encodes myosin light chain 3, an alkali light chain also referred to in the literature as both the ventricular isoform and the slow skeletal muscle isoform. Mutations in MYL3 have been identified as a cause of mid-left ventricular chamber type hypertrophic cardiomyopathy.<ref name="entrez">{{cite web | title = Entrez Gene: MYL3 myosin, light chain 3, alkali; ventricular, skeletal, slow| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4634| accessdate = }}</ref>
}}


==References==
==Clinical significance==
{{reflist|2}}
 
==Further reading==
Mutations in MYL3 have been identified as a cause of familial [[hypertrophic cardiomyopathy]], and associated with a mid-left ventricular chamber type hypertrophy.<ref name="cite PMID | 21415409">{{cite journal | vauthors = Harris SP, Lyons RG, Bezold KL | title = In the thick of it: HCM-causing mutations in myosin binding proteins of the thick filament | journal = Circulation Research | volume = 108 | issue = 6 | pages = 751–64 | date = March 2011 | pmid = 21415409 | pmc = 3076008 | doi = 10.1161/CIRCRESAHA.110.231670 }}</ref> Five mutations in MYL3 have been identified to date: M149V, R154H, E56G, A57G and E143K.<ref>{{cite journal | vauthors = Poetter K, Jiang H, Hassanzadeh S, Master SR, Chang A, Dalakas MC, Rayment I, Sellers JR, Fananapazir L, Epstein ND | title = Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle | journal = Nature Genetics | volume = 13 | issue = 1 | pages = 63–9 | date = May 1996 | pmid = 8673105 | doi = 10.1038/ng0596-63 }}</ref><ref>{{cite journal | vauthors = 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 | title = Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy | journal = Circulation | volume = 107 | issue = 17 | pages = 2227–32 | date = May 2003 | pmid = 12707239 | doi = 10.1161/01.CIR.0000066323.15244.54 }}</ref><ref>{{cite journal | vauthors = Lee W, Hwang TH, Kimura A, Park SW, Satoh M, Nishi H, Harada H, Toyama J, Park JE | title = Different expressivity of a ventricular essential myosin light chain gene Ala57Gly mutation in familial hypertrophic cardiomyopathy | journal = American Heart Journal | volume = 141 | issue = 2 | pages = 184–9 | date = February 2001 | pmid = 11174330 | doi = 10.1067/mhj.2001.112487 }}</ref><ref>{{cite journal | vauthors = Olson TM, Karst ML, Whitby FG, Driscoll DJ | title = Myosin light chain mutation causes autosomal recessive cardiomyopathy with mid-cavitary hypertrophy and restrictive physiology | journal = Circulation | volume = 105 | issue = 20 | pages = 2337–40 | date = May 2002 | pmid = 12021217 | doi = 10.1161/01.cir.0000018444.47798.94 }}</ref> 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.<ref name="cite PMID | 21415409"/>
{{refbegin | 2}}
 
{{PBB_Further_reading
== References ==
| citations =  
{{reflist|33em}}
*{{cite journal  | author=Schaub MC, Hefti MA, Zuellig RA, Morano I |title=Modulation of contractility in human cardiac hypertrophy by myosin essential light chain isoforms. |journal=Cardiovasc. Res. |volume=37 |issue= 2 |pages= 381-404 |year= 1998 |pmid= 9614495 |doi= }}
 
*{{cite journal | author=Shi Q, Li RK, Mickle DA, Jackowski G |title=Analysis of the upstream regulatory region of human ventricular myosin light chain 1 gene. |journal=J. Mol. Cell. Cardiol. |volume=24 |issue= 11 |pages= 1221-9 |year= 1993 |pmid= 1479618 |doi= }}
== Further reading ==
*{{cite journal | author=Stragier P, Kunkel B, Kroos L, Losick R |title=Chromosomal rearrangement generating a composite gene for a developmental transcription factor. |journal=Science |volume=243 |issue= 4890 |pages= 507-12 |year= 1989 |pmid= 2536191 |doi= }}
{{refbegin|33em}}
*{{cite journal | author=Cohen-Haguenauer O, Barton PJ, Van Cong N, ''et al.'' |title=Chromosomal assignment of two myosin alkali light-chain genes encoding the ventricular/slow skeletal muscle isoform and the atrial/fetal muscle isoform (MYL3, MYL4). |journal=Hum. Genet. |volume=81 |issue= 3 |pages= 278-82 |year= 1989 |pmid= 2784124 |doi= }}
* {{cite journal | vauthors = Schaub MC, Hefti MA, Zuellig RA, Morano I | title = Modulation of contractility in human cardiac hypertrophy by myosin essential light chain isoforms | journal = Cardiovascular Research | volume = 37 | issue = 2 | pages = 381–404 | date = February 1998 | pmid = 9614495 | doi = 10.1016/S0008-6363(97)00258-7 }}
*{{cite journal  | author=Fodor WL, Darras B, Seharaseyon J, ''et al.'' |title=Human ventricular/slow twitch myosin alkali light chain gene characterization, sequence, and chromosomal location. |journal=J. Biol. Chem. |volume=264 |issue= 4 |pages= 2143-9 |year= 1989 |pmid= 2789520 |doi= }}
* {{cite journal | vauthors = Stragier P, Kunkel B, Kroos L, Losick R | title = Chromosomal rearrangement generating a composite gene for a developmental transcription factor | journal = Science | volume = 243 | issue = 4890 | pages = 507–12 | date = January 1989 | pmid = 2536191 | doi = 10.1126/science.2536191 }}
*{{cite journal | author=Hoffmann E, Shi QW, Floroff M, ''et al.'' |title=Molecular cloning and complete nucleotide sequence of a human ventricular myosin light chain 1. |journal=Nucleic Acids Res. |volume=16 |issue= 5 |pages= 2353 |year= 1988 |pmid= 3357795 |doi= }}
* {{cite journal | vauthors = Fodor WL, Darras B, Seharaseyon J, Falkenthal S, Francke U, Vanin EF | title = Human ventricular/slow twitch myosin alkali light chain gene characterization, sequence, and chromosomal location | journal = The Journal of Biological Chemistry | volume = 264 | issue = 4 | pages = 2143–9 | date = February 1989 | pmid = 2789520 | doi =  }}
*{{cite journal | author=Kurabayashi M, Komuro I, Tsuchimochi H, ''et al.'' |title=Molecular cloning and characterization of human atrial and ventricular myosin alkali light chain cDNA clones. |journal=J. Biol. Chem. |volume=263 |issue= 27 |pages= 13930-6 |year= 1988 |pmid= 3417683 |doi= }}
* {{cite journal | vauthors = Hoffmann E, Shi QW, Floroff M, Mickle DA, Wu TW, Olley PM, Jackowski G | title = Molecular cloning and complete nucleotide sequence of a human ventricular myosin light chain 1 | journal = Nucleic Acids Research | volume = 16 | issue = 5 | pages = 2353 | date = March 1988 | pmid = 3357795 | pmc = 338240 | doi = 10.1093/nar/16.5.2353 }}
*{{cite journal | author=Henry GD, Trayer IP, Brewer S, Levine BA |title=The widespread distribution of alpha-N-trimethylalanine as the N-terminal amino acid of light chains from vertebrate striated muscle myosins. |journal=Eur. J. Biochem. |volume=148 |issue= 1 |pages= 75-82 |year= 1985 |pmid= 3979397 |doi=  }}
* {{cite journal | vauthors = Kurabayashi M, Komuro I, Tsuchimochi H, Takaku F, Yazaki Y | title = Molecular cloning and characterization of human atrial and ventricular myosin alkali light chain cDNA clones | journal = The Journal of Biological Chemistry | volume = 263 | issue = 27 | pages = 13930–6 | date = September 1988 | pmid = 3417683 | doi = }}
*{{cite journal | author=Kovalyov LI, Shishkin SS, Efimochkin AS, ''et al.'' |title=The major protein expression profile and two-dimensional protein database of human heart. |journal=Electrophoresis |volume=16 |issue= 7 |pages= 1160-9 |year= 1996 |pmid= 7498159 |doi= }}
* {{cite journal | vauthors = Henry GD, Trayer IP, Brewer S, Levine BA | title = The widespread distribution of alpha-N-trimethylalanine as the N-terminal amino acid of light chains from vertebrate striated muscle myosins | journal = European Journal of Biochemistry | volume = 148 | issue = 1 | pages = 75–82 | date = April 1985 | pmid = 3979397 | doi = 10.1111/j.1432-1033.1985.tb08809.x }}
*{{cite journal | author=Poetter K, Jiang H, Hassanzadeh S, ''et al.'' |title=Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle. |journal=Nat. Genet. |volume=13 |issue= 1 |pages= 63-9 |year= 1996 |pmid= 8673105 |doi= 10.1038/ng0596-63 }}
* {{cite journal | vauthors = Kovalyov LI, Shishkin SS, Efimochkin AS, Kovalyova MA, Ershova ES, Egorov TA, Musalyamov AK | title = The major protein expression profile and two-dimensional protein database of human heart | journal = Electrophoresis | volume = 16 | issue = 7 | pages = 1160–9 | date = July 1995 | pmid = 7498159 | doi = 10.1002/elps.11501601192 }}
*{{cite journal | author=Takeuchi K, Senba S, Furukawa K, ''et al.'' |title=Localization of 17-kDa myosin light chain isoforms in cultured aortic smooth muscle cells. |journal=J. Biochem. |volume=125 |issue= 2 |pages= 334-42 |year= 1999 |pmid= 9990131 |doi= }}
* {{cite journal | vauthors = Poetter K, Jiang H, Hassanzadeh S, Master SR, Chang A, Dalakas MC, Rayment I, Sellers JR, Fananapazir L, Epstein ND | title = Mutations in either the essential or regulatory light chains of myosin are associated with a rare myopathy in human heart and skeletal muscle | journal = Nature Genetics | volume = 13 | issue = 1 | pages = 63–9 | date = May 1996 | pmid = 8673105 | doi = 10.1038/ng0596-63 }}
*{{cite journal | author=Andersen PS, Havndrup O, Bundgaard H, ''et al.'' |title=Myosin light chain mutations in familial hypertrophic cardiomyopathy: phenotypic presentation and frequency in Danish and South African populations. |journal=J. Med. Genet. |volume=38 |issue= 12 |pages= E43 |year= 2002 |pmid= 11748309 |doi= }}
* {{cite journal | vauthors = Takeuchi K, Senba S, Furukawa K, Eto M, Morita F | title = Localization of 17-kDa myosin light chain isoforms in cultured aortic smooth muscle cells | journal = Journal of Biochemistry | volume = 125 | issue = 2 | pages = 334–42 | date = February 1999 | pmid = 9990131 | doi = 10.1093/oxfordjournals.jbchem.a022291 }}
*{{cite journal | author=Olson TM, Karst ML, Whitby FG, Driscoll DJ |title=Myosin light chain mutation causes autosomal recessive cardiomyopathy with mid-cavitary hypertrophy and restrictive physiology. |journal=Circulation |volume=105 |issue= 20 |pages= 2337-40 |year= 2002 |pmid= 12021217 |doi= }}
* {{cite journal | vauthors = 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 | title = Myosin light chain mutations in familial hypertrophic cardiomyopathy: phenotypic presentation and frequency in Danish and South African populations | journal = Journal of Medical Genetics | volume = 38 | issue = 12 | pages = E43 | date = December 2001 | pmid = 11748309 | pmc = 1734772 | doi = 10.1136/jmg.38.12.e43 }}
*{{cite journal | author=Moretti A, Weig HJ, Ott T, ''et al.'' |title=Essential myosin light chain as a target for caspase-3 in failing myocardium. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 18 |pages= 11860-5 |year= 2002 |pmid= 12186978 |doi= 10.1073/pnas.182373099 }}
* {{cite journal | vauthors = Olson TM, Karst ML, Whitby FG, Driscoll DJ | title = Myosin light chain mutation causes autosomal recessive cardiomyopathy with mid-cavitary hypertrophy and restrictive physiology | journal = Circulation | volume = 105 | issue = 20 | pages = 2337–40 | date = May 2002 | pmid = 12021217 | doi = 10.1161/01.CIR.0000018444.47798.94 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
* {{cite journal | vauthors = Moretti A, Weig HJ, Ott T, Seyfarth M, Holthoff HP, Grewe D, Gillitzer A, Bott-Flügel L, Schömig A, Ungerer M, Laugwitz KL | title = Essential myosin light chain as a target for caspase-3 in failing myocardium | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 18 | pages = 11860–5 | date = September 2002 | pmid = 12186978 | pmc = 129359 | doi = 10.1073/pnas.182373099 }}
*{{cite journal | author=Richard P, Charron P, Carrier L, ''et al.'' |title=Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy. |journal=Circulation |volume=107 |issue= 17 |pages= 2227-32 |year= 2003 |pmid= 12707239 |doi= 10.1161/01.CIR.0000066323.15244.54 }}
* {{cite journal | vauthors = 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 | title = Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations, and implications for a molecular diagnosis strategy | journal = Circulation | volume = 107 | issue = 17 | pages = 2227–32 | date = May 2003 | pmid = 12707239 | doi = 10.1161/01.CIR.0000066323.15244.54 }}
*{{cite journal | author=Xie B, Huang R, Huang L, ''et al.'' |title=The functional domains of human ventricular myosin light chain 1. |journal=Biophys. Chem. |volume=106 |issue= 1 |pages= 57-66 |year= 2004 |pmid= 14516912 |doi= }}
* {{cite journal | vauthors = Xie B, Huang R, Huang L, Zhou G, Gong Z | title = The functional domains of human ventricular myosin light chain 1 | journal = Biophysical Chemistry | volume = 106 | issue = 1 | pages = 57–66 | date = October 2003 | pmid = 14516912 | doi = 10.1016/S0301-4622(03)00172-8 }}
*{{cite journal | author=Suzuki Y, Yamashita R, Shirota M, ''et al.'' |title=Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions. |journal=Genome Res. |volume=14 |issue= 9 |pages= 1711-8 |year= 2004 |pmid= 15342556 |doi= 10.1101/gr.2435604 }}
* {{cite journal | vauthors = Suzuki Y, Yamashita R, Shirota M, Sakakibara Y, Chiba J, Mizushima-Sugano J, Nakai K, Sugano S | title = Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions | journal = Genome Research | volume = 14 | issue = 9 | pages = 1711–8 | date = September 2004 | pmid = 15342556 | pmc = 515316 | doi = 10.1101/gr.2435604 }}
*{{cite journal | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
== External links ==
{{WikiDoc Sources}}
* [http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P08590 Mass spectrometry characterization of MYL3 at COPaKB]
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=hyper-card  GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview]

Latest revision as of 07:13, 4 September 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

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

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

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

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

  1. ↑ 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.
  2. ↑ 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.
  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 (July 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 (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.
  6. ↑ 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. PMID 8900193.
  7. ↑ 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. 1340 (1): 105–14. doi:10.1016/s0167-4838(97)00031-9. PMID 9217020.
  8. ↑ 8.0 8.1 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.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ 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

External links

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