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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

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

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. M-protein is expressed in adult

cardiac muscle Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle th ...

and fast

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 ...

, 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 muscles are composed of tubular muscle cells (called musc ...

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), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...

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 collage ...

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 ami ...

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, 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 the protein is ...

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 in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...

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 family found in the M-line of the sarcomere structure. Myomesin has various forms throughout the body in striated muscles with specialized functions. This includes both slow and fast muscle fibers. Myomesin are made of 13 do ...

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

vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...

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 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 rect 66 216 386 25 ...

(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 detected ...

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 binds ...

s near the transcriptional start point. The giant protein

titin Titin (contraction for Titan protein) (also called connectin) 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 t ...

, 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 superfamily of motor proteins best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are ATP-dependent and responsible for actin-based motility. The first myosin ...

; 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 together ...

. 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 ventri ...

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 RNA at first non-coding RNA molecules, typically 20-24 (normally 21) base pairs in length, similar to miRNA, and operating wi ...

reduction of M-protein in neonatal

cardiomyocytes Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that ...

showed that the absence of M-protein causes significant

contractile Contractility refers to the ability for self-contraction, especially of the muscles or similar active biological tissue *Contractile ring in cytokinesis *Contractile vacuole *Muscle contraction **Myocardial contractility *See contractile cell for ...

dysfunction (77% reduction in contraction velocity), thus illuminating the importance of M-protein for normal

function. M-protein can be

post-translationally modified Post-translational modification (PTM) is the covalent and generally enzyme, enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by r ...

in vivo. M-protein fragments generated via cleavage by

matrix metalloproteinase 2 Gelatinase A, also known as MMP2 (, ''72-kDa gelatinase'', ''matrix metalloproteinase 2'', ''type IV collagenase'', ''3/4 collagenase'', ''matrix metalloproteinase 5'', ''72 kDa gelatinase type A'', ''collagenase IV'', ''collagenase type IV'', ''M ...

in left ventricular

myocardium Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that ...

have been identified as a factor in the development of pulmonary hypertension and

ascites Ascites 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 abdominal size, increased weight, ab ...

broiler chicken A 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 slaughte ...

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 (contraction for Titan protein) (also called connectin) 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 t ...

* CKM *

MYH7 MYH7 is a gene encoding a 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 the fast isoform of cardiac myosin heavy chain, MYH6, re ...

Structure

Function

Clinical Significance

Interactions

References

Further reading