Myomesin-2, also known as M-protein 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 ...

that in humans is encoded by the ''MYOM2''

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 ...

. M-protein is expressed in 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 ...

and fast

skeletal muscle Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...

, and functions to stabilize the three-dimensional arrangement of proteins comprising M-band structures in a

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

Human M-protein is 165.0 kDa and 1465 amino acids in length. ''MYOM2'' is localized to the human chromosome 8p23.3. M-protein belong to the superfamily of cytoskeletal proteins having

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 ...

fibronectin Fibronectin is a high- molecular weight (~500-~600 kDa) glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteins called integrins. Fibronectin also binds to other extracellular matrix proteins such as col ...

repeats; M-protein contains two

C2-type repeats in the

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 ...

region, five

type III repeats in the central region, and an additional four

C2-type repeats in the

C-terminal The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...

region. M-protein is expressed only in striated muscle, including fast

and

Function

M-protein exhibits a different pattern of expression in

cardiac The heart is a muscular organ found in humans and other animals. This organ pumps blood through the blood vessels. The heart and blood vessels together make the circulatory system. The pumped blood carries oxygen and nutrients to the tissu ...

and

, as well as fast- versus slow-

during development, suggesting different regulatory mechanisms for expression quantity and temporal appearance. In

, expression of M-protein continues to increase from neonatal to adult; however, in

, M-protein

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

expression is biophasic. M-protein is initially present in both slow- and fast-

embryonic fibers, then M-protein is suppressed in slow fibers. The embryonic splice variant of

myomesin Myomesin is a protein Protein family, family found in the M-line of the sarcomere structure. Myomesin has various forms throughout the body in Striated muscle tissue, striated muscles with specialized functions. This includes both Slow twitch fiber ...

, termed EH-myomesin, is expressed in a complementary pattern with M-protein during development in higher

vertebrate Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...

s. It was also shown that the

expression of M-protein is exquisitely sensitive to

thyroid hormone File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones triiodothyronine, T3 and T4 rect 376 268 820 433 Thyroid-stimulating hormone rect 411 200 849 266 Thyrotropin-releasing hormone rect 297 168 502 200 Hypothalamus r ...

(T3); M-protein expression, but not

MYOM1 Myomesin-1 is a protein that in humans is encoded by the ''MYOM1'' gene. Myomesin-1 is expressed in muscle cells and functions to stabilize the three-dimensional conformation of the thick filament. Embryonic forms of Myomesin-1 have been detecte ...

or its variant, EH-myomesin, was rapidly reduced by T3 in vivo and in vitro. The M-protein promoter is responsive to T3, and was suggested to contain thyroid

hormone response element ''Response elements'' are short sequences of DNA within a gene promoter or enhancer region that are able to bind specific transcription factors and regulate transcription of genes. Under conditions of stress, a transcription activator protein bi ...

s near the transcriptional start point. The giant protein

titin Titin (; also called connectin) is a protein that in humans is encoded by the ''TTN'' gene. The protein, which is over 1 μm in length, functions as a molecular spring that is responsible for the passive elasticity of muscle. It comprises 2 ...

, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The

end of the

string extends into the M line, where it binds tightly to M-band constituents

and M-protein, of apparent molecular masses of 190 kD and 165 kD, respectively. M-protein functions to stabilize the M-line cross-linking

and

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- ...

; the central portion of M-protein is around the M1-line, and the

and

regions are arranged along

thick filaments Myofilaments are the three protein filaments of myofibrils in muscle cells. The main proteins involved are myosin, actin, and titin. Myosin and actin are the ''contractile proteins'' and titin is an elastic protein. The myofilaments act tog ...

. An animal model of

(T3)-induced

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 ventr ...

showed that T3 rapidly reduced levels of M-protein; and

siRNA Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded non-coding RNA molecules, typically 20–24 base pairs in length, similar to microRNA (miRNA), and operating within the RN ...

reduction of M-protein in neonatal

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 ...

showed that the absence of M-protein causes significant contractile dysfunction (77% reduction in contraction velocity), thus illuminating the importance of M-protein for normal

function. M-protein can be

post-translationally modified In molecular biology, post-translational modification (PTM) is the covalent process of changing proteins following protein biosynthesis. PTMs may involve enzymes or occur spontaneously. Proteins are created by ribosomes, which translate mRNA into ...

in vivo. M-protein fragments generated via cleavage by

matrix metalloproteinase 2 72 kDa type IV collagenase also known as matrix metalloproteinase-2 (MMP-2) and gelatinase A is an enzyme that in humans is encoded by the ''MMP2'' gene. The ''MMP2'' gene is located on chromosome 16 at position 12.2. Function Proteins of the ...

in left ventricular

myocardium 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 ...

have been identified as a factor in the development of

pulmonary hypertension Pulmonary hypertension (PH or PHTN) is a condition of increased blood pressure in the pulmonary artery, arteries of the lungs. Symptoms include dypsnea, shortness of breath, Syncope (medicine), fainting, tiredness, chest pain, pedal edema, swell ...

and

ascites Ascites (; , meaning "bag" or "sac") is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdo ...

broiler chicken Breed broiler is any chicken (''Gallus gallus domesticus'') that is bred and raised specifically for meat production. Most commercial broilers reach slaughter weight between four and six weeks of age, although slower growing breeds reach slau ...

s. Another study demonstrated that M-protein is S-thiolated during post-ischemic reperfusion. It was also determined that domains Mp2 to Mp3 in M-protein binds

, and this specific interaction can be regulated by phosphorylation.

Clinical Significance

Interactions

M-protein interacts with: *

Titin Titin (; also called connectin) is a protein that in humans is encoded by the ''TTN'' gene. The protein, which is over 1 μm in length, functions as a molecular spring that is responsible for the passive elasticity of muscle. It comprises 2 ...

* CKM *

MYH7 Myosin-7 is a protein that in humans is encoded by the ''MYH7'' gene. It is the myosin heavy chain beta (MHC-β) isoform (slow twitch) expressed primarily in the heart, but also in skeletal muscles (type I fibers). This isoform is distinct from ...

Structure

Function

Clinical Significance

Interactions

References

Further reading