
Myomesin is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
family
Family (from ) is a Social group, group of people related either by consanguinity (by recognized birth) or Affinity (law), affinity (by marriage or other relationship). It forms the basis for social order. Ideally, families offer predictabili ...
found in the
M-line M line may refer to:
* M-line (mittel line or middle line), a structure in a muscle sarcomere
* M Ocean View, a light rail and former streetcar line in San Francisco, California
* M-Line Trolley, a streetcar line in Dallas, Texas
* M (Los Angeles R ...
of the
sarcomere
A sarcomere (Greek σάρξ ''sarx'' "flesh", μέρος ''meros'' "part") is the smallest functional unit of striated muscle tissue. It is the repeating unit between two Z-lines. Skeletal striated muscle, Skeletal muscles are composed of tubular ...
structure. Myomesin has various forms throughout the body in
striated muscles with specialized functions. This includes both
slow and
fast
Fast or FAST may refer to:
Arts and entertainment
* "Fast" (Juice Wrld song), 2019
* "Fast" (Luke Bryan song), 2016
* "Fast" (Sueco song), 2019
* "Fast" (GloToven song), 2019
* ''Fast'', an album by Custom, 2002
* ''Fast'', a 2010 short fil ...
muscle fibers. Myomesin are made of 13 domains including a unique
N-terminal
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 amin ...
followed by two
immunoglobulin
An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...
-like (Ig) domains, five
fibronectin type III (Fn) domains, five more Ig domains. These domains all promote binding which indicates that myomesin is regulated through binding.
Functions
Sarcomere structure

Myomesin plays an important role in the structure of sarcomeres. They are found in the
M-band region of the sarcomere, between the thick filaments (
myosin
Myosins () are a Protein family, family of motor proteins (though most often protein complexes) best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are adenosine triphosphate, ATP- ...
). Its main purpose in this setting is to provide structural integrity by linking the antiparallel myosin fibers and titin filaments which are connected to the
Z-disc
A sarcomere (Greek σάρξ ''sarx'' "flesh", μέρος ''meros'' "part") is the smallest functional unit of striated muscle tissue. It is the repeating unit between two Z-lines. Skeletal muscles are composed of tubular muscle cells (called muscl ...
s.
These myosin filaments form a hexagonal lattice with titin and myomesin. This shape allows the M-band to withstand large conformational changes during muscle contraction and return to their original shape upon relaxation.
Since the Z-disc region of the sarcomere is very stiff and unable to bend for contraction, the elastic activity of myomesin in the M-band is what makes muscle contraction possible as it acts as a molecular spring.
Sarcomere assembly
In addition to sarcomere activity, it has been shown that myomesin also plays a role in the assembly of the sarcomere. In order for myomesin to be implemented into the sarcomere, myosin and titin must be present, indicating that myomesin is the last component to be added during assembly of the lattice. It is believed that this postponed addition is due to the role of myomesin to act as an "integrity check" to ensure the sarcomere has been formed correctly and monitor its integrity. This is extremely important as if even one piece of the M-line is missing, the
A-band of the sarcomere will collapse and the muscle will be paralyzed.
Response to injury
Myomesin has also been shown to play a role in injury response and expression. It was previously thought that myosin chaperones were the first alert of sarcomere damage, but recent studies show a flux of expression the
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
myomesin1a much earlier than that of the myosin, suggesting that there is a myomesin-dependent injury response pathway in striated muscles. Additionally, it is thought that this gene could be used as an enhanced
biomarker
In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...
for sarcomere damage compared to the current biomarker,
muscle creatine kinase (CKM). When tested
in vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, an ...
in
zebrafish
The zebrafish (''Danio rerio'') is a species of freshwater ray-finned fish belonging to the family Danionidae of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (an ...
, myom1a expression was displayed much earlier than creatine kinase, indicating that the latter is less specific to muscle diseases. This supports the use of myomesin
assay
An assay is an investigative (analytic) procedure in laboratory medicine, mining, pharmacology, environmental biology and molecular biology for qualitatively assessing or quantitatively measuring the presence, amount, or functional activity ...
s for detection of muscular
pathologies earlier than the current practices.
Myomesin variants

There are three types of myomesin that are found in various striated muscles of the body: myomesin 1,
myomesin 2, and myomesin 3. It is thought that each myomesin binds to myosin in a different spot, regulating the formation of the M-band.
Myomesin 1
Myomesin 1 is the most researched of the forms of myomesin due to its presence in all striated muscles and that it is the largest of the myomesin class. It is sometimes just simply called myomesin because of it widespread expression. Myomesin 1 is found in mainly on the M4/M4' lines of the M-band. It is encoded by the ''
MYOM1'' gene. There are two variants of myomesin 1, one located between the My6 and My7 domains, and the other at the end of the C-terminal after the My13 domain. The prior is known as the
embryonic heart (EH)-sequence and the latter, which has only been found in birds, is called the H or S splice variant (H is for heart and S is for skeletal). EH-myomesin can be found during embryonic development of the human heart (later replaced by myomesin 2). As the muscle matures, EH-myomesin is downregulated in favor of myomesin 1 with no genetic variations.
Myomesin 2
Myomesin 2 (also known as
M-protein) is located in the M1 line of the M-band. It is encoded by the ''
MYOM2'' gene. There is currently only one known variant of myomesin 2 and it can be found in fast skeletal muscles and adult
cardiac muscle
Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall o ...
s.
Myomesin 2 has been shown to have an inverse relationship with the expression of EH-myomesin; as cardiac muscles mature, EH-myomesin is downregulated while myomesin 2 is upregulated.
Myomesin 3
Myomesin 3 is the least researched in the myomesin class due to it being the most recently discovered. It is encoded by the ''
MYOM3'' gene. It is located in the M6/M6' lines of the M-band and is expressed in
intermediate skeletal muscles and adult cardiac muscles (specifically in the left
ventricle and left
atrium).
''MYOM3'' is especially expressed in
neonatal skeletal muscles,
extraocular muscles
The extraocular muscles, or extrinsic ocular muscles, are the seven extrinsic muscles of the eye in human eye, humans and other animals. Six of the extraocular muscles, the four recti muscles, and the superior oblique muscle, superior and inferior ...
, slow muscles, and
IIA skeletal fibers. Myomesin 3 is the only member of the myomesin protein family to be completely absent from cardiac expression. Myomesin 3 displays an inverse relationship with myomesin 2.
Pathologies
Myocardial atrophy
Deficiency in myomesin 1 causes atrophy and dysfunction in its tissue.
In
cardiomyocytes
Cardiac muscle (also called heart muscle or myocardium) is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall of ...
, sarcomere length and uniformity are decreased when ''MYOM1'' is absent, resulting in smaller cardiomyocytes. This is also linked to issues in contractile function due to the disruption of calcium levels in the tissue.
Dilated cardiomyopathy (DCM)
Re-emergence of EH-myomesin in adult cardiac muscles has been associated with
dilated cardiomyopathy
Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. C ...
. It is still uncertain if this expression is to help stabilize the sarcomere during strenuous contractions or if it is a result of misaligned sarcomere filaments due to lessened contractile forces. It has been shown that this uncommon expression is the result of altered
alternative splicing
Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene ma ...
.
References
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Proteins