Myocardin

Template:Short description Template:Cs1 config Template:Infobox gene Myocardin is a protein that in humans is encoded by the MYOCD gene.

Myocardin is a smooth muscle cell and cardiac muscle cell-specific transcriptional coactivator of serum response factor (SRF). When expressed in smooth muscle precursor cells and abnormally in nonmuscle cells, myocardin can induce smooth muscle cell differentiation. Myocardin can also function in the differentiation of myocardial cells.

File:Annotated AlphaFold Myocardin Structure.png

The SAP DNA-binding domain is shown in purple and spans amino acids 541–807. The basic region, in turquoise, spans amino acids 280-295. The glutamine-rich region, in brown, spans amino acids 321-346. The leucine zipper analog, shown in green, spans amino acids 513-556. Domains for binding of protein partners, MEF2C and HCAC5, are shown in magenta (spanning amino acids 12-27) and orange (spanning amino acids 153-205), respectively.

Structure

Myocardin consists of four distinct regions, one of which is the SAF-A/B, Acinus, and PIAS (SAP) domain. SAP domains are highly conserved motifs containing alpha helices that generally contain hydrophobic, polar, and bulky amino acids.

Myocardin also contains a basic region and a glutamine-rich region believed to be involved in binding SRF.

Through a series of deletion mutations, researchers have also identified a dimerization motif spanning amino acid residues 513–713, containing an alpha helical leucine zipper analog between residues 513-556.

Function

Myocardin is a transcriptional coactivator, enhancing the activity of specific genes involved in smooth muscle development and function by interacting with transcription factor, SRF. Myocardin can induce smooth muscle cell differentiation when it is expressed in appropriate cells. Researchers have also found that myocardin plays a role in myocardial cell differentiation by inhibiting myocardin in Xenopus embryos.

Amino acid residues 541–807 of myocardin are believed to play a key role in mediating its ability to activate transcription. Upon its initial discovery, researchers fused myocardin with the well studied GAL 4 transcription factor and examined how the regulation of GAL4-associated genes was affected. Myocardin is believed to activate transcription by binding to CArG box regions of DNA, characterized by the sequence CC(A/T)₆GG, of muscle function genes, because mutations to these regions have led to an observed reduction in their sensitivity to myocardin.

Myocardin contributes to the expression of cardiac muscle cell differentiation by interacting with myocyte enhancer factor 2 (MEF2) or SRF, enhancing their transcriptional activity. Conversely, in smooth muscle cells, myocardin associates with the transcriptional coactivator, p300, stimulting acetylation and consequent expression of smooth muscle cell genes, as well as acetylation of myocardin itself. Class II HDAC proteins are responsible for histone deacetylation, and have been found to inhibit the activity of myocardin.

Gene

There are four known transcript variants (isoforms) of the MYOCD gene. While the exact function of each isoform is not well understood, it is suggested that each variant may have tissue-specific functions. Real-time polymerase chain reaction (RT-PCR) have realved two tissue-specific isoforms, myocardin-856, expressed in smooth muscle and found to interact with SRF, and myocardin-935, expressed in cardiac muscle and found to interact with either MEF2 or SRF.

Expression of MYOCD is specifically observed in the cardaic and smooth muscle tissues, such as the arteries, female reproductive organs and colon. Expression is also observed in the heart, aorta, and bladder, tissues in which smooth muscle can be found.