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MYL4  -  myosin, light chain 4, alkali; atrial,...

Homo sapiens

Synonyms: ALC1, AMLC, GT1, MLC1, Myosin light chain 1, embryonic muscle/atrial isoform, ...
 
 
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Disease relevance of MYL4

 

Psychiatry related information on MYL4

 

High impact information on MYL4

  • Whereas sequences proximal to the two MLC promoters do not appear to contain tissue-specific regulatory elements, a 0.9-kb DNA segment, located greater than 24 kb downstream of the MLC1 promoter, dramatically increases CAT gene expression in differentiated myotubes but not in undifferentiated myoblasts or nonmuscle cells [7].
  • Two skeletal myosin light chains, MLC1 and MLC3, are generated from a single gene by transcription from two different promoters and alternate splicing of the pre-mRNAs [7].
  • We conclude that the expression of ALC-1 in the human heart modulates cross-bridge cycling kinetics accelerating shortening velocity and isometric tension production [5].
  • This study was designed to examine the expression of atrial/fetal-type myosin light chain 1 (ALC1) in human ventricles with old myocardial infarction and in control hearts [2].
  • The expression of immunoreactive (ir) ALC1 was examined in the subendocardial and subepicardial myocardium of the infarcted and the noninfarcted regions in the left ventricles with old myocardial infarction (n = 12) and of the control left ventricles (n = 8) [2].
 

Biological context of MYL4

  • In fact, developed left ventricular pressure as well as maximal velocity of pressure development and relaxation were significantly higher in shunt-operated TGR/hALC-1 as compared to shunt-operated WKY [1].
  • Comparison of overall nucleotide sequences of ALC1 and VLC1 cDNA clones has revealed that, while these two inserts show significant DNA sequence homology (78.4%) with respect to their coding regions, the 5'- and 3'-untranslated regions are highly divergent [8].
  • We have isolated essentially full-length cDNA clones for atrial (ALC1) and ventricular (VLC1) myosin alkali light chains from a human fetal heart cDNA library [8].
  • This VLC-1/ALC-1 isoform shift is correlated with an increase in cross-bridge cycling kinetics as measured using skinned fibers from the hypertrophied ventricles of human hearts [9].
  • The gene coding for MLC1 and MLC3 is located on human chromosome 2 [10].
 

Anatomical context of MYL4

  • Using synthetic hVLC-1/1-15 as a TAT fusion peptide labeled with the fluorochrome TAMRA, we observed specific accumulation of the N-terminal MLC-1 peptide at the sarcomere predominantly within the actin-containing I-band, but also within the actin-myosin overlap zone (A-band) in intact adult cardiomyocytes [11].
  • RNA blot analysis shows that ALC1 mRNA is expressed in fetal ventricular and fetal skeletal muscles as well as fetal and adult atrial muscles and VLC1 mRNA is expressed in adult slow skeletal muscle as well as fetal and adult ventricular muscles [8].
  • We conclude that the reexpression of ALC1 in infarcted ventricles occurs as one of the regional responses to increased load and may be a useful biochemical marker for the appearance of fetal-type myocytes [2].
  • The weak activity of the MLC1 promoter was markedly enhanced in myotubes when DNA from the 3' gene flanking sequence was included in the chloramphenicol acetyltransferase constructs [12].
  • Approximately 120 nucleotides of the MLC1 promoter and 80 nucleotides of the MLC3 promoter were sufficient for the transcriptional activation in primary myotubes and to a lower degree also in fibroblasts and hepatocytes [12].
 

Associations of MYL4 with chemical compounds

  • No differences were detected between FLC-1 and ALC-1 using three different proteases and amino acid compositions were similar with the exception of glycine content [13].
  • Comparison of human FLC-1/ALC-1 with VLC-1 suggested marked structural and chemical differences in these light chain isotypes, in particular in the contents of methionine, proline, lysine and alanine residues [13].
  • Similarly, we investigated the expression of ALC-1 by two-dimensional polyacrylamide gel electrophoresis and the clinical and hemodynamic parameters of the patients with hypertrophic cardiomyopathy [14].
  • In the placebo group, MLC-1 was associated with increased mortality (29% vs 12%, p = 0.025), whereas there was no significant difference among patients receiving flosequinan [3].
  • Further subgrouping of ALC patients showed that those with alcohol intake ranging between 100 and 200 g/day (ALC1) had malonildialdehyde and lipid hydroperoxide concentrations significantly lower than those with an intake higher than 200 g/day (ALC2) [15].
 

Physical interactions of MYL4

  • Synthetic N-terminal peptides revealed specific actin binding, with a significantly (P<0.01) lower dissociation constant (K(D)) for the hVLC-1/1-15-actin complex compared with the K(D) value of the hALC-1/1-15-actin complex [11].
 

Other interactions of MYL4

 

Analytical, diagnostic and therapeutic context of MYL4

  • Comparative peptide mapping studies and amino acid analyses were carried out on FLC-1 and ALC-1 [13].
  • Characterizing the functional effects of hALC-1 at the whole organ level represents a step towards gene therapy of heart failure [9].
  • The present study involves the determination of ALC1 content in a control group and in patients with aortic stenosis or insufficiency before and 56 +/- 23 months after valve replacement and compares the hemodynamic and angiographic parameters [18].
  • A sequence analysis revealed that BpUGAT is related to the glycosyltransferase 1 (GT1) family of the glycosyltransferase superfamily (according to the Carbohydrate-Active Enzymes (CAZy) data base) [19].
  • NRHC expressed large amounts of hALC-1 upon infection with AdCMV.hALC-1 which could easily been detected by protein staining and Western blot analysis [20].

References

  1. Human atrial myosin light chain 1 expression attenuates heart failure. Abdelaziz, A.I., Pagel, I., Schlegel, W.P., Kott, M., Monti, J., Haase, H., Morano, I. Adv. Exp. Med. Biol. (2005) [Pubmed]
  2. Increased expression and regional differences of atrial myosin light chain 1 in human ventricles with old myocardial infarction. Analyses using two monoclonal antibodies. Nakao, K., Yasue, H., Fujimoto, K., Jougasaki, M., Yamamoto, H., Hitoshi, Y., Takatsu, K., Miyamoto, E. Circulation (1992) [Pubmed]
  3. Relation of circulating cardiac myosin light chain 1 isoform in stable severe congestive heart failure to survival and treatment with flosequinan. Hansen, M.S., Stanton, E.B., Gawad, Y., Packer, M., Pitt, B., Swedberg, K., Rouleau, J.L. Am. J. Cardiol. (2002) [Pubmed]
  4. Renal tranplantation in type 1 glycogenosis. Failure to improve glucose metabolism. Emmett, M., Narins, R.G. JAMA (1978) [Pubmed]
  5. Regulation of human heart contractility by essential myosin light chain isoforms. Morano, M., Zacharzowski, U., Maier, M., Lange, P.E., Alexi-Meskishvili, V., Haase, H., Morano, I. J. Clin. Invest. (1996) [Pubmed]
  6. Association of WKL1/MLC1 with catatonic schizophrenia. Leegwater, P.A., Boor, P.K., Pronk, J.C., van der Knaap, M.S. Mol. Psychiatry (2002) [Pubmed]
  7. A muscle-specific enhancer is located at the 3' end of the myosin light-chain 1/3 gene locus. Donoghue, M., Ernst, H., Wentworth, B., Nadal-Ginard, B., Rosenthal, N. Genes Dev. (1988) [Pubmed]
  8. Molecular cloning and characterization of human atrial and ventricular myosin alkali light chain cDNA clones. Kurabayashi, M., Komuro, I., Tsuchimochi, H., Takaku, F., Yazaki, Y. J. Biol. Chem. (1988) [Pubmed]
  9. Functional characterization of the human atrial essential myosin light chain (hALC-1) in a transgenic rat model. Abdelaziz, A.I., Segaric, J., Bartsch, H., Petzhold, D., Schlegel, W.P., Kott, M., Seefeldt, I., Klose, J., Bader, M., Haase, H., Morano, I. J. Mol. Med. (2004) [Pubmed]
  10. Alkali myosin light chains in man are encoded by a multigene family that includes the adult skeletal muscle, the embryonic or atrial, and nonsarcomeric isoforms. Seidel, U., Bober, E., Winter, B., Lenz, S., Lohse, P., Goedde, H.W., Grzeschik, K.H., Arnold, H.H. Gene (1988) [Pubmed]
  11. Minigenes encoding N-terminal domains of human cardiac myosin light chain-1 improve heart function of transgenic rats. Haase, H., Dobbernack, G., Tünnemann, G., Karczewski, P., Cardoso, C., Petzhold, D., Schlegel, W.P., Lutter, S., Pierschalek, P., Behlke, J., Morano, I. FASEB J. (2006) [Pubmed]
  12. Identification of the functional promoter regions in the human gene encoding the myosin alkali light chains MLC1 and MLC3 of fast skeletal muscle. Seidel, U., Arnold, H.H. J. Biol. Chem. (1989) [Pubmed]
  13. Isolation of cardiac myosin light-chain isotypes by chromatofocusing. Comparison of human cardiac atrial light-chain 1 and foetal ventricular light-chain 1. Vincent, N.D., Cummins, P. Eur. J. Biochem. (1985) [Pubmed]
  14. Expression of atrial myosin light chains but not alpha-myosin heavy chains is correlated in vivo with increased ventricular function in patients with hypertrophic obstructive cardiomyopathy. Ritter, O., Luther, H.P., Haase, H., Baltas, L.G., Baumann, G., Schulte, H.D., Morano, I. J. Mol. Med. (1999) [Pubmed]
  15. Monitoring oxidative damage in patients with liver cirrhosis and different daily alcohol intake. Clot, P., Tabone, M., Aricò, S., Albano, E. Gut (1994) [Pubmed]
  16. Novel monoclonal antibodies specific for human cardiac myosin light-chain 1: useful tools for analysis of normal and pathological hearts. Fujimoto, K., Yasue, H., Nakao, K., Yamamoto, H., Hitoshi, Y., Jougasaki, M., Okumura, K., Ogawa, H., Takatsu, K., Miyamoto, E. J. Histochem. Cytochem. (1993) [Pubmed]
  17. Different time courses of cardiac contractile proteins after acute myocardial infarction. Mair, J., Wagner, I., Jakob, G., Lechleitner, P., Dienstl, F., Puschendorf, B., Michel, G. Clin. Chim. Acta (1994) [Pubmed]
  18. Hemodynamic performance and myosin light chain-1 expression of the hypertrophied left ventricle in aortic valve disease before and after valve replacement. Sütsch, G., Brunner, U.T., von Schulthess, C., Hirzel, H.O., Hess, O.M., Turina, M., Krayenbuehl, H.P., Schaub, M.C. Circ. Res. (1992) [Pubmed]
  19. UDP-glucuronic acid:anthocyanin glucuronosyltransferase from red daisy (Bellis perennis) flowers. Enzymology and phylogenetics of a novel glucuronosyltransferase involved in flower pigment biosynthesis. Sawada, S., Suzuki, H., Ichimaida, F., Yamaguchi, M.A., Iwashita, T., Fukui, Y., Hemmi, H., Nishino, T., Nakayama, T. J. Biol. Chem. (2005) [Pubmed]
  20. Analysis of the energetic state of heart cells after adenovirus-mediated expression of hALC-1. Zacharzowsky, U.B., Wolff, G., Kott, M., Haase, H., Bartsch, H., Nuessler, A.K., Baltas, L.G., Karawajew, L., Morano, I. J. Cell. Biochem. (2002) [Pubmed]
 
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