MEF2C

Myocyte enhancer factor 2C
PDB rendering based on 1c7u.
Available structures PDB 1c7u, 1egw
Identifiers
Symbols	MEF2C;
External IDs	OMIM: 600662 MGI: 99458 HomoloGene: 31087 GeneCards: MEF2C Gene
Gene Ontology Molecular function • sequence-specific DNA binding transcription factor activity • protein binding • activating transcription factor binding • sequence-specific DNA binding • transcription regulatory region DNA binding • protein heterodimerization activity Cellular component • nucleus • nucleoplasm • nucleoplasm • nucleolus • nuclear speck • intracellular membrane-bounded organelle Biological process • negative regulation of transcription from RNA polymerase II promoter • MAPKKK cascade • MAPKKK cascade • toll-like receptor signaling pathway • regulation of germinal center formation • MyD88-dependent toll-like receptor signaling pathway • MyD88-dependent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • transcription, DNA-dependent • apoptosis • multicellular organismal development • nervous system development • muscle organ development • learning or memory • Toll signaling pathway • neuron differentiation • toll-like receptor 1 signaling pathway • toll-like receptor 2 signaling pathway • toll-like receptor 3 signaling pathway • toll-like receptor 4 signaling pathway • B cell proliferation • muscle cell differentiation • innate immune response • regulation of megakaryocyte differentiation • positive regulation of survival gene product expression • positive regulation of transcription from RNA polymerase II promoter • positive regulation of transcription from RNA polymerase II promoter • nerve growth factor receptor signaling pathway • neuron development • positive regulation of muscle cell differentiation • stress-activated MAPK cascade • regulation of synaptic activity Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4208	17260
Ensembl	ENSG00000081189	ENSMUSG00000005583
UniProt	Q06413	Q3V1B5
RefSeq (mRNA)	NM_001131005.2	NM_025282
RefSeq (protein)	NP_001124477.1	NP_079558
Location (UCSC)	Chr 5: 88.01 – 88.2 Mb	Chr 13: 83.64 – 83.81 Mb
PubMed search	[1]	[2]

Myocyte-specific enhancer factor 2C also known as MADS box transcription enhancer factor 2, polypeptide C is a protein that in humans is encoded by the MEF2C gene.^[1] MEF2C is a transcription factor in the Mef2 family.^[2][3]

Genomics

The gene is located at 5q14.3 on the minus (Crick) strand and is 200,723 bases in length. The encoded protein has 473 amino acids with a predicted molecular weight of 51.221 kiloDaltons. Three isoforms have been identified. Several post translational modifications have been identified including phosphorylation on serine-59 and serine-396, sumoylation on lysine-391, acetylation on lysine-4 and proteolytic cleavage.

The mature protein is found in the nucleus and the gene's expression is maximal in the post natal period.

Interactions

MEF2C has been shown to interact with MAPK7,^[4] EP300,^[5] Sp1 transcription factor,^[6] TEAD1,^[7] SOX18^[8]HDAC4, HDAC7 and HDAC9.^[9][10]

Biological significance

This gene is involved in cardiac morphogenesis and myogenesis and vascular development. It may also be involved in neurogenesis and in the development of cortical architecture. Mice without a functional copy of the Mef2c gene die before birth and have abnormalities in the heart and vascular system.^[11] It is one of the targets of an oncomiR, MIRN21.

In humans mutations of this gene have resulted in severe psychomotor retardation, periodic tremor and an abnormal motor pattern with mirror movement of the upper limbs observed during infancy, hypotonia, abnormal EEG, epilepsy, absence of speech, autistic behavior, bruxism, and mild dysmorphic features, mild thinning of the corpus callosum and delay of white matter myelination in the occipital lobes^[12]

See also

• Mef2

References

1. ^ McDermott JC, Cardoso MC, Yu YT, Andres V, Leifer D, Krainc D, Lipton SA, Nadal-Ginard B (April 1993). "hMEF2C gene encodes skeletal muscle- and brain-specific transcription factors". Mol. Cell. Biol. 13 (4): 2564–77. PMC 359588. PMID 8455629. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=359588. 
2. ^ Molkentin JD, Black BL, Martin JF, Olson EN (1996). "Mutational analysis of the DNA binding, dimerization, and transcriptional activation domains of MEF2C". Mol Cell Biol. 16 (6): 2627–36. PMC 231253. PMID 8649370. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=231253. 
3. ^ "Entrez Gene: MEF2C myocyte enhancer factor 2C". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4208. 
4. ^ Yang, C C; Ornatsky O I, McDermott J C, Cruz T F, Prody C A (Oct. 1998). "Interaction of myocyte enhancer factor 2 (MEF2) with a mitogen-activated protein kinase, ERK5/BMK1". Nucleic Acids Res. (ENGLAND) 26 (20): 4771–7. doi:10.1093/nar/26.20.4771. ISSN 0305-1048. PMC 147902. PMID 9753748. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=147902. 
5. ^ Sartorelli, V; Huang J, Hamamori Y, Kedes L (Feb. 1997). "Molecular mechanisms of myogenic coactivation by p300: direct interaction with the activation domain of MyoD and with the MADS box of MEF2C". Mol. Cell. Biol. (UNITED STATES) 17 (2): 1010–26. ISSN 0270-7306. PMC 231826. PMID 9001254. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=231826. 
6. ^ Krainc, D; Bai G, Okamoto S, Carles M, Kusiak J W, Brent R N, Lipton S A (Oct. 1998). "Synergistic activation of the N-methyl-D-aspartate receptor subunit 1 promoter by myocyte enhancer factor 2C and Sp1". J. Biol. Chem. (UNITED STATES) 273 (40): 26218–24. doi:10.1074/jbc.273.40.26218. ISSN 0021-9258. PMID 9748305. 
7. ^ Maeda, Tomoji; Gupta Mahesh P, Stewart Alexandre F R (Jun. 2002). "TEF-1 and MEF2 transcription factors interact to regulate muscle-specific promoters". Biochem. Biophys. Res. Commun. (United States) 294 (4): 791–7. doi:10.1016/S0006-291X(02)00556-9. ISSN 0006-291X. PMID 12061776. 
8. ^ Hosking, B M; Wang S C, Chen S L, Penning S, Koopman P, Muscat G E (Sep. 2001). "SOX18 directly interacts with MEF2C in endothelial cells". Biochem. Biophys. Res. Commun. (United States) 287 (2): 493–500. doi:10.1006/bbrc.2001.5589. ISSN 0006-291X. PMID 11554755. 
9. ^ Wang, A H; Bertos N R, Vezmar M, Pelletier N, Crosato M, Heng H H, Th'ng J, Han J, Yang X J (Nov. 1999). "HDAC4, a Human Histone Deacetylase Related to Yeast HDA1, Is a Transcriptional Corepressor". Mol. Cell. Biol. (UNITED STATES) 19 (11): 7816–27. ISSN 0270-7306. PMC 84849. PMID 10523670. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=84849. 
10. ^ Wang, A H; Yang X J (Sep. 2001). "Histone Deacetylase 4 Possesses Intrinsic Nuclear Import and Export Signals". Mol. Cell. Biol. (United States) 21 (17): 5992–6005. doi:10.1128/MCB.21.17.5992-6005.2001. ISSN 0270-7306. PMC 87317. PMID 11486037. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=87317. 
11. ^ Bi W, Drake CJ, Schwarz JJ (1999). "The transcription factor MEF2C-null mouse exhibits complex vascular malformations and reduced cardiac expression of angiopoietin 1 and VEGF". Developmental Biology 211 (2): 255–67. doi:10.1006/dbio.1999.9307. PMID 10395786. 
12. ^ Nowakowska BA, Obersztyn E, Szymańska K, Bekiesińska-Figatowska M, Xia Z, Ricks CB, Bocian E, Stockton DW, Szczałuba K, Nawara M, Patel A, Scott DA, Cheung SW, Bohan TP, Stankiewicz P (March 2010). "Severe mental retardation, seizures, and hypotonia due to deletions of MEF2C". Am J Med Genet B Neuropsychiatr Genet 153B (5): 1042–51. doi:10.1002/ajmg.b.31071. PMID 20333642. 

Further reading

• Leifer D, Krainc D, Yu YT, et al. (1993). "MEF2C, a MADS/MEF2-family transcription factor expressed in a laminar distribution in cerebral cortex". Proc. Natl. Acad. Sci. U.S.A. 90 (4): 1546–50. doi:10.1073/pnas.90.4.1546. PMC 45911. PMID 7679508. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=45911. 
• Hobson GM, Krahe R, Garcia E, et al. (1996). "Regional chromosomal assignments for four members of the MADS domain transcription enhancer factor 2 (MEF2) gene family to human chromosomes 15q26, 19p12, 5q14, and 1q12-q23". Genomics 29 (3): 704–11. doi:10.1006/geno.1995.9007. PMID 8575763. 
• Krainc D, Haas M, Ward DC, et al. (1996). "Assignment of human myocyte-specific enhancer binding factor 2C (hMEF2C) to human chromosome 5q14 and evidence that MEF2C is evolutionarily conserved". Genomics 29 (3): 809–11. doi:10.1006/geno.1995.9927. PMID 8575784. 
• Molkentin JD, Li L, Olson EN (1996). "Phosphorylation of the MADS-Box transcription factor MEF2C enhances its DNA binding activity". J. Biol. Chem. 271 (29): 17199–204. doi:10.1074/jbc.271.29.17199. PMID 8663403. 
• Black BL, Ligon KL, Zhang Y, Olson EN (1996). "Cooperative transcriptional activation by the neurogenic basic helix-loop-helix protein MASH1 and members of the myocyte enhancer factor-2 (MEF2) family". J. Biol. Chem. 271 (43): 26659–63. doi:10.1074/jbc.271.43.26659. PMID 8900141. 
• Gradwohl G, Fode C, Guillemot F (1997). "Restricted expression of a novel murine atonal-related bHLH protein in undifferentiated neural precursors". Dev. Biol. 180 (1): 227–41. doi:10.1006/dbio.1996.0297. PMID 8948587. 
• Sartorelli V, Huang J, Hamamori Y, Kedes L (1997). "Molecular mechanisms of myogenic coactivation by p300: direct interaction with the activation domain of MyoD and with the MADS box of MEF2C". Mol. Cell. Biol. 17 (2): 1010–26. PMC 231826. PMID 9001254. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=231826. 
• Han J, Jiang Y, Li Z, et al. (1997). "Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation". Nature 386 (6622): 296–9. doi:10.1038/386296a0. PMID 9069290. 
• Kato Y, Kravchenko VV, Tapping RI, et al. (1998). "BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C". EMBO J. 16 (23): 7054–66. doi:10.1093/emboj/16.23.7054. PMC 1170308. PMID 9384584. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1170308. 
• Krainc D, Bai G, Okamoto S, et al. (1998). "Synergistic activation of the N-methyl-D-aspartate receptor subunit 1 promoter by myocyte enhancer factor 2C and Sp1". J. Biol. Chem. 273 (40): 26218–24. doi:10.1074/jbc.273.40.26218. PMID 9748305. 
• Yang CC, Ornatsky OI, McDermott JC, et al. (1998). "Interaction of myocyte enhancer factor 2 (MEF2) with a mitogen-activated protein kinase, ERK5/BMK1". Nucleic Acids Res. 26 (20): 4771–7. doi:10.1093/nar/26.20.4771. PMC 147902. PMID 9753748. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=147902. 
• Swanson BJ, Jäck HM, Lyons GE (1998). "Characterization of myocyte enhancer factor 2 (MEF2) expression in B and T cells: MEF2C is a B cell-restricted transcription factor in lymphocytes". Mol. Immunol. 35 (8): 445–58. doi:10.1016/S0161-5890(98)00058-3. PMID 9798649. 
• Zhao M, New L, Kravchenko VV, et al. (1999). "Regulation of the MEF2 Family of Transcription Factors by p38". Mol. Cell. Biol. 19 (1): 21–30. PMC 83862. PMID 9858528. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=83862. 
• Wilson-Rawls J, Molkentin JD, Black BL, Olson EN (1999). "Activated Notch Inhibits Myogenic Activity of the MADS-Box Transcription Factor Myocyte Enhancer Factor 2C". Mol. Cell. Biol. 19 (4): 2853–62. PMC 84078. PMID 10082551. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=84078. 
• Yang SH, Galanis A, Sharrocks AD (1999). "Targeting of p38 Mitogen-Activated Protein Kinases to MEF2 Transcription Factors". Mol. Cell. Biol. 19 (6): 4028–38. PMC 104362. PMID 10330143. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=104362. 
• Wang AH, Bertos NR, Vezmar M, et al. (1999). "HDAC4, a Human Histone Deacetylase Related to Yeast HDA1, Is a Transcriptional Corepressor". Mol. Cell. Biol. 19 (11): 7816–27. PMC 84849. PMID 10523670. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=84849. 
• Lu J, McKinsey TA, Nicol RL, Olson EN (2000). "Signal-dependent activation of the MEF2 transcription factor by dissociation from histone deacetylases". Proc. Natl. Acad. Sci. U.S.A. 97 (8): 4070–5. doi:10.1073/pnas.080064097. PMC 18151. PMID 10737771. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=18151. 
• Morin S, Charron F, Robitaille L, Nemer M (2000). "GATA-dependent recruitment of MEF2 proteins to target promoters". EMBO J. 19 (9): 2046–55. doi:10.1093/emboj/19.9.2046. PMC 305697. PMID 10790371. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=305697. 
• Wu Z, Woodring PJ, Bhakta KS, et al. (2000). "p38 and Extracellular Signal-Regulated Kinases Regulate the Myogenic Program at Multiple Steps". Mol. Cell. Biol. 20 (11): 3951–64. doi:10.1128/MCB.20.11.3951-3964.2000. PMC 85749. PMID 10805738. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85749. 

External links

• MeSH MEF2C+protein,+human
• FactorBook MEF2C