| 词条 | MYL7 |
| 释义 |
Atrial Light Chain-2 (ALC-2) also known as Myosin regulatory light chain 2, atrial isoform (MLC2a) is a protein that in humans is encoded by the MYL7 gene.[1][2] ALC-2 expression is restricted to cardiac muscle atria in healthy individuals, where it functions to modulate cardiac development and contractility. In human diseases, including hypertrophic cardiomyopathy, dilated cardiomyopathy, ischemic cardiomyopathy and others, ALC-2 expression is altered. StructureHuman ALC-2 protein has a molecular weight of 19.4 kDa and is composed of 175 amino acids.[3] ALC-2 is an EF hand protein that binds to the neck region of alpha myosin heavy chain.[4] ALC-2 and the ventricular isoform, VLC-2, share 59% homology, showing significant differences at their N-termini and at the regulatory phosphorylation site(s), Serine-15 and Serine/Asparagine-14.[5] FunctionALC-2 expression has proven to be a useful marker of cardiac muscle chamber distinction, development and differentiation.[6][7][8][9][10] ALC-2 shows a pattern distinct from atrial essential light chain (ALC-1) during cardiogenesis. ALC-2 expression in adult murine hearts is cardiac-specific throughout embryonic days 8-16, and from day 12 and on is restricted to atria, showing very low levels in aorta and undetectable in ventricles, skeletal muscle, uterus, and liver. This atrial patterning occurs prior to septation.[11] Expression of ALC-2 has been shown to correlate with expression of alpha-myosin heavy chain in cardiac atria of non-human primates.[12] ALC-2 and VLC-2 appear to function in the stabilization of thick filaments and regulation of contractility in the vertebrate heart.[13] Functional insights into ALC-2 function have come from studies employing transgenesis. A study in which the ventricular isoform of regulatory light chain was overexpressed to replace the ALC-2 in cardiac atria was performed. This substitution resulted in atrial myocytes that contract and relax more forcefully and quickly, resulting in atrial cardiomyocytes that behave as ventricular cardiomyocytes.[14] In disease models, ALC-2 expression in some instances can be downregulated and replaced by the ventricular isoform (VLC-2). In spontaneously hypertensive rats, VLC-2 mRNA expression is three times higher in atria; and this change precedes any detectable pressure overloading of the heart, suggesting that this change is a very early functional adaptation to cardiac hypertrophy.[15] Moreover, in a porcine model of atrial fibrillation, VLC-2 mRNA expression showed the greatest change, being upregulated 9.4-fold and 7.3-fold in left and right atria, respectively.[16] In a porcine model of left atrial remodeling following mitral regurgitation, VLC-2 was shown to be upregulated.[17] Human ALC-2 is phosphorylated at its N-terminus at Serine-15 by a cardiac-specific myosin light chain kinase;[18][19] ALC-2 has a serine at position 14, which is an Asparagine in the ventricular isoform that is shown to be deamidated (thus producing a negative charge similar to phosphorylation). Whether serine-14 of human ALC-2 is also phosphorylated remains to be determined. Endogenous phosphorylation level is around 30% of the total ALC-2.[20] Alpha(1)-adrenergic stimulation by phenylephrine in atrial muscle strips showed an 80% increase in ALC-2 phosphorylation coordinate with enhanced contractile force, which was inhibited by both Rho kinase and myosin light chain kinase inhibition.[21] In a canine model of atrial fibrillation, decreased atrial contractility was associated with decreased ALC-2 and myosin binding protein C phosphorylation.[22] Moreover, the slow force response induced by stretch in human atrial muscle was shown to be modulated by enhanced phosphorylation of ALC-2 by myosin light chain kinase.[23] Clinical SignificancePatients with hypertrophic cardiomyopathy shown an increased expression of ALC-2 in whole heart tissue.[24] In patients with mitral valve disease, ischemic cardiomyopathy, dilated cardiomyopathy, coronary heart disease and pressure overload-induced cardiac hypertrophy, ALC-2 was shown to be replaced with VLC-2 in cardiac atria; in dilated cardiomyopathy, this change was concomitant with enhanced sensitivity of atrial fibers to calcium.[25][26] In patients with congenital atrial septal defect carrying a missense mutation Ile820Asn in alpha myosin heavy chain, it was shown that binding of ALC-2 to alpha myosin heavy chain is disrupted.[27] InteractionsALC-2 is shown to interact with:
References1. ^{{cite journal | vauthors = Kubalak SW, Miller-Hance WC, O'Brien TX, Dyson E, Chien KR | title = Chamber specification of atrial myosin light chain-2 expression precedes septation during murine cardiogenesis | journal = The Journal of Biological Chemistry | volume = 269 | issue = 24 | pages = 16961–70 | date = June 1994 | pmid = 8207020 | pmc = | doi = }} 2. ^{{cite web | title = Entrez Gene: MYL7 myosin, light chain 7, regulatory| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=58498| accessdate = }} 3. ^{{cite web|title=Protein sequence of human MYL7 (Uniprot ID: Q01449)|url=http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=Q01449|website=Cardiac Organellar Protein Atlas Knowledgebase (COPaKB)|accessdate=30 June 2015}} 4. ^1 {{cite journal | vauthors = Winkelmann DA, Baker TS, Rayment I | title = Three-dimensional structure of myosin subfragment-1 from electron microscopy of sectioned crystals | journal = The Journal of Cell Biology | volume = 114 | issue = 4 | pages = 701–13 | date = August 1991 | pmid = 1869586 | doi = 10.1083/jcb.114.4.701 | pmc=2289899}} 5. ^{{cite web|title=Protein sequence alignment for human cardiac atrial and ventricular regulatory light chains|url=https://www.uniprot.org/align/A2015063014HZ0FDXQJ|website=Uniprot Knowledgebase|accessdate=30 June 2015}}{{dead link|date=January 2018 |bot=InternetArchiveBot |fix-attempted=yes }} 6. ^{{cite journal | vauthors = Ovchinnikov DA, Hidalgo A, Yang SK, Zhang X, Hudson J, Mazzone SB, Chen C, Cooper-White JJ, Wolvetang EJ | title = Isolation of contractile cardiomyocytes from human pluripotent stem-cell-derived cardiomyogenic cultures using a human NCX1-EGFP reporter | journal = Stem Cells and Development | volume = 24 | issue = 1 | pages = 11–20 | date = January 2015 | pmid = 25075536 | doi = 10.1089/scd.2014.0195 | citeseerx = 10.1.1.1012.2726 }} 7. ^{{cite journal | vauthors = Hudson J, Titmarsh D, Hidalgo A, Wolvetang E, Cooper-White J | title = Primitive cardiac cells from human embryonic stem cells | journal = Stem Cells and Development | volume = 21 | issue = 9 | pages = 1513–23 | date = June 2012 | pmid = 21933026 | doi = 10.1089/scd.2011.0254 }} 8. ^{{cite journal | vauthors = Small EM, Krieg PA | title = Molecular regulation of cardiac chamber-specific gene expression | journal = Trends in Cardiovascular Medicine | volume = 14 | issue = 1 | pages = 13–8 | date = January 2004 | pmid = 14720469 | doi = 10.1016/j.tcm.2003.09.005 }} 9. ^{{cite journal | vauthors = Franco D, Markman MM, Wagenaar GT, Ya J, Lamers WH, Moorman AF | title = Myosin light chain 2a and 2v identifies the embryonic outflow tract myocardium in the developing rodent heart | journal = The Anatomical Record | volume = 254 | issue = 1 | pages = 135–46 | date = January 1999 | pmid = 9892427 | doi = 10.1002/(sici)1097-0185(19990101)254:1<135::aid-ar17>3.3.co;2-j }} 10. ^{{cite journal | vauthors = Doevendans PA, Bronsaer R, Lozano PR, Kubalak S, van Bilsen M | title = The murine atrial myosin light chain-2 gene: a member of an evolutionarily conserved family of contractile proteins | journal = Cytogenetics and Cell Genetics | volume = 90 | issue = 3–4 | pages = 248–52 | date = 2000 | pmid = 11124527 | doi = 10.1159/000056782 }} 11. ^{{cite journal | vauthors = Kubalak SW, Miller-Hance WC, O'Brien TX, Dyson E, Chien KR | title = Chamber specification of atrial myosin light chain-2 expression precedes septation during murine cardiogenesis | journal = The Journal of Biological Chemistry | volume = 269 | issue = 24 | pages = 16961–70 | date = June 1994 | pmid = 8207020 }} 12. ^{{cite journal | vauthors = Henkel RD, Kammerer CM, Escobedo LV, VandeBerg JL, Walsh RA | title = Correlated expression of atrial myosin heavy chain and regulatory light chain isoforms with pressure overload hypertrophy in the non-human primate | journal = Cardiovascular Research | volume = 27 | issue = 3 | pages = 416–22 | date = March 1993 | pmid = 8490941 | doi = 10.1093/cvr/27.3.416 }} 13. ^{{cite journal | vauthors = Rottbauer W, Wessels G, Dahme T, Just S, Trano N, Hassel D, Burns CG, Katus HA, Fishman MC | title = Cardiac myosin light chain-2: a novel essential component of thick-myofilament assembly and contractility of the heart | journal = Circulation Research | volume = 99 | issue = 3 | pages = 323–31 | date = August 2006 | pmid = 16809551 | doi = 10.1161/01.res.0000234807.16034.fe }} 14. ^{{cite journal | vauthors = Pawloski-Dahm CM, Song G, Kirkpatrick DL, Palermo J, Gulick J, Dorn GW, Robbins J, Walsh RA | title = Effects of total replacement of atrial myosin light chain-2 with the ventricular isoform in atrial myocytes of transgenic mice | journal = Circulation | volume = 97 | issue = 15 | pages = 1508–13 | date = April 1998 | pmid = 9576432 | doi = 10.1161/01.cir.97.15.1508 }} 15. ^{{cite journal | vauthors = Kumar C, Saidapet C, Delaney P, Mendola C, Siddiqui MA | title = Expression of ventricular-type myosin light chain messenger RNA in spontaneously hypertensive rat atria | journal = Circulation Research | volume = 62 | issue = 6 | pages = 1093–7 | date = June 1988 | pmid = 3383359 | doi = 10.1161/01.res.62.6.1093 }} 16. ^{{cite journal | vauthors = Lai LP, Lin JL, Lin CS, Yeh HM, Tsay YG, Lee CF, Lee HH, Chang ZF, Hwang JJ, Su MJ, Tseng YZ, Huang SK | title = Functional genomic study on atrial fibrillation using cDNA microarray and two-dimensional protein electrophoresis techniques and identification of the myosin regulatory light chain isoform reprogramming in atrial fibrillation | journal = Journal of Cardiovascular Electrophysiology | volume = 15 | issue = 2 | pages = 214–23 | date = February 2004 | pmid = 15028053 | doi = 10.1046/j.1540-8167.2004.03423.x }} 17. ^{{cite journal | vauthors = Chen MC, Chang JP, Chang TH, Hsu SD, Huang HD, Ho WC, Wang FS, Hsiao CC, Liu WH | title = Unraveling regulatory mechanisms of atrial remodeling of mitral regurgitation pigs by gene expression profiling analysis: role of type I angiotensin II receptor antagonist | journal = Translational Research | volume = 165 | issue = 5 | pages = 599–620 | date = May 2015 | pmid = 25500755 | doi = 10.1016/j.trsl.2014.11.005 }} 18. ^{{cite journal | vauthors = Ding P, Huang J, Battiprolu PK, Hill JA, Kamm KE, Stull JT | title = Cardiac myosin light chain kinase is necessary for myosin regulatory light chain phosphorylation and cardiac performance in vivo | journal = The Journal of Biological Chemistry | volume = 285 | issue = 52 | pages = 40819–29 | date = December 2010 | pmid = 20943660 | pmc = 3003383 | doi = 10.1074/jbc.m110.160499 }} 19. ^{{cite journal | vauthors = Scruggs SB, Reisdorph R, Armstrong ML, Warren CM, Reisdorph N, Solaro RJ, Buttrick PM | title = A novel, in-solution separation of endogenous cardiac sarcomeric proteins and identification of distinct charged variants of regulatory light chain | journal = Molecular & Cellular Proteomics | volume = 9 | issue = 9 | pages = 1804–18 | date = September 2010 | pmid = 20445002 | doi = 10.1074/mcp.m110.000075 | pmc=2938104}} 20. ^{{cite journal | vauthors = Svensson C, Morano I, Arner A | title = In vitro motility assay of atrial and ventricular myosin from pig | journal = Journal of Cellular Biochemistry | volume = 67 | issue = 2 | pages = 241–7 | date = November 1997 | pmid = 9328829 | doi = 10.1002/(sici)1097-4644(19971101)67:2<241::aid-jcb9>3.0.co;2-x }} 21. ^{{cite journal | vauthors = Grimm M, Haas P, Willipinski-Stapelfeldt B, Zimmermann WH, Rau T, Pantel K, Weyand M, Eschenhagen T | title = Key role of myosin light chain (MLC) kinase-mediated MLC2a phosphorylation in the alpha 1-adrenergic positive inotropic effect in human atrium | journal = Cardiovascular Research | volume = 65 | issue = 1 | pages = 211–20 | date = January 2005 | pmid = 15621049 | doi = 10.1016/j.cardiores.2004.09.019 }} 22. ^{{cite journal | vauthors = Wakili R, Yeh YH, Yan Qi X, Greiser M, Chartier D, Nishida K, Maguy A, Villeneuve LR, Boknik P, Voigt N, Krysiak J, Kääb S, Ravens U, Linke WA, Stienen GJ, Shi Y, Tardif JC, Schotten U, Dobrev D, Nattel S | title = Multiple potential molecular contributors to atrial hypocontractility caused by atrial tachycardia remodeling in dogs | journal = Circulation: Arrhythmia and Electrophysiology | volume = 3 | issue = 5 | pages = 530–41 | date = October 2010 | pmid = 20660541 | doi = 10.1161/circep.109.933036 }} 23. ^{{cite journal | vauthors = Kockskämper J, Khafaga M, Grimm M, Elgner A, Walther S, Kockskämper A, von Lewinski D, Post H, Grossmann M, Dörge H, Gottlieb PA, Sachs F, Eschenhagen T, Schöndube FA, Pieske B | title = Angiotensin II and myosin light-chain phosphorylation contribute to the stretch-induced slow force response in human atrial myocardium | journal = Cardiovascular Research | volume = 79 | issue = 4 | pages = 642–51 | date = September 2008 | pmid = 18503051 | doi = 10.1093/cvr/cvn126 | pmc=2614393}} 24. ^{{cite journal | vauthors = Lim DS, Roberts R, Marian AJ | title = Expression profiling of cardiac genes in human hypertrophic cardiomyopathy: insight into the pathogenesis of phenotypes | journal = Journal of the American College of Cardiology | volume = 38 | issue = 4 | pages = 1175–80 | date = October 2001 | pmid = 11583900 | pmc = 2776821 | doi = 10.1016/s0735-1097(01)01509-1 }} 25. ^{{cite journal | vauthors = Wankerl M, Böhm M, Morano I, Rüegg JC, Eichhorn M, Erdmann E | title = Calcium sensitivity and myosin light chain pattern of atrial and ventricular skinned cardiac fibers from patients with various kinds of cardiac disease | journal = Journal of Molecular and Cellular Cardiology | volume = 22 | issue = 12 | pages = 1425–38 | date = December 1990 | pmid = 2089158 | doi = 10.1016/0022-2828(90)90986-c }} 26. ^{{cite journal | vauthors = Cummins P | title = Transitions in human atrial and ventricular myosin light-chain isoenzymes in response to cardiac-pressure-overload-induced hypertrophy | journal = The Biochemical Journal | volume = 205 | issue = 1 | pages = 195–204 | date = July 1982 | pmid = 6215032 | doi = 10.1042/bj2050195 | pmc=1158463}} 27. ^1 {{cite journal | vauthors = Ching YH, Ghosh TK, Cross SJ, Packham EA, Honeyman L, Loughna S, Robinson TE, Dearlove AM, Ribas G, Bonser AJ, Thomas NR, Scotter AJ, Caves LS, Tyrrell GP, Newbury-Ecob RA, Munnich A, Bonnet D, Brook JD | title = Mutation in myosin heavy chain 6 causes atrial septal defect | journal = Nature Genetics | volume = 37 | issue = 4 | pages = 423–8 | date = April 2005 | pmid = 15735645 | doi = 10.1038/ng1526 }} Further reading{{refbegin|33em}}
1 : EF-hand-containing proteins |
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