MEF2C (human, Q06413) curation notes

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Molecular function

• MADS-box/MEF2 transcription factor. It binds A/T-rich MEF2 sites as a dimer and transactivates PMID:8455629; PMID:9858528.
• Partner DNA-binding TFs bind it through the DNA-binding domain:
• MyoD/myogenin PMID:8548800
• HAND1 PMID:16043483
• HAND2 PMID:15486975
• TBX5 PMID:19204083
• NKX2-5 PMID:19035347
• SOX10 PMID:21610032
• Repression by class II HDACs PMID:10983972.
• Coactivators: MAML1 PMID:16510869; p300, recruited after skMLCK phosphorylates T80 PMID:21556048.
• Activated by p38 PMID:9069290. MEF2C is the kinase's substrate, not a component of the MAPK cascade.

Heart

• Mef2c-null mice PMID:9162005.
• Second heart field: direct ISL1/GATA target PMID:15253934.
• Positive loop with NKX2-5 PMID:9857019. In double mutants the ventricular defect reflects differentiation, not proliferation PMID:19035347.
• The linear heart tube still forms in nulls, so primary heart field specification is marked as an over-annotation.

Other tissues (pleiotropic, kept as non-core)

• Bone/cartilage PMID:17336904.
• Neurons:
• synapse number PMID:18599438
• cortical neuron differentiation PMID:18599437
• human haploinsufficiency syndrome PMID:19592390
• B cells PMID:18438409.
• Megakaryocytes/platelets PMID:19211936.
• Melanocytes/neural crest PMID:21610032.

Review decisions (summary)

• Core:
• GO:0000981 Pol II DbTF activity
• GO:0045944 positive regulation of transcription by Pol II
• Heart and cardiac muscle cell differentiation terms: GO:0007507, GO:0055012, GO:2000727
• Skeletal myoblast differentiation
• GO:0061629 partner-TF binding
• GO:0042826 HDAC binding
• Generic protein binding rows were changed to HDAC, coactivator, partner-TF, kinase, HAT or E3-ligase binding where the partner is informative. MEK5 and CACNA1C rows were removed.
• Postsynapse IEA was removed, because MEF2C is a nuclear TF.
• Over-annotations: MAPK cascade, EPSP and NMDA/AMPA pathway terms, response to ischemia/xenobiotic/TSA, muscle cell fate determination, primary heart field specification, and negative regulation of ossification (a SOST reporter-assay inference that contradicts in vivo pro-ossification data).
• Kidney, sinoatrial valve, macrophage apoptosis and shear stress ISS terms are UNDECIDED, because their sources could not be checked.