MEF2A

Myocyte-specific enhancer factor 2A ;
Serum response factor-like protein 1 ;

disease:Defects in MEF2A might be a cause of autosomal dominant coronary artery disease 1 with myocardial infarction (ADCAD1) [MIM:608320]. ,function:Transcriptional activator which binds specifically to the MEF2 element , 5'-YTA[AT] (4) TAR-3' , found in numerous muscle-specific genes. Also involved in the activation of numerous growth factor- and stress-induced genes. Mediates cellular functions not only in skeletal and cardiac muscle development , but also in neuronal differentiation and survival. Plays diverse roles in the control of cell growth , survival and apoptosis via p38 MAPK signaling in muscle-specific and/or growth factor-related transcription. In cerebellar granule neurons , phosphorylated and sumoylated MEF2A represses transcription of NUR77 promoting synaptic differentiation. ,PTM:Acetylation on Lys-403 activates transcriptional activity. Acetylated by p300 on several sites in diffentiating myocytes. Acetylation on Lys-4 increases DNA binding and transactivation (By similarity) . Hyperacetylation by p300 leads to enhanced cardiac myocyte growth and heart failure. ,PTM:Constitutive phosphorylation on Ser-408 promotes Lys-403 sumoylation thus preventing acetylation at this site. Dephosphorylation on Ser-408 by PPP3CA upon neuron depolarization promotes a switch from sumoylation to acetylation on residue Lys-403 leading to inhibition of dendrite claw differentiation. Phosphorylation on Thr-312 and Thr-319 are the main sites involved in p38 MAPK signaling and activate transcription. Phosphorylated on these sites by MAPK14/p38alpha and MAPK11/p38beta , but not by MAPK13/p38delta nor by MAPK12/p38gamma. Phosphorylation on Ser-408 by CDK5 induced by neurotoxicity inhibits MEF2A transciptional activation leading to apoptosis of cortical neurons. Phosphorylation on Thr-312 , Thr-319 and Ser-355 can be induced by EGF. ,PTM:Proteolytically cleaved in cerebellar granule neurons on several sites by caspase 3 and caspase 7 following neurotoxicity. Preferentially cleaves the CDK5-mediated hyperphosphorylated form which leads to neuron apoptosis and transcriptional inactivation. ,PTM:Sumoylation on Lys-403 is enhanced by PIAS1 and represses transcriptional activity. Phosphorylation on Ser-408 is required for sumoylation. Has no effect on nuclear location nor on DNA binding. Sumoylated by SUMO1 and , to a lesser extent by SUMO2 and SUMO3. PIASx facilitates sumoylation in postsynaptic dendrites in the cerebellar cortex and promotes their morphogenesis. ,similarity:Belongs to the MEF2 family. ,similarity:Contains 1 MADS-box domain. ,similarity:Contains 1 Mef2-type DNA-binding domain. ,subunit:Binds DNA as a homo- or heterodimer. Dimerizes with MEF2D. Interacts with HDAC7 (By similarity) . Interacts with PIAS1; the interaction enhances sumoylation. Interacts with HDAC4 , HDAC9 and SLC2A4RG. Interacts (via the N-terminal) with MAPK7; the interaction results in the phosphorylation and transcriptional activity of MEF2A. ,tissue specificity:Isoform MEF2 and isoform MEFA are expressed only in skeletal and cardiac muscle and in the brain while isoform RSRFC4 and isoform RSRFC9 are expressed in all tissues examined. ,

transcription , regulation of transcription , DNA-dependent , apoptosis , muscle organ development , cell death ,programmed cell death , death , regulation of transcription , regulation of RNA metabolic process ,

Nucleus .