MADS box transcription enhancer factor 2, polypeptide C
Myocyte enhancer factor 2C
Myocyte specific enhancer factor 2C
Myocyte-specific enhancer factor 2C
Similar to MADS box transcription enhancer factor 2 polypeptide C
Transcription activator which binds specifically to the MEF2 element present in the regulatory regions of many muscle-specific genes. Controls cardiac morphogenesis and myogenesis, and is also involved in vascular development. Plays an essential role in hippocampal-dependent learning and memory by suppressing the number of excitatory synapses and thus regulating basal and evoked synaptic transmission. Crucial for normal neuronal development, distribution, and electrical activity in the neocortex. Necessary for proper development of megakaryocytes and platelets and for bone marrow B lymphopoiesis. Required for B-cell survival and proliferation in response to BCR stimulation, efficient IgG1 antibody responses to T-cell-dependent antigens and for normal induction of germinal center B cells. May also be involved in neurogenesis and in the development of cortical architecture (By similarity). Isoform 3 and isoform 4, which lack the repressor domain, are more active than isoform 1 and isoform 2.
Expressed in brain and skeletal muscle.
Involvement in disease
Defects in MEF2C are the cause of mental retardation-stereotypic movements-epilepsy and/or cerebral malformations (MRSME) [MIM:613443]. It is a disorder characterized by severe mental retardation, absent speech, hypotonia, poor eye contact and stereotypic movements. Dysmorphic features include high broad forehead with variable small chin, short nose with anteverted nares, large open mouth, upslanted palpebral fissures and prominent eyebrows. Some patients have seizures.
Belongs to the MEF2 family. Contains 1 MADS-box domain. Contains 1 Mef2-type DNA-binding domain.
Expression is highest during the early stages of postnatal development, at later stages levels greatly decrease.
The beta domain, missing in a number of isoforms, is required for enhancement of transcriptional activity.
Phosphorylation on Ser-59 enhances DNA binding activity (By similarity). Phosphorylation on Ser-396 is required for Lys-391 sumoylation and inhibits transcriptional activity. Acetylated by p300 on several sites in diffentiating myocytes. Acetylation on Lys-4 increases DNA binding and transactivation. Sumoylated on Lys-391 by SUMO2 but not by SUMO1 represses transcriptional activity. Proteolytically cleaved in cerebellar granule neurons, probably by caspase 7, following neurotoxicity. Preferentially cleaves the CDK5-mediated hyperphosphorylated form which leads to neuron apoptosis and transcriptional inactivation.