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Symbol MYOCD contributors: shn/mct - updated : 27-04-2017
HGNC name myocardin
HGNC id 16067
Location 17p12      Physical location : 12.569.206 - 12.670.651
Synonym symbol(s) MYCD
TYPE functioning gene
STRUCTURE 97.46 kb     15 Exon(s)
regulatory sequence Promoter
text structure
  • overexpression of SMAD3, but not SMAD2, inhibited MYOCD promoter activity
  • MAPPING cloned Y linked N status provisional
    Map pter - D17S1808 - D17S1803 - MYOCD - D17S947 - D17S1808 - cen
    TRANSCRIPTS type messenger
    text at least fifteen exons, including two alternately spliced exons designated 2a and 10a (PMID: 20385216 )
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 2817 - 938 expressed in cardiac muscle 2010 20385216
  • an N-terminal extension containing a MEF2 binding domain
  • could be regulated more strictly by an ERK1/2 pathway than isoforms excluding exon 10A
  • 14 - 2961 - 986 expressed in cardiac muscle 2010 20385216
  • without exon 2A
  • its activity was augmented in the presence of the cardiac transcription factor, MEF2C
  • an N-terminal extension containing a MEF2 binding domain
  • could be regulated more strictly by an ERK1/2 pathway than isoforms excluding exon 10A
  • 9 - 2344 - 684 in smooth muscle cell (SMC)-rich tissues (aorta and bladder) with little expression in heart 2010 20385216
    exon 2A, excluding exon 10A
    - - - - - in smooth muscle cell (SMC)-rich tissues (aorta and bladder) with little expression in heart 2010 20385216
  • excluding exon 10A
    Type restricted
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheartatrium  moderately Homo sapiens
     heartventricle  moderately Homo sapiens
    Digestiveintestinelarge intestinecolon moderately
     intestinesmall intestine  highly
     stomach   moderately
    Reproductivefemale systemuterus  lowly
     male systemprostate  lowly
    Urinarybladder   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularsmooth  specific Homo sapiens
    Muscularstriatumcardiacmyocardiumspecific Homo sapiens
    SystemCellPubmedSpeciesStageRna symbol
    Muscularmyocyte Homo sapiens
    cell lineage
    cell lines
  • cultured rat aortic SMCs (SMC) and endothelial cells (EC)
  • differentiated A404 cells, 10T1/2 cells, 10T1/2 cells treated with and NIH/3T3 cells
  • fluid/secretion
    at STAGE
    physiological period embryo
    Text heart muscle, smooth muscle, in progenitors of skeletal muscle
  • SAP (SAF-A/B,Acinus,PIAS) domain with two alpha helices
  • 3 RPEL repeats, RPEL motif bound to actin-related protein 5 (ACTR5) instead of conventional actin, resulting in a significant suppression of MYOCD activity
  • a stretch of glutamine residues
  • a MADS-box domain
  • C-terminal region contains a general transcription activation domain
  • N-terminal region comprises a basic and a Gln-rich domain
    interspecies ortholog to Myocd, Mus musculus
    ortholog to MYOCD, pan troglodytes
    ortholog to Myocd, Rattus norvegicus
  • SAP, acinus, and PIAS domain family of nuclear proteins
  • SAP-containing myocardin and MRTFs family
  • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
  • key factor in smooth muscle cell differentiation, that is constitutively located in the nucleus
  • basic FUNCTION
  • smooth and cardiac muscle-specific transcriptional coactivator of serum response factor
  • acts as a cofactor of SRF and modulates SRF-target genes
  • an important component of a molecular switch for the smooth muscle differentiation program (acting as a bifunctional switch for smooth versus skeletal muscle differentiation)
  • functions as a transcriptional repressor of MYOG, inhibiting skeletal muscle differentiation while activating SMC-specific genes
  • playing a role in repressing the skeletal muscle differentiation program and acts as a bifunctional molecular switch for the smooth versus skeletal muscle phenotypes
  • may be contributing to heart hypertrophy
  • cardiac- and smooth muscle-specific SAP domain transcription factor that functions as a coactivator for serum response factor (SRF), which controls genes involved in muscle differentiation and cell proliferation
  • necessary for insulin and IGF1 to induce hypertrophy
  • Regulates the expression of a set of cardiac and smooth muscle-specific genes
  • Plays a crucial role in cardiogenesis and differentiation of the smooth muscle cell lineage
  • a master regulator of smooth muscle gene expression
  • acts as a transcriptional repressor of Myog and as a bifunctional molecular switch for smooth versus skeletal muscle phenotypes
  • plays a critical role in differentiation of neural crest-derived SMCs populating the great arteries abd in maintenance of the contractile SMC phenotype
  • acts as a potent repressor of MyoD-mediated skeletal muscle cell differentiation in an SRF-CArG element independent manner
  • MYOCD controls amyloid beta-peptide clearance from cerebral vascular smooth muscle cells in Alzheimer’s disease (AD), the degree of cerebral amyloid angiopathy (CAA) and focal amyloid beta-peptide brain accumulations in animal models of CAA and AD
  • required for maintenance of cardiomyocyte structure and sarcomeric organization and cell-autonomous loss of myocardin in cardiac myocytes triggers programmed cell death
  • transcriptional coactivator required for maintenance of heart function and, ultimately, cardiomyocyte survival
  • may function there to extinguish the skeletal muscle program of differentiation in favor of smooth muscle cells differentiation
  • is a cardiac and smooth muscle-specific expressed transcriptional coactivator of Serum Response Factor (SRF) and is able to potently activate cardiac and smooth muscle gene expression during development
  • important molecular switch for the programs of SMC and cardiac myocyte differentiation
  • important regulatory role of SOX9 and MYOCD in controlling the transcription program during Smooth muscle cells (SMCs) transdifferentiation into chondrocytes
  • antagonism between SOX9 and MYOCD as central regulators in controlling SMC and chondrogenic gene transcription in SMCs in response to injury
  • is a muscle lineage-restricted transcriptional coactivator that has been shown to transduce extracellular signals to the nucleus required for SMC differentiation
  • functions as a transcriptional coactivator of SRF and is sufficient and necessary for smooth muscle gene expression
  • MYOCD plays likely a critical role in Ca(2+) signal-induced cardiomyocyte hypertrophy, which may serve as a novel mechanism that is important for cardiac hypertrophy
  • is a muscle-restricted transcriptional coactivator that activates a serum response factor (SRF)-dependent gene program required for cardiogenesis and embryonic survival
  • is required for maintenance of vascular and visceral smooth muscle homeostasis during postnatal development
  • MYOCD and its relative MRTF-A (MKL1) are transcriptional coactivators that control genes which promote smooth muscle differentiation
  • CELLULAR PROCESS nucleotide, transcription, regulation
  • MYOCD/BMP10 signaling pathway that regulates cardiomyocyte proliferation and apoptosis in the embryonic heart
  • a component
  • essential component of a molecular switch for the expression of contractile genes in smooth muscle and cardiac muscle cells
    DNA binds DNA as a multimer, probably a dimer
    small molecule
  • transcriptional repressor of MYOG
  • interacting with the DNA binding domain of serum response factor(SRF)
  • megakaryoblastic leukemia factor-1 (MKL1)
  • Foxo4
  • Nuclear receptor coactivator 3 (NCOA3)
  • Myocardin and TBX5 physically interact and their interaction domains were mapped to the basic domain and the coil domain of myocardin and TBX5, respectively
  • LMOD1 is a Smooth muscle cell-restricted SRF/MYOCD target gene
  • potent SRF coactivator, it transactivate the LMOD1 promoter and induce the endogenous transcript and protein in cells that otherwise exhibit very low levels of MYOCD expression
  • YAP1 protein regulates vascular smooth muscle cell phenotypic switch by interaction with MYOCD
  • MYOCD suppresses SOX9-mediated chondrogenic gene COL2A1 expression
  • is a direct target for EP300-mediated acetylation
  • SOX9 does not affect MYOCD expression but significantly reduces the expression of MYOCD/SRF-dependent smooth muscle genes, suggesting that down-regulation of SOX9 is a prerequisite for MYOCD activity
  • FOXF1 and FOXQ1 directly bind to distinct regions of MYOCD
  • TEAD1 is a novel general repressor of smooth muscle-specific gene expression through interfering with MYOCD binding to SRF
  • ANGPTL6 is a key regulator of MYOCD activity
  • KLF4 is a regulator of cardiac hypertrophy by modulating the expression and the activity of MYOCD
  • is a co-factor of serum response factor (SRF) and is considered to be the master regulator of VSMC differentiation
  • FOXF2 attenuated MYOCD/SRF signaling in smooth muscle cells through direct binding to the N-terminal region of MYOCD
  • STAT3 protein regulates vascular smooth muscle cell phenotypic switch by interaction with MYOCD
  • PRKCA inhibits MYOCD-induced cardiomyocyte hypertrophy through the promotion of myocardin phosphorylation
  • correlations of MYOCD with CAV1 in a majority of human tissues and in the heart, correlation with MKL2
  • TCF21 blocks MYOCD and SRF association by direct TCF21-MYOCD interaction in smooth muscle cell differentiation
  • cell & other
    activated by mediated by PI3K pathway
    inhibited by SMAD3 sequestration of NKX2.5, a critical transcription factor for MYOCD transcription
    Other Nuclear receptor coactivator 3 (NCOA3) enhances myocardin-mediated transcriptional activation of vascular smooth muscle cell-specific genes
    inhibition of MYOCD gene activation in the early stage of TGFB induction is due to SMAD3 nuclear translocation
    acetylation of MYOCD is required for myocardin to activate smooth muscle genes
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in response to vascular injury
    tumoral   translocation    
    translocation t(17;22) (q22;q13) with chimeric proteins 5' - COL1A1 - PDGFB - 3'in dermatofibrosarcoma protuberans
    tumoral     --other  
    dysregulation of expression in meningiomas
    constitutional     --over  
    upon induction of hypertrophy in cultured cardiomyocytes and in patients with left ventricular hypertrophy
    Susceptibility to inter-individual differences in the development of cardiac hypertrophy
    Variant & Polymorphism other polymorphism in the promoter contributing to inter-individual differences in the development of cardiac hypertrophy
    Candidate gene
    Therapy target
  • embryos homozygous for a myocardin loss-of-function mutation died by embryonic day 10.5 and showed no evidence of vascular smooth muscle cell differentiation
  • mice harboring cardiomyocyte-restricted null mutations of the myocardin gene should provide new insights into the pathogenesis of dilated and arrhythmogenic cardiomyopathy and identify novel therapeutic targets for these debilitating diseases