MEF2D

This gene is a member of the myocyte-specific enhancer factor 2 (MEF2) family of transcription factors. Members of this family are involved in control of muscle and neuronal cell differentiation and development, and are regulated by class II histone deacetylases. Fusions of the encoded protein with Deleted in Azoospermia-Associated Protein 1 (DAZAP1) due to a translocation have been found in an acute lymphoblastic leukemia cell line, suggesting a role in leukemogenesis. The encoded protein may also be involved in Parkinson disease and myotonic dystrophy. Alternative splicing results in multiple transcript variants.

myocyte enhancer factor 2D

Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT]4TAR-3', found in numerous muscle-specific, 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. Plays a critical role in the regulation of neuronal apoptosis (By similarity).

Adult heart development Source: UniProtKB
Apoptotic process Source: UniProtKB-KW
Cell differentiation Source: GO_Central
Chondrocyte differentiation Source: Ensembl
Endochondral ossification Source: Ensembl
Muscle organ development Source: ProtInc
Nervous system development Source: UniProtKB-KW
Osteoblast differentiation Source: Ensembl
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Positive regulation of vascular associated smooth muscle cell proliferation Source: BHF-UCL
Regulation of transcription by RNA polymerase II Source: GO_Central
Skeletal muscle cell differentiation Source: Ensembl

Nucleus
Note: Translocated by HDAC4 to nuclear dots.

Phosphorylated on Ser-444 by CDK5 is required for Lys-439 sumoylation and inhibits transcriptional activity. In neurons, enhanced CDK5 activity induced by neurotoxins promotes caspase 3-mediated cleavage leading to neuron apoptosis. Phosphorylation on Ser-180 can be enhanced by EGF. Phosphorylated and activated by CaMK4.
Acetylated on Lys-439 by CREBBP. Acetylated by EP300. Deacetylated by SIRT1 and HDAC3.
Sumoylated on Lys-439 with SUMO2 but not SUMO1; which inhibits transcriptional activity and myogenic activity. Desumoylated by SENP3.
Proteolytically cleaved in cerebellar granule neurons on several sites by caspase 7 following neurotoxicity. Preferentially cleaves the CDK5-mediated hyperphosphorylated form which leads to neuron apoptosis and transcriptional inactivation (By similarity).