Protein-coding gene in the species Homo sapiens
Myocyte-specific enhancer factor 2C also known asMADS box transcription enhancer factor 2, polypeptide C is aprotein that in humans is encoded by theMEF2C gene .[ 4] [ 5] transcription factor in theMef2 family.[ 6] [ 7]
The gene is located at 5q14.3 on theminus (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 onserine -59 and serine-396, sumoylation onlysine -391, acetylation on lysine-4 and proteolytic cleavage.
MEF2C has been shown tointeract with:
Biological significance [ edit ] 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 theMef2c gene die before birth and have abnormalities in theheart andvascular system .[ 15] MIRN21 .
In humans mutations of this gene result inautosomal dominant mental retardation 20 (MRD20),[ 16] tremor and an abnormal motor pattern with mirror movement of the upper limbs observed during infancy,hypotonia , abnormalEEG ,epilepsy , absence of speech,autistic behavior ,bruxism , and milddysmorphic features , mild thinning of thecorpus callosum and delay ofwhite matter myelination in theoccipital lobes [ 17]
MEF2C-binding site is associated with minor allele of SNP rs630923, associated with the risk of multiple sclerosis, and responsible for reducedCXCR5 gene promoter activity in B-cells during activation, that could lead to decreased autoimmune response[ 18]
^a b c GRCh38: Ensembl release 89: ENSG00000081189 –Ensembl , May 2017^ "Human PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^ Leifer D, Krainc D, Yu YT, McDermott J, Breitbart RE, Heng J, Neve RL, Kosofsky B, Nadal-Ginard B, Lipton SA (Feb 1993)."MEF2C, a MADS/MEF2-family transcription factor expressed in a laminar distribution in cerebral cortex" .Proceedings of the National Academy of Sciences of the United States of America .90 (4):1546– 50.Bibcode :1993PNAS...90.1546L .doi :10.1073/pnas.90.4.1546 PMC 45911 PMID 7679508 . ^ McDermott JC, Cardoso MC, Yu YT, Andres V, Leifer D, Krainc D, Lipton SA, Nadal-Ginard B (Apr 1993)."hMEF2C gene encodes skeletal muscle- and brain-specific transcription factors" .Molecular and Cellular Biology .13 (4):2564– 77.doi :10.1128/mcb.13.4.2564 .PMC 359588 PMID 8455629 . ^ Molkentin JD, Black BL, Martin JF, Olson EN (Jun 1996)."Mutational analysis of the DNA binding, dimerization, and transcriptional activation domains of MEF2C" .Molecular and Cellular Biology .16 (6):2627– 36.doi :10.1128/mcb.16.6.2627 .PMC 231253 PMID 8649370 . ^ "Entrez Gene: MEF2C myocyte enhancer factor 2C" .^ 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" .Molecular and Cellular Biology .17 (2):1010– 26.doi :10.1128/mcb.17.2.1010 .PMC 231826 PMID 9001254 . ^ Wang AH, Bertos NR, Vezmar M, Pelletier N, Crosato M, Heng HH, Th'ng J, Han J, Yang XJ (Nov 1999)."HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor" .Molecular and Cellular Biology .19 (11):7816– 27.doi :10.1128/mcb.19.11.7816 .PMC 84849 PMID 10523670 . ^ Wang AH, Yang XJ (Sep 2001)."Histone deacetylase 4 possesses intrinsic nuclear import and export signals" .Molecular and Cellular Biology .21 (17):5992– 6005.doi :10.1128/MCB.21.17.5992-6005.2001 .PMC 87317 PMID 11486037 . ^ Yang CC, Ornatsky OI, McDermott JC, Cruz TF, Prody CA (Oct 1998)."Interaction of myocyte enhancer factor 2 (MEF2) with a mitogen-activated protein kinase, ERK5/BMK1" .Nucleic Acids Research .26 (20):4771– 7.doi :10.1093/nar/26.20.4771 .PMC 147902 PMID 9753748 . ^ Hosking BM, Wang SC, Chen SL, Penning S, Koopman P, Muscat GE (Sep 2001). "SOX18 directly interacts with MEF2C in endothelial cells".Biochemical and Biophysical Research Communications .287 (2):493– 500.Bibcode :2001BBRC..287..493H .doi :10.1006/bbrc.2001.5589 .PMID 11554755 . ^ Krainc D, Bai G, Okamoto S, Carles M, Kusiak JW, Brent RN, Lipton SA (Oct 1998)."Synergistic activation of the N-methyl-D-aspartate receptor subunit 1 promoter by myocyte enhancer factor 2C and Sp1" .The Journal of Biological Chemistry .273 (40):26218– 24.doi :10.1074/jbc.273.40.26218 PMID 9748305 . ^ Maeda T, Gupta MP, Stewart AF (Jun 2002). "TEF-1 and MEF2 transcription factors interact to regulate muscle-specific promoters".Biochemical and Biophysical Research Communications .294 (4):791– 7.Bibcode :2002BBRC..294..791M .doi :10.1016/S0006-291X(02)00556-9 .PMID 12061776 . ^ Bi W, Drake CJ, Schwarz JJ (Jul 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 . ^ Online Mendelian Inheritance in Man (OMIM):613443 ^ 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 (Jul 2010)."Severe mental retardation, seizures, and hypotonia due to deletions of MEF2C" .American Journal of Medical Genetics Part B .153B (5):1042– 51.doi :10.1002/ajmg.b.31071 PMID 20333642 .S2CID 3895117 . ^ Mitkin NA, Muratova AM, Schwartz AM, Kuprash DV (Nov 2016)."The A Allele of the Single-Nucleotide Polymorphism rs630923 Creates a Binding Site for MEF2C Resulting in Reduced CXCR5 Promoter Activity in B-Cell Lymphoblastic Cell Lines" .Front. Immunol .7 (515): 515.doi :10.3389/fimmu.2016.00515 PMC 5112242 PMID 27909439 . Leifer D, Krainc D, Yu YT, McDermott J, Breitbart RE, Heng J, Neve RL, Kosofsky B, Nadal-Ginard B, Lipton SA (Feb 1993)."MEF2C, a MADS/MEF2-family transcription factor expressed in a laminar distribution in cerebral cortex" .Proceedings of the National Academy of Sciences of the United States of America .90 (4):1546– 50.Bibcode :1993PNAS...90.1546L .doi :10.1073/pnas.90.4.1546 PMC 45911 PMID 7679508 . Hobson GM, Krahe R, Garcia E, Siciliano MJ, Funanage VL (Oct 1995). "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, Lipton SA, Bruns G, Leifer D (Oct 1995)."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 (Jul 1996)."Phosphorylation of the MADS-Box transcription factor MEF2C enhances its DNA binding activity" .The Journal of Biological Chemistry .271 (29):17199– 204.doi :10.1074/jbc.271.29.17199 PMID 8663403 . Black BL, Ligon KL, Zhang Y, Olson EN (Oct 1996)."Cooperative transcriptional activation by the neurogenic basic helix-loop-helix protein MASH1 and members of the myocyte enhancer factor-2 (MEF2) family" .The Journal of Biological Chemistry .271 (43):26659– 63.doi :10.1074/jbc.271.43.26659 PMID 8900141 . Gradwohl G, Fode C, Guillemot F (Nov 1996)."Restricted expression of a novel murine atonal-related bHLH protein in undifferentiated neural precursors" .Developmental Biology .180 (1):227– 41.doi :10.1006/dbio.1996.0297 PMID 8948587 . 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" .Molecular and Cellular Biology .17 (2):1010– 26.doi :10.1128/mcb.17.2.1010 .PMC 231826 PMID 9001254 . Han J, Jiang Y, Li Z, Kravchenko VV, Ulevitch RJ (Mar 1997). "Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation".Nature .386 (6622):296– 9.Bibcode :1997Natur.386..296H .doi :10.1038/386296a0 .PMID 9069290 .S2CID 4234197 . Kato Y, Kravchenko VV, Tapping RI, Han J, Ulevitch RJ, Lee JD (Dec 1997)."BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C" .The EMBO Journal .16 (23):7054– 66.doi :10.1093/emboj/16.23.7054 .PMC 1170308 PMID 9384584 . Krainc D, Bai G, Okamoto S, Carles M, Kusiak JW, Brent RN, Lipton SA (Oct 1998)."Synergistic activation of the N-methyl-D-aspartate receptor subunit 1 promoter by myocyte enhancer factor 2C and Sp1" .The Journal of Biological Chemistry .273 (40):26218– 24.doi :10.1074/jbc.273.40.26218 PMID 9748305 . Yang CC, Ornatsky OI, McDermott JC, Cruz TF, Prody CA (Oct 1998)."Interaction of myocyte enhancer factor 2 (MEF2) with a mitogen-activated protein kinase, ERK5/BMK1" .Nucleic Acids Research .26 (20):4771– 7.doi :10.1093/nar/26.20.4771 .PMC 147902 PMID 9753748 . Swanson BJ, Jäck HM, Lyons GE (Jun 1998). "Characterization of myocyte enhancer factor 2 (MEF2) expression in B and T cells: MEF2C is a B cell-restricted transcription factor in lymphocytes".Molecular Immunology .35 (8):445– 58.doi :10.1016/S0161-5890(98)00058-3 .PMID 9798649 . Zhao M, New L, Kravchenko VV, Kato Y, Gram H, di Padova F, Olson EN, Ulevitch RJ, Han J (Jan 1999)."Regulation of the MEF2 family of transcription factors by p38" .Molecular and Cellular Biology .19 (1):21– 30.doi :10.1128/mcb.19.1.21 .PMC 83862 PMID 9858528 . Wilson-Rawls J, Molkentin JD, Black BL, Olson EN (Apr 1999)."Activated notch inhibits myogenic activity of the MADS-Box transcription factor myocyte enhancer factor 2C" .Molecular and Cellular Biology .19 (4):2853– 62.doi :10.1128/mcb.19.4.2853 .PMC 84078 PMID 10082551 . 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(1) Basic domains
(1.1) Basic leucine zipper (bZIP )(1.2) Basic helix-loop-helix (bHLH )
Group A Group B Group CPAS Group D Group E Group F
(1.3) bHLH-ZIP (1.4) NF-1 (1.5) RF-X (1.6) Basic helix-span-helix (bHSH)
(2.1) Nuclear receptor (Cys4 )
subfamily 1 subfamily 2 subfamily 3 subfamily 4 subfamily 5 subfamily 6 subfamily 0
(2.2) Other Cys4 (2.3) Cys2 His2 (2.4) Cys6 (2.5) Alternating composition (2.6) WRKY
(4)β-Scaffold factors with minor groove contacts
(0) Other transcription factors
