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 Hypertrophic cardiomyopathy (HCM, or HOCM when obstructive) is a condition in which the heart becomes thickened without an obvious cause. The parts of the heart most commonly affected are the interventricular septum and the ventricles. This r ...

ischemic cardiomyopathy Ischemic cardiomyopathy is a type of cardiomyopathy caused by a narrowing of the coronary arteries which supply blood to the heart. Typically, patients with ischemic cardiomyopathy have a history of acute myocardial infarction, however, it may occ ...

and others, ALC-2 expression is altered.

Structure

Human ALC-2 protein has a molecular weight of 19.4 kDa and is composed of 175 amino acids. ALC-2 is an EF hand protein that binds to the neck region of alpha myosin heavy chain. 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 Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...

-15 and

/ Asparagine-14.

Function

ALC-2 expression has proven to be a useful marker of cardiac muscle chamber distinction, development and differentiation. 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

embryo An embryo is an initial stage of development of a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male spe ...

nic 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 Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscl ...

, uterus, and liver. This atrial patterning occurs prior to

septation In biology, a septum (Latin for ''something that encloses''; plural septa) is a wall, dividing a cavity or structure into smaller ones. A cavity or structure divided in this way may be referred to as septate. Examples Human anatomy * Interatri ...

. Expression of ALC-2 has been shown to correlate with expression of alpha-myosin heavy chain in cardiac atria of non-human primates. ALC-2 and VLC-2 appear to function in the stabilization of thick filaments and regulation of contractility in the vertebrate heart. 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. In disease models, ALC-2 expression in some instances can be downregulated and replaced by the ventricular isoform (VLC-2). In spontaneously

hypertensive Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

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 Ventricular hypertrophy (VH) is thickening of the walls of a ventricle (lower chamber) of the heart. Although left ventricular hypertrophy (LVH) is more common, right ventricular hypertrophy (RVH), as well as concurrent hypertrophy of both ventri ...

. 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. In a porcine model of left atrial remodeling following

mitral regurgitation Mitral regurgitation (MR), also known as mitral insufficiency or mitral incompetence, is a form of valvular heart disease in which the mitral valve is insufficient and does not close properly when the heart pumps out blood.

, VLC-2 was shown to be upregulated. Human ALC-2 is phosphorylated at its

N-terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...

-15 by a cardiac-specific myosin light chain kinase; ALC-2 has a

serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...

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 In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

). Whether

-14 of human ALC-2 is also phosphorylated remains to be determined. Endogenous

level is around 30% of the total ALC-2. Alpha(1)-adrenergic stimulation by phenylephrine in atrial muscle strips showed an 80% increase in ALC-2

coordinate with enhanced contractile force, which was inhibited by both Rho kinase and myosin light chain kinase inhibition. In a canine model of atrial fibrillation, decreased atrial contractility was associated with decreased ALC-2 and myosin binding protein C

. Moreover, the slow force response induced by stretch in human atrial muscle was shown to be modulated by enhanced

of ALC-2 by myosin light chain kinase.

Clinical Significance

Patients with

shown an increased expression of ALC-2 in whole heart tissue. In patients with mitral valve disease,

, dilated cardiomyopathy, coronary heart disease and pressure overload-induced

, 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. In patients with congenital atrial septal defect carrying a missense mutation

Ile Ile may refer to: * iLe, a Puerto Rican singer * Ile District (disambiguation), multiple places * Ilé-Ifẹ̀, an ancient Yoruba city in south-western Nigeria * Interlingue (ISO 639:ile), a planned language * Isoleucine, an amino acid * Another ...

820 Asn in alpha myosin heavy chain, it was shown that binding of ALC-2 to alpha myosin heavy chain is disrupted.

Interactions

ALC-2 is shown to interact with: * MYH6

Structure

Function

Clinical Significance

Interactions

References

Further reading