Myocardin

Myocardin is a protein that in humans is encoded by the MYOCD gene.^[5][6][7][8]

MYOCD
Identifiers
Aliases	MYOCD, MYCD, myocardin, MGBL
External IDs	OMIM: 606127; MGI: 2137495; HomoloGene: 17043; GeneCards: MYOCD; OMA:MYOCD - orthologs
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17p12 Start 12,665,890 bp[1] End 12,768,949 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 B3 Start 65,067,387 bp[2] End 65,160,815 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in tail of epididymis saphenous vein cardiac muscle tissue of right atrium right ventricle nipple urethra right coronary artery superficial temporal artery ascending aorta smooth muscle tissue Top expressed in ascending aorta aortic valve tunica media of zone of aorta umbilical cord myocardium of ventricle interventricular septum atrium vas deferens migratory enteric neural crest cell cumulus cell More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transcription coactivator activity R-SMAD binding DNA-binding transcription activator activity, RNA polymerase II-specific transcription factor binding histone deacetylase binding core promoter sequence-specific DNA binding protein binding histone acetyltransferase binding cis-regulatory region sequence-specific DNA binding RNA polymerase II-specific DNA-binding transcription factor binding RNA polymerase II cis-regulatory region sequence-specific DNA binding Cellular component nucleus Biological process cellular component maintenance positive regulation of transforming growth factor beta receptor signaling pathway response to hypoxia regulation of transcription, DNA-templated negative regulation of cyclin-dependent protein serine/threonine kinase activity urinary bladder development regulation of transcription by RNA polymerase II vascular associated smooth muscle cell differentiation cardiac ventricle development regulation of cell growth by extracellular stimulus positive regulation of DNA-binding transcription factor activity negative regulation of transcription by RNA polymerase II smooth muscle cell differentiation transcription, DNA-templated regulation of phenotypic switching vasculogenesis positive regulation of transcription, DNA-templated uterus development negative regulation of skeletal muscle cell differentiation negative regulation of cardiac muscle cell apoptotic process heart development muscle cell differentiation negative regulation of amyloid-beta clearance positive regulation of smooth muscle cell differentiation regulation of myoblast differentiation regulation of histone acetylation positive regulation of cell population proliferation negative regulation of myotube differentiation positive regulation of transcription from RNA polymerase II promoter involved in smooth muscle cell differentiation positive regulation of cardiac vascular smooth muscle cell differentiation positive regulation of cardiac muscle cell differentiation ventricular cardiac muscle cell differentiation positive regulation of DNA binding lung alveolus development digestive tract development positive regulation of smooth muscle contraction cardiocyte differentiation ductus arteriosus closure positive regulation of transcription by RNA polymerase II negative regulation of cell population proliferation regulation of smooth muscle cell differentiation transcription by RNA polymerase II cardiac muscle cell differentiation positive regulation of gene expression negative regulation of vascular associated smooth muscle cell proliferation negative regulation of vascular associated smooth muscle cell migration negative regulation of platelet-derived growth factor receptor-beta signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 93649 214384 Ensembl ENSG00000141052 ENSMUSG00000020542 UniProt Q8IZQ8 Q8VIM5 RefSeq (mRNA) NM_001146312 NM_001146313 NM_153604 NM_001378306 NM_145136 NM_146386 RefSeq (protein) NP_001139784 NP_705832 NP_001365235 NP_660118 NP_666498 Location (UCSC) Chr 17: 12.67 – 12.77 Mb Chr 11: 65.07 – 65.16 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Myocardin is a smooth muscle cell and cardiac muscle cell-specific transcriptional coactivator of serum response factor (SRF).^[7][8] When expressed in smooth muscle precursor cells and abnormally in nonmuscle cells, myocardin can induce smooth muscle cell differentiation.^[9] Myocardin can also function in the differentiation of myocardial cells.^[8]

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.^[5] SAP domains are highly conserved motifs containing alpha helices that generally contain hydrophobic, polar, and bulky amino acids.^[10][11]

Myocardin also contains a basic region and a glutamine-rich region believed to be involved in binding SRF.^[5]

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.^[12]

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.^[12][13][14] Myocardin can induce smooth muscle cell differentiation when it is expressed in appropriate cells.^[15] Researchers have also found that myocardin plays a role in myocardial cell differentiation by inhibiting myocardin in Xenopus embryos.^[13]

Amino acid residues 541–807 of myocardin are believed to play a key role in mediating its ability to activate transcription.^[13] 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.^[13] 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.^[13]

Myocardin contributes to the expression of cardiac muscle cell differentiation by interacting with myocyte enhancer factor 2 (MEF2) or SRF, enhancing their transcriptional activity.^[16] 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.^[17][18] Class II HDAC proteins are responsible for histone deacetylation, and have been found to inhibit the activity of myocardin.^[17]

Gene

There are four known transcript variants (isoforms) of the MYOCD gene.^[16][19] While the exact function of each isoform is not well understood, it is suggested that each variant may have tissue-specific functions.^[20] 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.^[16]

Expression of MYOCD is specifically observed in the cardaic and smooth muscle tissues, such as the arteries, female reproductive organs and colon.^[13][15][21] Expression is also observed in the heart, aorta, and bladder, tissues in which smooth muscle can be found.^[15][22]