MYOM2

M-protein, also known as Myomesin-2 is a is_associated_with::protein that in humans is encoded by the MYOM2 is_associated_with::gene. M-protein is expressed in adult is_associated_with::cardiac muscle and fast is_associated_with::skeletal muscle, and functions to stabilize the three-dimensional arrangement of proteins comprising M-band structures.

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 is_associated_with::immunoglobulin/is_associated_with::fibronectin repeats; M-protein contains two is_associated_with::immunoglobulin C2-type repeats in the N-terminal region, five is_associated_with::fibronectin type III repeats in the central region, and an additional four is_associated_with::immunoglobulin C2-type repeats in the C-terminal region. M-protein is expressed only in striated muscle, including fast is_associated_with::skeletal muscle and is_associated_with::cardiac muscle.

Function
M-protein exhibits a different pattern of expression in cardiac and is_associated_with::skeletal muscle, as well as fast- versus slow-is_associated_with::skeletal muscle during development, suggesting different regulatory mechanisms for expression quantity and temporal appearance. In is_associated_with::cardiac muscle, expression of M-protein continues to increase from neonatal to adult; however, in is_associated_with::skeletal muscle, M-protein is_associated_with::mRNA expression is biophasic. M-protein is initially present in both slow- and fast-is_associated_with::skeletal muscle embryonic fibers, then M-protein is suppressed in slow fibers. Interestingly, the embryonic splice variant of myomesin, termed EH-myomesin, is expressed in a complementary pattern with M-protein during development in higher is_associated_with::vertebrates. It was also shown that the is_associated_with::mRNA expression of M-protein is exquisitely sensitive to is_associated_with::thyroid hormone (T3); M-protein expression, but not is_associated_with::MYOM1 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 is_associated_with::hormone response elements near the transcriptional start point.

The giant protein is_associated_with::titin, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The C-terminal end of the is_associated_with::titin string extends into the M line, where it binds tightly to M-band constituents is_associated_with::MYOM1 and M-protein, of apparent molecular masses of 190 kD and 165 kD, respectively. M-protein functions to stabilize the M-line cross-linking is_associated_with::titin and is_associated_with::myosin; the central portion of M-protein is around the M1-line, and the N-terminal and C-terminal regions are arranged along is_associated_with::thick filaments.

An animal model of is_associated_with::thyroid hormone (T3)-induced is_associated_with::cardiac hypertrophy showed that T3 rapidly reduced levels of M-protein; and is_associated_with::siRNA reduction of M-protein in neonatal is_associated_with::cardiomyocytes 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 is_associated_with::sarcomere function.

M-protein can be post-translationally modified in vivo. M-protein fragments generated via cleavage by is_associated_with::matrix metalloproteinase 2 in left ventricular is_associated_with::myocardium have been identified as a factor in the development of is_associated_with::pulmonary hypertension and is_associated_with::ascites in is_associated_with::broiler chickens. Another study demonstrated that M-protein is S-thiolated during post-ischemic is_associated_with::reperfusion. It was also determined that domains Mp2 to Mp3 in M-protein binds is_associated_with::myosin, and this specific interaction can be regulated by phosphorylation.

Interactions
M-protein interacts with:
 * is_associated_with::Titin
 * is_associated_with::CKM
 * is_associated_with::MYH7