MYL3

Last updated
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
Orthologs
SpeciesHumanMouse
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 [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Myosin essential light chain (ELC), ventricular/cardiac isoform is a protein that in humans is encoded by the MYL3 gene. [5] [6] [7] 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.

Contents

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, [8] 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. [9] 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, [10] and further studies demonstrated that this region of ELC modulates the affinity of myosin for actin. [11]

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. [12] Five mutations in MYL3 have been identified to date: M149V, R154H, E56G, A57G and E143K. [13] [14] [15] [16] 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. [12]

Related Research Articles

Hypertrophic cardiomyopathy is a condition in which muscle tissues of the heart become thickened without an obvious cause. The parts of the heart most commonly affected are the interventricular septum and the ventricles. This results in the heart being less able to pump blood effectively and also may cause electrical conduction problems.

<span class="mw-page-title-main">Desmin</span> Mammalian protein found in humans

Desmin is a protein that in humans is encoded by the DES gene. Desmin is a muscle-specific, type III intermediate filament that integrates the sarcolemma, Z disk, and nuclear membrane in sarcomeres and regulates sarcomere architecture.

<span class="mw-page-title-main">Titin</span> Largest-known protein in human muscles

Titin is a protein that in humans is encoded by the TTN gene. Titin is a giant protein, greater than 1 µm in length, that functions as a molecular spring that is responsible for the passive elasticity of muscle. It comprises 244 individually folded protein domains connected by unstructured peptide sequences. These domains unfold when the protein is stretched and refold when the tension is removed.

<span class="mw-page-title-main">MYH7</span> Protein-coding gene in the species Homo sapiens

MYH7 is a gene encoding a myosin heavy chain beta (MHC-β) isoform expressed primarily in the heart, but also in skeletal muscles. This isoform is distinct from the fast isoform of cardiac myosin heavy chain, MYH6, referred to as MHC-α. MHC-β is the major protein comprising the thick filament in cardiac muscle and plays a major role in cardiac muscle contraction.

<span class="mw-page-title-main">TNNI3</span> Protein-coding gene in the species Homo sapiens

Troponin I, cardiac muscle is a protein that in humans is encoded by the TNNI3 gene. It is a tissue-specific subtype of troponin I, which in turn is a part of the troponin complex.

<span class="mw-page-title-main">TNNT2</span> Protein-coding gene in the species Homo sapiens

Cardiac muscle troponin T (cTnT) is a protein that in humans is encoded by the TNNT2 gene. Cardiac TnT is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration.

<span class="mw-page-title-main">TPM1</span> Protein-coding gene in the species Homo sapiens

Tropomyosin alpha-1 chain is a protein that in humans is encoded by the TPM1 gene. This gene is a member of the tropomyosin (Tm) family of highly conserved, widely distributed actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells.

<span class="mw-page-title-main">Myosin light chain</span> Small polypeptide subunit of myosin

A myosin light chain is a light chain of myosin. Myosin light chains were discovered by Chinese biochemist Cao Tianqin when he was a graduate student at the University of Cambridge in England.

<span class="mw-page-title-main">ACTC1</span> Protein-coding gene in the species Homo sapiens

ACTC1 encodes cardiac muscle alpha actin. This isoform differs from the alpha actin that is expressed in skeletal muscle, ACTA1. Alpha cardiac actin is the major protein of the thin filament in cardiac sarcomeres, which are responsible for muscle contraction and generation of force to support the pump function of the heart.

<span class="mw-page-title-main">Myosin binding protein C, cardiac</span> Protein-coding gene in the species Homo sapiens

The myosin-binding protein C, cardiac-type is a protein that in humans is encoded by the MYBPC3 gene. This isoform is expressed exclusively in heart muscle during human and mouse development, and is distinct from those expressed in slow skeletal muscle (MYBPC1) and fast skeletal muscle (MYBPC2).

<span class="mw-page-title-main">TNNI1</span> Protein-coding gene in the species Homo sapiens

Troponin I, slow skeletal muscle is a protein that in humans is encoded by the TNNI1 gene. It is a tissue-specific subtype of troponin I, which in turn is a part of the troponin complex.

<span class="mw-page-title-main">MYH10</span> Protein-coding gene in the species Homo sapiens

Myosin-10 also known as myosin heavy chain 10 or non-muscle myosin IIB (NM-IIB) is a protein that in humans is encoded by the MYH10 gene. Non-muscle myosins are expressed in a wide variety of tissues, but NM-IIB is the only non-muscle myosin II isoform expressed in cardiac muscle, where it localizes to adherens junctions within intercalated discs. NM-IIB is essential for normal development of cardiac muscle and for integrity of intercalated discs. Mutations in MYH10 have been identified in patients with left atrial enlargement.

<span class="mw-page-title-main">MYL2</span> Protein-coding gene in the species Homo sapiens

Myosin regulatory light chain 2, ventricular/cardiac muscle isoform (MLC-2) also known as the regulatory light chain of myosin (RLC) is a protein that in humans is encoded by the MYL2 gene. This cardiac ventricular RLC isoform is distinct from that expressed in skeletal muscle (MYLPF), smooth muscle (MYL12B) and cardiac atrial muscle (MYL7).

<span class="mw-page-title-main">MYH6</span> Protein-coding gene in the species Homo sapiens

Myosin heavy chain, α isoform (MHC-α) is a protein that in humans is encoded by the MYH6 gene. This isoform is distinct from the ventricular/slow myosin heavy chain isoform, MYH7, referred to as MHC-β. MHC-α isoform is expressed predominantly in human cardiac atria, exhibiting only minor expression in human cardiac ventricles. It is the major protein comprising the cardiac muscle thick filament, and functions in cardiac muscle contraction. Mutations in MYH6 have been associated with late-onset hypertrophic cardiomyopathy, atrial septal defects and sick sinus syndrome.

<span class="mw-page-title-main">MYL4</span> Protein-coding gene in the species Homo sapiens

Atrial Light Chain-1 (ALC-1), also known as Essential Light Chain, Atrial is a protein that in humans is encoded by the MYL4 gene. ALC-1 is expressed in fetal cardiac ventricular and fetal skeletal muscle, as well as fetal and adult cardiac atrial tissue. ALC-1 expression is reactivated in human ventricular myocardium in various cardiac muscle diseases, including hypertrophic cardiomyopathy, dilated cardiomyopathy, ischemic cardiomyopathy and congenital heart diseases.

<span class="mw-page-title-main">Obscurin</span> Protein-coding gene in the species Homo sapiens

Obscurin is a protein that in humans is encoded by the OBSCN gene. Obscurin belongs to the family of giant sarcomeric signaling proteins that includes titin and nebulin. Obscurin is expressed in cardiac and skeletal muscle, and plays a role in the organization of myofibrils during sarcomere assembly. A mutation in the OBSCN gene has been associated with hypertrophic cardiomyopathy and altered obscurin protein properties have been associated with other muscle diseases.

<span class="mw-page-title-main">MYOZ2</span> Protein-coding gene in the species Homo sapiens

Myozenin-2, also referred to as Calsarcin-1, is a protein that in humans is encoded by the MYOZ2 gene. The Calsarcin-1 isoform is a muscle protein expressed in cardiac muscle and slow-twitch skeletal muscle, which functions to tether calcineurin to alpha-actinin at Z-discs, and inhibit the pathological cardiac hypertrophic response. This differs from the fast-skeletal muscle isoform, calsarcin-2.

<span class="mw-page-title-main">PDLIM3</span> Protein-coding gene in the species Homo sapiens

Actin-associated LIM protein (ALP), also known as PDZ and LIM domain protein 3 is a protein that in humans is encoded by the PDLIM3 gene. ALP is highly expressed in cardiac and skeletal muscle, where it localizes to Z-discs and intercalated discs. ALP functions to enhance the crosslinking of actin by alpha-actinin-2 and also appears to be essential for right ventricular chamber formation and contractile function.

<span class="mw-page-title-main">MYL7</span> Protein-coding gene in the species Homo sapiens

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. 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.

<span class="mw-page-title-main">MYBPC2</span> Protein-coding gene in the species Homo sapiens

Myosin binding protein C, fast type is a protein that in humans is encoded by the MYBPC2 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000160808 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 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.

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